shukoor65/lab-rag-model huggingface dataset:
Dissociation of second messenger activation by parathyroid hormone fragments in osteosarcoma cells. PTH activates multiple second messengers in its target cells, but the level at which the hormonal signal splits into different pathways is still unknown. To achieve insights on this issue, we have studied the structure-function relationship of PTH by analyzing the effects of bovine PTH-(1-34) [bPTH-(1-34)] and PTH fragments truncated at the N-terminus on the intracellular calcium concentration [( Ca2+]i) and cAMP production in the rat osteogenic sarcoma cell line UMR 106-01. [Ca2+]i was measured in single cells using fura-2. When exposed to 10(-7) M bPTH-(1-34), 20% of the cells responded with a transient increase in [Ca2+]i of variable amplitude. Equimolar doses of bPTH-(2-34), propionyl bPTH-(2-34) [(pbPTH-(2-34)], and bPTH-(3-34) also transiently increased [Ca2+]i, whereas both [tyrosine34]bPTH-(7-34) amide [bPTH-(7-34)] and bPTH-(30-34) were ineffective. The amplitude of the [Ca2+] i transients was dose-dependent, with threshold concentrations of 10(-10) M for bPTH-(1-34) and bPTH-(2-34), and 10(-9) M for bPTH-(3-34). The response rate to the active peptides ranged between 10-30%, without a clear dose-relatedness. A second addition of 10(-7) M bPTH-(1-34) to cells prestimulated with equimolar doses of bPTH-(2-34), pbPTH-(2-34), or bPTH-(3-34) produced another transient, whereas after exposure to 10(-7) M bPTH-(1-34), the cells were completely desensitized to a second homologous stimulation, suggesting that the binding affinity of the truncated peptides for the PTH receptor is lower than that of the intact bPTH-(1-34) fragment. In addition, both bPTH-(1-34) and bPTH-(2-34) dose-dependently stimulated cAMP production, but the former was more potent (ED50 = 10(-9) vs. 10(-7) M, respectively). On the contrary, pbPTH-(2-34), bPTH-(3-34), and bPTH-(7-34) had no effect on cAMP. Pretreating the cells with pertussis toxin to enhance cAMP responses via inhibition of Gi potentiated the effect of bPTH-(1-34) and bPTH-(2-34) and disclosed weak but detectable agonist action of pbPTH-(2-34). These results indicate that specific domains of the PTH molecule are linked to activation of different second messenger pathways; while the first two amino acids are indispensable for activating the cAMP system, generation of the [Ca2+]i signal appears to involve a longer domain, including the amino acid residue in position 3.
Molecular evaluation of response to all-trans-retinoic acid therapy in patients with acute promyelocytic leukemia. The advent of retinoic acid (RA) in the treatment of acute promyelocytic leukemia (APL) has led to a high frequency of short-lasting complete remissions (CR). We studied the response to RA by molecularly analyzing the RA receptor alpha (RAR alpha) locus, which has recently been shown to be rearranged in all APLs. Southern blot analysis demonstrated that the RAR alpha rearrangements persisted in the APL samples containing maturing myeloid cells 2 to 3 weeks after the start of RA treatment, but disappeared after 5 to 8 weeks, when the patients achieved CR. Our investigations provide clear evidence that CR occurs at molecular level and that there is reconstitution of an apparently normal, nonclonal hematopoiesis. Further, it shows that RA acts by triggering differentiation rather than by exerting a cytotoxic effect on the leukemic clone.
The role of intraluminal radiotherapy and concurrent 5-fluorouracil infusion in the management of carcinoma esophagus: a pilot study. Fifty patients with carcinoma of the esophagus were entered in a randomized pilot study to test the efficacy of intraluminal radiotherapy (ILRT) and concurrent 5-fluorouracil (5-FU) infusion. The median age was 65 years, with 80% having middle third lesions; in 62%, the lesions were longer than 5 cm. After external beam therapy of 50 Gy in 5 weeks, patients were randomized to receive chemotherapy. Significant improvement in dysphagia was recorded in 76% patients with complete response in 47 cases ranging from 6 to 27 months. The overall survival at 2 years was 15% with ILRT alone versus 22% with ILRT plus 5-FU infusion.
