Medical treatment of liver hydatidosis.

There are currently three treatment options for liver hydatidosis: urgery, which remains the mainstay of radical treatment; ultrasound-guided aspiration (puncture/aspiration/injection/reaspiration--PAIR); and chemotherapy with benzimidazole compounds (albendazole and mebendazole). Chemotherapy is a noninvasive treatment and is less limited by the patient's status than surgery or PAIR but is not ideal when used alone. Albendazole, the drug most often used, appears to have the greatest efficacy of any agent used so far; nevertheless, apparent cure (shrinkage or disappearance of cysts) ranges only between 20% and 30% of cases. The possible contribution of perioperative chemotherapy offers the prospect of preventing recurrent disease, but it requires more clinical trials to establish that pre- or postoperative chemotherapy does prevent recurrence. The main adverse events are related to changes in liver enzyme levels and bone marrow suppression. About 10% to 20% of patients develop self-limited, reversible rises in transaminase levels; clinically severe pancytopenia or agranulocytosis is exceptional. Alopecia is observed during long-term treatment with albendazole. In all cases these events disappear once treatment is interrupted. According to the World Health Organization guidelines, chemotherapy is the preferred treatment when the disease is inoperable, when surgery or PAIR is not available, or when the cysts are too numerous. Another important indication for chemotherapy is the prevention of secondary echinococcosis. There is not yet formal consensus, as the efficacy and safety of some of the methods require further evaluation before we can establish comprehensive guidelines for the medical treatment of hydatidosis.

Accelerated obstructive pulmonary disease in HIV infected patients with bronchiectasis.

Human immunodeficiency virus (HIV) infection has been associated with a wide spectrum of pulmonary disease. We report three HIV-seropositive patients with rapidly worsening airway obstruction associated with bronchiectasis. All subjects (age range 33-39 yrs) were cigarette smokers. Two had previously used intravenous drugs. The CD4 lymphocyte count ranged 40-250 cells x mm(-3). All individuals had complained of increasing dyspnoea for 3-6 months. Within 1 yr, they all developed severe airway obstruction with a decrease in both forced expiratory volume in one second (FEV1) and ratio of FEV1 to forced vital capacity (FEV1/FVC) to less than 60% of predicted value, and a decrease in mean forced expiratory flow at 25-75% of the forced vital capacity (FEF25-75) to less than 35% of predicted value. Computed tomography of the chest disclosed bilateral dilated and thickened bronchi. No classical causes of genetic or acquired bronchiectasis were identified in our patients. Recurrent bacterial bronchitis occurred in the follow-up period of the three patients. In conclusion, unusually rapid airway obstruction associated with bronchiectasis should be added to the wide spectrum of respiratory complications of human immunodeficiency virus infection.

[Pulmonary cryptococcosis during HIV infection. 15 cases]. / Cryptococcose pulmonaire au cours de l'infection à VIH. 15 observations.

We reviewed the records of 15 Human Immunodeficiency Virus (HIV) infected patients with pulmonary cryptococcosis (PC). PC was the first AIDS-defining manifestation in nine patients. HIV infection was identified simultaneously with the onset of PC in 4 patients. The CD4+ lymphocyte count was low in all cases (median, 24/m3). Chest radiography showed interstitial infiltrates in 13 instances, associated with pleural effusion in 5 cases and hilar adenopathy in 2 cases. In one case, chest-X-ray showed isolated pleural effusion and was normal in one patient. For 11 of 12 patients, bronchoalveolar lavage fluid culture was positive for Cryptococcus neoformans. Seven of 15 patients had evidence of extrapulmonary cryptococcal disease with positive cerebrospinal fluid culture. Serum cryptococcal antigen was detected in all 15 patients. Concomitant lung infection with Pneumocystis carinii was diagnosed in 4 patients. First-line regimen was fluconazole in 10 patients and amphotericin B in 4 patients. Fluconazole has been prescribed in 7 patients as a permanent suppressive therapy and should be continued indefinitely.

