Skeletal muscle of stroke-prone spontaneously hypertensive rats exhibits reduced insulin-stimulated glucose transport and elevated levels of caveolin and flotillin.

Insulin resistance is of major pathogenic importance in several common human disorders, but the underlying mechanisms are unknown. The stroke-prone spontaneously hypertensive (SHRSP) rat is a model of human insulin resistance and is characterized by reduced insulin-mediated glucose disposal and defective fatty acid metabolism in isolated adipocytes (Collison et al. [Diabetes 49:2222-2226, 2000]). In this study, we have examined skeletal muscle and cultured skeletal muscle myoblasts for defects in insulin action in the male SHRSP rat model compared with the normotensive, insulin-sensitive control strain, Wistar-Kyoto (WKY). We show that skeletal muscle from SHRSP animals exhibits a marked decrease in insulin-stimulated glucose transport compared with WKY animals (fold increase in response to insulin: 1.4 +/- 0.15 in SHRSP, 2.29 +/- 0.22 in WKY; n = 4, P = 0.02), but the stimulation of glucose transport in response to activation of AMP-activated protein kinase was similar between the two strains. Similar reductions in insulin-stimulated glucose transport were also evident in myoblast cultures from SHRSP compared with WKY cultures. These differences were not accounted for by a reduction in cellular GLUT4 content. Moreover, analysis of the levels and subcellular distribution of insulin receptor substrates 1 and 2, the p85alpha subunit of phosphatidylinositol 3'-kinase, and protein kinase B (PKB)/cAKT in skeletal muscle did not identify any differences between the two strains; the insulin-dependent activation of PKB/cAKT was not different between the two strains. However, the total cellular levels of caveolin and flotillin, proteins implicated in insulin signal transduction/compartmentalization, were markedly elevated in skeletal muscles from SHRSP compared with WKY animals. Increased cellular levels of the soluble N-ethylmaleimide attachment protein receptor (SNARE) proteins syntaxin 4 and vesicle-associated membrane protein (VAMP)-2 were also observed in the insulin-resistant SHRSP strain. Taken together, these data suggest that the insulin resistance observed in the SHRSP is manifest at the level of skeletal muscle, that muscle cell glucose transport exhibits a blunted response to insulin but unchanged responses to activation of AMP-activated protein kinase, that alterations in key molecules in both GLUT4 trafficking and insulin signal compartmentalization may underlie these defects in insulin action, and that the insulin resistance of these muscles appears to be of genetic origin rather than a paracrine or autocrine effect, since the insulin resistance is also observed in cultured myoblasts over several passages.

A 12-month follow up of the implementation of clinical indicators in a consultation-liaison service.

OBJECTIVES: This paper reviews the use of clinical indicators in a consultation-liaison (C-L) service over a 12-month period at the Royal Melbourne Hospital, Melbourne, Australia. METHOD: Clinical indicators and C-L data were collected during the 1999 calendar year. A review of the process was conducted during and after completion of the 12-month period. RESULTS: The system was found to be practical and useful. The use of clinical indicators led to the identification of problems and stimulated effective interventions. The use of the clinical indicators was associated with improvement in communication between C-L staff, parent units and practitioners providing follow-up. CONCLUSIONS: The implementation of a database and clinical indicators was a useful addition to the C-L service. The use of clinical indicators was effective in improving clinical performance. These benefits need to be balanced against increased administrative burden.

Regulation of glucose transport in aortic smooth muscle cells by cAMP and cGMP.

We have studied the ability of cGMP and cAMP to modulate platelet-derived growth factor (PDGF)-stimulated 2-deoxy-D-glucose (deGlc) transport in primary cultures of vascular smooth muscle cells (VMSC) from rat aorta. PDGF stimulated deGlc transport in a time- and concentration-dependent manner. 8-Bromo-cGMP and atrial natriuretic peptide(1-28) [ANP(1-28)] were found to reduce PDGF-stimulated deGlc transport without affecting basal (unstimulated) transport activity. In contrast, 8-bromo-cAMP and dibutyryl-cAMP stimulated basal deGlc transport 2-fold and were without effect on PDGF-stimulated deGlc transport. 8-Bromo-cGMP also inhibited 8-bromo-cAMP-stimulated deGlc transport. The stimulation of deGlc transport by PDGF was sensitive to the mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK) kinase (MEK) inhibitor PD98059, and we show that ERK1/2 was activated by PDGF. Neither 8-bromo-cGMP nor ANP(1-28) inhibited PDGF-stimulated ERK activation, suggesting that the effects of cGMP and ANP(1-28) were not mediated by inhibition of this kinase. Our data also argue against a role for cGMP-dependent protein kinase in mediating the effects of cGMP or ANP(1-28). Collectively, our data suggest that in VSMC: (i) cGMP and cAMP have opposing effects on deGlc transport; (ii) PDGF and cAMP have common elements in the pathways by which they activate deGlc transport; and (iii) a common element may be the target of the cGMP-mediated inhibition of deGlc transport.

Deaths from trauma in Auckland: a one year study.

We report a one year prospective study of all deaths from trauma in the Auckland region. Data was collected on the circumstances of death from coroner's, police and hospital records. All cases had autopsies and the injuries were scored using the abbreviated injury scale (AIS) system. The group of 236 had a median age of 27 years and 73% were under the age of 45. Seventy-two percent were male. Blunt trauma, predominantly the result of road crashes, accounted for 89% of the fatalities. Most deaths occurred at the site of injury and only 37% survived to reach hospital. Cases were audited if death occurred without a critical or unsurvivable injury. Thirteen cases were considered to be potentially salvageable if medical treatment had been optimal. The implications for the organisation of prehospital and inhospital trauma care are discussed.

