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Biomedical subjects

C Binder

Publications and source records attributed to C Binder.

At least 19 recordsLinked to original sources

Isolated meningeal chloroma (granulocytic sarcoma)--a case report and review of the literature.

Isolated chloromas (granulocytic sarcomas) are rare tumors, most of them progressing to acute myeloblastic leukemia within months. There are still no conclusive treatment strategies for this entity; however, early antileukemic chemotherapy seems to lower the probability of developing systemic disease and prolong survival. We report on a patient with isolated meningeal chloroma, primarily misdiagnosed as a high-grade Non-Hodgkin's lymphoma. Two cycles of antileukemic induction chemotherapy were administered, followed by local irradiation and intensified consolidation therapy with autologous stem cell transplantation. After 20 months, he is still in complete remission.

Adult↗

Structured parent education in the management of childhood atopic dermatitis: the Berlin model.

Childhood atopic dermatitis (AD) is a common disease with the prevalence rates increasing. Its chronic course with frequent relapses puts a special burden on both children and their parents. To maximise positive long-term outcome in the management of AD it is important to support parents in dealing with the chronic condition of their child in addition to treating symptoms. In the present article, we describe in detail the goals, structure, and content of the Berlin education program for parents of children with AD. The program aims to contribute towards a comprehensive, family-oriented management of childhood AD. Its objective is to improve parent's self-management skills with regard to their child's disease and to positively impact the course of the disease as well as the family's quality of life. Medical, nutritional and psychological issues are covered in six group sessions which are conducted by a multiprofessional team of paediatricians, psychologists and dieticians. Preliminary data show that the program has a desirable effect on aspects of quality of life and coping.

Adult↗

Case report. Mixed systemic mycosis with fatal outcome in a patient with acute myeloblastic leukaemia.

Fungal infections represent an increasing problem in immunocompromised patients. The majority of cases are caused by one single fungal pathogen and infections with more than one fungus are very rare. Here we describe a case of combined infection with Aspergillus and a zygomycete species, involving the lungs, spleen and the brain and leading to fatal outcome in spite of early antimycotic therapy.

Aspergillosis↗

Two enzyme immunoassays and PCR for detection of Helicobacter pylori in stool specimens from pediatric patients before and after eradication therapy.

This study of pediatric patients was intended to determine the suitability of stool PCR and two antigen enzyme immunoassays (EIAs; Premier Platinum HpSA and the novel FemtoLab H. pylori), which detect Helicobacter pylori antigens in feces, as pretreatment diagnostic tools and especially as posttreatment control. Forty-nine H. pylori-infected children with dyspepsia received eradication therapy. Successful treatment was determined by a negative [(13)C]urea breath test 4 and 12 weeks after discontinuation of therapy. Fecal specimens were collected prior to eradication therapy as well as 4 weeks after the end of treatment. Successfully treated children delivered stool samples at 6, 8, and 12 weeks posttreatment also. Specimens were examined by seminested PCR and Premier Platinum HpSA and were reexamined by both EIAs as soon as FemtoLab H. pylori was available. In the first test series, the overall sensitivities of PCR and Premier Platinum HpSA were 93.0 and 91.1%, respectively. With specimens collected at 4 weeks after treatment, the respective specificities were 68.8 and 79.3%. After longer follow-up periods, however, they gradually increased to 100 and 96.9%, respectively. In the new test series, Premier Platinum HpSA delivered a considerably lower number of false-positive results (4 versus 18), indicating intertest variations. The overall test sensitivity was 94.6%, and the overall specificity was 97.5%. FemtoLab H. pylori showed an excellent performance with an overall sensitivity and specificity of 98.2 and 98.1%, respectively. Thus, in contrast to PCR, both EIAs were shown to be suitable for early posttreatment control.

Adolescent↗

Outcome of double-blind, placebo-controlled food challenge tests in 107 children with atopic dermatitis.

