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Biomedical subjects

D Mackintosh

Publications and source records attributed to D Mackintosh.

At least 19 recordsLinked to original sources
PubMed2006

Measuring memory impairment in community-based patients with schizophrenia. Case-control study.

BACKGROUND: The majority of memory impairment studies in schizophrenia are cohort studies using laboratory-based tests, which make it difficult to estimate the true extent and relevance of memory impairment in patients with schizophrenia in the community. AIMS: To examine the extent of memory impairment in community-based patients with schizophrenia using a clinically relevant test. METHOD: All patients with schizophrenia (n=190) in one catchment area were identified, of whom 133 were potentially eligible for the study; 73 patients volunteered to take part. They were assessed using the Rivermead Behavioural Memory Test (RBMT), the National Adult Reading Test, the Positive and Negative Syndrome Scale, the Health of the Nation Outcome Scales and the Scales and the Office for National Statistics Classification of Occupation. Their performance on the memory test was compared with that of matched controls (n=71). RESULTS: Patients as a group performed significantly worse (P<0.001) than controls on the RBMT. Using the RBMT normative scores, 81% of patients were found to have impaired memory compared with 28% of controls. CONCLUSIONS: Using a clinically relevant test, the majority of community-based patients with schizophrenia may have memory impairment.

Adolescent↗
PubMed2003

Comparison of prognostic factors in patients in phase I trials of cytotoxic drugs vs new noncytotoxic agents.

The aims of this study were to identify prognostic variables for toxicity and survival in patients with cancer participating in phase I clinical trials and compare characteristics of those treated with cytotoxic chemotherapy (CT) and non-cytotoxic drugs (non-CT). Data were collected from 420 (114 CT, 306 non-CT) patients enrolled in 16 phase I trials (five CT and 11 non-CT trials) in one cancer centre. Analyses of all patients were used to compare treatment groups, identify predictive variables for toxicity and to estimate prognostic factors in overall survival (OS). These were used to develop a prognostic index (PI). Multivariate analysis found those patients with better performance status, fewer sites of metastases, baseline Hb>12 g dl(-1) and WBC or LDH in the normal range had significantly better OS. Male gender, platelet count <450 x 10(9) l(-1), high WBC or treatment with a non-CT phase I agent significantly reduced the chance of grade 3/4 toxicity. Overall survival was not significantly different between the CT and non-CT groups (260 vs 192 days, P=0.47) except for those with liver metastases (228 vs 137 days, P=0.02). Overall tumour response was 4.9% (95% CI: 2.7-7.0%). The PI identified three distinct patient groups with median survival of 321, 257 and 117 days. In conclusion, entry into a phase I trial of a non-CT drug is a safe option for heavily pretreated patients with cancer. The PI generated from these data can estimate the survival probability for patients entering phase I studies.

Adult↗
PubMed1994

Prevalence of asthma and wheeze in the Highlands of Scotland.

To establish the prevalence of asthma and wheeze in 12 year old children in a region with low background pollution levels, a population of children resident in the Highland Region of Scotland was studied by questionnaire supported by objective data. A respiratory questionnaire was distributed to the parents of 1919 children aged from 12-13 years and attending secondary schools in the educational divisions of Lochaber, Ross and Cromarty, and Inverness including Skye in Highland Region to ascertain history of wheeze and parental awareness of a diagnosis of asthma. Peak expiratory flow (PEF) measurements were carried out before and after a standardised exercise test. Ozone levels were noted. Questionnaires were completed by 1825 parents (95% of those invited) and 1702 (93%) of those returning questionnaires took part in the exercise test. The overall prevalence of reported asthma was 14% and wheeze 25%. Defined as a fall in PEF of more than 15% with exercise, the overall prevalence of exercise induced bronchospasm was 9%. In Skye the prevalence of reported asthma was 17%, wheeze 28%, and exercise induced bronchospasm 30%. There were no significant differences between areas for reported asthma or wheeze. There was, however, a highly significant difference between areas for exercise induced bronchospasm, most of which was accounted for by the very high incidence in Skye, which is one of the most rural of the areas studied. The results of this study do not support the hypothesis that asthma is commoner in urban than rural areas, whether we compare the Highlands with the rest of the UK or areas within the Highlands, or whether we examine reported symptoms or exercise induced bronchospasm. The results do not support an association between atmospheric pollution and the prevalence of asthma.

Adolescent↗
PubMed1993

UDP-sugar metabolism in Swarm rat chondrosarcoma chondrocytes.

