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PubMed1999

Equity of renal replacement therapy utilization: a prospective population-based study.

This 1-year prospective survey assessed the incidence and characteristics of all patients starting renal replacement therapy (RRT) for end-stage renal disease in Scotland, and whether there is equity of utilization of RRT in terms of age, domicile and social circumstance. In the year studied, 104 patients per million population (533 patients) started RRT (390 per million population aged 65-75). In 23.5% the cause of ESRD could not be determined. Diabetes was the single most frequently identified cause (16%). The requirement for RRT rose with age, but over the country as a whole, patients aged over 75 years were under-represented. The majority of health boards provided RRT at a rate within 20% of the national rate. There was no difference in the median age at starting RRT between health boards. The spectrum of social deprivation of patients starting RRT was the same as that of the general population. There was no evidence that social deprivation influences acceptance on to the RRT program, although the relationship between ESRD and deprivation is complex. The utilization of RRT exceeded the minimum rate recommended by the Renal Association, although there was fluctuation between health board areas. The national requirement for resources to provide RRT is likely to rise further to care for an increasingly elderly population.

Adolescent↗
PubMedDate not supplied

Brimonidine .2% as a replacement for beta blockers in geriatric patients with glaucoma.

This 3-month multicenter, open-label study of 89 geriatric patients with glaucoma evaluated the substitution of brimonidine twice daily for topical beta blockers that had been used for at least 6 months. The primary outcome measures were reduction in intraocular pressure (IOP) from baseline at 2 hours postdose, change in cardiac and respiratory function, quality of life, and patient satisfaction. Patients were queried about adverse events at each visit and completed a quality-of-life questionnaire at the final evaluation. In this cohort with a mean age of 75.4 years, the average duration of topical beta-blocker therapy was 5 years. Brimonidine twice daily produced an additional mean reduction in IOP of 8.2% (1.4 mm Hg; P<.001). Eighty-eight percent of patients (60/68) reported being at least as satisfied with brimonidine as with their previous beta-blocker regimen, and 46% (31/68) reported greater satisfaction with brimonidine. Additionally, 40% of patients (27/68) noted increased energy after the switch, and 43% (29/68) described brimonidine as more soothing than topical beta blockers. In this elderly population, the replacement of topical beta blockers with brimonidine twice daily significantly decreased IOP, improved quality of life, and enhanced patient satisfaction.

Adrenergic alpha-Agonists↗
PubMed2005

Epidemiology of total knee replacement in the United States Medicare population.

BACKGROUND: There are limited population-based data on the utilization and outcomes of total knee replacement. The aim of the present study was to describe the rates of primary and revision total knee replacement and selected outcomes in persons older than sixty-five years of age in the United States. METHODS: Using Medicare claims, we computed annual incidence rates of unilateral elective primary and revision total knee replacement among United States Medicare beneficiaries in the year 2000. Poisson regression was used to assess the relationships between demographic characteristics and the incidence rates of primary and revision knee replacement. Proportional hazards models were used to examine the relationships between the ninety-day rates of complications and demographic and clinical factors. RESULTS: The rate of primary knee replacement was lower in blacks than in whites and in those qualifying for Medicaid supplementation than in those with higher incomes. The complications observed during the ninety days following primary knee replacement included mortality (0.7%), readmission (0.9%), pulmonary embolus (0.8%), wound infection (0.4%), pneumonia (1.4%), and myocardial infarction (0.8%). The complications observed during the ninety days following revision knee replacement were mortality (1.1%), readmission (4.7%), pulmonary embolus (0.5%), wound infection (1.8%), pneumonia (1.4%), and myocardial infarction (1.0%). Blacks had higher rates of mortality, readmission, and wound infection after primary knee replacement than whites did. Patients who qualified for Medicaid supplementation had higher complication rates, particularly after primary knee replacement. CONCLUSIONS: Overall, the rates of postoperative complications during the ninety days following total knee replacement are low. In the United States, blacks and individuals with low income undergo total knee replacement less frequently and generally have higher rates of adverse outcomes following primary knee replacement.

Aged↗
PubMed2005

Analysis of criteria for metabolic syndrome in a population-based study of Japanese-Brazilians.

