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Biomedical subjects

A Menon

Publications and source records attributed to A Menon.

At least 37 records · Page 2Linked to original sources

Undernotification of tuberculosis in Otago: national implications.

AIM: To ascertain the reliability of notification of tuberculosis in Otago; to establish a more accurate incidence rate for cases of tuberculosis in Otago. METHODS: Official notification information 1985-93 was cross checked against other record systems. RESULTS: In the 1985-90 period the official notifications were underestimated by 33% (28/84) and during 1991-2 by 48.5% (17/35). The crude annual incidence rates for all cases were 7.3 per 100,000 for the 1985-90 period and 9.1 per 100,000 for the 1991-3. CONCLUSION: The average annual crude incidence rates for tuberculosis were considerably higher than the official rates. Tuberculosis remains an important clinical and public health issue. Improvements in notification locally and nationally are required if the impact of the projected increase in tuberculosis is to be minimised.

Adolescent↗

Disseminated Burkitt's lymphoma presenting as multiple cranial nerve palsies.

A case of disseminated Burkitt's lymphoma with nervous system involvement in a HIV negative 35 year old lady is described. She primarily presented with multiple cranial nerve palsies. At autopsy, diffuse involvement of parenchymatous organs and lymphomatous meningitis with conspicuous sparing of gastrointestinal system was observed. In addition, there was an unusual feature of paraneoplastic demyelinating peripheral neuropathy. Incidentally, a large hydatid cyst was also seen in the left lobe in addition to the lymphomatous involvement of the liver.

Adult↗

The costs of mammography screening in New Zealand: evidence from the pilot programmes.

AIMS: To measure the public health service costs associated with New Zealand's pilot mammography screening programmes. To compare the early evidence on cost per woman screened and per cancer detected in those programmes to that of overseas screening programmes. To estimate the cost of introducing a national screening programme in New Zealand. METHODS: Costs in each screening centre were obtained by a careful examination of screening budgets and public health service accounts; these were inflation adjusted using a consumers price index, and analysed in terms of equivalent annual operating costs. RESULTS: In the first year of screening the cost per woman screened (in $1991) was $182 in Waikato and $178 in Otago/Southland. The cost per woman screened in the third year of screening (with an assumed full screening throughput of 8,000 women per annum) is estimated to fall to $106 and $113 for the Waikato and Otago/Southland programmes respectively. The cost per cancer detected in the first screening round differs between the two programmes. In the first year of screening the cost per cancer detected was $35,975 in Waikato and $21,908 in Otago/Southland. The difference was primarily attributable to a lower cancer detection rate in Waikato in that period (0.51% of women screened compared with 0.81% in Otago/Southland). CONCLUSIONS: The initial performance of the New Zealand pilot programmes, both in terms of cost per woman screened and cost per cancer detected, falls within the range indicated from overseas experience. An established national screening programme is estimated to add between $9.3 and $9.9 million dollars (in 1991 dollar terms) to health service costs each year. These costs will be partly offset by savings resulting from the earlier detection of cancers.

Aged↗

Development and evaluation of a monolithic floating dosage form for furosemide.

The poor bioavailability of orally dosed furosemide (60%), a weakly acidic drug, is due to the presence of a biological window comprised of the upper gastrointestinal tract. The purpose of the present study was to develop and optimize in vitro a monolithic modified-release dosage form (MMR) for furosemide with increased gastric residence time and to evaluate the in vivo performance of the dosage form. The principle of floatation was used to restrict the MMR to the stomach. A two-factor three-level full factorial experimental design was employed for formulation development. A flow-through cell was designed to evaluate in vitro dissolution parameters. Quadratic regression models indicated the polymer viscosity and polymer:drug ratio to be significant (p < 0.05) formulation factors in determining the duration of buoyancy and the release profile. Statistical optimization using response surface methodology with certain physiological constraints relating to gastric emptying time predicted an optimal MMR. In vivo evaluation of the optimized MMR in beagle dogs resulted in a significant increase (p < 0.05) in the absolute bioavailability for the MMR dosage form (42.9%) as compared to the commercially available tablet (33.4%) and enteric product (29.5%). Significant in vitro/in vivo correlations (p < 0.05) were obtained for the MMR using deconvolution analysis normalized for bioavailability. The floating dosage form was found to be a feasible approach in delivering furosemide to the upper gastrointestinal tract to maximize drug absorption.