BACKGROUND AND OBJECTIVE: Little is known about late phase clinical reactions during oral food challenges and the value of specific IgE in terms of sensitivity and specificity. METHODS: We therefore analysed retrospectively the clinical outcome of 387 oral provocations during double-blind, placebo-controlled food challenge tests in 107 children with atopic dermatitis. RESULTS: Eighty-seven (81%) children showed a positive clinical reaction to at least one challenge. The vast majority of children (94%) showed clinical symptoms to one or two allergens. One hundred and thirty-one of 259 (51%) of verum challenges and 1/128 (0.8%) placebo challenge were assessed as positive. Oral provocations with hen's egg showed the highest percentage of positive reactions (70%). Sensitivity of specific IgE to the four allergens tested was 90%, specificity 30%. Sensitivity of the parental history as a predictive factor was 48%, specificity 72%. Ninety-two of 131 (70%) children with positive verum provocations showed early reactions, 33 (25%) late and six (5%) combined early and late reactions. In 84/131 (64%) positive provocations one organ system was involved, while in 44 (34%) provocations two and in three (2%) challenges three organ systems were involved. Skin reactions were the most frequent clinical manifestation leading to positive reactions followed by gastro-intestinal and respiratory symptoms. There was no correlation between titration dose and specific IgE. The subgroup of non-sensitized children did not differ in terms of sex, age or titration dose from the total study population. CONCLUSION: Double-blind, placebo-controlled oral food challenges are helpful in distinguishing children with clinically manifested symptoms from those with food sensitization. Accurately identifying children with a clinical relevant food allergy may help to prescribe specific diets on a scientific basis, avoiding dietary limitations which may be unnecessary or even harmful.

Administration, Oral↗

In vivo and in vitro studies on the residual allergenicity of partially hydrolysed infant formulae.

AIM: Because allergen-reduced formulae are widely used in the prevention and treatment of cow's milk allergy in children and because anaphylactic reactions have been reported for some hydrolysed formulae, it is of clinical relevance to know about the residual allergenicity of so-called hypoallergenic formulae. METHOD: We therefore studied the reactions of 20 children (mean age 1.6 years) with proven cow's milk allergy to a variety of formulae, using skin prick test, specific IgE in serum, protein content and RAST inhibition. RESULTS: Whereas all but two children with a clinically relevant cow's milk allergy had a positive skin prick test to cow's milk, some children still showed positive responses to the partially hydrolysed formulae. No child had a positive skin test to the amino acid formula. Specific IgE to the partially hydrolysed whey formula (median 0.28 U/ml) was significantly lower (p < 0.003) than to cow's milk. Specific IgE to the partially hydrolysed whey/casein formula, soy/pork collagen hydrolysate and the amino acid formula was in a low range (median values 0.19, 0.23 and 0.21 U/ml, respectively). While determination of the protein content of the formulae gave no valid information, RAST/EAST inhibition was highest for cow's milk, followed by the partially hydrolysed whey formula, partially hydrolysed whey/casein formula, soy/pork collagen formula, and the amino acid formula. CONCLUSION: Skin prick test and RAST inhibition test are suitable methods for determining the residual allergenicity of hydrolysed infant formulae, while determination of protein content using the applied modified Lowry method is not helpful.

Amino Acids↗

Intact proinsulin and beta-cell function in lean and obese subjects with and without type 2 diabetes.

