Splanchnic insulin dynamics and secretion pulsatilities in abdominal obesity.

Insulin secretion, clearance dynamics, and their relationship to peripheral plasma insulin and glucose levels were monitored during three 12-h periods of overnight rest, intake of three meals, and continuous enteral feeding of mixed nutrients. The low-frequency ultradian and the high-frequency insulin secretion pulsatility characteristics during the steady-states of overnight rest and continuous enteral feeding were also examined. In abdominally obese subjects, the insulin secretion rate was consistently higher than normal by 2.3-fold. Peripheral plasma insulin levels were increased by 3.4-fold during the overnight period and by 4- to 5-fold during the two fed states. Endogenous insulin clearance was significantly reduced during feeding. Both low- and high-frequency insulin secretory pulsatilities were detected in the abdominally obese subjects. Pulse periods were within the normal range. Pulse maxima, nadirs, and absolute amplitudes were increased concomitant with the increase in insulin secretion. Ultradian relative pulse amplitudes, however, were blunted. A significantly higher pulse-to-pulse variability was observed in the abdominally obese subjects compared with normal subjects. Furthermore, a significantly higher level of interindividual variability in the nutrient-stimulated insulin secretion and in the ultradian pulse characteristics was observed. Thus in abdominal obesity, the increase in pancreatic insulin output is limited and the secretory pulsatilities are aberrant, suggesting a defect in the insulin secretory process. Diminished insulin clearance contributes to the degree of peripheral hyperinsulinemia compensating for the insulin resistance characteristic of this form of obesity.

Changes in cortical functioning with acute hypoglycemia and hyperglycemia in type I diabetes.

In this study, 18 type I (insulin-dependent) diabetic subjects aged 22-35 yr (mean age 29.3) and within 10 yr of diagnosis (mean 7.7) performed a battery of cognitive and psychomotor tasks under conditions of hypoglycemia (50 mg/dl), normoglycemia (100 mg/dl), and hyperglycemia (300 mg/dl). Blood glucose levels during testing were precisely maintained at the preselected level via a Biostator insulin/glucose-infusion system. The order of glycemic level was counterbalanced across subjects in a single-blinded design. Performance on tasks requiring visual tracking, visuomotor speed, concentration, and planning ability (pursuit rotor and trails B) were significantly impaired under conditions of hypoglycemia compared with normoglycemic levels. Visual reaction time was not significantly impaired under conditions of hypoglycemia or hyperglycemia.

Protease inhibitor combination therapies and perceptions of gay men regarding AIDS severity and the need to maintain safer sex.

BACKGROUND: Advances in the treatment of HIV disease with protease inhibitor combination therapies have been widely documented in the media. OBJECTIVES: To investigate perceptions concerning the severity of HIV/AIDS and the need to maintain safer sex practices in the light of recent HIV treatment advances. METHODS: A survey eliciting demographic characteristics, HIV serostatus and treatment information, and HIV/AIDS severity and safer sex perceptions was administered to a community sample of 379 homo-/bisexual men who reported awareness of combination therapy regimens. RESULTS: Ten per cent of all respondents agreed or strongly agreed with the statement that 'AIDS is now very nearly cured' and 13% felt that the threat of AIDS is less serious than in the past. HIV-positive men were more likely to perceive AIDS as a less serious threat or as very nearly cured. Overall, 8% of men in the sample indicated that they practice safer sex less often since new AIDS treatments came along; 18% of HIV-positive men on combination therapy regimens said they practice safer sex less frequently since treatments have advanced. Regardless of serostatus, nearly 20% of men indicated they would stop practicing safer sex if an AIDS cure was announced. CONCLUSION: It is essential to integrate behavior change counseling into HIV treatment programs and to temper optimism concerning treatment advances with recognition that the threat of HIV/AIDS remains great.

Development of an ELISA to detect anti-BP180 autoantibodies in bullous pemphigoid and herpes gestationis.

