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Biomedical subjects

I Schedel

Publications and source records attributed to I Schedel.

At least 19 recordsLinked to original sources

[New medications for treatment of systemic mycoses].

The past few years have seen the advent of several new antifungal agents. The echinocandin, caspofungin, has greatly expanded the antifungal armamentarium by providing a cell wall-active agent with candidacidal activity as well as demonstrated clinical efficacy in the therapy of aspergillosis refractory to available therapy. In addition, in clinical trials, caspofungin exhibited efficacy comparable to amphotericin B for invasive and/or fluconazole-resistant Candida infections. According to a randomised trial, voriconazole has added a significantly improved therapeutic option for primary therapy of invasive aspergillosis. Additionally, voriconazole may be used successfully as salvage therapy for other fungal infections, i.e. cryptococcosis. Despite the advances offered by each of these drugs, the morbidity and mortality associated with invasive fungal infections remains high. Considering the adverse effects of the available antifungal agents and the considerable costs for their application, meaningful clinical trials for a precise indication in different clinical situations are urgently needed.

Antifungal Agents↗

[Fever after travel return].

Between 20 and 70 percent of the 50 million people who travel from the industrialized world to the developing world each year report some illness associated with their travel. Approximately 3 percent of people traveling internationally for short periods (<2 weeks) report fever even after travel. Careful assessment of the travel history, likely incubation period, exposure history, associated signs and symptoms, duration of fever, immunization status use or nonuse of antimalarial chemoprophylaxis, and degree of compliance with a chemoprophylactic regimen, if used, helps to establish the diagnosis. Determining an approximate incubation period can be particular helpful in ruling out possible causes of fever. Specific examinations targeting the individual infection, assumed to be responsible for the development of febrile disease may ascertain diagnosis and lead to effective treatment.

Communicable Diseases↗

Acute CMV-colitis in a patient with a history of ulcerative colitis.

A symptomatic cytomegalovirus (CMV) infection usually occurs in patients with debilitating diseases, immunosuppression, transplantations and acquired immunodeficiency syndrome (AIDS). Gastrointestinal infections with CMV, especially colitis, are usually found in immunocompromised patients and rarely affect immunocompetent subjects. Here we report the case of a young female patient with a history of ulcerative colitis (UC) who presented with an acute attack of colitis caused by CMV infection. This was documented by the presence of CMV early antigen, antibodies and evidence of CMV in the colonic mucosa. After combined anti-inflammatory and antiviral treatment the patient recovered completely. As most attention is given to CMV-pathogeneity in immunocompromised patients, here we discuss the relationship to inflammatory bowel diseases.

Acute Disease↗

[Intestinal tuberculosis: Easier overlooked than diagnosed].

Intestinal tuberculosis: Easier overlooked than diagnosed. The medical history of two Asian immigrants suffering from intestinal tuberculosis demonstrates the difficulties in finding the correct diagnosis. Intestinal tuberculosis resembles Crohn's disease with regard to clinical symptoms, macroscopic and microscopic intestinal findings. Sonographic, radiologic, endoscopic, and histological examinations facilitate distinguishing both entities. Diagnosis of intestinal tuberculosis is made by identification of the causative microorganism in tissue specimens. As this may be difficult and time-consuming, a therapeutic trial with anti-tuberculous agents may be warranted.

Adult↗

Phase II study of anti-CD4 idiotype vaccination in HIV positive volunteers.

A clinical phase II trial of postinfectional idiotype vaccination was performed in early stage HIV + volunteers. The mAb 13B8.2 is directed against the CDR3-homologous CD4/D1 region implicated in HIV-gp120 binding. We have previously shown that this mAb induces HIV-gp120 cross-reactive immunity. In addition, the mAb 13B8.2 was well tolerated in a clinical phase-Ia trial. In this phase-II trial, 158 patients with 350-500 CD4+ cells/microl blood were randomised to receive either 1.2 mg of alum-precipitated mAb 13B8.2 or placebo. The mAb was well tolerated evoking predominantly local side effects. Multivariant analysis of clinical study endpoints demonstrated a significant response in the verum group (intend-to-treat analysis). Titres of HIV-1 neutralisation in vitro were raised along with HIV/gp120 antigen binding titres. Our data indicate that patients treated with the idiotype vaccine will produce an augmented specific anti-viral immune response. The vaccine might thus have a positive impact on the course of HIV disease.

