Creatinine related reference ranges for urinary homovanillic acid and vanillylmandelic acid at 6 months of age

The relationship between homovanillic acid (HVA), vanillylmandelic acid (VMA), and creatinine in the urine of 6 month old babies has been studied and reference ranges in the form of centiles constructed for HVA and VMA against creatinine. Over 10,000 urine samples were collected from babies in four health districts in the north of England. HVA and VMA concentration, either independently or when divided by creatinine concentration, were dependent upon the absolute concentration of creatinine in the sample. After adjustment for creatinine significant differences in the mean concentration of HVA were found between sexes. No such differences were found for VMA. HVA and VMA were also found to be age dependent. Centiles were constructed using a procedure which makes no distributional assumptions about the data. The net effect of utilising these centiles was to increase the predictive value of a positive screening test from 20% to 40% without any increase in the false negative rate.     

Smoking habits, exposure to passive smoking and attitudes to a non-smoking policy among hospital staff

A survey was carried out into the smoking habits and exposure to passive smoking among health staff in the hospitals of Faenza, Forli and Rimini (Emilia-Romagna, Northern Italy). 2453 subjects answered anonymously a 41 question questionnaire. 53% of the subjects were professional nurses, 16% doctors, 15% maintenance staff, 10% ancillary staff, 1% non-medical graduates, 2% were administrators and 3% were assigned to the category ‘others’.Of the subjects answering the questionnaire 39% were smokers, 19% ex-smokers and 42% non smokers. The highest number of smokers was found among women (41%) compared to men (37%) and among ancillary staff (48%) compared to nurses (41%) and doctors (31%). The males were mostly heavy smokers (≥20 cigarettes/d) and smoked strong cigarettes (≥12 mg/cig condensate content). The females were mostly light smokers (<10 cigarettes/d) and smoked light cigarettes (1–6 mg/cig condensate content). A high percentage of subjects (87%) smoked at work especially in areas reserved for staff. 43% and 26% of shift workers and non-shift workers tended not to modify their habit when on morning or afternoon shifts. During night shifts the majority of them increased their tobacco consumption.Around 87% of hospital employees stated they were exposed to passive smoking inside the hospital especially in cooking areas, at information desks and corridors. Nurses, ancillaries and maintenance staff were those most exposed and for a greater number of hours per day compared to doctors. Almost all subjects were aware of the harm caused by passive smoking. 56% of smokers, 65% of ex-smokers and 72% of non smokers said they were willing to participate in future campaigns to limit smoking in their hospitals.     

Serum lipids, “double pre-beta lipoproteinemia,” and distribution of the apo-very-low-density (VLDL) lipoprotein peptides in hypothyroid patients before and after substitution therapy

Thirty-six hypothyroid patients had total thyroidectomy for cancer. Thirty of them were studied before and during hormone replacement therapy, 1-1 .1 μg/kg triiodothyronine (T₃) per day. Mean treatment period was 90 days. During treatment mean serum total cholesterol (TC), triglycerides (TG), the ratio of TC to TG in very-low-density lipoprotein and the prevalence of the “double pre-beta VLDL lipoproteinemia” (Double-PBL) were significantly reduced as compared to the pretreatment values. The VLDL peptides were separated by isoelectric focusing (IEF) in polyacrylamide gel. The relative content of apolipoprotein E (arginine-rich apoprotein) and the $\text{E}\text{C}\text{-peptides}$ ratio were significantly reduced after T₃ therapy. On the contrary, the content of C_II peptide was significantly increased. Apoprotein E was positively correlated with serum TC. The proportion of the intermediate density lipoprotein fraction, evaluated by agarose gel electrophoresis, consistently decreased after treatment. The results of our study suggest that thyroid hormones affect the metabolism of remnant lipoproteins.     

Specific inhibition of Rous sarcoma virus byα-amanitin

Summary The inhibition of the Rous sarcoma virus replication by -amanitin suggests that the cellular RNA polymerase II may play a part at some stage of the viral replication.     

The plant-type ferredoxin-NADP+ reductase/ferredoxin redox system as a possible drug target against apicomplexan human parasites

Apicomplexa are unicellular, obligate intracellular parasites of great medical importance. They include human pathogens like Plasmodium spp., the causative agent of malaria, and Toxoplasma gondii, an opportunistic parasite of immunosuppressed individuals and a common cause of congenital disease (toxoplasmosis). They alone affect several hundred million people worldwide so that new drugs, especially for plasmodial infections, are urgently needed. This review will focus on a recently emerged, potential drug target, a plant-type redox system consisting of ferredoxin-NADP(+) reductase (FNR) and its redox partner, ferredoxin (Fd). Both reside in an unique organelle of these parasites, named apicoplast, which is of algal origin. The apicoplast has been shown to be required for pathogen survival. In addition to other pathways already identified in this compartment, the FNR/Fd redox system represents a promising drug target because homologous proteins are not present in host organisms. Furthermore, a wealth of structural information exists on the closely related plant proteins, which can be exploited for structure-function studies of the apicomplexan protein pair. T. gondii and P. falciparum FNRs have been cloned, and the T. gondii enzyme was shown to be a flavoprotein active as a NADPH-dependent oxidoreductase. Both phylogenetic and biochemical analyses indicate that T. gondii FNR is similar in function to the isoform present in non-photosynthetic plastids whereby electron flow is from NADPH to oxidized Fd. The resulting reduced Fd is then presumably used as a reductant for various target enzymes whose nature is just starting to emerge. Among the likely candidates is the iron-sulfur cluster biosynthesis pathway, which is also located in the apicoplast and dependent on reducing power. Furthermore, lipoic acid synthase and enzymes of the isoprenoid biosynthetic pathway may be other conceivable targets. Since all these metabolic steps are vital for the parasite, blocking electron flow from FNR to Fd by inhibition of either FNR activity or its molecular interaction with Fd should also interfere with these pathways, ultimately killing the parasite. Although the three-dimensional structure of FNR from T. gondii is not yet known, experimental and computational evidence shows that apicomplexan and plant enzymes are very similar in structure. Furthermore, single amino acid changes can have profound effects on the enzyme activity and affinity for Fd. This knowledge may be exploited for the design of inhibitors of protein-protein interaction. On the other hand, specifically tailored NAD(P) analogues or mimetics based on previously described substances might be useful lead compounds for apicomplexan FNR inhibitors.     

