123rc/medical_text huggingface dataset:
Antinociceptive interaction between opioids and medetomidine: systemic additivity and spinal synergy. The antinociceptive interaction on the tail flick (TF) and hot plate (HP) tests between opioid analgesics and medetomidine after intravenous (iv) or intrathecal administration were examined by isobolographic analysis. Male Sprague-Dawley rats received fixed ratios of medetomidine to morphine, fentanyl, and meperidine of 1:10 and 1:30, 10:1, and 1:3, respectively, by iv administration or 10:1, 3:1 and 10:1, and 1:3 by intrathecal administration, respectively. Data were expressed as the percentage maximal possible effect (%MPE). The A50 (dose producing 50% MPE) for each drug or drug combination was determined from the dose-response curve. Isobolographic analysis revealed that the effect of medetomidine combined with fentanyl, morphine, or meperidine was additive after iv administration. The intrathecal administration of combinations of medetomidine with the opioids produced a synergistic antinociceptive effect in the TF but not HP test. These data confirmed that the interaction between medetomidine and opioids in producing antinociception may be additive or synergistic, depending on the route of administration, drug ratio administered, and level of processing of the nociceptive input (i.e., spinal vs. supraspinal). Moreover, these results were consistent with a spinal role for alpha-2 adrenoceptors in mediating antinociception. The authors suggest that the interaction between the opioid and alpha-2 adrenergic receptors occurs within the spinal cord.
Rapid eye movement sleep deprivation as a probe in elderly subjects. The effects of a 2-night rapid eye movement (REM) sleep deprivation (RSD) procedure on electroencephalographic sleep and mood were examined in 15 healthy elderly control subjects, 14 elderly patients with endogenous depression, and 15 patients with primary degenerative dementia. Compared with control subjects, both patient groups maintained a higher amount of REM sleep time and REM activity during RSD. Unexpectedly, depressed patients showed little rebound in visually scored or automated REM sleep measures following RSD, and they showed stability of REM activity temporal distribution from baseline to recovery conditions. This contrasted with the rebound in REM sleep activity seen in control subjects, and the more modest increase in demented patients. The RSD was fairly specific, with some impact on delta sleep during the procedure but not during recovery sleep. Mood ratings were unaffected by RSD. These findings demonstrated a greater plasticity of REM sleep regulation in the healthy elderly control subjects and suggested a higher REM "pressure" with a "ceiling effect" in depressed patients. Patients with dementia appeared to have an impaired capacity to respond to the challenge of RSD.
Cortical asymmetry of REM sleep EEG following unilateral pontine hemorrhage. A 24-year-old woman with a left pontine hematoma showed marked asymmetry in the EEG of REM sleep, suggesting that a unilateral pontine lesion is sufficient to disrupt normal REM sleep EEG in the ipsilateral hemisphere. Other REM sleep characteristics (rapid eye movements, muscle atonia) were unaffected by this lesion.
Presence of identical mitochondrial proteins in unstimulated constitutive steroid-producing R2C rat Leydig tumor and stimulated nonconstitutive steroid-producing MA-10 mouse Leydig tumor cells. The acute regulation of steroidogenesis in steroidogenic tissues requires de novo protein synthesis. It is believed that these newly synthesized proteins are instrumental in the delivery of the substrate, cholesterol, to the inner mitochondrial membrane where the cholesterol side-chain cleavage complex converts cholesterol to pregnenolone. A number of studies have attempted to characterize the protein(s) synthesized in response to hormone stimulation and, hence, function in the delivery of cholesterol to the cholesterol side-chain cleavage complex. While a number of potential protein candidates have been described, there is at present no unequivocal evidence which indicates that they are involved in steroidogenic regulation. We and others have described proteins that are induced in a variety of steroidogenic tissues in response to hormone stimulation and are localized in the mitochondria of these tissues. In an attempt to determine whether these induced proteins may be involved in steroidogenesis, we compared mitochondrial protein profiles in two separate Leydig tumor cell line. One cell line, the MA-10 mouse Leydig tumor cell line, has a very low basal steroid production, but synthesizes large amounts of progesterone in response to both tropic hormone and cAMP analog. The other cell line, the R2C rat Leydig tumor cell line, produces constitutively large amounts of progesterone, which cannot be increased further with hormone stimulation. Two-dimensional polyacrylamide gel electrophoresis profiles of newly synthesized mitochondrial proteins demonstrated that four 30-kDa proteins are induced in response to hormonal stimulation in MA-10 cells. Further, it was shown that proteins identical to these induced proteins are present constitutively in the mitochondria of R2C cells and cannot be further increased with hormone stimulation. These results strongly suggest that the 30-kDa mitochondrial proteins shown to be induced in several steroidogenic tissues are involved in the acute regulation of steroid production.
