shukoor65/lab-rag-model huggingface dataset:
IgA antigliadin antibodies, cellobiose/mannitol sugar test, and carotenemia in the diagnosis of and screening for celiac disease. Serum IgA antigliadin antibodies (IgAAGA) assay, cellobiose/mannitol sugar permeability test (ST), and carotenemia were evaluated prospectively as diagnostic tests in 60 consecutive adult patients with suspected celiac disease (CD). CD was confirmed histologically in 26 patients. IgAAGA, ST, and carotenemia had a sensitivity of 65.4%, 96.2%, and 76.9%, a specificity of 97.1%, 73.5%, and 70.6%, and positive likelihood ratio of 22.2, 3.6, and 2.6, respectively. Multivariate logistic regression showed that IgAAGA and ST had a sensitivity and specificity of 96.2% and 70.6% and a positive likelihood ratio of 47.3 if both were positive. Assuming a prevalence of CD of 1:2000 in the general population, for every 89 positive IgAAGA and 549 altered ST there would be one celiac patient, whereas, if both tests were positive, the patient was certain to have CD. We conclude that, of the tests studied, IgAAGA and ST are respectively the most specific and the most sensitive and that, used together, they can diagnose CD.
Conjunctival cysts in anophthalmic orbits. Five out of 149 patients (3%) who received an intraorbital implant to prevent or treat the disfiguring symptoms associated with the postenucleation socket syndrome developed intraorbital conjunctival cysts. All five patients had received a secondary implant two 14 months previously. After excision of the cysts four patients required additional surgery for lack of conjunctiva and/or recurrent cyst formation. The clinical findings, mechanism of development, and management of this rare but serious complication of socket surgery are described.
GM1-gangliosidosis (genetic beta-galactosidase deficiency): identification of four mutations in different clinical phenotypes among Japanese patients. GM1-gangliosidosis is a genetic neurological disorder caused by mutations in the lysosomal acid beta-galactosidase gene. While its phenotypic expression is complex, it is usually classified as being of infantile, juvenile, or adult form, on the basis of age at onset, the rate of symptomatic progression, and severity of central nervous system involvement. We have analyzed the acid beta-galactosidase gene in 12 Japanese patients from nine families. The aim was to identify mutations in individual patients and then to examine possible correlation between the mutations and the clinical phenotypes. Northern blotting studies with a full-length human beta-galactosidase cDNA showed that the mRNA ranged from undetectable to substantially decreased in the infantile patients but was normal in quantity and size in all juvenile and adult patients. Four distinct missense mutations have been identified, each limited to the respective clinical forms within our small-size samples. In the infantile patient with decreased but detectable mRNA, a point mutation was found resulting in Arg49----Cys. In the infantile patient with nearly undetectable mRNA, mutation Arg457----Ter was identified. The mutation Arg201----Cys was found in all four of the juvenile patients, while all six adult patients were homozygous for the point mutation Ile51----Thr. The mutations found in the juvenile and adult patients alter restriction sites in the normal gene and thus are amendable to quick screening. The prediction that these mutations are responsible for the clinical disease was confirmed by no expression of the catalytic activity of the mutant proteins in the COS-I cell expression system.
Biocompatibility of radiolucent breast implants. Current implants for breast augmentation containing silicone gel, saline, or both are radiopaque on mammographic examination and can totally obscure microcalcifications and soft-tissue masses. The effect of these implants on the detection of early breast cancers in patients who have undergone augmentation mammaplasty remains unproven and controversial. Implants filled with medium-chain triglycerides (peanut oil) are radiolucent on mammographic examination and allow visualization of both soft-tissue masses and microcalcifications. To investigate the biocompatibility of radiolucent implants, 10 cc of sterile, nonpyrogenic peanut oil was injected subcutaneously into rats using silicone gel as a control. Twenty-one rabbits had two 125-cc silicone shell implants inserted on either side of the chest wall. The right-sided shell was filled with 125 cc of sterile saline, and the left-sided shell was filled with 125 cc of sterile, nonpyrogenic peanut oil. Results were determined by both histologic and radiographic examination. Rats injected with peanut oil equivalent to 7 percent of their body weight rapidly absorbed the freely injected oil without detriment. Histologic examination of the lungs, liver, kidneys, and tissues adjacent to the injection sites demonstrated no abnormalities. There was no evidence of allergic, toxic, inflammatory, or neoplastic response. Eighteen of 21 rabbits survived more than 3 months. Radiographs showed the oil-filled implants to be radiolucent, whereas the saline-filled controls obscured the surrounding soft and bony tissues. Histologic examination demonstrated a fibrous capsule surrounding both types of implants. Histologic examination of the lungs, liver, and kidneys showed no significant abnormalities. These and previous studies have shown peanut oil to be biocompatible when freely injected either intramuscularly or subcutaneously. This study demonstrates that a radiolucent, peanut oil-filled implant is biocompatible in animals and that further long-term studies for its use in humans are merited.
