[Malignant lymphoma associated with HIV infection]. / Mit der HIV-Infektion assoziierte maligne Lymphome.

The course of disease in 119 HIV-infected patients (117 men, 2 women; median age 38.5 years) with malignant tumours other than Kaposi's sarcoma was analyzed in a multi-centre retrospective study. This was conducted to obtain initial information concerning the incidence, clinical features and results of therapy in HIV-associated neoplasms, especially malignant lymphomas. The most frequent tumour was malignant non-Hodgkin's lymphoma (98 patients, 82.5%), seven patients had Hodgkin's disease, five had solid tumours, four a polyclonal lymphoproliferative syndrome, three an acute lymphocytic leukaemia, and two had other lymphoproliferative diseases. 58% of the non-Hodgkin's lymphomas occurred in patients with marked immunodeficiency, 85% were high grade malignancies and 47% had primary extranodal disease. 56% of primary nodal lymphomas also had visceral spread (Stage IV). Lymphoblastic non-Hodgkin's lymphoma was more common in patients with favourable immunological status, presented less frequently with primary extranodal disease, was diagnosed earlier than other non-Hodgkin's lymphomas, and appeared to carry a better prognosis. 78 out of the 98 patients with non-Hodgkin's lymphoma had been treated, 66 with cytotoxics. The median survival time was 6 months. Longer remission periods, of at least 12 months, were seen in ten of the 78 patients (13%). Despite the overall poor prognosis and the pre-existing immune defect, palliative (chemo-)therapeutic measures are both justified and promising, and may also result in life-prolonging remissions.

[Myelodysplastic syndrome--a retrospective study of 38 patients]. / Das myelodysplastische Syndrom--eine retrospektive Untersuchung an 38 Patienten.

38 patients diagnosed as myelodysplastic syndrome (MDS) were retrospectively evaluated for clinical course, prognostic factors, diagnostical power of cytology and histology and relevance of hypoplastic myelodysplastic syndrome. Median observation time was 14.5 (0 to 104) months. 15 patients (40%) developed an acute myelogenous leukemia after two to 67 (median eleven) months. Prognosis was negatively influenced by age, suggested myelotoxic agents in prior history and leukemia in first-grade relatives as well as ESR greater than or equal to 30 mm Hg (first hour). FAB-classification and Bournemouth-score reflected prognosis in respect to survival time and development of an acute leukemia. Cytology and histology revealed contradictory results in four of 14 comparable cases (28.6%). Hypoplastic myelodysplastic syndrome was diagnosed by histology in seven out of eight cases. This entity showed significantly lower WBC-values and a considerable longer survival time.

[Malnutrition--a clinically relevant problem in HIV-1 infection?]. / Mangelernährung--ein klinisch relevantes Problem der HIV-1-Infektion?

Until now, recommendations for nutrition therapy of HIV-infected subjects can only be regarded as preliminary, because of the lack of scientific results regarding the interactions between HIV-infection and nutrition. HIV-infected patients have a high risk to become malnourished during the course of the disease, as a consequence of multiple pathogenetic factors--similar to the nutritional problems of tumor patients. At the moment, the following procedure is recommended in order to treat or prevent HIV-associated malnutrition: The nutritional status and history should be assessed in each HIV-positive subject as early as possible. Independent of the actual nutritional status, each patient should obtain a nutrition education. A continuous nutrition therapy becomes necessary in the case of evident or imminent malnutrition. Nutrients should be applied by oral access as long as possible. But especially for patients with opportunistic infections of the GI-tract accompanied by malabsorption, total parenteral nutrition may be the only effective way of nutrition.

[Randomized comparative study of secondary prevention of Pneumocystis carinii pneumonia in patients with acquired immunologic deficiency syndrome]. / Randomisierte Vergleichsuntersuchung zur Sekundärprophylaxe einer Pneumocystis-carinii-Pneumonie bei Patienten mit erworbenem Immundefektsyndrom.

