Biomedical subjects

S S Lo

Publications and source records attributed to S S Lo.

At least 55 records · Page 3Linked to original sources

PubMed1996

Surgical management of primary retroperitoneal sarcoma.

BACKGROUND: Retroperitoneal sarcoma is a rare and challenging group of diseases for surgeons, characterized by extensive growth and high recurrent rate. We analyzed data from our patients to identify the factors of survival. METHODS: From 1971 to 1993, medical records of 40 patients with primary retroperitoneal sarcoma were reviewed. Clinical factors including age, sex, tumor size, histopathology, type of operation, disease-free interval, and number of operation were collected to correlate with patient's survival. RESULTS: Most patients presented with huge abdominal mass. There were 22 liposarcomas, 8 leiomyosarcomas, 5 malignant fibrous histiocytomas, 2 fibrosarcomas, 2 malignant mesenchymomas and one rhabdomyosarcoma. Twenty-eight patients received complete resection and 12 had incomplete resection. The group with complete resection showed a better survival than incomplete resection group (p = 0.0001). Nineteen patients with complete resection had tumor recurrence. The recurrent rate was 68%. Patients having been disease-free for more than 12 months showed to have better survival than those less than 12 months (p = 0.005). Aggressive surgical resection was done in case of tumor recurrence. Patients who received more than 2 (> or = 3) operations also showed a better survival than those with less than 2 operations (p = 0.0247). CONCLUSIONS: Complete surgical resection and aggressive repeated surgical intervention are the most effective treatment modality for better survival in patients with retroperitoneal sarcoma.

Adult↗

PubMed1995

Levonorgestrel intrauterine device in the treatment of menorrhagia in Chinese women: efficacy versus acceptability.

Ten Chinese women who had menorrhagia without organic cause and suffered from anaemia were treated with levonorgestrel intrauterine device for a total of 129 woman-months. There was a 54%, 87% and 95% reduction in menstrual blood loss at the first, third and sixth month of treatment when compared with the pretreatment cycle. These percentages of reduction were statistically significant, with p values of 0.004, 0.03 and 0.008, respectively. There was a median increase in menstrual cycle length of 12 days in nine months. Fifteen percent of the menstrual cycles were longer than 60 days. The total bleeding days increased by 4 days at the third menstrual cycles, but reduced to a median of 6 days at 6 months. Seventy-six percent of the menstrual bleeding was in the form of spotting. These Chinese women accepted such menstrual alterations. There was no hormonal side effects. All women preferred the device to hysterectomy. Levonorgestrel intrauterine device appeared to be an effective and acceptable treatment for menorrhagia in perimenopausal Chinese women.

Adult↗

PubMed1995

Effects of type 1 diabetes mellitus on cardiac function: a study of monozygotic twins.

OBJECTIVE: To investigate left ventricular size and function in type 1 diabetes and their relation with diabetes duration, glycaemic control, autonomic dysfunction, and complications of diabetes. DESIGN: Cross sectional study using a pulsed wave Doppler echocardiogram to assess left ventricular dimensions, wall thickness, and transmitral blood flow velocity signals. PATIENTS: 40 monozygotic twin pairs (23 male, mean age 26 years) discordant for type 1 diabetes and 40 non-diabetic singleton controls with no clinical evidence of cardiac ischaemia. RESULTS: For all Doppler echocardiographic measurements there were strong correlations between monozygotic twins but not between twins and control subjects. Left ventricular dimensions, wall thickness and systolic function, peak E velocity, and the velocity integrals of early left ventricular filling were similar in all three groups. Peak A velocity and the velocity integrals of late ventricular filling (mean (SD)) were greater in diabetic twins (45 (12) v 38 (8) cm/s, P = 0.002; and 32 (11) v 26 (6), P = 0.0002). Diabetic twins had lower E/A ratio (1.59 (0.39) v 1.83 (0.39), P < 0.001), greater atrial filling fraction to total diastolic filling (28 (6) v 25 (5)%, P = 0.002), and prolonged isovolumic relaxation time (72 (12) v 63 (9) ms, P < 0.001). The differences in Doppler findings between diabetic and non-diabetic twins were related to disease duration whereas the prolongation of the isovolumic relaxation time was related to cardiac autonomic dysfunction. CONCLUSIONS: These results show that twins with type 1 diabetes have left ventricular diastolic dysfunction related to diabetes duration and cardiac autonomic dysfunction but not to glycaemic control or microvascular complications. In addition, genetic factors contribute to left ventricular dimension and function.

