Lack of awareness in both patients and physicians contributes to a high rate of late presentation in a South West German HIV patient cohort.

PURPOSE: To assess rate of late presentation with HIV in Southwestern Germany and to identify patient characteristics correlated with CD4 nadir. METHODS: Patients with primary diagnosis who presented to one of ten participating clinics rated on knowledge and behavior towards HIV testing on a self-developed questionnaire, whereas clinical data was assessed by the physician. RESULTS: 161 patients were included. Risk factors were homosexual (59.5 %) or heterosexual contacts (26.8 %), drug use (2.0 %), migration (3.9 %), or others (7.8 %). 63.5 % had a CD4 T cell count < 350/µl. 52.5, 17.4, and 31.1 % were diagnosed in CDC stadium A, B or C, respectively. 209 disease episodes were reported, from whom 83.7 % had led to the diagnosis of HIV. 75.2 and 68.3 % said to have been well-informed about ways of transmission and testing offerings, respectively, and 20.4 % admitted to have psychologically repressed the possibility of being infected. 48 patients rated their personal behavioral risk as "high" or "very high". Of these, however, only ten had performed at test in the precedent year. Performing a regression analysis, younger age and previous testing were correlated with a higher CD4 T cell nadir (p = 0.005, and 0.018, resp.). CONCLUSION: The rate of late presentation in this region was even higher compared to national or European surveys. Most infected patients perceived to have had only a low risk. Several disease episodes did not lead to the initiation of HIV testing by the physician.

Growth hormone and bone mineral densitiy in HIV-1-infected male subjects.

The aim of this study was to characterize the GH-IGF-I axis of patients with HIV-1-infection without any symptoms of AIDS-associated wasting. A special emphasis was placed on determine bone mineral density (BMD) and biochemical markers of bone metabolism. Therefore 42 male fasting HIV-1-infected outpatients were included and estimation of serum GH, IGF-I, IGFBP-1 and 3, osteocalcin, TNF-alpha, 1,25dihydroxycholecalciferol, and endocrine markers of the gonad function by commercially available RIA's performed. DEXA-measurements of the lumbar spine and the Ward's triangle of the left hip were done. The GH, IGF-1, IGFBP-1 and 3 serum levels were within the normal range Performing Spearman-correlation test, we established significance between IGF-I serum levels and BMD lumbar spine and Ward's triangle (p < 0.01, p < 0.05), CD4 cell-count (p < 0.05), 1,25dihydroxycholecalciferol (p < 0.05), osteocalcin (p < 0.05), TNF-alpha (p < 0.05), body mass index (BMI) (p < 0.05) and total testosterone (p < 0.01). IGFBP-1 correlates both inversely significantly with CD4 cell-count (p < 0.05) and serum-calcium (p < 0.05). The IGFBP-3 correlates with BMI (p < 0.05) and serum osteocalcin (p < 0.05). Correlation both with markers of bone metabolism and vitamin D metabolites showed the important role of GH/IGF-I axis in modulating the availability of calcium in chronic conditions. This axis may be in a part responsible for the manifestation of the HIV-associated osteopenia.

Changes in calciotropic hormones and biochemical markers of bone metabolism in patients with human immunodeficiency virus infection.

Data on the bone metabolism of human immunodeficiency virus (HIV)-infected patients are still extremely rare. To investigate the influence of HIV infection on the calciotropic hormones and markers of bone metabolism, we therefore performed a cross-sectional study on 100 patients (65 males and 35 females) with proven HIV infection. The following criteria were used for exclusion from the study: age less than 20/more than 50 years, confinement to bed, wasting symptoms, treatment with agents containing ketoconazole, renal or hepatic insufficiency, clinical or echographic signs of liver cirrhosis, endocrine diseases, or treatment with medications known to influence bone metabolism. Bone mineral content (BMC) was determined by single-photon absorptiometry on the left forearm. Reduced BMC was found among the male and female HIV-infected patients. Additional long-term use of heroin resulted in a severe loss of mineralization in the respective females. The markers of bone metabolism were determined in urine and serum samples. Significantly lower osteocalcin concentrations were found, indicating a reduced bone formation rate whose severity showed a significant correlation with the progressive loss of CD4 helper cells and was independent of low vitamin D3 levels (1,25-dihydroxycholecalciferol) and alterations of protein metabolism. Increased urinary excretion of cross-links as an expression of enhanced bone resorption was likewise significantly correlated with the loss of CD4 helper cells and independent of the vitamin D concentration and protein metabolism. It is therefore concluded that the changes in bone metabolism are mainly due to mechanisms of the impaired immune defense of HIV-infected patients.

