Severe dwarfism with cataracts. A new osteo-chondrodysplasia.
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Adolescent↗
Biomedical subjects
R F Fletcher
Publications and source records attributed to R F Fletcher.
Communicating with Asian patients.
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Adolescent↗
Sodium restriction and blood pressure in hypertensive type II diabetics: randomised blind controlled and crossover studies of moderate sodium restriction and sodium supplementation.
OBJECTIVE: To determine the effect of moderate dietary sodium restriction on the hypertension of non-insulin-dependent (type II) diabetes. DESIGN: Randomised parallel controlled study of moderate sodium restriction for three months compared with usual diabetic diet, followed by randomised double blind crossover trial of sustained release preparation of sodium for one month versus placebo for one month in patients continuing with sodium restriction. SETTING: Patients attending diabetic outpatient clinic of city hospital. PATIENTS: Thirty four patients with established type II diabetes complicated by mild hypertension (systolic blood pressure greater than 160 mm Hg or diastolic pressure greater than 95 mm Hg on three consecutive occasions). Patients already taking antihypertensive agents (but not diuretics) not barred from study provided that criteria for mild hypertension still met. Conditions precluding patients from study were diabetic or hypertensive nephropathy, cardiac failure, and pregnancy. INTERVENTIONS: After run in phase with recordings at seven weeks, three weeks, and time zero patients were allocated at random to receive moderate dietary sodium restriction for three months (n = 17) or to continue with usual diabetic diet. Subsequently nine patients in sodium restriction group continued with regimen for a further two months, during which they completed a randomised double blind crossover trial of sustained release preparation of sodium (Slow Sodium 80 mmol daily) for one month versus matching placebo for one month. END POINT: Reduction in blood pressure in type II diabetics with mild hypertension. MEASUREMENTS AND MAIN RESULTS: Supine and erect blood pressure, body weight, and 24 hour urinary sodium and potassium excretion measured monthly during parallel group and double blind crossover studies. After parallel group study sodium restriction group showed significant reduction in systolic blood pressure (supine 19.2 mm Hg, erect 21.4 mm Hg; p less than 0.001) and mean daily urinary sodium excretion (mean reduction 60 mmol/24 h). There were no appreciable changes in weight, diabetic control, or diastolic pressure. No significant changes occurred in controls. In double blind crossover study mean supine systolic blood pressure rose significantly (p less than 0.005) during sodium supplementation (to 171 mm Hg) compared with value after three months of sodium restriction alone (159.9 mm Hg) and after one month of placebo (161.8 mm Hg). CONCLUSIONS: Moderate dietary restriction of sodium has a definite hypotensive effect, which may be useful in mild hypertension of type II diabetes.
Clinical Trials as Topic↗
Randomised blind controlled trial of a high fibre, low fat and low sodium dietary regimen in mild essential hypertension.
Thirty-four patients with essential hypertension were allocated, in a controlled trial, to a treatment diet of high fibre, low fat and low sodium composition, or to a control diet by the hospital dietitian. Clinical observations were made by a separate 'blinded' nursing sister. After three months treatment, the modified diet-treated group showed a significant reduction in mean systolic (169.4 +/- 23.4 to 150.6 +/- 16.1 mmHg) and diastolic blood pressure (101.5 +/- 7.3 to 89.4 +/- 6.8 mmHg), accompanied by significant reductions in urinary sodium excretion (140.4 +/- 34.6 to 93.7 +/- 44 mmol/day) and weight (73.1 +/- 10 to 71.2 +/- 8.4 kg). The changes in control were; systolic 171.2 +/- 14.1 to 162.1 +/- 19.5 mmHg and diastolic pressure 97.2 +/- 10.8 to 91.7 +/- 9.7 mmHg. The mean differences in reductions between treated and control were 8.8 mmHg Systolic (95% confidence intervals: -2.6 to 21.2 mmHg) and 7.0 mmHg diastolic blood pressure (95% confidence intervals: 0.4 to 14.4 mmHg). The number of patients with normal blood pressure in the diet treated group at three months was double that in the control (eleven versus five). No relationships were shown between blood pressure changes and those of weight or urinary sodium excretion during the trial. The findings in this study are broadly in agreement with similar ones in essential hypertension and suggest that this form of dietary regimen has a clinically worthwhile hypotensive effect and this should be readily achievable in routine clinical practice.
Aged↗
Alterations in the U3 region of the long terminal repeat of an infectious thymotropic type B retrovirus.
