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Evaluation of women with possible appendicitis using technetium-99m leukocyte scan, The authors evaluated the use of technetium-99m albumin colloid white blood cell (TAC-WBC) scan in women with possible appendicitis. One hundred and nine women underwent 110 TAC-WBC scans. One woman had a second scan on a separate admission and was considered two individual patients in the analysis. Twenty-six women had appendicitis. 10 of whom had a perforated appendix at surgery. The TAC-WBC scan was indeterminate (abnormal but nondiagnostic for appendicitis) in 52 women (47%). nine of whom had appendicitis. Fifty-eight scans were read as positive or negative for appendiceal pathology. There were 16 true positives. 5 false positives. 36 true negatives. and 1 false negative. The predictive value of a positive scan was 76%. and the predictive value of a negative scan was 97%. The TAC-WBC scan was positive in 62% of patients with appendicitis and negative in 43% of the patients without appendicitis resulting in an overall accuracy of 47% in the 109 women. The main value of TAC-WBC scan in women with possible appendicitis is its high negative predictive value and the main problem with the TAC-WBC scan is its high indeterminate rate.
| 5 |
Cause of death in an emergency department, A retrospective review was done of 601 consecutive emergency department deaths. Nontrauma causes accounted for 77% of the deaths and this group had an average age of 64 years and a male to female ratio of 1.9:1. Trauma caused 23% of the fatalities and this group had a younger average age of 29 years and a male to female ratio of 4.6:1. The most common causes of nontrauma death were sudden death of uncertain cause (34%). coronary artery disease (34%). cancer (5%). other heart disease (4%). chronic obstructive lung disease (3%). drug overdose (3%). and sudden infant death syndrome (2%). The most common causes of trauma death were motor vehicle accidents (61%) and gunshot wounds (16%). The overall autopsy rate was 40%. Death certificates were often in error.
| 13 |
Intermittent obstruction of an incarcerated hiatal hernia with a total thoracic stomach, A case of intermittent obstruction of a sliding hiatal hernia is presented. The obstruction occurred when the patient's stomach was totally above the diaphragm. The anatomy of sliding hiatal hernias is discussed. as well as the presenting signs and symptoms of obstruction in sliding hiatal hernias.
| 5 |
Excitatory amino acids in the developing brain: ontogeny, plasticity, and excitotoxicity, Besides their role as neurotransmitters. excitatory amino acids (EAAs) in the developing brain are crucially involved in plasticity and excitotoxicity which are modified by their distinct ontogeny. Along with incomplete neuritogenesis and synaptogenesis. presynaptic markers of the EAA system are immature in the developing brain; however. postsynaptic EAA system activities. particularly of the N-methyl-D-aspartate and quisqualate receptors. are transiently enhanced early in life. This transient enhancement is presumably beneficial to the immature brain because physiologic activation of the EAA system plays a critical role in plasticity of early learning and morphogenesis. At the same time. this transient hypersensitivity renders the immature brain vulnerable to pathologic excitation of the EAA system (excitotoxicity) as observed during neonatal hypoxia-ischemia.
| 9 |
Anencephaly: clinical determination of brain death and neuropathologic studies, Twelve liveborn anencephalic infants were serially examined to determine if they would meet our clinical criteria for whole brain death within a 7-day period: Protocol 1 infants (6) received intensive care including intubation from birth; and Protocol 2 infants (6) received intensive care during the period in which death was imminent. Brain death was determined by absence of brainstem function. including loss of all cranial nerve responses and sustained apnea (PCO2 greater than 60 torr) for 48 hours with confirmation of findings by an outside consulting child neurologist. The initial examinations of these 12 infants revealed spontaneous movements and startle myoclonus (12). suck. root. and gag responses (7). increased tone (8). deep tendon reflexes (9). absent pupillary responses (9). absent oculocephalic and corneal responses (6). absent auditory/Moro responses (7). and nonvisualization of the optic nerve (8). Mild depression of neurologic function occurred during the first several days of life; subsequently. the infants' responses were easier to elicit and more sustained. Only 2 infants met the clinical criteria for brain death. Neuropathologic findings indicated that observed complex motor responses were not based upon cortical activity because no infant had a normally-formed cerebrum. Brainstem neuronal activity may have accounted for these motor responses in some patients but even at this level neurons were scanty or absent. Our findings suggest that. although rare. clinical brain death can be determined in liveborn anencephalic infants; ophthalmologic and otologic developmental abnormalities may confound examination of cranial nerve function; and absence of cortical neurons supports the widely held opinion that these infants do not experience sensation.
| 9 |
ACTH therapy in infantile spasms: relationship between dose of ACTH and initial effect or long-term prognosis, The relationship between the dose of ACTH and the initial effect was investigated in 41 children with infantile spasms. More than 0.015 mg (0.6 IU)/kg/day of ACTH was needed for a good initial response of seizures and electroencephalographic abnormalities. The relationship between the dose of ACTH and long-term prognosis was investigated in 29 patients. There was no relationship between the daily or total ACTH dosage. provided the dose was greater than 0.015 mg (0.6 IU)/kg/day. and the outcome of seizures and electroencephalographic abnormalities; however. ACTH 0.04-0.06 mg (1.6-2.4 IU)/kg/day and a total ACTH dose of 1.1-1.5 mg (44-60 IU)/kg resulted in better mental development than smaller doses of ACTH. Side effects of ACTH increased with dosage. Too small or too large a dose of ACTH does not lead to better mental development. The proper dose of ACTH should be used with careful attention to potential side effects.
| 9 |
Gross motor patterns in children with cerebral palsy and spastic diplegia, Rolling. sitting. and crawling patterns were motoscopically analyzed in 72 children with cerebral palsy and spastic diplegia; the relation between these patterns and the severity of the locomotive disability was studied. In rolling. trunk rotation and elbow support were difficult for the most severely diplegic children. When sitting. most patients had a between-heel sitting pattern in which the thighs were adducted and the knees were flexed. When crawling. the reciprocal thigh movements were insufficient and accompanied by lateral bending of the trunk in many patients. In the more impaired patients. the thighs supported the weight in flexion and did not move reciprocally. Creeping on the elbows without reciprocal leg movements was demonstrated in the most severely affected children after 2 years of age.
| 9 |
Dystrophin analysis in the differential diagnosis of autosomal recessive muscular dystrophy of childhood and Duchenne muscular dystrophy, We report 2 patients with childhood autosomal recessive muscular dystrophy. Both patients had slight muscle weakness without enlargement of the calf muscles or involvement of the facial muscles. Their clinical courses are static. Muscle histology revealed characteristic features of muscular dystrophy. Dystrophin was identifiable in the sarcolemma of both patients by immunocytochemical staining with an antidystrophin antibody. At an early age. immunocytochemical analysis with antidystrophin antibody was useful in distinguishing between childhood autosomal recessive and Duchenne muscular dystrophies.
| 15 |
Cerebellopontine angle lipoma in a teenager, Lipomas of the cerebellopontine angle are very rare lesions. To date. 18 patients have been reported. 17 of whom were adults. A second child is described with cerebellopontine angle lipoma.
| 3 |
The role of bacterial adherence in otitis media with effusion, Adherence of nontypable Haemophilus influenzae and Streptococcus pneumoniae to nasopharyngeal epithelial cells was investigated in vitro. Both strains had higher affinity to the epithelial cells of children than to those of adults. In children. the adherence was significantly greater in patients with otitis media with effusion than in normal subjects. Secretory IgA in nasopharyngeal secretions was found to have antibody activity against the bacteria. Adherence of both bacteria was significantly smaller in the group having secretory IgA antibody activity than in the group having no activity. These results suggest that bacterial adherence to the nasopharynx may play an important role in the pathogenesis of otitis media with effusion in children. and that secretory IgA in nasopharyngeal secretions may be related to the decrease of adherence.
| 8 |
Tissue expansion of the head and neck. Indications, technique, and complications, Tissue expansion is indicated in the reconstruction of various defects of the head and neck in instances where there is inadequate adjacent tissue to allow either primary closure of the defect or repair with a local flap. It may also be indicated in instances where repair of a defect by an alternative method such as a local. regional. or distant flap will result in an unacceptable donor or recipient site deformity. Although tissue expansion is simplistic in concept. it does require judgment and indepth preoperative planning to ensure optimal results. The complication rate is high for tissue expansion in the head and neck. particularly in the cheek and neck area. Despite the frequency of complications. in the vast majority of cases the intended reconstruction is successful.
| 22 |
Salivary gland cancer. A case-control investigation of risk factors, Unlike most upper aerodigestive tract cancers. salivary gland cancers are relatively infrequent. are characterized by a diversity of histologic subtypes. and have never been etiologically associated with tobacco exposure. We present the results of a case-control study of risk factors for these cancers. with risk estimates derived from self-administered comprehensive risk-factor questionnaires distributed to patients at The University of Texas M. D. Anderson Cancer Center. Houston. Cases were 64 patients with histologically confirmed salivary gland cancer. Control subjects. randomly selected from the same patient population excluding patients with cancer of the head and neck or nonmelanoma skin cancer. were frequency-matched to the cases by age. sex. and ethnicity to achieve a 2:1 control subjects/cases ratio. On multivariate analysis. prior radiotherapy was a significant risk factor for both men (odds ratio [OR] = 2.1) and women (OR = 2.3). Among women. higher educational attainment (OR = 2.4). alcohol use (OR = 2.0). and hairdye use (OR = 2.5) were also significantly associated with risk. There were no significant differences between cases and control subjects with respect to tobacco exposure or specific occupational or leisure-time exposures. There is biological plausibility for associations with hairdye use and alcohol exposure.
| 6 |
Transtympanic endoscopic findings in patients with otitis media with effusion, Using a fine. rigid endoscope (Olympus. SES-1711K). we examined the middle ear. including the tympanic orifice of the eustachian tube. of children with otitis media with effusion (OME) in its active stage (26 ears). in the convalescent stage (13 ears). and during treatment with ventilation tubes for 10 days to 6 months (five ears) through myringotomy with the patients under general anesthesia. Several color photographs of representative ears are shown. In the active stage of OME. edema (73.1%) and hyperemia (23.1%) were characteristic features of the middle ear mucosa. and normal mucosa was seen in only one ear (3.1%). The tympanic orifice of the eustachian tube. which could be examined in 12 ears. were stenosed with edema in four ears (33.3%) or plugged with effusion in three ears (25.0%) in this group. In the convalescent stage of OME. dilated vessels were most often seen (69.2%). but the rest of the patients had normal mucosa (30.8%) in the middle ear. and none of them had edema nor hyperemia. The tympanic orifice of the eustachian tube. which could be examined in five ears. was clearly patent in all the patients in this group. One ear that was treated with a ventilation tube for 1 month showed dilated vessels and less severe inflammation than did ears that were in the active stage of OME. and three ears that were treated for more than 3 months showed almost normal middle ear mucosa.
| 8 |
Computed tomography of metastatic cervical lymph nodes. A clinical, computed tomographic, pathologic correlative study, A retrospective comparative study of 63 neck dissections was undertaken to evaluate further the accuracy of high-resolution computed tomography (CT) in the detection of nodal metastases. as previous studies have indicated a trend toward the superiority of CT scanning over palpation. The respective values of neck examination. CT scanning. and histopathologic examination were assessed in 51 patients with head and neck cancer who underwent a total of 63 neck dissections. The overall agreement between clinical examination findings and histopathologic findings was 92% vs 81% for CT scanning. A retrospective analysis of the CT findings failed to reveal greater accuracy. We found nodes measuring 10 mm or more with central low density always to be malignant. Because CT scanning seems to offer little advantage over palpation in the nonirradiated neck. it should not be regarded as an essential tool in the staging of nodal disease. After radiation therapy. as neck dissection is only performed because of clinical or radiologic suspicion. CT scanning is of utmost importance.
| 3 |
Ultrasonic integrated backscatter two-dimensional imaging: evaluation of M-mode guided acquisition and immediate analysis in 55 consecutive patients, We have shown previously that cardiac cycle-dependent integrated backscatter characterizes the physical state of myocardium in patients with ischemic heart disease and cardiomyopathy. In the present study the clinical applicability of M-mode guided two-dimensional integrated backscatter imaging was defined in evaluation of 55 nonselected patients. The mean amplitude of cyclic variation of integrated backscatter in normal segments (long-axis view) was as follows: basal septum. 4.2 +/- 1.3 dB (mean +/- SD; n = 27). mid-septum. 4.5 +/- 1.0 dB (n = 26). basal posterior. 4.8 +/- 1.0 dB (n = 30). and mid-posterior. 4.8 +/- 1.2 decibels (n = 27). The respective mean delay values (R wave to nadir) were as follows: 0.89 +/- 0.09. 0.84 +/- 0.09. 0.86 +/- 0.09. and 0.85 +/- 0.12. At least one cardiac cycle could be analyzed fully in 62% of patients. Limitations included technically difficult two-dimensional echocardiography. inadequate M-line orientation. technically remediable errors. or poor quality integrated backscatter images. In abnormal segments (n = 13) cyclic variation was reduced and delay was prolonged (1.2 +/- 1.1 dB and 1.21 +/- 1.1. respectively). Intraobserver and interobserver variability for amplitude measurements were modest. with respective correlation coefficients of r = 0.93; r = 0.72. The findings demonstrate that M-mode--assisted integrated backscatter is a practical approach for characterization of regional myocardial properties promptly and at the bedside in a large portion of patients with cardiac disease.
