Intestinal Anastomoses from Diabetic Rats Contain Supranormal Levels of Gelatinase Activity

PURPOSE: Early postoperative strength in intestinal anastomoses is reduced in diabetic rats, whereas collagen deposition is essentially unchanged, suggesting that increased matrix degradation may be the cause of diminished wound strength. The aim of this study was to investigate whether (gelatin-degrading) matrix metalloproteinase activity is enhanced in intestinal anastomoses from diabetic rats. METHODS: Sixty male young adult Wistar rats underwent resection and anastomosis of both ileum and colon. In half the animals diabetes was induced seven days before operation by streptozotocin injection (50 mg/kg intravenously). Gelatinase activities in extracts from uninjured intestine and anastomoses at one, three, or seven days after surgery were measured by quantitative gelatin zymography. RESULTS: After surgery, profound changes were observed with time for gelatinase activities with molecular weights of 50 and 60 kDa, thought to represent matrix metalloproteinase-2, and of 66, 80, 105, 140, 220, and 260 kDa, thought to represent various forms of matrix metalloproteinase-9. In many cases, specific activities were significantly (P < 0.05) higher in the anastomotic extracts from diabetic rats. Total anastomotic activities present at Day 7 were strongly elevated for most matrix metalloproteinase forms in ileum and colon from diabetic animals. CONCLUSION: Experimental diabetes leads to a sustained and elevated presence of gelatinase activity in intestinal anastomoses. Increased local matrix degradation may contribute significantly to impaired anastomotic strength in the intestine observed under this condition.     

Mechanisms involved in the loss of excitatory post-stimulus responses by inflammation

AIM: Electrical stimulation of colonic muscles elicits a response during the stimulation period, and a transient excitation after the stimulus. Post-stimulus or "rebound" excitation has been linked to pathways involving inhibitory neurotransmitters, prostaglandins and substance P but the mechanism is incompletely understood. Because rabbit colitis is characterized by a loss of inhibitory neurotransmission we hypothesized it might affect the rebound response. Therefore we characterized rebound responses in non-inflamed and inflamed tissue by comparing the effect of antagonists/blockers of putative (nitric oxide [NO], ATP, substance P, prostaglandins) and new (serotonin) neurotransmitters. METHODS: Strips from rabbits with colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) were subjected to electrical field stimulation. Because rebound responses are more prominent under nonadrenergic noncholinergic (NANC) conditions, the effect of specific antagonists (N(omega)-nitro-L-arginine methyl ester (L-NAME), indomethacin, SR140333, methiothepin) on the rebound response was compared under normal and NANC conditions. RESULTS: NANC-conditions increased rebound responses in non-inflamed strips, but this effect was reduced or abolished in inflamed strips. Rebound responses were reduced by pretreatment with the NO-synthase inhibitor, L-NAME, under NANC conditions in non-inflamed strips but not affected in inflamed tissue. In contrast, the P(2) purine receptor antagonist, suramin, did not affect rebound responses in inflamed and non-inflamed strips. The effect of the cyclo-oxygenase inhibitor (COX), indomethacin, on rebound responses was reversed from excitatory to inhibitory by inflammation. Under NANC conditions rebound contractions were also reduced by the neurokinin-1 (NK(1)) antagonist, SR140333, both in normal and inflamed strips. The most pronounced reduction in rebound responses in inflamed and non-inflamed strips under normal conditions was observed with the 5-hydroxytryptamin (1,2) (5-HT(1,2)) antagonist, methiothepin. CONCLUSION: Rebound responses are mainly non-cholinergic and involve NO, substance P, serotonin and inhibitory prostaglandins. In inflamed tissue the nitrergic pathway is absent, excitatory prostaglandins prevail and the cholinergic and tachykinergic components are relatively more important. However there remains an important serotonergic contribution. Our data suggest that inflammation damages different neural pathways to a different extent and is most selective for nitrergic pathways.     