From tissue angiotensin converting enzyme inhibition to antihypertensive effect. The renin-angiotensin system (RAS) has long been regarded as a classical hormonal system, with angiotensin II (ANG II) being the circulating effector peptide. In recent years, evidence for additional RAS in various organs, including vascular wall, kidney, adrenal gland, heart, and brain, has been obtained. Drugs interfering with the RAS such as the converting enzyme (CE) inhibitors may, therefore, not only inhibit the plasma RAS but also inhibit these tissue RAS. Such a "tissue" RAS inhibition has been repeatedly demonstrated in animal experiments, and in some cases it correlated better with the cardiovascular actions of the CE inhibitors than did inhibition of plasma RAS. In the vascular wall, a local inhibition of ANG II synthesis may contribute not only to the reduction of vascular tone but also to the marked regression of media hypertrophy seen after CE inhibitor treatment. Vascular ANG II generation by CE appears to occur almost exclusively at the luminal surface of the endothelium. Locally formed ANG II may then contribute to the pool of circulating ANG II (endocrine ANG II) or feed back to adjacent cells without being transported by the blood (paracrine ANG II). Thus, CE inhibitors may not have to penetrate into deeper layers of the vascular wall to inhibit the vascular RAS, but may rather prevent the paracrine actions of locally generated ANG II.
Effect of clean intermittent catheterisation on radiological appearance of the upper urinary tract in children with myelomeningocele. Of the 102 consecutive children with myelomeningocele who were treated by intermittent catheterisation between 1977 and 1985, 89 were investigated with regard to the development of the upper urinary tract. The median follow-up period was 6.7 years. Dilatation and vesicoureteric reflux were assessed by means of repeated urography and voiding cystourethrography. Of the 49 children with normal radiology at the start of catheterisation, all but 2 remained normal. In 27 with isolated dilatation of the upper urinary tract or reflux at the start, 17 subsequently became normal. Dilatation together with reflux was seen in 13 patients at the start; 3 became normal, 4 still had reflux and in 6 patients both dilatation and reflux persisted. Intermittent catheterisation thus had a positive effect on the upper urinary tract in the vast majority of cases. In children with both dilatation and reflux, however, there is a risk of deterioration and they should be followed up closely.
Helicobacter pylori-negative duodenal ulcer. Most patients with chronic duodenal ulcer (DU) craters have gastritis associated with Helicobacter pylori (HP), now thought to be the major cause of DU. A smaller proportion of DU patients have no detectable HP. In this study, we examined the frequency and causes of HP-negative duodenal ulcers. In 302 consecutive patients with endoscopic diagnosis of duodenal ulcer, 284 (94%) were found to have associated HP gastritis, whereas 18 (6%) were HP-negative on histology, culture, and urease test. The largest subgroup of HP-negative patients (8/18) was made up of those who had been taking nonsteroidal antiinflammatory drugs (NSAIDs), followed closely (4/18) by patients with recent intake of antibiotics. Causes of DU in the remaining subgroups included two patients with duodenal Crohn's disease, two with Gastrospirillum hominis infection, one with penetrating carcinoma of the pancreas and one with no detectable cause. We conclude that, although the most common causal factor of duodenal ulcer is HP, some 6% of DU's will be HP-negative, signaling unusual etiology. It is now important to identify the cause of duodenal ulcer so as to initiate appropriate therapy.
Neurosarcoidosis--demonstration of meningeal disease by gadolinium enhanced magnetic resonance imaging. Arriving at a firm diagnosis of neurosarcoidosis continues to pose serious problems, particularly when evidence of granulomatous disease outside the nervous system is lacking. The commonest mode of presentation of neurosarcoidosis is with cranial nerve palsies. Two cases of presumed neurosarcoidosis with cranial nerve palsies showed clear evidence of focal meningeal disease on gadolinium-DTPA enhanced MRI brain scans. Although not specific for sarcoidosis, this technique may be very useful in aiding the diagnosis in suspected cases.
