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To explore the potential usefulness of a strategy of hospital-based pneumococcal immunization, we studied a population-based linked record of hospital discharges for Medicare enrollees living in the Shenandoah region of Virginia. A retrospective study of 1633 persons discharged with pneumonia in 1983 showed that 61% to 62% had been discharged within the previous 4 years. Among these patients, 87% had had one or more high-risk conditions recognized during previous hospital admissions. A cohort study demonstrated that discharged patients had a 6% to 9% probability of readmission with pneumonia within 5 years. Each such readmission could be prevented by immunizing few (approximately 100) discharged patients with pneumococcal vaccine. Furthermore, the costs of vaccination would be approximately one-third the costs of hospital care for unvaccinated discharged patients readmitted with pneumonia. These results provide an epidemiologic rationale for current recommendations that elderly patients discharged from hospitals should be immunized with pneumococcal vaccine. [ABSTRACT FROM AUTHOR]

Objective: To establish the prevalence of reliable self-monitored blood glucose (r-SMBG) data at office visits for diabetes and to determine whether r-SMBG is associated with changes in glycemic control and other clinical parameters., Methods: We conducted a chart review of 500 patients followed in an Endocrinology Faculty/Commercial Insurance Practice (FP) or a Managed Medicare/Medicaid Diabetes Clinic (MDC). Follow-up visits for patients with type 1 or type 2 diabetes from January 1, 2012 to June 30, 2012 were analyzed for anthropometric data, creatinine (Cr), glomerular filtration rate (GFR), low-density lipoprotein cholesterol (LDL-C), medications, hemoglobin A1C (A1C), change in A1C from the previous visit (ΔA1C), and availability of r-SMBG data at the visit., Results: Our sample was composed of 215 MDC patients (43%) and 285 FP patients (57%). Overall, 151 patients (30%) provided r-SMBG data at their visit, with no difference between MDC or FP patients. Mean A1C at MDC was 9.1%, while mean A1C at FP was 7.9% (P<.001). MDC patients with A1C >8.0% demonstrated an A1C reduction of 1.2% if they provided r-SMBG, compared to an increase of 0.1% for MDC patients who did not (P<.05). Providing r-SMBG did not affect A1C in FP patients in any A1C range., Conclusion: Only a minority of diabetes patients, mostly insulin-treated, made r-SMBG data available to their providers. Insulin-requiring Managed Medicare/Medicaid patients with poorly controlled diabetes had an A1c reduction associated with r-SMBG. Prospective studies are needed to determine whether this patient population may be more likely to benefit from r-SMBG at their visits.

Objective: To assess the clinical effectiveness of influenza vaccination in preventing influenza-associated hospitalization and death., Design: Case-control study., Setting and Patients: Noninstitutionalized persons aged 45 years or older living in Manitoba, on December 1, 1982, and December 1, 1985., Methods: Linked records of the Manitoba population registry, hospital-discharge abstracts, physician claims for ambulatory-patient visits and influenza vaccination, and vital statistics were used. A matched-set analysis estimated the clinical effectiveness of influenza vaccination in preventing hospital admissions and deaths from influenza-associated conditions during influenza A (H3N2) outbreak periods in 1982 to 1983 (12 weeks) and 1985 to 1986 (10 weeks). The analysis adjusted for hospital discharge and ambulatory care for high-risk conditions within the previous 15 months and 3 months, respectively., Results: Influenza vaccination prevented 32% to 39% of hospital admissions with pneumonia and influenza and 15% to 34% of admissions with all respiratory conditions. Vaccination was 43% to 65% effective in preventing hospital deaths with these conditions (all listed diagnoses) and 27% to 30% effective in preventing deaths from all causes., Conclusion: Influenza vaccination has substantial clinical effectiveness in preventing hospital admission and death from influenza-associated conditions in noninstitutionalized individuals.

Pancreas transplantation has been proven effective in supplying an endogenous insulin supply in diabetics. However, alterations in glucose metabolism after transplantation suggest a possible "insensitivity" to its action in the periphery. We hypothesized that sulfonylurea treatment of canines who had received segmental pancreas autotransplants would correct these alterations by altering peripheral insulin sensitivity. Glipizide therapy (5 mg p.o. b.i.d.) did appear, in fact, to enhance basal insulin sensitivity by lowering fasting glucose (100 +/- 3 to 81 +/- 11 mg/dl pre-treatment to post-treatment) while not affecting basal insulin levels. However, glipizide therapy was associated with decreased insulin response to challenge by either oral glucose (2 gm/kg) or sustained intravenous hyperglycemia (150 mg/dl above basal). We conclude that our model of pancreas autotransplantation documents alterations in glucose metabolism which are devoid of the effect of immunosuppression. Glipizide treatment appears to affect fasting sensitivity to insulin, but results in a decrement of insulin response to oral or intravenous glucose challenge.

