[Fecal incontinence--new surgical treatments. ABS-artificial bowel sphincter]. / Stuhlinkontinenz--Neue chirurgische Wege der Behandlung. ABS--Artificial bowel sphincter (Künstlicher Darmschliessmuskel).

Feacal incontinence is a severe symptom in our society. The main treatment of incontinence in cases of anterior muscle defect, was done by anterior sphinkteroplany. The successrate is very high. All the other alternatives of restoring continence were not very effective The final treatment was always a permanent stoma. New developments over the last years showed us two more possibilities of restoring continence. The dynamic graciloplasty and the artificial bowel sphinkter (ABS) are two new ways of treating feacal incontinence.

Antipsoriatic effect of fumaric acid derivatives. Results of a multicenter double-blind study in 100 patients.

BACKGROUND: Psoriasis vulgaris may benefit from treatment with fumaric acid and/or its derivatives; however, because different preparations have been used, results have been contradictory and difficult to interpret. OBJECTIVE: The purpose of this clinical trial was to evaluate the therapeutic value of fumaric acid derivatives. METHODS: A randomized double-blind study was carried out in patients with psoriasis, comparing a well-characterized formulation of fumaric acid derivatives with placebo. RESULTS: The results indicated statistically significant superiority of the fumaric acid derivatives over placebo. Adverse events (flush, gastrointestinal disturbances) were initially relatively frequent, but decreased thereafter. CONCLUSION: Fumaric acid derivatives were found to be effective and safe in the treatment of psoriasis.

[Adjuvant therapy of primary malignant melanoma with natural human interferon-beta. Significant survival advantage in 96 treated patients in comparison with 288 untreated symptomatic controls]. / Adjuvante Therapie des primären malignen Melanoms mit natürlichem humanen Interferon-beta. Signifikanter Uberlebensvorteil bei 96 behandelten Patienten im Vergleich zu 288 unbehandelten Symptomenzwillingen.

In the dermatological department of Dortmund's Municipal Medical Centre, between May 1986 and April 1991 a total of 105 patients with primary malignant melanoma (stage I) underwent adjuvant treatment with 5 million IU natural interferon beta as a 30-min i.v. infusion three times weekly for 6 months. During follow-up the patients were examined at short intervals and all recurrences and disease-related cases of death were documented up to September 1992. We evaluated the outcome of patients treated with interferon beta (n = 96 with valid notes of tumour thickness) compared with untreated historical controls (n = 288) matched for tumour thickness, localization, and sex, taken from the Central Malignant Melanoma Registry (CMMR) of the German Dermatological Society. Therefore, the main prognostic factors were identical between cases and controls. A computerized randomization was used to fit three control patients to each treated patient. Survival rate and recurrence-free survival were estimated in both groups for a period of 5 years. During the follow-up 3 patients died in the interferon beta group and the 5-year survival rate was 95%, as against 89% in the control group (P < 0.05 for difference between survival curves). Recurrence-free survival curves were also more favourable for interferon-treated patients than for the control group (P = 0.06). A detailed analysis of high-risk patients with tumour thickness of over 1.5 mm also demonstrated obviously better survival (5 years: 95% vs 77%; P = 0.012) and recurrence-free survival rates (5 years: 75% vs 53%; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute behavioral toxicity of sulfolane: influence of hypothermia.

Sulfolane is a solvent which produces hypothermia and decreased oxygen consumption following acute exposure. In the present experiment, we investigated effects of sulfolane on a behavioral measure of toxicity at ambient temperatures which would either prevent or facilitate the development of hypothermia. Adult male Long-Evans rats (N = 10/dose) received a single i.p. injection of saline, 200, 400 or 800 mg/kg sulfolane. Motor activity in figure-of-eight mazes was assessed 1 h after dosing in testing rooms maintained at either 20.8 degrees C or at 32.3 degrees C. At the warm ambient temperature, sulfolane produced hypoactivity but not hypothermia. At the cooler temperature, sulfolane-induced hypoactivity was more pronounced, and rats were hypothermic. Therefore, a behavioral change could be detected at sublethal dosages of sulfolane in the absence of hypothermia.

Development of locomotor activity of rat pups in figure-eight mazes.

