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Biomedical subjects

J M Reynolds

Publications and source records attributed to J M Reynolds.

At least 19 recordsLinked to original sources
PubMed2000

Adjusting dissolution specifications for the variability induced by storage conditions.

The United States Pharmacopeia requires that drug products meet established dissolution specifications throughout their shelf life. Whereas chemical stability for six months at accelerated storage conditions is generally regarded as providing a two-year expiry period, stress conditions are not considered predictive of dissolution stability at controlled room temperature. This paper presents an application of response surface methodology intended to incorporate the variability induced by storage temperature and relative humidity into robust product dissolution specifications. Contour plots, depicting one-sided tolerance limits of percent released, are presented as a function of crushing strength and dissolution time.

Compressive Strength↗
PubMed1998

A Le Fort I osteotomy approach to lateral sphenoid sinus encephalocoeles.

Meningo-encephalocoeles of the skull base may present as spontaneous cerebrospinal fluid rhinorrhoea or acute meningitis. Previous approaches to midline skull base lesions have been either intracranial, via a craniotomy, or by transfacial or endoscopic extracranial approaches. This paper presents an alternative approach to lateral sphenoid sinus encephalocoeles through a Le Fort I osteotomy approach.

Encephalocele↗
PubMed1998

Growth in renal failure: a longitudinal study of emotional and behavioural changes during trials of growth hormone treatment.

Growth and psychological functioning were studied in 30 patients with renal failure over a two year period following the offer of growth hormone treatment for significant short stature. Parents' concerns about growth decreased significantly during the study. Twenty eight parents (93%) accepted growth hormone treatment; most (74%) were satisfied with it and would opt for it again (89%). The views of these parents were unrelated to growth outcome in their child. This suggests that the positive responses were related more to the effort to improve growth than to any objective treatment success. In contrast children's reduction in concern about growth, satisfaction with treatment (36%), and decision to opt for growth hormone again (50%) were all significantly related to improvement in growth. Parents' reports of non-compliance increased significantly from 41% at 1 year to 91% at 2 years in the group as a whole. No significant changes were identified in maternal mental distress and no additional costs to the psychological health of the children seem to have resulted from the introduction of growth hormone treatment. A group of children was identified who accepted treatment but had continued poor growth. These appeared to be at particular risk of both physical problems and associated or consequent psychological difficulties.

Adolescent↗
PubMed1997

A sampling and analytical method for the simultaneous determination of multiple organonitrogen pesticides in air.

An air sampling and analytical method was developed for organonitrogen pesticides using a combined filter and XAD-2 sorbent sampler and high performance liquid chromatography-ultraviolet detection. The method was evaluated for 14 organonitrogen pesticides by National Institute for Occupational Safety and Health evaluation guidelines and procedures. Evaluation experiments addressed limits of detection and quantitation, analytical recovery, sampler capacity, sample stability, and precision and bias over a range of 12 to 240 micrograms per sample. Samples were stable when stored for up to 30 days under either ambient or refrigerated conditions. Based on the finding of this work, 10 of the 14 compounds studied (aldicarb, captan, carbaryl, carbofuran, chlorpropham, diuron, formetanate, methiocarb, oxamyl, propham) can be successfully determined simultaneously using one method with an accuracy of better than +/- 25% of the true value with 95% confidence. Two other compounds (carbendazim/benomyl, methomyl) can be measured with the same accuracy over a more limited concentration range. The remaining two compounds (propoxur, thiobencarb) may meet this criterion, but additional samples would need to be included in the data analysis. With the current data, these two compounds can be determined with an accuracy of better than +/- 27% of the true value with 95% confidence.

Agricultural Workers' Diseases↗
PubMed1997

The blood contribution to early myocardial reperfusion injury is amplified in diabetes.

