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Biomedical subjects

J D Walker

Publications and source records attributed to J D Walker.

At least 37 records · Page 2Linked to original sources
PubMed1999

Methadone maintenance treatment: outcomes from the Otago methadone programme.

AIM: To provide information on methadone treatment outcomes for opiate-dependent individuals. METHODS: Questionnaires and random urine tests were completed for 112 Otago clients comparing outcomes before and during methadone maintenance treatment. RESULTS: Treatment retention rates were high, with 86% of clients remaining on the programme six months or more. The number of clients on benefits reduced by almost 30% during treatment, with employment rates doubling from 19% to 40% (including attendance at educational programmes). For the 89 clients injecting opiates daily at initial presentation, 64% reported no opiate use in the three months prior to review. Of the remaining 36%, opiate use reduced significantly. Rates of sharing injecting equipment reduced by almost 90%. Almost 50% of cannabis users reduced their use from daily to less than daily use. Clients reporting no current use of illicit benzodiazepines increased by 85%. Heavy binge drinking weekly or more reduced by almost 75%. Use of other illicit drugs reduced by almost 90%. Drug-related convictions reduced by almost 60%, while accidental drug overdoses reduced by over 90%. CONCLUSION: The widespread benefits of methadone maintenance treatment demonstrated underline the importance of making quality methadone programmes readily accessible within the health system. Currently, there are long waiting lists and many individuals cannot gain access to active treatment. We believe the health system urgently needs to look at expanding existing services and/or establishing private methadone clinics similar to those in New South Wales.

Adolescent↗
PubMed1999

Allele-specific interactions between ttg and gl1 during trichome development in Arabidopsis thaliana.

Trichome development in Arabidopsis thaliana is a well-characterized model for the study of plant cell differentiation. Two genes that play an essential role in the initiation of trichome development are GL1 and TTG. Mutations in either gene prevent the initiation of most trichomes. The GL1 gene encodes a myb-related transcription factor. Mutations in TTG are pleiotropic, affecting anthocyanins, root hairs, and seed coat mucilage in addition to trichomes. Six ttg alleles were examined and shown to form a hypomorphic series. The severity of all aspects of the ttg phenotype varied in parallel in this allelic series. The weakest allele, ttg-10, causes frequent clusters of adjacent trichomes, suggesting a role for TTG in inhibiting neighboring cells from choosing the trichome fate. This allele results from a mutation in the 5'-untranslated region of ttg and creates an out-of-frame upstream AUG codon. The ttg-10 allele shows several unusual genetic interactions with the weak hypomorphic gl1-2 allele, including intergenic noncomplementation and a synthetic glabrous phenotype. These interactions are specific for the gl1-2 allele. The implication of these results for current models of trichome development is discussed.

Alleles↗
PubMed1999

Neovascularization at the vascular pole region in diabetic glomerulopathy.

BACKGROUND: Diabetic nephropathy is associated with renal structural changes involving all of the compartments. Most characteristic is the diabetic glomerulopathy. Studies of the histological changes during the early phases of nephropathy have included the glomerulopathy and also the juxtaglomerular structures. Neovascularization, well-known in diabetic retinopathy, has also been observed in the kidney. The present study concerns estimates of frequency of neovascularization at the vascular pole region in early stages of diabetic nephropathy. METHODS: Extra efferent arterioles at the glomerular vascular pole were detected during measurements of the vascular pole area applying 1-microm serial sections through kidney biopsies. It was observed that more than one efferent arteriole existed occasionally. The present study was carried out with the aim of estimating the frequency of this phenomenon in diabetic patients and in non-diabetic controls, the diabetic patients categorized according to the level of albumin excretion rate. RESULTS: Neovascularization was first observed in IDDM patients with microalbuminuria. Some of the cases presented the phenomenon in all of the glomeruli studied. As the examinations of many kidney biopsies continued the phenomenon was observed also in the non-diabetic control group and in one IDDM patient with normoalbuminuria. However, the frequency was statistically highly significantly increased in patients with elevated albumin-excretion. Within this group a strong correlation between frequency of neovascularization and the severity of diabetic glomerulopathy is seen. CONCLUSIONS: The vascular abnormality localized to the vascular pole region is observed occasionally in the normal kidney, but the frequency is increased in patients with diabetic glomerulopathy. The abnormality may develop as a consequence of a long-standing diabetic glomerulopathy and might lead to less pronounced elevation of albumin excretion.