Pneumocystis carinii pneumonia is one of the most frequent infectious complications in patients with the acquired immunodeficiency syndrome (AIDS). A prospective trial was initiated to compare azidothymidine alone with azidothymidine plus aerosolized pentamidine as a secondary prophylaxis for pneumocystis carinii pneumonia. 27 patients (24 male, three female, average age 39 years) were enrolled, 14 patients receiving azidothymidine and pentamidine aerosol and 13 azidothymidine alone. After 166 days of follow-up, this trial had to be terminated prematurely, since the efficacy of pentamidine aerosol in the prevention of pneumocystis carinii pneumonia was clearly demonstrated in two recently published studies. Two patients died during the study period, one in either group, but neither due to pneumocystis carinii pneumonia. Two patients developed histologically proven pneumocystis carinii pneumonia; both patients were allocated to the azidothymidine arm. Pneumocystis carinii pneumonia was suspected clinically but not proven in four patients, three were randomized in the azidothymidine arm. Pentamidine was well tolerated and produced no severe side effects. The sample size is too small to draw definitive conclusions concerning the efficacy of pentamidine aerosol in AIDS patients.

[Preventive pentamidine inhalation of Pneumocystis carinii pneumonia in patients with immune deficiency. Preliminary evaluation of a multicenter study]. / Pentamidin-Inhalationsprophylaxe der Pneumocystis-carinii-Pneumonie bei Patienten mit Immunschwäche. Zwischenauswertung einer multizentrischen Studie.

In the first evaluation of an uncontrolled multicenter study on inhalative pentamidine prophylaxis (300 mg pentamidine-isethionate monthly) of pneumocystis carinii pneumonia in immunocompromised patients, 48 patients (all 48 patients HIV1-infected, 36 without preceding pneumocystis carinii pneumonia (primary prophylaxis), twelve after pneumocystis carinii pneumonia (secondary prophylaxis); age 20 to 68 years (median 38); 45 male, two female, one unknown; 22 patients AIDS) were observed for 0 to 8.5 months (mean 4 +/- 2 months, intended observation time twelve months). No proven pneumocystis carinii pneumonia was found in the observed patients. One patient was treated with cotrimoxazole because of a suggested pneumocystis carinii pneumonia-relapse, which could not be proven. Out of seven (14.6%) patients, whose therapy was discontinued, three patients died, three refused further therapy, one patient had a relapse of a cerebral toxoplasmosis. Six patients (12.5%) reported adverse reactions (cough, metallic or bitter taste, slight nausea). New opportunistic infections appeared in four patients (8.3%).

Intracellular free amino acid patterns in duodenal and colonic mucosa.

We report for the first time the concentrations of free amino acids in human intestinal biopsies obtained by routinely performed endoscopy. We studied 15 medical patients with no changes of the mucosa and six HIV-infected persons with duodenitis. The mean (and SD) sum of all amino acids, taurine excepted, was 61.9 (5.4) mmol/kg dry weight in duodenal biopsies of HIV-negative subjects (n = 11) and 82.9 (0.6) mmol/kg in colonic specimens: 50% (44%) of the total (minus taurine) consisted of aspartate and glutamate and 14% (12%), of the essential amino acids. The relative amino acid pattern in duodenum and colon differed completely from that for muscle: aspartate was fourfold higher; glutamate, phenylalanine, glycine, valine, leucine, and isoleucine were about twofold higher. In contrast, glutamine amounted only to 4% (duodenum) to 14% (colon) of muscle glutamine. In duodenal biopsies of the HIV-infected persons, we found significantly (P less than 0.01, except glutamine: P less than 0.025) increased concentrations of glutamate (24.1 vs 17 mmol/kg dry weight), ornithine (1.4 vs 0.4), valine (2.2 vs 1.7), and glutamine.

[Cardiac involvement within the scope of HIV-1 infection: preliminary results of echocardiography study]. / Kardiale Beteiligung im Rahmen der HIV-1-Infektion: Vorläufige Ergebnisse einer echokardiographischen Untersuchung.

