shukoor65/lab-rag-model huggingface dataset:
Pharmacokinetics of activated protein C in guinea pigs. Protein C is a vitamin K-dependent zymogen of the serine protease, activated protein C (APC), an important regulatory enzyme in hemostasis. In view of the potential of human APC as an anticoagulant and profibrinolytic agent, the pharmacokinetics and tissue distribution of APC were studied in guinea pigs. The plasma elimination of a trace dose of 125I-APC was biphasic following an initial rapid elimination of approximately 15% of the injected dose within 1 to 2 minutes. This rapid removal of 125I-APC from the circulation was found to be a result of an association with the liver regardless of the route of injection. Essentially identical results were obtained with active site-blocked forms of APC generated with either diisopropylfluorophosphate or D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone, which indicates that the active site was not essential for the liver association. Accumulation of all three forms of APC in the liver peaked at 30 minutes and then declined as increasing amounts of degraded radiolabeled material appeared in the gastrointestinal tract and urine. Removal of the gamma-carboxyglutamic acid (gla) domain of diisopropylphosphoryl-APC resulted in a 50% reduction in the association with liver and an accumulation in the kidneys. Protein C and protein S were cleared from the circulation at rates approximately one-half and one-fourth, respectively, that of APC. Both in vitro and in vivo, APC was found to form complexes with protease inhibitors present in guinea pig plasma. Complex formation resulted in a more rapid disappearance of the enzymatic activity of APC than elimination of the protein moiety. These findings indicate two distinct mechanisms for the elimination of APC. One mechanism involves reaction with plasma protease inhibitors and subsequent elimination by specific hepatic receptors. The other mechanism involves the direct catabolism of APC by the liver via a pathway that is nonsaturable over a substantial dose range and independent of the active site. This pattern of elimination is distinctly different from that observed with the homologous coagulation enzymes thrombin, factor IXa, and factor Xa.
Intracarotid chemotherapy with etoposide and cisplatin for malignant brain tumors. Chemotherapy for tumors of the central nervous system has a limited efficacy presumably because of restricted blood-brain barrier permeability. The advantage of regional intra-arterial administration of anticancer drugs is an increased uptake during the first passage of the drugs through tumor capillaries. Twenty patients with high-grade astrocytomas (HGA) and 28 patients with metastatic brain tumors (MBT) received intracarotid/intravertebral infusion of etoposide and cisplatin. Eight patients with HGA who underwent incomplete resection responded to chemotherapy alone. Four additional patients had complete resection of the tumor. Median survival time of the group (responders and nonresponders) has been 14 months. Twelve patients with MBT responded to chemotherapy alone (six had complete response [CR], and six had partial response [PR]) with a median survival time of 7 months. Intra-arterial chemotherapy (IAC) appears to be effective with acceptable toxicities. Accrual of additional patients is required before a final conclusion can be reached.
High mebendazole doses in pulmonary and hepatic hydatid disease. Thirty nine children with 71 hydatid cysts were given mebendazole orally in a dose of 100-200 mg/kg/day for 12 weeks and were followed up for a mean (SD) of 63 (24) months. Twenty children (three of them after a second course) were cured and another two avoided at least one operation. No serious side effects of the drug were observed.
Concomitant lymphangioma and arteriovenous malformation of the orbit. An 8-year-old girl had an orbital-adnexal lymphangioma and ipsilateral orbital and middle cranial fossa arteriovenous malformations. High-resolution magnetic resonance image scanning, orbital ultrasonography, and digital subtraction angiography were used for diagnosis and preoperative assessment. Complications related to this vascular neoplasm included amblyopia, acute hemorrhage with proptosis, exposure keratitis, cosmetic deformity, and recurrent preseptal cellulitis. The girl was treated with both embolization and orbital surgery for recurrent hemorrhage and proptosis. We postulated that the coexistence of a lymphangioma and arteriovenous malformation represents an unusual and extensive maldevelopment of vascular embryogenesis.
