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Biomedical subjects

M Varma

Publications and source records attributed to M Varma.

At least 19 recordsLinked to original sources

Significance of protocol biopsies in living related renal transplant recipients.

INTRODUCTION: Subclinical rejection (SCR) in a normally functioning renal allograft may have an impact on long-term graft outcome. SCR detection is best done by protocol biopsies in clinically normal grafts. METHODS: We evaluated 20 stable living related renal allografts with protocol biopsies on days 7 and 90 posttransplant. SCR when detected was treated with a 3-day pulse of methylprednisolone therapy. The outcomes of these grafts were compared with 63 other clinically stable renal allografts that did not undergo protocol biopsies. RESULTS: SCR was observed in 60% of cases. The patients who received antirejection therapy for SCR based on protocol biopsies showed better graft survival and mean serum creatinine values at the end of the follow-up period.

Adolescent↗

Diagnostic utility of immunohistochemistry in morphologically difficult prostate cancer: review of current literature.

Varma M & Jasani B (2005) Histopathology47, 1-16 Diagnostic utility of immunohistochemistry in morphologically difficult prostate cancer: review of current literatureImmunohistochemistry is widely used to distinguish prostate cancer from benign mimics and to establish the prostatic origin of poorly differentiated carcinoma. We critically review the recent advances in prostate cancer immunohistochemistry, including the introduction of newer basal cell markers such as p63 and the discovery of the overexpression of alpha-methylacyl coenzyme A racemase (AMACR) in prostate cancer. The description of newer urothelial markers to aid the distinction of prostate cancer from urothelial carcinoma is also presented together with refinements in the quality control of PSA and PSAP immunostaining. Although AMACR is a useful immunohistochemical marker for prostate cancer, it has significant limitations. These limitations are discussed and the need for interpreting AMACR immunoreactivity in the appropriate morphological context and in conjunction with basal call markers is emphasized. We also describe the utility of an immunohistochemical panel composed of PSA, PSAP and high molecular weight cytokeratin for distinguishing poorly differentiated prostate cancer from high-grade urothelial carcinoma. A morphological differential diagnosis based selection of immunohistochemical markers is highlighted as a novel approach in the diagnosis of prostate cancer in routine surgical pathology practice.

Biomarkers, Tumor↗

Comparison of populations of mould species in homes in the UK and USA using mould-specific quantitative PCR.

AIMS: To compare the populations of 81 mould species in homes in the USA and UK using mould-specific quantitative polymerase chain reaction (MSQPCR) technology. METHODS AND RESULTS: Dust samples were obtained from randomly selected homes in the UK (n=11). The mould populations in British homes were compared with those found in typical homes (no visible mould) in the USA (in the state of Ohio, n=45). Only 13 of 81 species screened showed significantly different concentrations in these two sets of home. CONCLUSIONS: Although only a small survey, the results suggest that typical mould profiles in the USA (Ohio) and British homes are very similar. Analysis of 26 mould indicator species revealed that the British homes fell into two clusters, tentatively identified as 'atypical' and 'typical' mould conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: MSQPCR analysis of dust samples can provide an objective measure of indoor moulds which could lead to better management of their health effects.

Air Pollution, Indoor↗

Release of diltiazem hydrochloride from hydrophilic matrices of polyethylene oxide and carbopol.

The mucoadhesion, swelling, and drug release behavior of polyethylene oxide (PEO) and carbopol (CP) matrices were studied using a water soluble model drug diltiazem hydrochloride. The mucoadhesive strength of the matrices increased with increase in polymer content. The results showed that PEO was more mucoadhesive than CP. Mucoadhesion of the tablets was dependent upon the swelling. Swelling was ascertained by measuring the axial and radial expansion of matrix tablets following exposure to media of physiological ionic strength. There was a marked increase in the swelling index of matrices containing high polymer content of PEO as compared to CP. Drug release kinetics were found to be closely related to dissolution and swelling properties of the matrices. The release was found to be non-Fickian with n (release exponent) values ranging from 0.45-0.58. At a constant polymer content (15.84% w/w), the main contributing factor for the mucoadhesion, swelling, and release was the amount of PEO.

Acrylic Resins↗

Technical variations in prostatic immunohistochemistry: need for standardisation and stringent quality assurance in PSA and PSAP immunostaining.

