Neonatal hypoglycaemia and withdrawal symptoms after exposure in utero to valproate

AIMS: To define, in a prospective study, the risk of hypoglycaemia-defined as blood glucose concentration < 1.8 mmol/l-in term infants exposed in utero to valproate and to describe the withdrawal symptoms. METHODS: Twenty epileptic women were treated with valproate only during pregnancy and two were treated with valproate and carbamazepine. In the first trimester, the daily median dose of valproate was 1.0 g (range 0.3-4.2) and in the third trimester 1.2 g (range 0.3-4.8). RESULTS: Thirteen of the 22 infants became hypoglycaemic. One infant had eight episodes of hypoglycaemia, one had three episodes, two had two episodes, and nine had one episode each. The lowest blood glucose concentration was 1.0 mmol/l. All episodes were asymptomatic. The maternal mean plasma concentration of total valproate during the third trimester correlated negatively with blood glucose concentration one hour after delivery (p < 0.0003) and with the development of hypoglycaemia (p < 0.0001). There was no evidence for hyperinsulinaemia as the cause of hypoglycaemia. Ten infants developed withdrawal symptoms, which correlated positively with the mean dose of valproate in the third trimester and the concentration of the free fraction of valproate in maternal plasma at delivery (p < 0.02). CONCLUSIONS: Infants exposed to valproate in utero had a significantly elevated risk of hypoglycaemia, and withdrawal symptoms were often observed.     

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.     

Modulation of daunorubicin toxicity by liposomal encapsulation and use of specific inhibitors in vitro

Anthracyclines serve as a valuable tool in chemotherapy, but their usefulness is often limited by the occurrence of resistance mechanisms in tumor cells. Resistance of tumor cells is a multifactorial event, where several mechanisms act concurrently, including drug efflux and enzymatic drug inactivation. Liposomal encapsulation of anthracyclines has been discussed as a successful regimen to overcome drug resistance. Our investigations were carried out on a daunorubicin (DRC) sensitive breast cancer cell line and two DRC resistant sublines generated thereof. In all three cell lines, the extent of DRC detoxification via carbonyl reduction to daunorubicinol (DRCOL) was determined. In addition, rutin, the most effective inhibitor of carbonyl reducing enzymes, was tested to affect DRCOL formation. DRC IC(50) values were determined in relation to several combinations of DRC administration, (a) liposomal encapsulated DRC, (b) addition of verapamil (inhibitor of drug efflux), (c) addition of rutin (inhibitor of DRC carbonyl reduction). We could show that DRC sensitive and resistant breast cancer cell lines are able to catalyze DRC detoxification via carbonyl reduction to DRCOL. Rutin was shown to inhibit this reaction, but could not serve as an enhancer of DRC toxicity in MTT tests. Verapamil was effective only in resistant cells due to the overexpression of P-glycoprotein 170. Liposomal encapsulation of DRC did not show the expected increase in DRC toxicity in the present tumor cell model.     

Scanning time-domain optical mammography: detection and characterization of breast tumors in vivo

Optical mammography is one of several new techniques for breast cancer detection and characterization presently under development for clinical use that provide information other than morphologic, in particular on the biochemical and metabolic state of normal and diseased tissue. In breast tissue, scattering of red to near infrared (NIR) light dominates absorption and NIR light may penetrate several centimeters through the breast. Optical mammography avoids the use of ionizing radiation and offers the power of diffuse optical spectroscopy. However, because of strong light scattering, spatial resolution of optical mammography is generally low. The paper reviews the results of a clinical study on scanning time-domain optical mammography comprising 154 patients carrying a total of 102 carcinomas validated by histology. Ninety two of these tumors were detected in optical mammograms retrospectively and for 87 of the detected tumors optical properties and tissue parameters were derived. In addition developments on instrumentation and data analysis are covered and possible improvements of optical mammography are briefly discussed.     

Screening for drugs of abuse in oral fluid--correlation of analysis results with serum in forensic cases

The testing of saliva or oral fluid at the roadside could be a powerful tool to detect drivers under the influence of drugs and has several advantages over urine screening. In 177 cases of individuals suspected of driving under the influence of drugs, oral fluid was collected at the roadside and analyzed in parallel to serum samples. The study was performed to investigate the variability of oral fluid analysis results in relation to blood/serum. In 45% of the cases single-drug use was found, and in 50% poly-drug use was found. Cannabis was most prevalent (78%), and 70% of these individuals were also positive for tetrahydrocannabinol in serum. Overall, 97% of oral fluid samples positive for any substance were also positive in serum. Comparing data of oral fluid and serum for amphetamine, MDMA, morphine, benzoylecgonine, and tetrahydrocannabinol, the sensitivities were 100%, 97%, 87%, 87%, and 92%, respectively. Overall specificity and accuracy were in the range of 91-98%. Discrepancies between a negative oral fluid sample and a positive serum sample could be explained by analytical insensitivity in the lower volume of oral fluid analyzed (estimated for 0.1 mL confirmation vs. 1 mL of serum) or a shorter detection window in oral fluid. The low prevalence of discrepancies with positive oral fluid and negative serum results (2-9% of the cases) may be explained by persistent oral contamination especially for orally consumed drugs, like MDMA and cannabis. It is concluded that the detection of a psychoactive substance in oral fluid taken at the roadside is highly predictive for the detection of the corresponding drug or its metabolite in serum. Oral fluid testing is therefore suitable for the efficient confirmation of drug use of drivers suspected of being under the influence of drugs.     

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