Growth hormone, cortisol, and glucagon concentrations during plasma free fatty acid depression: different effects of nicotinic acid and an adenosine derivative (BM 11.189).

Two chemically unrelated inhibitors of lipolysis were used in order to differentiate between the effect of FFA depression and a possible FFA-unrelated drug effect, respectively, on the plasma concentrations of GH, cortisol, and glucagon. Saline infusion served as a control experiment. In eight healthy male volunteers, a similar FFA depression by either iv infusion of nicotinic acid (3-pyridine-carboxylic acid, NA) or oral intake of an adenosine derivative, N(6)-allyl-N(6)-cyclohexyl-adenosine (AD-D), was followed by a significant GH increase (to 22.1 +/- 6.2 and 9.6 +/- 2.9 ng/ml at 240 and 270 min, respectively). Due to the large scatter of the GH concentrations during NA infusion, these responses were not significantly different. No GH increase occurred when the FFA depression was prevented by addition of a lipid infusion. In contrast, plasma cortisol and glucagon both increased significantly (by 107.4 micrograms/liter at 270 min and by 48.4 pg/ml at 60 min, respectively) during NA- but not during AD-D-induced FFA depression. Addition of the lipid infusion abolished the cortisol increase during NA infusion but had no influence on basal cortisol concentrations during AD-D intake. It lowered glucagon to values slightly below basal concentrations when added to the NA infusion and more markedly during AD-D administration. The results provide evidence that 1) depression of plasma FFA per se stimulates the secretion of GH, and 2) the increase of cortisol and glucagon during NA infusion is probably unrelated to the FFA depression. Hence, the stimulatory effect of FFA lack on glucagon secretion needs to be reconsidered.

Prolonged infusions of Ile5-angiotensin-II in sodium replete and deplete man: effects on aldosterone, ACTH, cortisol, blood pressure, and electrolyte balance.

Angiotensin II (Ile5) was infused for 72 h into 4 sodium replete (3 ng/kg/min) and 8 sodium deplete (3 or 6 ng/kg/min) healthy young men after appropriate control periods, and the effects on aldosterone secretion, plasma cortisol, ACTH, renin activity, plasma and urinary electrolytes, and blood pressure were assessed. Sustained contrived elevation of plasma angiotensin II levels in sodium replete subjects to the range of moderate sodium depletion led to a sustained increase in plasma and urinary aldosterone levels, which further and significantly increased between the 1st and 2nd days of angiotensin II infusion, when gross sodium retention during infusion was prevented. This additional increase may be explained as the expression of a "trophic" effect of angiotension II on the zona glomerulosa. In the sodium deplete state, the absolute increment of aldosterone secretion for a given elevation of angiotensin II levels diring infusion was larger than in sodium replete subjects. This confirms the conclusions from previous short-term angiotensin II infusion experiments that sodium deficiency sensitizes the zona glomerulosa against angiotensin II. The "trophic" effect of angiotensin II on the adrenal gland seems to be one mechanism by which the sensitization is brought about, but insufficient for its full explanation. Since plasma ACTH and cortisol, plasma sodium and potassium concentrations, and potassium blance did not change significantly across sodium depletion or angiotensin II infusion, the mechanism of sensitization awaits its full elucidation. The effect of angiotensin II on blood pressure was blunted by soidum depletion. The opposite shifts in sensitivity against angiotensin II of the zona glomerulosa and of resistance blood vessels with changes in the sodium state seem to be an effective and important means in the regulation of body sodium.

[67Ga scintigraphy in retroperitoneal fibrosis (RPF): indications, application and clinical relevance--report of five patients]. / 67Ga-Szintigraphie bei retroperitonealer Fibrose (RPF): Indikation, Durchführung und klinische Bedeutung.

AIM: The aim of the study was to evaluate the indication for 67Ga-citrate imaging and its clinical impact on patients with retroperitoneal fibrosis (RPF). METHOD: The scanning with ventral and dorsal projections was done 48 an 72 h after i.v.-injection of 370 Mbq 67Ga-citrate. RESULTS: In the 5 patients with idiopathic RPF included in the study, there was a remarkably high correlation between the clinical symptoms, the surgical and histologic findings, the activity of the disease and the results of 67Ga-scintigraphy. CONCLUSION: While CT and--maybe even better--MRI might perfectly show the extension, shape and contour of the fibrotic tissue, Gallium-67 scan appears to be superior in assessing the intensity and activity of the disease process.

HIV-related nontuberculous mycobacterial infection: incidence, survival analysis and associated risk factors.

