123rc/medical_text huggingface dataset:
Nonmucous glycoproteins as pronucleating agents. Cholesterol crystallization-promoting factors probably play an important role in the pathogenesis of gallstone disease. We have isolated one of the factors involved by using lectin-affinity chromatography. A potent promoting activity binds to concanavalin A-Sepharose. The activity is heat labile and sensitive to digestion by glycosidase but remarkably insensitive to proteases. The concanavalin A-binding pronucleator affects cholesterol solubilization in model bile in two ways. It induces a shift of cholesterol and phospholipid from the micellar to the vesicular phase but also interacts directly with cholesterol-phospholipid vesicles. The concanavalin A-binding protein fraction contains at least two different promoting factors with gel permeation molecular weights of about 150 kD and 5 kD, respectively. The higher molecular weight activity could be assigned to a protein with an apparent molecular weight of 130 kD. Concanavalin A-binding-promoting activity was present in bile from both patients with and without stones, indicating that it is a normal constituent of bile. However, the activity was strongly increased in bile from patients with multiple cholesterol gallstones, suggesting that it could play a key role in gallstone formation in these patients.
Effect of omeprazole and high doses of ranitidine on gastric acidity and gastroesophageal reflux in patients with moderate-severe esophagitis Thirty to fifty percent of patients with reflux esophagitis fail to heal after treatment with conventional doses of H2-receptor antagonists, whereas omeprazole administration induces more than 90% healing. To investigate the effect of omeprazole and higher-than-presently-recommended doses of H2-blockers, we evaluated gastric acidity and gastroesophageal reflux in 17 patients with severe-moderate esophagitis before and after treatment with 300 mg ranitidine twice daily or 20 mg omeprazole once daily. Three pH-metric studies were performed, in a cross-over design, before and after 8 days of treatment with omeprazole or ranitidine. Both drugs significantly reduced intragastric acidity (p less than 0.001) during both night and day hours. Median hourly 24-h intragastric pH was 1.8 in the basal study, 2.9 after ranitidine, and 3.4 after omeprazole. Intragastric acidity fell from 84.0 mmol/L in the basal study to 14.2 mmol/L (79% inhibition) with ranitidine and 9.3 mmol/L (84% inhibition) with omeprazole. Patients with esophagitis were significantly more exposed to acid than healthy subjects, in both the supine and upright position (p less than 0.01). The time with esophageal pH less than 4 dropped from 23.9% in the basal study to 8.5% with ranitidine and to 7.2% with omeprazole (p less than 0.001). Both drugs significantly reduced esophageal exposure to acid in both the supine and upright positions (p less than 0.001), whereas neither had any effect on esophageal acid clearance.
Hypoxia-induced in vivo sickling of transgenic mouse red cells. To develop an animal model for sickle cell anemia, we have created transgenic mice that express a severe naturally occurring human sickling hemoglobin, Hb S Antilles. Due to its low solubility and oxygen affinity, Hb S Antilles has a greater propensity to cause red cell sickling than Hb S. To make transgenic animals that express a high level of Hb S Antilles, the erythroid-specific DNAse I hypersensitive site II from the human beta-globin cluster was linked independently to the human alpha 2-globin gene and to the beta S Antilles gene. Embryos were injected with both constructs simultaneously and seven transgenic mice were obtained, three of which contained both the human alpha and the human beta S Antilles transgene. After crossing the human transgenes into the mouse beta-thalassemic background a transgenic mouse line was derived in which approximately half the beta-globin chains in the murine red cells were human beta S Antilles. Deoxygenation of the transgenic red cells in vitro resulted in extensive sickling. An increase of in vivo sickling was achieved by placing these transgenic mice in a low oxygen environment. This murine model for red cell sickling should help to advance our understanding of sickle cell disease and may provide a model to test therapeutic interventions.
