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Biomedical subjects

R D Carter

Publications and source records attributed to R D Carter.

At least 37 records · Page 2Linked to original sources

Chemotherapy by regional perfusion for limb melanoma.

The administration of chemotherapy by isolated regional perfusion was developed in 1957 at Tulane University and was found to be of greatest benefit for patient with melanoma of the limbs. From 1957 to 1984, 897 patients were treated by this method. The 10-year survival rate for 831 patients with primary melanoma was 77 per cent. Women survived longer than men, with 10-year rates of 81 per cent and 65 per cent, respectively. Prophylactic lymph node dissection was of benefit for males with poor prognosis distal lower limb lesions, but other groups did not benefit. Primary lesions on the arm and thigh did better than lesions of the hand or foot, with plantar and subungual lesions having the least favorable results. Thickness, level, and histologic type were also significant prognostic indicators. Thirty-three patients with locally recurrent melanoma (stage II) treated by perfusion and excision had a 10-year survival rate of 59 per cent. For 129 patients with metastases to the regional lymph nodes (IIIB), perfusion plus RLND produced a 10-year rate of 51 per cent; survival rates for those with a single positive node was 64 per cent. Seventy patients with satellitosis or intransit metastases (IIIA) had a 10-year survival rate of 23 per cent. Thirty-eight patients with metastases to limbs from unknown primaries had a 10-year survival rate of 52 per cent. The overall 10-year rate for all stage III patients was 41 per cent. Perfusion produced useful palliation in 144 patients with limb melanoma in the presence of systemic metastases.

Chemotherapy, Cancer, Regional Perfusion↗

Possible role of the carbohydrate residues on the structure of the N-terminus of glycophorin AM.

Natural-abundance 13C nuclear magnetic resonance (13C-n.m.r.) was used to study the effect of monoglycosylation on the structure and dynamics of a pentapeptide related to the N-terminus of glycophorin AM. The results of this study indicate that a single point of glycosylation, on the pentapeptide, can significantly affect its structure. Moreover, glycosylation of this pentapeptide also affects its dynamic motion in solution. This study further defines the role that the carbohydrate residue plays in determining the structure about the N-terminus of glycophorin AM.

Carbohydrate Sequence↗

Determinants of ADP-induced platelet aggregation in diabetes mellitus.

ADP-induced platelet aggregation was measured in 15 Type 1 (insulin-dependent) diabetic patients, 15 Type 2 (non-insulin-dependent) diabetic patients and in 15 non-diabetic control subjects. Simultaneous measurements were made of fasting blood glucose, glycosylated haemoglobin, serum insulin, total plasma cholesterol, cholesterol in the lipoprotein subfractions, total triglycerides and platelet phospholipid fatty acid levels. Regression analysis of aggregation against the biochemical variables within the three groups revealed that there was no significant difference in the associations with aggregation between the groups. When the data was pooled, blood glucose (p less than 0.01) and glycosylated haemoglobin (p less than 0.05) demonstrated significant associations with aggregation. Multiple regression analysis was then applied; only blood glucose (p less than 0.05) had an independent effect on aggregation. Platelet aggregation in diabetic patients and non-diabetic patients appears to be related directly only to blood glucose levels.

Adenosine Diphosphate↗

Sucrose in the diet of diabetic patients--just another carbohydrate?

The effects of regularly eating sucrose were studied in 23 diabetic patients, 12 Type 1 (insulin-dependent) and 11 Type 2 (non-insulin-dependent), with differing degrees of glycaemic control. Two diets, each lasting 6 weeks, were compared in a randomised cross-over study. Both diets were high in fibre and low in fat. In one diet 45 g of complex carbohydrate was replaced by 45 g of sucrose taken at mealtimes. There were no significant biochemical differences between the two diets in either Type 1 or Type 2 patients. In Type 1 patients the mean (+/- SEM) fasting plasma glucose was 10.5 (1.8)mmol/l on the control diet and 10.3 (1.5) mmol/l on sucrose. In Type 2 patients the levels were 9.1 (0.8) mmol/l and 8.9 (0.8) mmol/l respectively. Glycosylated haemoglobin for the Type 1 patients was 9.9% on control and 10.3% on sucrose; for Type 2 patients the figures were 9.3% and 9.0% respectively. There were no differences in mean daily plasma glucose levels or diurnal glucose profiles. Cholesterol (total and in lipoprotein fractions) was unchanged, as were diurnal triglyceride profiles and plasma insulin profiles in the Type 2 patients. There were no changes in medication or body weight. We conclude that a moderate amount of sucrose taken daily at mealtimes does not cause deterioration in metabolic control in diabetic patients following a high fibre/low fat diet.