Interrelationship between histopathologic characteristics of melanoma and estrogen receptor status. To evaluate whether the increase in disease-free survival and survival previously reported for women with melanomas with estrogen receptors (ER) was a reflection of the histopathology of the primary melanoma, the interrelationship of histopathologic characteristics of 143 patients with such tumors was examined. The ER was assayed in the primary tumor from 44 patients and in 99 metastatic deposits from the other patients. Tumor thickness, level of invasion, prognostic index, mitoses/mm2, ulceration, vascular invasion, necrosis, histologic grade, preexisting nevus, and predominant malignant cell type were examined. There was no relationship between ER presence and any histopathologic characteristic examined, irrespective of the tumor source (primary or metastatic). Examination of histopathologic characteristics as a function of sex and receptor status showed a slight but insignificant predominance of more well-differentiated, thinner tumors in women whose lesions were positive for the ER. These results suggest that the increased disease-free survival in patients with ER-positive lesions is not attributable to the pathologic characteristics of the primary tumor examined during this study.
Benign positional vertigo: incidence and prognosis in a population-based study in Olmsted County, Minnesota. A retrospective review of our population-based medical records linkage system for residents of Olmsted County, Minnesota, revealed 53 patients (34 women and 19 men; mean age, 51 years) with newly diagnosed benign positional vertigo in 1984. The age- and sex-adjusted incidence was 64 per 100,000 population per year (95% confidence interval, 46 to 81 per 100,000). The incidence of benign positional vertigo increased by 38% with each decade of life (95% confidence interval, 23 to 54%). One patient had an initial stroke during follow-up; thus, the relative risk for new stroke associated with benign positional vertigo was 1.62 (95% confidence interval, 0.04 to 8.98) in comparison with the expected occurrence based on incidence rates for an age- and sex-adjusted control population. The observed survival among the 53 Olmsted County residents with benign positional vertigo diagnosed in 1984 was not significantly different from that of an age- and sex-matched general population. Patients with benign positional vertigo seem to have a good prognosis.
Update: drug therapy for acute myocardial infarction. Acute myocardial infarction is potentially a highly treatable disease. Immediate interventions are directed to decreasing tissue hypoxia with oxygen and improving bloodflow to ischemic myocardium using nitrates and thrombolytic agents. Cardiac workload should be reduced by eliminating endogenous catecholamine release with analgesia and sedation, and beta blockade in patients without CHF to decrease heart rate and myocardial oxygen demand. Treatment of the complications of AMI include dysrhythmia prophylaxis, monitoring and specific therapy. Treatment of pump failure includes using vasodilators, vasopressors and positive inotropic agents. Early recognition and timely initiation of appropriate therapy should be every physician's goal.
Optic nerve sheath decompression for nonarteritic ischemic optic neuropathy improves multiple visual function measurements. Optic nerve sheath decompression was performed in seven patients with nonarteritic anterior ischemic optic neuropathy. Visual function was evaluated by measurement of visual acuity with standardized Early Treatment Diabetic Retinopathy Study charts, color vision testing, quantitation of relative afferent pupillary defects with neutral-density filters, and Goldmann and Humphrey perimetry. Visual acuity improved markedly in all patients (at least doubling of the visual angle); the peripheral visual field expanded by at least 20 degrees (as measured by Goldmann perimetry) in six patients. Three patients also experienced marked improvement in color vision, relative afferent pupillary defect, and foveal sensitivity. Our experience supports the possible beneficial effect of optic nerve sheath decompression in patients with nonarteritic anterior ischemic optic neuropathy.
On the mechanisms of ventricular tachycardia acceleration during programmed electrical stimulation. BACKGROUND. The pathophysiological mechanisms leading to acceleration of ventricular tachycardia (VT) are still unclear. METHODS AND RESULTS. High-resolution epicardial mapping was used to study the mechanisms of VT acceleration by programmed electrical stimulation (PES) in a model of sustained reentrant VT in Langendorff-perfused rabbit hearts (n = 40). Three different mechanisms responsible for acceleration of VT were identified: 1) induction of double-wave reentry (n = 6), defined as the occurrence of two successive activation waves circulating in the same direction in the same circuit; 2) change to a functionally determined circuit (n = 4), defined as reentry of the impulse around a functional line of block without involvement of a fixed obstacle; and 3) change of the reentrant circuit to reentry within a different, faster anatomic pathway (n = 3). Analysis of 81 episodes of sustained monomorphic VT induced by PES in 74 patients with clinically documented sustained VT in the setting of chronic coronary artery disease showed that in 22 episodes VT was suddenly accelerated by PES (mean cycle length, from 345 +/- 73 to 277 +/- 71 msec, p less than 0.01). CONCLUSIONS. With the observations made in the experimental model, the following tentative classification of the mechanisms of VT acceleration of the 22 episodes was made: 1) induction of double-wave reentry in two, 2) change to a functionally determined circuit in four, and 3) change to reentry within a faster anatomic circuit in 16. Simple criteria suggest that these mechanisms may apply in the clinical situation.