Autoantibodies associated with the subepidermal blistering disorders bullous pemphigoid and herpes gestationis react with a 180-kD transmembrane hemidesmosomal protein, designated BP180. The BP180 ectodomain is composed of a series of interrupted collagen triple helical domains. Located on one of the noncollagenous extracellular segments of this protein is an immunodominant epitope, designated MCW-1, recognized by patient autoantibodies. In this investigation we have developed an enzyme-linked immunosorbent assay system to detect antibody reactivity against the MCW-1 epitope with the use of a bacterial fusion protein containing the BP180 autoantibody-reactive site. The following sera were assayed for reactivity with this recombinant protein: bullous pemphigoid (n = 62), herpes gestationis (n = 28), endemic pemphigus foliaceus (n = 17), lupus erythematosus (n = 15), and normal human sera (n = 22). This enzyme-linked immunosorbent assay-based protocol was shown to be highly specific (98.3%) in detecting autoantibody activity in bullous pemphigoid and herpes gestationis patients. Fifty-three percent of bullous pemphigoid sera and 71% of herpes gestations sera, but none of the control sera, yielded positive results in this assay. Of the patient sera that were known to react with full-length BP180, almost all showed reactivity with the MCW-1 antigenic site of this protein. Autoantibodies detected in this assay were predominantly of the immunoglobulin G class. The results presented here lend support to the hypothesis that this well-defined antigen/antibody system may be relevant in pathogenesis.

An active focus of high prevalence of fogo selvagem on an Amerindian reservation in Brazil. Cooperative Group on Fogo Selvagem Research.

Fogo Selvagem (FS) is an autoimmune disease characterized by subcorneal vesicles and antidesmoglein-1 autoantibodies. Previous epidemiologic data have linked the onset of FS to exposure to an environmental antigen(s). This investigation describes a unique human settlement with an extraordinarily high prevalence of FS. This community is made up of Amerindians belonging to the Terena tribe, which has settled on the Limao Verde reservation in the state of Mato Grosso do Sul in Brazil. Twenty-six well-characterized FS cases have been identified within a total population of 998, yielding a prevalence of 2.6%. Seventeen of the patients (65 %) were males, and over 50% were older than 30 y of age. The incidence of the disease shows temporal periodicity, i.e., years with several cases of FS alternating with years with no cases. Over one-half of the cases occurred in genetically related family members. Another Terena reservation, the Ipegue/Taunay, located 90 km west of the Limao Verde reservation, was also evaluated as a control group. This reservation, with a population of 2203, had no recorded cases of FS. Thus, the Limao Verde reservation represents a new focus of FS in which the disease exhibits temporal, geographic, and familial clustering. These results suggest that the environmental antigen or antigens precipitating FS are endemic to the Limao Verde reservation. This reservation appears to be an ideal population for carrying out sero-epidemiologic, genetic, and environmental studies aimed at disclosing the etiology of FS.

Effects of indomethacin on myogenic contractile activation and responses to changes in O2 and CO2 in isolated feline cerebral arteries.

We used an isolated, pressurized, and perfused feline middle cerebral artery preparation to measure how changes in intraluminal pressure and alterations in O2 and CO2 affect vessel diameter and myogenic contractile activation before and after treatment with indomethacin (IND). Vessel diameters were measured over the pressure range 60-140 mm Hg. The arteries were then exposed to low O2 (50 torr) and/or high CO2 (65 torr) and diameters remeasured over the same range. Under control conditions, the arteries exhibited myogenic contractile activation. Exposure to low O2, high CO2, or a mixture of low O2/high CO2, increased vessel diameter but did not change the vessels' myogenic contractile responsiveness to changes in pressure. Arteries exposed to IND decreased in diameter but retained myogenic contractile activity. In the presence of IND, vessels dilated to both low O2 and a mixture of low O2/high CO2, but did not dilate to high CO2 alone. Under all conditions, vessels retained myogenic contractile activity. Results obtained under control conditions and low O2 confirm those of others using similar systems. Myogenic contractile activity in the presence of high CO2 or a mixture of low O2/high CO2 has not been previously reported. The dilation to low O2 but not to high CO2 in the presence of IND suggests that this drug's effects in cerebral arteries are not limited solely to inhibition of prostaglandin synthesis.

