PubMed Health⌕ Search

Biomedical subjects

H Gümbel

Publications and source records attributed to H Gümbel.

17 recordsLinked to original sources

Ecotoxicity quantitative structure-activity relationships for alcohol ethoxylate mixtures based on substance-specific toxicity predictions.

Traditionally, ecotoxicity quantitative structure-activity relationships (QSARs) for alcohol ethoxylate (AE) surfactants have been developed by assigning the measured ecotoxicity for commercial products to the average structures (alkyl chain length and ethoxylate chain length) of these materials. Acute Daphnia magna toxicity tests for binary mixtures indicate that mixtures are more toxic than the individual AE substances corresponding with their average structures (due to the nonlinear relation of toxicity with structure). Consequently, the ecotoxicity value (expressed as effects concentration) attributed to the average structures that are used to develop the existing QSARs is expected to be too low. A new QSAR technique for complex substances, which interprets the mixture toxicity with regard to the "ethoxymers" distribution (i.e., the individual AE components) rather than the average structure, was developed. This new technique was then applied to develop new AE ecotoxicity QSARs for invertebrates, fish, and mesocosms. Despite the higher complexity, the fit and accuracy of the new QSARs are at least as good as those for the existing QSARs based on the same data set. As expected from typical ethoxymer distributions of commercial AEs, the new QSAR generally predicts less toxicity than the QSARs based on average structure.

Alcohols↗

Diagnosis of invasive fungal infections in hematology and oncology--guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO).

Invasive fungal infections are a primary cause of morbidity and mortality in patients with hematological malignancies. Establishing a definite diagnosis of invasive fungal infection in febrile neutropenic patients is particularly challenging and time-consuming, but a delay of antifungal treatment leads to higher mortality. This situation has lead to the strategy of initiation "empirical" antifungal therapy prior to the detection of fungi. Meanwhile, improvements in diagnostic procedures are achieved, especially with imaging techniques and non-culture based methods which include antigen-based assays, metabolite detection and molecular detection of fungal DNA from body fluid samples using conserved or specific genome sequences. The AGIHO presents recommendations for the diagnosis of invasive fungal infections with risk-adapted screening concepts for the neutropenic and febrile episodes of patients with hemato-oncological disorders.

Hematology↗

[Toxoplasmosis retinochorioiditis, a therapy comparison between spiramycin and pyrimethamine/sulfadiazine].

BACKGROUND: The treatment of toxoplasma retinochoroiditis with spiramycin is an alternative to sulfadiazine and pyrimethamine. The treatment with sulfadiazine is associated with multiple side effects. Sulfadiazine is contraindicated during pregnancy and breastfeeding period. Spiramycin has less side effects and is recommended during pregnancy and breastfeeding period. The efficacy of spiramycin in treatment of toxoplasma retinochoroiditis is still a matter of controversy. PATIENTS AND METHODS: In a retrospective study, side effects and outcome of therapy in 44 patients with toxoplasma retinochoroiditis treated with sulfadiazine and pyrimethamine (n = 30) or spiramycin (n = 14) were compared. We assessed duration of therapy and healing, ophthalmoscopic findings and observed side effects. RESULTS: The mean healing time in the group of spiramycin was 63.83 days in comparison to 88 days for the group of patients treated with sulfadiazine/pyrimethamine. The frequency of side effects was lower in the group treated with spiramycin. CONCLUSION: In comparison to a combined application of sulfadiazine and pyrimethamine the treatment with spiramycin alone requires a shorter duration of therapy and healing period. Additionally, side effects and contraindications appear to be less frequent. In view of these findings, spiramycin therapy must be considered as a promising approach in the treatment of toxoplasma retinochoroiditis.

Adult↗

[Pars plana implantation of a ganciclovir drug carrier in patients with cytomegalovirus retinitis and AIDS. Indications, follow-up and postoperative complications].