OBJECTIVE: Criteria for metabolic syndrome (MS) differ particularly regarding the definition of central obesity and consequently, there could be differences in the assessment of cardiovascular risk. We estimated the prevalence of metabolic syndrome, compared the agreement of the World Health Organization (WHO) criteria with the standard and a modified National Cholesterol Education Program (NCEP) criterion and investigated whether additional factors were associated with the diagnosis of the syndrome in a Japanese descendant population. METHODS: In this cross-sectional, population-based survey, 1166 Japanese-Brazilians (533 men, 633 women) aged 57.4 +/- 12.4 years with mean body mass index (BMI) and waist of 25.2 +/- 4.0 kg/m(2) and 84.5 +/- 10.6 cm, respectively, were included. McNemar and kappa statistics were used to assess the concordance between WHO criteria with the standard and a modified NCEP criteria (waist of 90 and 80 cm, for men and women, respectively). In logistic regression analysis, a number of metabolic variables and albumin-to-creatinine ratio were included to test independent associations with metabolic syndrome defined by the modified NCEP criteria. RESULTS: According to WHO, 55.4% (95% CI 52.5-58.2%) of the subjects had MS and to NCEP 47.4% (95% CI 44.6-50.0%). WHO criterion detected 48.3% of central obese subjects while NCEP only 14.0%. Kappa statistics showed a good strength of agreement (k = 0.67, p < 0.01) between WHO and NCEP standard definitions of MS. Using the modified NCEP criterion for Asians, more subjects with metabolic syndrome were identified (58%) and agreement with WHO was improved (k = 0.72, p < 0.001). However, similar Framingham risk scores were attributed to the subsets of subjects classified by any of the three criteria. Areas under the receiver operating characteristic curves, obtained for the modified waist values to diagnose metabolic syndrome according to WHO, were > 0.80 and corresponded, respectively, to sensitivity and specificity of 63 and 83% for men and 77 and 72% for women. In final logistic regression model, age, male sex, BMI and homeostasis model assessment-insulin resistance but not with albumin-to-creatinine ratio (ACR) were independently associated with the syndrome. CONCLUSIONS: High prevalence of MS, independent of the criterion considered, was found in this Japanese-Brazilian population. The replacement of waist cutoff by those proposed by WHO for Asians lead to this diagnosis in a higher number of subjects with elevated cardiovascular risk. Our data did not support that ACR should be included in the classical definition of MS in Japanese descendants as previously suggested by WHO.

Adipose Tissue↗
PubMed1991

Transdermal oestrogen replacement therapy in a Finnish population.

In an open, multicentre study, transdermal administration of oestradiol (E2) by means of skin patches was investigated in a Finnish patient population suffering from typical post-menopausal symptoms. A total of 249 women applied a patch twice weekly for 6 months. Whereas 85% of the subjects were experiencing hot flushes and 83.5% sweating before therapy, only 5.7% and 11.8%, respectively, reported these symptoms at the end of the trial. Furthermore, 97.6%, 95.7% and 94.8% of the subjects reported that depression, headache and sleep disturbances, respectively, had disappeared during therapy. Skin irritation occurred in 18.2% of these predominantly fair-skinned women. Frequent sauna bathing did not interfere with the patch therapy. General acceptance of the treatment was excellent, 84.8% of the patients completing the treatment, of whom 78% were willing to continue the treatment after the trial. These results show that transdermal administration of E2 is effective in relieving post-menopausal symptoms. Local tolerability was good and the majority of the patients considered the transdermal treatment to be superior to their previous oral replacement therapy.

Administration, Cutaneous↗
PubMed2000

Influence of estrogen deficiency and replacement on T-cell populations in rat lymphoid tissues and organs.

