Topical Interferon Cream for the Treatment of Herpes Genitalis: A Double-blind Controlled Trial

Thirty-five women with primary herpes genitalis and 34 women with recurrent herpes genitalis were treated with either placebo, or beta Interferon cream (20,000 iu/g). In comparison with the placebo group, the treatment group showed no benefit in either symptom relief, speed of healing of lesions or length of viral shedding time from lesions.     

Inducible transformation of fibroblasts using a metallothionein-v-myc gene construct

An inducible oncogene construct has been engineered by coupling the MC29 v-myc oncogene to the sheep metallothionein promoter. Transfection of this plasmid, which also contains the neomycin resistance gene, into Rat-1 cells, has resulted in the isolation of independent clones resistant to G418. Certain of these clones were found to exhibit inducible transformation in response to ZnSO4. Transformation was graded with increasing ZnSO4 levels and was reversible when ZnSO4 was removed from the media. By analyzing v-myc mRNA levels, the inducible alterations in cellular morphology and growth were found to be associated with increased v-myc expression. The metallothionein promoter exhibited negligible constitutive expression of v-myc and none of the clones isolated exhibited spontaneous transformation. Our results show that the use of a metallothionein promoter v-myc construct facilitates the study of inducible fibroblast transformation.     

Systemic production of human granulocyte colony-stimulating factor in nonhuman primates by transplantation of genetically modified myoblasts

Clinical use of human granulocyte-colony stimulating factor (hG-CSF) to treat various diseases involving neutropenia has been previously shown to (1) successfully increase circulating neutrophils, (2) reduce condition-related infections, and (3) cause few side effects in patients. To alleviate the symptoms of neutropenia, the patient must receive frequent injections of recombinant hG-CSF. Permanent ways to deliver stable levels of the molecule to the patient are being investigated. Among them, the transplantation of hG-CSF-secreting cells has been proposed and performed successfully in rodents, using fibroblast cell lines and primary muscle cells. We thus investigated whether similar results could be obtained by intramuscular myoblast transplantation in a large animal model. When 1-3 x 10(8) myoblasts were injected into three Macaca mulatta, hG-CSF was detected at high levels (300-900 pg/ml), which in turn led to a four- to fivefold increase in circulating neutrophils. However, both the concentrations of hG-CSF and neutrophil levels were found to decrease over time. Nonetheless, neutrophils were found at higher levels from the fourth week until the end the experiment (up to 29 weeks) in G-CSF monkeys compared with control animals. These results show that transplantation of hG-CSF-secreting myoblasts may indeed be a therapeutic option for the treatment of neutropenic patients.     

Seroprevalence of human T-lymphotropic virus, hepatitis C virus, and human immunodeficiency virus in Asian American potential bone marrow donors

BACKGROUND: Asian Americans are generally underrepresented both as volunteer blood and bone marrow donors. STUDY DESIGN AND METHODS: To investigate the risk of transfusion transmission of viruses that is associated with increasing participation by Asian American donors, antibodies to human T-lymphotropic virus (HTLV), hepatitis C, and human immunodeficiency virus in Asian American volunteers recruited as potential bone marrow donors were measured. A total of 1354 Asian Americans were enrolled in the study, of whom 54 percent were Chinese, 26 percent Japanese, 9 percent Filipino, 4 percent Korean, 3 percent Indian, and 5 percent of other Asian or mixed Asian and other ethnicity. The majority of the study population was aged 20 through 49 and of high socioeconomic status, as indicated by education and income. Viral antibodies were measured with both screening enzyme-linked immunosorbent assays and supplemental testing, and polymerase chain reaction was used to resolve discrepant HTLV results. RESULTS: Confirmed seroprevalence rates for HTLV were 0.15 percent with one manufacturer's Western blot and 0.3 percent with the other; however, no sample was positive for HTLV types I or II in polymerase chain reaction. Confirmed seroprevalence to hepatitis C virus was 0.5 percent. No subject was seropositive for human immunodeficiency virus. CONCLUSION: On the basis of the moderate size and high education level of this study population, it is concluded that Asian American volunteer bone marrow donors do not pose a greater risk for transmission of HTLV type I or II, human immunodeficiency virus, or hepatitis C virus than does the average American blood donor.     