Adolescent↗

Levels of antibodies to endotoxin and cytokine release in patients with severe trauma: does posttraumatic dysergy contribute to organ failure?

BACKGROUND: We conducted a prospective study in patients with multiple injuries investigating the time course of trauma-related changes of systemic immunologic defense mechanisms. METHODS: Patients with multiple injuries with Injury Severity Scores of more than 20 were included if they survived for more than 4 days after injury. Further inclusion criteria were no local or systemic infection (pneumonia, sepsis, soft-tissue infection, acquired immunodeficiency syndrome, tuberculosis, etc.) at the time of injury and no history of liver disease, bowel disease, or abdominal surgery. Serum endotoxin levels were measured from peripheral venous blood, as were the immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies against lipid A and against the core polysaccharide of endotoxin (lipopolysaccharide [LPS]), during the course of intensive care management. Serial central venous levels of interleukin-6 were determined as a marker of the inflammatory response. RESULTS: The patients were grouped according to their survival, with the survivors belonging to group S (48 patients) and the nonsurvivors belonging to group N (16 patients). The time of death for the nonsurvivors was between days 10 and 32 after the initial trauma. Thirteen of these patients (81%) died of multiple organ failure between days 12 and 17, two died of head trauma, and one died of sepsis. In patients who died of multiple organ failure, a significantly lower production of the IgM and IgG antibodies (AB) against lipid A and LPS was found before death (lipid A IgM-AB, day 11: group N, 29 +/- 11 U/mL; group S, 106 +/- 16 U/mL; p = 0.008; lipid A IgG-AB, day 11: group N, 18 +/- 9 U/mL; group S, 57 +/- 18 U/mL; p = 0.007; LPS IgM-AB, day 11: group N, 36 +/- 14 U/mL; group S, 122 +/- 23 U/mL; p = 0.009; LPS IgG-AB, day 11: group N, 17 +/- 12 U/mL; group S, 56 +/- 19 U/mL; p = 0.03). Interleukin-6 levels were significantly increased in the nonsurvivors (day 1: group N, 1,095 +/- 112 pg/mL; group S, 393 +/- 67 U/L; p = 0.008). CONCLUSION: In patients who died of severe trauma and in whom the cause of death was multiple organ failure, a significantly lower production of antiendotoxin antibodies was measured shortly before death. An insufficient immune defense (dysergy) may be involved in the pathomechanisms leading to the development of organ dysfunction.

Adult↗

CD4-imitating human antibodies in HIV infection and anti-idiotypic vaccination.

Anti-idiotypic vaccination against HIV infection aims at inducing an anti-gp120 immune response through anti-CD4 Abs mimicking epitopes of the gp120 molecule. The mAb IOT4a induces anti-gp120 Abs in rabbits. This study investigates the presence of human serum Abs cross-reacting with anti-CD4 mAbs and gp120 during HIV infection and after parenteral vaccination with IOT4a. Ten HIV-infected volunteers without immunodeficiency were inoculated s.c. with 0.6, 1.2, or 2.4 mg IOT4a. Six booster injections followed until day 35. Sera from study patients, 80 HIV-positive, and 43 seronegative controls were examined by a panel of assays, including an ELISA using competition against biotinylated recombinant CD4, flow cytometry assaying inhibition of anti-CD4 mAbs and biotinylated gp120 binding to CD4-positive lymphocytes, and an IOT4a immunoblot. After vaccination, an increase in competitive binding activity, which was quantitative in ELISA and flow cytometry, was observed. In the ELISA, competition against biotin-CD4 was quantitatively quenched by preincubating sera with r-gp120 or anti-CD4 mAbs such as IOT4a and Leu3a. Naive sera or sera from blood donors had no such effect in the assays employed, while 5/80 HIV sera showed binding qualities similar to vaccinees. These results suggest that 1) CD4 internal-image Abs emerge in a small proportion of HIV-positive individuals, and 2) parenteral vaccination with mAb IOT4a can induce a gp120 cross-reacting immune response that inhibits gp120 binding to CD4.

