123rc/medical_text huggingface dataset:
Protein phosphorylation during ischemia. Many investigations have shown that calcium and adenosine triphosphate are crucial to central nervous system functions. It is probable that alterations of these substances during central nervous system ischemia are involved in the processes that cause irreversible neural damage. Calcium regulates several protein kinases that are responsible for phosphorylation of proteins vital for many central nervous system functions. Using a rabbit spinal cord ischemia model, we found protein kinase C and calcium/calmodulin-dependent kinase were severely affected during the first hour of ischemia. Protein kinase A was not significantly affected. The time course of lost protein kinase C enzyme activity closely corresponded to irreversible loss of neurologic function, and there is evidence that protein kinase C inhibitor activity is generated. Also, drugs that inhibit protein kinase C increased neurologic damage when administered during the early phases of ischemia. These results suggest that protein phosphorylation, particularly by protein kinase C, is critical to maintenance of neurologic function.
Bimanual simultaneous motor performance and impaired ability to shift attention in Parkinson's disease. The ability to share time and to shift attention between bimanual simultaneous motor tasks were studied in 18 patients with Parkinson's disease (PD) and 19 age- and intelligence-matched controls. The task consisted of drawing triangles with the dominant hand and squeezing a rubber bulb with the nondominant hand. Motor performance was measured using the variables: amplitude of squeezing, frequency of squeezing and velocity of drawing triangles. After eliminating variance due to baseline differences in single-handed performance, the bimanual simultaneous performance of PD and controls turned out to be similar to the frequency of squeezing and the velocity of drawing triangles. The amplitude of squeezing, however, differed between the two groups: it was significantly reduced in PD. Arguably the disturbance in the bimanual performance of PD patients was not due to a disorder of time sharing, but to a decreased ability to shift attention from the visually cued task to the non visually cued task. The results agree with current evidence that PD patients are more impaired when they have to rely upon internal control for the regulation of shifting attention than when external cues are available.
Use of neuroleptic-induced extrapyramidal symptoms to predict future vulnerability to side effects. OBJECTIVE: Susceptibility to neuroleptic-induced extrapyramidal syndromes varies widely, even within age and sex subgroups. Individual vulnerability to extrapyramidal syndromes has been assumed to explain this, but the utility of past history for predicting future occurrence of extrapyramidal syndromes has not been studied extensively. This investigation was undertaken to determine whether patients' previous histories of extrapyramidal syndromes predict future episodes of extrapyramidal syndromes and to compare the importance of this predictive factor with patient age, sex, neuroleptic dose, and anticholinergic dose as predictors of extrapyramidal syndromes. METHODS: The charts of 62 schizophrenic patients with multiple neuroleptic treatment episodes were reviewed. Extrapyramidal syndromes, neuroleptic drug doses, and anticholinergic drug doses during the first 21 days of each treatment episode were recorded. RESULTS: Previous extrapyramidal syndromes correctly predicted extrapyramidal syndromes in subsequent treatments for 84% of the patients. Variations in neuroleptic potency, neuroleptic dose, and anticholinergic dose partially explained incorrect predictions. CONCLUSIONS: These results support the hypothesis that patients with a history of extrapyramidal syndromes are at greater risk for future extrapyramidal syndromes. If confirmed, these results strongly support individual susceptibility as a major predictor of extrapyramidal syndromes and indicate that prophylaxis of extrapyramidal syndromes should be considered for patients who have previously suffered extrapyramidal syndromes from similarly prescribed neuroleptic therapy.
All-trans retinoic acid in acute promyelocytic leukemias. II. In vitro studies: structure-function relationship. All-trans retinoic acid induces leukemic cells from patients with acute promyelocytic leukemia (M3) to differentiate in vitro to mature granulocytes which express the CD15 antigen and are capable of respiratory burst function. Of 35 M3 samples, only one failed to respond. In eight cases, we compared the efficacy of two naturally occurring isomers of retinoic acid, all-trans RA and 13-cis RA. Both isomers induce maximal differentiation at 10(-6) mol/L. The maximal response was maintained at 10(-7) mol/L for the all-trans but not for the 13-cis RA. We also observed that the metabolites 4-oxo-all-trans and 4-oxo-13-cis were effective at 10(-6) mol/L. This 1 order of magnitude difference in the in vitro differentiating potencies of all-trans RA and 13-cis RA in the blasts of promyelocytic leukemias predicts a difference in the clinical efficacy of the two drugs.