Stress and sudden death. The case of the long QT syndrome. The idiopathic long QT syndrome (LQTS) represents a unique clinical example of stress-related sudden cardiac death. LQTS is characterized by the association of several distinctive electrocardiographic features, among which prolongation of the QT interval is the best known, with life-threatening arrhythmias that usually occur under conditions of physical or psychological stress. Effective therapies exist and are represented by antiadrenergic interventions; beta-adrenergic-blocking agents are the treatment of choice. When they fail, left cardiac sympathetic denervation has also proven to be very effective. The latter result suggests a role for alpha-adrenergic mechanisms in the arrhythmias of LQTS. The stressors more frequently associated with syncopal events in LQTS patients include fear, exercise fraught with emotions, swimming, and awakening because of a loud noise. Experimentally, life threatening arrhythmias have been induced during a highly emotional situation in conscious cats with normal hearts in which right stellate ganglia have been ablated, resulting in QT interval prolongation. This selective denervation creates a sympathetic imbalance of the type proposed by one of the pathogenetic hypotheses for LQTS.
Adenocarcinomas of the colon and rectum in persons under 40 years old. A population-based study. Data collected by nine population-based tumor registries participating in the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute were analyzed to characterize the epidemiology of noncarcinoid adenocarcinomas of the colon and rectum in young adults. Tumors diagnosed in persons under 40 years old between 1973 and 1984 (n = 1736) were compared with those in persons 40 years and older (n = 106,760). This first large U.S. population-based study of colorectal adenocarcinomas in the young shows a higher incidence in blacks than whites and later detection in black males. It also shows a higher proportion of tumors of mucinous and signet ring histological type than in older age groups. Among the younger group, the average annual age-adjusted incidence rate was 34% higher in black males than in white males (12.6 vs. 9.4 per million persons) and 46% higher in black females than in white females (13.0 vs 8.9 per million persons). The proportion of tumors that were right-sided varied by age: 0-29 years, 30%; 30-39 years, 26%; 40-49 years, 22%; 50-59 years, 21%; 60-69 years, 24%; 70-79 years, 30%; and 80+ years, 35%. Males under age 40 were less likely to present with localized disease (whites, 27%; blacks, 21%) than were those aged 40 and older (whites, 39%; blacks, 36%). The proportion of tumors classified as mucinous decreased with age, from 28% among those aged 0-19 years to 5% among those 40 years and older. A similar trend was observed for signet ring tumors. Although this latter type accounted for 10% of large-bowel tumors among subjects aged 0-19 years, this proportion decreased with age to 0.2% in those 40 years and older.
Multiple breakpoint method for measuring effect of antibiotics on endocarditis strains of streptococci. The activity of penicillin alone and combined with aminoglycoside on endocarditis strains of streptococci was examined. Good assay reproducibility was obtained by the use of logarithmic phase cultures standardised by opacity, careful inoculation of well-plates, removal of antibiotic by membrane transfer and incubating survival counts in hydrogen plus carbon dioxide. The use of 10-fold intervals for penicillin concentration simplified assay design without loss of efficiency.
