shukoor65/lab-rag-model huggingface dataset:
Tonic pain perception in the mouse: differential modulation by three receptor-selective opioid agonists. The proposition that tonic nociception models are more analogous to clinical pain than traditional acute models prompted our previous development of a modified mouse paw formalin test. To discern possible modulatory roles and site(s) of action of endogenous opioid systems, the receptor-preferring agonists sufentanil (mu), U-50,488H (kappa) and [D-Pen2,5]enkephalin (DPDPE, delta) were evaluated for antinociceptive activity in the formalin paradigm by systemic (except DPDPE), spinal and supraspinal routes. All observations were done under blind conditions. Doses causing overt behaviors that indicated a breach of receptor specificity (during the observation period) were rejected. Higher doses of centrally administered DPDPE (greater than 0.3 micrograms/mouse, intrathecal; greater than 3 micrograms/mouse, intracerebroventricular) induced a behavioral syndrome traditionally associated with mu agonism, and thus were not considered for this study. A50 values from behaviorally acceptable dose ranges for mean percent analgesia (reduction of paw licking compared to controls) were: trans-(+/- )-3,4-dichloro-N-methyl-N-[U-50,488H 2-pyrrolidinyl)cyclohexyl]-benzeneacetamide methanesulfonate,U-50,488H--3200 nmol/kg, subcutaneous, 1100 nmol/kg, intrathecal and 314 nmol/kg, intracerebroventricular; sufentanil--11.1 nmol/kg, subcutaneous, 8.6 nmol/kg, intrathecal; and DPDPE--inactive. On the basis of our dose-response data, we suggest that, in mice, kappa and mu, but not delta, opioid receptors modulate tonic pain perception at both spinal and supraspinal loci. The results also support inclusion of the modified formalin test in preclinical evaluations of potential kappa agonists.
Myocardial infarct size reduction by the synergistic effect of hyperbaric oxygen and recombinant tissue plasminogen activator. Fasting mongrel dogs underwent hyperbaric oxygen treatment (HBOT), recombinant tissue plasminogen activator (rt-PA) treatment, and simultaneous HBOT and rt-PA treatment following prior experimental left anterior descending coronary artery occlusion for 2 hours. Thrombosis in and around a copper coil was recorded angiographically at regular intervals, and immediately prior to treatment conclusion. Controls (n = 10) were untreated. Group two animals (n = 10) were treated additionally with 90 minutes of HBOT at 2 atm absolute. Group three animals (n = 8) were treated additionally with 50 mg rt-PA over 90 minutes. Group four animals (n = 10) were treated additionally with simultaneous HBOT and rt-PA over 90 minutes. Myocardial injury was determined by a combination of triphenyltetrazolium chloride histochemical staining and by formazan dye extraction. Damage was measured as a percent of left ventricular cross-sectional area studied. HBOT alone restored 35.9% of oxidative enzyme activity (p greater than 0.001). Treatment with rt-PA alone restored 48.9% of enzyme activity (p greater than 0.001). The combination of HBOT and simultaneous rt-PA resulted in 96.9% restoration of oxidative enzyme activity versus the control group (p greater than 0.001).
Sequence variations in the 5' flanking and IVS-II regions of the G gamma- and A gamma-globin genes of beta S chromosomes with five different haplotypes. We have amplified and sequenced the 5' flanking and the second intervening sequence (IVS-II) regions of both the G gamma- and A gamma-globin genes of the beta S chromosomes from sickle cell anemia (SS) patients with homozygosities for five different haplotypes. The sequencing data, compared with previously published sequences for the normal chromosomes A and B, show many similarities to chromosome B for haplotypes 19, 20, and 17, while haplotypes 3 and 31 are remarkably similar to chromosome A and also similar to each other. Several unique mutations were found in the 5' flanking regions (G gamma and A gamma) of haplotypes 19 and 20 and in the IVS-II segments of the same genes of haplotypes 19, 20, and 17; the IVS-II of haplotypes 3 and 31 were identical to those of chromosome A. Dot-blot analyses of amplified DNA from additional SS patients with specific probes have confirmed that these mutations are unique for each haplotype. The two general patterns that have been observed among the five haplotypes have most probably arisen by gene conversion events between the A and B type chromosomes in the African population. These patterns correlate with high and low fetal hemoglobin expression, and it is speculated that these and other yet unknown gene conversions may contribute to the variations in hemoglobin F and G gamma levels observed among SS patients. In vitro expression experiments involving the approximately 1.3-kb 5' flanking regions of the G gamma- and A gamma-globin genes of the beta S chromosomes with the five different haplotypes failed to detect differences between the levels of expression, suggesting that the sequence variations observed between these segments of DNA are not the primary cause of the differences in hemoglobin F levels among the SS patients.
