shukoor65/lab-rag-model huggingface dataset:
Effects of urokinase receptor occupancy on plasmin generation and proteolysis of basement membrane by human tumor cells. The goal of the present study was to assess the relative importance of receptor-bound and secreted plasminogen activator urokinase (u-PA) in generating cell-surface plasmin and fostering destruction of normal tissue by tumor cells. We first showed that active site-inhibited u-PA could displace endogenous u-PA from the surface of the human colon adenocarcinoma cell line HCT 116. We then prepared expression vectors for u-PA and for a mutant molecule in which the codon for the active site serine residue was changed to encode alanine. Expression of non-functional mutant u-PA decreased the level of cell-bound active u-PA by more than 95% via a mechanism that involved competition for receptor sites. Decreased cell-surface u-PA activity was associated with a decrease in cell-bound plasmin activity to undetectable levels, suggesting that receptor-bound u-PA plays an important role in the generation of plasmin on the cell surface. Transfectants that secreted eightfold to 20-fold elevated levels of active wild-type u-PA showed approximately 50% increases in cell-associated u-PA and only twofold to fourfold increases in cell-associated plasmin, suggesting that the role of secreted u-PA in generating cell-surface plasmin activity was relatively minor. In parent cells and both types of transfectants there was a good correlation between the amount of plasmin bound to the tumor cell surface and the extent to which a basement membrane substrate was degraded. These studies show that receptor-bound u-PA provides an efficient mechanism for plasmin generation on the surface of tumor cells, which, in turn, contributes significantly to their degradative potential.
Isradipine twice daily lowers blood pressure over 24 H. The objective of this study was to compare the effects of isradipine and placebo on blood pressure (BP) at the end of the dosing interval ('trough'). Following a three-week placebo period, 187 patients who had previously shown a response to treatment with isradipine (based on office BP measurements) were randomized to double-blind treatment with 2.5 mg isradipine twice daily or placebo for six weeks. Four of these patients withdrew from the study during the double-blind phase because of adverse events (one taking isradipine and three taking placebo). Blood pressure during the double-blind study was always measured 12 h after drug administration (trough values). The rate of normalization [defined as diastolic BP (DBP) less than or equal to 90 mm Hg] was 52/96 (54%) in the isradipine-treated group compared with 30/87 (33%) in the placebo group. A further 12/96 (12%) patients taking isradipine showed a fall in DBP of greater than or equal to 10 mm Hg, although their DBP was still not less than 90 mm Hg, compared with 5/87 (6%) patients receiving placebo. This difference was statistically significant (P = .003). Thus, isradipine in a dose of 2.5 mg twice daily lowers blood pressure over 24 h.
Early hepatocellular carcinoma: MR imaging. All areas in hepatic lesions designated as adenomatous hyperplasia (AH) with malignant foci have recently been recognized as cancer. AH with malignant foci can be classified into two types, depending on the presence of overt cancerous nodules. Lesions without macroscopic nodules are defined as early hepatocellular carcinoma (HCC), while those with a macroscopic component are defined as HCC with early components. A comparative study of early HCC and HCC with early components was performed with magnetic resonance imaging. Early HCC lesions (n = 20) were isointense (n = 11) and hyperintense (n = 9) on T1-weighted spin-echo images and isointense (n = 17), partially hyperintense (n = 2), or hypointense (n = 1) on T2-weighted spin-echo images relative to the surrounding liver. Lesions classified as HCC with early components (n = 8) were hyperintense (n = 5), isointense (n = 2), and of mixed signal intensity (n = 1) on T2-weighted images. T1-weighted imaging was superior to T2-weighted imaging in depicting early HCC, but the latter could be useful in evaluating the progression of HCC in the histopathologically early stages.
