Search PubMed⌕ Search

Biomedical subjects

D Young

Publications and source records attributed to D Young.

At least 307 records · Page 17Linked to original sources
PubMed1994

True believers? Characteristics of general practitioners in Victorian community health centres.

General practitioners have been part of multidisciplinary services in Victoria Community Health Centres (CHCs) for 20 years. This model institutionalizes a high degree of integration between general practitioners and other primary care and community service personnel. Of 51 eligible full-time general practitioners in Victorian CHCs, 46 were interviewed, using a structured questionnaire. General practitioners in CHCs were younger, less experienced and more likely to be female than other general practitioners. Nearly three-quarters were salaried. The philosophy of practice and the conditions of employment were the commonest reasons for entering CHC practice. Teamwork and the conditions of employment were felt to be the biggest advantages of CHC practice, while difficulties with management and the perceived loss of professional ownership and control were the commonest disadvantages. None reported interference from the CHC management in their clinical practice. Nearly a quarter of full-time CHC general practitioners do not undertake any formal community health promotion activities. Forty-five per cent of respondents intended to leave their CHC within the next five years. Universal health insurance has diminished the impact of CHC general practice. The philosophy of CHCs and the salaried nature of the employment continues to attract general practitioners. High staff turnover is a feature of CHC general practice, in part related to young doctors making an initial, but not long-term commitment to CHC practice. However, the loss of professional control and management difficulties should be addressed, as these may contribute to the high turnover.

Adult↗
PubMed1994

The effects of 4-aminopyridine in multiple sclerosis patients: results of a randomized, placebo-controlled, double-blind, concentration-controlled, crossover trial.

Because 4-aminopyridine (AP) improves residual deficits in some multiple sclerosis (MS) patients but has a narrow toxic-to-therapeutic margin, we compared the safety and efficacy of two target peak serum concentration ranges (low: 30 to 59 ng/ml and high: 60 to 100 ng/ml). We enrolled eight MS patients with temperature-sensitive visual and motor deficits in a randomized, placebo-controlled, double-blind, crossover trial of short-term oral AP treatment. We randomized patients to a sequence of three treatments on three separate days: placebo, low serum concentration, and high serum concentration. We determined dosing to achieve the desired steady-state peak serum concentration ranges from a test dose and population pharmacokinetic parameters using bayesian estimation. Contrast sensitivity, standard neurologic examination, ratings of videotaped neurologic examinations, and quantitative strength assessment all improved with treatment, but flicker fusion frequency, visual evoked response latencies, and Expanded Disability Status Scale scores did not. All patients experienced side effects during the high-serum-concentration arm. A grand mal seizure occurred at a serum AP level of 104 ng/ml, and an acute confusional episode occurred at 114 ng/ml. AP treatment produced improvements in residual deficits in MS patients, but the occurrence of significant toxicity suggests that AP serum levels should be monitored and peak levels above 100 ng/ml should be avoided. Concentration-control methodology may be useful in testing putative treatments for other neurologic diseases.

4-Aminopyridine↗
PubMed1994

Comparison of human CAP and CAP2, homologs of the yeast adenylyl cyclase-associated proteins.

We previously reported the identification of human CAP, a protein that is related to the Saccharomyces cerevisiae and Schizosaccharomyces pombe adenylyl cyclase-associated CAP proteins. The two yeast CAP proteins have similar functions: the N-terminal domains are required for the normal function of adenylyl cyclase, while loss of the C-terminal domains result in morphological and nutritional defects that are unrelated to the cAMP pathways. We have amplified and cloned cDNAs from a human glioblastoma library that encode a second CAP-related protein, CAP2. The human CAP and CAP2 proteins are 64% identical. Expression of either human CAP or CAP2 in S. cerevisiae cap- strains suppresses phenotypes associated with deletion of the C-terminal domain of CAP, but does not restore hyper-activation of adenylyl cyclase by RAS2val19. Similarly, expression of either human CAP or CAP2 in S. pombe cap- strains suppresses the morphological and temperature-sensitive phenotypes associated with deletion of the C-terminal domain of CAP in this yeast. In addition, expression of human CAP, but not CAP2, suppresses the propensity to sporulate due to deletion of the N-terminal domain of CAP in S. pombe. This latter observation suggests that human CAP restores normal adenylyl cyclase activity in S. pombe cap- cells. Thus, functional properties of both N-terminal and C-terminal domains are conserved between the human and S. pombe CAP proteins.

