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Biomedical subjects

R Krishnan

Publications and source records attributed to R Krishnan.

At least 109 records · Page 6Linked to original sources

Quantitative assessment and reduction of long-term autoradiographic background.

Quantitative autoradiography can measure distribution patterns in an animal exposed to radiolabeled compounds. A comparison of autoradiographs of rat brain containing low levels of 14C showed that a highly variable background signal had been produced. This resulted in several overexposed autoradiographs which could not be quantitatively compared. The background, believed to be produced by light emanating from the phosphor coating in the X-ray cassette, was a major impediment because it hindered correct analysis of the specimen. This article details our experiments demonstrating the sources of variance contributing to background and offers methods for its reduction. We found that placement of black polyethylene plastic between the slides and phosphor in the X-ray film cassette minimized autoradiographic background and effectively eliminated the effects caused by inherently different levels of radioactivity in the glass slides.

Animals↗

Repair of prostatomembranous urethral strictures by a bulboprostatic intussusception technique.

The repair of post-traumatic strictures of the prostatomembranous urethra in 22 patients by a bulboprostatic intussusception technique is described. Minor wound infection occurred in 12 patients. No other complications were encountered in up to 5 years of follow-up. This operation is a useful and relatively easy technique for dealing with all but the very long strictures of this region.

Adolescent↗

A study of depressive typologies using grade of membership analysis.

Grade of Membership (GOM) analysis, a multivariate technique for studying disease, was used to explore depressive typology and relationships between depression and anxiety. One hundred and ninety patients with RDC diagnoses of major or minor depression were assessed by the Hamilton and SCL-90 symptom rating scales, the Newcastle diagnostic indices for endogenous depression and for anxiety and depression. Demographic, family and treatment response information were used as external validators. Five pure types provided the most satisfactory solution to these data. One group corresponded to classical melancholia, occurring in older, stable, in-patients, who lacked panic-phobic symptoms. All patients with agoraphobia fell into two distinct in-patient and out-patient groups, which differed from each other in several ways. In one group, a link was found between panic attacks, agitated melancholia and familial pure depression. The second group was less symptomatic and had more atypical vegetative symptoms. Two more groups comprised mildly symptomatic, hypochondriacal, depression, and a highly neurotic, obsessive, anxious, non-phobic depression, which was commonly related to a physical stressor.

Adolescent↗

Post-embedding methods for immunolocalization of elastin and related components in tissues.

Elastic tissue is composed of amorphous-appearing elastin and 12-nm diameter microfibrils, one component of which has recently been isolated and characterized as the 31 KD microfibril-associated glycoprotein MAGP. Monospecific antibodies to each of these components have been developed in this laboratory. The parameters that determine optimal localization of colloidal gold probes for post-embedding immunolabeling of elastic tissue components have been systematically studied in a variety of normal and developing tissues in mammals and birds. Protein A-gold probes stabilized with dextran have been shown to provide complexes that remain stable after more than 2 years. Conditions have been defined that permit precise localization within the extracellular matrix of antibodies to MAGP and to elastin, singly and together. Best results were obtained with acrylic resins (Lowicryl K4M or LR White). Fixation in glutaraldehyde or other aldehydic fixatives, with or without osmium, did not affect the immunostaining of elastic tissue with affinity-purified antibodies to tropoelastin, or to anti-[alpha-elastin] or anti-[alkali-insoluble elastin]. Immunostaining with the anti-MAGP antibody was less robust and was possible in tissues which had been fixed only lightly before embedding in Lowicryl K4M or LR White. This staining was enhanced by metaperiodate oxidation of the sections as well as by reduction of the tissues with sodium borohydride en bloc, followed by hyaluronidase digestion of the sections. The effects on immunostaining of a range of enzyme digestions have also been examined. Conditions have thus been defined that make possible detailed study of the relationship between elastic tissue, elastin-associated microfibrils, and other microfibrillar structures in normal and abnormal tissues during development and aging.

Animals↗

Effects of gamma-interferon on the endocrine system: results from a phase I study.

