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Biomedical subjects

A Berghold

Publications and source records attributed to A Berghold.

At least 19 recordsLinked to original sources

Serum osteoprotegerin is a major determinant of bone density development and prevalent vertebral fracture status following cardiac transplantation.

Osteoprotegerin (OPG) is an antiresorptive cytokine and a key regulator of osteoclastogenesis and activity. Since OPG is downregulated by glucocorticoids and cyclosporine A in vitro we examined whether immunosuppressive therapy would play a role in the development of transplantation osteoporosis. We enrolled 57 cardiac transplant recipients (median time since transplantation, 3.2 years (1.1-11.5 years)) in this cross-sectional study. Standardized spinal X-rays as well as hip bone density measurements were performed in all patients. Serum OPG was determined using a commercially available ELISA. Vertebral fractures were present in 56% of the patients. Bone densities of all femoral neck subregions were correlated to serum OPG concentrations (r values between 0.40 and 0.48, all P < 0.005). Multiple regression analysis revealed OPG levels to be independently correlated to femoral neck Z scores (r = 0.49, P = 0.002). After adjustment for age, BMI, neck Z score, renal function, and months since transplantation, serum OPG was the only significant predictor of prevalent vertebral fractures (P = 0.001). In a separate 6-month prospective study of 14 heart transplant recipients receiving calcium and vitamin D serum OPG levels fell by 41% (P = 0.0004) after 3 months and 47% (P = 0.0001) after 6 months following cardiac transplantation. Bone loss at the lumbar spine and femoral neck after 6 months was correlated to the decrease in serum OPG at 6 months (r = 0.82, P < 0.0001, and r = 0.60, P = 0.02, respectively) as well as 3 months after cardiac transplantation (r = 0.65, P = 0.01, and r = 0.69, P = 0.006, respectively). Serum OPG alone accounted for 67% of the variance of lumbar spine bone density changes over the first 6 months posttransplantation. We conclude that serum OPG levels decline consistently in all patients following initiation of immunosuppressive therapy and are independently correlated with changes in bone density. We hypothesize that OPG plays a major role in the development of transplantation osteoporosis.

Aged↗

Plasma N-terminal pro-brain natriuretic peptide in Type 1 diabetic patients with and without diabetic nephropathy.

AIMS: Plasma N-terminal pro-brain natriuretic peptide (NT proBNP) is produced and released from cardiac ventricles; it is elevated in patients with heart failure, hypertension and chronic renal failure. This study aimed to examine the plasma levels of NT proBNP and their relationship in Type 1 diabetic patients with and without diabetic nephropathy. METHODS: We developed a non-competitive immunoluminometric assay with in-house antibodies to the N- and C-terminal domains of NT proBNP. We compared NT proBNP levels between 47 normoalbuminuric patients (group 1), 12 microalbuminuric patients (group 2) and 12 patients with macroalbuminuria (group 3). RESULTS: There were significant differences in 24-h systolic and diastolic blood pressure, diabetes duration, serum creatinine, LDL-cholesterol and HbA1c between the three groups; other parameters did not differ significantly. NT proBNP (median and range) levels were 5 (0.75-68), 22 (0.75-82) and 23 (0.75-374) fmol/ml for groups 1-3, respectively. Log-transformed data of NT proBNP were used to compare all three groups (P=0.016). The Pearson correlation between NT proBNP and albuminuria (R=0.27; P=0.02) was positive; HbA1c (R=0.25; P=0.03) and age (R=0.33; P=0.005) correlated significantly as well. On the basis of multiple regression analysis, the adjusted difference remained significant between the three groups. CONCLUSIONS: This is the first demonstration that NT proBNP levels are significantly higher in Type 1 diabetic patients with albuminuria. This may be caused by a down-regulation of A-type guanylate cyclase-coupled natriuretic peptide receptors in renal tubules or by elevated NT proBNP levels leading to higher glomerular hydraulic pressure or higher capillary permeability and possibly increased albumin excretion. Further studies are required to investigate the potential role of NT proBNP in patients with diabetic nephropathy and such other co-morbidities as cardiovascular disease.

