Role of new selective aromatase inhibitor in therapy for metastatic breast cancer in postmenopausal women.

Anastrozole offers a new option for many postmenopausal women with metastatic breast cancer who no longer respond to antiestrogen therapy. It has a lower side effect profile for weight gain and peripheral edema and equivalent efficacy to the current second-line therapy, megestrol acetate, which may improve quality of life. Due to its selectivity and lack of clinically significant effects on cortisol metabolism, it does not have the toxicity problems of other aromatase inhibiting agents such as aminoglutethimide. Long-term studies are needed to adequately evaluate the impact of this degree of estrogen suppression on cardiovascular and bone mass risk factors [12]. Cost of therapy will certainly have an impact on the choice of second-line endocrine therapy in those with limited income sources and lack of prescription coverage. In summary, there is likely to be an increased use of nonsteroidal aromatase inhibitor agents for second-line hormonal therapy of breast cancer. Due to increased length of survival, these individuals will not be seen exclusively by oncologists; their care will be shared with their primary care provider [21]. Providers must have an understanding of these agents and their potential impact on the long-term health care of the individual in order to provide knowledgeable and comprehensive care.

Randomized controlled trial of residents as gatekeepers.

BACKGROUND: Managed care advocates suggest that primary care gatekeepers may improve patient care and reduce costs. Training internal medicine residents in these gatekeeping functions has not been emphasized in most internal medicine programs. OBJECTIVE: To determine if residents could perform gatekeeper functions and if patient costs and satisfaction would be favorable. METHODS: Patients (n = 254) followed up by residents (n = 26) in continuity clinics at the Denver Veterans Affairs Medical Center in Denver, Colo, were divided into 2 groups. A control group of 128 was followed up by residents with no restrictions on appointments made for them. An intervention group of 126 patients were followed up by residents who had to approve all referrals made for their patients. A research nurse assisted with the approvals when the residents were rotating through other institutions. Utilization of resources, satisfaction with care, and health status were monitored over a 1-year period. RESULTS: A minor reduction of resource utilization was found in the intervention group, particularly in medication use. Significantly more visits were made to primary care providers in the intervention group (3.01 vs 2.59; P = .03). Patient satisfaction and health status were similar in both groups with a trend toward better satisfaction in the intervention group in some areas. CONCLUSIONS: Our study showed that residents can function as gatekeepers of highly complex patients and that satisfaction with care and utilization of resources does not suffer. Drug utilization and costs may be less when a gatekeeper exists.

Protein wasting due to acidosis of prolonged fasting.

During a total fast in obese subjects, the daily rate of nitrogen excretion undergoes only a small further decline after 2 wk, the excretion rate being about 5 g N/day. At this time, ammonium and urea each constitute about one-half of this excretion. The purpose of this study was to consider two alternative hypotheses: first, that the near plateau in nitrogen excretion represents an irreducible minimum rate of net protein breakdown in order to supply essential organs with calories in the form of glucose; second, that protein breakdown could be further reduced by minimizing the requirement to provide nitrogen for ammonium excretion during the ketoacidosis of fasting. Because ammonium excretion is largely controlled by acid-base balance, 150 mmol of sodium bicarbonate plus 60 mmol of potassium chloride were administered daily to decrease ammonium excretion in eight obese subjects who were totally fasting for more than 14 days. Urine ammonium nitrogen fell with this treatment (from 3.8 +/- 0.4 to 2.0 +/- 0.4 g N/g creatinine). In addition, there was a smaller fall in the rate of urea excretion (from 2.5 +/- 0.2 to 2.1 +/- 0.3 g N/g creatinine) together with a fall in the blood urea nitrogen. Therefore, it appears that ammonium excretion contributes to the negative nitrogen balance of a prolonged total fast, as assessed over a 3-day period of observation, is responsible for about one-third of the net lean body mass loss.

Role of acidosis in the protein wasting of fasting in the rat and the rabbit.

The purpose of these experiments was to determine if augmented renal ammoniagenesis in chronic metabolic acidosis could increase the negative nitrogen balance during prolonged fasting. To explore this question, rats and rabbits were fasted for up to 10 days because acidosis would markedly augment ammonium excretion in the rat but not in the rabbit. Since the ketoacidosis of fasting was mild in both species (less than 2 mM) and ketonuria virtually absent, a hydrochloric acid load was given to stimulate renal ammoniagenesis. Under these conditions, nitrogen balance was significantly more negative during acidosis in the rat but not in the rabbit. This increment in nitrogen excretion appeared as ammonium with no detectable difference in urea nitrogen excretion. Therefore, it appears that if more nitrogen is excreted as ammonium, net protein breakdown increases to furnish the substrate for ammoniagenesis rather than reducing the excretion of the other nitrogenous waste component urea. The implications of these findings will be discussed.

Selected aspects of the pathophysiology of metabolic acidosis in diabetes mellitus.

Metabolic acidosis with a normal anion gap results from either bicarbonate loss or a urine acidification defect. The bicarbonate loss may be via the gastrointestinal tract or the urine, or may be indirect due to excretion of the sodium and potassium as opposed to the ammonium salts of ketone body anions. Defects in urine acidification in the diabetic have several etiologies: first, hydrogen ion secretion may be decreased because of an intrinsic defect in the hydrogen ion pump (i.e., diseases of the renal medulla); second, there may be a failure to augment hydrogen ion secretion by a favorable electrical gradient (e.g., reduced mineralocorticoids); and third, there may be a failure to generate a favorable chemical gradient to augment hydrogen ion secretion (e.g., reduced urine ammonia). Reduced levels of aldosterone associated with hyporeninemia has been termed type IV RTA, and these patients have specific therapeutic needs.