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Biomedical subjects

S M Marshall

Publications and source records attributed to S M Marshall.

At least 19 recordsLinked to original sources

Circadian variation of blood pressure in patients with diabetic nephropathy.

The association between diurnal blood pressure variation and diabetic nephropathy was assessed in four groups of Type 1 (insulin-dependent) diabetic patients who underwent 24-h ambulatory blood pressure monitoring using an oscillometric technique. Patients with nephropathy, who had never been treated for hypertension (group D3, n = 13), were individually matched for age, sex and diabetes duration to a group of microalbuminuric patients (D2, n = 26), to normoalbuminuric patients (D1, n = 26) and to healthy control subjects (C, n = 26). Group D3 was also compared to patients with advanced nephropathy receiving treatment for hypertension, mainly a combination of angiotensin converting enzyme inhibitors, metoprolol and diuretics (D4, n = 11). In group D3 24-h diastolic blood pressure (85 +/- 8 mm Hg) was comparable to the results obtained in D4 (85 +/- 8 mm Hg) but significantly higher than in D2 (78 +/- 7 mm Hg), D1 (73 +/- 7 mm Hg) and C (73 +/- 7 mm Hg, p < 0.05, Tukey's test). The night/day ratio of diastolic blood pressure was higher in D3 (86 +/- 5%) and D2 (85 +/- 7%) than in C (80 +/- 7%, p < 0.02). This ratio was also elevated in group D4 (94 +/- 8%) compared to D3 (p < 0.05) corresponding to a marked smoothing of the diurnal blood pressure curve. The 24-h heart rate (beats per min) was significantly elevated in D3 (84 +/- 8) and D2 (80 +/- 10) compared with C (73 +/- 11, p < 0.05 Tukey's test), suggesting the presence of parasympathetic neuropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Octreotide administration in diabetic rats: effects on renal hypertrophy and urinary albumin excretion.

Initial renal hypertrophy in experimental diabetes is prevented by administration of a long-acting somatostatin analogue octreotide (SMS). To investigate the long-term effects of SMS on renal hypertrophy and urinary albumin excretion (UAE), streptozotocin-diabetic and non-diabetic rats were treated with two daily subcutaneous injections of SMS (100 micrograms x 2) for six months. Untreated diabetic and non-diabetic animals were used as reference groups. No differences were seen between the two diabetic groups in respect to body weight, food intake, blood glucose levels, urinary glucose output, hemoglobin A1C(HbA1C), fructosamine, serum growth hormone (rGH) or creatinine clearance, but kidney weight (896 +/- 36 vs. 1000 +/- 24 mg, P less than 0.02), UAE (417 +/- 131 vs. 1098 +/- 187 micrograms/24 hr, P less than 0.02), kidney insulin-like growth factor I (IGF-I) (167 +/- 16 vs. 239 +/- 17 ng/g, P less than 0.01) and serum IGF-I (301 +/- 26 vs. 407 +/- 17 micrograms/liter, P less than 0.01) were all reduced in the SMS-treated diabetic animals when compared to the untreated diabetic group. In non-diabetic rats SMS reduced body weight (274 +/- 3 vs. 293 +/- 5 g, P less than 0.01), kidney weight (695 +/- 9 vs. 764 +/- 17 mg, P less than 0.01), UAE (83 +/- 29 vs. 364 +/- 114 micrograms/24 hr, P less than 0.02), kidney IGF-I (202 +/- 12 vs. 280 +/- 12 ng/g, P less than 0.01), serum IGF-I (428 +/- 21 vs. 601 +/- 54 micrograms/liter, P less than 0.01) and serum rGH (67 +/- 6 vs. 126 +/- 27 micrograms/liter, P less than 0.05) when compared to untreated controls. When kidney weights were expressed in relation to body weight no difference was found between SMS-treated and untreated controls, while the difference between SMS-treated and untreated diabetic animals was still present (P less than 0.01). In conclusion, chronic administration of SMS has abating effects on diabetic renal hypertrophy and UAE, and thus indicates that SMS may reduce development of diabetic kidney lesions in experimental diabetes. The long-term suppressive effects of SMS on renal enlargement and UAE may in part be mediated through reduction in circulating and kidney IGF-I levels.