Adult↗

Carcinoma of the larynx: predictors of diagnostic delay.

OBJECTIVES: In tumors of the upper aerodigestive tract a dose-response relationship between tumor stage and its prognosis raises the chance of a reduction in the diagnostic delay. The interval between the first symptom and the start of tumor-specific therapy and the influencing factors is not well known. The goals of this study were to investigate the diagnostic delay and the influencing factors and to predict the factors that prolong the diagnostic process. STUDY DESIGN: Prospective, nonrandomized study. METHODS: The intervals between first symptom and first consultation of a physician (patient delay) and between first consultation and first tumor-specific therapy (doctor delay) were investigated. Predictors for increased patient or doctor delay were evaluated, and a multiple logistic regression model for increased doctor delay was developed. RESULTS: The total diagnostic delay (sum of patient and doctor delays) was 3 to 4 months. A multifactorial model for the ratio of odds revealed that for women and glottic cancers (1.73) the chance was twice as high for a doctor delay greater than 30 days, whereas subjects with an increased patient delay (>30 d) had reduced odds of being delayed by the physician. CONCLUSIONS: The higher chance of extended doctor delay for glottic tumors compared with supraglottic tumors should be reflected in differential therapeutic strategies. Even unspecific lesions of the vocal folds should be followed up at the end of the therapy, at least. Therapies of glottic lesions without final control have the chance of resulting in delays in treatment. Women, especially, should be included in a follow-up examination. On the other hand, patients with increased patient delay have lower odds of longer doctor delay, which may be the result of tumor growth and, consequently, easier diagnosis.

Carcinoma, Squamous Cell↗

Vehicles reversing or rolling backwards: an underestimated hazard.

OBJECTIVES: A retrospective analysis of injuries caused by vehicles that were reversing or rolling backwards to establish guidelines for prevention was performed. PATIENTS AND METHODS: Medical records and questionnaires completed by parents for 32 children admitted to the Department of Pediatric Surgery, Graz, within the past eight years, were analysed. RESULTS: The median age was 2.1 years (1.0-14.0 years). Fourteen of 32 of the cars were driven by family members (43.8%); three were rolling backwards without a driver (9.4%). The median injury severity score was 3 (1-27) and the most common injuries were contusions (40.6%), fractures (31.3%), and lacerations/burns (21.9%). Most incidents occurred in driveways (37.5%) or farmyards (21.9%). Altogether 70.3% of children sustained "run-over" injuries, 29.6% were hit by the rear bumper or injured by a breaking window. CONCLUSIONS: Toddlers playing in driveways or farmyards are at risk of a injury caused by reversing vehicles/vehicles rolling backwards.

Accidents, Home↗

Chlamydia pneumoniae in multiple sclerosis: humoral immune responses in serum and cerebrospinal fluid and correlation with disease activity marker.

Humoral immune responses to Chlamydia pneumoniae (C. pneumoniae) were studied in paired sera and cerebrospinal fluid (CSF) of patients with definite multiple sclerosis (MS) and other inflammatory and non-inflammatory neurological diseases. Seropositivity was not significantly different between these groups. However, C. pneumoniae-specific IgG titers were significantly higher in CSF of MS than in controls. Sixteen out of 52 seropositive MS patients (30.8%) showed intrathecal synthesis of C. pneumoniae-specific IgG but only one of 43 seropositive controls (2.3%). In MS, this was strongly associated with intrathecal synthesis of polyclonal IgG in 13/16 patients. However, these elevated C. pneumoniae antibody titers in CSF did not significantly correlate with disease duration, disease course, clinical or MRI disease activity, disability or presence of oligoclonal IgG in MS.

Adolescent↗

A model and application for estimating completeness of registration.

