Serum levels of insulin-like growth factor system components and relationship to bone metabolism in Type 1 and Type 2 diabetes mellitus patients.

Osteopenia has been ascribed to diabetics without residual insulin secretion and high insulin requirement. However, it is not known if this is partially due to disturbances in the IGF system, which is a key regulator of bone cell function. To address this question, we performed a cross-sectional study measuring serum levels of IGF-I, IGF-binding protein-1 (IGFBP-1), IGFBP-3, IGFBP-4 and IGFBP-5 by specific immunoassays in 52 adults with Type 1 (n=27) and Type 2 (n=25) diabetes mellitus and 100 age- and sex-matched healthy blood donors. In the diabetic patients, we further determined serum levels of proinsulin, intact parathyroid hormone (PTH), 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3 and several biochemical bone markers, including osteocalcin (OSC), bone alkaline phosphatase (B-ALP), carboxy-terminal propeptide of type I procollagen (PICP), and type I collagen cross-linked carboxy-terminal telopeptide (ICTP). Urinary albumin excretion was ascertained as a marker of diabetic nephropathy. Bone mineral density (BMD) of hip and lumbar spine was determined by dual-energy X-ray absorptiometry. Data are presented as means+/-s.e.m. Differences between the experimental groups were determined by performing a one-way analysis of variance (ANOVA), followed by Newman-Keuls test. Correlations between variables were assessed using univariate linear regression analysis and partial correlation analysis. Type 1 diabetics showed significantly lower IGF-I (119+/-8 ng/ml) and IGFBP-3 (2590+/-104 ng/ml) but higher IGFBP-1 levels (38+/-10 ng/ml) compared with Type 2 patients (170+/-13, 2910+/-118, 11+/-3 respectively; P<0.05) or healthy controls (169+/-5, 4620+/-192, 3.5+/-0.4 respectively; P<0.01). IGFBP-5 levels were markedly lower in both diabetic groups (Type 1, 228+/-9; Type 2, 242+/-11 ng/ml) than in controls (460+/-7 ng/ml,P<0. 01), whereas IGFBP-4 levels were similar in diabetics and controls. IGF-I correlated positively with IGFBP-3 and IGFBP-5 and negatively with IGFBP-1 and IGFBP-4 in all subjects. Type 1 patients showed a lower BMD of hip (83+/-2 %, Z-score) and lumbar spine (93+/-2 %) than Type 2 diabetics (93+/-5 %, 101+/-5 % respectively), reaching significance in the female subgroups (P<0.05). In Type 1 patients, BMD of hip correlated negatively with IGFBP-1 (r=-0.34, P<0.05) and IGFBP-4 (r=-0.3, P<0.05) but positively with IGFBP-5 (r=0.37, P<0. 05), which was independent of age, diabetes duration, height, weight and body mass index, as assessed by partial correlation analysis. Furthermore, biochemical markers indicating bone loss (ICTP) and increased bone turnover (PTH, OSC) correlated positively with IGFBP-1 and IGFBP-4 but negatively with IGF-I, IGFBP-3 and IGFBP-5, while the opposite was observed with bone formation markers (PICP, B-ALP) and vitamin D3 metabolites. In 20 Type 2 patients in whom immunoreactive proinsulin could be detected, significant positive correlations were found between proinsulin and BMD of hip (r=0.63, P<0.005), IGF-I (r=0.59, P<0.01) as well as IGFBP-3 (r=0.49, P<0.05). Type 1 and Type 2 patients with macroalbuminuria showed a lower BMD of hip, lower IGFBP-5 but higher IGFBP-4 levels, suggesting that diabetic nephropathy may contribute to bone loss by a disturbed IGF system. In conclusion, the findings of this study support the hypothesis that the imbalance between individual IGF system components and the lack of endogenous proinsulin may contribute to the lower BMD in Type 1 diabetics.

Pleiotropic effects of hepatocyte growth factor in proximal tubule involve different signaling pathways.

