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Biomedical subjects

H Hofmann

Publications and source records attributed to H Hofmann.

At least 55 records · Page 3Linked to original sources

[Intra-chamber lidocaine in addition to tetracaine eyedrop anesthesia in clear cornea phacoemulsification].

BACKGROUND: We have been successfully using topical tetracaine 1% anesthesia in clear corneal phacoemulsification since 1992. Adding intracameral lidocaine to topical anesthesia in cataract surgery has been reported since 1996. PATIENTS AND METHODS: We examined the effectiveness of intracameral lidocaine 1%, which we dyed with methylene blue 2% in 600 cases. During surgery we merely inject 0.3 ccl lidocaine 1% twice over the iris under a shield of a viscoelastic substance. After only a few seconds time of action we remove it again from the anterior chamber. RESULTS: With intracameral lidocaine 1% postoperative pain was totally eliminated for one to two hours, and usually no pain was felt thereafter. Non of our cases showed any negative signs of postoperative reaction of the eye. With the use of intracameral lidocaine we were able to omit pre- and postoperative systemic pain medication completely. This has proven to be very advantageous in elderly outpatients. Staining the lidocaine with methylene blue 2% helps prevent mixups and emphasizes its significance. Yet, an intracameral blue flow was not visible enough to determine the spread of lidocaine. CONCLUSIONS: Intracameral lidocaine represents an ideal addition to topical tetracaine anesthesia in clear corneal phacoemulsification.

Aged↗

Diagnostic value of PCR for detection of Borrelia burgdorferi in skin biopsy and urine samples from patients with skin borreliosis.

Skin biopsies of 36 patients with erythema migrans and acrodermatitis chronica atrophicans (ACA) before therapy and those of 8 patients after therapy were examined for Borrelia burgdorferi DNA by PCR. Skin biopsies of 27 patients with dermatological diseases other than Lyme borreliosis and those of 10 healthy persons were examined as controls. Two different primer sets targeting 23S rRNA (PCR I) and 66-kDa protein (PCR II) genes were used. PCR was performed with freshly frozen tissue (FFT) and paraffin-embedded tissue (PET). For FFT specimens of erythema migrans, 73% were positive by PCR I, 79% were positive by PCR II, and 88% were positive by combining PCR I and II. For PET specimens, PCR was less sensitive (PCR I, 44%; PCR II, 52%). For FFT specimens of ACA, PCR I was positive for two of five patients and PCR II was positive for four of five patients. B. burgdorferi was cultured from 79% of the erythema migrans specimens but not from any of the ACA lesions. Elevated B. burgdorferi antibodies were detected in sera of 74% of erythema migrans patients and 100% of ACA patients. All urine samples were negative by PCR II, whereas PCR I was positive for 27%. However, hybridization of these amplicons was negative. Sequencing of three amplicons identified nonborrelial DNA. In conclusion, urine PCR is not suitable for the diagnosis of skin borreliosis. A combination of two different primer sets achieves high sensitivity with skin biopsies. In early erythema migrans infection, culture and PCR are more sensitive than serology.

Adult↗

Intermittent sequential compression of the lower limbs prevents venous stasis in laparoscopic and conventional colorectal surgery.

PURPOSE: This study was designed to evaluate the influence of intraoperative intermittent sequential compression (ISC) on venous blood return from the lower limbs during laparoscopic and conventional colorectal colectomy. METHODS: Fifty patients undergoing laparoscopic (n = 25) or conventional (n = 25) colorectal surgery were included in a prospective study. Peak venous flow (PFV) and the cross-sectional area (CSA) of the femoral vein were assessed by Doppler ultrasound examination intraoperatively. RESULTS: Age, gender, and body mass index were comparable between both groups. Baseline PFV was 21 +/- 6.6 cm/s in the conventional and 18.4 +/- 6.4 cm/s in the laparoscopic group (P = 0.2). ISC increased PFV to 156 +/- 29 percent of the baseline value in the conventional group and to 161 +/- 29 percent in the laparoscopic group. PFV decreased after abdominal insufflation to 127 +/- 19 percent of the baseline value in the laparoscopic group and after laparotomy to 134 +/- 27 percent in the conventional group (P = 0.3). PFV decreased slightly in both groups during surgery but remained well above the baseline value. Baseline CSA was 1.02 +/- 0.17 cm2 in the conventional group and 1 +/- 0.23 cm2 in the laparoscopic group. ISC decreased CSA to 0.91 +/- 0.18 cm2 (conventional) and 0.85 +/- 0.18 cm2 (laparoscopic) after initiation of ISC. CSA was 0.92 +/- 0.18 cm2 after abdominal insufflation in the laparoscopic group, and it was 0.93 +/- 0.18 cm2 after laparotomy in the conventional group (P = 0.4). During surgery, there were no differences in absolute CSA or CSA changes compared with the baseline value in both groups. Postoperative circumference of the calf and thigh were not different between both groups. Postoperative thromboembolic complications did not occur. CONCLUSION: ISC effectively increases venous blood flow from the lower limbs during conventional and laparoscopic colorectal resections and may decrease the risk of postoperative deep vein thrombosis. Therefore, ISC is strongly recommended in every prolonged laparoscopic procedure.