Structure and distribution of an Alu-type deletion mutation in Sandhoff disease. Sandhoff disease is a recessively inherited lysosomal storage disease resulting from a deficiency of beta-hexosaminidase activity. The enzyme occurs in two major forms, beta-hexosaminidase A, composed of an alpha- and beta-subunit and beta-hexosaminidase B, composed of two beta-subunits. Both isozyme activities are deficient in Sandhoff disease, owing to mutations of the HEXB gene encoding the common beta-subunit. We have cloned and fully characterized a deletion at the HEXB gene from fibroblasts of a patient with the infantile form of Sandhoff disease. The deletion removes approximately 16 kb of DNA including the HEXB promoter, exons 1-5 and part of intron 5. It most likely arose from recombination between two Alu sequences, with the breakpoints occurring at the midpoint between the left and right arms in each case and regenerating an intact Alu element in the deletion sequence. The deletion allele accounts for 27% of the Sandhoff mutant alleles we analyzed. Two cell lines were shown to be homozygous for the deletion and both had the infantile form of the disease. Four additional patients were compound heterozygotes with other mutations, all of whom displayed a different clinical phenotype. Finally, the mutant allele was present in different ethnic backgrounds, suggesting that it may have been subject to genetic drift.
Enlarged cisterna magna and the Dandy-Walker malformation: factors associated with chromosome abnormalities. Thirty-three fetuses with an enlarged cisterna magna (10 mm or more) were evaluated to determine factors that might be associated with an underlying chromosome abnormality. Eighteen fetuses (55%) proved to have a chromosome abnormality, including trisomy 18 or trisomy 18 variant (12), trisomy 13 (three), Turner syndrome (one), or other rearrangements (two). Among various risk factors analyzed, the absence of ventricular dilatation correlated most strongly with a chromosome abnormality. Chromosome abnormalities were found in 17 of 22 fetuses (77%) lacking ventricular dilatation, compared with only one of 11 fetuses (9%) with ventricular dilatation (P less than .001). Other factors statistically associated (P less than .01) with an underlying chromosome abnormality included mild enlargement of the cisterna magna (10-14 mm), concurrent anomalies detected sonographically, and fetal growth retardation. However, stepwise logistic regression showed that only the absence of ventricular dilatation and the presence of concurrent anomalies were significant when multiple factors were evaluated. These observations support the utility of evaluating the cisterna magna as part of a routine anatomical survey.
Clinical and instrumental evaluation of sensory function before and after percutaneous anterolateral cordotomy at cervical level in man. Sensory perception thresholds were assessed by clinical testing and by quantitative instrumental testing before and after operation in 16 subjects for whom unilateral percutaneous cervical cordotomy was performed for the relief of pain due to malignant disease, and compared with clinical assessments of sensory function. We were able to confirm the association between deficit in pin-prick sensation and pain relief in the majority of instances, though the completeness or otherwise of pain relief does not correspond to absence of pin-prick sensation. There is no objective interference with low threshold mechanical sensation as measured instrumentally, although cordotomised subjects do not experience startle, tickle, or cutaneous erotic sensation when subjected to appropriate low intensity tactile sensation. Quantitative instrumental testing shows that the greatest deficits produced by cordotomy are in the sensations of skinfold pinch (? = tissue-damage pain) and skin cooling. The latter is transduced in the periphery by A delta fibres; sensations of warmth and hot pain, transduced by primary afferent C fibres, are much less significantly affected. Our findings thus fail to resolve the question as to whether chronic clinical pain is mainly an A delta- or a C fibre-mediated phenomenon.
