Rekonstruktive Fußchirurgie bei diabetisch-neuropathischer Osteoarthropathie

ZusammenfassungFragestellung Die neurogene Osteoarthropathie zieht oft eine invalidisierende und konservativ nicht mehr beherrschbare Deformität des Fußes nach sich. Eine Operationsindikation ergibt sich bei rezidivierenden Ulzera, tiefen Infektionen und bei dekompensierter Statik mit progredienter Deformierung. Die Methode der externen Fixation steht dabei auf dem Prüfstand.Methodik 65 zwischen 1997 und 2003 operierte Füße mit Neuroarthropathie bei 21 Frauen und 43 Männern konnten retrospektiv untersucht werden. Bei 56 Patienten lag eine diabetische Polyneuropathie vor. Als Operationsmethode kam in 59 Fällen ein Fixateur externe zur Anwendung, 9-mal erfolgte die Fixation mit Steinmann-Nägeln. Die Nachbehandlung sah die Mobilisation in einer Unterschenkelorthese bis zu 1 Jahr Dauer vor.Ergebnisse Bei den Diabetikern betrug die durchschnittliche Erkrankungsdauer für Typ 1 24,8 und für Typ 2 13,7 Jahre. Alle Füße entsprachen dem Levin-Stadium 3 oder 4, hinsichtlich der Sanders-Klassifikation waren die Typen II bis V vertreten. In 5 Fällen sahen wir reine Luxationen, weitere 9-mal eine Kombination aus ligamentären und ossären Veränderungen. Operative Revisionen infolge von Komplikationen waren in 7 Fällen erforderlich, zum Teil mehrfach. Folgeoperationen im weiteren Krankheitsverlauf waren 13-mal erforderlich, in 6 Fällen wegen eines Korrekturverlustes. Durchschnittlich 752 Tage nach der Fußkorrektur führten 3 Nachamputationen bei 2 Patienten zu einer prothetischen Versorgung. Pin-Infekte und Wundheilungsstörungen waren häufig, aber konservativ beherrschbar und unabhängig von vorbestehenden Ulzerationen oder Infekten. Innerhalb des ersten Jahres nach der Operation kam es bei 13,9% der Füße zu einem Ulkus. Alle Patienten wurden mit Hilfsmitteln mobilisiert, 47 mit einer Unterschenkelorthese und 15 mit Maßschuhen.Schlussfolgerungen Die externe Fixation zur Stellungskorrektur bei Neuroarthropathie stellt ein geeignetes und variables Verfahren mit geringer Komplikationsrate dar. Es können floride wie auch zum Stillstand gekommene Osteoarthropathien behandelt werden. In der Regel wird eine fibröse Ankylose hergestellt, die eine schmerzfreie Mobilisation unter Vollbelastung erlaubt. In geeigneten Fällen—bei gutem Alignement des Fußes und guter Mitarbeit des Patienten—ist nach etwa 12-monatiger Tragedauer der Unterschenkelorthese eine Versorgung mit Maßschuhen möglich.     

Aspochalamins A-D and aspochalasin Z produced by the endosymbiotic Fungus aspergillus niveus LU 9575. I. Taxonomy, fermentation, isolation and biological activities

Aspochalamins A-D, a family of new cytochalasan antibiotics have been isolated from Aspergillus niveus, an endosymbiotic fungus isolated from the gut of a woodlouse belonging to the family Trichoniscidae. Besides aspochalamins, aspochalasin Z, a new member of the aspochalasin family, as well as the known mycotoxins aspochalasin D and citreoviridins A/C and B were isolated from the mycelium. Aspochalamins showed cytostatic effects towards various tumor cell lines and a weak antibacterial activity against Gram-positive bacteria.     