Adolescent↗
PubMed1999

Carepartner experiences with hospital care.

OBJECTIVES: Family members and other "carepartners" often play an important role in the care and support of patients during and after hospitalization, yet little is known about how they assess their hospital experience or the factors that may influence their perceptions. METHODS: A nationwide telephone survey of 1,800 recently discharged patients and their carepartners about their hospital experience was conducted. Carepartner responses in six domains of care were summarized, and multivariable regression analysis was used to detect independent predictors of more frequent problem reports by carepartners. RESULTS: Carepartners reported problems most frequently in the domains of emotional support (23.9%), discharge planning (20.3%), and family participation (17.6%). Independent predictors of more frequent carepartner problem reports included poor subjective patient health status, emergency hospitalization, nonsurgical admission, carepartner income less than $7,500/year, younger carepartner age, noninvolvement of the patient's regular doctor, less frequent carepartner visits during the hospitalization, and less time spent with the patient after discharge. CONCLUSIONS: Better awareness of the problems carepartners experience and attention to improving quality in these areas may facilitate family involvement in patient care and enhance carepartner and patient satisfaction.

Attitude to Health↗
PubMed1999

Diabetic nephropathy is associated with an increased familial risk of stroke.

OBJECTIVE: To test the hypothesis that genetic susceptibility to diabetic nephropathy is associated with an increased familial risk of vascular disease, we have examined the causes and rates of death of parents of individuals with type 1 diabetes complicated by diabetic nephropathy compared with the causes and rates of death of parents of control subjects with diabetes uncomplicated by nephropathy. RESEARCH DESIGN AND METHODS: Individuals with at least a 14-year duration of type 1 diabetes complicated by diabetic nephropathy were identified and matched for age, sex, and duration of diabetes to control subjects. A total of 118 patients and 118 matched control subjects were identified and approached to obtain information on parental age and cause of death. For parents who had died, the cause of death was ascertained from the death certificate. RESULTS: Kaplan-Meier curves showed that parents of subjects with nephropathy (PN) had reduced survival compared with parents of diabetic subjects without nephropathy (PC) (log rank test P < 0.05). There was an excess of all vascular deaths and, in particular, strokes in the parents of subjects with nephropathy (PN: 20 of 103 deaths, 19% vs. PC: 3 of 66 deaths, 4%; Fisher's exact test P < 0.01). CONCLUSIONS: Parents of diabetic patients with nephropathy have reduced survival. This seems to be largely explained by an increase in vascular deaths and, in particular, a four-fold increase in the number of strokes. This supports the hypothesis that a common hereditary risk factor predisposes to both vascular death and diabetic renal disease.

Adult↗
PubMed1999

Winning the Stanley Cup Final Series is related to incurring fewer penalties for violent behavior.

Catastrophic and disabling injuries are being reported more frequently in ice hockey. Within the science of injury prevention, all possible avenues are being explored to address this devastating problem, especially in the areas of protective equipment playing rules, teaching techniques, and awareness programs. Ice hockey injuries are in many cases caused by violent player behavior, which may be supported by coaches who believe that such behavior contributes to winning. To determine whether a relationship existed between violent player behavior and game outcome, 1462 recorded penalties from all 18 Stanley Cup Final Series from 1980 through 1997 were analyzed with a 2 x 2 chi-square analysis. A statistically significant association (chi-square = 7.111, P = .008) was found between violent player behavior and series outcome, with the team drawing fewer violent penalty minutes being the winner of 13 of the 18 series. A period-by-period analysis of violent penalties incurred by the losing teams revealed a statistically significant difference between the first and third periods, with losing teams demonstrating more violent player behavior in the first period than in the third period. The results suggest that violent player behavior may be counterproductive to a favorable game outcome. Coaches at the highest level of competition may wish to adjust their team policies and recruiting practices to benefit from the plausible strategic advantage of reducing violent player behavior. This research was presented at the 1998 Ice Hockey World Championship International Symposium on Medicine and Science in Ice Hockey in Zurich, Switzerland, on Saturday, May 9, 1998, and published in the symposium's supplement, "Safety in Ice Hockey IIHF 1998."

