Synthesis and Properties of Haptens for the Development of Radioimmunoassays for Thioridazine,Mesoridazine, and Sulforidazine

For the separate development of radioimmunoassay procedures for thioridazine and its two major active metabolites, mesoridazine and sulforidazine, three haptens, respectively, 2-methylthio-, 2-methylsulfinyl-, and 2-methylsulfonyl-substituted 10-[2-[l-(2-carboxyethyl)-2-piperidinyl]ethyl]-10H-phenothiazine, were synthesized and characterized. Thioridazine hapten was coupled to bovine serum albumin, whereas the haptens for mesoridazine and sulforidazine were coupled to porcine thyroglobulin. The number of hapten residues per mole of carrier protein was determined in each case by an ultraviolet spectrophotometric method. Polyclonal antibodies to each hapten–protein conjugate were obtained in rabbits, and titers of the antisera were checked by evaluating their binding characteristics to the appropriate tritiated analyte. A hapten for the ring sulfoxide metabolite of thioridazine was also synthesized.     

Short term effect of diltiazem on portal hypertension in patients with non-cirrhotic portal fibrosis

Fourteen patients of non-cirrhotic portal fibrosis (NCPF) with portal hypertension were put on oral diltiazem hydrochloride (90 mg/day) or placebo on a prospective, randomised, single blind basis for 15 days. Predrug hemodynamic and biochemical status were similar in both groups. Diltiazem produced significant reduction (p less than 0.001) in mean intrasplenic pressure: from 41.88 (SD +/- 6.18) to 21.5 (+/- 7.91) cm of normal saline as against 45.56 (+/- 9.45) to 43.33 (+/- 8.27) in the placebo group. Mean arterial pressure (MAP), heart rate and cardiac output (CO) did not change in either group. Thus, the calcium channel blocker diltiazem reduces portal pressure in patients with NCPF, independent of reduction in MAP and CO; this is advantageous in situations where compromised cardiac hemodynamics may prove deleterious.     

Sarcomas of head and neck — A 10 yrs experience

38 cases of sarcoma of head and neck region were analysed in a retrospective way in relation to age, anatomic location, histological, clinical profile, and surgical approaches. Compared to other types of head and neck neoplasms, such as squamous cell carcinoma, soft tissue sarcomas have low rates of regional metastases. However the biological behaviour of soft tissue sarcoma is more aggressive specially in paediatric age group. In the present series, CT scan was considered as the primary modality of investigation. Surgery generally has been recommended as the primary method of treatment for achieving local control, except in those high-grade tumours arising in sites not amenable to resection. 3-year and 5-year survival rates in this present series 50% and 31.6% respectively.     

Epidemiology and cause of deaths among women in rural Bangladesh

A total of 542 women aged 15 to 44 years died during the 10-year period 1976 to 1985 in the control area of Matlab, an area with a population of 90,000, representative of many other rural areas of southern Bangladesh. The corresponding age-specific mortality rate was 290 per 100,000 women 15-44 years. These deaths have been analysed retrospectively, using information collected through the Demographic Surveillance System set up by the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) and verbal autopsies conducted in the homes. Of these deaths, 175 (32%) were due to infectious diseases, 163 (30%) to direct obstetric complications, 67 (12%) to injuries, and the remaining 26% to other causes. Cause-specific and proportionate mortality rates showed a positive association with age for deaths due to infectious diseases, non-infectious diseases and unspecified causes, and an inverse association with age for deaths due to injuries. These rates showed a peak in the intermediate age group 25 to 34 years for deaths due to direct obstetric causes. No consistent trends were visible when annual rates were studied over time. Prior to death, 42% of the women were attended by traditional practitioners, and 33% were not attended at all. Demographic impact is discussed, emphasizing the contribution of obstetric causes to overall mortality. Priorities for health policy implications are proposed, focusing upon a strong maternity care programme, and improved availability of female health personnel, in the context of the socio-cultural constraints imposed on women in poor rural areas.     