The results of one- and two-dimensional echocardiography in 128 patients (117 males, 11 females; median age 37 years) who were seropositive for HIV-1 were analyzed in addition to clinical, electrocardiographic, and laboratory data. Follow-up controls are available for 51 patients over an observation period of 1 to 24 months, median 9.5 months. Probably HIV-related echocardiographic abnormalities were identified in 36 patients (28%): small to moderate pericardial effusions (n = 34) and left ventricular dilation (n = 5). Pericardial effusions resolved in seven patients during follow-up, in three cases after tuberculostatic chemotherapy. Compared to patients without cardiac involvement patients with HIV-related echocardiographic abnormalities showed lower CD4-lymphocyte counts (143 +/- 138 vs 289 +/- 219/microliters, p less than or equal to 0.01), and left ventricular endsystolic dimensions were increased (34.2 +/- 4.5 vs 32.6 +/- 3.0 mm, p less than or equal to 0.05). Cardiac involvement occurred predominantly in the advanced stages of the HIV-1 infection with unclear etiology in the majority of cases, even though active concomitant diseases could be frequently demonstrated. The clinical course of some patients might be consistent with intercurrently completed perimyocarditis, probably of viral genesis. CD4-lymphocyte counts less than or equal to 100/microliters could be identified as a risk factor for the development of cardiac manifestations. The significance of a demonstrated involvement of the heart with regard to therapeutic consequences and prognosis appeared to be slight. Use of echocardiography as a routine method for the detection of cardiac involvement in HIV-1 infection has proved to be valuable, since indicative clinical symptoms were lacking in almost all cases.

Cellular immunologic parameters in HIV-positive patients with AIDS-related complex and intravenous immunoglobulin therapy.

In a randomized double-blind longitudinal study with 30 HIV-1-positive patients with AIDS-related complex or stage Walter-Reed 5 disease, the effectiveness of intravenous immunoglobulin (IVIG) was tested for correcting eventual immune dysregulation. Although the IVIG-treated patients showed an improvement of their clinical score, no significant changes were observed in lymphocyte phenotypes, activation markers, immunoglobulins and subclasses, lymphocyte turnover or in indicators of acute inflammation. Since severe bacterial infections or autoimmune processes usually leading to IVIG therapy were not prevalent in the patients of the study, such therapy should probably be reserved for later stages of the disease. HIV-1 antigen expression in blood lymphocytes remained uninfluenced by IVIG treatment.

[AIDS-related complex: a superfluous concept?]. / Der AIDS-related complex: Ein überflüssiger Begriff?

The clinical value of different classification systems of HIV-infection has been examined in a cohort of 99 HIV-infected individuals. AIDS-related complex (ARC), Walter-Reed (WR) stage 5 and Centers for Disease Control (CDC) group IV without AIDS cases were equally capable of identifying patients with bad prognosis: Out of 12 patients progressing to AIDS, 9 WR 5, 7 CDC IV and 7 ARC. Prognostic parameters (Erythrocyte sedimentation rate, Haemoglobin, Leucocytes, CD4-lymphocytes and Beta 2-Microglobulin) did not differ in the three groups. However, there were great differences in the frequency of patients infected by homosexual contacts and of intravenous drug-abusers. Drug-abusers were more often seen in the ARC-group, whereas there was a slight dominance of homosexuals in the WR 5-group (and a marked preponderance in the AIDS-group). Using 3 different ARC-definitions we found an ARC-frequency of 10%, 24% and 41% in our cohort. Thus the great variability of the ARC-concept could be demonstrated. In conclusion we believe that for the purpose of clinical documentation and studies the ARC-concept is unnecessary. Further studies have to evaluate other classification systems (Walter-Reed, CDC) or to establish new ones.

T-lymphocyte subsets in the duodenal lamina propria of patients infected with the human immunodeficiency virus type 1 and influence of high-dose immunoglobulin therapy.