| 13 |
Left and right ventricular flows by Doppler echocardiography: serial measurements in patients with aortic regurgitation during exercise, cold pressor stimulation, and vasodilation, To test the practicality of Doppler echocardiography to measure serial change. biventricular outputs were measured in 15 patients with aortic regurgitation during control periods and during interventions of bicycle exercise. cold pressor stimulation. and vasodilation. Biventricular stroke volumes were measured in 10 normal subjects for validation of methods and differed by 2.8%. Reading errors were 3.7%. Signal quality improved between the first and last observation (p less than 0.05). Velocity signals were corrected for intercept angles. which averaged 12 and 19 degrees for right heart flows and 31 and 32 degrees for the left side of the heart in all subjects. Negative correlations occurred between intercept angles and the chronologic order in which the patients were studied for left (p = 0.02) and right (p = 0.05) flows. Mean flow areas varied 9% in the left ventricle and 20% in the right ventricle. Total variability for measuring flow determined from control values was 11% to 13%. When twice the variability was used as the detectable level of change. only exercise provoked real increases in biventricular flows in the majority of patients. We conclude that serial measurements of flow by Doppler echocardiographic methods had to exceed 20% to 25% to achieve significant change. Measuring intercept angle. resolving flow area. and learning are variables that need greater emphasis.
| 13 |
Flow patterns in dilated cardiomyopathy: a pulsed-wave and color flow Doppler study, In 48 patients with dilated cardiomyopathy. pulsed-wave and color Doppler examination were performed. In addition. 14 normal patients served as control subjects. Peak inflow velocity at the level of the mitral valve. middle left ventricle. and apex and outflow velocity at the level of the apex. middle left ventricle. and subaortic area were measured. In normal patients there was brisk propagation of inflow velocity to the apex. Patients with dilated cardiomyopathy demonstrated delayed propagation and prolongation of the duration of inflow compared with control subjects (p less than 0.04). Continuous apical flow was visualized in 25% of dilated cardiomyopathies and in no normal patients. Apical velocities were significantly increased in cardiomyopathies with significant mitral regurgitation. Outflow velocities were decreased in dilated cardiomyopathy. In patients with dilated cardiomyopathy and apical dyskinesis. flow directed toward the base was measured in the middle left ventricle during isovolumic relaxation secondary to dyskinetic rebound. Patterns of abnormal flow in dilated cardiomyopathies are readily apparent by color M-mode and two-dimensional color Doppler.
| 13 |
Prevalence of aortic regurgitation by color flow Doppler in relation to aortic root size, To determine whether there is a correlation between aortic root size and the prevalence of aortic regurgitation. we performed color flow Doppler echocardiographic studies on 1015 consecutive patients during a 3-month period. Patients were grouped according to their M-mode aortic root diameter as measured in the left parasternal position. The measured groups ranged from 2.0 to 4.5 cm. grouped at 0.1 cm intervals. As the aortic root size enlarged. the prevalence of aortic regurgitation increased linearly (p less than 0.001; correlation coefficient. r = 0.75). At an aortic root size in the "small normal" range of 2.0 to 2.4 cm. the prevalence of aortic regurgitation was 0% to 15%. In the "intermediate" and "top normal" ranges of 2.9 to 3.7 cm. the prevalence of aortic regurgitation increased linearly from 15% to 47%. With aortic root dilation. the prevalence of aortic root regurgitation was generally more than 50%. The severity of aortic regurgitation was semiquantified. Aortic root size was not a good indicator for the severity of aortic regurgitation. Patients with moderate and severe aortic regurgitation had variable aortic root sizes. Throughout the range of aortic root sizes. mild aortic regurgitation predominated. We conclude that aortic regurgitation is a common finding in patients with aortic roots that are dilated or are in the "top normal" size range. that the prevalence of aortic regurgitation increases linearly with aortic root size. and that aortic root size does not correlate with the severity of aortic regurgitation.
| 13 |
Two-dimensional echocardiographic features of double outlet left ventricle, In a cyanotic newborn infant. the diagnosis of double outlet left ventricle was made from the two-dimensional echocardiographic examination. The diagnosis was later confirmed at cardiac catheterization and surgery. The parasternal and subcostal views were especially useful for identification of the origin of both great arteries from the morphologic left ventricle. A review of the medical literature since 1967 revealed 77 cases of double outlet left ventricle. most of which were diagnosed only at surgery or postmortem examination. The anatomic features demonstrated with two-dimensional echocardiography in this case are representative of the findings cited most often in the cases reported in the medical literature.
| 13 |
Evolution of the continuity equation in the Doppler echocardiographic assessment of the severity of valvular aortic stenosis, The use of Doppler techniques has greatly enhanced the noninvasive ultrasound technique for evaluation of valvular aortic stenosis. M-mode and two-dimensional echocardiography could not reliably distinguish patients with severe aortic stenosis from those with milder obstructions. The hemodynamic information offered by Doppler complemented echocardiographic imaging and provided an alternative modality for evaluation of patients with aortic stenosis. By application of the modified Bernoulli equation. the pressure gradient across the stenotic aortic valve could be estimated by Doppler echocardiography. Though helpful and widely used. the information provided by the pressure gradient across the valve about the severity of the obstruction was not complete. The assessment of valvular aortic stenosis therefore includes an estimation of the valve area by application of the continuity equation. This review examines the maturation of the continuity equation by Doppler techniques and discusses the implications of the procedure.
| 13 |
The determination of aortic valve area by the Gorlin formula: what the cardiac sonographer should know, The application of the Gorlin formula in the cardiac catheterization laboratory is the standard of reference for the determination of aortic valve area. The continuity equation now enables the cardiac sonographer to determine aortic valve area noninvasively in the echocardiography laboratory. The comparison of the results obtained by the two methods is inevitable. The cardiac sonographer should have a basic understanding of the theory and pitfalls of the Gorlin formula so that when conflicting results are obtained. the possible reasons why will be clear.
| 13 |
The evaluation of the abdominal aorta: a "how-to" for cardiac sonographers, A thorough evaluation of the abdominal aorta can be readily achieved by use of the standard views of the echocardiographic examination. The ultrasound evaluation of the abdominal aorta represents a logical extension of the standard echocardiographic examination of the adult patient. This article provides the information needed to carry out a complete ultrasound examination of the abdominal aorta including the anatomy. the vascular disease. and the steps involved in accomplishing the ultrasound examination of the abdominal aorta.
| 13 |
Multivariate analysis in the prediction of death in hospital after acute myocardial infarction, Prognostic factors in patients with acute myocardial infarction based on clinical and investigative data on admission were evaluated prospectively in 111 consecutive patients. Seventeen patients (15.3%) died during hospital stay. Age. a previous infarct. high Killip class. cardiomegaly. high serum concentrations of cardiac enzymes. a low ejection fraction. and a high wall motion score index correlated significantly with in-hospital mortality; whereas sex. risk factors. and pericardial effusion did not. Multivariate analysis showed that age and the wall motion score index were the best predictors of death in hospital. Wall motion detected by cross sectional echocardiography may reflect the extent of myocardial involvement. Age and wall motion score index predicted in-hospital mortality with a sensitivity of 76.5%. a specificity of 91.5%. and a predictive accuracy of 89.2%. Age and the wall motion score index can be determined on admission and are useful for identifying patients at high risk of cardiac death who might benefit from early intervention.
| 13 |
Ischaemic left ventricular failure: evidence of sustained benefit after 18 months' treatment with xamoterol, The long term effects of treatment with xamoterol in 14 patients aged 44-73 with mild to moderate heart failure as a result of ischaemic heart disease are reported. After 18 months' treatment with xamoterol. patients were assessed in a randomised double blind crossover comparison of xamoterol (200 mg twice a day) and placebo. each given for one month. Compared with placebo. xamoterol significantly increased exercise duration and work done on a bicycle ergometer and reduced the maximum exercise heart rate. Assessment of symptoms and activities at 12 months by visual analogue and Likert scales showed a trend towards the relief of symptoms of breathlessness and tiredness and an improvement in activity. There was an improvement in the clinical signs of heart failure and no haemodynamic deterioration over a 12 month period as assessed by ejection fraction. The improvement in exercise tolerance. symptoms. and activities was sustained for 18 months without side effects or development of tolerance.
| 13 |
Geographical clustering of risk factors and lifestyle for coronary heart disease in the Scottish Heart Health Study, A large cross sectional study. the Scottish Heart Health Study. of 10.359 men and women from 22 districts of Scotland was undertaken to try to explain the geographical variation of coronary heart disease mortality. Analysis by district showed that of the classic risk factors only cigarette smoking was strongly associated with heart disease mortality among both men and women. Mean diastolic blood pressure was weakly associated with rates among men and high density lipoprotein cholesterol showed a strong negative association among women. Total cholesterol showed a weak negative association with heart disease mortality. but. because the serum concentrations of cholesterol were uniformly high in all districts. a strong association with mortality would not be expected. In both men and women many dietary factors showed moderate or strong associations with mortality from coronary heart disease in a district--of these a low consumption of vitamin C was most notable. Other factors associated with heart disease included alcohol consumption and serum triglycerides among men. and obesity. physical activity. and serum triglycerides among women. Many factors associated with heart disease showed strong intercorrelations. Clustering of risk factors (including smoking. alcohol. and diet among men. and smoking. diet. and obesity among women) was associated with much of the regional variation in heart disease mortality in Scotland.
| 13 |
Cardiac catheterisation with 5 French catheters, From the beginning of November 1987 to the end of January 1989. 526 coronary arteriograms and left ventricular angiograms were performed with 5 French coronary catheters. In 448 (85%) patients diagnostic pictures were obtained with three standard types of 5 French catheters (No 4 Judkins): that is. left coronary. right coronary. and pigtail catheters. In 60 patients (11.4%) various other 5 French catheters were required to complete the study. In nine patients (1.7%). a 7 or 8 French catheter was used. Major complications causing cardiac arrest or requiring urgent operation developed in five patients. Sixty two patients (11.77%) had minor complications that required sublingual nitrates or a single bolus of atropine. or developed a haematoma that did not need intervention or had a mild reaction to the contrast material. Complications of moderate severity developed in 17 patients (3.2%): severe chest pain. arrhythmia requiring a temporary pacemaker. contrast reaction associated with hypotension. haematoma requiring blood transfusion. or a transient ischaemic episode. There were no deaths. 5 French catheters were used for routine coronary angiography and left ventriculography in 98.3% of patients. There were no major complications related to femoral artery puncture. The routine use of 5 French coronary catheters should increase the feasibility of safe coronary angiography in outpatients and should reduce the cost of this investigation.
| 13 |
Discrepancies in the measurement of isovolumic relaxation time: a study comparing M mode and Doppler echocardiography, Mitral valve cusp separation on M mode echogram. the mitral valve opening artefact. and the onset of forward transmitral flow recorded by Doppler echocardiography have all been taken to mark the end of isovolumic relaxation. while its onset has been taken either as the aortic closure sound (A2) recorded phonocardiographically or the aortic closure artefact determined by Doppler technique. Possible differences in the measurement of the isovolumic relaxation time were studied when these landmarks were used in 44 healthy people. 14 patients with mitral stenosis. 21 patients with left ventricular hypertrophy. and 24 patients with dilated cardiomyopathy by recording M mode echograms of the mitral valve. and pulsed and continuous wave Doppler spectra of transmitral flow. with simultaneous electrocardiograms and phonocardiograms. A2 was effectively synchronous with the aortic artefact. However. when the onset of Doppler flow was regarded as the end of isovolumic relaxation. the interval was significantly longer than when mitral cusp separation on M mode echograms was used: by 25 (10) ms in healthy individuals. by 25 (15) ms in patients with left ventricular hypertrophy. and by 50 (35) ms in patients with dilated cardiomyopathy. In patients with mitral stenosis the interval was only 5 (5) ms longer. The mitral valve opening artefact consistently followed the onset of flow and corresponded much more closely to the E point on the M mode echogram. This shows that it occurred during the rapid filling period and well beyond isovolumic relaxation by any definition. Thus isovolumic relaxation time measured from A2 to the onset of transmitral flow or the mitral valve opening artefact differs from that derived from A2 to mitral valve cusp separation. These intervals cannot be used interchangeably to measure "isovolumic relaxation time".
| 13 |
Invasive migration of epidemic Kaposi's sarcoma cells in vitro, Kaposi's sarcoma (KS) is a low grade malignant neoplasm which shows invasive growth and often occurs in immunosuppressed patients with the Acquired Immune Deficiency Syndrome (AIDS; epidemic KS). It is also found in elderly men where it is usually limited to the skin (classic KS). The present study investigated the chemotaxis and invasive migration of epidemic KS cells in vitro and compared them to cells grown from classic KS lesions and to fibroblasts. Epidemic KS cells demonstrated invasive migration through reconstituted basement membrane (Matrigel) as well as through interstitial connective tissue (collagen I) in early passages. whereas fibroblasts did not invade either barrier. Epidemic KS cells in late passages did not show any invasive migration. Following pretreatment with tumour necrosis factor alpha (TNF-alpha) there was no enhanced migration through the Matrigel and collagen I for epidemic KS cells. whereas classic KS cells showed an increased migration through the type I collagen barrier.
| 3 |
Neutrophil zinc levels in psoriasis and seborrhoeic dermatitis, The median zinc content of neutrophils was significantly reduced in 16 patients with psoriasis in comparison to both normal controls and six patients with seborrhoeic dermatitis (P less than 0.05). This reduction was unrelated to the extent of skin involvement. Plasma and erythrocyte zinc levels were unchanged.
| 16 |
Autologous mixed lymphocyte reaction is reduced in patients with psoriasis, The autologous mixed lymphocyte reaction (auto-MLR) was studied to test the interactions between immunocompetent cells in patients with psoriasis. The auto-MLR in 20 patients with psoriasis was significantly lower than in 16 normal controls. Lower values were found in untreated psoriatic patients than in those in remission following treatment. The values in the latter group were significantly lower than in controls and in six patients with atopic dermatitis in remission. The tendency for an increase in the auto-MLR with a decrease in disease activity was further confirmed in five patients studied before and after treatment. In contrast. the allogeneic lymphocyte reaction (allo-MLR) in psoriatics was similar to that in normal controls.
