Effect of intensive treatment in insulin dependent diabetes mellitus with microalbuminuria. Work in non-insulin diabetes corroborates study's findings.
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Biomedical subjects
Publications and source records attributed to H Tindall.
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We compared the urinary excretion of albumin, transferrin, N-acetyl-beta-D-glucosaminidase and alpha-1-microglobulin in 78 Type 1 (insulin-dependent) diabetic patients: 39 with retinopathy and 39 without. The two groups were matched for age, sex and duration of diabetes. The patients with retinopathy had increased excretion (median and range) of albumin [1.7(0.3-399.1) versus 1.0(0.3-116.6) mg/mmol creatinine, P less than 0.05], transferrin [114.2 (4.1-37126.2) versus 33.4 (1.0-4176.7) micrograms/mmol creatinine, P less than 0.01] and N-acetyl-beta-D-glucosaminidase [23.8 (1.1-119.1) versus 15.0 (0.1-65.1) mumol/h/mmol creatinine, P less than 0.05] but not alpha-1-microglobulin. Transferrin excretion correlated with albumin excretion. The prevalence of increased transferrin excretion (transferrinuria) was greater than that of microalbuminuria in patients both with and without retinopathy (P less than 0.01 in both cases). Urinary transferrin seems likely to be predominantly of glomerular origin and merits prospective longitudinal evaluation as a potential index of the microangiopathic process.
A phase I, double-blind, single-dose, randomized, two-period crossover study was conducted to investigate the effects of pimobendan on renal function to assess whether renal events were a contra-indication to its administration. Results in eight healthy volunteers indicated no significant adverse events on renal plasma flow, glomerular filtration rate, or laboratory safety screens; side-effects were also found to be minimal. Further studies are indicated to assess whether, in the proposed treatment group, i.e. patients with heart failure (in whom compromised renal function is common), pimobendan similarly elicits no serious adverse renal effects.
Nine patients with Type I diabetes mellitus, diastolic blood pressure of 90 to 100 mmHg and persistent microalbuminuria of greater than or equal to 30 micrograms/min were treated with 50 to 100 mg atenolol daily for 3 years in an uncontrolled pilot study to assess the effect of long-term reduction of blood pressure on microalbuminuria. Treatment with atenolol prevented progression of microalbuminuria with a median (range) urinary albumin excretion rate before treatment of 74 (33 to 196) micrograms/min and 50 (5 to 123) micrograms/min after 3 years of therapy (p less than 0.05). Blood pressure was significantly reduced from 156 (121 to 187) mmHg systolic and 95 (90 to 100) mmHg diastolic before treatment to 143 (112 to 168) mmHg systolic (p less than 0.04) and 82 (66 to 84) mmHg diastolic (p less than 0.0003) at 3 years. Measurements of renal function and diabetic control remained unchanged throughout the study period. These results suggest that early and prolonged use of antihypertensive therapy is beneficial in slowing down progression of microalbuminuria.
Glomerular and tubular microproteinuria precede the development of overt nephropathy in Type 1 diabetes mellitus. However, in Type 2 diabetes urinary protein excretion and its relationship to diabetic nephropathy has not been clearly characterized. Twenty consecutive, newly diagnosed patients with Type 2 diabetes, whose urine was Albustix-negative and sterile on culture, were studied. Two timed overnight urine samples were collected at diagnosis, and after 2 months and 2 years, and excretion rates of albumin, alpha-1-microglobulin and N-acetyl-beta-D-glucosaminidase were calculated. HbA1c fell from 12.1 +/- 2.4% at diagnosis to 9.5 +/- 1.5% at 2 months and 9.6 +/- 2.2% at 2 years. Albumin excretion rate fell marginally from 6.5 (2.1-242.5) micrograms min-1 at diagnosis to 5.5 (1.7-274.0) micrograms min-1 at 2 months (p less than 0.05) rising again to 6.1 (1.9-201.7) micrograms min-1 at 2 years. alpha-1-Microglobulin excretion rate fell from 13.5 (3.6-59.9) micrograms min-1 at diagnosis to 8.4 (2.9-16.1) micrograms min-1 at 2 months and 8.8 (1.8-54.1) micrograms min-1 at 2 years (both p less than 0.05). Albumin excretion rate was found to correlate significantly with creatinine clearance at diagnosis (rs = 0.61, p less than 0.005), though not subsequently. In contrast, excretion rates of alpha-1-microglobulin and N-acetyl-beta-D-glucosaminidase correlated with HbA1c (rs = 0.68 and 0.66, respectively, p less than 0.005 at diagnosis and rs = 0.57 and 0.53, p less than 0.05 subsequently in both cases).(ABSTRACT TRUNCATED AT 250 WORDS)
Thymolipoma is an uncommon benign tumour of the anterior mediastinum, consisting of fat and thymic tissue. The diagnosis is easily missed because the tumour may simulate multiple intrathoracic pathological entities. It was first described by Lange in 1916, and since then about 50 cases have been reported. We describe a patient who presented with recurrent episodes of central chest pain and abnormal cardiac silhouette due to a thymolipoma.
