Comparison of 1073 MBq and 3700 MBq iodine-131 in postoperative ablation of residual thyroid tissue in patients with differentiated thyroid cancer.

In a randomized prospective study, we compared the efficacy of low dose (1073 MBq) and high dose (3700 MBq) iodine-131 administration in postoperative ablation of residual functioning thyroid tissue in 63 patients with differentiated thyroid cancer. We were unable to demonstrate any difference between the low- and the high-dose of radioactive iodine in scintigraphic ablation of remnant tissue. In 81% (21/26) of the patients, 1073 MBq ablated after the first dose, 77% (21/26 + 3/5 = 24/31) after the first plus second dose, and 69% (24/31 + 0/4 = 24/35) after the first, second, and third dose. Radioiodine (3700 MBq) ablated in 84%, 73%, and 69% of the patients after respectively 1., 1. plus 2., and 1. plus 2. plus 3. dose. Forty percent of the patients ablated with the low dose and 44% ablated with the high dose had elevated thyroglobulin levels at the time of complete scintigraphic ablation. In conclusion, we did not find any difference between 3700 MBq and 1073 MBq iodine-131 as regard to number of doses needed for complete scintigraphic ablation of residual functioning thyroid tissue.

Diabetes in the UK West indian community: the Wolverhampton survey.

A survey was carried out to determine the prevalence of known diabetes amongst West Indians living in Wolverhampton. Two hundred and fifty-one West Indians with diabetes were identified from a computerized register, which records all diabetic patients in the Wolverhampton area attending either the hospital diabetic clinic or general practitioner mini-clinics, and from questionnaire data obtained through local general practitioners. An estimated 4.4% of the Wolverhampton population are of West Indian origin determined by the 1981 census, giving a prevalence of known diabetes of 2.2% compared with 1.2% in the indigenous UK white Caucasian population. Only 4% of these patients were truly insulin-dependent but 38% were insulin-treated, 43% were on oral hypoglycaemic agents and 19% on diet alone. Only 1.6% were diagnosed below the age of 20 years, with peak frequency of diabetes occurring in the age group 45-64 years. Thirty-eight percent of all patients were obese, 40% were hypertensive, but only 4% had a history of angina or myocardial infarction. In UK West Indians non-insulin-dependent diabetes is common and is predominantly a disease of middle age, whereas insulin-dependent diabetes is relatively uncommon.

Trans-racial studies implicate HLA-DQ as a component of genetic susceptibility to type 1 (insulin-dependent) diabetes.

Type 1 (insulin-dependent) diabetic patients and control subjects of Afro-Caribbean Negroid racial origin were investigated by serological HLA-DR-typing and restriction fragment length polymorphism analysis using DNA probes corresponding to the DQ alpha, DQ beta and DR beta chain genes. Combined analysis indicated that four DR antigens are positively associated with the condition in Negroid subjects - DR3, 4, 7 and w9. DR3 and 4 are also associated in Caucasians, but the relative risk for DR3 is lower in Negroid subjects. The DR7 association is specific for the Negroid race, and DRw9 is only weakly associated in Caucasoid subjects. Restriction fragment length polymorphism analysis demonstrated a DQ beta restriction pattern in Negroid subjects which is absent from Caucasoid subjects. This pattern was associated with DRw9 and a subset of DR7, and was markedly increased in frequency in diabetic patients compared with control subjects (48.7% vs 10.4%, respectively; p less than 10(-4). In the absence of this pattern, DR7 showed no positive association. DR3 in Negroid subjects was associated with two distinct DQ alpha-DQ beta patterns, only one of which was positively associated with diabetes. A DQ beta pattern, in linkage disequilibrium with different DR antigens in different races, conferred a consistent protective effect against the development of Type 1 diabetes. Trans-racial genetic analysis thus supports a primary role for DQ in susceptibility to Type 1 diabetes.

