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Biomedical subjects

E B Helm

Publications and source records attributed to E B Helm.

At least 37 records · Page 2Linked to original sources

Bioelectrical impedance analysis as a predictor of survival in patients with human immunodeficiency virus infection.

In patients with AIDS, short-term survival has been related to body weight, body composition, and serum nutritional parameters, but their prognostic impact at earlier stages of the HIV infection is not known. With an individual follow-up period of 1,000 days, we investigated the prognostic relevance of electrical tissue conductivity [resistance R, reactance Xc, phase angle alpha, extracellular mass (ECM), body cell mass (BCM)] measured by bioelectrical impedance analysis, of the CD4+ cell count, and of serum parameters indicating malnutrition in 75 HIV-infected male patients at Walter Reed stages 3-5. After initial recording, 29 patients (38.7%) died from AIDS during this period. Among 12 parameters estimated with a semiparametric Cox regression model adjusted for therapy (pentamidine, azidothymidine), the phase angle alpha (parameter estimate: -1.043, 95% confidence interval of -0.61 to -1.47; p < or = 0.0001), the ECM/BCM ratio, Xc, BCM, serum cholesterol, number of CD4+ cells, and serum albumin had significant prognostic influence on survival, whereas age, body weight, body mass index, resistance, serum protein, and serum triglycerides did not. In a model with four covariates (CD4+ cells, phase angle, pentamidine, azidothymidine), the prognostic impact of the CD4+ cell count (parameter estimate: -0.549) was lower compared with the phase angle alpha (parameter estimate: -0.799; p < or = 0.0001) and did not gain statistical significance (p = 0.0626). The phase angle alpha was the best single predictive factor for survival among all 12 parameters (comparison of the respective Cox models with the likelihood ratio test).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

AIDS-free survival and overall survival in HIV infection: the new CDC classification system (1993) for HIV disease and AIDS.

The clinical history of 1538 HIV positive patients was analyzed on the basis of the new CDC classification system of HIV disease and AIDS. This classification system combines three CD4 cell categories (1, 2, and 3) with three clinical categories (A, B, and C) into nine subgroups A1-C3. We examined the overall survival for all subgroups and the AIDS-free survival for subgroups A1-B3. AIDS-free survival for patients in subgroups A1, A2, and B1 was considerably longer than survival in patients from subgroups A3, B2, and B3 (P < 0.0001). According to these findings, the new CDC classification system could be simplified into three stages, stage I and II comprising the above mentioned six subgroups, and stage III comprising clinical AIDS defining categories C1, C2, and C3. These three stages correspond to different periods in the management of HIV positive patients, i.e., period of observation, period of prophylaxis, and period of treatment.

Acquired Immunodeficiency Syndrome↗

In vitro improvement of bone marrow-derived hematopoietic colony formation in HIV-positive patients by alpha-D-tocopherol and erythropoietin.

The majority of patients with progressive HIV infection develop a severe hematopoietic failure which is aggravated by the hematotoxic effect of azidothymidine (AZT) treatment. Since it was shown in a mouse model that alpha-D-tocopherol (vitamin E derivative) antagonizes the inhibitory influence of AZT on the growth of burst-forming units-erythrocyte (BFU-E), it was the aim of this study to investigate whether alpha-D-tocopherol and high dosages of erythropoietin (EPO) increase the hematopoietic colony-forming capacity of bone marrow cells from patients with progressive HIV disease and especially if they reverse the inhibitory effects of AZT. The data demonstrate that tocopherol (1-100 mumol/l) significantly increases the growth of BFU-E and colony-forming units granulocyte-monocyte (CFU-GM) from HIV-infected patients. This stimulatory effect is dose-dependent (maximum at 30-100 mumol/l) and only occurs when the agent is present from the beginning of the cultures. EPO (5-10 U/ml) also augments the numbers of BFU-E from HIV-infected patients. Tocopherol equally ameliorates the growth of BFU-E and CFU-GM from the HIV-positive cohort in the presence of AZT (10-100 mumol/l). For healthy controls, no such increase was observed, either with tocopherol or with higher dosages of EPO. In conclusion, both tocopherol and EPO partially reverse the myelosuppressive action of AZT in HIV-positive patients.

Adult↗

Kaposi's sarcoma in HIV infected women in Germany: more evidence for sexual transmission. A report of 10 cases and review of the literature.