Nutrition: its relationship to orthopedic infections. The malnutrition of orthopedic surgical patients plays an important role in the development of complications, including infection. A high index of suspicion that malnutrition exists or will soon exist in patients who are subjected to significant stress, trauma, or surgery will lead the clinician to take measures to avoid further protein calorie deficits and replenish the patient's nutritional needs. There are many pathways in which malnutrition causes a propensity for infection, and these have been discussed. Meeting the patient's nutritional needs should avoid some of the complications of infections in orthopedic surgery.
Tissue oxygenation in hemorrhagic shock measured as transcutaneous oxygen tension, subcutaneous oxygen tension, and gastrointestinal intramucosal pH in pigs BACKGROUND AND METHODS: Tissue oxygenation, measured in peripheral tissue as transcutaneous PO2 (PtCO2) and subcutaneous PO2, was compared with the oxygenation in GI mucosa, which was measured as intramucosal wall pH (pHi), during experimental hemorrhagic shock and resuscitation in pigs. The pigs were hemorrhaged stepwise to a BP of 80 and 45 mm Hg, followed by retransfusion. PtCO2 was measured in the groin and subcutaneous PO2 was measured in the hip region. Intraluminal PCO2 was measured in the stomach, in the small intestine, and the sigmoid colon using silicone catheters. A simultaneous determination of arterial blood HCO3 concentration allowed pHi to be calculated using Henderson-Hasselbalch equation. Cardiac output was determined by thermodilution, and oxygen delivery (DO2) was calculated. RESULTS: Early indications of shock were decreases in PtCO2 and intestinal pHi (p less than .01). All measured variables decreased at the second step of bleeding. PtCO2 and subcutaneous PO2 was correlated to DO2 through the entire experiment (r2 = .25 and .49, respectively). Also, the pHi of the small intestine and the sigmoid colon correlated with DO2 (r2 = .36 and .25, respectively). PtCO2 and subcutaneous PO2 correlated with pHi in the small intestine and sigmoid colon. CONCLUSIONS: PtCO2 and pHi in the small intestine and sigmoid colon were the variables that most rapidly indicated blood volume loss. Subcutaneous PO2 and PtCO2, and small intestine and sigmoid colon pHi were correlated to total body oxygen transport. Peripheral tissue perfusion followed intestinal perfusion to some extent.
Mechanical cardiac valvular prostheses. Mechanical cardiac valvular prostheses currently enjoy a 60% to 40% market-share advantage over tissue prostheses in the United States and worldwide. Only the Starr-Edwards caged Silastic (Dow Corning) ball, Medtronic-Hall, St. Jude Medical, and Omniscience valves remain available in the United States. Although each valve has certain advantages and disadvantages, no design has achieved functional mechanical perfection. Late follow-up of valve-related complications from the literature favors the St. Jude Medical and Medtronic-Hall valves.
Sudden death due to disease flare with luteinizing hormone-releasing hormone agonist therapy for carcinoma of the prostate. Luteinizing hormone-releasing hormone agonist therapy for prostate cancer is a new method of management for metastatic disease. During the initial 1 to 2-week period of administration an increase in serum testosterone concentration can lead to an exacerbation of clinical symptoms (flare phenomenon). Two patients are summarized who received luteinizing hormone-releasing hormone agonist therapy without flare blockade and died suddenly during month 1 of therapy. A review of 765 patients in 9 series found 10.9% who suffered disease flare and 15 who died during disease flare. Of these 17 patients 12 were similar to our 2. These data suggest that any patient placed on luteinizing hormone-releasing hormone agonist therapy for prostate cancer merits some form of flare blockade during the initial 1 or 2 months of therapy.
