Renal hemodynamic and tubular responses to salt in women using oral contraceptives

BACKGROUND: The use of oral contraceptives is associated with an increased risk of developing hypertension but the mechanisms of this hypertensive effect are not completely defined. The purpose of the present study was to assess prospectively the systemic and renal hemodynamic and tubular responses to salt in women taking oral contraceptives. METHODS: Twenty seven young healthy normotensive women taking oral contraceptives containing monophasic combination of 30 microg ethynilestradiol and 150 microg desogestrel for>6 months were enrolled. All women were assigned at random to receive a low (40 mmol/day) or a high (250 mmol/day) sodium diet for 1 week on two consecutive menstrual cycles during the active oral contraceptive phase. At the end of each diet period, 24-hour ambulatory blood pressure, renal hemodynamics, sodium handling, and hormonal profile were measured. RESULTS: The blood pressure response to salt on oral contraceptives was characterized by a salt-resistant pattern with a normal circadian rhythm. Salt loading results in an increase in glomerular filtration rate (GFR) (P < 0.05 vs. low salt), with no change in the renal plasma flow, thus leading to an increase in the filtration fraction (P < 0.05). At the tubular level, women on oral contraceptives responded to a low salt intake with a marked increased in proximal sodium conservation (P < 0.01 vs. high salt) and with an almost complete reabsorption of sodium reaching the distal tubule. After sodium loading, both the proximal and the distal reabsorption of sodium decreased significantly (P < 0.01). CONCLUSION: The use of oral contraceptives is not associated with an increased blood pressure response to salt in young normotensive women. However, oral contraceptives affect the renal hemodynamic response to salt, a high salt intake leading to an increase in GFR and filtration fraction. This effect is possibly mediated by the estrogen-induced activation of the renin-angiotensin system. Oral contraceptives also appear to increase the tubular responsiveness to changes in sodium intake. Taken together, these data point out evidence that synthetic sex steroids have a significant impact on renal function in women. The renal effects of oral contraceptives should be taken into account when managing young women with renal diseases.     

A role for curative surgery in the treatment of selected patients with metastatic breast cancer

Although metastatic breast cancer is widely believed to carry a grim prognosis, treatment developments over the past 25 years have greatly improved survival outcomes in these patients. In selected cases, aggressive treatment approaches may occasionally result in long-term survival of 15 years or more. This review considers the role of surgery in the treatment of single or multiple metastatic lesions restricted to one site. For each site, available literature from 1992-2002 was assessed to determine the role of surgery on survival outcomes and to determine appropriate criteria for selecting the best candidates for surgery. For lung, liver, brain, and sternum metastases, the use of surgery with or without adjuvant therapy resulted in greater median survival times and 5-year survival rates. The best candidate for surgery had no evidence of additional metastatic disease, good performance status, and a long disease-free interval after treatment of the primary tumor. Current treatment standards for breast cancer follow-up do not include imaging studies other than mammography. The addition of chest x-rays as part of routine follow-up should be considered as a cost-effective approach for early assessment of metastases to the lung or sternum that may be appropriate for surgical excision.     

Complication,local recurrence,and survival rates after radiofrequency ablation for hepatic malignancies

RFA is a technology that can be applied to unresectable hepatic malignancies without significant morbidity when patients and treatment approach are chosen carefully. The results of therapy provide patients with an improved chance for survival despite their unresectable disease. There are limitations of imaging to monitor treatment and treatment response. At this point, an intraoperative technique has greater treatment success than a percutaneous technique and this is likely associated with periprocedural imaging limitations with a percutaneous technique and the ability to more easily perform inflow vascular occlusion with an intraoperative approach. RFA is a potentially effective local tumor therapy for unresectable hepatic malignancies. Improved technology and concurrent application of RFA with other treatment modalities should continue to improve tumor response and patient survival for patients with unresectable hepatic malignancies.     

Do depressive episodes lead to accumulation of vulnerability in the elderly?

The vulnerability-accumulation (or scarring) hypothesis postulates that the experience of depression induces a lasting increase in vulnerability, and through this raises the risk of recurrence. We examined the validity of the vulnerability-accumulation model for depressive episodes in later life. The sample comprised 26 elderly persons who had remitted from a depressive episode and 96 control respondents who were all selected from the participants of a large community survey among persons aged 57 years or more. Several psychosocial vulnerability indicators were assessed premorbidly, during the depressive episode and after remission. High levels of psychological distress, low life satisfaction, chronic somatic diseases, high neuroticism, and low scores on extraversion, mastery, and self-efficacy appeared to be predictors of depression in this sample. During the depressive episode, psychological distress was higher and life satisfaction, physical, role, and social functioning, as well as feelings of self-efficacy lower than before the episode. Physical and role functioning, cognitive function, and self-efficacy were lower after remission compared to premorbid levels, but (other) personality indices had not changed after remission compared to premorbid levels. Furthermore, we failed to find differences between first and recurrent episodes. Support for the vulnerability-accumulation model was limited at the most. Although psychosocial scarring may occur in the elderly, our findings tentatively suggest that this accumulation does not manifest itself in major vulnerability indicators such as neuroticism.     

Who are patients on conventional antipsychotics?