Albuminuria

Insulin-like growth factor I in initial renal hypertrophy in potassium-depleted rats.

We investigated insulin-like growth factor I (IGF-I) in the kidney during the initial renal enlargement induced by dietary K depletion in rats. Kidney weight increase was significant after 3 days of K depletion and amounted to 29% after 7 days compared with pair-fed controls [839 +/- 34 vs. 648 +/- 17 mg (SE), P less than 0.01]. The kidney growth occurred despite almost complete arrest in body weight gain in K-depleted animals (8 +/- 3 vs. 34 +/- 4 g/7 days in controls, P less than 0.01). Whole kidney protein, RNA, and DNA estimations indicated that cellular hypertrophy during the first 4 days was followed by hyperplasia. Immunoassayable kidney IGF-I concentration increased by 106% (673 +/- 30 vs. 327 +/- 14 ng/g, P less than 0.01) in K-depleted animals 24 h after induction of K depletion, stayed elevated until day 4, and returned to control levels on day 7. After K depletion for 24 h, IGF-I immunostaining was markedly increased in the medullary parts of the collecting ducts from K-depleted animals, whereas kidney IGF-I gene expression (IGF-I mRNA) had decreased by 36%. The increase in total kidney IGF-I concentration and immunostainable IGF-I in collecting ducts in kidneys from K-depleted rats precedes the renal hypertrophy and thereby suggests a renotropic role for IGF-I. The increase in kidney IGF-I concentration is not associated with increased IGF-I mRNA levels, indicating that non-transcriptional mechanisms may be responsible for the renal IGF-I accumulation.

Animals

Micral-test strips evaluated for screening for albuminuria.

We have evaluated Micral-Test, an immunochemical strip test specific for albumin, as a screening tool for slight ("micro") albuminuria. First morning urine samples containing albumin concentrations (by radioimmunoassay) of 0.4-440 mg/L were collected from 112 diabetic patients. The Micral-Test result for each sample was assessed by one observer. All 34 samples having albumin concentrations greater than or equal to 20 mg/L and 71 of 78 samples less than 20 mg/L were correctly identified, giving 100% sensitivity and 91% specificity. Six samples were measured 10 times by one observer: three samples were read consistently; one, albumin concentration 86 mg/L, was read as 50 and 100 mg/L; and two, albumin concentrations 32 and 38 mg/L, were read as 20 and 50 mg/L, respectively. Contact with urine for 2 s rather than the recommended 5 s resulted in an underestimation of the albumin concentration in 13 of 35 samples (Z = -3.18, P = 0.001), as did taking readings earlier than the recommended 5 min (Z = -3.92, P less than 0.001). Six observers independently performed Micral-Test measurements on 10 samples. Eight samples were correctly classified as greater than or equal to 20 or less than 20 mg/L by all observers, but two (albumin concentrations 25 and 18 mg/L) were misclassified by at least one observer. The Micral-Test is a sensitive and specific screening tool, but is semiquantitative and critically time dependent.

Albuminuria

Renal insulin-like growth factor I and growth hormone receptor binding in experimental diabetes and after unilateral nephrectomy in the rat.

We have measured specific binding of insulin-like growth factor I and growth hormone to renal plasma membranes from control, streptozotocin-diabetic, insulin-treated diabetic, uninephrectomised and combined diabetic-uninephrectomised male Wistar rats. Control, insulin-treated and uninephrectomised rats had similar body weights after 7 days (243 +/- 2 g), whereas diabetic and diabetic-uninephrectomised animals were significantly lighter (219 +/- 4 and 203 +/- 4 g, p less than 0.05). Blood glucose concentrations were similar in the diabetic and diabetic-uninephrectomised animals (around 26 mmol/l) but significantly lower in the insulin-treated group. Right kidney weight increased by 14% in the control, insulin-treated and sham-nephrectomised animals, by 33% in the diabetic group, 38% in thenephrectomised animals and 60% in the diabetic-nephrectomised group. The renal content of insulin-like growth factor I was similar and stable in the control, insulin-treated and sham-nephrectomised animals (208 +/- 14 ng/g wet weight) but rose to a peak of 669 +/- 35 ng/g in the diabetic group (p less than 0.001), 871 +/- 34 ng/g in the nephrectomised animals (p less than 0.001) and 1012 +/- 43 ng/g in the diabetic-uninephrectomised group (p less than 0.001). Maximum binding of insulin-like growth factor I fell on day 1 in the diabetic group (8.3 +/- 1.4 vs 5.2 +/- 0.71 x 10(-11) mol/l; p less than 0.01) but thereafter was identical to control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Screening for microalbuminuria: which measurement?

