shukoor65/lab-rag-model huggingface dataset:
Regulation of gene expression in renal compensatory growth. Compensatory renal hypertrophy is characterized by an increase in cell protein content. There are a number of different cellular mechanisms by which such an increase could be mediated. The relative contributions of transcriptional and posttranscriptional regulation of gene expression to the increase in constitutively expressed cellular proteins were examined in mouse kidneys undergoing compensatory growth following unilateral nephrectomy (UNI-NX). Over the 14-day study period, total protein per kidney increased by up to 37%. Northern blot analysis of the expression of the mRNAs for a number of genes associated with cell growth indicated that there was no significant increase in steady-state levels of these selected genes in nephrectomized compared with sham-operated animals. In vitro assays to measure transcriptional regulation of the same set of genes in compensatory growth showed no increase in the rate of transcription. However, transcription of the 18S ribosomal RNA gene was increased 24 hours after nephrectomy. Immunoblots of two representative proteins showed that the concentration of these proteins in total kidney protein remained constant in the different experimental groups. Since total protein increased, the concentration of these proteins in the hypertrophied kidney must have increased. Taken together, these data suggest that posttranscriptional mechanisms may account for the increase in at least some constitutively expressed proteins in cells undergoing compensatory growth.
Concurrent hydralazine administration prevents nitroglycerin-induced hemodynamic tolerance in experimental heart failure. BACKGROUND. Organic nitrates such as nitroglycerin and isosorbide dinitrate are useful in the treatment of congestive heart failure (CHF), but tolerance develops rapidly during continuous administration. Because combination therapy of nitrate and hydralazine has been shown to provide both short- and long-term benefit but nitrate alone produces hemodynamic tolerance, we questioned whether hydralazine can preserve the favorable preload effects of nitroglycerin. METHODS AND RESULTS. Using an in vivo model of nitroglycerin tolerance in the CHF rat, we examined the effects of hydralazine bolus dosing during continuous nitroglycerin infusion. Continuous infusion of nitroglycerin alone (10 micrograms/min) produced initial reductions in left ventricular end-diastolic pressure of 40-50%, which returned to baseline by 8 hours (tolerance development). Coadministration of hydralazine (2 x 0.1 mg) maintained the effects of nitroglycerin infusion on left ventricular end-diastolic pressure (45% reduction at 10 hours). This hydralazine dose alone reduced left ventricular peak systolic pressure by approximately 12 +/- 3% but had no effect on left ventricular end-diastolic pressure. Hydralazine dosing did not affect steady-state plasma concentrations of nitroglycerin or metabolites, and hydralazine was unable to prevent nitroglycerin tolerance induced in vitro. CONCLUSIONS. The beneficial interaction of hydralazine on the preload effects of nitroglycerin may explain the long-term clinical efficacy of hydralazine/nitrate combination in CHF. Our results also suggest that the mechanism of in vivo nitrate tolerance in CHF may be systemic rather than vascular in origin.
Clonidine inhibits vesico-sphincter reflexes in patients with chronic spinal lesions. When administered systemically to spinalized animals, clonidine, the prototypic alpha 2 adrenergic receptor agonist, purportedly acts at spinal sites to suppress motor responses related to painful peripheral and vesical stimulation and spasticity, and to improve vesicourethral coordination. Hence, the action of clonidine (400 micrograms in three divided doses in a 16-hour span) on spinal vesical and somatic reflexes was examined in five patients with suprasacral spinal cord lesions by assessing volume-induced micturition reflexes and limb motor discharges that occurred spontaneously or were elicited by noxious and nonnoxious cutaneous stimulation. Clonidine caused a significant reduction in (1) blood pressure, (2) amplitude of detrusor contraction, and (3) vesical external urethral sphincter dyssynergia. Limb motor electromyography discharges were not markedly attenuated, although spatiotemporal changes (eg, irradiation, after-discharges) were observed in some of the patients. The results are ascribed to binding to spinal cord alpha 2 adrenergic receptors located on segmental and intersegmental (propriospinal) interneurons, released from descending inhibition, with greater motor system specificity on striated sphincter innervation. Clonidine may be clinically effective in the treatment of hyperactive micturition reflexes in patients with chronic spinal lesions.