| 16 |
Pentoxifylline inhibits the proliferation of human fibroblasts derived from keloid, scleroderma and morphoea skin and their production of collagen, glycosaminoglycans and fibronectin, Pentoxifylline. an analogue of the methylxanthine theobromine. inhibits the proliferation and certain biosynthetic activities of fibroblasts derived from normal human skin. Fibroblasts from the skin of patients with keloids. scleroderma and morphoea were cultured in vitro in the presence and absence of pentoxifylline (100-1000 micrograms/ml) to determine whether it inhibits fibroblast proliferation and the production of collagen. glycosaminoglycans (GAG). fibronectin and collagenase activity. The exposure of subconfluent fibroblast cultures to pentoxifylline resulted in non-lethal. dose-dependent reductions in serum-driven fibroblast proliferation. with 1000 micrograms/ml pentoxifylline virtually negating the proliferative effect of serum on the cells. The fibroblasts assayed as confluent cultures produced reduced amounts. by up to 95%. of collagen and GAG. dependent on the concentration of pentoxifylline. both in the presence and absence of serum. Pentoxifylline similarly inhibited the fibronectin production by keloid and scleroderma fibroblasts. but had no effect on collagenase activity.
| 16 |
Effects of haem arginate on variegate porphyria, Four patients with variegate porphyria (VP) were treated with repeated haem arginate infusions daily for 4 days and then weekly for 4 weeks. After the initial four daily doses of haem arginate (haem 3 mg/kg). the excretion of faecal protoporphyrin (mean 579 nmol/g dry wt) fell to an almost normal level (mean 123 nmol/g dry wt). and that of coproporphyrin (mean 162 nmol/g dry wt) to the normal level (mean 21 nmol/g dry wt) in all patients. However. during the period of the four weekly infusions of haem the excretion of porphyrins increased almost to the pretreatment level. Phototesting showed no changes in the photoreactivity of the skin. and no improvement in skin lesions was seen during the treatment. Except for one case of thrombophlebitis no side-effects occurred. In a child with homozygous VP. four daily infusions of haem arginate (2 mg/kg) normalized the faecal protoporphyrin content. but had no effect on the increased erythrocyte protoporphyrin concentration.
| 16 |
Effects of recombinant human interleukin-3 in aplastic anemia, In a phase I/II study. nine patients with aplastic anemia were treated with recombinant human interleukin-3 (rhIL-3) to assess the toxicity and biologic effects of this multipotential hematopoietic growth factor. Doses ranging from 250 micrograms/m2 to 500 micrograms/m2 were administered as subcutaneous bolus injections daily for 15 days. An increase in platelet counts from 1.000/microL to 31.000/microL was induced by rhIL-3 in one patient. and an increase in reticulocyte counts by more than 10.000/microL in four patients. The blood leukocyte counts temporarily increased in eight patients 1.5- to 3.3-fold (median. 1.8-fold). mainly due to an increase in the number of neutrophils. eosinophils. lymphocytes. and monocytes. In two patients. bone marrow cellularity increased from 7% to 33% and from 10% to 80%. respectively. but without resulting in a substantial improvement of peripheral blood counts. Mild side effects (headache and flushing) were observed in some patients. while low-grade fever occurred in all patients. Transient thrombocytopenia necessitating discontinuation of rhIL-3 treatment occurred in one patient. In conclusion. rhIL-3 can stimulate hematopoiesis in patients with aplastic anemia; however. no lasting effects were obtained.
| 14 |
Impact of marrow cytogenetics and morphology on in vitro hematopoiesis in the myelodysplastic syndromes: comparison between recombinant human granulocyte colony-stimulating factor (CSF) and granulocyte-monocyte CSF, Marrow cells from 36 patients with myelodysplastic syndromes (MDS) (13 refractory anemia [RA]. 14 refractory anemia with excess of blasts [RAEB]. 9 RAEB in transformation [RAEB-T]) were evaluated for their in vitro proliferative and differentiative responsiveness to recombinant human granulocyte colony-stimulating factor (G-CSF) or granulocyte-monocyte CSF (GM-CSF). GM-CSF exerted a stronger proliferative stimulus than G-CSF for marrow myeloid clonal growth (CFU-GM) in these patients (44 v 12 colonies per 10(5) nonadherent buoyant bone marrow cells [NAB]. respectively. P less than .025). GM-CSF stimulated increased CFU-GM growth in the 16 patients with abnormal marrow cytogenetics in comparison with the 20 patients who had normal cytogenetics (52 and 30 colonies per 10(5) NAB. respectively. P less than .05). whereas no such difference could be demonstrated with G-CSF (11 and 16 colonies per 10(5) NAB. respectively). In contrast. granulocytic differentiation of marrow cells was induced in liquid culture by G-CSF in 15 of 32 (47% patients). while GM-CSF did so in only 4 of 18 (22%) patients (P less than .025) including. for RAEB/RAEB-T patients: 9 of 18 versus 0 of 9. respectively (P less than .025). For MDS patients with normal cytogenetics. G-CSF- and GM-CSF-induced marrow cell granulocytic differentiation in 12 of 18 (67%) versus 3 of 11 (27%). respectively (P less than .025). contrasted with granulocytic induction in only 3 of 14 (21%) and 1 of 7 (14%) patients with abnormal cytogenetics. respectively. We conclude that G-CSF has greater granulocytic differentiative and less proliferative activity for MDS marrow cells than GM-CSF in vitro. particularly for RAEB/RAEB-T patients and those with normal cytogenetics.
| 14 |
Selective regulation of the activity of different hematopoietic regulatory proteins by transforming growth factor beta 1 in normal and leukemic myeloid cells, The viability of normal bone marrow myeloid precursor cells induced by interleukin-6 (IL-6) or IL-1 alpha and the ability of IL-6 and IL-1 alpha to induce the formation of colonies of granulocytes. macrophages. or megakaryocytes in densely seeded bone marrow cultures was suppressed by transforming growth factor-beta 1 (TGF-beta 1). Induction of normal bone marrow colony formation by IL-3 was much less sensitive to TGF-beta 1. and there was little or no effect of TGF-beta 1 on colony formation induced by macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage CSF (GM-CSF). In different clones of myeloid leukemic cells. TGF-beta 1 suppressed differentiation induced with IL-6. IL-1 alpha. or lipopolysaccharide (LPS). but did not suppress differentiation induced with IL-3 or GM-CSF. The effect of TGF-beta 1 on differentiation of the leukemic cells can be dissociated from its effect on cell growth. TGF-beta 1 suppressed the production of IL-6 in normal bone marrow cells cultured with IL-1 alpha and the production of IL-6 and GM-CSF in leukemic cells cultured with IL-1 alpha or LPS. The suppression of IL-6 production can explain the suppression by TGF-beta 1 of the effects of IL-1 alpha and LPS that are mediated by IL-6. TGF-beta 1 also suppressed differentiation in clones of myeloid leukemic cells induced with differentiation factor/leukemia inhibitory factor and tumor necrosis factor. In different leukemic clones TGF-beta 1 suppressed or enhanced induction of differentiation with dexamethasone. The results show that TGF-beta 1 can selectively control the activity of different molecular regulators of normal and leukemic hematopoiesis.
| 19 |
A specific in vitro bioassay for measuring erythropoietin levels in human serum and plasma, The accurate measurement of biologically active erythropoietin (Ep) in human serum and plasma using present in vivo and in vitro bioassays is difficult because of the presence of both inhibitors and non-Ep stimulators of erythropoiesis. We have developed a simple procedure to quantitatively purify Ep from serum and plasma for subsequent testing in the phenylhydrazine-treated mouse spleen cell assay. The method involves absorption of Ep to an immobilized high-affinity anti-Ep monoclonal antibody and acid elution of the antibody-bound material. After neutralization. the eluted EP is then tested directly in the in vitro bioassay without interference by other serum proteins. By using magnetic beads as a solid support for the antibody. washing and elution steps can be performed rapidly and efficiently. Recoveries of Ep after this procedure show very little sample-to-sample variation and are consistently between 45% and 55%. which is close to the maximum binding expected for the anti-Ep antibody. Coupled with the 7.4-fold concentration that this procedure affords. there is an overall increase in sensitivity of three- to fourfold. which makes this assay suitable for accurately measuring Ep levels in patients with below-average titers. Results with this magnetic bead assay indicate that accurate and reproducible estimates for Ep levels in the serum and plasma from healthy donors as well as from patients with hematologic disorders can be obtained. Titers of biologically active Ep in the sera from a group of patients with either leukemia or lymphoma were found to be elevated. and the values correlated well with titers of immunoreactive Ep measured in the Ep radioimmunoassay. Because of its specificity and high sensitivity. the magnetic bead assay is a valuable alternative to immunoassays for the measurement of elevated. normal. and even subnormal Ep levels in human serum and plasma.
| 14 |
Induction of mixed erythroid-megakaryocyte colonies and bipotential blast cell colonies by recombinant human erythropoietin in serum-free culture, The effects of recombinant human erythropoietin (rEp) on murine hematopoietic progenitors were studied using a serum-free culture. A high concentration of rEp stimulated the formation of mixed erythroid-megakaryocyte colonies (EM colonies) and blast cell colonies. as well as erythroid colonies. erythroid bursts. and megakaryocyte colonies from normal mouse bone marrow cells. Direct effects of rEp on EM colony. megakaryocyte colony. and erythroid burst formation were confirmed by depletion of accessory cells such as T cells. B cells. and macrophages from crude bone marrow cells. and inhibition of the colonies by the addition of rabbit anti-rEp antibody to the culture in a dose-dependent fashion. Replating experiments were performed to confirm the differentiating ability of blast cell colonies grown in the presence of rEp. Most of the blast cell colonies yielded not only secondary erythroid colonies but also megakaryocyte colonies in the presence of 2 IU/mL rEp. Some of the blast cell colonies produced secondary EM colonies in the presence of 16 IU/ml rEp of 2 IU/mL rEp plus interleukin-3. although no granulocyte-macrophage colonies were found in the secondary culture. These results suggest that Ep acts not only as a late-acting factor that is specific for erythroid progenitors. but also as a bipotential EM-stimulating factor for murine hematopoietic cells.
| 22 |
Uremic platelets have a functional defect affecting the interaction of von Willebrand factor with glycoprotein IIb-IIIa, Uremic patients have an impaired platelet function that has been related to membrane glycoprotein (GP) abnormalities. Using a perfusion system. we have studied the interaction of normal and uremic platelets with vessel subendothelium (SE) under flow conditions. Reconstituted blood containing washed platelets. purified von Willebrand factor (vWF) (1 U/mL). and normal washed red blood cells was exposed to de-endothelialized rabbit segments for 10 minutes at two different shear rates (800 and 1.600 seconds-1). In some experiments a monoclonal antibody to the GPIIb-IIIa complex (EDU3) was added to the perfusates. With normal platelets. the percentage of the vessel covered by platelets (%CS) was 23.1% +/- 3.7% at 800 seconds-1 and 30% +/- 4.3% at 1.600 seconds-1. Platelets were observed in contact or forming monolayers on vessel SE. EDU3 inhibited the spreading of normal platelets. The %CS (11.1% +/- 3.3%) was statistically decreased (P less than .01) and most of the platelets were observed in contact with the vessel surface. These data indicate that. under flow conditions. the interaction of vWF with GPIIb-IIIa can support the spreading of normal platelets in the absence of exogenous fibrinogen. Under the same experimental conditions. the interaction of uremic platelets with SE was markedly impaired at both shear rates studied (P less than .01 v normal platelets). The presence of EDU3 did not modify the interaction of uremic platelets. These results confirm the impairment of the platelet adhesion observed in uremic patients. Furthermore. they indicate the presence of a functional defect in the interaction of vWF with GPIIb-IIIa. The fact that perfusions with normal and uremic platelets in the presence of an antibody to the GPIIb-IIIa complex did not show any differences gives indirect evidence on a functionally normal interaction vWF/GPIb in uremic patients.
| 11 |
Distinct characteristics of lymphokine-activated killer (LAK) cells derived from patients with B-cell chronic lymphocytic leukemia (B-CLL). A factor in B-CLL serum promotes natural killer cell-like LAK cell growth, We show that lymphokine-activated killer (LAK) cell precursors derived from patients with B-cell chronic lymphocytic leukemia (B-CLL) and cultured in the presence of recombinant interleukin-2 and normal human serum (NHS). develop into primarily NK cell-like (CD 57+) LAK cells. whereas identically prepared LAK cell precursors from normal subjects develop into mainly T cell-like (CD 3+. CD 8+) LAK cells. B-CLL LAK cells exhibited greater proliferative capacity than did normal LAK cells. When normal LAK cells were grown in B-CLL serum instead of NHS. their proliferation increased; NK cell levels also increased to those found in B-CLL LAK cells. suggesting that B-CLL serum contains a factor that promotes NK cell-like growth. LAK cells derived from normal or B-CLL patients demonstrated similar lytic activity toward K562 and Raji cells. Growth in B-CLL serum did not reduce their lytic potential. Thus. the altered phenotype and growth exhibited by B-CLL LAK cells and normal LAK cells grown in B-CLL serum does not lead to abnormalities in their cytolytic functions. We propose instead that the predominance of NK-like cells in B-CLL LAK cell populations and the presence of an NK cell-like growth factor in B-CLL serum reflect abnormalities related to NK cell-mediated B-cell regulation; ie. either inhibition of normal B-cell growth and/or growth stimulation of the leukemic clone in B-CLL.