It now seems worth while to identify Type 1 diabetic patients with microalbuminuria, as improved blood glucose control and reduction of arterial blood pressure will slow if not prevent the progression to persistent proteinuria. Measurement of albumin excretion rate (AER) in a timed urine sample remains the gold standard for the definition of microalbuminuria, but is not a practical screening procedure. Thus attempts have been made to relate the albumin concentration of albumin:creatinine ratio in random or first morning urine samples to AER. There is a weak correlation of albumin concentration (r = 0.32 to 0.68) and albumin:creatinine ratio (r = 0.43 to 0.54) in a random urine sample with AER, and low sensitivity and specificity of a variety of different albumin concentrations and albumin:creatinine ratios to predict microalbuminuria. The correlation of albumin concentration (r = 0.86 to 0.90) and albumin:creatinine ratio (r = 0.74 to 0.91) in an early morning urine sample with AER is stronger. Measurement of albumin:creatinine ratio in an early morning urine sample appears to be the most reliable method of screening for microalbuminuria, with sensitivity of 88 to 100% and specificity 81 to 100% depending on the cut-off ratio chosen and the definition of microalbuminuria used. If the albumin:creatinine ratio in an early morning urine sample is less than or equal to 3.5 mg mmol-1, the patient can be classed as normoalbuminuric and re-screened annually. If the ratio is greater than or equal to 10.0 mg mmol-1, confirmation of microalbuminuria should be sought in a timed urine collection and appropriate therapy begun.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria

Inhibitory effect of octreotide on growth hormone-induced IGF-I generation and organ growth in hypophysectomized rats.

We investigated the effect of a somatostatin analogue octreotide (SMS) on the stimulatory effect of recombinant human growth hormone (hGH) on insulin-like growth factor I (IGF-I) generation and growth in hypophysectomized rats. Two weeks after hypophysectomy, treatment was given for 11 days with either saline, SMS (100 micrograms/day), hGH (140 micrograms/day), or hGH plus SMS. Compared with saline-injected controls, hGH stimulated body weight gain [1.1 +/- 0.7 vs. 40.9 +/- 0.8 (SE) g, P less than 0.001] and width of epiphysial cartilage (138.0 +/- 4.5 vs. 356 +/- 3.8 microns, P less than 0.001). Combined treatment with hGH and SMS significantly reduced both body weight gain (29.1 +/- 2.5 g, P less than 0.001) and width of epiphysial cartilage (315.3 +/- 5.8 microns, P less than 0.001) compared with the effects of hGH alone. During 11 days of hGH treatment, serum IGF-I increased from 22 +/- 5 to 1,288 +/- 92 micrograms/l (P less than 0.001) but increased only 40% (513 +/- 71 vs. 1,288 +/- 92 micrograms/l, P less than 0.001) when SMS was given in combination with hGH. In gastrocnemius muscle, heart, and lung, but not in liver, kidney, and brain, SMS suppressed organ weight increase when given both with and without hGH substitution. Thymus and gastrointestinal tract weight were significantly reduced in the group receiving SMS alone and tended to be reduced in the hGH-substituted group given SMS as well. Tissue IGF-I was increased in liver, lung, kidney, and heart with hGH treatment (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Insulin-like growth factor 1 and renal growth following ureteral obstruction in the rat.