Aged↗

[Atypical zosteriform segmental embolia cutis medicamentosa].

A 35-year-old male suffered from an extremely painful embolia cutis medicamentosa. The atypical segmental localization first led to the diagnosis of herpes zoster and an antiviral therapy. Regarding the unusual course of the complication following an intramuscular injection in this case, the question for the real pathomechanisms still remains.

Adult↗

[Fluconazole-resistant Candida species from HIV infected patients with recurrent Candida stomatitis: cross resistance to itraconazole and ketoconazole].

In vitro susceptibility to fluconazole of Candida species isolated from 83 HIV-infected patients treated with fluconazole because of recurrent Candida stomatitis was monitored over a period of two years. A microdilution assay with high-resolution antifungal assay (HR) medium and RPMI 1640-medium were compared. In vitro less susceptible and fluconazole resistant C. species were observed in 23 patient at the end of the study. The Candida isolates recovered from oral rinsing fluids at the beginning and the end of study were tested for crossresistance to itraconazole and ketoconazole. Susceptibility to ketoconazole and to itraconazole was reduced using RPMI 1640-medium. Susceptibility of the isolates to fluconazole was not influenced by the assay medium. In 21 patients in vitro fluconazole resistant or less susceptible C. albicans were observed. 9 of 21 isolates showed crossresistance to itroconazole and ketoconazole, in 10 isolates only crossresistance to itraconazole was observed. During fluconazole treatment double infections due to combination of C. albicans and C. glabrata or C. krusei increased from 20% to 78% C. krusei was resistant to the three azoles. C. glabrata was less susceptible (4-8 mg/l) or resistant (> 8 mg/l) to fluconazole and resistant to itraconazole and ketoconazole High dosed intravenous fluconazole treatment with 400 to 600 mg daily failed in 11 patients with fluconazole resistant C. albicans and in 3 (3/10) patients with les susceptible C. albicans isolates.

AIDS-Related Opportunistic Infections↗

The superantigen-homologous viral immediate-early gene ie14/vsag in herpesvirus saimiri-transformed human T cells.

Herpesvirus saimiri C488 transforms human T lymphocytes to stable growth in culture. The growth-transformed human T cells harbor the viral genome in a nonintegrated episomal form without production of virus particles. In these cells, virus gene expression was previously found to be confined to the transforming genes stpC and tip. In order to analyze virus gene expression in more detail, we applied a subtractive hybridization technique and compared stimulated virus-transformed cells with uninfected parental T cells of the same donor. A number of known T-cell activation genes were isolated. Viral stpC/tip cDNAs were enriched after subtraction. In addition, the viral immediate-early, superantigen-homologous gene ie14/vsag was represented by numerous cDNA clones that comprised the entire spliced transcript. Whereas a weak basal expression of ie14/vsag was detected by reverse transcription-PCR only, the phorbol ester-induced transcripts were readily shown by Northern blotting. ie14/vsag, which before had been classified as a major immediate-early gene of herpesvirus saimiri, is localized within a highly conserved region with extensive homologies to the cellular genome. Mutant viruses without the ie14/vsag gene are replication competent and fully capable of transforming human and marmoset T cells. Since ie14/vsag is transiently expressed after stimulation, it may increase T-cell proliferation in an activation-dependent and superantigen-like but apparently Vbeta-independent way.

