Basal ganglia involvement of a patient with SCA 17--a new form of autosomal dominant spinocerebellar ataxia.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
J Schwarz
Publications and source records attributed to J Schwarz.
Dopamine transporter: involvement in selective dopaminergic neurotoxicity and degeneration.
The carrier molecule that transports dopamine (DA) into dopamine neurons by an electrogenic, Na(+)- and Cl(-)-transport-coupled mechanism is known as the dopamine transporter (DAT). This uptake system is exclusively expressed in DA neurons with significantly higher levels of DAT expression in cells of the substantia nigra pars compacta than those of the ventral tegmental area and arcuate hypothalamic neurons. The expression density of DAT strongly correlates with the extent of DA cell loss in Parkinson's disease (PD). There are also DAT gene polymorphisms associated with PD. These data suggest a role of the DAT in the pathogenesis of PD. Though selective for its respective neurotransmitter, the DAT can also transport synthetic/natural analogues of the transmitter. Should such compounds interact with vital intracellular structures, their penetration into the neuron might have significant consequences. This sequence of toxic events could indeed demonstrated for the synthetic toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which produces selective degeneration of DA neurons characteristic of PD. Dopaminergic toxicity of its active metabolite 1-methyl-4-pyridinium (MPP(+)) is mediated by the DAT through accumulation into DA neurons, where it inhibits mitochondrial complex I activity. Various endogenous and exogenous heterocyclic molecules, which are structurally related to MPTP/MPP(+), such as isoquinolines and beta-carbolines, have been reported to exhibit similar toxic properties on DA cells, which are conferred by their uptake by the DAT. Taken together, there is large body of evidence from morphological, molecular biological and toxicological studies indicating that the DAT might be responsible for the selectivity of DA cell death in PD.
Animals↗
Serum parathyroid hormone predicts time to fall independent of vitamin D status in a frail elderly population.
Very frail older people constitute an increasing proportion of ageing populations and often have vitamin D deficiency. Falls are frequent in this population and have usually been associated with vitamin D deficiency. In this prospective study we measured serum 25-hydroxyvitamin D (25OHD), serum PTH, and falls in 637 ambulatory subjects living in institutional aged care facilities (intermediate-care hostels or nursing homes). The study sample comprised 121 men (mean age, 82.1 yr) and 516 women (mean age, 86.7 yr). Two hundred and seventy-four subjects fell one or more times over a mean duration of follow-up of 10.2 months. Vitamin D deficiency, defined as a serum 25OHD level below 39 nmol/liter was present in 73.6%. Baseline serum 25OHD and PTH were significantly associated with falls in univariate analyses. In multivariate analyses that also corrected for balance and health status, PTH remained a significant predictor of falls independent of 25OHD. Serum PTH is a predictor of time to first fall in the frail elderly independent of vitamin D status and measures of general health.
Accidental Falls↗
Serum parathyroid hormone is associated with increased mortality independent of 25-hydroxy vitamin d status, bone mass, and renal function in the frail and very old: a cohort study.
Very frail older people constitute an increasing proportion of the aging population and often have vitamin D deficiency and impaired renal function. Primary hyperparathyroidism has been associated with increased mortality, but it is unclear whether secondary hyperparathyroidism is associated with increased mortality independent of renal function and vitamin D status. This study aimed to examine the effect of vitamin D deficiency and secondary hyperparathyroidism on mortality in frail older people after accounting for renal function and general measures of health. We evaluated 842 subjects (182 men with a mean age of 81.9 yr and 660 women with a mean age of 86.2 yr) living in residential aged care facilities in Sydney, Australia in a prospective, cohort study. Over a mean duration of follow-up of 31 months, 345 subjects died. Baseline serum 25-hydroxy vitamin D, serum PTH, and bone ultrasound attenuation were significantly associated with mortality in univariate and multivariate analyses (for PTH, a hazard ratio of 1.39 for time to death) after correcting for age and gender. In multivariate analyses that corrected for health status, nutritional status, and renal function, PTH remained a significant predictor of mortality but not 25-hydroxy vitamin D or bone ultrasound attenuation. Serum PTH appears to be associated with increased mortality in the frail elderly independent of vitamin D status, renal function, bone mass, and measures of general health. The mechanism of this effect requires further investigation.
Aged↗
[Gastric carcinoma and D2 lymphadenectomy--technique and possible complications].