T-lymphocyte subsets in duodenal biopsies of human immunodeficiency virus type 1 (HIV-1)-infected patients were studied by immunocytochemical staining to determine the alterations of CD4- and CD8-cell subsets in comparison with HIV-1 antibody-negative controls and to examine the association with stage, gastrointestinal symptoms, and peripheral lymphocyte subsets and the influence of high-dose intravenous immunoglobulins. A significant decrease in duodenal CD4 cells (p less than 0.001) and CD4/CD8 ratio (p less than 0.001) follows HIV-1 infection when compared to HIV-1-negative controls, more accentuated both in patients of stage WR6 and suffering from diarrhea than in those of stages WR1-5 or without diarrhea. In addition, a significant increase in CD8 cells (p less than 0.01) could be found in HIV-1-infected patients, again with lower levels in patients of stages WR6 than WR1-5. A strong correlation was found between the intestinal and peripheral CD4/CD8 ratio (R = 0.80), but the correlation was weak if HIV-1-negative persons were excluded from analysis (R = 0.29). Treatment with high-dose intravenous immunoglobulins improved diarrhea in four of five patients; two patients gained weight. Diffuse lymphocytic infiltration of the lamina propria, villous atrophy, CD4- and CD8-cell percentage, and CD4/CD8 ratio were not influenced.

High-dose intravenous immunoglobulins in HIV-1-infected adults with AIDS-related complex and Walter-Reed 5.

The influence of high-dose intravenous immunoglobulins (HD-IVIG) on the clinical status and T4 cell count of adults with AIDS-related complex (ARC) and Walter-Reed 5 (WR5) was evaluated in a randomized double-blind longitudinal study. Inclusion criteria were: (1) T4 cells less than 400/microliters and (2a) oral thrush or cutaneous anergy or (2b) two clinical ARC criteria (fever, diarrhea, weight loss, fatigue, night sweats). Thirty patients [28 males, 2 females, median age 41 (24-64) years] with ARC (n = 8), WR5 (n = 12) and both (n = 10) were stratified according to their T4 cell count (greater than or equal to vs. less than 300/microliters). Fifteen patients received 0.4 g/kg body weight IVIG and 15 placebo (albumin 0.03%) every other week for 26 weeks with follow-up for another 26 weeks. The clinical status was defined as a score consisting of fever, diarrhea, night sweats, fatigue, weight loss, oral candidiasis and mucosal or cutaneous herpes simplex. Clinical examination and routine laboratory assessments were performed before initiation of the study and before each administration, lymphocyte phenotyping every 4 weeks and cutaneous reaction, serology and lymphocyte stimulation every 12 weeks. Both groups were comparable in initial clinical symptoms and laboratory values. Seven patients developed AIDS (treatment group: 3, placebo group: 4), 1 patient died by homicide. After 26 weeks, the clinical score (particularly fatigue and fever) was significantly improved in the treatment group, while the T4 cell count and other clinical and immunological parameters remained unaltered. This limited effect was still evident at termination of the study after 52 weeks. In conclusion, HD-IVIG can improve the clinical status of patients with advanced HIV-1 infection without obviously correcting the underlying impaired cellular immunity. The substitution of intact antibodies in the state of functional hypogammaglobulinemia is suggested as possible therapeutic mechanism.

[Assessment of nutritional status--a part of routine clinical diagnosis: cholinesterase activity as a nutritional indicator]. / Erhebung des Ernährungszustandes--ein Bestandteil der klinischen Routine-Diagnostik: Cholinesterase-Aktivität als Ernährungsindikator.

