123rc/medical_text huggingface dataset:
Carnitine palmitoyltransferase in cardiac ischemia. A potential site for altered fatty acid metabolism. The sensitivity of carnitine palmitoyl coenzyme A (CoA) transferase I to inhibition of its activity by malonyl-CoA is progressively reduced in mitochondria isolated from ischemic cardiac cells as blood flow decreases to 30% or less of the preocclusion flow. The activity of carnitine palmitoyl-CoA transferase I in mitochondria isolated from nonischemic cardiac cells demonstrates incomplete inhibition, even at high concentrations of malonyl-CoA. Kinetic analyses of these data gave results most consistent with the expression of two overt enzyme activities: one activity that is sensitive to inhibition by malonyl-CoA and one activity that demonstrates little or no sensitivity to such inhibition. The decrease in malonyl-CoA-sensitive activity associated with ischemia results from a 13% decrease in the activity of the sensitive component and a corresponding 13% increase in the activity of the insensitive component. Decreased sensitivity of ischemic carnitine palmitoyl-CoA transferase I to inhibition by malonyl-CoA, together with potential fluctuations in the content of malonyl-CoA in tissue, would increase the synthesis of palmitoylcarnitine during ischemia and facilitate return to the use of fatty acid as a preferred metabolic fuel on reperfusion. This apparent conversion occurs concomitantly with a decrease in the free protein thiol content of the mitochondrial membranes isolated from ischemic cardiac cells. Treatment of the mitochondria from ischemic cardiac cells with dithiothreitol in vitro partially reverses the loss in sensitivity to malonyl-CoA, suggesting the possible role of thiol oxidation in the altered metabolism of ischemic mitochondria. Western blot analysis of these mitochondria using an antibody against carnitine palmitoyltransferase II purified from beef heart demonstrates a 68-kDa protein, which under ischemic conditions apparently is decreased by 2 kDa. These results are more indicative of a modification in protein folding of carnitine palmitoyltransferase than proteolytic changes during ischemia.
Epithelial cells immortalized by human papillomaviruses have premalignant characteristics in organotypic culture. Three HPV-16--and four HPV-18--immortalized human foreskin keratinocyte cell lines were analyzed on organotypic epidermal raft cultures at various passage levels. This culture system allowed normal cultured keratinocytes to stratify and differentiate in a manner similar to normal epidermis. All seven HPV-immortalized cell lines displayed epidermal morphologies on organotypic cultures, which were clearly abnormal and resembled premalignant lesions in vivo. Features of premalignant lesions that were shared by all of the HPV-immortalized cell lines included disorganized tissue architecture, mitotic cells present throughout the living layers of the epidermal sheet, abnormal mitoses, enlarged nuclei, and variable cell size and shape. Most HPV-immortalized cell lines were stable in terms of epidermal morphology with long-term passage in culture. Two of the HPV-18--immortalized cell lines, however, lost all morphologically apparent terminal squamous differentiation potential after long-term passage in monolayer culture. These results strongly support the idea that immortalization of squamous epithelial cells in culture by HPV-transforming genes generates a morphologically premalignant cell.
The relationship of headache symptoms with severity and duration of attacks. Efforts to develop clinically useful headache classification schemes have generally focused on linking specific symptom groupings with specific headache subtypes. An alternative conceptual approach, the "severity model" of headache, considers a continuum of headache ranging from mild to severe forms with specific headache subtypes distinguished by level of severity rather than unique constellations of symptoms. A population-based telephone interview was carried out among 10,169 subjects aged 12-29 to estimate the prevalence of serious headaches and better characterize symptoms that accompany headache attacks. In an analysis of frequency of occurrence, pain and duration of recent (within 4 weeks prior to interview) headache attacks, the data revealed that common symptoms (such as forehead pain and pain in the back of the head, neck and shoulders) were reported frequently, but headaches with these symptoms were generally characterized by low levels of pain and short duration. Although not an original study objective, the data were analyzed to determine whether distinct symptom constellations could be identified or whether symptoms overlapped between headache types. Symptoms of migraine were frequently experienced concomitant with tension-type symptoms; the resultant headaches were usually characterized as moderate in intensity. In contrast, symptoms usually associated with migraine in the absence of concomitant tension-type symptoms were infrequently experienced, but resulted in headaches causing the greatest disability. The data provide some support for the severity model of headache.