Adult↗

Indirect evidence of impairment of platelet desaturase enzymes in diabetes mellitus.

We measured the platelet total phospholipid fatty acid profiles of 20 insulin treated (Type I) diabetics, 20 non-insulin treated (Type II) diabetics and 20 matched non-diabetic controls to determine the relationship between the omega 6 and omega 3 series of fatty acids in diabetes. A significant inverse correlation between linoleic acid and arachidonic acid occurred in the normal subjects (r = -0.61; P less than 0.001) but was not seen in the Type I diabetics (r = -0.13; P = NS) or in the Type II diabetics (r = -0.27; P = NS). No significant correlation was seen between linolenic acid and eicosapentaenoic acid in the normal controls (r = -0.34; P = NS) or in the Type I diabetics (r = 0.21; P = NS) or in the Type II diabetics (r = -0.20; P = NS). The results suggest that a functional impairment of platelet delta 5 and delta 6 desaturase may occur in diabetes which disrupts the normal equilibrium between linoleic acid and arachidonic acid. However, the level of eicosapentaenoic acid appears to be less dependent on conversion from linolenic acid. Our findings are of importance to studies designed to reduce platelet aggregation in diabetics and non-diabetics by manipulation of the levels of the precursor fatty acids of thromboxane.

Adult↗

Isolated perfusion of extremities for metastatic melanoma from an unknown primary lesion.

Since 1957, 822 patients with invasive malignant melanoma of the limbs were treated by regional perfusion at the Tulane Medical Center. Between 1958 and 1982, there were 32 patients with regional metastatic melanoma from an unknown primary site involving either the upper limb and axillary lymph nodes or lower limb and femoral or inguinal lymph nodes. This group represents 3.5% of patients with regional melanomas treated during this period. There were 16 patients with upper limb regional metastases and 14 patients with lower limb metastases. Sixteen patients had stage IIIB disease (ie, regional lymph node metastases), ten had stage IIIA disease (ie, satellitosis), and four had stage IIIAB disease. Six patients had a history of a suggestive limb lesion that had completely regressed and showed no residual tumor on biopsy. All 30 patients were treated by regional isolated perfusion and regional lymph node dissection, with surgical excision of in-transit disease when possible. The cumulative five-year survival for all patients is 50%. Interestingly, the patients with a history of a lesion that regressed had 85% cumulative five-year survival, and the patients with stage IIIB disease did almost as well, with 62% surviving for five years.

Adult↗

Platelet aggregation in non-insulin-dependent diabetes is associated with platelet fatty acids.

Platelet aggregation was measured in 15 patients having non-insulin-dependent diabetes mellitus (NIDDM) at the time of diagnosis and after three months of dietary treatment. Mean fasting plasma glucose fell from 13.0 to 8.8 mmol/l (p less than 0.0002), glycosylated haemoglobin fell from a mean of 11.3% to 9.0% (p less than 0.005) and insulin levels fell from a mean of 17.5 to 13.8 mU/l (p less than 0.005). Platelet aggregation showed a variable response and did not correlate with plasma glucose, glycosylated haemoglobin or plasma insulin. Multiple linear regression analysis was carried out on the aggregation values against the biochemical variables and platelet phospholipid fatty acid levels following logarithm transformation. Platelet linolenic acid and eicosapentaenoic acid levels were significantly inversely associated with aggregation but the difference between the relationship at diagnosis and after three months was not statistically significant. The association between platelet omega 3 fatty acids and platelet aggregation suggest that dietary change aimed at increasing the proportions of these fatty acids might favourably influence vascular disease in NIDDM via an effect on platelet function.

Adult↗

Increased arachidonic acid level in diabetic platelets following improvement in diabetic control.

