Persistent reduction of pancreatic Beta-cell mass after a limited period of protein-energy malnutrition in the young rat

Summary Kwashiorkor, the human disease of protein-energy malnutrition, has been implicated in the aetiology of malnutrition-related diabetes mellitus, a form of diabetes not uncommon in developing countries. We have previously demonstrated that temporary protein-energy malnutrition in young rats causes a persisting impairment of insulin secretion. The present study investigates whether this secretory deficiency is accompanied by structural alterations of the endocrine pancreas. Three-week-old rats were weaned onto semi-synthetic diets containing either 15% or 5% protein and these diets were maintained for 3 weeks. From 6 weeks of age all rats were fed a commercial chow containing 18% protein. The endocrine pancreas was investigated by light and electron microscopic morphometry at 3, 6 and 12 weeks of age. In rats not subjected to protein-energy malnutrition there was a progressive increase, with age, of total pancreatic Beta-cell weight and individual Beta-cell size. In 6-week-old rats fed the low protein diet total pancreatic Beta-cell weight and individual Beta-cell size were diminished. In 12-week-old rats previously fed the low protein diet total Beta-cell weight remained lower compared to control rats. It is concluded that protein-energy malnutrition early in life may result in a diminished reserve for insulin production. This may predispose to glucose intolerance or even diabetes in situations with an increased insulin demand.This work was presented in part at the 26th Annual Meeting of the European Association for the Study of Diabetes in Copenhagen, Denmark 10–13 September 1990     

Protein digestion and absorption in man. Normal mechanisms and protein-energy malnutrition.

Protein is an essential nutrient normally assimilated in an efficient manner following the action of gastric, pancreatic and small intestinal enzymes. After hydrolysis, protein digestion products in the form of amino acids and small peptides undergo mucosal uptake by distinct transport mechanisms. Although gastric and pancreatic enzymes are important, the small intestine appears to be the critical rate-limiting tissue in this process. Impaired intake, assimilation or excessive enteric protein loss may occur with several diseases leading to protein-energy malnutrition. Although the clinical and laboratory features of this condition are nonspecific and wide ranging in spectrum, their presence may provide a clue to underlying disease and serve as an index of patient nutritional status. Disease of the exocrine pancreas or small intestine may cause significant protein-energy malnutrition which, in turn, can cause major structural and functional abnormalities in these tissues.     

Effects of prolonged ethanol intake and malnutrition on rat pancreas.

Nutritional factors, especially the protein and fat content of the diet, may change pancreatic morphology after ethanol induced injury. This study was performed to delineate the combined effects of a low fat diet and longterm ethanol ingestion on the rat pancreas. Male Sprague-Dawley rats were maintained with five different diets for 12 weeks and the pancreas removed on the day they were killed. Rats fed a very low fat diet without ethanol (5% of total calories as lipid) developed malnutrition, pancreatic steatosis, and reduction in zymogen granules content. Animals fed a 35% lipid diet with ethanol also developed pancreatic steatosis but changes in zymogen granules content were not detected. Both malnutrition and longterm ethanol consumption increased pancreatic cholesterol ester content, and their effects were additive. Pancreatic steatosis was accompanied with hypercholesterolaemia. Amylase, lipase, and cholesterol esterase content were reduced in malnourished rats; but longterm ethanol ingestion, regardless of the nutritional state, increased lipase content and decreased amylase. It is suggested that high serum cholesterol concentrations and increased pancreatic lipase activity could cause accumulation of cholesterol esters in acinar cells. Fat accumulation in the pancreas has been reported as the earliest histopathological feature in alcoholic patients and may be responsible for cytotoxic effects on the acinar cells at the level of the cell membrane. Although it is difficult to extrapolate results in this animal study to the human situation, the results presented in this work might explain the higher incidence of pancreatitis is malnourished populations as well as in alcoholic subjects that is reported in dietary surveys.     

Pancreatic acinar cell carcinoma in familial adenomatous polyposis

Pancreatic carcinoma is rarely associated with familial adenomatous polyposis (FAP). Ten patients with this association have been reported in the literature. However, detailed data were available in only a few cases. The first case of pancreatic acinar cell carcinoma associated with FAP is reported. A 51-year-old man who had undergone total colectomy and ileoproctostomy for colonic polyposis 29 years previously was admitted with a cancer in the residual rectum. Preoperative examinations revealed a tumor in the head of the pancreas. Pancreaticoduodenectomy and very low anterior resection of the rectum were performed. Histologically, the tumor of the pancreas was acinar cell carcinoma. In patients with FAP, we recommend careful surveillance of not only the gastrointestinal tract but also of other organs such as those of the pancreaticobiliary system and the endocrine organs.     