Cardiovascular disease is excessive in diabetes, and blood cell function is altered. It is not clear, however, if alterations in the blood contribute to the excessive cardiovascular complications of this disease. In this study, we compared the contribution of nondiabetic and diabetic blood to myocardial reperfusion injury. The recovery of cardiac contractile function following no-flow ischemia was studied in isolated diabetic and nondiabetic rat hearts perfused with diabetic or nondiabetic diluted whole blood. Hearts were isolated from 10- to 12-week-old diabetic (streptozotocin, 65 mg/kg, i.v.) and nondiabetic rats and perfused with a Krebs-albumin-red cell solution (K2RBC, Hct 20%). After a 30-min pre-ischemic control period, during which cardiac pump function was evaluated, diabetic and nondiabetic hearts were perfused for 5 min with diluted whole blood (DWB; Hct 20%) collected from either diabetic or nondiabetic donor animals. Coronary flow was then stopped and the hearts subjected to 30 min of no-flow ischemia. Following ischemia, the hearts were reperfused with the K2RBC perfusate. Cardiac contractile function was evaluated throughout the 60-min reperfusion period. Six groups were studied: diabetic and nondiabetic hearts perfused before ischemia with either K2RBC, nondiabetic DWB (NDDWB), or diabetic DWB (DDWB). Perfusion with DWB prior to ischemia impaired the recovery of contractile function in all cases. The impairment to recovery was greater with DDWB than with NDDWB. Although diabetic hearts perfused with K2RBC throughout recovered quite well, the effect of DDWB perfusion in the diabetic hearts was dramatic. In an effort to determine why diabetic blood impaired functional recovery, measures of blood filterability and the generation of reactive oxygen species (ROS) were made. We found that diabetic blood was less filterable than nondiabetic blood; that is, the diabetic blood cells tended to plug the 5-microm filter pores more readily than the nondiabetic blood cells. Also, we found that the diabetic blood was capable of generating significantly greater ROS (oxygen free radicals) than nondiabetic blood (P < 0.05). These findings suggest that the blood contribution to myocardial reperfusion injury is amplified in diabetes. A tendency for diabetic blood cells to plug capillary-sized pores and show enhanced oxygen free radical production may account for the excessive contribution of diabetic blood to reperfusion injury in the heart.

Animals↗
PubMed1995

Dose dependency of the kinetics of dextrans in rats: effects of molecular weight.

The effects of dose on the serum and tissue kinetics of high and low molecular weight (M(r)) dextrans were studied in rats. Single intravenous (iv) doses of 1, 25, or 100 mg of fluorescein-labeled dextrans with average M(r) of approximately 4 kD (FD-4) or 150 kD (FD-150) per kilogram of body weight were administered to rats, and serum, urine, and various tissues were collected over time. The samples were analyzed by a sensitive and specific chromatographic method. For FD-150, the area under the serum concentration-time curves (AUCs) increased disproportionately when the dose was increased from 1 to 100 mg/kg; the dose-corrected AUCs were 50.1 +/- 1.9, 85.9 +/- 2.4, and 122 +/- 3 micrograms.h/mL for the doses of 1, 25, and 100 mg/kg, respectively (p < 0.05). This increase in the dose-corrected AUCs was associated with a high and nonlinear accumulation of FD-150 in the liver; that is, the percent dose recovered in the liver decreased from 68.5 +/- 2.4% to 41.5 +/- 3.4% when the dose was increased from 1 to 100 mg/kg (p < 0.05). On the other hand, the serum kinetics of FD-4 exhibited dose independence [the dose-corrected AUCs were 2.38 +/- 0.04, 2.19 +/- 0.07, and 2.30 +/- 0.07 microgram.h/mL for the doses of 1, 25, and 100 mg/kg, respectively (p > 0.05)]. This dose independence was attributed to a high and linear excretion of FD-4 into urine as indicated by the percent doses of FD-4 excreted into urine [i.e., 82.0 +/- 1.8, 78.7 +/- 4.4, and 82.2 +/- 7.2 for the doses of 1, 25, and 100 mg/kg, respectively (p > 0.05)].(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Recruiting patients to clinical trials: lessons from studies of growth hormone treatment in renal failure.

