Roxithromycin induced hypersensitivity pneumonitis.
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Biomedical subjects
Publications and source records attributed to M Cherian.
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BACKGROUND: Following our experience with minimally invasive valve replacement operation, we utilized this technique for surgical management of cardiac tumors. METHODS: Between April 1997 and September 1999, 5 consecutive patients with cardiac tumors underwent minimally invasive excision of the tumors. The patients were 4 women and 1 man with an age range of 32 to 50 years. The tumor was located in the left atrium in 4 patients and the right atrium in 1 patient. The common presenting symptoms were dyspnea on exertion (100%), chest pain (60%), palpitation (60%), and transient ischemic attack (20%). Diagnosis was established preoperatively by echocardiography only. RESULTS: In 2 patients the approach was right parasternal and the subsequent 3 patients had direct-access partial sternotomy. The myxoma was resected transseptally in all patients. There was no hospital mortality. One patient had postoperative embolic episode leading to left hemiparesis. Follow-up did not reveal any complication related to this technique and all were in New York Heart Association (NYHA) functional class I. CONCLUSIONS: Minimal access partial sternotomy is an effective approach that adheres to all the identified surgical principles in successful removal of these tumors. The smaller incision does not compromise the efficacy or safety of the operation, reduces hospital stay, and has a good cosmetic result.
Teratomas are rare congenital neoplasms that arise from pluripotent cells. They consist of tissue from all three embryonic germ layers. According to most studies, teratomas of the head and neck account for only 2 to 9% of all cases. In this article, we report the first case of a teratoma of the nasal vestibule in a newborn. We also discuss methods of diagnosis and treatment of upper airway teratomas, and we include a brief review of the literature.
BACKGROUND: Previous studies have suggested that cimetidine, a histamine-2 receptor antagonist with immunostimulatory effects, may improve survival in patients with colorectal carcinoma. This effect may be apparent by an increase in the number of peritumoral lymphocytes. A prospective, double blind, randomized, placebo-controlled trial of a short course of preoperative treatment with cimetidine in patients with colorectal carcinoma was performed to assess the effect of cimetidine on survival and on the number of peritumoral lymphocytes. METHODS: One hundred and twenty-five patients who were scheduled to undergo elective colon or rectal excision for carcinoma were randomized to receive either placebo or cimetidine preoperatively for 5 days. In addition to standard histopathology, immunohistochemistry and computer video image analysis were used to assess the number of peritumoral lymphocytes in an objective manner. Interim survival analysis according to the Kaplan-Meier method was performed. RESULTS: A trend toward a survival advantage in the group of patients receiving cimetidine (800 mg twice daily) compared with the placebo group was observed (P = 0.20, log rank test) that was most marked in patients with replication error negative tumors (P = 0.04). Similarly, in these two groups there was a trend toward an increase in the number of patients with a conspicuous lymphocytic infiltration (P = 0.10, chi-square test). However, there was no difference in the number of peritumoral lymphocytes as measured by image analysis. CONCLUSIONS: Based on the results of the current study, a short course of preoperative treatment with cimetidine does appear to have an effect on patient survival; however, the exact mechanism is unknown. The failure of this study to demonstrate a clear increase in the local lymphocyte response does not exclude an immunologic mechanism of action.
In an earlier report we showed that incubation of alpha-crystallin with oxidized glutathione results in significant loss of its chaperone-like activity. In the present study, we determined the effect of protein-glutathione mixed disulfides (PSSG), formed at Cys-131 in bovine alphaA-crystallin, and Cys-131 and Cys-142 in human alphaA-crystallin, on the function of alpha-crystallin as a molecular chaperone. After incubation of calf and young human alphaL-crystallin fractions with oxidized glutathione, levels of PSSG were determined by performic acid oxidation of the mixed disulfides followed by reversed-phase high pressure liquid chromatography separation of phenylisothiocyanate-derivatized glutathione sulfonic acid. Levels of PSSG increased from 0.01 to 0.14 nmol/nmol (20 kDa) in bovine alphaL-crystallin and from 0.022 to 0.25 nmol/nmol in human alphaL-crystallin. The presence of glutathione adducts at Cys-131 and Cys-142 were confirmed by mass spectral analysis. The chaperone-like activity was determined by the heat denaturation assay using betaL-crystallin as the target protein. To examine the reversibility of the effect of mixed disulfides on chaperone activity, studies were done before and after reduction with the glutathione reductase system. Increased levels of PSSG resulted in lower chaperone activities. Treatment with the glutathione reductase system led to 80% reduction in PSSG levels with a concomitant recovery of the chaperone activity. These results suggest that cysteine(s) in the alphaA-crystallin subunit play an important role in the function of alpha-crystallin as a molecular chaperone.