AIMS: To assess variations in prostate specific antigen (PSA) and prostate specific acid phosphatase (PSAP) immunohistochemistry with particular reference to the antibody type (monoclonal or polyclonal) and the tissues used for optimising immunostaining conditions and as external positive controls. METHODS: A questionnaire was sent to all laboratories registered with the UK National External Quality Assurance Scheme for immunohistochemistry enquiring about the immunohistochemical methods routinely used for the diagnosis of prostate cancer. RESULTS: Responses were received from 220 (68%) laboratories. All UK respondents routinely performed PSA immunostaining but PSAP immunostaining was available in only 57% of these laboratories. Monoclonal anti-PSA, polyclonal anti-PSA, monoclonal anti-PSAP, and polyclonal anti-PSAP were used by 40%, 60%, 29%, and 27% of UK respondents, respectively. Benign prostate tissue was most commonly used to determine optimal antibody dilutions and as external quality control for PSA/PSAP, with only 6% and 3% of respondents, respectively, including high grade prostate cancer in the tissues used for these purposes. CONCLUSIONS: The wide variation in the methods used highlights the need for standardisation and more stringent quality assurance of the immunohistochemical staining techniques used for PSA and PSAP. The widespread use of benign prostate tissue to determine optimal antibody dilutions and as an external positive control for PSA and PSAP immunostaining is of particular concern because this approach may result in a method that is not sufficiently sensitive to detect the reduced PSA and PSAP expression associated with high grade prostate cancer.

Acid Phosphatase↗

Fixed dose combinations for tuberculosis: Lessons learned from clinical, formulation and regulatory perspective.

Worldwide, tuberculosis (TB) remains one of the most important communicable diseases in terms of morbidity and mortality. Its control requires multi-drug therapy for at least six months, which could lead to patient non-compliance, failure of therapy and ultimately resulting in the emergence of drug resistance. Fixed dose combinations (FDCs) in TB therapy reduce the number of tablets to be consumed and thereby increase patient compliance with recommended treatment regimens. Thus, FDCs play a significant role in preventing the emergence of drug resistance and successful treatment. However, the quality of FDCs with respect to variable bioavailability and their registration requirements are major hurdles to their implementation in national TB control programs. It is anticipated that a large global market for FDCs will encourage large-scale production and increased competition, which in turn will result in FDCs at affordable prices. The Global Drug Facility (GDF), established by the World Health Organization (WHO), aims to ensure universal uninterrupted access to quality TB drugs for implementation of directly observed treatment short-course (DOTS) in resource-poor countries. In this program, four FDCs were accepted as the drugs of first choice because of their obvious advantages in controlling TB. This demands the necessity of addressing quality and registration requirements of FDCs systematically. In light of this current knowledge on anti-TB FDCs, their dosage, combinations, available clinical studies and the experiences with TB therapy has been discussed in this article, which should serve as lessons for selection of appropriate FDCs for other diseases such as malaria and AIDS.

Antitubercular Agents↗

High molecular weight cytokeratin antibody (clone 34betaE12): a sensitive marker for differentiation of high-grade invasive urothelial carcinoma from prostate cancer.

AIMS: There is no well-established positive immunomarker for urothelial carcinoma. We evaluated the diagnostic utility of high molecular weight cytokeratin (HMWCK) antibody clone 34betaE12 in differentiating high-grade invasive urothelial carcinoma from prostate cancer. METHODS AND RESULTS: Formalin-fixed paraffin-embedded sections from 28 cases of high-grade invasive urothelial carcinoma (20 not otherwise specified (UC-NOS), eight with glandular differentiation) and 20 cases of poorly differentiated prostate carcinoma were immunostained with a monoclonal antibody to carcinoembryonic antigen (CEA), clone 85A12 and with HMWCK antibody clone 34betaE12 after microwave pretreatment or protease 24 predigestion. All cases of UC-NOS expressed HMWCK on 34betaE12 immunostaining after microwaving or enzyme predigestion. Immunoreactivity was intense and diffuse in all the cases after microwave pretreatment, whilst with enzyme predigestion immunoreactivity was sometimes patchy with <50% tumour cells positive in 20% of cases. In comparison with 34betaE12, 85A12 was insensitive with 15% of UC-NOS cases totally CEA-negative and <50% tumour cell immunoreactivity in 60% of cases. Rare positive cells were present in two (10%) cases of prostate cancer with monoclonal anti-CEA and 34betaE12 on microwaved sections, but all the cases were HMWCK-negative using 34betaE12 on sections pretreated by enzyme digestion. CONCLUSIONS: HMWCK antibody clone 34betaE12, particularly when used with microwave heat retrieval, is a very sensitive positive marker for high-grade invasive urothelial carcinoma.

Adenocarcinoma↗

Variations in the processing of prostatic needle cores in the UK; what is safe?

