shukoor65/lab-rag-model huggingface dataset:
Increased risk of myelodysplasia and leukaemia after etoposide, cisplatin, and bleomycin for germ-cell tumours. Among the cytostatic drugs only the alkylating agents have been firmly established as being leukaemogenic. This report describes 4 cases of acute myeloid leukaemia and 1 of myelodysplasia occurring in a cohort of 212 patients with germ-cell tumours treated with etoposide, cisplatin, and bleomycin. The mean cumulative risk of leukaemic complications was 4.7% (SE 2.3) 5.7 years after start of etoposide-containing chemotherapy, and, compared with the risk in the general population, the relative risk of overt leukaemia was 336 (95% CI 92-861). No leukaemias were detected in a previous cohort of 127 patients with germ-cell tumours treated with cisplatin, bleomycin, and vinblastine. The increased risk of leukaemia was most probably due to etoposide alone or in combination with cisplatin or bleomycin, since other published work has also not revealed an excess of leukaemias among patients with germ-cell tumours treated with only cisplatin, bleomycin, and vinblastine. The risk of leukaemia was dose related since all 5 patients with leukaemic complications were among the 82 who had received a cumulative dose of more than 2000 mg/m2 etoposide, whereas no leukaemias were observed among 130 patients who had received up to 2000 mg/m2 (p = 0.004). 3 of the leukaemic patients had balanced chromosome translocations affecting bands 11q23 and 21q22. These translocations, and perhaps also other balanced aberrations, seem to be characteristic of myelodysplasia and acute leukaemia occurring after therapy with cytostatic agents acting on DNA-topoisomerase II.
Gamma imaging with negatively charge-modified monoclonal antibody: modification with synthetic polymers Antimyosin Fab has been modified to carry highly negatively charged synthetic polymers containing DTPAs (DTPA-PL) as chelating agents, of starting molecular weights 3.3 and 17 kD. The immunoreactivities of the modified antibodies were unaffected by the modification procedure. The isoelectric points (PI) of unmodified antimyosin (AM) Fab (PI range 7-9, Mr = 52kD) were changed to PIs predominantly between 4 and 5 (Mr = 59 kD for DTPA-PL3.3kD-AM-Fab and 67kD for DTPA-PL17kD-AM-Fab). These AM-Fab preparations were tested for specific target localization and visualization in vivo in an experimental canine model of acute myocardial infarction. The charge-modified 111In-labeled AM-Fab preparations showed enhanced target (necrotic myocardium) visualization within 30 min of intravenous infusion and decreased background activity in normal myocardium (mean %ID/g +/- s.e.m., 0.0076 +/- 0.0006, n = 164, and 0.0056 +/- 0.0004, n = 92, for 111In-DTPA-PL3.3kD- and DTPA-PL17kD-AM-Fab respectively) relative to conventional 111In-DTPA-AM-Fab (0.0263 +/- 0.0037, n = 135) (p less than 0.001) or radioiodinated AM-Fab (0.0098 +/- 0.0006, n = 256) (p less than or equal to 0.001). Furthermore, the concentration of negatively charged 111In-labeled antimyosin Fab decreased in non-target organs such as the liver and kidneys. In diagnostic and therapeutic applications, charge-modified macromolecules may improve target localization and reduce non-target organ activity.
Abnormal pattern of luteinizing hormone pulsatility in women with epilepsy. Dysfunction of the hypothalamic-pituitary-ovarian axis in epileptic females has been suggested in the latest years. To further elucidate this issue, we assessed reproductive endocrine function in 10 normally cycling, drug-free epileptic women and in 5 normal controls, evaluating the basal hormonal profile and luteinizing hormone (LH) pulsatility in the midfollicular phase. Luteinizing hormone pulse frequency was significantly higher in epileptic women with a consequent reduction of the LH interpulse interval. We suggest that epilepsy may interfere with the functional activity of the gonadotropin-releasing hormone pulse generator. The pathogenetic mechanisms for this phenomenon may be the spreading of paroxysmal activity within the hypothalamic areas or, alternatively, a neurotransmitter dysfunction giving rise both to the seizure disorder and to the abnormal LH pulsatile pattern.
