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Biomedical subjects

H Schmidt

Publications and source records attributed to H Schmidt.

At least 37 records · Page 2Linked to original sources

Pubertal height gain in Ullrich-Turner syndrome.

Short stature and ovarian failure are the main features in Ullrich-Turner syndrome (UTS). The aim of this retrospective analysis was to evaluate the influence of age at initiation of puberty on final height. Sixty-five girls were treated with growth hormone (GH) and had a final height of 150.6 +/- 5.7 cm; 12/65 entered puberty spontaneously. A non-GH treated group of 12 girls with UTS reached a final height of 147.3 +/- 6.6 cm. Subdividing the GH treated group (n = 53) based on the age at induction of puberty, before or after 13 years, there was no significant difference in final height. Final height was affected by the age at which GH treatment was initiated, height SDS at the beginning of puberty, and by the duration of GH therapy. Therefore, early treatment with GH for short stature in UTS should be attempted so that an age adequate initiation of puberty will be feasible.

Adolescent↗

Neuropsychological sequelae of bacterial and viral meningitis.

Survivors of meningitis often complain about neurological and neuropsychological consequences. In this study, the extent of these sequelae was quantified and correlated to MRI findings. Neurological, neuropsychological and neuroradiological examinations were performed with adult patients younger than 70 years, 1-12 years after recovery from bacterial meningitis (BM; n = 59), or from viral meningitis (VM; n = 59). Patients with other potential causes for neuropsychological deficits (e.g. alcoholism) were carefully excluded. Patients were compared to 30 healthy subjects adjusted for age, gender and length of school education. With the exception of attention functions, both patient groups showed more frequently pathological results than the control group for all domains examined. Applying an overall cognitive sum score, patients after BM did not differ significantly in their performance from patients after VM. Separate analyses of various cognitive domains, however, revealed a higher rate of persistent disturbances in short-term and working memory after BM than after VM. Moreover, patients after BM exhibited greater impairment of executive functions. Associative learning of verbal material was also reduced. These deficits could not be ascribed to impaired alertness functions or decreased motivation in BM patients. Applying a logistic regression model, the neuropsychological outcome was related to the neurological outcome. Patients with a Glasgow Outcome Scale (GOS) of <5 had more frequently impaired test results for non-verbal learning and memory. GOS was also correlated with performance in executive functions. Brain volume was lower and ventricular volume was higher in the bacterial than in the VM group, and cerebral volume and the amount of white matter lesions of patients after BM were negatively correlated with short-term and working memory. In conclusion, patients after both BM and VM with favourable outcome showed affected learning and memory functions. More patients after BM than after VM displayed pathological short-term and working memory. BM resulted in poorer performance in executive functions, language, short-term memory and verbal learning/memory tests. As a result of neurological and neuropsychological sequelae, BM with a GOS > or = 4 led to decreased activities of daily living but only a minority of patients were disabled in a way that social functions were affected. The extent of neuropsychological sequelae of BM might have been overestimated in earlier studies which often had not been controlled for comorbidity factors such as alcoholism.

Activities of Daily Living↗

Dietary antioxidants in preventing atherogenesis.

Several naturally occurring constituents have received considerable attention because of their potential antioxidant activity. Consuming a diet rich in natural antioxidants has been associated with prevention from and/or treatment of atherosclerosis. Bioactive components of food, which are of special interest, include the Vitamins E and C, polyphenols, carotenoids-mainly lycopene and beta-carotene, and coenzyme Q10, featured by antioxidant properties. Antioxidant therapy is supposed to be effective in the early stages of atherosclerosis by preventing LDL oxidation and the oxidative lesion of endothelium. This review focuses on the effect of dietary antioxidants pertained to LDL oxidation and to the vascular endothelial dysfunction. Now that the human genome has been completely sequenced, genetic factors involved in oxidation may open new horizons to identify persons at risk for cardiovascular disease, allowing effective dietary intervention strategies to recover normal homeostasis and to prevent diet-related implications. On this basis, current studies on the action of selected antioxidant nutraceuticals on the activity of transcription factors, such as final targets in the signal transduction cascade and gene regulation, may emerge into new treatment concepts.

Animals↗

Elevated neutrophil and monocyte counts in peripheral blood are associated with poor survival in patients with metastatic melanoma: a prognostic model.