Platelet monoamine oxidase and phenolsulphotransferase M and P in cancer

Phenolsulphotransferase and monoamine oxidase inactivate a wide range of dietary and endogenous phenols/monoamines by sulphoconjugation and oxidative deamination respectively. In this study, both enzymes were measured in platelets from cancer patients and controls. Of the two variants of phenolsulphotransferase, activity of the P form was normal in all groups. Activity of the M form was, however, significantly less than control values in patients with cancer of the rectum and bowel but not in other cancer patient groups. If this finding reflects enzyme activity elsewhere in the body and is not merely a manifestation of an abnormal platelet population, the deficit could expose affected subjects to the action of potentially carcinogenic dietary phenols. Platelet monoamine oxidase activity was significantly raised in the cancer group as a whole, and in all sub-types investigated apart from breast cancer. The increase in the cancer group as a whole was independent of sex, age, drugs, radiotherapy, smoking or platelet count. Its mechanism and significance are unknown but there may be links with the patients' psychiatric state.     

Comparison of the mechanical performance of three types of external fixators: linear, circular and hybrid

Different configurations of the Monticelli-Spinelli and Ilizarov external fixation systems were tested to define their mechanical properties. In five configurations the external fixator consisted of rings with tensioned wires (circular), while in one configuration two pairs of the tensioned wires and their correspondent ring were replaced by threaded pins (hybrid). Testing was performed in axial compression, bending and torsion. The results were compared to the characteristics of a selected linear fixator group. Both the circular and the hybrid configurations were non-linear in compression. In bending, circular fixators had a similar pattern in both anteroposterior and oblique loading directions. The bending load-displacement pattern for the hybrid fixators was similar to the linear fixators, higher stiffness in the plane of the pins. Torsion was linear for both circular and hybrid fixators, as for the linear fixators. By combination of wires and pins (hybrid configuration), the mechanical behaviour had characteristics from both linear and circular fixators. It is concluded that the three studied groups own different mechanical performance and can be considered as different types of fixators. While it has been demonstrated that osteogenesis can be achieved independently of the mechanical behaviour of the fixator, this study supports the suggestion that some complications can be related to the mechanical behaviour of the fixator.     

Factors used by female pelvic medicine and reconstructive surgery fellowship directors to select their fellows

Introduction and hypothesis  

We report the attributes of Female Pelvic Medicine and Reconstructive Surgery (FPM&RS) fellowship applicants that are most valued by fellowship program directors during the ranking process.     

A longitudinal analysis of prenatal exposure to methylmercury and fatty acids in the Seychelles

Background

Maternal fish consumption during pregnancy exposes the fetus simultaneously to methylmercury (MeHg) and long chain polyunsaturated fatty acids (LCPUFA). Data from the Seychelles Child Development Nutrition Study (SCDNS) showed a negative association of MeHg with child development when children were 30 months of age, only when controlling for LCPUFA. Concomitantly, n − 3 LCPUFA were found to have a significant positive association only at 9 months. These findings suggest that the effects of MeHg and LCPUFA may vary with age over the first few years of life. We address this by including outcomes at two ages and adjusting for the child's age at testing.

Methods

A longitudinal analysis utilizing linear mixed models was performed to assess the associations of maternal hair total mercury (THg, a biomarker for MeHg) and maternal LCPUFA with children's Bayley Scales of Infant Development Psychomotor Developmental Index (BSID-II PDI) at 9 and 30 months of age, and to determine whether these associations change over time. Data from 228 children were included.

Results

Maternal hair MeHg had a negative effect on BSID PDI, while maternal n − 3 LCPUFA had a positive effect. These effects did not change significantly from 9 to 30 months in this analysis.

Conclusions

The longitudinal analysis provides increased power for estimating the relationships of prenatal MeHg and LCPUFA exposures during child development. Significant associations of these exposures in opposite directions confirm the importance of LCPUFA in development and the need to adjust for maternal nutrition when studying prenatal MeHg exposure.     

Air pollutants and cough

Epidemiological studies have shown that exposure to air pollution is associated with respiratory symptoms and decreases in lung function. This paper reviews recent literature showing that exposure to particulate matter, irritant gases, environmental tobacco smoke (ETS), mixed pollutants, and molds is associated with an increase in cough and wheeze. Some pollutants, like particulate matter and mixed pollutants, appear to increase cough at least as much as wheeze. Others, like irritant gases, appear to increase wheeze more than cough. For ETS, exposure during childhood is associated with cough and wheeze in adulthood, suggesting that the pollutant permanently alters some important aspect of the lungs, immune system or nervous system. We have shown in animal studies that pollutants change the neural control of airways and cough. Second hand smoke (SHS) exposure lengthened stimulated apnoea, increased the number of stimulated coughs, and augmented the degree of stimulated bronchoconstriction. The mechanisms included enhanced reactivity of the peripheral sensory neurones and second-order neurones in the nucleus tractus solitarius (NTS). NTS effects were due to a substance P mechanism at least in part. Ozone and allergen increased the intrinsic excitability of second-order neurones in the NTS. The animal studies suggest that the cough and wheeze experienced by humans exposed to pollutants may involve plasticity in the nervous system.