Use of soluble fibrin antigen instead of D-dimer as fibrin-related marker may enhance the prognostic power of the ISTH overt DIC score

The overt DIC score of the DIC subcommittee of the ISTH includes a fibrin-related marker (FRM) as indicator of intravascular fibrin formation. The type of marker to be used has not been specified, but D-dimer antigen, or fibrin degradation products are used by most investigators. Soluble fibrin complexes have been suggested as more specific indicators of acute intravascular fibrin formation. The aim of the present study was to compare the predictive value of the overt DIC score concerning clinical outcome in a surgical intensive care cohort, using either D-dimer antigen, or soluble fibrin antigen as FRM. The cutoff values for 2 and 3 score points for the FRM were assigned on the basis of the 25% and 75% quartiles of 1870 plasma samples obtained from 359 ICU patients during a period of 6 months. For 331 patients with complete diagnostic workup and day 1 blood samples, the Iatro SF as FRM component of the overt DIC score displayed the highest prognostic power concerning clinical outcome. The 28-day mortality of patients with overt DIC at day 1, using Iatro SF as FRM assay was 50.0%, whereas 28-day mortality of patients without overt DIC was 14.0% (p <0.0001). Using MDA D-dimer, and TINAquant D-dimer, 28-day mortality was between 35.5% and 39.3% in patients with overt DIC, and 15.5% to 15.6% in patients without overt DIC. Selection of the FRM as component of the DIC score has a small, but relevant impact on the prognostic performance of the overt DIC score. The present data on the distribution of values may provide a basis for the selection of appropriate cutoff points for assigning 2, and 3 points in the score.     

An in vitro study on the mechanisms of coagulation activation in acute myelogenous leukemia (AML): role of tissue factor regulation by cytotoxic drugs and GM-CSF

AML patients may suffer from a disseminated coagulopathy, which can aggravate a pre-existing bleeding tendency due to thrombocytopenia and platelet dysfunction. The cellular and molecular mechanisms underlying this coagulopathy, however, are not completely understood. Indeed, the broad and increasing therapeutic use of cytotoxic drugs and growth factors is likely to contribute to the complexity of hemostatic abnormalities encountered in this hematologic malignancy. The nature of coagulation activation in AML was therefore investigated in vitro using the human leukemic cell line, HL60. Tissue factor (TF) was almost entirely located on the cell surface and bound factor VIIa, but only 15-25% of this TF was primarily functionally active. Treatment with increasing concentrations of daunorubicin or cytosine-beta-D-arabinofuranoside, two cytotoxic drugs commonly used in AML therapy, induced apoptosis and secondary necrosis of HL60 cells and resulted in marked decryption of TF PCA independent of de novo protein synthesis. This PCA-modulating effect was concomitant with and functionally dependent on the exposure of phosphatidylserine on the outer membrane leaflet. Similar observations were made in analogous ex vivo studies on patient-derived myeloblasts. Incubation of HL60 cells with GM-CSF, a cytokine expressed in the bone marrow microenvironment and used as an adjunct to AML treatment, evoked a cellular response, which included both enhanced TF production and release of VEGF-A and uPA into the culture medium. We conclude that both decryption of pre-formed TF PCA by chemotherapeutic drugs and de novo induction of TF by cytokines such as GM-CSF can regulate the pro-coagulant phenotype of HL60 cells in vitro.     

Sperm retrieval procedures and intracytoplasmatic spermatozoa injection with epididymal and testicular sperms

