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Biomedical subjects

M Meltzer

Publications and source records attributed to M Meltzer.

At least 19 recordsLinked to original sources

Validity and reproducibility of resting metabolic rate measurements in rural Bangladeshi women: comparison of measurements obtained by Medgem and by Deltatrac device.

OBJECTIVE: To assess reproducibility and validity of resting metabolic rate (RMR) of Bangladeshi women as measured with the MedGem device and using the Deltatrac metabolic monitor as a reference; and (2) to evaluate the FAO/WHO/UNU basal metabolic rate (BMR)-prediction equations. DESIGN: In each of two sessions, resting oxygen consumption was measured in triplicate by MedGem and in triplicate by Deltatrac device. SETTING: Matlab area, the rural field research area of the Centre for Health and Population Research, Bangladesh (ICDDR,B). SUBJECTS: A total of 37 nonpregnant, nonlactating women, aged 27.6 +/- 4.5 y, BMI 20.8 +/- 3.1 kg/m(2) participated. RESULTS: The difference in oxygen consumption by MedGem and Deltatrac device was significantly level dependent. Within-subject within-session variations (expressed as CV) were 9.0 and 3.0% (P < 0.01) and within-subject between-session variations were 8.2 and 4.5% (P < 0.01) for MedGem and Deltatrac, respectively. Mean RMR measured by Deltatrac (5.17 +/- 0.51 MJ/day) was not significantly different from the BMR predicted by the FAO/WHO/UNU equations (5.16 +/- 0.42 MJ/day) in the second session and only 0.19 MJ/day higher than predicted in the first session (P < 0.05). CONCLUSION: Reproducibility and validity of the MedGem device was poor compared to the Deltatrac reference method. The FAO/WHO/UNU BMR-prediction equations give a good estimation of the BMR of rural, nonpregnant, nonlactating Bangladeshi women of 18-35 y. SPONSORSHIP: Wageningen University (The Netherlands) and ICDDR,B (Bangladesh).

Adult↗

The public health response to a case of Lassa fever in London in 2000.

OBJECTIVES: Evaluation of the Department of Health 1996 guidance, the Memorandum on the Management and Control of Viral Haemorrhagic Fevers. METHODS: Description of the public health management in 2000 of the fifth UK patient confirmed to have Lassa fever. RESULTS: Delayed risk categorisation of the patient occurred for a variety of reasons. DH Guidance was followed once infection control advice was sought. Active surveillance of 125 contacts was extremely resource intense, involving over 3000 communications. Self-monitoring by healthcare workers should be considered in future. Advice on use of ribavirin prophylaxis is not included in the Memorandum, nor advice or templates for information sheets for contacts. Information sheets are now available from the Health Protection Agency in the event of future cases. International aspects not adequately addressed include the need for reliable risk assessment to be carried out before patients are medically evacuated from the country of origin, and the steps required to repatriate UK nationals. Effective and efficient communication is required between national and international organisations involved in such incidents. CONCLUSIONS: If guidelines are unclear or impracticable they will not be followed. It is important that lessons are learned and documented and that national guidance be regularly reviewed.

Communicable Disease Control↗

Specialist vaccination advice and pockets of resistance to MMR vaccination: lessons from an outbreak of measles.

An outbreak of measles was associated with a private nursery school in north west London. Sixteen cases were identified of whom 13 were laboratory confirmed. The majority of cases were aged three years or younger. Older cases were siblings of younger cases. None of the cases had been vaccinated against measles. In the nursery school 33% of the children had not received MMR vaccination. Based on specialist advice from the Health Protection Agency the outbreak control team recommended that children with no history of MMR vaccination should have a first MMR dose as soon as possible and that children with one MMR dose should receive the second dose as soon as possible (minimum of one month between doses). Some parents had strong negative views about MMR and represented 'pockets of resistance' to vaccination advice. The specialist vaccination advice, which was different to national immunisation guidelines, also caused some confusion amongst other health professionals. With a decrease in MMR vaccination uptake and resulting increased potential for future measles outbreaks, clinicians should be aware of and understand specialist vaccination advice intended to deal with outbreaks.

Child↗

Molecular epidemiology of a large outbreak of hepatitis B linked to autohaemotherapy.

