Botulinum toxin type-a in therapy of patients with anismus

INTRODUCTION: Anismus is a common cause of constipation and outlet obstruction. Standard therapy with laxatives or biofeedback has conflicting results. Surgical treatment gives poor results and has practically been abandoned. PURPOSE: This study was designed to evaluate the efficacy of botulinum toxin type-A (Botox) injection to the puborectalis muscle in patients with anismus. METHODS: Twenty-five patients (15 females; mean age, 23.2) with history of constipation and symptoms of outlet obstruction underwent anorectal perfusion manometry and video-proctography. All patients were found to have a nonrelaxing puborectalis muscle on both modalities. All have been unable to expel a rectal balloon. Each patient who participated in the study was randomly assigned to undergo local injection of Botox--10 units to each side of the puborectalis or 20 units to the posterior aspect of this muscle. Eight patients underwent further injections1-5 every 3 months in accordance with previous results. Follow-up was conducted 1, 4, 12, and 24 weeks after injection. Straining, anorectal pain, and overall satisfaction were assessed on a visual analog scale. Weekly evacuation, fecal incontinence, and complications were recorded. At the weekly meeting, each patient underwent anorectal manometry with a balloon expulsion test. RESULTS: Manometric relaxation was achieved after the first injection in 18 patients (75 percent). Once relaxation was achieved, it lasted throughout the follow-up. Nine patients (37.5 percent) expelled the rectal balloon after the first injection. Seven of 16 patients who failed the first injection had an additional one. In 2 patients it was successful (28.6 percent). Symptom improvement of 29.2 percent in straining index was recorded during follow-up. In 3 patients (12.5 percent) pain developed after injection. No other complications were observed. Overall satisfaction with Botox injection results was observed in 58.3 percent. CONCLUSIONS: Botox injection to the puborectalis muscle has been found to have a limited therapeutic effect on patients suffering from anismus. Our results justify the need for further double-blind placebo-controlled trials to determine the exact role of botulinum toxin type-A in anismus.     

Prophylactic oophorectomy in premenopausal women with stage II breast carcinoma

Prophylactic oophorectomy, as an additional treatment for stage II breast cancer, is controversial. In a retrospective study, a group of 37 premenopausal women with stage II infiltrating duct carcinoma and one to three positive axillary lymph node involvement after modified radical mastectomy and bilateral oophorectomy were compared to a matched group of 34 women treated by modified radical mastectomy only. Prophylactic oophorectomy prolonged the disease free interval significantly as compared to the control group. However, it did not prolong survival. This raises the question whether the prolongation of survival achieved by late oophorectomy in women with advanced breast cancer is preferable to an improvement in quality of life resulting from longer disease free intervals.     

Antitumor effects of inhibitors of arachidonic acid cascade on experimentally induced intestinal tumors

The antitumor action of inhibitors of cyclooxygenase (indomethacin) and lipoxygenase activity (nordihydroguaiaretic acid) of arachidonic acid cascade was investigated in the chemically induced large bowel tumors in Sprague-Dawley rats. Indomethacin treatment completely prevented the carcinogenic effect of methylazoxymethanol. Thus, no tumors were found in the 14 rat test group, compared with 13 of 14 tumor-bearing rats in the unteated control group. Although nordihydroguaiaretic acid treatment does not abolish prostaglandin synthesis, it does reduce the effect of the carcinogen and tumors were found in only five of 14 treated rats. From this study it can be postulated that not only is reduction in prostaglandin formation responsible for the inhibition of tumor growth, but also leukotrienes may play some role. This work was supported partially by a grant from the Chief Scientist of the Ministry of Health Israel.     

Artificially induced endometrial cycles and establishment of pregnancies in the absence of ovaries

In eight women with ovarian failure, we induced histologically normal endometrial function during a preparatory cycle consisting of sequential administration of estrogen and progesterone. During a subsequent cycle, endometrial stimulation was synchronized with surrogate-embryo transfer performed on days 16 to 21. Among the eight women, two pregnancies were established by embryo transfer on days 18 and 19. In both women, ovarian tissue was absent, and these patients therefore serve as an in vivo model for the isolated effects of estrogen and progesterone on implantation and maintenance of pregnancy. Treatment with exogenous estrogen was mandatory up to the 11th week of gestation, and treatment with progesterone until the 18th to 22nd weeks. We conclude that it is biologically feasible to simulate the essential hormonal and endometrial milieu of a fertile menstrual cycle and early gestation solely by the administration of estrogen and progesterone. Days 18 to 19 of the cycle are recommended for successful embryo implantation with this treatment program.     

Unravelling Adrenal Oncocytic Neoplasm

Oncocytic neoplasms are rare tumors arising in the adrenal glands and usually considered as nonfunctional and benign. We report 4 cases of adrenal oncocytic neoplasm. The paucity of literature describing this entity increases the chance for misdiagnosis. Confirmatory diagnosis is by tissue sampling with adrenalectomy as the mainstay of treatment.     

Fetal response to vibratory acoustic stimulation in periods of low heart rate reactivity and low activity

The fetal response to vibratory acoustic stimulation during periods of low fetal activity and low fetal heart rate reactivity was studied in 10 healthy pregnant women at term. In each case, two periods of low reactivity were studied. Consecutive cases alternated: The vibratory acoustic stimulus was applied 10 minutes after the first nonreactive period in half of the cases; the remainder were stimulated during the second nonreactive period. The unstimulated period served as a control. After vibratory acoustic stimulation the baseline fetal heart rate, the mean number of fetal heart rate accelerations, and, the number of fetal movements were significantly increased with values in the control nonstimulated periods (p less than 0.0001). This consistent response to vibratory acoustic stimulation may prove to be clinically useful in altering periods of low reactivity observed during nonstress testing of normal fetuses.     

Schwere Infektionen

The sepsis syndrome has only recently been defined as a clinical syndrome but despite its unspecific definition it has evolved rapidly into an important concept. Although specific therapeutic interventions targeting the inflammatory pathway have not yet been effective in treating sepsis, a better understanding of mechanisms leading to organ dysfunction has led to better management of patients with sepsis. Clinical signs of systemic inflammatory response syndrome (SIRS) or sepsis are hallmarks for the definition of severe infections. Current guidelines are presented for the management of a number of severe infectious syndromes.     

The role of immune cells in metabolism-related liver inflammation and development of non-alcoholic steatohepatitis (NASH)

The low grade inflammatory state present in obesity promotes the progression of Non-Alcoholic Fatty Liver Disease (NAFLD). In Non-Alcoholic Steatohepatitis (NASH), augmented hepatic steatosis is accompanied by aberrant intrahepatic inflammation and exacerbated hepatocellular injury. NASH is an important disorder and can lead to fibrosis, cirrhosis and even neoplasia. The pathology of NASH involves a complex network of mechanisms, including increased infiltration of different subsets of immune cells, such as monocytes, T-lymphocytes and neutrophils, to the liver, as well as activation and in situ expansion of liver resident cells such as Kupffer cells or stellate cells. In this review, we summarize recent advances regarding understanding the role of the various cells of the innate and adaptive immunity in NASH development and progression, and discuss possible future therapeutic options and tools to interfere with disease progression.