Influence of GSTT1 and GSTM1 genotypes on sunburn sensitivity

Background: Exposure to sunlight may cause sunburn, skin cancer or phototoxic reactions to certain drugs such as Hypericum extract. All these are ultraviolet B (UVB)-mediated reactions which may be modulated by individual genetic susceptibility. UVB exposure results in oxidative stress. Many products of oxidative stress are detoxified by glutathione-S-transferases mu 1 (GSTM1) and theta 1 (GSTT1). Deletion polymorphisms (genotype *0/*0) of GSTM1 and GSTT1 occur in 50% and 20% of Caucasians, respectively. By affecting the individual ability to detoxify oxidative stress-related products, they may influence the severity of the cutaneous photoreaction. Methods: Minimal erythema doses (MED) of UVB irradiation on the skin were determined in 110 subjects who were selected according to their GSTT1 genotype (28 GSTT1*0/*0, 54 GSTT1*A/*0, and 28 GSTT1*A/*A). Genotypes were detected with novel polymerase chain reaction (PCR) assays that allow the differentiation between homozygous and heterozygous GSTT1 and GSTM1 deletions. Results: In the absence of GSTT1 enzyme, the susceptibility of individuals to UVB-induced inflammatory skin reactions increased significantly (p = 0.02, ANCOVA). ‘Gene-equivalents’ were calculated from the number of functional GSTM1 and GSTT1 alleles as a measure of the gene-dose. UVB sensitivity correlated with gene dose up to a threshold above which additional GSTT1 or GSTM1 alleles did not provide additional protection. Volunteers who were homozygously deficient in GSTT1 and GSTM1 were most sensitive to UVB. Interestingly, individuals with high GSTM1 gene-doses showed increased photosensitization after administration of Hypericum extract (St. John’s wort). Conclusion: Individuals harboring the *0/*0 genotype of GSTT1 and/or GSTM1 showed enhanced UVB-induced cutaneous damage. Moreover, GST genotypes modulated Hypericum-induced photosensitization.     

Electromagnetic field hazards involving adjustable shunt valves in hydrocephalus

OBJECT: Standard therapy for hydrocephalus involves shunts and valves, which are frequently adjustable. Because of increasing "electromagnetic smog" (for example, that generated by cellular phones), these valves are often exposed to electromagnetic fields. METHODS: Various magnetic fields were tested for their effects on two different kinds of adjustable valves. The minimum magnetic flux density affecting the adjustment of the valve was determined. Results were compared with magnetic fields found in contemporary everyday life. In homogeneous magnetic fields the adjustment of one valve (Sophysa model SM8) was changed at 5 mT, whereas the second valve (Codman Hakim model CM) was not affected. In nonhomogeneous fields the SM8 valve was affected at 25 mT and the CM valve at 15 mT. Thus, these valves may be affected by headphones and telephone receivers. Surroundings such as the Japanese magnetic suspension railway and the lead cabin of electrical railway engines, in which critical levels of magnetic flux may be present, may also affect adjustable valves. The high-frequency fields of cellular phones, however, have no effect on these valves. CONCLUSIONS: Every surgeon who implants these valves and every patient who receives them should know the possible hazards. The valve selection should be adapted to the environment of the patient. Devices with critical levels of electromagnetic flux that are used in the homes of patients should be replaced by ones with lower magnetic fields. The future construction of these valves should be modified in such a way that their adjustment requires a higher magnetic flux density, so that the valves become less sensitive to unwanted effects from environmental magnetic fields.     

Chemotherapy versus hormonal adjuvant treatment in premenopausal patients with breast cancer

Comparisons between the effects exerted by adjuvant cyclophosphamide, methotrexate and 5-fluorouracil (CMF)-based polychemotherapy and endocrine treatment in premenopausal breast cancer patients are validly drawn in the presence of steroid hormone receptor responsiveness. First, ovarian ablation still remains to show activity compared with chemotherapy in large patient groups. Second, tamoxifen is at least as active in this cohort and, by comparison, produces a significant effect in mortality reduction. Third, induction of reversible amenorrhoea by LHRH analogue administration has shown comparable effects in terms of recurrence-free survival. Finally, recent European investigations have indicated significant recurrence reductions with LHRH analogue-tamoxifen combination strategies. In conclusion, various endocrine treatment modalities have been substantiated as equiefficient to polychemotherapy. Tamoxifen added to a LHRH analogue further diminishes the recurrence rates and now appears to be a valid treatment alternative. We argue that selection of adjuvant systemic therapy for premenopausal breast cancer patients be increasingly guided by knowledge of the steroid hormone receptor levels.     

Randomized adjuvant trial of tamoxifen and goserelin versus cyclophosphamide, methotrexate, and fluorouracil: evidence for the superiority of treatment with endocrine blockade in premenopausal patients with hormone-responsive breast cancer--Austrian Breast and Colorectal Cancer Study Group Trial 5.

