Development and validation of the Diabetes Care Profile

To determine the reliability and the validity of the Diabetes Care Profile (DCP), an instrument that assesses the social and psychological factors related to diabetes and its treatment, two studies with separate populations and methodologies were conducted. In the first study, the DCP was administered to, and physiologic measures collected from, individuals with diabetes being cared for in a community setting (n = 440). In the second study, the DCP and several previously validated scales were administered to individuals with diabetes receiving care at a university medical center (n = 352). Cronbach's alphas of individual DCP scales ranged from .60 to .95 (Study 1) and from .66 to .94 (Study 2). Glycohemoglobin levels correlated with three DCP scales (Study 1). Several DCP scales discriminated among patients with different levels of disease severity. The results of the studies indicate that the DCP is a reliable and valid instrument for measuring the psychosocial factors related to diabetes and its treatment.     

Further studies on the action of 5-hydroxytryptamine on lumbar motoneurones in the rat isolated spinal cord

Summary Using the hemisected spinal cord of the neonate rat, the effects of altered external Ca, thyrotrophin-releasing hormone (TRH) and a number of antagonists were tested on depolarizations evoked by 5-hydroxytryptamine (5-HT). Responses of populations of motoneurones were recorded via a ventral root. 5-Hydroxytryptamine depolarizations were not Ca-dependent but were enhanced in amplitude in Ca-free solutions. Raised Mg reversed this enhancement. 5-Hydroxytryptamine depolarizations persisted in the presence of Mn (1.53 mmol/l). TRH depolarized motoneurones; there was no evidence of modulation of 5-HT responses on concurrent application of TRH. Ritanserin (0.1 mol/l) had a modest blocking action on 5-hydroxytryptamine depolarizations reducing the maximum; 1mol/l ritanserin caused a greater antagonism which was unsurmountable (pIC₅₀ 5.2). Ritanserin (0.1 or 1 mol/l) did not depress responses to noradrenaline (NA). Ketanserin (0.1 mol/l) caused a blockade of slow onset, equilibrium with the receptors requiring 1 h. Blockade by 0.01, 0.1 and 1 mol/l ketanserin was concentration-dependent (pIC₅₀ 6.2). Ketanserin 1 mol/l, but not at lower concentrations, depressed noradrenaline responses. Mianserin (0.1 mol/l) also caused a blockade of slow onset; 0.1 or 1 mol/l produced a flattening of the 5-hydroxytryptamine concentration-response curve but did not depress noradrenaline responses (pIC₅₀ 4.7). The pIC₅₀ for spiperone was 8.0. DOI (10–100 mol/l) had no detectable agonist action but at concentrations of 0.01 and 0.1 mol/l it acted as an antagonist. Equilibration with the receptors occurred over 2 h. DOI (0.01 mol/l) depressed 5-hydroxytryptamine but not noradrenaline responses; higher concentrations of DOI also depressed noradrenaline responses. The pharmacological profile of the 5-hydroxytryptamine receptor mediating depolarization of spinal and facial motoneurones suggests that it belongs to the 5-HT_1C-5-HT₂, group of 5-hydroxytryptamine receptors but is not identical to 5-HT_1C or the 5-HT₂ CNS binding sites. Alternatively, the response might arise from a mixed population of 5-HT₁-like and 5-HT₂ receptors. Send offprint requests to D. I. Wallis at the above address     

Nutritional management of children and adolescents with insulin-dependent diabetes mellitus: a review by the diabetes care and education dietetic practice group

Although individuals with insulin-dependent diabetes mellitus (IDDM) represent only a small proportion of the total number of persons with diabetes, IDDM is one of the most prevalent chronic childhood diseases. The goals of management in IDDM include normal growth and development, control of blood glucose, maintenance of optimal nutritional status, and prevention of complications. Insulin replacement is the mainstay of treatment in IDDM; however, optimal therapy requires a careful balance of food, insulin, and physical activity. To our knowledge, this is the first comprehensive nutrition review of IDDM that emphasizes research specifically in the area of IDDM (vs non-insulin-dependent diabetes mellitus), including data on children and adolescents when available. the process of nutrition education utilizes a staged approach beginning with "survival" information and progressing to in-depth or continuing education and counseling. Important considerations should be to guide the child/adolescent to a meal plan that fits individual life-style, promotes optimal compliance, and advances the goals of management. Throughout the diabetes nutrition education process, the dietitian can positively affect the lives of children/adolescents and their families. More research is needed to better define ways of meeting the nutrition needs of children and adolescents with IDDM in the areas of fiber and glycemic control, fish oil and lipids, sodium and hypertension, and weight control.     

Volunteers at risk.