Characterization of cytokines present in middle ear effusions. Retention of inflammatory mediators and cells in the middle ear cleft during chronic otitis media with effusion (COME), results in ongoing inflammation with the potential for pathologic changes and hearing loss. Cytokines are glycoproteins produced by macrophages and other cells. Activities of cytokines include fever production, osteoclast, fibroblast, phagocyte and cytotoxic cell activation, regulation of antibody formation, and inhibition of cartilage, bone and endothelial cell growth. Using enzyme-linked immunospecific assays we measured levels of six cytokines in middle ear effusions (MEE) from children with COME. Significant levels of four cytokines: interleukin-1-beta (greater than 50 pg/ml), interleukin-2 (greater than 300 pg/ml), tumor necrosis factor-alpha (greater than 40 pg/ml), and gamma-interferon (greater than 6.25 pg/ml) were found in 51%, 54%, 63%, and 19% of MEE, respectively. In contrast, levels of a fifth cytokine, granulocyte-macrophage colony-stimulating factor, and a sixth cytokine, interleukin-4, were undetectable. Age was observed to have a significant effect on the levels of specific cytokines. Interleukin-1 (IL-1) correlated inversely (P less than .02) with age such that the younger the child, the higher the level of IL-1 in MEE. Tumor necrosis factor-alpha (TNF) correlated directly (P less than .005) with age such that the older the child, the higher the level of TNF in MEE. Children undergoing tympanostomy on multiple occasions had average MEE TNF levels (234.2 +/- 109.1 pg/mg total protein) that were nearly 14 times higher (P less than .005) than those from children undergoing their first tympanostomy (16.9 +/- 3.0 pg/mg total protein). Thus IL-1 correlated with the early stages of COME, while TNF correlated with persistence of disease. The presence of these cytokines in MEE may be responsible for the mucosal damage, bone erosion, fibrosis, and resulting hearing loss seen in some cases of COME.
Effects of benazepril and metoprolol OROS alone and in combination on myocardial ischemia in patients with chronic stable angina The efficacy of benazepril, metoprolol OROS and their combination was evaluated in 29 patients (42 to 74 years of age) with chronic stable angina and documented coronary artery disease in a placebo-controlled, double-blind, crossover trial using serial quantitated exercise testing and ambulatory electrocardiographic (ECG) monitoring. The mean (+/- SEM) exercise time was 8.5 +/- 0.7 min with placebo, 8.3 +/- 0.6 min (95% confidence interval [CI]-1.06 to 0.54) with benazepril, 9.4 +/- 0.5 min (95% CI -0.32 to 2.14) with metoprolol OROS and 9.6 +/- 0.5 min (95% CI -0.25 to 2.47) with the combination of benazepril and metoprolol OROS. The mean exercise time to the development of 1 mm ST segment depression was prolonged from 6.0 +/- 0.6 min with placebo to 6.3 +/- 0.6 min (95% CI -0.93 to 1.45) with benazepril, 7.9 +/- 0.5 min (95% CI 0.83 to 3.0) with metoprolol OROS and 8.1 +/- 0.6 min (95% CI 0.88 to 3.29) with the combination of benazepril and metoprolol OROS. Benazepril did not alter the rest or maximal heart rate, whereas metoprolol OROS alone and in combination significantly lowered the heart rate at rest and during maximal exercise. Systolic blood pressure at rest was nonsignificantly reduced, whereas diastolic blood pressure was lowered significantly by all treatments in comparison with placebo. At maximal exercise, only metoprolol OROS, whether given alone or in combination with benazepril, was able to blunt significantly systolic blood pressure and rate-pressure product.
