[Different effects of various embedding techniques on confocal laser scanning microscopy image and mechanical properties of cortical bone].
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Biomedical subjects
Publications and source records attributed to J Beyer.
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Fungal infections are of increasing importance in severely neutropenic and immunosuppressed patients because of their high incidence and their high mortality once systemic dissemination has occurred. Various prophylactic strategies have been developed that include environmental measures as well as topical and systemic antimycotic prophylaxis. In this review the causative pathogens and patients at risk for developing fungal infections will be identified. Specific strategies will be discussed for each patient population and suggestions made for areas of future research.
BACKGROUND: The optimal treatment of patients with recurrent or refractory germ cell tumors is still a debated topic. High dose chemotherapy (HDCT) with autologous stem cell rescue (ASCR) might be promising for intensification of first or subsequent salvage treatment. However, the long-term results of this approach remain largely unknown. METHODS: Between August 1989 and September 1992, 74 patients with recurrent and/or refractory germ cell tumors were treated in a Phase I/II trial with HDCT consisting of carboplatin (1500-2000 mg/m2), etoposide (1200-2400 mg/m2), and ifosfamide (0-10 g/m2). In September 1995 all patients were reevaluated to determine overall response, late toxicities, and survival. RESULTS: Two patients died from treatment-related toxicity shortly after HDCT, and 47 had recurrence or progression of disease after a median of 3 months (range, 1-44 months). Of these latter patients, three were living continuously disease free at the conclusion of this study after a second HDCT regimen, salvage surgery, or chronic oral etoposide treatment. The results were an overall survival of 38% (95% confidence interval, 27-50%) and a failure free survival of 31% (95% confidence interval, 21-43%) at 5 years. There were no long-term survivors among patients whose disease progressed while they were receiving conventional doses of cisplatin before HDCT. Late toxicities consisted mainly or renal impairment (in 21% of patients), paresthesias (in 29%), and ototoxicity (in 18%). CONCLUSIONS: HDCT can be curative for patients with germ cell tumors who do not become disease free after conventional dose chemotherapy but respond to this treatment.
In 1988 the German testicular working group was set up by leading experts in the fields of urology, medical and radio-oncology. Since then, the working group has initiated several clinical studies and conferences with the aim of defining current standards in the treatment of testicular germ cell tumours. After a series of preliminary joint meetings with representatives from the AUO, AIO and ARO of the "Deutsche Krebsgesellschaft", a conference was held in May 1996 to agree on a consensus in diagnosis and treatment of testicular germ cell tumours. The standards which have been agreed on at the conference refer to the current international literature and provide recommendations for the majority of clinical situations. Treatment strategies differing from these standards should not be chosen except for well argued individual settings or patients treated in clinical trials. No consensus could be reached for nonseminomatous stage I, IIA and IIB tumours. As a consequence, the differing treatment strategies for these stages are summarized in this paper. A subsequent conference in later years is needed to possibly find an agreement for these tumour stages and to update the current standards according to new clinical experience and knowledge.
High-dose chemotherapy (HDCT) is a promising treatment for patients with germ cell tumours and a poor prognosis. The selection of patients who may profit from this intervention is challenging for the urologist, as the indication has to be carefully established. Exclusion criteria primarily concern impaired organ functions. Prior to HDCT haematopoietic stem cells are obtained after the administration of conventional-dose chemotherapy plus G- or GM-CSF stimulation. HDCT consists of a combination of carboplatin, etoposide and ifosfamide or cyclophosphamide. After HDCT, haematologic monitoring and maximal supportive care are essential. It is therefore recommended that HDCT only be administered at specialized centres.
Second generation enzyme immunoassays (EIA-2) for antibodies to hepatitis C virus (anti-HCV) have a higher specificity and sensitivity than first generation enzyme immunoassays (EIA-1). We studied how many anti-HCV-positive blood donors were missed by the EIA-1, how many were false positive, how false-positive donors should be dealt with and how the results of the EIA-2 correlate to demographic data and serum alanine aminotransferase (ALT) level. A total of 208, 544 northern German blood donors, not preselected for anti-HCV negativity, were tested for anti-HCV with EIA-2 and, if repeatability reactive (rr), were retested with a licensed supplementary test (RIBA-2). 0.43% of the donors were EIA-2 rr, but only 0.12% of women and 0.09% of men were RIBA-2 positive. RIBA-2 positivity rates were very low in donors 18 to 27 years old (0.03% and 0.05%) and rose with age in women but not in men. Infected women were significantly more often Rhesus-negative than men. The rate of unspecifically positive EIA-2 results (entirely negative in RIBA-2) increased with age in both sexes and did not correlate with ALT. The ALT distribution was age-dependent with a different pattern for men and women. Confirmation of EIA-2 results with RIBA was rare when ALT was low and frequent when ALT was high. ALT screening before introduction of Anti-HCV detected one out of six infected donors. To exclude this one infectious donation, 46 uninfected donations had to be excluded in addition. Only 8% of the then RIBA-2-positive donors were not detected by EIA-1. Apparent seroconversions in EIA-2 are usually not specific; only 1 out of 66 apparent seroconversions could be confirmed by RIBA-2 suggesting recent HCV infection. 0.15% of the donor population showed an inconsistent EIA-2 pattern during follow-up. We conclude that donors should not be excluded from further donations, even on the basis of multiple EIA-1 positive results or on the basis of only one EIA-2 positive donation. Anti-D-immunoglobulin prophylaxis may have been a source of infection in some Rhesus-negative women. ALT screening should not be discontinued because recent HCV infection can be detected earlier by ALT than by anti-HCV, but exclusion limits should be elevated to increase specificity and limit unnecessary exclusion of donations.