An experiment is described in which three male volunteers, who fully understood the nature of the project, were given doses of heroin which could have led to addiction if the subjects had proved to be physiologically or psychologically vulnerable to developing a state of addiction. The experiment was discussed most carefully by the Ethics Committee of the unit where it was conducted, and the subjects were themselves the investigators. The objective was to learn about the initial stages of the adaptation to heroin, of which nothing was known as heroin addicts usually come to the doctor when the habit is firmly established. A physician, who has studied the subject of drug addiction in a special clinic, is the first commentator, the second a lawyer and the third an associate professor of social ethics. These three experts are not discussing the results or the methodology of the experiment but whether the decision of the Ethics Committe was the right one.     

Nutritional status and diarrhoeal pathogen in hospitalized children in Bangladesh

We studied the relationship between nutritional status and infection due to specific enteropathogens in young children with diarrhoea. Overall, 26% of the children were severely underweight, 27% were severely wasted and 19% were severely stunted. Children with Shigellae and V. cholerae O1 were significantly more severely underweight, wasted and stunted than those with rotavirus diarrhoea ( p < 0:0001). Our results indicate that an effective nutrition programme for young children might have greater impact on diarrhoeal illness caused by Shigella and V. cholerae than by rotavirus diarrhoea.     

Total but not resting energy expenditure is increased in infants with ventricular septal defects

OBJECTIVE: The purpose of this study was to determine the effect of left-to-right shunting on the resting energy expenditure (REE), total energy expenditure (TEE), and energy intake in a group of 3- to 5-month-old infants with moderate to large unrepaired ventricular septal defects (VSDs) compared with age-matched, healthy infants. METHODS: Eight infants with VSDs and 10 healthy controls between 3 to 5 months of age participated in the study. Indirect calorimetry was used to measure REE and the doubly-labeled water method was used to measure TEE and energy intake. An echocardiogram and anthropometric measurements were performed on all study participants. Daily urine samples were collected at home for 7 days. Samples were analyzed by isotope ratio mass spectrometry. Data were compared using analysis of variance. RESULTS: No significant differences were found in REE (VSD, 42.2 +/- 8.7 kcal/kg/d; control, 43.9 +/- 14.1 kcal/kg/d) or energy intake (VSD, 90.8 +/- 19.9 kcal/kg/d; control, 87.1 +/- 11.7 kcal/kg/d) between the groups. The percent total body water was significantly higher in the VSD infants and the percent fat mass was significantly lower. TEE was 40% higher in the VSD group (VSD, 87.6 +/- 10.8 kcal/kg/d; control, 61.9 +/- 10.3 kcal/kg/d). The difference between TEE and REE, reflecting the energy of activity, was 2.5 times greater in the VSD group. CONCLUSIONS: REE and energy intake are virtually identical between the two groups. Despite this, infants with VSDs have substantially higher TEE than age-matched healthy infants. The large difference between TEE and REE in VSD infants suggests a substantially elevated energy cost of physical activity in these infants. These results demonstrate that, although infants with VSDs may match the energy intake of healthy infants, they are unable to meet their increased energy demands, resulting in growth retardation.     

Isolation and characterization of propagable cell lines (HUNC) from the androgen-sensitive Dunning R3327H rat prostatic adenocarcinoma

The Dunning H rat prostate tumor (R3327H) is a widely used experimental model of human prostatic adenocarcinoma (CaP). The Dunning H tumor has been characterized as androgen-sensitive, androgen-receptor (AR) positive, prostate-specific antigen and prostatic acid phosphatase (PAP) positive. To date, the tumor has been maintained by serial passage in vivo because of the lack of an in vitro cell line that retains the characteristics of the in vivo tumor. The objective of the present study was to establish a propagable cell line from R3327H adenocarcinoma that maintained androgen sensitivity and expression of AR, PSA and PAP. Tissue harvested from an in vivo R3327H tumor was dissociated with collagenase and placed into Richter's improved media (with supplements). A cytokeratin-positive epithelial cell line (HUNC- E) and a vimentin-positive stromal cell line (HUNC-S) were generated from the primary culture, subcultured continuously for >300 days, and passaged >50 times. Survival of the HUNC-E cell line in vitro depended on several media supplements, including nicotinamide, insulin, transferrin, selenium and epidermal growth factor (EGF). HUNC-E cells expressed AR and produced PSA and PAP throughout the culture period, as confirmed by immunocytochemistry and Western blot analyses. Addition of 14 nM testosterone (T) or dihydrotestosterone (DHT) to HUNC-E cells, stimulated DNA synthesis as well as anchorage-independent growth and PSA production, which demonstrated the androgen-sensitive nature of the cells in vitro. When HUNC-E and HUNC-S cells were combined in a 3:1 ratio and introduced subcutaneously into syngeneic male hosts, tumors formed in 2/3 animals with an average latency of 7 months. RT-PCR and immunocytochemical characterization of the HUNC cell lines revealed that the cells expressed several growth factors and their cognate receptors, including HGF, TGF-alpha and the TGF-betas, indicating the establishment of potential autocrine loops in the neoplastic cells. The HUNC-E and HUNC-S CaP cell lines, which retain the characteristics of the epithelial and stromal components of the in vivo R3327H tumor, will allow a more thorough and informative molecular and biological analysis of prostatic adenocarcinoma.      