Adaptor Proteins, Signal Transducing↗
PubMed1994

THE SCALING OF SONG FREQUENCY IN CICADAS

In male cicadas, sound is generated by a pair of tymbals on the abdomen (Pringle, 1954). The tymbals buckle inwards causing pressure changes in the abdominal cavity, from which sound is radiated through the tympana (Young, 1990). A recent model of sound production in cicadas suggests that the abdominal cavity and tympana act as the components of a Helmholtz resonator that is excited by the drive from the tymbals (Bennet-Clark and Young, 1992). A Helmholtz resonator consists of a cavity open to the outside via a hole which has a real or notional neck, and the resonant frequency fo is given by the general equation: where c is the speed of sound in the fluid, taken as 340 m s-1 for air, A is the area of the neck, L is the length of the neck and V is the volume of the cavity. Where the resonator has two holes, these terms should be somewhat modified: A is the combined area of the two holes, L is 16/3pi r (~1.7r) for a simple hole in a thin-walled vessel and r is the radius of one hole (Seto, 1971). These modifications to equation 1, which include corrections for the acoustic end-effect at either side of a simple hole in the wall of a vessel, are applicable to a model of the male cicada, in which there are two tympana close to the ventral surface of the abdomen.

Journal Article↗
PubMed1994

Factors associated with dangerous behavior in forensic inpatients: results from a pilot study.

This study was designed to identify risk factors associated with violence within a forensic inpatient hospital setting. The primary purpose was to develop a screening tool to aid in the rapid identification of patients requiring high versus low security ward placement. Subjects included 232 consecutive admissions during a five-month period to a 300-bed forensic division within a public-sector psychiatric hospital. Demographic, historical, and current clinical variables were collected, and dangerous behaviors were documented by nursing staff on a daily basis. The associations between dangerous outcomes and various risk factors were examined using chi-square or t tests, as appropriate. Stepwise logistic regression analysis was performed to assess the contribution of each risk factor significantly associated with violent behavior. A strong association was found between 10 risk factors and the incidence of violence in our forensic population. These factors included current clinical factors (grossly inappropriate behavior observed on the ward, an assessment of current escape risk); historical factors (psychiatric hospitalization history, criminal history variables, and a self-report of prior violence); and one demographic variable (length of stay). Of the 10 risk factors then included in the stepwise regression analysis, four contributed significantly to the final predictive model. Grossly inappropriate behavior, patient self-report of prior violence, history of psychiatric hospitalization, and a history of 10 or more prior psychiatric hospitalizations were most predictive of a violent outcome. Although situational and environmental variables also must be incorporated into final assessments and decisions, the identified significant variables can provide an additional tool in the rapid assessment of violence potential.

Dangerous Behavior↗
PubMed1994

Reported management of patients with sore throat in Australian general practice.

BACKGROUND: Sore throat is one of the commonest presenting symptoms in general practice in Australia, and results in the prescription of an antibiotic in 50-90% of cases, despite the finding of bacterial throat infection in around 30% of cases or fewer. AIM: This study set out to examine whether inaccurate knowledge about the pathophysiological features and management of sore throat helps to explain the high level of inappropriate antibiotic prescribing for sore throat by general practitioners. METHOD: A questionnaire with four case vignettes of sore throat presentations was sent to 400 randomly selected general practitioners, practising in Victoria, Australia. Of 367 eligible respondents, 284 responded (77%). RESULTS: Of the respondents 97% reported that they would prescribe an antibiotic for the case of tonsillitis, 70% for the case of possible glandular fever, 29% for the child with probable viral sore throat and 9% for the adult with probable viral infection. There were no differences in prescribing rates between general practitioners of different sex, practice location, practice type or qualification. Overall, 25% of the antibiotics which formed the respondents' first choice were inappropriate broad-spectrum antibiotics. CONCLUSION: General practitioners are generally accurate in their assessment of the features of sore throats, but less accurate in their knowledge of appropriate antibiotics.