We aimed to create a prognostic model in metastatic melanoma based on independent prognostic factors in 321 patients receiving interleukin-2 (IL-2)-based immunotherapy with a median follow-up time for patients currently alive of 52 months (range 15-189 months). The patients were treated as part of several phase II protocols and the majority received treatment with intermediate dose subcutaneous IL-2 and interferon-alpha. Neutrophil and monocyte counts, lactate dehydrogenase (LDH), number of metastatic sites, location of metastases and performance status were all statistically significant prognostic factors in univariate analyses. Subsequently, a multivariate Cox's regression analysis identified elevated LDH (P<0.001, hazard ratio 2.8), elevated neutrophil counts (P=0.02, hazard ratio 1.4) and a performance status of 2 (P=0.008, hazard ratio 1.6) as independent prognostic factors for poor survival. An elevated monocyte count could replace an elevated neutrophil count. Patients were assigned to one of three risk groups according to the cumulative risk defined as the sum of simplified risk scores of the three independent prognostic factors. Low-, intermediate- and high-risk patients achieved a median survival of 12.6 months (95% confidence interval (CI), 11.4-13.8), 6.0 months (95% CI, 4.8-7.2) and 3.4 months (95% CI, 1.2-5.6), respectively. The low-risk group encompassed the majority of long-term survivors, whereas the patients in the high-risk group with a very poor prognosis should probably not be offered IL-2-based immunotherapy.

Adult↗

Risk factors for progression of brain atrophy in aging: six-year follow-up of normal subjects.

OBJECTIVES: To determine the rate of brain atrophy in neurologically asymptomatic elderly and to investigate the impact of baseline variables including conventional cerebrovascular risk factors, APOE epsilon4, and white matter hyperintensity (WMH) on its progression. METHODS: We assessed the brain parenchymal fraction at baseline and subsequent annual brain volume changes over 6 years for 201 participants (F/M = 96/105; 59.8 +/- 5.9 years) in the Austrian Stroke Prevention Study from 1.5-T MRI scans using SIENA (structural image evaluation using normalization of atrophy)/SIENAX (an adaptation of SIENA for cross-sectional measurement)(www.fmrib.ox.ac.uk/fsl). Hypertension, cardiac disease, diabetes mellitus, smoking, and regular alcohol intake were present in 64 (31.8%), 60 (29.9%), 5 (2.5%), 70 (39.3%), and 40 (20.7%) subjects, respectively. Plasma levels of fasting glucose (93.7 +/- 18.6 mg/dL), glycated hemoglobin A (HbA1c; 5.6 +/- 0.7%), total cholesterol (228.3 +/- 40.3 mg/dL), and triglycerides (127.0 +/- 75.2 mg/dL) were determined. WMH was rated as absent (n = 56), punctate (n = 120), early confluent (n = 14), and confluent (n = 11). RESULTS: The baseline brain parenchymal fraction of the entire cohort was 0.80 +/- 0.02 with a mean annual brain volume change of -0.40 +/- 0.29%. Univariate analysis demonstrated a higher rate of brain atrophy in older subjects (p = 0.0001), in those with higher HbA1c (p = 0.0001), higher body mass index (p = 0.02), high alcohol intake (p = 0.04), severe WMH (p = 0.03), and in APOE epsilon4 carriers (p = 0.07). Multivariate analysis suggested that baseline brain parenchymal fraction, HbA1c, and WMH score explain a major proportion of variance in the rates of brain atrophy in the cohort (corrected R2 = 0.27; p = 0.0001). CONCLUSIONS: Neurologically asymptomatic elderly experience continuing brain volume loss, which appears to accelerate with age. Glycated hemoglobin A (HbA1c) was identified as a risk factor for a greater rate of brain atrophy. Clustering of factors associated with the so-called metabolic syndrome in subjects with high HbA1c suggests a link between this syndrome and late-life brain tissue loss.

Age Distribution↗

[Reversible autonomic dysfunction in a young woman with septic multiple organ dysfunction syndrome].

HISTORY: A 24-year-old woman was admitted for treatment of a meningococcal infection accompanied by fulminant autonomic dysfunction. INVESTIGATIONS: Laboratory tests indicated acute renal failure and disseminated intravascular coagulopathy (creatinine 183 mmol, D-dimer 1.52 mg/l). The initial central venous oxygen saturation was 60-65%. The diagnosis of severe septic shock was supported by a high procalcitonin level of 66.7 ng/ml, CRP of 79.8 mg/l, and a WBC count of 12.2 Gpt/l. TREATMENT AND COURSE: Treatment of sepsis with antibiotics (ciprofloxacin, penicillin G, ceftriaxon and erythromycin in standard dosages), activated protein-C, hydrocortisone and GMA-embedded immunoglobulin led to complete cure and restoration of normal autonomic function. CONCLUSIONS: This case shows that even in multiple organ dysfunction syndrome autonomic dysfunction can occur which is improved by adequate treatment.

