Computed tomography and pulmonary function abnormalities in sickle cell disease.

The aim of this study was to determine whether patients with sickle cell disease (SCD) in steady state had pulmonary abnormalities seen on high-resolution computed tomography (HRCT) and whether any abnormalities correlated with contemporaneously diagnosed lung function abnormalities. A subsidiary question was whether the results of a noninvasive measure of haemolysis (end-tidal carbon monoxide (ETCO) levels) correlated with pulmonary function abnormalities. Thirty three patients with SCD, median (range) age 36 yrs (17-67 yrs) were examined. The degree of lobar volume loss and ground-glass opacification and prominence of central vessels on HRCT were quantitatively assessed. Pulmonary function was assessed by measurements of lung volumes, spirometry, gas transfer and oxygen saturation. ETCO levels were measured using an end-tidal CO monitor. Forced expiratory volume in one second (FEV1), forced vital capacity and total lung capacity significantly correlated with HRCT findings, particularly lobar volume loss. ETCO levels significantly negatively correlated with FEV1, vital capacity measured using a plethysmograph, specific airway conductance and arterial oxygen saturation measured by pulse oxymetry. In conclusion, the present results suggest that high-resolution computed tomography noninvasive assessment of haemolysis might be useful to identify sickle cell disease patients with respiratory function impairment.     

Autoimmune hepatitis: a study of 50 patients.

INTRODUCTION: Autoimmune hepatitis (AIH) is a well-defined entity in the West but there are sparse Indian data on this disease. AIM: To study the clinical profile and response to treatment of Indian patients with AIH. METHODS: This is a part retrospective and part prospective study of 50 patients (median age 48 years, range 11-82; 43 women) seen between 1995 to 2001, diagnosed to have AIH as per the revised scoring system. Clinical and laboratory profile, response to treatment, and complications of treatment were analyzed. RESULTS: AIH accounted for 6% of all patients with liver disease seen during the period. The presenting symptoms were gastrointestinal in 43 and non-gastrointestinal in 7, with median symptom duration of 6 months (range 2 weeks to 40 years). Forty patients (80%) had chronic liver disease. Associated illnesses were present in 28 patients. Twenty-six patients were classified as definite and the rest as probable AIH. Forty-nine patients had Type 1 AIH. Five patients had overlap syndrome. Forty-five patients (90%) received immunosuppressive therapy. Twelve of 18 patients receiving only prednisolone and 21 of 27 patients receiving prednisolone and azathioprine combination responded. Thirteen (26%) patients had therapy-related complications (infectious 5, non infectious 8) with two treatment-related deaths. CONCLUSION: Type 1 AIH was the predominant type of AIH. The majority of patients with AIH presented with chronic liver disease. There was good response to immunosuppressive therapy. Therapy-related complications occurred in one-fourth of patients.     

Increased production of peroxidation products associated with cardiac operations. Evidence for free radical generation

We investigated the degree and time course of neutrophil sequestration into human lungs during cardiac operations. At the same time, measurement of the concentration of peroxidation products in the plasma was used as an index of oxidant free radical activity. The study was performed in two groups of patients. Group A (n = 11) had studies extending over the entire operative period and showed a highly significant sequestration of neutrophils into the lung, together with a highly significant (p less than 0.001) rise in peroxidation products from 2.8 +/- 0.12 nmol/ml(mean +/- standard error of the mean)before bypass to a peak of 5.05 +/- 0.13 nmol/ml at the end of bypass. As these changes occurred only during the time after release of the aortic cross-clamp, we investigated this period in more detail in a second group of patients (Group B, n = 7). Results from this group showed that significant release of peroxidation products occurred at the same time as pulmonary neutrophil sequestration. This study has produced evidence of increased oxidant activity in the lung associated with cardiac operations. Nevertheless, it is not known whether the neutrophils sequestered into the lung alone induced the increased activity. Similarly, whether neutrophil-derived oxidant species are the sole cause of lung tissue injury remains unproved.     

Value of acute-phase angiography in the detection of vascular injuries caused by gunshot wounds to the head: analysis of 12 cases.

A study of the angiographic findings in consecutive civilian patients with cranial gunshot wounds examined in the acute stage has not been done. Most prior clinical studies have evaluated the findings in survivors in the subacute or chronic stages and have often been of war-time casualties. We determined the clinicoradiologic features of six cases of posttraumatic intracranial aneurysm, vascular occlusion, or arteriovenous fistula caused by penetrating missiles among 12 civilian patients who were examined in the acute posttraumatic stage (within 48 hr of injury) during a 1-year period. Three internal carotid/vertebral artery aneurysms, one external carotid artery aneurysm, one combined aneurysm/arteriovenous fistula of the vertebrobasilar circulation, and one cerebral venous occlusion were identified. The 50% overall prevalence of major vascular lesions in this series of civilian patients with penetrating missile injuries examined in the acute stage suggests these injuries are more common than previously suspected. It may indicate that selective cerebral angiography should be considered in the evaluation of the cranial vascular system of such persons.     