Adult↗
PubMed1994

A phase I/II study of interleukin-3 in patients with aplastic anemia and myelodysplasia.

We performed a phase I/II study of recombinant human interleukin-3 (rhIL-3) in 21 patients with aplastic anemia (AA) or myelodysplasia (MDS). Patients received 21-day cycles of IL-3 (0.5, 1.25, 2.5, 5.0, or 10 micrograms/kg/d) by subcutaneous injection followed by a 10- to 14-day washout period. Nineteen patients completed at least one 21-day cycle of IL-3. Frequent toxicities of IL-3 included headache, low-grade fever, and erythema at the injection site; at higher doses, weight gain and peripheral edema was seen. Eleven patients developed eosinophilia. Of the 20 evaluable patients, eight had increases in absolute neutrophil counts (seven with MDS, one with AA) including six of the nine patients receiving > or = 5.0 micrograms/kg/d. One AA patient became transfusion-independent for 8 months, while another AA patient had decreased transfusion requirements. Three patients with MDS had at least a doubling of their platelet count, and another patient experienced a 1.9-fold increase. One patient with RAEB progressed to aleukemic AML by the end of one treatment cycle. IL-3 was well-tolerated, but multilineage effects were seen in only 25% of patients with primary bone marrow failure states (five of 20 evaluable) and more commonly in patients with myelodysplastic syndromes. Its optimal use may be as part of combination hematopoietic growth factor therapy.

Adult↗
PubMed1993

Non-NMDA glutamate receptors are involved in the maintenance of status epilepticus.

The role of N-methyl-D-aspartate (NMDA), non-NMDA glutamate, metabotropic and muscarinic receptors in the maintenance of status epilepticus (SE) was investigated. SE induced in rat brain by continuous electrical stimulation to the hippocampus was terminated by intracerebroventricular (i.c.v.) injection of the non-NMDA antagonists DNQX and NBQX, but not by the muscarinic antagonists scopolamine or atropine, or the metabotropic antagonist AP3. The NMDA antagonist, MK-801 suppressed motor seizure activity but did not terminate electrographic seizures when generalized SE was induced, suggesting that both non-NMDA and NMDA receptors maintain generalized convulsive SE. However, when limbic SE was induced, MK-801 also had an anticonvulsant effect suggesting differences in the mechanisms maintaining limbic SE and generalized SE.

Animals↗
PubMed1993

The Schizosaccharomyces pombe pde1/cgs2 gene encodes a cyclic AMP phosphodiesterase.

We previously reported the identification of eight Sz. pombe cDNA clones that are capable of suppressing the heat-shock sensitive phenotype associated with deletion of IRA1 in S. cerevisiae. We report that one of these cDNA clones, pPSI5, encodes a protein, Pde1, that is 24% identical to the S. cerevisiae low-affinity cAMP phosphodiesterase. The pde1/cgs2 gene encoding this protein has been previously identified, and studies have shown that deletion of this gene results in elevated levels of intracellular cAMP and inhibition of meiosis. To demonstrate that Pde1 is a cAMP phosphodiesterase we expressed it in an S. cerevisiae strain which lacks the genomic cAMP phosphodiesterase genes. Extracts from such cells that express the Sz. pombe Pde1 exhibit high levels of cAMP phosphodiesterase activity.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1993

Identification and genetic analysis of Schizosaccharomyces pombe cDNAs that suppress deletion of IRA1 in Saccharomyces cerevisiae.

