Publications

Involucrin is a major protein of the cornified envelope of keratinocytes that provides much of the structural integrity of skin. Its expression is stimulated by a number of agents including calcium and 1,25-dihydroxy-vitamin D3 that promote the differentiation process in keratinocytes. Within the distal regulatory region of the involucrin promoter lies an AP-1 site and an element homologous to other vitamin D response elements. In previous studies mutation of the AP-1 site was found to reduce basal activity and block calcium stimulation of the involucrin promoter, whereas the vitamin D response element was not critical for calcium regulation. In this study both elements proved to be important for 1,25-dihydroxyvitamin D3 stimulation of the involucrin promoter. Mutation of the AP-1 site reduced basal activity and blocked 1,25-dihydroxyvitamin D3 stimulation of the involucrin promoter. In contrast, mutation of the vitamin D response element did not reduce basal expression of the involucrin promoter or prevent calcium stimulation of involucrin gene expression, but blocked 1,25-dihydroxyvitamin D3 stimulation. The vitamin D response element from the involucrin gene bound the vitamin D receptor and the retinoid X receptor, but not the retinoic acid receptor, in a specific manner. We conclude that the AP-1 site and the vitamin D response element in the involucrin promoter play important roles in mediating the action of 1,25-dihydroxyvitamin D3 on involucrin expression, but the vitamin D response element provides specificity for the 1,25-dihydroxyvitamin D3 response lacking at the AP-1 site.

BACKGROUND

Because they have chronic airway inflammation, adults with asthma may be particularly susceptible to indoor air pollution. Despite widespread exposure to environmental tobacco smoke (ETS), gas stoves, and woodsmoke, the impact of these exposures on adult asthma has not been well characterised.

METHODS

Data were used from a prospective cohort study of 349 adults with asthma who underwent structured telephone interviews at baseline and 18 month follow up. The prospective impact of ETS, gas stove, and woodsmoke exposure on health outcomes was examined.

RESULTS

ETS exposure at baseline interview was associated with impaired health status at longitudinal follow up. Compared with respondents with no baseline self-reported exposure to ETS, higher level exposure (>/=7 hours/week) was associated with worse severity of asthma scores at follow up, controlling for baseline asthma severity, age, sex, race, income, and educational attainment (mean score increment 1.5 points; 95% CI 0.4 to 2.6). Higher level baseline exposure to ETS was also related to poorer physical health status (mean decrement -4.9 points; 95% CI -8.4 to -1.3) and asthma specific quality of life (mean increase 4.4 points; 95% CI -0.2 to 9.0) at longitudinal follow up. Higher level baseline ETS exposure was associated with a greater risk of emergency department visits (OR 3.4; 95% CI 1.1 to 10.3) and hospital admissions for asthma at prospective follow up (OR 12.2; 95% CI 1.5 to 102). There was no clear relationship between gas stove use or woodstove exposure and asthma health outcomes.

CONCLUSION

Although gas stove and woodstove exposure do not appear negatively to affect adults with asthma, ETS is associated with a clear impairment in health status.

The aim of this study was to determine whether or not the skin acts as a reservoir for cocaine. Cocaine-d5 (1 mg/kg) was administered to five nondependent, cocaine-experienced volunteers. Skin tissue, interstitial fluid, sebum, stratum corneum, and plasma were collected for 72 h after drug administration. Cocaine and benzoylecgonine (BE) levels were determined using GC-MS. Cocaine concentrations peaked in plasma at 1 h after administration, with pharmacokinetic parameters (t(1/2), CL, Vd) also in the expected ranges. In skin, cocaine levels peaked around 1.5 h after administration and became undetectable by 6 h. A correlation was found between the plasma and skin AUC for cocaine (R = 0.99, p = 0.006, N = 4). BE was not detected in skin. In interstitial fluid (N = 4), cocaine concentrations peaked around 5 h after drug administration and were undetectable by 24 h. BE peaks varied between 2 and 24 h and were not detectable at 48 h. In sebum, cocaine levels peaked between 3 and 24 h. BE was found in three samples between 12 and 24 h. In stratum corneum, cocaine was measurable in only one sample from one subject. These findings suggest that skin does not act as a reservoir for cocaine. Rather, cocaine appears to be distributed rapidly to the skin and eliminated, following a time course similar to that of plasma.

