Fatal self-induced hyperinsulinaemia: a delayed post-mortem analytical detection.

The inconspicuous number of cases of self-induced hyperinsulinaemia reported in the literature may suggest that many are obscure enough to escape their detection. A case of fatal suicidal hyperinsulinaemia in a non-diabetic is reported here, and in whom only a retrospective biochemical analysis provided an explanatory cause of death. A quantitative radioimmuno assay (RIA) estimation of the refrigerated postmortem blood sample stored at 4 degrees C for three weeks gave a positive insulin yield. It reiterates the need, in forensic cases, for a very low threshold of suspicion and a good back-up for the appropriate body fluid analysis or tissue microexamination, especially when full details of the circumstances surrounding the death are not available at the autopsy. A brief résumé on insulin is presented as a background to the current forensic interest in the apparent increase in sudden deaths in young diabetics amidst the controversy about the bio-designed 'human' insulin and subjective unawareness of severe hypoglycaemia.     

Fournier''s gangrene of the scrotum following day case vasectomy.

A case of Fournier's gangrene of the scrotum is reported in a 31-year old man who had outpatient vasectomy during an intercurrent diarrheal illness. The surgery was done through a midline incision, under local anesthesia of plain 2% lignocaine, with a preoperative chlorhexidine scrub. Although his scrotum was red and swollen within 3 hours, he did not have medical care until admission to hospital 48 hours later. At admission he had Fournier's gangrene of the scrotum and penis, Gram-negative septic shock, and acute renal failure. In the intensive care unit he was treated with continuous dialysis, parenteral metronidazole, benzylpenicillin, Ceftazidime and inotropes. He had a cardiorespiratory arrest after emergency radical debridement. After resuscitation he developed adult respiratory distress syndrome and disseminated intravascular coagulation. Pathological exam showed necrosis of the dermis and subcutaneous layers, thrombosis and beta-hemolytic streptococci. After adding gentamicin and vancomycin, 2 weeks of ventilator care, 4 more surgical debridements, a left orchidectomy, and a despite a grossly abnormal EEG recording, the man regained consciousness and recovered. His scrotal and penile skin re-epithelialized over 3 months. Patients requesting vasectomy should be assessed for local and systemic illness before performing the procedure.     

Trigger fingers and thumb: when to splint, inject, or operate.

Fifty trigger fingers were treated by splinting of the metacarpophalangeal joint at 10 to 15 degrees of flexion for an average of 6 weeks (range, 3 to 9 weeks). Another 50 trigger fingers were injected with 0.5 ml of betamethasone sodium phosphate and acetate suspension (Celestone) and 0.5 ml of lidocaine. All patients were followed up for a minimum of 1 year (range, 1 to 4 years). Treatment was successful in 33 (66%) of the splinted digits and 42 (84%) of the injected digits. Fifty percent of the 10 splinted thumbs and 70% of the 40 splinted fingers had a successful outcome. Of the 17 unsuccessfully treated digits in the splinted group, 15 were later cured with injections and 2 required surgery. All of the 7 unsuccessfully treated digits in the injected group were cured with surgery. Patients with marked triggering, symptoms of more than 6 months' duration, and multiple involved digits had a higher rate of failure in both groups. Splinting offers an alternative for patients who have a strong objection to cortisone injection.     

Human breast cancer cells contain a phosphoramidon-sensitive metalloproteinase which can process exogenous big endothelin-1 to endothelin-1: a proposed mitogen for human breast fibroblasts.

Endothelin-1 (ET-1) levels are elevated in human breast tumours compared with normal and benign tissues, and in the presence of insulin-like growth factor 1 (IGF-I) ET-1 is a potent mitogen for human breast fibroblasts. In this study we have examined the ability of intact human breast cancer cell lines to process exogenously added big ET-1 (1-38) to the active mature ET-1 peptide by using a specific radioimmunometric assay. In both hormome-dependent (MCF-7, T47-D) and hormone-independent (MDA-MB-231) breast cancer cell lines the putative endothelin-converting enzyme (ECE) exhibited apparent Michaelis-Menten kinetics when converting added big ET-1 to ET-1. Both basal ET-1 production and exogenously added big ET-1 to ET-1 conversion were greatly reduced in all three cell lines in response to the metalloproteinase inhibitor phosphoramidon but were insensitive to other classes of protease inhibitors. Inhibition was also observed when cells were incubated in the presence of the divalent cation chelators 1,10-phenanthroline and EDTA. In MCF-7 cells the optimal pH for the ECE activity using a saponin cell permeabilisation procedure was found to residue within a narrow range of 6.2-7.26. Our results indicate that human breast cancer cells contain a neutral phosphoramidon-sensitive metalloproteinase which can process big ET-1 to ET-1. In the breast this conversion could contribute substantially to the local extracellular levels of this proposed paracrine breast fibroblast mitogen.     