OBJECTIVE: To assess the natural history of Kaposi's sarcoma (KS) in HIV-positive women living in Germany. METHODS: All physicians reporting the diagnosis of KS in a female patient were contacted and asked for detailed information. DESIGN: Descriptive study of clinical, epidemiological and immunological data of ten women with biopsy-proven KS living in Germany were evaluated. The results are compared with those of other previously published studies of women with KS from Italy, France and the USA. SETTING: Five centres in Germany. RESULTS: Of 765 German women with AIDS, only 10 (1.3%) were reported to suffer from Kaposi's sarcoma (KS) compared with 1771 of 8128 men (21.8%). Mean age in these women was 39.7 years. KS was the first AIDS defining event in nine women and the reason for HIV-testing in three. The mean CD4 count was 215/microliters. Two patients were of African origin, had only recently come to Germany and were most likely to have acquired their HIV-infection in Africa. Three patients were i.v.-drug users (IVDU). Two of these (and most likely all three) had worked as prostitutes. Of five women who had contracted HIV via heterosexual contacts, one worked as a prostitute and the other four were married to or were living together with a bisexual HIV-positive man. All four male partners have also developed KS. The course of the disease seems to be particularly aggressive in female patients with eight of 10 women presenting with or progressing to widely disseminated disease with extensive involvement of internal organs. In this cohort survival was longer in females who acquired their HIV infection heterosexually compared to IVDU and was strongly correlated with higher CD4-counts at diagnosis. CONCLUSIONS: KS seems to run a particularly aggressive course in women. Our data are consistent with a sexually transmittable aetiological agent of KS. Prostitution, an issue yet to be addressed by other authors reporting series of women with KS, was reported in four of our patients. Further studies are needed to clarify the significance of this finding.

Acquired Immunodeficiency Syndrome↗

[Epidemiology of tuberculosis in patients with HIV infection of the Frankfurt University Clinic].

Frequency and risk of tuberculosis were studied among a large group of HIV-infected patients (n = 2556), 869 of whom had AIDS, over a period of ten years (February 1982 through February 1992) at the University Hospital Frankfurt. A total of 148 (5.8%) out of 2.556 patients had tuberculosis. With increasing immunodeficiency, the frequency of tuberculosis rose. The rate of tuberculosis in post-mortem was even higher, i.e. 17.3%. I.v. drug-addict AIDS patients were inflicted with 18.5% considerably more often than homo-/bisexual patients with 12.3%. The same holds true with 25% of tuberculosis infections for AIDS patients from endemic areas as compared with 13% for patients from countries with lower tuberculosis incidence. 18% of patients contracted tuberculosis already at > 200 CD4-positive cells/microliters before AIDS manifestation. Coming from endemic areas, drug addiction and lower number of T-cells signify a high risk for HIV-infected patients to acquire a post-primary or primary tuberculosis, respectively. HIV-infected patients represent a relevant danger of infection for partners and health-care personnel. In contrast to the United States, no increase in the tuberculosis incidence, except for some areas like Frankfurt, has been noted. Preventive measures, which include the IHN prophylaxis for patients with T-cell counts < 150/microliters, should be discussed.

AIDS-Related Opportunistic Infections↗

Early changes of body composition in human immunodeficiency virus-infected patients: tetrapolar body impedance analysis indicates significant malnutrition.

Total body water, body fat, body cell mass (BCM), extracellular mass (ECM), and the ECM-BCM ratio by impedance analysis were determined in 193 human immunodeficiency virus (HIV)-infected patients and 340 control subjects. Walter Reed (WR) classification was WR 2 in 26, WR 3-5 in 85, and WR 6 in 82 patients. Whereas resistance was increased, reactance and the phase angle were significantly reduced in all patient groups. Neither body weight nor body mass index (BMI) was affected in WR 2 patients, but BCM was reduced (31.9 +/- 4.3 vs 35.8 +/- 7.3 kg, P < 0.007) and ECM (31.2 +/- 4.4 vs 28.8 +/- 3.8 kg) as well as ECM-BCM ratio increased (0.99 +/- 0.14 vs 0.83 +/- 0.16, P < 0.001). In contrast to WR classification, diarrhea did not correspond with malnutrition. A loss of BCM (malnutrition) occurred already in otherwise symptomless HIV-infected patients (WR 2). This effect can be measured by tetrapolar impedence analysis but not by body weight or BMI.

Adult↗

Treatment of diarrhoea in human immunodeficiency virus-infected patients with immunoglobulins from bovine colostrum.