Hockey↗
PubMed1998

Time-dependent changes in matrix metalloproteinase activity and expression during the progression of congestive heart failure: relation to ventricular and myocyte function.

The development of congestive heart failure (CHF) is associated with left ventricular (LV) dilation and myocardial remodeling. However, fundamental mechanisms that contribute to this remodeling process with the progression of CHF remain unclear. The matrix metalloproteinases (MMPs) have been demonstrated to play a significant role in tissue remodeling in a number of pathological processes. The present project tested the hypothesis that the LV dilation and remodeling during the progression of CHF is associated with early changes in MMP expression and zymographic activity. LV and myocyte function, collagen content, and MMP expression and zymographic activity were serially measured during the progression of CHF caused by pacing-induced supraventricular tachycardia (SVT) in pigs. After 7 days of SVT, LV end-diastolic dimension and myocyte length both increased by 15% from control values, and LV fractional shortening fell by 20%. At the level of the myocyte, percent shortening fell by 16% after 7 days of SVT, with no change in the steady-state velocity of shortening. Longer durations of SVT caused progressive LV dilation, LV pump failure, and myocyte contractile dysfunction. Specifically, 21 days of SVT resulted in a >50% increase in LV dimension, a 56% fall in LV fractional shortening, and a 33% decline in myocyte velocity of shortening. The decline in LV and myocyte function with 21 days of SVT was accompanied by signs and symptoms of CHF. Thus, SVT causes time-dependent changes in LV geometry and function and the subsequent development of CHF. LV myocardial collagen content and confluence fell by >25% after 7 days of SVT and were accompanied by an 80% increase in LV myocardial MMP zymographic activity against the substrate gelatin. After 14 days of SVT, total LV myocardial collagen content was reduced by 24%, and LV myocardial MMP zymographic activity increased by >100% from control values. Interstitial collagenase (MMP-1), stromelysin (MMP-3), and 72-kD gelatinase (MMP-2) were increased by approximately 2-fold after 7 days of SVT. LV MMP zymographic activity and abundance remained elevated with longer durations of SVT. The results of the present study demonstrated that in this model of CHF, early changes in LV myocardial MMP zymographic activity and protein levels occurred with the initiation and progression of LV dilation and dysfunction. These findings suggest that an early contributory mechanism for the initiation of LV remodeling that occurred in this model of developing CHF is enhanced expression and potentially increased activity of LV myocardial MMPs.

Animals↗
PubMed1998

Type 1 diabetes mellitus and Down's syndrome: prevalence, management and diabetic complications.

Type 1 insulin-dependent, diabetes mellitus (Type 1 DM) is thought to be more prevalent in individuals with Down's syndrome. To ascertain the local prevalence of Type 1 DM in patients with Down's syndrome in a geographically defined area, the four diabetes clinics in Lothian were surveyed and 13 patients with Down's syndrome and Type 1 DM were identified. Using data from previous epidemiological surveys which determined the prevalence of Down's syndrome in the general population, the prevalence rate of Type 1 DM in patients with Down's syndrome was calculated to be between 1.4 and 10.6%, a prevalence considerably higher than in the general population. Although 7 (54%) of the Down's syndrome patients were treated with once daily administration of insulin, the mean HbA1c value of the group was similar to that observed in a control group of 39 age-, sex- and duration-matched Type 1 patients, all of whom were taking two or more injections of insulin daily. Glycaemic control was therefore of similar quality to matched Type 1 patients without Down's syndrome, despite the frequent use of simple insulin regimens, which may relate to the more stable lifestyle of these patients.

Adult↗
PubMed1998

Myosin heavy chain synthesis during the progression of chronic tachycardia induced heart failure in rabbits.