Unlabeled uses of botulinum toxins: a review, part 1.

PURPOSE: Efficacy and safety data regarding the unlabeled uses of botulinum toxins are reviewed, and the pharmacology, adverse effects, and characteristics of commercially available botulinum toxins are discussed. SUMMARY: More than 300 articles have been published on the use of botulinum toxins, particularly botulinum toxin type A, to treat conditions characterized by excessive smooth or skeletal muscle spasticity. Botulinum toxins are synthesized by Clostridium botulinum and cause temporary local paralysis of the injected muscle by inhibiting acetylcholine release at the neuromuscular junction. While botulinum toxins have Food and Drug Administration-approved labeling to treat a limited number of spasticity disorders, including cervical dystonia and blepharospasm, the toxins have more than 50 reported therapeutic uses. Among these uses, the most rigorously studied indications include achalasia, essential tremors, palmar hyperhidrosis, chronic anal fissures, headache prophylaxis, and limb spasticity. The main adverse effects of the toxins are pain and erythema at the injection site, although unintended paralysis of muscles adjacent to the site of toxin injection may also occur. CONCLUSION: Clinical studies support the use of botulinum toxins for certain conditions, although more studies are needed to establish the role of the drug relative to conventional therapies and to determine patient predictors of response. Although botulinum toxins are generally well tolerated, a patient-specific risk-benefit assessment should precede any decision to use them for unlabeled indications.     

Expression of a single dopamine transporter cDNA can confer two cocaine binding sites.

Radiolabeled cocaine analogs can bind to low and high affinity sites on striatal dopamine transporters (DAT). Recently, a cDNA encoding a rat brain dopamine transporter pDAT1 has been cloned. COS cells transfected with the pDAT1 in a eukaryotic expression vector express both a high (KD = 3.4 nM) and low affinity (KD = 163.6 nM) cocaine binding sites, suggesting that both sites are provided by a single gene product.     

A classification for dry eyes following comparison of tear thinning time with Schirmer tear test.

In a double-blind study a non-invasive method of examining the stability of the precorneal tear film was used to record tear thinning time on a population of 34 independently diagnosed dry eye patients. The results were compared with those for tear output, as inferred from the standard Schirmer tear test, and a correlation coefficient of 0.20 determined. The mean tear thinning time and Schirmer results for the population sample were 6.87 +/- 2.97 sec, and 5.62 +/- 5.69 mm wetting in 5 min, respectively. From a plot of tear thinning time against Schirmer a simple classification for dry eyes can be made. A Type A with normal tear stability and low output accounting for 14.70% of the dry eyes. A Type B with low tear stability and normal output, also accounting for 14.70% of the dry eyes. A Type C with low stability (less than 9.84 sec), and low output (less than 11.31 mm wetting in 5 min) accounting for 70.60% of the dry eyes.     

A novel series of non-quaternary oxadiazoles acting as full agonists at muscarinic receptors

1 A novel series of non-quaternary oxadiazole-based muscarinic agonists demonstrated high affinity for muscarinic receptors. 2. These agonists possessed high efficacy in the nanomolar range at muscarinic receptors in the superior cervical ganglion, atrium and ileum but did not show selectivity across the tissue preparations. 3. Two amino oxadiazoles, one from a quinuclidine series (L-660,863) and one from a 1-azanorbornane series (L-670,207) possessed a high ratio of potency for displacing the binding of [3H]-N-methyl-scopolamine ([3H]-NMS) to potency for displacing the agonist [3H]-oxotremorine-M cortex. 4. The two azanorbornane derivatives L-670,548 and L-670,207 stimulated the turnover of phosphatidylinositol in the cortex with a potency higher than that obtained with any other known muscarinic agonist (ED50 0.26 and 0.18 microM respectively). 5. The maximum response obtained with L-670,207 was greater than that observed for carbachol but was comparable to that of the natural ligand acetylcholine. 6. These oxadiazole muscarinic agonists are among the most potent and efficacious non-quaternary muscarinic agonists ever described.