Objective: To determine what proportion of patients who have poor health perceptions are physically healthy and to explore why some patients perceive a healthy state while others perceive illness., Design: A prospective consecutive series of office patients completed the Rand Corporation's General Health Perceptions Questionnaire, and their physicians rated their physical health. Their use of health care services was determined for the following 12 months., Setting: A rural teaching office practice., Patients: Of 243 adult patients asked to complete the questionnaire, 32 were excluded, for dementia (8), illiteracy (4), illness (8), incomplete questionnaires (6), and other reasons (6). 208 patients (86%) formed the final study group., Measurements and Main Results: 62 of 208 patients had poor health perception scores. 39 of the 62 were rated by physicians as physically healthy and were not statistically different in physical health ratings or numbers of prescribed medications from the 146 patients who had higher health perception scores. However, these 39 patients had significantly more health-related worry, acute pain, and depression than did the other 146 patients. They also made more office visits and telephone calls and had higher total primary care charges., Conclusions: This study suggests that 21% of adult primary care patients (39 of 208) have health perceptions lower than expected for their levels of physical health. These low health perceptions are correlated with increased emotional distress and higher utilization of health care resources. Strategies to identify these patients and interventions to improve their views of their health could reduce utilization.

Because most nosocomial infections are caused by enteric flora, it was undertaken to determine whether diarrhea predisposes to nosocomial infections by conducting a retrospective cohort study involving patients with and without nosocomial diarrhea who were hospitalized during a 12-month period. The rate of urinary tract infection per person-day after onset of diarrhea was significantly greater in patients with diarrhea (relative risk = 10.3; 95% confidence interval = 1.7-63.1, P = .006). When indwelling bladder catheter and duration of catheter placement were considered, diarrhea remained an independent risk factor for urinary tract infection in logistic regression analysis (P = .009). These data suggest that diarrhea and consequent urethral meatal contamination may be a cause of nosocomial urinary tract infection, especially in patients with a catheter, and that removal of the catheter should be considered whenever possible in patients with diarrhea.

To investigate the role of testosterone (T) in the pubertal elevation of somatomedin-C (SmC), six prepubertal GH-deficient boys were each given 7-day courses of GH alone (0.05 U/kg X day, im), T alone (T propionate; 25 mg/day, im), and a combination of GH and T at the same dosages. Plasma SmC levels were determined on samples drawn at the start and finish of each period, and each course was separated by a 7-day period. SmC was also measured before and after a course of T propionate (25 mg/day, im) in four GH-sufficient boys with delayed adolescence. In the GH-deficient boys, GH and the combination of GH and T resulted in comparable and significant increments of SmC (mean change, 0.68 U/ml after GH and 0.63 U/ml after the combination of GH and T). T alone caused no change in SmC in the GH-deficient boys (mean change, 0.09 U/ml), but resulted in increases in all four GH-sufficient subjects (mean change, 1.29 U/ml). In a single subject with constitutionally delayed puberty, the integrated 24-h GH concentration rose from 2.8 ng/ml before to 5.8 ng/ml after T therapy. Both the number and amplitude of GH secretory events were greater after therapy. These data show that T stimulates SmC production in prepubertal boys who can secrete GH, but not in those who are GH deficient. We postulate that the effect of T in this regard is due to its effect on pituitary GH secretion. Although the T levels were within the pharmacological range, physiological levels of T (e.g. at puberty) may be responsible for the adolescent SmC increment in men.

We studied the dopaminergic control of lactotroph cells in the anterior pituitary of parkinsonian patients and age-matched normal subjects. The resting levels of prolactin and the TRH-induced rise in prolactin were normal in Parkinson disease. Levodopa elicited a normal suppression of prolactin concentrations in parkinsonian subjects; the major abnormality to emerge was attenuation of the response to thyrotropin-releasing hormone (TRH) in the parkinsonian patients following administration of Sinemet (levodopa plus carbidopa) or bromocriptine. These findings imply pathology of extrastriatal dopamine systems in Parkinson disease. Since the addition of carbidopa enhanced the suppression of prolactin induced by levodopa, exogenous levodopa probably acts predominantly through the formation of dopamine in the hypothalamus, but inside the blood-brain barrier, rather than as a direct effect of circulating dopamine on the anterior pituitary or areas of the hypothalamus outside the blood-brain barrier.

A total of 1,001 consecutive episodes of nosocomial pneumonia in 901 patients was identified by routine surveillance at the University of Virginia Medical Center between 1979 and 1983 (8.6 episodes/1,000 admissions). When only initial episodes were examined, 890 patients comprised the study sample. The overall case fatality rate was 30%. Stepwise logistic regression indicated that time from admission to pneumonia (p = 0.0006), age (p less than 0.0001), prior use of mechanical ventilation (p = 0.0032), and neoplastic disease (p = 0.0062) were associated with mortality. Multiple regression analysis indicated that the factors associated with increased length of hospitalization included posttracheostomy status (p = 0.0001), prior mechanical ventilation (p = 0.0001), immunosuppressive or leukopenic status (p = 0.0009), nasogastric intubation (p = 0.0003), and prior bacteremia (p = 0.0127). A sampled, individually matched cohort study (n = 74 pairs) was conducted to determine the proportion of mortality in cases that was attributable to infections (33%) and to determine excess hospital stay (seven days) among the patients with nosocomial pneumonia. Excess stay was statistically significant (p less than 0.0001), but proportional mortality was only marginally significant (p = 0.0892). Our findings suggest that nosocomial pneumonia accounts for approximately 33% of the crude mortality and contributes significantly to the economic burden associated with prolonged hospitalization.

A total of 401 cases of chronic traumatic aneurysm reported during the past 30 years plus 12 cases from the University of Virginia Medical Center were analyzed. Forty-two percent of the patients developed signs or symptoms of aneurysm expansion within 5 years of injury: 85% within 20 years. Pain was the most frequently occurring sign or symptom, followed by serial enlargement on chest roentgenogram. Of the 60 patients who were followed without operative intervention, 20 died of their aortic lesions. For these patients, the combined risk of dying or developing signs or symptoms was 41% at 5 years. Over 300 patients underwent operative repair of the aneurysm. Operative mortality was 4.6%. Bleeding was the major cause of death as well as the most common major complication. When the survival probability of patients treated operatively was compared with that of patients treated nonoperatively, the operative group demonstrated a significantly higher survival probability.