UDP-sugars and adenine nucleotides were extracted from freshly isolated chondrocytes and primary cell cultures and analysed by anion-exchange h.p.l.c. The pool sizes of UDP-N-acetylglucosamine, UDP-N-acetylgalactosamine, UDP-glucose-galactose, UDP-glucuronate and UDP-xylose were 2.9, 1.2, 2.5, 0.6 and 0.03 nmol/10(6) freshly isolated chondrocytes. When chondrocytes were maintained in Dulbecco's modified Eagle medium supplemented with 15% foetal-bovine serum, synthesis of [35S]proteoglycan and [3H]protein decreased over the first 48 h in culture, as did the pools of UDP-glucuronate and ATP. In contrast, the size of the UDP-N-acetylhexosamine pools underwent little change during culture. [35S]Proteoglycan and [3H]protein syntheses were stimulated in cultures supplemented with serum or insulin compared with those maintained in medium alone, in agreement with previous results. However, the UDP-sugar pool sizes were the same in both supplemented and non-supplemented cultures. In cultures maintained in the presence of [1-3H]glucose, the UDP-sugars were labelled to a constant 3H specific radioactivity which was very similar to that of the labelling medium. UDP-N-acetylhexosamines were labelled to constant 3H specific radioactivity with [6-3H]glucosamine as a precursor, but only about 1 in 375 of these UDP-sugars was derived from the amino sugar in the presence of glucose. The half-life (t1/2) for UDP-hexoses, UDP-glucuronate and UDP-N-acetylhexosamines was about 12, 12 and 50 min respectively.

Animals↗
PubMed1988

Pharmacological actions of 17 beta-oestradiol on articular cartilage chondrocytes and chondrosarcoma chondrocytes in the absence of oestrogen receptors.

(1) Pharmacological concentrations (greater than 10(-5) M) of 17 beta-oestradiol inhibited 35S-labelled proteoglycan synthesis in bovine articular cartilage explant cultures. They also inhibited 35S-labelled proteoglycan synthesis and 3H-labelled protein synthesis in cell cultures of chondrocytes from bovine articular cartilage and Swarm rat chondrosarcoma. Maximal inhibition was about 30-50%. Physiological concentrations (10(-9)-10(-8) M) of oestradiol had no effect on the synthesis of either protein or proteoglycan. (2) The inhibitory action of high concentrations of oestradiol on these biosynthetic pathways is not common to all steroids since 10(-4) M cortisol had no effect on articular chondrocyte cell cultures. 10(-4) M testosterone had a similar action to oestradiol. (3) Neither physiological nor pharmacological concentrations of 17 beta-oestradiol had any effect on 35S-labelled proteoglycan turnover in the cartilage explant system. (4) 10(-5) M oestradiol inhibited cell division in cultures of articular chondrocytes which had entered the log growth phase. 10(-7) M oestradiol had no effect on articular chondrocyte growth. (5) In male rats implanted with silastic capsules releasing 17 beta-oestradiol, increase in body weight was retarded by about 25% over a period of 6 weeks, compared to control rats. Rat chondrosarcoma grew to the same size in oestrogen-treated rats as it did in controls. (6) Oestrogen receptors could not be detected in freshly isolated bovine articular chondrocytes or in rat chondrosarcoma. (7) In conclusion, neither the mitotic rate of articular chondrocytes nor their proteoglycan metabolism is under the direct physiological control of oestradiol. Growth and biosynthetic activity of the rat chondrosarcoma chondrocytes are independent of either direct control by the hormone or control effected by oestradiol regulation of a second hormone or growth factor.

Animals↗
PubMed1984

Glycaemia, arterial pressure and micro-albuminuria in type 1 (insulin-dependent) diabetes mellitus.

Plasma glucose control and arterial pressure were assessed in 28 Type 1 (insulin-dependent) diabetic patients with different degrees of micro-albuminuria. They were divided into two groups according to their urinary albumin excretion rate: a low micro-albuminuria group (n = 16) with albumin excretion ranging between 12.1 and 28.9 micrograms/min and a high micro-albuminuria group (n = 12) with albumin excretion between 32.4 and 91.3 micrograms/min. The groups were matched for age, sex and duration of diabetes with the same number of normo-albuminuric (2.0-10.4 micrograms/min) diabetic control subjects. Both the low and high micro-albuminuria groups had significantly higher glycosylated haemoglobin levels and mean plasma glucose concentrations during a 24-h profile than their respective normo-albuminuric control subjects. A correlation between glycosylated haemoglobin level and urinary albumin excretion rate was found in the whole study group (r = 0.48; p less than 0.001). Arterial pressure (both systolic and diastolic) was significantly higher in the high micro-albuminuria group than in either the control group or the low micro-albuminuria group. A significant correlation was found between arterial pressure and albumin excretion rate in the whole study population (r = 0.49; p less than 0.001) as well as in the pooled micro-albuminuria groups (r = 0.43; p less than 0.05). Multiple regression analysis showed that glycosylated haemoglobin and arterial pressure levels were independently correlated with albumin excretion rates. Diabetic patients with micro-albuminuria of any degree have worse glycaemic control than normo-albuminuric patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1983

