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Elevated insulin concentrations are independent predictors of coronary heart disease (CHD) and are related to high blood pressure, low serum HDL-cholesterol and elevated serum triglyceride. Insulin resistance is a major determinant of the plasma insulin concentration. Computer modelling of plasma glucose, insulin and C-peptide concentrations during an intravenous glucose tolerance test enables quantification of the determinants of plasma insulin concentration. The association between risk markers of CHD and model-derived measures of determinants of plasma insulin concentration in a group of healthy males has been investigated. In univariate linear regression analysis of the glucose, insulin and C-peptide data, the incremental insulin area during the second phase (10-180 min.) was found to be the strongest predictor of lipid, lipoprotein and blood pressure variables. Variations in insulin sensitivity and hepatic insulin throughput contribute to variation in the insulin response and may be secondary correlates of lipids, lipoproteins and blood pressure.

SUMMARY To investigate the relationship between unilateral hip dislocation or subluxation and scoliosis, the records were examined of 31 patients aged 10 to 26 years with myelomeningocele and an initial neurosegmental level of L3 or L4. 11 patients had deteriorated neurologically over time; the remainder had stable neurological examinations, with an average follow-up of 14,3 years. Scoliosis occurred in three of the nine patients with unilateral hip instability, compared with five of the 11 remaining patients. Only two patients had the expected pattern of unilateral hip instability on the high side of an oblique pelvis, with scoliosis convex to the opposite (low) side. Several unexpected patterns were observed. The functional neurosegmental level is not stable in many patients with myelodysplasia. In neurologically stable patients, unilateral hip instability and scoliosis are comorbid factors and no causal relationship was identified. RESUME Hanche myelodysplasique et scoliose Les dossiers de 31 spina bifida avec niveau segmentate initial L3 ou L4, âges de 10 a 26 ans, ont eteetudies pour apprecier la relation entre une luxation ou subluxation unilaterales et une scoliose. 11 patients s'etaient deteriores neurologiquement avec le temps, les autres etant stables au cours d'examens neurologiques durant un suivi moyen de 14,3 ans. Une scoliose existait chez trois des neuf patientes avec instabilite unilaterale de hanche, comparees a cinq parmi les 11 autres patients. Seulement deux patients presentaient le groupement attendu dune instabilite unilaterale deux patients presentaient le groupement attendu d'une instabilite unilaterale de hanche du cote haut d'un bassin oblique avec convexite scoliotique de cote bas oppose. Plusieurs groupements inatendus ont ete observes. Le niveau neurosegmentaire fonctionnel n'est pas stable chez de nombreux spina bifida; en cas de stabilite neurologique, l'instabilite unilaterale de hanche et la scoliose sont des facteurs simplement et aucune relation causale n'a ete mise en evidence. ZUSAMMENFASSUNG Myelodysplastische Hufte und Skoliose Zur Beurteilung der Beziehung zwischen unilateraler Huftdislokation oder Subluxation und Skoliose wurden die Krankengeschichten von 31 Patienten im Alter von 10 bis Jahren mit Myelomeningocele und einem ersten Neurosegment bei L3 oder L4 durchgesehen. 11 Patienten hatten sich im Verlauf neurologisch verschlechtert, die restlichen hatten uber einen durchschnittlichen Untersuchungszeitraum von 14,3 Jahren unveranderte neurologische Befunde. Drei der neun Patienten mit unilateraler Huftinstabilitat hatten eine Skoliose, verglichen mit funf der restlichen 11 Patienten. Nur zwei Patienten hatten das erwartete Muster der unilateralen Huftinstabilitat an der erhohten Seite eines schiefen Bekkens mit einer zur anderen (niedrigen) Seite konvexen Skoliose. Mehrere unerwartete Muster wurden beobachtet. Der funktionelle neurosegmentale Bereich ist bei vielen Patienten mit Myelodysplasie nicht stabil. Bei Patienten mit gleichbleibender Neurologie sind unilaterale Huftinstabilitat und Skoliose co-morbide Faktoren und es konnte kein kausaler Zusammenhang gefunden werden. RESUMEN Cadera mielodisplasica y escoliosis Con el objeto de investigar la relacion entre la dislocacion o subluxacion unilateral de la cadera y la escoliosis, se examinaron las historias de 31 pacientes de 10 a 26 anos de edad con mielomeningocele y un nivel neurosegmentario inicial en L3 o L4. 11 pacientes habian sufrido una deterioracion neurologica con el tiempo, mientras que el resto tenian examenes neurologicos estables, con un seguimiento medio de 14,3 anos. La escoliosis aparecio en tres de los nueve pacientes con inestabilidad unilateral de la cadera, en comparacion con cinco de los otros 11 pacientes. Solo dos de los pacientes presentaban el patron esperado de inestabilidad unilateral de la cadera, en el lado alto de una pelvis oblicua, con escoliosis convexa del lado (bajo) opuesto. Se observaron diferentes patrones inesperados. El nivel neurosegmentario funcional no era estable en muchos pacientes con mielodisplasia. En pacientes neurologicamente estables, la inestabilidad unilateral de la cadera y la escoliosis son factores coincidentes, no habiendose identificado ninguna relacion causal.

