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Biomedical subjects

I Stein

Publications and source records attributed to I Stein.

At least 19 recordsLinked to original sources

Selection of continence products: perspectives of people who have incontinence and their carers.

PURPOSE: The needs, issues and concerns of people with incontinence and their carers were explored in order to inform the development of a comprehensive Australian consumer guide to continence products. PARTICIPANTS AND METHODS: Semi-structured interviews and focus groups were conducted with a wide range of people with incontinence and carers. Questions centred around issues and concerns regarding continence product selection, what information people need to make informed choices, and how the information should be presented. Qualitative analysis highlighted common themes and specific issues. RESULTS: Issues raised by consumers included the paucity of written information currently available, ignorance among health professionals concerning continence products and the lack of information about sources of help. Most consumers selected products by trial and error and were unaware of the range of products and services available. They wanted a consumer guide to continence products to be user-friendly and easily accessible, with information on product availability, cost, quality, comfort and design. They also wanted more general information on incontinence, sources of help, and how to select, care for and dispose of products. Participants wanted the guide to be made available in different languages, in large print and simple language. CONCLUSIONS: The findings highlight the need and provide a framework for a consumer guide and information on continence products.

Australia↗

The application of the potassium-titanyl-phosphate (KTP) laser in the management of subglottic hemangioma.

BACKGROUND: Subglottic hemangioma is the most common neoplasm of the infant airway. Most lesions involute spontaneously; however, some may grow to cause life-threatening respiratory tract distress. The standards of treatment have been tracheotomy, corticosteroids, and laser vaporization. However, use of the carbon dioxide laser has been associated with increased risk of damage to adjacent mucosa and an increased risk for the development of subglottic stenosis postoperatively. OBJECTIVE: To review our experience with the use of the potassium-titanyl-phosphate laser in the treatment of subglottic hemangioma. PATIENTS AND METHODS: A retrospective review of 6 patients with subglottic hemangioma treated with the potassium-titanyl-phosphate laser was carried out at a tertiary care children's hospital. Patients' medical charts were evaluated for factors such as age, sex, degree of airway obstruction, location of hemangioma, number of laser procedures performed, and postoperative results, including short- and long-term complications. RESULTS: All 6 patients had significant relief of airway obstruction after use of the potassium-titanyl-phosphate laser. Five of the patients had localized disease, and one had circumferential subglottic involvement. The average number of procedures was 1.7. There were no intraoperative complications. One patient had prolonged intubation following surgery, and only one developed grade 1 subglottic stenosis requiring dilation. Long-term results have been promising in that all patients are asymptomatic and follow-up laryngoscopy and bronchoscopy have shown complete resolution of the hemangioma. CONCLUSION: The potassium-titanyl-phosphate laser can be used to provide significant clinical relief of airway obstruction due to grade 1 and 2 subglottic hemangioma, with minimal complications.

Child, Preschool↗

Towards (re)conciliation: (re)constructing relationships between indigenous health workers and nurses.

Currently in Australia, both Aboriginal and non-Aboriginal Australians are attempting to reconcile themselves with a history of colonization/invasion, which resulted in human rights violations against Australia's indigenous people. Australian nursing has to examine its past in relation to the treatment of Aboriginal Australians. Relationships between nurses and Aboriginal health workers are the most commonly occurring professional relationships between nurses and Aboriginal people and are of key importance to the successful delivery of health services to Aboriginal communities. This qualitative study, grounded in feminism, aimed to explore the professional relationships between Aboriginal health workers and nurses and to develop insights which could assist the Australian nursing profession through a process of reconciliation with Aboriginal Australians. Feminist analysis of narrative text revealed several key themes as being crucial to this process. These were: learning to know and understand; towards workplace equity; and skill sharing -- learning from each other. Implications for nursing, in its journey toward reconciliation with Aboriginal Australians, are drawn from this study.

Australia↗

Postacute care for older aboriginal people: an exploratory-descriptive study.

Many Aboriginal people reside in rural and remote Australia. Aboriginal health workers were the informants in this exploratory-descriptive study, which explored issues pertaining to postacute care for older Aboriginal people. Qualitative analysis of interview data revealed several issues were viewed as being of crucial importance in the provision of effective postacute services to older Aboriginal people. These were: (i) identification of Aboriginality; (ii) perceived racism and stereotypical attitudes among hospital staff and healthcare workers; and (iii) effective discharge planning. Other issues which were believed to impact upon service use were identified as: (i) availability of services; (ii) knowledge of services and level of use; and (iii) the notion of mainstream versus Aboriginal-specific services. Findings are discussed in relation to available literature. Implications for further research are drawn from the findings of this exploratory study.

Aged↗

The antiangiogenic agent linomide inhibits the growth rate of von Hippel-Lindau paraganglioma xenografts to mice.