Oral contraceptives and reproductive system cancer. Benefits and risks. Large epidemiologic studies conducted to date in the United States and abroad have not demonstrated any statistically significant increase in the overall incidence of breast cancer among women who used oral contraceptives (OCs). The cumulative risk of breast cancer among women less than 60 years of age is clearly not related to OC use, although the incidence of breast cancer in certain subgroups of premenopausal women who used OCs may be increased and warrants monitoring. Evidence of a latency period in the development of breast cancer among OC users is not convincing. Studies to date have indicated that the risk of invasive cervical cancer appears to be unaffected by OC use. The data on cervical intraepithelial neoplasia are inconclusive and fraught with confounding variables. There is unequivocal evidence that OC use reduces the incidence of other reproductive system cancers, notably ovarian and endometrial.
Evaluation of optic nerve sheath fenestration in pseudotumor cerebri using automated perimetry. Evaluation of the efficacy of optic nerve sheath fenestration in pseudotumor cerebri has been hindered by a lack of quantitative indicators of visual function before and after treatment. Nine patients (14 eyes) were treated who had pseudotumor with optic nerve sheath fenestration, in whom automated perimetry was used as a major parameter in the decision to undertake surgery and in evaluating the results. Visual field results demonstrated significant improvement in this group of patients. Seven of 8 eyes with total loss less than 1500 dB had improvement or no further deterioration. Using results of the last preoperative examination as baseline, it was found that six of the eight had improvement over 150 dB. In one patient, a slight deterioration occurred postoperatively. Those eyes with total loss above 1500 dB demonstrated stabilization of fields postoperatively. Statistical analysis of total loss preoperatively and postoperatively for this group of patients demonstrated significant improvement for five of the six comparisons investigated. Average preoperative total loss and average postoperative total loss were not significantly different. Comparisons of results of the last preoperative examination to those of the first postoperative and most recent follow-up examinations, and evaluation of average total loss postoperatively showed significant improvement had occurred. Results of the first postoperative examination and those of the most recent follow-up examination showed significant improvement from the average preoperative total loss.
Interaction between T cell receptor beta chain and immunoglobulin heavy chain region genes in susceptibility to insulin-dependent diabetes mellitus. Despite some reports of an association between insulin-dependent diabetes mellitus (IDDM) and a BglII RFLP in the T cell receptor beta chain (TCRB) constant region, results of several recent studies, including our own, have failed to support such an association. However, we here report evidence for an IDDM-TCRB relationship which is dependent on immunoglobulin heavy-chain-region genes. We analyzed 198 unrelated diabetics and 84 normal siblings (maximum one sibling per diabetic) typed for the BglII TCRB RFLP and Gm immunoglobulin allotypes Glm(1), Glm(2), G2m(23), and G3m(5), which identify the four common Gm haplotypes. The BglIII TCRB genotype frequencies were significantly different between diabetics positive and negative for G2m(23) (P = .017) and G3m(5) (P = .021) but were not different between normal siblings positive and negative for those allotypes (P = .94 and P = .77, respectively). Thus, there were significant interactions between TCRB, Gm, and IDDM for two of the four immunoglobulin allotypes examined. We have previously reported interactions between HLA, Gm (particularly G2m(23)), and IDDM and postulate that the TCRB-Gm-IDDM and HLA-Gm-IDDM interaction effects may be functionally related.
Comparing clinical information with claims data: some similarities and differences How well can hospital discharge abstracts be used to estimate patient health status? This paper compares information on comorbidity obtained from hospital discharge abstracts for patients undergoing prostatectomy or cholecystectomy at a Winnipeg teaching hospital with clinical data on preoperative medical conditions prospectively collected during an Anesthesia Follow-up study. The diagnostic information on cardiovascular disease, respiratory disease, and metabolic disorders showed considerable agreement, ranging from 65 to over 90% correspondence across the two data sets. Certain conditions noted by the anesthesiologist were often absent from the claims data; cardiovascular disease was recorded in the clinical data but absent from the claims for 31% of prostatectomy and 17% of cholecystectomy cases. Such patients were less likely to have been assigned a high score on the ASA Physical Status measure or to have high-risk diagnoses on the hospital file. Similar findings resulted from comparing the two sources in their ability to predict such adverse outcomes as mortality and readmission to hospital: the anesthesia file generally included less serious comorbidity.