Minimal model analysis of glucose and insulin concentrations in the intravenous glucose tolerance test (IVGTT) has been widely used to obtain a measure of insulin sensitivity in humans. Issues of model validity and IVGTT protocol have been explored extensively. Less attention has been paid, however, to the computer programming protocol for estimating the model parameters (programming implementation). Minimal model analysis of data from an IVGTT protocol involving a high glucose dose (0.5 g/kg) and a reduced sample schedule, employed in healthy pre- or post-menopausal women, healthy men or men with coronary heart disease or chronic heart failure (20 in each group), was undertaken according to 12 different programming implementations using a commercially available model-equation-solving program. The ability of the program to arrive at an acceptable solution to the model equations gave a success rate of between 39% and 96%, depending on the implementation. Variation in basal glucose assignment significantly affected the magnitude of estimates of insulin sensitivity. The maximum modelling success rate was achieved by introduction of an imputed glucose measurement at 360 min from the glucose injection, taking the basal glucose level as the fasting glucose concentration, and overweighting the initial glucose measurement after a delay for mixing. Use of this implementation to analyse data from a study comparing insulin sensitivities obtained using the minimal model and a euglycaemic clamp reference gave a correlation of 0.80 (P < 0.001) between the two methods. Straightforward variations in programming implementation, involving appropriate assignment of the basal glucose concentration and use of an imputed glucose measurement signifying re-establishment of basal glucose levels following the IVGTT, can considerably improve modelling success rate.

This study was conducted to explore whether the quality of provider care may contribute to blood pressure reduction and whether other factors related to the treatment of hypertension may explain decline in blood pressure. In the study, 46 uncontrolled ( ⩾ 140 90 mm Hg), medically treated hypertensive patients who received more personalized care differed significantly in the magnitude of blood pressure reduction from 36 usual-care patients ( 10 7 vs 2 2 mm Hg means for systolic and diastolic blood pressure reduction, respectively). About twice as many experimental patients as controls were reclassified as having “controlled” blood pressure, and this difference reached statistical significance. A multiple regression analysis for personalized-care subjects showed that no dynamic variables were related to blood pressure changes. It was postulated that more personalized care may have accounted for the significant difference between groups in blood pressure reduction. Similar personalized monitoring services might be important additions to usual medical care in order to control blood pressure more fully in high-risk hypertensive patients.

With the current interest in bipolar stimulation, there is a need for greater understanding of the electrical contributions of the two electrodes in this type of pacing. This has been investigated using a specially designed cell in which an electrode under test was immersed in a buffered saline solution (pH 7.42) at 37–38°C. Four electrode types were studied: a single stimulating electrode (6 mm2 dish tip, Pt-black coated) and three indifferent electrodes. The indifferent electrodes were a 41 mm2 polished Pt ring, a Pt-black coated version of the same electrode, and a titanium pacemaker enclosure which was included to allow comparison with the unipolar situation. These electrodes were tested individually against a chlorided silver reference electrode of negligible (1–2Ω) impedance, the results being processed in such a way as to allow estimation of the properties of the stimulating electrode taken in combination with each of the indifferents. Constant current pulses (1–10 mA amplitude, 0.5 and 1.0 ms duration) were applied and measurements made from the resulting voltage waveforms. These were V1 and V2, the potential at the leading and trailing edge of the pulse, and Va, the post-pulse potential at 20 ms following the trailing edge. The potential V1 - V2 is electrode dependent and allows the determination of the energy loss due to polarization to be calculated. Sinusoidal AC signals (0.1 Hz-10 kHz, 20 μA maximum amplitude) were also employed, allowing determination of sensing impedance. Under all conditions, the calculated performance of the stimulating electrode with the coated ring was nearly equivalent to that with the pacemaker enclosure. The performance with the uncoated ring was in all respects markedly inferior, displaying almost double the energy loss on pulsing, post-stimulus potentials an order of magnitude larger and sensing impedance increased by a factor of up to 8.

