Pre-clinical Cushing's syndrome: an unexpected frequent cause of poor glycaemic control in obese diabetic patients

OBJECTIVE Autonomous cortisol secretion without clinical stigmata of Cushing's syndrome (CS) has been recently recognized and termed pre-clinical or sub-clinical CS. The common assumption is that CS is an extremely rare cause of uncontrolled diabetes; however, the prevalence of this entity has not been studied. We assessed the prevalence of pre-clinical CS among obese patients with uncontrolled diabetes. PATIENTS AND DESIGN (1) In a retrospective analysis, the medical records of 63 patients with endogenous CS were reviewed. (2) In a cross-sectional study, 90 obese patients (BMI >25 kg/m²) followed in a University Hospital and the local Health Fund endocrine and diabetes clinics, with poorly controlled diabetes (glycosylated haemoglobin >9%), underwent an overnight 1 mg dexamethasone suppression. In patients with non-suppressible cortisol levels (>140 nmol/l), Liddle's 2 and 8 mg dexamethasone suppression tests and imaging studies were performed. MEASUREMENTS The prevalence of poorly controlled diabetes, the major presenting symptom of CS, was assessed in the retrospective analysis. The prevalence of ‘true’ CS and the false positive rate in the overnight dexamethasone suppression test were calculated. The endocrine evaluation of the patients with pre-clinical CS and the effects of surgical cure on glycaemic control are described. RESULTS In the retrospective analysis, 11 (17.5%) had diabetes and 2 (3.2%) lacked the classic physical characteristics of the syndrome. In the cross-sectional study, 4 patients failed to suppress plasma cortisol (<140 nmol/l). In one patient the diagnosis of CS was not confirmed by a standard Liddle’s test and was therefore considered false positive. In the other 3, the diagnosis of CS was confirmed (prevalence of 3.3%, 95% confidence interval 1–9%). In all other patients the overnight cortisol suppression test was normal (cortisol level 47.3 ± 2.5 nmol/l (mean ± SEM)). After surgical treatment of CS, glycaemic control was markedly improved in all 5 patients (2 from retrospective and 3 from cross-sectional studies). CONCLUSIONS The prevalence of pre-clinical Cushing's syndrome in obese patients with poorly controlled diabetes appears to be considerably higher than previously believed. The overnight dexamethasone suppression test proved to be a simple, sensitive and highly specific screening test for Cushing's syndrome despite the presence of obesity and hyperglycaemia.     

Ventriculosubcutaneous shunt for temporary treatment of neonatal post-IVH hydrocephalus: a technical note

A technique for temporary ventricular drainage using a subcutaneous pouch is described for use in neonatal hydrocephalus after intraventricular hemorrhage. The advantages include continuous, valve-regulated ventricular decompression, no exposed tubing, avoidance of electrolyte imbalance and of the loss of CSF, obviation of the need for repeated tapping, and the ability to convert to a peritoneal shunt on an elective basis.     

Post‐traumatic reactions among rescue personnel 96 hours after the Hilton Hotel bombing in Sinai: The effect of previous exposure

This paper considers the immediate post‐traumatic reactions of rescue personnel who were exposed to the Hilton Hotel bombing in Sinai. The entire rescue personnel (n = 26) were assessed and separated into two groups on the basis of previous exposure to the same type of trauma. The results suggest that among rescue personnel, those with previous exposure had a lower level of post‐traumatic symptoms than those who were being exposed for the first time. This supports the hypothesis that previous exposure to the same type of trauma has an immunizing effect for subsequent same type of traumatic event among rescue personnel. Copyright © 2005 John Wiley & Sons, Ltd.     

The control of hypertension, atherosclerotic diseases, and diabetes in a family practice

A community-orientated programme for the control of hypertension, atherosclerotic disease, and diabetes has been developed in a family practice in a neighbourhood of Jerusalem. Intervention is directed mainly towards the control of risk factors associated with these diseases.

The programme has specific objectives for diet, smoking, obesity, blood pressure, serum cholesterol, glucose intolerance, and diabetes mellitus, and the identification and treatment of patients with cardiovascular diseases. The survey seeks to identify the nature and extent of problems, intervention by medicinal and educational means, and continuing surveillance and evaluation.

The programme aims to test and demonstrate the feasibility of carrying out multifactorial community health care within the framework of a family practice, thereby developing a joint practice of primary health care and community medicine.