Importance of 6-mercaptopurine dose in lymphoblastic leukaemia. To explore the possibility that higher total dosage of 'maintenance' treatment may have contributed to the recent improvement in outlook of children in the United Kingdom with lymphoblastic leukaemia, details of the amount of 6-mercaptopurine prescribed during the first two years of treatment were studied in an unselected cohort of children diagnosed between 1973 and 1987. Eighty five patients were studied, 30 diagnosed before and 55 after 1980. The group diagnosed after 1980 showed an 18% improvement in relapse free survival at five years. Their median total dose of 6-mercaptopurine had increased by 22%, whereas according to the protocol it should have risen by an average of only 9%. After 1980 boys were prescribed significantly more 6-mercaptopurine than girls, and had fewer dose reductions because of myelosuppression. These findings support the clinical impression that after 1980 an important therapeutic difference resulting from the new United Kingdom acute lymphoblastic leukaemia protocols was an increase in the amount of 6-mercaptopurine that children actually received as a result of changes in prescribing guidelines rather than dose. They also provide further evidence that boys tolerate 6-mercaptopurine better than girls, which may be related to the still unexplained difference in prognosis between the sexes.
The National Heart, Lung, and Blood Institute Workshop on antihypertensive drug treatment. The benefits, costs, and choices. Implications for research. Selected portions of the workshop's closing discussion are summarized. Major ongoing clinical trials of antihypertensive drug treatment are described. Some recommendations offered by workshop participants for future research directions are summarized.
Hypercholesterolemia: the cost of treatment in perspective. Would the money spent on treating hypercholesterolemia save more lives if spent elsewhere? How many dollars must be spent on a treatment to make one person live 1 year longer? This cost-effectiveness analysis uses the cost per year of life gained to compare a wide variety of health care interventions ranging from carcinogen research to screening tests to liver transplants. The comparison calls into question some popular trends.
Oral ketamine. Its use for mentally retarded adults requiring day care dental treatment. Four cases of severely mentally handicapped young adults requiring day care dental treatment are reported. All had required varying degrees of restraint during previous dental treatments, which had been distressing for the patient, the relatives and the ward staff. In all cases, administration of oral ketamine 10 mg/kg, 30-60 minutes before the procedure, facilitated subsequent induction of anaesthesia.
Laparoscopic cholecystectomy: evolution, early results, and impact on nonsurgical gallstone therapies Laparoscopic cholecystectomy, a surgical technique first performed in France, has gained widespread acceptance among surgeons in the United States. The abdominal cavity is inflated by carbon dioxide, a video monitor is inserted via a laparoscope placed periumbilically, and the gallbladder is freed and removed from the liver bed by using small subcostal ports for access and dissection. Intraoperative cholangiography is routinely performed, but uncertainty exists about how best to manage choledocholithiasis. Compared with traditional cholecystectomy, initial reports describing laparoscopic cholecystectomy cite shorter recovery times because no large incisions are made, thus potentially reducing the cost and morbidity of cholecystectomy. A survey of 614 early cases supports these claims, with a reported complication rate of 1.5% and quick resumption of normal activities by patients. Because of its promise for reduced morbidity, laparoscopic cholecystectomy is challenging open cholecystectomy as the therapeutic gold standard for symptomatic cholelithiasis. Thus, the standard to which the nonsurgical gallstone therapies, such as lithotripsy and contact dissolution, will be compared may shift to laparoscopic cholecystectomy. As the laparoscopic complications are similar to those of traditional cholecystectomy, such as abscesses and bile leaks, their percutaneous treatment should not change.
Renal abscess in childhood: diagnostic and therapeutic progress. During the past decade new techniques such as computed tomography (CT) and ultrasonography have been reported to have changed the diagnostic investigation and treatment of renal abscess in adults. To evaluate whether similar changes have taken place in the pediatric age group, a retrospective study of all patients seen between 1979 and 1989 was performed. Seven patients, 0.8 to 14 (mean, 9) years old, with renal abscesses in eight kidneys were identified. Ultrasound and computed tomography proved to be the most valuable diagnostic tools, revealing the diagnosis by showing a hypoechoic or hypodense mass. All patients had an initial trial of intensive antibiotic treatment, which led to resolution of the abscesses in two of the eight kidneys. In all other cases the abscesses were additionally drained, which was done surgically in two and by ultrasonography- or CT-guided percutaneous drainage in four patients. Abscess cultures grew Staphylococcus aureus (three), Escherichia coli (one) and Salmonella Group B (one) and were sterile in one case. Drainage was unsuccessful in only one patient, who subsequently underwent nephrectomy for uncontrolled infection of a diffusely damaged kidney. We conclude that the diagnosis of renal abscesses is greatly facilitated by ultrasonography and CT and that most patients can be cured without operation by antibiotics and, if necessary, by additional percutaneous drainage.