Ira1 is a negative regulator of Ras proteins in Saccharomyces cerevisiae. Deletion of IRA1 leads to constitutive activation of the Ras/cyclic AMP (cAMP) pathway, which results in several phenotypes including sensitivity to heat-shock (HS) treatment. We have identified eight Schizosaccharomyces pombe cDNAs that, when overexpressed, suppress the HS-sensitive phenotype associated with the deletion of IRA1 in S. cerevisiae. To determine where these cDNAs act, we tested their ability to suppress other mutations that activate the Ras/cAMP pathway in S. cerevisiae. Two of the cDNA clones, pPSI1 and pPSI2, failed to suppress the HS-sensitive phenotype induced by the activating RAS2Val19 mutation. Clone pPSI2 encodes Gap1/Sar1, a Sz. pombe homologue of Ira1, which has been previously identified. Three of the six RAS2Val19 suppressors could suppress the deletion of PDE1 and PDE2, the cAMP phosphodiesterase (Pde)-encoding genes, suggesting that they act downstream from adenylyl cyclase (Cyr). The remaining three clones, pPSI3, pPSI6 and pPSI7, encode proteins that may suppress the HS-sensitive phenotype by reducing Ras and/or Cyr activity. One of these, pPSI3, contains a cDNA that encodes the C-terminal region (aa 166-550) of the Sz. pombe Dbp2 protein, a homologue of the human p68 RNA helicase. We have amplified cDNAs encoding the full-length Sz. pombe Dbp2 protein by the polymerase chain reaction method and have cloned them into a S. cerevisiae expression vector. The ira1- cells harboring these plasmids retained their HS-sensitive phenotype. These results suggest that the truncated Dbp2, but not the full-length protein, is capable of interfering with Ras and/or Cyr activity.

Amino Acid Sequence↗
PubMed1993

Molecular chaperones and the immune response.

Molecular chaperones belonging to heat shock protein families have been identified as prominent antigens in the immune response to a wide variety of infections. Recognition of such highly conserved antigens may contribute to protective immunity but, in some circumstances, may also have pathological autoimmune consequences. Recognition of chaperones may be an inherent feature of the immune system. Peptide mapping experiments revealed an overlap between hsp 70-binding sites and immunodominant regions of three protein antigens, consistent with a possible functional activity for molecular chaperones in the processing and presentation of peptides during class II-restricted T lymphocyte responses. A functional role for molecular chaperones in antigen processing may be a factor which contributes to their immunogenicity.

Animals↗
PubMed1993

Effect of quinidine on the interconversion kinetics between haloperidol and reduced haloperidol in humans: implications for the involvement of cytochrome P450IID6.

Haloperidol (HAL) is a potent butyrophenone antipsychotic agent which is reversibly metabolized to reduced haloperidol (RHAL). In order to determine if this reversible metabolic pathway is linked to the debrisoquine 4-hydroxylase isozyme of cytochrome P-450 (P450IID6). HAL (5 mg) or RHAL (5 mg) was orally administered to healthy male volunteers in a randomized crossover design both with and without a prior (1 h) oral dose of quinidine (250 mg bisulfate), a potent inhibitor of this isozyme. Thirteen volunteers, 11 extensive metabolizers, 2 poor metabolizers, completed all four phases of the study. Plasma samples harvested over seven days were analysed for HAL and RHAL. An expression for the apparent fractional availability of metabolite from the parent compound given (Fapppm) was derived and was used to determine whether HAL or RHAL is the preferred metabolite, and whether quinidine co-administration alters Fapp for either compound. The AUC (0-t) for both HAL and RHAL were significantly greater following the administration of either compound with quinidine compared with AUC (0-t) values obtained in the absence of quinidine. The maximum plasma concentration (Cmax) of the administered compound was also greater following the administration of quinidine. Quinidine had no effect on the half-lives of the administered compounds. The Fapp for HAL and RHAL were not significantly affected by the administration of quinidine, indicating that the interconversion of HAL and RHAl is not linked to P450IID6. The Fapp of RHAL after administration of HAL was significantly greater than the Fapp of HAL after RHAL administration, indicating that RHAL is the preferred metabolic form. This difference was not affected by quinidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Tumour profile of N-[2-(dimethylamino)ethyl]acridine-4-carboxamide after intraperitoneal administration in the mouse.

