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C Wanke

Publications and source records attributed to C Wanke.

At least 19 recordsLinked to original sources
PubMed2006

Current concepts in the diagnosis and management of metabolic complications of HIV infection and its therapy.

Changes in fat distribution, dyslipidemia, disordered glucose metabolism, and lactic acidosis have emerged as significant challenges to the treatment of human immunodeficiency virus (HIV) infection. Over the past decade, numerous investigations have been conducted to better define these conditions, identify risk factors associated with their development, and test potential therapeutic interventions. The lack of standardized diagnostic criteria, as well as disparate study populations and research methods, have led to conflicting data regarding the diagnosis and treatment of metabolic and body shape disorders associated with HIV infection. On the basis of a review of the medical literature published and/or data presented before April 2006, we have prepared a guide to assist the clinician in the detection and management of these complications.

Dyslipidemias↗
PubMed2001

The fat redistribution syndrome in patients infected with HIV: measurements of body shape abnormalities.

OBJECTIVE: To describe the body shape changes in the syndrome of fat redistribution or lipodystrophy seen in patients infected with HIV. DESIGN: An objective description of patients with HIV with fat redistribution syndrome. Body-height, weight, shape, and composition were measured by anthropometrics and biolectrical impedance analysis by a single observer. Clinical data were collected by chart review. SUBJECTS/SETTING: Thirty-nine patients with HIV receiving primary HIV care at a university hospital-affiliated infectious disease clinic who presented with complaints of body shape changes or who were referred by their primary care providers for body shape changes. ANALYSIS: Descriptive statistics were performed. RESULTS: Four of the 39 patients (10%) had not used protease inhibitor therapy. HIV status (by clinical presentation, CD4 and VL) varied widely. Laboratory abnormalities were moderate. Percent body fat differed widely when measured by bioelectrical impedance analysis and anthropometry (23% vs 13%). The mean body mass index was 25.6 kg/m2 for men and 25.8 kg/m2 for women. The mean waist/hip ratio was above normal, at 1.02. The mean mid-arm circumference and triceps skinfolds were below national standards for both men (30.4 cm and 8.1 mm, respectively) and women (26.7 cm and 7.5 mm, respectively). Nine patients (23%) had an increased dorso-cervical pad. Seventeen patients returned for follow-up measurements at 3 months; no significant differences were found between baseline and follow-up measurements. CONCLUSIONS: The waist/hip ratio, mid-arm and mid-thigh circumference, and triceps skinfolds were useful measures to define and follow the fat redistribution syndrome in patients with HIV. These body composition changes were not transitory in this short follow-up period.

Adipose Tissue↗
PubMed2000

Polar application of test substances in an organotypic environment and under continuous medium flow: a new tissue-based test concept for a broad range of applications in pharmacotoxicology.

We have established a new test concept for in vitro pharmacological trials. Our model employs tissue explants to test compounds for toxicity which arises with the metabolic interactions among different cell types. Microsurgical preparation of tissue explants avoids the destruction of the organ-specific tissue architecture. Explants were mounted in tissue carriers to improve nutrition and handling of the sample. To allow for the omission of serum supplementation of the culture medium, explants were cultured under continuous medium flow. Test substances are applied considering the polar architecture of most tissues in vivo, for example, covering the apical aspect of epithelia. In principal, all tissues obtained from any species, including man, can be used in this system. A trial application was performed with vitreous body substitutes, substances used in ophthalmology. One compound had passed cell culture tests, but caused massive blood vessel deterioration in vivo. Using our test system based on the developing renal vessel system, we could confirm, within 24 hours, severe vessel damage which resembles the injury suffered by the rabbit retina. We demonstrate that an improved tissue culture assay is a suitable tool for the detection of toxicity that remained unidentified in cell culture tests.

Animals↗
PubMed2000

Determination of eicosanoid and cytokine production in salvaged blood, stored red blood cell concentrates, and whole blood.