Effects of caffeine on tobacco withdrawal. Smoking cessation increases caffeine blood levels, and this has been hypothesized to cause some of the symptoms of tobacco withdrawal (e.g., anxiety and insomnia). To test this hypothesis, 10 coffee drinkers who smoked cigarettes were entered into a completely within-subjects experimental design in which the effects of caffeine dose (0, 50, and 100 mg/coffee serving) and smoking status (smoking versus abstinence) were examined over a 4-day period. Self-reported and observed measures of tobacco withdrawal, caffeine withdrawal, and intoxication, as well as psychomotor tasks and vital signs, were completed daily; blood was drawn at the end of each period. Temporary abstinence produced typical withdrawal symptoms but did not significantly increase caffeine blood levels. Caffeine did not increase the severity of symptoms but did decrease the severity of withdrawal-induced hunger. These findings suggest that, in the absence of increased blood levels, caffeine does not increase the severity of tobacco withdrawal.
Angiography is useful in detecting the source of chronic gastrointestinal bleeding of obscure origin. The treatment of patients with chronic gastrointestinal bleeding can be a frustrating diagnostic challenge. In the past 10-15 years, a variety of new diagnostic procedures (e.g., fiber-optic endoscopy, scintigraphy, and double-contrast barium studies) have become available to examine these patients. Despite these new procedures, a small number of patients continue to bleed without a defined cause. We sought to evaluate the role of visceral angiography in patients with chronic gastrointestinal bleeding in whom findings on an extensive noninvasive workup have been normal. Between 1983 and 1990, we obtained angiograms on 36 such patients. The cause of bleeding was established by angiography in 16 patients (44%). In 11 of these 16, angiography revealed only a structural abnormality without active bleeding. Twenty patients had normal angiographic findings. No angiograms were false-positive, but three were false-negative (8%). No complication occurred as a result of the angiographic procedures. Our experience shows that visceral angiography can provide a positive diagnosis in a significant number of patients with chronic gastrointestinal bleeding of obscure origin in whom all other diagnostic measures have been unrevealing. Despite improvements in noninvasive diagnostic techniques, angiography still remains an important tool for examining this group of patients.
Thoracoabdominal aneurysm resection after previous infrarenal abdominal aortic aneurysmectomy. Thoracoabdominal aneurysms in 51 patients were repaired over 5 years ending in February 1991. Fourteen (27%, 14 of 51) patients had a prior infrarenal aneurysm resection (PRA); their data are analyzed separately. The average age of patients who had undergone PRA was 67 years (range: 56 to 86 years). The mean aneurysm diameter was 8.6 cm (range: 5 to 12 cm), and the mean time interval between initial aneurysm surgery and subsequent resection of the thoracoabdominal aneurysm was 8.5 years (range: 2 to 17 years). Three patients in the PRA group were operated on emergently, two because of clinical evidence of rupture; the other patients underwent elective repair. Early mortality (30 days) in the PRA group was significantly related to age (72 years or older versus younger than 72 years: 75% versus 10%, p = 0.04), proximal extent of aneurysm (above diaphragm versus below diaphragm: 50% versus 0%, p = 0.05), ruptured aneurysm (ruptured versus nonruptured: 100% versus 16%, p = 0.06), and a cardiac history of myocardial infarction (57% versus 0%, p = 0.03), congestive heart failure (66% versus 0%, p = 0.01), or arrhythmia (80% versus 0%, p = 0.005). Similar results were seen with the entire group of patients with thoracoabdominal aneurysms except that the proximal extent of the aneurysm was not related to mortality. These results demonstrate that thoracoabdominal aneurysm resection after prior infrarenal aneurysmectomy is not associated with increased mortality or morbidity.
Closure of a tracheoesophageal fistula by bronchoscopic application of fibrin glue and decontamination of the oral cavity. A tracheoesophageal fistula was successfully closed with a fibrin adhesive applied by means of a fiberoptic bronchoscope, instead of by esophagoscopy. To facilitate closure of the fistula, the technique was combined with decontamination of the oral cavity, to avoid bacterial contamination. The procedure is proposed as an alternative to surgery for critically ill patients.