Diarrhoea and weight loss are found in more than 50% of patients with the acquired immunodeficiency syndrome (AIDS). In some patients the symptoms can be very severe, leading to death even in the absence of opportunistic infections. In 30% of these patients, enteric pathogens cannot be identified, and approximately only half of the identifiable aetiologic agents of diarrhoea in patients infected with the human immunodeficiency virus (HIV) were treatable with antibiotics. Immunoglobulins from bovine colostrum (Lactobin, Biotest, Dreieich, FRG) contain high titers of antibodies against a wide range of bacterial, viral and protozoal pathogens as well as against various bacterial toxins. Lactobin (LIG) is quite resistant to 24-h incubation with gastric juice. In a multi-center pilot study 37 immunodeficiency patients with chronic diarrhoea [29 HIV-infected patients, 2 patients with common variable immunodeficiency (CVID), one unidentified immunodeficiency, five patients with graft versus host disease (GvHD) following bone marrow transplantation] were treated with oral LIG (10 g/day for 10 days). Good therapeutic effects were observed. Out of 31 treatment periods in 29 HIV-infected patients 21 gave good results leading to transient (10 days) or long-lasting (more than 4 weeks) normalisation of the stool frequency. The mean daily stool frequency decreased from 7.4 to 2.2 at the end of the treatment. Eight HIV-infected patients showed no response. The diarrhoea recurred in 12 patients within 4 weeks (32.4%), while 19 patients were free of diarrhoea for at least 4 weeks (51.3%). In 5 patients intestinal cryptosporidiosis disappeared following oral LIG treatment. LIG treatment was also beneficial in 4 out of 5 GvHD patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

[Intestinal permeability in patients with acquired immunodeficiency syndrome (AIDS)].

Intestinal permeability has been assessed as a parameter of the small intestinal barrier function in 33 patients with AIDS (WR 6), in 25 healthy volunteers, 32 patients with Crohn's disease, 18 patients with ulcerative colitis and in 12 patients with untreated coeliac disease. Permeability was measured by means of the 5 hour urinary excretion of lactulose and rhamnose after administration of these sugars (1 g rhamnose, 10 g lactulose) which allowed to calculate the urinary lactulose/rhamnose--ratio (L/R-r) as an index of intestinal permeability. Compared to the controls (L/R-r = 0.014 +/- 0.010) patients with AIDS had significantly increased lactulose/rhamnose--ratios (0.189 +/- 0.164; p less than 0.01) indicating abnormal permeation both of lactulose and rhamnose. This alteration of intestinal permeability was more pronounced than the significant increase of the L/R-r in the patients with either Crohn's disease or coeliac disease. However, intestinal permeability was not altered in the patients with ulcerative colitis. Among the patients with AIDS, the most abnormal permeability ratios were observed in two subjects with intestinal cryptosporidiosis. This investigation demonstrates by means of the "double sugar ratio", that intestinal permeability in patients with AIDS is highly abnormal, the impairment being even more abnormal than in patients with other small intestinal disease.

Acquired Immunodeficiency Syndrome↗

[Malignant lymphoma associated with HIV infection].

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.

Adult↗

Fluconazole prophylaxis of recurrent oral candidiasis in HIV-positive patients.

In a randomized, open study, the efficacy of fluconazole as a prophylaxis of recurrent oral candidiasis in patients with advanced stages of HIV-infection (CD4 cell count less than 100/mm3) was studied. For this purpose, the frequency of episodes of oral candidiasis during two different prophylaxis regimens (50 mg/day vs. 100 mg/day) were compared to an untreated control group. Sixty-five HIV-positive patients were included in the study from May, 1989 to January, 1990. Of these, 58 were evaluated over an observation time of 137-215 days. Prophylaxis with fluconazole clearly reduced the occurrence of oral candidiasis. In 20 out of 21 patients in the untreated control group, a total of 60 relapses occurred. In the prophylaxis group receiving 50 mg/day (group 2), two out of 18 patients had four relapses. In the group receiving 100 mg/day (group 3), four out of 19 patients had nine relapses in total. Of 3575 observation days in the control group, treatment due to oral candidiasis was necessary on 393 days (28%). In group 2, on 57 of 3316 days (2%), fluconazole in a higher dosage was administered for treatment. In group 3, relapse treatment with fluconazole 200 mg/day, or treatment with ketoconazole, became necessary in 116 out of 3314 observation days (3%). In all relapses, Candida albicans cfu greater than 10(3)/ml were isolated in the oral wash-outs. As compared to the untreated control group, fluconazole prophylaxis in a daily dosage of 50 as well as 100 mg led to significantly less frequent relapses of oral candidiasis (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

[Therapeutic alternative or 2d choice drug. Trisodium phosphonoformate in cytomegalovirus retinitis].

From 01. 01. 1988 to June 1990, a total of 275 patients with AIDS had been examined in our ophthalmological out-patient clinic. The clinical diagnosis of a cytomegalovirus (CMV) retinitis was recorded in 56 of these patients (= 20.1%). The initial therapy, as usual, took the form of infusions of the virustatic drug ganciclovir at an induction dose of 10 mg/kg body weight per day (3 weeks), with a maintenance dose of 3.5-5 mg/kg body weight per day (5 days per week) thereafter. During maintenance therapy recurrences were observed in 15 cases and herpes simplex retinitis in 3, with progressive retinal destruction. Therefore we began treatment with trisodium phosphonoformate (Foscavir) at a dosage of 60 mg/kg body weight per day (3 weeks), continuing with maintenance therapy at 90 mg/kg body weight per day (7 days a week). After the induction dose 14 patients showed subjective improvement and satisfactory cicatrization of the retinal lesions. We monitored the retina by a standardized method and 50 wide-angle retinal photographs. One case of acute retinal necrosis (ARN) did not show any response to foscavir therapy. Typical side-effects of therapy with trisodium phosphonoformate were seldom seen: adverse events included renal dysfunction, neutropoenia, and asymptomatic hypocalcaemia. We conclude that trisodium phosphonoformate is an effective and well-tolerated agent for the treatment and prevention of relapse of CMW retinitis and can be used as an alternative ganciclovir.