AIMS: To determine the variation in the processing of prostatic needle cores in the UK and to compare the results with suggested guidelines. METHODS: A standard questionnaire was sent to 210 pathology departments enquiring about current practices. RESULTS: One hundred and thirty replies were received, which showed considerable variation in current methods. The number of cores received for each case ranged from three to 21, with the number of cores processed for each cassette varying from one to 10. Sixty per cent of centres used no special embedding techniques, and the number of sections cut for each case varied from two to 128, with a median of 12 sections for each case. Forty two per cent of laboratories did not take spare slides for immunochemistry. CONCLUSIONS: There is great variation in the processing of prostatic cores in the UK. In particular, some laboratories process a large number of cores in each cassette and do not use special embedding techniques. At present there are no established guidelines for the processing of these specimens. Enhanced techniques may well increase the sensitivity of the test but would increase the workload and costs to the pathology department. In view of the increasing workload from these specimens, a consensus for their optimum processing is required.

Biopsy, Needle↗

Species-specific detection of three human-pathogenic microsporidial species from the genus Encephalitozoon via fluorogenic 5' nuclease PCR assays.

This study describes fluorogenic 5' nuclease PCR assays suitable for rapid, sensitive, high-throughput detection of the human-pathogenic microsporidial species Encephalitozoon hellem, E. cuniculi and E.intestinalis. The assays utilize species-specific primer sets and a genus-specific dual fluorescent-labeled probe that anneals to a region within the Encephalitozoon 16S rRNA gene. The assay design theoretically permits the probe to be used either with one set of primers for species-level determination or with a combination of all three primer sets for a genus-level screening of samples. The linear range of all three species-specific calibration curves that were developed using serial ten-fold dilutions of genomic DNA isolated from hemacytometer counted spores was determined to be between 10(4) and 10(-1) spores per PCR sample. The coefficients of variation were < or =5.2% over the entire 5-log span of each calibration curve. When DNA isolated from flow cytometric enumerated spores from each of the three Encephalitozoon species was used to evaluate the quantitative capability of the species' respective calibration curves, the results from 34 out of 36 (94%) samples were within 2 standard deviations. The species-specificity of each assay was confirmed using DNA isolated from 10(4) spores from each of the other two Encephalitozoon species as well as DNA extracted from numerous other protozoa, algae and bacteria.

Animals↗

Role of hypothalamic monoamines in nicotine-induced anorexia in menopausal rats.

BACKGROUND: Nicotine reduces body weight by reducing appetite. Estradiol modulates food intake. Menopause or ovariectomy (Ovx) increases food intake and body weight. Nicotine and estradiol individually influence hypothalamic dopamine (DA) and serotonin (5-HT), whose interaction influences food intake and body weight. We investigated whether lower weight gain in menopausal smokers is mediated via changes in hypothalamic DA/5-HT. METHODS: Ovx or sham-operated female rats had 2 microdialysis guide cannulas simultaneously implanted in ipsilateral ventromedial nucleus of hypothalamus (VMN) and contralateral lateral hypothalamic area (LHA). Rats were divided into 4 groups and received a continuous subcutaneous infusion of nicotine or saline Ovx and sham. DA and 5-HT in LHA and VMN were measured by in vivo microdialysis. RESULTS: Nicotine infusion decreased food intake and body weight in Ovx and sham groups. Increase in LHA-DA and VMN-5-HT in sham group occurred with nicotine, whereas an increase in VMN-DA in Ovx groups with and without nicotine and VMN-5-HT in Ovx group with nicotine was observed. CONCLUSIONS: In the presence of estradiol (ovary intact sham-operated rats), nicotine lowers food intake and body weight via increased LHA-DA and VMN-5-HT. In menopause (Ovx rats), nicotine lowers food intake and body weight only via increased VMN-DA and 5-HT. Data show that lower weight gain is mediated via changes in hypothalamic monoamines, primarily via ventromedial hypothalamus.

Animals↗

Sticks and stones: racism as experienced by adolescents in New Brunswick.

The purpose of the study was to describe both the nature of racism as experienced by adolescent self-described victims in the province of New Brunswick and their response to the perceived racist incidents. A qualitative methodology based on the constructivist paradigm was used. In-depth interviews were conducted with non-White adolescent victims of racism and with parents of victims. Although the study was initiated in response to an eruption of publicity about teenage racial violence, the findings indicate that racist incidents were not a new phenomenon for the participants. They described a low-key but long-term problem that had begun when they entered the public school system. Name-calling was by far the most common form of racism identified and it played a part in most of the other incidents described; dismissed as harmless by authority figures, it appeared to have long-term consequences for its targets. The participants' response to racism was found to have three phases: splintered universe, spiralling resistance, and disengagement. The results suggest that nurses working in the field of school health should address issues of racism among children and adolescents.

