Cranial nerve dysfunction in metastatic cancer of the prostate

We report 11 patients with cranial nerve dysfunction due to bone metastases from advanced prostatic cancer. Diplopia, speech disturbances, tongue deviation and headache were the typical clinical symptoms. X-ray and/or computed tomography of the base of the skull demonstrated bone destruction (and the surrounding soft tissue tumour) in 8 cases. In 1 patient the bone destruction was visualised only by bone scan. In 2 cases no bone destruction could be demonstrated in spite of the clinical findings. In 9 of the 10 evaluable patients the clinical symptoms improved after high voltage radiotherapy and high dose corticosteroid treatment. Cranial nerve dysfunction is a late complication of hormone-resistant prostatic cancer. The symptoms are usually due to bone destruction at the base of the skull. Radiotherapy combined with corticosteroid treatment is an excellent palliative measure if started immediately after the onset of symptoms.     

Bioavailability of Soil-Bound TCDD: Dermal Bioavailability in the Rat

Bioavailability of Soil-Bound TCDD: Dermal Bioavailability inthe Rat. SHU, H., TEITELBAUM, T., WEBB, A. S., MARPLE, L., BRUNCK,B. DEI ROSSI, D., MURRAY, J., AND PAUSTENBACH, D. (1988). Fundam.Appl. Toxicol. 10, 335-343. 2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD), an unwanted by-product formed during the manufactureof hexachlorophene and phenoxyherbicides, has been found asan environmental contaminant in many U.S. and Western Europeansites. This study examines in the rat the degree of dermal absorptionof TCDD bound to soil. Such information would assist regulatoryagencies in evaluating the degree of exposure of humans whocome in contact with TCDD-contaminated soil. Several parameterswhich may influence dermal absorption were studied, includingTCDD dose, duration of contact, presence of crankcase oil asa co-contaminant, and environmentally contaminated vs laboratory-preparedsoil. The dermal penetration of TCDD following 4 hr of contactwith skin was approximately 60% of that following 24 hr of contact(P 0.05). Following 24 hr of contact with the skin, the degreeof dermal uptake of TCDD contaminated soil was approximately1% of the administered dose. Under the conditions of the presentstudy, the degree of uptake does not appear to be influencedto any significant extent by the concentration of TCDD on soil,the presence of crankcase oil as co-contaminants, or by environmentallyvs laboratory-contaminated soil. Although a number of parametersexamined in this study did not significantly influence the degreeof dermal absorption of TCDD in the rat following 24 hr of contactwith the contaminated soil, the unqualified use of the 1% valueto estimate human exposure would overestimate human exposure,since there is general agreement among researchers that ratskin tends to be more permeable than human skin to highly lipid-solublecompounds such as TCDD.     

Intermale aggression and infanticide in aged C57BL/6J male mice: Behavioral deficits are not related to serum testosterone (T) levels and are not recovered by supplemental T

Healthy aged adul (24–26 months of age) and young adult (2–4 months of age) C57BL/6J male mice were assessed for intermale aggression, pup-killing behavior (infanticide), and circulating levels of testosterone (T). When compared to young adult male mice, aged adult males were highly variable in the exhibition of both androgen-dependent behaviors. Significant numbers of aged males exhibited deficits in aggression and pup-killing while other animals were as behaviorally active as their young male counterparts. Assessment of serum T showed that aging did not produce a reduction in levels of the steroid and individual variability in androgen-dependent behavior of aged males was not related to plasma levels of the hormone. When aged non-aggressive and non-killer males were exposed to supplemental T by way of subcutaneously implanted silastic capsules, circulating levels of the steroid were elevated but T-dependent behavior was not recovered. These findings, in combination with those previously reported for copulatory behavior, indicate that the deficits observed in the androgen-dependent behavior of aged male mice cannot be attributed to a breakdown in the production of testicular androgens. While neural refractoriness to T may account in part for deficits in androgen-dependent behavior of aged males, the variability that is observed in the reproductive behaviors of aged male rodents ultimately may be related to other sources of variation such as perinatal environment.     