Long term correction of hyperglycaemia and progression of renal failure in insulin dependent diabetes.

The effect of long term correction of hyperglycaemia on the rate of deterioration of renal function was studied in six insulin dependent diabetics with proteinuria due to diabetic nephropathy. After a planned run in observation period of 10 to 24 months patients entered a programme of continuous subcutaneous insulin infusion for up to 24 months. Glycaemic control was promptly and significantly improved and optimal glycaemic values sustained throughout the study. Blood pressure was maintained stable. A control group of six nephropathic diabetics was studied receiving conventional insulin injection treatment but also with blood pressure control over the same period.Despite greatly improved metabolic control in the infusion treated group no significant change in the rate of decline of glomerular filtration rate could be shown, the plasma creatinine concentrations continued to increase, and the fractional clearance of albumin and IgG rose progressively, indicating progression of glomerular damage. The conventionally treated control group behaved similarly. In a single patient receiving the continuous infusion the rate of decline of the glomerular filtration rate slowed considerably, suggesting that the response to strict diabetic control may differ in some patients.These findings suggest that by the time glomerular function has started to fail in diabetic nephropathy the process culminating in end stage renal failure has become self perpetuating and is little influenced by the degree of metabolic control. A new definition of potential clinical diabetic nephropathy is proposed that will permit identification of patients at risk and earlier intervention by glycaemic correction in an attempt to arrest diabetic renal disease.

Adult↗
PubMed1983

Failure of sodium aurothiomalate and triethyl phosphine gold to cause renal tubular injury in rheumatoid arthritis: implications for the aetiology of gold-related nephropathy.

The urinary excretion of two proteins, B-2-microglobulin (beta 2M) and N-acetyl-B-D-glucosaminidase (NAG) was measured in 25 patients with rheumatoid arthritis (RA) on nonsteroidal anti-inflammatory drugs (NSAID). Although beta 2M excretion was normal NAG excretion was raised. As NAG excretion by a group of osteoarthritis patients receiving similar doses of NSAIDs was normal, it is concluded that rheumatoid disease per se may be associated with mild renal tubular dysfunction. Twelve of the above 25 patients were then given oral triethylphosphine-gold (auranofin) 6 mg daily and urinary beta 2M and NAG were measured after 6 months' treatment. Urinary excretion of beta 2M and NAG was also measured in 13 patients with RA established on intramuscular sodium aurothiomalate (MGST) and NSAIDs. Neither auranofin nor myocrisin were found to further significantly increase beta 2M and NAG excretion. These results suggest that gold compounds are not toxic to renal tubular epithelium.

Acetylglucosaminidase↗
PubMed1983

Monitoring glomerular function in diabetic nephropathy. A prospective study.

Glomerular function was monitored prospectively in 13 patients with insulin-dependent diabetes and diabetic nephropathy for up to 51 months. Glomerular filtration rate, measured by 51Cr-EDTA clearance, showed a linear decline in all patients. Rates of fall ranged between 0.63 and 2.4 ml/minute per month (mean +/- SEM 1.2 +/- 0.16). Plasma creatinine concentration proved to be an insensitive marker of glomerular function, especially in the early phase of nephropathy. A good correlation was found between the rate of change of 51Cr-EDTA glomerular filtration rate and that of inverse creatinine levels when plasma creatinine concentrations exceeded 200 mumol/liter. Inverse plasma beta 2-microglobulin concentrations, however, showed a highly significant correlation (r = 0.93; p less than 0.001) with 51Cr-EDTA glomerular filtration rate over the whole range of values, making it sensitive in screening for early impairment of renal function. A significant relationship (r = 0.85; p less than 0.01) was found between the rates of change of the 51Cr-EDTA glomerular filtration rate and of inverse beta 2-microglobulin levels for plasma beta 2-microglobulin concentrations above 3 mg/liter. A progressive increase in the fractional clearance of albumin, IgG, and beta 2-microglobulin was noted as the glomerular filtration rate fell, indicating an evolving defect in the renal handling of proteins. The rate of decline of the glomerular filtration rate was unrelated to age, sex, duration of diabetes, duration of diabetes before onset of proteinuria, glomerular filtration rate, initial albumin clearance, blood glucose control, and arterial pressure, when diastolic values were below 100 mm Hg. The effect of therapeutic intervention (e.g., blood glucose, blood pressure, or diet) on the progression of diabetic nephropathy can be reliably evaluated by precise measures of rate of decline of glomerular filtration rate and changes in fractional clearance of plasma proteins. The factor(s) determining the individual rate of decline of renal function still remain obscure.