Osteopenia in HIV-infected women prior to highly active antiretroviral therapy.

BACKGROUND AND OBJECTIVES: Multiple endocrine and metabolic consequences of human immunodeficiency (HIV) infection exist that alter bone metabolism in patients with acquired immune deficiency syndrome (AIDS). Osteopenia in AIDS patients has been associated with antiretroviral therapy particularly with protease inhibitors. However, there is very little data on bone metabolism in female subjects with AIDS prior to highly active antiretroviral therapy. METHODS: Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry (DEXA) in 50 HIV-infected female outpatients (mean age 37 years) both in the lumbar spine and the Ward's triangle of the left hip. Additional parameter assessed were demographics, smoking, CD4 counts, fasting metabolic parameters and biochemical markers of bone metabolism. None of the patients received reverse transcriptase inhibitors or protease inhibitors, vitamin D or calcium-supplementation. RESULTS: The serum levels of parathyroid hormone and 1,25-dihydroxyvitamin D (1,25(OH2)D) were significantly reduced compared to 50 age-matched female healthy controls. Urinary calcium and pyridinium crosslinks-excretion corrected for creatinine excretion were elevated (P<0.01) and were likewise significantly correlated with the loss of CD4 cells (P<0.05). Serum osteocalcin was significantly lowered (P<0.01). Reduced BMD of the lumbar spine (t -score <-2.5 SD below normal) was found in seven patients (14%) and osteopenia (t -score -1.0 to -2.5 SD below normal) was diagnosed in 31 (62%). No patient had a fracture since being infected with HIV. The BMD was reduced both in lumbar spine and the hip measured in the left Ward's triangle. There were significant positive correlation between the CD4 counts and 1,25(OH2)D (P<0.05). Neither the CD4 counts nor the duration of disease correlated with BMD. The reduced bone formation rate was linked to progressive loss of CD4-cell count. CONCLUSION: Osteopenia in HIV-infected female subjects is commonly manifested both in lumbar spine and Ward's triangle of the hip. There is a dissociation between lowered markers of bone formation rate and the increased bone resorption expressed as elevated urinary crosslinks and calcium excretion. Furthermore, the decreased levels of 1,25(OH2)D may contribute to a negative calcium balance and inhibition of bone formation. Our results suggest that further research is necessary to determine, whether low levels of 1,25(OH2)D lead to an accelerated inflammatory process in AIDS, since 1,25(OH)2D is known as an endogenous immune modulator suppressing formation of activated T cells and cell proliferation.

Elevated serum-calcium and parathormone-levels in HIV afflicted female heroin addicts.

Alterations of calcium and bone metabolisms have been observed in numerous studies of small groups of male HIV-infected patients. However, our knowledge regarding the manifestation of AIDS-associated hypoparathyroidism in female subjects is limited. In order to investigate the influence of heroin on the calciotropic hormones we performed a cross-sectional study on 45 female patients with proven HIV infection. The following criteria were used for exclusion from the study: age less than 20/ more than 50 years; confinement to bed; wasting symptoms; treatment with agents containing ketoconazole, renal or hepatic insufficiency; clinical or echographic signs of liver cirrhosis; endocrine diseases, or treatment with drugs known to influence calcium metabolism. A reduced parathormone (PTH) level was found among the female HIV-infected patients. Additional long-term use of heroin resulted in a significant increase of PTH compared to sex- and age matched controls and a second group of non-HIV-afflicted heroin dependent females. Significantly lowered serum magnesium concentrations were found in all three groups. Both serum calcium and urinary excretion of calcium were elevated in the group of HIV-infected heroin addicts and were independent from low vitamin D3 levels (1,25-dihydroxycholecalciferol) and alterations of protein metabolism. Therefore, it is concluded that the changes of PTH secretion are mainly due to mechanisms both of the impaired immune defense of HIV-infected females and the additional effect of opiates.