Metabolic and destructive brain disorders in children: findings with localized proton MR spectroscopy. The diagnostic potential of volume-selective proton magnetic resonance (MR) spectroscopy in vivo was evaluated in 20 children and young adults with various neurodegenerative brain disorders. All patients were examined with MR spectroscopy in conjunction with MR imaging of the brain on a whole-body imager at 1.5 T. Comparison of spectra in our patients with those of children with normal myelination (prominent signals from N-acetylaspartate [NAA], creatine/phosphocreatine, and choline) revealed a marked decrease of NAA in 12 of 17 patients with focal or generalized demyelination. In patients with Canavan disease, NAA signal intensity was markedly increased, but no choline signal was found. Increased signal intensity from lactate occurred in patients with Leigh disease, neuroaxonal dystrophy, Schilder disease, and Cockayne disease, which indicated a disturbed energy metabolism in the examined region. These results demonstrate that proton MR spectroscopy can be applied in a clinical environment to facilitate diagnosis of hereditary and acquired brain disorders in children.
Longitudinal followup of patients with Meniere's disease. The etiology, pathophysiology, and natural history of Meniere's syndrome are poorly understood. The reported studies have had inadequate followup or insufficient numbers of patients to allow conclusions about the natural history. Our study group was 119 patients who had the classic symptom complex of episodic vertigo, tinnitus, and hearing loss in the year 1970. After initial review of these charts, follow-up information was obtained by questionnaire, telephone interview, chart review, or repeat examination, when possible, both in 1983 and in 1988, for a total followup of 18 years. In the patients with followups of at least 14 years, vertiginous episodes had disappeared completely in 50% of patients and somewhat resolved in 28%; hearing was absent in 48% and worse in 21%. Surprisingly, 43% of patients underwent surgery at some point for control of vertigo. Bilateral disease was present initially in 13% and developed subsequently in 45% of patients. Other areas reviewed included the efficacy of long-term medical treatment, frequency and severity of vertiginous attacks, and contralateral ear symptoms.
Increased intestinal permeability in endotoxic pigs. Mesenteric hypoperfusion as an etiologic factor. Infusing pigs with lipopolysaccharide (LPS) decreases superior mesenteric artery blood flow (Qsma), suggesting that mesenteric hypoperfusion may be responsible for LPS-induced alterations in gut mucosal permeability. To test this hypothesis, we studied four groups of anesthetized swine. Group 1 animals (N = 6) were infused with LPS (250 micrograms/kg over 1 hour beginning at 60 minutes) and continuously resuscitated with Ringer's lactate (48 mL/kg per hour). In group 2 (N = 5), Qsma was decreased by 50% by means of a mechanical occluder to mimic the LPS-induced alterations in Qsma observed in group I. Group 3 (N = 5) was included to document our ability to detect ischemia/reperfusion-induced alterations in mucosal permeability; in these pigs, Qsma was decreased in steps to zero flow (at 150 to 210 minutes) and then perfusion was restored (at 210 to 270 minutes). Pigs in group 4 (N = 6) served as normal controls; these animals were resuscitated with Ringer's lactate at the same rate as in group 1 but were not infused with LPS. To assess mucosal permeability, we measured plasma-to-lumen clearances for two markers, chromium 51-labeled edetic acid monohydrate (EDTA) and urea. Loading and maintenance infusions of the markers were given intravenously, and a 20-cm isolated segment of small intestine was continuously perfused at 2 mL/min with Ringer's lactate at 37 degrees C. Results were expressed as the ratio of the clearances for the two probes (CEDTA/CUREA). In group 3, CEDTA/CUREA was 999% +/- 355% of baseline at 270 minutes. In group 1, CEDTA/CUREA was 572% +/- 235% of baseline at 270 minutes. In groups 2 and 4, however, CEDTA/CUREA did not change significantly from the baseline value over the duration of the study. These data suggest that increased mucosal permeability after LPS is due to factors other than (or in addition to) mesenteric hypoperfusion.