To evaluate the incidence and survival time for AIDS-patients affected by different stages of nontuberculous mycobacterial (NTM) infection we performed a retrospective study. Data of 1540 hospitalised AIDS-patients was analyzed with respect to survival time and incidence rates. The overall incidence rate of NTM following AIDS was 16.6/100 person-years (PY), with an increase from 12.1/100PY (1987-1990) to 18.9/100PY (1991-1994). Antiretroviral therapy (ART) and toxoplasmosis prophylaxis reduced the risk of NTM disease whereas CD4 cells <40/ microl at time of the first AIDS defining illness led to a 2.5 fold higher risk. Pneumocystis carinii pneumonia (PCP), wasting syndrome and PCP prophylaxis increased the risk of progression from colonization to dissemination. Cryptococcus neoformans infection, wasting syndrome, PCP prophylaxis and CD4 cells <40/ microl were linked to immediate NTM dissemination. Though the incidence of NTM dissemination increased by the factor 1.56 in 1991-1994, survival did not differ between patients with and without NTM infection.

Sensitivity and specificity of indirect immunofluorescence and Grocott-technique in comparison with immunocytology (alkaline phosphatase anti alkaline phosphatase = APAAP) for the diagnosis of Pneumocystis carinii in broncho-alveolar lavage (BAL).

The purpose of the study was to compare the sensitivity and specificity of the indirect method of immunofluorescence with the immunocytological technique of alkaline phosphatase anti alkaline phosphatase complex (APAAP) for the detection of Pneumocystis carinii by bronchoalveolar lavage (BAL) in HIV-1 positive patients. - 83 HIV-1 positive patients with clinical presentations suggestive of Pneumocystis carinii pneumonia (PcP) were included in the study. 28 samples were found Pc-positive by immunofluorescence (IFT), 26 by Grocott and 29 by APAAP. In comparison to the lab results 33 patients were diagnosed as PcP according to the clinical course (i.e. therapeutic outcome, drugs used, and therapy changes). Compared to the clinical diagnoses, the following lab tests proved to be false positive and false negative: false positive: IF = 1, Grocott = 0, APAAP = 4 (3F6). false negative: IF = 5, Grocott = 7, APAAP = 4 (3F6). - Grocott stain shows insufficient correlation to the clinical diagnoses (p = 0.0156, McNemar-Test, two-tailed). - The two different detection methods (IFT and APAAP) showed no significant statistical difference with regard to their sensitivity (p = 0.3438, McNemar-Test, two tailed) and specificity. Considering cost and time the immunofluorescence technique seems to be the most suitable for the diagnosis of PcP in HIV-1 positive patients.

How do patients with HIV perceive their general practitioners?

OBJECTIVE: To study the perceptions of patients with HIV of their general practitioners in terms of knowledge, abilities, confidence, and satisfaction. DESIGN: Questionnaire survey of inpatients, outpatients, and members of a self help group. SETTING: Two city hospitals, three outpatient clinics, and one AIDS self help group in Munich and Berlin, Germany. SUBJECTS: All 402 patients available between 1 September 1988 and 31 May 1989. MAIN OUTCOME MEASURES: General practitioners' attitudes towards the patients' HIV status; patients' experience of treatment rejection; reception in the general practitioner's office; the doctor's perceived knowledge about HIV and AIDS. RESULTS: 394 of 402 patients consented to interview; 87% were registered with a general practitioner and 91% of those indicated that the doctor was aware of their HIV diagnosis. The overwhelming majority of patients (94%) had a friendly or at least neutral reception in the general practitioner's surgery and only six patients' general practitioner changed his or her behaviour for the worse because of the HIV diagnosis. Two thirds of patients said they would consult first with their primary care doctor for a physical problem, but only 13% would do so for psychological problems. Over a third of the patients did not routinely inform other doctors or medical staff about their HIV status, but there was no significant correlation between this concealment and ever having been rejected by a doctor (7%) or a dentist (12%). CONCLUSION: Most patients expressed a high degree of satisfaction with their general practitioners in terms of confidential issues, attitudes, knowledge, and management.

[Unwanted drug side effects with pentamidine inhalation]. / Unerwünschte Arzneimittelwirkungen unter Pentamidin-Inhalation.

The incidence of systemic side effects under aerosolized pentamidine treatment or prophylaxis for pneumocystis carinii pneumonia is low when compared to intravenous application. Erythema, hypotension, hypoglycemia, renal failure are infrequently seen. Local side effects--cough, bronchial spasm, metallic taste--are frequent complications of aerosolized pentamidine treatment. Cystic lung disease, pneumothorax, and atypical pneumonia may be a late sequelae of pneumocystis carinii pneumonia, and not a primary effect of pentamidine. Poor apical ventilation due to suboptimal inhalation technique etc. and decreased deposition of pentamidine in these areas may be of some consequence for the development of these unusual complications. Extrapulmonary pneumocystis infections under preventive pentamidine aerosol treatment for pneumocystis carinii pneumonia have been seen in single cases, a causal relationship to pentamidine application is not yet established.