During a 71-month interval 3,024 nosocomial urinary tract infections were identified by prospective surveillance at our hospital. The annual attack rate varied between 2.0 and 3.1 per 100 admissions. Gram-negative bacilli caused 74 per cent of all urinary infections and recurrent infections in the hospital accounted for only 1 per cent. The most frequent pathogens were Escherichia coli (24 per cent), Pseudomonas aeruginosa (8 per cent), Streptococcus faecalis (7 per cent), Klebsiella pneumoniae (6 per cent) and Proteus mirabilis (6 per cent). Candida species caused 10 per cent of the infections and may represent a hospital-acquired pathogen of increasing importance. The burn unit had a significantly higher proportion of Enterobacter infections (21 per cent) than any other service (p less than 0.05). The plastic surgery service had more Serratia infections (24 per cent), whereas obstetrics and gynecology had more Escherichia coli infections (47 per cent) relative to other hospital services. More than 99 per cent of the patients with nosocomial urinary tract infections received antimicrobial drugs; in 63 per cent the chart documented that drug therapy was prescribed specifically for treatment of the urinary infections. Hospital-acquired urinary infections added approximately 1 million dollars to hospital expenses during the study interval. Estimates were made of the economic benefits of successful control programs.

Costs of treating 174 adult patients with acute leukemia were compiled and analyzed over the five-year period 1974 to 1979. The average overall cost per patient was $18,760, and increased over the period of study. Increased total hospital costs were incurred by patients who achieved a favorable response to induction chemotherapy and by those with a diagnosis of acute lymphocytic leukemia (ALL). To assess the impact of successful treatment on hospital expenditures, total months of survival were compared with total hospital costs to determine cost per month of life. Using this analysis, improved survival, favorable response to chemotherapy, and a diagnosis of ALL were associated with significant decreases in cost per month of life. The long-term survivors (alive greater than or equal to 2 years from diagnosis) best demonstrated this effect, with a mean hospital cost per month of survival from diagnosis of $563, which was significantly less than $6,937 for those who achieved a partial remission, $10,703 for those with treatment failure, and $8,240 for those who were untreated. These costs linked to outcome are comparable to those reported in other disorders that require prolonged and intensive hospital care. With the progressive improvement in response rate and in percentage of long-term survivors that is being observed in adults with acute leukemia, these costs should continue to decrease.

The effects of synthetic hpGRF-40 on GH release from continuously perifused male rat anterior pituitary cells were studied. Pulses (2.5 min) of hpGRF-40 stimulated GH release in a log-linear dose response relationship: concentrations of 0.03, 0.1, 0.3, 1, 3, 10, 30 and 100 nM given in a random order elicited a GH response above baseline of 1.2 +/- 0.3, 2.4 +/- 0.4, 2.8 +/- 0.2, 4.3 +/- 0.2, 6.2 +/- 0.7, 7.0 +/- 1.0, 8.7 +/- 1.7, and 10.8 +/- 0.8 micrograms/10(7) cells (mean +/- SEM; n = 3; r = 0.93), respectively. During a 5-h hpGRF-40 infusion, GH stimulation peaked within 5 min and waned to near baseline by the end of the fifth h. The integrated GH responses to 0.03, 0.1 and 0.3 nM hpGRF-40 were 37.6 +/- 7.4, 52.9 +/- 8.5, and 66.15 +/- 8.2 micrograms/10(7) (mean +/- SEM; n = 3; r = 0.72), respectively. The interaction of TRH and hpGRF-40 in the control of GH secretion was studied to investigate the mechanism of the "paradoxical" TRH stimulation of GH release associated with GH excess states in humans. Dispersed cells were perifused with either 100 nM TRH for 0.5 h, 5 nM hpGRF-40 for 4 h, or 5 nM hpGRF-40 for 4 h, to which a 0.5 h pulse of TRH was added at 2 h. GH levels did not change significantly in the presence of TRH alone. When TRH was added to the ongoing hpGRF-40 perifusion, GH release increased from 1.4 +/- 0.06 to 4.0 +/- 1.0 micrograms/min.10(7) cells (n = 4; P = 0.03). Thus, dispersed pituitary cells are highly sensitive to very low concentrations of hpGRF-40 administered as both an acute pulse and as a tonic infusion. When the cells are exposed to a maximal concentration of hpGRF-40 (i.e. 5 nM), TRH becomes a secretagogue at the pituitary level, thus suggesting the site and mechanism of the "paradoxical" GH response to TRH observed in some acromegalics.

The design of investigations of hospital infections often will make a difference between results that are useful and results that only appear to be. The importance of study design and dimensions cannot be overemphasized. Much has been written about methods of research. Most universities and many large hospitals have persons trained in research design and analysis. The more that investigators of nosocomial infections talk with and collaborate with persons who have such training, the more accurate and more productive their research is likely to be.