| 3 |
Transfusion and alloimmunization in sickle cell disease. The Cooperative Study of Sickle Cell Disease, In 1.814 patients with sickle cell disease who had been transfused. the overall rate of alloimmunization to erythrocyte antigens was 18.6%. The rate of alloimmunization in this group appears to be an explicit function of the number of transfusions received because it increases exponentially with increasing numbers of transfusions. Alloimmunization usually occurred with less than 15 transfusions. although the rate of alloimmunization continued to increase when more transfusions were given. The rate of alloimmunization was less in patients with hemoglobin SC disease and sickle-beta+ thalassemia because these patients had received fewer transfusions. Children less than 10 years old had a slightly lower rate of alloimmunization than patients in other age groups even after correction for the number of transfusions given. Women were more frequently alloimmunized than men; this was largely due to the fact that women received more transfusions than men. but in the age group 16 to 20 years the increase may have been due in part to alloimmunization owing to pregnancy. Forty-five percent of those alloimmunized made antibodies of only one specificity; 17% made four or more antibodies reacting with different antigens. Antibodies to the C and E antigens of the Rh group. the Kell antigen. and the Lewis antigens were most commonly made. These findings may be important in formulating a rational transfusion policy in sickle cell disease.
| 14 |
Coordinate secretion of interleukin-1 beta and granulocyte-macrophage colony-stimulating factor by the blast cells of acute myeloblastic leukemia: role of interleukin-1 as an endogenous inducer, Acute myeloblastic leukemia (AML) blasts have been shown to produce a variety of cytokines in culture such as interleukin-1 (IL-1). IL-6. granulocyte-. macrophage-. and granulocyte-macrophage colony-stimulating factor (GM-CSF). and tumor necrosis factor-alpha (TNF alpha). Using two sensitive and specific enzyme-linked immunosorbent assays for IL-1 beta and GM-CSF. we document in the present study that the production of the two cytokines by AML blasts in culture is coordinated. First. we observe a striking correlation between the levels of GM-CSF and IL-1 beta released by the cells. Thus. a high production of IL-1 beta is always concordant with a high production of GM-CSF and. conversely. low production of IL-1 beta is concordant with low levels of GM-CSF. Second. neutralization of intrinsic IL-1 using antibodies that are specific for IL-1 alpha and -1 beta suppresses the release of GM-CSF by the cells. Third. neutralization of the endogenous source of IL-1 also results in an abrogation of GM-CSF mRNA. Fourth. the production of both IL-1 beta and GM-CSF is up-regulated by exposing AML blasts to an exogenous source of IL-1. suggesting a positive regulation of autocrine growth factor production. Taken together. our results indicate that GM-CSF production by AML blasts is mediated by endogenously produced IL-1. Both IL-1 beta and -1 alpha are produced by AML blasts. although IL-1 beta appears to be more abundant. Spontaneous colony formation by AML blasts is abrogated by the addition of neutralizing antibodies against IL-1 beta and GM-CSF. whereas each antibody alone has little effect on blast proliferation. Taken together. our results are consistent with the view that the production of IL-1 beta by AML blasts supports autocrine growth in culture. through induction of CSFs or other cytokines that stimulate blast proliferation.
| 19 |
The pharmacokinetics of plasminogen activator inhibitor-1 in the rabbit, The pharmacokinetics of the activated and latent forms of plasminogen activator inhibitor-1 (PAI-1) isolated from HT1080 fibrosarcoma cells (HT1080 PAI-1) and a nonglycosylated form of human PAI-1 isolated from a yeast expression system (rPAI-1) were followed in the rabbit. As assessed by an immunologic assay specific for human PAI-1. guanidine HCI activated HT1080 PAI-1 and rPAI-1 entered the total plasma volume following intravenous bolus administration and exhibited a biphasic clearance pattern. The t1/2s of HT1080 PAI-1 for the initial and beta phases equalled 6.0 and 24.8 minutes. respectively. The t1/2s of rPAI-1 for the initial and beta phases equalled 8.8 and 34.0 minutes. respectively. Similar results were obtained by measuring PAI-1 activity in plasma and with trace amounts of 125I-rPAI-1. suggesting that the above pharmacokinetic behavior could also apply to endogenous PAI-1. The liver was the main site of rPAI-1 clearance. Unactivated. latent PAI-1 exhibited a very different pharmacokinetic profile. Over 80% of latent rPAI-1 cleared from the circulation within 10 minutes (t1/2 = 1.7 minutes). The difference in clearance behavior between activated and latent PAI-1 may be related to the ability of activated PAI-1. but not latent PAI-1. to rapidly form high-molecular-weight complexes with plasma binding factors which were observed in vitro and in vivo. Because PAI-1 could potentially tilt the fibrinolytic balance toward a prothrombotic state. its rapid clearance may represent an important control mechanism governing the circulating levels of this key component of the fibrinolytic pathway.
| 3 |
Recombinant lipoprotein-associated coagulation inhibitor inhibits tissue thromboplastin-induced intravascular coagulation in the rabbit, Lipoprotein-associated coagulation inhibitor produces feed-back inhibition of tissue factor (tissue thromboplastin)-induced coagulation in the presence of factor Xa Recombinant lipoprotein-associated coagulation inhibitor (rLACI) was tested for its ability to modify thromboplastin-induced intravascular coagulation in a rabbit model that allows monitoring of iodine-125 fibrin accumulation/disappearance in the lung and sampling of blood for the measurement of coagulation parameters. Infusion of thromboplastin into the rabbit caused a rapid increase of radioactivity over the lungs. possibly due to the accumulation of 125I fibrin in the lungs. followed by a rapid decline of radioactivity. suggestive of removal of fibrin from the lungs. Thromboplastin also caused a rapid decrease of systemic fibrinogen that was accompanied by a lengthening of the activated partial thromboplastin time and prothrombin time. The effect of coinfusion of rLACI with thromboplastin or bolus injection of rLACI before thromboplastin infusion was studied. At a high dose of rLACI (800 micrograms/kg body weight). the thromboplastin-induced radioactivity increase in the lungs and the systemic fibrinogen decrease were completely suppressed. The activated partial thromboplastin time and prothrombin time of the plasma samples lengthened. possibly due to the presence of thromboplastin in circulation. The thromboplastin-induced radioactivity increase over the lungs was not completely suppressed by lower doses of rLACI (135 to 270 micrograms/kg body weight). but these doses of rLACI prevented systemic fibrinogen decrease. At a bolus dose of 23 micrograms/kg body weight. rLACI provided 50% protection of the fibrinogen consumption (fibrinogen decreased to 82% compared with 65% in rabbits treated with thromboplastin alone). These results show that rLACI is effective in the inhibition of thromboplastin-induced coagulation in vivo.
| 14 |
Effect of recombinant human granulocyte-macrophage colony-stimulating factor administration on the lymphocyte subsets of patients with refractory aplastic anemia, Human recombinant granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was administered to 14 patients with refractory aplastic anemia (AA). The effect of rhGM-CSF therapy on the lymphocyte phenotype; on the proliferative responses to the mitogen phytohemagglutinin. Candida albicans. and tetanus toxoid antigens; and on the natural killer (NK) activity of the circulating lymphocytes was studied. Samples were collected before (baseline) and twice during the rhGM-CSF administration. The absolute number of circulating lymphocytes remained relatively constant during the first period. but experienced a significant increase (P less than .001) during the second period. The increase was most prominent in the B cells (P less than .001). but the T cells (P less than .016) also increased. Detailed investigation of lymphocyte subsets showed an increase of the markers CD38 (Leu17). HLA-DR. and the transferrin receptor throughout the treatment course giving evidence of lymphoid cell activation. The NK cell activity was suppressed (P less than .008) throughout the treatment. However. proliferative responses to phytohemagglutinin. Candida antigen. and tetanus toxoid were unaffected. Although the mechanism is not yet defined. GM-CSF does induce activation and increase in absolute lymphoid cell number. especially B cells. together with a decrease in NK cytotoxicity. The implication of these immune cell changes in relation to host resistance to microorganisms remains to be established.
| 14 |
The role of cellular maturation in neutrophil heterogeneity, Previous studies have shown that many neutrophil (PMN) characteristics are heterogeneous but the origin of PMN heterogeneity is unknown. It is unclear if PMN functional heterogeneity is secondary to maturational differences or due to distinct subpopulations of cells that possess different functional capacities. The PMN 31D8 antigen is a useful probe for evaluation of PMN subpopulations. The majority of PMNs (approximately 85%) exhibit a high intensity fluorescence after 31D8 monoclonal antibody (MoAb) labeling (31D8 enriched or "bright" PMNs) as determined by flow cytometric analysis. These cells are more functional than cells with low intensity fluorescence (31D8 diminished or "dull" PMNs). Various immunologic. clonogenic and functional techniques were used to study the expression of the 31D8 antigen in HL-60 cells and myeloid cells in order to evaluate antigenic and functional heterogeneity during morphologic maturation. The results of this study indicate that the percentage of 31D8 antigen positive (31D8 antigen enriched and diminished) bone marrow cells increases from 20 +/- 11% in myeloblast cells to 68 +/- 10% in promyelocytes. 93 +/- 2% in myelocytes and 99 +/- 1% in bands and PMNs. 31D8 antigen enriched cells first appear at the myelocyte stage (32 +/- 10%) and increase in bands (52 +/- 13%). marrow PMNs (62 +/- 13%) and peripheral blood PMNs (88 +/- 4%). These data indicate that the heterogeneous expression of 31D8 antigen in PMNs is due. at least in part. to maturational differences within the PMN population and raise the possibility that other heterogeneously expressed PMN characteristics are also maturationally derived. They also suggest that 31D8 antigenic expression may be a more precise indicator of myeloid functional maturation than maturation as identified by cellular morphology.
| 3 |
B-cell differentiation following autologous, conventional, or T-cell depleted bone marrow transplantation: a recapitulation of normal B-cell ontogeny, The circulating lymphocytes of 88 consecutive patients following autologous. conventional. or T-cell depleted bone marrow transplantation were serially analyzed for B-cell surface antigen expression and function. In the majority of patients. except for those who developed chronic graft-versus-host disease. the number of circulating CD20+ B cell normalized by the fourth posttransplant month. The earliest detectable B cells normally expressed HLA-DR. CD19. surface immunoglobulin (slg). CD21. Leu-8. and lacked expression of CD10 (CALLA). In addition. the circulating B cells expressed CD1c. CD38. CD5. and CD23 for the first year following transplant. antigens that are normally expressed on a small percentage of circulating B cells in normal adults. but highly expressed on cord blood B cells. Similar to cord blood B cells. patient B cells isolated during the first year following transplant. proliferated normally to Staphylococcus aureus Cowan strain I (SAC). and produced IgM. but minimal or no IgG when stimulated with pokeweed mitogen and SAC. unlike normal adult B cells that produce both. The similar phenotype and function of posttransplant and cord blood B cells. and their similar rate of decline in patients and normal children adds further evidence to support the hypothesis that B-cell differentiation posttransplant is recapitulating normal B-cell ontogeny.
| 19 |
Adrenaline and nocturnal asthma, OBJECTIVE--To determine whether the nocturnal fall in plasma adrenaline is a cause of nocturnal asthma. DESIGN--Double blind placebo controlled cross-over study. In the first experiment the nocturnal fall in plasma adrenaline at 4 am was corrected in 10 asthmatic subjects with an infusion of adrenaline after parasympathetic blockade with 30 micrograms/kg intravenous atropine. In the second experiment 11 asthmatic subjects showing similar variations in peak expiratory flow rate had the nocturnal fall in plasma adrenaline corrected by infusion before atropine was given. PATIENTS--Asthmatic subjects with a diurnal variation in home peak expiratory flow rate of greater than 20% for at least 75% of the time in the two weeks before the study. MAIN OUTCOME MEASURES--Peak expiratory flow rate and plasma adrenaline. RESULTS--Correction of the nocturnal fall in plasma adrenaline at 4 am to resting 4 pm levels did not alter peak expiratory flow rate either before or after parasympathetic blockade with atropine. CONCLUSION--A nighttime fall in plasma adrenaline is not a cause of nocturnal asthma.
| 19 |
Menstrual state and exercise as determinants of spinal trabecular bone density in female athletes, OBJECTIVE--To study the effects of amenorrhoea and intensive back exercise on the bone mineral density of the lumbar spine in female athletes. DESIGN--Cross sectional study comparing amenorrhoeic with eumenorrhoeic athletes and rowers with non-rowers. SETTING--The British Olympic Medical Centre. Northwick Park Hospital. PATIENTS--46 Elite female athletes comprising 19 rowers. 18 runners. and nine dancers. of whom 25 were amenorrhoeic and 21 eumenorrhoeic. MAIN OUTCOME MEASURE--Trabecular bone mineral density of the lumbar spine measured by computed tomography. RESULTS--Mean trabecular bone mineral density was 42 mg/cm3 (95% confidence interval 22 to 62 mg/cm3) lower in the amenorrhoeic than the eumenorrhoeic athletes; this difference was highly significant (p = 0.0002). Mean trabecular bone mineral density was 21 mg/cm3 (1 to 41 mg/cm3) lower in the non-rowers than the rowers; this was also significant (p = 0.05). There was no interaction between these two effects (p = 0.28). CONCLUSION--The effect of intensive exercise on the lumbar spine partially compensates for the adverse effect of amenorrhoea on spinal trabecular bone density.
| 22 |
Efficacy of potassium and magnesium in essential hypertension: a double-blind, placebo controlled, crossover study, OBJECTIVE--To evaluate the antihypertensive activity of potassium given alone or in combination with magnesium in patients with mild hypertension. DESIGN--A double blind. randomised. placebo controlled. crossover trial of 32 weeks' duration. SETTINGS--Cardiology outpatient department. Sassoon General Hospitals. Pune. India. PATIENTS--37 Adults with mild hypertension (diastolic blood pressure less than 110 mm Hg). INTERVENTION--Patients received either placebo or potassium 60 mmol/day alone or in combination with magnesium 20 mmol/day in a crossover design. No other drug treatment was allowed. MEASUREMENTS--Blood pressure and heart rate assessed at weekly intervals and biochemical parameters at monthly intervals. RESULTS--Potassium alone or in combination with magnesium produced a significant reduction in systolic and diastolic blood pressures (p less than 0.001) and a significant reduction in serum cholesterol concentration (p less than 0.05); other biochemical variables did not change. Magnesium did not have an additional effect. Urinary potassium excretion increased significantly in the groups who received potassium alone or in combination with magnesium. The drug was well tolerated and compliance was satisfactory. CONCLUSION--Potassium 60 mmol/day lowers arterial blood pressure in patients with mild hypertension. Giving magnesium as well has no added advantage.