Trans-racial studies implicate HLA-DQ as a component of genetic susceptibility to Type 1 (insulin-dependent) diabetes

Type 1 (insulin-dependent) diabetic patients and control subjects of Afro-Caribbean Negroid racial origin were investigated by serological HLA-DR-typing and restriction fragment length polymorphism analysis using DNA probes corresponding to the DQO, DQá and DRá chain genes. Combined analysis indicated that four DR antigens are positively associated with the condition in Negroid subjects - DR3, 4, 7 and w9. DR3 and 4 are also associated in Caucasians, but the relative risk for DR3 is lower in Negroid subjects. The DR7 association is specific for the Negroid race, and DRw9 is only weakly associated in Caucasoid subjects. Restriction fragment length polymorphism analysis demonstrated a DQá restriction pattern in Negroid subjects which is absent from Caucasoid subjects. This pattern was associated with DRw9 and a subset of DR7, and was markedly increased in frequency in diabetic patients compared with control subjects (48.7 percent vs 10.4 percent respectively; p<10 -4). In the absence of this pattern, DR7 showed no positive association. DR3 in Negroid subjects was associated with two distinct DQO-DQá patterns, only one of which was positively associated with diabetes. A DQá pattern, in linkage disequilibrium with different DR antigens in different races, conferred a consistent protective effect against the development of Type 1 diabetes. Trans-racial genetic analysis thus supports a primary role for DQ in susceptibility to Type 1 diabetes. (AU)

Class II HLA DNA polymorphisms in type 1 (insulin-dependent) diabetic patients of north Indian origin.

Genetic associations with Type 1 (insulin-dependent) diabetes may be primary or secondary to linkage disequilibrium. Studies of different racial groups should allow these to be distinguished. We have reported that Type 1 diabetes is associated with HLA-DR3 and -DR4 in subjects of North Indian (Punjab) origin and now present the results of a study of HLA class II DNA polymorphisms in this group and in white caucasoid subjects. DR4 in North Indian Type 1 diabetic patients was associated with DQ beta and DX alpha DNA polymorphisms identical to those found in DR4-positive white caucasoid patients. This DQ beta/DX alpha pattern was increased in frequency in North Indian diabetic patients vs control subjects (33.3% vs 8.5%, p less than 0.001, relative risk = 5.12 (95% confidence limits: 1.96-13.4)). A DQ beta polymorphism with very low relative risk for Type 1 diabetes in white caucasoid subjects was also markedly reduced in North Indian diabetic patients vs control subjects (2.3% vs 24.7%, p less than 0.02, relative risk = 0.10 (95% confidence limits: 0.02-0.46)). This pattern was associated with DR2 in white caucasoid subjects, but with DRw6 in North Indians. A DR3-associated DR beta polymorphism was markedly increased in North Indian diabetic patients vs control subjects (90.2% vs 40.7%, p less than 10(-6), relative risk = 12.1 (95% confidence limits: 4.32-33.9)). The DQ subregion may be a primary site of genetic influence on susceptibility to Type 1 diabetes. Further studies in different racial groups will clarify the HLA associations of Type 1 diabetes.

Autoantibodies in Indian-Asians with insulin-dependent diabetes in the UK.

Classical insulin-dependent diabetes mellitus (IDDM) is relatively uncommon in Indian-Asians whether in India or in the UK and this may be related to immunogenetic factors. We have studied the presence or absence of islet cell antibodies and other auto-antibodies in 36 subjects with IDDM and 41 controls, all of Indian origin. Islet cell antibodies (ICA-IgG) were found in 8 subjects with IDDM but in none of the controls. Four of the 8 patients with ICA-IgG also possessed the complement fixing variety (CF-ICA). There was no definite association between possession of ICA and HLA-DR antigens. Thyroid antibodies were commoner in patients (22%) compared with controls (7%) as were parietal cell antibodies (8.3% vs 4.8%). None of the patients or controls had adrenal antibodies. The frequency of organ-specific antibodies in Indian-Asians with IDDM is similar to that of white Caucasians. The overall frequency of ICA is, however, lower than that reported for white Caucasians although the temporal distribution is similar. We conclude that even though the prevalence of IDDM in Indian-Asians is lower than in white Caucasians there is no evidence that different immunological mechanisms are involved in the pathogenesis of IDDM in the two groups.