The metabolic consequences of a "washed" cardiopulmonary bypass pump-priming fluid in children undergoing cardiac operations. The substrate load of the pump-priming fluid, especially glucose and lactate, has a major influence on the metabolic response of children during cardiac operations and may be detrimental neurologically. It is possible to cleanse the priming fluid of these excess substrates by ultrafiltration followed by the addition of a balanced electrolyte solution. We have used this technique in the bypass management of nine children over 1 year of age and weighing less than 18 kg who were studied from induction of anesthesia to 6 hours postoperatively. Frequent blood samples were taken for measurement of electrolytes, intermediary metabolites, and stress-related hormones. Throughout the study period electrolyte concentrations were maintained within the physiologic range and changes in blood glucose and lactate were minimized compared with those of matched historical controls from previous studies. During the period of cardiopulmonary bypass mean serum glucose concentrations varied between 4.4 and 7.7 mmol/L and peaked at 10.7 mmol/L just before skin closure. The mean serum lactate concentration did not exceed 2.3 mmol/L during the period studied. Thus ultrafiltration of the priming fluid and replacement with a balanced electrolyte solution results in the delivery to the patient of a reasonably physiologic substrate load, which is reflected in improved control of mean plasma intermediary metabolite concentrations. The method may form the basis of further clinical studies to determine specific aspects of the metabolic stress response in children.
Cystic medionecrosis of the coronary arteries and fatal coronary vasospasm. The histopathological basis of coronary vasospasm is not well defined. We report a patient with directly observed coronary artery spasm in whom cystic medionecrosis of the coronary arteries and great vessels and myxomatous degeneration of the mitral valve were evident. We suggest that myxoid connective tissue lesions of the heart may be linked to coronary vasospasm.
Cognitive and behavioural impairment among elderly people in institutions providing different levels of care. OBJECTIVE: To compare the prevalence and degree of cognitive and behavioural impairment in elderly patients in institutions providing different levels of care. DESIGN: Prevalence study. SETTING: A nursing home, a home for the aged and psychogeriatric wards in a provincial psychiatric hospital. PATIENTS: Only subjects 65 years of age or older were eligible for inclusion. A random sample was selected comprising 25% of the residents in the nursing home and the home for the aged; of the 119 asked to participate 95 agreed (44 in the nursing home and 51 in the home for the aged). All 50 on the psychogeriatric wards agreed to participate. MAIN OUTCOME MEASURES: The Mini-Mental State Examination (MMSE) and the Kingston Dementia Rating Scale (KDRS). RESULTS: An MMSE score of less than 24 (cognitive impairment) was given to 37 (84%) of the residents in the nursing home, 43 (84%) of those in the home for the aged and 48 (96%) of the patients in the psychiatric hospital; the corresponding numbers for a KDRS score of more than 0 (cognitive impairment) were 41 (93%), 48 (94%) and 50 (100%). The seven patients receiving the highest level of care at the home for the aged (special care) had more behavioural problems than those in the psychiatric hospital did (p less than 0.001). CONCLUSIONS: Cognitive and behavioural impairment was widespread in the three institutions regardless of the level of care. When planning services and allocating resources government funding agencies should consider the degree and prevalence of such impairment among elderly people in institutions.