In vitro glycation was previously shown to influence alpha-crystallin chaperone function. In the present study we show that this function is compromised in diabetes. The alpha H, alpha L and the total alpha fractions were isolated by gel permeation chromatography from the water-soluble protein of streptozotocin-diabetic as well as age-matched normal rats. Based on the beta L-crystallin thermal denaturation assay the chaperone function was significantly decreased in the diabetic rats.
We studied the effect of oxidation, mixed disulfide formation and glycation of alpha-crystallins on their molecular chaperone property. The ability of alpha-crystallins to protect heat-induced denaturation and aggregation of beta L-crystallin was significantly diminished by these modifications. alpha-Crystallin from senile human lenses also showed significant loss of chaperone-like property. Age-dependent increase in posttranslationally modified alpha-crystallins is the likely cause for this change.
Germanium compounds have been shown to be effective in preventing the formation of advanced glycation end-products and for reversible solubilization of glycated proteins. As protein glycation has been proposed to play a role in lens opacification, we initiated studies to evaluate the effects of 2-carboxyethyl germanium sesquioxide (germanium compound 132 or Ge-132) on galactose-induced cataractogenesis. For this study young Sprague-Dawley rats were fed a 50% galactose diet. One group of rats received topical saline and another group was administered Ge-132 in saline four times a day. The lenses were periodically examined with an ophthalmoscope and at desired intervals processed for light and scanning electron microscopy. Our observations, beginning at 3 days and continuing to 21 days of galactose feeding, exhibited the characteristic galactose-induced morphological alterations, which include the formation of vacuoles, cysts, membrane disruption and swelling of fibers and epithelial cells as well as disorganization of the bow in lenses of rats in both groups. However, in the majority of rats administered Ge-132 these alterations were delayed as compared to the lenses of rats administered saline. Our findings show that, although the initiation, progression and pattern of lens opacification in rats receiving saline and Ge-132 were similar, in the majority of lenses the progression and establishment of mature cataracts in the Ge-132 group of rats were delayed. Analysis of the water-soluble and water-insoluble lens-protein fractions for glycated proteins showed increased levels of the Amadori products and advanced glycation related fluorescent products in galactosemic rats treated with saline eye drops. In rats receiving the topical Ge-132 treatment the levels of these glycation products were substantially reduced to levels lower than control values. Prevention of glycation seems to be a mechanism by which cataract progression is delayed.
Athetosis and dystonia are well known clinical signs, described in disorders of basal ganglia. As opposed to pseudoathetosis, true athetosis was hitherto not reported in cord lesions. We here report three patients with athetosis and dystonia of hands due to intramedullary lesions of cervical cord: two patients with syringomyelia and one with glioma. Even though pseudoathetosis can be produced by lesions of posterior columns and likely to be confused with the involuntary movements of our patients, they had clinical and EMG findings consistent with true athetosis. A possible explanation for the athetosis and dystonia due to cord lesion is being postulated.
The release of vasoactive mediators by vascular (VEC) and endocardial endothelial cells (EEC) has not been directly compared. In this study, in vitro morphological and cell growth characteristics and the rate of prostanoid release were compared in cultured sheep endothelial cells from great vessels (VEC; pulmonary artery and aorta) and endocardium (EEC; right and left ventricles) harvested from the same animals. Morphologically, in flasks, VEC demonstrated the classic cobblestone pattern, whereas EEC developed numerous cytoplasmic interdigitations and overlaps. Rate of cell proliferation was greater for EEC than for VEC (P < 0.05): doubling time was shorter for EEC (34 +/- 3 h) than for VEC (45 +/- 5 h). Under static (no-flow) conditions, in response to arachidonic acid and calcium ionophore A-23187, the rate of prostacyclin (PGI2) and prostaglandin E2 release by VEC and EEC was not different. In contrast, in response to flow and acute hypoxia (O2 tension = 35 Torr), the rate of PGI2 release was greater in EEC than in VEC (P < 0.0001). After 2 h of perfusion, the rate of PGI2 release was 19-fold greater for EEC than for VEC during normoxia and 34-fold greater during hypoxia. Thus our study showed anatomic site of origin-dependent heterogeneity in prostanoid release between VEC and EEC. Endocardial endothelium is a greater source of PGI2 than great vessel endothelium; in vivo, endocardial endothelial PGI2 may inhibit local platelet aggregation and modulate downstream vascular tone.
We determined the site selectivity of glycation by glucose (glucosylation) in alpha A- and alpha B-crystallins using two independent approaches. HPLC purified 14C-glucose labeled chymotryptic peptides and affinity chromatography/HPLC purified fully glycated peptides were identified by FAB-MS. Lys 11 and 78 of alpha A-crystallin and Lys 90 and/or 92 of alpha B-crystallin were the fast reacting sites of glucosylation.