Hepatocyte growth factor (HGF) accelerates renal tubule cell regeneration and induces tubulogenic differentiation via the intracellular tyrosine kinase (TK) domain of its receptor, the proto-oncogene c-Met. We tested whether different signaling pathways may be involved by examining HGF binding and effects on cell proliferation, migration, scattering, and tubulogenic differentiation in the bipolar differentiating rabbit proximal tubule cell line PT-1 under serum-free conditions in the presence or absence of the protein TK inhibitors (PTKIs) herbimycin-A, genistein, methyl-2,5-dihydroxycinnamate, and geldanamycin. These PTKIs inhibit pp60(c-src), a nonreceptor TK involved in cell-growth control. HGF bound to a single high-affinity receptor class, increased microvilli numbers 1.5-fold, enhanced cell proliferation and migration 1.8-fold, and stimulated formation of tubule structures 2.2-fold. PTKI inhibited the mitogenic and motogenic effects of HGF with different potencies and comparable maximal effects but had no specific influence on HGF-induced tubulogenic cell differentiation. These data underline the importance of pp60(c-src) in mediating mitogenic and motogenic effects of HGF, whereas stimulation of tubulogenic cell differentiation may be transduced by a pp60(c-src)-independent pathway.

Effects of glucagon-like peptide-1 (GLP-1) in RINm5F insulinoma cells. Stimulation of insulin secretion, insulin content, and insulin receptor binding.

Glucagon-like peptide-1 (GLP-1) is the major incretin hormone from the distal small intestine which stimulates basal and glucose-induced insulin secretion. Using the rat insulinoma cell line RINm5F (Gazdar et al. 1980) we investigated the effects of GLP-1 on insulin secretion, insulin content, and insulin receptor binding. During a 1 hour incubation, GLP-1 [1 nM] stimulated insulin secretion 2-fold (p < 0.01 vs controls). Incubating RINm5F for 24 h with GLP-1 [1 nM], a 1.6-fold higher cellular insulin content was observed (p < 0.01 vs controls). Moreover, GLP-1 induced a 2-fold higher capacity and a 15-fold higher affinity of 125I-insulin binding on the cell surface (p < 0.01 vs controls). Glucagon, known as a potent stimulator of insulin secretion, yielded a similar effect only in 1,000-fold higher concentrations, whereas the intracellular insulin content as well as insulin receptor binding was not increased. Taken together, in RINm5F insulinoma cells GLP-1 potently stimulates insulin secretion and insulin content, and improves insulin receptor binding.

Positive-outcome bias: comparison of emergency medicine and general medicine literatures.

OBJECTIVE: The existence of positive-outcome bias in the medical literature is well established. Positive-outcome bias in two emergency medicine journals was compared with that found in two general medicine journals. METHODS: Published original contributions from Annals of Emergency Medicine, American Journal of Emergency Medicine, JAMA, and New England Journal of Medicine were reviewed. Articles were categorized as demonstrating a positive or negative outcome or showing no difference using new criteria. Descriptive articles were excluded. RESULTS: Of 700 articles reviewed, 177 emergency medicine and 211 general medicine articles met the study criteria. The emergency medicine journals had 142 articles (80%) with positive outcomes, 27 (15%) with negative outcomes, and 8 (5%) with no difference. The general medicine journals had 169 articles (80%) with positive outcomes, 33 (16%) with negative outcomes, and 9 (4%) with no difference. There was no significant difference between journal groups (chi-square; p = 0.99). The power of the study was 0.80 to detect a difference of 15% between groups with alpha set at 0.05. CONCLUSION: There was no significant difference in the proportions of positive-outcome studies published in this sample of the emergency medicine literature compared with the general medicine literature. The potential impact of positive-outcome bias and methods of dealing with the problem are reviewed.

The influence of demographic factors on seatbelt use by adults injured in motor vehicle crashes.