Left ventricular regional wall motion assessment by radionuclide ventriculography: a comparison of cine display with Fourier imaging Radionuclide ventriculography and contrast ventriculography were performed in two comparable projections on 50 patients with suspected coronary artery disease. The efficacy of conventional cine display and Fourier image analysis of the radionuclide ventriculogram was compared using contrast ventriculography as the gold standard. Of seven different combinations of Fourier images, the combination of left anterior oblique amplitude and phase and left posterior oblique amplitude and phase provided the highest sensitivity (87%), specificity (83%), accuracy (86%), and kappa coefficient (0.64). To increase statistical power, segment data were collapsed to global data in which a heart was considered normal if all segments were normal and abnormal if one or more segments were abnormal. Fourier images had higher sensitivity (Fourier 87%, cine 47%); lower specificity (Fourier 83%, cine 92%), higher accuracy (Fourier 86%, cine 58%), and higher kappa coefficient (Fourier 0.64, cine 0.25), and these differences were statistically significant (p less than 0.01).
Variable histotoxicity of histoacryl when used in a subcutaneous site: an experimental study. Histoacryl (butyl-2-cyanoacrylate) is one of the least histotoxic cyanoacrylate derivatives and is used as a tissue adhesive. Clinical applications primarily include skin closure (blepharoplasty incisions, etc.). In a recent study, we demonstrated that Histoacryl elicits minimal histotoxicity when used to glue bone grafts to rabbit-ear cartilage. Acute inflammation was limited to areas where Histoacryl escaped from between the bone graft and ear cartilage to contact well-vascularized soft tissue. In this study, Histoacryl was applied between bone graft and cartilage in one rabbit ear and adjacent to well-vascularized soft tissue with no graft in the opposite ear. Histologic analysis revealed minimal if any inflammation when small amounts of glue was used in the nonvascular region between bone graft and cartilage. However, subcutaneous implantation contacting well-vascularized soft tissue resulted in increased acute inflammation and prolonged foreign-body giant-cell response. Further studies are required to rule out any long-term problems associated with subcutaneous implantation of Histoacryl.
Stroke and hypertension and its prevention. Systolic and diastolic hypertension in both men and women is a well-established risk factor for the development of ischemic and hemorrhagic stroke. Antihypertensive treatment decreases the risk, but questions remain as to the precise level of hypertension to be treated, whether the effects of antihypertensive treatment are blunted with increasing age, and the best type of antihypertensive drug or combination of drugs to be used. Further questions remain concerning the incidence of pseudohypertension and the potentially harmful effects of its treatment on the brain, and the possibility that fluctuations in blood pressure may be worse than elevation alone. A pragmatic approach would be to treat hypertension with vigor in the young, with caution in the mature, and with reluctance in the old.
Management options in fulminant hepatic failure. The diagnosis of FHF carries with it a high mortality rate. Though the early results of OLT for FHF are encouraging, some have called for caution as these results are in a select population and may be similar to the optimistic early reports of now-discredited therapies. However, OLT differs fundamentally from all other interventions and, as such, it is ethically unjustified to withhold potentially life-saving therapy from patients with a predicted mortality in excess of 60%. Therefore, patients with FHF should be transferred at an early stage to an experienced liver unit where the option of liver transplantation can be considered.