Coronary sinus occlusion: effect on ischemic left ventricular dysfunction and reactive hyperemia. Pressure-controlled intermittent coronary sinus occlusion (PICSO) has been shown to reduce experimental infarct size. To examine the role of PICSO in limiting the consequences of brief ischemia on left ventricular function, we studied the effect of PICSO in nine open-chest anesthetized dogs. PICSO was performed using a pump-inflated, balloon-tipped catheter in the coronary sinus until coronary sinus occlusion pressure reached a plateau (10 +/- 3 seconds). The balloon was then rapidly deflated (2 seconds) and the cycle was repeated. Regional left ventricular function in the ischemic zone was assessed by sonomicrometry. Coronary blood flow was measured with a flow probe around the left anterior descending artery (LAD) proximal to an occluding suture. Measurements were obtained at baseline, during a 3-minute LAD occlusion, and for 10 minutes of reperfusion. In an additional five dogs, this sequence was repeated during an infusion of adenosine at a dose that abolished reactive hyperemia following LAD occlusion. The addition of PICSO beginning 15 minutes prior to ischemia and continuing throughout LAD occlusion and reperfusion did not prevent, reduce, or shorten ischemic left ventricular dysfunction. PICSO uniformly blunted reactive hyperemia during reperfusion. However, PICSO also reduced coronary blood flow during maximal vasodilatation achieved by adenosine infusion prior to LAD occlusion. Therefore, it is likely that PICSO decreases reactive hyperemia due to mechanical factors arising from venous engorgement rather than by reducing the ischemic stimulus causing vasodilation.
Fascinating rhythm: a primer on chaos theory and its application to cardiology. Nonlinear dynamics is an exciting new way of looking at peculiarities that in the past have been ignored or explained away. We have attempted to give a general introduction to the basics of the mathematics, applications to cardiology, and a brief review of the new tools needed to use the concepts of nonlinear mathematics. The careful mathematical approach to problems in cardiac electrical dynamics and blood flow is opening a window on behaviors and mechanisms previously inaccessible.
The classification and diagnosis of headache disorders. Headache disorders recently have been reclassified, and new operational diagnostic criteria assist in making the correct diagnosis. These diagnostic criteria have been accepted worldwide.
Cardiovascular responses to arm cranking and FNS-induced leg exercise in paraplegics. Twelve spinal cord-injured males performed arm-crank exercise (ACE) with and without concurrent functional neuromuscular stimulation (FNS) of paralyzed leg muscles to investigate the hypothesis that FNS would augment cardiovascular performance during submaximal ACE. Six men who exhibited vigorous isometric contractions of thigh and calf muscles were classed as "responders" to FNS (R), and the remaining subjects with poor or nonexistent contractions served as "nonresponder controls" (C). Steady-state heart rate and oxygen uptake during ACE at 30, 60, and 90 W were not appreciably different from the ACE + FNS condition. However, cardiac outputs in R were augmented by 30% during FNS at rest (from 4.9 to 6.4 l/min), by 18% during 30-W ACE + FNS (from 8.6 to 10.1 l/min), and by 28% during 90-W ACE + FNS (from 12.1 to 15.6 l/min). Similarly, resting stroke volumes were increased by 18% (9 ml) and by 23% (19 ml) at 60 W during FNS in the R group. Calculated total peripheral resistance was reduced at rest and during 90-W ACE + FNS by approximately 24%. In contrast, no alterations of circulatory hemodynamics were observed for C subjects. These data indicate that FNS-induced contractions of paralyzed leg muscles augment venous return to aid central cardiovascular control during upper-body submaximal exercise in paraplegics.
Ototoxicity of cis-platinum and its relationship to eye colour. The following hypothesis is presented: that the susceptibility of an individual patient to hearing loss as a result of cis-platinum administration can be predicted on the basis of eye colour. The rationale is that the melanin content of the inner ears is related to that of the eyes; dark eyes contain more melanin than light-coloured eyes; and melanin causes the accumulation of the ototoxic drug within the inner ear. Hence those with dark eyes will suffer greater damage to the hearing than those with pale eyes. An investigation that confirmed this hypothesis is reported. In addition to cochlear damage there is a significant likelihood of damage to the auditory nerve as a result of the treatment.