In vitro studies with rat lens crystallins were conducted to explore the mechanism by which aspirin (ASA-acetylsalicylic acid) could inhibit cataractogenesis. The purpose of the present study is to show whether gamma-crystallin is the primary target for glycation by glucose and acetylation by ASA. Lens soluble fractions from one and seven month old Sprague-Dawley rats were incubated with 5 mM [14C]glucose with and without 10 mM ASA. alpha, beta, and gamma-crystallins were separated by molecular sieve HPLC and specific activities of each crystallin determined. In vitro acetylation was also studied by measuring protein bound [14C]acetyl groups after incubation with [14C]acetyl ASA. There was 2 to 4-fold faster glycation of gamma-crystallin than all other crystallins from 1-month-old rats and ASA inhibited glycation of gamma-crystallin four times more than that of alpha and beta-crystallins, thus showing preferential glycation of gamma-crystallin and its selective inhibition by ASA. [14C]acetyl incorporation showed increased acetylation of gamma-crystallin in one month old rats, whereas in older lenses acetylation of other crystallins predominated. Treatment with 10 mM ASA showed 35% decrease in free -NH2 groups but protein thiols remained unchanged.
Human lenses of three different ages were used to study the effect of age and aspirin treatment on glycation of alpha-, beta- and gamma-crystallins. Soluble lens proteins were subjected to in vitro glycation with 5 mM [14C]glucose in the presence and absence of 10 mM aspirin. With crystallins from a 27-year-old lens alpha-crystallin was the most readily glycated protein. Glycation of all crystallins decreased substantially (37-77%) in 46- and 67-year-old lenses indicating an age-dependent decline in glycation sites. On the basis of a sensitive chemical assay for protein-bound glycogroups in lenses of 2-82 years of age this decline is apparently due to a 60% increase in in vivo glycation. Aspirin did not show any selectivity with regard to its ability to inhibit glycation of various crystallins. Irrespective of the age glycation of all crystallins was inhibited to a varying extent.
Human epithelial cell density was determined from flat preparation of 195 cataractous lenses from 108 males and 87 females between 30 and 80 years of age. The mature cataracts had significantly lower cell counts than the other cataracts. Cell density was significantly higher in the females than in the males. Morphohistological study of the epithelia was focused on the following cataract types: (1) nuclear, (2) posterior subcapsular, (3) mature, (4) mixed, (5) hypermature, and (6) black. The major cataractous changes in all types involved vacuolization of the cytoplasm. The mature types of cataractous epithelia showed 56% superimposed cells; the epithelia in nuclear, posterior subcapsular, and black cataracts showed between 6% and 16%. In the hypermature cataracts, four of five tissues analyzed showed superimposed cells. The superimposed areas are probably the source of increased and altered cell activity. We propose that the metaplastic processes leading to posterior capsular opacification originate from these areas. The majority of nuclear and black cataracts were almost similar to the normal human lens epithelium with more or less uniform distribution of cells. Nucleus shrinkage (5 microns) was more evident in nuclear cataracts; in subcapsular cataracts most of the nuclei were large (average 9 microns diameter). Variation in morphological changes like vacuolization of cytoplasm and nuclei, pyknotic nuclei, and superimposed cells was more evident in the mixed type of cataracts.
Glutathione (GSH) and GSH-related enzymes, glutathione reductase (GR), gamma-glutamyl cysteine synthetase (gamma-GCS), gamma-glutamyl transpeptidase (gamma-GTP), glutathione S-transferase (GST) and adenosine triphosphatase (ATPase) enzymes were analysed to study the effect of busulfan on the defence mechanisms of the lens. All these enzymes were found to increase significantly except GSH which showed only 7.9% increase as compared to controls in precataractous stage. These results affirm that busulfan is capable of evoking a response from the enzymes involved in the various pathways of GSH enabling the lens to prolong its clarity. The cataractous lenses showed significant decrease in all these parameters. Here, the impairment of the defense mechanism (GST, GR) and the total ATPase may be attributed to the cumulative action of the drug which can react with -SH groups of these enzymes, ultimately causing opacification.
Most small carcinomas arise from polyps. Small lesions with cellular features of malignancy and early invasion, but with no histologic evidence of residual adenoma, are rare. Diagnosed by endoscopy, three such lesions are described. They were recognized as mucosal plaques, measuring between 6 and 8 mm in diameter. In each case, there was either synchronous or metachronous carcinoma elsewhere in the colon, as well as benign adenomatous polyps. Colonoscopic identification of such lesions allows inclusion of that bowel segment in any planned resection.
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