Estrogen deficiency following ovariectomy or menopause results in bone loss. Although evidence strongly suggests that the immune system is involved in the pathogenesis of estrogen-deficient osteoporosis, it is not clear what role, if any, the T-lymphocyte plays in this process. Therefore, we examined the distribution of T-cell subsets in lymphoid organs and tissues, under varying estrogenic states in the rat. Six-month-old female Sprague-Dawley rats, ovariectomized (Ovx) and sham-operated, were randomized 5 d post-surgery into six groups to receive the following treatments: (A) sham/placebo; (B) sham/low-dose E2; (C) sham/high-dose E2; (D) Ovx/placebo; (E) Ovx/low-dose E2; (F) Ovx/high-dose E2. Half of the treated rats (groups A-F) were sacrificed on d 14; the remainder on d 28. Following euthanasia, mononuclear cells were isolated from the thymus, peripheral blood, spleen, lymph node and bone marrow, and were labeled for flow cytometric analysis using mouse anti-rat monoclonal antibodies directed against CD5, CD4, and CD8 antigenic markers. In the thymus, ovariectomy caused a dramatic increase and E2 treatment caused a dose-dependent decrease in weight that was proportional to the number of thymocytes. In the bone marrow, ovariectomy caused a significant reduction in the percentage of all T-cell subsets examined and this effect persisted throughout the duration of the study. Estrogen replacement therapy at the low-dose reversed the effects of ovariectomy and high-dose E2 treatment caused an increase in T-cell subsets in both the sham and Ovx groups, an effect that was more pronounced at d 14 compared with d 28. Although the percentages of some T-cell subsets in the other lymphoid organs/tissues were altered by ovariectomy or E2 treatment at d 0 and 14, all these changes had normalized by d 28 except for CD5 and CD4 cells in peripheral blood. In summary, with the exception of T-lymphocytes in the bone marrow, the effects of varying estrogenic states on T-cells were variable and transient. The influence of estrogen status on bone marrow T-lymphocytes suggests that these cells may play a role in mediating the effects of estrogen on bone turnover and warrant additional studies focusing on the functional role of T-cells in the bone marrow compartment.

Animals↗
PubMed1999

Postmenopausal estrogen replacement therapy and risk of AD: a population-based study.

OBJECTIVE: To study the association between estrogen replacement therapy in postmenopausal women and AD using a case-control design. BACKGROUND: Studies of the effect of estrogen therapy on the risk of AD have been limited and have yielded conflicting results. METHODS: Case patients were all postmenopausal women who developed AD in the quinquennium 1980 through 1984 in Rochester, MN (n = 222). One control subject from the same population and free of dementia was matched to each case patient by age (+/-3 years) and length of enrollment in the records-linkage system (n = 222). Estrogen exposure was defined as any form of estrogen (oral, parenteral, topical, suppository) used for at least 6 months after the onset of menopause and before the onset of AD (or corresponding year in the matched control subject). Information on dose and duration of use was abstracted. Consistent with the matched design, analyses entailed conditional logistic regression. RESULTS: AD patients and control subjects had identical age at menarche (median: 13.0 versus 13.0 years) and age at menopause (median: 50.0 versus 50.0 years). The frequency of estrogen use was higher among control subjects than AD patients (10% versus 5%; odds ratio = 0.42; 95% confidence interval 0.18 to 0.96; p = 0.04). There was a significant trend of decreasing odds ratios with increasing duration of use. The inverse association between estrogen therapy and AD remained significant after adjustment for education and age at menopause. CONCLUSION: These results from a population-based study suggest that estrogen replacement therapy is associated with a reduced risk of AD in postmenopausal women.

Adult↗
PubMed1996

Dopamine D4 receptor variant in Africans, D4valine194glycine, is insensitive to dopamine and clozapine: report of a homozygous individual.

The D4Valine194Glycine receptor is a variant of the dopamine D4 receptor and is found in 12.5% of the Afro-Caribbean population. Glycine replaces valine at a position one amino acid away from a serine which is critical for the attachment of dopamine. To determine whether this mutation had an effect on the properties of the dopamine D4 receptor, we constructed this variant and tested the sensitivity of the expressed protein with various drugs. We found that the variant receptor was two orders of magnitude less sensitive to dopamine, clozapine and olanzapine. The variant receptor was insensitive to guanine nucleotide, indicating the absence of a high-affinity state or functional state. The one 15-year-old individual found homozygous for this variant also had sickle cell disease. The patient revealed an overall pattern of low weight and no axillary or pubic hair.

Adolescent↗
PubMed2000

Familial hypercholesterolemia study in Sardinia using 6 LDLR polymorphic markers based on PCR.