To test the hypothesis that the rise in arterial pressure occurring with maturation is due to an increase in the vascular responsiveness to angiotensin II, sequential cumulative doses of angiotensin II were infused intravenously into chronically catheterized newborn lambs maintained on a constant, weight-adjusted sodium intake from birth to 8 weeks of age. Basal mean arterial pressure correlated with both age and weight, but age was a stronger determinant of mean arterial pressure than was weight. No change in the mean arterial pressure response to angiotensin II occurred with maturation. Basal plasma renin activity and plasma aldosterone concentrations were low and did not change significantly with age. Therefore, in the newborn lamb in the sodium replete state, age is a better determinant of arterial pressure than is weight. However, an age-related change in vasoconstrictor responsiveness to angiotensin II does not occur and, therefore, cannot account for the rise in arterial pressure that is observed with maturation.

Pergolide mesylate is a synthetic ergoline with dopamine agonist properties. The endocrine profile was studied in a double blind crossover design in six normal males. Circulating PRL, TSH, GH, LH, FSH, and cortisol were measured in the basal state and after TRH (500 micrograms iv) administration at 4.5, 11.5, and 23.5 h after placebo or pergolide (100 micrograms orally). Pergolide caused suppression of basal PRL from 2-8 ng/ml to less than 2 ng/ml commencing 60 min after administration and persisting throughout the 23.5-h study period. For the three TRH tests, a suppression of peak PRL (mean +/- SEM) response to TRH of 54.6 +/- 5.1 vs. 1.9 +/- 0.5, 45.2 +/- 4.1 vs. 4.5 +2- 0.6, and 34.4 +/- 2.9 vs. 6.9 +/- 1.4 ng/ml, respectively, for placebo and pergolide was noted. Basal TSH levels were unaffected by pergolide, but after pergolide the peak TSH response to the first two TRH challenges was blunted (placebo vs. pergolide: 12.3 +/- 1.2 vs. 6.8 +/- 1.0 and 14.8 +/- 2.0 vs. 9.6 +/- 1.0, respectively); however, the third TSH response (9.8 +/- 1.1 vs. 9.3 +/- 1.2) was not blunted after pergolide. GH secretion was stimulated by pergolide with a consistent pulse observed within 60 min of pergolide administration and an enhancement in the number and amplitude of subsequent GH pulses throughout the 24-h period. Cortisol levels rose after pergolide and returned to levels seen on the control day at 16.5 h. FSH levels were unaffected but LH levels were lowered pergolide. Side effects including nausea, vomiting, and hypotension were observed in all subjects. Pergolide is a potent dopamine agonist with the anticipated endocrine profile and clinical effects; its long duration of actions offers promise of single daily dose therapy for hyperprolactinemia.

The merit of carotid endarterectomy for patients who previously have sustained a completed stroke remains controversial. Between January 1976 and December 1983, 118 stroke patients with mild to severe permanent neurologic deficits were evaluated. Fifty-nine patients were managed nonoperatively and 59 operatively. Both cohorts were similar in age and sex distribution, incidence of hypertension (69%), diabetes mellitus (25%), and cardiac disease (39%). In the long-term follow-up (medical cohort average was 44.1 +/- 5.0 months; surgical cohort average, 41.8 +/- 3.7 months) the overall survival rate was comparable, that is, there were nine medical deaths and eight surgical deaths. However, there was a significant difference in the development of new neurologic deficits. Twelve of the 59 unoperated patients had new neurologic deficits and three patients died at 12, 36, and 48 months as a result of a recurrent stroke. New neurologic deficits developed in only two of the 59 surgical patients and there were no stroke-related deaths. When the cumulative probability of remaining free from recurrent deficits was examined in the surviving patients at 6 years, all of the patients in the operated group remained free from recurrent deficits, whereas only 58% of the patients in the unoperated group were free of new neurologic deficits (p = 0.02). These data suggest that stroke patients with fixed mild to moderate neurologic deficits and with carotid lesions may be protected from recurrent neurologic complications by carotid endarterectomy.

Two six-month randomized, controlled double-blind trials of the efficacy of virucidal nasal tissues in the prevention of natural colds were conducted in Charlottesville, Virginia, between 1983 and 1986. Tissues impregnated with malic and citric acids and sodium lauryl sulfate were used in both trials. Placebo tissues contained saccharin in the first trial and a mixture including succinic acid in the second. A total of 186 families were evaluable after completion of trial I, and 98 families were evaluable in trial II. The antiviral tissues were associated with 14 and 5% relative reductions in the overall rate of colds in the first and second trials, respectively. In the first study, this appeared to be due to an appropriate fall in secondary illnesses with a relative reduction in the ratio of secondary to primary illnesses of 32%. In trial II, however, the small and statistically insignificant reduction was primarily due to a drop in the rate of primary illness (which cannot be attributed to tissue efficacy), and the ratio of secondary to primary illness was actually 5% higher in the group with active tissues than in the placebo group. We conclude that when rigorously used in a study protocol, virucidal tissues may offer a modest reduction of secondary colds in the home, but for reasons currently unknown, do not have a major effect on the overall rate of colds.