Animals↗

Systemic antifungal treatment of children with terbinafine.

BACKGROUND: At present, griseofulvin is the only licensed drug for oral treatment of dermatophyte infections in children. OBJECTIVE: Children were treated with the fungicidal allylamine terbinafine. Efficacy and tolerability were evaluated. METHODS: Fifteen children (14 months to 11 years old, below 40 kg body weight) with culture-confirmed tinea capitis or tinea corporis were systemically treated with terbinafine. Five children suffered from tinea capitis, 6 from tinea corporis and 4 from a combined infection of the scalp and body. As causing agents Trichophyton violaceum (5), Microsporum canis (8) and Trichophyton mentagrophytes (2) were isolated. RESULTS: Mycological and clinical cure was achieved in all children after oral treatment with terbinafine for 4-8 weeks. Cure after discontinuation of therapy could be observed in 13 children. Two children with tinea capitis caused by M. canis relapsed within 1-2 months after the end of therapy. The overall tolerability of terbinafine in children was good; 1 child suffered from acute urticaria during treatment, which might be related to the medication. CONCLUSIONS: The applied therapy regimes were effective in most cases. In scalp infections by M. canis, the children should be treated for more than 4 weeks or with a higher dose. To find the optimal dosage and treatment periods for children, further prospective studies are necessary.

Administration, Oral↗

No .NO from NO synthase.

The nitric-oxide synthase (NOS; EC 1.14.13.39) reaction is formulated as a partially tetrahydrobiopterin (H4Bip)-dependent 5-electron oxidation of a terminal guanidino nitrogen of L-arginine (Arg) associated with stoichiometric consumption of dioxygen (O2) and 1.5 mol of NADPH to form L-citrulline (Cit) and nitric oxide (.NO). Analysis of NOS activity has relied largely on indirect methods such as quantification of nitrite/nitrate or the coproduct Cit; we therefore sought to directly quantify .NO formation from purified NOS. However, by two independent methods, NOS did not yield detectable .NO unless superoxide dismutase (SOD; EC 1.15.1.1) was present. In the presence of H4Bip, internal .NO standards were only partially recovered and the dismutation of superoxide (O2-.), which otherwise scavenges. .NO to yield ONOO-, was a plausible mechanism of action of SOD. Under these conditions, a reaction between NADPH and ONOO- resulted in considerable overestimation of enzymatic NADPH consumption. SOD lowered the NADPH:Cit stoichiometry to 0.8-1.1, suggesting either that additional reducing equivalents besides NADPH are required to explain Arg oxidation to .NO or that .NO was not primarily formed. The latter was supported by an additional set of experiments in the absence of H4Bip. Here, recovery of internal .NO standards was unaffected. Thus, a second activity of SOD, the conversion of nitroxyl (NO-) to .NO, was a more likely mechanism of action of SOD. Detection of NOS-derived nitrous oxide (N2O) and hydroxylamine (NH2OH), which cannot arise from .NO decomposition, was consistent with formation of an .NO precursor molecule such as NO-. When, in the presence of SOD, glutathione was added, S-nitrosoglutathione was detected. Our results indicate that .NO is not the primary reaction product of NOS-catalyzed Arg turnover and an alternative reaction mechanism and stoichiometry have to be taken into account.

Electron Transport↗

Microbial biotransformation products of cyclosporin A.

In order to mimic the human metabolic pathway of cyclosporin A (CyA) a total of 28 bacterial and 72 fungal strains was screened for their ability to transform CyA. Among 3 bacteria and 11 fungi, which produced the main human metabolite OL-17 [eta HyMeBmt1]CyA, Actinoplanes sp. (ATCC 53771) achieved the best transformation rate (5.4%). Furthermore, the two N-demethylated minor products [Leu4]CyA (3.2%) and [Leu9]CyA (4.7%) were isolated, both known as minor natural metabolites and the first one also as a human biotransformation product. Microbial conversion of CyA using the actinomycete Sebekia benihana (NRRL 11111) yielded [gamma HyMeLeu4]CyA (35%), [gamma HyLeu4]CyA (4.5%) and [gamma HyMeLeu4, gamma HyMeLeu6]CyA (8.6%). The structures of these derivatives correspond with those of the human metabolic pathway. The related compounds [Nva2]CyA (CyG) and [D-MeSer3]CyA were similarly converted to the corresponding 4-gamma-hydroxylated analogues. None of the biotransformation products showed a better immunosuppressive effect than CyA, although in various cases the cyclophilin binding affinity was comparable to that of CyA.