Twenty-two Sardinian families with multiple cases of hypercholesterolemia were investigated with six polymorphic markers of the low-density lipoprotein receptor (LDLR) gene that could be quickly analyzed by PCR-based methods. Five single nucleotide polymorphisms (SNP) in exons 8, 10, 13, 15, and 18 and a microsatellite marker flanking the 3' end of the LDLR gene were used to define the haplotypes at the LDLR locus for familial hypercholesterolemia (FH) diagnosis within families. No significant differences were observed between the allele frequencies of the normal and mutant chromosomes. In two families, hypercholesterolemia did not cosegregate with the LDLR locus. In the remaining 20 FH chromosomes, seven different haplotypes were identified. The same haplotypes were found with a similar frequency among the 61 normal chromosomes. Other five haplotypes were characteristic only of normal chromosomes. These data provide no evidence for a gene founder effect in the Sardinian population and, instead, highlight a pattern of genetic heterogeneity comparable with that found in mainland European populations. The replacement of the restriction fragment length polymorphisms currently used in the genetic analysis of FH with PCR-based markers proved to be a simple and less time-consuming method and did not reduce informativity in the molecular analysis of FH families.

Alleles↗
PubMed2005

Taxonomic affinities and evolutionary history of the Early Pleistocene hominids of Java: dentognathic evidence.

Temporal changes, within-group variation, and phylogenetic positions of the Early Pleistocene Javanese hominids remain unclear. Recent debate focused on the age of the oldest Javanese hominids, but the argument so far includes little morphological basis for the fossils. To approach these questions, we analyzed a comprehensive dentognathic sample from Sangiran, which includes most of the existing hominid mandibles and teeth from the Early Pleistocene of Java. The sample was divided into chronologically younger and older groups. We examined morphological differences between these chronological groups, and investigated their affinities with other hominid groups from Africa and Eurasia. The results indicated that 1) there are remarkable morphological differences between the chronologically younger and older groups of Java, 2) the chronologically younger group is morphologically advanced, showing a similar degree of dentognathic reduction to that of Middle Pleistocene Chinese H. erectus, and 3) the chronologically older group exhibits some features that are equally primitive as or more primitive than early H. erectus of Africa. These findings suggest that the evolutionary history of early Javanese H. erectus was more dynamic than previously thought. Coupled with recent discoveries of the earliest form of H. erectus from Dmanisi, Georgia, the primitive aspects of the oldest Javanese hominid remains suggest that hominid groups prior to the grade of ca. 1.8-1.5 Ma African early H. erectus dispersed into eastern Eurasia during the earlier Early Pleistocene, although the age of the Javanese hominids themselves is yet to be resolved. Subsequent periods of the Early Pleistocene witnessed remarkable changes in the Javanese hominid record, which are ascribed either to significant in situ evolution or replacement of populations.

Adult↗
PubMed1991

Intraspinal transplants.

Transplants of embryonic central nervous system tissue have long been used to study axon growth during development and regeneration, and more recently to promote recovery in models of human diseases. Transplants of embryonic substantia nigra correct some of the deficits found in experimental Parkinson's disease, for example, by mechanisms that are thought to include release of neurotransmitter and reinnervation of host targets, as well as by stimulating growth of host axons. Similar mechanisms appear to allow intraspinal transplants of embryonic brainstem to reverse locomotor and autonomic deficits due to experimental spinal cord injuries. Embryonic spinal cord transplants offer an additional strategy for correcting the deficits of spinal cord injury because, by replacing damaged populations of neurons, they may mediate the restoration of connections between host neurons. We have found that spinal cord transplants permit regrowth of adult host axons resulting in reconstitution of synaptic complexes within the transplant that in many respects resemble normal synapses. Transplants of fetal spinal cord may also contribute to behavioral recovery by rescuing axotomized host neurons that otherwise would have died. Electrophysiological and behavioral investigations of functional recovery after intraspinal transplantation are preliminary, and the role of transplants in the treatment of human spinal cord injury is uncertain. Transplants are contributing to our understanding of the mechanisms of recovery, however, and are likely to play a role in the development of rational treatments.

Animals↗
PubMed2002

Selective specification of CNS stem cells into oligodendroglial or neuronal cell lineage: cell culture and transplant studies.