A growth-hormone-releasing factor has been characterised and sequenced from a pancreatic tumour removed from a patient with acromegaly. It is a 40-residue linear peptide. Synthetic human pancreatic growth-hormone-releasing factor (hpGRF-40), 1 microgram/kg bodyweight, was administered as an intravenous bolus to six healthy men. hpGRF-40 selectively stimulated growth-hormone secretion. Serum growth-hormone concentrations were increased within 5 min, reaching a peak between 30 and 60 min (20 . 4 +/- 6 . 5 ng/ml compared with 2 . 1 +/- 0 . 1 ng/ml after placebo). Serum levels of prolactin, thyrotropin, luteinising hormone, and corticotropin (measured indirectly through plasma cortisol) were not increased after administration of hpGRF-40. Similarly, the concentrations of blood glucose, plasma insulin, glucagon, pancreatic polypeptide, cholecystokinin, gastrin, gastric inhibitory peptide, motilin, and somatostatin were unaffected by hpGRF-40. There were no changes in blood pressure, pulse rate, or body temperature, and no side-effects were noted. The characteristics of this peptide fulfil many of the criteria required of the hypophysiotropic growth-hormone-releasing hormone. hpGRF holds promise for a new approach to the diagnosis and treatment of various disorders of growth-hormone secretion.

We used a statewide program for the surveillance and reporting of infections acquired in the hospital to examine the relation between volume of surgery and the incidence of postoperative wound infection. Over a 29-month period 25,941 surgical procedures performed at 22 hospitals were studied. For all procedures studied, the mean number of operations performed was directly related to hospital size (number of beds). A highly significant inverse relation was found between the logarithm of the frequency of operation and the infection rate for appendectomy, herniorrhaphy, cholecystectomy, colon resection, and abdominal hysterectomy. (The relation was borderline [P = 0.055] for laminectomy and not significant for cesarean section.) Although these data clearly demonstrate higher morbidity in hospitals performing relatively little surgery, there are several possible explanations, and no conclusions for health policy can yet be drawn.

Nine patients (seven men and two women, mean age 36.3 +/- SD 6.7 years), six of whom had schizophrenic disorders, two of whom had bipolar disorder (manic-depressive illness), and one of whom had schizoaffective disorder, manifested psychosis, intermittent hyponatremia, and polydipsia (PIP syndrome). Their stable pattern of hyposthenuria allowed us to predict 24-hr urinary volume on the basis of estimated daily urinary creatinine and early morning urinary creatinine concentration. Lithium and carbamazepine (Tegretol) had little, if any, effect on polyuria. Correlations of parameters of urinary excretion with serum osmolality among our nine PIP patients failed to implicate water consumption as the exclusive cause of serum hypoosmolality and attendant complications usually ascribed to "water toxicity" in the PIP syndrome. Discussed, also, is the overlap of the clinical and laboratory features of the PIP syndrome with the clinical and laboratory features of both diabetes insipidus and the syndrome of inappropriate antidiuresis.

We investigated the effects of single doses of mesulergine on basal and thyrotropin-releasing hormone (TRH)-stimulated serum levels of several anterior pituitary hormones in healthy men and defined its kinetics. We also compared the effects on serum prolactin (PRL) levels of three doses (0.1, 0.35, and 0.5 mg) of mesulergine to those in response to 2.5 mg bromocriptine. Secretory rates of PRL before the first dose of TRH were not affected by any dose of mesulergine or bromocriptine. TRH-stimulated PRL secretion was not altered by 0.1 mg mesulergine but was blunted by both the 0.35- and 0.5-mg doses at 10 A.M. and 1 P.M. Bromocriptine inhibited TRH-stimulated PRL secretion at 10 A.M. and 8 P.M. When analyzed as the 8 A.M. to 8 P.M. and the 8 P.M. to 9 A.M. (day 2) intervals, PRL secretion was not changed by 0.1 or 0.35 mg mesulergine but was suppressed during both periods by the 0.5-mg dose. A dose-response relationship was evident, however, between mesulergine and PRL secretion during both the 8 A.M. to 8 P.M. (R2 = 0.27) and the 8 P.M. to 9 A.M. (day 2; R2 = 0.18) intervals. Bromocriptine lowered PRL secretion during both intervals. Secretory rates of growth hormone during these intervals were not affected by 0.1 mg or 0.35 mg mesulergine but were increased during both intervals by the 0.5-mg dose. Neither the secretory rates of thyrotropin in response to TRH nor those of cortisol, luteinizing hormone, or follicle-stimulating hormone were changed by 0.1 or 0.35 mg mesulergine.(ABSTRACT TRUNCATED AT 250 WORDS)

After initial challenges with vehicle alone and then 10 micrograms/kg human pancreatic tumor GH-releasing factor (hpGRF)-40, six adult subjects who had presented in childhood with idiopathic GH deficiency were given 0.33 micrograms/kg hpGRF-40, iv, every 3 h for 5 days. Serum GH levels were monitored daily for 90 min after the 0800 h doses of 0.33 micrograms/kg hpGRF-40, and serum somatomedin C was measured at 0800 and 2000 h. In addition, plasma levels of cholesterol, high density lipoprotein cholesterol, and triglycerides were measured daily at 0800 h. Three hours after the last 0.33 micrograms/kg dose, all subjects were rechallenged with 10 micrograms/kg hpGRF-40. In response to the initial 10 micrograms/kg challenge with hpGRF-40, and although serum GH levels rose in two of six subjects, the mean maximum GH level achieved was no different from that after treatment with vehicle alone. Within 12 h after initiation of the intermittent administration of hpGRF-40, mean +/- SEM serum somatomedin C had risen by 0.1 +/- 0.05 U/ml, and at the end of the 5-day period, had increased from 0.24 +/- 0.07 to 0.78 +/- 0.32 U/ml. In response to the second challenge with 10 micrograms/kg hpGRF-40, serum GH levels rose in three of the four subjects who initially failed to respond or had a less than 1 ng/ml GH response. The increase in serum GH was greater in one of the two subjects who had responded to the first dose. In addition, unlike the first dose, the mean maximal serum GH level achieved in response to the second 10 micrograms/kg dose of hpGRF-40 was higher than that in response to vehicle (P = 0.031). Although there was no statistically significant change during the 5-day period, in plasma cholesterol, high density lipoprotein cholesterol, or triglycerides, the latter exhibited a trend toward increased levels. Our preliminary data show that 5 days of intermittent hpGRF-40 administration augment GH secretion in some adults with GH deficiency, suggesting that somatotropes are present in idiopathic GH deficiency and may be primed by hpGRF-40. The rise in serum somatomedin C to normal levels after multiple injections of hpGRF-40 is encouraging, since circulating levels of somatomedin C may be more important than the increase in immunoreactive GH levels as an index of response for induction of linear growth. The demonstration of biological effects of hpGRF-40 in all six subjects without any serious adverse effects suggests that hpGRF-40 has promise in the treatment of GH deficiency.