Mapping of the locus for X-linked cardioskeletal myopathy with neutropenia and abnormal mitochondria (Barth syndrome) to Xq28. X-linked cardioskeletal myopathy with neutropenia and abnormal mitochondria is clinically characterized by congenital dilated cardiomyopathy, skeletal myopathy, recurrent bacterial infections, and growth retardation. We analyzed linkage between the disease locus and X-chromosomal markers in a family with seven carriers, four patients, and eight unaffected sons of carriers. Highest lod scores obtained by two-point linkage analysis were 2.70 for St14.1 (DXS52, TaqI) at a recombination fraction of zero and 2.53 for cpX67 (DXS134) at a recombination fraction of zero. Multipoint linkage analysis resulted in a maximum lod score of 5.24 at the position of St35.691 (DXS305). The most distal recombination detected in this family was located between the markers II-10 (DXS466) and DX13 (DXS15). These data indicate the location of the mutated gene at Xq28.
Overdose reperfusion of blood cardioplegic solution. A preventable cause of postischemic myocardial depression. Reperfusion of warm blood cardioplegic solution is useful in minimizing reperfusion damage after ischemia. This study tests the hypothesis that overzealous administration of blood cardioplegic solution at reperfusion counteracts these benefits and can lead to a prevalence of depressed ventricular performance and mortality similar to that seen after normal blood reperfusion. Thirty-one dogs underwent 45 minutes of 37 degrees C global ischemia on vented bypass. Six received normal blood reperfusion and 25 were reperfused with a warm aspartate/glutamate-enriched blood cardioplegic solution; of these, eight received high-dose (3600 +/- 600 ml) and 17 received limited-dose (1180 +/- 120 ml) blood cardioplegic reperfusion over 10 to 20 minutes. High-dose blood cardioplegic perfusion (5100 +/- 200 ml) without prior ischemia was tested in an additional five dogs. High-dose blood cardioplegia without preceding ischemia did not alter ventricular function (peak stroke work index 96% of control). After ischemia, normal blood reperfusion (no cardioplegia) resulted in marked left ventricular dysfunction (peak stroke work index 36% of control, p less than 0.05 versus control) and a 33% mortality rate (2/6 died). High-dose cardioplegic reperfusion yielded marginal recovery of stroke work index (40% of control, p less than 0.05 versus control) and a 25% mortality rate (2/8 died). In contrast, limited-dose reperfusion of blood cardioplegic solution allowed 100% survival (17/17) and restored stroke work index to 90% of control (1.3 versus 1.45 gm.m/kg). We conclude that reperfusion damage can be avoided by initial reoxygenation with limited doses of substrate-enriched blood cardioplegic solution. Conversely, high-dose reperfusion of blood cardioplegic solution offsets this benefit, reduces recovery substantially, and may be lethal.
Palliation of malignant esophageal obstruction. Progressive dysphagia is common in patients with advanced esophageal carcinoma. Multiple nonsurgical techniques are available to provide palliation and improved nutrition. Simple dilatation is the oldest technique and newer methods may offer greater efficacy. Laser therapy now provides an excellent opportunity to treat obstructing tumors. Placement of an esophageal prosthesis may become particularly useful when dilatation must be performed too frequently or has become ineffective or in the patient with an esophageal-pulmonary fistula. Newer techniques including BICAP tumor probe, intracavitary radiotherapy, or absolute alcohol injection offer promise. This review discusses the advantages and disadvantages of these different palliative techniques for patients with the extremely poor prognosis associated with esophageal cancer.
Coronary trapping of a complement activation product (C3a des-Arg) during myocardial reperfusion in open-heart surgery. Accumulation of complement factors has been found to occur in the myocardium after infarction. We studied the possibility that the complement activation product C3a des-Arg is trapped within the coronary circulation during reperfusion of the ischemic myocardium. In 11 patients undergoing routine coronary artery bypass grafting, arterial blood was sampled before, during and after cardiopulmonary bypass. Blood was drawn from the coronary sinus concomitantly with arterial blood sampling 5 and 30 min after release of the aortic cross-clamp (n = 10). From a preoperative value of 92 +/- 13 ng/ml, C3a des-Arg rose during CPB to a maximum of 1816 +/- 393 at the end of CPB. Following reperfusion for 5 min, C3a des-Arg was 1284 +/- 232 ng/ml in arterial and 1106 +/- 100 in coronary sinus blood, a significant difference (p less than 0.05). The amount of C3a des-Arg trapped in the heart at 5-min reperfusion showed positive correlation with its arterial concentration (p less than 0.05). No significant difference was found after 30 min of reperfusion. Complement activation products trapped in the heart in the early reperfusion period may play a pathogenetic role in myocardial ischemia-reperfusion injury.