Bacteria↗

Thiol dependence of nitric oxide synthase.

Nitric oxide synthases (NOS) require NADPH and tetrahydrobiopterin (H4biopterin) to convert L-arginine to L-citrulline. The additional requirement and effects of thiols during purification and activity assays of NOS are unclear; for example, glutathione (GSH) has been reported to stimulate or, in the presence of catalase, to inhibit enzyme activity. We therefore studied the effects of different thiols, thiol reagents, antioxidants, and H4biopterin-regenerating systems on purified porcine cerebellum NOS. GSH in the presence of catalase did not inhibit NOS. In contrast, GSH and, to a lesser degree, several other thiols consistently stimulated total L-arginine turnover up to 4-fold. In the presence of GSH, Vmax of NOS was increased, the usually observed loss of activity during the 15 min assay was less dramatic, and the apparent S0.5 value for H4biopterin decreased. Stabilization of NOS activity by GSH was augmented by protein disulfide isomerase (PDI), indicating that, at least in part, GSH acted by reductive protection of NOS protein thiols. Consistent with this, four different protein thiol reagents abolished NOS activity. In other experiments, specific allosteric binding was excluded as a potential mechanism of GSH regulation of NOS. In addition, GSH may affect NOS kinetics by recycling or preventing the autoxidation of H4biopterin. In support of this, the non-thiol reductant ascorbate and dihydropteridine reductase mimicked the effects of GSH on NOS kinetics, but not on NOS stability. Thus, NOS activity depends on both H4biopterin and the reduced state of essential protein thiols.

Animals↗

Slice cultures of the imprinting-relevant forebrain area MNH of the domestic chick: quantitative characterization of neuronal morphology.

The persistence of morphological features of neurons in slice cultures of the imprinting-relevant forebrain area MNH (mediorostral neostriatum and hyperstriatum ventrale) of the domestic chick was analysed at 7, 14, 21 and 28 days in vitro. After having been explanted and kept in culture the neurons in vitro have larger soma areas, longer and more extensively branched dendritic trees and lower spine frequencies compared to the neurons in vivo. During the analyzed culturing period, the parameters soma area, total and mean dendritic length, number of dendrites, number of dendritic nodes per dendrite and per neuron as well as the spine densities in different dendritic segments showed no significant differences between early and late periods. Highly correlated in every age group were the total dendritic length and the number of dendritic nodes per neuron, indicating regular ramification during dendritic growth. Since these morphological parameters remain stable during the first 4 weeks in vitro, this culture system may provide a suitable model to investigate experimentally induced morphological changes.

Animals↗

Treatment of toenail onychomycosis. A randomized, double-blind study with terbinafine and griseofulvin. LAGOS II Study Group.

BACKGROUND AND DESIGN: The fungicidal mode of action of terbinafine should make it feasible to reduce treatment duration in onychomycosis. For this reason, a randomized, double-blind study in 195 patients with severe dermatophyte infections of the toenails was performed comparing a 24-week treatment with terbinafine (250 mg/d) with a 48-week treatment with micronized griseofulvin (1000 mg/d). RESULTS: After 48 weeks, effective treatment was achieved in 67% of the patients treated with terbinafine and in 56% of those treated with griseofulvin (two-tailed P = .120). At a follow-up visit 24 weeks later, cure rates had decreased to 60% in the terbinafine group and to 39% in the griseofulvin group (two-tailed P = .006). At the same time, the mycological cure rate was 81% with terbinafine and 62% with griseofulvin (two-tailed P = .02). CONCLUSIONS: This study has demonstrated the longterm therapeutic superiority of terbinafine to high-dose griseofulvin in the treatment of toenail mycosis. Furthermore, with the new antifungal terbinafine, treatment is no longer necessary until all affected nail material has grown out.

Adult↗