Adult↗
PubMed1983

Determinants of the penetration of proteins through the glomerular barrier in insulin-dependent diabetes mellitus.

To investigate the determinants of the glomerular filtration of proteins in insulin-dependent diabetic patients we studied the fractional clearance of albumin (theta Alb) and IgG (theta IgG) and the selectivity index (SI = IgG clearance/Alb clearance) in 32 subjects with macroproteinuria (albustix positive), in 29 subjects with microproteinuria (albustix negative), and in 24 healthy control subjects. Fractional clearances of both albumin and IgG were higher in macroproteinuric than in microproteinuric patients, with both groups having higher values than controls (all P less than 0.001). In microproteinuric patients with albumin excretion rate (AER) not exceeding 60 micrograms/min, there was a highly significant correlation between the clearance of albumin and that of IgG. The SI was normal for AERs up to 30 micrograms/min, but above that albumin filtration increased disproportionately and SI progressively fell. In insulin-dependent diabetics with macroproteinuria, there was a negative correlation between SI and glomerular filtration rate (GFR) (r = -0.68; P less than 0.001); the lower SI (0.133 +/- 0.06) at higher GFRs also was due to a preferential increase in albumin clearance. Selectivity was progressively lost as GFR declined, and the SI returned to normal values when GFR fell below 10 ml/min/1.73 m2; this was due to a progressively higher rise in the fractional clearance of IgG relative to albumin. We suggest that glomerular filtration of proteins is governed by different determinants at different stages of the disease. In microproteinurics with AER below 60 micrograms/min, increased intraglomerular pressure seems primarily responsible for the higher proportional filtration of both albumin and IgG.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1983

beta 2 microglobulin plasma levels reflect disease activity in rheumatoid arthritis.

Elevated plasma levels of beta 2 microglobulin have been described in rheumatoid arthritis (RA) but their relationship to disease activity is unclear. In patients treated for 6 months with auranofin (AF) there was a significant fall (p less than 0.05) in beta 2M levels pari passu with improvement in disease activity as measured by a fall in C-reactive protein. In addition, 26 patients with mild RA had beta 2M levels within the normal range. It is concluded that beta 2M plasma levels reflect disease activity in RA.

Anti-Inflammatory Agents↗
PubMed1982

Proteinuria in diabetes mellitus: role of spontaneous and experimental variation of glycemia.

The excretion rates of albumin, IgG and beta 2-microglobulin were studied in insulin-dependent diabetic patients with (Albustix positive) and without (Albustix negative) clinical proteinuria and in a group of nondiabetic controls. In patients negative for clinical proteinuria, the mean excretion rate of albumin and IgG was increased but that of beta 2-microglobulin was normal. HbA1, a measure of excess glycemia, was positively correlated with both albumin and IgG urinary excretion rates. Vigorous correction of glycemic control significantly reduced IgG excretion in nine patients. In patients positive for clinical proteinuria, albumin and IgG clearances were inversely correlated with GFR, the filtration of IgG increasing relatively more than that of albumin as GFR declined. A negative hyperbolic correlation was found between GFR and beta 2-micro-globulin excretion. In this group HbA1 was unrelated to excretion rates or clearances of albumin and IgG. In clinically proteinuric patients, long-term correction of hyperglycemia by continuous subcutaneous insulin infusion failed to check the increasing albumin and IgG filtration. The microproteinuria of diabetes is glomerular in origin, is influenced by prevailing glycemia, and is reversible by vigorous glycemic control. In the clinically proteinuric phase, by contrast, selectivity is progressively lost and, as GFR falls, proteinuria becomes of a mixed glomerular and tubular origin. There is no evident association with prevailing glycemia, and metabolic near-normalization dose not appear to affect progression over the period of observation considered. This study suggests that clinical proteinuria denotes the installation of a self-maintaining process, largely independent of the diabetic metabolic disturbance which gave rise to it. Prevention of clinical diabetic nephropathy by metabolic correction may be achievable only in the phase of early microproteinuria.