STUDY OBJECTIVE: To determine the production of the eicosanoids prostaglandin 2 (PGE2) and thromboxane 2 (TxB2) and the cytokines interleukin 1 beta (IL-1-beta) and interleukin 6 (IL-6) in whole blood (WB), unfiltered red blood cell (RBC), and filtered RBC concentrates, and salvaged blood. DESIGN: Prospective study. SETTING: University hospital of Erlangen. PATIENTS: 32 healthy volunteers and 14 ASA physical status I, II, and III radical prostatectomy patients (mean age 65 yrs). INTERVENTIONS: Sixteen WB units and 16 RBC units (divided into 16 filtered and unfiltered units each) were taken from 32 volunteers. Fourteen salvaged RBC units were obtained from the 14 radical prostatectomy patients. Sixteen WB units were stored for 35 days. From the 16 WB donations, RBC concentrates (PAGGS-M) were prepared. The RBC concentrates were halved, one half had its leukocytes removed at day 0; both halves were stored for 49 days. Salvaged blood (n = 14) was stored up to 2 hours during surgery and then retransfused. MEASUREMENTS AND MAIN RESULTS: Immediately at the start of the study, in all blood units (WB, RBC filtered, and RBC unfiltered units) at days 0 and 21, and at the end of the storage period (WB: 35 days, RBC concentrates: 49 days) and in the salvaged RBC units, the following parameters were measured: PGE2, TxB2, IL-1-beta, IL-6, hematocrit, platelet number, leukocytes, blood volume, and hemoglobin. During storage, different levels of PGE2, TxB2, IL-1-beta, IL-6 for WB, filtered RBC concentrates, and unfiltered RBCs were found. The higher levels of PGE2, TxB2, IL-1-beta, and IL-6 were found in the WB and RBC salvaged units than the filtered RBCs or unfiltered RBC units. There was no statistically significant difference between WB and salvaged RBCs. Higher levels of leukocytes and platelets were found in WB units and salvaged RBCs as compared to filtered or unfiltered RBCs. CONCLUSIONS: The eicosanoid and cytokine levels in the salvaged, filtered RBC, unfiltered RBC, and WB units stayed within physiological limits, suggesting that these levels do not contribute to the risk of nonhemolytic, immunomodulated transfusion reactions, even in massive transfusions.

Adjuvants, Immunologic↗
PubMed2000

c-Jun and RACK1 homologues regulate a control point for sexual development in Aspergillus nidulans.

Amino acid limitation results in impaired sexual fruit body formation in filamentous fungi such as Aspergillus nidulans. The starvation signal is perceived by the cross-pathway regulatory network controlling the biosynthesis of translational precursors and results in increased expression of a transcriptional activator encoded by a c-Jun homologue. In the presence of amino acids, the gene product of the mammalian RACK1 homologue cpcB is required to repress the network. Growth under amino acid starvation conditions permits the initiation of the sexual developmental programme of the fungus, but blocks fruit body formation before completion of meiosis. Accordingly, arrest at this defined control point results in microcleistothecia filled with hyphae. Addition of amino acids results in release of the block and completion of development to mature ascospores. The same developmental block is induced by either overexpression of c-Jun homologues or deletion of the RACK1 homologue cpcB of A. nidulans in the presence of amino acids. Therefore, the amino acid starvation signal regulates sexual development through the network that also controls the amino acid biosynthetic genes. Expression of the RACK1 gene suppresses the block in development caused by a deletion of cpcB. These data illuminate a connection between metabolism and sexual development in filamentous fungi.

Amino Acids↗
PubMed1999

Recombinant human growth hormone improves the fat redistribution syndrome (lipodystrophy) in patients with HIV.

OBJECTIVE: To determine the efficacy of recombinant human growth hormone (rhGH) in the treatment of the fat redistribution syndrome (FRS) in patients with HIV. DESIGN: A prospective, open-label study. SETTING: An urban, university-affiliated Infectious Disease Clinic. PATIENTS: Ten HIV-infected patients (seven men, three women) with FRS. INTERVENTIONS: Treatment with 6 mg of rhGH a day, subcutaneously for 12 weeks. MAIN OUTCOME MEASURES: Body mass index (BMI), body composition by bioelectrical impedance analysis (BIA), body composition by anthropometrics (including waist/hip ratio), buffalo hump. RESULTS: The mean age was 41.7 years, the CD4 cell count was 247, and the HIV RNA was 95 735 copies/ml; 50% had undetectable viral RNA. The BMI was significantly increased from baseline to the end of treatment with growth hormone (25.3-26.9 kg/m2; P < 0.04); the waist/hip ratio significantly decreased from baseline levels, after treatment with growth hormone (1.03-0.9; P < 0.04); mid-thigh circumference increased significantly when baseline was compared with measures after treatment (49.1-51.8 cm; P < 0.03). One patient had to discontinue therapy because of hyperglycemia. CONCLUSION: Short-term treatment with rhGH improved the alterations in body shape that occur with FRS in HIV-infected patients. Waist/hip ratios and mid-thigh circumference are useful measures to follow alterations in body shape in FRS.

Adult↗
PubMed1999

Sexual development of Aspergillus nidulans in tryptophan auxotrophic strains.