Lymphadenectomy in gastric cancer became vital and obligatory part of staging procedure. Therapeutic effect of lymphadenectomy with patient's prognosis improvement still remains uncertain. In subgroups, extensive lymphadenectomy enhance radicality of the procedure, enables to reach R0 resection in the area of tumour bed and hopefully improves survival. D2 lymphadenectomy is now becoming as a standard also in our country. Technique and possible complications of D2 lymphadenectomy are the matter of this article.
Adult↗
Helicobacter heilmannii gastroduodenal disease and clinical aspects in children with dyspeptic symptoms.
AIM: To evaluate the occurrence and clinical characteristics of Helicobacter heilmannii infection among children presenting with dyspeptic symptoms. METHOD: Prospective cohort study of 580 patients. RESULTS: Of all examined dyspeptic children, 26.4% were infected with spiral-shaped organisms, and 0.9% of patients were found to be infected with spiral H. heilmannii-like organisms. CONCLUSION: In children with dyspeptic symptoms, the possible presence of gastroduodenal disease due to H. heilmannii should be considered. Further studies are needed to clarify H. heilmannii-related gastroduodenal pathology in the paediatric population.
Adolescent↗
[11C](R)-PK11195 PET imaging of microglial activation in multiple system atrophy.
Microglia, the brain's intrinsic macrophages, bind (R)-PK11195 when activated by neuronal injury. The authors used [11C](R)-PK11195 PET to localize in vivo microglial activation in patients with multiple system atrophy (MSA). Increased [11C](R)-PK11195 binding was primarily found in the dorsolateral prefrontal cortex, putamen, pallidum, pons, and substantia nigra, reflecting the known distribution of neuropathologic changes in MSA. Providing an indicator of disease activity, [11C](R)-PK11195 PET can thus be used to characterize the in vivo neuropathology of MSA.
Aged↗
[Association of parathyroid adenoma and malignant blood disease].
Explore the source record for details and available documents.
Adenoma↗
[Expression of cyclin-dependent kinase inhibitors in leukemia].
BACKGROUND: Leukemias develop due to defects in proliferation, differentiation and apoptosis, which take place in stem cells or progenitors of hematopoiesis. These processes have several crossing points, one of them is the role of inhibitors of cyclin-dependent kinases. The aim of this study was to study the expression of cyclin-dependent kinases inhibitors p21 Cip and p27 Kip and expression of proliferative antigen Ki-67 in leukocytes of human leukemia. METHODS AND RESULTS: The expression of cyclin-dependent kinases inhibitors was detected at mRNA level mainly by comparative reverse-transcription polymerase chain reaction and in selected samples also by the real-time polymerase chain reaction. While p27 Kip expression in leukocytes of leukemic patients and healthy persons was universal, large differences in expression of p21 Cip were found both among individual patients of the same type of leukemia and between different types of leukemias and healthy persons. The p21 Cip expression was significantly higher in acute leukemias than in chronic ones and healthy persons. A comparison of p21 Cip expression with the clinical outcome of the leukemic patients showed that the group of 14 acute leukemia patients surviving more than 30 months had a significantly lower expression of p21 Cip than 12 patients of this type of leukemia who died within this time limit. Moreover, the results obtained on a smaller set of acute promyelocytic leukemia patients indicated that the lower p21 expression is connected with a better prognosis. CONCLUSION: Our results pointed out the importance of the cyclin-dependent kinase inhibitor p21 Cip in human leukemias and indicated that the lower p21 Cip expression might be a positive prognostic factor in acute myeloid leukemia patients.
Cell Cycle Proteins↗
Sentinel node biopsy in gastric cancer: preliminary results.
BACKGROUND: Extent of lymphadenectomy in gastric cancer is one of the still unresolved and ongoing questions. Whether extensive procedures lead to better survival remains controversial. The detection of sentinel node could become a helpful method to define the desirable extent of lymph node dissection for each particular patient. MATERIAL AND METHODS: Prospective, single-centre, clinical trial. Sentinel node is identified using vital blue dye. After performance of D2 lymphadenectomy, the pathologist minutely investigates all lymphatic nodes by histological and immunohistochemistry techniques. RESULTS: During a period of 36 months, an attempt to localise the sentinel node for biopsy was made in 22 patients. The successful rate of sentinel node detection with a good relation between metastatic involvement of the sentinel node and other nodes was 56% (13 out of 22 patients). All these patients suffered from small tumours and early stage of the disease. In large tumours and advanced stages, blue dye stained the tissue around the tumour diffusely rendering the identification of true sentinel node impossible. Fresh frozen section of the sentinel node resulted in two patients in a false negative outcome because of micrometastatic involvement. CONCLUSIONS: Sentinel node biopsy in gastric cancer using vital staining is a feasible method. Reliable results were seen in early stage of the disease. Fresh frozen section of sentinel node has probably a low sensitivity for detection of micrometastases.
