Pharmacology of the internal anal sphincter and its relevance to faecal incontinence

1 The internal anal sphincter (IAS) has a spontaneous tone and is the main contributor to the maintenance of faecal continence. The spontaneous resting tone exhibited by the sphincter can be modified by neurotransmitters from the autonomic and enteric nervous systems. 2 In this review, the influence of the sympathetic and parasympathetic nervous systems on IAS tone are discussed and the putative roles of nitric oxide, carbon monoxide, vasoactive intestinal peptide and adenosine triphosphate in non‐adrenergic non‐cholinergic transmission are considered. 3 Faecal incontinence is a common condition that places a heavy financial burden on the health service and severely affects patients’ quality of life. Resting anal pressure is reduced in patients with faecal incontinence and agents that increase sphincter tone tend to relieve symptoms. The results of clinical studies of the use of phenylephrine to treat faecal incontinence are reviewed. 4 It is concluded that the IAS is a potential target for drug development for the treatment of faecal incontinence.     

The health-related quality of life of male and female heavy smokers

Objectives: Heavy smokers are a segment of the smoking population who are at increased risk of smoking-related morbidity and least likely to achieve cessation. This study identifies the impact of heavy smoking on quality of life by gender and describes the subpopulation for improved targeting.Methods: South Australian representative population data (n = 3010) was used to compare the health-related quality of life status of male and female heavy smokers as assessed by the SF-36.     

Pain management in ambulatory surgery.

Successful ambulatory surgery is dependent on analgesia that is effective, has minimal adverse effects, and can be safely managed by the patient at home after discharge. A number of studies have identified that the provision of effective postoperative analgesia is inadequate for a significant proportion of patients. The following discussion details the current available analgesic options for ambulatory surgery patients and the rationale for their use. Preemptive analgesia should be given to all patients unless there are specific contraindications. Consideration should be given to the use of long-acting oral COX-2 selective nonsteroidal anti-inflammatory drugs (NSAIDs) and long-acting oral opioids to treat postoperative pain. A standardized multimodal postdischarge analgesic regimen tailored to the patient's expected postoperative pain levels should be prescribed. Patient follow-up by telephone questionnaire will confirm those surgical procedures that result in mild or moderate-to-severe postoperative pain and the effectiveness of treatment plans.     

Histopathological characterisation of effects of the mouse Pax6 missense mutation on eye development

Mutations in PAX6/Pax6 lead to a variety of ocular anomalies in humans and mice. The aim of the study was to characterise the ocular abnormalities caused by the missense Pax6^Leca4 mutation and compare them to published observations on Pax6 alleles that are functionally equivalent to Pax6⁻ null alleles (such as Pax6^Sey and Pax6^Sey-Neu) and human inherited eye diseases. Ocular features of homozygous Pax6^Leca4/Leca4 and heterozygous Pax6^Leca4/+ embryos at E12.5-E18.5, heterozygous Pax6^Leca4/+ young mice at P18 and heterozygous Pax6^Leca4/+ adults at 12 weeks were analysed histologically with their wild-type Pax6^+/+ littermates. Homozygous Pax6^Leca4/Leca4 fetuses died perinatally with no eyes although an optic cup rudiment with pigmented cells developed. Pax6^Leca4/+ mice were microphthalmic and a range of other severe ocular phenotypes affected both the anterior and the posterior segments. In contrast to Pax6^+/−, the Pax6^Leca4/+ eyes had no goblet cells in the corneal epithelium, the iris was not hypoplastic and there was no lens-corneal epithelial plug. However, microphthalmia was more severe, corneal vascularisation occurred earlier (during fetal stages), pigmented cells were present in the vitreous and corneal stroma and the ciliary body was malformed or abnormal. These results show that, although Pax6^Leca4/+ lacked some eye abnormalities commonly seen in Pax6^Sey/+ and Pax6^Sey-Neu/+ eyes, in most respects their eyes were more severely affected. These differences probably reflect both differences between the Pax6^Leca4 and the Pax6^Sey-Neu mutations and differences in modifier gene expression in different genetic backgrounds. The presence of pigmented cells in the cornea is a novel observation. Some Pax6^Leca4/+ ocular abnormalities were similar to those present in human Peters' anomaly and persistent hyperplastic primary vitreous (PHPV) so Pax6^Leca4/+ mice provide a useful model for some inherited eye diseases.     

Computed tomography (CT) analysis of the effects of chemonucleolysis

Computed tomography (CT) was performed on 30 patients with herniated lumbar discs before chemonucleolysis and at three and 12 months postinjection. At three months the compression produced by the herniated disc was reduced in 20 of the 30 patients; at 12 months there was complete relief of compression in all but four patients. Twenty-four patients developed diffuse bulging of the annulus. There was good correlation between the clinical results at three months and the reduction in compression as shown by the CT scan. At 12 months, no correlation was found between the remaining focal abnormalities and the clinical result. None of the patients developed epidural fibrosis. Chemonucleolysis has thus been shown to be an effective treatment of herniated lumbar discs, but it is definitely not indicated in cases where compression of the nerve root or dural sac is due to a bulging annulus.     

Long and short-term outcomes in patients requiring continuous renal replacement therapy post cardiopulmonary bypass.

OBJECTIVE: The development of acute renal failure following cardiac surgery is a rare but devastating complication with high morbidity and mortality. This study aimed to assess the incidence of acute renal failure necessitating continuous renal replacement therapy (CRRT) in patients who required cardiopulmonary bypass, to determine the factors associated with mortality and to evaluate long-term outcome. METHODS: Patients who underwent cardiac surgery between October 1997 and 2003 and treated with CRRT were included (n=98). Six patients were then excluded (already in established renal failure pre-operatively) and one patient lost to follow-up. A retrospective analysis was carried out. RESULTS: Overall CRRT was used in 2.9% (92/3172). The mean (SD) age of patients was 68 (10) years. Their mean pre-operative creatinine level and duration of cardiopulmonary bypass were 154 (87)micromol/l and 160 (84)min, respectively. Mean duration from surgery to establishment of CRRT was 50 (42)h. Mean creatinine level prior to hospital discharge was 168 (93)micromol/l. Thirty-day mortality was 42%. Significant risk factors for death were complex procedures (odds ratio=9.9), gastro-intestinal complications (OR=7.2), cross-clamp time over 88min (OR=5.9), re-exploration (OR=4.0) and patients age over 75 years (OR=3.3). Actuarial 1 and 5-year survivals (95% CI) were 53 (43, 63) % and 52 (42, 62) %, respectively. Only 2 (2.2%) patients required long term renal support. CONCLUSIONS: Acute renal failure necessitating the use of CRRT is a rare but serious complication post cardiopulmonary bypass. In the long-term, surviving patients are not likely to require further renal support.