BACKGROUND

The majority of women diagnosed with early-stage breast cancer have an excellent long-term prognosis, but many will undergo temporary or permanent chemotherapy-induced amenorrhea.

METHODS

While breast cancer is more common in older women, about 1 in 200 women under the age of 40 is at risk to develop breast cancer. Many of these women benefit from chemotherapy but are afraid to risk the opportunity to bear children. The authors review the current studies on the impact of adjuvant chemotherapy on amenorrhea and fertility in women with breast cancer.

RESULTS

The likelihood of amenorrhea is based on the specific adjuvant chemotherapy regimen administered and the age of the patient. Future childbirth is a viable option for women treated for breast cancer at an early stage. While the use of tamoxifen as a hormonal therapy in premenopausal breast cancer is now the standard of care, no conclusive data confirm the benefit of GnRH agonists in adjuvant therapy after treatment with chemotherapy followed by tamoxifen.

CONCLUSIONS

As more women over the age of 35 consider pregnancy, fertility issues are becoming important areas of investigation for the adjuvant treatment of breast cancer. Whether chemotherapy-induced amenorrhea has a prognostic effect remains unclear, and further studies are warranted.

Oral health, taste, and smell are critical components to an older person's overall sense of well-being and quality of life. Oral health problems can cause pain and discomfort and can hinder the maintenance of a satisfying and nutritious diet. Loss of taste and smell interferes with pleasure derived from food and food-related activities. Attention should be given to preserving teeth and optimizing oral function. Likewise, close evaluation of older adults' medications may identify the causes of taste and smell disorders. In instances in which nutrient intake is inadequate and chemosensory perception is considered a likely contributor, a trial of flavor enhancers or monosodium glutamate may improve both quality and quantity of intake. Much more information is needed to understand the interrelationship between chemosensory perception, food intake regulatory mechanisms, and nutritional status. Multidisciplinary studies will be required to understand how to improve nutrition through manipulation of oral characteristics, taste, and smell.

Background. Studies of medical admissions have questioned the validity of using claims data to adjust for preexisting medical conditions (comorbidities), but the impact of using comorbidities from claims data to risk-adjust mortality rates for high-risk surgery is not well characterized. The purpose of this study was to evaluate the relationship between comorbidities and mortality in administrative data in surgical populations and identify better risk-adjustment methods. Methods. Using the national Medicare database (1994-1997), we identified admissions for elective abdominal aortic aneurysm repair (140,577) and pancreaticoduodenectomy (10,530). We calculated the relative risk of mortality (adjusted for age, sex, race, and admission acuity) for 5 chronic conditions that are known (from clinical series) to increase the risk of postoperative mortality and are commonly used in claims-based risk-adjustment models. To explore the potential value of alternative risk-adjustment strategies, we examined relationships between surgical mortality and comorbidities using diagnosis codes identified from previous admissions. Results. Overall, in-hospital mortality for elective abdominal aortic aneurysm (AAA) repair and pancreaticoduodenectomy were 5.1% and 10.4%, respectively. For both procedures, 3 of the 5 comorbidities were associated with decreased risk of mortality: prior myocardial infarction (MI) [RR = 0.38; 95% confidence interval (CI), 0.33-0.43 for AAA; RR = 0.38; 95% CI, 0.21-0.69 for pancreaticoduodenectomy), malignancy (RR = 0.67; 95% CI, 0.59-0.76 for AAA; RR = 0.74; 95% CI, 0.45-1.21 for pancreaticoduodenectomy], and diabetes (RR = 0.76; 95% CI, 0.64-0.84 for AAA; RR = 0.59; 95% CI, 0.49-0.69 for pancreaticoduodenectomy). Using comorbidities identified from prior admissions increased the mortality risk estimates for prior MI (RR = 1.22; 95% CI, 1.08-1.38 for AAA; RR = 0.80; 95% CI, 0.49-1.30 for pancreaticoduodenectomy) and diabetes (RR = 1.41; 95% CI, 1.25-1.59 for AAA; RR = 0.94; 95% CI, 0.78-1.14 for pancreaticoduodenectomy). Conclusions. Because comorbidities coded on the index admission appear protective, incorporating them in risk-adjustment models for studies comparing surgical performance may penalize providers for taking care of sicker patients. When available, comorbidity information from prior hospitalizations may be more useful for risk adjustment.