Interferon causes profound biological changes when given to patients with cancer and many of these could not be predicted from in vitro or animal model systems. We documented significant changes in hormonal levels for a group of 18 patients who were participants in a Phase I gamma-interferon trial. Adrenocorticotropic hormone, cortisol, and growth hormone were all significantly elevated 2 h after treatment with gamma-interferon, with cortisol and adrenocorticotropic hormone returning to base line by 24 h. A placebo group failed to show this change, suggesting a specific interferon effect. Possible mechanisms for these findings and implications for the use of interferons are discussed.

Adrenocorticotropic Hormone↗

Intrarater reliability of manual muscle testing and hand-held dynametric muscle testing.

Physical therapists require an accurate, reliable method for measuring muscle strength. They often use manual muscle testing or hand-held dynametric muscle testing (DMT), but few studies document the reliability of MMT or compare the reliability of the two types of testing. We designed this study to determine the intrarater reliability of MMT and DMT. A physical therapist performed manual and dynametric strength tests of the same five muscle groups on 11 patients and then repeated the tests two days later. The correlation coefficients were high and significantly different from zero for four muscle groups tested dynametrically and for two muscle groups tested manually. The test-retest reliability coefficients for two muscle groups tested manually could not be calculated because the values between subjects were identical. We concluded that both MMT and DMT are reliable testing methods, given the conditions described in this study. Both testing methods have specific applications and limitations, which we discuss.

Adult↗

Failure of long term high-dose lecithin to retard progression of early-onset Alzheimer's disease.

We conducted a six-month, randomized, double-blind trial of lecithin therapy in early-onset Alzheimer's disease. We hypothesized that such therapy would retard the progression of the clinical and neuropsychological manifestations of this illness. Of the 73 referred patients, 37 met strict requirements for diagnosis and compliance. The 21 placebo and 16 lecithin-treated patients (mean age 63 years) had a comparable degree of severity of dementia (mean Clinical Dementia Rating 1.6). Lecithin therapy produced an increase in mean plasma choline levels from a baseline of 15.9 to 28.8 nmol/ml. Patients were evaluated by the physician using clinical assessments (CDR, Lawton ADL and other rating scales) and by the neuropsychologist who determined the outcome of therapy on a battery of tests (Mini Mental State Examination, Wepman Aphasia Screen, Verbal Fluency Test, Verbal Selective Reminding Test and Spatial Memory Test). Only 6 (37.5%) of the 16 lecithin-treated patients were considered by the neurologist to be clinically stable or improved as compared to 12 (57.1%) of the 21 patients given placebo (difference -19.6%, 95% confidence limits of -51% to 12%). The neuropsychologic scores showed no differences in the stability of the dementing process over time between the lecithin-treated (50.0%) and placebo (47.6%) groups. On the basis of these clinical and neuropsychological findings, it appears that lecithin alone has no important therapeutic effect in early-onset Alzheimer's disease.

Alzheimer Disease↗

Preliminary study of thyrotrophin releasing hormone stimulation test in chronic low back pain patients.

Chronic pain has been considered as a variant of depression or as a masked depression. In an attempt to unravel the complex relationship between chronic pain and depression, we administered the TRH stimulation test to a uniform group of chronic pain patients classified into those with and without major depression using DSM-III criteria. Eighteen percent showed blunting of TSH response to TRH. There was no significant difference between the two groups.

Adult↗

Standardization of monoclonal antibodies for use in autologous bone marrow transplantation for common acute lymphoblastic leukemia.

Two monoclonal antibodies suitable for leukemia cell purging of remission bone marrow from patients with common acute lymphoblastic leukemia (common-ALL) are described. WM-21, reacting with the gp 100 common-ALL associated antigen (CALLA), and FMC-8, reactive with a p24 surface antigen, both bind to the majority of leukemic blast cells from cases of common ALL, and promote complement-mediated lysis of CALLA+ leukemias and cell lines. After initial dye exclusion studies to standardize antibody and rabbit complement concentrations and incubation times, an in vitro plating assay using CALLA+ p24+ cell lines was used to investigate the lytic ability of monoclonal antibody treatment. Incubation with WM-21, FMC-8, and complement produced up to 5 logs inhibition of growth in this system. Under similar conditions, no inhibition of in vitro growth of normal bone marrow myeloid progenitor cells was seen. These antibodies therefore appear to be useful therapeutic reagents for removing residual common ALL blast cells from bone marrow prior to autologous marrow transplantation.

Antibodies, Monoclonal↗