Autonomic denervation in jejunal mucosa of homosexual men infected with HIV.

Autonomic nerves in jejunal mucosa of HIV-infected patients show severe structural damage on electron microscopic examination. The aim of this study was to quantify loss of autonomic axons from the lamina propria of HIV-infected patients in different clinical stages of disease. Jejunal biopsies were taken from 19 HIV-antibody-positive homosexual men and from 10 control patients. Autonomic fibres in the mucosa were stained with a neurone-specific polyclonal antibody, PGP 9.5. The density of axons was quantified by a point-counting technique using a Lennox eyepiece graticule under light microscopic examination. There was significant reduction in axonal density in the villi of HIV-infected patients [mean, 9.0; standard deviation (s.d.), 4.7] compared with controls (mean, 15.3; s.d., 5.2; P = 0.003), and in the pericryptal lamina propria of HIV-infected patients (mean, 17.8; s.d., 5.4) compared with controls (mean, 27.3; s.d., 6.2; P = 0.0002). Although autonomic denervation occurs throughout the jejunal mucosa of HIV-infected patients, there was no correlation between the clinical stage of HIV disease and the degree of denervation. The denervation was greatest in patients with the most severe diarrhoea, but this difference was not significant. This study provides the first quantitative morphological evidence for depletion of autonomic nerves in the jejunum of patients infected with HIV. Autonomic neuropathy may contribute to chronic diarrhoea in HIV disease.

HIV infection of human fetal intestinal explant cultures induces epithelial cell proliferation.

OBJECTIVE: The concept that HIV infection per se alters small intestinal mucosal structure and function (HIV enteropathy) remains controversial and in this study we report in vitro experiments designed to elucidate the matter. METHODS: Twenty pairs of human fetal intestinal tissue explants were maintained in vitro for up to 14 days; one explant of each pair was incubated and infected with HIV, and the other served as a matched uninfected control. At various times after infection, explant culture fluid and tissue were removed, p24 concentration was measured and tissue formalin fixed. Explant tissue was embedded in paraffin wax and sections stained by an immunoperoxidase method directed against proliferating cell nuclear antigen (PCNA). The percentage of proliferating crypt and villous epithelial cells, stained by PCNA, was calculated in paired samples. The difference between the percentage for paired samples was designated delta crypt proliferation (delta CP) and delta villous proliferation (delta VP), respectively. Epithelial cell proliferation was deemed to be enhanced if the percentage of PCNA-stained cells was greater in the HIV-infected than in the control tissue. RESULTS: Explant culture fluid from tissue exposed to HIV showed a progressive rise in p24 antigen (Ag) level, indicating HIV infection of these explants. Fifteen pairs of explants showed progressively positive delta CP with time (P < 0.01) indicating crypt hyperplasia and all 20 pairs of explants showed positive delta VP, indicating hyperplasia of villous epithelial cells. CONCLUSIONS: This study provides direct evidence that HIV stimulates epithelial cell proliferation in intestinal mucosa. HIV-infected human intestinal explants provide a model of crypt hyperplastic villous atrophy previously described as HIV enteropathy and detected in clinical biopsy specimens from HIV-infected patients.

Metastasising pilar tumour of scalp.

A case of pilar tumour of the scalp, treated by local excision and radiotherapy, later metastasised to the neck. The variable histological growth patterns of the primary tumour and its metastases are described. It is concluded that the pilar tumour is a genuine neoplasm of the hair follicle that is occasionally capable of malignant behaviour.

Atypical progression of multiple myeloma with extensive extramedullary disease.

Multiple myeloma is a neoplastic disorder caused by the proliferation of a transformed B lymphoid progenitor cell that gives rise to a clone of immunoglobulin-secreting cells. Other plasma cell tumours include solitary plasmacytoma of bone (SPB) and extramedullary plasmacytomas (EMP). Despite an apparent common origin there exist pathological and clinical differences between these neoplasms and the association between them is not completely understood. A case of IgG multiple myeloma that presented with typical clinical and laboratory features, including a bone marrow infiltrated by well differentiated plasma cells, is reported. The tumour had an unusual evolution, with the development of extensive extramedullary disease while maintaining mature histological features.

Depletion of neuroendocrine cells in rectal biopsy specimens from HIV positive patients.