Primary acinar cell carcinoma of the ampulla of Vater

Acinar cell carcinoma of the pancreatobiliary system is a relatively rare malignant neoplasm arising usually in the pancreatic parenchyma. We experienced a 68-year-old woman who presented with obstructive jaundice due to an ampullary mass 1.0 cm in diameter, detected by abdominal computed tomography and endoscopic examination. The patient underwent a curative surgical operation, and histopathological examination revealed that the tumor was confined to the ampulla of Vater with no continuity to the pancreatic parenchyma. The tumor cells showed acinar or tubular arrangement with eosinophilic to basophilic granular cytoplasm, findings identical to those of acinar cell carcinoma of the pancreas. Immunohistochemically, the tumor cells were positive for lipase. From these findings, we concluded that the tumor was primary acinar cell carcinoma arising in the ampulla of Vater, probably originating from heterotopic pancreatic tissue. This is the first reported case of primary acinar cell carcinoma in the ampulla of Vater.     

A patient presenting with diffuse cutaneous leishmaniasis (DCL) as a first indicator of HIV infection in India

Opportunistic parasitic infections such as leishmaniasis are common in human immunodeficiency virus (HIV)-infected patients and are usually acquired several days after initial diagnosis of HIV infection. Here, we report on a patient who presented with diffuse cutaneous leishmaniasis (DCL) caused by Leishmania tropica as the first and only clinical manifestation of HIV infection. To the best of our knowledge, this is the first case that illustrates that DCL could be the first clinical indicator of HIV infection. Cutaneous leishmaniasis (CL) and DCL are becoming frequent opportunistic infections in HIV-infected individuals throughout the world. To date, all documented cases of CL and HIV coinfections have been reported in patients who were known cases of HIV and who subsequently developed CL. In this report, we present a case that illustrates that DCL could be the first clinical indicator of HIV infection.     

A rare case of disseminated Mycobacterium kansasii infection

Mycobacterium kansasii infection has been reported to be about 20 percent of non-tuberculous mycobacteriosis, and its disseminated type is uncommon and the prognosis is reported to be generally poor. We experienced one case of disseminated Mycobacterium kansasii infection. A 81 year-old man who had been short-bowel syndrome due to the operation for superior mesenteric artery occlusion since 1998 was admitted on April 24th, 2001 to our hospital because of slowly progressive consciousness disturbance and anorexia. He had shown progressive productive cough and respiratory failure and laboratory findings were C-reactive protein elevation and pancytopenia. Human immunodeficiency virus (HIV) antibody was negative. Chest X-ray and computed tomography showed diffuse miliary nodules and infiltrative shadow. Sputum examination was positive for mycobacteria. The cultured isolate was identified as Mycobacterium kansasii. Bone marrow aspirations revealed inflammatory granuloma with necrosis. He was diagnosed as disseminated Mycobacterium kansasii infection and heart failure, and was treated by anti-tuberculosis drugs and diuretics. Treatment was very effective and Chest X-ray findings and respiratory failure had been completely improved. In this case we speculated that the malnutrition due to short-bowel syndrome could be one of the most suspected reasons of Mycobacterium kansasii dissemination. Disseminated Mycobacterium kansasii infection has been rarely reported comparing with the other mycobacterial infections in Japan. However, due to the increasing numbers of immunocompromised hosts with aging, HIV infection, cancer, and steroid therapy, this type of infection will become more common and its earlier diagnosis and adequate treatment will be important to improve the prognosis.     