The effect of caffeine on postprandial hypotension in the elderly In a double-blind, randomized trial the effects of caffeinated and decaffeinated drinks on postprandial hemodynamic and neurohumoral changes were studied in seven fit, elderly subjects after a standard 2.4MJ meal. There was a significant difference in supine postprandial systolic blood pressure between the placebo and caffeine phases (P less than 0.01); at 60 minutes, supine systolic blood pressure had fallen 14 mmHg [95% confidence interval (CI)-7 to-21 mmHg, p less than 0.01) after placebo, but was unchanged after caffeine (+9 mmHg, CI 0 to 18 mmHg, NS]. Similar differences between placebo and caffeine were seen in erect systolic and diastolic blood pressure (P less than 0.01), although orthostatic tolerance was maintained throughout each study period. Postprandial plasma noradrenaline levels were higher (P less than 0.02) and the increase greater (P less than 0.02) after caffeine than after placebo. Caffeine administered at the end of a standard test meal prevents the postprandial fall in blood pressure in fit, elderly subjects. The clinical relevance of this finding has yet to be determined, but it may offer a simple remedy for patients with symptomatic postprandial hypotension.
Advances in the understanding and treatment of urinary tract infections in young women. Despite relative ease of management, the high rate of urinary tract infections (UTI) among young women presents substantial problems for the health care community. Although the majority of UTIs in young women are simple and uncomplicated, the rate of recurrence is substantial. Each treatment of UTI recurrence brings greater antibiotic resistance, requiring the use of broader spectrum and more expensive antibiotic therapy. Moreover, infection in patients with underlying urinary tract or systemic diseases can lead to serious medical and financial consequences. A better understanding of antibiotic resistance, particularly in regard to beta-lactamase-producing pathogens, has allowed us to develop more appropriate criteria for selecting antibiotics as well as the duration of therapy. The overall cost for treating UTIs in young women is a substantial health care expenditure, and requires an ongoing examination of new information concerning pathogenesis and available antibiotic therapies.
Staged repair of interrupted aortic arch and ventricular septal defect in infancy. Staged repair of interrupted aortic arch and ventricular septal defect was carried out in 20 infants from 1979 through 1990. Among the important associated cardiac defects were transposition of the great arteries, truncus arteriosus, and anomalous origin of the right pulmonary artery. The first stage, usually consisting of the placement of an 8- or 10-mm polytetrafluoroethylene graft, pulmonary artery banding, and ligation of the patent ductus arteriosus, resulted in 20 survivors (100%) There were two interim deaths (10%) before the second stage of ventricular septal defect closure and pulmonary artery band removal, which had 15 survivors (83%, 15/18). Because the major morbidity and mortality early in this experience could be traced to leaving the pulmonary artery band on too long, early removal (within 2 to 3 months) was begun. Since 1985, 8 (100%) of 8 infants have survived both stages and are now doing well. Because of the relatively large polytetrafluoroethylene graft, only 1 child (aged 9 years) has experienced substantial late aortic arch obstruction and undergone placement of an 18-mm Dacron graft without difficulty. Of interest is the finding that in only 1 (5%) of the 20 patients has major (greater than or equal to 40-mm Hg gradient) left ventricular outflow tract obstruction developed. In summary, the staged repair of interrupted aortic arch with ventricular septal defect has become very reliable despite the condition of the infant or major associated cardiac anomalies and can be recommended for infants at high risk for primary repair. More long-term information will be needed to determine which approach will be the best choice for the majority of infants.