[Treatment of mild to moderately severe Pneumocystis carinii pneumonia with cotrimoxazole versus pentamidine aerosol. Preliminary results of a prospective randomized therapy study]. / Die Behandlung der leichten bis mittelschweren Pneumocystis-carinii-Pneumonie mit Cotrimoxazol versus Pentamidin-Aerosol. Zwischenergebnisse einer prospektiven randomisierten Therapiestudie.

In an open, prospective, randomized study we compared efficacy and side effects of 8 g/d cotrimoxazole (TMP/SMX) i.v. vs. 600 mg aerosolized pentamidine. 29 of 60 planned case record forms are now evaluated. Efficacy in both groups was comparable, but side effects in the pentamidine arm were very rare (7.2% vs. 40% in the TMP/SMX group). In moderate pneumocystis carinii pneumonia aerosolized pentamidine could be the first choice therapy. Necessary conditions are to use proper inhalation systems, experience, and the treatment of relevant accompaning bacterias, which we found in 80% of pneumocystis carinii positive bronchoalveolar lavages.

[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]. / Wirkungsvergleich zweier Therapiekonzepte zur Behandlung der Pneumocystis-carinii-Pneumonie. Cotrimoxazol für 21 Tage versus Sequenztherapie mit Cotrimoxazol und anschliessender Pentamidin-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.

[Manifestations of AIDS in the gastrointestinal tract]. / AIDS-Manifestationen im Gastrointestinaltrakt.

Besides central nervous system, pulmonary and cutaneous manifestations, the gastrointestinal tract and the hepatobiliary system are major organs in AIDS. Gastrointestinal symptoms due to opportunistic infections or HIV-associated tumours are common in AIDS patients. Nevertheless, a huge variety of endoscopically diagnosed mucosal lesions may not always be correlated to microbiological findings, clinical symptoms and histological aspects. Cytomegalovirus being the most important opportunistic infection in the GI tract in symptomatic AIDS patients, is correlated with erosive and ulcerative lesions, often accompanied by complications like perforation or bleeding. HIV-associated tumours in the GI tract like Non Hodgkin-lymphoma or Kaposi sarcoma may present with atypical endoscopic findings. Diagnostic procedures should include microbiological and histological investigations of biopsies looking for opportunistic infections. Besides, typical immunological changes involving the mucosa as direct target organ of the HIV virus, are important to understand morphological and functional abnormalities in HIV-patients with GI symptoms.

Control of mineralocorticoid substitution in Addison's disease by plasma renin measurement.

In 7 out-patients with Addison's disease, plasma renin activity (PRA), plasma concentrations of angiotensin II (AT II), renin substrate (PRS), potassium, sodium and total protein, hematocrit, blood pressure, heart rate and body weight were studied after 2 weeks each on 2 mg of dexamethasone, 25 mg hydrocortisone (HC), 25 mg HC + 0.05 mg 9-alpha-fluorohydrocortisone (FC), 25 mg HC + 0.1 mg FC and 25 mg HC + 0.2 MG FC. Four further patients were less extensively studied. Mean PRA (upper normal limit, ambulatory: 12 ng AT I-ml-1-h-1) after the 5 steps of incremental substitution, starting with dexamethasone, was 192, 59, 38, 24 and 9 ng AT I-ml-1-h-1 rsp. PRS did not change with increasing substitution. PRA and AT II were significantly correlated (r = 0.91; p less than 0.0001) and proved to be the most sensitive parameters of insufficient mineralocorticoid substitution. With decreasing significance, PRA also correlated with plasma protein concentration, plasma sodium concentration (negative), delta body weight (negative), heart rate, delta mean blood pressure (negative) and plasma potassium concentration. PRA or AT II measurements are useful clinical tools to control mineralocorticoid substitution in Addisonian patients. Inappropriately high substitution can be prevented by keeping PRA in the upper normal range.

[Peracute disseminated course of fatal Aspergillus fumigatus infection in liver failure and corticoid therapy. A case report on the epidemiology, pathogenesis and diagnosis of the systemic course of Aspergillus infections]. / Perakute disseminiert verlaufene, tödliche Aspergillus fumigatus-Infektion bei Leberversagen und Kortikoidtherapie. Ein kasuistischer Beitrag zur Epidemiologie, Pathogenese und Diagnostik systemisch verlaufender Aspergillus-Infektionen.