Contribution of Polyunsaturated Fatty Acids to Intestinal Repair in Protein-Energy Malnutrition

The aim of this study was to assess the effect of polyunsaturated fatty acids supplied in the diet on intestinal mucosa repair in a rat model of protein-energy malnutrition. Rats were fed either a standard semipurified diet or the same diet containing lactose as the only source of carbohydrate to cause protein-energy malnutrition. Diarrhea was induced within 24 h and was maintained for 2 weeks, after which both groups of rats were fed for 1 week either the standard diet or the standard diet supplemented with different sources of fatty acids, such as olive oil (OO), fish oil (FO), and purified phospholipids from pig brain (BPL). The lactose-enriched diet caused loss of enterocyte microvilli, lymphocyte infiltration, supranuclear cytoplasmic vesiculation, decreased number of goblet cells, low-density enlarged mitochondria, and less cristae. The FO diet improved the pathology score according to the histological and ultrastructural analysis, with an increased number of goblet cells, ratio of microvilli length to crypt depth, and percentage of intraepithelial lymphocytes compared to those found in rats with protein-energy malnutrition. We previously reported that chronic diarrhea depletes the antioxidant defense in rat intestine; we now show that both, the FO and the BPL diets, increase GSH levels in colon and that some antioxidant enzyme activities vary according to the source of fatty acids, with higher catalase and superoxide dismutase by the FO diet in jejunum, increased catalase by the BPL diet in jejunum, and elevated glutathione peroxidase by the OO diet in colon. The fatty acid profile of intestinal mucosa reflects the source of fat in the diet, with the lowest ratio of n-6/n-3 for rats fed the FO diet. These results suggest that dietary polyunsaturated fatty acids, particularly those in the n-3 series, may play an important role in intestinal repair in chronic diarrhea due to protein-energy malnutrition. This work was supported by Grant CI1-CT91-0078 from the European Union.     

Solid and Papillary Neoplasm Arising from an Ectopic Pancreas in the Mesocolon

A case of solid and papillary neoplasm of a mesocolonic ectopic pancreas in a 13-yr-old girl is presented. An 8-cm, well-encapsulated, and partly calcified tumor which protruded from the mesocolon was resected surgically. Histologically, the tumor showed either solid sheets or papillary arrangements (around the vascular core) of uniformly small cells with alpha 1-antitrypsin-positive cytoplasm. Some of the tumor cells had zymogenlike granules, suggesting acinar cell differentiation. At the base of this tumor, small pancreatic tissues (islet, acinar, and ductular cells) were detected in the mesocolonic tissue. Incidences of both ectopic pancreas outside the gastrointestinal wall and solid and papillary neoplasm of the pancreas are rare, and this is the first case reported in the literature.     

Leishmania/HIV co-infection in Brazil: an appraisal

Given the epidemiology of human leishmaniasis and AIDS in Brazil, numerous cases of Leishmania/HIV co-infection might be expected. Relatively few Brazilian cases have been reported, however, even from regions where the overall incidences of HIV and Leishmania infection are both relatively high. Many cases of co-infection probably go undetected because of a lack of awareness among clinicians or limited access to appropriate diagnostic methods. In contrast to the situation in Europe, intravenous-drug users do not predominate among those exposed to HIV infection in Brazil. The success of the Brazilian programme for the free and universal distribution of antiretroviral drugs has decreased the prevalences of the commoner opportunistic infections among HIV-positives and increased the longevity of AIDS cases. Recent changes in the epidemiological patterns of HIV and Leishmania infections are likely to lead to a greater degree of overlap and a greater risk of co-infection and they justify increased alertness. This review of the co-infection in Brazil addresses three main topics: the current situation, in terms of the epidemiology of AIDS and Leishmania infection; the related epidemiological trends and their likely impact on the co-infection; and the co-infection cases reported in Brazil by June 2003.     

Invasive non-typhoidal salmonella disease: an emerging and neglected tropical disease in Africa

Invasive strains of non-typhoidal salmonellae have emerged as a prominent cause of bloodstream infection in African adults and children, with an associated case fatality of 20-25%. The clinical presentation of invasive non-typhoidal salmonella disease in Africa is diverse: fever, hepatosplenomegaly, and respiratory symptoms are common, and features of enterocolitis are often absent. The most important risk factors are HIV infection in adults, and malaria, HIV, and malnutrition in children. A distinct genotype of Salmonella enterica var Typhimurium, ST313, has emerged as a new pathogenic clade in sub-Saharan Africa, and might have adapted to cause invasive disease in human beings. Multidrug-resistant ST313 has caused epidemics in several African countries, and has driven the use of expensive antimicrobial drugs in the poorest health services in the world. Studies of systemic cellular and humoral immune responses in adults infected with HIV have revealed key host immune defects contributing to invasive non-typhoidal salmonella disease. This emerging pathogen might therefore have adapted to occupy an ecological and immunological niche provided by HIV, malaria, and malnutrition in Africa. A good understanding of the epidemiology of this neglected disease will open new avenues for development and implementation of vaccine and public health strategies to prevent infections and interrupt transmission.     