N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (AC) is an experimental antitumour agent that is being considered for phase I trials. After i.p. administration of 150 mg/kg [3H]-AC to tumour-bearing mice, AC was absorbed rapidly into the plasma and tissues such as the heart, liver, kidney and brain but more slowly into the s.c. tumour. The maximal AC concentration (86 +/- 36 mumol/kg) in the tumour occurred at 35-60 min and was 3-fold the maximal plasma concentration, which occurred at 15 min. Although higher maximal concentrations were observed in other tissues, these concentrations fell rapidly in parallel with plasma concentrations. In contrast, AC concentrations in the tumour remained elevated, the t1/2 value (16.3 h) and mean residence time (MRT, 9.5 h) being prolonged in comparison with those in the plasma and other tissues (t1/2 range, 1.0-2.9 h; MRT, 1.2-1.4 h). AC concentrations were not detectable by our high-performance liquid chromatographic (HPLC) method (limit of detection, 0.02 mumol/l) in the plasma or other tissues at 24 or 48 h after administration but were measurable in the tumour (1.6 +/- 0.8 and 0.6 +/- 0.3 mumol/kg, respectively). Radioactivity concentrations in the plasma, tissues and tumour were very variable but were greater than the corresponding levels of unchanged parent AC. By 24 h, radioactivity concentrations in the plasma, tissues and tumour had fallen to similar levels with prolonged elimination profiles. Thus, the exposure of the s.c. implanted tumour to a threshold AC concentration for a prolonged time (> 24 h) tumour, whereas the shorter period of exposure of blood and other tissues may explain its low haematological toxicity.

Acridines↗
PubMed1993

Pharmacokinetics of acridine-4-carboxamide in the rat, with extrapolation to humans.

The pharmacokinetics of N-[2-(dimethyl-amino)ethyl]acridine-4- carboxamide (AC) were investigated in rats after i.v. administration of 18, 55 and 81 mumol/kg [3H]-AC. The plasma concentration-time profiles of AC (as measured by high-performance liquid chromatography) typically exhibited biphasic elimination kinetics over the 8-h post-administration period. Over this dose range, AC's kinetics were first-order. The mean (+/- SD) model-independent pharmacokinetic parameters were: clearance (Cl), 5.3 +/- 1.1 1 h-1 kg-1; steady-state volume of distribution (Vss), 7.8 +/- 3.0 l/kg; mean residence time (MRT), 1.5 +/- 0.4 h; and terminal elimination half-life (t1/2Z), 2.1 +/- 0.7 h (n = 10). The radioactivity levels (expressed as AC equivalents) in plasma were 1.3 times the AC concentrations recorded at 2 min (the first time point) and remained relatively constant for 1-8 h after AC administration. By 6 h, plasma radioactivity concentrations were 20 times greater than AC levels. Taking into account the species differences in the unbound AC fraction in plasma (mouse, 16.3%; rat, 14.8%; human, 3.4%), allometric equations were developed from rat and mouse pharmacokinetic data that predicted a Cl value of 0.075 (range, 0.05-0.10; 95% confidence limits) 1 h-1 kg-1 and a Vss value of 0.63 (range, 0.2-1.1) l/kg for total drug concentrations in humans.

Acridines↗
PubMed1993

Blood-brain glucose transfer in the mouse.