Phase II study of liposomal encapsulated daunorubicin in the treatment of AIDS-associated mucocutaneous Kaposi's sarcoma.

OBJECTIVE: To evaluate the efficacy and safety of liposomal encapsulated daunorubicin (DaunoXome) in the treatment of AIDS-associated mucocutaneous Kaposi's sarcoma. DESIGN: A Phase II, multicentre, European, non-comparative, open study to assess the use of DaunoXome in patients with no prior anthracycline chemotherapy for Kaposi's sarcoma. The response rate, time to disease progression, and the incidence and severity of adverse events were documented. SETTING: Hospital-based HIV units. PATIENTS: Thirty HIV-seropositive patients with mucocutaneous Kaposi's sarcoma were enrolled and treated. INTERVENTIONS: Treatment with DaunoXome at a dose of 40 mg/m2 intravenously once every 2 weeks. Treatment with antiretroviral agents and prophylaxis of opportunistic infections where indicated. RESULTS: Of the 30 evaluable patients, 22 patients (73%) achieved a partial response. Median time to treatment response was 30 days (range, 15-202). For patients with a partial response, median time to treatment failure was 153 days (range, 15-558). Patients received a median of 10 cycles (range, 1-44). Adverse events were minimal. The most common side effect was granulocytopenia in 16 patients (53%). CONCLUSION: DaunoXome is an effective and well-tolerated treatment for AIDS-associated mucocutaneous Kaposi's sarcoma and can be administered for prolonged periods. The myelosuppression can be managed by dose reductions and dose not preclude the concurrent use of antiretroviral therapies.

Qualitative and quantitative analysis of human cytotoxic T-lymphocyte responses to HIV-1 proteins.

OBJECTIVE: To study the degree of immunogenicity of each HIV-1 protein. DESIGN: In most viral systems, antiviral cytotoxic T-lymphocytes (CTL) from a given donor preferentially recognize only one or a small number of viral proteins. METHODS: Anti-HIV CTL were generated by in vitro stimulation of peripheral blood mononuclear cells from seropositive donors and tested against multiple HIV-1 proteins or groups of proteins encoded by seven genes (env, gag, pol, nef, rev, tat and vif). Using autologous target cells infected with recombinant vaccinia viruses expressing one of the HIV-1LAI proteins, we compared the cytolytic activities obtained from bulk culture with those found in limiting dilution analysis (LDA). RESULTS: Our results were noteworthy for the following reasons. (1) Each responding donor reacted simultaneously to multiple proteins; this is very unusual in other viral systems. Anti-Gag CTL were detected in most, and anti-Pol in approximately three-quarters, of the patients, together with very high amounts of the corresponding CTL precursors in LDA. CTL against Env and Nef were found in two-thirds of the patients, while Vif- and Rev-specific CTL were less frequent. Finally, Tat was seldom recognized by CTL, but its antigenicity was revealed in LDA. (2) All responding cells revealed in bulk cultures as well as in LDA were CD8+ T-cells, and their in vitro differentiation did not require the help of CD4+ T-cells. (3) Proteins from the HIV-1LAI isolate were recognized with high frequency by CTL from seropositive donors, most certainly being infected by other isolates, which suggests that relatively conserved epitopes are predominant targets of CTL. CONCLUSION: Taken together, these results are encouraging for vaccine purposes, since anti-HIV-1 CTL stimulation is thought to be a requirement for such a vaccine.

[Pneumocystis carinii pneumonia in HIV infection. Diagnosis, prognostic factors and curative treatment]. / Pneumopathie à Pneumocystis carinii au cours de l'infection à VIH. Diagnostic, facteurs pronostiques et traitement curatif.