The aim of this study was to ascertain the potential usefulness of the antiangiogenic compound linomide for treatment of von Hippel-Lindau (VHL)-related tumors. Paraganglioma tissue fragments obtained at surgery from a VHL type 2a patient were transplanted s.c. to male BALB/c nu/nu (nude) mice: (a) 2-3-mm fragments for "prevention" experiments; and (b) 2-3-mm fragments allowed to grow to 1 cm for "intervention" studies. Both groups received either 0.5 mg/ml linomide in drinking water or acidified water and were followed until tumor diameter reached 3 cm or for 4 weeks. In both the prevention and intervention experiments, a significant diminution of tumor size and weight was observed in the drug-treated animals. In vivo nuclear magnetic resonance analysis of tumor blood flow in linomide-treated animals showed localization of blood vessels almost exclusively to the periphery of the poorly vascularized tumors with a significant reduction of both vascular functionality and vasodilation. Histological examination of tumors from linomide-treated animals revealed marked avascularity. Treated animals also displayed a 2.4-fold reduction of tumor vascular endothelial growth factor mRNA levels. Taken together, our data indicate that in VHL disease, therapy directed at inhibition of constitutively expressed VEGF induction of angiogenesis by VHL tumors may constitute an effective medical treatment.

Administration, Oral↗

Intercellular communication between vascular smooth muscle and endothelial cells mediated by heparin-binding epidermal growth factor-like growth factor and vascular endothelial growth factor.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF), a potent mitogen and migration factor for vascular smooth muscle cells (SMC), promoted neovascularization in vivo in the rabbit cornea. MRI demonstrated quantitatively the angiogenic effect of HB-EGF when introduced subcutaneously into nude mice. HB-EGF is not directly mitogenic to endothelial cells but it induced the migration of bovine endothelial cells and release of endothelial cell mitogenic activity from bovine vascular SMC. This mitogenic activity was specifically blocked by neutralizing anti-vascular endothelial growth factor (VEGF) antibodies. In contrast, EGF or transforming growth factor-alpha (TGF-alpha) had almost no effect on release of endothelial mitogenicity from SMC. In addition, RT-PCR analysis demonstrated that VEGF165 mRNA levels were increased in vascular SMC 4-10-fold by 0.35-2 nM of HB-EGF, respectively. Our data suggest that HB-EGF, as a mediator of intercellular communication, may play a new important role in supporting wound healing, tumor progression and atherosclerosis by stimulating angiogenesis.

Animals↗

Translation of vascular endothelial growth factor mRNA by internal ribosome entry: implications for translation under hypoxia.

Vascular endothelial growth factor (VEGF) is a hypoxia-inducible angiogenic growth factor that promotes compensatory angiogenesis in circumstances of oxygen shortage. The requirement for translational regulation of VEGF is imposed by the cumbersome structure of the 5' untranslated region (5'UTR), which is incompatible with efficient translation by ribosomal scanning, and by the physiologic requirement for maximal VEGF production under conditions of hypoxia, where overall protein synthesis is compromised. Using bicistronic reporter gene constructs, we show that the 1,014-bp 5'UTR of VEGF contains a functional internal ribosome entry site (IRES). Efficient cap-independent translation is maintained under hypoxia, thereby securing efficient production of VEGF even under unfavorable stress conditions. To identify sequences within the 5'UTR required for maximal IRES activity, deletion mutants were analyzed. Elimination of the majority (851 nucleotides) of internal 5'UTR sequences not only maintained full IRES activity but also generated a significantly more potent IRES. Activity of the 163-bp long "improved" IRES element was abrogated, however, following substitution of a few bases near the 5' terminus as well as substitutions close to the translation start codon. Both the full-length 5'UTR and its truncated version function as translational enhancers in the context of a monocistronic mRNA.

3T3 Cells↗

Intratympanic steroid treatment of inner ear disease and tinnitus (preliminary report).

Intratympanic instillation of Depo-Medrol (80 mg/cc), dexamethasone ophthalmic solution (1 mg/cc), or dexamethasone intravenous (4 mg/cc) solution produces improvement of cochlear function in certain patients with Meniere's disease, autoimmune inner ear disease and sudden sensorineural deafness. Tinnitus improved in 47%, most often in patients with Meniere's disease (9 of 15; 60%). The SRT improvement of greater than 10 dB or SD greater than 15% was documented in 41% (average improvement in SRT: 15 dB; SD: 24%). Patients with tinnitus and bilateral sensorineural hearing loss (i.e., presbycusis) did not benefit from the treatment. Prior to treatment with intratympanic medication, laser assisted tympanostomy with middle ear exploration, using otoendoscopy to determine the status of the round window niche and remove mucosal folds, helps in making the round window membrane accessible to local application of drops. Placing Gelfoam into the round window niche under direct vision, and using a Venturi Bobbin tube in the tympanic membrane, appears to be a satisfactory method for delivering medication to the inner ear fluids. The medication can be injected by the physician through the tube into the middle ear, or the patient can perform self-treatment at home, placing medication in the external auditory canal. A double-blind, cross-over study in patients with Meniere's disease is now in progress with Institutional Review Board (IRB) approval, which will be reported at a later date. This preliminary study has shown that intratympanic steroids may affect the symptoms of hearing loss and tinnitus in patients with various inner ear problems. Patients with Meniere's disease appear to respond in the highest percentage of cases. Hopefully, additional research will suggest the appropriate drugs which can be used to treat inner ear disease. Direct application of the drug to the round window membrane may increase the concentration in the inner ear fluids, thus avoiding the systemic effects.