The role of insulin-like growth factor 1 (IGF-1) in renal growth of obstructed and contralateral kidneys was investigated for 10 days following unilateral ureteric obstruction in male Wistar rats. The weight of the obstructed kidney increased rapidly, rising from 671 +/- 10 to 1,378 +/- 42 mg on day 10, an increase of 105%. IGF-1 content of the obstructed kidney was significantly less than in control kidneys from day 2 onwards, reaching a nadir of 70 ng/mg, a fall of 64%. The protein concentration, expressed as milligrams per gram kidney weight, also fell rapidly from 141 +/- 11 to 88 +/- 3 mg/g on day 6. The weight of the contralateral kidney increased by 32%, from 671 +/- 10 to 887 +/- 48 mg on day 10. The IGF-1 content of this kidney was increased by 48% from baseline on day 1 (268 +/- 23 vs. 191 +/- 13 ng/g) and remained increased compared to sham-operated animals on days 6 and 8. The protein content, expressed as milligrams per gram kidney weight, remained constant throughout the study. We conclude that in the acutely obstructed left kidney increasing kidney weight is associated with falling concentration of IGF-1 and protein and may be due to oedematous and reactive change. Growth of the contralateral kidney is preceded by a rise in the concentration of IGF-1 and may represent true renal compensatory growth.

Animals

Microvascular complications of NIDDM in Hispanics and non-Hispanic whites. San Luis Valley Diabetes Study.

The goal of this article was to examine the differences in the rates of microvascular complications of non-insulin-dependent diabetes mellitus (NIDDM) in Hispanic and non-Hispanic white subjects. This was a geographically based case-control study where prevalent cases of NIDDM were identified in medical records. Subjects attended a 4-h clinic to confirm NIDDM diagnosis and assess complication end points. Retinopathy was defined by stereofundus photographs. Distal symmetric neuropathy was determined by standardized clinical examination. Nephropathy was indicated by serum creatinine level, urine protein-creatinine ratio, and urine albumin concentration. This study consisted of 279 NIDDM subjects confirmed by oral glucose tolerance test and World Health Organization criteria aged 20-74 yr (187 Hispanic and 92 non-Hispanic white subjects). Duration-adjusted prevalence of retinopathy was significantly higher in non-Hispanic white subjects (54.1 per 100, 95% confidence interval [CI] 44.4-63.7) than in Hispanics (41.8 per 100, 95% CI 34.8-48.8). This excess occurred only in non-Hispanic white subjects with background retinopathy but not in those with more severe retinopathy. Hispanics and non-Hispanic white subjects did not differ significantly for the prevalence of neuropathy (31.6 per 100 in non-Hispanic white subjects and 26.3 per 100 in Hispanics) or nephropathy by any measure. There were no significant differences in duration of diabetes or mean glycohemoglobin levels between ethnic groups. Microvascular complications of NIDDM are not in excess among Colorado Hispanics, and retinopathy may be somewhat more common in non-Hispanic white people.

Adult

Kidney IGF-I mRNA in initial renal hypertrophy in experimental diabetes in rats.

It has recently been demonstrated that immunoassayable kidney insulin-like growth factor I concentration increases 24-48 h after induction of diabetes, preceding the initial renal hypertrophy. To elucidate whether this increase is due to increased local production we studied rat kidney insulin-like growth factor I gene expression during the first four days after induction of streptozotocin diabetes. Eighteen hours after injection with streptozotocin the diabetic animals were divided into two groups, one of which was treated with insulin, and daily for four days animals from each group were taken out for investigation. After four days the wet kidney weight had increased from baseline by 20% (from 687 +/- 23 to 827 +/- 6 mg (mean +/- SEM), p less than 0.01) in the untreated diabetic group, while no significant increase occurred in the insulin-treated group (687 +/- 23 vs 732 +/- 21 mg, NS). Kidney insulin-like growth factor I increased rapidly from baseline, the rise amounting to 52% after 48 h (from 271 +/- 11 to 411 +/- 32 ng/g, p less than 0.01) with a decline to control level on day four in the untreated diabetic group. Kidney insulin-like growth factor I remained unchanged in the insulin-treated diabetic group. Insulin-like growth factor I mRNA was measured by solution-hybridization assay. No differences were found in kidney insulin-like growth factor I mRNA between the two diabetic groups over the study period, while in liver, insulin-like growth factor I mRNA tended to be lower on day four in diabetic rats when compared to insulin-treated rats (p = 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Additive increase in kidney insulin-like growth factor I and initial renal enlargement in uninephrectomized-diabetic rats.