The diagnosis of Pneumocystis carinii pneumonia (PCP) rests on the isolation of this micro-organism in patients whose latest blood count, less than 2 months old, shows less than 250 CD4 lymphocytes per cubic mm and who present with signs of impaired lung function. Bronchoalveolar lavage (BAL) is the reference diagnostic method, but induced expectoration may be the initial examination, in which case BAL is performed only when the latter fails or gives negative results. Prognostic factors are those of any interstitial pneumonia plus those specific to PCP and those associated with HIV infection. It is only when no initial severity factor is present that cure can be contemplated, provided the effectiveness of treatment is evaluated daily. Cotrimoxazole is the reference drug for comparisons with all new treatments; the indications of corticosteroid therapy and the necessity of intensive care techniques are now better determined. The frequency of PCP and its mortality rate should be reduced, and one may look forward to a time when this disease will be rare and atypical, thereby raising other diagnostic and therapeutic problems.

Immunohistochemical evidence for human immunodeficiency virus-1 infection of liver Kupffer cells.

To investigate the possibility of human immunodeficiency virus-(HIV) 1 infection of liver cells, liver samples from 17 patients with either acquired immunodeficiency syndrome (AIDS, 13), AIDS-related complex (ARC, 3), or lymphadenopathy syndrome (LAS, 1) were studied. A monoclonal antibody directed against the p24 gag HIV-1 protein was used in an immunoperoxidase assay and yielded positive results in seven out of 17 samples. Staining by anti-p24 antibody was of three types: diffuse in Kupffer cells of most samples, inside granuloma in cells that were probably histiocytes, and in some sinusoidal cells whose origin was difficult to ascertain. Attempts to locate the CD4 membrane antigen showed that it was mainly present on endothelial sinusoidal cells. These results indicate that liver cells, including Kupffer cells, might be infected by HIV-1, and that these cells might be involved in certain liver lesions observed during HIV-1 infection, particularly sinusoidal abnormalities.

[Hepatic involvement in AIDS. A retrospective clinical study in 71 patients]. / Atteintes hépatiques au cours du SIDA. Etude anatomo-clinique rétrospective chez 71 patients.

In order to determine the extent of liver abnormalities occurring during acquired immunodeficiency syndrome, the available histological analyses of liver samples (32 biopsies, 52 autopsies) from 71 AIDS patients, for the period 1982-1986, were studied retrospectively. Hepatomegaly was the most common clinical symptom (23 patients, 32.4%), while jaundice was rare, being seen in only 5 cases (7%). Progressive anicteric cholestasis was the most frequently observed biological anomaly (29/52, 55.7%). Ten patients had liver infections: 2 Mycobacterium tuberculosis, 8 Mycobacterium avium intracellulare. Cytomegalovirus was present in 3 patients and 1 individual was infected with Cryptococcus neoformans. Granulomatous hepatitis was associated with these infectious agents in 11 patients, but remained unexplained in 11 others. Three patients had cholangitis (2 with CMV inclusions, 1 unexplained). Among the 32 biopsies, 5 elucidated the origin of unexplained fever. Kaposi's sarcoma of the liver was found in 10/52 autopsy samples (19%) and hepatic lymphoma in 2 cases. Non-specific histological lesions were common: inflammation of the portal spaces (48 cases, 67.6%), steatosis (32 patients, 45%), peliosis hepatis (9 cases, 12.6%) and sinusoidal dilations (39 cases, 54.9%).

Intestinal infections in patients with acquired immunodeficiency syndrome. A prospective study in 132 patients.

We studied prospectively 132 patients with acquired immunodeficiency syndrome to define the spectrum of enteric pathogens during this disease, with special reference to the correlation between the lesions, the infections, and the symptoms. Forty-four percent of the patients harbored at least one enteric pathogen: the most frequently recovered were Cryptosporidium (28), cytomegalovirus (16), Entamoeba histolytica (13), Giardia lamblia (9), and Mycobacterium avium intracellulare (7). Patients harboring pathogens were more likely to be diarrheics (69%) than patients without a pathogen (38%; P = 0.01) and more likely to have endoscopic lesions (29%) than patients without a pathogen (4%; P less than 0.001). The most common pathogen associated with diarrhea was Cryptosporidium. Cytomegalovirus, Entamoeba histolytica, and Salmonella typhimurium were each significantly associated with endoscopic lesions. Patients with cytomegalovirus infection tended to have a greater incidence of ulcer than patients without cytomegalovirus infection. Stool analysis diagnosed 61% of the infections, while endoscopy diagnosed 44%. Seven percent were recognized by stool analysis and endoscopy. When considering the 24 patients in whom accurate diagnosis warranted endoscopic biopsies, stool examination alone would have given an incomplete diagnosis in 14 patients (due to the presence of polyinfection). The frequency of inaccurate diagnosis of infection by stool determination alone, plus the development of new antiviral agents that suppress cytomegalovirus, may favor the earlier application of endoscopic evaluation in these patients.