The intracarotid injection method has been utilized to examine blood-brain barrier (BBB) glucose transport in normal mice, and after a 2-day fast. In anesthetized mice, cerebral blood flow (CBF) rates were reduced from 0.86 ml.min-1 x gm-1 in control to 0.80 ml.min-1 x gm-1 in fasted animals (p > 0.05). Brain Uptake Indices were significantly (p < 0.05) higher in fasted (plasma glucose = 4.7 mM) than control (plasma glucose = 6.5 mM) mice, while plasma glucose was significantly lower. The maximal velocity (Vmax) for glucose transport was 1562 +/- 303 nmoles.min-1 x g-1, and the half-saturation constant (Km =) 6.67 +/- 1.46 mM in normally fed mice. In fasted mice the Vmax was 2053 +/- 393 nmoles.min-1 x g-1 (p > 0.05), and the half-saturation constant (Km =) 7.40 +/- 1.60 mM (not significant, P > 0.05). A rabbit polyclonal antiserum to a synthetic peptide encoding the 13 C-terminal amino acids of the human erythrocyte glucose transporter (GLUT-1) immunocytochemically confirmed that the mouse brain capillary endothelial glucose transporter is a GLUT-1 transporter, and immunoreactivity was similar in brain endothelia from fed and fasted animals. In conclusion, after a 2-day fast in the mouse, we saw significant reductions in forebrain weight (7%), and plasma glucose levels (27%). Increased brain glucose extraction (25%, p < 0.05), and a 22% increase in the unsaturated permeability-surface area product (p < 0.05) was also observed.

Animals↗
PubMed1993

Role of carcinoembryonic antigen in predicting resectability of recurrent colorectal cancer.

The reported low resectability rate for patients with recurrent colorectal cancer who have carcinoembryonic antigen (CEA) levels > 11 has led us to perform this study. One hundred twenty-four patients who underwent Radioimmunoguided Surgery (RIGS) procedures for recurrent colorectal cancer from 1986 to the present were studied. In surgery, all patients underwent a traditional exploration followed by survey with a hand-held, gamma-detecting probe to detect preinjected radiolabeled monoclonal antibodies attached to cancer cells. Sites of metastases included: 72 liver (58.1 percent), 23 pelvis (18.5 percent), 15 distant lymph nodes (12.1 percent), 2 anastomotic (1.6 percent), and 12 other sites (9.7 percent). The resectability rate was 43.5 percent (54 patients). The mean preoperative CEA level for patients with resectable disease was significantly lower than for patients with unresectable disease (P = 0.017): unresectable--mean, 87.1; SD, 141.0; minimum, 0.3; maximum, 501; resectable--mean, 36.6; SD, 59.3; minimum, 0.3; maximum, 329. The CEA level for patients with liver metastasis did not vary significantly from those patients without metastasis: 70 vs. 58.2 (P = 0.58). Those patients with resectable liver tumors had lower mean CEA levels than those with unresectable liver, approaching significance: 41.6 vs. 91.9 (P = 0.065). Other metastatic sites had a mean CEA level of: pelvic, 72.6; distant lymph nodes, 47.8; anastomotic, 2.7; and other sites, 53.8. These data suggest that there is a significant difference between the preoperative CEA level of the resectable and unresectable recurrent colorectal cancer patients, but the large standard deviation does not justify abandonment of exploration for any CEA level.

Antibodies, Monoclonal↗
PubMed1993

The protein of pigmented Polynesian dental enamel.

This enamel contained 1.4-3.7% protein, calculated from amino acid residues, in which glutamic acid and leucine were the most generally abundant and lysine was the most abundant basic amino acid. The amino acid profiles of both French Polynesian and Maori pigmented enamel protein were similar and closely resembled that of tuft protein and certain non-amelogenins. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis of extracts of pigmented enamel showed an absence of amelogenin protein and the presence of two principal proteins at M(r) 55,000-66,000, indicating that the protein of pigmented Polynesian enamel was non-amelogenin. This contrasts with hypomaturation amelogenesis imperfecta in which the protein has the amino acid profile of amelogenin.

Adolescent↗