Inhibition of cigarette smoke-related lipophilic DNA adducts in rat tissues by dietary oltipraz

The present study investigated the effects of dietary oltipraz on cigarette smoke-related lipophilic DNA adduct formation. Female Sprague- Dawley rats were exposed daily to sidestream cigarette smoke in a whole- body exposure chamber 6 h/day for 4 consecutive weeks. One group of rats was maintained on control diet while another group received the same diet supplemented with either a low (167 p.p.m.) or high (500 p.p.m.) dose of oltipraz, starting 1 week prior to initiation of smoke exposure until the end of the experiment. Analysis of lipophilic DNA adducts by the nuclease P1-mediated 32P-post-labeling showed up to five smoke-related adducts. Adduct no. 5 predominated in both the lung and the heart while adduct nos 3 and 2 predominated in the trachea and bladder, respectively. Quantitative analysis revealed that the total adduct level was the highest in lungs (270+/-68 adducts/10(10) nucleotides), followed by trachea (196+/-48 adducts/10(10) nucleotides), heart (141+/-22 adducts/10(10) nucleotides) and bladder (85+/-16 adducts/10(10) nucleotides). High dose oltipraz treatment reduced the adduct levels in lungs and bladder by >60%, while the reduction in lungs in the low-dose group was approximately 35%. In trachea, the effect of low and high dietary oltipraz on smoke DNA adduction was equivocal, while smoke-related DNA adducts in the heart were minimally inhibited by high-dose oltipraz. In a repeat experiment that employed a 3-fold lower dose of cigarette smoke, oltipraz (500 p.p.m.) was found to inhibit the formation of DNA adducts in rat lungs and trachea by 80 and 65%, respectively. These data clearly demonstrate a high efficacy of oltipraz in inhibiting the formation of cigarette smoke-induced DNA adducts in the target tissues.      

Cd36 and molecular mechanisms of insulin resistance in the stroke-prone spontaneously hypertensive rat

Insulin resistance is of pathogenic importance in several common human disorders including type 2 diabetes, hypertension, obesity and hyperlipidemia, but the underlying mechanisms are unknown. The spontaneously hypertensive rat (SHR) is a model of these human insulin resistance syndromes. Quantitative trait loci (QTLs) for SHR defects in glucose and fatty acid metabolism, hypertriglyceridemia, and hypertension map to a single region on rat chromosome 4. Genetic analysis of an SHR derived from a National Institutes of Health colony led to the identification of a causative mutation in the SHR Cd36. We have investigated glucose and fatty acid metabolism in the stroke-prone SHR (SHRSP). We demonstrate defects in insulin action on 2-deoxy-D-glucose transport (SHRSP 3.3 +/- 1.5 vs. 21.0 +/- 7.4 pmol x min(-1) x [20 microl packed cells](-1), SHRSP vs. WKY, respectively, P = 0.01) and inhibition of catecholamine-stimulated lipolysis (P < 0.05 at all concentrations of insulin) in adipocytes isolated from SHRSP. In contrast, basal levels of catecholamine-stimulated nonesterified free fatty acid (NEFA) release and plasma levels of NEFA are similar in SHRSP and WKY. These results are in agreement with the data on the SHR.4 congenic strain, which suggested that the QTL containing Cd36 mutations accounted for the entire defect in basal catecholamine action but only for approximately 40% of the SHR defect in insulin action. In the SHR, both abnormalities appear consequent of defective Cd36 expression. Because Cd36 sequence and expression are apparently normal in SHRSP, it is likely that the molecular mechanism for defective insulin action in this strain is caused by a gene(s) different than Cd36.     

Airborne Infection with Bacillus anthracis��from Mills to Mail

The lack of identified exposures in 2 of the 11 cases of bioterrorism-related inhalation anthrax in 2001 raised uncertainty about the infectious dose and transmission of Bacillus anthracis. We used the Wells-Riley mathematical model of airborne infection to estimate 1) the exposure concentrations in postal facilities where cases of inhalation anthrax occurred and 2) the risk for infection in various hypothetical scenarios of exposure to B. anthracis aerosolized from contaminated mail in residential settings. These models suggest that a small number of cases of inhalation anthrax can be expected when large numbers of persons are exposed to low concentrations of B. anthracis. The risk for inhalation anthrax is determined not only by bacillary virulence factors but also by infectious aerosol production and removal rates and by host factors.