Predictors of relapse into major depressive disorder in a nonclinical population. OBJECTIVE: This study sought to describe, the natural history of major depressive disorder in a large group of nonclinical subjects. In particular, the analysis determined demographic and clinical risk factors for the recurrence of major depressive disorder. METHOD: Relatives, comparison subjects (matched to relatives for age and sex), and spouses of affectively ill probands underwent structured clinical assessments before and after a 6-year interval. RESULTS: Of 396 individuals who had had only major depressive disorder that ended before the initial evaluation, 33.8% (N = 134) developed a new episode during the 6-year follow-up period. Youth, but not sex, was an important demographic risk factor. The presence of minor depression at the time of initial evaluation and the number of symptoms recalled from the worst previous episode were additional clinical risk factors. At the initial evaluation, 200 other subjects had described a previous history of both major depressive disorder and a nonaffective mental disorder. When compared to the subjects who recalled only a history of major depressive disorder, these subjects were more likely to have been in an episode of chronic intermittent depression at the initial evaluation and to recall a greater number of episodes as well as a greater number of symptoms in the worst episode. A history of a nonaffective mental disorder significantly increased the risk of relapse into major depressive disorder. CONCLUSIONS: These findings agree well with a recent review of clinically based follow-up studies. Thus, youth and a history of nonaffective illness are important risk factors for the recurrence of major affective disorder in a broad variety of settings.
Postoperative epidural morphine is safe on surgical wards. The use of epidural morphine for postoperative analgesia outside of intensive care units remains controversial. In this report our anesthesiology-based acute pain service documents experience with 1,106 consecutive postoperative patients treated with epidural morphine on regular surgical wards. This experience involved 4,343 total patient days of care and 11,089 individual epidural morphine injections. On a 0-10 verbal analog scale, patient-reported median pain scores at rest and with coughing or ambulation were 1 (inter-quartile range 3) and 4 (interquartile range 4), respectively. The incidence of side effects requiring medication were as follows: pruritus 24%, nausea 29%, and respiratory depression 0.2%. There were no deaths, neurologic injuries, or infections associated with the technique. Migration of epidural catheters into the subarachnoid space and into epidural veins each occurred twice. Overall, 1,051 of the 1,106 patients (95%) experienced none of the following problems: catheter obstruction, premature dislodgement, painful injections, catheter migration, infection, or respiratory depression. We conclude that postoperative pain can be safely and effectively treated with epidural morphine on surgical wards.
Frequency of deep venous thrombosis in asymptomatic patients with coronary artery bypass grafts. The frequency of deep vein thrombosis (DVT) in patients undergoing coronary artery bypass graft (CABG) surgery has not been established. Therefore to estimate the frequency of clinically silent DVT, we performed ultrasound examinations of the leg veins in 29 asymptomatic CABG patients before hospital discharge. We used high-resolution B-mode ultrasonography with color Doppler imaging. Fourteen (48.3%, 95% confidence interval 30.1 to 66.4%) had 20 documented leg vein thromboses, and all but one patient had DVT limited to the calf veins. Of the 20 thrombi 10 (50.0%) were present in the leg ipsilateral and 10 (50.0%) in the leg contralateral to the saphenous vein harvest site. None of the DVTs were suspected clinically. DVT was not associated with any local sign attributed to saphenous vein harvest such as pitting edema, incisional drainage, or local tenderness or with any putative risk factor for DVT such as cigarette use, distant history of malignancy, or varicose veins. Follow-up of these patients 5 to 11 months after CABG surgery showed no clinical evidence of DVT or pulmonary embolism. Our findings indicate that asymptomatic DVT of the calf occurs with surprisingly high frequency, 44.8% after CABG surgery. Future studies in patients undergoing CABG surgery should address the natural history of asymptomatic DVT, determine its clinical importance, and develop optimal strategies for prophylaxis and treatment.
Expansion of immature thymic precursor cells in peripheral blood after acute marrow suppression. Leukemoid reactions occur in response to a number of infectious agents and sometimes may be associated with bone marrow suppression. After acute suppression of the bone marrow, a resurgent hyperplasia occurs that may appear as synchronous maturation of a single cell type. The authors describe the case of a 13-year-old child in whom a remarkable lymphocytosis developed during a period of pancytopenia associated with a febrile syndrome resembling Ehrlichiosis. Most of these lymphoid cells were morphologically similar to large granular lymphocytes (LGLs), but many appeared to be less mature. Immunophenotypic studies demonstrated most of these lymphoid cells to be immature T cells at an "intermediate" or "transitional" stage of thymocyte differentiation characterized by the CD1-CD3+CD4-CD8- phenotype, as well as positivity for nuclear terminal deoxynucleotidyl transferase. In T-cell ontogeny, this stage represents a transition between thymic precursors and mature thymocytes. Their presence in the peripheral blood of this child is thought to represent a lymphocytic leukemoid response to his infection. Cases such as this may be confused with malignancy.