The interplay between sexual development and amino acid biosynthesis in the ascomycete Aspergillus nidulans was studied. The growth and differentiation of four tryptophan auxotrophic strains that are unable to regulate their tryptophan biosynthesis, were examined. These strains are sterile on medium containing low tryptophan concentrations. Fruitbody formation was restored by supplementation with high concentrations of tryptophan and was promoted by supplementation with indole or auxin. Tryptophan supplementation resulted in auxin production of A. nidulans. Fertility of ascospores of the tryptophan auxotrophic strains could only be partially re-established. trpC transcript levels and enzyme activities remained stable in cleistothecia and conidiophore extracts as compared to those of mycelium, while levels of gene transcripts involved in glycolysis were lower in fruitbodies and conidiospores. Auxotrophic strains unable to form fruitbodies at intermediate amino acid supplementation levels turned on the cross-pathway regulatory system that is induced by amino acid starvation. We conclude that there is a connection between the genetic network of cross-pathway control and sexual development in A. nidulans.

Aspergillus nidulans↗
PubMed1999

Cytokine generation in whole blood, leukocyte-depleted and temporarily warmed red blood cell concentrates.

BACKGROUND AND OBJECTIVES: It has been suggested that inflammatory cytokines such as Interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha (TNF-alpha) and IL-8 might be responsible for a large number of non-antibody-mediated adverse reactions to the transfusion of blood components, especially of platelet concentrates (PCs). The aim of this study was to compare the levels of proinflammatory cytokines in different blood components containing red cells such as buffy-coat-free packed red cells (RBCs), filtered RBCs and whole blood (WB) during storage under several conditions. MATERIALS AND METHODS: WB (CPD-A1, n = 16) was stored for 35 days at 2-6 degrees C; samples were taken on days 0, 21 and 35. Buffy-coat-poor RBCs in additive solution PAGGS-M (n = 16) were divided into halves, one half was leukocyte (WBC)-depleted by filtration on day 0, both halves were stored for 49 days at 2-6 degrees C (samples: days 0, 21, 49). Furthermore, buffy-coat-poor, unfiltered SAG-M RBCs (n = 16) were halved immediately after production and stored at 2-6 degrees C until day 42 (samples: days 0, 21, 42). One half remained at room temperature for 24 h on day 3. Cytokine levels were determined with commercial enzyme-linked immunosorbent assays. RESULTS: Levels of IL-1beta and TNF-alpha rose during storage of WB and RBCs. IL-6 could be detected markedly above the detection threshold in WB only. At the end of storage, we detected IL-8 in 1 of 16 units of WB tested, in 10 of 16 standard PAGGS-M RBCs and in 15 of 16 temporarily warmed SAG-M RBCs. Prestorage filtration of RBCs prevented the accumulation of IL-1beta and TNF-alpha. Temporarily warming of RBCs for 24 h did not cause any substantial increase in cytokine levels other than IL-8. RBCs stored in different additive solutions (PAGGS-M versus SAG-M) showed similar cytokine concentrations during storage. The cytokine content of WB was very similar to that of buffy-coat-poor RBCs. CONCLUSION: Cytokine levels measured in WB and buffy-coat-poor RBCs result in levels which are unlikely to cause febrile reactions even in the case of massive transfusion. We conclude that, according to present knowledge, there is no reason for prestorage filtration of buffy-coat-poor RBCs or WB to avoid febrile transfusion reactions due to cytokine accumulation during storage.

Blood Preservation↗
PubMed1998

Basic fibroblast growth factor is a morphogenic modulator in kidney vessel development.

During kidney organogenesis the development of renal vessels must be synchronized with the maturation of nephrons and the collecting duct system. Several reports showed that hormones and mitogenic peptides as basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF) are involved in this regulatory process. It is a known fact that bFGF receptors are expressed by differentiating tubular epithelium and mesenchyme, but little information is available about the function of bFGF in kidney organogenesis. The role of bFGF during kidney development was investigated using an organotypic culture system and immunohistological techniques. Renal cortex explants were prepared from the kidneys of neonatal rabbits with a microsurgical method, retaining the natural tissue composition. The explants were cultured serum free under continuous medium perfusion. Our results indicate a new and unexpected role of bFGF during the differentiation process. When bFGF alone was applied, vessels could no longer be detected. The inhibitory influence of bFGF could be overcome by addition of VEGF or hormones such as retinoic acid and aldosterone/vitamin D3. The combination of these factors with bFGF resulted in the expression of small vessel-like structures. We conclude that bFGF has a morphogenic rather than a mitogenic function during kidney vessel development.

Animals↗
PubMed1998

Single-agent/combination therapy of human immunodeficiency virus-related wasting.