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A clinical trial was conducted in Argentina to determine the efficacy of clarithromycin plus lansoprazole for the treatment of Helicobacter pylori in duodenal ulcers and non-ulcer dyspepsia. PCR-RFLP was conducted on an 820-bp amplified product of the ureC gene of H. pylori to determine the genetic heterogeneity of 83 pretreatment and 21 post-treatment isolates. Twelve different restriction patterns were observed when digested with Sau 3A or Hha I, resulting in 40 different RFLP types. Comparison of isolates before treatment to after treatment showed that 20 of 20 patients had the same RFLP type. In addition, the presence of the cytotoxin-associated gene (cagA) and the vacuolating gene (vacA) were determined. All pretreatment isolates were positive for vacA whereas 75% of the pretreatment isolates were positive for cagA. The results of this study indicate that a high degree of heterogeneity exists among H. pylori and that infection is not limited to a small number of RFLP types.
High-dose carboplatin, etoposide and ifosfamide (CEI) is an active chemotherapy regimen (HDCT) in solid tumors and lymphomas. In patients with previous exposure to cisplatin, its nephrotoxicity is dose-limiting. To determine the implications of nephrotoxicity on hematological recovery and clinical outcome, we analyzed 150 consecutive patients with germ cell tumors treated between August 1989 and September 1995 with carboplatin 1500-2000 mg/m2, etoposide 1200-2400 mg/m2, and ifosfamide 0-10 g/m2 followed by either BM or PBPC rescue. Five patients died (3%), three in the context of severe renal toxicity and early multiorgan failure. Overall, acute nephrotoxicity occurred in 43/150 (29%) patients, particularly at doses of carboplatin >1500 mg/m2. Hemodialysis was required in 12/150 (8%) patients, but could be discontinued until discharge in all except two survivors. Nephrotoxicity did not delay hematologic recovery when adjusted for the use of PBPC and hematopoietic growth factors by multivariate analysis, but resulted in higher transfusion requirements, more overall toxicities and a longer hospital stay. There were no differences in the response rates or survival in patients with or without nephrotoxicity. Acute nephrotoxicity is a frequent and clinically relevant complication of CEI in germ cell tumors. The acute side-effects from CEI are reversible in the majority of patients.
Reactivation of infections with herpes viruses is a frequent and major cause of morbidity after bone marrow transplantation. In this case report we stress that HSV infections of the colon and small intestine should be considered in the differential diagnosis of diarrhea and intestinal bleeding in the early post-transplantation period. Severe acute GVHD and subsequent intensive immunosuppressive treatment may increase the risk for reactivation of HSV infection particularly in situations in which acyclovir prophylaxis has been omitted.
OBJECTIVE: Octreotide scintigraphy has been reported to visualize chromaffine tumours. This study in patients with malignant phaeochromocytoma was designed to assess octreotide in comparison with standard m-iodobenzylguanidine (MIBG) scintigraphy and to study functional activity of somatostatin receptors. Finally, two cases of octreotide treatment are reported. DESIGN: Open, prospective clinical trial. PATIENTS: In 12 patients with histologically proven malignant phaeochromocytoma, 111In-octreotide scintigraphy, 123I-MIBG scintigraphy and computed tomography were performed. In ten patients plasma catecholamine response to a single dose of octreotide (200 micrograms i.v.) was monitored up to 5 hours after injection. Two patients were treated with octreotide over several months. MEASUREMENTS: Plasma catecholamines were measured by high performance liquid chromatography (HPLC). Scintigraphy was performed using a large field gamma camera and SPECT technique where appropriate. RESULTS: At least one metastatic lesion was visualized by octreotide scintigraphy in eight patients while the remaining four patients had negative findings. In total, 43 out of 54 known metastases (79.6%) were detected by MIBG, 24 (44.4%) by octreotide. Nevertheless, octreotide scintigraphy detected six metastases that were negative by MIBG. There was no correlation between the results of octreotide scintigraphy and catecholamine suppression after i.v. octreotide. In two patients on octreotide treatment, symptomatic improvement, but not mass reduction, could be documented. CONCLUSIONS: Octreotide scintigraphy behaves in part complementary to MIBG, thus, increasing diagnostic sensitivity. Presence of somatostatin receptors, as demonstrated by octreotide scintigraphy, does not necessarily predict functional activity or therapeutic response.