Potassium accumulation in the globally ischemic mammalian heart. A role for the ATP-sensitive potassium channel. We investigated the contribution of opening of the ATP-sensitive K+ channel to extracellular accumulation of K+ during ischemia with the use of glibenclamide, a specific blocker of this K+ channel. To characterize the electrophysiological effects of glibenclamide during metabolic inhibition (by either application of dinitrophenol or hypoxia) we performed patch-clamp studies in isolated membrane patches of guinea pig myocytes and in intact guinea pig myocytes and studied action potential parameters in isolated superfused guinea pig papillary muscle. We studied the effect of glibenclamide on extracellular accumulation of K+ and H+ in isolated retrogradely perfused globally ischemic hearts of rat, guinea pig, and rabbit. Experimental evidence is presented that supports the conclusions that glibenclamide 1) effectively blocks open K+ATP channels, 2) reverses the dinitrophenol-induced increase of the outward current and prevents the hypoxia-induced shortening of the action potential, 3) decreases the rate of K+ accumulation during the first minutes of ischemia in stimulated hearts, an effect which was entirely absent in quiescent hearts, and 4) does not influence the rate and extent of ischemia-induced extracellular acidification.
Percutaneous endoscopic gastrostomy and early mortality. To assess morbidity, mortality, and benefit associated with percutaneous endoscopic gastronomy (PEG), we retrospectively studied 42 patients who had had PEG. Mortality was exceptionally high during the first 60 days after PEG (43%), and then stabilized. In nearly half of the cases (20/42) the PEG tube was removed during the first 60 days because of either death or improvement. Patients with malignancy had a significantly higher morbidity and 60-day mortality than the neurologically impaired. We concluded that patients should be carefully selected for PEG because early mortality is high; a 60-day trial of soft nasogastric feedings should be considered before PEG, and could reduce by nearly half the number of patients failing to receive long-term benefit; and patients with malignancy have significantly greater morbidity and mortality after PEG and may not receive the same advantage from the procedure.
Urologic sarcoma in adults. Memorial Sloan-Kettering Cancer Center experience based on a prospective database between 1982 and 1989. Urologic sarcoma is a group of rare tumors with a generally poor prognosis. These sarcomas share prognostic characteristics with soft-tissue sarcomas arising from other sites. A staging system that incorporates tumor grade and size is valuable in identifying patients at high risk of dying of disease. Patients with sarcomas that are high-grade, greater than 5 cm in diameter, or metastatic at the time of presentation (MSKCC stages 3 and 4) have a combined 3-year relapse-free survival rate of 26%. Complete surgical resection, preferably with negative margins, still offers the best chance of cure. For reasons that are not clear, multimodality therapy in rhabdomyosarcoma is less effective in adult than in pediatric disease. Present-day chemotherapeutic regimens are ineffective in controlling disseminated sarcoma. The adoption of a uniform staging system coupled with multi-institutional collaboration may allow progress to be made in this otherwise deadly form of genitourinary cancer.