Chronic tachycardia causes LV dilatation and dysfunction, with no hypertrophy. However, the contributing mechanisms responsible for the left ventricular (LV) remodeling in the absence of myocardial growth in this model of heart failure remain unclear. Therefore, the goal of the present study was to serially examine changes in LV function, steady state myosin heavy chain (MHC) mRNA levels, in vivo synthesis rates, and abundance with the progression of chronic tachycardia induced heart failure. Adult rabbits (3.5-4.5 kg) were studied after one, two, or three weeks of pacing ventricular tachycardia (VT; 400 bpm) and in controls (n = 6 for all groups). LV fractional shortening was reduced by 30% at week one and by over 50% at week three of chronic VT. End-diastolic dimension (EDD) increased at week two compared to controls (1.66 +/- 0.10 vs 1.35 +/- 0.11 cm, p < 0.05) and increased further at week three of VT (1.70 +/- 0.06 cm, p < 0.05). The progressive changes in LV geometry and function with chronic VT were not associated with concomitant time dependent changes in LV mass or MHC mRNA levels. In contrast, MHC fractional synthesis rates increased and reached statistical significance at week three of VT compared to controls (8.3 +/- 0.8 vs 5.5 +/- 0.5%/day, p < 0.05). Despite the stable or increased MHC protein synthesis rates, there was no change in MHC protein abundance at any point during the progression of VT induced heart failure, implicating enhanced MHC protein degradation. Thus, this study demonstrated that a contributory mechanism for the LV remodeling and lack of myocardial growth, which occurs with VT induced heart failure, is enhanced contractile protein degradative processes.

Animals↗
PubMed1998

Changes in L-type calcium channel abundance and function during the transition to pacing-induced congestive heart failure.

OBJECTIVE: The development of congestive heart failure (CHF) is accompanied by left ventricular (LV) and myocyte contractile dysfunction. However, time-dependent cellular and ionic events which contribute to the initiation and progression of CHF remain unclear. This study tested the central hypothesis that changes in L-type Ca2+ channel current (ICa) and abundance (Bmax) are early events in the transition to CHF. METHODS: LV fractional shortening by echocardiography, isolated LV myocyte shortening velocity by videomicroscopy, ICa by voltage-clamp, and Bmax by [3H]nitrendipine binding were determined at each week during the progression of pacing-induced CHF in pigs (240 bpm; n = 6/week for 3 weeks). Myocyte and L-type Ca2+ channel function were determined under basal conditions and after beta-adrenergic receptor stimulation with 25 nM isoproterenol. RESULTS: After 1 week of pacing, myocyte and L-type Ca2+ current responses to beta-adrenergic receptor stimulation were reduced by 20% from control values and was accompanied by over a 210% increase in plasma catecholamine levels. After 2 weeks of pacing, reductions in LV fractional shortening and myocyte shortening velocity from control values (20 +/- 1 vs. 34 +/- 2% and 36.7 +/- 2.9 vs. 50.6 +/- 2.4 microns/s, respectively, P < 0.05) were paralleled by decreased ICa (2.47 +/- 0.10 vs. 3.63 +/- 0.25 pA/pF, P < 0.02) and Bmax (149 +/- 16 vs. 180 +/- 12 fmol/mg, P < 0.03). After 3 weeks of pacing, LV fractional shortening was reduced by over 50%, myocyte shortening velocity by 37%, and ICa and Bmax were reduced by over 25% from control values. Furthermore, after 3 weeks of pacing, the ICa/Bmax ratio was reduced from control values (16.2 +/- 0.9 vs. 20.6 +/- 1.2 [fA/pF]/[fmol/mg], P < 0.03), which suggests functional defects in the remaining L-type Ca2+ channels. CONCLUSIONS: An early event during the transition to pacing-induced CHF was diminished beta-adrenergic receptor augmented L-type Ca2+ current, which was followed by an absolute loss of steady-state L-type Ca2+ current and channel abundance. The development of severe CHF was accompanied by a loss of Ca2+ carrying capacity through residual channels. These unique findings suggest that a contributory molecular mechanism for the initiation and progression of CHF is changes in the structure and function of the L-type Ca2+ channels.

Adrenergic beta-Agonists↗
PubMed1998

Chronic dual inhibition of angiotensin-converting enzyme and neutral endopeptidase during the development of left ventricular dysfunction in dogs.

