Victoria C. Musey

Long-Term Effect of a First Pregnancy on the Secretion of Prolactin

An early first pregnancy is known to protect against subsequent breast cancer. We speculated that this effect may be mediated by a long-term depression of prolactin secretion after pregnancy. We therefore measured basal and post-stimulation serum levels of prolactin, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in two groups--15 women 18 to 23 years of age and 9 women 29 to 40--before and after a first full-term pregnancy, and in 40 appropriate nulliparous controls. We observed no significant change in basal levels of serum LH or FSH or in the levels stimulated by gonadotropin-releasing hormone in any group. A significant decrease was seen, however, in basal and perphenazine-stimulated levels of prolactin after pregnancy in both the younger and older first-pregnancy groups but not in the controls. In a separate cross-sectional study, we compared basal serum prolactin levels in 29 parous and 19 nulliparous women of similar age. The serum prolactin levels were significantly lower in the parous group but were not related to the number of pregnancies (one to three) or the time elapsed (12 to 150 months) since the last delivery. We conclude that a first pregnancy leads to a long-term decrease in serum prolactin secretion, lasting at least 12 to 13 years.

Diabetes in Urban African-Americans. I. Cessation of Insulin Therapy Is the Major Precipitating Cause of Diabetic Ketoacidosis

OBJECTIVE To identify the causes of diabetic ketoacidosis (DKA) in a large urban hospital. RESEARCH DESIGN AND METHODS Consecutive patients admitted during a 3-month period with a primary diagnosis of DKA and who had moderate-to-severe illness as shown by serum glucose >13.9 mmol/l (>250 mg/dl), bicarbonate <15 mmol/l, and pH <7.35 were studied. Diabetes nurse educators interviewed patients and reviewed their medical records for the following: precipitating causes of DKA; content of previous diabetes education; frequency of blood glucose monitoring; recognition of symptoms of metabolic decompensation; and types of medical assistance obtained once patients were ill. RESULTS There were 56 episodes of DKA, and 75% of the episodes were in patients with known diabetes. In the known diabetic patients, the most common cause of DKA was stopping insulin therapy, which occurred in 67% of episodes. Half of the patients (50%) stopped insulin because of reported lack of money to buy insulin from an outside pharmacy or get transportation to the hospital; 21% stopped insulin because of lack of appetite; 14% stopped insulin because of behavioral or psychological reasons; and 14% did so because they did not know how to manage diabetes on sick days. Of the known diabetic patients, >80% recalled having been instructed as to blood glucose testing and acute and chronic complications, but fewer patients recalled having been instructed as to insulin dose adjustment (28%) or sick day management (35%). Symptoms of decompensated diabetes were recognized in 55% of the 42 episodes of DKA in patients with known diabetes. However, only 5% of patients contacted the Diabetes Unit when they became ill; the majority (95%) went directly to the emergency room. CONCLUSIONS DKA occurred most often in patients with known diabetes who stopped insulin therapy because of reported lack of money for purchasing insulin or for transportation to the hospital and limited self-care skills in diabetes management. In urban African-American populations, up to two-thirds of the episodes of DKA may be preventable by improving patient education and access to care.

Diabetes in Urban African-Americans. IX. Provider Adherence to Management Protocols

OBJECTIVE Staged diabetes management should permit glycemic goals to be attained in a timely manner, but the success of such an approach requires conformity by health care providers. To test performance, we analyzed the adherence of practitioners to a protocol for staged management of NIDDM patients. RESEARCH DESIGN AND METHODS Records of patients treated at the Grady Memorial Hospital Diabetes Clinic were reviewed retrospectively over a 3-year period. For each patient, intensification of therapy was indicated if fasting plasma glucose was > 7.8 mmol/l and a prior HbA1c was > 7.0%. Protocols dictated a progression from dietary therapy alone to increasing dosages of sulfonylureas to increasing dosages of insulin. Patients were seen at bimonthly intervals. RESULTS During the 3-year period, 1,051 patient visits met protocol criteria for intensification. Adherence to the protocol improved significantly in the 3rd year compared with the first 2 years (30, 31, and 47% adherence in the 1st, 2nd, and 3rd years, respectively). Patients treated with diet alone were significantly less likely to have their therapy intensified than patients on sulfonylureas or insulin (intensification rates 25, 41, and 47%, respectively). In the management of patients treated with diet alone, practitioners were reluctant to intensify therapy at early visits, but were more likely to do so later, 19% of patients beyond goal range at the 2-month visit were started on pharmacological therapy vs. 28% at the 4-month visit, and 39% at the 6-month visit (P < 0.01). In contrast, there was no significant difference in the frequency of therapy intensification between early and late visits for patients on sulfonylureas or insulin. Practitioners appeared to base the decision to intensify on the fasting plasma glucose level more than on the most recent HbA1c. Age did not appear to be a significant factor in the decision to intensify. CONCLUSIONS Although staged management protocols constitute critical tools to achieve glycemic goals, the adherence of health care providers may be suboptimal. Special efforts may be needed to assure compliance.