Characteristics of patients resistant to antihypertensive drug therapy. In order to determine the features that characterize refractory hypertension (RH), patients aged less than 65 years in a hypertension clinic were screened. Thirty-six patients on triple drug therapy with a supine diastolic blood pressure (DBP) of greater than or equal to 5 mmHg above an identified target pressure (90-100 mmHg), or a systolic blood pressure (SBP) greater than or equal to 170 mmHg for the last 6 months (greater than or equal to 3 measurements) underwent a thorough clinical investigation. The frequency of renal artery stenosis (RAS) in the RH patients was 30%. The non-RAS patients had a low occupational status, 76% being either manual workers or unskilled non-manual workers (reference group: 42%; P less than 0.01). They were more obese (body mass index (BMI) 28.8 vs. 25.8; P less than 0.01), and had a longer duration of hypertensive disease. RH patients had a higher prevalence of non-insulin-dependent diabetes mellitus (18 vs. 6%; P less than 0.05), and showed a higher prevalence of nervous complaints and mental distress (44% vs. 12%; P less than 0.001) and musculo-skeletal pain (39% vs. 7%: P less than 0.001). It is suggested that refractory hypertension should be investigated and treated bearing psychosocial factors in mind, concurrently with a screening for secondary hypertension.
Transcanal infracochlear approach to the petrous apex. Computerized tomography and magnetic resonance imaging have now made it possible to reliably differentiate cholesteatoma from cholesterol granuloma of the petrous apex. The treatment for cholesteatoma is complete surgical excision when possible, whereas cholesterol granuloma needs only adequate drainage for control. A new transcanal infracochlear approach for drainage of cholesterol granuloma involving the anterior petrous apex is described. Absolute measurements from 10 cadaveric temporal bones were obtained to determine the distances between the cochlea, jugular bulb, carotid artery, and facial nerve. In all specimens the petrous apex was entered without invading the cochlea, carotid, or jugular bulb. Advantages of this technique include a more direct route to the petrous apex, dependent drainage, and preservation of the normal hearing mechanism, including the tympanic membrane. Clinical indications for this technique include failure of other treatment approaches and a high jugular bulb obstructing an infralabyrinthine approach. Experience to date shows that patients experience little difficulty from the procedure.
Insulin pulses less effective than continuous insulin in inhibiting PEPCK mRNA levels stimulated by cAMP and dexamethasone in perifused hepatoma cells. Hepatic glucose production is stimulated in vitro twice as effectively by pulsatile as by continuous glucagon, given equivalent time-averaged doses. Efficacy studies of pulsatile insulin have yielded conflicting results. In the rat hepatoma cell line H-4-II-E-C3, insulin rapidly (t1/2 15 min) inhibits transcription of the gene and lowers mRNA levels for the gluconeogenic enzyme. PEPCK via a receptor-mediated process. We attached H-4-II-E-C3 cells to Cytodex-3 microcarriers and used a perifusion column system to test whether pulsatile insulin is more or less effective than equivalent time-averaged doses of continuous insulin. PEPCK transcription was induced by inclusion of cAMP analogue 8-(4-chlorophenyl-thio)-cAMP (0.1 mM) and dexamethasone (0.5 microM) in the perifusion medium. Three columns were exposed either to continuous, pulsatile, or no insulin. After 3 h, total nucleic acid was extracted, and mRNA(PEPCK) was measured with a sensitive-solution hybridization assay. Continuous insulin inhibited PEPCK expression in a dose-dependent fashion with EC50 1 x 10(-11) M. Equivalent time-averaged amounts of insulin delivered as pulses achieved significant inhibition but less effectively than continuous insulin. The apparent EC50 for pulsatile insulin increased from 2 x 10(-11) M to 5 x 10(-11) M as the oscillatory period was raised from 5 to 20 min, respectively. These observations suggest that insulin-mediated inhibition of PEPCK gene transcription is diminished by a pulsatile mode of administration in marked contrast to the pulse enhancement demonstrated for glucagon-mediated hepatic glucose production.