Preventing upper gastrointestinal bleeding in patients receiving nonsteroidal antiinflammatory drugs. Severe upper gastrointestinal (GI) bleeding is a serious adverse effect of nonsteroidal antiinflammatory drugs (NSAIDs) and the elderly are at increased risk of developing this complication. Bleeding episodes can be prevented. Replacing NSAIDs with acetaminophen may be appropriate when a simple analgesic is needed that eliminates the risk of GI bleeding. Using the lowest effective NSAID dose may decrease the incidence and severity of NSAID gastropathy. Histamine H2-receptor antagonists, sucralfate, and misoprostol have been studied for the prevention of NSAID gastropathy, but only misoprostol prevents mucosal injury in both the stomach and duodenum. Patients who have a history of peptic ulcer disease or gastric bleeding from NSAIDs are candidates for prophylactic measures. Although other patients are at risk, no one knows who should receive prophylactic therapy for NSAID gastropathy. Future studies should attempt to define patient populations that warrant prophylactic therapy.
An analysis of ten-year trends in infections in adults on continuous ambulatory peritoneal dialysis (CAPD). Infectious complications are the Achilles heel of CAPD. To determine trends in these events, we analyzed the CAPD related infections of 303 adults on CAPD at a single university center between 1979 and 1989. During this decade the percentage of insulin-dependent diabetics increased from 14% to 39% (p less than 0.005). Peritonitis rates fell from 2.4 episodes/y in 1979 to 0.8 episodes/y in 1989. The proportion of patients with multiple episodes of peritonitis decreased (40% of the patients in 1979-1982 vs 15% in 1983-1989, p = 0.0001) while the proportion of patients with no episodes of peritonitis increased during the same periods (29% vs 49%, p = 0.005). The proportion of peritonitis episodes due to S. aureus rose over the 10-year period (p = 0.005), while those due to S. epidermidis decreased (p less than 0.10). The overall incidence of S. aureus peritonitis remained unchanged. Catheter infection rates initially increased and then fell during the decade; S. aureus remained the predominant cause. The proportion of peritonitis episodes associated with catheter infection rose (13% in 1982 vs 24% in 1989, p = 0.025), and in 1989, 80% of these episodes were caused by S. aureus. Catheter loss was also primarily due to S. aureus infections in 1989 (80%). Infections due to P. aeruginosa were a persistent problem. The proportion of patients transferring to hemodialysis each year paralleled catheter loss rates, which in turn appeared to be more related to catheter infection rates than to peritonitis rates. We conclude that control of S. aureus and P. aeruginosa will be the key to future reductions in the infectious complications of CAPD patients.
The silence: the asbestos industry and early occupational cancer research--a case study. To gain insight into corporate activities regarding the identification of occupational carcinogens earlier in this century, the actions of one industry, the asbestos industry, were reviewed. This industry, in concert with many of its insurers, systematically developed and then suppressed information on the carcinogenicity of asbestos. The development of warnings for those exposed to the asbestos was delayed. As a result, millions of workers were exposed to the carcinogen and hundreds of thousands died. These events are placed into the context of similar activities in other industries during this time.