We isolated and characterized a type B thymotropic retrovirus (DMBA-LV) which is highly related to mouse mammary tumor virus (MMTV) isolates and which induces T-cell thymomas with a high incidence and a very short latent period. Regions of nonhomology between the DMBA-LV genome and the MMTV genome were identified by heteroduplex mapping and nucleotide sequence studies. In the electron microscope heteroduplex mapping studies the EcoRI-generated 5' and 3' fragments of the DMBA-LV genome were compared with the corresponding fragments of the MMTV (C3H and GR) genome isolated from mammary tumors. The results indicated that DMBA-LV contained a region of nonhomologous nucleotide sequences in the 3' half of the U3 region of the long terminal repeat (LTR). Nucleotide sequence studies confirmed these results and showed that in this region 440 nucleotides of the MMTV (C3H) sequences were deleted and substituted with a segment of 122 nucleotides. This substituted segment in the form of a tandem repeat structure contained nucleotide sequences derived exclusively from sequences which flanked the substitution loop. The distal glucocorticoid regulatory element was unaltered, and two additional copies of the distal glucocorticoid regulatory element-binding site were present in the substituted region. The restriction endonuclease map of the reconstructed molecular clone of DMBA-LV was identical to that corresponding to unintegrated linear DMBA-LV DNA present in DMBA-LV-induced tumor cell lines. Since the nucleotide sequences of the LTRs present in four different DMBA-LV proviral copies isolated from a single thymoma were identical, we concluded that they were derived from the same parental virus and that this type B retrovirus containing an alteration in the U3 region of its LTR could induce thymic lymphomas. Thus, DMBA-LV represents the first example of a productively replicating type B retrovirus that contains an LTR modified in the U3 region and that has target cell and disease specificity for T cells.
Base Sequence↗
Acute mountain sickness.
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Acetazolamide↗
Differences in lipid and lipoprotein levels in white, black and Asian non-insulin dependent (type 2) diabetics with hypertension.
We have examined the prevalence of hyperlipidaemia (defined as representing fasting serum cholesterol greater than 7.1 mmol/L; fasting serum triglyceride greater than 2.1 mmol/L) in 188 hypertensive type 2 diabetics of different ethnic groups. The overall prevalence of hyperlipidaemia was 36.0% with hypertriglyceridaemia at 25% being more frequent than hypercholesterolaemia at 19%. Blacks at 20.5% had strikingly less hyperlipidaemia than whites at 43.3% (p less than 0.01) and Asians, at 53.7% (p less than 0.001). This ethnic difference was noted for each variety of hyperlipidaemia, being most marked for hypertriglyceridaemia. Reflecting these data blacks had lower mean triglyceride levels than whites (p less than 0.001) and Asians (p less than 0.01). In addition, blacks had higher HDL-cholesterol than whites (p less than 0.01) and Asians (p less than 0.001) and HDL2-cholesterol was higher in blacks than Asians (p less than 0.001). In summary we have confirmed that in hypertensive type 2 diabetics similar ethnic differences of lipid and lipoprotein levels exist as that in non-diabetics. In light of the common occurrence of hyperlipidaemia in the white and Asian hypertensive type 2 diabetic, it may be appropriate to screen for this abnormality. However, in black hypertensive type 2 diabetic subjects this would be less rewarding.
Asia↗
Effect of a high carbohydrate, low sodium and low fat diet in type 2 diabetics with moderate hypertension.
The effect of an intended diet, high in cereal fibre, low in fat and sodium was assessed over a 3-month period in 13 type 2 diabetic patients with moderate hypertension (diastolic blood pressure greater than 105 and less than 115 mmHg without antihypertension drug therapy). Eleven patients completed the study and two patients were withdrawn owing to an increase of blood pressure above initial values after 1 month. Using a compliance scoring system by an observer unaware of blood pressure response, patients were divided into those compliant to the dietary regimen (n = 7; group A) and those who were not, and therefore were considered controls (n = 4; group B). Group A demonstrated significant reductions in systolic (190.4 +/- 18 to 166.6 +/- 22.4 mmHg; P less than 0.02) and diastolic blood pressure (113.1 +/- 3.7 to 103.3 +/- 9.1 mmHg; P less than 0.01), weight (78.5 +/- 5.6 to 74.3 +/- 6.8 kg; P less than 0.02), daily urinary sodium excretion (210.3 +/- 79.9 to 120.3 +/- 56.1 mmol; P less than 0.02) and serum LDL levels (P less than 0.02). A reduction in glycosylated haemoglobin of 2.2 per cent was also noted. Three patients achieved a diastolic blood pressure level below 100 mmHg. In contrast, no significant changes occurred in group B. In particular, systolic and diastolic blood pressure (111.0 +/- 2.2 to 110.3 +/- 8.9 mmHg) remained unchanged. We conclude that the modified diet may have a hypotensive effect in diabetic subjects with moderate hypertension. However, the degree of blood pressure reduction suggests that this diet could, at best, only be considered an adjunct to conventional antihypertensive drug therapy.
Blood Glucose↗
High fibre, low sodium and low fat diet in white and black type 2 diabetics with mild hypertension.