Adult↗

[Neurolisteriosis with acute myelitis].

Listeriosis is a bacterial infection with Listeria monocytogenes mostly affecting immunocompromised patients. In every fourth case, the CNS is involved, usually as meningoencephalitis. This case report of an immunocompetent woman represents the first one of neurolisteriosis initially presenting as cervical myelitis and progressing to supratentorial areas of the brain. Diagnosis was based on universal polymerase chain reaction from a cortical brain biopsy, followed by sequencing of the amplified rDNA gene. Under antibiotic treatment with gentamycin and ampicillin, the patient slowly recovered and has been improving ever since.

Acute Disease↗

Flavone initiates a hierarchical activation of the caspase-cascade in colon cancer cells.

There is emerging evidence that dietary factors can prevent cancer by affecting the process of carcinogenesis. Flavonoids present in vegetarian food possess antioxidant activities, have scavenging effects on activated carcinogens and mutagens, affect cell cycle progression and alter gene and protein expression. We report here that flavone, the core structure of the flavone subgroup, potently inhibits proliferation and induces apoptosis in HCT-116 colon cancer cells. Flavone induces the activation of caspases 2, 3, 8, 9 and 10 and a decrease of mitochondrial anti-apoptotic Bcl(2) protein expression. Further analysis revealed that caspase 10 activation is mediated via caspase 1. Additionally, treatment with flavone results in release of the mitochondrial apoptosis-inducing factor (AIF), the key trigger of caspase-independent apoptosis, into the cytosol. In summary, our data show that flavone induces apoptosis in a caspase-dependent and -independent manner.

Amino Acid Chloromethyl Ketones↗

Localized pulmonary infection associated with Mycobacterium tilburgii in an HIV-infected patient.

The case of an HIV-infected patient with low CD4+ cell count and localized pulmonary infection associated with Mycobacterium tilburgii, a recently recognized atypical mycobacterial species, is reported. Diagnosis was confirmed by repeated detection of mycobacterial DNA in lung biopsy specimens. After surgical removal of the pulmonary nodules, treatment with antimycobacterial combination therapy led to a complete and sustained recovery of the respiratory symptoms.M. tilburgii so far has only been described to cause disseminated infection in three patients, two of them suffering from acquired immunodeficiency syndrome. To our knowledge, this is the first report of localized pulmonary disease attributed to this mycobacterial species. As it responds to antimycobacterial combination therapy, efforts to establish the diagnosis using PCR methods in patients with suspected pulmonary disease due to mycobacteria other than tuberculosis should be undertaken.

AIDS-Related Opportunistic Infections↗

Fixed-dose single administration of Pegfilgrastim vs daily Filgrastim in patients with haematological malignancies undergoing autologous peripheral blood stem cell transplantation.

Infectious complications are frequent events in patients undergoing high-dose cytotoxic chemotherapy with subsequent autologous peripheral blood stem cell transplantation (PBSCT). To evaluate whether a single subcutaneous injection of pegfilgrastim (6 mg) is as safe and effective as daily filgrastim (5 mug/kg/day), 60 consecutive autologous stem cell transplantations performed for various haematological malignancies have been analysed. In total, 24 patients undergoing 30 consecutive PBSCT received a single subcutaneous injection of 6 mg pegfilgrastim on day 5 after transplantation and were compared retrospectively with 30 patients receiving 5 mug/kg/day of filgrastim starting from day 7 post transplantation. The mean duration of grade 4 neutropenia in the pegfilgrastim and filgrastim groups was 8.3 and 9.5 days, respectively (P=0.047). The results of the two groups were not significantly different for incidence of febrile neutropenia and toxicity profile. However, duration of febrile neutropenia (1.6 vs 3.0 days) and total days of fever (1.73 vs 4.1) were different (P=0.017 and 0.003, respectively), favouring the pegfilgrastim arm. Consequently, a higher incidence of transplants with documented infectious complications associated with the filgrastim group could be observed (56 vs 26%) (P=0.02). A single injection of pegfilgrastim administered at day 5 post transplant shows comparable safety and efficacy profiles to daily injections of filgrastim.