We attempted to assess compliance using both a pharmacologic indicator (low-dose phenobarbital) and a return tablet count in 225 patients who were taking part in three separate studies. There were 216 patients (96%) who kept a follow-up appointment after 28 days; 161 patients appeared to have good compliance (90% to 109%) by return tablet count. Of these 161 patients, 51 (32%) had plasma phenobarbital concentrations (corrected for dose and weight) that were less than 90% of the lowest value previously found in normal volunteers, which suggested poorer compliance. When compared with the age-related volunteer values, 77 (48%) had values that were less than 90% of the lowest volunteer value. There were 6 of 10 patients with apparently excessive (greater than or equal to 110%) compliance by return tablet count and 4 of 12 who failed to return their container who also had phenobarbital concentrations that were less than 90% of the lowest volunteer value. We concluded that return tablet count grossly overestimates compliance.
We assessed in a pilot study the effect on some aspects of renal function of 6 weeks' administration of a combination of aspirin-dipyridamole (990 mg/225 mg daily) administered on a double-blind crossover schedule in 16 insulin-dependent diabetic patients with nephropathy. Total 24-h urinary protein excretion (16 patients) was significantly reduced during aspirin-dipyridamole administration from a geometric mean (range) of 1.9 (0.4-7.7) g/24 h to 1.4 (0.5-9.9) g/24 h (2P less than 0.05). Indium-labelled platelet survival (eight patients), glomerular filtration rate and renal blood flow (eight patients) showed no significant change following aspirin-dipyridamole therapy, even though plasma creatinine concentration increased from 118 (65-371) to 130 (76-438) mumol/l (2P less than 0.05). Diabetic control and blood pressure remained unchanged throughout the study. Although the results showed that this treatment significantly reduced proteinuria in patients with diabetic nephropathy, the mechanism of action was not entirely clear.
Two patients with acromegaly who also developed primary hyperthyroidism are described. One case presented de novo with Graves' disease and acromegaly and the other developed hyperthyroidism several years after the diagnosis of acromegaly had been made. No associated adenomas could be demonstrated. The association between acromegaly and thyroid disease is discussed.
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Poor compliance with medication is often suspected, but difficult to confirm. The compliance of fourteen newly diagnosed hypothyroid patients was assessed using both TSH levels and low-dose phenobarbitone as a pharmacological marker. The study confirms the value of phenobarbitone as an indicator of compliance over a protracted period and suggests that it could be used to differentiate under-treatment from poor compliance.
Sixty-six patients with secondary failure to oral hypoglycaemic therapy were assessed in hospital, and those whose fasting blood glucose concentration was greater than or equal to 10.0 mmol l-1 were treated with insulin once a day for 6 months. Only 22 patients fulfilled this criterion, and they were randomly allocated to a daily injection of either Humulin-Zn (12 patients) or Neulente insulin (10 patients). The remaining patients were considered to be noncompliant with therapy. At the end of 6 months' insulin therapy a significant (p less than 0.05) improvement occurred in HbA1c from a median (range) of 13.2(9.8-16.4)% and 13.1(10.5-16.2)% to 10.6(8-14.2)% and 11.2(8.7-13.5)% in patients given Humulin-Zn and Neulente, respectively. However, there were 46 episodes of hypoglycaemia reported by patients who received Humulin-Zn, 36 of which occurred between 0300 and 0600 h. Only four episodes were reported by the Neulente-treated group. In addition, six patients treated with Humulin-Zn (but only one patient on Neulente insulin) required the addition of short-acting insulin. The patients not treated with insulin showed a significant (p less than 0.05) improvement in blood glucose control 2 months after in-patient assessment but this improvement was not sustained to 6 months.
A patient is described who became poikilothermic following surgery for removal of a craniopharyngioma. Episodes of disturbed behaviour, neurological abnormalities, pancytopenia and deranged liver function could be correlated with episodes of more profound hypothermia on a background of a chronically lowered core temperature. The association of pancytopenia and neuropsychiatric disturbances with hypothermia is discussed with reference to reported cases of periodic spontaneous hypothermia.
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The exercise-induced increase in albumin excretion was measured in six patients with insulin-dependent diabetes mellitus, in whom there was no evidence of established diabetic renal disease. Urinary albumin excretion was measured on urine samples taken at rest and immediately after a 20 minute period of exercise on a bicycle ergometer at 600 kpm/min. Following a three week course of aspirin (330 mg)--dipyridamole (75 mg) taken three times daily there was significant reduction in exercise-induced albuminuria (expressed as the ratio of albumin excretion rate during exercise to that at rest before exercise) when compared to administration of placebo (P less than 0.05). These results suggest that aspirin-dipyridamole might modify the development of persistent proteinuria in patients with insulin-dependent diabetes mellitus.
An acute overdosage of 30 mg of pizotifen causing a pyrexial illness is reported. The clinical features suggest that the effects of overdosage are principally due to the anticholinergic activity of this drug. Resolution of symptoms occurred after 10 hours, without specific therapy.
One hundred and thirty-one consecutive requests for thyroid scintigraphy were analysed to assess their diagnostic contribution to the subsequent medical management of the patient. Forty one per cent of requests were to investigate the presence of a clinically detectable solitary nodule and, of these, one fifth had hot nodules. Diffuse goitres accounted for 38% of all referrals, but in only two patients (non-toxic hot nodule) did the results change management. A further 11% of referrals were for multinodular goitres and 8% for retrosternal goitres. In all cases of goitre no additional useful information was obtained from scintigraphy. It is concluded that thyroid scintigraphy was an unnecessary investigation in approximately 45% of cases. Its primary role was in the investigation of the solitary nodule and in detecting toxic nodules in thyrotoxic patients who had no evidence of Graves' disease. Greater discrimination of requests would avoid investigating patients unnecessarily and reduce costs.