From these data and data from the literature, our recommended treatment for well-differentiated cancer is as follows: For papillary cancer, resection should be adequate to encompass the entire tumor, which in most cases would be complete lobectomy and possibly isthmusectomy. Prophylactic neck dissection is of no value; therapeutic modified neck dissection should be done for stage II disease. Follicular cancer can be treated by lobectomy (for small lesions) or subtotal thyroidectomy. Although total or near-total thyroidectomy may be required in selected patients with large primary cancers or in those with extensive capsular invasion or extrathyroid extension, the number of cases indicating this is small. There were only a few such patients with large primaries requiring total thyroidectomy in this study. Total thyroidectomy is best avoided in most cases, considering the price of hypoparathyroidism and the lack of significant improvement in survival compared with lesser ablative techniques. Postoperative ablation with iodine-131 did not improve survival in staged patients with papillary cancer (the number of patients with follicular cancer was too small for analysis). Postoperative thyroid suppression by exogenous thyroid hormone postoperatively appeared to improve survival. Although the data were not adequate for evaluation in follicular cancer, there seems to be no reason not to use this postoperatively in high-risk patients with either papillary or follicular cancer.

Glycopyrrolate, a quaternary ammonium anticholinergic compound is a potentially useful bronchodilator. To determine the efficacy, optimal dose, and duration of action of inhaled glycopyrrolate, we gave the drug to 11 asthmatic patients. Each subject received placebo or glycopyrrolate (100, 200, 600, or 1,200 micrograms) by inhalation in a double-blind, randomized, crossover design. Measurements included FEV1, FVC, heart rate, and blood pressure before administration of the drug and periodically for 12 hours. For eight hours following all doses of glycopyrrolate, both FEV1 and FVC (both as percent of predicted) were significantly greater for drug than for placebo. Glycopyrrolate may be a useful long-acting drug for the treatment of asthma.

To determine whether the plasma aldosterone response to metoclopramide, a dopamine antagonist, is mediated by the autonomic nervous system in man, five healthy male volunteers were injected with metoclopramide during an infusion of either 5% dextrose in water or trimethaphan, a ganglionic blocker. Despite evidence of ganglionic blockade during the trimethaphan infusion, the aldosterone response to metoclopramide remained intact. This suggests that the aldosterone response to metoclopramide is not mediated by the autonomic nervous system in man as it appears to be in the sheep, and suggests species variation in the mechanism of this this mineralocorticoid response.

We describe a pulse-flow method of measuring static lung compliance (CL) that is sensitive to rapid transients in CL. CL is measured by blowing air at a constant flow into the mouth and lungs for 2 s and calculated by dividing airflow in 1/s by the change in transpulmonary pressure in CMH2O/s. Pulse and static inspiratory CL was measured in five normals, four obstructives, five obese, and two patients with pulmonary fibrosis, Pulse CL after tidal breathing was correlated with static CL measured after deep breaths (r = 0.96). Pulse CL after deep breaths was higher than pulse CL after tidal breathing (p less than 0.01) and then static CL after deep breaths (p less than 0.05). In all subjects the lower the forced expiratory volume in 1 s, expressed as a percentage of vital capacity (FEV1/FVC), the greater the increase in pulse CL after a deep breath will be (r = 0.93). After deep breaths pulse CL fell from maximum CL to base-line CL at a rate related to 1/t2 where t equals the time in seconds from the last deep breath. We conclude that the increase in CL after a deep breath is related to the degree of airway obstruction and that the subsequent fall in CL is related to 1/t2.

After our observation of the failure of bromocriptine to inhibit LH secretion in hyperprolactinemic women, we have investigated the effects of bromocriptine and dopamine (DA) on LH secretion in normal ovulatory women within 5 days of the midcycle LH peak. Both bromocriptine (2.5 mg, orally) and DA (4 micrograms/kg . min, iv) for 4 h lowered serum PRL levels by more than 80%. Bromocriptine was ineffective in suppressing LH secretion and, in fact, resulted in a slight but significant stimulation, while, in contrast, DA was effective in lowering circulating LH levels by approximately 30% and reducing spontaneous LH fluctuations. The dissociation of the effects of these two dopaminergic agents on LH secretion may be explained by the existence of multiple DA receptors. The slight stimulatory effect of bromocriptine might be due to a preferential presynaptic action of bromocriptine inhibiting endogenous DA secretion in the hypothalamus and thus reducing this catecholamine's tonic inhibitory influence on LH secretion.