Neural stem cells (NSCs) were isolated from embryonic day 16 Sprague-Dawley rats and cultured in a novel serum-free stem cell medium that selected for the growth of NSCs and against the growth of GFAP(+) cells (astrocytes). NSCs maintained in culture for extended periods of time retained immunoreactivity for both nestin and PSA-NCAM, two markers characteristic of the stem cell phenotype. Moreover, using an oligodendrocyte (OL) specification medium, NSCs differentiated into OL as evidenced by their morphology and expression of multiple oligodendrocyte/myelin-specific markers. In addition, NSCs are capable of acquiring a neuronal phenotype as evidenced by expressing neuronal markers, such as neurofilament (NF) and NeuN when cultured in a defined medium for neurons indicating that these cells are also a good source of neuroblasts, which could be used to replace neuronal populations in the brain. We also showed successful propagation and differentiation of NSCs into OL after cryostorage, allowing for the later use of stored NSCs. The long-term goal of culturing NSCs and committed oligodendrocyte progenitors (OLP) is to obtain homogeneous populations for transplantation with the goal of remyelinating the myelin-deficient CNS. Our preliminary experiments carried out on normal and myelin deficient rats demonstrate that these cells survive and migrate extensively in both types of hosts. NSCs grafted as such, as well as cells derived from NSCs exposed to selective specification before grafting, are able to differentiate within the host brain. As expected, NSCs are capable of giving rise to astrocytes in a medium favoring this phenotype.

Animals↗
PubMed1993

Right ventricular function in early septic shock states.

OBJECTIVES: To define a variable which could reliably predict when fluid resuscitation as monotherapy is not expected to improve organ perfusion pressure, owing to limitations in cardiac output responsiveness in patients with severe sepsis. DESIGN: Prospective controlled trial. SETTING: Anesthesiological ICU in a university hospital. PATIENTS: Twenty seven patients in early septic shock states (MAP < 60 mmHg). INTERVENTIONS: Infusion therapy was titrated until no further increase in cardiac index and mean arterial pressure could be achieved. Fluid resuscitation as monotherapy was deemed unsuccessful at the end of 2 h if inotropic or vasoactive pharmacologic support was required to maintain a mean arterial pressure > 60 mmHg. MEASUREMENTS AND RESULTS: We investigated the hemodynamic course during fluid resuscitation (2850 +/- 210 ml crystalloids) with special emphasis on right heart function using the thermodilution technique. Eleven patients (group A) had a right ventricular (RV) ejection fraction below 45%. In this group positive inotropic and/or vasoactive drugs were obligatory to achieve and maintain a sufficient perfusion pressure (MAP > 60 mmHg) after fluid challenge. CONCLUSIONS: In 27 septic shock patients investigated, we diagnosed right ventricular dysfunction in 41%. In this specific patient population fluid replacement alone did not succeed in stabilizing hemodynamic variables, therefore necessitating catecholamine therapy.

Adult↗
PubMed1981

PWM-induced generation of immunoglobulin-secreting cells in patients with multiple myeloma.

The pokeweed-mitogen-induced transformation of B-lymphocytes into immunoglobulin-secreting cells was studied in vitro in 25 patients with multiple myeloma using a reverse hemolytic plaque assay. Fifteen patients showed a good response in generating immunoglobulin-secreting cells, whereas 10 patients showed a decreased B cell reactivity which was not due to intermittent melphalan/steroid therapy administered to 15 patients. Experiments with lymphocyte subpopulations demonstrated that the inability of some multiple-myeloma patients to generate immunoglobulin-secreting cells was always based on a defect in the B-cell subset. Co-culture experiments with lymphocytes from normal individuals and patients revealed a cell-mediated suppression in one case, whereas humoral suppressive factors in the patients' serum could not be observed using the reverse hemolytic plaque assay. Patients were classified into three groups: (a) patients with a normal B-cell function, (b) patients with a reversible, tumor-dependent suppression of B-cell reactivity and (c) patients in whom the normal B-cell population was replaced by non-reactive cells.

Adult↗
PubMed1996

Human central neurocytoma cells show neuronal physiological properties in vitro.