Completeness of population-based registration systems is recognized to be an important aspect of the quality of information in registries which has to be examined. In this paper a model is presented which was used to estimate completeness of reporting of Down syndrome data notified to the Styrian Malformation registry between 1985-92. The model introduced is based on the two-source capture-recapture method allowing for time-varying parameters. For estimation of the parameters a discrete-time filtering algorithm was developed. For the used data set, an estimate of completeness derived from this model was in good agreement with an independent estimator based on demographic data and maternal age-specific Down syndrome risks whereas the usual two-source capture-recapture method gave a higher estimate.

Algorithms↗

Bilateral sensorineural hearing disorders in children: etiology of deafness and evaluation of hearing tests.

OBJECTIVE: The purpose of this study was to determine the etiology of bilateral sensorineural hearing disorders in children and to evaluate the performed hearing tests by comparison of the results of the objective and subjective tests. METHODS: The medical history and the hearing tests (behavioral observation audiometry, acoustic evoked potentials and pure tone audiometry) of 106 bilaterally hearing impaired children were analyzed in a retrospective follow-up study. RESULTS: The total group included 52 males and 54 females. The ages at first diagnosis ranged from 4 months to 11 years with a mean age of 42 months and a median of 33 months. The degree of hearing loss for the better hearing ear was mild in one child, moderate in 28 children, severe in 29 children, profound in 32 children and total in 16 children. The delay between the first examination and diagnosis ranged from 0 to 597 days with a mean of 83 days and a median of 28 days. In 47 children (44%) no cause of hearing impairment could be determined. Nineteen children (18%) had a history of familial hearing loss, 40 (38%) suffered from acquired hearing loss (seven children had prenatal causes, 21 perinatal and 12 postnatal). A comparison between behavioral observation audiometry and brainstem evoked response audiometry revealed a statistically good agreement. Twenty-nine children (32%) showed progressive hearing loss, which was defined as a threshold shift of +10 dB or more in the pure tone average in at least one ear. CONCLUSIONS: In a significant number of children with early hearing impairments the etiology still remains uncertain. Further research in the field of genetic disorders will diminish this number. Evaluation of hearing tests showed that behavioral observation audiometry still is an excellent tool in the hands of an experienced examiner. The age at identification of hearing disorders in industrialized countries still is unacceptably high. To obtain ideal care of hearing impaired children, universal neonatal hearing screening programs are mandatory.

Age Distribution↗

Variable bone mass recovery in hyperthyroid bone disease after radioiodine therapy in postmenopausal patients.

OBJECTIVES: Long-term follow-up of postmenopausal hyperthyroid females after radioiodine therapy, since hyperthyroidism is known to cause impressive bone loss which may increase the risk of bone fractures. METHODS: Bone mineral density (BMD) and biochemical parameters of bone metabolism in hyperthyroid postmenopausal patients were investigated before and 2 years after radioiodine therapy and compared with euthyroid age-matched controls. RESULTS: At baseline, the incidence of low BMD with t-scores more than 2.5 S.D. below normal was significantly higher in hyperthyroid patients (54%) than in controls (20%, P<0.001). Regardless of initial BMD values, osteocalcin (OC) was also higher in all hyperthyroid patients (P<0.0001). After 2 years, all treated patients were euthyroid and OC levels were in the upper normal range. In hyperthyroid patients with initially low BMD, bone density values had increased significantly by +6.5% (P<0.008) as compared with baseline values. In contrast, hyperthyroid patients with initially normal BMD showed a further decrease in lumbar BMD values of -4.3% despite radioiodine treatment. BMD in euthyroid controls decreased by -6.5% within 2 years. CONCLUSIONS: We conclude that hyperthyroid postmenopausal patients with generally increased bone turnover may show individual differences in bone loss and BMD recovery after radioiodine treatment. The mechanisms for this variable manifestation of osteoporosis have still to be elucidated, since this has implications for prophylactic and therapeutic strategies in these elderly patients.

Aged↗

Longitudinal change of white matter abnormalities.