Colorectal cancer patients with high risk of hematogenous metastasis: correlation with CEA levels in peripheral and draining venous blood during the period of operation. Correlations between carcinoembryonic antigen (CEA) levels of peripheral (p) and draining (d) venous blood during the period of operation, and pre- and post-operatively detected hematogenous metastases were examined in 78 patients with colorectal cancer. The metastases were found in 28 patients (HM group), but not found in the other 50 patients (non-HM group). The mean values (43 and 198 ng/ml) and positive rates (61 and 96%) greater than 5 ng/ml of p- and d-CEA levels in the HM group were significantly higher than those (6 and 14 ng/ml, and 22 and 48%, respectively) in the non-HM group. The differences (mean 184 ng/ml and positive rate 49%) of d-CEA levels between both groups were more significant than those (39 ng/ml and 30%) of p-CEA levels. The mean value (155 ng/ml) and positive rate (82%) greater than 5 ng/ml of the gradient between d- and p-CEA levels (d-p CEA gradient) in the HM group were significantly higher than those (8 ng/ml and 34%) in the non-HM group. These results suggest that patients with a high risk of hematogenous metastases are more effectively checked by the determination of d-CEA levels and d-p CEA gradient than of p-CEA levels, and that they are patients with positive d-CEA and d-p CEA gradient levels.
Contemporary management of neurofibromatosis. The neurofibromatoses are two distinct entities with different genetic origins. The phenotypic expressions and required treatments are different. The devastating nature of neurofibromatosis-2 may be more effectively controlled through the application of advanced imaging techniques and contemporary neurotologic procedures. The most common manifestation of neurofibromatosis-2 is that of bilateral acoustic neuromas. The eventual total bilateral sensorineural deafness associated with this condition can be obviated in selected cases if the diagnosis is established early. Follow-up data are reported for three patients in whom hearing was preserved in at least one ear. When removal with hearing preservation is not possible, subtotal tumor removal with decompression of the internal auditory canals may delay progression of hearing loss. A new approach to tumors of the pterygomaxillary fossa that have extended to the middle cranial fossa has been successfully applied and is described.
The effects of chronic endoscopic variceal sclerotherapy on portal pressure in cirrhotics. The effect of obliterating esophageal varices by endoscopic sclerotherapy on portal pressure was prospectively studied in 11 cirrhotic patients with variceal hemorrhage. Portal venous pressure gradient, determined as the difference between transhepatic portal and hepatic vein pressure, increased by a mean of 31.1% +/- 14.5% in 8 (73%) and decreased by a mean of 30.1% +/- 11.7% in 3 (27%) patients, with no statistically significant change overall (P = 0.1). These changes in portal venous pressure gradient occurred despite an improvement in the laboratory and clinical parameters of hepatic function. Deep abdominal sonography with color flow imaging at variceal obliteration showed patent paraumbilical veins in 6 (55%) patients, 3 of whom had decreases in portal venous pressure gradient (29%, 19%, 42.5%) at variceal obliteration. In 5 (45%) patients without patent paraumbilical veins, a statistically significant increase in portal venous pressure gradient between initial endoscopic variceal sclerotherapy and variceal obliteration was noted (P = 0.008). Rebleeding (single episode in all 4 patients, before obliteration in 3 patients) occurred in those with an increase in portal venous pressure gradient; all patients with portal venous pressure gradient decreases were nonbleeders. No correlation between changes in portal venous pressure gradient and time to variceal obliteration, number of sclerotherapy treatments, or rebleeding episodes was observed. Thus, an increase in portal venous pressure gradient was noted in the majority of patients at variceal obliteration. Although the portal venous pressure gradient decrease may be explained by a patent paraumbilical vein, the mechanism of portal venous pressure gradient increase is not clear. It is speculated that this portal venous pressure gradient increase may be caused by an increase in collateral resistance or flow or a combination of both, resulting from obliteration of esophageal varices by endoscopic sclerotherapy.