'Body-packer' syndrome: an important disease with forensic-medical aspects

A 45-year-old man called for the hospital in a confused and anxious state. Another man of around 30 walked into a hospital sweating and complaining of abdominal pain, and subsequently suffered several epileptic seizures and died before being recognised as a body packer. A 39-year-old man suffered an epileptic seizure on the aeroplane and a 21-year-old man was found dead, having suffered from abdominal pain the previous day. All were found to have swallowed cocaine packets. The two eldest men underwent emergency surgery: one died as the result of cocaine intoxication and one recovered. Body packers, people carrying cocaine packets in their bodies, are arriving in Europe in increasing numbers, mainly from South America. Body-packer syndrome consists of intestinal occlusion or potentially lethal intoxication caused by rupture of the packets. Awareness of the body packers' circumstances and the clinical signs of body-packer syndrome makes early recognition possible. In Amsterdam, the identification of body packers after arrival at the airport by the Schiphol-team and the medical follow-up by the Forensic Medicine Department of the Municipal Health Service of Amsterdam, result in a relatively low mortality risk. Early detection of intoxication will save lives.     

Results of the pilot study for the Hypertension in the Very Elderly Trial

BACKGROUND: The risks and benefits of treating hypertension in individuals older than 80 years are uncertain. A meta-analysis has suggested that a reduction in stroke events of 36% may have to be balanced against a 14% increase in total mortality. OBJECTIVES: To report the results of the pilot study of the Hypertension in the Very Elderly Trial (HYVET), which is in progress to address these issues. METHODS: The HYVET-Pilot was a multicentre international open pilot trial. In 10 European countries, 1283 patients older than 80 years and with a sustained blood pressure of 160-219/90-109 mmHg were allocated randomly to one of three treatments: a diuretic-based regimen (usually bendroflumethiazide; n = 426), an angiotensin-converting enzyme inhibitor regimen (usually lisinopril; n = 431) or no treatment (n = 426). The procedure permitted doses of the drug to be titrated and diltiazem slow-release to be added to active treatment. Target blood pressure was < 150/80 mmHg and mean follow-up was 13 months. RESULTS: In the combined actively treated groups, the reduction in stroke events relative hazard rate (RHR) was 0.47 [95% confidence interval (CI) 0.24 to 0.93] and the reduction in stroke mortality RHR was 0.57 (95% CI 0.25 to 1.32). However, the estimate of total mortality supported the possibility of excess deaths with active treatment (RHR 1.23, 95% CI 0.75 to 2.01). CONCLUSIONS: The preliminary results support the need for the continuing main HYVET trial. It is possible that treatment of 1000 patients for 1 year may reduce stroke events by 19 (nine non-fatal), but may be associated with 20 extra non-stroke deaths.     

Retrospective study of topiramate in a paediatric population with intractable epilepsy showing promising effects in the West syndrome patients

Topiramate (TPM) is a new anti-epileptic drug with proven efficacy against partial seizures in adults. Its use in children is less well documented. In a retrospective study, 41 patients with intractable childhood epilepsy were treated with TPM as add-on therapy for an average period of 15 months. They were classified according to seizure type and etiology. The dose was titrated for effect and ranged between 2 and 24 mg/kg/d. Of the 41 patients being treated, six became seizure free, ten had a seizure reduction of more than 75% and eight a seizure reduction of between 50 and 75%. The most remarkable effect was seen in seven patients with West syndrome. Of these, four patients became seizure free and one had more than 75% seizure reduction. Adverse effects including sedation, fatigue, difficulties with verbal expression and anorexia were noted in 15 patients. None of these effects were important enough to interrupt treatment. We conclude that TPM as adjunctive therapy is a promising drug in children with intractable epilepsy, especially in the patients with West syndrome.     

Conventional or adhesive external breast prosthesis? A prospective study of the patients' preference after mastectomy.

After having been subjected to radical mastectomy for breast cancer, women are usually fitted with an external breast prosthesis. Different types of prostheses are available, but oncology nurses have few data enabling them to advise their patients adequately. In this prospective randomized crossover study of 101 women undergoing one-sided mastectomy for breast cancer, the self-adhesive breast prosthesis was compared with the traditional external prosthesis. Questionnaires were used to evaluate the woman's judgment of the prosthesis in relation to her final preference for one type of prosthesis. Complete data were available for 91 women, 59.3% of whom finally preferred the self-adhesive type. Preference was independent of age, randomization, order, or the possible use of adjuvant chemotherapy. Satisfaction with the self-adhesive prosthesis was independent of randomization order but satisfaction with the traditional type was significantly more when it was the first type of prosthesis. Preference for the self-adhesive prosthesis over the traditional type mas mainly related to an increased perception of the prosthesis as a part of the body. Preference for the traditional prosthesis over the other type was mainly related to the greater ease of application and the lesser local irritation of the skin. Findings from this study can be useful in oncology nursing practice.