Adolescent↗

PubMed1995

Morbidity and mortality after radical gastrectomy for patients with carcinoma of the stomach.

BACKGROUND: This study sought to analyze the morbidity and mortality rates after radical gastrectomy for carcinoma, since the operation has been criticized as too morbid for the benefits it may provide. STUDY DESIGN: A prospective study of 474 patients who underwent radical gastrectomy was conducted. RESULTS: The overall morbidity and mortality rates were 20.1 and 3.0 percent, respectively. The morbidity and mortality rates fell significantly from 27.0 to 15.7 percent (p = 0.003) and 5.5 to 1.1 percent (p < 0.001), respectively, after the first 200 cases. By logistic regression analysis, it was found that male gender, combined organ(s) resection, extended lymphadenectomy, respiratory system disease, and tumor location were significantly related to postoperative morbidity. In regard to the extent of lymphadenectomy, relative to R2 resection (n = 102), the odds ratio for morbidity after R3 resection (n = 217) was 2.13, and for R4 resection (n = 155) it was 3.12. Age older than 65 years, total gastrectomy, combined organ(s) resection, and respiratory system disease were factors that negatively affected operative mortality. CONCLUSIONS: These observations suggested that radical gastrectomy can be performed with an acceptable risk of morbidity and mortality in a general hospital.

Age Factors↗

PubMed1995

Pseudomyxoma peritonei: does a true mucolytic agent exist? In vitro and in vivo studies.

Reproducibility of the so-called "mucolytic effect" of the 2%-10% dextrose-water solution is questioned. To test the mucolytic effect of 5% and 10% dextrose-water solutions and to determine what could be a true mucolytic agent, in vitro and in vivo studies were undertaken in two proven pseudomyxoma peritonei cases. In vitro study: Immediately after the mucin jelly was taken out of the peritoneal cavity, the jelly was immersed in various 40 cc solutions including: 1) 5% dextrose-water; 2) 10% dextrose-water; 3) normal saline; 4) lactated Ringer; 5) distilled water. The mucolytic effects of these solutions were observed once every hour after vigorous mixing. In vivo study: After completion of the operation, the peritoneal cavity was repeatedly irrigated with massive warm 5% dextrose-water and normal saline solutions in an attempt to dissolve the residual mucin cake and jelly. Neither 5% and 10% dextrose-water solution nor control solutions of normal saline, lactated Ringer, and distilled water could dissolve the mucin jelly in test tubes at 0, 1, 2, and 3 hours. The "claimed" mucolytic agent, 5% dextrose-water solution could not facilitate the removal of both mucin jelly and cake in the peritoneal cavity. The 5% dextrose-water solution was not superior to the normal saline solution in terms of mucolytic effect. In the present study, a true mucolytic agent does not exist. Currently, multiple laparotomy for aggressive cytoreduction remains the treatment of choice for pseudomyxoma peritonei.

Aged↗

PubMed1995

Is pancreatoduodenectomy justified for periampullary cancers with regional lymph node involvement?

Justification of pancreatoduodenectomy for highly malignant periampullary cancers with regional lymph node involvement is questioned. Attempting to clarify the therapeutic dilemma, we compared the prognoses of resectable periampullary cancers with and without lymph node involvement, as well as unresectable cancers with lymph node involvement. The medical records of surgical patients with periampullary adenocarcinoma were reviewed. We compared the survival times of resectable cancers with (resectable TanyN1M0) and without (resectable TanyN0M0) regional lymph node involvement, and the survival times of resectable cancers with lymph node involvement (resectable TanyN1M0) and unresectable cancers with lymph node involvement (unresectable TanyN1M0). There were 138 resectable and 115 unresectable periampullary cancers including 117 cancers of the pancreatic head, 117 cancers of ampulla of Vater, 7 cancers of duodenum, and 12 cancers of distal common bile duct. The prognosis was very poor in cancer of the pancreatic head. Neither resectability nor status of lymph node involvement could influence the survival time of the cancer of pancreatic head. In resectable non-pancreatic periampullary cancers, the prognosis was significantly better in the group without lymph node involvement. However, once the lymph node was involved, the outcomes were the same in the resectable and unresectable groups. Although pancreatoduodenectomy does not seem to be justified for periampullary cancers with regional lymph node involvement, this procedure should be considered for periampullary cancers without nodal involvement.

Adenocarcinoma↗

PubMed1994

Lymph node metastasis from carcinoma of the distal one-third of the stomach.