Cytomegalovirus colitis in patients with acquired immunodeficiency syndrome.

Twenty-four AIDS patients, who underwent gastrointestinal evaluation, died from their disease and were autopsied. Seven had Cytomegalovirus colitis (group I) and 17 did not (group II). Clinical manifestations, digestive lesions, and infections were compared in the two groups. Chronic watery diarrhea was present in all the patients with colitis but was also present in 65% of the patients without colitis. Hematochezia was present only in the group with colitis (one of seven patients) but appeared late in the diarrheal course, due to necrotizing colitis. No other difference were noted between the two groups (mean duration of diarrhea, frequency and nature of the other infections). As for group I specifically, colonic ulcerations due to Cytomegalovirus were present in all the patients, varying from punctate and superficial erosions to deep ulcerations, with granular and friable intervening mucosa. Severe colonic lesions appeared during the course of Cytomegalovirus colitis in two patients who developed lethal necrotizing colitis. Finally, the clinical and pathologic features of these seven cases were compared to other reports of Cytomegalovirus infection of the colon.

[Buccopharyngeal Kaposi's sarcoma in AIDS. Apropos of 51 cases]. / Le sarcome de Kaposi buccopharyngé au cours du SIDA. A propos de 51 cas.

The authors present a series of 51 cases of buccopharyngeal Kaposi's sarcoma observed in patients with AIDS. The diagnosis of Kaposi's sarcoma is generally obvious due to its appearance, its constantly violaceous colour and its site, especially palatine and velar. When Kaposi's sarcoma is the first manifestation of the disease, it appears to be associated with a relatively favourable pejorative connotation when the nevertheless extremely modest median survival of these patients is compared with that of patients who initially presented with an opportunistic infection not associated with Kaposi's sarcoma. Buccopharyngeal Kaposi's sarcoma is usually only an epiphenomenon. It is rare that the local course requires any tumour reduction treatment. When such treatment is required, radiotherapy with 35 Gys is currently considered to be the best solution.

[Digestive manifestations in acquired immunodeficiency disease]. / Les manifestations digestives au cours du syndrome d'immunodéficience acquise.

Digestive manifestations of AIDS were studied retrospectively in 87 patients with respect to clinical, microbiological, endoscopic and histological data. Chronic or intermittent diarrhea was observed in 62 p. 100 of patients and frequently associated with major weight loss. The digestive opportunistic infections were: oesophageal candidiasis (42 p. 100), cryptosporidiosis (24 p. 100), cytomegalovirus infections (22 p. 100), isosporiasis (3.4 p. 100), atypical mycobacteriosis (2.2 p. 100), toxoplasmosis (2.2 p. 100). Thirty non-opportunistic agents were detected in 26 patients. Gastrointestinal Kaposi sarcoma occurred in 18 p. 100 of cases. The etiology of diarrhea remained unknown in 16 p. 100 of patients. The value of endoscopy is discussed: esophagogastroduodenal fibroscopy, is usually required to assess oesophageal candidiasis, colonoscopy is required to assess cytomegalovirus colitis on histological data.

[Clinical and virological study of a case of infection with the HIV-LAV 2 virus]. / Etude clinique et virologique d'un cas d'infection par le virus HIV-LAV 2.