Metachronous pancreatic acinar cell carcinoma discovered in early stage during follow-up of breast cancer: report of a case

We present an extremely rare case of early-stage acinar cell carcinoma of the pancreas. A 49-year-old woman, who had undergone radical surgery for breast cancer 3?years earlier, was suspected to have a rib metastasis during follow-up. She also had a family history of cancer. No accumulation was seen in the left rib on ¹⁸F-fluorodeoxyglucose positron emission tomography with computed tomography, but incidental high uptake into the pancreatic head suggested malignant pancreatic tumor. The tumor was completely resected by pancreatoduodenectomy, and pancreatic acinar cell carcinoma was demonstrated histopathologically. To the best of our knowledge, this is the first reported case of a pancreatic acinar cell carcinoma smaller than 1?cm to be detected by ¹⁸F-fluorodeoxyglucose positron emission tomography and computed tomography.     

Implication of Reg I in human pancreatic duct-like cells in vivo in the pathological pancreas and in vitro during exocrine dedifferentiation

A feature associated frequently with the pathologic pancreas is the presence of tubular complexes produced by a phenotypic modulation of acinar cells that take on the characteristics of ductular cells. Since the type I Reg gene, an acinar cell product, is increased in the pancreas following an acinar injury, we aimed to evaluate whether the Reg I protein might be involved in this dedifferentiation process in the human pancreas. We studied duct-like structures in fixed human pathologic pancreatic tissues and human cells with a ductal phenotype obtained by culturing human exocrine preparations. Immunocytochemistry, Western blotting, and RT-PCR were applied for detection of type I Reg. Reg I was observed not only in acinar cells but also in the duct-like cells and dilated duct cells, both positive for cytokeratin 19. However, none of the other acinar markers was observed in these cells. In vitro, human acinar cells dedifferentiated, losing their acinar phenotype, but expression of Reg I remained constant throughout the culture duration. Furthermore, Reg I was not associated with proliferation. We demonstrated that Reg I expression was linked to acinar cell dedifferentiation. We postulate that Reg I might be used as a marker to understand the events leading to phenotypic changes of acinar cells to address the physiological role of Reg I in the pancreas.     

Pancreatic involvement in human immunodeficiency virus infection

Involvement of the pancreas by human immunodeficiency virus (HIV) infection has not been adequately addressed and is the object of this review. I analyzed the English language literature, including single case reports of pancreatic involvement and larger series reporting detailed pathological findings of patients with HIV infection. Nonspecific pathological changes in the pancreas are frequently seen at autopsy of HIV-infected patients, but are not more common than in controls. Several types of infections (mainly cytomegalovirus, Cryptococcus neoformans, and Mycobacteria) and neoplasms (lymphoma and Kaposi's sarcoma) can involve the pancreas because they are usually disseminated. Although the serum amylase may be elevated, the patient remains asymptomatic. Occasional instances of severe and even fatal pancreatitis have been reported with HIV infections and attendant drug toxicity. Pentamidine has a predictable incidence of hypoglycemic episodes and 2',3'-dideoxyinosine provokes pancreatitis in a minority of treated patients. Such drug toxicity seems to deserve greater clinical concern than opportunistic infections or neoplasms.     

Dermatomyositis and HIV infection: case report and review of the literature

Since the 1980s, a host of autoimmune phenomena and rheumatologic illnesses have been linked to infection with the human immunodeficiency virus (HIV). Given the broad effects of this virus on both the humoral and cell-mediated arms of the immune system, illnesses such as polymyositis and Reiter’s syndrome appear to be more prevalent in HIV-infected individuals and occur in the absence of well-described predispositions. The activities of some rheumatologic illnesses exhibit an inverse relationship with the course of HIV infection, such as rheumatoid arthritis, which becomes more quiescent with advancing disease. Dermatomyositis is a rheumatologic illness that very infrequently occurs and during our review of literature only three other cases were reported. We present the case of a Caucasian male in his mid-20s who presented with acquired immunodeficiency syndrome and subsequently developed dermatomyositis. In this review, we highlight the current relationship between HIV infection and autoimmunity, the possible ways HIV infection may foster an environment favorable for the development of dermatomyositis, and review the previously reported cases of individuals with HIV infection who developed dermatomyositis. The complex issues of how to treat individuals with HIV and dermatomyositis is also discussed.     