Comparison of efficacy of automatic implantable cardioverter defibrillator in patients older and younger than 65 years of age.

PURPOSE: The efficacy of the automatic implantable cardioverter defibrillator (AICD) was compared in elderly patients and younger patients with life-threatening ventricular tachyarrhythmias. Clinical characteristics, surgical complications, and long-term survival rates were compared between the two age groups. PATIENTS AND METHODS: A retrospective study was conducted of 54 elderly patients (greater than 65 years) and 79 younger patients (less than 65 years) who had had AICDs implanted for recurrent symptomatic ventricular tachycardia and/or ventricular fibrillation. RESULTS: In 85% of elderly patients and 78% of younger patients, coronary artery disease was the underlying disease (NS). The mean left ventricular ejection fraction was 31.4 +/- 14.3% in the elderly patients and 35.7 +/- 17.6% in the younger patients (NS). Concomitant myocardial revascularization was performed in 37% of elderly patients and 29% of younger patients (NS); however, only 4% of elderly patients had concomitant left ventricular resection or cryoablation, compared with 15% of younger patients (p less than 0.001). Two patients in each age group died perioperatively (4% versus 3%, NS), and no significant difference in surgical morbidity or length of hospital stay following AICD implantation was noted between the age groups. In conjunction with AICD, elderly patients more commonly received antiarrhythmic drugs, with 54% of elderly patients taking amiodarone at the time of hospital discharge compared with 29% of the younger patients (p less than 0.008). In contrast, beta-blockers were more commonly used in younger patients (16% versus 2%, p less than 0.03). At a mean follow-up of 25 months, 11 (20%) elderly patients and 16 (20%) younger patients had died. Six deaths in elderly patients and five deaths in younger patients were classified as arrhythmic deaths (NS); however, only one younger patient and three elderly patients died suddenly (NS). Calculated survival curves demonstrated similar survival rates in the two age groups with approximately 90%, 87%, and 80% of the patients alive at 1, 2, and 3 years, respectively. Theoretic survival curves calculated from appropriate AICD shocks demonstrated significantly lower survival compared with actual survival. CONCLUSION: It is concluded that AICD is a very effective treatment for life-threatening ventricular tachyarrhythmias, and this benefit applies to elderly patients as well as younger patients.

The pathophysiologic and roentgenologic effects of chest irradiation in breast carcinoma.

We studied the effects of radiation therapy on lung function in 21 patients who underwent modified radical mastectomy and radiotherapy for breast carcinoma. The patients had pulmonary function studies and chest X rays prior to radiation therapy and at six weeks, and three, six, and twelve months following radiation therapy. All pulmonary function studies showed a small but statistically significant decline within the first three months following radiation therapy. Changes in the moderate and large airways continued to occur after three months. None of the changes in pulmonary function were reversible. Radiographic changes occurred in 12 patients. These changes occurred later than the lung function changes (median time for the changes was twelve months) and were unrelated to changes in lung function.

Neurohumoral and metabolic effects of short-term dietary NaCl restriction in men. Relationship to salt-sensitivity status.

Published observations suggest that not everyone benefits from severe dietary NaCl restriction, since blood pressure responses appear heterogeneous and adverse metabolic effects may occur. We studied the cardiovascular, neurohumoral, and metabolic effects of 7 day periods of 20 v 200 mEq/day NaCl diets in 27 men. Twelve subjects were salt sensitive (SS), defined as mean intraarterial pressure (MAP, mm Hg) during high NaCl greater than or equal to 5% above MAP on low NaCl. Eleven subjects were salt resistant (SR), defined as MAP during the low NaCl phase greater than or equal to MAP during the high NaCl phase. The SR subset had a tendency to greater neurohumoral activity, assessed by changes in mean values for plasma norepinephrine (NE, P = .12) and plasma renin activity (PRA, P less than .001) on the low v high NaCl diet. In SR subjects the low v high NaCl diet also raised mean values for creatinine (P = .03), uric acid (P = .001), and low density cholesterol (LDL-C, P = .03), but not fasting insulin (P = .15). In SS subjects, the low v high NaCl diet did not raise NE (P = .35), although the PRA was greater (P = .002). Among SS subjects, mean values for uric acid (P = .005) and insulin (P = .02) were greater during the low v high NaCl phase, while creatinine (P = .15) and LDL-C (P = .67) were not different. The data suggest that severe, short-term NaCl restriction can be undesirable, especially in SR subjects, since potentially adverse neurohumoral and metabolic changes are not counterbalanced by the benefits of a lower MAP.

