AID, HIV and general practice.
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Biomedical subjects
Publications and source records attributed to B Gazzard.
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The findings of 27 lymph node biopsies performed on 24 homosexual patients with lymphadenopathy are presented. Six had acquired immune deficiency syndrome (AIDS) and 18 lymphadenopathy only, of whom one subsequently developed AIDS. All these patients had antibodies to the human T-cell lymphotropic virus type III (HTLV-III) suggesting that HTLV-III is currently the commonest cause of lymphadenopathy in homosexual men. The histopathological findings of six of seven nodes from AIDS patients showed either follicular depletion alone or follicular and paracortical lymphocyte depletion. Nodes from four patients showed Kaposi's sarcoma, three of which also showed follicular hyperplasia. In two of these patients there were no cutaneous manifestations of this condition. One lymph node from a patient with persistent generalized lymphadenopathy (PGL) showed Mycobacterium tuberculosis. Six nodes from six other patients have had features of toxoplasmosis although there was no serological or clinical evidence of recent toxoplasma infection. The remaining 11 lymph nodes from patients with PGL and one node from a patient with transient lymphadenopathy, showed reactive follicular hyperplasia only. We conclude that homosexuals with lymphadenopathy who are HTLV-III antibody positive do not need a routine node biopsy unless an alternative diagnosis is strongly suspected.
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A lymph node biopsy obtained from a patient with human T-cell lymphocytotropic virus III/lymphadenopathy-associated virus (HTLV-III/LAV) antibody, presenting with an acute glandular fever-like illness, was examined by electron microscopy. Numerous pathological changes were present in the biopsy, including hypertrophy of smooth endoplasmic reticulum, intracytoplasmic rod-like inclusions within the cisternae of endoplasmic reticulum, multivesicular bodies, test-tube and ring-shaped forms, and tubulo-reticular structures. Intranuclear and intracytoplasmic viral-like particles measuring 105-120 nm in diameter and small cytoplasmic particles measuring 50-70 nm in diameter were found in some degenerating lymph node cells. These pathological findings may reflect a host cell response to various pathological and viral stimuli resulting from immune deficiency owing to infection with HTLV-III/LAV.
The effect of oral secoverine hydrochloride on neostigmine-stimulated sigmoid motility in 12 patients with irritable bowel syndrome was studied in a double-blind placebo-controlled cross-over study. Both spontaneous and stimulated motor activity were significantly reduced by the compound in comparison with placebo. The most sensitive indices were the frequency of wave activity, maximum amplitude and motility index. Two patients reported mild dizziness after secoverine.
The clinical notes and histology of 374 patients treated by colectomy and ileo-rectal anastomosis for ulcerative colitis were reviewed. Only those with definite diagnosis of ulcerative colitis and follow-up rectal biopsies were included (171 cases). Morphology and patterns of mucin secretion were investigated to assess whether abnormal mucin with predominance of sialomucins is a useful indicator of malignancy-risk. Carcinoma has developed in six patients and 'precancer' in seven. The results show coexistence of dysplasia and sialomucin even in the absence of inflammation in all but three biopsies; in contrast the presence of both dysplasia and normal mucin profile was found in less than 1%. A significant correlation was noted between an inflamed mucosa and the development of cancer or precancer, the presence of sialomucins and the appearance of dysplasia. Sialomucins showed a greater sensitivity in detecting cancer than dysplasia (75% versus 30%). However, dysplasia was notably more specific (94% compared with 50%), hence its greater predictive value as indicator of malignancy (50% as against 15% for a positive sialomucin result). Mucin stains on routine fixed paraffin-embedded tissue provide a simple screening method to sharpen the assessment of dysplasia and cancer-risk in patients with ulcerative colitis despite the limitations referred to above. The lack of definite evidence of dysplasia in four patients who developed malignancy without premalignant changes in the rectal biopsies emphasises the need for frequent multiple biopsies in patients with an ileo-rectal anastomosis for ulcerative colitis.
A joint prospective long term study of gastric biopsies has been undertaken to survey intestinal metaplasia Types I, II, and III in terms of their incidence, distribution and value in the selection of high risk cancer patients. This study is based on protocols agreed between three centres for endoscopy, histological interpretation, and mucin histochemistry. The results on the first 1350 gastric biopsies examined during 1981-1982 are presented. Intestinal metaplasia was found in 267 biopsies (20%), being common in association with carcinoma (71%), less so in benign conditions such as gastric ulcer (39%), and chronic gastritis (24%), but rare in 'normal' (3%). Type I intestinal metaplasia was predominant (73%) in all the biopsies with intestinal metaplasia and was most common in benign conditions, 70% in gastric ulcer and 76% in chronic gastritis. Type III intestinal metaplasia (incomplete sulphomucin-secreting intestinal metaplasia) was recorded in only 9.8% of all the biopsies with intestinal metaplasia and had a higher incidence in carcinoma (35%), than in benign conditions (7%) (p less than 0.0001). These results suggest that intestinal metaplasia types may have different malignant potential and their identification may be useful in screening patients for early detection of cancer.
Ultrastructural changes (tubuloreticular structures and tube and ring shaped forms) previously described in patients with acquired immunodeficiency syndrome (AIDS) are described for the first time in the lymph nodes and circulating lymphocytes of patients with persistent lymphadenopathy. These observations support the view that the persistent lymphadenopathy syndrome and AIDS are caused by the same transmissible agent(s).