This study determined demographic factors associated with reported seatbelt use among injured adults admitted to a trauma center. A retrospective chart review was conducted including all patients admitted to a trauma center for injuries from motor vehicle crashes (MVC). E-codes (i.e. ICD-9 external cause of injury codes) were used to identify all patients injured in a MVC between January 1995 and December 1997. Age, sex, race, residence zip code (i.e. a proxy for income based on geographic location of residence), position in the vehicle, and seatbelt use were obtained from the trauma registry. Forward logistic regression was used to identify significant predictors of seatbelt use. Complete data was available for 1366 (82%) patients. Seatbelt use was reported for 45% of patients under age of 25 years, 52% of those 25-60 years, and 68% of those over 60 years. Overall, seatbelt use was reported for 45% of men and 63% of women, as well as for 56% of Caucasians (i.e. Whites) and 34% of African Americans. In addition, seatbelt use was reported for 33% of those earning less than $20,000 per year and 55% of those earning over $20,000. Finally, seatbelt use was reported for 57% of drivers and 43% of passengers. Logistic regression revealed that age, female gender, Caucasian race, natural log of income, and driver were all significant predictors of reported seatbelt use. These results show that seatbelt use was more likely to be reported for older persons, women, Caucasians, individuals with greater incomes, and drivers. Seatbelt use should be encouraged for everyone; however, young people, men, African Americans, individuals with lower incomes, and passengers should be targeted specifically.

Bicarbonate.

Bicarbonate is a laboratory value of considerable importance in emergency medicine. It is essential in the diagnosis of acid-base disorders, but must be interpreted in the context of a number of other parameters, including electrolytes, arterial blood gases, and renal function. As most laboratory evaluations, its prime importance is confirmation of impressions drawn from the history and physical examination. Still, in the emergency department, it is frequently found as an unsuspected component of a variety of pathologic processes. Except in extreme deviations from the normal range, the clinician is encouraged to seek an understanding of primary and compensatory processes before the initiation of therapy.

Ultrasonography in blunt abdominal trauma.

This article discusses studies of the use of ultrasound in patients with blunt abdominal trauma, both in initial assessment and ongoing evaluation. Reviews of studies of children and adults to detect the presence and extent of hemoperitoneum and organ injuries are presented. Ultrasound results are compared with diagnostic peritoneal lavage, computed tomography, clinical course, and autopsy results. The central question addressed is to what extent can ultrasonography replace or supplement other techniques, particularly diagnostic peritoneal lavage, in the assessment of patients with blunt abdominal trauma. Ultrasound equipment, technique, scoring scales, limitations, and training issues are also addressed.

Ectopic pregnancy.

The incidence of ectopic pregnancies has increased dramatically over the past 20 years, resulting in significant maternal morbidity and mortality. This article reviews the epidemiology, pathogenesis, clinical manifestations, diagnostic testing, differential diagnosis, treatment, prognosis, and medico-legal considerations in the evaluation of the patient with a suspected or confirmed pregnancy.

The red blood cell distribution width.

The availability of automated blood cell analyzers that provide an index of red blood cell distribution width (RDW) has lead to new approaches to patients with anemia. While the emergency physician is primarily responsible for the detection of patients with anemia, the inclusion of the RDW in the complete blood count has made diagnosing certain anemias easier, especially those that are microcytic. The derivation of the RDW and its clinical application to emergency physicians is discussed and a categorization of anemias based on the mean corpuscular volume (MCV) and RDW is included.

Emergency department echocardiography in the diagnosis and therapy of cardiac tamponade.

A 44-year-old male presented to the emergency department in shock with jugular venous distension and upper chest cyanosis. Superior vena cava syndrome was ruled out by computed tomography (CT scan). However, a large pericardial effusion was found on CT scan and confirmed by sonography. Pericardial tamponade was diagnosed by emergency physicians and sonography-guided pericardiocentesis was performed with marked improvement in symptomatology.

The impact of a major televised sporting event on emergency department census.

This study examines the effect of a major televised sporting event, the Super Bowl, on emergency department (ED) census. Daily patient census figures for the month of January 1988-1992 were obtained. Individual shift census was divided by monthly mean census to compare relative volume. Census figures for 4 of the 5 Super Bowl days were significantly lower than the remaining 143 days studied. The day of the Super Bowl was the month's slowest shift for 3 of the 5 days. When the local team was a playoff participant, a stronger association was noted. The results demonstrate a significant decrease in ED utilization coinciding with the Super Bowl broadcast. Major televised events can significantly decrease ED volume, especially when local interest is present. Staffing changes may then be made accordingly.