Alterations in the metabolism of glycosaminoglycans (GAG) may play a role in the pathogenesis of diabetic-associated microangiopathy. Consequently, the relationship between diabetic nephropathy and retinopathy and urinary GAG distribution was assessed in 96 IDDM patients in comparison to 103 healthy controls. GAG concentration in 24h urine samples was determined by precipitation with cetylpyridinium chloride and potassium acetate in ethanol followed by a colorimetric test with carbazole. A marked difference (P = 0.0008) in urinary GAG excretion between patients (24.3 +/- 1.5 mg/24 h, mean +/- SEM) and controls (16.2 +/- 0.75 mg/24 h) could be detected. In patients with IDDM of longer duration, GAG excretion was increased (< or = 10 yr: 20.8 +/- 2.1 vs > 10 yr: 27.4 +/- 2.1 mg/24 h; P = 0.03). Furthermore, IDDM patients with class 4 nephropathy and retinopathy exhibited a markedly higher GAG excretion compared to those without nephropathy (33.1 +/- 3.0 vs 22.6 +/- 1.7 mg/24 h, P = 0.005) or retinopathy (29.7 +/- 2.8 vs 21.2 +/- 1.7 mg/24 h, P = 0.009). An increased urinary GAG concentration was detected in IDDM patients with albuminuria (> 300 mg/24 h: 29.9 +/- 3.3 vs < 30 mg/24 h: 23.0 +/- 1.7 mg/24 h; P = 0.048), proteinuria (> 0.5 g/24 h: 30.3 +/- 3.7 vs < 0.05 g/24 h: 22.7 +/- 1.6 mg/24 h) and in patients with augmented serum creatinine in comparison to those with normal values (> 0.12 mg/L: 34.9 +/- 2.3 vs < 0.12 mg/L: 22.4 +/- 1.6 mg/24 h; P = 0.01). The results demonstrate a close relationship renal GAG excretion and the presence of microangiopathy in IDDM patients.
The effect of diabetes mellitus on bone metabolism and bone mineral density is discussed controversially. Diabetes mellitus due to an autoimmune process seems to be associated with low turnover osteopenia either in the animal model or in children and adolescents. A number of factors are discussed as being involved, but in this age group clinical symptoms are missing. Adult patients of either sex with IDDM show a reduced bone mineral density when measured at peripheral sites such as the distal forearm or the femoral neck, diabetic complications such as neuropathy and microangiopathy seem to pronounce the deficit of bone mass. In these patients, osteopenia is accompanied by a high turnover situation of bone metabolism, possibly due to microvascular complications. In contrast, patients with NIDDM and here especially overweight women have a normal or even increased bone mineral density. Up to now, there is no convincing evidence for an increased incidence of osteoporotic fractures in diabetic patients. Systemic diabetic osteopenia therefore does not seem to be of great epidemiological relevance.
A multi-country clinical trial was conducted in ten European countries to determine the efficacy of clarithromycin-omeprazole dual therapy for treating Helicobacter pylori infection in peptic ulcers. Gastric biopsies were cultured for H. pylori before and after treatment. PCR-RFLP was used to determine the genetic heterogeneity of 100 H. pylori isolates from pretreatment and posttreatment biopsies. An 820 bp amplified fragment of the ureC gene was digested with the restriction enzymes Sau3A and Hhal. Fourteen different Sau3A patterns and 15 different Hhal patterns were identified among the pretreatment isolates. In combination, 42 different RFLP types were identified. Comparison of isolates before treatment with those after treatment showed that five of ten patients on clarithromycin-omeprazole dual therapy had the same RFLP type and that all 12 patients on omeprazole therapy alone had the same RFLP type. All isolates were susceptible to clarithromycin prior to treatment, while seven of ten patients on clarithromycin-omeprazole therapy had H. pylori that was resistant to clarithromycin after therapy and 11 of 12 patients on omeprazole therapy had isolates susceptible to clarithromycin after treatment. In addition to PCR-RFLP typing, the presence of the cytotoxin-associated gene (cagA) and the vacuolating gene (vacA) was determined; 79% of the isolates were cagA-positive and all were vacA-positive. The results of this study indicate that infection of H. pylori in Europe is not restricted to a few RFLP types.
We have developed a rapid PCR-oligonucleotide ligation assay that can discriminate single base substitutions that are associated with clarithromycin resistance in Helicobacter pylori. Susceptible isolates were wild type at positions 2143 and 2144 (cognate to 2058 and 2059 in Escherichia coli), while 93% of the resistant isolates contained A-to-G mutations at either position and 7% of the isolates contained A-to-C mutations at position 2143. In addition, the MIC for 86% of the resistant isolates with an A2143 mutation was > or = 64 micrograms per ml, and that for 89% of the resistant isolates with an A2144 mutation was < or = 32 micrograms per ml.
The molecular typing of 81 pretreatment Helicobacter pylori isolates and the comparison of 18 pretreatment-posttreatment pairs is described by restriction fragment length polymorphism (RFLP) of the ureC gene. The results of our study show the extreme genomic diversity of H. pylori and indicate that infection by H. pylori in the United States does not appear to be limited to a small number of RFLP types.