Heart disease in blacks of Africa and the Caribbean. Cardiovascular pathology in African and Afro-Caribbean blacks features three major conditions: hypertension, rheumatic heart disease, and the cardiomyopathies. Ischemic heart disease is as yet distinctly uncommon in these societies but the adoption of Western lifestyle and its inevitable risk factors for atherosclerosis makes it likely that coronary artery disease will emerge ultimately. Hypertension poses special problems in these regions--its prevalence rate is high both in rural and urban settings, its consequences devastating in its severity of target organ involvement, and its management strategy complicated by the high cost of drugs, poor patient compliance, and the lack of clinical resources for effective monitoring of detected and referred cases. Rheumatic heart disease remains an eminently preventable condition. The ultimate strategy lies in improving the quality of life in these communities through adequate housing, sanitation, and health education, and integrating primary prophylaxis into national health care programs to forestall the development of rheumatic fever. Cardiomyopathy poses the greatest challenge as its etiology remains elusive. Its dilated form has been linked with Toxoplasma and with Coxsackie B viruses, but hard evidence of a cause-effect relationship is still lacking.
Serial gadolinium-enhanced magnetic resonance imaging scans in patients with early, relapsing-remitting multiple sclerosis: implications for clinical trials and natural history. Six patients with early, mild, relapsing-remitting multiple sclerosis were studied with monthly gadolinium-enhanced magnetic resonance imaging scans for 8 to 11 months. Numerous enhancing lesions were observed irrespective of clinical activity. Four of the 6 patients had one or more enhancing lesions present on each examination. The other 2 patients had enhancing lesions noted in 7 and 9 of 11 months. In contrast, only two clinical exacerbations were observed during the study period. Neither the exacerbations nor other changes in symptoms or signs correlated with occurrence of the enhancing lesions. Enhancement generally persisted for less than 1 month. The opening of the blood-brain barrier as reflected by gadolinium enhancement on magnetic resonance imaging may represent ongoing disease activity in patients with mild, relapsing-remitting multiple sclerosis who are clinically stable. The frequency of these lesions appears to be sufficient to use as an outcome measure in clinical trials testing clinical efficacy in patients with early, relapsing-remitting multiple sclerosis.
Diagnostic sensitivity of polymerase chain reaction and Southern blot hybridization for the detection of human papillomavirus DNA in biopsy specimens from cervical lesions. Human papillomaviruses (HPVs) are associated with benign and malignant neoplasms of the cervix. One of the criteria for their etiologic role requires an assessment of whether virtually all or only a small fraction of lesions contain viral genomes. DNA preparations from colposcopically directed punch biopsies of cervical lesions were analyzed by Southern blot hybridization and the polymerase chain reaction (PCR) for the presence of HPV DNA. The biopsy specimens represented different pathologic entities (koilocytosis, condyloma, cervical intraepithelial neoplasia, and invasive carcinoma). In Southern blot hybridization with radioactive probes for HPV 11, 16, 18, 31, and 33, HPV DNA was detected in 74% of the biopsy specimens (42 of 57 cases), with the predominant types being HPV 16 and HPV 18. In contrast, after PCR amplification with primers yielding fragments of characteristic size for HPV 11, 16, and 18, the analysis of the same 57 biopsy specimens revealed that all samples were positive for at least one HPV type. To exclude false-positive PCR results, controls without HPV DNA were interspersed at regular intervals, and results were evaluated only if these controls remained HPV negative. To exclude false-negative results due to failure of the reaction, a target sequence within the c-Ha-ras-1 gene was used as an internal control. All HPV typing results obtained by Southern blot hybridization were in agreement with HPV typing by PCR. The higher number of positive samples in the latter analysis stems from the increased sensitivity of PCR, which was which was effective in identifying as few as 10-100 HPV DNA molecules; in contrast, the sensitivity of Southern blot hybridization was 1 pg, or approximately 10(5) molecules of HPV DNA. The authors conclude that, with sufficiently sensitive diagnostic methods, HPV DNA can be detected in most, if not all, neoplastic cervical lesions.
Abdominal musculature abnormalities as a cause of groin pain in athletes. Inguinal hernias and pubalgia. There has been increasing interest within the European sports medicine community regarding the etiology and treatment of groin pain in the athlete. Groin pain is most commonly caused by musculotendinous strains of the adductors and other muscles crossing the hip joint, but may also be related to abdominal wall abnormalities. Cases may be termed "pubalgia" if physical examination does not reveal inguinal hernia and there is an absence of other etiology for groin pain. We present nine cases of patients who underwent herniorrhaphies for groin pain. Two patients had groin pain without evidence of a hernia preoperatively (pubalgia). In the remaining seven patients we determined the presence of a hernia by physical examination. At operation, eight patients were found to have inguinal hernias. One patient had no hernia but had partial avulsion of the internal oblique fibers from their insertion at the public tubercle. The average interval from operation to return to full activity was 11 weeks. All patients returned to full activity within 3 months of surgery. One patient had persistent symptoms of mild incisional tenderness, but otherwise there were no recurrences, complications, or persistence of symptoms. Abnormalities of the abdominal wall, including inguinal hernias and microscopic tears or avulsions of the internal oblique muscle, can be an overlooked source of groin pain in the athlete. Operative treatment of this condition with herniorrhaphy can return the athlete to his sport within 3 months.