Effects of cholecystokinin and hydrocortisone on DNA and protein synthesis in immature rat pancreas.

To define the developmental pattern of the trophic effects of cholecystokinin octapeptide (CCK-8) and hydrocortisone on immature rat pancreas, we injected newborn rats, rats aged 4, 7, 11, 18, and 25 days and 3 months, and adult rats with CCK (5 and 10 micrograms/kg) in gelatin and hydrocortisone (10 mg/kg) for 3 days. Animals were killed, the pancreata were removed, and the concentrations of DNA and protein were measured and DNA and protein synthesis rates determined by incorporation of [3H]thymidine and [14C]leucine, respectively. These values were compared with those of saline-injected controls. DNA concentration was significantly increased over control at ages 2 days to adult by hydrocortisone and by CCK (10 micrograms/kg) in the adult. Protein concentration was increased on days 3-14 by hydrocortisone. DNA synthesis was increased by CCK and decreased by hydrocortisone at 3 months and adult. Protein synthesis was decreased by hydrocortisone at ages 3-14 days. Thus, each agent has its own developmental pattern with age on the rat pancreas.

Ontogeny of secretory function and cholecystokinin binding capacity in immature rat pancreas.

Isolated acini were prepared from the pancreas of immature rats (age less than 1 hr. - 48 hrs) in order to study the development of the secretory process. The ultrastructural integrity of the acinar cells was maintained after digestion and stimulation with secretagogues. Acini prepared from rats aged 24 - 48 hours responded to both CCK-8 and carbachol with significant increases in amylase release. Although typical biphasic dose response curves were obtained, the curves were shifted to the right by 1 - 2 log units, compared to the responses of adult acini. At ages younger than 24 hours, acini were insensitive to secretagogues but were sensitive to the calcium ionophore A23187. CCK receptors were virtually absent from membranes prepared from newborn pancreases, but binding of CCK, although small, was measurable at 12 hours and slowly increased up to 48 hours. A greater amount of binding was seen at 72 hours, which appeared constant up to 14 days. At 21 days, adult levels of binding were found. These results confirm previous studies that the rat pancreas is insensitive to secretagogues in the first 24 hours of life. After age 24 hours the secretory process is intact but less sensitive to secretory agents than the more mature pancreas. In the case of CCK, this may be due to lesser numbers of CCK receptors and/or affinity of CCK for its receptor.

Clinical utility of Wechsler Memory Scale-Revised and predicted IQ discrepancies in closed head injury.

Comparisons between Wechsler Memory Scale-Revised (WMS-R) indexes and Wechsler Adult Intelligence Scale-Revised (WAIS-R) IQ scores have been proposed to identify severity of memory deficits. However, many neurologic conditions reduce both intellectual and memory functioning, and thus, examining differences between these scores may be of little value. Closed head injured subjects who completed the WMS-R were divided into either mild injury (MI, n = 41) or moderate/severe (SI, n = 41) injury groups based on trauma severity indicators and were matched on age and level of education. The Oklahoma Premorbid Intelligence Estimation (OPIE), a regression formula that takes into account demographic variables as well as IQ performance, was calculated for each subject. Discrepancy scores were calculated between predicted IQ scores and WAIS-R IQ and WMS-R indexes. SI head-injured subjects displayed significantly larger discrepancies (19 points) between OPIE scores and Delayed Recall Indexes from the WMS-R than the MI subjects (10 points). Significantly larger percentages of subjects in the SI group displayed significant (>SD) reductions in many of the WMS-R and WAIS-R scores from estimates than subjects in the MI group. Comparing current memory functioning to estimates of premorbid intellectual ability appears to be a sensitive indicator of presence and degree of intellectual and memory dysfunction in head trauma patients. Results also provide evidence that estimates of premorbid intellectual ability can serve as estimates of premorbid memory functioning.