A case of AIDS due to HIV/LAV2 is reported. The patient was a 32 year old man from Guinea-Bissau with no known risk factors. He had brain toxoplasmosis, oral thrush and chronic genital herpes. Investigations for IgG anti-HIV/LAV1' (Elisa, Western Blot, Ripa) were negative. Antibodies to HIV/LAV2 were found and cultures of peripheral blood lymphocytes and cerebro-spinal fluid were positive. HIV/LAV2 seems to be similar to STLV-III (mac), STLV-III (agm), and probably HTLV-IV.

[Eosinophilic granulomatous hepatitis. Apropos of 3 cases]. / Les hépatites granulomateuses à éosinophiles. A propos de trois observations.

The authors report three cases of eosinophilic granulomatous hepatitis observed among 325 liver puncture biopsies. The patients had urinary bilharziasis and had just been treated with oltipraz. These cases were probably due to eosinophilic reactions which sometimes follow treatment of schistosomiasis.

[Cerebral toxoplasmosis in immunosuppressed patients: diagnosis and treatment]. / Toxoplasmose cérébrale de l'immunodéprimé: diagnostic et traitement.

Central nervous system toxoplasmosis was diagnosed in 12 immunosuppressed patients, eleven of whom had AIDS. Fever (9/12), confusion (7/12) and focal neurological manifestations (6/12) were the main clinical signs. Lumbar puncture yielded abnormal cerebrospinal fluid in 6/6 cases. Cerebral computed tomographic scan abnormalities, homogenous (2/12) or ring-like (9/12) contrast-enhancing mass lesions and/or low density lesions (6/12), were present in all patients. Brain biopsy confirmed T. gondii infection in 7/8 cases. The combination pyrimethamine-sulfadiazine accounted for complete resolution (4/8) or partial improvement (4/8) in eight out of 12 patients. Mean duration of therapy was 6.5 months (1-21.5 months) in 11 patients. No relapse was observed. In three cases spiramycin was ineffective in the prevention of neurotoxoplasmosis.

An international study on the serological differential diagnosis of human cystic and alveolar echinococcosis.

An enzyme-linked immunosorbent assay (ELISA) for the serological differentiation of cystic (Echinococcus granulosus) and alveolar (E. multilocularis) echinococcosis in man has been evaluated. A discrimination rate of 95.1% was found for 82 sera from patients of geographically disparate endemic areas. This rate was essentially the same as that found for 57 Swiss patients, indicating that inter- and intraspecific strain differences do not influence the test results. The assay method is suitable for immunodiagnostic purposes as well as for seroepidemiological studies.

Clinical and echocardiographic observations in pulmonary valve endocarditis.

Clinical and echocardiographic data from 12 patients with pulmonary valve endocarditis are described. Seven patients had isolated pulmonary endocarditis and in 5 patients other valves were infected (aortic, tricuspid, mitral or all 3). Two patients were heroin addicts and 4 had underlying heart disease (congenital heart disease in 3 and aortic regurgitation in 1 patient). The organisms involved were alpha streptococci in 3 patients (all with underlying heart disease), Staphylococcus aureus in 4, Streptococcus D bovis in 1 patient and Candida guillermondii in 1. M-mode and 2-dimensional echocardiography was performed in 10 patients and revealed vegetations in 8. Pulsed Doppler echocardiography was performed in 6 patients and revealed pulmonary regurgitation in all 6. Seven patients had pulmonary emboli. Four patients underwent surgery. Four patients died, including 1 after cardiac surgery. Five patients, including the patient infected with Candida guillermondii, recovered with antibiotic treatment.

Hepatitis B virus DNA sequences in lymphoid cells from patients with AIDS and AIDS-related complex.

A lymphotropic virus HTLV-III/LAV was recently identified as the etiologic agent of the acquired immune deficiency syndrome (AIDS). In a study of concomitant hepatitis B infections in patients with AIDS or the AIDS-related complex, DNA sequences of hepatitis B virus (HBV) were found in fresh and cultured lymphocytes from patients with AIDS even in the absence of conventional HBV serological markers. Furthermore, the restriction DNA pattern was consistent with the integration of the viral DNA. These results should prompt additional studies to reevaluate a possible role of HBV as a cofactor in AIDS in addition to the HTLV-III/LAV causal agent.