AIMS: To compare the density of neuroendocrine cells in rectal biopsy specimens from human immunodeficiency virus (HIV) infected individuals with that of a control group. METHODS: Neuroendocrine cells in rectal biopsies were identified using an immunohistochemical stain for chromogranin and subsequently quantified using a method of linear intercept. RESULTS: Neuroendocrine cells were found to be significantly decreased in the HIV positive group. CONCLUSIONS: Loss of neuroendocrine cells may contribute to apoptotic bodies seen in this condition. This could be related to infection of these cells with HIV and could contribute to diarrhoeal disease in HIV infection.

Granulocytic sarcoma of the rectum: a rare complication of myelodysplasia.

A 67 year old man with myelodysplasia was admitted as an emergency with a six week history of rectal bleeding and diarrhoea. Barium enema showed an irregular polypoid filling defect in the lateral wall of the proximal rectum near the rectosigmoid junction. Histology showed this to be a granulocytic sarcoma (extramedullary granulocytic leukaemia; chloroma) infiltrating the bowel. A low index of suspicion of this lesion results in an incorrect diagnosis in many such cases. A chloroacetate esterase immunoperoxidase stain will confirm the granulocytic nature of the tumour cells.

Jejunal enteropathy associated with human immunodeficiency virus infection: quantitative histology.

Jejunal biopsy specimens from 20 human immunodeficiency virus (HIV) positive male homosexual patients were analysed and compared with those of a control group to determine whether the abnormalities were caused by the virus or by opportunistic infection. The degree of villous atrophy was estimated with a Weibel eyepiece graticule, and this correlated strongly with the degree of crypt hyperplasia, which was assessed by deriving the mean number of enterocytes in the crypts. The density of villous intraepithelial lymphocytes fell largely within the normal range, either when expressed in relation to the number of villous enterocytes or in relation to the length of muscularis mucosae. Villous enterocytes showed mild non-specific abnormalities. Pathogens were sought in biopsy sections and in faeces. Crypt hyperplastic villous atrophy occurred at all clinical stages of HIV disease and in the absence of detectable enteropathogens. An analogy was drawn between HIV enteropathy and the small bowel changes seen in experimental graft-versus-host disease. It is suggested that the pathogenesis of villous atrophy is similar in the two states, the damage to the jejunal mucosa in HIV enteropathy being inflicted by an immune reaction mounted in the lamina propria against cells infected with HIV.

Diabetic hepatitis preceding the onset of glucose intolerance.

A patient who abstained from alcohol consumption but who had asymptomatic chronic progressive hepatomegaly, mild disturbance of liver function tests and hepatitis resembling alcoholic hepatitis (nonalcoholic steatohepatitis) developed glucose intolerance several years after the hepatitis was diagnosed. The patient had a family history of both diabetes and chronic liver disease. A lesion resembling alcoholic hepatitis in a patient who denies alcohol consumption, may be diabetic or pre-diabetic in aetiology and such a patient should be followed up with glucose tolerance tests.

Death due to air embolism during sexual intercourse in the puerperium.

We describe the cases of two young women who died due to air embolism during sexual intercourse early in the puerperium.

HIV enteropathy: comparative morphometry of the jejunal mucosa of HIV infected patients resident in the United Kingdom and Uganda.

AIMS: To compare jejunal mucosal morphometry in HIV infected patients resident in London and Uganda. PATIENTS: Twenty HIV positive patients from London and 16 from Uganda were studied, and compared with HIV negative control subjects from both sites. METHODS: Stools and biopsy specimens were examined for enteropathogens. Surface area to volume (S:V) ratio was estimated morphometrically, mean crypt length of jejunal biopsy specimens was measured, and HIV infected cells detected immunohistochemically were quantified. RESULTS: Enteric pathogens were detected in none of the London patients, and in three Ugandan patients. S:V ratio was lower, and mean crypt length higher, in the specimens of London patients than in normal subjects, but there was no difference in S:V ratio or mean crypt length between Ugandan patients and controls. A negative correlation was present between S:V ratio and mean crypt length in all biopsy specimens analysed. HIV infected cells were detected only in lamina propria. CONCLUSION: Infection of cells in the lamina propria of the jejunum with HIV stimulates crypt cell proliferation, and a fall in villous surface area. The mucosal response to HIV is masked by other pathogens in the African environment.