OBJECTIVE: Type 2 diabetes is a heterogeneous disease in which both beta-cell dysfunction and insulin resistance are pathogenetic factors. Disproportionate hyperproinsulinemia (elevated proinsulin/insulin) is another abnormality in type 2 diabetes whose mechanism is unknown. Increased demand due to obesity and/or insulin resistance may result in secretion of immature beta-cell granules with a higher content of intact proinsulin. RESEARCH DESIGN AND METHODS: We investigated the impact of obesity on beta-cell secretion in normal subjects and in type 2 diabetic patients by measuring intact proinsulin, total proinsulin immunoreactivity (PIM), intact insulin, and C-peptide (by radioimmunoassay) by specific enzyme-linked immunosorbent assays in the fasting state and during a 120-min glucagon (1 mg i.v.) stimulation test. Lean (BMI 23.5 +/- 0.3 kg/m2) (LD) and obese (30.1 +/- 0.4 kg/m2) (OD) type 2 diabetic patients matched for fasting glucose (10.2 +/- 0.6 vs. 10.3 +/- 0.4 mmol/l) were compared with age- and BMI-matched lean (22.4 +/- 0.6 kg/m2) (LC) and obese (30.8 +/- 0.9 kg/m2) (OC) normal control subjects. RESULTS: Diabetic patients (LD vs. LC and OD vs. OC) had elevated fasting levels of intact proinsulin 6.6 +/- 1.0 vs. 1.6 +/- 0.3 pmol/l and 7.7 +/- 2.0 vs. 1.2 +/- 0.2 pmol/l; PIM: 19.9 +/- 2.5 vs. 5.4 +/- 1.0 pmol/l and 29.6 +/- 6.1 vs. 6.1 +/- 0.9 pmol/l; and total PIM/intact insulin: 39 +/- 4 vs. 15 +/- 2% and 35 +/- 5 vs. 13 +/- 2%, all P < 0.01. After glucagon stimulation, PIM levels were disproportionately elevated (PIM/intact insulin based on area under the curve analysis) in diabetic patients (LD vs. LC and OD vs. OC): 32.6 +/- 6.7 vs. 9.2 +/- 1.1% and 22.7 +/- 5.2 vs. 9.1 +/- 1.1%, both P < 0.05. Intact insulin and C-peptide net responses were significantly reduced in type 2 diabetic patients, most pronounced in the lean group. The ratio of intact proinsulin to PIM was higher in diabetic patients after stimulation in both LD versus LC: 32 +/- 3 vs. 23 +/- 2%, and OD versus OC: 28 +/- 4 vs. 16 +/- 2%, both P < 0.01. In obese normal subjects, intact proinsulin/PIM was lower both in the fasting state and after glucagon stimulation: OC versus LC: 22 +/- 3 vs. 33 +/- 3% (fasting) and 16 +/- 2 vs. 23 +/- 2% (stimulated), both P < 0.05. CONCLUSIONS: Increased secretory demand from obesity-associated insulin resistance cannot explain elevated intact proinsulin and disproportionate hyperproinsulinemia in type 2 diabetes. This abnormality may be an integrated part of pancreatic beta-cell dysfunction in this disease.

Body Mass Index↗

Induction of inducible nitric oxide synthase is an essential part of tumor necrosis factor-alpha-induced apoptosis in MCF-7 and other epithelial tumor cells.

TNF-alpha-induced cytotoxicity is mediated by the intracellular "death domain" of the 55-kDa TNF-alpha receptor and has been demonstrated to be coupled with induction of inducible nitric oxide synthase (iNOS), leading to generation of nitric oxide radicals (NO*). Because it is still widely unknown, to what extent NO* participates in the execution of TNF-alpha-induced apoptosis, NO* production, iNOS expression, and enzyme activity in relation to TNF-alpha-induced apoptotic cell death were investigated in the human breast cancer cell line MCF-7 and various other malignant cell lines. Incubation with TNF-alpha led to induction of iNOS mRNA and protein as well as enhancement of NOS activity. Augmented synthesis of NO2, the stable end product of NO* generation, was significantly correlated with augmented rates of cell death. Measurement of TNF-alpha-triggered production of reactive oxygen species (ROS) suggested a major role for NO* within the generated oxygen radicals. Dying cells showed characteristic features of apoptosis. Addition of cycloheximide (CX) enhanced apoptotic cell death by increasing iNOS activity. L-Nitro-arginine-methylester (L-NAME), a competitive NOS-inhibitor, and iNOS antisense oligonucleotides effectively prevented NO2 generation and apoptosis. Evaluation of iNOS expression during TNF-alpha-induced cell death in various malignant cell lines demonstrated iNOS positivity for all TNF-alpha-sensitive cells. The only primarily resistant line was iNOS negative. In a resistant variant of MCF-7, iNOS mRNA was still detectable; however, treatment with TNF-alpha did not enhance NOS activity. TNF-alpha sensitivity and NO2 production were completely restored by the addition of CX. Taken together, iNOS induction plays an essential role in TNF-alpha-induced apoptosis of the investigated cell lines. Further studies are necessary to define the impact of NO* in relation to other specific effectors of apoptosis such as the caspases.