Life events and low birthweight--analysis by infants preterm and small for gestational age. Social stress was assessed in 92 women with low-birthweight babies and 92 controls using the detailed LEDS measure of life events and severe chronic difficulties. The low-birthweight group was divided into preterm delivery (n = 40), small for gestational age (SGA) (n = 40) and mixed groups. Multivariate analysis was performed using a binomial-logit model to examine whether social factors were independently and significantly associated with low birthweight once the effect of demographic factors, obstetric factors and smoking/drinking were taken into account. Comparison of preterm births with controls indicated that three factors were significantly associated: a previous low-birthweight baby, severe life event/difficulty and bleeding during pregnancy. For SGA babies the factors were: previous low-birthweight baby, low social support and smoking. By using a reliable measure of life events and adequate numbers of low-birthweight babies, this study overcame the potential inaccuracies of previous studies and indicates a more specific relation between social stress and low birthweight.
Ventricular responses to mental stress testing in patients with coronary artery disease. Pathophysiological implications. Recent research examining the effects of mental stress on left ventricular wall motion and/or ejection fraction has used four techniques to measure contractile function: radionuclide ventriculography, a stationary nuclear probe, two-dimensional echocardiography, and an ambulatory radionuclide left ventricular function monitor. This research has consistently revealed that mental stress-induced myocardial ischemia occurs frequently during laboratory stress testing, particularly among patients with exercise-induced ischemia. This ischemia is usually silent, occurs at low heart rate elevations but with significant blood pressure increases compared with exercise-induced ischemia, and is frequently not detected when electrocardiographic markers are used alone. Exploration of factors underlying differences between mental stress- and exercise-induced ischemia has provided a means for studying the complex pathophysiology of myocardial ischemia.
Further mapping of an ataxia-telangiectasia locus to the chromosome 11q23 region. We recently mapped the gene for ataxia-telangiectasia group A (ATA) to chromosome 11q22-23 by linkage analysis, using the genetic markers THY1 and pYNB3.12 (D11S144). The most likely order was cent-AT-S144-THY1. The present paper describes further mapping of the AT locus by means of a panel of 10 markers that span approximately 60 cM in the 11q22-23 region centered around S144 and THY1. Location scores indicate that three contiguous subsegments within the [S144-THY1] segment, as well as three contiguous segments telomeric to THY1, are each unlikely to contain the AT locus, while the more centromeric [STMY-S144] segment is most likely to contain the AT locus. These data, together with recent refinements in the linkage and physical maps of 11q22-23, place the AT locus at 11q23.
Stroke after heavy marijuana smoking. I examined two young men who developed cerebral infarction associated with heavy marijuana smoking. Both were light tobacco smokers, but they did not drink alcohol or use other street drugs. Diagnostic work-up for nonatherosclerotic causes of stroke was unremarkable. I postulate that marijuana-associated alterations in systemic blood pressure resulted in vasospasm, leading to strokes in these patients.
Cosmetic, functional, independent: self-help aids. Self-help orthotics have been developed to assist functional activities for high-level spinal cord injured patients. The goal of rehabilitation has been to do this with as little intrusion on independence and cosmesis as possible. This paper describes devices to help a patient with C6 quadriplegia independently place his own utensils and eat with an almost normal appearance. The new self-help aids are made from standard silverware, a rivet, and two one-eighth-inch Kydex loops. The loops are riveted centrally on the utensil, allowing for free rotation. The device was evaluated on a patient with C6, complete quadriplegia. The subject demonstrated independence in donning and doffing the device and in eating with an almost normal appearance.