BACKGROUND: A detailed and thorough pathoanatomic study of lymph node (LN) metastases of adenocarcinoma of the distal one-third of the stomach is lacking. METHODS: From December 1987 to March 1992, 190 patients who underwent radical gastrectomy was analyzed. All LN were dissected and labeled according to the Japanese General Rules for the Gastric Cancer Study. RESULTS: A total of 7052 LN with an average of 37.1 per specimen were removed. LN metastases were encountered in 121 patients (63.7%). The most frequent LN metastases were perigastric, above common hepatic artery, along left gastric artery, and hepatoduodenal ligament. The incidence of LN metastasis varied and was highest when tumor was located close to either curvature and extended to duodenum or midbody. The high incidence of LN metastases in the hepatoduodenal ligament was a unique pathologic feature of adenocarcinoma of the distal one-third of the stomach (P = 0.0012). Univariate and multivariate analysis revealed that depth of cancer invasion was the only factor related to LN metastases. CONCLUSIONS: Cancer in the distal one-third of the stomach had a high incidence of LN metastasis to hepatoduodenal ligament nodes. The LN metastasis is correlated with depth of cancer invasion.

Adenocarcinoma↗

PubMed1994

Importance of persistent cellular and humoral immune changes before diabetes develops: prospective study of identical twins.

OBJECTIVES: To determine the pattern of cellular and humoral immune changes associated with insulin dependent diabetes before diabetes develops. DESIGN: Prospective study over 10 years of 25 non-diabetic identical twins of patients with insulin dependent diabetes. The non-diabetic twins were followed up either till they developed diabetes or to the end of the study. SETTING: Teaching hospital. SUBJECTS: 25 non-diabetic identical cotwins of patients with diabetes; 46 controls of the same sex and similar age tested over the same period. Of the 25 twins (total follow up 144 patient years), 10 developed diabetes (prediabetic twins); the remainder were followed up for a mean of 7.7 years. MAIN OUTCOME MEASURES: Results of glucose tolerance tests or fasting blood glucose concentrations at each sample point. Measurements of activated T lymphocytes, expressing the HLA-DR antigen, islet cell antibodies, and insulin autoantibodies in samples. RESULTS: All 10 prediabetic twins had both cellular and humoral changes initially and in most samples before diabetes was diagnosed (activated T lymphocytes in 39/40, islet cell antibodies in 45/47, and insulin autoantibodies to islet cells and insulin were detected infrequently (in 8/54, 6/69, and 0/69 samples, respectively). The combination of cellular and humoral (islet cell antibodies or insulin autoantibodies) immune changes were detected in all 10 of the prediabetic twins but in only one of the 15 non-diabetic twins (P < 0.001). The positive predictive value in this cohort of increased percentages of activated T cells and the presence of antibodies to islet cells or insulin on two consecutive occasions was 100%. CONCLUSION: Most of the twins had cellular or humoral immune changes at some stage. A combination of cellular and humoral immune changes and their tendency to persist is highly predictive of insulin dependent diabetes and distinguishes twins who develop diabetes from those who do not.

Adolescent↗

PubMed1994

Lymph node metastasis from carcinoma of the distal one-third of the stomach.

BACKGROUND: A detailed and thorough pathoanatomic study of lymph node (LN) metastases of adenocarcinoma of the distal one-third of the stomach is lacking. METHODS: From December 1987 to March 1992, 190 patients who underwent radical gastrectomy was analyzed. All LN were dissected and labeled according to the Japanese General Rules for the Gastric Cancer Study. RESULTS: A total of 7052 LN with average of 37.1 per specimen were removed. LN metastases were encountered in 121 patients (63.7%). The most frequent LN metastases were perigastric, above common hepatic artery, along left gastric artery, and hepatoduodenal ligament. The incidence of LN metastasis varied and was highest when tumor was located close to either curvature and extended to duodenum or midbody. The high incidence of LN metastases in the hepatoduodenal ligament was a unique pathologic feature of lower stomach cancer (P = 0.0012). Univariate and multivariate analysis revealed that depth of cancer invasion was the only factor related to LN metastases. CONCLUSIONS: Cancer in the distal one-third of the stomach had a high incidence of LN metastasis to hepatoduodenal ligament nodes (No. 12). The LN metastasis is correlated with depth of cancer invasion.

Adenocarcinoma↗

PubMed1994

Can the hormonal receptor status of primary breast cancer be altered by neoadjuvant chemotherapy?