The influence of smoking on complications after primary amputations of the lower extremity. A total of 165 primary above-the-knee (AK) and below-the-knee (BK) amputations in 137 patients were reviewed retrospectively. Of the 77 patients who smoked, 44 smoked cigarettes, 30 cheroots, and three a pipe. There were 88 nonsmokers. At the time of surgery, the smokers were on average 6.4 years younger than the nonsmokers. The review revealed no discrepancy between smokers and nonsmokers with regard to amputation level, the BK to AK ratio being 2:1. In cigarette smokers the risk of infection and reamputation was 2:5 times higher than in cheroot smokers or nonsmokers. The poor results obtained in cigarette smokers may be ascribed to the fact that this group of patients smoked during the phase of healing and that only cigarette smokers tend to inhale. Inhalation of smoke leads to high concentrations of nicotine, which compromise the cutaneous blood-flow velocity and increase the risk of the formation of microthrombi. Consequently, amputees should abstain from cigarette smoking during the phase of healing. Preferably, the habit should be broken one week before surgery, which is the requisite period for the process of coagulation and the fibrinogen level to normalize and for free radicals to be eliminated.
Surgical management of metastatic renal carcinoma of the spine. A total of 33 patients with renal cell carcinoma metastatic to the spine underwent spinal decompression over a 5-year period; 20 were operated on for neurologic dysfunction, and the remainder for pain alone. Surgery was performed anteriorly in 21, posteriorly in 9, and combined in 3 cases. The surgical approach was determined by the preoperative anatomic localization of the tumor. Of these patients 88% had fusions with instrumentation and polymethylmethacrylate; 88% of patients had partial or complete relief of pain; and 64% of bedridden patients subsequently were able to walk. Neurologic function improved in 60% of patients with a neurologic deficit; however, only 36% of incontinent patients regained bladder control. Survival averaged 8.0 +/- 1.5 months. Survival correlated with the degree of neurologic dysfunction and the presence of other known metastases. Recurrent cord compression developed in 49% of patients, usually at the same level; 9 of these 16 patients had repeat decompression, with similar operative results as the primary procedure in terms of pain and neurologic function. Blood loss was variable but often significant. Preoperative embolization appeared to be beneficial. Precise tumor localization preoperatively directing the surgical approach and better patient selection would likely improve results and decrease morbidity. Good palliation appeared to be achieved in regards to both pain relief and improved neurologic function.
Attenuation of myocardial ischemia during coronary occlusion by ultrashort-acting beta adrenergic blockade. To assess the effect of the ultrashort-acting beta blocker esmolol on ischemia induced by acute coronary occlusion, we studied 16 patients undergoing coronary angioplasty. Doppler echocardiography and ECG monitoring were performed continuously before, during, and after balloon occlusion in the drug-free state and during esmolol infusion. Fourteen of the 16 patients had ST segment elevation during balloon inflation. However, maximal ST segment elevation (2.1 +/- 1.5 mm vs 1.7 +/- 1.3 mm, p less than 0.001) and duration of ST segment elevation (68 +/- 20 seconds vs 54 +/- 19 seconds, p less than 0.05) were both significantly reduced during esmolol infusion. Furthermore, the decrease in ejection fraction seen during drug-free balloon occlusions was significantly blunted during esmolol infusion. In the baseline state ejection fraction decreased from 55% to 38% (p less than 0.05) during coronary occlusion compared with a decrease from 52% to 49% (p = NS) during esmolol infusion. In addition, esmolol appeared to delay the onset of segmental wall motion abnormalities after coronary occlusion, occurring at a mean of 40 seconds after balloon inflation versus a mean of 31 seconds in the absence of beta blockade (p less than 0.05). Thus the use of ultrashort-acting beta blockade appears to diminish the extent and delay the onset of myocardial ischemia during acute coronary occlusion.