A multi-state survey of videotaping practices for major trauma resuscitations.

The objective of this study was to determine the prevalence and problems, both perceived and actual, associated with videotaping major trauma resuscitations. A cross-sectional two-part survey of trauma centers was conducted. Part 1 determined demographic information and videotaping status. Part 2 asked trauma centers that were not doing videotaping (NVTCs) about their plans, past experience, and perceived problems. Videotaping trauma centers (VTCs) were asked about mechanics, responsibility, utilization, and problems. A total of 221 centers were surveyed; 20% VTCs, 70% NVTCs, and 10% NVTCs that had videotaped in the past (PVTC). Among VTCs, 53% reported problems with videotaping including lack of personnel (40%) and time (40%) to administer the program. Videotaping, however, was found to be an effective quality improvement tool in 95% of the VTCs. Of the NVTCs, 70% perceived problems with implementing a videotaping program; these included medicolegal (34%) and patient confidentiality (22%) concerns. Of the PVTCs, 90% stated that they had problems with videotaping including lack of staff support (33%) and lack of personnel to assist with the program (24%). In conclusion, staff participation and adequate personnel outweigh medicolegal concerns as actual videotaping problems. Videotaping is perceived to be an effective performance improvement tool.

[Lead and cadmium content of baby food and their nutritional hygienic-toxicological significance]. / Uber die Blei- und Cadmiumgehalte von Kleinkindernahrung und ihre lebensmittelhygienisch-toxikologische Bedeutung

Little is known of the amounts of lead and cadmium which the infantile organism takes up from the total diet. The author's analyses of more than 150 jars or packs of ready-to-use baby food produced in the German Democratic Republic (trade mark: Für's Kind) revealed lead contents of less than 100 mug/kg and cadmium contents of less than 10 mug/kg. Only spinach showed higher lead values. In liver -containing ready-to-use foods the cadmium contents were higher than 10 mug/kg (25-50 mug/kg). Like liquid milk, powdered milk-base foods contained no cadmium. From these values it was calculated that the daily lead and cadmium intake of an infant during his first year of life amounts to 42-47 mug of lead and to 6,4-11,5 mug of cadmium, respectively. A conversion to mg/kg of body weight shows that, in both cases, the load on an infant equals that on an adult or is even greater. Literature data lead intake are in good agreement with these results. Corresponding studies for cadmium are not known.

Effect of alcohol consumption on outcome of pedestrian victims.

The influence of alcohol consumption on the severity of pedestrian injuries has not been studied extensively. In this retrospective study, we reviewed the cases of 143 pedestrian accident victims admitted to our trauma center during 1982 and 1983. Alcohol consumption was present in 30% of patients; 74% of them had blood alcohol levels of more than 100 mg/dL. There was a significant difference in age distribution (P less than .001); the alcohol-related accidents peaked in the 25- to 34-year-old age group, and the nonalcohol-related accidents peaked in the less than 18- and more than 55-year-old groups. Mean Injury Severity Score (25.0 vs 17.8, P less than .01) and mean length of stay (30.9 vs 17.2 days, P less than .005) were significantly greater in the patients who had consumed alcohol. Those patients with ethanol in their blood had significantly more frequent injuries to the spine (25.6% vs 10%, P less than .05) and the chest (32.6% vs 13%, P = .01). Overall mortality (11.6% vs 20%, P = .23) and mortality excluding emergency department deaths (11.6% vs 11.1%, P = .93) were not significantly different between the drinking and nondrinking groups. However, the ED mortality was higher in the nonalcohol group (0% vs 10%, P = .03). We conclude that pedestrian victims are commonly intoxicated and that chest and spine injuries are more common in this population.

Acoustic otoscopy in the diagnosis of otitis media.