Primary pneumococcal peritonitis as a presenting feature of HIV infection

We report a case of primary pneumococcal peritonitis in a 28-year old previously healthy woman. There are no previously reported associations between this rare form of spontaneous peritonitis and HIV infection, and it is usually associated with underlying cirrhosis, ascites or other immune compromise. In this case this was the presenting illness of HIV infection. When atypical infections such as this arise in previously healthy adults the clinician must have a high index of suspicion of HIV or other underlying immunodeficiency.     

Occupational HIV infection and health care workers in the tropics

A literature review revealed 33 reports of health care workers who have contracted HIV infection as a result of their work. Four of these were expatriate doctors who had worked in Africa. The commonest mode of transmission was needlestick injury, but several infections acquired through contact or skin or mucous membrane with infected blood have been reported. In this paper we outline how the risk of HIV infection in a health care worker can be estimated for a given number of exposures. The formula is based on the known likelihood of transmission per needlestick, the seroprevalence rate among patients, and the number of needlestick injuries that occur. We also suggest a list of measures by which the risk of HIV transmission to hospital staff can be minimized.     

Epidemiology of bloodstream infections in a bacille Calmette-Guérin-vaccinated pediatric population in Malawi

The risk of Mycobacterium bovis bloodstream infection (BSI) in bacille Calmette-Guérin (BCG)-vaccinated children with human immunodeficiency virus (HIV) infection remains uncharacterized. We studied pediatric inpatients during the 1998 dry season in Malawi. After a detailed clinical evaluation, blood was drawn for culture and HIV testing. Of 229 children, 128 (56%) were male, 35 (15.3%) had BSI, and 30% of children aged >1.5 years (median, 2.7 years; range, 1 month-13 years) had HIV infection. The predominant pathogen was non-typhi Salmonella; neither Mycobacterium tuberculosis nor M. bovis was isolated. A diagnosis of malnutrition or sepsis was predictive of BSI; malnutrition alone correlated with both death and BSI. The bloodstream dissemination of M. tuberculosis and M. bovis BCG is uncommon in HIV-infected children vaccinated with BCG. Correlates such as malnutrition or sepsis can provide algorithms for identifying children who need observation or empirical antimicrobial therapy for BSI in the absence of appropriate laboratory testing.     

Involvement of the pancreas in AIDS: a prospective study of 109 post-mortems

BACKGROUND: Pancreatic involvement in AIDS is rarely mentioned in medical literature. AIMS: To identify the main morphological patterns of the pancreas using optical and electron microscopy in AIDS patients. DESIGN: An open, prospective, and sequential study in a tertiary institutional hospital. METHODS: Consecutive post-mortems of 109 AIDS patients and 38 controls (1995). Baseline characteristics of AIDS patients and controls were evaluated. Morphological analysis consisted of: (i) semi-quantitative score of acinar and parenchymal elements; (ii) qualitative analysis of ducts, vascular components, nerves, and Langerhans' islets; (iii) specific stains and immunohistochemistry for opportunistic agents; (iv) ultrastructural data. RESULTS: The mean age of AIDS patients was 37 years; 80% were male; 60% were white; 21% were alcoholic. All patients with AIDS had normal blood amylase, blood glucose, and pancreatic ultrasound. Histological findings were: acinar atrophy (60%), few zymogen granula in acinar cytoplasm (52%), abnormalities in acinar nucleus (65%), pancreatic steatosis (66%), and focal necrosis (17%). Immunohistochemistry revealed: mycobacteriosis (22%), toxoplasmosis (13%), cytomegalovirus (9%), Pneumocystis carinii (9%), and HIV p24 antigen in macrophage cytoplasm (22%). Ultrastructural examination showed: decreased zymogen granula, enlargement and proliferation of the endoplasmic reticulum and mitochondria, nuclear abnormalities, and increased lipid droplets in acinar cytoplasm. CONCLUSION: Pancreatic involvement in AIDS is very frequent (90%) and is usually asymptomatic. Morphological changes showed three patterns of pancreatic alterations: 'nutritional-like', inflammatory and both of these together. The 'nutritional-like' pattern (atrophy, few zymogen granula and steatosis) may be due to many factors such as nutritional characteristics (Kwashiorkor-like) induced by the HIV infection or related to the HIV virus itself.