UNLABELLED: We performed an open clinical trial to assess the safety and efficacy of a 1 microgram/h ganciclovir implant for the treatment of newly and pretreated cytomegalovirus (CMV) retinitis in patients with the acquired immunodeficiency syndrome (AIDS). PATIENTS AND METHODS: Thirty-two eyes (20 patients) received the ganciclovir intraocular device and were prospectively followed up from 30 to 365 days. We used a modified technique for fixation of the device in half of the patients. The modification improved the fixation of the implant with a two-hole technique in the strut. RESULTS: Thirty eyes showed stabilization of the retinitis over the time, but in two patients resistance against ganciclovir and other nucleoside analogue compounds developed. Postoperative complications included vitreous hemorrhage (n = 1), cataract (n = 1), and uveitis anterior (n = 1). Late retinal detachment was seen in five eyes (25%) at 30 to 60 days after implantation. Followup until 1 year after implantation did not show progression of CMV retinitis in 18 to 20 patients. All received antiviral CMV therapy to protect noninfected eyes and intestinum against CMV infection. CONCLUSIONS: The ganciclovir intraocular device seemed to be effective in most cases of CMV retinitis and offers a promising alternative for cytomegalovirus retinitis. Patients pretreated longer than 6 months with i.v. ganciclovir have to be carefully selected for implantation, because resistance against ganciclovir could be three times more likely than in i.v.-therapy naive patients.

AIDS-Related Opportunistic Infections↗

Povidone-iodine liposomes--an overview.

In recent years, liposomes have been increasingly explored as novel drug delivery systems, and several liposome-based drug products have been approved in Europe, the USA and Japan. Depending on size, composition and surface characteristics, liposomes interact specifically with biological structures. Liposomal drug products provide a topical activity at the desired locus of action and are deemed more effective and less toxic than conventional drug formulations. The combination of povidone-iodine (PVP-I) and liposomes unites the exceptional microbicidal activity of the antiseptic substance with the excellent tolerability and lack of immunogenicity of liposomes; in addition, liposomes provide a moist molecular film for the wound environment. The multilamellar vesicles act as microreservoirs hence prolonging the release of the active ingredient. Although no commercial product for repeated application on the eye is currently available, PVP-I has been used in ophthalmology not only for pre- and postoperative antisepsis, but also for the treatment of bacterial and viral conjunctivitis and for prophylaxis against ophthalmia neonatorum. For these indications, liposomal formulations with 2.5 and 5.0% PVP-I were developed. These eye drops are isotonic with tear fluid at pH 6. First in vitro tests demonstrated an excellent antimicrobial efficacy, and a placebo-controlled clinical study on volunteers showed a very good local tolerability. A study on rabbits demonstrated positive results of the PVP-I liposome eye drops compared to placebo and the broadspectrum antibiotic Polyspectran in a standardized model of Staphylococcus aureus deep eye infection. The other aim is a well-tolerated liposomal PVP-I hydrogel for improved antiseptic wound treatment with moisturizer. It has been reported that liposomes are enriched at the wound bottom for direct action against infection and support of wound healing. An animal study on the efficacy and tolerability of different formulations of a hydrogel with PVP-I liposomes in deep dermal burn wounds has indicated an outstanding quality of wound healing with smooth granulation tissue, less inflammation, less wound contraction and no hyperkeratotic reactivity, especially with the 3% PVP-I liposome formulation.

Administration, Cutaneous↗

[Regulation of glutathione level in venous plasma and aqueous humor in cataracta senilis provecta].

UNLABELLED: Glutathione is a major component of the mechanisms protecting the eye against oxidants. To analyse the functional status and the regulation of the glutathione system in the eyes of patients with advanced cataract, glutathione concentrations were quantified in venous plasma and aqueous humor. METHODS: In all, 42 patients with advanced cataract (29 women, 13 men; mean age (+/- SEM) 70 +/- 2 years; vision < or = 0.3) were evaluated. Aqueous humour and venous plasma were obtained at the beginning of cataract surgery. RESULTS: Levels of total glutathione [reduced (GSH) + oxidized glutathione (GSSG)] in plasma were 2.34 +/- 0.23 microM. There was 2.08 +/- 0.15 microM in the reduced form and 0.27 +/- 0.17 microM oxidized glutathione, which means that 94.7 +/- 2.1% of the total glutathione was GSH, the form fully functional as an antioxidant. Levels of total glutathione in the aqueous humor were 1.2 +/- 0.16 microM, i.e. 54.5 +/- 4.8% of plasma levels. Surprisingly, the percentage of GSSG in aqueous humor (0.24 +/- 0.07 microM, 31 +/- 10.5% of the total glutathione) was much higher than that in plasma (P < 0.001). The correlation between glutathione concentrations in plasma and aqueous humor was on the borderline of significance (rs = 0.32, P < 0.04). CONCLUSION: The proportion of oxidized glutathione is higher in aqueous humor than in plasma of patients with advanced senile cataracts, indicating increased oxidant stress in the eye. Further, the regulation of the glutathione system in the eye, at least in aqueous humor, is dependent on plasma glutathione levels. This correlation reflects the importance of sufficient glutathione levels in venous plasma and suggests the possibility of modulating the glutathione system in the eye via manipulation of plasma glutathione levels.