Nutritional assessment has not yet been established as integral part of basic clinical diagnostic procedures everywhere, eventhough the prognostic relevance of malnutrition is well known. One of the reasons is the lack of nutritional indicators, which are specific of and sensitive for changes of the nutritional status on the one hand, and routinely analyzed on the other. We report on the utility of serum cholinesterase, which has the shortest half-life of all plasma proteins, to identify malnourished patients. 54 internal inpatients with malignant diseases or in septic state were followed up prospectively with respect to courses of cholinesterase (CHE), albumin (ALB), transferrin (TRA), and body weight over periods of 4 weeks. A correct correlation to malnutrition was defined as plasma concentrations less than reference ranges or continuous concentr. fall greater than 10%. Based on 132 observations (65 with continuous weight loss, mean: -5.5% of original w.; 54 w. gain, mean +4.6%, 13 constant w.), changes of CHE had the highest correlation to weight changes (r = 0.79, p less than 0.001), compared to the courses of TRA- or ALB-levels (r = 0.65/0.68). Incorrect positive results (conc. fall or conc. less than ref. range without weight loss): absolute levels - CHE 4%, ALB 4%, TRA 22%; conc. courses - CHE 0%, ALB 0%, TRA 6%. Incorrect negative: absolute c. - CHE 63%, ALB 30%, TRA 28%; courses - CHE 15%, ALB 19%, TRA 17%. The common determination of CHE and ALB-courses allowed a correct identification of malnutrition in 96% of all observations, with the same result as the courses of ALB + TRA.(ABSTRACT TRUNCATED AT 250 WORDS)

[Diagnosis and clinical aspects of gastrointestinal cytomegalovirus diseases in patients with human immunodeficiency virus 1 infection]. / Diagnostik und Klinik gastrointestinaler Zytomegalievirus-Erkrankungen bei Patienten mit einer Human Immunodeficiency Virus 1-Infektion.

Eleven Human Immunodeficiency Virus 1 (HIV1)-infected patients (10 male, 1 female; age 23-51 years (median 36); 10 male homosexuals, 1 IV drug abuser; WR3 1 patient, WR5 5, WR6 5) with intestinal Cytomegalovirus (CMV)-manifestations were compared with a group of 78 HIV1-infected patients in respect to their clinical, immunological and virus-serological data and the results of the histological and microbiological examination of endoscopically obtained biopsies. No differences were observed on age, sex, risk of infection, stage and immunological status. Bloody diarrhea was most important in discriminating CMV-colitis and non-CMV-related intestinal manifestations. Dysphagia and other symptoms occurring in patients with CMV-esophagitis were not able to predict CMV-esophagitis specifically. 6 of 11 patients with serological findings consistent with an active CMV-infection had no detectable CMV-manifestations; 6 of 11 patients with intestinal CMV-manifestations did not show serological findings suggestive of active CMV-infection. Ulcerative alternations of intestinal mucosa represent the most powerful indicator of intestinal CMV-disease in endoscopical examination. Only in two patients, ulcerative alterations were seen without diagnosis of CMV-disease being established. CMV was isolated in one of 11 patients, in two patients CMV was isolated from biopsies of unchanged mucosa. Simultaneous infection by HSV and CMV was detected in three patients, in one patient in the same localisation. Histology revealed inclusion bodies in 8 of 11 patients with intestinal CMV-disease, in no case inclusion bodies were seen without CMV-disease.

Plasma amino acid pattern of patients with HIV infection.

We measured the free amino acids in plasma of 58 patients with HIV infection and in six persons in the risk group. The HIV+ patients had significantly increased concentrations of arginine, phenylalanine, and glutamate in comparison with both age- and sex-matched controls and the members of the risk group. Glutamate concentrations increased only in an advanced stage of the disease (WR 5 and 6 of the Walter Reed staging classification), whereas arginine and phenylalanine increased independently of the stage. There was no correlation between the amino acid concentrations and the number of T4 and T8 lymphocytes, the sedimentation rate, and the existence or absence of Kaposi's sarcoma. The amino acid pattern of HIV-infected persons is similar to that of cancer patients or those with other immune deficiencies.

[X-ray diagnosis of invasive thymoma]. / Zur Röntgendiagnostik invasiver Thymome.

Between January 1981 and September 1985, invasive thymomas were diagnosed in 13 patients attending the municipal hospital at Köln-Merheim. All these patients were examined radiologically and the tumour removed at thoracotomy, and irradiated in our Radiotherapy Clinic. Invasive thymomas appear as space-occupying lesions on chest radiographs taken in two planes, or on computed tomography. Infiltration by the thymoma in stages III and IV can be demonstrated by computed tomography.