Issues raised by the recruitment of children to trials of growth hormone treatment for short stature in chronic renal failure are reported. Information needs of parents and children are discussed, the latter should take account of the children's developmental level and anticipated involvement in decision making. When the incidence of certain side effects is low and probably unquantifiable there are particular problems; failure to include these in information sheets may compromise informed consent but inclusion will, at least for some families, make an already difficult decision even more complicated. A process of recruitment is described which attempts to protect against bias and which balances the requirement to impart neutral information with appropriate clinical involvement in the decision to enter the study. Other functions of the recruitment process are identified. Analysis of understanding and decision making demonstrates that good understanding is neither necessary nor sufficient for ease of decision making. The recruitment process was time consuming and needs planning and funding in future studies. Many of these issues are of general importance for trials of treatment in children.

Adolescent↗
PubMed1995

Short stature and chronic renal failure: what concerns children and parents?

Multicentre trials are evaluating growth hormone treatment in short children (height > 2 SDs below mean) with chronic renal failure (CRF), on dialysis, or with a transplant. Thirty children and parents from four centres were interviewed to assess psychological functioning and evaluate their concerns about growth in the context of CRF. There were 24 males and six females, age range 2-18 years. Fifty per cent of patients had additional non-renal complications and 30% had learning difficulties. Differences between the respective concerns of parents and children were striking. Parents' predominant concern was their child's future health (50%) and prospects (37%) while children's main concern was the impact of illness on their family (50%). Growth was a major concern for 30% of parents and 28% of children. Growth problems are important and should be considered within the context of other illness issues. Improved understanding of parental and child concerns may help maximise the benefits of growth hormone and assist in the management of children with CRF.

Adolescent↗
PubMed1994

Molecular weight dependent tissue accumulation of dextrans: in vivo studies in rats.

The effects of molecular weight (M(r)) on the serum and urine pharmacokinetics and tissue distribution of dextrans, potential macromolecular carriers for drug delivery, were studied in rats. A single 5 mg/kg dose of fluorescein-labeled dextrans (FDs) with a M(r) of 4000 (FD-4), 20,000 (FD-20), 70,000 (FD-70), or 150,000 (FD-150) was administered into the tail vein of separate groups of rats. At different times after the administration of each FD, animals were sacrificed, and blood, urine, and various tissues were obtained. The concentrations of FDs in the samples were subsequently determined by using a sensitive and specific high performance size exclusions chromatographic method. Among the tissues studied, high accumulation of dextrans was found only in the liver (liver:serum AUC ratios < or = 29) and spleen (spleen:serum AUC ratios < or = 10), with high concentrations in these tissues persisting even at the last sampling time (96 h). In contrast, the serum concentrations of the studied FDs were not measurable beyond 12 h. The serum and urine kinetics and the liver, spleen, and kidney accumulation of FDs demonstrated a significant degree of M(r) dependency. The total and renal clearance of FDs consistently decreased with an increase in M(r). However, the effects of M(r) on the tissue accumulation of dextrans was tissue dependent. For the liver, the tissue:serum AUC ratios increased from 0.346 for FD-4 to 15.2 for FD-20 and 28.8 for FD-70, while a further increase in M(r) to 150 kDa (FD-150) resulted in lowering the ratio to 8.59 in this tissue. For the spleen, the ratios increased from 0.095 for FD-4 to 9.56 for FD-150.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Psychiatric adjustment in end-stage renal disease: a follow up study of former paediatric patients.

Life-time psychiatric adjustment was studied in forty-five young adult survivors of a paediatric dialysis and transplantation programme and in a comparison group matched for age and sex. Renal patients reported more psychological problems in childhood and had lower self-esteem in adulthood, but adult lifetime psychiatric morbidity was comparable in both groups. There were differences in the pattern of psychiatric disorder with a trend for more depressive states in the renal group. Lower self-esteem was linked to early onset renal disease and to educational and social dysfunction. Results indicate relatively favourable adult adjustment of juvenile renal patients.

Adaptation, Psychological↗
PubMed1994

Persistent hyperdynamic cardiovascular state at rest and during exercise in children after successful repair of coarctation of the aorta.