Coronary artery bypass grafting in the octogenarian. We have performed coronary bypass grafting in 25 patients 80 years of age or more. The patients' preoperative conditions were characterized by recent myocardial infarction (16/25, or 64%), obesity (15/25, or 60%), hypertension (14/25, or 56%), and left ventricular dysfunction (21/25, or 84%). There were no deaths in the hospital or within 30 days of operation (0/25, or 0%). Postoperative complications occurred in five cases (20%). Complications were leg incision infection (2/25, or 8%), urinary tract infection (1/25, or 4%), stroke (1/25, or 4%), and transient neurologic deficit (1/25, or 4%). There were no instances of reoperation for bleeding, perioperative myocardial infarction, renal failure, pulmonary failure, intraaortic balloon pump use, or sternotomy infection in these patients. Eleven patients (44%) were hospitalized for fewer than 10 days after operation, and all but two (23/25, or 92%) were discharged within 20 days after operation. All patients were followed up, and survival and New York Heart Association functional class were determined. Cumulative survival rate was 94% at 1 year and 88% at 5 years. The cumulative percent survival rate with class I or II function was 92% at 1 year and 80% at 5 years. No patient had recurrent angina.
Myocardial oedema and ventricular function after cardioplegia with added mannitol. Myocardial oedema may contribute to the impaired myocardial performance which commonly follows open heart surgery with cardioplegia-induced cardiac arrest. The rate of oedema formation during crystalloid cardioplegia and the relation of this to changes in ventricular compliance and ventricular function following reperfusion were studied using an isolated rabbit heart preparation. Myocardial tissue water content increased during cardioplegic arrest and the water content prior to reperfusion demonstrated an inverse correlation with ventricular function after reperfusion. In further studies the effect of adding mannitol to a standard crystalloid cardioplegic solution was investigated. The preparations were divided into two groups: nine were administered a standard cardioplegic solution (Plegisol*) (control group) and a further eight were administered the same solution mixed with mannitol to adjust the osmotic pressure to 360 mOsmol.L-3 (mannitol group). The mannitol group demonstrated less increase in RV water content and superior LV dP/dtmax following reperfusion. It is concluded that mannitol enhances protection of the myocardium during cardioplegic cardiac arrest.
Sternohyoid muscle biopsy. A diagnostic technique in respiratory failure of neuromuscular origin. Patients with neuromuscular disease may develop respiratory failure requiring mechanical ventilation. We describe a sternohyoid muscle biopsy technique as a diagnostic aid in such patients undergoing tracheostomy for prolonged ventilatory support. The biopsy procedure is quick and without added discomfort or morbidity for the patient. Our preliminary observations in three patients suggest that the sternohyoid muscle biopsy may be a useful diagnostic tool in this selected group of patients.
Mechanical complications associated with mentor inflatable penile prosthesis. The Mentor inflatable penile prosthesis was developed in an attempt to decrease the mechanical failure rate of the various prostheses' components. We herein report on the reliability of the device in 46 men implanted with the Mentor device from December 1982 to June 1987. Prior to manufacturer device modification in 1985, mechanical failure mainly attributable to input tubing cracks occurred in 10 of 30 implantations. Since device improvement in April 1985, the mechanical failure rate has decreased to 4 percent. The Mentor inflatable penile prosthesis has been a mechanically reliable device since design improvement in 1985.
Pituitary hormone response to thyrotropin-releasing hormone in secondary amenorrheic women associated with simple weight loss. OBJECTIVE: To investigate endocrine dysfunction in simple weight loss amenorrhea. DESIGN: We studied pituitary hormone responses to thyrotropin-releasing hormone (TRH) in 10 women with simple weight loss amenorrhea. SETTING: Department of Obstetrics and Gynecology, University Hospital, University of Tokushima at Tokushima, Japan. PATIENTS, PARTICIPANTS: Secondary amenorrheic women associated with simple weight loss who did not have anorexia nervosa. INTERVENTIONS: Intravenous injection of 500 micrograms of synthetic TRH. MAIN OUTCOME MEASURE: Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyrotropin, and prolactin were measured before and 15, 30, and 60 minutes after TRH injection. RESULTS: In normally menstruating women on day 7 of the cycle TRH did not affect serum LH and FSH levels. In women with simple weight loss amenorrhea, however, TRH raised serum LH and FSH levels significantly (P less than 0.01, respectively). Prolactin response to TRH was significantly (P less than 0.05) lower in women with simple weight loss amenorrhea than in normally menstruating women. CONCLUSIONS: These results indicate that TRH causes a significant rise in serum LH and FSH and the impaired prolactin response in women with simple weight loss amenorrhea.