In a series of four experiments, social and experiential factors that influence the development of motor activity in rat pups were examined. Motor activity was monitored from postnatal Days 13 to 21 as photocell interruptions in figure-eight mazes and comparisons were made between pups maintained in a nest box containing a dam and siblings and allowed access to the maze for 23 hr/day, pups tested daily for 1 hr/day vs pups tested only on postnatal Days 15, 18, or 21, pups tested daily for either 5 min, 30 min, or 1 hr/day, and pups tested daily for 30 min/day either singly in a maze, paired with a littermate, or paired with an anesthetized pup of the same age. A monotonic increase in activity was seen for nest-box testing, minimal developmental change was seen for pups tested on only a single day or for pups tested with an anesthetized pup, whereas all other groups showed an inverted U-shaped profile of activity which was influenced by the duration of testing and/or the presence of a littermate. These data emphasize the relevance of environmental factors as determinants of preweaning behavior.

Development of locomotor activity of rat pups exposed to heavy metals.

Cadmium (Cd), triethyltin (TET), and trimethyltin (TMT) are heavy metals which are neurotoxic to developing animals. In the present experiment, preweaning assessment of locomotor activity was used to detect and differentiate between the developmental toxicity of these metals. On postnatal day (PND) 5, rat pups received a single injection of either Cd, TET, or TMT. A within-litter design was used for dosing; 1 male and 1 female pup from each litter (N = 10 litters/compound) received either the vehicle, low, medium, or high dosage of the compound. Preweaning motor activity was assessed in 30-min sessions in figure-eight mazes from PND 13 to 21. Motor activity of control animals progressively increased in the initial days of testing, and then both within-session and between-session habituation developed. A single exposure to Cd, TET, and TMT produced hyperactivity by the end of the preweaning period but these metals differed in the day of peak activity, the onset of hyperactivity, and the development of habituation.

Trimethyltin disrupts acoustic startle responding in adult rats.

Trimethyltin (TMT) is a limbic-system toxicant which also produces sensory dysfunction in adult animals. In the present experiment, we examined the effects of TMT on the acoustic startle response. Adult male, Long-Evans rats (N = 12/dose) received a single i.p. injection of either 0, 4.0, 5.0 or 6.0 mg/kg TMT hydroxide as the base. The number of responses, latency and peak amplitude of the startle response to a 13 kHz, 120 dB tone were measured 2 h, 2 weeks, and 4 weeks after dosing. For each test session, 10 stimuli were presented at each of three background noise levels (50, 65 and 80 dB). By 2 h after dosing, the number of responses and response amplitude were decreased following 4.0-6.0 mg/kg TMT; these treatment effects persisted through 4 weeks after dosing. Increases in latency were also seen following all dosages of TMT. These data suggest that TMT produces disruption of function within the acoustic-startle pathway.

Behavioral toxicity of trialkyltin compounds: a review.

Triethyltin (TET) and trimethyltin (TMT) are neurotoxic organotin compounds which produce different patterns of toxicity in adult animals. Exposure to TET produces behavioral toxicity (decreased motor activity, grip strength, operant response rate and startle response amplitude) which reflects impaired neuromotor function. These deficits are consistent with the reported myelin vacuolation and cerebral edema produced by TET, and with its direct effects on muscle. Exposure to TMT produces both hyperactivity and impaired learning and performance. These impairments are consistent with reported neuronal cell death produced by TMT, particularly in limbic system structures. While the behavioral deficits produced by repeated exposure to TET are reversible when dosing is terminated, the behavioral impairments produced by a single exposure to TMT appears to be irreversible.

Neurobehavioral toxicity of triethyltin in rats as a function of age at postnatal exposure.

Triethyltin (TET) has been shown to be neurotoxic when injected on postnatal day (PND) 5. In the present experiment we examined the toxicity of a single exposure to TET at several postnatal ages. Rat pups were injected ip with 0 (saline), 1.5, 3.0, or 6.0 mg/kg TET bromide on PND 1, 5, 10 or 15. In agreement with our previous data, PND-5 exposure to 6 mg/kg TET produced behavioral toxicity and decreased adult brain weight. High dose pups were less successful in descending on a rope at 20 and 21 days of age, and were hyperactive in figure-eight mazes at 29-30 and 57-58 days of age. The spatial distribution of activity was also altered: photocell counts were increased primarily in the figure-eight area of the maze. The size of the milk bands was reduced in 6 mg/kg pups injected on either PND 1 or PND 5. Preweaning growth was decreased following all injection ages; this reduction was most pronounced for pups exposed to TET on PND 1 and PND 5. Mating behavior was disrupted in 6 mg/kg males irrespective of age at exposure. These data demonstrate a differential sensitivity to the toxicity of TET during postnatal life, with maximal susceptibility on PND 5.