Feasibility Studies↗
[Lymphocyte immunophenotyping and cytogenetics for more precise prognosis in patients with type B chronic lymphatic leukemia].
BACKGROUND: The B-chronic lymphocytic leukemia (B-CLL) has highly variable prognosis. Possibility of more relevant prognosis has a great impact for the beginning and mode of therapy. METHODS AND RESULTS: One hundred patients diagnosed as having B-CLL were included into the study. Beside usual examinations necessary to establish the diagnosis, cytogenetic examination for the detection of deletion 13q14, 17p13, 11q23 and trisomy 12 and immunophenotyping was done. The mean age of the patients was 58.2 years, there were 62 men and 38 women. 91 evaluated patients were divided into two groups--those with the steady disease (55 pts) and those with progressive disease (36 pts). No relation between the number of cytogenetic abnormalities and the Rai stage of the disease was found. We identified a relation between the bone marrow infiltration pattern (diffuse) and the number of cytogenetic abnormalities and the del 13q14 (p.05). Using the immunophenotyping of the lymphocytes we found a relation between the expression of CD38 and CD11c and the disease progression (p < 0.05). Neither of the method (FISH and immunophenotyping) revealed differences between results from bone marrow samples and those from peripheral blood. CONCLUSIONS: Though the cytogenetic (FISH) and immunophenotype evaluation at the time of diagnosis did not improve the ability to define better the clinical course of the B-CLL, we suggest to use both methods routinely as an important tool to identify patients who would develop the progressive disease.
Adult↗
[Ultrasonography as an auxiliary method in diagnosis of acute appendicitis].
The diagnosis of acute appendicitis remains a difficult task for even the experienced surgeon. For this reason every supplementary examination affords help for the surgeon its diagnosis. The goal of our study was to evaluate the significance of ultrasonography (USG) in diagnosing right lower quadrant abdominal pain. 204 patients admitted for suspect acute appendicitis were evaluated retrospectively. The accuracy of USG was studied by comparing this finding with preoperative, histopathological findings respectively. In comparison leucocytosis was also studied. In our studied cohort, USG examination had a sensitivity of 88.4% and specificity of 93.0%. Leucocytosis for diagnosis gave a sensitivity of 88.6% and specificity of 60.0%.
Acute Disease↗
[Lymphadenectomy in gastric carcinoma--present status, new trends and personal experience].
The only hope for long time survival in gastric cancer is radical surgery with complete tumour removal. Lymphadenectomy as a part of surgical procedure helps to remove tumour completely. The value of lymphadenectomy for staging is clear and surgeons have no doubt about it. Therapeutic effect of lymphadenectomy with improvement of the prognosis remains uncertain. In this work we would like to discuss current trends in lymphadenectomy in gastric cancer, especially evaluating the value and extent of the procedure.
Adult↗
[Diagnosis of Helicobacter pylori infection in childhood with a novel immunoenzyme method (HpStAR) which detects antigens in feces using monoclonal antibodies ].
BACKGROUND: Premier Platinum HpSA EIA is an enzyme immunoassay developed for diagnosis of H. pylori infection using polyclonal antibodies against H. pylori in human stool. A new H. pylori stool antigen test, based on monoclonal antibodies, has been developed. Our aim was to evaluate prospectively the accuracy of the novel antigen stool test (DAKO HpStAR) using monoclonal antibodies for detection of H. pylori infection in children. METHODS AND RESULTS: Total of 93 children undergoing upper gastrointestinal endoscopy were included in the study. Biopsy specimens were sampled from the gastric antrum and from the corpus. Patients were classified as H. pylori positive if histology and urease test were positive. All children provided a stool sample within 3 days after gastroscopy. IgG serology against H. pylori was also employed. HpStAR test was performed according to the manufacturers protocol. Results were read at 450/630 nm by spectrophotometry (cut-off point 0.150). Of the 93 children, 26 were H. pylori positive (13.1 +/- 3.2 yr), and 67 patients were H. pylori negative (12.8 +/- 4.7 yr). Only 2 children were misclassified (1 false negative, and 1 false positive). Sensitivity was 96.1%, specificity 98.5%, the positive and negative predicting values were 96.1% and 98.5%, respectively. Serology showed sensitivity 88.5%, specificity 70.2%; the positive and negative predicting values were 53.5% and 94% respectively. CONCLUSION: HpStAR test based on monoclonal antibodies can be considered an accurate, non-invasive, reliable method for the diagnosis of H. pylori infection in children.
