123rc/medical_text huggingface dataset:
Continuous infusion carboplatin on a 21-day schedule: a phase I and pharmacokinetic study. A phase I study with continuous infusion carboplatin for 21 days every 6 weeks using a venous access port and portable pump was performed over a dose range of 12 to 32 mg/m2/d, with increments of 2 mg/m2/d. Forty-four patients received 107 courses (median, two; range, one to nine). World Health Organization (WHO) grade III/IV leukopenia and thrombocytopenia occurred in one of seven patients at 30 mg/m2/d, and in two of six and four of six patients at 32 mg/m2/d. Cumulative platelet depression was found at dose levels of 28 mg/m2/d or more. Median glomerular filtration rate (GFR) and effective renal plasma flow, monitored by radioisotope clearances at doses greater than or equal to 20 mg/m2/d, decreased 8.2% (P less than .05) and 10.9% (P less than .01) after two courses. There was a relationship (r = .50, P less than .0002) between the percentage of platelet depression and GFR. No other toxicity was observed. Of the 17 patients who were evaluable, one complete response and four partial responses were observed. In addition, six patients had stable disease. Pharmacokinetic analysis of total and ultrafiltrable platinum (UFPt) was performed by atomic absorption spectrophotometry. Steady-state plasma levels for UFPt were reached after 8 hours. These levels could be detected from the 20 mg/m2/d dose. During steady state, carboplatin dose and UFPt plasma levels were not correlated, but steady-state UFPt and GFR (r = -.27, P less than .05) were. Twenty-four percent of total platinum (Pt) was present as UFPt during steady state (x = 160 +/- 10 micrograms/L). Total body clearance of UFPt exceeded GFR 2.2 times. Mean area under the curve (AUC) for UFPt during continuous infusion was 4,921.8 +/- 301.72 mg.min/L. For total Pt, steady-state plasma levels were not reached; total Pt plasma levels increased between day 7 and day 21 (P less than .0001). There was a significant relation between total Pt serum levels day 7, 14, and 21 and the drug dose administered. Immunohistochemical analysis of DNA-bound Pt in leukocytes showed a linear increase from day 7 to day 14 to day 21 (r = .97) between DNA-bound Pt and duration of infusion in individual patients. The maximum-tolerable dose of carboplatin is 30 mg/m2/d for 21 days (total dose 630 mg/m2) and is recommended for phase II studies.
Involvement of sodium in the protective effect of 5-(N,N-dimethyl)-amiloride on ischemia-reperfusion injury in isolated rat ventricular wall. During reperfusion in the isolated right ventricular wall of the rat after 60 min of ischemia, developed tension and resting tension were 35 +/- 4 and 221 +/- 12%, respectively, of preischemic values. Including 35 microM ouabain in the perfusate before and after ischemia resulted in more severe cardiac dysfunction during reperfusion than in drug-untreated hearts. Introduction of the Na(+)-H+ exchange inhibitor, 5-(N,N-dimethyl)-amiloride (DMA), could effectively protect the right ventricular wall against ischemia-reperfusion dysfunction in the presence or absence of ouabain. The ion content in the right ventricular wall was measured with atomic absorbance spectrophotometry. Before ischemia, Na+,Ca++ and K+ content were 53.4 +/- 6.4, 2.70 +/- 0.22 and 262 +/- 7.7 mumol/g of dry weight tissue, respectively. After 60 min of ischemia and 6 min of reperfusion, Na+,Ca++ and K+ content were 73.4 +/- 7.2, 3.79 +/- 0.31 and 180 +/- 15 mumol/g of dry weight tissue, respectively (P less than .05). Introduction of 20 microM DMA normalized ion content in the muscles which was consistent with the contractile function recovery during reperfusion. The data suggest that a rise in intracellular Na+ in the early stage of reperfusion represents a crucial or primary step for the development of cardiac contractile dysfunction. DMA, which protects against severe reperfusion-induced cardiac contractile dysfunction, appears to act via a normalization of tissue sodium levels. This action is consistent with its proposed role as a blocker of transsarcolemmal Na(+)-H+ exchange.