Human pancreatic GRF (hpGRF-40; 1 microgram/kg, iv) selectively stimulates GH release in normal men (9). We now report the effects of graded doses of hpGRF-40 on GH release in 12 normal men. Mean peak increments in serum GH after vehicle and the various doses of hpGRF-40 were 1.13, 11.40, 14.60, 17.01, 14.45, and 15.60 ng/ml after vehicle and 0.1, 0.33, 1.0, 3.3, and 10 micrograms/kg hpGRF-40 (iv bolus), respectively. Peak values were observed 30-60 min after hpGRF-40 treatment. There was considerable variability of responsiveness among individual subjects, and no dose-response relationship between the doses and maximal GH values was found. However, the higher doses of 3.3 and 10.0 micrograms/kg resulted in a more prolonged and biphasic pattern of GH release. A side effect of facial flushing of less than 5-min duration occurred in 4 or 6 subjects who received 3.3 micrograms/kg and in all 5 who received 10 micrograms/kg of hpGRF-40. No changes in serum glucose, LH, TSH, PRL, plasma cortisol, or 8 enteropancreatic hormones occurred after hpGRF-40 treatment. There were small increases in serum somatomedin C levels 24 h after the administration of various doses of hpGRF-40 in 11 of 13 studies. Plasma immunoreactive GRF levels measured 5 min after injection were 0.09, 2.0, 4.9, 23.9, and 66.6 ng/ml after 0.1, 0.33, 1.0, 3.3, and 10 micrograms/kg hpGRF-40, respectively. Serum GH responses after insulin-induced hypoglycemia were compared to GH responses after hpGRF-40. Comparable peak GH stimulation occurred with both provocative tests. Mean +/- SEM peak GH was 20.2 +/- 1.0 ng/ml after insulin and 20.9 +/- 3.2 after hpGRF-40 treatment. hpGRF-40 selectively stimulates GH release in normal men over a dose range of 0.1-10 micrograms/kg and is an effective probe to investigate the dynamics of GH release.

Human pancreatic tumor GH-releasing factor-40 (hpGRF-40) selectively stimulates GH secretion in normal men and in some adults with GH deficiency. To study its effects in women, we administered hpGRF-40 (3.33 micrograms/kg) or an equivalent volume of vehicle as an iv bolus at 0900 h to 10 normal women during the early follicular, late follicular, and midluteal phases of the menstrual cycle. Serum concentrations of GH, PRL, LH, and FSH were measured at intervals between 0800-1100 h. Serum somatomedin-C concentrations were measured before and 24 h after the administration of vehicle of hpGRF-40. Within 1-3 min after the injection of hpGRF-40 all women described warmth localized to the head and neck and exhibited facial flushing. No changes in pulse rate or blood pressure were noted. When expressed as change from baseline and compared to control values, peak levels of serum GH (nanograms per ml; mean +/- SEM) were higher after hpGRF-40 treatment during the early follicular (5.4 +/- 3.2 vs. 34.9 +/- 8.3; control vs. test day; P = 0.011), late follicular (5.6 +/- 1.5 vs. 25.2 +/- 6.8; P = 0.014), and luteal (0.8 +/- 1.0 vs. 32.7 +/- 12.8; P = 0.033) phases of the menstrual cycle. Similarly, integrated serum GH levels (nanograms per ml/h) were higher after hpGRF-40 administration during the early follicular (0.72 vs. 16.1; P = 0.011), late follicular (0.83 vs. 9.9; P = 0.037), and luteal (-1.54 vs. 17.0; P = 0.036) phases of the cycle. When the increases in serum GH after hpGRF-40 treatment were compared among the phases of the menstrual cycle, however, no differences were found. Serum somatomedin-C values 24 h after hpGRF-40 treatment were higher than those 24 h after vehicle at all stages of the menstrual cycle. hpGRF-40 did not stimulate the release of PRL, LH, or FSH. We conclude that hpGRF-40 stimulates the release of GH, but that in response to the dose used, hpGRF-40-stimulated GH release does not vary during the menstrual cycle.

From these data and data from the literature, our recommended treatment for well-differentiated cancer is as follows: For papillary cancer, resection should be adequate to encompass the entire tumor, which in most cases would be complete lobectomy and possibly isthmusectomy. Prophylactic neck dissection is of no value; therapeutic modified neck dissection should be done for stage II disease. Follicular cancer can be treated by lobectomy (for small lesions) or subtotal thyroidectomy. Although total or near-total thyroidectomy may be required in selected patients with large primary cancers or in those with extensive capsular invasion or extrathyroid extension, the number of cases indicating this is small. There were only a few such patients with large primaries requiring total thyroidectomy in this study. Total thyroidectomy is best avoided in most cases. considering the price of hypoparathyroidism and the lack of a significant improvement in survival compared with lesser ablative techniques. Postoperative ablation with iodine-131 did not improve survival in staged patients with papillary cancer (the number of patients with follicular cancer was too small for analysis). Postoperative thyroid suppression by exogenous thyroid hormone postoperatively appeared to improve survival. Although the data were not adequate for evaluation in follicular cancer, there seems to be no reason not to use this postoperatively in high risk patients with either papillary or follicular cancer.

Ultrasonic renal volume and length measurements are easily performed in pediatric patients. Increases in volume over the normal level provide a potentially attractive method of assessing the severity and progression or regression of renal diseases. However, an analysis of data on 59 children with clinical renal disease and nephromegaly did not demonstrate any correlation with severity of the disease. We conclude that increases in renal length and volume in pediatric patients may indicate the presence of disease but not its severity.