The relationship between locomotor disability, autonomic dysfunction, and the integrity of the striatal dopaminergic system in patients with multiple system atrophy, pure autonomic failure, and Parkinson's disease, studied with PET. 18F-dopa and S-11C-nomifensine (NMF) are positron emitting tracers whose caudate and putamen uptake reflects striatal dopamine storage capacity and the integrity of dopamine reuptake sites, respectively. Using these two tracers, the integrity of the presynaptic striatal dopaminergic system has been studied with positron emission tomography (PET) in 10 subjects with multiple system atrophy (MSA, Shy-Drager syndrome) who had an akinetic-rigid syndrome that was poorly responsive to L-dopa, autonomic failure, and cerebellar ataxia. PET findings for the 10 MSA patients were compared with those for 13 age-matched controls, 8 subjects with L-dopa responsive Parkinson's disease (PD), and 7 subjects with pure autonomic failure (PAF). Influx constants, Ki, reflecting specific 18F-dopa uptake into striatal tissue, were severely reduced in the putamen and caudate of the 10 MSA subjects (mean putamen Ki 0.005 min-1 MSA vs 0.013 min-1 controls; mean caudate Ki 0.007 min-1 MSA vs 0.013 min-1 controls). Reduction of putamen, but not caudate, 18F-dopa uptake correlated with severity and duration of locomotor disability. Eight patients with PD, and a similar degree and duration of locomotor disability to the patients with MSA, demonstrated equal impairment of mean putamen 18F-dopa uptake, but significant preservation of mean caudate function. The 7 PAF patients had normal mean levels of putamen and caudate 18F-dopa uptake, although 1 individual PAF patient had significantly impaired striatal function. The MSA and PD groups of subjects both showed significantly reduced levels of specific striatal S-11C-NMF binding, again caudate function being relatively preserved in PD. It is concluded that in both MSA and PD there is a parallel decline of striatal dopamine storage capacity and reuptake site integrity, probably reflecting a loss of nigrostriatal nerve terminals. Caudate function is relatively preserved in PD compared with MSA. The majority of PAF patients have an intact nigrostriatal dopaminergic system, suggesting that PAF is a condition distinct from PD and MSA in spite of some pathological similarities. PET is capable of detecting subclinical nigrostriatal involvement in PAF patients when this is present.
Muscle regeneration following segmental necrosis in tenotomized muscle fibers. The aim of this study was to determine how the new myotendinous junctions were re-established at the proximal and distal ends of the soleus muscle after tenotomy. Both proximal and distal tendons of the soleus muscle in mature female rats were severed. The animals were killed and the soleus muscles were removed and prepared for light and electron microscopic examination 1, 3, 5, 7, 14, 21, 28, and 42 days after the operation. It was found that segmental fiber destruction followed by removal by macrophages occurred at the ends of the soleus muscle fibers. This resulted in the liberation and myogenic activation of satellite cells. By 3 days after tenotomy the fusion of myoblasts to form myotubes could be seen. The myotubes developed within the original basal lamina and reattached to the surviving non-necrotic segments and grew in both length and width so that by 6 weeks postoperation, normal myotendinous junctions had been reformed. This study is the first to show that re-establishment of the myotendinous junction following tenotomy is accomplished by regeneration of the necrotic ends of the tenotomized fibers.
Composition of atherosclerotic plaques in coronary arteries in women less than 40 years of age with fatal coronary artery disease and implications for plaque reversibility. This study analyzes the composition of atherosclerotic plaques in the 4 major epicardial coronary arteries in 8 women less than 40 years of age (mean 34) with fatal coronary artery disease (CAD) and compares these data to previous studies of 37 adults greater than 45 years of age (mean 59) with fatal CAD. Histologic sections were taken at 5-mm intervals from the entire lengths of the right, left main, left anterior descending and left circumflex coronary arteries. With the use of a computerized morphometry system, analysis of the 4 major epicardial coronary arteries showed the major component of plaque to be a combination of cellular (mean percent total plaque area = 65%, standard error = 6%) and dense (19%, standard error = 6%) fibrous tissue. Arterial segments narrowed greater than 75% in cross-sectional area from these young women were compared with similarly narrowed arteries from 37 older patients (32 men [86%]) with fatal CAD previously reported by this laboratory, and showed significantly more cellular fibrous tissue and lipid-rich foam cells, and lesser amounts of dense fibrous and heavily calcified tissue. The large amount of lipid-containing foam cells and relative lack of acellular scar tissue in coronary plaques in these young women suggests a greater potential for reversibility of these plaques in this subset of patients with CAD.