Morphological and biochemical changes in gastric mucosa of aging rats. Although previous data from this laboratory have indicated that aging is associated with increased gastric mucosal proliferative activity, no direct assessment of proliferative potential of the tissue has been made during aging. In order to assess this, and to determine whether changes in mucosal proliferative potential would be reflected in growth of the tissue, we have examined the labeling index (LI), height and morphology of the gastric mucosa in young (4-month-old) and aged (24-month-old) Fischer-344 rats. In addition, tyrosine kinase (Tyr-k) activity and the levels of phosphotyrosine proteins were determined to evaluate their relationship to mucosal proliferative activity. Histologic evaluation revealed a marked atrophy of the mucosal glandular component with 32% reduction in height in aged rats when compared with young animals. In aged rats, there was also a decrease in gland density, resulting in a reduction in the number of epithelial cells of all types with evidence of decreased secretory activity. Despite the occurrence of mucosal atrophy in aged rats, LI in these animals was significantly increased by 28%. This was associated with a parallel rise in mucosal Tyr-k activity, and a two- to threefold increase in the relative concentrations of seven phosphotyrosine membrane proteins with Mr of 120, 105, 90, 60, 55, 48 and 32 kDa. We conclude that (1) although aging is associated with increased gastric mucosal proliferative activity, this does not result in mucosal growth and that (2) Tyr-k and tyrosine phosphorylation of certain proteins play a role in the regulation of gastric mucosal cell proliferation during aging.
Thermal balance and tremor patterns during epidural anesthesia. Five healthy, nonpregnant volunteers were studied before and after induction of lumbar epidural anesthesia to determine the cause of central hypothermia during epidural anesthesia. Cutaneous heat loss was measured from 10 area-weighted sites using thermal flux transducers. Oxygen consumption was measured and converted to heat production in watts (W). After a 2-h control period at approximately 20 degrees C, epidural anesthesia was induced by injection of 30-50 ml 3% chloroprocaine. Additional boluses were given to extend the sensory blockade to at least the T5 dermatome. Tremor during epidural anesthesia was compared with normal shivering induced by rapid central venous infusion of approximately 4 l iced saline in six unanesthetized volunteers. Average skin temperature and cutaneous heat loss decreased during the control period, while tympanic membrane temperature remained stable. During the 1st h of epidural blockade, tympanic membrane temperature decreased 1.1 +/- 0.3 degrees C, and average skin temperature increased 0.9 +/- 0.5 degrees C. Cutaneous heat loss increased 16 +/- 6% (15 +/- 5 W), but metabolic heat production increased even more (and was associated with a shivering-like tremor). Tremor during epidural anesthesia and shivering induced by iced saline infusion had similar synchronous waxing-and-waning patterns. No abnormal EMG patterns were detected during epidural anesthesia. We conclude that central hypothermia during the 1st h of epidural anesthesia does not result from heat loss to the environment in excess of metabolic heat production, but results primarily from redistribution of body heat from central to peripheral tissues. Analysis of the tremor patterns suggests that oscillations recorded during epidural anesthesia in nonpregnant individuals is normal thermoregulatory shivering. Shivering occurred sooner and was more intense during iced saline infusion than during epidural anesthesia, despite comparable central hypothermia. The low intensity of shivering during epidural anesthesia, and in some individuals the delay in onset, may result from blockade of afferent cutaneous cold signals.
Association of Helicobacter pylori infection with dyspeptic symptoms in patients undergoing gastroduodenoscopy. PURPOSE: To determine the prevalence of Helicobacter pylori in patients with non-ulcer dyspepsia and ulcer disease as well as in a control population undergoing endoscopic retrograde cholangiopancreatography (ERCP) for suspected pancreatic or biliary disease. PATIENTS AND METHODS: Forty-six eligible patients undergoing upper endoscopy at Massachusetts General Hospital were studied over a period of 18 months, as well as 24 patients undergoing ERCP for presumed pancreatic or biliary disease. Two biopsy specimens from the fundus and two from the antrum were taken for microbiologic and histopathologic analysis. Sera were examined by enzyme-linked immunoabsorbent assay. All specimens were processed in a blind fashion. Chi-square test with Yates' correction was used for statistical analysis. RESULTS: H. pylori was found in 31 of 46 (67%) study patients and in six of 24 (25%) control patients (by microbiologic or histologic techniques) (p less than 0.01). H. pylori was found in all patients with peptic ulcer disease and in 60% of patients without ulcers. No association between H. pylori and any specific gastrointestinal symptom was observed. H. pylori was identified in the fundus as often as in the antrum, although in the antrum the organism was more often associated with histologic gastritis. Compared with histology, serologic assays for IgG and IgA antibodies to H. pylori had sensitivities of 100% and 94%, and specificities of 86% and 76%, respectively. Reexamination of selected specimens without knowledge of their identity revealed that the specificity of serology exceeded 94% while the sensitivity of histologic and microbiologic studies may have been closer to 80%. CONCLUSIONS: H. pylori was more common in dyspeptic patients than in our control subjects undergoing ERCP. Multiple biopsy sites from fundus and antrum are required to exclude infection. Serologies of IgG and IgA were sensitive and specific for H. pylori, suggesting a possible role for non-endoscopic diagnosis of this infection. The frequent association of H. pylori with active inflammation rather than with quiescent gastritis is consistent with a pathologic role of this organism.