Weight loss and wasting are significant contributors to morbidity in patients infected with the human immunodeficiency virus (HIV). The approach to the patient with HIV and weight loss needs to be proactive and comprehensive, as early intervention may be beneficial and the weight loss may be multifactorial. Evaluation for weight loss needs to be directed at any apparent contributing cause and can include dietary evaluation, treatment of intercurrent complicating infections or malignancies, and maximization of HIV therapy. Some patients will also benefit from an evaluation of the gastrointestinal tract to document malabsorption and/or opportunistic enteric infections. It is also prudent to evaluate testosterone levels in male patients. Interventions in the patient who is not able to take in sufficient calories should include dietary advice and/or nutritional supplements, as well as the use of appetite stimulants. Megace (Bristol-Myers Squibb, Princeton, NJ) has been shown to effectively increase appetite, oral intake, and body weight. For the patient with malabsorption and/or diarrhea, treatment of enteric infections should be attempted. These patients may benefit from the replacement of some dietary fat with medium-chain triglycerides, either in a nutritional product or to replace cooking oils. Other patients may benefit from the use of anabolic agents such as growth hormone, nandrolone, testosterone, or oxandrolone, which are all effective at increasing lean body mass. For select patients, agents such as thalidomide might be of benefit, although its mechanism of action is not clear. There are few data from prospective, controlled trials of combinations of these agents, but these studies are underway. It is likely that the optimal interventions for patients will be combinations of agents to improve oral intake and add lean body mass, which will permit a reduction in morbidity from weight loss and an improvement in quality of life for the HIV-infected patient.

Anabolic Agents↗
PubMed1997

The Aspergillus niger GCN4 homologue, cpcA, is transcriptionally regulated and encodes an unusual leucine zipper.

The general control transcriptional regulator gene cpcA of Aspergillus niger was cloned by complementation of a Saccharomyces cerevisiae delta gcn4 mutant strain. The encoded protein conferred resistance to amino acid analogues when expressed in yeast. Disruption of cpcA in A. niger resulted in a strain which is sensitive towards 3-aminotriazole and fails to respond to amino acid starvation, cpcA encodes a transcript of approximately 2400 nucleotides in length that includes a 5' leader region of 900 nucleotides. The 5' leader region contains two small open reading frames, suggesting translational control of gene expression. Steady-state mRNA levels of cpcA increase by a factor of three upon amino acid starvation. The coding region of cpcA is interrupted by a 57 bp intron and the deduced amino acid sequence displays an approximately 30% overall identity to yeast GCN4p and Neurospora crassa cpc1p. Critical amino acid residues of the transcriptional activation domains of GCN4p are conserved in cpcAp. The basic DNA-binding domain shows up to 70% amino acid sequence identity to other basic zipper (bZIP)-type transcriptional activators. cpcAp binds specifically to a GCN4p recognition element in gel retardation experiments. The C-terminal dimerization domain encodes a leucine zipper with only a single leucine residue.

Amitrole↗
PubMed1997

Hypercalcemia in an AIDS patient treated with growth hormone.

METHOD: Recombinant human growth hormone (rhGH) is a newly approved treatment for weight loss and wasting in patients with AIDS. We report a male patient with advanced AIDS who developed hypercalcemia 2 weeks after institution of rhGH therapy. RESULTS: Parathyroid hormone, parathyroid hormone-related peptide and 1,25-dihydroxyvitamin D levels were suppressed, suggesting that hypercalcemia was mediated through alternative mechanisms. The hypercalcemia responded to discontinuation of rhGH and a single dose of intravenous pamidronate disodium and has not recurred in 8 months of follow-up. CONCLUSION: We believe this to be the first reported case of rhGH-induced hypercalcemia in an HIV-infected patient.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Microsporidian sinusitis in patients with the acquired immunodeficiency syndrome.

Sinusitis in patients with human immunodeficiency virus (HIV) infection usually arises from the same organisms that are infective in the nonimmunosuppressed population. The authors of this article report that optimal antimicrobial treatment and functional endoscopic sinus surgery failed to eradicate sinonasal disease in three of five patients with acquired immunodeficiency syndrome (AIDS) and refractory sinusitis. The sinonasal disease was manifested by congested, edematous, and polypoid mucosa, often with a superimposed bacterial infection from ostial obstruction. After tissue was sent for electron microscopy (EM), the patients were eventually diagnosed with microsporidiosis of the sinonasal cavities. Microsporidia are obligate intracellular protozoans that have been seen in AIDS patients with diarrhea. These protozoans have only recently been identified in sinonasal tissue. Microsporidia are often missed on routine histopathology. The authors present case reports on their five AIDS patients with refractory sinusitis. The management of refractory sinusitis in the HIV-infected population, including mandatory EM of sinonasal tissue, is also discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Multiorgan microsporidiosis: report of five cases and review.

