The Relative Importance of Mutagens and Carcinogens in the Diet

Known mutagens and carcinogens in the diet were compiled and the risk of cancer was estimated on the basis of average exposure levels in Switzerland and carcinogenic potencies from rodent bioassays. The analysis showed that, except for alcohol, the sum of all known dietary carcinogens could only explain a few percent of the cancer deaths attributed by epidemiologists to dietary factors. The discrepancy was explained by a “carcinogenicity” of excess macronutrients. This hypothesis was based on an evaluation of dietary restriction experiments in rats and mice, where a dramatic reducing effect on spontaneous tumour formation was seen. From these experiments, a "carcinogenic potency" was deduced for food in excess (TD₅₀ approximately 16 g/kg per day). Overnutrition in Switzerland was converted into excess food intake and the cancer risk estimated on the basis of the TD₅₀ value. The resulting risk of 60,000 cases per one million lives would allow to explain by overnutrition almost all "diet-related" cancer deaths in humans.     

Poisoning in children

Drug-induced poisoning of children represents a serious medical as well as a social problem linked both to the fields of prevention and therapy. This paper analyses the occurrence and the causative agents of poisoning cases of children under the age of 15, hospitalized in a children's hospital over a two-year period (1985–1986). 33 Poisoning cases represented 1.7% of all hospitalizations, and 49% thereof were induced by drugs.     

Effects of carbonyl cyanide p-trichloromethoxyphenylhydrazone (CCCP) and of ruthenium red (RR) on capsaicin-evoked neuropeptide release from peripheral terminals of primary afferent neurones

Summary In the superfused isolated rat urinary bladder, capsaicin as well as electrical field stimulation evoked the release of calcitonin gene-related peptide-like immunoreactivity (CGRP-IR). Carbonyl cyanide p-trichloromethoxyphenylhydrazone (CCCP, threshold 2 M) reduced both, the capsaicin- and the electrical field stimulation-evoked release of CGRP-IR while a low concentration of Ruthenium Red (RR, 0.6 M and 2 M) selectively attenuated the capsaicin-evoked release of CGRP-IR but did not influence the effect of electrical field stimulation. 20 M RR nearly abolished the capsaicin-evoked release, but also attenuated the effect of electrical field stimulation.In the isolated guinea-pig bronchus, electrical field stimulation and capsaicin induced non-cholinergic contractions which are known to be caused by tachykinin release from afferent nerve terminals. CCCP (0.6 M) only reduced the response to field stimulation; a ten-fold higher concentration of CCCP attenuated field stimulation as well as capsaicin-induced contractions. This is in contrast to the reported selective inhibition of capsaic-ininduced contractions by RR.The present data demonstrate that CCCP generally inhibits evoked neuropeptide release, regardless of the kind of stimulation used while low concentrations of RR preferentially inhibit capsaicin-evoked neuropeptide release.Send offprint requests to: R. Amann at the above address     

Temporary strecker stent for management of acute dissection in popliteal and crural arteries

Stent placement is a widely used bail-out treatment for dissection of peripheral arteries. Below the level of the superficial femoral artery permanent stenting is complicated by a high incidence of subacute thrombosis and restenosis. We present two cases of arterial occlusion due to acute iatrogenic dissection of the popliteal and distal fibular arteries. Successful treatment was achieved with a new bail-out procedure. Strecker stents were implanted to seal off the dissection flap. Stents were retrieved easily after 24 hr using a myocardial biopsy forceps. After stent retrieval the temporarily stented segments were patent and showed a larger lumen compared with segments treated by balloon dilatation alone. Temporary stenting is a simple and safe procedure and offers the advantage of tacking up dissection membranes and preventing recoil. Persistent presence of a metallic implant as a source of continued injury and stimulus for intimal proliferation is avoided.     

A molecular scheme for the reaction between γ-aminobutyric acid and the most abundant chloride channel on crayfish deep extensor abdominal muscle

Single-channel measurements were performed with the aim of constructing a detailed molecular scheme for the reaction between -aminobutyric acid (GABA) and a chloride channel of crayfish deep extensor abdominal muscle (DEAM). GABA was applied in pulses to outside-out patches of muscle membrane, and, based on the dose-response of the peak currents and of their rise times, a linear model with five binding steps has been proposed. Evaluation of the single-channel kinetics indicated at least three open states. Two of them originate most probably from the fully liganded receptor state and are grouped in mixed bursts due to their different life times. The third one appears independently, outside the bursts, and originates from a lower liganded receptor state. Simulations of the dose-responses and the open time distributions with this model led to a set of rate constants which generated relatively optimal fits.     