Regulation of fibrillar collagen types I and III and basement membrane type IV collagen gene expression in pressure overloaded rat myocardium. Left ventricular hypertrophy is based on cardiac myocyte growth. The hypertrophic process can be considered heterogeneous based on whether it also includes a remodeling and accumulation of fibrillar types I and III collagens that are responsible for impaired myocardial stiffness. In the heart, the messenger RNA (mRNA) for fibrillar collagen types I and III has been detected only in cardiac fibroblasts, whereas mRNA for basement membrane collagen type IV is present in both fibroblasts and myocytes. We studied the early and long-term expression of these collagenous proteins in rat myocardium after abdominal aortic banding with renal ischemia. Complementary DNA probes for rat pro-alpha 2 (I), mouse type III and mouse type IV collagens, and chicken beta-actin were used. Northern and dot blot analysis on total RNA extracted from left ventricular tissue indicated a sixfold increase in steady-state levels of mRNA for collagen type I on day 3 of abdominal aortic banding, which had declined to control levels by day 7 where it remained rather constant at 4 and 8 weeks. Type III collagen showed a similar pattern of gene expression after banding. mRNA levels for type IV collagen, on the other hand, were elevated on day 1 after banding, returning to control at day 7 and remaining constant. Actin mRNA levels also increased on day 1 of banding, followed by a rapid return to control levels. Monospecific antibody to types I and III collagens and immunofluorescent light microscopy on frozen sections of the myocardium revealed that at 1 week after banding, the distribution and density of these collagens were similar to those of control animals.
Long-term effects of delapril on renal function and urinary excretion of kallikrein, prostaglandin E2, and thromboxane B2 in hypertensive patients. The effects of delapril, an angiotensin converting enzyme (ACE) inhibitor, on renal function and the renin-angiotensin and kallikrein-prostaglandin systems were investigated in 10 hypertensive patients who were treated for between 4 months and 1 year. There was a significant (P less than .05) increase in renal blood flow (RBF) without affecting glomerular filtration rate. Filtration fraction increased, while renal vascular resistance decreased. There were also significant (P less than .05) increases in urinary kallikrein and prostaglandin excretion, while thromboxane excretion decreased. There was no change in urinary aldosterone excretion. These results suggest that renal hemodynamic changes seen during long-term therapy with delapril are caused, in part, by activation of the kallikrein-prostaglandin system, as well as suppression of the renin-angiotensin system.
Emergency surgical treatment for nonvariceal bleeding of the upper part of the gastrointestinal tract. Endoscopic and biochemical data were collected prospectively from 1,530 patients admitted with nonvariceal bleeding of the upper part of the gastrointestinal tract between September 1985 and June 1989. Therapeutic endoscopy was done for 93 patients who underwent emergency surgical treatment for bleeding, subsequently required in 29 patients with seven postoperative fatalities. In contrast, 31 (15.7 per cent) of 198 patients (mortality rate of 9.6 per cent at 30 days) died in the hospital who had undergone emergency operation in whom therapeutic endoscopy had not been performed; data for this latter group is now presented. At admission, a greater likelihood of emergency operation was associated with a systolic blood pressure of 100 millimeters of mercury and endoscopic stigmatas of recent hemorrhage (ESRH) (p less than 0.001). Rebleeding rates for the presence of fresh blood, active spurting and oozing hemorrhage or visible vessel in an ulcer base were 26.5, 28.9 and 35.9 per cent, respectively. Endoscopic stigmatas were thus associated with an increased risk of bleeding (p less than 0.0001) and rebleeding led to a sixfold increase in the mortality rate. Congestive cardiac failure, chronic obstructive airway disease, chronic renal failure and a history of previous malignant disease were each associated with postoperative mortality rates of more than 50 per cent. An increased risk of mortality after emergency operation was related to age (p less than 0.0001), preoperative (p less than 0.002) and total (p less than 0.0001) blood transfusion requirement. Immediate operation after resuscitation and endoscopy was required in 87 patients; 11 deaths (hospital mortality rate of 12.7 per cent and 9.2 per cent at 30 days) occurred in this group compared with 20 fatalities (18.0 per cent) documented in 111 patients (9.9 per cent at 30 days) who underwent surgical treatment for rebleeding. We conclude that age, concomitant medical illness and preoperative and total transfusion requirements are each related to outcome after emergency operations. Such urgent intervention is best avoided if at all possible in patients with severe concomitant medical illness.