Aged↗

[Selective inhibition of replication of human cytomegalovirus by desferrioxamine in vitro and in vivo (case report)].

UNLABELLED: In AIDS patients cytomegalovirus (HCMV) retinitis is one of the most frequent opportunistic infections. Antiviral therapy aims at preserving vision as long as possible, but more and more HCMV isolates are proving to be resistant to ganciclovir (GCV) and foscarnet (PFA) in vitro. We tested whether desferrioxamine (DFO), an iron chelator with antiherpetic activity, can inhibit clinical virus isolates and laboratory strains. Clinical isolates were obtained from urine samples of AIDS patients with HCMV retinitis. The concentrations of DFO required for 50% and 90% reduction of the production of HCMV in several HCMV strains ranged from 3.1 to 4.9 microns and from 14.2 to 17.3 microns, respectively, Inhibitory effects of DFO on HCMV replication were completely prevented by co-incubation with stoichiometric amounts of FE3+. CASE REPORTS: DFO was administered by daily dose of 1 g i.v. to a patient with AIDS in whom HCMV retinitis continued to progress despite combination therapy with GCV and PFA. The addition of DFO to the combination inhibited progression of the disease. No relapse of HCMV retinitis was seen with 3 months of DFO therapy. The treatment was free of side effects.

AIDS-Related Opportunistic Infections↗

[Central serous chorioretinitis. Therapy experience over 20 years with and without laser coagulation].

Since 1969, 1,179 eyes with central serous chorioretinopathy have been examined with fluorescein fundus angiography. The classic form with fluorescein leakage (type I) decreased in incidence from 86.4% to 55.4%, while an atypical form with frequent serous pigment epithelial detachment (type II) increased from 12.6% to 33.0%, and the mixed form (type I + II) increased from 1 to 11.6%. In type I with delayed healing laser coagulation of the leakage was performed, which improved the visual acuity from 0.64 to 0.92 an average (n = 122), while in cases without laser coagulation the percentage improved only from 0.66 to 0.84 on average (n = 34) with a statistically significant difference (t = 2.64, P < 0.01). Laser coagulation was especially beneficial in the mixed form (n = 16), in which the visual acuity improved from 0.42 to 0.86 on average. The proportion of women increased from 10.7 to 17.9%. The patient age tended to be higher in women more than in men.

Adult↗

[Vitreous involvement in cytomegalovirus retinitis].

In our outpatient department we often see patients with vitreous inflammation. Recent reports emphasize that vitreous inflammation is very rare, so we looked for patients with cytomegalovirus (CMV) retinitis and vitreous inflammation. We investigated 359 HIV-positive patients for at least 1 year; all patients reached the stage of AIDS disease. We included patients without any retinal signs of CMV retinitis at the beginning or CMV recurrence during the study. A slit-lamp investigation, binocular funduscopy and b-picture ultrasound were done at regular intervals. The results show an increase in vitreous inflammation with the frequency of CMV retinitis recurrences. Patients very often develop retinal detachment. Vitreous inflammation is a critical factor when examining CMV retinitis. In the future a larger series of patients should be examined.

AIDS-Related Opportunistic Infections↗

[Ophthalmologic manifestations in early and late stages of AIDS].

In a prospective study of 101 patients with HIV infection and a medium CD4 lymphocyte cell count of 350 x 10(6)/l and a retrospective study of the records of 79 AIDS patients, we compared the first ocular symptoms in HIV-infected patients to the CD4 count. In Walter-Reed stages 2-4 (n = 101) we found sicca syndrome in 9.2%, in 52% lens opacities in the cortex and only in less than 1% HIV-related angiopathy of the retina. In Walter Reed stages 5-6 (n = 79), 26% of the AIDS patients developed CMV retinitis, 33% HIV angiopathy of the retina and only 1% retinal toxoplasmosis. The average CD4 lymphocyte cell count was never better than 100 x 10(6). Lens opacities in HIV-infected patients could be an early ophthalmological symptom of HIV infection.