Apoptosis↗

[Bacterial colonization of conjunctiva with Propionibacterium acnes before and after polyvidon iodine administration before intraocular interventions].

BACKGROUND: Propionibacterium acnes has been described as a causative agent of postoperative endophthalmitis. This gram-positive, immotile, non-spore-forming bacterium is highly pleomorphic and grows under conditions of low to no oxygen concentration. It is commonly found on the skin at the openings of sebaceous glands and on hairs. A near-symptomless postoperative endophthalmitis occurs particularly when Propionibacteria are enclosed in the capsular bag. We investigated to what extent the number of P. acnes in the conjunctival sac can be reduced by preoperative disinfection with polyvidone iodine (1%). PATIENTS AND METHODS: A total of 261 patients with intrabulbar surgery had two conjuctival swabs taken: the first immediately prior to preoperative preparation in the operating theatre, following in-patient application of antibiotic eye drops (Polymyxin-B-sulfat, Neomycinsulfat and Gramicidin in combination); the second swab was taken after disinfection with polyvidone iodine before opening the conjunctiva. RESULTS: Of the 261 swabs, 60 (23%) taken prior to polyvidone iodine application were positive for Propinibacterium acnes. Following polyvidone iodine treatment, a further 5 (1.9%) remained culture-positive. After disinfection, 55 (92%) of the 60 positive swabs for Propionibacterium acnes remained culture-negative. CONCLUSIONS: We concluded that a significant reduction of P. acnes can be achieved by preoperative application of polyvidone iodine (1%) (P < 0.001).

Anti-Infective Agents, Local↗

[Severe toe gangrene as an early manifestation of Wegener granulomatosis in a young patient].

Gangrene of digits is a very rare manifestation of Wegener's granulomatosis (WG). We report a case of a 29-year-old woman with nonspecific symptoms like fever, weight loss, arthralgia, arthritis and high systemic inflammatory signs. On the grounds of a presumed infection the patient was treated with antibiotics which showed no effect. Within short she complained of pain and paresthesia of the right foot with a rapid lividity. Angiography demonstrated multiples stenoses and multisegmental occlusions of the lower leg arteries. Together with renal and pulmonal symptoms a WG was suspected, the diagnosis being confirmed by kidney biopsy and positive cANCAs. A few months after starting a combined therapy with cyclophosphamide and corticosteroids the patient showed a partial remission with a residual toe gangrene. Comparing the five worldwide reported cases with digital gangrene and our presentation there is a concordance of all in the occurrence of an extremely high disease activity together with a glomerulonephritis. The findings of p-ANCAs in our patient and positive Hbs antigen in another case of WG with digital gangrene suggests a relation to panarteriitis nodosa, where gangren is more common.

Adult↗

Role of nonallergic hypersensitivity reactions in children with chronic urticaria.

BACKGROUND: IgE-independent (pseudoallergic) reactions to food and food ingredients are common in a subgroup of adult patients with chronic urticaria, who have daily spontaneous occurrence of wheals. However, for children with chronic urticaria (duration longer than 6 weeks, no physical influence), no data on the importance of pseudoallergen-induced chronic urticaria are available. Therefore, we investigated the role of nonallergic hypersensitivity to food in all children seen with chronic continuous urticaria in our two clinics over the last 2 years (n = 16). METHODS: All patients were given a low-pseudoallergen diet for 3 weeks followed by provocation with food rich in pseudoallergens. To identify the main eliciting agents, a subgroup of responders was exposed to food additives by double-blind, placebo-controlled food challenges. RESULTS: Pseudoallergen-induced urticaria was diagnosed in 12 cases (75%). Reactions occurred mainly to coloring agents and preservatives, but also to monosodium glutamate and a sweetener (saccharin/cyclamate). CONCLUSIONS: These results confirm that nonallergic hypersensitivity reactions play a role in children with chronic urticaria, although the latter disease is rare at that age. In children, food additives, especially coloring agents and preservatives, appear to play a more important role in eliciting nonallergic hypersensitivity reactions than in adult patients, where naturally occurring pseudoallergens in fruits and vegetables are mainly responsible.

Adolescent↗

Insulin secretion rates estimated by two mathematical methods in pancreas-kidney transplant recipients.