Cross-validation of predicted Wechsler Memory Scale-Revised scores in a normative sample of 25- to 34-year-old patients.

Equations for prorating Wechsler Memory Scale-Revised General Memory (GM) and Delayed Recall (DR) index scores ([Woodard and Axelrod, 1995]) were confirmed in the [Mittenberg et al. (1992)] normative WMS-R sample of 50 subjects between the ages of 25 and 34, and confirmed in a separate clinical sample of 30 patients with closed head injury who were age, education, and gender matched with 30 subjects from that normative sample. Predicted GM and DR index scores fell within 6 points of the obtained scores for 98% of the [Mittenberg et al. (1992)] sample and 93% to 100% of the matched head injury and normative samples, despite statistically significant differences between these groups in obtained GM, DR, and percent retention of LM I and II and VR I and II. Six points is well within the standard error of measurement of these index scores. These findings confirm the earlier cross-validation results reported by [Axelrod et al. (1996)] in a mixed sample of traumatic brain injury and other neurological insult, and suggest that this method of estimating weighted score sums for WMS-R General Memory and Delayed Recall indices may be safely used in normative samples of patients in this age range as well as neurologically compromised patients without significantly impacting index score accuracy.

Randomized study of adjuvant chemotherapy for head and neck cancer.

The ability of surgery and radiotherapy to control advanced squamous cell carcinoma of the head and neck has reached its maximal potential. We initiated a randomized, prospective, stratified study of adjuvant chemotherapy. Patients with stage II disease of the pyriform sinus and stage II and IV disease of the oral cavity, larynx, hypopharynx, oropharynx, nasopharynx, and paranasal sinuses were eligible. Patients were randomized to receive either standard therapy alone or two courses of 5-fluorouracil (B-CMF) chemotherapy prior to and two courses after the completion of standard therapy. Standard therapy consisted of preoperative irradiation followed by radical surgery. Of 133 patients with advanced disease, 83 were included in the study--43 in the chemotherapy group and 40 in the control group. Rates of residual and recurrent disease, as well as distant metastases, were similar for the two groups. The survival rates of patients without persistent disease at the end of treatment showed no significant difference for the two groups. The study has been discontinued because statistical analysis indicated that the addition of more patients would not materially increase the statistical significance of the study.

The factor structure of the MacAndrew alcoholism scale.

This study attempted to replicate the factor structure of the MacAndrew alcoholism scale using a large sample of both male (n = 1563) and female (n = 293) alcoholics and employing several methodological changes not used in past studies. Male and female factor solutions were found to be highly similar. Following adjustments for mean item differences between males and females, the overall factor structure was examined and six factors were found which were similar to past studies. However, the factors accounted for only a small portion of the MacAndrew scale item variance, scales constructed from the factors had, at best, modest internal consistency reliabilities, and it was suggested that these scales are of limited clinical use. It was concluded that the scale appears to have an insufficient item pool for uncovering more than a few dimensions of personality and behavior among alcoholics.

Effects of acute hypoxemia on responses to dopamine and dobutamine in neonatal swine.