The clinical utility of prostate-specific antigen and bone scintigraphy in prostate cancer follow-up. To assess the value of serum prostate-specific antigen (PSA) in prostate cancer follow-up, we prospectively studied 107 consecutive patients with: (1) pathologically confirmed prostate cancer; (2) definitive prostatectomy and/or radiation therapy greater than or equal to 3 mo prior to bone scanning; and (3) one bone scan and serum PSA sampling within 3 mo of each other. The mean and range of patient follow-up since definitive therapy was 1.6 and 0.5-8 yr, respectively. Abnormal bone scans were correlated with pertinent radiographs. Of 107 bone scans, 16 demonstrated metastatic bone disease. A PSA value of less than or equal to 8 ng/ml excluded bone metastases with a predictive value of a negative test of 98.5%. Without radiographic correlation, abnormal bone scans rarely represented metastases if the PSA value was less than or equal to 8 ng/ml. In summary, serum PSA concentration determines the need for follow-up bone scanning and assists in scan interpretation in patients status post definitive therapy for prostate cancer.
Inflammatory edema induced by interactions between IL-1 and the neuropeptide calcitonin gene-related peptide. The neuropeptide calcitonin gene-related peptide (CGRP) is a potent vasodilator with a long duration of action. CGRP is widely distributed and is present in perivascular nerves of tissues that include skin and the synovium. In this study we have investigated the possibility that CGRP can modulate the inflammatory actions of the cytokine IL-1 by using an inflammatory model in rabbit skin. The intradermal injection of IL-1 (1.4 x 10(-14) mol/site) alone stimulated little edema formation. However, when IL-1 was injected with CGRP (10(-11) mol/site), a highly significant edema was observed, and neutrophil accumulation induced by IL-1 was potentiated. These results suggest that the action of IL-1 as a potent mediator of increased microvascular permeability is only observed when skin blood flow is increased in this model. This was confirmed by experiments in which PGE2 (3 x 10(-9) mol/site) at a dose with a similar duration of vasodilator action as CGRP (10(-11) mol/site) also potentiated edema induced by IL-1. Further experiments investigated the mechanism by which IL-1 increased microvascular permeability. Edema induced by IL-1 was dependent on de novo protein synthesis and the presence of circulating neutrophils. However, selective platelet-activating factor and histamine H1 antagonists had no inhibitory effect on this response. Thus it appears that when a microvascular bed is dilated by the long-lasting vasodilator CGRP, edema induced by IL-1 is clearly observed. These results highlight a potentially important synergistic interaction between cytokines and neuropeptides in inflammation.
Propranolol compared with propranolol plus isosorbide-5-mononitrate for portal hypertension in cirrhosis. A randomized controlled study. OBJECTIVE: To investigate whether isosorbide-5-mononitrate (Is-5-Mn) given with propranolol reduces hepatic portal pressure more than does propranolol alone in patients with cirrhosis. DESIGN: A randomized controlled trial. PATIENTS: Fifty patients with cirrhosis and esophageal varices entered and 42 completed the study. INTERVENTION: Twenty-one patients received oral propranolol at increasing doses until their resting heart rate was reduced by 25%, and 21 patients received oral propranolol (on the same schedule) plus oral Is-5-Mn, 40 mg twice a day. MEASUREMENTS: Hepatic vein pressure gradient, liver function, and splanchnic and systemic hemodynamics before and after 3 months of continuous therapy. MAIN RESULTS: At 3 months, the hepatic venous pressure gradient decreased more (P less than 0.01) in patients given propranolol plus Is-5-Mn (19%, from 18.4 +/- 3.9 to 14.9 +/- 3.8 mm Hg; 95% CI, -2.4 to -4.5 mm Hg) than in those given propranolol alone (10%, from 18.2 +/- 3.5 to 16.3 +/- 3.1 mm Hg; CI, -1.1 to -2.7 mm Hg). The hepatic venous pressure gradient decreased by more than 20% of the baseline value in 10% of patients receiving propranolol, but in 50% of patients receiving combined therapy (P less than 0.02). There were statistically significant decreases in hepatic blood flow and the intrinsic clearance of indocyanine green after propranolol therapy, but not after combined therapy. The treatments caused similar reductions in azygos blood flow and cardiac output. CONCLUSIONS: The long-term combined administration of propranolol plus Is-5-Mn reduces portal pressure more than propranolol alone without adverse effects on hepatic perfusion and liver function. Whether this greater hemodynamic effect translates into better clinical efficacy should be determined in randomized controlled trials.