| 13 |
Flexible cystoscopy as an adjunct to extracorporeal shockwave lithotripsy, Ancillary procedures associated with extracorporeal shockwave lithotripsy (ESWL) include placement and subsequent removal of double pigtail ureteric stents. A simple new technique has been developed for the insertion of these stents. Using the flexible cystoscope. the procedure is performed on an out-patient basis under local anaesthesia. Placement of the stents was successful in 30/34 patients and removal was successful in 14/14 patients.
| 11 |
Immunofluorescent and histochemical staining confirm the identification of the many diseases called interstitial cystitis, Interstitial cystitis comprises a complex of diseases typified by symptoms of pelvic pain. Functional complaints do not aid the clinician in determining loss of anatomical capacity. Histochemical staining with PAS-colloidal iron/Van Geison's counterstain offers improved diagnostic ability for the pathologist and correlates well with immunofluorescent findings. Four distinct diseases can be identified through immunofluorescent staining. indicating that each is the result of different responses of the urothelium and endothelium to injury. Loss of bladder capacity associated with these diseases can be expected with age. but immunofluorescent staining for IgM within the capillaries of the interstitium is a more sensitive predictor.
| 11 |
Do women with idiopathic sensory urgency have early interstitial cystitis, Interstitial cystitis is rarely considered as a cause of urinary symptoms in referrals to gynaecology clinics. Recent concepts in the diagnosis of this condition mean that it is emerging as a much more common entity. with both early and late forms of the disease being described. Mast cell density in the detrusor muscle has been reported to be useful as a disease marker to substantiate the diagnosis of interstitial cystitis where no classical diagnostic features exist. We assessed mast cell counts in bladder biopsies from 27 women with idiopathic sensory urgency and 10 control patients about to undergo a colposuspension procedure for pure genuine stress incontinence; 30% of the study group had a clear increase in the detrusor muscle mast cell population (detrusor mastocytosis). No control patient showed such an increase. Early interstitial cystitis should be considered as a possible cause of lower urinary tract symptoms in patients with apparently idiopathic sensory urgency.
| 11 |
Symptoms versus flow rates versus urodynamics in the selection of patients for prostatectomy, Many prostatectomies are performed on the basis of symptoms alone; 39% of patients referred by their family doctors and 23% of patients who were on waiting lists for prostatectomy of other hospitals. but who had not undergone any urodynamic investigations. were found to be unobstructed on urodynamic criteria. A screening peak urinary flow rate of 12 ml/s or less was associated with urodynamic evidence of obstruction in 95% of cases; 35% of patients with symptoms of outflow obstruction and a flow rate greater than 12 ml/s were also found to be obstructed. One year post-operatively. 84% of patients who were selected for surgery on combined symptomatic and urodynamic criteria were pleased symptomatically with their result. The failure of detrusor instability to resolve following prostatectomy was associated with symptomatic failure of treatment. Residual obstruction was demonstrated in 5 patients who had undergone prostatectomy and were asymptomatic at this time. This study illustrates that objective measures are necessary in the assessment of patients prior to prostatectomy in order to select only patients who are obstructed. The importance of a screening flow rate is emphasised. All patients who underwent surgery had cystometric evidence of obstruction but the symptomatic results of surgery were no better than the results in patients who had been assessed according to non-urodynamic selection criteria. We have thus failed to identify a need for routine cystometry in the pre-operative assessment of these patients. Cystometry does. however. have a role in assessing patients with pre-operative flow rates greater than 12 ml/s and in those who remain symptomatic following prostatectomy.
| 11 |
CA72-4: a new tumour marker for gastric cancer, To date. tumour markers for gastric cancer have proved unreliable. In this study the value of a new serum marker. CA72-4. was compared with the serum activities of carcinoembryonic antigen (CEA) and CA19-9 in a consecutive series of patients with gastric cancer. The results show that the CA72-4 assay is significantly better at separating stage I and II disease from normal controls (P less than 0.01) than CEA (n.s.) or CA19-9 (n.s.). CA72-4 also gave better differentiation between patients with positive and negative nodes (P less than 0.01) and between those who were serosa positive and negative (P less than 0.01). CEA differentiated between patients with positive and negative nodes (P less than 0.05) but CA19-9 could not. CA19-9 and CEA could not discriminate between patients who were serosa positive and negative. In this study. at a specificity of 95 per cent. the sensitivities of CEA. CA19-9 and CA72-4 were 0.25. 0.41 and 0.94 respectively. These preliminary findings indicate that CA72-4 is a reliable tumour marker of disease stage and activity in gastric cancer. Further longitudinal studies are required for full evaluation of its clinical utility.
| 3 |
Treatment of adenocarcinoma of the cardia with synchronous chemotherapy and radiotherapy, Twenty-nine evaluable patients with adenocarcinoma of the cardia were treated with synchronously administered chemotherapy (two cycles of 5-fluouracil and cisplatin and 30-36 Gy of radiation to determine whether these tumours are responsive to such treatment. Complete regression of tumour was observed endoscopically in 19 patients. and partial regression in four. Fourteen patients had their tumours resected and in six no microscopic tumour was found in the specimen. Nine patients received additional radiotherapy to a total dose of 54-60 Gy instead of surgery. Tumour response was associated with rapid reversal of dysphagia. Only one patient required subsequent intervention for relief of dysphagia due to fibrous stricture. Enhanced survival was associated with a complete endoscopic response to initial chemotherapy and radiotherapy. and a tumour of less than 5 cm in length. The median survival of responding patients was 15 months. Synchronous chemotherapy and radiotherapy was of major palliative benefit in this series and merits further evaluation.
| 3 |
Manometric evaluation of jejunal limb after total gastrectomy and Roux-Orr anastomosis for gastric cancer, Total gastrectomy with Roux-Orr anastomosis is frequently performed for gastric cancer. Since intestinal motility of the Roux limb has never been evaluated after this operation. pressure activity was investigated in the Roux limb of ten patients (aged 51-77 years) who had undergone total gastrectomy and Roux-Orr reconstruction. Investigations were carried out during a 6-h fast and 3 h after a 605 kcal mixed meal. During fasting only two patients had activity fronts and these were abnormal. All ten patients displayed non-propagating bursts of contractions and three had discrete clustered contractions and high amplitude jejunal contractions. The fed state was characterized by a severely reduced motor activity pattern and other abnormalities. Total gastrectomy with Roux-Orr anastomoses provokes a relatively severe disturbance in intestinal activity.
| 3 |
Single lumen ileum with myectomy: a possible alternative to the pelvic reservoir in restorative proctocolectomy, An alternative procedure to construction of a pelvic ileal reservoir was assessed which avoids the need for a pouch. while providing an adequate rectal substitute and good continence. Thirty-six female adult beagles were allotted randomly to undergo total colectomy with (a) ileo-anal anastomosis alone. (b) ileo-anal anastomosis with two 15 cm myectomies. (c) ileo-anal anastomosis and myectomy with an ileo-ileal valve. or (d) ileo-anal anastomosis with a duplicated J pouch. The animals were studied before operation and at 4-weekly intervals for 20 weeks after operation. Mortality rates were similar. Ileal compliance was increased significantly by myectomy from 0.64 ml/mmHg (median. interquartile range 0.49-0.78) after ileo-anal anastomosis alone to 1.65 mmHg (1.16-1.93). P less than 0.01. an increase which was maintained. Ileal capacity was also increased both by myectomy and by the J pouch: ileo-anal anastomosis = 85 ml (75-100 ml). ileo-anal anastomosis and myectomy = 139 ml (116-156 ml). ileo-anal anastomosis and myectomy and ileo-ileal valve = 125 ml (range 85-145 ml). ileo-anal anastomosis and J pouch = 130 ml (range 75-165 ml) (P less than 0.01). Bowel function in the other three groups was markedly superior to ileo-anal anastomosis alone. Mean transit time was significantly less after ileo-anal anastomosis. 5.2 h (2.6-8.2 h) than after both ileo-anal anastomosis and myectomy. 10.5 h (9.6-13.9 h). P less than 0.05 and ileo-anal anastomosis and J pouch. 11.0 h (8.4-13.0 h). P less than 0.05. but addition of an ileo-ileal valve did not produce a further increase in transit time. 12.9 h (range 10.5-14.5 h). P = n.s. Myectomy of single lumen ileum may be a useful alternative to a pelvic ileal reservoir in restorative proctocolectomy.
| 22 |
Resympathectomy of the upper extremity, Resympathectomy was performed in 27 patients (eight bilaterally) with ischaemic hand phenomena. An extended operative technique. resecting parts of the second and third intercostal nerves and their surrounding tissue. was used. In all 35 procedures the posterior extrapleural approach was used. Follow-up was from 3 to 12 years. Only the sympathetic ganglia had been removed during the previous surgery by the axillary approach (67 per cent of these patients had had a transient response for between 6 months and 2 years; 33 per cent had had no response at all). A direct subjective improvement was seen after 27 of the 35 reoperations (77 per cent). In 14 patients continuous wave Doppler ultrasound studies were available and showed a significant increase in peak forward frequency after operation (P less than 0.001). From these data it may be concluded that it is possible to obtain a resympathectomy effect. but reoperation should be reserved for special cases for whom survival of digits is essential.
| 13 |
Intraoperative ultrasonography and the detection of liver metastases in patients with colorectal cancer, A total of 213 patients with carcinoma of the colon and rectum were examined to detect liver metastases. The study compared preoperative ultrasonography and inspection and palpation of the liver during surgery with intraoperative ultrasonography. Preoperative ultrasonography. inspection and palpation identified 238 metastases in 42 patients. Intraoperative ultrasonography detected 116 previously unrecognized metastatic tumours during 40 surgical procedures (P less than 0.01). High resolution intraoperative ultrasonography is safe and more accurate than preoperative imaging and surgical exploratory methods. The examination is simple to perform and success appears to be related to careful attention to detail.
| 3 |
Changing indications for penetrating keratoplasty in Vancouver, 1978-87, Indications for penetrating keratoplasty (PK) were assessed by clinicopathological review of 659 corneal buttons submitted from 1978 to 1987 to the Ophthalmic Pathology Service in Vancouver. Leading indications for PK were bullous keratopathy (22.2%). keratoconus (17.1%). scarring with or without chronic inflammation (13.5%). graft failure (12.1%). scarring or active keratitis secondary to virus (9.0%) and Fuchs' dystrophy (8.3%). The principal factors responsible for graft failure were also judged by clinicopathological correlation. The authors compare their findings with those in other series.
| 10 |
Acanthamoeba keratitis with two species of Acanthamoeba, We describe a case of Acanthamoeba keratitis related to soft contact lens wear. The patient presented with a 3-week history of severe uniocular pain. radial stromal infiltrates and subepithelial infiltrates with no epithelial defect. Acanthamoeba was cultured from the corneal biopsy specimen. contact lens and lens case. The corneal biopsy culture grew both A. castellani and A. polyphaga as well as Escherichia coli. The patient was treated with topical dibromopropamidine isethionate (Brolene) drops. neomycin and polymyxin B drops and fortified gentamicin drops. Gradual clinical improvement ensued.
| 2 |
The effect of the gastrin receptor antagonist proglumide on survival in gastric carcinoma, Gastric cancer remains a disease with a very poor prognosis. and there is no safe and effective form of therapy for advanced disease. Evidence is now abundant to show that gastrin stimulates the growth of both gastric and colorectal cancer cells in vitro and in vivo. and that blockade of gastrin receptors can prolong survival in xenografted nude mice. We have thus performed a randomized. controlled study of the gastrin/cholecystokinin receptor antagonist proglumide as therapy in 110 patients with gastric carcinoma. Proglumide had no overall effect on survival (Mantel-Cox statistic = 0.5. P = 0.48). The 95% confidence interval for the proglumide treated group was 260 to 474 days compared to 230 to 372 days for the control group. No significant difference was seen with proglumide. which has a relatively low affinity with the gastrin receptor and also has partial agonist activity. Drugs that are far more specific and potent gastrin receptor antagonists are becoming available. which may have a greater effect on survival. and further clinical trials of such compounds are clearly indicated to determine the efficacy of hormonal control of gastrointestinal malignancy.
| 3 |
Autopsy-documented cure of multiple myeloma 14 years after M2 chemotherapy, Multiple myeloma was diagnosed in a 65-year-old woman in 1974 who thereafter received five-drug M2 chemotherapy. All protein abnormalities subsequently returned to normal and serial bone marrow studies documented complete bone marrow remission. Destructive bone lesions persisted radiographically. but did not progress. In 1987. a localized sigmoid adenocarcinoma was resected. In 1988. the patient presented with multiple brain metastases associated with a primary pulmonary adenocarcinoma that proved rapidly fatal. At autopsy. no evidence of multiple myeloma was found. This report describes the first tissue-documented cure of multiple myeloma 14 years after diagnosis and initiation of M2 chemotherapy. The possible association of multiple myeloma with other malignancies is also discussed.