Cytostatic-treated persons and cases of severe hepatic failure under corticoid therapy are predisposed to disseminating Aspergillus infections. Constant exposure to Aspergillus spores may result in a fatal Aspergillus infection. The triad of hepatic failure, corticoid therapy and constant exposure to Aspergillus spores is described in a 70-year-old female patient. A painless icterus was clinically diagnosed as non-A non-B hepatitis, with a protracted cholestatic course. She had been treated with an oral corticoid preparation. After leaving the hospital at her own insistance when still in the icteric stage, severe pneumonia due to Aspergillus developed within 14 days; this was confirmed radiologically. The autopsy results showed unexpected infarction, similar to pneumonic foci, in all lobes and dissemination in the myocardium, stomach, kidneys and brain. The liver showed subacute dystrophy. Constant exposure to the conidia of A fumigatus came about as a result of the soil of potted ornamental plants in the patient's living room. The fungus could only be successfully cultured by putting infected tissue particles on Sabouraud dextrose agar; it was not possible by the common method of fractionated streaking.

Persistence of Cryptococcus neoformans in seminal fluid and urine under itraconazole treatment. The urogenital tract (prostate) as a niche for Cryptococcus neoformans.

The open questions of the persistence of Cryptococcus neoformans in the urogenital tract under antimycotic treatment can be examined under optimal mycological-diagnostic conditions only. The example of a case of cryptococcosis in an AIDS patient diagnosed and treated with itraconazole in the early secondary stage of cryptococcosis is used to discuss the problems of the persistence of Cr. neoformans involvement in the urogenital tract (prostate). Data from a ten-week follow-up study are presented and discussed. The observations made have shown that itraconazole is effective in all regions of the body, with the exception of the urogenital tract. In addition to clinical examinations, cases treated with itraconazole should be finally subjected to cultural examination of prostatic secretion and/or seminal fluid, to exclude the possible presence of a symptom-free involvement of the prostate by Cr. neoformans.

[The therapy of Candida esophagitis in AIDS patients with fluconazole]. / Die Therapie der Candida-Osophagitis bei AIDS mit Fluconazol.

Esophageal candidosis was found endoscopically in 135 of 496 AIDS patients with upper gastrointestinal symptoms. Vomiting, dysphagia and retrosternal pain were the leading symptoms. Endoscopy showed different stages of esophagitis with Candida patches as early changes up to severe esophagitis with hemorrhage. 36 patients were treated with fluconazole orally or intravenously administered (100 mg per day). In 33 of 36 patients clinical, endoscopic and microbiological results were good with complete cure of the lesions after 7, 14 or 21 days of treatment. In 3 patients with wasting syndrome and severe opportunistic infections a resistance to the drug was discussed because of lack of sufficient therapy results. Maintenance therapy seems to be necessary to prevent relapses.

Short time kinetics of deoxycorticosterone, deoxycortisol, corticosterone and cortisol during single dose metyrapone test.

In 4 young healthy males, serum levels of 11-deoxycortisol (S), cortisol (F), 11-deoxycorticosterone (DOC) and corticosterone (B) were determined at short intervals after oral administration of 30 mg/kg of metyrapone (M) at midnight. 11-hydroxylase blockade was calculated from the formula (formula: see text). Significant blockade was demonstrable 15 to 30 min after drug administration. Maximum blockade (greater than 90%) was found between 2 and 4 a.m., and fell to 60-70% at 8 a.m. The profile of blockade was very similar in all the subjects, although the absolute early rise in steroid levels showed large inter-individual differences. The F level at 8 a.m. (only slightly suppressed under these conditions) is not a safe indicator of adequate 11-hydroxylase blockade.

Non-interaction of spironolactone medication and cortisol metabolism in man.

In 5 healthy subjects and in 5 patients with decompensated liver diseases, the concentrations of cortisol, canrenone and canrenoate-K were determined after single doses and after a long-term treatment with spironolactone. The concentrations of the metabolites of spironolactone were determined fluorimetrically, those of cortisol by a highly specific radioimmunoassay with previous chromatographic separation. As a result, non-interaction between spironolactone medication and cortisol metabolism, even at high dose and long-term treatment conditions, was established neither in normal test subjects nor in patients with liver failure.

[Chronic pulmonary cryptococcosis. A case contribution for diagnosis of cryptococcosis in man from a pathologic-anatomic viewpoint]. / Chronische Lungenkryptokokkose. Ein kasuistischer Beitrag zur Diagnostik der Kryptokokkose des Menschen aus pathologisch-anatomischer Sicht.

Routine use of differential nutrients for isolating cryptococcus neoformans (Staib-Agar) during post-mortem examination revealed previously unsuspected chronic pulmonary cryptococcosis in a 64-year-old woman. Cause of recurrent pleural effusions over three years were probably sub-pleural cryptococcomas. In on-target and specific search for the cryptococcosis pathogen, the lung deserves special attention as a probable gateway.