HLA-DR and DQ DNA polymorphisms in subjects of Asian Indian and white Caucasian origin.

There is a close correspondence between serologically defined DR types and DR beta chain restriction fragment length polymorphisms (RFLPs). There is also an association between DR types and DQ alpha and DQ beta RFLPs because of linkage disequilibrium. We present the results of an analysis of DR beta, DQ alpha and DQ beta RFLPs in Asian Indians and white Caucasian subjects. DR beta RFLPs were similar in the two groups. Clearly distinguishable DR beta patterns were observed for DR1, 2, 3, 4, 5, 7 and w10. The DR beta patterns associated with DR3 were, however, also found with w6. The DR7 DR beta patterns were also found with w9. For DR specificities 1, 3, 4, 5, 7 and w10, the associated DQ alpha and DQ beta RFLPs were similar in both racial groups, but for DR2, however, marked differences were found. The DR2-positive white Caucasian subjects all possessed a single DQ alpha/DQ beta combination whereas the DQ alpha/DQ beta patterns in DR2-positive Asian Indians showed considerable heterogeneity. The pattern seen in white subjects was present in only a minority of Asians. DR-DQ relationships clearly vary in different racial groups. RFLP analysis of HLA-linked diseases in different populations should prove to be an important technique in identifying the primary genetic factor(s) in these disorders.

Insulin receptor antibodies in diabetes mellitus.

Sera from 80 subjects with IDDM and NIDDM, together with sera from 20 patients with miscellaneous autoimmune conditions and 20 healthy adult subjects were tested for insulin receptor antibodies by (1) inhibition of 125I-insulin binding to EBV-transformed lymphoid cells, and by (2) immunoprecipitation of solubilized insulin receptors in the presence of an excess of mono-specific anti-human IgG or IgM; this test allowed the assessment of the class of antibody activity. Anti-insulin antibodies in the sera were also measured using a double antibody technique. Anti-insulin receptor antibodies were found in 13 of 33 subjects with IDDM and six of 47 with NIDDM. These were principally in the IgM class, and in both groups of diabetics there was a good correlation between % inhibition of insulin binding to intact cells, and % of antibody precipitated by IgM (P less than 0.001), but not by IgG (P greater than 0.1). There was also a good correlation between the % inhibition of insulin binding to intact cells and the daily dose of insulin used in treatment (P less than 0.001). Insulin antibodies were found in seven of 33 subjects with IDDM and six of 12 with NIDDM, all of whom were on insulin treatment. These six subjects were the only ones with NIDDM who also had anti-insulin receptor antibody activity, suggesting that such antibodies may represent auto-anti-idiotype activity. This study shows that autoimmunity in insulin dependent (Type I) diabetes is not limited to islet cells and that such patients also develop antibodies to the insulin receptor. While three out of five patients with relative insulin resistance (requirement greater than 90 u/day) also showed evidence of insulin receptor antibody activity, the clinical significance of these antibodies has yet to be determined.

The HLA-D associations of type 1 (insulin-dependent) diabetes in Punjabi Asians in the United Kingdom.