| 3 |
Prospective evaluation of radiologically directed fine-needle aspiration biopsy of nonpalpable breast lesions, The application of fine-needle aspiration biopsy (FNAB) to the diagnosis of nonpalpable breast lesions was evaluated with a new method which uses standard needle localization under mammographic guidance to assure accurate sampling by FNAB. This method was prospectively applied to 100 mammographically detected breast lesions in 100 women (mean age. 53 years). All 100 patients underwent surgical excision of these nonpalpable lesions after cytologic aspiration. Sufficient aspirated material was obtained for cytologic diagnosis from 91 patients (91%). The histologic and cytologic interpretations were then compared. Twenty malignancies were ultimately diagnosed by histology (12 invasive ductal carcinoma. six ductal carcinoma in situ. and two lobular carcinoma in situ). of which 17 had been cytologically diagnosed. There were no false-positive diagnoses of malignancy by FNAB. False-negative readings (3.3%) included two cases of lobular carcinoma in situ and one case of ductal carcinoma in situ. This technique thus demonstrated a sensitivity of 85%. specificity of 100%. and overall diagnostic accuracy of 96.7% for the nonsurgical detection of malignancy in nonpalpable breast lesions. These results suggest that the established safety. reliability. and cost-effectiveness of FNAB can be maintained in this clinical setting. This procedure may obviate the need for open surgical biopsy in those patients with an unequivocal diagnosis of malignancy. It can also be done using standard techniques and equipment available in many community hospitals.
| 3 |
In vitro natural killer and lymphokine-activated killer activity in patients with bronchogenic carcinoma, The authors examined peripheral blood mononuclear cells from 45 patients with bronchogenic carcinoma to determine natural killer (NK) and lymphokine-activated killer (LAK) activity after in vitro incubation with media alone or media plus interferon gamma (IFN. 200 U/ml) and/or interleukin-2 (IL-2. 100 U/ml). Our results show that lymphocytes from patients with bronchogenic carcinoma can acquire LAK activity. but the level of activity acquired was significantly lower compared with lymphocytes from 25 control subjects when IL-2 cultures were supplemented with 10% autologous human serum (AHS) (15.6% +/- 2.1% specific release versus 26.0% +/- 2.9% specific release. P = 0.004). The LAK activity. defined as cytotoxicity of an NK-resistant cell line. of the patients' lymphocytes was augmented when cells were cultured with both IL-2 and IFN compared with IL-2 alone (P = 0.0001. paired t-test). Control subjects were unchanged (P = 0.09). There was no significant difference between groups of patients with different histologic types of tumor or different stages of disease. The NK activity. defined as killing of NK-sensitive K-562 target cells. of the patients' lymphocytes was not significantly different from that of the controls' lymphocytes (42.8% +/- 3.0% specific release versus 49.3% +/- 3.3% specific release. P = 0.16). These studies indicate the feasibility of IL-2 and IFN therapy in patients with bronchogenic carcinoma.
| 7 |
Acute T-cell leukemia/lymphoma mimicking Hodgkin's disease with secondary HTLV I seroconversion, The authors observed a pleiomorphic lymphoma mimicking Hodgkin's lymphoma in a French Guyana black woman lacking antibodies for human T-cell lymphoma/leukemia virus type I (HTLV I). After two courses of chemotherapy with either mechlorethamine. vincristine. procarbazine. and prednisone (MOPP) or doxorubicin. bleomycin. vincaleukoblastine. and dacarbazine (ABVD). a typical acute T-cell leukemia/lymphoma developed with HTLV I seroconversion. Specific HTLV I DNA sequences were detected using the polymerase chain reaction (PCR) on a lymph node biopsy obtained before chemotherapy. The mechanisms of the seroconversion are discussed.
| 3 |
Immunohistochemical studies on the main entrance-route of CA19-9 into the peripheral venous blood of gastric cancer patients. Correlation with CA19-9 levels in peripheral and portal blood, The correlation between CA19-9 levels of portal and peripheral venous blood. and immunohistochemical variables of cancer lesions was examined in 53 gastric cancer patients and eight patients with benign diseases. Immunohistochemically. CA19-9 was found in 33 (62.5%) of 53 primary lesions. The antigen was found in the cancer cells of invasive lymphatics and node metastases of every CA19-9 localized cancer. although the cancer cells in veins showed little or no CA19-9. There was little or no antigen in the cancer cells in veins. lymphatics. or metastases of 20 CA19-9 nonlocalized primary lesions. Patients with CA19-9 nonlocalized cancer or with benign diseases showed no elevation of the antigen levels in peripheral or portal blood. CA19-9 levels of portal blood (mean. 76.4 U/ml; positive rate. 33.3%) were not different from those of peripheral blood (mean. 91.5 U/ml; positive rate. 33.3%). Additionally. the antigen levels of the blood in patients with lymphatic invasion or node metastases were significantly higher than those in patients without the invasion or the metastases. and every patient without the invasion showed no elevation of the antigen. These results suggest that production of the antigen in cancer cells may be a premise of CA19-9 elevation in peripheral blood and that CA19-9 may be drained by the thoracic duct of the lymphatic system via node metastases or invasive lymphatics. but not by the hematogenous portal system.
| 3 |
Establishment of an erythroid cell line (JK-1) that spontaneously differentiates to red cells, The authors established a new hemopoietic cell line (JK-1) from a patient with chronic myelogenous leukemia in erythroid crisis. This JK-1 line predominantly consists of immature cells. but a small number of mature erythroblasts and red cells can be consistently seen without any specific differentiation inducer. The JK-1 cells grow in suspension culture supplemented with human plasma and carry double Philadelphia chromosomes. Hemoglobin staining with benzidine was positive for about 20% of cells and the type of the hemoglobin was for the most part HbF. Surface-marker analysis revealed JK-1 cells positive for glycophorin A. EP-1. and HAE9. The proportion of mature cells was elevated by the addition of delta-aminolevulinic acid. Erythropoietin (EPO) enhanced the growth of JK-1 cells either in the suspension or in methylcellulose semisolid culture. The total number of EPO receptors was 940 per cell. of which 220 sites had an affinity higher than the other 720 sites. This is the first report of an established human erythroid cell line which spontaneously undergoes terminal differentiation.
| 3 |
Mammographic screening of women with increased risk of breast cancer, Five hundred one women from Dallas County. Texas who participated in the American Cancer Society 1987 Texas Breast Screening Project were selected because of a self-reported family history of breast cancer (cases). They were matched with 501 randomly selected women from the same county with no family history (controls). Although there was a statistically significant trend with age for an increasing proportion of women to report having undergone mammography. there was no significant difference when comparing mammographic histories of cases with controls after controlling for age (31.5% versus 35.1%. P = 0.33). Significantly more cases (79%) perceived their risk for breast cancer to be moderate or greater compared with controls (54%. P less than 0.0001). but mammographic histories were not different when controlling for perceived risk. Both cases and controls cited lack of physician referral and cost as their reasons for not having undergone mammography. Women at increased risk for breast cancer (because of their family history) are not undergoing regular mammographic screening despite their self-awareness of the increase in their risk.
| 3 |
Cancer mortality in a higher-income black population in New York State. Comparison with rates in the United States as a whole, In the 1980 Census the median family income among blacks in Suffolk County. New York (i.e.. $19.604) was much higher than that for American blacks as a whole (i.e.. $12.618) and 94.1% of that for American whites (i.e.. $20.840). but the proportion below the poverty level was still higher for Suffolk County blacks than for American whites. Observed numbers of deaths from 1979 to 1985 for total cancers and most cancer sites in Suffolk County black men and women were not lower than expected on the basis of age-specific and gender-specific death rates for blacks in the US. Although numbers of deaths from cervical cancer and prostate cancer were slightly lower than expected in Suffolk County blacks versus American blacks. these numbers were still significantly greater than expected on the basis of death rates among American whites. Age-specific death rates for age groups 25 to 44 years to 55 to 64 years tended to be lower in Suffolk County for lung cancers in black men but not for breast cancer in black women. Specific cancer sites. which differ in the direction of the association between incidence and socioeconomic status. age. and gender must be considered in comparisons of cancer mortality by race and socioeconomic level. Implications of the comparisons were discussed with regard to the goal of reducing racial differences in cancer death rates.
| 3 |
Immunocytochemical estrogen and progestin receptor assays in breast cancer with monoclonal antibodies. Histopathologic, demographic, and biochemical correlations and relationship to endocrine response and survival, Breast cancer specimens from 600 women were assayed for estrogen receptors (ER) using an immunocytochemical assay (ICA) employing the monoclonal antiestrophilin antibody H222 Sp gamma. Results showed significant correlation with biochemical ER determinations as well as with tumor grade and menopausal status. In 449 cases. results of progesterone receptor assay by ICA using the monoclonal anti-PgR antibody KD 68. also correlated significantly with biochemical PgR measurements. The ERICA/PgRICA positivity was significantly more frequent in postmenopausal white women. Colloid carcinomas were most likely to be ERICA positive and PgRICA positive whereas medullary carcinomas were most often negative. In 47 patients with advanced mammary carcinoma. results of ERICA and PgRICA were more closely related to endocrine response than those of ER and PgR by dextran-coated charcoal assay (DCC). In 339 women with Stage I or Stage II breast cancer. ERICA was significantly associated with disease-free survival. Analysis by Cox's proportional hazard model. however. showed PgRICA to be the best predictor of survival and disease-free survival in 197 women at the same stages of disease. These data indicate that ICA is more predictive of prognosis than biochemical ER and PgR. The ease of ICA performance coupled with these results indicate that the method is an acceptable substitute for DCC in analyzing breast cancers for ER/PgR.
| 3 |
Teniposide (VM-26) and continuous infusion cytosine arabinoside for initial induction failure in childhood acute lymphoblastic leukemia. A Pediatric Oncology Group pilot study, Twenty-six evaluable children with newly diagnosed acute lymphoblastic leukemia (ALL) who failed to achieve initial remission after receiving two to seven drugs for at least a 4-week period were given teniposide (VM-26) and continuous infusion cytosine arabinoside (Ara-C). Twenty-two received 150 mg/m2 of VM-26 on days 1 and 2 with 100 mg/2 of Ara-C as a continuous infusion on days 1 through 5; a second shortened course was given on day 14 to eight patients who had evidence of some antileukemic effect or were clinically judged able to tolerate a second course. The last four patients received three daily doses of VM-26 and a 7-day infusion of Ara-C at the same daily dosages. Twelve (48%) achieved complete remission (CR) of ALL. There was a trend toward decreasing response rates with an increasing number of drugs used in the initial induction regimen. i.e.. five CR among seven patients with a prior two-drug induction attempt. six CR among 14 patients with a prior three- to four-drug induction attempt. and one CR among four patients with a prior five- to seven-drug induction attempt (P = 0.14). Ten of 17 non-T-cell patients and two of nine T-cell patients achieved remission (P = 0.10). The median time required to achieve a complete remission from the initiation of treatment was 26 days (range. 14-72 days). This period was shorter in those who required one course compared with those who required two induction courses. i.e.. 25 days median vs. 44 days median. Toxicity was significant and due mainly to marrow aplasia and infection; one patient had severe prolonged VM-26-induced hypotension. Of the 12 patients entering remission. two were removed for marrow transplant and one was removed due to parental request. In the remaining nine patients. median remission duration was only 2 months (range. 1-18 months). All nine patients relapsed in the marrow. Among the entire group of 26 patients. only one patient is alive and a long-term event-free survivor (after allogeneic marrow transplant). Due to the current use of more aggressive initial induction regimens and the extremely poor prognosis in children who fail to achieve initial remission. more intensive regimens of continuation therapy or alternative therapies. such as bone marrow transplant. should be considered.
| 3 |
Association of disease-free survival and percent of ideal dose in adjuvant breast chemotherapy, The relationship between percent of ideal dose and disease-free survival was examined in 256 Stage II and III patients who participated in a 2-year breast adjuvant chemotherapy trial consisting of cyclophosphamide. methotrexate. and 5-fluorouracil (CMF) given postoperatively. When analyzed analogously to previous work. the results confirmed a dose-response relationship: that is. there appeared to be an improved disease-free survival for patients receiving higher doses of adjuvant chemotherapy. The major criticism of such an analysis is its bias. This bias was addressed by considering only patients who were still receiving therapy at 6. 12. and 24 months; then. the dose-response relationship was no longer seen. Although causality cannot be inferred. the apparent differences in disease-free survival among the dose groups can be attributed to recurrences in the first 2 years among patients receiving lower doses of chemotherapy.
| 3 |
A phase I trial of cisplatin in hypertonic saline and escalating doses of 5-fluorouracil by continuous intravenous infusion in patients with advanced malignancies, Thirty-four patients with incurable solid tumors were treated in a Phase I trial with a fixed dose of high-dose cisplatin (CDDP) administered in hypertonic saline and escalating doses of infusional 5-fluorouracil (5-FU). Five treatment levels of 5-FU. ranging from 500 to 900 mg/m2/day for 5 days. were studied. Leukopenia. thrombocytopenia. and oral mucositis were the dose-limiting toxicities encountered. Nephrotoxicity was minimal. Ototoxicity and peripheral neuropathies were rare and mild in this patient group. but most patients received only a small number of treatment cycles. Diarrhea was not dose-limiting. Two complete responses (one non-small cell lung cancer and one sweat gland carcinoma) were observed. No other major responses were noted. With the dose of CDDP set at 35 mg/m2/day for 5 consecutive days. the maximum tolerated dose (MTD) of a concurrent 5-day 5-FU infusion was found to be 900 mg/m2/day. The recommended dosages for Phase II trials are 35 mg/m2/day CDDP and 800 mg/m2/day 5-FU for 5 consecutive days. Cancers of the lung. breast. gastrointestinal tract. and genitourinary tract would be reasonable targets for Phase II studies.
| 3 |
Treatment of advanced squamous cell carcinoma of the skin with cisplatin, 5-fluorouracil, and bleomycin, The authors treated 14 patients with advanced squamous cell carcinoma (SCC) of the skin or lip with one to four cycles of combination chemotherapy consisting of cisplatin by bolus injection. and 5-fluorouracil (5-FU) and bleomycin by continuous 5-day infusion. Objective responses were seen in 11 of the 13 evaluable patients (84%). Four patients had a complete remission (30%) and seven patients. a partial remission (54%). Local control after definitive complementary radiation and/or surgical treatment was achieved in seven patients. Toxic side effects was acceptable; they consisted of nausea and vomiting in all patients. transient skin changes. hematologic (Grade 3/4) abnormalities in four patients. and pulmonary fibrosis in one elderly patient. These results show that this chemotherapy combination could play a role in reducing the tumor mass and in facilitating definitive treatment to obtain better functional and cosmetic results in advanced SCC of the skin.