Geriatric diabetic nephropathy: an analysis of renal referral in patients age 60 or older. We report a series of 33 consecutive hospitalized geriatric diabetic patients who were referred for evaluation of diabetic nephropathy, defined as proteinuria greater than or equal to 1 g/d (1,000 mg/24 h) or a serum creatinine concentration greater than or equal to 177 mumol/d (greater than or equal to 2 mg/dL). The study population was 60 years old or older (mean age, 68 +/- 6 years), was comprised mainly of women (24 of 33, 72.7%), and was predominantly black (25 of 33, 75.8%). All patients had type II diabetes. A family history of diabetes in parent or sibling was elicited in 24 (72.7%) patients. There were eight patients undergoing maintenance hemodialysis and 25 with less severe nephropathy (mean proteinuria, 2.7 g/d [2,700 mg/24 h]; mean creatinine clearance, 0.57 mL-s [34 mL/min]). Cardiac disorders were noted in the majority of patients: congestive failure in 20 (60.6%), myocardial infarction in eight (24.2%), and active angina in five (15.2%). Other comorbid diseases were present in both hemodialysis patients and the subset of nondialyzed azotemic-proteinuric patients, and consisted of peripheral neuropathy in 31 (93.9%), gastroparesis in 16 (48.5%), retinopathy in 28 (84.8%), and legal blindness in 11 (33%). We conclude that geriatric diabetic nephropathy in type II diabetes is similar in presentation and severity of comorbid extrarenal complications to the syndrome described in younger adults. This inference must be tempered by both the small size and the limitation imposed by the demographics of the study population, which is predominantly composed of black patients receiving treatment at inner city hospitals.
Circulating C1q-binding macromolecules and their relationship to radiographic characteristics of laryngeal cancer. Circulating macromolecules capable of binding the first component of complement (C1qBM) may represent subcellular components of tissue/tumor debris generated from rapidly proliferating invasive disease. Thirty-eight patients were randomly selected from 74 untreated patients with laryngeal cancer on the basis of disease stage and C1qBM levels. C1qBM levels were correlated with computed tomographic evidence of tumor necrosis and/or thyroid cartilage destruction. Results show that patients with stage III/IV disease with tissue necrosis and/or cartilage invasion had demonstrably higher C1qBM levels than did individuals with similarly staged disease with no evidence of these radiographically defined characteristics (120 +/- 81 micrograms/mL vs 18 +/- 15 micrograms/mL); the strongest association was reflected by the area of necrosis within regional lymph metastases. Elevated C1qBM level in patients with stage III/IV laryngeal cancer thus reflects highly aggressive disease, which is less responsive to therapeutic intervention.
Chronic otitis media: the significance of nasal obstruction. The nasal airway resistance of 15 patients with unilateral chronic otitis media and 15 controls was measured by anterior active rhinomanometry. Airway resistance was measured on each side before and after decongestion to differentiate resistance due to structural abnormality from that due to mucosal swelling. The nasal resistance was significantly greater (P less than 0.01) on the side of the affected ear in patients with unilateral chronic otitis media before decongestion, but following decongestion the difference was not significant. Nasal obstruction is a significant determinant in unilateral chronic otitis media and although septal displacement may be the underlying cause, the major component of the obstruction appears to be due to an associated mucosal oedema.
Coccidioidomycosis during human immunodeficiency virus infection. A review of 77 patients. Through a retrospective review, we identified 77 previously unreported cases of coccidioidomycosis during HIV infection. Patients were classified into 1 of 6 categories based on their primary clinical presentation: 20 had focal pulmonary disease (Group 1), 31 had diffuse pulmonary disease (Group 2), 4 had cutaneous coccidioidomycosis (Group 3), 9 had meningitis (Group 4), 7 had extrathoracic lymph node or liver involvement (Group 5), and 6 has positive coccidioidal serology without a clinical focus of infection (Group 6). Coccidioidal serologies were positive on initial testing in 83% of the patients in whom such serologic testing was performed. Sera from 39% of patients were positive for TP antibodies while 74% had CF antibodies. Eleven of 12 seronegative patients had pulmonary disease (Group 1 or 2). Serologic results of other patients sent to a single reference laboratory were similar, with 26% positive for immunodiffusion TP antibodies and 79% positive for immunodiffusion CF antibodies. For the 77 patients in this study, the CD4-lymphocyte count was below 0.250 X 10(9) cells/L in 46 of the 55 patients who had this test performed, and a low CD4 count was significantly associated with mortality (p less than 0.01). At the time of follow-up, 32 of the 77 patients (42%) had died. There were significantly more deaths in those with diffuse pulmonary disease (Group 2) than in other groups (p less than 0.001). Amphotericin B, ketoconazole, fluconazole, and itraconazole were all used as antifungal therapies. Outcome could not be related to the therapy used. Of note, 3 patients developed coccidioidomycosis while receiving ketoconazole for other conditions.