Role of emergency medical services. For thrombolytic therapy to be effective in the treatment of acute myocardial infarction, the patient must enter the health care center delivery system in an efficient manner. Some entry delays are due to patient decisions and interactions with others. In the United States, prehospital care is delivered by a variety of different systems, varying from public service types such as fire-department based to private types of service. These personnel vary in level of training from paramedics with a high level of training to Emergency Medical Technicians-Ambulance with basic training (first aid), even less in some areas. The training should be upgraded so that training as an emergency medical technician with the ability to defibrillate would be the minimum level for emergency ambulance personnel; wherever economically and logistically feasible, ambulance personnel should be paramedics. Although the 911 emergency telephone system exists in some areas, there is no centralized, universal system for access, causing confusion and delays in obtaining care in critical situations such as cardiac arrest. There is a need for a national emergency number--911--with the ability to identify the calling number and address. Since dispatchers have little medical dispatch training, needed instructions are not given to the caller, which can reduce the patient's chance of survival. Trained dispatchers are needed to dispatch resources efficiently and to offer assistance until trained rescuers arrive. Ambulances are inefficiently located in some areas of the United States, slowing response to the patient.
Effort thrombosis of the axillosubclavian vein: a disabling vascular disorder. In the natural history of this disorder, resumption of normal activity after a period of recuperation (following an episode of thrombosis) frequently leads to symptoms of upper extremity venous hypertension exacerbated by using the arms in the overhead position. This position can be demonstrated venographically to further occlude collateral vessels in thoracic outlet. A number of patients develop more extensive symptoms of neurogenic thoracic outlet syndrome. Anticoagulation may protect the collateral vessels and interrupt the period of active clot propagation resulting in a better functional result than would be expected from the natural history of the thrombotic event. In our experience, local Urokinase was the most effective means for reestablishing venous patency. With clot dissolution the underlying compression of the vein at the thoracic outlet can be demonstrated. Balloon angioplasty should not be undertaken in the acute setting nor prior to relieving the tendinous compression. The acute phlebitic process should resolve under the protection of Coumadin for three months. At that time it can be determined more effectively which patients require additional therapy. Removal of the first rib will decompress the axillosubclavian vein and the thoracic outlet collaterals permitting the vein to regain its normal configuration particularly in younger patients with more acute onset of compression. In those patients with more chronic compression the vein becomes stenotic. Improvement of the luminal configuration has been accomplished with transvenous balloon angioplasty without the necessity for venous reconstructive procedures in this series. Patients with Paget-Schroetter syndrome have a symptom complex which often reflects more extensive neurovascular compression at the thoracic outlet than that which might result from venous hypertension alone. Although thrombolytic therapy can restore patency of the axillosubclavian vein, first rib resection is necessary to relieve the external compression. This procedure was very effective in patients who had restoration of subclavian vein patency, and to a lesser degree in those with residual occlusion.
HLA class I antigen expression as a measure of response to antiviral therapy of chronic hepatitis B. HLA class I antigen expression on peripheral blood mononuclear cells was evaluated by flow cytometry in 21 HBeAg-positive patients with chronic hepatitis B. Measurements were made before, during or after treatment with recombinant interferon-alpha-2b, either given alone or after a 6 wk course of prednisone. Immunohistochemical staining for human leukocyte class I antigen was also evaluated in 28 percutaneous liver biopsy specimens either obtained before or after therapy (N = 27) and during therapy in one instance. The amount of HLA class I antigen on peripheral blood mononuclear cells varied markedly among individual patients, but the overall results indicated that the level of inducible antigen did not correlate with increments of ALT during therapy or with a virological response to therapy. Hepatocyte staining for HLA class I antigen was observed in a minority of biopsy specimens (29%) and also did not appear to predict a response or correlate with the severity of histological disease. These data do not support current theories concerning pathogenetic mechanisms in chronic hepatitis B nor do they suggest that spontaneous display of HLA class I antigen on hepatocytes or interferon-induced expression of these antigens on peripheral blood mononuclear cells is a critical determinant for a response to therapy.