| 3 |
Effect of intraarterial versus intravenous cisplatin in addition to systemic doxorubicin, high-dose methotrexate, and ifosfamide on histologic tumor response in osteosarcoma (study COSS-86), In osteosarcoma. intraarterial (IA) administration of systemic treatment has been advocated to improve local tumor response preparing for. or even obviating. definitive surgery. Because data from the literature did not unequivocally support the local superiority of IA infusion. a comparative study was started in 1986. Preoperative chemotherapy consisted of 45 mg/m2 of doxorubicin on days 1 and 2; 12 g/m2 of high-dose methotrexate on days 15 and 22; and 3 g/m2 of ifosfamide on days 29. 30. 50. and 51 followed on days 31 and 52 by intravenous (IV) versus IA tourniquet infusion of cisplatin (DDP). A strict randomization of patients was not feasible. A balanced distribution of risk factors was strived for by stratifying and allocating the appropriate patients centrally. The infusion time was prolonged from 1 to 5 hours in the IV group. and the DDP dose was reduced from 150 to 120 mg/m2 in both arms when intolerable ototoxicity became apparent. A multivariate analysis was performed to exclude a bias on the response rates from risk factor distribution and from modifications of DDP infusion time and dosage. The overall fraction of histologic good responders (greater than 90% necrosis) was not found to be different after IA versus IV treatment (34/50 [68%] vs. 41/59 [69%]). Intraarterial instead of IV use of DDP within an aggressive systemic treatment does not seem to improve the local tumor response.
| 3 |
Long-term follow-up of 24 patients undergoing radical resection for ampullary carcinoma, 1953 to 1988, Potentially curative radical pancreaticoduodenectomy for ampullary adenocarcinoma was performed in 24 patients over a 35-year period. The overall operative mortality was 12.5%. Actuarial survival rate at 5 years was 61% +/- 13.4 standard error of the mean (SEM) and subsequently remained unchanged. In the same time period. 21 patients underwent potentially curative radical pancreaticoduodenectomy for periampullary tumors of pancreatic origin. Similar analysis showed an overall operative mortality of 23.8% and a survival rate at 5 years of 27% +/- 12.5 SEM. The results of radical pancreaticoduodenectomy for ampullary carcinoma in the most recent years (1976 to 1988) were compared with those of former years (1953 to 1975). There were no statistically significant differences in the 5-year survival rate; however. the operative mortality decreased from 25% in the former period to 6.3% in the recent period. Survival was dependent on nodal status. The 5-year survival rate was 78% +/- 11.5 SEM in the absence of nodal metastasis versus 50% +/- 25 SEM in the presence of regional nodal metastasis. These findings support the concept that radical pancreaticoduodenectomy offers a realistic probability for cure in a selected group of patients with carcinomas of the ampulla of Vater.
| 3 |
Expression of Ki-1 antigen (CD30) in mesenchymal tumors, Expression of CD30(Ki-1) antigen has long been considered to be restricted to activated lymphocytes and related tumors. However. expression of this antigen has also been detected in embryonal carcinomas. in nonembryonal carcinomas. in malignant melanomas. and even in some myeloid cell lines and macrophages at late stages of differentiation. In this study. using monoclonal antibody Ki-1. expression of CD30 antigen was immunohistochemically examined in frozen sections of 28 benign and 63 malignant mesenchymal tumors. The authors found CD30 expressed in two of four leiomyomas. seven of 11 leiomysarcomas. one of six rhabdomyosarcomas. two of two aggressive fibromatoses. one of three fibrosarcomas. two of four synovial sarcomas. one giant cell tumors of tendon sheaths. all five malignant fibrous histiocytomas. all three osteosarcomas. one of three Ewing's sarcomas. in a tumor cell subpopulation of two of ten malignant schwannomas. and in the Schwann cell compartment of one of two ganglioneuromas tested. Furthermore. CD30 was consistently expressed in the myoepithelial compartment of 13 fibroadenomas. However. all five lipomas. all seven liposarcomas. all three neuroblastomas. both ganglioneuroblastomas. both chondrosarcomas. and tumors of disputed origin tested were consistently CD30 negative. These findings indicate that. outside the lymphatic system. CD30 antigen is not restricted to epithelial neoplasms but may also be present in tumors of mesenchymal origin. The authors conclude that CD30 antigen. although having limited utility in the differential diagnosis of tumors of questionable histogenesis. may eventually define relevant subgroups within the main tumor categories.
| 3 |
Immunophenotypes in "classical" B-cell chronic lymphocytic leukemia. Correlation with normal cellular counterpart and clinical findings, This study evaluates the expression of a series of membrane antigens. normally expressed by B-lymphocytes of the lymphocytic mantle and marginal zone. in 90 selected cases of "classical" (mouse red blood cell-receptor+. CD20+. CD5+. surface immunoglobulin +/-) B-chronic lymphocytic leukemia (B-CLL) with the aim of contributing toward identifying the normal counterpart of B-CLL and any correlations between surface antigen pattern and certain clinical characteristics. Clustered (CD23. 25. 39. 40. 27. 1c. w75) and unclustered (NuB1. 7F7. KiB3) monoclonal antibodies (MoAb) were tested. Almost all cases showed high reactivity to CD23. 27. w75. 39. 40. and NuB1: expression of CD1c was very low and that of 7F7. KiB3. and CD25 was variable. The reactivity of 7F7 and KiB3 was strictly correlated. and they correlated individually with CD25. Results show that the most frequent B-CLL phenotype (CD19+. 5+. 23+. 27+. 39+. NuB1+. KiB3 +/-. 7F7 +/-. and CD25 +/-) corresponds to one or more cellular subsets in the mantle zone. No correlation was found between MoAb expression. surface immunoglobulin (SIg) class or type. clinical stage. disease activity. or age at diagnosis. The only difference (statistically borderline) was the expression of 7F7 and KiB3 (in young versus old patients). This suggests that modulations in the expression of surface antigens do not affect the clinical behavior of the disease.
| 3 |
Rearrangement of immunoglobulin, T-cell receptor, and bcl-2 genes in malignant lymphomas in Hong Kong, The pattern of malignant lymphomas in the Hong Kong Chinese population is characterized by a low incidence of Hodgkin's disease and follicular lymphomas. The authors studied the immunoglobulin (Ig). T-cell receptor (TCR). and bcl-2 gene rearrangement in 62 cases of malignant lymphoma in this population by Southern blot hybridization. Two cases of Hodgkin's disease showed no rearrangement of the Ig and TCR genes. All 42 cases of B-cell lymphoma had Ig heavy chain (JH) rearrangement with or without additional rearrangement of the light chains (C kappa and C lambda). One case of diffuse B-cell lymphoma had additional T-cell receptor beta-chain (C beta) rearrangement. Sixteen of 18 cases of T-cell lymphoma had C beta rearrangement. and one case of T-lymphoblastic lymphoma had additional JH rearrangement. Two of eight (25%) cases of follicular lymphoma but only one of the 34 (2.9%) cases of diffuse B-cell lymphoma had bcl-2 rearrangement that was detected by pFL-1 probe. None of the 62 cases showed bcl-2 rearrangement using the pFL-2 probe. In conclusion. the Ig and TCR gene rearrangement pattern of the lymphomas found in Hong Kong correlates well with the T-cell and B-cell lineage. which is similar to reports in the white population. However. the incidence of bcl-2 gene rearrangement in follicular B-cell lymphoma is lower than that reported in the US but comparable with that in Japan.
| 19 |
Lewis system alterations in gastric carcinogenesis, Alterations in the expression of type 1 blood group-related antigens (Lewis a and b) were examined immunohistochemically in 371 consecutives gastric biopsy and 80 surgical specimens from patients of gastric carcinoma. The ABH and Lewis phenotype and secretor status of the patients were correlated with histologic findings. An anomalous expression of Lewis a antigen was found in 88 of 249 gastric biopsy specimens of Lewis (a-b+) phenotype patients. The prevalence of this anomaly increased with the evolution of the premalignant process. in agreement with the commonly accepted model of gastric carcinogenesis. Thus. anomalous Lewis a antigen appeared in 66.6% of gastric dysplasia cases. in 64.6% of intestinal metaplasia. in 15.4% of atrophic gastritis. and in 7.4% of superficial gastritis. No alterations were found in subjects with normal gastric mucosa. Forty-seven of the 49 Lewis (a-b+) phenotype gastric carcinoma patients showed antigenic alterations in tumor cells (anomalous Lewis a antigen in 36 and loss of Lewis antigens in 11). In 26 of these gastric specimens an anomalous Lewis a antigen was present in areas of intestinal metaplasia and/or dysplasia away from the area of neoplastic transformation. The expression of Lewis a antigen in Lewis (a-b+) phenotype patients is a frequent phenomenon in gastric neoplastic cells and could result from the blocked synthesis of Lewis b antigen with accumulation of its precursors. These findings suggest that. during gastric carcinogenesis. antigenic alterations may precede neoplastic transformation. An anomalous Lewis a antigen could constitute a significant index of severity of the histologic lesion and contribute to identifying high-risk individuals.
| 3 |
Comparison of DNA content in gastric cancer cells between primary lesions and lymph node metastases, Cytophotomtric DNA contents of tumor cells in primary lesions and the corresponding metastatic lymph nodes were compared in 61 cases of gastric cancer to determine whether the DNA content remains stable during lymph node metastasis. The DNA distribution patterns were grouped into three types. according to the proportion of aneuploid cell population. Changes in DNA patterns between primary and metastatic lesions were evident in 36 of 61 patients (59.0%); in the remaining 25 (41.0%). the same DNA distribution patterns were noted for both lesions. In 33 of these 36. DNA pattern in the primary carcinoma was transformed into a more narrowly scattered one in the metastatic lesion of the lymph node. Mean and modal values and the frequency of cells over tetraploid (4c) or hexaploid (6c) were significantly higher in the primary lesion compared with findings in the metastatic lesions. This reduction in DNA content in the metastatic lesions was a more frequent occurrence in differentiated (18 of 23) than in undifferentiated adenocarcinoma (15 of 35) (P less than 0.01). Therefore. in primary lesions with a widely scattered DNA ploidy. the tumor cells with a smaller DNA ploidy frequently metastasized to lymph nodes. particularly in cases of a differentiated carcinoma. Such observations may be pertinent in future designing of treatment protocols.
| 3 |
Angiotropic (intravascular) large cell lymphoma. A clinicopathologic study of seven cases with unique clinical presentations, The authors recently reported the antigenic phenotypes of three cases of so-called "malignant angioendotheliomatosis" and suggested that angiotropic large cell lymphoma (ALCL) is a more appropriate designation for this disease. The authors now report an additional seven cases of ALCL with unique clinical presentations. One patient presented with prostate enlargement. the second with lytic bone lesions and thickened nasal sinus mucosa. the third had diffuse myalgia. the fourth had dyspnea and pulmonary infiltrates. the fifth had gangrene of the lower extremities. total-body skin involvement. and pancytopenia. the sixth had a lesion of the foreskin mimicking squamous cell carcinoma. and the seventh had a mediastinal mass. In all cases histologic features were characteristic of ALCL with. in two cases. extravascular spread into soft tissue. Immunohistologic studies showed a B-cell phenotype in five cases and a T-cell phenotype in one case. Two patients received combination chemotherapy using established treatment protocol for large cell lymphoma. and remain in complete clinical remission and two patients are responding clinically to combination chemotherapy. Two patients died shortly after receiving combination chemotherapy. One patient has only recently been diagnosed as having ALCL and no long-term follow-up is available. These data indicate that. although ALCL affects predominantly the central nervous system and skin. unusual clinical presentations may occur. and patients with ALCL may respond to combination chemotherapy for large cell lymphoma.
| 19 |
Mucinous adenocarcinoma of the submandibular gland, A rare tumor not easily classifiable among published histologic categories for salivary gland tumors is reported. The neoplasm developed within the submandibular gland of a 78-year-old woman with invasion of the mandible and metastasis to regional lymph nodes. Histopathologically. cuboidal cells possessing clear cytoplasm and displaced round nuclei proliferated and exhibited an adenomatous pattern. Many cystic spaces surrounded by tumor cell strands were seen. mucus substance filled in the cystic spaces. and the tumor cells seemed mucus-secreting. but neither epidermoid cells nor papillary appearance could be observed. Electromicroscopically. numerous mucous droplets of low electron density were prominent in the cytoplasm. and the tumor cells had sparse irregular microvilli on the luminal surface. Mucin histochemistry. including paradoxical concanavalin A staining. revealed that the tumor cells contained neutral and acid mucins. and these were identified as class II and III mucosubstances. No other neoplastic lesion. except recurrent metastatic neck nodes. has been detected 6 years after the first examination. and it seems that the tumor is a rare primary mucinous adenocarcinoma of the submandibular gland.
| 3 |
The use of flow cytometry for the prognosis of stage II adjuvant treated breast cancer patients, Characterization of breast cancer cells by histology. flow cytometry. and steroid receptors was performed on 197 Stage II breast node positive cancer patients given adjuvant chemotherapy. plus tamoxifen for patients with positive hormone receptors. Histologic and steroid receptor assays were performed using standard techniques; flow cytometric analysis was performed from paraffin-embedded blocks obtained from the primary tumor. Quality control studies on reproducibility. tissue heterogeneity. and analysis procedures have been included. Of the 197 patients studied. aneuploidy was found in 102 (52%); the median %S value was 8% with a range of 0.4% to 38%. Our results demonstrated that number of positive nodes. receptor status. and grade were of prognostic value. Cell cycle kinetic data were not of independent prognostic value in this series. However. ploidy could differentiate in prognosis in the receptor-negative subgroup. Patients with receptor-negative tumors had a significantly better overall survival if the tumor was diploid in nature. Cell kinetics was not significantly prognostic for either receptor subgroup. although patients with higher %S tended to have better relapse-free and overall survival. This is in disagreement with other studies and may demonstrate that treatment has confounded our results and diminished the ability of flow cytometry data to help predict outcome.