     

Rapid activation of glycogen synthase and protein phosphatase in human skeletal muscle after isometric contraction requires an intact circulation

The effects of isometric contraction (66% of maximal force) and recovery on glycogen synthase fractional activity (GSF) in human skeletal muscle have been studied. Biopsies were taken from the quadriceps femoris muscle at rest, at fatigue and 5 min postexercise on two occasions: after one of the contractions, the circulation to the thigh was occluded during the 5 min recovery (OCC), and after the other contraction, the circulation was intact (control, CON). During CON, GSF decreased from (mean ± SE) 0.34±0.05 at rest to 0.24±0.02 at fatigue and then increased to 0.74±0.04 at 5 min postexercise; corresponding values for OCC were 0.37±0.04, 0.25±0.04 and 0.48±0.05 (P<0.001 vs. CON for 5 min postexercise only). Compared with the value at fatigue, protein phosphatase activity (PP) increased by 79±16% during CON recovery (P<0.01), whereas no change was observed during OCC recovery. Uridine diphosphate glucose increased by approximately 2.5-fold at fatigue, remained elevated during OCC recovery, but reverted to the preexercise level during CON recovery (P<0.001 vs. OCC recovery). Glucose 6-P increased approximately 5-fold at fatigue and was higher at 5 min postexercise in OCC vs. CON recovery (8.6±1.5 vs. 4.1±0.9 mmol/kg dry wt; P<0.01). It is concluded that the rapid increase in GSF after intense exercise with an intact circulation may be at least partly attributed to an increase in the specific activity of PP. The increase in GSF during recovery in OCC may be at least partly attributed to the high glucose 6-P content in vivo, which enhances the substrate suitability of GS for PP. Thus, separate mechanisms exist for the activation of PP and GS during recovery from intense short term exercise.     

Evaluation of an accelerated protocol for detection of extended-spectrum beta-lactamase-producing gram-negative bacilli from positive blood cultures

We evaluated a protocol for the accelerated detection of extended-spectrum beta-lactamases (ESBLs) in gram-negative bloodstream pathogens. Two hundred eighty-three blood culture bottles were subjected to direct ESBL testing by inoculating samples directly from blood culture bottles onto agar plates containing cefotaxime and ceftazidime disks, with and without clavulanate. Standard ESBL testing in accordance with the NCCLS guidelines after subculturing on agar plates was performed in parallel. Results of the direct ESBL testing were reported 2.3 days sooner and were comparable to those of the standard NCCLS method with sensitivity, specificity, and positive and negative predictive values of 100, 98, 94, and 100%, respectively.     

Switching yeast from meiosis to mitosis: double-strand break repair, recombination and synaptonemal complex

Background:

When Saccharomyces cerevisiae cells that have begun meiosis are transferred to mitotic growth conditions (‘return-to-growth’, RTG), they can complete recombination at high meiotic frequencies, but undergo mitotic cell division and remain diploid. It was not known how meiotic recombination intermediates are repaired following RTG. Using molecular and cytological methods, we investigated whether the usual meiotic apparatus could repair meiotically induced DSBs during RTG, or whether other mechanisms are invoked when the developmental context changes.

Results:

Upon RTG, the rapid disappearance of meiotic features—double-strand breaks in DNA (DSBs), synaptonemal complex (SC), and SC related structures—was striking. In wild-type diploids, the repair of meiotic DSBs during RTG was quick and efficient, resulting in homologous recombination. Kinetic analysis of double-strand breakage and recombination indicated that meiotic DSB formation precedes the commitment to meiotic levels of recombination. DSBs were repaired in RTG in dmc1, but not rad51 mutants, hence repair did not occur by the usual meiotic mechanism which requires the Dmc1 gene product. In haploids, DSBs were also repaired quickly and efficiently upon RTG, showing that DSB repair did not require the presence of a homologous chromosome. In all strains examined, SC and related structures were not required for DSB repair or recombination following RTG.

Conclusions:

At least two pathways of DSB repair, which differ from the primary meiotic pathway(s), can occur during RTG: One involving interhomologue recombination, and another involving sister-chromatid exchange. DSB formation precedes commitment to recombination. SC elements appear to prevent sister chromatid exchange in meiosis.

     

Infection of a ventriculoatrial shunt with phenotypically variable Staphylococcus epidermidis masquerading as polymicrobial bacteremia due to various coagulase-negative Staphylococci and Kocuria varians

The diagnosis of bloodstream infection with coagulase-negative staphylococci is frequently based on the isolation of the same organism from more than one blood culture. Phenotypic variation is a common characteristic of pathogenic strains of Staphylococcus epidermidis which may affect species identification by the microbiology laboratory. We describe a patient with a new onset of nephritis and gram-positive bacteremia. Gram-positive cocci grew in multiple blood cultures and were identified by the Vitek 2 system as Kocuria varians, Staphylococcus hyicus, and S. epidermidis. Bacterial isolates grew on blood agar and Congo red agar plates as two distinct morphotypes and exhibited phenotypic variation. Neither morphotype could be identified by the API-Staph assay. Cellular fatty acid analysis identified one of the morphotypes as S. epidermidis but could not identify the other morphotype. All isolates were found to be identical by pulsed-field gel electrophoresis, and both colonial morphotypes were identified as S. epidermidis by 16S ribosomal gene sequencing. Phenotypic variation of S. epidermidis may affect identification to the species level by phenotype-based identification systems. Caution should be exercised when differentiating between true infection and contamination based on strain identification.