The effects of acute hypoxemia on cardiovascular responses to dopamine (DA) and dobutamine (DB) were studied in 2-4 day (n = 21) and 13-17 day (n = 27) old swine under sodium pentobarbital anesthesia. Sequential 10-min infusions of 2, 5 and 15 mu/kg/min of DA or DB or normal saline were administered under conditions of normoxemia and repeated during hypoxemia. Data are presented as mean percent of baseline value +/- SE. During normoxemia, DA increased aortic pressure, cardiac output, heart rate, LV dP/dt max and renal resistance and decreased mesenteric resistance in both ages, while DB increased heart rate, LV dP/dt max and cardiac output in both age groups and decreased total arterial resistance and renal resistance in the youngest. Increases in LV dP/dt max were larger with DA as compared to DB (p less than 0.05) with the highest dose in younger (152 +/- 5% vs. 124 +/- 4%) and older (201 +/- 29% vs. 157 +/- 9%) animals. Hypoxemia reduced heart rate responses to DA and DB in older piglets, contractility responses to DB in older animals, aortic pressure responses to DA in all animals and renal resistance responses to DA in older animals. Hypoxemia had little or no effect on cardiac output and total arterial, mesenteric and carotid resistance responses to DA and DB. Thus, in the newborn: 1) DA is a stronger inotropic agent during normoxemia and hypoxemia while the chronotropic effects of the two drugs did not differ. 2) Changes in cardiac output with both drugs did not differ significantly during normoxemia and were not affected by hypoxemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Hospital readmission and morbidity following early newborn discharge.

To examine causes of newborn hospital readmission and morbidity related to early nursery discharge, we reviewed the charts of 664 newborns readmitted from home under the age of 15 days, between 1993 and 1995. Early discharge (ED) was defined as nursery length of stay of < or = 2 days. Morbidity related to ED: onset of symptoms within 1 day of ED; and in diseases with insidious onset: serum bilirubin level > 20 mg/dL (340 mumol/L), or dehydration following poor breastfeeding since birth. Seventeen percent of all readmitted infants had ED-related morbidity; 9% had major morbidity. Onset of symptoms prior to the age of 3 days occurred in 43% of ductal-dependent cardiac lesions, intestinal obstruction, seizures, and major infections. Morbidity was less pronounced in infants who were followed up within 2 days following ED. Specific findings related to subsequent morbidity were identified in the perinatal history of infants who were readmitted with major infections and with hyperbilirubinemia. Our findings suggest that: (1) close to half of the cases with acute-onset major morbidity can be identified within 3 days of birth, and (2) attention to the perinatal history and timely follow-up will contribute to a reduction in both morbidity and complications.

Experimental hypothermia and cold perception.

Twelve subjects clothed in flotation suits were immersed in 10 degrees C cold water and their surface temperatures at the back and groin, as well as core temperatures, were continuously monitored. Subjects were unable to reliably assess how cold they were, with the highest correlation observed between perceived temperature and actual temperature reaching only 0.51. This was felt to be partially due to the uneven distribution of surface temperatures seen in this experiment and in most cold water immersions. Rapid cooling in cold water also produced the perceptual phenomenon of "overshooting" previously observed in cold air studies, characterized by sudden temperature drops being perceived as cold sensations of greater magnitude. The results suggest that subjects who are rapidly cooled in water may have considerable difficulty separating feelings of cold from feelings of pain and discomfort, which can have serious implications in survival situations and highlights the subjective and highly variable nature of cold perception. Perceived cold sensation may be a very poor, and possibly dangerous, predictor in cold water immersion situations.

Suppression of shivering by breath holding, relaxation, mental arithmetic, and warm water ingestion.

Four methods of suppressing cold-induced shivering were evaluated in 26 young male volunteers exposed to 0.0 +/- 1.0 degrees C air for 135 min. Voluntary relaxation of musculature (R), breath holding (BH), warm (50 degrees C) water ingestion (W), and performance of a mental arithmetic task (MA) were applied in a counterbalanced order following 2 h of cold exposure. Surface electromyograms of seven muscles were recorded and converted to root mean square voltage (RMS) as a measure of shivering intensity. Mean skin and rectal temperatures decreased significantly, 4.9 degrees C and 0.3 degrees C, respectively (p < or = 0.01). Mean reduction of EMG activity was 35% during R, 24% during BH, 18% during MA, and 5% during W. R was significantly more effective than BH, MA, and W, and BH and MA were significantly more effective than W in reducing shivering. These results indicate that, at small decreases in rectal temperature, shivering can be voluntarily suppressed to some extent during relaxation, breath holding, and mental arithmetic.