Usefulness of excitable gap and pattern of resetting in atrial flutter for determining reentry circuit location. Clinical and experimental data show that type I atrial flutter is due to a reentry mechanism with an excitable gap. To define the location of the reentry circuit of atrial flutter, width of excitable gap, poststimulation cycle and pattern of reset after premature stimulus were analyzed in 18 patients during atrial flutter at multiple atrial sites (high, lateral, posterior and septal right atrium, and coronary sinus). The pattern of reset was defined as flat or increasing whether the return cycle remained unchanged or prolonged with increasing prematurity. Shorter values of the excitable gap were found at the coronary sinus (33 +/- 8 ms) and high right atrium (30 +/- 10 ms) than at the posterior (43 +/- 9 ms) or septal right atrium (45 +/- 11 ms). Intermediate values (36 +/- 8 ms) were measured at the lateral right atrium. Poststimulation cycle, corrected for atrial flutter cycle length, was shorter in the posterior (6 +/- 7 ms) and septal right atrium (5 +/- 7 ms) than in the coronary sinus (35 +/- 9 ms), and the high (23 +/- 10 ms) and lateral right atrium (15 +/- 9 ms). A flat pattern of resetting occurred more frequently at the septal (18 of 18 patients) and posterior right atrium (15 of 18) than at the lateral (8 of 18) and high right atrium (2 of 17), and was never observed at the coronary sinus. Atrial flutter was successfully terminated by overdrive atrial pacing in 15 of 18 patients, and termination was more easily obtained from the septal and posterior right atrium.
Blood leukotrienes in headache: correlation with platelet activity. Platelet hyperactivity, one of the commonest findings associated with migraine, has been related to increased release of biologically active substances such as catecholamines and arachidonic acid metabolites, which seem to play a role in the pathogenesis of migraine. In this study, in vitro platelet aggregation tests were performed on samples from patients with different types of headache. The presence of platelet hyperactivity was clearly demonstrated in 11 patients with classical migraine between attacks, but not in 4 patients between attacks of common migraine. Nevertheless, the presence of a marked platelet hyporesponsivity was found during the attack phase of both classical and common migraine. No difference in platelet aggregability was found between attack and post-attack phases in 5 patients with cluster headache. Blood leukotrienes were analyzed in 8 patients with classical migraine and in the 5 patients with cluster headache. During the attack phase of classical migraine both LTC4 and LTB4 were present in the peripheral blood, while the post-attack phase was characterized by the disappearance of LTC4 and the presence of LTB4 and its transisomer delta 6-trans-LTB4. Blood leukotrienes were constantly absent during both phases of cluster headache. Incubation of normal platelets with LTC4 or delta 6-trans-LTB4 was followed by inhibition of platelet response to epinephrine. delta 6-trans-LTB4, at higher concentrations, induced the opposite effect. A possible role of blood leukotrienes in the changes occurring in platelet aggregability during the different phases of classical migraine, is discussed.
Expression of brain natriuretic peptide gene in human heart. Production in the ventricle. To elucidate the expression of the brain natriuretic peptide gene in the human heart, we have measured brain natriuretic peptide mRNA levels in hearts using the Northern blot hybridization method. Brain natriuretic peptide mRNA was present with a size of approximately 0.9 kb in the ventricle as well as in the atrium. The brain natriuretic peptide mRNA level in the ventricle was 52% of that in the atrium, whereas the atrial natriuretic peptide mRNA level in the ventricle was approximately two orders of magnitude lower than that in the atrium. Taking atrial and ventricular weights into account, the total amount of brain natriuretic peptide mRNA in the ventricle represented 77% of that in the whole heart. These results demonstrate that most of brain natriuretic peptide mRNA occurs in the ventricle, in contrast with atrial natriuretic peptide mRNA, which is present mainly in the atrium, indicating that the ventricle is a major production site of brain natriuretic peptide.
Stress failure in pulmonary capillaries. In the mammalian lung, alveolar gas and blood are separated by an extremely thin membrane, despite the fact that mechanical failure could be catastrophic for gas exchange. We raised the pulmonary capillary pressure in anesthetized rabbits until stress failure occurred. At capillary transmural pressures greater than or equal to 40 mmHg, disruption of the capillary endothelium and alveolar epithelium was seen in some locations. The three principal forces acting on the capillary wall were analyzed. 1) Circumferential wall tension caused by the transmural pressure. This is approximately 25 dyn/cm (25 mN/m) at failure where the radius of curvature of the capillary is 5 microns. This tension is small, being comparable with the tension in the alveolar wall associated with lung elastic recoil. 2) Surface tension of the alveolar lining layer. This contributes support to the capillaries that bulge into the alveolar spaces at these high pressures. When protein leakage into the alveolar spaces occurs because of stress failure, the increase in surface tension caused by surfactant inhibition could be a powerful force preventing further failure. 3) Tension of the tissue elements in the alveolar wall associated with lung inflation. This may be negligible at normal lung volumes but considerable at high volumes. Whereas circumferential wall tension is low, capillary wall stress at failure is very high at approximately 8 x 10(5) dyn/cm2 (8 x 10(4) N/m2) where the thickness is only 0.3 microns. This is approximately the same as the wall stress of the normal aorta, which is predominantly composed of collagen and elastin. The strength of the thin part of the capillary wall is probably attributable to the collagen IV of the basement membranes. The safety factor is apparently small when the capillary pressure is raised during heavy exercise. Stress failure causes increased permeability with protein leakage, or frank hemorrhage, and probably has a role in several types of lung disease.