Adult↗
PubMed1981

Beta 2-microglobulinaemia: a sensitive index of diminishing renal function in diabetics.

A sensitive single measure of diminishing renal function is of importance in attempts to modify the progression of diabetic nephropathy. In 12 insulin-dependent diabetics with proteinuria plasma concentrations of beta 2-microglobulin were found to correlate more closely than plasma creatinine concentrations or creatinine clearance with glomerular function as measured by clearance of 52Cr-EDTA. The plasma beta 2-microglobulin concentration was raised in all patients with diminished glomerular filtration rate (below 80 ml/min/1.73 m2). By contrast, in two of these patients plasma creatinine concentration was normal. Plasma beta 2-microglobulin concentrations were stable throughout the day and not affected by food intake, unlike plasma creatinine concentrations, which rose in the afternoon and evening and after a meat meal. Plasma beta 2-microglobulin concentrations were the same in venous and capillary blood, the capillary blood being readily self-collected. Concentrations of beta 2-microglobulin were stable for up to 24 hours when whole blood was stored at 4 degrees C; adding aprotinin inhibited loss of beta 2-microglobulin for up to seven days. The results of this study suggest, therefore, that measuring beta 2-microglobulin concentrations is a simple and accurate method of detecting minor degrees of renal impairment and monitoring the effects of treatment.

Adult↗
PubMed1981

The influence of glucose-induced hyperinsulinaemia on renal glomerular function and circulating catecholamines in normal man.

The circulatory, renal, and hormonal responses to physiological elevation of plasma insulin induced with oral glucose have been studied in seven healthy subjects. glomerular filtration rate, urinary excretion rates of albumin and Beta2-microglobulin, haematocrit, pulse rate, blood pressure and plasma catecholamine concentrations have been measured. Physiological hyperinsulinaemia following glucose ingestion was associated with an increase in noradrenaline levels and brief tachycardia. No effect was noted on haematocrit, creatinine clearance, urinary albumin excretion, plasma adrenaline concentrations and arterial blood pressure. Urinary Beta2-microglobulin excretion rates fell shortly after the elevation of plasma insulin, probably indicating enhanced tubular reabsorption. Thus, glucose-induced physiological hyperinsulinaemia does not reduce glomerular filtration rate nor does it increase transglomerular passage of albumin, effects seen after the intravenous bolus injection of 6-8 U of insulin in diabetics.

Adult↗
PubMed1981

Correction of exercise-induced microalbuminuria in insulin-dependent diabetics after 3 weeks of subcutaneous insulin infusion.

The effect of metabolic near-normalization, induced by continuous subcutaneous insulin infusion, on the exaggerated microalbuminuria of exercise was studied in eight insulin-dependent diabetic men selected for normal resting albuminuria. Patients were studied in randomized order during the ordinary glycemic control of conventional insulin treatment (CIT) and after 3 wk of "super-control" with continuous subcutaneous insulin infusion (CSII). Seven age-matched healthy men were used as controls. In the diabetics the albuminuric response to fixed-load bicycle exercise (600 kpm/min for 20 min) during CIT greatly exceeded that of the normal controls (P less than 0.01). After 3 wk of optimal plasma glucose control, urinary albumin excretion rates in response to the same exercise load were significantly reduced (P less than 0.02) in the diabetics and became statistically indistinguishable from that of the normal controls. The urinary excretion rate of beta 2-microglobulin, an index of tubular function, was not increased significantly by exercise either during CIT or CSII. The plasma glucose fall after exercise was greater (P greater than 0.001) on CIT (8.5 +/- 0.9 mmol/L) than on CSII (4.0 +/- 0.6 mmol/L). The pulse rate acceleration in response to exercise was significantly reduced after 3 wk of CSII (P less than 0.05). The exercise-induced systolic blood pressure rise was similar in controls and diabetics on both therapeutic regimens. Thus, a period of metabolic near-normalization in the diabetic corrects the abnormal transglomerular passage of albumin induced by moderately strenuous muscular exercise and reduces the exercise tachycardia. Improved control with CSII appears to reduce greatly the risk of exercise-induced hypoglycemia, despite much tighter glycemic control.

Adult↗