Adult↗

Wilson disease: high prevalence in a mountainous area of Crete.

Wilson disease (WD) is an autosomal recessive disorder of copper metabolism. The disorder is caused by mutations in the ATP7B gene, encoding a copper transporting P-type ATPase. The worldwide incidence is in the order of 30 cases per million, with a gene frequency of 0.56% and a carrier frequency of 1 in 90. The increased number of Wilson disease patients in the island of Crete led us to study the spectrum of mutations in a small village close to the city of Heraklion, from where many patients have been referred during the last 25 years. In order to estimate the frequency of the disease, we firstly investigated the number of births and the number of WD patients in the village since 1978. Six out of 90 births were diagnosed as WD patients, presenting the highest prevalence of WD reported so far. Analysis of the whole gene in three Wilson disease patients, and relatives of a boy who died from WD, led to the detection of 4 different point mutations. Two of them were missense (p.I1148T and p.G1176R) and cosegregated in cis in the same patient; the other allele of this patient carried a nonsense mutation (p.Q289X). This is the first report in the literature of three mutations co-segregating in the same WD patient. The fourth mutation identified was a novel frameshift mutation (c.398delT) with documented cosegregation. When screening 200 inhabitants originating from the same area, 18 were found to be carriers of one of these mutations. These findings indicate the need for health education intervention, genetic counselling and newborn screening for the Wilson disease.

Adenosine Triphosphatases↗

Juvenile granulosa cell tumour (JGCT) of the ovary in a 6-year-old girl: laparoscopic resection achieves long-term oncological success.

Juvenile granulosa cell tumours (JGCT) represent a rare malignancy in childhood and their laparoscopic resection has not been advocated yet. We report on a 6-year-old girl with signs of precocious pseudo-puberty and an abdominal tumour. Work-up revealed premature thelarche, vaginal discharge, elevated estrogen levels, and a solid tumour in the lower pelvis (6 x 4 x 3 cm in MRI). The girl underwent laparoscopy (3 ports, 5-mm instruments), during which a non-invasive, mobile tumour of the left ovary was found. Since all margins of resection could be clearly identified, salpingo-oophrectomy was performed, using the harmonic scalpel for dissection and 5-mm clips to ligate the fallopian tube. Histopathology revealed a JGCT with an intact capsule (FIGO 1 a) which required no further chemotherapy. Within 3 months postoperatively the girl's signs of precocious puberty had resolved and at present, after a follow-up of more than 3 years, there is no evidence of tumour recurrence. Minimally invasive surgery of solid ovarian tumours in children remains controversial. However in the present case, laparoscopic resection did not compromise the surgical and oncological safety.

Abdominal Pain↗

Advances in the molecular diagnosis of ochratoxin A-producing fungi.

Ochratoxin A (OTA) is detected worldwide in various food and feed sources. The compound is produced by Penicillium nordicum and P. verrucosum, as well as by various species within the sections Nigri and Circumdati of the genus Aspergillus, with A. ochraceus and A. carbonarius known to be the predominant producers. Recently, various pairs of PCR primers based on AFLP, RFLP, RAPD and the calmodulin gene were developed to set up novel diagnostic approaches for OTA producers in the Aspergillus and Penicillium genera. Real-time PCR assays based on well-characterized genomic sequences in A. ochraceus and P. nordicum have also been set up. Since the application of such assays to the analysis of contaminated sample material was demonstrated in only a few cases, future studies should be focused on applying such methods in rapid, robust and user-friendly applications, and implementing them in HACCP concepts. The recent detection and characterization of OTA biosynthetic pathway genes in the Penicillium genus is an important step towards understanding what mechanisms influence production of the toxin in order to redesign production processes in the food and feed industry and to keep de-novo synthesis to a minimum.

Aspergillus↗

Epidemic and endemic spread of Klebsiella pneumoniae producing SHV-5 beta-lactamase in Dubrava University Hospital, Zagreb, Croatia.