Uterine leiomyoma with skeletal muscle differentiation. Report of a case. Skeletal muscle differentiation is reported in a uterine leiomyoma from a 54-year-old woman. Evidence of rhabdomyoblastic features included a typical light microscopic appearance, immunoreactivity with antimyoglobin antibodies by immunoperoxidase studies, and the presence of myofibrils by electron microscopic examination. The patient is well more than two years after surgery.
Treatment of hypercalcemia of malignancy with intravenous etidronate. A controlled, multicenter study. The Hypercalcemia Study Group In a prospective, randomized, double-blind, multicenter study, 202 patients with cancer from 19 medical centers were treated for hypercalcemia of malignancy with daily intravenous infusions of etidronate disodium (136 patients) or saline alone (66 patients) for 3 consecutive days. Patients also received up to 3.25 L of saline daily during the treatment period. Of 157 patients for whom data could be evaluated for efficacy, 63% (72/114) of etidronate-treated and 33% (14/43) of saline-treated patients had a normalization of total serum calcium levels. When serum calcium levels were adjusted for albumin (147 assessable patients), 24% of the etidronate- and 7% of the saline-treated patients responded to treatment. No serious side effects or treatment-related deaths occurred. When accompanied by adequate hydration and diuresis, intravenous etidronate was safe and more effective than hydration and diuresis alone in controlling hypercalcemia of malignancy.
The efficacy of fiberoptic endoscopic examination and biopsy in the detection of early nasopharyngeal carcinoma. Fiberoptic endoscopic examination and biopsy of the nasopharynx was done in 130 patients as a prospective study. They all had elevated titers of antibodies against the viral capsid antigen of Epstein-Barr virus but no symptoms or signs of nasopharyngeal carcinoma. Each underwent a biopsy from six fixed sites in the nasopharynx. Of the 780 biopsy specimens taken from seven patients, 11 showed the presence of nasopharyngeal carcinoma. Techniques to improve the yields of such biopsies with fiberoptic endoscopy are discussed. The presence of tumor was unrelated to the macroscopic endoscopic findings. The highest incidence of subclinical tumor is in the pharyngeal recess.
Different metastasis patterns of a human melanoma cell line in nude mice and rats: influence of microenvironment. The metastatic capacity of intravenously injected human FEMX-I melanoma cells in athymic nude mice and rats was compared. Young rats given 1 x 10(6) ascites tumor cells all died of lung tumors with a life span of 50 +/- 10 days (mean +/- SD). In contrast, in accordance with previous findings, only extrapulmonary metastases developed in mice. This host-dependent difference in metastasis pattern permitted studies on the role of factors that may influence the organ specificity of metastases. The tissue distribution of 125I-labeled FEMX-I cells did not differ in the two nude species during the first 12 hours after cell injection. The plating efficiency of FEMX-I cells in soft agar was increased by the addition of conditioned medium prepared from rat lungs, resulting also in a significant increase in colony size. In contrast, conditioned medium prepared from mouse lungs reduced the clonogenic capacity of the FEMX-I cells in a dose-dependent manner. Conditioned media prepared from rat and mouse liver, kidney, and spleen tissues either inhibited or had no effect on colony formation. The results suggest that the unexpected differential metastatic patterns observed in vivo may reflect differences in the presence of growth-modulating paracrine factors in the host lungs.
Body weight is more important than family history of hypertension for left ventricular function. Left ventricular function was studied in young men with a positive family history of hypertension for two generations (n = 15). The findings were compared with three control groups: one age-, sex-, and weight-matched group with a negative family history of hypertension (n = 14); one normotensive control group unselected as regards family history of hypertension (n = 27); and one group also unselected regarding family history of hypertension but selected with blood pressure criteria to have mild blood pressure elevation (n = 59). The group with a positive family history of hypertension, in comparison with the normotensive control group, was heavier, had higher blood pressure, increased left ventricular wall thickness, increased left ventricular mass, and signs of changes in diastolic and systolic left ventricular function. There were no differences in these variables between the group with a positive family history and the other two control groups. Data clearly indicated that subjects with a positive family history of hypertension, as well as subjects with mild blood pressure elevation, were heavier than the normotensive control group. It is not possible to judge, with available data, if the changes in left ventricular morphology and function in the two groups with a different family history of hypertension and in the group with mild blood pressure elevation occurred as a physiological response to the increase in afterload or if the neurohormonal and metabolic disturbances leading to the condition of slight overweight also affected left ventricular function.