BACKGROUND: Unregulated skin-piercing procedures potentially facilitate the transmission of bloodborne pathogens. In February, 1998, a patient who had recently received autohaemotherapy at an alternative medicine clinic in the UK was diagnosed with acute hepatitis B. The autohaemotherapy procedure involved the drawing of 1 mL of the patient's blood, mixing with saline, and reinjection of the autologous blood mixture. We investigated the extent of hepatitis B virus (HBV) infection in patients and staff of the clinic. METHODS: Patients who had attended the clinic between January, 1997, and February, 1998, were tested for serological markers of HBV, and for HBV DNA by PCR. HBV DNA was sequenced to assess the relatedness of the virus identified in the cases. We analysed the number and dates of visits with regard to HBV status. FINDINGS: Serum samples were received from 352 patients and four staff members. Serological evidence of exposure to HBV was found in 57 (16%). Of the 33 patients and staff who were positive for hepatitis B surface antigen, 30 (91%) showed complete nucleotide identity in the DNA segments derived from the surface and core genes. Five patients with linked infection had markers of chronic hepatitis B, and one of these was regarded as the likely source of the outbreak. The attack rate was associated with the number of visits (p<0.0001) and the week of visit (p=0.011). Contaminated saline in a repeatedly used bottle was the probable vehicle of transmission. INTERPRETATION: We have described a large community-based outbreak of hepatitis B due to transmission by a single HBV variant. Our findings emphasise the continuing risk of transmission of bloodborne viruses in all health-care settings where skin-piercing procedures are used.

Adult↗

Limited genetic susceptibility to severe Graves' ophthalmopathy: no role for CTLA-4 but evidence for an environmental etiology.

Graves' disease (GD) is an autoimmune thyroid disease (AITD) characterized by hyperthyroidism and by the occurrence of a distinctive ophthalmopathy (orbitopathy), which presents with varying degrees of severity. Graves' disease clusters in families but the importance of heredity in the pathogenesis of the associated ophthalmopathy is unclear. We have studied the family history of 114 consecutive, ethnically mixed patients with severe Graves' ophthalmopathy (GO). Patients were selected by unambiguous single ascertainment. Seventy-seven percent of patients were female and 59% smoked. The mean age at onset of their GD was 43 years (range 17-78 years). Forty-one patients (36%) had a family history of AITD, defined as a first- and/or a second-degree relative affected with either Graves' disease (GD) or Hashimoto's thyroiditis (HT). The segregation ratio for AITD in nuclear families in our ascertained Graves' ophthalmopathy families was 0.07 (0.12 in Caucasians only). Hence, the higher prevalence of AITD among relatives of Graves' ophthalmopathy patients agreed with the known genetic predisposition to AITD and this predisposition was stronger in women than in men. However, only 3 of the 114 patients had a family history of severe Graves' ophthalmopathy (all second-degree relatives) and the segregation ratio for GO was 0. These data did not support a major role for familial factors in the development of severe Graves' ophthalmopathy distinct from Graves' disease itself. In addition, we tested 4 candidate genes, human leukocyte antigen (HLA), tumor necrosis factor-beta (TNF-beta), CTLA-4 and the thyrotropin receptor (TSHR), for association with Graves' ophthalmopathy. These were negative except for the HLA and CTLA-4 genes, which were found to be weakly associated with GO giving similar relative risk (RR) as in GD patients without ophthalmopathy. These data suggested that environmental factors, rather than major genes, were likely to predispose certain individuals with AITD to severe Graves' ophthalmopathy. Smoking remains one example of such potential external insults.

Abatacept↗

Eyelid healing after carbon dioxide laser skin resurfacing: histological analysis.

OBJECTIVE: To clarify in vivo healing of eyelid skin after carbon dioxide (CO2) laser resurfacing. DESIGN: Patients requesting upper eyelid blepharoplasty consented to undergo previous CO2 laser skin resurfacing of the upper eyelid skin segments to be excised at various time intervals. After blepharoplasty, the skin specimens were analyzed histopathologically by 2 masked pathologists. PATIENTS: Eight patients with Fitzpatrick skin types I and II. INTERVENTION: Upper eyelid CO2 laser resurfacing 1,2, 4, or 12 weeks before planned upper eyelid blepharoplasty. MAIN OUTCOME MEASURES: Epidermis: thickness, polarity, contour, and constituents. Dermis: repair zone thickness, vascular and inflammatory pattern, collagen deposition, and elastic fiber changes. RESULTS: The epidermis regenerated within 7 to 10 days. By 3 months, the epidermis revealed flattening of the rete peg pattern with restoration of polarity, keratinocytes, and melanocytes. The 3-month dermis demonstrated a fibrotic repair zone (500-700 microm), new elastic fibers, and telangiectatic capillaries. CONCLUSIONS: Eyelids heal similarly to other skin regions treated by CO2 laser resurfacing. This cutaneous healing is analogous to that previously reported with use of chemical peels. Histological changes may explain the skin smoothing and wrinkle reduction seen clinically.

Aged↗

Reduced virulence of rifampicin-resistant mutants of Francisella tularensis.