Central neurocytoma is a rare brain tumor composed of small round synaptophysin-positive cells, suggesting a neuronal origin of these tumor cells. Glial properties are inferred, however, from the observation that the tumor cells exhibit a strong morphological similarity to oligodendroglioma cells and show an astrocytic differentiation in vitro. To test for neuronal or glial physiological properties, we studied cultured neurocytoma cells derived from a surgical specimen from a 44-year-old man, employing the patch-clamp technique. Early primary cultures were composed of morphologically unique bi- or multipolar cells which were positive for synaptophysin and negative for the astrocyte marker glial fibrillary acidic protein. In the majority of these cells, whole-cell membrane current recordings revealed physiological properties of neurons, i.e., a high density of Na+ currents, the capacity to generate action potentials, and the expression of inotropic neurotransmitter receptors. Metabotropic neurotransmitter receptors could be demonstrated by Ca2+ imaging techniques. The remaining bi- or multipolar cells and almost all cells in later culture stages and in vitro passage lacked these neuronal properties and showed physiological features characteristic of glial cells. We conclude that the major population of neurocytoma cells shows physiological properties of neurons and that with time in culture this population is replaced by electrically passive cells.

Action Potentials↗
PubMed2002

The utility of functional magnetic resonance imaging in epilepsy and language.

Functional magnetic resonance imaging (fMRI) is a viable presurgical tool for use with the pediatric epilepsy population as replacement for the intra-carotid sodium amobarbital test (IAT) used to identify hemispheric language dominance. This paper reviews the current imaging research on the identification of language cortex in pediatric epilepsy patients and in normal children. A review of the literature comparing fMRI to the IAT and electrocortical stimulation suggests that fMRI reliably identifies the dominant hemisphere, with pediatric and adult studies producing comparable results. Within-hemisphere localization of eloquent cortex with fMRI is more problematic. Paradigm selection, data analysis techniques, and considerations specific to imaging children are discussed. Utility of fMRI for studying neural plasticity as a result of brain insult (e.g., epilepsy) is also considered.

Brain↗
PubMed1986

Token swap test of significance for serial medical data bases.

Established tests of statistical significance are based upon the concept that observed data are drawn randomly from a larger, perhaps infinite source population. The significance value, p, is the probability that the observations are drawn from a source population satisfying the null hypothesis; if p is small enough (less than 5 percent, 1 percent, etc.), then the null hypothesis is rejected. Serial medical data bases, such as a hospital clinic intake or autopsy case accessions, often do not have an identifiable source population from which they are randomly drawn. In an effort to make a reasonable interpretation of these less-than-ideal data, this report introduces a "token swap" test of significance, in which the usual paradigm of repeated drawing from a source population is replaced by a paradigm or misclassification within the observed data themselves. The token swap test consists of rearranging the data into a balanced distribution, and determining the disparity between the observed and the balanced distribution of data. In a two-by-two contingency table, patients are represented as "tokens" distributed into four "cells." Significance is determined by the proportion of "token swaps" that are able to transform the balanced table into the observed table. The token swap test was applied to three series of autopsy observations, and gave results roughly comparable to the corresponding (two-tail) chi-square and one-tail Fisher exact tests. The token swap test of significance may be a useful alternative to classic statistical tests when the limiting assumptions of a retrospective, serial medical data base are present.

Computer-Assisted Instruction↗
PubMed1991

Basic algorithms for random sampling and treatment randomization.

Five BASIC programs to select random samples from populations or to randomize treatments are presented. Program 1 is used to obtain randomization of any number of treatments in an equal number of positions or test units for any number of replicates. Program 2 produces latin squares of any size for treatment randomization. Program 3 is used to obtain a specific number of randomly selected samples from a population without replacement. Program 4 produces quasi-latin squares that have treatments repeated equally in all rows and columns, with identical treatments either spaced or not. Program 5 can be used with any size grid to place 3-100 treatments in equal proportions and with spacing of identical treatments. Both programs 4 and 5 allow for horizontal and vertical separation between identical treatments at sampling places while still retaining the quality of randomness. These programs should facilitate random sampling and randomization procedures which are required to correctly analyze experiments by the methods of statistical probability.

Algorithms↗