A group of non-insulin dependent diabetics taking oral hypoglycaemic therapy were studied to determine the effect of improved diabetic control on the platelet levels of the prostaglandin precursor fatty acids. The patients were randomised to receive either a low carbohydrate diet (35% of total energy) for six weeks or a high carbohydrate diet (55% of total energy), high fibre diet for six weeks and the diets were then reversed. At the end of the high carbohydrate, high fibre diet the mean fasting blood glucose (6.6 mmol section 1) and mean percentage glycosylated haemoglobin (8.2%) were significantly lower than after the low carbohydrate diet (7.8. mmol/l, p less than 0.05: 9.9%, p less than 0.01). Mean platelet phospholipid arachidonic acid percentage was significantly higher after the high carbohydrate, high fibre diet (24.2%) than after the low carbohydrate diet (19.9%, p less than 0.01). There were no significant changes in the other platelet fatty acids.

Aged↗

A 13C-methylation study of glycophorin A intact erythrocytes by 13C-NMR spectroscopy.

N-terminal N alpha-[13C]monomethylamino derivatives for the N-terminal serine and leucine residues of glycophorins AM and AN, respectively, were obtained by reductively 13C-methylating homozygous human erythrocytes (MM, NN). The 13C-labeled glycophorins, AM and AN, were then isolated. A unique structural state was observed in solution reductively 13C-methylated glycophorin AM that was not observed in glycophorin AM derived from 13C-methylated erythrocytes. We attribute this state to the fact that some of the glycophorin AM forms a head-to-head dimer when subjected to reductive 13 C-methylation in aqueous solution. The 13C chemical shift data and pH titration data for the N-terminal [13C]dimethylamino and [13C]monomethylamino groups of glycophorin AM and AN derived from reductively 13C-methylated erythrocytes were in agreement with the chemical shift and titration data previously obtained for the N-terminal [13C]dimethylamino groups of solution reductively 13C-methylated glycophorins and related glycopeptides and peptides and N-terminal [13C]monomethylamino groups of related glycopeptides and peptides.

Chemical Phenomena↗

Response to aminoglutethimide after failure of tamoxifen therapy in breast cancer.

A 54-year-old woman had a primary breast cancer with an estrogen receptor of 11.9 fmoles/mg of protein. One year later bony metastases were treated with tamoxifen. The disease progressed rapidly, and therapy was changed to aminoglutethimide, which has resulted in an almost complete remission. This case shows that patients who fail to respond to tamoxifen therapy may have a good response to other endocrine manipulation--in this instance, aminoglutethimide.

Aminoglutethimide↗

Polyunsaturated fatty acids and diabetic retinopathy.

One hundred and forty nine diabetic patients were ophthalmologically assessed seven years after randomisation to a low carbohydrate or modified fat diet (rich in linoleic acid). Glycaemic control, regardless of the type of diet, was a major determinant of the development of retinopathy. Poorly controlled patients (haemoglobin A1c greater than 8%) with low levels of linoleic acid in cholesterol ester had a significantly greater frequency of retinopathy than well controlled patients or patients with similarly unsatisfactory control but higher levels of linoleic acid. The findings support an earlier suggestion that linoleic acid might protect against diabetic retinopathy.

Cholesterol Esters↗

Low-dose guar improves diabetic control.

Twenty diabetic outpatients (12 non-insulin-treated and 8 insulin-treated) were given guar granulate in a dose of 10 g daily for two months in order to study the effect on glycaemic control and lipid levels. Mean glycosylated haemoglobin levels (HbA1c%) fell from 11.1 +/- 2.0% pre-guar to 10.5 +/- 2.2% (P less than 0.001) after one month on guar and to 10.1 +/- 2.3% (P less than 0.0001) after two months. Following discontinuation of guar, HbA1c% rose to 11.1 +/- 2.5% (P less than 0.002). However, there were no significant changes in fasting blood glucose, 1 h postprandial blood glucose following a test meal, 24 h urinary glucose excretion or in lipid levels. Gastrointestinal side effects occurred in 4 patients during treatment with guar. Four patients reduced their dose of insulin and 2 patients reduced their dose of sulphonylurea therapy during this time because of symptoms suggestive of hypoglycaemia. We suggest that the low dose of guar used in this study may help improve glycaemic control in diabetic patients and that this may be achieved with a low incidence of gastrointestinal side effects.