After pancreas-kidney transplantation, it is difficult to obtain an accurate estimate of the insulin secretion of the pancreas graft, since several pitfalls are involved using peripheral C-peptide and/or insulin measurements in this determination. In this study, the individual kinetic parameters of C-peptide and then the rates of insulin secretion were estimated by two mathematical methods, the deconvolution method and the "combined model" during slow (oral glucose) and fast (intravenous glucagon) changes in insulin secretion in six successful pancreas-kidney transplant recipients with systemic delivery of insulin (Px), six nondiabetic kidney-transplant recipients with portal insulin secretion (Kx), six nondiabetic controls (NS), and six C-peptide-negative insulin-dependent diabetes mellitus patients (IDDM). Decreased C-peptide clearance and basal and poststimulatory hyperinsulinemia were found in both Px and Kx compared with NS (P < 0.05). Similar glucose responses were observed after intravenous glucagon in all groups, whereas the responses after oral glucose were 30% higher in Px and Kx than in NS (P < 0.05). During oral glucose and after intravenous glucagon, both mathematical methods resulted in significantly lower maximal and incremental insulin secretion rates (ISR) in Px than in Kx (P < 0.05). In contrast, calculations of incremental ISR in NS and Px induced by the two beta-cell stimuli were about the same but significantly higher in Kx than in NS (P < 0.05). These results differed markedly from those obtained using peripheral measurements of insulin and C-peptide alone. In conclusion, when C-peptide clearance and insulin metabolism change, such as in pancreas-kidney transplant recipients, accurate evaluation of insulin secretion from the graft can be obtained only by using individual kinetics of the peptides before calculating the ISR. This study also clearly demonstrates that insulin secretion after pancreas transplantation is still defective.

Adult↗

Clinical outcome and economic impact of aminoglycoside peak concentrations in febrile immunocompromised patients with hematologic malignancies.

The aim of this study was to investigate the clinical and economic significance of aminoglycoside peak concentrations in febrile neutropenic patients with hematologic malignancies. Sixty-one patients were treated according to protocol II of the Paul-Ehrlich-Gesellschaft: initial application of gentamicin or tobramycin in combination with a cephalosporin or ureidopenicillin and, after 3 days, a potential change of antibiosis to be decided in case of nonresponse. At the same time, samples were collected by an independent controller. We found a significant dependence of clinical outcome on aminoglycoside peak concentrations (P = 0.004). Twelve of 17 patients with peak concentrations > 4.8 mg/L, but only 13 of 44 patients with concentrations < or = 4.8 mg/L, responded to initial therapy. Average infection-related costs per patient with peak values > 4.8 mg/L were US$1429, $1790, and $1701 for nursing, diagnostics, and therapeutics, respectively (total $4920). Expenses for patients with peak concentrations < or = 4.8 mg/L were approximately 1.8-fold higher (average total $8718). If all 61 patients had achieved peaks > 4.8 mg/L, the potential savings would have totalled $167,112. We conclude that neutropenic patients form a target group for successful pharmacokinetic intervention and cost saving.

Adult↗

Influence of cycloheximide-mediated downregulation of glucose transport on TNF alpha-induced apoptosis.

Enhancement of cellular sensitivity to TNF alpha-induced apoptosis by cycloheximide (CX) has been attributed to its quality as an inhibitor of protein synthesis, presumably by prevention of the synthesis of short-lived death antagonists. CX is also known to interfere with glucose transport, which in turn influences cell death. Hexose uptake, expression of glucose transporter (Glut) mRNAs and proteins, and other related factors were therefore examined upon induction of apoptosis with TNF alpha and CX in breast cancer cell lines. In the early phase of apoptosis, a dramatic decrease in glucose transport was observed, preceded by stimulation of Glut 1 and 3 mRNAs. Transport downregulation was also detectable upon incubation with CX alone, albeit to a lesser extent. With the doses used, TNF alpha had no such effect. Protein synthesis was inhibited to the same degree in TNF alpha/CX-treated apoptotic cells compared to viable CX-treated cells. Diminished hexose uptake was associated with decreased Vmax, while Glut affinity remained unaffected. As there was no evidence for changes in total cellular Glut content or for Glut translocation from the plasma membrane, a diminished intrinsic activity of Gluts must be postulated. In conclusion, CX is proposed to contribute to TNF alpha-induced apoptosis predominantly by interference with glucose transport; the exact nature of this effect remains to be elucidated.