AIDS-Related Opportunistic Infections↗

[Laser therapy of eyelid and conjunctival tumors, especially in AIDS patients].

We treated patients with Kaposi's sarcoma of the lid or conjunctiva, molluscum contagiosum and papilloma of the lid with dye laser photocoagulation. This therapeutic device is extremely efficient as the chosen wavelength of 577 nm is absorbed selectively by haemoglobin. Since Kaposi's sarcoma is a haemoglobin-containing tumour composed of endothelial cells and papilloma is a benign tumour composed of connective tissue and branching vessels, dye laser photocoagulation causes selective damage to abnormal vessels and surrounding connective tissue. After local anaesthesia a small incision was made at the margin of the lesion five patients each with papilloma and with molluscum contagiosum. In six patients with Kaposi's sarcoma no incision had to be done. Starting from the incision or the margin of the Kaposi's sarcoma 50-100 shots of 0.3-0.5 mm diameter and 1 s duration were applied until the lesion was completely gone. We used a dye laser with 577 nm wavelength and 1 W energy. In patients with papilloma, the tumour basis was coagulated and the tumour itself underwent histological examination. There was a marked decrease of the size of the lesion or even complete disappearance. Since Kaposi's sarcoma in AIDS patients can be relatively fast growing, resulting in cosmetically irritating manifestations and, rarely, haemorrhages, treatment may become necessary. AIDS patients with molluscum contagiosum may also benefit from treatment, as spreading of DNA virus particles may result in viral follicular conjunctivitis. Dye laser photocoagulation, however, cannot protect against relapse.

AIDS-Related Opportunistic Infections↗

In vitro anti-human immunodeficiency virus activity of 2',3'-dideoxynucleosides and their effect on clonal growth of hemopoietic cells from human bone marrow.

Seven 2',3'-dideoxynucleosides synthesized by substitution of nucleosides using nucleoside deoxyribosyltransferase from Lactobacillus leichmanii were tested for their anti-human immunodeficiency virus (HIV) activity. Two of them, including 2,6-diaminopurine-2',3'-dideoxyriboside (DAPDDR) and 6-chlorpurine-2',3'-dideoxyriboside (CPDDR) demonstrated high antiviral activity against several strains of HIV-1 and one strain of HIV-2. The selectivity index of the drugs (SI; ratio of the drug concentration required for 50% of cell killing to drug concentration required to inhibit 50% of virus-induced cell killing) was established by application of tetrazolium (MTT) colorimetric assay. SI ranged for different HIV strains from 501 to 850 and from 60 to 118 for DAPDDR and CPDDR, respectively. Both DAPDDR and CPDDR retained their antiviral activity against HIV-1 strain D148/88 which was resistant to Zidovudine (3'-azido-3'-deoxythymidine, AZT). Assays for clonal growth of human bone marrow cells in semisolid fibrin clot culture medium demonstrated that DAPDDR possesses significantly lower inhibitory activity for erythroid (BFU-E), multipotent (GEMM-CFC) and granulocyte-monocyte (GM-CFC) bone marrow progenitor cells than CPDDR or AZT. These results suggest that DAPDDR is a nucleoside analog which should be further tested as an anti-HIV compound especially in combination with other anti-retroviral drugs.

Antiviral Agents↗

[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↗

[The conjunctival flora of HIV-positive patients in an advanced stage].

We evaluated the incidence of bacterial cultures taken from 23 outpatient and nosocomial AIDS patients. It was found that 36.6% of the 11 outpatients had non-pathogenic bacterial flora (Staphylococcus epidermis). Staphylococcus aureus as a pathogenic bacterium was found in 25% of the positive cultures in a group of 12 nosocomial patients. Candida albicans, a fungus, was also found in 25%, and Pseudomonas aeruginosa, the only gram-negative bacteria, was identified in 8.3%. Staphylococcus epidermidis was found in 18.8%. It was concluded that preoperative cultures of the conjunctival sac of hospitalized AIDS patients are essential before intraocular procedures are carried out. There must be no apparent infection of the conjunctiva.

Adult↗