Orbit-related variation in spatial resolution as a source of artifactual defects in thallium-201 SPECT The cause of 180-degree diametrical artifactual defects in clinical thallium-201 SPECT imaging was investigated using phantom simulation. This artifact was observed on SPECT images acquired with a "body contour" or "peanut" orbit. It was hypothesized that this artifact was caused by differences in spatial resolution that occur when the heart-to-detector distance changes employing noncircular orbits. To test this hypothesis, a series of planar static images of a normal cylindrical phantom was obtained at varying distances from the camera detector head. From these images, tomographic acquisition files were created that simulated tomographic data acquired with circular orbits and elliptical orbits. The reconstructed phantom short-axis slices showed no artifacts for circular orbits. However, for various elliptical orbits, significant regional nonuniformity, similar to the artifacts noted in patients, was observed. The degree of nonuniformity correlated with the long-short axis ratio of elliptical orbits (r = 0.98). In addition, circular orbits with the phantom in an eccentric position resulted in similar nonuniformities. It is concluded that a noncircular tomographic orbit can create characteristic artifacts on thallium-201 SPECT images. For rotational thallium 201 SPECT, a circular orbit with the heart in the center of rotation should be employed.
Bowel obstruction: evaluation with CT Eighty-four computed tomographic (CT) scans from patients referred for bowel obstruction between January 2, 1988, and December 31, 1989, were retrospectively evaluated. A pair of radiologists without knowledge of patient histories determined the presence or absence of bowel obstruction. Sixty-four patients ultimately proved to have intestinal obstruction, and 20 did not. Diagnosis was established by means of surgery (n = 39), barium studies (n = 17), and clinical course (n = 28). Causes of obstruction included adhesions (n = 37), metastases (n = 6), primary tumor (n = 7), Crohn disease (n = 4), hernia (n = 3), hematoma (n = 2), colonic diverticulitis (n = 2), and other (n = 3). In addition, 83 CT examinations in patients with no history or indication of intestinal obstruction were simultaneously reviewed. The overall sensitivity was 94%, specificity was 96%, and accuracy was 95%. The cause of obstruction was correctly predicted in 47 of 64 cases (73%). Intestinal obstruction was not diagnosed in any of the 83 control patients. CT is most useful in patients with a history of abdominal malignancy and in patients who have not been operated on and who have signs of infection, bowel infarction, or a palpable abdominal mass.
Thermochemotherapy in inoperable head and neck cancer. A combined hyperthermia and chemotherapy approach was used to treat five patients with locally advanced or recurrent squamous cell carcinoma of the head and neck whose tumors had failed to respond to chemotherapy. In two patients, tumor had recurred after initial combined modality therapy (surgery/radiation) and had failed to respond to one course of cisplatin/5-fluorouracil (cisplatin/5-FU) chemotherapy. The three remaining patients were enrolled onto a phase II evaluation of induction chemotherapy with cisplatin/fluorouracil for advanced head and neck carcinomas and had failed to achieve a partial remission after one treatment cycle. Palpable cervical tumors were heated to 40 degrees to 42 degrees C for 30 to 40 minutes, during which time cisplatin (100 mg/m2) was infused intravenously. A 5-day infusion of 5-fluorouracil (1000 mg/m2/d) followed. Despite less than a partial response to previous cisplatin/fluorouracil chemotherapy alone, two patients had complete clinical resolution of the heated tumor volume with two cycles of the combined thermochemotherapy approach. One patient achieved a partial remission with this approach. The remaining two patients died shortly after the initial thermochemotherapy treatment, as a result of progressive tumor growth. The two complete responders were subsequently treated with radiation (1 patient) and radical neck dissection (1 patient) and remained without evidence of disease 2 and 26 months after the completion of therapy, respectively. The toxicity of this combined modality approach was acceptable and appeared to be no greater than had been experienced during earlier treatment with chemotherapy alone. Further studies using a combination of these treatment modalities for locally advanced head and neck carcinomas are warranted.
Cytomegalovirus infection in Gambian mothers and their babies. A 15 month longitudinal study of cytomegalovirus (CMV) infection in 178 Gambian mothers and their babies was undertaken. Twenty five (14%) of the babies were congenitally infected despite the fact that 87% of their mothers were antibody positive to the virus. Two of the 25 congenitally infected infants had evidence of severe neurological damage; skin sepsis was also a prominent feature in congenitally infected infants. The other children soon became infected. At 6 months of age, 53% of the infants were shedding virus either in urine or saliva. By the age of 12 months 86% of the infants had serological evidence of CMV infection. Preliminary evidence suggests that sibling to sibling infection in crowded compounds might be a major route of transmission.