Childhood pedestrian deaths: experience of the Auckland coronial area 1977-1983.

The Auckland coronial district experience of 65 childhood pedestrian deaths over a seven year period is presented. The behaviour of this group of pedestrians is reviewed and a major factor was the unpredictable behaviour of children. Suggestions as to prevention are made.

Fatal injuries to bicycle riders in Auckland.

Twenty bicycle riders were fatally injured in Auckland between 1974 and 1984. Eighteen were male and nine aged under 15 years. The age distribution of fatalities corresponds closely to the known age distribution of the cycling population. Few differences in pattern of injury were demonstrable between younger (under 15 years) and older riders. Sixteen died of fatal injury to multiple organ systems. Fourteen had fatal injury to brain, including four with no other significant organ injury. Fatal cardiopulmonary trauma was seen in seven riders and fatal abdominal trauma in seven. Cervical and high thoracic fracture dislocation with cord injury were seen in seven riders. Compared to the population base, incidence of fatalities is low, and no recent significant increase is detected.

Accidental drownings in Auckland children.

We consider the circumstances surrounding 60 consecutive cases of accidental drowning of children in the Auckland coronial district. More deaths occurred around the home than anywhere else. Forty-one of the fatalities occurred around the home with only two being over the age of six years. The unfenced or inadequately fenced domestic swimming pool was the most common hazard. The household bath and partly filled buckets represent further although less frequent dangers. The study reaffirms the need for legislation making the fencing of domestic swimming pools mandatory. Elsewhere, young children playing in or near water need constant supervision. More victims received either no resuscitation or inadequate resuscitation until an ambulance crew arrived at the home. This further emphasises the value of a sound knowledge of cardiopulmonary resuscitation techniques in the general population.

Deaths from electricity.

This paper reviews the circumstances of 95 fatalities from electrical injuries. Eighty-nine were accidental, four were suicides and two occurred during autoerotic electrical stimulation. Forty-nine of the accidental fatalities occurred at work, Twenty-eight in the home and twelve in the course of outside recreational activities. In many accidents the circumstances were distressingly similar and included: (1) Contact with overhead distribution lines by a length of conductor such as a yacht mast or crane. (2) Faulty wiring or electrical repairs performed by unqualified people. (3) Badly deteriorated cords, plugs and occasionally appliances. (4) Failure to use isolating transformers when indicated. Deaths involving children are a particular cause of concern. Nine fatalites involved children under the age of five years who contacted inadequately protected wires.

Deaths from drowning.

During an eight year period in the Auckland coronial district, 225 persons over the age of fifteen years died from drowning and were subject to autopsy. Of these, 129 males and 21 females drowned because of accidents whilst 31 males and 29 females committed suicide by drowning. There was one homicide and in 14 cases it was unclear as to whether drowning was accidental or suicidal. At least half of the accidents showed analytical evidence of having consumed alcohol and in 37% of these the blood alcohol level was over 100 mg per 100 ml of blood. The activities in which the accidentally drowned were engaged at the time of their deaths are documented and the role of intercurrent illnesses in some drownings illustrated.

Deaths from drugs and poisons.

In the eight years from 1975 to 1982, 11 262 ***coronial**autopsies were performed in the School of Medicine, Auckland. Three hundred and ninety-four of the deaths were due to the action of a drug or poison. In this paper we examine the motives and circumstances, age and sex distribution, drugs used and other aspects of these 394 deaths.

Death from electrocution during auto-erotic procedures.

Two cases of death from electrocution during auto-erotic procedures are presented. These are accidental deaths and need to be distinguished from suicidal deaths.

Fulminant pneumococcal septicaemia in an adult following splenectomy: case report.

A case is reported of fulminant pneumococcal septicaemia occurring in a 22-year-old male six years after surgical removal of the spleen.

Cardiac rupture: 30 consecutive cases from a series of medicolegal autopsies.

Factors underlying spontaneous cardiac rupture were studied in a consecutive series of 30 hearts with ruptured infarcts removed at medicolegal autopsy. Normal and diseased heart muscle and narrowed coronary arteries were examined microscopically. The average age of the 15 women at death was 80 years, and of the 15 men, 73 years. All of the ruptures occurred through a recent transmural left ventricular myocardial infarction which was associated with coronary arteries severely narrowed by atherosclerosis. Nine (33 percent) of the cases showed an occlusive coronary thrombosis. Many of the subjects had no symptoms of recent myocardial ischaemia.

Apparatus for measurement of luminescence spectra with a digital recording system.

An apparatus is designed for use in obtaining fluorescence spectra, excitation spectra, and delayed fluorescence spectra, usually at low temperatures. A photometrically regulated 6500-W xenon lamp is used as excitation source, a double monochromator or varioilluminator as excitation monochromator; a variable temperature liquid helium cryostat as specimen holder; a double grating monochromator or varioilluminator as detection monochromator; and a photomultiplier as detector. A quartz-iodine lamp calibrated against a standard tungsten-quartz lamp is used for intensity calibrations. Fluorescence spectra are recorded by a digital system with a shaft position encoder for digitizing wavelength and an analog-to-digital converter for intensity. Data are recorded on magnetic tape which can be processed directly by an IBM system 360 computer. The selection of components of adequate resolution, speed, and capacity is discussed, and the computer programs are described. Installation of the recording system 1ms facilitated greater wavelength accuracy and long calculations on the experimental data. Examples are given.