INTRODUCTION: Male infertility caused by azoospermia due to non-reconstructable obstruction or non-obstructive azoospermia can be treated by microsurgical epididymal aspiration (MESA) or testicular sperm extraction (TESE) followed by an intracytoplasmatic spermatozoa injection (ICSI). MATERIAL AND METHODS: From 9/93 to 6/01, we carried out 1,025 ICSI procedures with aspirated epididymal or testicular sperms in 684 cases. 163 ICSI cycles were performed with epididymal sperms and 862 ICSI cycles with testicular sperms or spermatids. The TESE was carried out by open biopsy, frequently in a multilocular technique. The aspirated spermatozoas were used after cryopreservation (frozen) or immediately after aspiration (fresh). RESULTS: 538 patients had obstructive azoospermia or ejaculation failure. In 487 cases the underlying cause of azoospermia was an impaired spermatogenesis, following maldescensus testis, chemotherapy, radiotherapy, or caused by Sertoli-cell-only syndrome, a genetic disorder or an unknown etiology. The transfer rates, pregnancy rates and birth rates per ICSI cycle showed no statistically significant differences between testicular and epididymal sperms in the cases of seminal obstruction (28% average birth rates in both cases). However, highly significant was the difference in birth rates with regard to the underlying cause of infertility. In contrast, in treating non-obstructive azoospermia we observed a birth rate of 19% per cycle. In all patient groups the birth rate with fresh spermatozoas did not differ from those with cryopreserved spermatozoa. 40% of patients after multilocular TESE showed clinical signs of testicular lesion. CONCLUSION: The underlying cause of azoospermia is the most important factor for the outcome of ICSI using epididymal and testicular sperms. In cases of non-obstructive azoospermia, the pregnancy rate is low compared with the results in cases of obstructive azoospermia. There is no difference between fresh and cryopreserved sperms. TESE with ICSI is the most efficient treatment of azoospermia caused by hypergonadotropic hypogonadism. The morbidity of the TESE procedure is highly relevant and must be considered if this technique is indicated.     

Male factors determining the outcome of intracytoplasmic sperm injection with epididymal and testicular spermatozoa

During a period of 8 years, 1,079 intracytoplasmic sperm injection (ICSI) procedures with aspirated epididymal or testicular spermatozoa were performed. Epididymal spermatozoa were used in 172 cycles and testicular spermatozoa or spermatids in 907 cycles. Multiple biopsies were obtained from at least two different locations in the testes. Retrieved spermatozoa were used after cryopreservation (frozen) or immediately after aspiration (fresh). Three hundred patients had obstructive azoospermia (OA) or ejaculation failure. In 414 cases, azoospermia was caused by impaired spermatogenesis resulting from maldescended testes, chemotherapy/radiotherapy, or by Sertoli-cell-only syndrome, genetic disorders or unknown aetiology. Transfer rates, pregnancy rates and birth rates per ICSI cycle showed no statistically significant differences between testicular and epididymal spermatozoa in men with OA (28% average birth rates in both cases). However, birth rates differed significantly with regard to the status of spermatogenesis. Treatment of men with nonobstructive azoospermia (NOA) resulted in a birth rate of 19% per cycle. In all patient groups, there was no difference in the birth rates achieved with fresh and cryopreserved spermatozoa. While testicular volume, follicle-stimulating hormone level and age of the male patient are no statistically significant prognostic factors, the underlying cause of azoospermia is the most important factor determining the outcome of ICSI with epididymal and testicular spermatozoa. The pregnancy rate is lower in NOA patients than in those with OA.     

Brivudine as an alternative systemic therapy to aciclovir and ganciclovir in acute retinal necrosis syndrome due to varicella-zoster virus

BACKGROUND: Two cases of acute retinal necrosis (ARN-) syndrome caused by an infection with varicella zoster virus (VZV) are demonstrated. VZV-DNA was detected in vitreous biopsies by polymerase-chain-reaction (PCR). The course of retinal necrosis was decisively improved by changing antiviral therapy from aciclovir and/or ganciclovir to brivudine. MATERIAL AND METHODS: Patient 1: 51 years, male, initial visual acuity 20/40; patient 2: 17 years, female, initial visual acuity 20/30. Both patients were immunocompetent and presented with an unilateral acute retinal necrosis syndrome with peripheral chorioretinitis, retinal vasculitis, vitreous inflammation and optic disc swelling, which resulted in progressive visual loss in a few days. RESULTS: In both patients VZV-DNA was detected in vitreous biopsies with PCR. A regression of intraocular inflammation and necrotic retinal foci was only observed after changing the initial systemic therapy from aciclovir (Zovirax) intravenously 1500 mg/day) and/or ganciclovir (Cymeven) intravenously 250 mg/day) to brivudine (Zostex) per os 500 mg/day). Vitreoretinal surgery was necessary in both patients because of rhegmatogenous retinal detachment. Visual acuity stabilised in patient 1 to 20/200 and in patient 2 to 20/25 during a follow-up of 16 or 32 months, respectively. CONCLUSION: Brivudine represents an alternative therapy, if standard treatment with aciclovir and/or ganciclovir failed in cases of ARN-syndrome due to presumed drug-resistant varicella zoster virus-subtypes. Complete remission and preservation of a satisfactory function can be achieved.     