Postocclusive cutaneous vasodilatation mediated by substance P

1. The cutaneous vasodilatation following arterial occlusion ("reactive hyperemia") was studied in the rat hind paw. A peak increase in venous outflow of 200-250% was observed within 1 min after a 3 min occlusion period. 2. Chronic denervation as well as capsaicin pretreatment reduced the postocclusive cutaneous vasodilatation by more than 60% (P less than 0.01). This demonstrates that the reactive vasodilatation is of neurogenic origin and mediated by small diameter afferent fibres. 3. Reduction of the postocclusive cutaneous vasodilatation after histamine depletion by compound 48/80 indicates the involvement of histamine. 4. Among all neuropeptides known to occur in primary sensory neurones only substance P and vasoactive intestinal polypeptide cause vasodilatation when infused i.a. into the rat paw. In contrast to antidromic sensory nerve stimulation or i.a. substance P infusion, vasoactive intestinal polypeptide does not cause plasma extravasation. The vasodilator potency of vasoactive intestinal polypeptide is about 1/500 of substance P in the rat paw. Therefore only substance P is able to mimic the reactive vasodilatation. 5. It is concluded that the postocclusive cutaneous vasodilatation is caused mainly by the release of substance P from peripheral endings of small diameter nerve fibres. The "axon reflex", also involving neurogenic vasodilatation, is assumed to be exerted by the same mechanism.     

The pathophysiology of enterocutaneous fistulas

The patient with an enterocutaneous fistula represents a high-risk situation with overall mortality rates of up to 20%, depending on the series. Treatment of these patients to a successful outcome requires attention to detail and, if necessary, meticulous operative technique. For convenience, care of these patients is divided into 5 phases:

1. Stabilization. Resuscitation with crystalloid colloid and/or blood. Drainage of only obvious abscesses. Beginning of local wound care. Initiation of nutritional support.
2. Investigation. Radiographic investigation of local fistula area, principally by sinography and, if necessary, other contrast studies. Purpose of these studies is to determine likelihood of spontaneous closure with nutritional support.
3. Decision. Is operation indicated and, if so, when? A decision must be made as to the necessity for operative closure in situations in which the fistula appears anatomically favorable but shows no signs of closure.
4. Definitive therapy—either spontaneous closure or operation. If the latter, careful preparation is required. Resection and end-to-end anastomosis gives the best results.
5. Healing phase. Nutritional support should not be discontinued too soon for fear of breakdown of newly laiddown protein.

With experience and proper management, relatively high success rates can be achieved.     

Changes in Intestinal Transit Time after Proctocolectomy Assessed by the Lactulose Breath Test

After proctocolectomy with ileal pouch-anal anastomosis (IPAA) patients have increased stool frequency and intermittently use antidiarrheal medication. In addition to other factors, gastrointestinal transit time (MTT) could influence stool frequency. The aim of this study was to investigate how MTT changes after IPAA and to study whether MTT has an influence on daily stool frequency. In a prospective trial MTT was investigated with the lactulose breath test in 12 patients undergoing surgery for chronic ulcerative colitis (CUC) or familial adenomatous polyposis coli (FAPC) at different stages: before proctocolectomy, after IPAA with loop ileostomy, and 3 months and 1 year after ileostomy closure. MTT was also measured in 12 patients with IPAA, 12 patients with subtotal colectomy and ileorectal anastomosis (IRA), and 8 patients with conventional proctocolectomy and Brooke ileostomy (CPC) several years after surgery. Twelve healthy volunteers served as controls. Before IPAA, MTT was prolonged in CUC versus FAPC and controls. After restoration of gut continuity MTT was markedly accelerated. After 1 year MTT was slowed again, though values before proctocolectomy and those in controls were not reached. Several years after surgery MTT was significantly prolonged in IPAA and IRA versus controls. In CPC, MTT could not be determined by lactulose breath test. Stool frequency showed an inverse correlation to MTT in IPAA. In conclusion, this study shows that orocecal and oropouch transit are accelerated in the early postoperative period after (procto)colectomy but prolonged in the long-term course. Adaptation of the small bowel takes longer than 1 year. Impairment of stool frequency may be partly due to this adaptation.