Angiotensin-converting enzyme (ACE) inhibition as well as neutral endopeptidase (NEP) inhibition was demonstrated to influence hemodynamics in various cardiac disease states. However, specific effects of chronic combined ACE and NEP inhibition on left ventricular (LV) and myocyte geometry and function remain unclear. In this study, a dual-acting metalloprotease inhibitor (DMPI), which possesses both ACE and NEP inhibitory activity, was used in a rapid-pacing model of LV dysfunction. LV and myocyte geometry and function were examined in control dogs (n = 6), in dogs with pacing-induced LV dysfunction (216 +/- 2 beats/min, 28 days, n = 7), and in dogs with DMPI treatment during rapid pacing (10 mg/kg p.o., b.i.d., n = 6). With chronic rapid pacing, LV end-diastolic volume increased (84 +/- 4 vs. 49 +/- 3 ml), and LV ejection fraction decreased (38 +/- 3% vs. 68 +/- 3%) compared with control (p < 0.05). DMPI concomitantly administered during long-term rapid pacing did not change LV ejection fraction (35 +/- 3%), but LV end-diastolic volume was reduced (70 +/- 5 vs. 84 +/- 4 ml; p < 0.05) when compared with rapid pacing only. With long-term rapid pacing, myocyte cross-sectional area was decreased (278 +/- 5 vs. 325 +/- 5 microm2), and resting length increased (178 +/- 2 vs. 152 +/- 1 microm) when compared with control (p < 0.05). With DMPI concomitantly administered during rapid pacing, myocyte cross-sectional area (251 +/- 5 microm2) and resting length (159 +/- 4 microm) were reduced when compared with rapid pacing only (p < 0.05). Myocyte velocity of shortening decreased from control values with long-term rapid pacing (39.3 +/- 3.9 vs. 73.2 +/- 5.9 microm/s; p < 0.05) but improved with DMPI treatment during rapid pacing when compared with rapid pacing only (58.9 +/- 6.7 microm/s; p < 0.05). Myocyte velocity of shortening with beta-adrenergic-receptor stimulation (25 nM isoproterenol) was reduced from controls with rapid pacing (125 +/- 12 vs. 214 +/- 30 microm/s; p < 0.05) but was improved with DMPI treatment during rapid pacing when compared with rapid pacing only (178 +/- 12 microm/s; p < 0.05). In a model of rapid pacing-induced LV failure, concomitant DMPI treatment significantly reduced the degree of LV dilation with no apparent effect on LV pump function. At the level of the LV myocyte, long-term DMPI treatment with rapid pacing improved myocyte performance and beta-adrenergic response. Thus the improvement in isolated myocyte contractile function was not translated into improved global LV-pump performance. The mechanisms by which improved myocyte contractility was not translated into a beneficial effect on LV-pump function with DMPI treatment during rapid pacing remain speculative, but likely include significant changes in LV remodeling and loading conditions.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Transient improvement in glycemic control. The impact of pregnancy in women with IDDM.

OBJECTIVE: Good glycemic control throughout pregnancy in patients with diabetes is of paramount importance but often appears to deteriorate in the postpartum period. The aim of this study was to ascertain the timing of the improvement in glycemic control associated with pregnancy in women with IDDM and to examine changes in glycemic control after delivery. RESEARCH DESIGN AND METHODS: Peripartum glycemic control was assessed in a retrospective study of 30 women with IDDM whose age was 28 +/- 6 years (means +/- SD) and whose diabetes duration was 14 +/- 6 years. RESULTS: Mean total HbA1 fell incrementally from a peak at 2-3 years preconception to a nadir between 24 weeks and term, only to return to preconception levels within a year after delivery. Of the 30 women, 15 (50%) attained an HbA1 in the nondiabetic range for pregnancy at some point during their pregnancy, and 7 (23%) women achieved this by 24 weeks gestation. Women with an HbA1 > 9% at booking had a significantly higher HbA1 at 0-6 and 6-12 months preconception, and throughout pregnancy their HbA1 was significantly higher. After delivery, attendance rates at routine diabetes review clinics were low, with 11% of women not attending for longer than 24 months. CONCLUSIONS: Nearly all women with IDDM can achieve near normoglycemia during pregnancy, irrespective of previous glycemic control, although those with high HbA1 levels at booking are less likely to achieve this. After delivery, glycemic control deteriorates. Efforts to improve glycemic control should be intensified in the preconception period and maintained after delivery. The poor postpartum attendance at diabetes clinics requires specific action.