Transfer of humoral and cellular hepatitis B immunity by allogeneic hematopoietic cell transplantation

BACKGROUND: Previous data indicate that a transfer of specific humoral and cellular immunity by way of allogeneic hematopoietic cell transplantation (HCT) should, in principle, be possible. METHODS: In the HCT setting with a follow-up of up to 55 months, we studied the transfer of hepatitis B virus (HBV) specific immunity from electively immunized donors into HLA compatible recipients suffering from chronic myeloid leukemia (CML). After excluding preexisting HBV specific immunity in donor-recipient pairs, 27 prospective donors were vaccinated against HBV. In addition, on an average of 22 months postHCT, 8 of the 19 recipients were immunized once for HBV. RESULTS: Donor vaccination resulted in detectable hepatitis B surface (HBs) antibodies in 85% of donors and specific cellular in vitro responses in 77%. Two weeks postHCT, 86 and 67% of the recipients displayed positive humoral and cellular HBV reactions, respectively, which then decreased. Afterwards, HBV immunity reappeared in 83% of the recipients without revaccination. Following a single vaccination in recipients, seven of eight displayed a typical memory response. An HBV specific response was already detectable 1 week after vaccination, approximately 1,300-fold (humoral) and 60-fold (cellular) higher than observed in the corresponding donors after a single immunization. CONCLUSIONS: The "spontaneous" recurrence of HBV immunity and the memory response in recipients give evidence for an elective immune transfer (e.g., for viral antigens) by way of allogeneic HCT.     

HIV risk among a sample of Mexican and Puerto Rican men and women

HIV/AIDS has disproportionately affected the Hispanic communities in the United States. Consequently, Hispanic communities at risk for HIV infection should be considered a high priority for prevention and education efforts. Although such efforts ideally consider variations across subpopulations, including differences in high-risk behaviors and routes of transmission by national origin, gender, and acculturation levels, relatively few studies of risk behavior have considered such differences. This paper reports on an interview-based study of HIV knowledge, risk behavior, and protective behaviors among a sample of 143 men and women of Mexican ethnicity in San Diego County, California and 189 men and women of Puerto Rican ethnicity in Cuyahoga County, Ohio. The authors' findings indicate that individuals who have been in the United States for longer periods of time and who are younger in age are at increased risk of HIV infection. Increased perceived risk may also be predictive of increased actual risk.     

Reported exposures, stressors, and life events among Gulf War Registry veterans

We investigated the association of 15 exposures, 10 stressors, and 18 life events with illness symptoms reported by 978 veterans who believe they suffer from Gulf War-related illnesses. A mail survey was completed by veterans (60% response rate) from the Gulf War Health Registry. Variables most associated with high symptom group membership were reported chemical/biologic warfare (CBW), concerns with infection and faulty equipment, feelings of mistrust in the military, and disability leading to work stoppage within 2 years after the war. These data suggest that belief in CBW exposure, and the experience of war stress and serious negative life events after the war, are important concomitants of Gulf War illness. Models seeking to explain Gulf War symptoms need to incorporate a range of exposure and psychosocial factors to fully account for important influences.