Plasma renin activity (PRA) may be high among teenage and young adult insulin-dependent diabetic subjects. Supine PRA and stimulated PRA were therefore measured in 50 female and 50 male diabetic subjects, 13-20 years old, diagnosed before the age of 16. Fifty percent have been restudied after 4.6 +/- 0.2 (mean +/- SEM) years. Initially, 43% had high PRA (supine 4.0 +/- 0.37, stimulated 12.02 +/- 0.8 ng/ml/hr angiotensin I), 45% had normal activity (supine 2.89 +/- 0.26, stimulated 6.47 +/- 0.34 ng/ml/hr/angiotensin I), and 12% had low activity (supine 1.57 +/- 0.05, stimulated 3.09 +/- 0.08 ng/ml/hr/angiotensin I). Levels were directly associated with prepubertal duration of diabetes and were inversely associated with duration of diabetes after onset of puberty but not with total duration or patient age. Within 4.6 +/- 0.2 years the percentage of subjects with high PRA fell to 13%, and the percentage of those with low PRA rose to 35%. Initially 51% of the cohort had normal albumin excretion rates (AER) at rest and during exercise equal to or less than 10 micrograms/min/m2; 32% had elevated rates only during exercise of 39 +/- 5 micrograms/min/m2; 13% had elevated rates at rest of 41 +/- 8 micrograms/min/m2 and during exercise of 116 +/- 21 micrograms/min/m2; and 4% had clinical proteinuria at rest and during each exercise period equal to or greater than 150 micrograms/min/m2. After 5 years, 58% continued to have normal AER, or their AER improved.(ABSTRACT TRUNCATED AT 250 WORDS)

A retrospective cohort study of 97 patients identified by prospective hospital-wide surveillance was conducted to determine the length of hospital stay and mortality attributed to hospital-acquired enterococcal bacteremia. The mean duration of hospitalization for cases was 83 days compared with 44 days for matched controls (p = 0.0001). The mortality rate during the study period was 43% among cases and 12% in matched controls (p less than 0.001). Thus the mortality rate attributable to enterococcal bacteremia was 31% and the risk ratio was 4.75. Stepwise discriminant function analysis indicated that the use of vascular catheters and renal dialysis and the presence of immune deficiency were predictors of fatal outcome in cases. Enterococcal bacteremia has become a prominent nosocomial pathogen and is associated with mortality rates well above those expected from the underlying disease.

The effect of the opioid antagonist, naloxone, on recovery of serum glucose concentrations from insulin-induced (0.1 U/kg) hypoglycemia was determined in five normal adult men. Each subject was studied on 2 separate days, at least 2 weeks apart, during an infusion of either normal saline (6.5 ml/h) or naloxone (0.8 mg/h). The order of the infusions was randomized and double blinded. Although glucose recovery was complete by 120 min after insulin administration during each study, the fractional rate of glucose recovery as determined by analysis of covariance was significantly slower during the naloxone infusions (P = 0.008). Plasma glucagon, serum cortisol, and serum GH concentrations were not different during glucose recovery on either study day. These studies suggest that endogenous opioids contribute to glucose recovery from insulin-induced hypoglycemia and therefore may be important to glucose homeostasis in normal man.

This study was designed to determine the effects of dopaminergic receptor stimulation on basal and stimulated catecholamine release in man. Five normal white male volunteer subjects were studied in metabolic balance at constant 150-meq sodium, 60-meq potassium intake and then daily for 8 days on an isocaloric constant diet of 10 meq sodium and 60 meq potassium/day in each of two separate protocols. In one protocol, the subjects received the dopamine agonist bromocriptine for 14 days before and during the study; in the other protocol, placebo was substituted for bromocriptine. During normal sodium intake, bromocriptine suppressed supine plasma norepinephrine concentrations from 193 +/- 10 to 159 +/- 9 pg/ml (P = 0.01). Dietary sodium depletion increased supine plasma norepinephrine concentrations in subjects taking placebo from 193 +/- 10 to 229 +/- 10 pg/ml (P less than 0.001). Bromocriptine prevented the supine plasma norepinephrine response to sodium depletion. After discontinuation of bromocriptine treatment, supine plasma norepinephrine concentrations returned to placebo control values. Upright posture stimulated an increase in plasma norepinephrine concentrations from 193 +/- 10 to 419 +/- 30 pg/ml (P = 0.0001) during normal sodium intake, and bromocriptine suppressed this response from 419 +/- 30 to 286 +/- 29 pg/ml (P = 0.004). Dietary sodium depletion enhanced the plasma norepinephrine response to upright posture, and bromocriptine markedly suppressed this enhancement. After discontinuation of bromocriptine treatment, supine and upright plasma norepinephrine concentrations returned to placebo control values. Bromocriptine induced a parallel downward shift in the inverse hyperbolic relationship between the plasma norepinephrine concentration and urinary sodium excretion in erect subjects, and decreased overnight urinary norepinephrine excretion in supine subjects from 1.1 +/- 0.1 to 0.6 +/- 0.1 ng/h (P = 0.0002). No consistent effects of bromocriptine on plasma epinephrine or dopamine concentrations were observed. The results of this study strongly suggest an inhibitory action of dopamine receptor stimulation by bromocriptine on basal and stimulated norepinephrine output at noradrenergic nerve terminals in the central nervous system and/or the periphery.