Real Time-PCR HBV-DNA Analysis: Significance and First Experience in Armed Forces

Background

HBV DNA quantitation is used extensively world wide for the diagnosis and monitoring of treatment of Hepatitis B virus (HBV) infection. However, it has still to be popular in India. The aim of this study was to quantitate HBV – DNA by Real time – PCR method in Hepatitis B and in immuno-compromised patients, to compare the results with HBeAg detection and to monitor the response to therapy of chronic Hepatitis B patients to antivirals.

Methods

Ninety one serum samples of Hepatitis group of patients (all HBsAg positive), 41 samples from immuno-compromised patients (all HBsAg negative) and 49 patients of Chronic Hepatitis B group (all HBsAg positive) were the subjects of this first ever study in Armed Forces. Twenty serum samples from healthy volunteers and non-hepatitis B patients served as negative controls. The amplification detection was carried out in a Rotor-Gene 2000-sequence detector

Results

Amongst Hepatitis B group, 33% (30/91) of the samples were positive for HBV-DNA and 26% (24/91) of samples were positive for HBeAg. In the immuno-compromised group of patients 14.6% (6/11) of samples were positive for HIV-DNA and 9.7% (4/41) were positive for HBeAg. Of the Chronic Hepatitis B patients on treatment, all (100%) were positive by HBV-DNA, whereas 29/49 (59.2%) were positive by HBeAg before treatment. After treatment with antivirals, 06/49 (12.2%) were positive by both tests and 11/49 (22.5%) were positive only by HBV-DNA. 32/49 (65.3%) patients became negative serologically after therapy.

Conclusion

HBeAg status did not necessarily reflect HBV-DNA level in the serum, as 10/91 (11%) in the Hepatitis B group, 2/41 (4.9%) in the immuno compromised group and 20/49 (40.8%) patients in the Chronic Hepatitis B group were positive for HBV-DNA but negative for HBeAg. HBV-DNA was not found to be positive amongst any of the negative controls. Real time – PCR is a sensitive and reproducible assay for HBV-DNA quantitation and may be started in Armed Forces referral centers in the near future.Key Words: Real time – PCR, Chronic Hepatitis B, HBV – DNA, Antivirals     

Asymmetric atrophy of the supraspinatus muscle following tendon tear.

Muscle atrophy is a known consequence of muscle disuse, muscle denervation and tendon tear. Whereas after nerve injury muscle atrophies in the denervated area, the distribution of muscle atrophy following tear of its tendon is not known. Standardized MRI scans of 64 consecutive, painful shoulders were evaluated for supraspinatus tendon tearing, myotendinous retraction, supraspinatus muscle atrophy, fatty infiltration, ratio of the scapular (deep) and fascial (superficial) muscle area ("symmetry") and position of the central tendon within the supraspinatus fossa. There were thirteen shoulders with no and eleven shoulders with partial thickness supraspinatus tendon tears. In the forty cases with full thickness tendon tear, there was significant muscle atrophy and fatty infiltration. Atrophy of the fascial muscle portion was 43%, on the bony side it was 9% (p<0.005). The position of the central tendon within the supraspinatus fossa, was unaltered. Muscular changes following tendon tear occur highly asymmetrically: the muscle portion originating from the fascia primarily atrophies, the portion originating from the scapula primarily undergoes fatty infiltration. Muscular changes are not simply a consequence of muscle disuse, but dependent on architectural changes in the muscle.     

Varicella-zoster virus seroprevalence in nursery and day-care workers in Lyon (France)

OBJECTIVE: Varicella is a potential occupational hazard for susceptible individuals working in pediatric institutions because infected adults run a greater risk of severe or even fatal varicella and because the disease is so common in children and so contagious. The seroprevalence of varicella-zoster virus (VZV) was examined in a sample of day-care workers in Lyon (France) to determine whether a targeted vaccination policy was needed. METHODS: Two hundred forty-one sera were sampled and analysed with an Elisa test between March and May 2001. Histories of past VZV infection were collected via questionnaires documented either before or after consultation of medical records or other sources of information. RESULTS: The overall VZV seroprevalence was 99.6%. The positive predictive values of past varicella histories (documented or not) were>99% showing that a history of previous varicella in day-care workers was reliable. However, only 68 to 71% of these with serologically confirmed varicella reported a prior history of varicella. All subjects reporting a non-positive history of varicella were seropositive. CONCLUSIONS: Virtually all day-care workers enrolled in this study presented serological evidence of VZV so that sub-populations at risk for varicella infection for which VZV vaccination may be effective could not be identified. However, the VZV seroprevalence of the workers in pediatric institutions being presumably higher than that of the general adult population (94-96.3%), vaccination of susceptible young recruits before any exposure to the VZV, or even vaccination of students willing to work in a pediatric institution, may be positive.