Chylothorax after childbirth. We report a case of chylothorax which appeared in a mother after childbirth. Disruption of the thoracic duct occurred with the high intrathoracic pressures generated by the Valsalva maneuver used by the patient during labor to "push." No evidence of other trauma or malignancy were found and the patient did well after use of total parenteral nutrition, thoracotomy with thoracic duct ligation, and pleurodesis.
Stereotactic radiosurgery for arteriovenous malformations of the brain. Stereotactic radiosurgery successfully obliterates carefully selected arteriovenous malformations (AVM's) of the brain. In an initial 3-year experience using the 201-source cobalt-60 gamma knife at the University of Pittsburgh, 227 patients with AVM's were treated. Symptoms at presentation included prior hemorrhage in 143 patients (63%), headache in 104 (46%), and seizures in 70 (31%). Neurological deficits were present in 102 patients (45%). Prior surgical resection (resulting in subtotal removal) had been performed in 36 patients (16%). In 47 selected patients (21%), embolization procedures were performed in an attempt to reduce the AVM size prior to radiosurgery. The lesions were classified according to the Spetzler grading system: 64 (28%) were Grade VI (inoperable), 22 (10%) were Grade IV, 90 (40%) were Grade III, 43 (19%) were Grade II, and eight (4%) were Grade I. With the aid of computer imaging-integrated isodose plans for single-treatment irradiation, total coverage of the AVM nidus was possible in 216 patients (95%). The location and volume of the AVM were the most important factors for the selection of radiation dose. Magnetic resonance (MR) imaging was performed at 6-month intervals in 161 patients. Seventeen patients who had MR evidence of complete obliteration underwent angiography within 3 months of imaging: in 14 (82%) complete obliteration was confirmation being 4 months (mean 17 months) after radiosurgery. The 2-year obliteration rates according to volume were: all eight (100%) AVM's less than 1 cu cm; 22 (85%) of 26 AVM's of 1 to 4 cu cm; and seven (58%) of 12 AVM's greater than 4 cu cm. Magnetic resonance imaging revealed postirradiation changes in 38 (24%) of 161 patients at a mean interval of 10.2 months after radiosurgery; only 10 (26%) of those 38 patients were symptomatic. In the entire series, two patients developed permanent new neurological deficits believed to be treatment-related. Two patients died of repeat hemorrhage at 6 and 23 months after treatment during the latency interval prior to obliteration. Stereotactic radiosurgery is an important method to obliterate AVM's, especially those previously considered inoperable. Success and complication risks are related to the AVM location and the volume treated.
HMB-45 immunohistochemical staining of conjunctival melanocytic lesions. HMB-45 is a monoclonal antibody recently described as being highly specific for melanocytic proliferations of the skin and in metastases of melanotic lesions. To determine a possible role for HMB-45 in ophthalmic pathology, 45 conjunctival lesions, including 23 melanomas, were analyzed using immunohistochemical techniques with anti-S-100 and HMB-45 as primary antibodies. Nineteen (82.6%) of the melanomas exhibited HMB-45 positivity, and 19 (82.6%) contained S-100 protein, with concordance of all but two cases. Seven cases of primary acquired melanosis were studied; one (33%) of three with atypia was HMB-45 positive, as were two (50%) of four without atypia. Among nevi, 1 (9.1%) of 11 showed faint staining with HMB-45. Fifteen conjunctival epithelial dysplasias were negative with HMB-45. At present, HMB-45 appears to offer no great advantage over S-100 protein in the analysis of conjunctival melanomas. Its role in the distinction of benign from atypical or malignant junctional melanocytic proliferations remains unclear.