A three year follow-up of 273 participants (mean age 60+/-6.1 years) of the Austrian Stroke Prevention Study provides first information on the rate, clinical predictors, and cognitive consequences of MRI white matter hyperintensity in elderly individuals without neuropsychiatric disease. Lesion progression was found in a total of 49 (17.9%) individuals. It was minor in 27 (9.9%) and marked in 22 (8.1%) participants. Diastolic blood pressure (odds ratio 1.07/mmHg) and early confluent or confluent white matter hyperintensities at baseline (odds ratio 2.62) were the only significant predictors of white matter hyperintensity progression. Lesion progression had no influence on the course of neuropsychologic test performance over the observational period.

Aged↗

HLA patterns in patients with nasal polyposis.

The etiology of nasal polyposis is still unknown, although risk factors include Aspirin intolerance, asthma, cystic fibrosis and primary ciliary dyskinesia. We studied frequencies of HLA A, B, DR and DQ in patients with nasal polyposis in order to determine a possible genetic component in the multifactorial pathogenesis of nasal polyps. Previous work has suggested an association of HLA-A1B8 with nasal polyposis and Aspirin intolerance. We investigated 89 patients with nasal polyposis, 11 of whom had Aspirin-intolerance, 19 asthma and 22 allergies to inhalation allergens. HLA patterns of these patients were compared to the ones of 1,070 healthy controls. No significant association of HLA-A1B8 was found with nasal polyps in the Aspirin-sensitive subgroup of our patients, but a significant association was seen with HLA-A74 and nasal polyposis.

Aspirin↗

Bunk beds--a still underestimated risk for accidents in childhood?

UNLABELLED: A retrospective analysis of 218 bunk-bed accidents and a random sample survey with 991 family interviews were performed in order to establish guidelines for bunk-bed accident prevention. Falls from the top bed during sleep (35.1%) or while playing (34.4%) and falling off the ladder (23.2%) are the leading causes of bunk-bed accidents. Of the 218 children, 91 (41.7%) had sustained major injuries, including 3 polytrauma, 7 skull fractures, 44 cerebral concussions, 33 long bone fractures, 2 Lisfranc injuries, and 2 lacerations of the spleen. Of these accidents, 58.3% resulted in minor injuries with 18 fractures in other locations than the long bones or cranial vault, 89 contusions and sprains, 18 skin lacerations and 2 tooth fractures. A total of 23.8% of the accidents occurred in children under 3 years of age. The random sample survey demonstrated that in relation to age groups of children 30.8% (0%-45.8%) of families interviewed had been using bunk beds, with peaks at 3 years (29.8%), 7 years (36.5%) and 11 years (45.8%) of age. Of these bunk beds, 75.3% were equipped with side-rails, 57.3% had placed carpets alongside the bunk bed and 43.0% had used night lights. CONCLUSION: There is only one recommendation: no bunk beds!!!

Accidents↗

Morphologic characteristics of disciform scarring after radiation treatment for age-related macular degeneration.

OBJECTIVE: To investigate the influence of radiation therapy on the development of disciform lesions in patients with age-related macular degeneration (AMD). DESIGN: A prospective, nonrandomized, comparative trial (patient self-controlled). PARTICIPANTS: Forty eyes with exudative AMD involving the central fovea in 40 consecutive patients were enrolled in this study. INTERVENTION: Radiation was administered to the posterior pole with an 8-mV photon beam from a linear accelerator. A dose of 14.4 Gy, 1.8 Gy per day, five fractions per week was delivered through a single port. MAIN OUTCOME MEASURES: The visual acuity and the morphologic characteristics, demonstrated by fundus photography, fluorescein, and indocyanine green angiography, were investigated before treatment and every 3 months after treatment over a period of 24 months. In 10 patients with bilateral disease the disciform lesions were compared. RESULTS: Twenty five patients could be followed regularly over the period of 24 months. The disciform lesions occurring after radiation were classified in three types. Type I (10 patients) was characterized by being smaller than 2 DD in size, with little fibrotic tissue underneath the retina, but pronounced retinal pigment epithelial changes. Type II (seven patients) showed extensive growth of the choroidal neovascularization (CNV) extending to and beyond the arcades with angiographically active loops in the peripheral parts. Eight patients had type III lesions develop characterized by a size greater than 2 DD but fewer than 6 DD and by a different amount of fibrotic tissue, hemorrhage, and lipid. Type I scarring was significantly associated with occult CNV without pigment epithelial detachments, whereas type II scarring was associated with classic CNV at the initial presentation (P<0.05). CONCLUSIONS: Although no severe side effects have been reported after radiation therapy for AMD, a subgroup of patients may experience extensive growth of CNV after radiation, causing greater functional damage than occurs spontaneously.