In order to know whether neoadjuvant chemotherapy would change the hormonal receptor status of primary breast cancer, 10 patients with locally advanced breast cancer treated with neoadjuvant CEF (endoxan, epirubicin, 5-fluorouracil) were studied. Tissue was obtained by incisional biopsy before chemotherapy and by mastectomy after three courses of treatment. All the specimens were subjected to histology study and the tests of estrogen (ER) and progesterone (PgR) receptors. The results revealed that the only hormonal status of one out of 10 tumors was altered. Among the 10 tumors, 2 out of 10 ER and 3 out of 10 PgR were changed after neoadjuvant CEF. From our results together with other findings, it is concluded that neoadjuvant CEF dose not significantly change the hormonal receptor status of primary breast cancer. The hormonal receptor assay is unnecessary before chemotherapy.

Adult↗

PubMed1994

Variability of serum thyroglobulin levels is determined by a major gene.

OBJECTIVE: There are large variations in the circulating concentrations of thyroglobulin. The purpose of this study was to explore the possibility of a genetic basis for the variability of serum concentration of thyroglobulin (Tg) in euthyroid individuals. DESIGN: The serum concentration of thyroglobulin (Tg) varies several-fold in euthyroid individuals. Other circulating proteins also show wide normal ranges of concentration and these variations have been shown to have a genetic as well as an environmental basis. To explore the possibility of a genetic basis for variability in serum Tg levels, an analysis was made of serum Tg levels in 44 pairs of identical twins and 66 nuclear families who were euthyroid and thyroid autoantibody negative (thereby eliminating subclinical autoimmune thyroid disease and Tg autoantibody interference with the Tg assay). RESULTS: Each pair of identical twins tended to have a similar Tg level and the overall correlation was highly significant (r = 0.734, P < 0.001). There was no relation between Tg and TSH levels in the twins (r = 0.119; P = 0.366). Segregation analysis of the 66 families showed that where both parents had Tg levels above the overall median for the subjects (males, 19 micrograms/l; females, 33 micrograms/l), 73% of the offspring also had concentrations above these levels, compared with 30% of the offspring when one parent had a high Tg level and only 16% in families where neither parent had a high Tg level. CONCLUSIONS: Complex segregation analysis using the computer program Pointer suggested that variability in Tg levels was the result of a major dominant-like gene effect (accounting for 80% of the variability) combined with a multifactorial component. Thyroglobulin, a template for thyroid hormone production, is also a major thyroid autoantigen and inherited variations in serum Tg levels may have implications for the pathogenesis of autoimmune thyroid disease.

Adolescent↗

PubMed1994

Exercise electrocardiography and aortic Doppler velocimetry in asymptomatic identical twins discordant for type 1 (insulin dependent) diabetes.

OBJECTIVE: To determine the influence of insulin dependent diabetes on the prevalence of myocardial ischaemia and on global left ventricular systolic performance. DESIGN: Stress treadmill electrocardiograms and simultaneous Doppler measurement of aortic maximum acceleration were obtained during exercise on symptom free subjects. The electrocardiograms were scored blindly according to the Minnesota code. PARTICIPANTS: 39 identical twin pairs (22 male) discordant for insulin dependent diabetes and 39 non-diabetic controls of similar age and sex were examined. The twins and controls had a mean age of 37 (range 25-69) with a mean (SD) duration of diabetes in the diabetic twin of 17 (7) years. Those selected were normotensive and had no renal impairment. RESULTS: Systolic blood pressure was significantly higher in the diabetic twins than in their non-diabetic cotwins both at rest (p < 0.05) and at peak exercise (p < 0.01). Electrocardiographic evidence of ischaemia was not correlated within twin pairs and was found in similar numbers of diabetic twins, their non-diabetic cotwins, and control subjects. Abnormal electrocardiograms were found in a similar number of diabetic twins (23%), non-diabetic cotwins (18%), and controls (15%). There was a significant correlation in Doppler measurements of global left ventricular systolic function within the identical twins; no significant difference was found for these Doppler measurements in the diabetic twins, non-diabetic cotwins, or controls. CONCLUSION: Exercise characteristics and cardiac function seem to be subject to shared genetic or shared environmental influences or both, whereas electrocardiographic features of ischaemia seem to be environmentally determined. In a selected cohort of diabetic identical twins without evidence of nephropathy there was no evidence that diabetes influenced the prevalence of myocardial ischaemia or global left ventricular systolic function.