Plasmid-encoded resistance to broad-spectrum cephalosporins and aztreonam is becoming a widespread phenomenon in clinical medicine. These antibiotics are inactivated by an array of different extended-spectrum beta-lactamases (ESBLs) which have evolved by point mutations of parental TEM or SHV beta-lactamases. In a previous study conducted during 1994-1995, SHV-2, SHV-2a and SHV-5 beta-lactamases were found among Klebsiella pneumoniae isolates in Dubrava University Hospital. High prevalence of ESBLs among K. pneumoniae strains in this hospital (20%) required further investigation. In this investigation, beta-lactamases from 42 K. pneumoniae strains collected in 1997 and 15 in 2004 from Dubrava University Hospital, were characterized in order to study the evolution of plasmid-encoded resistance to extended-spectrum cephalosporins and aztreonam in that hospital over a prolonged study period. Susceptibility to antibiotics was determined by disk-diffusion and broth microdilution method. beta-lactamases were characterized by isoelectric focusing, determination of hydrolysis of beta-lactam substrates, polymerase chain reaction and sequencing of bla(SHV) genes. All K. pneumoniae strains and their Escherichia coli transconjugants produced beta-lactamase with an isoelectric point of 8.2. Based on sequencing of bla(SHV) genes enzymes of all transconjugants were identified as SHV-5 beta-lactamase which conferred on the producing isolates high level of ceftazidime and aztreonam resistance. In this study, an outbreak of nosocomial infections caused by SHV-5 producing K. pneumoniae was described in 1997 which evolved to endemic spread of SHV-5 producing K. pneumoniae due to multiple plasmid transfer in the Dubrava University Hospital. The strains from 1997 and 2004 were not clonally related. Hospital hygiene measures should be applied in order to control the spread of epidemic strains through the hospital wards and the consumption of the broad-spectrum cephalosporins needs to be restricted to reduce the selection pressure which enables the proliferation of ESBL producers in hospital.

Anti-Bacterial Agents↗

Comparative efficacy of local and systemic antibiotic treatment in lactating cows with clinical mastitis.

The intramuscular administration of penethamate hydriodide over 3 consecutive days and the intramammary administration of an ampicillin/cloxacillin combination were compared in lactating cows suffering from infectious clinical mastitis in one quarter, through an open, randomized, controlled multicenter field trial. Clinical examinations were carried out on d 1 (immediately before treatment), 3, 8, 17, and 22. Milk samples were taken from affected quarters for bacteriological analysis on d 1, 17, and 22, and from all quarters for somatic cell count (SCC) determination on d 1, 8, 17, and 22. There was no significant difference in bacteriological and clinical cure rates between the 2 treatment groups. The systemic treatment with penethamate resulted more frequently in a reduction of the milk SCC below the threshold of 250,000 cells/mL. This also occurred in the adjacent quarters not affected by clinical mastitis but with an SCC above 250,000 cells/mL before treatment. These findings suggest that the parenteral treatment with penethamate provides collateral cure on the quarters of the cows affected by subclinical mastitis. The number of quarters per cow affected by clinical or subclinical mastitis should be considered when selecting an antibiotic treatment by the local or systemic route.

Ampicillin↗

Musculoskeletal and functional muscle-bone analysis in children with rheumatic disease using peripheral quantitative computed tomography.

Bone demineralization is a severe complication of juvenile idiopathic arthritis (JIA) and other rheumatic diseases. To identify patients, who are at risk of bone disease, musculoskeletal analysis is performed. Furthermore, a more functional approach is needed to assess, whether bone strength is adequate for muscle force and whether muscle force is adequate for body size. In patients with a chronic disease it is most important to differentiate between primary bone problems and those that are secondary to low muscle force. To implement this approach, we measured musculoskeletal parameters of the radius in 94 patients with juvenile idiopathic arthritis of different subtypes and connective tissue disease using peripheral quantitative computed tomography. The four groups consisted of patients with oligoarticular (n = 31), polyarticular (n = 27), systemic JIA (n = 20) and connective tissue disease (CTD) (n = 16). All patients with systemic JIA and CTD and 56% of the patients with polyarticular JIA were under treatment with glucocorticoids. In general, the longer the duration of the disease and the more severe the subtype of the rheumatic disease, the shorter the height and the lower the bone density and bone strength parameters. Mean height, bone mineral content (BMC) and muscle cross-sectional area (CSA) were low for age, but muscle CSA was normal for height with the exception of patients with polyarticular disease. In the systemic JIA group the ratio of BMC per muscle CSA was decreased by -1.7+/-2.7 SD (P < 0.05), suggesting that bone strength was not adequately adapted to muscle force. This was even more expressed in females than in males (14 versus 3). These patients need closer follow up and potential specific therapeutic intervention.

Adolescent↗