Aged↗

Synthesis pattern of matrix metalloproteinases (MMPs) and inhibitors (TIMPs) in human explant organ cultures after treatment with latanoprost and dexamethasone.

PURPOSE: To determine changes in production of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in the ciliary body, the trabecular meshwork and the retinal pigment epithelium induced by both prostaglandins and corticosteroids. METHODS: Explant organ cultures were removed by a scleral incision 3 mm posterior to the limbus. Retinal pigment epithelium was grown to confluence. Organ and cell cultures were treated with latanoprost and/or dexamethasone for 72 h. The activity of MMP-2, -3 and -9 was assessed using zymography. The synthesis pattern of MMPs and TIMP-1 and -2 was identified using immunostaining. RESULTS: Treatment of explant organ cultures with 10 micrograms/ml of latanoprost induced a mean upregulation of MMP-2 by 36%, MMP-3 by 112% and MMP-9 by 156% as seen by zymography. Dexamethasone 500 nm reduced the amounts of secreted MMP-2 by 13%, MMP-3 by 69%. MMP-9 was not detectable in the media of corticosteroid-treated explant organ cultures. The addition of 10 micrograms/ml of latanoprost to dexamethasone-treated cultures increased MMP-2 by 14%, MMP-3 by 43% and MMP-9 by 49%. Using immunohistochemistry we found staining with antibodies against MMP-2, -3, -9 and TIMP-1 and -2 within the ciliary body, and only to a lesser degree in the trabecular meshwork. Latanoprost treatment caused an increase of 29% in MMP-2 (p < 0.0001), 98% in MMP-3 (p < 0.0001) and 108% in MMP-9 (p < 0.0001). Dexamethasone reduced the staining for MMP-2 by 32% (p < 0.0001), for MMP-3 by 33% (p < 0.0001) and for MMP-9 by 83% (p < 0.0001). Almost no change in staining for MMPs was detectable in the trabecular meshwork. Neither latanoprost treatment nor dexamethasone induced significant changes (p < 0.93) in the secretion of TIMPs. In the media of non-treated retinal pigment epithelium (RPE) cells the only MMP detected was MMP-2. RPE cells in culture did not respond to either treatment with a change in their MMP secretion. CONCLUSION: We detected a profound upregulation of both MMP-3 and MMP-9 and a mild induction of MMP-2 through latanoprost in the ciliary body, but not the trabecular meshwork or RPE cells. Corticosteroids, on the other hand, downregulated MMP expression in both tissues. This inhibiting effect of corticosteroids on MMP production was reversed by latanoprost.

Aged↗

Association of the vitamin D receptor genotype BB with low bone density in hyperthyroidism.