Dispersion of ventricular repolarization in the long QT syndrome. To identify markers of dispersion of the ventricular repolarization in the idiopathic long QT syndrome, body surface potential maps were analyzed in 40 such patients (mean age +/- standard deviation 21 +/- 11 years) and in 30 healthy control subjects (mean age 24 +/- 7 years). In each subject, 117 chest leads were recorded and maps of the integral values of the QRST interval were calculated. A multipolar distribution of the values, a marker of gross electrical inequalities of repolarization, was found only in 4 patients. To detect minor regional disparities of ventricular recovery, all the ST-T waveforms were analyzed in each subject. The ST-T waves were represented by a discrete series of potential values. The "similarity index" was computed by applying a principal component analysis, which represents (in percent) to what extent 1 fundamental pattern of ST-T reproduces all the recorded waveforms. The mean value of the similarity index was significantly lower in patients with long QT syndrome than in control subjects (49 +/- 10 vs 77 +/- 8%, p less than 0.0001). A value less than 61% (corresponding to 2 standard deviations below the mean value for controls) was found in 35 of 40 patients and in only 1 control subject (sensitivity 87%, specificity 96%). Thus, the similarity index is a more sensitive marker than the multipolar distribution of QRST integral maps in revealing electrical disparities of the ventricular recovery times.
Spatial misregistration of vascular flow during MR imaging of the CNS: cause and clinical significance. Spatial misregistration of signal recovered from flowing spins within vascular structures is a common phenomenon seen in MR imaging of the CNS. The condition is displayed as a bright line or dot offset from the true anatomic location of the lumen of the imaged vessel. Its origin is the time delay between application of the phase- and frequency-encoding gradients used to locate spins within the plane of section. The principal condition necessary for the production of spatial misregistration is flow oblique to the axis of the phase-encoding gradient. Flow-related enhancement (entry slice phenomenon), even-echo rephasing, and gradient-moment nulling contribute to the production of the bright signal of spatial misregistration. Familiarity with the typical appearance of flow-dependent spatial misregistration permits confirmation of a vessel's patency; identification of the direction of flow; estimation of the velocity of flow; and differentiation of this flow artifact from atheromas, dissection, intraluminal clot, and artifacts such as chemical shift.
Trends in the operative management of invasive squamous carcinoma of the vulva at Indiana University, 1974 to 1988. From January 1974 to March 1988, 150 patients with primary invasive squamous cell carcinoma of the vulva underwent surgery at Indiana University. There has been a trend toward more conservative surgical management of this disease. To determine the impact of this trend on clinical outcome, cases were divided into three groups according to date of operation: group I, 1974 to 1978; group II, 1979 to 1983; and group III, 1984 to 1988. Overall, 80 patients had en bloc radical vulvectomy and groin dissection, 20 had modified radical vulvectomy and bilateral groin dissection through three separate incisions, and 36 had modified radical vulvectomy and unilateral superficial groin dissection. Fourteen patients had other operations. Forty-two patients (27.3%) had radiotherapy in addition to surgery. Among the three groups, there were no differences when mean age, International Federation of Gynecology and Obstetrics stage distribution (1988 system), mean lesion size, mean depth of invasion, or grade distribution were compared. A significant trend toward more conservative surgical therapy was observed. En bloc radical vulvectomy was performed in 77.4% of group I patients, 71.1% of group II patients, and 35.8% of group III patients (p less than 0.001). Mean days of hospitalization were also reduced significantly. Group I had a mean stay of 30 days, group II had a mean stay of 23 days, and group III had a mean stay of 11 days (p less than 0.001). Mean operative blood loss (group I, 754.8 ml; group II, 620.0 ml; group III, 393.6 ml; p = 0.03), mean units of blood transfused (group I, 1.4 units; group II, 1.3 units; group III, 0.4 units; p less than 0.01), and mean hours of operating time (group I, 3.7 hours; group II, 3.7 hours; group III, 3.2 hours; p = 0.02) were also reduced.
Detubularisation in cystoplasty: clinical review. Cystoplasty using a detubularised bowel segment is preferable to using a tubularised length of intestine. This has been shown experimentally to result in a reduction in the contractility of the neobladder, although contractions are not completely abolished. Incontinence, especially nocturnal, may still be a problem. Assessment of renal function has shown a marked incidence of upper tract dysfunction despite detubularisation. All patients remain at risk of upper tract obstruction following cystoplasty. Because bowel contraction waves are brought on by distension, it may be possible either to postpone or to prevent the onset of contractions by avoiding an excessive build-up of bladder volume. Clean intermittent self-catheterisation is an efficient means of emptying the bladder, although sphincter rebalancing may also be required.