The effects of changes in stimulus interval and the infusion of isoprenaline upon myocardial depolarization and repolarization times have been determined using the unipolar ventricular evoked potential. An isolated perfused rabbit heart was the experimental vehicle and the stimulus-to-R wave (St-R) and R wave-to-end (R-E) of complex time intervals were used as measures of depolarization and repolarization times, respectively. Variation in the stimulus interval was shown to have highly statistically significant effects upon both of the parameters of the unipolar paced evoked potential that were investigated. Myocardial repolarization time is increased at longer intervals, while activation time is reduced. Isoprenaline was found to reduce the duration of the R-E interval of the unipolar ventricular evoked potential when infused at a constant rate at a fixed stimulus interval. At the maximum concentration of the drug, when stimulus interval was just shorter than the intrinsic RR interval, it was estimated that one third of the total change in the R-E interval was due purely to the effects of decreased stimulus interval. It proved impossible to identify any effect of isoprenaline infusion upon the St-R interval. The absence of any effect of isoprenaline on the St-R interval of the evoked potential suggests that it may serve as a monitor of purely stimulus interval dependent variations of the signal.

The endocardial unipolar paced evoked response has excited a great deal of interest due to its possible use in the measurement of the metabolic state of the body and other pacer-related areas. Although rate-responsive pacing utilizing this signal has been clinically evaluated, little is known regarding the behavior of the components of this waveform under normal physiological conditions. We have developed an electronic circuit which allows the recording of the evoked response within a few milliseconds of a pacing stimulus of 5 V and 0.5 ms duration being applied using a single unipolar, smooth platinum electrode of 14 mm2 surface area. The paced evoked response was measured using a total of 20 isolated rabbit heart preparations. Five were run for 8 hours and the remaining fifteen were run for 5 hours. Our results indicate that the waveform components of the evoked response remain stable while the preparation is viable, but that two of the time-related measurements change with loss of viability. A significant lengthening of the stimulus-R interval was seen together with a dramatic shortening of the R-T period. The net result of these changes was an overall reduction of 17% in the complex duration. In addition, we found the H-T shortening to be a sensitive measure of myocardial integrity. We conclude that the combination of our interface charge elimination circuit and the isolated heart preparation has proved a useful system for the investigation of the paced evoked potential. Furthermore, the loss of myocardial viability has a complex action on this response.

Investigation of the unipolar properties of the paced-evoked response requires special measures to eliminate the post-stimulus potential, and this in turn requires a knowledge of the properties of the electrode-tissue interface which is not supplied by any single source in the literature. We have therefore drawn together published information and some of our own experimental results. The behavior of a particular type of pacemaker electrode was investigated in vitro under a range of conditions. The application of DC potentials revealed an extremely nonlinear voltage-current characteristic with conduction thresholds at about +1 V and -1 V. Small signal AC response to applied voltages well within these values (20 mV pk-pk) was found to be linear when a nonpolarizable counterelectrode was used. Nonlinearities were introduced by the use of a stainless steel counterelectrode. The response of an in vitro model of a paced patient to voltage pulses (amplitude 5 V, duration 0.5 ms) was also investigated. We have made extensive use of previously published work to demonstrate the mechanisms underlying these results and also their relationship to each other. We have concluded with some theoretical comments upon the design requirements for a device to eliminate the post-stimulus afterpotential in order to detect the paced-evoked response.