Bone mineral density (BMD) is modulated by genetic and environmental factors or certain diseases. In several conditions such as low calcium intake, an influence of vitamin D receptor (VDR) polymorphisms on BMD has been suggested. In the present study, we investigated the relationship of Bsm I and Fok I polymorphisms of the VDR gene and BMD in patients with hyperthyroidism, a disease that often results in low BMD. Bsm I and Fok I genotypes were determined in 76 postmenopausal hyperthyroid patients and 62 healthy postmenopausal women as controls. Patients and controls were matched for age, time since menopause, and lifestyle factors and were free of estrogen medication. BMD evaluation included axial dual X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (PQCT). Low BMD was defined as -2.5 STD below the young adult mean value. Biochemical parameters investigated were thyroid hormones, osteocalcin, and 25-(OH)-vitamin D3 as well as routine laboratory data. Low BMD was found in 61% of hyperthyroid patients and in only 23% of euthyroid controls. In the group of hyperthyroid patients with low bone density, the BB genotype (VDR Bsm I polymorphisms) was significantly more frequent (39%) than in controls (13%; p = 0.003) and hyperthyroid patients with normal BMD (6%; p = 0.013). The odds ratio (OR) for low BMD in patients with BB genotype was 5.7 (95% CI, 1.7-19.1; p < 0.005) as compared with the Bb and bb genotypes and 5.5 (95% CI, 2.3-13.2; p < 0.0001) for hyperthyroidism alone. The cumulative risk for low BMD in patients with hyperthyroidism and BB genotype was 31.4 (95% CI, 3.9-256; p < 0.0003). VDR Fok I genotypes showed no significant relationship with BMD or other general or bone-specific parameters. Thus, hyperthyroidism and the genetic background of a BB genotype may promote synergistically the development of low BMD in hyperthyroid patients. Screening for the BB genotype in these patients therefore could help to identify those with particularly high risk for the development of low BMD and allow early treatment.

Absorptiometry, Photon↗

CD44 expression in sinonasal melanomas: is loss of isoform expression associated with advanced tumour stage?

The expression of the adhesion molecule CD44 was examined in 14 primary sinonasal melanomas (SMs), aggressive neoplasms with short survival times, as CD44 overexpression has been linked to poor survival in human cancers. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded sections with CD44 isoform-specific monoclonal antibodies to the CD44 standard (s) and variant isoforms (v) v5 and v6. CD44s, v5, and v6 were strongly expressed in a membranous pattern in SM in situ, early invasive SM, and in uninvolved respiratory/squamous epithelium. In invasive SM, membranous CD44s expression was identified in a large proportion of melanoma cells. Membranous staining of CD44v5 and v6 was lost in invasive SM, independently of the histological subtype. Diffuse cytoplasmic staining was observed focally in invasive SM and loss of cytoplasmic expression of CD44v6 and v5 was associated with advanced tumour stage in the linear-by-linear association test (p = 0.042 and 0.066, respectively). CD44s may not be important for malignant transformation, as it is expressed in both benign and malignant melanocytes. Loss of membranous CD44 isoform expression in widely invasive SM suggests that loss of cellular adhesion facilitates matrix and vascular infiltration and dissemination of sinonasal melanoma cells.

Adult↗

Methodological problems and the role of statistics in cluster response studies: a framework.

More and more citizens urge public health authorities to investigate reports of disease excess in their neighbourhood. These environmental concerns are legitimate and it is part of good public health practice to respond to these complaints. However, the methodological and practical problems are severe and a lot of controversy exists about the usefulness of these investigations. To clarify the possibilities and limitations in this situation, this paper proposes a typology of cluster studies. According to this framework, cluster response is distinguished from two other types of cluster studies: Cluster monitoring. screening proactively for clusters to act as an early warning system, and cluster research, scrutinizing clustering to generate and test aetiological hypotheses. To each of these three types of cluster studies corresponds a different public health context; respectively public health action, public health surveillance and public health research. Probably, part of the controversy mentioned stems from not acknowledging sufficiently the corresponding intrinsic differences in rationality and practical constraints. Cluster response is crisis management and not scientific research. In a relatively short time, an informed decision should be taken by a multidisciplinary team of experts using readily available information and knowledge. In accordance with this point of view, cluster reports should be handled stepwise and the role of statistics is to quantify a cluster exploring different points of view as an input to the decision process.

Cluster Analysis↗