Genetic analysis and attribution of microbial forensics evidence

Because of the availability of pathogenic microorganisms and the relatively low cost of preparing and disseminating bioweapons, there is a continuing threat of biocrime and bioterrorism. Thus, enhanced capabilities are needed that enable the full and robust forensic exploitation and interpretation of microbial evidence from acts of bioterrorism or biocrimes. To respond to the need, greater resources and efforts are being applied to the burgeoning field of microbial forensics. Microbial forensics focuses on the characterization, analysis and interpretation of evidence for attributional purposes from a bioterrorism act, biocrime, hoax or inadvertent agent release. To enhance attribution capabilities, a major component of microbial forensics is the analysis of nucleic acids to associate or eliminate putative samples. The degree that attribution can be addressed depends on the context of the case, the available knowledge of the genetics, phylogeny, and ecology of the target microorganism, and technologies applied. The types of genetic markers and features that can impact statistical inferences of microbial forensic evidence include: single nucleotide polymorphisms, repetitive sequences, insertions and deletions, mobile elements, pathogenicity islands, virulence and resistance genes, house keeping genes, structural genes, whole genome sequences, asexual and sexual reproduction, horizontal gene transfer, conjugation, transduction, lysogeny, gene conversion, recombination, gene duplication, rearrangements, and mutational hotspots. Nucleic acid based typing technologies include: PCR, real-time PCR, MLST, MLVA, whole genome sequencing, and microarrays.     

Cytopathic effect of in situ gene therapy in prostate cancer

This is a morphologic study of in situ gene therapy effects in patients with prostate cancer using the Herpes Simplex VirusThymidine Kinase gene (HSV-tk) followed by ganciclovir. Prostatectomy specimens from the first 4 patients showed the following morphologic changes: (1) various degrees of necrosis were seen in cancer foci; (2) cytopathic changes were seen across the whole spectrum of Gleason grades; (3) the normal prostate was rarely affected by necrosis, but contained an intense mononuclear infiltrate; (4) loss of nuclear detail was a common finding. Volumetric studies showed that only portions of the tumor show morphologic effects as well as an inverse relationship between percentage of affected tumor and prostate and tumor size. An inflammatory response was observed, with predominance of CD20-positive cells in normal prostate tissue, CD8 (cytotoxic T cells) in the tumor, and macrophages in all areas of the treated prostates. We believe that these changes represent the cytopathic effect of our in situ gene therapy on prostate cancer, and that they trigger a local immune response.     

Pseudoappendicitis caused by Plesiomonas shigelloides.

A 20-year-old patient was hospitalized with clinical signs of acute appendicitis. After surgery, the histological findings in the appendix and a lymphatic node suggested the diagnosis of pseudoappendicitis caused by Plesiomonas shigelloides, which was isolated in pure culture from the lymphatic node. The strain of P. shigelloides was found to elaborate a heat-stable toxin and harbored two plasmids of 280 and 4 kilobases. A large plasmid has previously been implicated as a virulence marker in P. shigelloides infections.     

The gene coding for protein p60 of Listeria monocytogenes and its use as a specific probe for Listeria monocytogenes.

The gene of Listeria monocytogenes that encodes a major extracellular protein (p60) was cloned in Escherichia coli. The gene was designated iap, as p60 was previously shown to represent an invasion-associated protein (M. Kuhn and W. Goebel, Infect. Immun. 57:55-61, 1989). The recombinant E. coli clone expressed p60, as shown by immunoblotting. The complete nucleotide sequence of iap was determined. The deduced amino acid sequence of p60 (484 amino acids) contains a putative N-terminal signal sequence of 27 amino acids and an extended repeat region consisting of 19 threonine-asparagine units. Hybridization with the entire iap gene revealed the presence of homologous sequences in most other Listeria species. In contrast, a 400-base-pair internal iap probe which contained the whole repeat region hybridized only with genomic DNA from L. monocytogenes. Four oligonucleotides previously described as specific probes for the detection of L. monocytogenes (A. R. Datta, B. A. Wentz, D. Shook, and M. W. Trucksess, Appl. Environ. Microbiol. 54:2933-2937, 1988) were shown to be part of the iap gene.