Developmental and behavioral toxicity following acute postnatal exposure of rat pups to trimethyltin.

The purpose of this study was to extend our investigations on the developmental neurotoxicity of trialkyltin compounds. On postnatal day 5 (PND 5), rat pups received a single intraperitoneal injection of either 0 (saline), 4, 5 or 6 mg/kg trimethyltin hydroxide (TMT) calculated as the base. The size of the milk bands was decreased in 6 mg/kg TMT pups 48-96 hr after dosing, while in 5 mg/kg TMT pups, milk bands were reduced 96 hr after dosing only. Dosages of 5 and 6 mg/kg TMT reduced growth and impaired performance in rope descent during the preweaning period. As adults, motor activity in figure-eight mazes was increased for 6 mg/kg TMT animals. The startle response to an acoustic stimulus (a 13 kHz, 120 dB tone) was also affected by TMT when measured both during ontogeny and in adulthood. During development, on days 10-21, both 5 and 6 mg/kg TMT reduced the number of responses during 30-trial sessions for both males and females. Amplitudes were decreased for the 5 and 6 mg/kg dose on days 12-13, and for all dosages on days 18-19 and 20-21. Startle amplitude of adults was decreased at all dosages for males but not for females. These behavioral changes were accompanied by decreases in adult brain weight for both sexes. Whole brain weight and weight of the olfactory bulbs were decreased following all dosages of TMT, while hippocampal weight was decreased following both 5 and 6 mg/kg TMT. These results indicate that acute postnatal exposure to TMT produces long-term effects on the nervous system and behavior.

Comparative developmental toxicity of triethyltin using split-litter and whole-litter dosing.

Previous work in our laboratory suggested that toxicity resulting from acute postnatal administration of triethyltin (TET) was influenced by the treatment condition of littermates. To test this possibility, two dosing models were compared. For the split-litter model (N = 20 litters/dose), 1 male and 1 female pup per litter received a single dose of O (saline), 3, 6, or 9 mg TET/kg on postnatal d 5; the remaining 6 littermates were not injected. In the whole-litter model, all 8 littermates received 0, 3, 6, or 9 mg TET/kg (N = 5 litters/dose). Differences between dosing models were found for preweaning body weight and adult figure-eight maze activity. Body weights were reduced in all TET-dosed pups; for 3-mg/kg animals, the reduction in preweaning growth was more persistent for pups in the split-litter group. Motor activity in a figure-eight maze was increased in both 6- and 9-mg/kg animals; for the high dose, the increase in activity was greater for animals in the split-litter group. There were no differences between dosing models in mortality, brain weight, or postweaning body weight. Approximately 50% of the 9-mg/kg animals died; there was no treatment related mortality at lower doses. Adult body weight also remained decreased only in the 9-mg/kg animals. Brain weight was reduced for all TET dose groups. These results indicate that developmental toxicity produced by TET is not primarily determined by the dosing regimen.

Acute behavioral toxicity of carbaryl and propoxur in adult rats.

Motor activity and neuromotor function were examined in adult CD rats exposed to either carbaryl or propoxur, and behavioral effects were compared with the time course of cholinesterase inhibition. Rats received an IP injection of either 0, 2, 4, 6 or 8 mg/kg propoxur or 0, 4, 8, 16 or 28 mg/kg carbaryl in corn oil 20 min before testing. All doses of propoxur reduced 2 hr activity in a figure-eight maze, and crossovers and rears in an open field. For carbaryl, dosages of 8, 16 and 28 mg/kg decreased maze activity whereas 16 and 28 mg/kg reduced open field activity. In order to determine the time course of effects, rats received a single IP injection of either corn oil, 2 mg/kg propoxur or 16 mg/kg carbaryl, and were tested for 5 min in a figure-eight maze either 15, 30, 60, 120 or 240 min post-injection. Immediately after testing, animals were sacrificed and total cholinesterase was measured. Maximum effects of propoxur and carbaryl on blood and brain cholinesterase and motor activity were seen within 15 min. Maze activity had returned to control levels within 30 and 60 min whereas cholinesterase levels remained depressed for 120 and 240 min for propoxur and carbaryl, respectively. These results indicate that both carbamates decrease motor activity, but behavioral recovery occurs prior to that of cholinesterase following acute exposure.

Trimethyltin-induced hyperactivity: time course and pattern.