Lymph node metastasis from papillary-follicular thyroid carcinoma in young patients. A total of 117 patients under 20 years of age with papillary and/or follicular thyroid cancer presented to the M. D. Anderson Cancer Center between 1949 and 1987. The most common presenting symptom was a cervical mass. Twenty percent of the patients had a history of prior irradiation. Sixty percent initially had palpable lymph nodes, while 26% who had clinically negative examinations had pathologically positive lymph nodes. Recurrence was highest in regional lymph nodes at 24%, with only a 4% recurrence rate at the primary site and a 3% recurrence rate at distant sites. There were no deaths due to the thyroid cancer. To maintain a low rate of recurrence, near-total thyroidectomy with neck dissection followed by iodine 131 treatment should be considered in these young patients.
Systolic hypertension in the elderly: reasons not to treat. Isolated systolic hypertension in the elderly is associated with increased morbidity and mortality. Accurate measurement of blood pressure in older patients is difficult. Therapy can be associated with various complications, and the special problems of the elderly, such as orthostatic hypotension and hyperkalemia, should be carefully considered. Drugs should be used in low doses and changes in dosage should be made infrequently. Patients should be monitored frequently for untoward effects of therapy. The benefits of blood pressure reduction and the optimal degree of blood pressure reduction remain unknown.
Proliferation and substrate effects on endothelial cell thrombogenicity. The effects of the cellular differentiation status and the adhesive-substrate on endothelial cell function in cell culture were measured with an enzyme based assay of surface thrombogenicity. A solid plastic, microporous polymeric, and fibronectin (FN) treated microporous polymeric were used as substrates for growth of endothelial cells. The microporous and FN treated synthetic substrates have been shown to aid in the induction of cellular differentiation mechanisms. Cells were studied under proliferative and nonproliferative growth conditions. The thrombogenicity of the surface created by the endothelial cell monolayers under various experimental conditions was determined using an enzyme based assay of fibrin deposition. Actively proliferating cells on the solid plastic substrate produced the most thrombogenic surface, while confluent endothelial cell monolayers grown on FN treated microporous substrate were the least thrombogenic surfaces. These data suggest that endothelial cell surface thrombogenicity is under substrate control, and also related to the cellular differentiation status. These findings are being used to design a novel approach to the small diameter synthetic vascular graft problem.
Diagnostic significance of flow separation within the carotid bifurcation demonstrated by digital subtraction angiography. The presence of an area of reversed blood flow due to flow separation in the interval carotid artery is a normal finding in Doppler ultrasound studies in vivo as well as in model carotid bifurcations. This flow separation phenomenon is caused by the geometry of the carotid bifurcation and the fluid dynamics of blood. We demonstrated the flow separation phenomenon on lateral-projection intra-arterial digital subtraction angiograms in 99 of 100 carotid bifurcations. The mean duration of flow separation was 5.8 seconds, with values up to 14 seconds in normal carotid bifurcations. The presence of this flow separation phenomenon is almost independent of atherosclerotic lesions and is not correlated with cerebral ischemia. Therefore, the angiographic finding of a flow separation has no diagnostic value. However, our results refer to a factor that may be important in the genesis of atherosclerosis at the carotid bifurcation, namely the duration of the stay of blood and its components within the area of flow separation.