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Comparison of the conventional method of lymph node staging with a comprehensive fat-clearing method for gastric adenocarcinoma, Discrepant results in long-term survival between United States and Japanese patients with resectable gastric adenocarcinoma may result from more accurate staging in the Japanese series. The authors compared a comprehensive fat-clearing method with the conventional pathology method of lymph node sampling in 11 patients undergoing curative gastrectomy and extended lymphadenectomy at their institution. Comprehensive fat-clearing doubled total lymph node counts (P less than 0.01). identified smaller lymph nodes (P less than 0.001). and identified more histologically involved nodes of significantly smaller size (P less than 0.001). Comprehensive fat-clearing pathologically upstaged 29% of the authors' eligible specimens. Accurate pathologic staging is necessary when comparing Japanese and United States survival data for resectable gastric adenocarcinomas.
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Neuropeptide Y and neuron-specific enolase levels in benign and malignant pheochromocytomas, Neuron-specific enolase (NSE) is the isoform of enolase. a glycolytic enzyme found in the neuroendocrine system. Neuropeptide Y (NPY) is a peptide recently discovered in the peripheral and central nervous systems. Serum NSE and plasma NPY levels have been reported to be increased in some patients with pheochromocytoma. The authors evaluated whether the measurement of these molecules could help to discriminate between benign and malignant forms of pheochromocytoma. The NSE levels were normal in all patients with benign pheochromocytoma (n = 13) and elevated in one half of those with malignant pheochromocytoma (n = 13). Plasma NPY levels were on the average significantly higher in the malignant (177.1 +/- 38.9 pmol/l. n = 16) than in the benign forms of the disease (15.7 +/- 389 pmol/l. n = 24). However. there was no difference in the percentage of patients with elevated NPY levels. These results show that determination of serum NSE may be useful for distinguishing between malignant and benign pheochromocytoma; the measurement of plasma NPY is not useful for differentiating the two kinds of tumors.
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Retrograde recanalization of an occluded posterior tibial artery by using a posterior tibial cutdown: two case reports, Recanalization of two occluded posterior tibial arteries was successfully achieved by utilizing a retrograde approach via a posterior tibial artery cutdown at the level of the ankle. Both cases were previously unsuccessfully attempted by using an antegrade approach. Thus. the choice of access vessel (arterial entry site) becomes a crucial determinant of angioplasty success.
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Simplified method for estimating true aortic valve mean gradient from simultaneous left ventricular and peripheral arterial pressure recordings, Estimation of the aortic valve gradient by simultaneous recording of left ventricular and peripheral arterial pressures is subject to error due to delay and modulation of the arterial pressure contour as it propagates from the ascending aorta. This error can be corrected by averaging the mean gradients derived from unaltered and temporally aligned simultaneous left ventricular-peripheral arterial pressure tracings. In 26 patients with aortic stenosis and simultaneous recordings of ascending aortic and femoral arterial pressure we compared this method with a simplified approach in which the peripheral arterial pressure is partially aligned by advancing it against the left ventricular pressure by 50% of the time delay of the simultaneously recorded upstrokes. Gradients measured this way predicted the true aortic valve gradients (left ventricular-ascending aortic) with a mean difference of +1.1 mm Hg (range = +10 to -5 mm Hg). We recommend use of this simplified method of correction because it predicts true aortic valve gradient equally well as the averaging technique (r = 0.977 vs. 0.979) and requires half the time and effort.
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Experience with the use of coronary autoperfusion catheter during complicated angioplasty, Between February and July of 1989. 22 patients underwent the use of the Stack autoperfusion catheter following acute occlusion or obstructive dissection during coronary angioplasty; in 20 cases conventional balloon was used in an attempt to correct the angiographic appearance followed by the use of Stack catheter when results were sub-optimal. Only 1 patient (4.5%) required surgical revascularization. Although our study is not prospective or randomized. our observations suggest a significant impact in decreasing the need for emergency surgical revascularization after complicated coronary angioplasty with the use of this approach.
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Use of a guiding catheter for contralateral femoral artery angioplasty, We describe a unique method employing a transseptal sheath as a "guiding catheter" that allows contralateral retrograde femoral artery access to perform balloon angioplasty of proximal superficial femoral artery lesions. This technique simplifies arterial access. provides support for crossing lesions. and allows angiographic visualization of target lesions during the procedure.
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Percutaneous valvuloplasty in a patient with mitral stenosis following surgical annuloplasty, A case is described in which a patient with a Carpentier-Edwards annuloplasty ring developed mitral stenosis and was treated with percutaneous mitral valvuloplasty. Possible mechanisms for the development of mitral stenosis are briefly discussed.
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Left main percutaneous transluminal coronary angioplasty with the autoperfusion catheter in an animal model, Left main coronary angioplasty is associated with high risk because of interruption of blood flow to much of the left ventricle during balloon inflation. An "autoperfusion" balloon angioplasty catheter that allows blood to flow passively distal to an inflated balloon was tested in dogs and compared with inflations with standard balloon catheters. During 3 min occlusions of the left main coronary artery with the autoperfusion catheter. regional myocardial blood flow was preserved at 0.60 +/- 0.14 ml/min/g. compared with 0.07 +/- 0.03 ml/min/g during inflation with standard balloon catheters (P less than 0.01). Similarly. at the end of 3 min of inflation. left ventricular systolic pressure and dP/dt were maintained with autoperfusion catheter inflation. but they were severely depressed after standard angioplasty balloon inflation. All seven dogs survived autoperfusion balloon inflation. whereas five of seven developed sustained ventricular tachycardia and/or ventricular fibrillation during or after standard balloon inflation. Thus. distal blood flow. hemodynamics. and survival were preserved during autoperfusion balloon inflation in the left main coronary artery.
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A rapid, effective technique for retrograde crossing of valvular aortic stenosis using standard coronary catheters, Retrograde crossing of valvular aortic stenosis can be challenging even to experienced angiographers. In 446 of 447 consecutive patients with aortic stenosis catheterized during the past 3 years. a technique using a standard Judkins right coronary catheter and a floppy straight tipped guide wire was successful in rapidly and efficiently crossing these pathologically distorted valves in retrograde fashion. Once the valve was crossed. the coronary catheter was replaced with a pigtail catheter for pressure and ventriculography. The majority of these valves required less than 2 min to cross using this technique. This method is valuable in limiting the time required for catheterization. thus helping to reduce procedure related morbidity in these oftimes critically ill patients.
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Nitrous oxide does not exacerbate pulmonary hypertension or ventricular dysfunction in patients with mitral valvular disease, Using the rapid-response thermistor pulmonary artery catheter and transoesophageal echocardiography. this study examined the effects of 100 per cent oxygen. 70 per cent nitrous oxide/30 per cent oxygen. and 70 per cent nitrogen/30 per cent oxygen on the pulmonary circulation and ventricular function in ten patients with pulmonary hypertension. In comparison with baseline measurements. nitrous oxide administration resulted in small but statistically significant (P less than 0.05) changes in mean arterial pressure (76 +/- 14 to 67 +/- 12). mean pulmonary arterial pressure (37 +/- 14 to 33 +/- 13 mmHg). and cardiac output (3.7 +/- 1.4 to 3.2 +/- 1.1 L.min-1). Seventy per cent nitrogen resulted in no significant changes from baseline. The repeat 100 per cent oxygen measurements were nearly identical to the nitrous oxide measurements. It is concluded that nitrous oxide does not exacerbate pulmonary hypertension or ventricular dysfunction during high-dose fentanyl anaesthesia in patients with mitral valvular disease.
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Ethyl chloride and venepuncture pain: a comparison with intradermal lidocaine, One hundred and twenty unpremedicated patients undergoing gynaecological surgery were randomly allocated to one of three equal treatment groups to assess the effectiveness of ethyl chloride in producing instant skin anaesthesia to prevent the pain of venepuncture from a 20 G cannula. They received either no anaesthetic. 0.2 ml one per cent lidocaine plain intradermally or a ten-second spray of ethyl chloride at the cannulation site. Ethyl chloride produced skin anaesthesia that significantly reduced the pain of venepuncture. However. it was not as effective as intradermal lidocaine. It had no effect on vein visualisation or ease of cannulation. Ethyl chloride can be recommended as a method of producing instant skin anaesthesia.
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Brain protection: physiological and pharmacological considerations. Part I: The physiology of brain injury, Ischaemia. whether focal or global in nature. produces a sequence of intracellular events leading to increased cell permeability to water and ions including Ca++. There is a loss of cellular integrity and function. with increased production of prostaglandins. free radicals. and acidosis with lactate accumulation. These events may be exacerbated by glucose administration. Pharmacological agents aimed at alleviating ischaemic injury could be directed at decreasing cerebral metabolic requirements for oxygen. improving flow to ischaemic areas. preventing Ca+(+)-induced injury. inhibition of free radical formation. lactate removal. inhibition of prostaglandin synthesis. and prevention of complement-mediated leukocyte aggregation. Part I of this paper describes some of the pathophysiological events leading to ischaemic brain injury. Part 2 of this paper will consider the current agents available for brain protection.
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Epidural analgesia for a parturient with herpes gestationis, A 23-yr-old parturient with herpes gestationis spontaneously delivered a normal healthy infant under epidural analgesia. She received five injections of bupivacaine 0.5 per cent over a ten-hour period. There was no infection at the lumbar region. even though her body was covered with vesicles and bullae including the face and neck. Eight months after delivery the patient still has a vesicular eruption which occurs mainly during her menses.
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Regulation of fibrillar collagen types I and III and basement membrane type IV collagen gene expression in pressure overloaded rat myocardium, Left ventricular hypertrophy is based on cardiac myocyte growth. The hypertrophic process can be considered heterogeneous based on whether it also includes a remodeling and accumulation of fibrillar types I and III collagens that are responsible for impaired myocardial stiffness. In the heart. the messenger RNA (mRNA) for fibrillar collagen types I and III has been detected only in cardiac fibroblasts. whereas mRNA for basement membrane collagen type IV is present in both fibroblasts and myocytes. We studied the early and long-term expression of these collagenous proteins in rat myocardium after abdominal aortic banding with renal ischemia. Complementary DNA probes for rat pro-alpha 2 (I). mouse type III and mouse type IV collagens. and chicken beta-actin were used. Northern and dot blot analysis on total RNA extracted from left ventricular tissue indicated a sixfold increase in steady-state levels of mRNA for collagen type I on day 3 of abdominal aortic banding. which had declined to control levels by day 7 where it remained rather constant at 4 and 8 weeks. Type III collagen showed a similar pattern of gene expression after banding. mRNA levels for type IV collagen. on the other hand. were elevated on day 1 after banding. returning to control at day 7 and remaining constant. Actin mRNA levels also increased on day 1 of banding. followed by a rapid return to control levels. Monospecific antibody to types I and III collagens and immunofluorescent light microscopy on frozen sections of the myocardium revealed that at 1 week after banding. the distribution and density of these collagens were similar to those of control animals.
| 13 |
Pulmonary edema induced by phagocytosing neutrophils. Protective effect of monoclonal antibody against phagocyte CD18 integrin, We studied the changes in pulmonary hemodynamics and lung wet weight induced with opsonized zymosan (OZ) in isolated guinea pig lungs perfused with Ringer-albumin solution containing neutrophils (PMNs). Addition of OZ to the PMN-perfused lungs caused pulmonary vasoconstriction and weight gain; neither OZ nor PMNs added individually to the perfusate altered pulmonary vasomotor tone or wet weight. The steady gain in lung weight by 1.588 +/- 464 mg over the 45-minute study period was associated with pulmonary capillary hypertension and an increase in the capillary filtration coefficient. indicative of increased lung vascular permeability. These responses may not be due to generation of oxygen radicals. because the alterations in pulmonary hemodynamics and lung weight were not reduced by addition of superoxide dismutase. catalase. or superoxide dismutase plus catalase. We examined the basis of the PMN-mediated effects by layering PMNs on bovine pulmonary artery endothelial monolayers. Challenge with OZ resulted in increased endothelial permeability to 125I-albumin. The monoclonal antibody IB4 (directed against CD18. the common beta-subunit of structurally related adhesion receptors on phagocytes. LFA-1. Mac-1. and P150.95) prevented the OZ-mediated increase in PMN adherence to endothelial cells and the increase in endothelial permeability to 125I-albumin. IB4 also inhibited the lung weight gain mediated by the OZ-stimulated PMNs in intact lungs. The protective effect of IB4 could be ascribed neither to inhibition of uptake of OZ by PMNs nor to inhibition of release of oxygen radicals. myeloperoxidase. and elastase.
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Dataset used in the paper:
A thorough benchmark of automatic text classification From traditional approaches to large language models
https://github.com/waashk/atcBench
To guarantee the reproducibility of the obtained results, the dataset and its respective CV train-test partitions is available here.
Each dataset contains the following files:
- data.parquet: pandas DataFrame with texts and associated encoded labels for each document.
- split_<k>.pkl: pandas DataFrame with k-cross validation partition.
- For each fold <k>:
- train_fold_<k>.parquet: pandas DataFrame with texts and associated encoded labels for each document on the training split k (according to split_<k>.pkl)
- train_fold_<k>.parquet: pandas DataFrame with texts and associated encoded labels for each document on the testing split k (according to split_<k>.pkl)
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