Adult↗

PubMed1994

Increased expression of T-cell markers of immunological memory associated with protection from type I diabetes. A study of identical twins.

Disturbances in the balance of CD4+ helper T-lymphocytes expressing the surface molecules CD45RA and CD45R0, which define naive and memory populations, respectively, are present at diagnosis of type I diabetes. In a prospective study over 10 years, these subsets were analyzed in samples obtained from 18 identical twins of patients with type I diabetes, 8 of whom became diabetic (prediabetic twins), whereas the rest remained nondiabetic after at least 8 years follow-up and are now unlikely to develop the disease (diabetes-protected twins). At the beginning of the study, percentage levels of naive (CD45RA+) CD4+ lymphocytes were significantly elevated in prediabetic twins compared with diabetes-protected twins (P < 0.05) and remained so throughout the study (P < 0.01). Percentage levels of naive cells in diabetes-protected twins were significantly reduced compared with control subjects both at the beginning and throughout the study (P < 0.05, P < 0.01, respectively). In contrast, diabetes-protected twins at the beginning of the study had elevated percentage levels of memory (CD45R0+) CD4+ lymphocytes that persisted throughout the study compared with prediabetic twins (P < 0.05 for both). Percentage levels of memory cells in prediabetic twins were significantly reduced compared with control subjects both at the beginning and throughout the study (P < 0.01, P < 0.05, respectively). Increased percentage levels of a population of CD4+ lymphocytes coexpressing CD45RA and CD45R0 were seen in both twin groups compared with control subjects at entry into and during the study (P < 0.05 for all), but persisted only in the prediabetic twins.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

Comparison of resectable and unresectable periampullary carcinomas.

Two hundred and fifty-eight patients with pathologically proved periampullary carcinomas who underwent surgical treatment between the years 1965 and 1992 were evaluated. Comparison was carried out between the resectable and unresectable groups. Carcinoma of the pancreatic head occurred in less than one-half (47 percent) of the patients, and only 23 percent were resectable. In contrast, carcinoma of the ampulla of Vater had a similar rate of occurrence, but a much higher resectable rate (86 percent). Thus, carcinoma of the pancreatic head was the minor group (19 percent) in the resectable patients we studied. The main clinical presentations and durations of symptoms before diagnosis did not differ in the resectable and unresectable groups, so it was impossible to predict the resectability by symptoms. Incidences of diabetes mellitus and diarrhea increased twofold in the unresectable group. Preoperative biopsy was difficult to perform for those with carcinoma of the pancreatic head. Comparing pancreatoduodenectomy and palliative operation, pancreatoduodenectomy resulted in a higher complication rate (43 versus 13 percent), a higher surgical mortality rate (17 versus 9 percent) and a longer hospitalization period (31 versus 20 days), but there was no statistical difference in the median survival time between the resectable and unresectable carcinomas of the pancreatic head (seven and one-half versus five months). Most of the patients (81 percent in the resectable group and 70 percent in the unresectable group) we studied died of cachexia with tumor recurrence. Although the advantage of pancreatoduodenectomy for resectable carcinoma of the pancreatic head was questioned, we still recommend this procedure for all periampullary carcinomas to avoid depriving the occasional patients with pancreatic carcinomas of long term survival and forfeiting the chance of cure for some misdiagnosed patients with other more favorable periampullary carcinomas.

Age Factors↗

PubMed1994

DNA flow cytometric analysis of primary breast cancer in Chinese women: the relationship of DNA aneuploidy to clinical characteristics.

One-hundred-and-forty fresh frozen breast tissue samples from Chinese patients collected from May 1991 to October 1992 were evaluated for DNA content by flow cytometric analysis. None of the 12 benign tumors displayed aneuploidy. One-hundred-and-twenty-eight of the 140 specimens were histologically proven to be malignant. Ploidy was compared to the clinical characteristics which included age, tumor size, lymph node involvement, menopausal status, steroid receptor status, histological grading and pathological staging. After univariate and multivariate analyses, aneuploidy was more frequently identified in progesterone receptor negative and high grade tumors. This study suggests that an aneuploid DNA content in a breast cancer specimen may indicate more aggressive cancer.

Asian People↗

PubMed1993

Information on type 1 diabetes mellitus and QT interval from identical twins.