Adult↗

Human papillomavirus is associated with the frequent detection of warty and basaloid high-grade neoplasia of the vulva and cervical neoplasia among immunocompromised women.

A total of 158 women who either HIV-infected or under iatrogenic immunosuppression were examined regularly during a 4-year period to evaluate if certain vulvar neoplasms and cervical neoplasia have similar associated risk factors. Patients with CIN were matched prospectively with immunocompetent controls with CIN. Forty-eight cervical lesions were detected among patients, including 2 invasive carcinoma and 15 CIN-3 lesions, compared to 11 vulvar lesions, including 2 invasive carcinoma and 7 VIN-3 lesions. Women who have more than five life-time partners were more likely to have HPV-DNA positive cervical swabs and vulvar scrapes as well as cervical and/or vulvar neoplasia. Compared to 2.7% of controls 15.2% of patients with CIN had coexisting high-grade lesions of the vulva. With 1 exception all patients with vulvar neoplasia either suffered from symptomatic immunodeficiency or received immunosuppressive drugs for more than 10 years. Except for 1 VIN-3 lesions, all vulvar neoplasms were associated with HPV-DNA types 16, 31, and/or 33. Six of nine patients as well as the 2 controls with coexisting vulvar and cervical neoplasia had the same HPV-type associated with both lesions. All vulvar lesions were classified as either "warty" or "basaloid". In conclusion cervical and bowenoid/basaloid vulvar neoplasia seem to have a similar HPV-related genesis. Malfunction of the cellular immune response appears to be a cofactor in the genesis of HPV-associated neoplasia at both sites.

Case-Control Studies↗

Ketotifen in HIV-infected patients: effects on body weight and release of TNF-alpha.

OBJECTIVE: Tumor necrosis factor alpha (TNF-alpha) is involved in the genesis of HIV-associated malnutrition. We performed an open-label trial on the effects of ketotifen, an in vitro inhibitor of TNF-alpha release from peripheral blood mononuclear cells (PBMCs), on the nutritional status and TNF-alpha release of HIV-infected subjects. PATIENTS: Six HIV-infected subjects received oral ketotifen 4 mg per day for 84 days and were followed up for an additional 70-day period. Body composition was measured by bioelectrical impedance analysis. TNF-alpha plasma levels, TNF-alpha release from PBMCs, and plasma concentration of soluble TNF receptors were measured repeatedly during the study and control period. RESULTS: During ketotifen intake, TNF-alpha release from stimulated PBMCs significantly decreased (68 vs 155 pg ml-1), but not TNF-alpha and soluble TNF receptor plasma concentrations. Subjects gained weight (+ 2.7 kg), whereas weight loss was observed after cessation of treatment (-1.6 kg). CONCLUSION: Ketotifen inhibits TNF-alpha release from stimulated PBMCs and might thus be useful in the management of HIV-associated malnutrition.

Adult↗

Percutaneous endoscopic gastrostomy in AIDS and control patients: risks and outcome.

OBJECTIVES: Wasting is a major feature of advanced HIV infection. Enteral nutrition via percutaneous endoscopic gastrostomy (PEG) is a safe and efficient therapy in malnutrition, but limited experience exists in wasted HIV patients. Here we report on outcome and risk of PEG-feeding in HIV patients compared with HIV-seronegative patients and with HIV patients without PEG. METHODS: In 47 HIV-infected patients, PEG was placed because of wasting (n = 33), neurologic deficits (n = 11), or dysphagia (n = 3). Clinical, immunological, and nutritional data were compared with those of i) 15 HIV patients who refused PEG placement despite an appropriate indication, ii) 76 HIV patients without signs of malnutrition, and iii) 43 miscellaneous PEG patients. RESULTS: PEG was as safe in HIV-infected as in HIV-seronegative patients. PEG feeding resulted in significant increases of body weight (+3.3 +/- 3.6 kg, p < 0.001), serum albumin concentration (+4.5 +/- 7.2 g/L, p < 0.005), and total iron-binding capacity (+9.5 +/- 11.5 mumol/L, p < 0.001). Moreover, our data indicate that PEG feeding may improve survival in wasted AIDS patients. CONCLUSIONS: PEG feeding is safe and effective in the treatment of the AIDS wasting syndrome. Further prospective investigations are necessary to answer the question of whether treatment of wasting improves patient survival.