Acquired Immunodeficiency Syndrome↗

Demonstration of cross-reactive antibodies able to elicit lysis of both HIV-1- and HIV-2-infected cells.

A total of 100% of sera from a large number of HIV-1-infected patients contained antibodies able to elicit Antibody-dependent cellular cytotoxicity lysis of cells infected with the HIV-1 isolates IIIB or RF. Levels of activity could not be correlated with activities in ELISA or neutralizing antibody assays nor with the clinical status of the patients. Surprisingly, 8 of 156 patients sera could additionally elicit lysis of HIV-2-infected cells, and cold target competition assays demonstrated that the cross-reactivity was apparently mediated via recognition of common epitope(s) expressed on the surface of cells infected with either group of HIV. The ADCC mechanism was shown to be mediated by a CD16+ lymphocyte. This demonstration of an effector mechanism able to attack and eliminate cells infected with a wide range of HIV strains has obvious implications for development of putative vaccines.

Antibody-Dependent Cell Cytotoxicity↗

[The morphology and clinical significance of pathologic changes of the adrenals and hypophysis in AIDS].

A semiquantitative morphometric technique (point counting) was applied to the pituitary and adrenals taken at necropsy from 130 AIDS patients (4 women, 126 men, mean age 39 [22-71] years) to ascertain the nature, extent and location of the pathological lesions. Abnormalities were found in 32% of the pituitaries and 76% of the adrenals. Only 17 patients had normal findings in both organs. The predominant lesions were due to opportunistic infections or infiltration by Kaposi's sarcoma or non-Hodgkin lymphoma. The commonest finding was necrotizing cytomegalovirus adrenalitis (n = 68); in one third of the cases this had caused severe destructive lesions involving over 50% of the parenchyma. The almost total destruction of the adrenals noted in some cases suggests that cytomegalovirus adrenalitis may run a progressive course; its clinical significance has hitherto been underestimated.

Acquired Immunodeficiency Syndrome↗

[Comparison of the effect of 2 therapy concepts in the treatment of Pneumocystis carinii pneumonia. Cotrimoxazole for 21 days versus sequential therapy with cotrimoxazole followed by pentamidine inhalation].

Standard therapy of pneumocystis carinii pneumonia with cotrimoxazole and intravenous pentamidine second line therapy both have a response rate of 75 to 90%. As severe side effects, myelotoxicity and skin reaction have been observed which may occur from treatment day 7 on. In order to prevent such side effects as well as reduce hospitalization times, an open, randomized pilot study was designed. Object of this study was the comparison of efficacy and safety of two different treatment schemes: standard therapy versus sequential treatment. Twelve patients were treated according to study design: five patients with cotrimoxazole only, and seven patients with sequential therapy consisting of cotrimoxazole followed by pentamidine aerosol. All patients were treated for 21 days. Four out of five patients with cotrimoxazole, and two out of seven patients with sequential therapy, were successfully treated and had no pneumocystis carinii pneumonia relapses within four weeks after termination of treatment. Each group had one treatment failure. Four patients under sequential treatment were not evaluable. - In spite of the rather unfavourable preliminary results, the study should be continued. However, patients with secondary opportunistic infections respectively other severe diseases should not be included into the study.

Administration, Inhalation↗

[Prospective study of primary and secondary prevention of Pneumocystis carinii pneumonia with pentamidine aerosol].

In an open prospective study in the AIDS Outpatient Department of the Frankfurt University Clinic the efficacy of pentamidine aerosol at a dosage of 200 mg every 14 days in the primary and secondary prophylaxis of pneumocystis carinii pneumonia was tested. The incidence of pneumocystis carinii pneumonia was reduced by more than 75% in the group of patients receiving pentamidine additionally by inhalation as compared with a historical cohort given azidothymidine alone. The results of the study suggest that a CD4-positive cell count of less than 50/microliters with a concomitant secondary lung infection promotes the development of pneumocystis carinii pneumonia. There was no correlation between the incidence of pneumocystis carinii pneumonia and the number of previous disease episodes. No systemic toxicity of pentamidine aerosol was established.

AIDS-Related Complex↗