Male breast cancer. Male breast cancer is uncommon but important. The diagnosis is easily made by breast biopsy, and patients are presenting earlier in the course of the disease than in the past. Despite this, patients are often first seen with tumors that have metastasized to the axillary nodes, which markedly decreases the survival rate. Therapy of localized disease includes simple excision, modified radical mastectomy, and radical mastectomy, but there is no consensus for which operation is appropriate. Radiation therapy should be strongly considered in patients with metastases to the axillary nodes, but the role of adjuvant hormonal therapy or chemotherapy is unclear. For treatment of disseminated disease, tamoxifen seems to be replacing orchiectomy. The favorable response rate, especially in patients with estrogen-receptor-positive tumors, the lack of side effects, and the high level of patient acceptability make it an attractive therapeutic choice.
Alterations of muscarinic acetylcholine receptors in the nasal mucosa of allergic patients in comparison with nonallergic individuals. Cholinergic nasal hyperresponsiveness in nasal allergy may be due to changes of the characteristics in muscarinic cholinergic receptors. Radioligand receptor binding and in vitro autoradiographic studies of nasal mucosa in nonallergic (NA) and allergic patients were performed to investigate this hypothesis. The heterogeneous NA group was subdivided into control individuals and patients with chronic sinusitis and vasomotor rhinitis. The 3H-(-)-Quinuclidinylbenzilate binding to muscarinic receptors in human nasal mucosa membranes was saturable and of high affinity in all groups. No significant differences could be demonstrated between the subgroups of the NA patients. In allergic patients the dissociation constants and receptor densities were significantly decreased in comparison with those of NA and with those of control individuals. No differences in agonist binding or coupling of the muscarinic receptor to the effector system via the G protein could be observed in allergic patients. In vitro autoradiographic experiments demonstrated specific 3H-(-)-Quinuclidinylbenzilate labeling of the glandular acini in NA and allergic patients. No specific labeling could be observed in the epithelium, blood vessels, or connective tissue. In conclusion, the increased sensitivity and decreased muscarinic receptor number may reflect the cholinergic-induced hypersecretion in nasal allergy but are probably too small to explain the complex allergic reaction.
Observations on the pathophysiology of Nelson's syndrome: a report of three cases. Nelson's syndrome is generally regarded as an unusual sequela of primary bilateral adrenalectomy when performed for Cushing's disease. It is classically defined by cutaneous hyperpigmentation, considerably elevated adrenocorticotropic hormone (ACTH) levels, and an enlarged sella turcica. In this report, we present three cases initially treated by transsphenoidal sellar exploration for Cushing's disease. In two of these cases, remission of hypercortisolism did not occur after the initial pituitary exploration. A microadenomectomy was performed in one case and, in the other, no microadenoma was found. In both, Nelson's syndrome occurred after adrenalectomy. A second transsphenoidal operation and radiotherapy were required to control tumor growth. In another case, transsphenoidal adenomectomy of an ACTH-secreting tumor initially led to a remission of hypercortisolism for 4 years, but recurrent Cushing's disease necessitated adrenalectomy, and again Nelson's syndrome occurred. The documentation of a pre-existing ACTH-secreting basophilic pituitary microadenoma before adrenalectomy, as seen in two of our cases, has not been previously reported, and these observations of "non-classical" courses have major implications for the pathophysiology of Nelson's syndrome.