Increased uptake of bromodeoxyuridine by hepatocytes from early stage of primary biliary cirrhosis. The relationship between DNA synthesis activities of hepatocytes in biopsied specimens and liver volume was studied in various stages of primary biliary cirrhosis using an in vitro bromodeoxyuridine (a thymidine analogue)-anti-bromodeoxyuridine reaction and computed tomography. The mean bromodeoxyuridine (+/- SE) labeling index for 10 patients in an early histological stage (stage I, 4, and stage II, 6, 3.4% +/- 0.4%) of primary biliary cirrhosis was 17 times that for 6 control subjects (0.2% +/- 0.1%, P less than 0.001), and was significantly higher than that for 19 female patients with chronic aggressive hepatitis (0.9% +/- 0.2%, P less than 0.001), 14 compensated cirrhotic patients of viral origin (all female, 1.1% +/- 0.3%, P less than 0.01), and 5 patients with stage III primary biliary cirrhosis (0.5% +/- 0.1%, P less than 0.001). The mean (+/- SE) liver volume in the early stage of primary biliary cirrhosis (1225 +/- 40 cm3) was about 1.5 times that in control subjects (835 +/- 42 cm3, P less than 0.001). These results suggest that liver volume has already become large in the early stage of primary biliary cirrhosis perhaps because of markedly increased DNA synthesis in hepatocytes.
Expression and characterization of TCA3: a murine inflammatory protein. TCA3 is a cDNA originally isolated from activated T cells. Transcription of this gene has been shown to correlate with Ag-induced cellular activation of both T cells and mast cells. Based on the predicted amino acid sequence encoded by the cDNA, we previously proposed that TCA3 represents a cytokine. In this report we have used rDNA technology to express TCA3 in two mammalian cell lines. In both cases, TCA3 was expressed as a secreted molecule with an apparent molecular mass of 16 kDa. Digestion of the (rTCA3) with the enzyme N-glycanase revealed that approximately 8 kDa is caused by N-linked glycosylation. Intradermal injection of rTCA3 into mouse footpads resulted in a rapid swelling response. The sites of injection were characterized histologically by a local accumulation of neutrophils. These findings are discussed with particular attention to a family of related proteins, some of whose members also have inflammatory properties.
Induction, blockade and restoration of a persistent hypersensitive state. A new model of chronic hypersensitivity was developed in the rat by daily intraplantar administration of either prostaglandin E2 dopamine or isoprenaline, for a period of 2 weeks. Like other hyperalgesic mediators, dibutyryl-cAMP, when applied to the paws, caused an acute effect but did not produce persistent hypersensitivity. The persistent hypersensitive state was not affected by a typical non-steroidal anti-inflammatory drug (indomethacin), was temporarily inhibited by a centrally acting analgesic (morphine), was partially inhibited by a protein synthesis inhibitor (cycloheximide) and abolished by a single dose of peripherally acting analgesics such as dipyrone or N-methyl morphine. Once the residual hypersensitivity had been abolished with dipyrone or N-methyl morphine, a small dose of prostaglandin E2, dopamine or Interleukin-1 beta, which in normal animals causes a mild and short lived effect, restored the persistent hypersensitive state. This ability to restore the persistent effect was not observed with intraplantar administration of dibutyryl-cAMP. Our results suggest the existence of a peripheral trace of inflammatory pain, a phenomenon which may be associated with stimulation of neuronal adenylate cyclase and protein synthesis. This concept may explain part of the puzzle of chronic inflammatory pain and lead to the development of new analgesics.
Syncope of unknown origin: clinical, noninvasive, and electrophysiologic determinants of arrhythmia induction and symptom recurrence during long-term follow-up. Ninety-one consecutive patients with syncope of unknown origin underwent electrophysiologic studies (EPS). Univariate analysis identified the following variables: age, + signal-averaged ECG (SAECG), left ventricular ejection fraction (LVEF), history of myocardial infarction, coronary artery disease, left ventricular aneurysm, and history of sustained monomorphic ventricular tachycardia (SMVT) on Holter; multivariate analysis identified +SAECG, LVEF, and history of SMVT as risk factors for induction of SMVT at EPS. All patients were followed up for 19.0 +/- 8.3 months and 17 had recurrence of syncope. Patients were divided into empiric, EP-guided, and no therapy groups. The EP-guided therapy group included all patients with SMVT at EPS. Recurrence rates among all three groups were similar. We conclude that: (1) Patients who have inducible SMVT at EPS can be identified using certain clinical and noninvasive variables. When these patients undergo EP-guided therapy, their rate of recurrence of syncope becomes compatible with that of patients who had no arrhythmia induced at EPS. (2) Empiric therapy does not offer any benefit over no therapy in reducing the rate of recurrent of scope.