Assessment of competency: the role of neurobehavioral deficits. We present a practical set of guidelines for assessing competency in patients with cognitive deficits due to neurologic disorders such as stroke, head injury, Alzheimer disease, and multi-infarct dementia. Our focus is the evaluation of cognitive processes underlying the ability to make competent decisions, with an emphasis on the identification of areas of preserved function that may be used to bypass intellectual deficits. The assessment of the cognitive processes underlying competency involves a series of steps designed to evaluate attention, language, memory, and frontal lobe function. The examiner must first show that the patient has an adequate level of attention for participation in the further testing of specific cognitive functions; second, that the patient is able to comprehend relevant instructions, retain information long enough to evaluate it in relation to relevant recent and remote experiences, and express his or her wishes; and finally, that the patient has sufficiently intact judgment and awareness. The examiner must determine whether the patient's preserved cognitive abilities are sufficient for him or her to make an adequate judgment in relation to the specific question being asked. If cognitive function is found to be significantly impaired, the examiner should do a detailed assessment for the presence of compensatory abilities that can be used to bypass the deficits. For example, the examiner should assess whether patients who cannot speak are still able to express their wishes by pointing, using gesture, or even by drawing pictures. Unless such an assessment has been done, patients should not be considered incompetent.
Entire ABL gene is joined with 5'-BCR in some patients with Philadelphia-positive leukemia. In four patients, the chromosome 9 breakpoint of the t(9; 22)(q34;q11) had occurred at different sites within an 8.25-kilobase (kb) region situated 5' of ABL exon 1B. Chromosome in situ hybridization and field inversion gel electrophoresis (FIGE) studies showed that ABL exons 1A and 1B were present on the Ph chromosome. Yet this large fusion gene produced an mRNA conventional for chronic myelogenous leukemia (CML). Splicing from BCR exon 3 to ABL exon 2 crossed more than 200 kb and deleted exons 1A and 1B. This breakpoint site may occur in about 10% of all CML patients. Three of our patients have pronounced thrombocytosis, and two had been diagnosed as having Ph-positive essential thrombocythemia. The platelet count of the other patient was not available.
Value and limitations of secondary femoropopliteal bypasses with polytetrafluoroethylene. Secondary femoropopliteal bypasses with polytetrafluoroethylene (PTFE) grafts are widely regarded to be of questionable value. This has prompted some to abandon all attempts at secondary revascularization with PTFE and others to recommend that primary femoropopliteal bypasses be performed preferentially with PTFE grafts so that vein may be used for secondary procedures. Because we questioned both of these views, we reviewed all femoropopliteal bypasses done at our institution in the past 12 years and identified 73 secondary PTFE femoropopliteal procedures performed after a failed ipsilateral infrainguinal bypass (69 failed femoropopliteal; 4 failed femorodistal). Seventy (96%) secondary bypasses were performed for limb salvage and 3 (4%) for severe disabling claudication. Insertion of grafts to the popliteal artery was above the knee in 26 (36%) and below the knee in 47 (64%). Primary life-table graft patency at 4 years was only 38%. Forty-eight reinterventions in 34 limbs were required to restore or maintain graft patency in thrombosed or failing grafts. For thrombosed grafts, 20 interventions consisted of 9 simple thrombectomies and 11 thrombectomies with additional revision procedures (5 distal or proximal extensions, 6 patch angioplasties). Twenty-eight lesions threatening graft patency were treated by percutaneous transluminal angioplasty in 3, proximal or distal extensions in 20, and patch angioplasty in 5. As a result of these reinterventions, the overall secondary patency rate was 55% at 4 years, and the limb salvage rate was 74% at 4 years. Although aggressive follow-up and reintervention may be required, the use of secondary PTFE conduits in the femoropopliteal position is a viable option in patients undergoing limb salvage procedures who are at high risk.