The small intestine is a major site of cholesterol biosynthesis and lipoprotein degradation. It is also the organ responsible for absorbing dietary and endogenously produced biliary cholesterol. Cholesterol metabolism in the intestine is regulated by factors that will alter cellular cholesterol requirements. Thus, during increased cholesterol flux, which occurs by bile acid-faciliated cholesterol absorption or by lipoprotein-mediated uptake of cholesterol, cholesterol synthetic rates decrease and esterification rates increase. The mechanisms by which dietary fats regulate intestinal cholesterol metabolism are complex. Dietary fats alter membrane fatty acid composition. Simultaneously, they also promote lipoprotein secretion and alter cholesterol absorption. Intestinal 3-hydroxyl-3-methylglutaryl coenzyme. A reductase activity is regulated by enzyme phosphorylation-dephosphorylation. The regulation of acylcoenzyme A-cholesterol acyltransferase activity by this mechanism remains controversial. Data on hormone regulation of intestinal cholesterol metabolism are not conclusive, although progesterone seems to be a potent inhibitor of acylcoenzyme A-cholesterol acyltransferase activity in intestinal cell culture and isolated cells. In a manner similar to the regulation of cholesterol metabolism in other cells, the enterocyte responds appropriately to factors that alter cholesterol flux. Therefore, changes that occur in the rates of cholesterol synthesis and esterification will reflect the cholesterol requirements of the cell.

The optimal degree and duration of suppression of gastric acidity required for the healing of peptic ulcers has never been established. Although very potent inhibitors of acid secretion are now available, the need for this degree of suppression has not been shown, and there is a possibility of adverse effects because of pronounced acid inhibition. Therefore, a model has been constructed that defines the relationship between duodenal ulcer healing and antisecretory therapy. Acid suppression data were obtained directly from investigators as raw data from 24-hour studies of acid secretion. Twenty-one experiments from seven investigators provided 490 24-hour studies using 19 different treatment regimens. Healing data were collected from a metaanalysis of published clinical trials of duodenal ulcer healing. A total of 144 published trials in 14,208 patients provided healing data at several endoscopic endpoints for the 19 drug regimens for which acidity data were provided. Weighted least-squares polynomial regression analysis was used to define those parameters of antisecretory therapy that contributed most to duodenal ulcer healing and to define the shape of the response surface. A highly significant correlation (r = 0.9814) was found between healing and the degree of acid suppression, the duration of acid suppression, and the length of therapy. The shape of the contour expression this relationship shows that healing increases as the duration of suppression increases and as gastric pH increases. However, suppression that increased pH beyond 3.0 was not found to increase ulcer healing further. It is concluded that a longer duration of antisecretory effect and/or a longer duration of therapy are of greater importance than potency for duodenal ulcer healing.

The existing clinical measures of disease activity for inflammatory bowel disease are insufficient to explain a patient's illness experience or health outcomes. Although many disease activity measures have been devised, they are not widely accepted by clinicians because existing ones are no better than a carefully obtained clinical assessment. Furthermore, health status is determined not only by disease activity, but also by the psychological state, cultural influences, degree of social support, and effects of complications, previous surgery, and medication. To develop more accurate appraisals of the impact and severity of IBD, we must prospectively evaluate the biological and psychosocial measures that predict clinically relevant outcomes. We should then be able to develop statistically weighted scales related to specific outcome variables. Such knowledge will help us to develop more sensitive measures of illness, particularly in patients with mild disease for whom present indices are insensitive. This type of assessment should also aid in the understanding of health care utilization, medical vs. surgical options, resource allocation, and the efficacy of therapeutic trials.

This chapter contains a detailed description of the range of psychiatric problems likely to present in HIV patients and their relatives, and a discussion of the principles of psychiatric management. Psychosocial problems at the various disease stages are reviewed, including those at the time of HIV testing, and in asymptomatic and symptomatic individuals. Mania and schizophrenia-like syndromes are discussed, as well as neuropsychiatric disorders occurring in early and advanced HIV disease. The impact of HIV disease on relatives and professional carers is reviewed. The role of physicians and nurses in the psychological care of HIV patients is outlined, together with the role of mental health specialists. Basic information about the recognition and treatment of major psychiatric syndromes is provided. Finally, issues involved in supporting staff working with HIV patients are discussed.