Hippocampal sclerosis in temporal lobe epilepsy demonstrated by magnetic resonance imaging. The value of magnetic resonance imaging in the detection of hippocampal sclerosis has been controversial. We studied 10 patients aged 22.5 +/- 6.0 years with intractable temporal lobe epilepsy selected because of a history of a prolonged childhood convulsion, which is characteristic of a group of patients in whom hippocampal sclerosis is a constant finding. All 10 patients showed reduction in size of one hippocampus associated with increased signal intensity on T2-weighted magnetic resonance images. These changes were reliably detected on coronal spin-echo images, perpendicular to the long axis of the hippocampus. Appreciation of the normal imaging anatomy of the hippocampus allowed correct interpretation of the relative changes in signal intensities of the hippocampus and adjacent temporal horn on sequential echo images. The side of the abnormal hippocampus on magnetic resonance imaging accorded with the electroencephalographic localization in all 10 patients, and with the lateralization of the early convulsions in all 6 patients where this was known. Temporal lobectomy was performed in all 10 patients. Hippocampal sclerosis was confirmed in the 3 patients in whom hippocampal tissue was available for histological examination. The value of this technique was reinforced by the excellent postoperative results, with 80% being seizure free at a mean follow-up time of 33 +/- 4 months.
Liver tumor imaging. Liver tumor imaging is the paradigm of the dilemma of diagnostic decision-making in the current era of abundant high technology. In part, this is a reflection of the multiplicity of imaging techniques now in wide use worldwide. These include ultrasound (US), radionuclide scintigraphy (RNS), computed tomography (CT), magnetic resonance imaging (MRI), and techniques especially designed for staging the extent of known liver cancer, such as computed tomography during arterial portography (CTAP) and intraoperative ultrasound (IOUS). Most authorities concede that CT scanning is the single test most closely fitting the designation "gold standard" for liver tumor imaging, although MRI, a less mature technique, is already preferred by some. Local factors profoundly influence the selection and sequence of imaging studies, including available equipment, radiologic skills, institutional interests, and especially the specific clinical circumstances of the patient. Thus, diagnostic algorithms or decision trees for sequential imaging workup of liver tumor suspects tend to be somewhat institution specific.
Carbamazepine maintenance treatment in outpatient schizophrenics. A double-blind crossover trial was used to evaluate carbamazepine as the sole maintenance treatment of chronic, nonmanic schizophrenic outpatients whose conditions had been stabilized with the use of neuroleptics prior to study. Criteria of treatment effectiveness included the number of patients relapsing and time to relapse over a 95-day neuroleptic-free period during which either carbamazepine or placebo was administered. Relapse was determined by the concordance of psychiatric ratings and independent clinical judgements indicating significant worsening. Results for 27 patients (13 receiving carbamazepine and 14 receiving placebo) involved in the first phase of this treatment comparison were nondifferentiating. Corroborating descriptive findings in the second phase were available for 14 of these patients. There was no evidence supporting the existence of a treatment-relevant subgroup defined by episodic dyscontrol phenomena.
Which cardiac disturbances should be treated with digoxin immune Fab (ovine) antibody? Digoxin excess can produce characteristic bradyarrhythmias, tachyarrhythmias, and hyperkalemia. The bradyarrhythmias, which consist of disturbances in conduction and block at the level of the atrioventricular and sinus nodes, are mediated by a direct and vagotonic effect. The vagotonic effect of excess digoxin may also result in a marked slowing of the sinus rate in the setting of severe toxicity. Digoxin increases automatic and triggered electrical activity in atrial muscle, His-Purkinje system, and ventricular muscle, which predisposes to tachycardias. Many of the tachyarrhythmias are relatively specific for the toxic effects of digoxin. Atrial tachycardias with variable atrioventricular block, accelerated junctional rhythms (especially in the setting of atrial fibrillation), and fascicular tachycardias are characteristic digoxin toxic rhythms. Digoxin-specific antibody fragments should be considered the treatment of choice for any digoxin toxic arrhythmia associated with hemodynamic compromise or the threat of hemodynamic compromise. Hyperkalemia, when due to acute severe digoxin toxicity, is also an appropriate indication for digoxin-specific Fab fragment therapy. When assessing the risk:benefit ratio for using digoxin-specific Fab fragment therapy, one needs to determine, in addition to the electrocardiographic manifestations and patient's hemodynamic status (1) the severity of toxicity, as indexed by the amount ingested and/or the serum digoxin concentration; (2) the expected time course for reversal of toxicity, which is usually determined by the status of renal function; (3) the need for digoxin to provide ventricular rate control or improved ventricular contractility and therapeutic alternatives to digoxin; (4) the presence of a strong allergy history; (5) the presence of such factors as increased age and severity of heart disease that may predispose to digoxin toxicity.