OBJECTIVES: The purposes of this study were to evaluate left ventricular performance and contractility at rest and during exercise to determine mechanisms and correlates for alterations in performance and blood pressure in pediatric patients after successful repair of coarctation of the aorta. BACKGROUND: Blood pressure and left ventricular function are elevated in children despite successful repair. The mechanisms for these changes are not understood. METHODS: Thirty asymptomatic pediatric patients with successful coarctation repair (mean age [+/- SD] 12.5 +/- 4 years) underwent echocardiographic determination of left ventricular mass, performance (shortening fraction), preload (indexed diastolic dimension), afterload (end-systolic wall stress), contractility (velocity of circumferential fiber shortening/wall stress relation) and Doppler gradient at rest and during exercise. Data were compared with those of 24 control subjects (mean age 21.0 +- 4 years). Because of the age discrepancy between groups, age-dependent echocardiographic data were indexed by body surface area. RESULTS: The mean age at operation was 5 +/- 4 years, and the average follow-up period was 7.5 +/- 3 years. The average blood pressure gradient between upper and lower limbs was 4 mm Hg. Left ventricular mass was higher in the postoperative group than in the control group (1.58 vs. 1.31 g/ht2.7, p = 0.04), as were values at rest for performance (44% vs. 31%, p = 0.0001), preload (3.9 vs. 3.7 cm/body surface area0.5), indexes systolic blood pressure (1.05 vs. 0.91, p = 0.0001) and contractility (0.23 vs. -0.05 circumferences/s, p= 0.001). Afterload was lower at rest (36 vs. 52 g/cm2, p = 0.0004). These differences between groups persisted during and after exercise. Contractility underwent an exaggerated increase after exercise in the postoperative group. CONCLUSIONS: Left ventricular performance in children after coarctation repair is higher at rest and during exercise than in control subjects as a result of higher preload and contractility and lower afterload. These changes may be due to associated hypertrophy. Persistent postoperative hypertension may be due to a hyperdynamic, hypercontractile state caused by residual gradients manifested only during exertion.

Adolescent↗
PubMed1994

Enantioselective kinetics of verapamil and norverapamil in isolated perfused rat livers.

The kinetics of the individual enantiomers of verapamil (VER) and its metabolite, norverapamil (NOR), were studied in isolated perfused rat livers (IPRLs) after administration of racemic drug or the preformed metabolite. After constant infusion of 20 micrograms/min of racemic VER to single-pass IPRLs, the hepatic availabilities (F) of the enantiomers were low (S-VER, 0.069 +/- 0.030; R-VER: 0.046 +/- 0.025) and stereoselective (S:R ratio, 1.6 +/- 0.2). After administration of similar doses, the F values of the preformed NOR enantiomers (S-NOR: 0.24 +/- 0.04; R-NOR, 0.10 +/- 0.02) were higher than those of the VER enantiomers. However, the stereoselectivity in F of NOR (S:R ratio, 2.2 +/- 0.1), was in the same direction of that of VER. Further, the fractions of R enantiomers unbound to bovine serum albumin in the perfusate were higher than those of their antipodes for both VER (R:S ratio, 1.9 +/- 0.1) and NOR (R:S ratio, 2.6 +/- 0.2). Therefore, for unbound moieties, modest stereoselectivity in the metabolism of VER in favor of the S-isomer and no stereoselectivity in the metabolism of NOR were observed. Overall, our data suggest that the stereoselective protein binding is a primary determinant of stereoselectivity in the hepatic availability of VER and NOR in IPRLs.

Animals↗
PubMed1994

Brief perfusion with diluted whole blood after global myocardial ischaemia increases reperfusion injury.