Adolescent↗

Hypothalamic dopamine and serotonin in the regulation of food intake.

Because daily food intake is the product of the size of a meal and the frequency of meals ingested, the characteristic of meal size to meal number during a 24-h light-dark cycle constitutes an identifiable pattern specific to normal states and obesity and that occurs during early cancer anorexia. An understanding of simultaneous changes in meal size and meal number (constituting a change in feeding patterns) as opposed to an understanding of only food intake provides a more insightful dynamic picture reflecting integrated behavior. We have correlated this to simultaneous changes in dopamine and serotonin concentrations and to their postsynaptic receptors, focusing simultaneously on two discrete hypothalamic food-intake-related nuclei, in response to the ingestion of food. The relation between concentrations of dopamine and serotonin limited to the lateral hypothalamic area (LHA) and the ventromedial nucleus (VMN) as they relate to the influence of meal size and meal number during the hyperphagia of obesity and anorexia of cancer as measured in our experiments are discussed. Based on these data, conceptual models are proposed concerning: 1) an "afferent-efferent neurotransmitter unit," with facilitatory or inhibitory neuropeptide properties to generate an appropriate neuroendocrine and neuronal response that ultimately modifies food intake; 2) initiation and termination of a meal, thereby determining the number and size of a meal under normal conditions; and 3) a schema integrating the onset mechanism of cancer anorexia. Nicotine is used as a tool to further explore the relation of meal size to meal number, with a focus on simultaneous changes in dopamine and serotonin concentrations in the LHA and VMN with the onset of acute anorexia of nicotine infusion and acute hyperphagia of nicotine cessation. Data concerning the role of sex-related hormones on dopamine and serotonin with regard to the LHA and VMN in relation to the modulation of food intake are also presented.

Animals↗

Objective measurement of functional upper-extremity movement using accelerometer recordings transformed with a threshold filter.

BACKGROUND AND PURPOSE: The consensus is that the most important outcome for rehabilitation is functional activity in the life situation. Constraint-Induced Movement Therapy, a new treatment that transfers in-clinic gains to the life situation, demands objective measurement of real-world movement. However, direct, objective, and accurate measures of arm use in the real world are not available. Previous attempts to use accelerometry to measure extremity movement have failed because of unacceptable variability. This problem has been addressed here by use of a threshold filter. METHODS: Nine stroke patients and 1 healthy individual wearing accelerometers were videotaped while they carried out their usual activities at home or in the clinic; the duration of their arm, torso, and ambulatory movements was judged by 2 observation teams. In addition, 11 college students performed 5 standardized activities of daily living for varying durations in the laboratory. The accelerometer data were transformed; the raw value recorded for a given epoch was set to a constant if it exceeded a low threshold. RESULTS: The threshold-filtered recordings measured the duration of movement accurately and with very little variability. Correlations between the threshold-filtered recordings and the observer ratings of the duration of arm, torso, and ambulatory movements were 0.93, 0.93 and 0.99, respectively; the corresponding correlations for the raw values were -0.17, 0.34, and 0.85. CONCLUSIONS: These results present initial evidence for the validity of threshold-filtered accelerometer recordings for objectively measuring the amount of real-world upper-extremity movement as an index of treatment outcome for rehabilitation patients.

Adult↗

Comparison of early feeding pattern dynamics in female and male rats after reversible ventromedial nucleus of hypothalamus block.

BACKGROUND: In the hypothalamus, a number of interconnected foci, including the ventromedial nucleus of hypothalamus (VMN), interact to control food intake (FI). FI is a function of meal number (MN) and meal size (MZ). Because gender differences exist in feeding patterns, we aimed at investigating the role of the VMN in determining the relationship of MZ and MN in female and male rats. METHODS: FI and feeding patterns of 10 female and 12 male Fischer-344 rats were studied after VMN block, achieved via stereotaxically located intra-VMN microinjection of the neuronal blocker, colchicine (0.32 microgram dissolved in 50 nL of isotonic injectate and instilled on each side into the VMN). RESULTS: After colchicine injection in normal female rats, an immediate and significant increase in FI occurs as a result of the following: 1) increased MZ in dark and light phases and 2) increased light phase MN with consequent loss of the normal diurnal cycle in FI. Recovery of feeding cycle and normal vaginal smear pattern occurred by study's end. In normal male rats, VMN block resulted in the following: 1) an increase in FI resulting from increased MN occurring predominantly during the light phase, thereby 2) disrupting the usual light/dark feeding cycle. CONCLUSIONS: Sexual differences in regulation of FI occur after temporary reversible VMN block: in female rats, MZ is more sensitive to experimental modulation, whereas in male rats it is MN.

Animals↗