Animals↗

Effect of corticosteroid therapy on human immunodeficiency virus-associated nephropathy.

PURPOSE: Human immunodeficiency virus-associated nephropathy (HIV-AN) occurs predominantly in blacks and is characterized histologically by focal segmental glomerulosclerosis or mesangial proliferation and a lymphohistiocytic tubulointerstitial infiltrate. Patients manifest heavy proteinuria and, once azotemia occurs, progress rapidly to end-stage renal disease within 2 to 6 months. No treatment has been shown to be useful for HIV-AN. The purpose of this study was to determine the effect of corticosteroid agents on the progression of HIV-AN. PATIENTS AND METHODS: Four consecutive HIV-infected adults with fewer than 200 CD4 cells/microL, moderate to severe renal insufficiency, proteinuria greater than 2 g per 24 hours, and HIV-AN demonstrated by renal biopsy were treated with 60 mg of prednisone daily for 2 to 6 weeks. Patients were followed with respect to serum creatinine level, 24-hour protein excretion, adverse drug reactions, and the occurrence of opportunistic infections. RESULTS: CD4 counts ranged from 30 to 80 cells/microL before therapy with steroids. The mean (+/- SD) pretreatment serum creatine concentration was 9.1 +/- 5.7 mg/dL and decreased to 3.3 +/- 1.8 mg/dL (P < 0.05) after 2 to 6 weeks of corticosteroid therapy. Twenty-four hour protein excretion did not change (5.2 +/- 2.4 g pretreatment versus 4.6 +/- 4.1 g posttreatment). One patient was able to discontinue dialysis after 10 days. Two patients developed Mycobacterium avium-complex infections and steroid-associated psychosis. One of these patients developed a recurrence of genital herpes, and the other developed dermatomal zoster. None of the four required dialysis during a 1.5- to 5.5-month period of follow-up after cessation of steroid treatment. CONCLUSION: In selected patients with HIV-AN, short-term treatment with corticosteroid agents improves renal function and prevents the development of end-stage renal disease during a 1.5- to 5.5-month period of observation, but may be associated with an increased risk of opportunistic infection.

Adult↗

A set of STS assays targeting the chromosome 22 physical framework markers.

The widespread use of the sequence-tagged site (STS) as a quick, efficient, and reproducible assay for comparing physical and genetic map information promises to facilitate greatly long-range goals of the mapping of the human genome. We have designed 21 STS assays for loci on human chromosome 22. These assays primarily tag the physical framework markers of the long arm of 22, but additional assays have been designed from known genes and loci in the neurofibromatosis 2 (NF2) region. The availability of these assays will make these loci available to the research community without physical transfer of materials and will serve as start points for further efforts to physically map chromosome 22 with yeast artificial chromosome clones.

Animals↗

Decline in meningococcal antibody levels in African children 5 years after vaccination and the lack of an effect of booster immunization.

Antibodies to group A meningococcal polysaccharide were measured by hemagglutination (HA) and by ELISA in sera obtained from Gambian children before vaccination and 3 weeks, 2 years, and 5 years after vaccination with a group A + group C meningococcal capsular polysaccharide vaccine. Children were 1-4 years old at the time of vaccination. Most showed a good initial response to vaccination, including those aged 1-2 years. However, antibody titers declined progressively during follow-up, and 5 years after vaccination, antibody titers measured by both HA and ELISA had returned to prevaccination levels. This decline was not influenced significantly by a booster dose of vaccine given 2 years after initial immunization. Administration of malaria chemoprophylaxis reduced the rate at which antibody levels fell after initial immunization. Sustained protection of children against group A meningococcal disease will require the development of vaccines that are immunogenic in infants and that can induce T cell memory.

Antibodies, Bacterial↗

Effect of mode of incorporation of disintegrants on the characteristics of fluid-bed wet-granulated tablets.