Intergenerational instability of the CAG repeat of the gene for Machado- Joseph disease (MJD1) is affected by the genotype of the normal chromosome: implications for the molecular mechanisms of the instability of the CAG repeat

Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder caused by unstable expansion of a CAG repeat in the MJD1 gene at 14q32.1. To identify elements affecting the intergenerational instability of the CAG repeat, we investigated whether the CGG/GGG polymorphism at the 3' end of the CAG repeat affects intergenerational instability of the CAG repeat. The [expanded (CAG)n-CGG]/[normal (CAG)n- GGG] haplotypes were found to result in significantly greater instability of the CAG repeat compared to the [expanded (CAG)n- CGG]/[normal (CAG)n-CGG] or [expanded (CAG)nGGG]/[normal (CAG)n-GGG] haplotypes. Multiple stepwise logistic regression analysis revealed that the relative risk for a large intergenerational change in the number of CAG repeat units (< -2 or > 2) is 7.7-fold (95% CI: 2.5-23.9) higher in the case of paternal transmission than in that of maternal transmission and 7.4-fold (95% CI: 2.4-23.3) higher in the case of transmission from a parent with the [expanded (CAG)n-CGG]/[normal (CAG)n-GGG] haplotypes than in that of transmission from a parent with the [expanded (CAG)n-CGG]/[normal (CAG)n-CGG] or [expanded (CAG)n- GGG]/[normal (CAG)n-GGG] haplotypes. The combination of paternal transmission and the [expanded (CAG)n-CGG]/[normal (CAG)n-GGG] haplotypes resulted in a 75.2-fold (95% CI: 9.0-625.0) increase in the relative risk compared with that of maternal transmission and the [expanded (CAG)n-CGG]/[normal (CAG)n-CGG] or [expanded (CAG)n- GGG]/[normal (CAG)n-GGG] haplotypes. The results suggest that an inter- allelic interaction is involved in the intergenerational instability of the expanded CAG repeat.      

Chromosomal aberrations and micronucleus frequency in nurses occupationally exposed to cytotoxic drugs

In this study, we evaluated the effect of low level occupationalexposure of nurses in a medical oncology unit in Cairo, Egypt,to anticancer drugs. Twenty nurses who constantly handled thesedrugs and 20 controls, matched according to age and sex, wereexamined. Metaphase chromosomes were studied. Percentages ofmetaphases with chromosomal aberrations were significantly higher(P < 0.001) in the exposed group (6.1 ± 2.7) versusthe controls (2.6 ± 1.6). The detected chromosomal aberrationswere in the form of chromatid gaps, chromatid breaks and acentricfragments. Micronucleated peripheral blood lymphocytes werealso analyzed in cytochalasin B treated binucleated lymphocytes.There was significant increase in cells with micronuclei (P< 0.001) in nurses (10.05 ± 4.71) in comparison tothe matched control (5.42 ± 2.22) (P < 0.001). Nursesexposed to the cytotoxic drugs for     

The mouse Mid1 gene: implications for the pathogenesis of Opitz syndrome and the evolution of the mammalian pseudoautosomal region

We have recently reported isolation of the gene responsible for X- linked Opitz G/BBB syndrome, a defect of midline development. MID1 is located on the distal short arm of the human X chromosome (Xp22. 3) and encodes a novel member of the B box family of zinc finger proteins. We have now cloned the murine homolog of MID1 and performed preliminary expression studies during development. Mid1 expression in undifferentiated cells in the central nervous, gastrointestinal and urogenital systems suggests that abnormal cell proliferation may underlie the defect in midline development characteristic of Opitz syndrome. We have also found that Mid1 is located within the mouse pseudoautosomal region (PAR) in Mus musculus , while it seems to be X- specific in Mus spretus. Therefore, Mid1 is likely to be a recent acquisition of the M. musculus PAR. Genetic and FISH analyses also demonstrated a high frequency of unequal crossovers in the murine PAR, creating spontaneous deletion/duplication events involving Mid1. These data provide evidence for the first time that genetic instability of the PAR may affect functionally important genes. In addition, we show that MID1 is the first example of a gene subject to X-inactivation in man while escaping it in mouse. These data contribute to a better understanding of the molecular content and evolution of the rodent PAR.      

Risk factors for urinary incontinence 1 year after the first vaginal delivery in a cohort of primiparous Danish women

Introduction and hypothesis

The objective was to examine the relationship between maternal and perinatal factors and the occurrence of stress (SUI) or mixed (MUI) urinary incontinence (UI) 1 year after the first vaginal delivery in primiparous women.