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When rectal biopsies from 65 patients with ulcerative colitis and 20 patients with Crohn's disease was stained for mucins, an abnormal pattern (excess of sialomucins) was seen in about half of them. This is in contrast with 65 cases of non-specific proctitis where the mucin pattern of rectal biopsies was normal in all except one case. The abnormal mucin secretion in patients with ulcerative colitis was apparently related to the activity, duration, and extent of the disease. All biopsies with dysplasia showed predominant sialomucin staining except one. All biopsies showing sialomucins during remission also had dysplasia, while during active disease a number of biopsies had increased sialomucins without the evidence of dysplasia. It is not known if such cases will subsequently develop morphological atypia.
Over a four-year period 21 cases of solitary ulcer syndrome (SUS) were studied for their clinical, histological, and mucus secretion patterns and compared with histological and mucus secretion patterns of 78 cases of non-specific proctitis collected over the same period. Normal mucus composition was found in non-specific proctitis while abnormalities of mucins with predominance of sialomucins were associated with SUS. Although histology remains the most important investigation in the diagnosis of SUS, mucin changes provide valuable additional evidence.
Serum alpha-fetoprotein (AFP) levels have been measured sequentially by a radio-immunoassay method in 64 patients with fulminant hepatic failure. In 15 of the 64 patients (23%) AFP levels were raised but in only two did they exceed 500 ng/ml. Of the 23 survivors 11 (48%) had raised AFP levels compared with four of the 41 (9-8%) fatal cases (P less than 0-005). This rise in AFP levels was found early after the development of grade IV coma and constitutes an encouraging prognostic sign at a time when the liver function tests and EEG are unhelpful. A radioimmunoassay must be used if these small but significant rises in plasma concentration are to be detected. Twelve patients survived without showing a rise in plasma AFP at anytime during the illness. The four fatal cases who had raised AFP levels all had serious complications of fulminant hepatic failure. Charcoal haemoperfusion did not seem to increase the survival of AFP negative patients.
The report aimed at obtaining information about patients' experience of how the diagnosis of AIDS was given to them by their doctors, and about patients' satisfaction with the consultation. Thirty people with AIDS completed a self-report questionnaire enquiring about their views and satisfaction with the process of communication of the diagnosis. Results showed that about two-thirds of patients were satisfied, while almost a quarter were definitely not satisfied with the consultation. Satisfaction was associated with the general attitude of the person giving the diagnosis and with the quality of the information given. The relevance of the findings for the training of doctors is discussed.
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Fifty surgeons and 72 preoperative patients in 2 central London hospitals were asked their views on preoperative HIV antibody testing, who is at risk of HIV infection and HIV test counseling. A substantial proportion of both surgeons and preoperative patients, 48% and 54% respectively, supported compulsory HIV antibody testing without patient consent. They believed this should occur as a routine practice prior to surgery. However, surgeons and patients differed in the preoperative patients to be considered for such testing. All surgeons advocating compulsory testing believed that it was only necessary for those patients belonging to high risk groups whilst preoperative patients believed that all patients should be HIV tested prior to surgery. Surgeons and patients also differed in their views on who was at risk of HIV infection. Surgeons believed those at risk to be members of identifiable risk groups whilst patients believed everyone was at risk, especially those engaging in high risk behaviours. Finally, when asked which health professionals they thought should be involved in HIV test counselling, both surgeons and patients agreed that hospital doctors, including surgeons themselves, should take on the responsibility of test counselling. The implications of this and routine HIV antibody testing are discussed.
This article reviews the immunology, genetics, epidemiology and treatment of two of the most important infectious diseases in the world, HIV and tuberculosis (TB). The pandemic of TB has been greatly magnified by the advent of the HIV epidemic. In the developing world, probably 50% of HIV seropositive individuals are co-infected with TB. The TB epidemic has expanded both because of increased susceptibility of patients to new tuberculous infection and also because of the greater chance of a primary complex leading to disseminated disease. The evidence that TB has had any effect on the HIV epidemic is less clear in the developed world with effective antiretroviral therapy. In resource-poor countries, many HIV infected individuals die prematurely of TB. Both organisms infect immunologically competent cells, and the control of infection in both has a large genetic component. The complex immunological response and process of cytokine release has a marked impact on both control of disease and the pathological effects of infection. Treatment of TB was associated with the development of resistance until the need for combination chemotherapy was recognised. It was then realised that one of the major factors making treatment of TB difficult was poor long-term adherence. Exactly the same sequence of events in terms of our understanding of the treatment of HIV infection has occurred more recently. These two infections undoubtedly present the most serious challenge to public health across the world, and are likely to be controlled only by a global mobilisation of resources not seen since the end of the last European war.
HIV-infected patients presenting with oral or oesophageal candidosis were randomised to four weeks treatment with itraconazole 200 mg, followed by itraconazole or matching placebo for a prophylaxis phase of 24 weeks. Clinical and mycological evidence of candidosis infection was assessed on a four-weekly basis. Seventy patients were enrolled, of whom 50 completed 28 days of itraconazole therapy; 74% (37 patients) were clinically cured and 40% were also mycologically cured. Fifteen patients were withdrawn for a variety of reasons including non-compliance, adverse events and the use of excluded medications. Forty-four patients were enrolled in the prophylactic phase. There were significantly more relapses of candidosis, and time to candidosis was significantly shorter in the placebo group than in the itraconazole treated group (p = 0.0001). Itraconazole 200 mg daily is effective and well tolerated for the treatment and prevention of oral and oesophageal candidosis in HIV-infected patients.
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