Do we need another antihypertensive agent? The factors to be considered in selecting antihypertensive agents have traditionally centered around balancing efficacy against adverse side effects. The former can be achieved by a variety of agents alone or in combination. The latter not only involves safety but is also concerned with whether an otherwise safe agent is tolerated by the patient so compliance with the treatment regimen can be achieved. A relatively new consideration is how antihypertensive agents affect other disease states that may or may not be associated with hypertension. For example, how a drug may affect diabetes, gout, myocardial hypertrophy, atherosclerosis, and coronary events must be evaluated. These concerns taken together answer the question of why yet another antihypertensive agent may be needed in the pharmacologic armamentarium.
Immunohistologic evaluation of parathyroid hormone-related protein in human lung cancer and normal tissue with newly developed monoclonal antibody. With a newly developed monoclonal anti-PTHrP antibody, 4B3, the immunohistochemical localization of the parathyroid hormone-related protein (PTHrP) was studied on the formalin-fixed and paraffin-embedded sections of normal human tissues and various subtypes of lung cancer. Among normal epithelial tissues, keratinocytes in squamous epithelia, transitional and bronchial epithelia with squamous metaplasia, meningoepithelial cells, and mammary ductal cells with lactating changes showed positive immunoreactivity. Also, among endocrine tissues, cells in the parathyroid gland, pancreatic islets, adrenal cortex, pituitary gland, and testis were sporadically positive for PTHrP. These distribution patterns suggested that in a physiologic condition, PTHrP was closely related to keratinization and local secretion and/or the metabolism of calcium in specifically differentiated tissues. In lung cancer, however, PTHrP was detected in all cases of well-differentiated and moderately differentiated squamous cell carcinoma and in most cases of small cell carcinoma, irrespective of the patients' serum calcium level. However, PTHrP was not detected in two of five cases of poorly differentiated squamous cell carcinoma and in all cases of adenocarcinoma. Consequently, it was found that PTHrP was commonly produced by squamous cell carcinomas of the differentiated type, and that humoral hypercalcemia of malignancy could be induced when the PTHrP transgressed the homeostatic mechanisms.
Development and prospective application of quantitative 2-day stress-rest Tc-99m methoxy isobutyl isonitrile SPECT for the diagnosis of coronary artery disease. The clinical diagnostic accuracy of 2-day stress/rest quantitative Technetium-99m (Tc-99m) methoxy-isobutyl-isonitrile (Tc-sestamibi) single photon emission computerized tomography (SPECT) was assessed in a validation population of 61 patients from two different sites using two different camera/computer systems. The study population was made up of 53 catheterized patients, 29 from Cedars-Sinai Medical Center (CSMC) and 24 from the University of Texas Southwestern Medical Center (UTSMC), and eight UTSMC patients with a less than 5% pre-test likelihood of coronary artery disease. Interpretation employed gender-specific normal limits developed in an additional 15 men and 8 women at CSMC with less than a 5% likelihood of significant coronary artery disease. The results from CSMC compared with those from UTSMC were not different from each other. The overall sensitivity for detection of patients with coronary artery disease (greater than or equal to 50% stenosis) was 94% (CSMC: 92%, UTSMC: 95%). Overall specificity in the five patients with normal coronary arteriograms was 80% (CSMC: 67%, UTSMC: 100%). The normalcy rate in patients with a low likelihood of coronary artery disease was 88%. Vessel sensitivity was 85% (CSMC: 84%, UTSMC: 85%), while vessel specificity was 71% (CSMC: 72%, UTSMC: 69%). There was also no significant difference in the sensitivities and specificities between male and female populations. In addition, the agreement with coronary angiography for assessment of disease extent (normal coronary arteriogram, single or multivessel disease) was 75% (kappa = 0.6 +/- 0.1). This study demonstrated that Tc-sestamibi SPECT by quantitative analysis is accurate for the detection and localization of coronary artery disease. Furthermore, the CSMC quantitative method was shown to provide similar diagnostic accuracy when applied to data acquired at a different site using a different camera/computer system.