Sternocleidomastoid muscle transfer and superficial musculoaponeurotic system plication in the prevention of Frey's syndrome Parotidectomy may be associated with a significant depression in the retromandibular region and a significant incidence of gustatory sweating (Frey's syndrome). Superiorly and inferiorly based sternocleidomastoid flaps and posterior plication of the superficial musculoaponeurotic system were evaluated for their ability to ameliorate both consequences. Sixteen patients with sternocleidomastoid flaps and 16 patients with superficial musculoaponeurotic system plication were compared to a control group of 104 patients. The incidence of Frey's syndrome was 47.1% in the control group, 12.5% (P = 0.025) in the sternocleidomastoid flap group, and 0% (P = 0.005) in the superficial musculoaponeurotic system plication group. The surgical techniques are described. The prevalence of Frey's syndrome is discussed with respect to age, sex, radiation therapy, and the type of parotidectomy performed. The indications and contraindications of the three surgical techniques are described.
Intraoperative I-125 seed implantation for extensive recurrent head and neck carcinomas. From 1978 to 1988, 41 patients with extensive recurrent carcinomas of the head and neck were treated with surgical resection plus intraoperative iodine-125 seed implantation. Surgery was performed to resect the tumors and to expose the tumor beds for implantation. I-125 seeds were implanted intraoperatively, with a spacing of 0.75-1 cm between adjacent seeds, either into the soft tissue in the tumor bed or onto small patches of gelatin sponges to cover the bone, nerve, or blood vessel involved with disease. Reconstructive flaps were used in 18 patients. The average I-125 dose delivered by the implanted seeds was 8,263 cGy. The determinate 5-year actuarial survival rate for the entire group was 40%. The 5-year local disease control rate was 44%. Major complications were transient wound infection (32%), flap necrosis (24%), fistula formation (10%), and carotid blowout (5%). These results indicate that surgical resection plus I-125 seed implantation provides a potentially curative treatment for patients with extensive recurrent head and neck carcinomas that would be considered traditionally unresectable and that would be treated only with palliative therapy.
Malignant left-sided large bowel obstruction managed by subtotal/total colectomy. Of 60 patients presenting with acute obstructing carcinoma of the left colon, 49 underwent immediate resection either by radical subtotal/total colectomy (31 patients, group I) or by radical segmental resection (18 patients, group II) of whom three had immediate anastomosis after on-table bowel irrigation and 15 had a planned staged procedure. The operative mortality rate was 3 per cent in group I and 11 per cent in group II (not a statistically significant difference). However, substantial differences were found for major morbidity (6 versus 44 per cent in groups I and II respectively; P less than 0.01) and mean length of hospital stay (17 days in group I versus 35 days in group II; P less than 0.05). All three patients who had on-table lavage developed anastomotic leaks which necessitated a second operation to form a stoma. Six patients (19 per cent) in group I required antidiarrhoeal medication in the immediate postoperative period. However, subsequent improvement in stool frequency was noted in all patients. It is concluded that subtotal/total colectomy is an acceptable means of managing patients with obstructing carcinoma of the left colon in that it is associated with a low morbidity and mortality rate and good functional results.
Argon versus krypton panretinal photocoagulation side effects on the anterior segment. The modification of corneal sensitivity, accommodation, pupillary diameter and endothelial cell density after argon versus krypton panretinal photocoagulation were studied prospectively in 88 eyes of 64 diabetic patients with proliferative diabetic retinopathy, randomized for one of the two laser treatments. In both groups a marked internal ophthalmoplegia and reduction of corneal sensitivity occurred after laser photocoagulation. At no time, 2, 90 and 180 days after PRP, were these parameters significantly different. Endothelial cell loss was non significantly greater in the krypton group. The results indicated that the side effects commonly observed on the anterior segment after PRP are comparable using argon or krypton lasers.