Evaluation of serum and urinary estrogen levels in male patients with HIV-infection.

Several endocrine functions are described which are altered in patients with human immunodeficiency virus infection. However, there is limited information available on estrogens and their function in these patients. The aim of this study was to relate the stage of the disease with urinary and serum estrogens and the influence of heroin consumption on gonadal steroids. Forty human immunodeficiency virus infected outpatients without AIDS or the clinical picture of AIDS were involved in this cross-sectional study. The subjects were divided in two groups: heroin addicts and non heroin addicts. Blood samples were taken and 24 h urines collected. Serum follicle stimulating hormone, luteinizing hormone, prolactin, estrone, estradiol, testosterone and urinary total estrogens were measured by commercially available radioimmunoassays. Prolactin levels were not affected in the patients. However, compared with controls, follicle stimulating hormone and luteinizing hormone were significantly higher for both groups tested. In contrast, the elevated serum estrone levels were significantly lower expressed in the patients with heroin abuse compared to those of the other group. Urinary estrogens in human immunodeficiency virus infected patients of both groups were found to be higher than those compared to healthy controls. Since these drugs are known to enhance estrogen levels, we conclude that other factors are modulating estrogen formation and degradation in these patients.

Bone mineral density in human immunodeficiency virus-1 infected men with hypogonadism prior to highly-active-antiretroviral-therapy (HAART).

Alterations of bone metabolism have been observed in numerous studies of HIV-infected patients. Sex steroids are known to profoundly influence bone mass and bone turnover. Hypogonadism is common in HIV-infection. Therefore, we performed a cross sectional study of 80 male HIV-infected patients without wasting syndrome, and 20 healthy male controls, in whom we analyzed urine and serum samples for both calciotropic hormones and markers of bone metabolism and of endocrine testicular function. Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry both in the lumbar spine and Ward's triangle of the left hip. None of the patients received highly-active-antiretroviral-therapy (HAART). Compared to eugonadal HIV-infected patients, subjects with hypogonadism (n = 32; 40%) showed statistically significant decrease of serum osteocalcin (p < 0.05) and elevated urinary excretion of crosslinks (p < 0.05). However, we found 13 and 15, respectively, patients with osteopenia (t-score -1.0 to -2.5 SD below normal) of the lumbar spine. The dissociation between bone formation and resorption and the reduction of of BMD (p < 0.05) is stronger expressed in patients with hypogonadism. Habitual hypogonadism appears to be of additional relevance for bone metabolism of male HIV-positive patients prior to HAART.

[Therapeutic complications from insulin antibodies--two case reports]. / Insulinantikörperbedingte Therapie-komplikationen--zwei Fallberichte.

Immunological complications of insulin therapy are extremely rare, since highly purified insulins, especially human semi- or biosynthetic insulin preparations became available for treatment of diabetes mellitus. Insulin antibodies of the immunoglobulin G or immunoglobulin E class can develop in 10-60%, however, in low titers in patients treated exclusively with human insulin. In rare cases these antibodies assume clinical significance, if the antigenic potential of the insulin used is high enough and if genetic predisposition exists. Two case reports presented here confirm this concept.

[Effect of histamine on bronchial hyperreactivity in sarcoidosis and other lung diseases]. / Einfluss des Histamins auf die bronchiale Hyperreaktibilität bei Sarkoidosen und anderen pulmonalen Erkrankungen.