Rifampicin-resistant mutants of a live vaccine strain (LVS) of Francisella tularensis were produced and screened for virulence in mice; 4 avirulent clones with intraperitoneal (ip) LD50s > 10(6) cfu, compared with 10(2) cfu for LVS, were characterized. Growth characteristics at 37 degrees C, surface envelope proteins, and lipopolysaccharide profiles of resistant mutants were identical to those of LVS. Polymerase activity of the mutants was more resistant than the enzyme from LVS to the inhibitory action of rifampicin. Growth rates for mutants and LVS were similar during the first 5 h at 42 degrees C, but viability of the mutants decreased to < 0.01% at 24 h. LVS and mutants differed in their ability to grow in vitro in host macrophages: LVS increased 580-fold over 72 h; mutants increased 33-fold. After ip inoculation of the organisms into mice, increasing numbers of LVS from peritoneal cells were isolated; mutants decreased over 4 days.

Animals↗

Phorbol ester reduces constitutive nuclear NF kappa B and inhibits HIV-1 production in mature human monocytic cells.

NF kappa B is a potent mediator of specific gene expression in human monocytes and has been shown to play a role in transcription of the HIV-1 genome in promonocytic leukemias. There is little information available on the response of NF kappa B to cytokines in normal human monocytes. We have used a 32P-labeled oligonucleotide derived from human immunodeficiency virus (HIV-1) long terminal repeat, which contains a tandem repeat of the NF kappa B binding sequence, as a probe in a gel retardation assay to study this transcription factor. Using this assay, we have detected NF kappa B in extracts of nuclei from normal human monocytes. Treatment of normal monocytes with 12-0-tetradecanoyl phorbol-13-acetate (TPA) for 4-24 h caused the complete disappearance of NF kappa B from nuclear extracts of monocytes. A similar result was obtained with the mature monocytic leukemia cell line THP-1. The constitutive transcription factor SP1 was unaffected by addition of TPA. The disappearance of NF kappa B from the nucleus was concentration dependent between 10 and 50 ng/ml of phorbol ester. In THP-1 cells, TPA also induced a new, faster-migrating NF kappa B species not induced in monocytes. Protein kinase C inhibitor staurosporine, but not cyclic nucleotide-dependent protein kinase inhibitor HA-1004, also dramatically reduced constitutive levels of nuclear NF kappa B. Finally, TPA addition to monocytes infected with HIV-1 inhibited HIV-1 replication, as determined by reverse transcriptase assays, in a concentration-dependent manner. These results are in striking contrast to the increase in nuclear NF kappa B and HIV-1 replication induced by phorbol esters in promonocytic leukemia cells U937 and HL-60, and emphasize the importance of studying cytokine regulation of HIV-1 in normal monocytes.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Rabies control in the Republic of the Philippines: benefits and costs of elimination.

We compared the benefits and costs of eliminating animal and human rabies in the Philippines. If rabies had been eliminated in 1988, economic benefits would total P52.8 (US$2.5) million in 1989. These benefits would largely arise from the abolition of expenses associated with rabies prevention: P29.7 (US$1.4) million for animal vaccination, P21.6 (US$1.0) million for human postexposure prophylaxis, and P0.3 (US$0.02) million for animal rabies examinations. Benefits also included P1.2 (US$0.06) million in additional earnings of humans whose death due to rabies would be prevented. Nationwide elimination was estimated to cost between P88.1 (US$4.2) million and P317.2 (US$15.0) million, assuming a canine-to-human ratio of 1:10, vaccine coverage of 60%, and a cost per vaccination of no less than P25 (US$1.19) and no more than P90 (US$4.27). These costs would be recouped 4.1-11.0 years after the initiation of a one-year elimination campaign. A sensitivity analysis showed that an elimination programme would be economically beneficial in all but the most extreme cases.

Animals↗

Determination of Ro 14-4767 (Loceryl) by LC using automated column switching with ultraviolet and electrochemical detection.