White and black mildly hypertensive Type 2 diabetics were given an intended diet high in unrefined carbohydrate (50% daily energy) and fibre (40-45 g/day) while low in fat (25% daily energy) and sodium (60-80 mmol/day) for 3 months. Both white and black diabetic hypertensive patient groups demonstrated a significant reduction of systolic (p less than 0.01 and p less than 0.001 respectively) and diastolic blood pressure (p less than 0.001 and p less than 0.01 respectively). This was accompanied by a significant reduction of daily urine sodium excretion, urine sodium: potassium ratio, weight and glycosylated haemoglobin in both groups. Only whites had a significant reduction of serum triglyceride level (p less than 0.05) although blacks showed similar trends. Compliance to the dietary regimen, assessed by a trends. Compliance to the dietary regimen, assessed by a scoring method appeared comparable in both groups. These data suggest this modified dietary regimen might be considered an attractive alternative to conventional antihypertensive drug therapy in mildly hypertensive Type 2 diabetic black as well as white patients.
Black People↗
Prevalence of hypertension in white, black and Asian diabetics in a district hospital diabetic clinic.
In a District General Hospital Diabetic Clinic 40.0% of a random sample of diabetics under the age of 65 years of age were hypertensive. Black patients (48.9%) had greater (p less than 0.05) prevalence of hypertension than Whites (37.5%) and Asians (35.4%). Hypertension was more prevalent in females (49.1%) than males (33.0%) (p less than 0.001) in each ethnic group except Asians, and patients not receiving insulin had greater prevalence (45.6%) than those on insulin (30.7%) (p less than 0.001), except black diabetics where the reverse was found. There was a positive relationship between age and systolic (p less than 0.00001) and diastolic blood pressure (p less than 0.00001) and a negative association between duration of diabetes and diastolic blood pressure (p less than 0.004) on multiple regression analysis but no relationship was noted between blood pressure and either weight or blood glucose. Forty-six percent of all hypertensives were receiving conventional anti-hypertensive drug therapy; 38.7% were normotensive with similar results in each ethnic group and between the sexes. Isolated systolic hypertension was the commonest form of hypertension (48.3%) with isolated diastolic hypertension (4.9%) the rarest. These findings were observed regardless of the ethnic group or gender. Although in the majority of cases hypertension was mild these data confirm the importance of routine blood pressure measurement in diabetic patients.
Cross-Sectional Studies↗
Long-term follow up of trans-sphenoidal hypophysectomy for Cushing's disease.
Fourteen patients with Cushing's disease treated by trans-sphenoidal hypophysectomy between 1962 and 1975 were reviewed in 1983. Complete ablation had been attempted. There were no surgical deaths and one episode of bacterial meningitis. Two patients required a second operation for a cerebrospinal fluid leak. There have been three late deaths from unrelated causes. All patients had a biochemical remission of their Cushing's disease postoperatively and no relapse has been recorded. Most patients need some hormone replacement but residual pituitary function and sella radiography have remained stable. This treatment seems satisfactory and the evidence implies a pituitary aetiology of the syndrome.
Adult↗
The clinical assessment of acute mountain sickness.
During three expeditions to high altitude the Birmingham Medical Research Expeditionary Society has studied the effects of the ascents on its members. The severity of acute mountain sickness (AMS) produced was assessed by three methods, interview, self assessment and peer review. Physical examination was unhelpful. The results of the three methods were closely correlated. Clinical interview permitted allowances to be made for individual factors such as fatigue. There was no tendency for self assessment to indicate effects consistently more or less than the other methods. Peer review revealed a wide spread of opinions but the large number of observers allowed the derivation of plausible mean values. Correlation of AMS with arterial pH and PaCO2 showed little relationship but correlation with PaO2 was good, particularly for self assessment. As all the methods are subjective a combination of techniques is recommended for future expeditions.
Acute Disease↗
The Environmental Symptoms Questionnaire in acute mountain sickness.
A self-completed questionnaire (modified Environmental Symptoms Questionnaire) was evaluated in a study of acute mountain sickness (AMS). The questionnaire scores for headache, nausea, and the general feeling of ill health correlated well with AMS scores obtained by clinical interview. Modifications in the instructions and the phrasing of some of the questions are suggested and we doubt whether factor analysis provides any better data than more simple statistical methods. The questionnaire is a useful additional method for the assessment of symptoms of AMS.
Acute Disease↗
Cigarette smoking, blood pressure and the control of blood glucose in the development of diabetic retinopathy.