OBJECTIVES: In vivo studies indicate that blood components, especially leucocytes, contribute to reperfusion injury after myocardial ischaemia. This study was designed to: (1) develop a small animal heart model of ischaemia-reperfusion that demonstrates the contribution of blood to reperfusion injury; (2) determine when the presence of blood in the heart--that is, during ischaemia or during early reperfusion--caused greater dysfunction; and (3) attempt to limit the blood contribution to reperfusion injury by leucocyte depletion. METHODS: Adult rat hearts were perfused in situ with a Krebs-albumin red cell solution (K2RBC), then isolated. Cardiac pump function was assessed with an intraventricular balloon as left ventricular developed pressure and contractility (dP/dt). Group I served as a non-ischaemic control group. Group II was subjected to global, no flow ischaemia for 30 min followed by 45 min reperfusion. In group III, diluted whole blood replaced the K2RBC for five min immediately before ischaemia. In group IV, diluted whole blood was perfused during the first five min reperfusion. In group V, the hearts were reperfused with leucocyte poor diluted whole blood. RESULTS: Pre-ischaemic pump function values were similar to other blood perfused, isolated heart models. Group I showed no increase in coronary resistance or decrease in pump function with time or in response to diluted whole blood. After 35 min reperfusion, the recovery (% control) of dP/dt in group II was 56(12), in group III it was 39(15) and in group IV it was only 19(6) (p < 0.05). Large increases in coronary vascular resistance, oedema, and contracture during reperfusion were also seen in group IV. When leucocytes were depleted from the diluted whole blood (group V), the recoveries were similar to reperfusion without diluted whole blood (group II). CONCLUSIONS: Thirty min of global, normothermic ischaemia caused significant cardiac dysfunction early during reperfusion. Perfusion with unstimulated blood for a limited period further impaired the recovery of function and enhanced myocardial oedema. Dysfunction was particularly evident when diluted whole blood was perfused during the first minutes of reperfusion. The leucocyte depletion studies suggest that leucocytes are necessary, but may not be sufficient, to demonstrate the blood contribution to reperfusion injury.

Animals↗
PubMed1994

Platelets do not modulate leukocyte-mediated coronary microvascular damage during early reperfusion.

Several studies indicate that leukocytes and platelets exacerbate the compromise of myocardial function that occurs after ischemia-reperfusion (I/R). However, it is unclear whether both leukocytes and platelets must be present to mediate coronary microvascular damage early during reperfusion after ischemia. To examine the effects of leukocytes and platelets on microvascular damage after I/R, we measured transcoronary albumin extravasation (O/I), perfused coronary capillary density (Caps), and transcoronary albumin extravasation per perfused capillary [(O/I)/Caps] in isolated rat hearts perfused with a Krebs-albumin-red blood cell solution [K(2)RBC], whole rat blood diluted with Krebs buffer (DWB), leukocyte-free, platelet-rich DWB (LFB), or leukocyte-rich, platelet-free DWB (LRB) before and after a 30-min period of global, no-flow ischemia. We found that in isolated hearts perfused with K(2)RBC before ischemia, O/I values were significantly increased (+68%, P < 0.01) and Caps values were significantly decreased (-25%, P < 0.05) after 25 min of reperfusion. A similar pattern of O/I values (+72%, P < 0.01) and Caps values (-40%, P < 0.05) was observed in hearts perfused with LFB. These effects were exacerbated in hearts perfused with DWB or LRB. O/I values were increased 90% (P < 0.01), and Caps values were decreased 62% (P < 0.01) in the DWB-perfused hearts. Similar increases in O/I values (+82%, P < 0.01) and decreases in Caps values (-65%, P < 0.01) were measured in the LRB-perfused hearts. Additionally, (O/I)/Caps values were significantly increased in the hearts perfused with DWB (+93%, P < 0.01) and LRB (+84%, P < 0.01) compared with the hearts perfused with K(2)RBC or LFB. These results suggest that interactions between leukocytes and platelets are not requisite for the development of coronary microvascular damage early during reperfusion after ischemia.

Animals↗
PubMed1993

Psychosocial adjustment of adult survivors of a paediatric dialysis and transplant programme.

The social adjustment of 45 young adult renal patients who commenced treatment for end stage renal disease (ESRD) as children and of 48 age and sex matched controls were compared. Renal patients were less socially mature than controls. More lived with their parents, fewer had an intimate relationship outside the family, they had fewer school qualifications, and there was more unemployment among them. The majority, however, were in employment and the level of subjective stress and support derived from most of these areas was comparable in renal patients and in controls. Having a close relationship with a member of the opposite sex was the only domain in which renal patients reported more stress than controls. Early start of illness and current health problems were associated with poorer social outcome. A lifelong history of ESRD leads to suboptimal or delayed social functioning on conventional indicators. However this does not lead to increased overall distress in the patients about their social circumstances and quality of life does not appear to be substantially impaired.

Adaptation, Psychological↗