Bronchial hyperreactivity is the central symptom of bronchial asthma which, however, can also be observed in various other diseases affecting the lungs and bronchi, such as, for example, sarcoidosis. In response to unspecific inhalative provocation, obstruction of the bronchi occurs; a genetic predisposition is thought to be involved. During this reaction, histamine is released by various cells, predominantly mast cells. In comparison with normal subjects, patients with bronchial asthma, sarcoidosis or a hyperreactive bronchial system are found to have significantly higher basal plasma levels if histamine. In response to unspecific provocation with acetylcholine and Carbachol, significantly higher histamine levels are observed in bronchial asthma and sarcoidosis. Although an increase is also observed in normal subjects and hyperreactives, it is appreciably lower than in the other two groups of patients. In contrast to asthmatics and patients with sarcoidosis, in particular in patients with hyperreactivity, a significant increase in plasma histamine is found following ergometer exercise. These results show that endogenous histamine is liberated by provocation challenges in various diseases, and may have a possible influence on bronchial obstruction.

[Determination of alpha-2-macroglobulin concentration using immunologic and amidolytic methods in diabetics and kidney patients]. / Alpha-2-Makroglobulin-Konzentrationsbestimmung mittels immunologischer und amidolytischer Methode bei Diabetikern und Nierenpatienten.

An increased alpha-2-macroglobulin level and a decreased functional capacity of the mononuclear phagocytic system in diabetics appears to be another important factor in the pathogenic cause of micro- and macro-angiopathy. Additionally, the disturbed immunobalance, especially in the micro-environment as well as the type and intensity of infections and inflammatory reactions are involved.

[Characteristics of lung function in patients with type I diabetes mellitus]. / Lungenfunktionscharakteristika bei Patienten mit Diabetes mellitus Typ I.

Employing routine clinical methods, the pulmonary function of 21 type 1 diabetics prior to and after exercise, was examined. In type 1 diabetics, at the time of the manifestation of the disorder, a reversible, seemingly metabolism-related emphysematous expansion was to be seen. In comparison with a control group and diabetics with no late complications, type 1 diabetics with secondary complications proved to have a significantly reduced vital and total capacity with relative hyperexpansion; an obstructive ventilation disorder was not demonstrable. These results are confirmed by those reported in the literature, and suggest the existence of a diabetic pneumopathy.

Extensive abdominal splenosis: imaging features.

We present the case of a 22-year-old patient who had splenectomy in childhood after trauma and had a known chronic active infection with hepatitis C. Imaging procedures in different radiologic modalities diagnosed diffuse intraabdominal splenosis. Splenosis is a rare, severe complication of splenic trauma or surgery, but the pathogenesis is not clear. Imaging features play a key role in the diagnosis of ectopic splenic tissue, which must be differentiated from malignancies, especially from lymphoma. Splenosis itself may induce relapse of hematologic diseases, mainly autoimmune thrombocytopenia.

[Recurrent hypoglycemia in the insulin autoimmune syndrome]. / Rezidivierende Hypoglykämien bei Insulin-Autoimmunsyndrom.

A 72-year-old man with recurrent hypoglycaemia was suspected of having an insulinoma. But several diagnostic methods (computed tomography; mesenteric and coeliac angiography; sella imaging) did not reveal any tumour. 72-hour hunger test did not precipitate any spontaneous hypoglycaemia. A falling insulin-glucose ratio spoke against an insulin-producing tumour. Reactive symptomatic hypoglycaemia occurred 4.5 hours after an oral glucose test. Measurement of insulin concentration demonstrated a slow but pronounced increase (3500 microU) over an already raised initial value (816 microU/ml), typical of prediabetic metabolic regulation. Demonstration of insulin autoantibodies confirmed the diagnosis of an insulin autoimmune syndrome, which has a good prognosis. The patient became free of symptoms on a regimen of frequent small, carbohydrate-poor but fat and bulk-rich meals. Hypoglycaemia recurred when the diet was not observed.

[Value of the flow-volume curve in the evaluation of non-obstructive dyspnea complaints]. / Wertigkeit der Flussvolumenkurve in der Beurteilung nicht obstruktiver Dyspnoebeschwerden.