PURPOSE: Effective adjuvant treatment modalities in premenopausal breast cancer patients today include chemotherapy, ovariectomy, and tamoxifen administration. The purpose of Austrian Breast and Colorectal Cancer Study Group Trial 5 was to compare the efficacy of a combination endocrine treatment with standard chemotherapy. PATIENTS AND METHODS: Assessable trial subjects (N = 1,034) presenting with hormone-responsive disease were randomized to receive either 3 years of goserelin plus 5 years of tamoxifen or six cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF). Stratification criteria included tumor stage and grade, number of involved nodes, type of surgery, and steroid hormone receptor content. Relapse-free survival (RFS) was defined as time from randomization to first relapse, local recurrence, or contralateral incidence, and overall survival (OS) as time to date of death. RESULTS: With a 60-month median follow-up, 17.2% of patients in the endocrine group and 20.8% undergoing chemotherapy developed relapses. Local recurrences emerged in 4.7% and 8.0%, respectively. RFS and local recurrence-free survival differed significantly in favor of endocrine therapy (P =.037 and P =.015), with a similar trend observed in OS (P =.195). CONCLUSION: Overall, our data suggest that the goserelin-tamoxifen combination is significantly more effective than CMF in the adjuvant treatment of premenopausal patients with stage I and II breast cancer.     

Low socio-economic position is associated with poor social networks and social support: results from the Heinz Nixdorf Recall Study

Background  

Social networks and social support are supposed to contribute to the development of unequal health within populations. However, little is known about their socio-economic distribution. In this study, we explore this distribution.     

Paclitaxel-containing high-dose chemotherapy in high-risk breast cancer patients

Despite standard-dose adjuvant chemotherapy, the prognosis for patients with breast cancer and extensive axillary lymph node involvement at diagnosis is poor. The efficacy of a paclitaxel-containing, high-dose chemotherapy protocol in 21 high-risk breast cancer patients is assessed. After standard-dose chemotherapy followed by peripheral blood stem cell (PBSC) mobilization, high-dose therapy with paclitaxel, carboplatin, and cyclophosphamide and CD34-selected PBSC rescue was given. Hematologic reconstitution after high-dose therapy was rapid. Main toxicity included diarrhea grade I or II in about half of the patients and infections were observed in 19%. Five-year probabilities for relapse and failure-free survival were 32% and 62%, respectively. High-dose consolidation with paclitaxel, carboplatin, and cyclophosphamide achieves a high failure-free survival in patients with high-risk breast cancer with acceptable toxicities and stable, long-term hematopoietic reconstitution. Evaluation of the benefit of high-dose therapy in these patients in larger prospective, randomized trials is warranted and currently under way.     

Pulsed Doppler tissue imaging in dystrophinopathic cardiomyopathy.

Cardiac dysfunction is a primary feature in patients and female carriers of Becker muscular dystrophy (BMD). Conventional echocardiography and pulsed Doppler tissue imaging (DTI) were performed in 28 patients with BMD, in 20 female carriers, and in 38 control participants (20 men and 18 women). Left ventricular ejection fraction (LVEF) was lower in BMD patients (P <.02) and carriers (P <.02) than in normal participants. Two subgroups of BMD patients were identified: A1 = LVEF > or = 55% (n = 20) and A2 = LVEF < 55% (n = 8). The carriers displayed LVEF > or = 55%. Compared with control participants the diastolic alterations by conventional echocardiography were lower early filling peak in the subgroup A1 (P <.05) and prolonged isovolumic relaxation time in A1, A2, and in carriers (at least P <.02). Furthermore, pulsed DTI showed lower early diastolic wave peak at basal septum in A2 (P <.05) and in carriers (P <.0001); at lateral mitral annulus and at basal inferior wall in A1, A2, and in carriers (at least P <.05); lower early/late diastolic wave ratio at basal septum and lateral mitral annulus (P <.05) in carriers; and prolonged isovolumic relaxation time in A1, A2, and in carriers (at least P <.02), except at lateral mitral annulus of carriers. Systolic parameters investigated by pulsed DTI detected lower peak systolic wave at basal septum in A1, A2, and carriers (P <.02); at lateral mitral annulus in carriers (P <.02); at basal inferior wall in A1, A2 (P <.02), and in carriers (P <.0001); and lower time-velocity integral of S wave at each segment in A1, A2, and in carriers. In dystrophinopathic cardiomyopathy, pulsed DTI may be a useful technique to assess diastolic dysfunction and appears to be a promising tool in identifying early regional systolic alterations in patients and carriers with normal LVEF.     

Second-generation K(ATP) channel openers

This review discusses structural aspects of second-generation K(ATP) channel openers (KCOs), which exhibit improved tissue-selectivity. Their therapeutic profile is debated with main focus on cardiac ischemia, asthma, and urinary incontinence.