Acquired Immunodeficiency Syndrome↗

Cellular immunodeficiency enhances the progression of human papillomavirus-associated cervical lesions.

Most cases of low-grade cervical intraepithelial neoplasia (CIN) associated with oncogenic human papillomavirus (HPV) types regress spontaneously within years. Unknown co-factors seem to be necessary for a progression to malignancy. To determine the possible role of cellular immunodeficiency as such a co-factor in the genesis of genital neoplasia, 48 HIV-infected women and 52 allograft recipients were examined periodically during a 3-year period. Colposcopy, cytology and HPV-DNA typing (ViraType) were performed at each visit. Each cervical lesion was matched prospectively with 2 lesions from immunocompetent controls. In all, 29/100 patients suffered from cervical neoplasms, including 2 advanced cervical cancers and 9 CIN3 lesions. Correlation between grade of lesion and HPV DNA 16/18 was significant. Low-grade lesions among patients progressed more often than among controls and recurrent lesions after destructive treatment were seen more frequently among patients than among controls. All patients with CD4-lymphocyte counts of < 400/microliters or immunosuppression for more than 3 years suffered from progressive lesions. We conclude that malfunction of the cellular immune response following either HIV-induced depletion or iatrogenic inhibition of CD4-lymphocyte activation, enhances the progression of HPV-induced cervical lesions to malignancy.

CD4-Positive T-Lymphocytes↗

Resting energy expenditure and weight loss in human immunodeficiency virus-infected patients.

Resting energy expenditure (REE) and body composition were investigated in 60 clinically stable patients with human immunodeficiency virus (HIV) infection varying with respect to immune impairment. REEs differed significantly from predicted values (> or < 10% of the Harris-Benedict [HB] equation) in 40% of patients. Seven percent of patients showed markedly increased REE (> +20% of HB prediction), whereas REE was decreased in 13% (< -10%). Increased REE was found during all clinical stages of the disease (Walter Reed [WR] 2 through 6) and was not strictly associated with the degree of immune impairment, presence of diarrhea or Kaposi's sarcoma, nutritional state, or anamnestic wasting. Twenty-seven patients were evaluated for a mean period of 319 days; 11 lost more than 5% of their initial body weight during the observation period. Weight-losing patients were normometabolic before but showed a significantly increased REE (+7% of predicted values or +8% when compared with previous measurements) during weight loss. The degree of deviation from estimated REE was strongly associated with the degree of weight loss. We summarize that increased REE is not a constant feature of HIV infection. It is not associated with clinical and laboratory parameters of immune deficiency, but may occur during weight loss. Thus increased REE represents an inadequate adaptation to malnutrition and contributes to wasting.

Acquired Immunodeficiency Syndrome↗

Diagnosis of cytomegalovirus infections of the nervous system by immunocytochemical demonstration of infected cells in cerebrospinal fluid.

OBJECTIVES: Infections caused by the cytomegalovirus (CMV) are frequent complications in patients with the acquired immunodeficiency syndrome. Diagnosis of CMV infections of the nervous system is still difficult. METHODS: We evaluated immunocytochemical staining for a CMV early antigen in cells prepared from the cerebrospinal fluid of patients with clinical evidence for neural CMV infections and from controls. RESULTS: CMV positive cells were found in four samples of patients with clinical evidence of CMV infection. Three of these patients were suffering from myeloradicalitis, one had a severe brain stem encephalitis. No CMV positive were found in controls. CONCLUSIONS: Immunocytochemical staining of CSF cells may be helpful in the diagnosis of CMV infection of the central nervous system and of the nerve roots.

AIDS-Related Opportunistic Infections↗