Aged↗

Pharmacoclinical correlations in schizophrenic patients treated with haloperidol decanoate: clinical evaluations, concentrations of plasma and red blood cell haloperidol and its reduced metabolite, and plasma homovanillic acid.

1. The aim of this open study was to determine whether a more rational therapeutic approach could be devised for psychotic patients (n = 11) treated for long periods with long-acting (LA) haloperidol. The mean multiplication factor for the transition from the oral formulation to the long-acting one was 12.8 (10.4, standard deviation), lower than the theoretically recommended factor of 20. 2. The best dose (mg/kg)-concentration correlations were found for haloperidol (HAL) and reduced HAL (RHAL) in the red blood cells (RBC) (representative of the free drug fraction) rather than in the plasma of patients that had attained the steady state (at the third cycle and afterwards) 3. Pharmacokinetic analyses were conducted at the same time as clinical evaluations, grading using the BPRS and determinations of plasma levels of total, free and conjugated homovanillic acid (HVA), a marker of central dopaminergic activity. 4. A between groups comparison at the steady state (patients (n = 20) with oral administration and the above patients (n = 11) with long-acting form of HAL), showed that the plasma and RBC RHAL/HAL ratios of long-acting HAL decreased significantly (p < 0,005) in comparison with oral administration, at least by half. 5. Plasma HVA values complete the information provided by plasma and more especially RBC HAL and RHAL levels. All these results taken together, as substantiated by the clinical assessment scales (BPRS), assure a better pharmacoclinical surveillance and can be predictive of a patient's response.

Adult↗

Stabilization of vascular endothelial growth factor mRNA by hypoxia and hypoglycemia and coregulation with other ischemia-induced genes.

Expression of vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen and a potent angiogenic factor, is upregulated in response to a hypoxic or hypoglycemic stress. Here we show that the increase in steady-state levels of VEGF mRNA is partly due to transcriptional activation but mostly due to increase in mRNA stability. Both oxygen and glucose deficiencies result in extension of the VEGF mRNA half-life in a protein synthesis-dependent manner. Viewing VEGF as a stress-induced gene, we compared its mode of regulation with that of other stress-induced genes. Results showed that under nonstressed conditions, VEGF shares with the glucose transporter GLUT-1 a relatively short half-life (0.64 and 0.52 h, respectively), which is extended fourfold and more than eightfold, respectively, when cells are deprived of either oxygen or glucose. In contrast, the mRNAs of another hypoxia-inducible and hypoglycemia-inducible gene, grp78, as well as that of HSP70, were not stabilized by these metabolic insults. To show that VEGF and GLUT-1 are coinduced in differentially stressed microenvironments, multicell spheroids representing a clonal population of glioma cells in which each cell layer is differentially stressed were analyzed by in situ hybridization. Cellular microenvironments conducive to induction of VEGF and GLUT-1 were completely coincidental. These findings show that two different consequences of tissue ischemia, namely, hypoxia and glucose deprivation, induce VEGF and GLUT-1 expression by similar mechanisms. These proteins function, in turn, to satisfy the tissue needs through expanding its vasculature and improving its glucose utilization, respectively.

Animals↗

The single translation product of the FUM1 gene (fumarase) is processed in mitochondria before being distributed between the cytosol and mitochondria in Saccharomyces cerevisiae.

The yeast mitochondrial and cytosolic isoenzymes of fumarase, which are encoded by a single nuclear gene (FUM1), follow a unique mechanism of protein subcellular localization and distribution. Translation of all FUM1 messages initiates only from the 5'-proximal AUG codon and results in a single translation product that contains the targeting sequence located within the first 32 amino acids of the precursor. All fumarase molecules synthesized in the cell are processed by the mitochondrial matrix signal peptidase; nevertheless, most of the enzyme (80 to 90%) ends up in the cytosol. The translocation and processing of fumarase are cotranslational. We suggest that in Saccharomyces cerevisiae, the single type of initial translation product of the FUM1 gene is first partially translocated, and then a subset of these molecules continues to be fully translocated into the organelle, whereas the rest are folded into an import-incompetent state and are released by the retrograde movement of fumarase into the cytosol.