Patterns of dyspepsia in patients with no clinical evidence of organic diseases. We studied 2000 dyspeptic patients with no obvious signs of organic disease at their first examination, in order to (1) verify how many diagnoses of idiopathic dyspepsia had really been made after exhaustive diagnostic procedures and (2) evaluate the diagnostic power of the symptoms in distinguishing organic from idiopathic dyspepsia. This latter was considered only when no structural abnormalities were found. In all the other cases, a distinction was made between "related" and "associated" organic dyspepsia according to whether or not there was a certain relationship between the abnormalities and the dyspeptic symptoms. The patients were referred to us as follows: (1) spontaneously, (2) sent by physicians collaborating with us, (3) referred to our open access endoscopic service. The results show the frequency of idiopathic dyspepsia was 26%, whereas associated structural abnormalities were present in 45.4%. Obvious organic causes of dyspepsia were seen in 28.6% (24% benign and 4.6% malignant diseases). When considered separately, no symptom alone allows a correct diagnosis. The simultaneous evaluation of the symptoms with linear discriminant analysis distinguishes between idiopathic and organic dyspeptic patients in about 70% of the cases. A higher discrimination percentage in about 70% of the cases. A higher discrimination percentage could probably be obtained using a wider range of clinical parameters and/or a more complex statistical analysis of the interrelationships which exist between the clinical symptoms and the final diagnosis.
Drug therapy for ventricular tachyarrhythmias: how many electropharmacologic trials are appropriate? To determine how many electropharmacologic drug trials should be performed to select therapy for patients with ventricular tachyarrhythmias, the outcome of 150 consecutive patients with inducible ventricular tachyarrhythmias undergoing serial electropharmacologic testing was examined. The probability of identifying predicted effective therapy (inductive of fewer than five ventricular responses with three ventricular extrastimuli at three pacing cycle lengths) and the probability of that therapy preventing sustained ventricular tachyarrhythmia recurrences were determined as a function of the number of preceding trials. The probability ( +/- SE) of identifying predicted effective therapy by the first trial (0.23 +/- 0.03) was significantly higher than that of the second (0.09 +/- 0.04), third (0.08 +/- 0.04) and fourth (0.05 +/- 0.04) trials (p = 0.001). No patient had predicted effective therapy identified by subsequent trials. The 2 year actuarial probability of freedom from sustained ventricular tachyarrhythmias on predicted effective therapy was higher for the first (0.79 +/- 0.08), second (0.73 +/- 0.13) and third (0.86 +/- 0.13) trials than for the fourth (0.33 +/- 0.27) trial (p = 0.02). Thus, the probability of selecting therapy with long-term efficacy was highest for the first trial (0.18), intermediate for the second (0.07) and third (0.07) trials and lowest for the fourth (0.02) and subsequent (0.00) trials. Accordingly, the electropharmacologic approach to therapy selection should be abandoned after three unsuccessful trials.
Seizures and other neurologic sequelae of bacterial meningitis in children. BACKGROUND. Although the mortality rate among children with bacterial meningitis has decreased dramatically in recent decades, some patients are left with neurologic sequelae. It has not been clearly established which features of the acute illness predict the chronic neurologic sequelae, including late seizures or epilepsy. METHODS. We followed 185 infants and children prospectively during and after acute bacterial meningitis. The mean duration of follow-up was 8.9 years (range, 0.1 to 15.5). During the first six years standard neurologic examinations were performed; telephone interviews were conducted thereafter. RESULTS. One month after meningitis, 69 children (37 percent) had neurologic abnormalities. Many of these signs resolved within a year, leaving only 26 children (14 percent) with persistent deficits: 18 (10 percent) had only sensorineural hearing loss, and 8 (4 percent) had multiple neurologic deficits. Thirteen children (7 percent) had one or more late seizures not associated with fever. The presence of persistent neurologic deficits indicative of cerebral injury was the only independent predictor of late afebrile seizures (P less than 0.001). CONCLUSIONS. After bacterial meningitis only children with permanent neurologic deficits are at high risk for epilepsy. Those with normal examinations after the acute illness have an excellent change of escaping serious neurologic sequelae, including epilepsy.