Adolescent↗
Quantitative ultrasound of the calcaneus and falls risk in the institutionalized elderly: sex differences and relationship to vitamin D status.
Very frail older people constitute an increasing proportion of aging populations and are likely to contribute substantially to costs due to osteoporosis. Quantitative ultrasound (QUS) of the calcaneus is potentially a simple method for assessing fracture risk in frail elderly, but there have been few studies of male/female differences in QUS or its relationship to falls risk or vitamin D status, which is often subnormal in this population. We studied QUS, falls risk and serum 25(OH)-vitamin D in subjects living in institutional aged care facilities (hostels or nursing homes). The study sample comprised 294 men (mean age 81.2 years, range 65-102 years) and 899 women (mean age 86.7 years, range 65-104 years). Broadband ultrasound attenuation (BUA) and velocity of sound (VOS) were higher in men than women by approximately 30% and 2% respectively ( p<0.0001) and this difference was maintained at all ages. Serum 25(OH)D levels were higher in men than women ( p<0.001) but vitamin D deficiency was very common in both sexes and serum 25(OH)D was not associated with QUS in either sex. There was no significant decline in BUA or VOS with age in men; however, for women BUA declined by 2.8-4.7% per decade and VOS by 1% per decade (both p<0.001). Mean BUA T-scores were -1.55 and -2.48 at age 90 years in men and women. Quadriceps strength and weight but not serum 25(OH)D were significantly associated with BUA. These data suggest only minor loss occurs at the calcaneal site in BUA and VOS with very old age in either sex.
Accidental Falls↗
Current state of stem cell research for the treatment of Parkinson's disease.
Current findings suggest that multipotent stem cells may be suitable for cell replacement therapies in the treatment of neurodegenerative disorders. Embryonic stem (ES) cells are pluripotent cells isolated from the inner cell mass of the preimplantation blastocyst, which give rise to all cells in the organism. Similarly, multipotent stem cells are also able to regenerate, but are believed to have a more restricted potential than ES cells, and are often defined by the organ from which they are derived. Neural stem cells have been categorized as multipotent stem cells derived from the nervous system with the capacity to regenerate and to give rise to cells belonging to all three cell lineages in the nervous system: neurons, oligodendrocytes, and astrocytes. It is hoped that research on stem cells may reveal methods for producing an infinite supply of dopamine neurons for transplant into Parkinson's disease (PD) patients. The problem is controlling cell growth and differentiation. We will briefly review the current state of stem cell research and will critically discuss the potential of stem cells for the treatment of PD.
Brain Tissue Transplantation↗
Practical importance of neuroprotection in Parkinson's disease.
Consensus could be reached that there is overwhelming evidence of preclinical neuroprotection. However, the evidence of neuroprotection/neurorescue under clinical conditions is limited. Lessons from clinical trials designed to show neuroprotection (selegiline, amantadine, dopamine agonists) demonstrate that with the drugs available neuroprotection/neurorescue has to start as early as possible. A PET-controlled clinical trial with ropinirole shows that there seems to be a good chance for neuroprotection in the early phase of Parkinson's disease in patients treated from the very beginning of the disease while there is no such benefit in patients with a late start of a neuroprotective therapeutic strategy. Also long-term clinical neuroprotection cannot be reached. Complicating factors to demonstrate clinical neuroprotection are discussed.
Amantadine↗
Steele-Richardson-Olszewski-syndrome: the relation of dopamine D2 receptor binding and subcortical lesions in MRI.
We compared (123)I-iodobenzamide single photon emission computed tomography (IBZM-SPECT) for imaging of striatal dopamine D(2) receptors in vivo, and MRI in 32 patients with the clinical diagnosis of progressive supranuclear palsy (PSP). We found a significant inter-dependence of reduction of specific striatal IBZM binding indicative of striatal degeneration and of the absence of multiple signal hyperintensities in MRI; age had no influence neither on IBZM binding nor on signal hyperintensities. We conclude that the presence of multiple signal hyperintensities should raise doubt on the correct clinical diagnosis.
Aged↗