Ro 14-4767, Loceryl is a member of a new class of antimycotics, and a number of dosage forms are being developed for its topical application. The active, impurities and its major oxidation products are amenable to ultraviolet detection at wavelengths of approximately 220 nm. As new delivery systems and lower strengths have been developed, it was recognized that a more sensitive detection method may be necessary to support product development. Ro 14-4767, Ro 14-3168 (impurity) and diastereomers are readily oxidized at potentials of 0.8 V (vs Ag/AgCl) at a glassy carbon electrode. Electrochemical detection substantially improved the sensitivity relative to UV detection. However, detection of impurities and oxidation products by either UV or electrochemical detection exhibited interference problems from the cream matrix. Employing column switching eliminated the interference problem from the cream matrix and adding tetrahydrofuran to the mobile phase (acetonitrile and pH 7.0 phosphate buffer) significantly increased the selectivity and sensitivity for both UV and electrochemical detection. The method requires the use of two pumps to continually deliver the mobile phase through both detectors before and after valve switching, preventing the baseline from shifting during a stop in the flow to the electrochemical detector. Quantitative recovery of the active, the potential degradation products, and Ro 14-3168 from a placebo cream using column switching and UV detection has been demonstrated. Utilizing this methodology it is possible to quantitate 0.1% of the formulation label claim for the potential degradation products and Ro 14-3168. Electrochemical detection provides greater selectivity in that only Ro 14-3168, Ro 14-4767 and its diastereomers are detected. However, the sensitivity of detection relative to UV is enhanced. The method is linear in the range of 50 to 150% of the working standard solution for 0.01% and 0.001% active concentration of the cream. The column switching technique can be automated for reproducible assay of a large number of samples.

Antifungal Agents↗

Bone mineral density and fracture in postmenopausal women.

This retrospective study examined bone mineral density (BMD) for discrimination of female patients with fractures. Bone densitometry was done in 146 patients over the age of 50 years at radius, lumbar spine, and proximal femur sites using single and dual photon absorptiometry. The patients were divided into three groups: (A) no osteoporotic fractures (n = 92); (B) mild spine fractures with greater than 15% compression (n = 38); and (C) hip fractures (n = 16). Groups B and C did not differ significantly from each other in BMD, but these groups differed significantly from group A for spine and femur BMD. No significant differences between groups were found for the radius. Receiver operating characteristic (ROC) analysis showed that the BMD of the proximal femur had the highest diagnostic sensitivity for both spine and femur fractures; the radius had the lowest overall sensitivity, and the spine was intermediate.

Aged↗

Purification and sequencing of glycosylation variants of BSF-1, as a MAF, from the EL-4 leukaemia cell line.

Macrophage activation activity was characterized from a PMA-induced subclone of the murine EL-4 leukaemic cell line. The MAF was purified from the cell line culture supernatant by concentration, CM-Sepharose and lentil lectin Sepharose chromatography, AcA 54 gel filtration, Mono Q FPLC and reverse phase HPLC. Four protein bands of different abundance were observed on SDS-PAGE with molecular weights of 17,500 to 21,000 Da. Three of the four proteins were sequenced from the N-terminal and shared homology with the published sequence of BSF-1. Variation of the molecular weight due to glycosylation was demonstrated by N-glycanase treatment, all four proteins gave a band of 14,200 Da after deglycosylation. Both glycosylated and deglycosylated forms of BSF-1 were equally active in the MAF assay. A monoclonal antibody to BSF-1 neutralized 80% of the activity from crude culture supernatants in the MAF assay. These studies have indicated that BSF-1 is the major, if not the only, MAF activity from this particular subline of the murine EL-4 leukaemic cell line.

Amino Acid Sequence↗

Serotonin uptake by platelets of suicidal and aggressive adolescent psychiatric inpatients.

Thirty-four adolescent psychiatric inpatients were studied in order to find out whether there is a correlation between serotonin platelet uptake (SPU), suicidality and aggression. The patients were divided into four main diagnostic groups according to clinical data: borderline personality disorder, affective disorder (unipolar) including schizoaffective disorder, schizophrenia and 'others'. These patients were also characterized by the quantitative symptoms profile from K-SADS scale (Children's Version of the Schedule of Affective Disorders and Schizophrenia) and by their behavior: aggression, suicide attempts and violent suicide attempts. In the schizophrenic group, a correlation was found between low Vmax values of SPU and aggressive behavior (p less than 0.05). In addition, in the 'other' group a correlation was found between low Vmax values of SPU and conduct disorder (p less than 0.05). On the other hand, in 'other' patients a correlation was found between low Km values of SPU and violent suicide attempt (p less than 0.05). It is noteworthy that the lowest (20-35%) Vmax values of SPU were found in the patients of the affective group as compared to values of the three other diagnostic groups. These findings are similar to those concerning unipolar depressive adults. It is assumed that there are less binding sites for serotonin on platelets of depressive adolescents than was suggested for depressive adults.

Adolescent↗

Dermatologic findings and manifestations of acquired immunodeficiency syndrome (AIDS).

We present a review of the spectrum of human T-lymphotropic virus type III (HTLV-III) infection with particular emphasis on cutaneous manifestations in 217 patients. Correlations are made with immunodeficiency as measured by absolute T-helper cell number. A classification is presented of these dermatologic findings.

Acquired Immunodeficiency Syndrome↗