Summary Seismic methods are becoming more common place in coal seam mining as an accurate and cost effective met hod of imaging the seam structure. Burton Downs colliery in Queensland, Australia is one such mine to take advantage of the seismic method. With no previous seismic work done in the area, reverse vertical seismic profiling (RVSP) and two-dimensional (2-D) surveys were initially shot. RVSP results showed that the seismic method was viable, imaging the coal seam of interest (VSP to CDP mapping) and provided acquisition parameters for the 2-D surveys. The 2-D lines gave high-resolution images of the coal seams across the mine area, and showed a complex faulting system which included low-angle reverse faulting and normal faulting. The success of the 2-D profiles prompted the acquisition of a three-dimensional (3-D) survey in the northern (Kerlong) area of the mine. After processing the 3-D depth volume, a much more complete structural interpretation could be made.

A recent study has revealed the extent of the obstacles to choice and control in residential settings for people with learning disabilities. In the first part of this article the first two authors highlight the key messages for practice. In the second part of the article the Social Care Institute for Excellence provides an overview of other research and resources on residential services and learning disabilities.

Godsland IF, Levya F, Walton C, Worthington M, Stevenson JC (Imperial College School of Medicine, London, UK). Associations of smoking, alcohol and physical activity with risk factors for coronary heart disease and diabetes in the first follow-up cohort of the Heart Disease and Diabetes Risk Indicators in a Screened Cohort study. J Intern Med 1998; 244: 33–41. Objectives To investigate the associations between risk factors for cardiovascular disease and cigarette smoking, alcohol intake, and physical activity in a group of predominantly healthy men. Design Cohort study with baseline characterisation, clinical follow-up, and identification of predictors of coronary artery disease and diabetes. Setting University hospital metabolic day ward. Subjects Participants in a company health programme (n= 742). Main outcome measures Routine haematology and biochemistry, cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol (on a subset of 522 subjects), and glucose and insulin levels during a 3 h oral glucose tolerance test (OGTT). Results Independent associations with previous cigarette smoking included high uric acid and low HDL cholesterol, and with current cigarette smoking, high haemoglobin and white cell count and low OGTT insulin. Increasing alcohol intake was associated with increasing blood pressure, uric acid, HDL cholesterol and fasting glucose. The moderate range of exercise intensity in this cohort was associated with decreasing systolic blood pressure, fasting insulin and OGTT glucose and insulin. Factor analysis distinguished principal factors comprising features of the metabolic syndrome with low physical activity, and high white cell count, high haemoglobin concentration and low HDL cholesterol with increasing previous and current cigarette smoking and alcohol intake. Conclusions Some characteristics of the metabolic syndrome were seen with previous but not current smoking habit. Regular alcohol consumption was associated with mainly unfavourable metabolic characteristics, although there was an independent beneficial association with HDL cholesterol. The improved metabolic syndrome profile seen with increasing exercise is consistent with even moderate degrees of physical activity having beneficial effects on metabolism.

Background Pleurostomophora richardsiae (formerly Phialophora richardsiae) is a dematiaceous fungus that is an uncommon cause of ocular infection. Herein, we present a case of endogenous endophthalmitis associated with disseminated P. richardsiae infection. Findings This is a descriptive case report with a brief review of literature. A 43-year-old male admitted to the hospital following an acute cerebellar hemorrhage was found to have a swollen and tender wrist. The patient was afebrile with leukocytosis. Visual acuity was hand motion in the right eye and 20/20 in the left. Right eye examination noted anterior chamber cells and flare, vitreous haze and multiple large, and fluffy retinal infiltrates. Diagnostic vitrectomy revealed a mixed inflammatory cell infiltrate with numerous fungal elements. Blood cultures were negative, multiple transesophageal echocardiography studies revealed no vegetations, and synovial fluid aspiration of the wrist and biopsy of the radius were unremarkable. The patient was treated with intravitreal cefazolin, vancomycin, and amphotericin B, topical ciprofloxacin and natamycin, and intravenous amphotericin B and voriconazole. Visual acuity in the right eye declined to light perception, and examination revealed increasing anterior and posterior chamber inflammation. The patient died several weeks after presentation due to a massive intracranial hemorrhage. Fungal culture results from the vitrectomy were received post mortem and were positive for P. richardsiae. Conclusions P. richardsiae endophthalmitis is rare, and outcomes are typically poor. Infections typically occur following traumatic skin inoculation; however, a long refractory period may occur before symptoms develop. Early diagnosis and combination antimicrobial therapy are essential to optimize visual outcomes.