Trial of ketotifen in childhood asthma

An open trial of Ketotifen was conducted on 29 children suffering from asthma of varying duration. The drug was given orally in a dose of 1 mg twice a day. Children were followed up weekly for a period of 3 months. It was found beneficial (though the benefit was not statistically significant) in children having asthma of less than 2 years duration who were taking one drug regularly or were on occasional treatment. There was marginal effect in children taking salbutamol and theophylline together, but irregularly and no benefit in children taking prednisolone.     

Acquired apolipoprotein B deficiency with chronic hepatitis C virus infection.

Chronic hepatitis C virus (HCV) infection is often associated with fatty liver. Apolipoprotein B (ApoB) deficiency is one of the known causes of fatty liver and acquired ApoB deficiency has recently been reported with HCV infection. We report two patients (47-year-old lady and 48-year-old man) who had asymptomatic transaminase elevation, fatty liver, anti-HCV positive with high viral load (genotype 3). Their lipid profile showed low total cholesterol, low-density lipoprotein, triglycerides and ApoB. One of the patients who received treatment for HCV infection showed improvement in lipid profile and ApoB levels.     

Stability studies of the components of a prototype penicillinase (β-lactamase)-linked ELISA kit

Penicillinase (β-lactamase) enzyme-linked immunosorbent assay (ELISA) for various reproductive hormones developed in the laboratory were found to have wide applicability in the fertility check clinic of the Institute. A need was thought to transform these assays into ready-to-use kit forms. Therefore, prototype ELISA kits for these hormones were developed and stability of the individual component was ascertained at various temperatures (room temperature, 37°C and 2-8°C). Stability studies were conducted on previously validated assay for pregnanediol-3α-glucuronide (PdG). The studies showed that immunosorbents (antibody coated plates) are stable at room temperature for a period of 2 weeks, at 37°C for 1 week and at 2-8°C for a period of 9 months when preserved after treatment with glycerol solution. The lyophilised conjugate, standard and immunoassay buffer, colour reagent, and its substrate were stable at 37°C up to 1 week and at room temperature up to 2 weeks and at 2-8°C for a period of 6 months, during which the stability was studied. © 1993 Wiley-Liss, Inc.     

Mutations of the human thyrotropin-beta subunit glycosylation site reduce thyrotropin synthesis independent of changes in glycosylation status.

In recent studies, site-directed mutagenesis has been used to alter the tripeptide glycosylation recognition sequences of glycoprotein hormone subunits, thereby affecting their structure and function. However, it is not known whether these effects result from changes in glycosylation status, amino acid sequence, or both. We therefore studied the synthesis of wild-type and mutant recombinant human thyrotropins produced by transient transfection of a human cell line. Mutating the TSH-beta subunit glycosylation recognition sequence, Asn-Thr-Thr (codons 23-25), to either Gln-Thr-Thr or Asn-Thr-Tyr abolished subunit glycosylation, as demonstrated by the inability to incorporate 3H-carbohydrates. However, a third mutation (Asn-Thr-Ser) contained an intact glycosylation recognition sequence site, and was shown to retain glycosylation. The mutations that abolished TSH-beta subunit glycosylation resulted in greater than 90% decreases in TSH synthesis. However, the glycosylation recognition sequence mutant that retained beta subunit glycosylation exhibited a 70% decrease in TSH production. These decreases were not attributable to the intracellular accumulation of TSH or its free beta subunit. We also engineered two TSH-beta subunit mutations that did not alter the glycosylation recognition sequence. A glycine to arginine mutation adjacent to the glycosylation recognition sequence, in a region thought to be critical for heterodimer formation, abolished TSH production. In contrast, shortening the TSH-beta subunit carboxyterminus by six amino acids increased TSH synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of the integrated 3-hour plasma cortisol concentration as a test for Cushing's syndrome

Twenty-four hour urinary free cortisol and mean and integrated 13h00-16h00 plasma cortisol levels were measured in 9 patients with proven Cushing's syndrome (5 with Cushing's disease, 2 with ectopic adrenocorticotrophic hormone production due to bronchial carcinoma and 2 with adrenal adenomas) and in 21 patients without Cushing's syndrome. The 24-hour urinary free cortisol levels and mean and integrated 13h00-16h00 plasma cortisol estimations clearly distinguished patients with Cushing's syndrome from those without. However, adequate suppression on dexamethasone suppression tests (false negatives) were obtained in 3 of the 9 patients with Cushing's syndrome. Since the integrated 13h00-16h00 plasma cortisol estimation is cheaper and simpler than the mean 13h00-16h00 plasma cortisol estimation, we recommend it as an adjunct in the diagnosis of Cushing's syndrome.