Animals↗

The central New Jersey neonatal brain haemorrhage study: design of the study and reliability of ultrasound diagnosis.

Over a 34-month period, 1105 newborns weighing between 501 and 2000 g at birth were enrolled in a prospective study of the aetiology and consequences of neonatal brain haemorrhage. The three participating hospitals care for approximately 85% of births in the study weight range in Middlesex, Monmouth and Ocean counties, New Jersey. Cranial ultrasonographic imaging through the anterior fontanelle was carried out a mean age of 4.9 +/- 2.2 hours, 25.5 +/- 4.8 hours and 7.2 +/- 0.8 days to detect haemorrhage and other brain lesions. In 93.2% of study infants, scans were read by two independent expert readers (blind to the clinical status of the child) with submission of the scan to a third reader in cases of disagreement. Confirmation of both presence or absence and, when present, scan of first diagnosis of germinal matrix and/or intraventricular haemorrhage (GM/IVH) by two independent readers was achieved in 76.3% of study infants. The first two readers agreed as to presence or absence of GM/IVH in 82.4% of infants (Kappa = 0.56). Interobserver agreement was affected by the reported scan quality and by the number of scans available, but not by the hospital of origin, race or birthweight of the infant.

Birth Weight↗

Sensitization to the toxic effects of cocaine in mice is associated with the regulation of N-methyl-D-aspartate receptors in the cortex.

Repeated exposure to cocaine results in sensitization to many of the behavioral effects of the drug. The present study was undertaken to examine the role of the N-methyl-D-aspartate (NMDA) type of glutamate receptors in the development of sensitization to the convulsive and lethal effects of cocaine in Swiss Webster mice. Repeated administration of subconvulsant doses of cocaine (45 mg/kg for 7 days) produced a progressive increase in the convulsive responsiveness to the drug. This phenomenon was accompanied by an increase in lethality rate after the 5th day of the treatment. Pretreatment with the noncompetitive NMDA receptor antagonist, MK-801 (5-methyl-10,11-dihydro-5H-dibenzo[a,d]- cyclohepten-5,10-imine) abolished completely the development of sensitization to cocaine-induced seizures and lethality. In addition, MK-801 attenuated cocaine-induced loss in animals body weight after 7 days of drug treatment. The lethal effects of acute administration of increasing doses of cocaine were also reduced by pretreatment with MK-801. In vitro receptor binding experiments demonstrated an increase (139% of control) in the number of NMDA receptors, labeled with the competitive NMDA receptor antagonist [3H]CGP 39653 ([3H]-2-amino-4-propyl-5-phosphono-3-pentenoic acid), in cortical membranes derived from the mice treated for 7 days with cocaine (45 mk/kg). In agreement with the latter finding, binding of [3H]MK-801 to the phencyclidine/NMDA site in cortical membranes of cocaine-treated mice was more sensitive to the stimulatory effect of glutamate compared to control (saline treatment).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Regulation of sigma receptors and responsiveness to guanine nucleotides following repeated exposure of rats to haloperidol: further evidence for multiple sigma binding sites.

The sigma binding sites are postulated to be involved in various central nervous system (CNS) disorders. The neuroleptic drug, haloperidol, displays high affinity for these receptor sites in the CNS. In the present study the effect of repeated exposure of rats to haloperidol (4 mg/kg/day for 14 days) on sigma binding sites labeled with (+)-3-(3-hydroxyphenyl)-N-1-(propyl)piperidine [+)-3-PPP) and 1,3-di-o-tolyl-guanidine (DTG) was investigated. In addition, the regulatory effect of guanine nucleotides on the binding of these two ligands to brain membranes derived from saline and haloperidol-treated rats was examined. Repeated administration of haloperidol induced down-regulation of (+)[3H]-3-PPP binding sites (75% decrease in the number of binding sites compared to control) which persisted for at least 7 days after termination of the haloperidol-treatment. The down-regulation of (+)-3-PPP binding sites was accompanied by reduced responsiveness to guanine nucleotides (i.e. 5-guanylylimidodiphosphate (Gpp(NH)p) compared to the sensitivity of (+)-3-PPP binding sites to the nucleotides tested in control membranes. However, at the 28th day after termination of the haloperidol-treatment, a complete recovery in the total number of (+)[3H]-3-PPP binding sites was observed, and the sensitivity to guanine nucleotides was regained. These findings suggest a marked plasticity in (+)-3-PPP/sigma receptor binding activity. In contrast, [3H]DTG binding sites expressed neither sensitivity to the repeated exposure to haloperidol nor to guanine nucleotides, suggesting a distinction between DTG and (+)-3-PPP binding sites in rat brain.

Adenosine Triphosphate↗