The flow-volume curves of 246 patients with dyspnoea on exertion were analysed. In the presence of normal lung volumes and capacities and normal airway resistance, 52% of the patients were found already to have pathologically changed forced expiration figures. In patients with non-bronchogenic disorders, a predominately inspiratory reduction in flow was detected, in particular a reduction in maximum flow. Characteristic findings can be established already in the initial stage of ventilation disorders. Patients with diffuse pulmonary diseases are characterised by a virtually normal PEF, a steep decline in phase II of forced expiration, and a restriction in inspiration. Goitre-associated stenoses with a functional effect are characterised by a reduced expiratory peak flow, homogeneous expiration and reduced inspiratory flow. In patients with bronchial diseases, a functional overdistension can be detected even in the symptom-free stage with the aid of the quotient ITGV % MEF50% VC. In our opinion, the flow-volume curve should therefore be considered an indispensable investigation within the framework of pulmonary function diagnostic evaluation.

[Expression of low-affinity Fc epsilon receptors on circulating monocytes in patients with inflammatory rheumatic diseases]. / Expression niedrig-affiner Fc epsilon-Rezeptoren auf zirkulierenden Monozyten bei Patienten mit entzündlich-rheumatischen Erkrankungen.

In patients with scleroderma, high proportions of circulating CD23+ monocytes could be detected by FACS analysis as compared with controls. Supernatants obtained from lymphocytes yielded high amounts of interleukin-4-(IL-4-)like activity. The results suggest that IL-4 contributes to monocyte activation in scleroderma. There were no correlations with serum IgE, or numbers of naive and memory-CD4+ lymphocytes.

[Determination of tumor markers NSE and CEA in patients with various lung diseases, especially carcinomas]. / Die Bestimmung der Tumormarker NSE und CEA bei Patienten mit verschiedenen Lungenerkrankungen, insbesondere Karzinomen.

Serum neuron-specific enolase (NSE) and carcinoembryonic antigen (CEA) are two very good tumor markers for diagnosis and for monitoring response to therapy in patients with lung carcinoma. Especially, NSE has a high sensitivity and specificity for early detection of small-cell lung cancer and for management of these patients.

[Insulin and immunology--a correlation]. / Insulin und Immunologie--eine Wechselbeziehung.

In comparison to former decenniums the relations between insulin and immunology have changed and continued to develop. Still up to 20 years ago the immunological side effects of an insulin therapy stood well to the fore concerning the clinical interest, nowadays, however, they are the autoantibodies against insulin and it is the role of insulin for a functioning immune system, which is not in the least exactly recognized.

Inhaled iloprost is a potent acute pulmonary vasodilator in HIV-related severe pulmonary hypertension.

As antiretroviral therapy has improved life expectancy in human immunodeficiency virus (HIV) infection, the life-limiting complication of HIV-related pulmonary hypertension has come into focus. Inhalation of the stable prostacyclin analogue iloprost is an effective treatment for various forms of precapillary pulmonary hypertension. The main objective of the present study was to evaluate the safety and efficacy of inhaled iloprost in HIV-related pulmonary hypertension. In eight patients with severe pulmonary hypertension related to HIV infection, right heart and femoral artery catheterisation were performed. The acute effect of oxygen, inhaled nitric oxide and aerosolised iloprost was investigated. Four patients underwent long-term treatment with inhaled iloprost. The rank order of pulmonary vasodilatory potency was iloprost>NO>O2, with a maximum reduction (mean +/- SEM) in pulmonary vascular resistance of 30.6 +/- 3.1% (p < 0.001), 5.9 +/- 3.9% and -0.6 +/- 3.9%, respectively. Concomitantly, inhaled iloprost significantly increased the cardiac index and central venous oxygen saturation. Chronic treatment with inhaled iloprost tended to improve the 6 min walking distance and decreased pulmonary vascular resistance in all patients (although not significantly). No serious adverse events and no major interactions with the ongoing antiretroviral therapy were noted. In conclusion, inhaled iloprost is a potent pulmonary vasodilator in human immune deficiency virus-related pulmonary hypertension. Future studies are warranted to confirm the encouraging long-term beneficial results observed in the present limited number of patients.