We describe five cases and review 34 reported cases of multiorgan microsporidiosis. Most of the patients with multiorgan involvement have been adults with AIDS. Organs most commonly infected include the small intestine, urinary tract, biliary tree, and eye; involvement of the respiratory tract, nasal sinuses, and central nervous system is also described but appears to be less frequent. Although patients with multiorgan disease may be asymptomatic, clinical presentation usually relates to the involved organs. Enterocytozoon bieneusi and Septata intestinalis are the most frequently identified species of pathogens. An affinity for certain tissues is observed among different microsporidial species. In all but one case of E. bieneusi infection, infection was limited to intestinal and hepatobiliary tracts, a finding suggestive of local extension. In contrast, the patients infected with S. intestinalis had widespread involvement, suggesting true hematogenous or lymphatic dissemination. Treatment may have to be based on findings regarding which organs and specific microsporidial species are involved. Further investigation of the pathogenic tendencies and route of acquisition of these organisms and the therapeutic agents active against them is needed.

AIDS-Related Opportunistic Infections↗
PubMed1995

Diagnosis of intestinal microsporidiosis by examination of stool and duodenal aspirate with Weber's modified trichrome and Uvitex 2B strains.

Severe, chronic diarrhea is a frequent complication of human immunodeficiency virus disease, and intestinal microsporidiosis is being recognized with increasing frequency in patients with AIDS. Noninvasive, cost-effective techniques are needed to optimize its diagnosis. Weber's modified trichrome stain (MTS) and the fluorochrome Uvitex 2B stain were used to detect microsporidial spores in smears of stool and duodenal aspirate (DA) samples received from human immunodeficiency virus-infected patients for examination for ova and parasites. Of 305 samples (292 stool and 13 DA samples) from 140 patients examined by MTS, 83 samples from 26 (18.6%) of the patients were positive for microsporidia (23 patients diagnosed initially and 3 diagnosed upon review). A subset of the samples studied by MTS consisting of 108 smears of stool and DA specimens from 60 patients was examined by Uvitex 2B. All 44 samples positive by MTS were also positive by Uvitex 2B. In addition, seven specimens and three patients were initially detected as positive by Uvitex 2B only (all three patients were positive also by MTS upon review). Confirmation of the diagnosis was obtained for 24 of 26 smear-positive patients by duodenal biopsy and/or stool transmission electron microscopy. Of 114 patients with stained smears negative for microsporidia, 23 had duodenal biopsies which showed no microsporidia. For the 43 patients who underwent duodenal biopsy, the sensitivity of both the MTS and the Uvitex 2B methods compared with biopsy results was 100%. Of six patients with negative duodenal biopsies and positive stained smears, four had microsporidia demonstrated by stool transmission electron microscopy. The examination of stool and DA smears stained by Uvitex 2B and/or MTS is a sensitive, noninvasive test for diagnosis of intestinal microsporidiosis which can be successfully implemented in a clinical laboratory. Strict adherence to precise diagnostic criteria is necessary to avoid incorrect results. The simultaneous use of both staining methods enhances performance and may provide greater accuracy, especially for patients with light infections.

AIDS-Related Opportunistic Infections↗
PubMed1995

Structural plasticity in the Drosophila brain.

The Drosophila brain is highly variable in size. Female flies grown in densely populated larval cultures have up to 20% more Kenyon cell fibers in their mushroom bodies than flies from low-density cultures. These differences in the number of Kenyon cell fibers are accompanied by differences in the volume of the calyx. During imaginal life, volume changes are observed in the calyces, all parts of the optic lobes, the central brain, and central complex. They occur not only in the first week of adulthood but also between days 8 and 16. Factors causing these changes are little understood. In flies kept in pairs for 1 week, the size of the calyx but not of the lobula is influenced by the sex of the partner. Females have larger calyces if the partner is female than if it is male. Males seem to be affected in the same way. Females living solitarily in little food vials for the first week of their imaginal life have smaller lobulae than females having spent the week in a populated flight cage. Males and females of heterosexual groups of 40 animals have still smaller lobulae, medullae, and calyces than their siblings kept in isolation. In addition, brain size is influenced by yet unidentified factors causing long and short trends. The data suggest that in Drosophila, most neuropil regions of the brain are continuously reorganized throughout life in response to specific living conditions.

Animals↗