Blood Glucose↗

Medical practice revenue and salaries of physician assistants.

Significant salary differences between male and female PAs have been noted. Several variables--hours worked per week, weeks worked per year, number of patients seen per week, and average fee per patient--were examined to assess their contribution to the differences in salary for PAs practicing in family medicine, internal medicine, and pediatrics. Although female PAs were found to earn significantly less than their male colleagues, the discrepancy could largely be explained when salary was examined as a proportion of revenue generated for the practice. The survey findings are compared with research findings on male and female physicians' salaries.

Female↗

13C-NMR spectral study of reductively [13C]methylated glycophorin B.

Glycophorin BN was reductively [13C]methylated and the 13C chemical shift of the N-terminal [13C]dimethyl-leucine residue was monitored as a function of pH. These results were compared to the pH-dependent chemical shift studies of the N-terminal [13C]dimethylleucine residues of intact glycophorin AN and N-terminal glyco-octapeptide AN. The results indicate that the titration data for [13C]dimethylleucine of glycophorin BN more closely resembles the titration data observed for the [13C]dimethylleucine residue of the N-terminal glyco-octapeptide AN rather than for the [13C]dimethylleucine residue of intact glycophorin AN. Integration of the 13C resonances indicated that glycophorin BN contains 3-4 lysine residues.

Glycophorins↗

A comparison of cholestyramine and probucol in the treatment of familial hypercholesterolaemia.

Twelve patients with familial hypercholesterolaemia (FH) who had not achieved satisfactory cholesterol levels on dietary advice alone were treated with cholestyramine for 6 months and probucol for 6 months in a randomised cross-over study to compare the relative effectiveness of the two drugs. Over the 6-month period, mean total cholesterol fell by 16.4% on cholestyramine and 12.7% on probucol. Cholestyramine produced a 17.4% fall in low density lipoprotein (LDL) cholesterol, no significant changes in very low density lipoprotein (VLDL) cholesterol or high density lipoprotein (HDL) cholesterol, a 21.4% increase in HDL cholesterol subfraction HDL2 and a 24.1% increase in the HDL/LDL cholesterol ratio. Triglyceride levels rose by 29.6% but remained within the normal range. Probucol produced a 11.7% fall in LDL cholesterol, a 9.9% fall in VLDL cholesterol, a 10% fall in total HDL cholesterol, a 37% fall in HDL cholesterol subfraction HDL2 and no change in the HDL/LDL cholesterol ratio. Triglyceride levels fell by 14%. The mean corrected QT interval increased from 0.418 to 0.434 s (P less than 0.01) on probucol but did not change significantly on cholestyramine (from 0.405 to 0.41 s). The two drugs have different metabolic effects on FH. Cholestyramine has a more marked effect on LDL cholesterol, favourably influences the HDL/LDL cholesterol ratio and is therefore considered to be the drug of choice.

Cholesterol↗

Fatty acid composition of platelet phospholipids in non-insulin-dependent diabetics randomized for dietary advice.

Two groups of patients with non-insulin-dependent diabetes mellitus (NIDDM), with dietary advice randomized between a low-carbohydrate (LC) diet and a modified-fat (MF) diet, were followed to determine the effect of diet on phospholipid fatty acid composition of platelets and on development of retinopathy in the 7 years following diagnosis. There was a tendency for retinopathy to occur more frequently in those randomized to the LC diet. This difference was not statistically significant, and fatty acid composition of platelets did not differ significantly in those with and without retinopathy. Linoleic acid values from platelet phospholipid fatty acids were significantly higher in NIDDM on an MF diet compared with an LC diet. There was no difference between the two dietary subgroups with respect to platelet arachidonic acid, but this was lower in the whole diabetic population when compared with non-diabetics. The arachidonic acid values correlated with neither glycosylated haemoglobin nor mean glycaemia. Significant correlation between the fatty acid values for platelets and plasma cholesterol esters was found only for 16:0.

Blood Platelets↗