Coronary angioplasty of diffuse coronary artery disease. From January 1983 through December 1987, 98 patients underwent angioplasty of at least one diffusely diseased coronary artery. Diffuse coronary disease was described as: group I, narrowing greater than or equal to 50% that involved the entire vessel (40 patients), group II, long lesions greater than or equal to 2 cm in length (39 patients), group III, three or more lesions in the same vessel (19 patients). There were 65 men and 33 women, with a mean age of 60 years; 64 patients (65%) had unstable angina, 23 patients (23%) were diabetic, 31 (32%) had prior myocardial infarctions, and 12 had prior bypass surgery. Multivessel disease was present in 89% of patients. Angioplasty of only the diffusely diseased vessel was performed in 41 patients, and additional vessels were dilated in 57 patients. Overall, of 396 lesions (four per patient) and 197 vessels (two per patient) attempted, success was achieved in 382 lesions (96%) and 187 vessels (95%); angiographic success was achieved in 112 of 120 diffusely diseased vessels (93%). Clinical success was achieved in 91 patients (93%). The overall complication rate (death, myocardial infarction, urgent bypass surgery) was 8% (8 of 98): six patients (6%) had myocardial infarction (one Q wave, five non-Q wave), one patient (1%) had urgent bypass surgery, and two patients (2%) died (one during bypass surgery). The majority of complications (7 of 8 or 87%), including the two deaths, occurred in group I patients, with a 17.5% rate, versus 2.5% in group II and 0% in group III, p less than 0.002.
Angiotropic intravascular large-cell lymphoma (malignant angioendotheliomatosis): report of a case and review of the literature. We present a case of angiotropic large-cell lymphoma and review the literature in order to define the neurologic features of this rare disorder. This is the first report of gadolinium-DTPA imaging in angiotropic large-cell lymphoma that demonstrates infarcts of multiple ages, as well as striking meningeal enhancement. Angiotropic large-cell lymphoma should be suspected in patients with clinical evidence of small and large cerebral vessel disease and diagnosis requires skin, liver, renal, meningeal, or brain biopsy. Single modality treatment, using either radiation therapy or steroids, has been ineffective, and new findings of a lymphomatous origin of this neoplasm suggest that combination chemotherapy may be indicated.
Phenobarbital and cerebral blood flow during hypertension in the newborn beagle. Phenobarbital sodium has been used in anticonvulsant concentrations (15 to 40 micrograms/mL serum) in premature newborns in attempts to prevent periventricular and intraventricular hemorrhages. Although its clinical usefulness in this regard is controversial, phenobarbital treatment has been shown to reduce periventricular and intraventricular hemorrhages after hypertensive insult in newborn beagles. In this study cerebral blood flow values in steady state and during phenylephrine-induced hypertension with and without phenobarbital pretreatment were measured in newborn beagles. At anticonvulsant dosage, phenobarbital sodium decreased mean arterial blood pressure transiently during steady state and significantly reduced total cerebral blood flow during phenylephrine-induced hypertension without reducing mean arterial blood pressure. This phenobarbital sodium effect on cerebral blood flow was not as great in the presence of acidosis, and the initial hypotensive effect of phenobarbital sodium was sustained for a longer period of time during acidosis. Phenobarbital sodium may reduce the incidence of hemorrhages in the newborn brain by providing protection against isolated hemodynamic stresses characterized by acute increases in cerebral blood flow, with or without increased mean arterial blood pressure.
Endosonography of peri-anal and peri-colorectal fistula and/or abscess in Crohn's disease. Transcolorectal endosonography (ES) was performed in 36 patients with Crohn's disease suspected clinically to have a fistula or abscess. A hypoechoic or anechoic duct-like lesion immediately adjacent to the anorectal lumen compatible with a fistula was found in 32 patients. A communication between the fistulous tract and adjacent structures such as the skin, anal canal, or vagina was detected in all 32 patients. An anechoic cavity adjacent to or communicating with the fistula was visualized in 29 of the 36 patients. A fistula was visualized in the remaining seven patients with no evidence of an abscess. This anechoic cavity compatible with an abscess was surgically confirmed in 14 of 17 patients. We judged the extent and configuration of the abnormalities to be more clearly visualized by ES when results were compared with fistulography in five patients. There were no ES complications, and we conclude that ES is the preferred diagnostic procedure in patients with peri-rectal pathology because of the low risk of bacterial dissemination and low incidence of patient discomfort. Utilizing ES after non-surgical treatment was successful in 19 patients for documentation of the response to therapy.