A full factorial experimental design was employed to investigate the effects of mode of disintegrant incorporation and concentration in wet-granulated paracetamol tablets manufactured by top-spray fluid-bed. Disintegrants (croscarmellose sodium, sodium starch glycolate, or crospovidone) were incorporated either intragranularly, extragranularly, or distributed equally between the two phases. The results were analysed by a general quadratic equation and response surfaces generated. On examining the results for dissolution studies the combined mode resulted in significantly faster dissolution rates than did the extragranular mode which, in turn, was superior to the intragranular mode of inclusion. These results were reflected in the disintegration studies where the combined mode exhibited the shortest disintegration times for all the disintegrants. Tablet crushing strength was not affected by the mode of incorporation of concentration of the disintegrants. Main as well as interaction effects between the types, mode of incorporation and percent disintegrant employed were significant (P < 0.05) for disintegration time and percent release at 15 min. Croscarmellose sodium exhibited the shortest while crospovidone displayed significantly (P < 0.05) longer disintegration times. Formulations containing crospovidone did not meet official compendial (USP XXII) requirements of 80% in 30 min. In general, croscarmellose sodium and sodium starch glycolate were found to be less sensitive to the mode of incorporation than crospovidone.

Acetaminophen↗

Sarcoidosis: a review of cases seen at the University Hospital, Kuala Lumpur.

Fourteen cases of sarcoidosis consisting of 7 male and 7 female patients with a mean age of 42.4 years were seen at the University Hospital from 1972 to 1990. There were 10 Indians, 2 Malays, and 2 Chinese. Twelve patients had thoracic involvement. The other common disease manifestations included weight loss, arthralgia, hepatomegaly, erythema nodosum, peripheral lymphadenopathy, and hypercalcaemia. At initial presentation, the disease was in radiographic stage I, II, and III in 8, 3 and one patient respectively. The Kveim test was positive in 7 out of 9 patients. Eight patients required steroid therapy.

Adult↗

Complete human NF1 cDNA sequence: two alternatively spliced mRNAs and absence of expression in a neuroblastoma line.

Neurofibromatosis type 1 (NF1) is caused by mutations in a large gene on chromosome 17q11.2. Previously described partial cDNAs for this gene predicted a protein related to yeast IRA1/IRA2 and the mammalian RAS GTPase activator protein GAP. To initiate a detailed study of the role of this gene in NF1, we have characterized a set of overlapping cDNAs that represent its complete coding sequence. Our results show that two differentially expressed human NF1 mRNAs differ by a 63-bp insertion in the GAP-related domain. These mRNAs predict two 2,818- and 2,839-amino acid proteins with calculated molecular masses of approximately 317 and 319 kD. Extensive similarity to IRA proteins is evident in a 1,450-amino-acid central segment, roughly between amino acids 900 and 2,350. However, the remainder of the NF1 protein is not significantly similar to other proteins. Interestingly, the SK-N-SH human neuroblastoma line expresses no detectable NF1 mRNA, indicating that expression of NF1 is not essential for viability of this neural crest-derived tumor cell line.

Alternative Splicing↗

Evidence for the association of unexplained pulmonary hypertension in children with the major histocompatibility complex.

BACKGROUND: A link between primary pulmonary hypertension (PPH) and autoimmune disorders has been postulated. To investigate this relation, we performed immunofluorescent antinuclear antibody tests (ANA) and serological human leukocyte antigen (HLA)-A, B, C, DR, and DQ typing on two groups of Caucasian children with unexplained pulmonary hypertension (PHT) and their parents. METHODS AND RESULTS: Group 1 consisted of 17 children with PPH including two patients with familial PPH and three patients with trivial congenital pulmonary to systemic communications. Group 2 consisted of 13 children with advanced PHT and anatomically large congenital pulmonary to systemic communications (PHT + shunt). Both groups had comparably severe pulmonary vascular disease documented by cardiac catheterization. The following statistically significant data (p less than 0.05) were obtained when the study groups were compared with those published for normal controls. Although positive ANAs and varying titers of autoantibodies were found in both groups of children and mothers (not fathers), +ANAs were only significant for the maternal groups. The PPH (group 1) children had increased frequencies of HLA-DR3, DRw52, and DQw2 and decreased DR5, whereas the group 2 (PHT + shunt) children (also their parents) had no statistically significant alterations in any of the DR or DQ alleles. The PPH mothers had decreased DQw3, an allele in linkage disequilibrium with DR5. CONCLUSIONS: These immunogenetic data suggest that childhood PPH appears to be associated with the major histocompatibility complex alleles HLA-DR3, DRw52, and DQw2. This newly found correlation of juvenile PPH with these alleles adds this disease to the DR3+ group of autoimmune diseases. Further studies are needed to determine whether there is also an immunological or autoimmune component in some children with PHT + shunt lesions because this group lacked an HLA association.