The advent of atypical antipsychotics presented psychiatrists with an effective way of treating psychosis without the many side effects associated with conventional agents. Given the superiority of atypical antipsychotics, we examined demographic information and treatment histories of patients currently treated with conventional antipsychotics, especially in regard to treatment with atypical agents. Medication histories and demographic information for 276 patients admitted to an urban hospital were obtained by patient/family interviews and review of medical records. Chi-square and logistic regression tests were used to analyze data for possible predictive factors of which patients within the sample were still receiving conventional antipsychotics for treatment. Seventy-eight (28%) patients were currently being treated with conventional antipsychotics. More than half of them had never received a trial of an atypical agent. African-Americans, who are more likely to suffer adverse effects from conventional antipsychotics, and substance abusers were overrepresented in this group. It is unclear to what extent ethnic or cultural bias played a role in determining medication choice. Because conventional antipsychotics are associated with more side effects and greater medication nonadherence, these patients should be evaluated for appropriateness of a trial with an atypical agent even if they are currently stable with a conventional antipsychotic.     

Communication and the hearing-impaired patient

Hearing impairment affects significant numbers of the people who are most likely to use healthcare services. Nursing skills in this area still fall short of acceptable standards. Awareness of the scale of the problem, identification of those affected and knowledge of how best to communicate with them are crucial to providing sensitive and individualized care.     

Whole grain intake is associated with lower body mass and greater insulin sensitivity among adolescents

The authors tested the hypothesis that consumption of whole grain is associated with greater insulin sensitivity and lower body mass index (BMI) (weight (kg)/height (m)(2)) in adolescents and that this association is stronger among the heaviest adolescents. Two 127-item food frequency questionnaires were administered at the mean ages of 13 years (standard deviation 1.2) and 15 years (standard deviation 1.3) to 285 Minnesota adolescents who underwent two euglycemic insulin clamp studies 2 years apart as part of a protocol evaluating the influence of insulin resistance on development of adverse cardiovascular disease risk factors. Intake of whole grain was examined for associations with BMI and insulin sensitivity (measured as milligrams of glucose uptake per kilogram of lean body mass (M(lbm)) per minute). After adjustment for age, gender, race, Tanner stage, and energy intake, mean BMI was 23.6 for adolescents consuming less than serving/day of whole-grain foods, 22.6 for -1 servings/day, and 21.9 for more than 1 servings/day (p = 0.05). After adjustment for age, gender, race, Tanner stage, energy intake, BMI, and physical activity, M(lbm) was 11.6, 12.3, and 13.2 mg/kg/minute, respectively, in the three whole grain intake groups (p = 0.02). This relation was stronger among adolescents with higher BMIs (p = 0.001). Whole grain intake was associated with greater insulin sensitivity and lower BMI in adolescents, especially among the heaviest persons.     

Hearing aids versus ventilation tubes in persistent otitis media with effusion: a survey of clinical practice

A postal survey was carried out to determine the current clinical practice amongst consultant otolaryngologists in the UK, regarding re-insertion of ventilation tubes or recommendation of hearing aids in cases of recurrence of otitis media with effusion (OME) after ventilation tube extrusion. Amongst the 319 respondents, 15 (4.70 per cent) routinely, 146 (45.77 per cent) sometimes, and 158 (49.53 per cent) either never, or very rarely, recommend hearing aids. Hearing aids and ventilation tubes were both suggested to be equally good options by some consultants but they preferred surgery for a number of reasons. There were inconsistencies in practice and some of the reasons for re-inserting ventilation tubes are not evidence-based. A hearing aid is a non-invasive option and this survey shows a need for a randomized control trial of hearing aids and ventilation tubes in the management of persistent and recurrent OME.     

Effect of Moisture on the Stability of a Lyophilized Humanized Monoclonal Antibody Formulation

Purpose. To determine the effect of moisture and the role of the glass transition temperature (T_g) on the stability of a high concentration, lyophilized, monoclonal antibody. Methods. A humanized monoclonal antibody was lyophilized in a sucrose/histidine/polysorbate 20 formulation. Residual moistures were from 1 to 8%. T_g values were measured by modulated DSC. Vials were stored at temperatures from 5 to 50°C for 6 or 12 months. Aggregation was monitored by size exclusion chromatography and Asp isomerization by hydrophobic interaction chromatography. Changes in secondary structure were monitored by Fourier transform infrared (FTIR). Results. T_g values varied from 80°C at 1% moisture to 25°C at 8% moisture. There was no cake collapse and were no differences in the secondary structure by FTIR. All formulations were stable at 5°C. High moisture cakes had higher aggregation rates than drier samples if stored above their T_g values. Intermediate moisture vials were more stable to aggregation than dry vials. High moisture samples had increased rates of Asp isomerization at elevated temperatures both above and below their T_g values. Chemical and physical degradation pathways followed Arrhenius kinetics during storage in the glassy state. Only Asp isomerization followed the Arrhenius model above the T_g value. Both chemical and physical stability at T T_g were fitted to Williams-Landel-Ferry (WLF) kinetics. The WLF constants were dependent on the nature of the degradation system and were not characteristic of the solid system. Conclusion. High moisture levels decreased chemical stability of the formulation regardless of whether the protein was in a glassy or rubbery state. In contrast, physical stability was not compromised, and may even be enhanced, by increasing residual moisture if storage is below the T_g value.