Acoustic otoscopy detects middle ear pathology by measuring the ability of the tympanic membrane to reflect sound. Fluid or thickening of the tympanic membrane increases sound reflection. We conducted a study to compare acoustic otoscopy with pneumatic otoscopy in identifying middle ear pathology in 80 children (160 ears) presenting to the emergency department with ear or upper respiratory complaints. We then evaluated the use of acoustic otoscopy in 34 adults (68 ears) with and without ear complaints. Using a reflectivity of 5 or more units to signify acute pathology in children, the sensitivity was 82%, and the specificity was 100%. Using a reflectivity of 6 or more units to indicate acute suppurative pathology in adults, the sensitivity was 83%, and the specificity was 95%. We found acoustic otoscopy to be objective, practical, and reproducible. We conclude that acoustic otoscopy is a valuable adjunct in the diagnosis of otitis media in children and adults.

[Effect of tin on rats. 1. Inverse voltammetric determination of tin in the presence of lead in biological material after extraction]. / Zinnwirkung auf Ratten. 1. Mitt. Die inversvoltammetrische Bestimmung von Zinn neben Blei in biologischen Material nach Extraktion.

By means of inverse polarography, the authors determined tin selectively after double extraction with diethylammonium diethyl dithiocarbamate (DADDTC) in perchloric solution. The recovery rates were: in potatoes, 91.7 +/- 5.8%; in beef kidney, 85.0 +/- 22.7%; in beef liver 79.9 +/- 13.8%; and in milk, 69.8 +/- 11.4%. Possible interferences from other elements with the tin determination are discussed.

Emergency department ultrasound in the evaluation of blunt abdominal trauma.

The main objective of this study was to compare bedside sonographic detection of hemoperitoneum with diagnostic peritoneal lavage/laparotomy in the patient with blunt abdominal trauma. A retrospective review was conducted of all blunt trauma patients that underwent emergency department (bedside) sonography to rule out intraperitoneal hemorrhage at a level I trauma center in 1991 to 1992. Patients were included in the study population only if: (1) the results of the ultrasound examination were interpreted before any other diagnostic studies, and (2) a diagnostic peritoneal lavage (DPL) or laparotomy was performed. The ultrasound examination consisted of a single right inter/subcostal longitudinal view with the patient in the trendelenburg position performed by the emergency physician or surgeon. A real-time sector scanner with a 3.5 MHz probe was used. The presence of an anechoic (black) stripe between the liver and the right kidney (Morrison's pouch) was interpreted as a positive study, and the absence of this finding was interpreted as a negative study. A positive DPL was defined as > or = 10 mL of gross blood or a blood cell count > or = 100,000/mm3 in the returned lavage fluid, and a positive laparotomy as > or = 100 mL of intraperitoneal blood. Forty-four patients met the inclusion criteria for the study. Eleven patients (24%) in this population had either a positive DPL or laparotomy. The sensitivity, specificity, and accuracy of bedside sonography in identifying intraperitoneal hemorrhage was 81.8%, 93.9%, and 90.9%, respectively. The ultrasound study provided an answer in less than 1 minute in most patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Elevated Toxoplasma IgG antibody in patients tested for infectious mononucleosis in an urban emergency department.

There are many infectious causes of fatigue, sore throat, and fever, including mononucleosis and toxoplasmosis. Toxoplasma antibody testing is rarely performed in most emergency departments; as a result, toxoplasmosis is diagnosed infrequently. We obtained Toxoplasma IgG IFA titers on ED patients who had mononucleosis testing performed to determine the frequency of toxoplasmosis in this population. Two hundred sixty patients were included in our study. Eleven (4.2%) had a positive mononucleosis test, and 14 (5.4%) had a positive Toxoplasma titer. In the detection of toxoplasmosis, Toxoplasma IgG titers of 1:1,024 or greater have been shown to be a sensitive means of detecting infection in the first six months. Further testing with IgM titers is needed to establish a positive diagnosis when necessary. We found more patients with elevated Toxoplasma IgG titers than with positive heterophil antibody titers in an ED population tested for mononucleosis over a two-year period. We conclude that toxoplasmosis may be as common as mononucleosis in our ED and that clinicians should consider this pathogen when working up patients with appropriate symptoms.