Adult↗

Pharmacokinetics and bioavailability of papaverine HCl following intravenous, peroral, rectal, vaginal, topical and buccal administration in beagle dogs.

This in vivo study was designed to obtain bioavailability data and a definite pharmacokinetic profile of papaverine HCl in Beagle dogs following intravenous (IV), peroral (PO), rectal, vaginal, topical, and buccal administration of different papaverine HCl formulations. Blood samples were analyzed by high-performance liquid chromatography. The pharmacokinetic parameters were determined using either a curve fitting program (RESID) or a compartment model independent program (AUC-RPP). The plasma concentration-time profiles show that papaverine HCl pharmacokinetics is best described by an open two-compartment model. The absolute bioavailability of papaverine HCl was determined to be 57.2 per cent, 25.2 per cent, 53.2 per cent, 3.2 per cent and 7.5 per cent, respectively, following P.O., rectal, vaginal, topical and buccal administration.

Administration, Buccal↗

TP53 gene mutations and 17p deletions in human astrocytomas.

Astrocytomas, including the most malignant form, glioblastoma multiforme, are the most frequent and deadly primary tumors of the human nervous system. Recent molecular genetic analyses of astrocytomas have demonstrated frequent chromosome 17 deletions involving the telomeric region of the short arm (17p12-pter). This region contains a candidate tumor suppressor gene, TP53, which has recently been implicated in the etiology of a broad array of human cancers. To study the possible role of TP53 in astrocytoma development, 24 randomly chosen human astrocytic tumors were examined for genomic TP53 sequence aberrations using primer-directed DNA amplification in conjunction with direct sequencing. Five of the 11 grade III astrocytomas (glioblastoma multiforme), but only one of seven grade II astrocytomas (anaplastic astrocytoma) and none of either the grade I astrocytomas or oligodendrogliomas demonstrated distinct point mutations involving the TP53 gene. These data suggest that TP53 mutations may play a role in astrocytoma development and are predominantly associated with higher grade tumors.

Adult↗

Biopharmaceutic evaluation of furosemide as a potential candidate for a modified release peroral dosage form.

An attempt was made to evaluate some of the criteria for developing a modified release peroral dosage form for furosemide which has a poor bioavailability when given in the conventional peroral dosage forms. The pathway of absorption for furosemide was studied ex vivo employing the Wilson-Wiseman test. Passive absorption was found to be the predominant mechanism of transport across the ileum of the guinea pig followed by active transport to the extent of about 17%. The in situ procedure to study the extent of absorption of furosemide from the various sites in the lumen of the gastrointestinal tract of the rat indicated the stomach to be the major site of absorption followed by the duodenum. It is hence postulated that due to the site-specificity and mechanism of absorption a peroral modified release dosage form having a longer gastric residence time could possibly increase the bioavailability of furosemide.

Administration, Oral↗

Utilization of village health workers within a primary health care programme in The Gambia.

The utilization of Village Health Workers (VHWs) was studied in a rural area of The Gambia 3 years after the introduction of a village-based Primary Health Care (PHC) programme. Of 23 children who died from conditions treatable at village level, only five were first seen by the VHW. Fourteen were seen elsewhere in the region by staff more qualified than the first tier workers. The implications of this pattern of utilization on the lack of impact of VHWs on mortality are discussed. Only half of the non-fatal illnesses were attended to by VHWs. Reasons for this included such factors as lack of knowledge of services available, shortages of money, absence of the VHW at critical periods and social or political disputes with VHWs. Attempts must be made to tackle these fundamental problems if VHWs are to be successfully incorporated into the health services.

Cause of Death↗