Usefulness of verapamil for congestive heart failure associated with abnormal left ventricular diastolic filling and normal left ventricular systolic performance. Normal left ventricular systolic performance with impaired left ventricular diastolic filling may be present in a substantial number of patients with congestive heart failure (CHF). To evaluate the effect of oral verapamil in this subset, 20 men (mean age 68 +/- 5 years) with CHF, intact left ventricular function (ejection fraction greater than 45%) and abnormal diastolic filling (peak filling rate less than 2.5 end-diastolic volumes per second [edv/s]) were studied in a placebo-controlled, double-blind 5-week crossover trial. All patients underwent echocardiography to rule out significant valvular disease, and thallium-201 stress scintigraphy to exclude major active ischemia. Compared to baseline values, verapamil significantly improved exercise capacity by 33% (13.9 +/- 4.3 vs 10.7 +/- 3.4 minutes at baseline) and peak filling rate by 30% (2.29 +/- 0.54 vs 1.85 +/- 0.45 edv/s at baseline) (all p less than 0.05). Placebo values were 12.3 +/- 4.0 minutes and 2.16 +/- 0.48 edv/s, respectively (difference not significant for both). Improvement from baseline in an objective clinico-radiographic heart failure score (scale 0 to 13) was significantly greater with verapamil compared to placebo (median improvement in score: 3 vs 1, p less than 0.01). Mean ejection fraction and systolic blood pressure were unchanged from baseline; diastolic blood pressure and heart rate decreased to a small degree. Verapamil may have therapeutic efficacy in patients with CHF, preserved systolic function and impaired diastolic filling.
Surgical correction of the snapping iliopsoas tendon. Eighteen patients with 20 symptomatic hips underwent lengthening of the iliopsoas tendon for persistent painful snapping of this "internal" variety of snapping hip. We referred to the pathologic, painful snapping of the iliopsoas in the deep anterior groin as the "internal" snapping hip. This is in contrast to the more common and better-known "external" snapping that involves the greater trochanter and its overlying soft tissues. The results of our iliopsoas lengthening procedure are presented here. Lengthening of the iliopsoas tendon was accomplished by step cutting of the tendinous portion of the iliopsoas. The pathoanatomy of this poorly understood symptom complex was described in 1984 paper from this institution and is reviewed here. Iliopsoas bursography demonstrated a sudden jerking movement of the iliopsoas tendon between the anterior inferior iliac spine and iliopectineal eminence, synchronous with the patient's pain and often accompanied by an audible snap. The average preoperative duration of symptoms was 2.9 years, and the average length of postoperative followup was 25 months. All patients, except one, had a marked reduction in the frequency of snapping after tendon lengthening, and 14 of 20 hips had no snapping postoperatively. Of the six patients who had recurrence of snapping, all but one stated that this occurred much less frequently and was much less painful compared to the preoperative state. Two hips required reoperation. Postoperatively, only three patients complained of subjective weakness, and most patients were unlimited in physical activity with return to activities such as competitive football, pole vaulting, and long-distance running.