Type 1 (insulin-dependent) diabetes is less common in Asian Indians than in white Caucasoids. Forty-five Punjabi Asians with Type 1 diabetes and 96 racially matched control subjects were HLA-DR typed. DR3 was increased in diabetic patients vs control subjects (82% vs 38%, p less than 10(-5)) with relative risk 7.7 and etiological fraction 0.72. DR4 was increased in diabetic patients vs control subjects (31% vs 7%, p less than 0.003) with relative risk 5.7 and etiological fraction 0.26. DR2 showed a negative association (relative risk 0.19, etiological fraction -0.28), as did DR7 (relative risk 0.21, etiological fraction -0.33). HLA-DQ beta-chain gene probing using restriction enzyme BamHI in 43 diabetic patients and 90 control subjects showed that the DR1-associated 6.2 and 3.2 kb fragments were less common in diabetic patients than in the control subjects (12% vs 36%, p less than 0.02). A 12 kb fragment was associated with DR4 in both diabetic patients and control subjects. DR3 is the major susceptibility factor for Type 1 diabetes in Punjabi Asians and DR4 is a second marker. Gene probing indicates that the same DR4 subset is associated with the condition as in white Caucasoids. DR1 and its associated DQ beta restriction fragments are reduced in Asian Type 1 diabetic patients making it unlikely that DR1 haplotypes carry a predisposing factor in this racial group. We conclude that the genetic component of Type 1 diabetes in Punjabis shows differences from that of the white Caucasoid population and that the lower frequency of DR4 in this population may contribute to the lower prevalence of Type 1 diabetes.

Beta-and alpha-adrenergic blockade and metabolic responses to insulin induced hypoglycaemia in diabetics.

The metabolic, autonomic and symptomatic effects of labetalol and metoprolol in comparison with placebo, were studied during insulin induced hypoglycaemia in 5 non-insulin dependent diabetics. Both drugs suppressed the expected increase in heart rate during hypoglycaemia, but did not affect awareness of hypoglycaemic symptoms. Neither drug produced a rise in blood pressure during hypoglycaemia nor delayed the recovery from insulin-induced hypoglycaemia. In both there was no inhibition of release of gluconeogenic substrates such as free fatty acids. The results indicate that both metoprolol, a selective beta-blocker, and labetalol, a combined alpha beta-blocker, do not impair awareness of hypoglycaemia nor alter the metabolic response to hypoglycaemia in diabetics.

Sulbactam/ampicillin: effects on glucose metabolism in diabetics with soft tissue infection.

Rats and dogs chronically treated with high doses of sulbactam are known to sequester protein-bound glycogen in their hepatocytes. As a result, previous UK studies of sulbactam/ampicillin excluded patients suffering from diabetes mellitus. This study examined the effects of sulbactam/ampicillin compared to flucloxacillin/ampicillin on diabetic control, the ability to mobilize glycogen and the pancreatic beta cell response to glucagon, in diabetic patients suffering from soft tissue infection. There was no significant effect between treatment groups on any of these parameters. Sulbactam/ampicillin is unlikely to have an adverse effect on diabetic control in clinical practice when used short term in the doses employed in this study.

Asian patients attending a diabetic clinic.

Patients of Asian origin comprised 8% of the patients attending a diabetic clinic. Of the 201 Asian patients (120 male), 110 had been diabetic for more than five years, and although 141 were 40 to 60 years old, over one quarter had been aged under 40 at diagnosis. Thirty patients were being treated with insulin, but only eight were truly dependent on insulin compared with 18% of the white patients attending the clinic. Insulin was stopped in eight patients who were receiving insulin inappropriately; control was achieved by diet plus oral hypoglycaemics or diet alone. Over three years 37 patients were admitted with ketoacidosis but none was Asian. During the same period, however, five Asians were admitted in hyperosmolar coma. Asian diabetics have a low prevalence of insulin dependence, possibly related to genetic and environmental factors, and some may be treated with insulin inappropriately.

Developing world. Patients' choice of anaesthetic techniques in a developing country.

A study of the choice between general and local anaesthetic techniques among 200 post-operative Nigerian patients was conducted, using a questionnaire. The patients were interviewed between two and seven days after various types of surgery. Most of the patients (59.5%) preferred general anaesthesia. The commonest reason was fear with psychological upset if they are awake during surgery. This appears to be a basic human feeling which does not appear to be related to sophistication or level of development. Adequate pre-operative communication between doctors and patients should minimise this apprehension. 18% preferred local anaesthetic techniques while 21.5% would not mind either.