The initial renal hypertrophy in experimental diabetes and in response to uninephrectomy is associated with renal accumulation of insulin-like growth factor I (IGF-I). Since the combination of diabetes and nephrectomy almost doubles the initial renal growth rate the aim of the present study was to investigate the kidney IGF-I levels in the combined situation in uninephrectomized diabetic rats. Three experimental groups were exposed to either unilateral nephrectomy, streptozotocin-diabetes or both conditions and for four days animals from each group were taken out for investigation. After 4 days the wet kidney weight increased from baseline by 31% (from 661 +/- 16 mg (SEM) to 866 +/- 27 mg) (P less than 0.01) in the uninephrectomized group, 32% (to 872 +/- 18 mg) (P less than 0.01) in the diabetic group and 46% (to 962 +/- 27 mg) (P less than 0.01) in the uninephrectomized-diabetic group. Kidney IGF-I concentrations were analyzed by radioimmunoassay and the increase from baseline on day 2 was 74% (from 262 +/- 12 ng/g (SEM) to 456 +/- 21 ng/g) (P less than 0.01) in the uninephrectomized group, 58% (to 414 +/- 18 ng/g) (P less than 0.01) in the diabetic group and 176 +/- % (to 722 +/- 56 ng/g) (P less than 0.01) in the combined group. Thereafter a decline in kidney IGF-I occurred in all groups, being normal at day 4 for the diabetic group, but still significantly higher in the uninephrectomized and uninephrectomized-diabetic groups compared to controls (P less than 0.05%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Na(+)-K+ pump in rat muscle: effects of hypophysectomy, growth hormone, and thyroid hormone.

We investigated the effects of growth hormone and thyroid hormone on the synthesis of Na(+)-K+ pumps in rat soleus muscle. Hypophysectomized rats were treated for 11 days with saline, human growth hormone (hGH; 140 micrograms/day), thyroxine (T4; 3 micrograms/day), or hGH plus T4. Age-matched nonhypophysectomized control rats received no treatment. The concentration of Na(+)-K+ pumps was reduced by 75% in the hypophysectomized rats. Treatment with hGH alone or combined with T4 restored the growth rate, whereas T4 alone did not stimulate growth. In contrast, the synthesis of Na(+)-K+ pumps was only responsive to T4 treatment when given alone or in combination with hGH. The concentration of Na(+)-K+ pumps increased around threefold in the T4-treated groups and showed full normalization to the control level after 11 days of treatment. It is concluded that growth hormone does not play any major role in the de novo synthesis of Na(+)-K+ pumps in skeletal muscle. More important, thyroid hormone, also at physiological doses, seems to be the major endocrine factor determining the concentration of Na(+)-K+ pumps in skeletal muscle.

Animals

Urinary excretion of human epidermal growth factor in the various stages of diabetic nephropathy.

Epidermal growth factor (EGF) is a polypeptide mitogen first isolated from mouse submaxillary glands and later from human urine. We have examined the pattern of urinary excretion of human EGF (hEGF) in normal subjects and in diabetic patients with varying degrees of nephropathy. hEGF was measured by homologous radioimmunoassay and expressed in terms of urinary creatinine excretion. On the basis of their albumin excretion rate, the diabetic patients were divided into those with normoalbuminuria (albumin excretion rate 3.5 (1.4-9.8) micrograms/min; mean (range)), microalbuminuria (albumin excretion rate 75 (30-128) micrograms/min) and macroalbuminuria (289 (169-879) micrograms/min). The albumin excretion rate for the normal subjects was 3.7 (1.6-9.7) micrograms/min. The mean (range) hEGF excretion (nmol hEGF/mmol creatinine) was 0.69 (0.47-1.29) for 19 healthy subjects, 0.60 (0.16-1.36) for the normoalbuminuric group (n = 18; NS), 0.47 (0.10-0.83) for the microalbuminuric patients (n = 19; P less than 0.001 vs controls and normoalbuminuric diabetics) and 0.38 (0.10-0.63) for the macroalbuminuric group (n = 18; P less than 0.001 vs controls and normoalbuminuric diabetics). There was an inverse correlation between albumin excretion rate and hEGF: creatinine ratio (r = -0.49; P = 0.02). These results show a progressive decline in hEGF excretion in diabetic patients with varying degrees of nephropathy and do not support the hypothesis that increased kidney size seen in early nephropathy is due to excessive amounts of EGF in the urine.