Diabetes in urban african americans. III. Management of type II diabetes in a municipal hospital setting

OBJECTIVE Management of type II diabetes is difficult, particularly in urban populations with limited resources and access to care. To evaluate the effectiveness of structured care delivered by non-physician providers, patients were studied prospectively for 6 months in a municipal hospital diabetes clinic. DESIGN AND METHODS The population was approximately 90% African American and had median known diabetes duration of approximately 1 year, 54% had incomes below the Federal Poverty Guideline. Primary management was provided by nurse-practitioners and dietitians, and primary outcome measures were hemoglobin A1c (HbA1c), fasting plasma glucose, and changes in body weight. RESULTS Responses were analyzed in 325 new patients returning for visits at 2, 4, 6, and 12 months; metabolic profiles at presentation were similar to those of subjects who missed intervening visits. Lean patients largely continued on pharmacologic therapy and improved HbA1c from 9.4% to 7.4% at 2 months (P < 0.001), remained stable through 6 months, then rose to 7.9% at 1 year. Obese patients (71%) received dietary instruction. Weaning of pharmacologic therapy was attempted for the first 2 months, resulting in a decline of HbA1c from 9.6% to 8.0% (P < 0.001), with 70% treated with diet alone. In the obese, HbA1c continued to decrease through 6 months (7.7%). Thereafter, providers saw patients at their own discretion and intensified therapy as needed. Although by 1 year, HbA1c had risen to only 8.2%, some patients required reinstitution of pharmacologic therapy; 59% were on diet alone. While 52% lost 4 lb or more (mean 9.3) by 2 months, little additional weight was lost. Interestingly, glycemic control was improved both in those who lost > or = 8.5 lb in the first 2 months (HbA1c 9.6% to 8.1% at 12 months), and in those who gained weight (HbA1c 10.2% to 8.2%). In the obese patients using pharmacologic agents at presentation, 35% were able to discontinue oral agents or insulin by 1 year, with good glycemic control (HbA1c < 8%). For patients who were initially on diet alone, a fasting plasma glucose > 177 mg/dL predicted the need for pharmacologic therapy with 97% certainty. CONCLUSIONS In urban African American patients, nonpharmacologic management of type II diabetes substantially improves metabolic control; decreases in HbA1c are comparable in those who do and do not lose weight. Therapy managed by nonphysician providers can be an effective cornerstone of diabetes care in this socioeconomically disadvantaged population.

Prolactin and Blood Pressure Responses to Perphenazine in Human Subjects: Comparison of the Oral and Intramuscular Routes

Although several phenothiazines are known to stimulate prolactin (PRL) secretion, only chlorpromazine is in general use for this purpose in humans. However, chlorpromazine has severe sedative and hypotensive effects. Therefore, the effects of perphenazine on human PRL release and on blood pressure were evaluated. Perphenazine was administered orally (8mg) and intramuscularly (5mg and 2mg) to determine the optimal route and dose for evaluating PRL release. The postural hypotensive effect of perphenazine was evaluated with the 2mg intramuscular (IM) dose. The mean time of peak PRL response (hr ± SD) was significantly shorter (p<0.05) for the 5mg IM (1.7 ± 0.4) than the oral (4.5 ± 0.6) rout. Also, the mean ratio of peak/baseline PRL was significantly greater for the 5mg IM (8.87 ± 5.69) than the oral (5.12 ± 2.90) route. The major side-effect produced by perphenazine was drowsiness, which was moderate to severe with the 5mg IM dose. A lower IM dose (2 mg) retained PRL releasing activity, reduced drowsiness, and did not produce hypotension. For clinical testing, intramuscular perphenazine is preferred over oral perphenazine because of the shorter latency period and the higher PRL levels. Intramuscular perphenazine (2mg) is preferred to chlorpromazine since it did not produce a clinically significant hypotensive effect. This is the first report on the dynamic responses of PRL and blood pressure to intramuscular perphenazine in humans.