Noninvasive identification of significant narrowing of the left main coronary artery by dipyridamole thallium scintigraphy. To evaluate the usefulness of dipyridamole thallium scintigraphy with low-level exercise for the identification of left main (LM) coronary artery disease (CAD), 466 consecutive patients with CAD were studied. Thirty-eight patients (8%) had LM stenosis (diameter narrowing greater than or equal to 50%). The LM scintigraphic pattern was present in 9 of 38 patients with LMCAD and 38 of 428 CAD patients without LMCAD (24 vs 9%; p less than 0.005). This pattern was present in 6 of 9 patients with LMCAD without right CAD and in only 3 of 29 patients with LM and right CAD (67 vs 10%; p = 0.0005). Patients with LMCAD had a higher incidence of premature cessation of low-level exercise (53 vs 21%; p less than 0.0001), chest pain (68 vs 48%; p less than 0.02), blood pressure decrease of greater than or equal to 20 mm Hg (44 vs 16%; p less than 0.002) and greater ST depression (0.17 +/- 0.13 vs 0.06 +/- 0.10 mV; p less than 0.001) during dipyridamole loading than patients without LMCAD. Stepwise discriminant analysis revealed that the LM scintigraphic pattern and markers of ischemia during dipyridamole loading best identified (p less than 0.0001) patients with LMCAD without right CAD (sensitivity 67%, specificity 91%), but this predictability is no better than the LM scintigraphic pattern alone. The combination of clinical markers of ischemia during dipyridamole loading and scintigraphic findings of diffuse slow washout, extensive fixed defects and the LM pattern best identified (p less than 0.0001) patients with LM and right CAD (sensitivity 72%, specificity 80%).
Ankle arthrodesis in children. The indications, surgical technique, and long-term functional results for ankle arthrodesis differ between children and adults. In children, the reasons for performing a tibiotalar fusion include pain, most commonly from traumatic and septic arthritis, and instability from congenital anomalies or paralytic disorders. The most appropriate procedure is Chuinard's fusion, which achieves a tibiotalar fusion without causing a growth arrest of the distal tibial growth plate. In the long term, young patients with ankle arthrodesis function very well with minimal pain or disability. Stressful activities such as hill climbing, stair climbing, and running may be restricted or require compensatory movements.
Receptor function in heart failure. In patients with congestive heart failure, down-regulation of beta-adrenoceptors is present, probably as a result of sympathetic overstimulation. In end-stage dilated cardiomyopathy, beta 1-adrenoceptor density is markedly reduced, while beta 2-adrenoceptor density is normal. This latter finding does not necessarily imply normal sensitivity to beta 2-stimulation, due to possible alterations in the beta-adrenoceptor/adenylate cyclase complex beyond the receptor. In some disease states, such as ischemic cardiomyopathy and mitral valve disease, there seems to be a concomitant reduction of the beta 1- and beta 2-adrenoceptor density. The finding of beta-adrenoceptor down-regulation has stimulated the search for novel therapeutic approaches in heart failure patients. Beta-agonists could even further down-regulate beta receptors, and this perhaps explains why they seem not to be useful in long-term use. Agents that directly stimulate adenylate cyclase activity, such as forskolin, or that increase cyclic adenosine monophosphate degradation, such as the phosphodiesterase inhibitors, are being tested. Beta-adrenoceptor blocking agents were used in treatment of heart failure before beta-adrenoceptor down-regulation was recognized in these patients. It is tempting to speculate that the beneficial clinical and hemodynamic effects seen in these patients treated with metoprolol is indeed due to an antagonism of the beta-adrenoceptor down-regulation. Studies testing whether beta-adrenoceptor blocking agents can improve survival in congestive heart failure patients are on-going.