Adenosine Triphosphate↗

Longitudinal study of fasting proinsulin in 148 siblings of patients with insulin-dependent diabetes mellitus. Study Group on Childhood Diabetes in Finland.

OBJECTIVE: To follow proinsulin immunoreactive material (PIM) in healthy siblings from the time of diagnosis of insulin-dependent diabetes mellitus (IDDM) in the proband, for at least 2 years. DESIGN AND METHODS: The study comprised 148 siblings representing 112 families. The siblings were recruited from the nationwide 'Childhood Diabetes in Finland' study and tested for immunological markers. If a sibling was found positive for islet cell antibodies (ICA) or insulin autoantibodies (IAA), PIM sampling was extended beyond 2 years. RESULTS: Of the 148 siblings, 12 developed IDDM 3-53 months after the diagnosis in the proband. Eleven of these siblings exhibited initially normal PIM concentrations. In nine siblings, samples were available both more than 6 months and during the last 6 months before the diagnosis of IDDM; PIM concentrations increased in seven, remained unchanged in one, and decreased in one in the period up to the diagnosis of IDDM (P < 0.05). Median PIM concentration did not change significantly during the examination period of 2 years in the 136 siblings who did not contract IDDM. Constantly increased PIM concentrations were found in 12 of the 136 siblings who did not develop IDDM. These 12 siblings were all ICA negative. CONCLUSION: In healthy siblings of IDDM patients exhibiting an initially low PIM concentration, an abrupt increase in PIM seems to precede the clinical manifestation of IDDM within 0-6 months. However, there were too few patients available to close follow-up to allow calculation of any predictive value of this increase. Persistently increased PIM concentrations were present in some healthy siblings who did not develop IDDM. The reason for that finding remains unclear, but it could be associated with previous B cell damage.

Adolescent↗

Bankart repair for anterior instability of the shoulder. Long-term outcome.

Anterior instability of the shoulder is a commonly encountered entity in orthopaedic practice. The Bankart procedure is considered by many surgeons to be the treatment of choice for this condition. Despite its widespread popularity, there have been no studies on the long-term outcome of the Bankart procedure as far as we know. Sixty shoulders (fifty-six patients) that had been followed for a minimum of eight years after a Bankart procedure were evaluated for range of motion, stability, and strength according to the data form of the American Shoulder and Elbow Surgeons for examination of the shoulder. The results for the involved shoulder were compared with the findings for the contralateral, normal shoulder. All patients completed a questionnaire regarding the history of the instability of the shoulder, the level of participation in sports before and after the operation, the preoperative and postoperative level of pain, and whether the patient had ever sustained a dislocation that needed reduction by a physician. Information about the current ability of the patient to function at home, at work, and during sports also was requested. In addition, the patients were asked to rate the results of the operation and to indicate whether they would have the same procedure again for the same problem. At a mean of 11.9 years after the operation, the mean loss of external rotation was 12 degrees (range, 0 to 30 degrees) (p < 0.0001). There were no significant differences in forward elevation, abduction, or internal rotation between the involved shoulder and the contralateral, normal shoulder. One patient had crepitus on glenohumeral motion. Fifty-five of the fifty-six patients returned to the occupation that they had had preoperatively, without having to alter their activities. Twenty-eight patients had mild pain with strenuous activity, and one patient had pain at rest. Three patients had a dislocation of the involved shoulder because of a new traumatic event more than three years postoperatively. Fifty-two patients rated the result as good or excellent; three, as fair; and one, as poor. Fifty-four patients said that they would have a Bankart procedure performed again for the same problem. We present a new system for rating the shoulder that emphasizes function and is based specifically on the goals stated by the patients to be most important with regard to the shoulder. Using this system, we found that the Bankart procedure offers an excellent objective long-term outcome with a high degree of patient satisfaction.

Activities of Daily Living↗