Methods

Participants in this prospective cohort were recruited consecutively from June 2003 to July 2005 from all eligible women who delivered in the department. A validated questionnaire, the International Consultation of Incontinence Questionnaire Short Form (ICIQ-SF) was completed by all participants 2–3 days after delivery, and a similar second questionnaire was filled out 1 year later. Additional data were obtained from the medical records. The first questionnaire was completed by 1,018 women (63 %) and the second by 859 women (84 %). The study group comprised the 575 women without any UI before the pregnancy and who had a vaginal delivery. The primary analysis comprised 117 women with either SUI or MUI 1 year after the vaginal delivery and 403 women without any UI.

Results

In univariate analyses, the following factors were associated with SUI or MUI: prepregnancy body mass index (BMI)?≥?30 (p?<?0.05), UI during the pregnancy (p?<?0.05), perineal lesions (p?<?0.05), and anal sphincter tears (p?=?0.05). Logistic regression analysis showed that SUI or MUI was strongly associated with UI during the pregnancy [adjusted odds ratio (OR) 4.7, 95 % confidence interval (CI) 2.9–7.7) and inversely associated with oxytocin augmentation (adjusted OR 0.5, 95 % CI 0.3–0.9).

Conclusions

SUI or MUI 1 year after the first vaginal delivery was strongly associated with UI during the pregnancy and inversely associated with oxytocin augmentation.     

1141154113Expression of natural cytotoxicity receptors in peripheral blood NK cell subsets of women with recurrent spontaneous abortions (RSA) or implantation failures

Aim:  To determine if IgA is required for protection against Chlamydia infection in the male reproductive tract (MRT).
Materials and Methods:  Male polyimmunoglobulin receptor knockout mice (PIgR^-/-) and wild-type C57BL/6 (WT) mice were immunised intranasally with chlamydial major outer membrane protein (MOMP) and cholera toxin (CT). MOMP-specific IgG and IgA in serum and prostatic fluids were measured by ELISA. Serum and PF were also assayed for inhibition of in vitro chlamydial infection. Immunized WT and PIgR^-/- mice were challenged by direct inoculation of C. muridarum into the meatus urethra. Four weeks post challenge Chlamydia levels in the penile urethra, epididymis and testis were determined by PCR.
Results:  Equivalent levels of IgG were found in the serum of both WT and PIgR^-/- mice however IgA in serum of PIgR^-/- mice was 19- to 20-fold higher than in WT animals consistent with the lack of the PIgR IgA transport molecule. IgA levels were significantly lower in PIgR^-/- PF compared to WT PF after both immunization and infection. Only PF from WT but not PIgR^-/- animals was able to inhibit in vitro chlamydial infection. Following challenge significantly higher levels of Chlamydia were recovered from the MRT of PIgR^-/- mice compared to WT animals.
Conclusions:  Male mice lacking a functional PIgR were unable to clear a genital tract Chlamydia infection despite high levels of serum IgA. These data show that mucosal IgA plays a major role in preventing chlamydial infection of the male genital tract and suggest that immunization strategies to protect males should target a strong mucosal IgA response.     

Trichomonas vaginalis in HIV/AIDS subjects in Nigeria

ObjectiveTo determine the prevalence of Trichomonas vaginalis (T. vaginalis) in HIV/AIDS patients attending two different hospitals in southeast Nigeria.MethodsWe collected 970 urine samples from HIV/AIDS patients attending two different hospitals in southeast Nigeria. Samples were processed by microscopy and cultural methods.ResultsOut of the 970 screened, 355 (36.60%) were positive for T. vaginalis. Subjects with the least CD4⁺ count in the range of 40-140 cells/mL had the highest number of positive samples (180, 50.70%), while those in the range of 480-580 cells/mL had the least value (2, 0.56%). Those in the rural areas had a higher number of positive samples (155, 38.75%) than their urban counterparts (200, 35.09%) with respect to the total number examined in each group but this was not statistically significant (P>0.05). Out of the 355 positive cases, the university undergraduate students’ group had the highest percentage incidence of 53.00% followed by the low-income group with 47.08%.ConclusionsIt can be concluded that the occurrence of T. vaginalis increases with decrease in the CD4⁺ counts in HIV/AIDS patients in Nigeria. Since T. vaginalis may be an important cofactor in promoting the spread of HIV and, in some circumstances, may have a major impact on the epidemic dynamics of HIV, there is a need to take measures to check the spread of this parasitic infection.