Adult male Long-Evans rats were intubated with either 0, 5, 6 or 7 mg/kg trimethyltin chloride. Activity was measured for 1 hr in a figure-eight maze 2 hr after dosing (day 0) and again on days 4, 8, 16 and 32 after dosing. On days 49-51, activity was measured in a figure-eight maze over a 23-hr period. There were no differences in activity on the day of dosing, but on all subsequent test days the 7 mg/kg TMT animals were hyperactive. TMT also altered the spatial pattern of activity: activity was increased in the "figure-eight" portion of the maze but not in the blind alleys. ACtivity of the 7 mg/kg TMT animals was increased during all periods in the 23-hr test. Decreases in the length of the pyramidal cell line (CA1 to CA3c of the hippocampus) confirmed neuronal cell loss in TMT-dosed rats.

Behavioral toxicity of acute and subacute exposure to triethyltin in the rat.

The behavioral effects of both acute and subacute triethyltin (TET) exposure were examined in the rat. Animals acutely exposed to TET at doses of 0, 1.5 and 3.0 mg/kg showed a dose-related decrease in motor activity when tested between 2 and 4 hr following exposure. Subacute (3 week) exposure to TET in the drinking water (5 or 10 ppm) resulted in performance decrements in the following: maze activity, open field behavior, acoustic startle response and landing foot-spread. Early signs of behavioral deficits were observed 2 weeks after 10 ppm TET. These effects were reversible within one month after termination of exposure.

Developmental and behavioral effects of early postnatal exposure to triethyltin in rats.

On Day 5 of postnatal life, rat pups received a single injection of triethyltin and were later tested for a variety of developmental and adult behaviors. A within-litter dosing design was used with one male and one female from each litter (N = 8 pups/litter) receiving either 0 (normal saline vehicle), 3, 6 or a high dose of either 9 or 12 mg/kg triethyltin bromide (TET). The high doses of TET produced 50% and 80% mortality, respectively. For the 3 and 6 mg/kg groups, TET-exposure resulted in a transient decrease in body weight, and a permanent decrease in brain weight. Preweaning TET-exposed pups were less successful in descending a rope, and were less active in both a homing orientation test and a figure-eight maze. When tested as adults, however, these animals were consistently more active than controls in the figure-eight maze. These results indicate that a single exposure to TET in ;the developing rat, unlike the adult, produces permanent alterations in both brain and behavior. Acute postnatal exposure to toxicants may have general applicability as a model for developmental neurotoxicity.

Neonatal treatment of hamsters with barbiturate alters adult sexual behavior.

Male and female hamsters were given 50 micrograms pentobarbital, 100 micrograms pentobarbital, or 100 micrograms d-amphetamine on postnatal Days 2-4. When tested for masculine sexual behavior in adulthood, males treated with 100 micrograms pentobarbital showed behavioral deficits when tested with testes intact as well as after castration and treatment with testosterone propionate. Deficits shown by 50 micrograms pentobarbital males were overcome by testosterone replacement. When tested for feminine sexual behavior, males treated with 50 micrograms pentobarbital showed enhanced lordotic responses whereas males treated with 100 micrograms d-amphetamine showed no differences from controls when tested for female sexual behavior or when tested for male sexual behavior. Drug treatments had no effect on adult masculine or feminine sexual behavior in neonatally treated females. The results of this study show that pentobarbital can inhibit normal masculinization of the male when given during behavioral sexual differentiation.

Inhibition of estrogen-induced sexual receptivity of female hamsters: comparative effects of progesterone, dihydrotestosterone and an estrogen antagonist.

In the first experiment ovariectomized female hamsters were administered varying dosages of progesterone (P), dihydrotestosterone (DHT) or CI-628 at the same time (concurrently) as estrogen (EB) or 48 hr after EB (sequentially). All groups also received 500 microgram P 4 hr before being tested for sexual receptivity. P was more effective in reducing receptivity when given sequentially with estrogen than when given concurrently. Thus, the inhibitory effect of P increased with an increased interval between EB and P treatment. More CI-628 than P was required to inhibit lordosis and unlike P, CI-628 was equally effective when given concurrently with EB as when given sequentially. DHT did not inhibit receptivity when given in either paradigm. In the second experiment ovariectomized hamsters were treated with varying dosages of DHT 12 hr before EB. An amount of DHT which had no effect in Experiment 1 significantly inhibited receptivity when given 12 hr before EB. The relative inhibitory effects of these three compounds were discussed in terms of the possible similarities and differences in their mechanisms of action for inhibiting lordosis.