Fecal incontinence is a challenging condition of diverse etiology and devastating psychosocial impact. Multiple mechanisms may be involved in its pathophysiology, such as altered stool consistency and delivery of contents to the rectum, abnormal rectal capacity or compliance, decreased anorectal sensation, and pelvic floor or anal sphincter dysfunction. A detailed clinical history and physical examination are essential. Anorectal manometry, pudendal nerve latency studies, and electromyography are part of the standard primary evaluation. The evaluation of idiopathic fecal incontinence may require tests such as cinedefecography, spinal latencies, and anal mucosal electrosensitivity. These tests permit both objective assessment and focused therapy. Appropriate treatment options include biofeedback and sphincteroplasty. Biofeedback has resulted in 90 percent reduction in episodes of incontinence in over 60 percent of patients. Overlapping anterior sphincteroplasty has been associated with good to excellent results in 70 to 90 percent of patients. The common denominator between the medical and surgical treatment groups is the necessity of pretreatment physiologic assessment. It is the results of these tests that permit optimal therapeutic assignment. For example, pudendal nerve terminal motor latencies (PNTML) are the most important predictor factor of functional outcome. However, even the most experienced examiner's digit cannot assess PNTML. In the absence of pudendal neuropathy, sphincteroplasty is an excellent option. If neuropathy exists, however, then postanal or total pelvic floor repair remain viable surgical options for the treatment of idiopathic fecal incontinence. In the absence of an adequate sphincter muscle, encirclement procedures using synthetic materials or muscle transfer techniques might be considered. Implantation of a stimulating electrode into the gracilis neosphincter and artificial sphincter implantation are other valid alternatives. The final therapeutic option is fecal diversion. This article reviews the current status of the etiology and incidence of incontinence as well as the evaluation and treatment of this disabling condition.

Etiology and management of fecal incontinence.

Nitrosamines form a large group of genotoxic chemical carcinogens which occur in the human diet and other environmental media, and can be formed endogenously in the human body. N-Nitroso compounds can induce cancer in experimental animals. Some representative compounds of this class induce cancer in at least 40 different animal species including higher primates. Tumours induced in experimental animals resemble their human counterparts with respect to both morphological and biochemical properties. Extensive experimental, and some epidemiological data suggest that humans are susceptible to carcinogenesis by N-nitroso compounds and that the presence of these compounds in some foods may be regarded as an aetiological risk factor for certain human cancers including cancers of the oesophagus, stomach and nasopharynx.

Carcinogenic N-nitrosamines in the diet: occurrence, formation, mechanisms and carcinogenic potential.

▪ Abstract The enzyme lactase that is located in the villus enterocytes of the small intestine is responsible for digestion of lactose in milk. Lactase activity is high and vital during infancy, but in most mammals, including most humans, lactase activity declines after the weaning phase. In other healthy humans, lactase activity persists at a high level throughout adult life, enabling them to digest lactose as adults. This dominantly inherited genetic trait is known as lactase persistence. The distribution of these different lactase phenotypes in human populations is highly variable and is controlled by a polymorphic element cis-acting to the lactase gene. A putative causal nucleotide change has been identified and occurs on the background of a very extended haplotype that is frequent in Northern Europeans, where lactase persistence is frequent. This single nucleotide polymorphism is located 14 kb upstream from the start of transcription of lactase in an intron of the adjacent gene MCM6. This change does...

Genetics of Lactase Persistence and Lactose Intolerance

It has been known for some 40 years that lactase production persists into adult life in some people but not in others. However, the mechanism and evolutionary significance of this variation have proved more elusive, and continue to excite the interest of investigators from different disciplines. This genetically determined trait differs in frequency worldwide and is due to cis-acting polymorphism of regulation of lactase gene expression. A single nucleotide polymorphism located 13.9 kb upstream from the lactase gene (C-13910 > T) was proposed to be the cause, and the −13910*T allele, which is widespread in Europe was found to be located on a very extended haplotype of 500 kb or more. The long region of haplotype conservation reflects a recent origin, and this, together with high frequencies, is evidence of positive selection, but also means that −13910*T might be an associated marker, rather than being causal of lactase persistence itself. Doubt about function was increased when it was shown that the original SNP did not account for lactase persistence in most African populations. However, the recent discovery that there are several other SNPs associated with lactase persistence in close proximity (within 100 bp), and that they all reside in a piece of sequence that has enhancer function in vitro, does suggest that they may each be functional, and their occurrence on different haplotype backgrounds shows that several independent mutations led to lactase persistence. Here we provide access to a database of worldwide distributions of lactase persistence and of the C-13910*T allele, as well as reviewing lactase molecular and population genetics and the role of selection in determining present day distributions of the lactase persistence phenotype.

Lactose digestion and the evolutionary genetics of lactase persistence

The prevalence of adult-type hypolactasia varies from less than 5% to almost 100% between different populations of the world. The lowest prevalence has been found in northwestern Europe, around the North Sea, and the highest prevalence in the Far East. The reason for the variation is that selective (primary) hypolactasia is genetically determined by an autosomal recessive single gene. It is assumed that thousands of years ago all people had hypolactasia in the same way as most mammals do today. At that time in cultures where milk consumption was started after childhood, lactase persistence had a selective advantage. Those people with lactase persistence were healthier and had more children than people with hypolactasia, and the frequency of the lactase persistence gene started to increase. The present prevalence of hypolactasia can be explained fairly well by this culture historical hypothesis. This article reviews the evidence for the inheritance of adult-type hypolactasia and the occurrence of hypolactasia in different countries and populations of the world.

Riis P

Papers

Therapeutic influence on the prognosis of ulcerative colitis.