We have investigated the relationship between diabetic retinopathy and cigarette smoking, blood pressure, control of blood glucose, duration of diabetes and insulin requirement in a cross sectional study of 193 adult patients attending 2 diabetic follow-up clinics. Multiple discriminate analysis demonstrated that the duration of diabetes was closely related to the development of retinopathy in both sexes. Cigarette smoking was related to retinopathy in men but not in women, although in that group the prevalence of smoking was low. The average blood glucose whilst attending the clinic was weakly related to retinopathy in men only whereas the presence of hypertension was weakly related in women only. Cigarette smoking in men at least may be an aggravating factor for diabetic retinopathy.
Age Factors↗
Thyroid function at high altitude.
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Altitude↗
A controlled trial of a high fibre, low fat and low sodium diet for mild hypertension in Type 2 (non-insulin-dependent) diabetic patients.
Fifty hypertensive Type 2 (non-insulin-dependent) diabetic patients were allocated, in a controlled trial, to a treatment diet of high fibre, low fat and low sodium composition, or to a control diet by the hospital dietitian. After 3 months treatment, the modified diet-treated group showed a highly significant reduction in mean systolic (180.5 +/- 19.0 to 165.0 +/- 20.7 mmHg) and diastolic blood pressure (96.6 +/- 9.3 to 88.0 +/- 10.5 mmHg), accompanied by significant reductions in urinary sodium excretion (183.0 +/- 62.1 to 121.7 +/- 65.8 mmol/day) glycosylated haemoglobin (12.4 +/- 3.1 to 10.5 +/- 2.9%), weight (74.6 +/- 13.5 to 71.7 +/- 12.1 kg) and serum triglyceride levels (p less than 0.05). The mean values of diastolic pressure (p less than 0.01), urinary sodium/potassium ratio (p less than 0.001), urinary potassium (p less than 0.01) was significantly reduced at 3 months compared to control. No changes in serum HDL-cholesterol levels were observed. The number of patients with normal blood pressure at 3 months was greater in the modified diet-treated group (ten versus five). Treatment of mild hypertension in diabetic subjects with this form of dietary regimen has a hypotensive response, with improvement in glycaemic control and no side effects. This modified diet may be an attractive alternative to anti-hypertensive drug therapy as a first line treatment.
Blood Glucose↗
Comparison of the hypotensive and metabolic effects of bendrofluazide therapy and a high fibre, low fat, low sodium diet in diabetic subjects with mild hypertension.
Fifty diabetic patients with mild hypertension were treated by a high fibre, low fat and low sodium diet or bendrofluazide for a three-month period. These two well-matched groups had a similar highly significant decrease in both systolic (P less than 0.001) and diastolic blood pressure (P less than 0.001). Both groups lost weight, the weight loss being greater in those receiving dietary therapy. Only dietary therapy was associated with a significant elevation of HDL2 level (P less than 0.05) and decrease in glycosylated haemoglobin (P less than 0.01). Bendrofluazide therapy resulted in significant elevation of glycosylated haemoglobin level (P less than 0.05) and at the end of the study this group had significantly higher glycosylated haemoglobin level (P less than 0.05) than the diet treated group. In those patients who were also hyperlipidaemic, dietary therapy resulted in a significant decrease of mean serum cholesterol (P less than 0.02), triglyceride (P less than 0.01) and glycosylated haemoglobin (P less than 0.01) while bendrofluazide treatment tended to elevate these levels. We conclude that a high fibre, low fat and low sodium dietary regimen lowers blood pressure, improves several other coronary risk factors and appears free of side-effects. This modified diet may be an attractive alternative to thiazide diuretic therapy in the mildly hypertensive diabetic subject.
Bendroflumethiazide↗
Effect of a high fibre, high carbohydrate dietary regimen on serum lipids and lipoproteins in type II hypertensive diabetic patients.
Fifty Type II diabetic patients with mild hypertension were treated by a high cereal fibre, low fat and low sodium diet in a controlled trial for a 3-month period. The modified diet and control diet groups were well matched although the control group had significantly increased levels of HDL2-cholesterol (p less than 0.05). The modified diet group had a significant reduction of mean serum triglyceride (p less than 0.05) and elevation of HDL2 (p less than 0.05) levels. There was also a reduction of systolic (p less than 0.001) and diastolic blood pressure (p less than 0.001), weight (p less than 0.01) and glycosylated haemoglobin (p less than 0.001). No changes were observed in the control group. In those patients with added hyperlipidaemia, dietary therapy resulted in a significant decrease of mean serum cholesterol (p less than 0.02), triglyceride (p less than 0.01) and glycosylated haemoglobin levels (p less than 0.01). The control group had a significant reduction of HDL-cholesterol (p less than 0.02). We conclude that a high cereal fibre, low fat and low sodium dietary regimen is associated with improvement in cardiovascular risk over a 3-month period, especially in those with hyperlipidaemia. Contrary to previous reports, no deleterious effect on serum triglyceride, HDL- and HDL2-cholesterol levels were recorded in this study. These data add further support to the recent dietary recommendations of several Diabetic Associations.
Blood Pressure↗