Transmural myocardial deformation in the ischemic canine left ventricle. The myocardium is a complex three-dimensional structure consisting of myocytes interconnected by a dense collagen weave that courses in different directions. Regional ischemia can be expected to produce complex changes in ventricular deformation. In the present study, we examined the effects of ischemia on two- and three-dimensional finite strains during acute transmural myocardial ischemia in 13 open-chest anesthetized dogs. In contrast to systolic deformation observed during the control period in which circumferential shortening exceeded longitudinal shortening, our results indicate that after 5 minutes of acute ischemia, end-systolic in-plane lengthening across the left ventricular wall occurs in approximately equal amounts in the circumferential and longitudinal directions. Along with these changes in extensional strains, there were significant negative transverse shearing deformations during ischemia. Myocardial ischemia also resulted in a loss of the normal end-systolic transmural gradients of shortening and thickening. Three-dimensional end-diastolic strains indicate that the left ventricular wall undergoes a significant passive reconfiguration that varies transmurally with lengthening in the epicardial tangent plane and wall thinning increasing from the epicardium toward the endocardium. The large systolic changes in shearing deformations with ischemia could potentially influence collateral blood flow and certainly indicate that uniaxial measurements of deformation in the ischemic myocardium, which do not account for shearing deformation, are incomplete and must be interpreted with caution. Moreover, normal transmural systolic gradients in deformation, which would be anticipated on geometric grounds, are lost during ischemia, implying that the material properties of ischemic tissue or the loading conditions imposed on the ischemic region by partially impaired adjacent myocardium vary transmurally.
Adenoid cystic carcinoma of the esophagus. A clinicopathologic study of three cases. In a group of 245 cases of primary carcinoma of the esophagus the authors found three cases of adenoid cystic carcinoma (ACC). Clinical and pathologic data of those patients (one female and two male; age range, 49-74 years) were analyzed. Tumors were localized in the middle third of the esophagus. One patient lived 15 months after surgery. Another is a case of early ACC who has been living 4.5 years after surgery and is without specific symptoms. The third patient had not had surgery and died 13 months after the onset of dysphagia. An autopsy showed only a locally invasive tumor growing into the surroundings of the esophagus, and regional lymph node metastases without distant parenchymal metastases. These findings support pathologic and biologic similarities between ACC of the esophagus and ACC of the salivary glands. There are synchronous tumors of the esophagus and the vital localization which makes the prognosis of ACC of the esophagus worse than ACC of the salivary glands.
Detection of human papillomavirus type 16 DNA in carcinomas of the palatine tonsil. Twenty eight tonsillar carcinomas of various histological types were investigated for the presence of Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human papillomavirus (HPV) types 6, 11, and 16 by in situ hybridisation using highly stringent procedures. In six cases an autoradiographic signal was obtained in the tumour cell nuclei with the HPV type 16 specific probe. No signal was obtained with any of the other probes. Immunohistochemical investigations with mouse monoclonal antibodies directed against the L1 protein of HPV type and a rabbit antiserum that detects common protein determinants of HPV gave negative results, thus indicating latent infection. Furthermore, a series of tonsils from controls with comparable age distribution was negative by both in situ hybridisation and immunohistology. These results indicate a possible role for HPV 16 in the aetiology of a proportion of tonsillar carcinomas.
Usefulness of digital angiography in the assessment of left ventricular ejection fraction. With modern digital cardiac systems the image data are digitized on-line and in real-time, allowing the replay and subsequent interpretation and analysis during or directly after the cardiac catheterization procedure. In this study we have evaluated the advantages and limitations of a manual tracing technique for left ventricular digital angiograms on the Phillips DCI system. Thirty-three patients who were catheterized for suspected coronary artery disease were studied. The manual tracings were performed by a senior cardiologist and an experienced function-analyst. It was found that the short- and long-term intraobserver variabilities in the assessment of the global ejection fraction were very small; short-term mean difference +/- standard deviation (correlation coefficient): 0.5 +/- 2.7 (r = 0.97) global EF%-units; long term; 0.7 +/- 2.7 (r = 0.96) EF%-units. The interobserver variabilities (5.1 +/- 4.8 (r = 0.93) EF%-units) were slightly higher than the intraobserver variabilities. A decrease by 25% in the amount of contrast medium administered did not significantly influence the variabilities in the contour tracings, which would suggest the use of smaller doses. At the average, the cardiologist and the function-analyst required 6 and 11 min of analysis time for a left ventricular study, respectively, emphasizing the need for further developments towards automated contour detection. Finally, an excellent correlation was found with a standard off-line cinefilm analysis procedure. Thus, it may be concluded that quantitative digital left ventricular angiography based on manual tracing of the outlines performed immediately following the cardiac catheterization (post-processing) is feasible as a routine procedure for the assessment of left ventricular function.