A nurse-managed special care unit. The authors describe the first year of operation of a nurse-managed intensive care unit (ICU). Concerned with the problems, costs, and inadequacies of caring for long-term patients in traditional ICUs, nurse administrators designed a special care unit that incorporates a physical design facilitating family involvement and rehabilitative care, registered nurse case management, and a shared governance management philosophy. Compared with traditional ICUs, the effectiveness of the special care unit is tested in terms of patient and nurse outcomes. Implications of this innovation for health-care delivery systems and the nursing profession are discussed.
Resting energy expenditure in chronic cardiac failure. 1. Resting energy expenditure has previously been shown to be elevated in the acute phase of heart failure, but the situation in the compensated state of chronic cardiac failure is unclear. Resting energy expenditure was assessed in 14 patients with stable chronic cardiac failure and 14 matched control subjects by using indirect calorimetry. 2. Resting energy expenditure was significantly elevated in the patients with chronic cardiac failure (112.6 +/- 18.1 versus 87.1 +/- 12.2 kJ day-1 kg-1 total body weight, P less than 0.0002; mean +/- SD) as were resting O2 consumption (3.88 +/- 0.64 versus 3.00 +/- 0.43 ml min-1 kg-1, P less than 0.0002), ventilation (164 +/- 40.3 versus 104 +/- 16.2 ml min-1 kg-1, P less than 0.0001) and heart rate (85.8 +/- 16.9 versus 66.6 +/- 6.9 beats/min, P less than 0.001). Both the resting plasma concentration of noradrenaline (4.48 +/- 1.52 versus 2.28 +/- 0.96 nmol/l, P less than 0.0001) and the serum concentration of free fatty acids (0.78 +/- 0.21 versus 0.57 +/- 0.27 mmol/l, P less than 0.03) were greater in the patients with chronic cardiac failure. Analysis of covariance indicated that most of the difference in resting energy expenditure could be accounted for by the elevated ventilation in the patients with chronic cardiac failure. Arm muscle area, an index of wasting, was lower in the patients with chronic cardiac failure (39.1 +/- 13.1 versus 50.5 +/- 9.4 cm2, P less than 0.02) and resting energy expenditure was found to account for some of this difference. 3. We conclude that an elevated basal metabolism occurs in chronic cardiac failure.
Complication of a penile prosthesis reservoir: venous compression masquerading as a deep venous thrombosis. We report a case of vascular compromise secondary to the reservoir of an inflatable penile prosthesis. The problem masqueraded as deep venous thrombosis in the lower extremity of a patient 3 years after a spinal cord injury.
Choledocholithiasis in acute gallstone pancreatitis. Incidence and clinical significance. A prospective study of choledocholithiasis was performed using 110 patients with presumptive diagnoses of acute gallstone pancreatitis. The incidence of migrating and persistent bile duct stones was determined using stool screening and intraoperative cholangiography, and the clinical significance of continued stone obstruction of the papilla was investigated using ultrasound assessment of migration time and a second evaluation of prognostic signs. Pancreatic inflammation was confirmed at surgery in 51 patients, of whom only 27 had stones in the stools (n = 22) or the bile duct (n = 5), suggesting that choledocholithiasis may not be the sole triggering factor of acute gallstone pancreatitis. Neither delayed migration nor persistent stone obstruction of the papilla promoted pancreatic inflammation.
A temperature-dependent rabbit model for production of dermal lesions by Haemophilus ducreyi. The fact that optimal in vitro growth of Haemophilus ducreyi occurs at 33 degrees C prompted evaluation of the effect of temperature on the ability of this organism to produce skin lesions in rabbits after intradermal inoculation. Animals housed at a reduced ambient temperature (15-17 degrees C) consistently developed necrotic lesions when injected intradermally with 10(5) cfu of H. ducreyi; this inoculum did not produce necrotic lesions in animals housed at normal room temperature (23-25 degrees C). Lesion production in this new model was dependent on both viability of the H. ducreyi inoculum and replication of these organisms after intradermal injection. Histopathologic examination of the lesions revealed that H. ducreyi infection of the rabbit dermis evolves from an acute inflammatory reaction to abscess formation. Evaluation of three additional strains of H. ducreyi in this model confirmed that lesion formation was not bacterial strain-dependent. This new temperature-dependent rabbit model for productive H. ducreyi infection will facilitate investigation of the molecular pathogenesis of chancroid.