Adult

Comparison of the prevalence and associated features of abnormal albumin excretion in insulin-dependent and non-insulin-dependent diabetes.

Overnight albumin excretion rates were measured in 940 diabetic patients, 416 with insulin dependent and 524 with non-insulin dependent diabetes, and in 106 healthy volunteers. A significantly higher number of non-insulin dependent diabetic patients had abnormal albumin excretion compared with the insulin-dependent group (X2 = 15.2, p less than 0.002). Ten per cent of non-insulin-dependent and 7 per cent of insulin-dependent diabetic patients had albumin excretion rates in the range 30-150 micrograms/min and thus were at risk of the cardiovascular and renal complications of diabetes. Six per cent of non-insulin-dependent and 5 per cent of insulin-dependent diabetic patients had albumin excretion rates above 150 micrograms/min and thus were entering the phase of clinical diabetic nephropathy. Multivariate analysis revealed that male sex and retinopathy in insulin-dependent diabetes, and systolic blood pressure and retinopathy and peripheral vascular disease in non-insulin-dependent diabetes, were significantly related to albumin excretion. Only one patient with insulin-dependent diabetes of less than 5 years known duration had an albumin excretion rate in the range 30-150 micrograms/min, whereas such an excretion rate indicating patients at risk was observed at all durations of non-insulin-dependent diabetes. It is possible that during the long silent phase of non-insulin-dependent diabetes, before diagnosis, significant renal damage occurred.

Adolescent

Urinary enzyme excretion after donor nephrectomy.

A number of recent studies of long-term kidney donors have reviewed glomerular function and blood pressure. Little attention has been paid to the potentially damaging effects of compensatory hyperfiltration on renal tubular cells after donor nephrectomy. The urinary excretion of high-molecular-weight enzymes is a sensitive indicator of renal tubular cell damage. This study compares the urinary excretion of four enzymes (alanine aminopeptidase, alkaline phosphatase, N-acetyl-beta-D-glucosaminidase, and lactate dehydrogenase) in a group of 77 subjects who had undergone unilateral nephrectomy up to 21 years previously with 52 healthy non-nephrectomized controls. The urinary excretion for all four enzymes by the remaining kidney after contralateral nephrectomy in the kidney donors was significantly greater than the enzyme excretion per single kidney in the control group (p less than 0.001). No correlation was found between the degree of enzymuria and either glomerular filtration rate or time since nephrectomy. The elevated activity of urinary enzymes in kidney donors may be related to increased metabolism by the renal tubular cells after contralateral nephrectomy. This study suggests that long-term compensatory hyperfiltration does not damage tubular cells, at least over this time scale.

Acetylglucosaminidase

Intermediary metabolism, insulin sensitivity and insulin receptor status under comparable long-term therapy with insulin injections and continuous subcutaneous insulin infusion.

We have compared metabolic parameters, insulin sensitivity and insulin receptor status in 12 patients with insulin-dependent diabetes after 6 months treatment with insulin injection therapy and continuous subcutaneous insulin infusion therapy (CSII) in random order. Mean 24-h blood glucose, intermediary metabolite, plasma free insulin and counter-regulatory hormone concentrations were equivalent on the two regimes despite a significantly lower insulin dose on CSII (49.8 +/- 4.0 vs 39.3 +/- 2.2 U/24 h, P less than 0.01). When compared with a group of matched normal subjects, mean blood glucose and M-value, blood 3-hydroxybutyrate and free insulin concentrations were significantly higher on both regimes whilst blood alanine levels were depressed. Peripheral insulin sensitivity as assessed by the euglycemic clamp, basal hepatic glucose output, glucose carbon recycling, adipocyte insulin binding, adipocyte insulin sensitivity and lipogenesis were all similar after the two treatments. Insulin-stimulated initial rates of glucose uptake by adipocytes were higher after CSII (1.78 +/- 0.16 vs 2.35 +/- 0.27 pmol per cm2 cell membrane per 20 sec, P less than 0.005).

Adipose Tissue