Adult↗
PubMed1998

The effect of glycemic control in the pre-conception period and early pregnancy on birth weight in women with IDDM.

OBJECTIVE: To examine data from pregnancies in women with IDDM to assess the relative effects of mean glycosylated hemoglobin levels before conception, at booking, and during the 3 trimesters of pregnancy on birth weight. Good glycemic control during pregnancy in women with IDDM is important to minimize the risk of fetal malformation and macrosomia. Recent studies have suggested that glycemic control in the 1st trimester is more important than glycemic control during the 2nd or 3rd trimesters. RESEARCH DESIGN AND METHODS: The case records of 65 deliveries to women with IDDM were reviewed. Fifty-seven deliveries were included in the present study. Of the deliveries reviewed, 32 women were in their first pregnancy and 25 women were multiparous. Only viable pregnancies were included because the major outcome variable of interest was birth weight. Glycosylated hemoglobin was recorded for each time period. RESULTS: The median standardized birth weight was 1.1 SD higher than the nondiabetic mean. When pregnancies, in which the birth weight was greater than 1 SD above the nondiabetic mean, were compared with pregnancies, in which birth weight was less than 1 SD above the mean, significant differences were observed between the groups in HbA1 at 6-12 months pre-conception (10.0 +/- 2.3 vs. 8.6 +/- 1.4%, P = 0.02), at 0-6 months pre-conception (10.2 +/- 2.4 vs. 8.7 +/- 2.0%, P = 0.03), at booking (9.5 +/- 2.2 vs. 8.4 +/- 1.6%, P = 0.04), and at 0-12 weeks' gestation (9.5 +/- 2.2 vs. 8.0 +/- 1.3%, P = 0.04), but HbA1 later in pregnancy did not differ significantly between the groups. Correlational analysis of all 57 pregnancies revealed significant correlations between birth weight and HbA1 at 0-6 months pre-conception (r = 0.44, P = 0.002), at booking (r = 0.43, P = 0.001), at 0-12 weeks' gestation (r = 0.48, P = 0.001), at 12-24 weeks' gestation (r = 0.45, P = 0.001), and at 24 weeks to term (r = 0.34, P = 0.009). However, with stepwise regression analysis, only HbA1 at 0-12 weeks' gestation entered into the equation with a multiple r value of 0.48. CONCLUSIONS: Glycemic control in the immediate pre-conception period and early 1st trimester appears to have a greater influence on birth weight than does glycemic control during the later weeks of pregnancy.

Adult↗
PubMed1998

A new technique for laparoscopic splenectomy with massively enlarged spleens.

Splenectomy is indicated in several hematological disorders and it can be particularly challenging in children with sickle cell disease, splenomegaly, and recurrent sequestration. Over the last 6 months, we have developed a new technique for laparoscopic splenectomy (LS) for hypersplenism and splenomegaly in five children with sickle cell disease. The average age of our patients was 6 years (range, 2-11), and the average weight was 18.7 kg (range, 13.2-30.1). On preoperative ultrasound, spleen size index ranged from 0.42 to 0.76. For the LS, four trochars were placed. One patient, who also underwent a laparoscopic cholecystectomy, had six trochars placed, two of which were used for both cholecystectomy and splenectomy. After laparoscopic mobilization of the spleen and hilar vascular stapling, a Steiner electromechanical morcellator was inserted through the 12-mm port to extract cores of splenic tissue until complete splenectomy was achieved. No patient required conversion to an open procedure or creation of a larger incision to remove the massively enlarged spleen. Operative time averaged 190 minutes; the combined LS and cholecystectomy took 245 minutes. Postoperative length of stay was <2 days for all patients. There were no complications, and no patient required postoperative transfusion. Based on these early findings, we conclude that intracorporeal coring of splenic tissue allows for safe and complete laparoscopic removal of very large spleens in small children. It provides expedient recovery and minimal postoperative pain and scarring. This new technique should enable surgeons to perform LS even in patients with massive splenomegaly, eliminating the need for large and cumbersome intracorporeal bags or the creation of additional incisions to remove the spleen.

Child↗