To determine whether QT interval is influenced by genetic factors and whether QT-interval prolongation occurs in type 1 diabetes or is related to diabetic autonomic neuropathy, QT intervals were measured, and autonomic function was assessed in 44 pairs of identical twins who were discordant for type 1 diabetes. Twins were compared with 44 normal control subjects of similar age and sex. QT intervals were corrected for heart rate (QTc). QTc in diabetic twins correlated with that in their nondiabetic co-twins (r = 0.41; p = 0.006). Diabetic twins had significantly longer QTc than did their nondiabetic co-twins and control subjects (416 +/- 18 vs 407 +/- 16 and 403 +/- 19 ms, respectively; p < 0.005). A greater number of abnormal autonomic function tests were detected in diabetic twins than in their nondiabetic co-twins and control subjects (8 vs 2 and 0%, respectively; p < 0.01). Diabetic twins with disease duration > 14 years (n = 22) had longer QTc than did their nondiabetic co-twins (420 +/- 17 vs 402 +/- 14 ms; p < 0.0005). Twins with diabetes for > 14 years had a greater frequency of abnormal autonomic function tests than did those with diabetes < 14 years (15 vs 2%; p < 0.001). QTc did not correlate with autonomic function in diabetic twins. It is concluded that QT interval is influenced by genetic factors, and in type 1 diabetes, QTc can be prolonged independently of autonomic neuropathy.

Adolescent↗

PubMed1992

Altered islet beta-cell function before the onset of type 1 (insulin-dependent) diabetes mellitus.

To define the glucose to insulin dose-response relationship before the onset of diabetes, we studied 22 non-diabetic co-twins of patients with Type 1 (insulin-dependent) diabetes mellitus and nine control subjects. All had intravenous glucose tests at 0.02, 0.1 and 0.5 g/kg and were followed-up prospectively for at least 6 years. Seven twins developed diabetes a mean of 7 months later; the remaining 15 are now unlikely to develop diabetes. The seven pre-diabetic twins had higher fasting insulin levels than control subjects (4.2 +/- 2.0 vs 1.8 +/- 1.8 nmol/l; p less than 0.05); but lower glucose clearance (1.0 +/- 0.5 vs 1.9 +/- 0.7 %/min; p less than 0.05), first phase insulin response at 0.5 g/kg (21.1 +/- 23.2 vs 143 +/- 50 nmol/l; p less than 0.0001), and total insulin responses at 0.1 g/kg (p less than 0.05) and 0.5 g/kg (p less than 0.00005). Using a curve-fitting programme, the normal glucose to insulin relationship was lost in prediabetic twins who had lower coefficient of determination (R2) than control subjects (p less than 0.01). In contrast, 15 low-risk twins and their nine control subjects had similar fasting glucose and insulin levels, glucose clearance, R2 and insulin secretory responses to different glucose loads. The positive predictive values of subnormal R2 and subnormal first phase insulin response were 67% and 58% respectively. These observations demonstrate an altered glucose to insulin dose-response relationship and loss of maximum insulin secretory response to glucose before the onset of Type 1 diabetes.

Adolescent↗

PubMed1992

Antibodies to GAD and tryptic fragments of islet 64K antigen as distinct markers for development of IDDM. Studies with identical twins.

Insulin-dependent diabetes mellitus (IDDM) is associated with antibodies to a 64,000-M(r) islet cell protein, at least part of which is identified as glutamic acid decarboxylase (GAD). These antibodies are detected as two distinct antibody specificities to 50,000-M(r) and 37,000/40,000-M(r) tryptic fragments of the autoantigen (50K and 37K antibodies, respectively). We determined the frequencies of antibodies to intact GAD, tryptic fragments of islet 64,000-M(r) antigen, islet cell antibodies (ICAs), and insulin autoantibodies (IAAs) in sera from 58 nondiabetic identical twins of patients with IDDM, of whom 12 subsequently developed diabetes. ICA, antibodies to intact GAD, and those to tryptic fragments were detected at similar frequencies in prediabetic twins (67-75%), but only 25% had IAA. Of 46 twins who remain nondiabetic, GAD antibodies, 50K antibodies, and ICA were detected in 6 (13%), 7 (15%), and 5 (11%), respectively, whereas only 1 (2%) possessed 37K antibodies and 2 (4%) had IAA. Eight of 9 twins with 37K antibodies and all 6 twins with ICA greater than 20 Juvenile Diabetes Foundation U have developed diabetes. Antibodies to GAD are sensitive markers for diabetes development but may also be present in genetically susceptible individuals who are unlikely to develop disease. Antibodies to 37,000/40,000-M(r) fragments of the 64,000-M(r) antigen or high-titer ICA were the best markers for diabetes development in these twins.

Antibody Specificity↗