KS and non-Hodgkin's lymphomas frequently involve the gut in patients with AIDS. These neoplasms establish the diagnosis of AIDS in an HIV-positive patient. KS is a spindle-cell tumour derived from lymphatic endothelia which is associated with luminal lesions in at least 40% of patients. Gastrointestinal KS is usually asymptomatic but may rarely bleed or obstruct. Treatment of KS with either interferon-alpha, radiation or chemotherapy can reduce tumour bulk, but does not alter overall survival in AIDS. Non-Hodgkin's lymphomas in AIDS are B cell neoplasms with many genotypic and phenotypic similarities to Burkitt's lymphoma. The tumours are usually highly aggressive, and present in extranodal sites in the majority of cases. Of these extranodal sites, gastrointestinal involvement is most common. Gastrointestinal lymphomas are usually symptomatic and almost always require treatment. Obstruction, perforation and bleeding may occur in patients with luminal involvement, whereas hepatic or biliary disease may lead to jaundice. Several chemotherapeutic regimens for lymphoma have been successfully used to achieve partial remission, although no prolongation of survival has been demonstrated. There appears to be an increased incidence of Hodgkin's disease in patients with AIDS, which is generally of advanced stage. This tumour does not meet the CDC criteria for AIDS as yet. Hepatic and/or splenic involvement in this setting are common.

Cryptosporidiosis in patients with AIDS presents as a chronic enteritis, with biliary complications in about 10% of sufferers. The disease is persistent and progressively fatal. Due to the widespread prevalence of the parasite in the community and amongst domesticated animals, persons with AIDS are constantly at risk. Treatment is extremely difficult in view of the apparent lack of a specific anticryptosporidial drug. Methods of immunomodulation are worth considering, but the main recourse may have to be a prolonged regimen of rehydration and parenteral nutrition. However, if T helper cell function improves, the disease may go into remission or the parasite could be eliminated. Vaccination of those at risk is not feasible at present.

Gastrointestinal disease is the commonest presentation of AIDS in the Third World. Diarrhoea and weight loss are particularly common. Although many pathogens may be found, chronic cryptosporidiosis is the most frequent and there remains no specific effective therapy. Isospora belli is found in less than 10% of cases, but may be treated with cotrimoxazole, and long-term maintenance treatment to prevent relapse is effective. Oral disease, especially with candidiasis, is increasingly recognized and may be controlled with topical antifungal agents. The outlook for patients in the Third World who present with gastrointestinal opportunistic infections associated with HIV infection is particularly dismal. Specific antiviral therapy, which has at least brought some hope and longer survival to patients in developed countries, remains largely unavailable in the Third World.

The small intestine is a major target in HIV infection. Chronic diarrhoeal disease associated with malabsorption is the principal clinical manifestation of such infection. Reduced intestinal immunity and opportunistic enteric infections play a major role in clinical disease, but an enteropathy induced by HIV per se has also been implicated. The immunopathology of reduced intestinal immunity and its progression during HIV infection is poorly understood. HIV genome and proteins have been detected reproducibly in cells of the lamina propria resembling macrophages, but direct epithelial infection with HIV is controversial. Another factor which may contribute to diarrhoea is autonomic neuropathy within the jejunum. Small intestinal disease causes malabsorption of fat and disaccharides and may contribute to the weight loss seen in advancing HIV infection. However, malnutrition seen in HIV infection is multifactorial and may occur as a constitutional sign of infection in the absence of overt intestinal disease. Reduced food intake does not appear to be a causative factor in the weight loss in constitutionally well stage IV patients and there is some evidence that release of cytokines (TNF alpha/cachectin) into plasma or locally into tissue may mediate such events. The response of HIV-infected individuals to nutritional support is variable, but it is becoming increasingly apparent that the response is limited by the presence of severe systemic infection. However, aggressive nutrition is an important therapeutic mode which should be offered to all HIV-infected patients.

Upper gastrointestinal tract infection in AIDS is a complex multifactorial process. The approach to diagnostic evaluation can be based upon knowledge of the large spectrum of bacteria, viruses and protozoa involved. The availability of effective therapy is the most decisive factor in determining the duration of upper gastrointestinal tract infections in AIDS patients. Awareness of the clinical, epidemiological, immunological and therapeutic aspects should help to direct the diagnostic evaluation of these patients and to highlight areas of research.