Genetic marker associations with proliferative retinopathy in persons diagnosed with diabetes before 30 yr of age.

It has been suggested that HLA-DR4 is a marker of genetic predisposition to proliferative retinopathy. To investigate this relationship and potential associations between other polymorphic genes and proliferative retinopathy, a sample (n = 428) of participants in the population-based Wisconsin Epidemiologic Study of Diabetic Retinopathy was selected for typing for HLA-A, -B, -C, and -DR and a panel of other polymorphic genes. The presence of proliferative retinopathy was determined from grading of stereoscopic color fundus photographs taken at 2 examinations, 4 yr apart. In logistic regression models with repeated measures, persons with HLA-DR4 who were negative for DR3 were five times more likely to have proliferative retinopathy than those negative for both antigens after adjusting for other potential risk factors (Odds ratio = 5.43, 95% Confidence Interval (Cl) = 1.04, 28.30). HLA-C2, AK-2, and MNSs-S also were associated positively with proliferative retinopathy, and HLA-DR8 was associated inversely with this complication of diabetes in each case before adjusting for the number of comparisons. These data suggest that the genetically determined immunopathic mechanisms leading to diabetes, and in linkage disequilibrium with DR4, may independently contribute to the development of proliferative retinopathy.

Early presentation of type 2 diabetes in Mexican-American youth.

OBJECTIVE: To describe features of pediatric-onset type 2 diabetes in the Hispanic population. RESEARCH DESIGN AND METHODS: The medical records of 55 Hispanic subjects with diabetes who were treated from 1990 to 1994 in a pediatric clinic serving lower income Mexican-Americans were reviewed to assess the frequency and clinical features of type 2 diabetes. Additionally, nondiabetic siblings of several patients underwent oral glucose tolerance testing, and a survey of six high schools in the same county was performed. RESULTS: Seventeen of 55 (31%) of the diabetic children and adolescents had type 2 diabetes. An additional 4 Hispanic children with type 2 diabetes treated in other clinics were also identified, yielding a total of 21 subjects who were used to describe the characteristics of childhood type 2 diabetes. At presentation, all were obese (mean BMI 32.9 +/- 6.2 kg/m2), 62% had no ketonuria, and fasting C-peptide levels were elevated (4.28 +/- 3.43 ng/ml). Diabetes was easily controlled with diet, sulfonylureas, or low-dose insulin. No autoantibodies were present in those tested, and family histories were positive for type 2 diabetes. Compliance was poor, and 3 subjects developed diabetic complications. Of the tested siblings, 2 of 8 had impaired glucose tolerance and 5 of 8 had stimulated hyperinsulinemia, correlated with BMI (r = 0.80, P < 0.05). The school survey identified 28 diabetic adolescents, 75% more than expected (P < 0.01). The Hispanic enrollment at each school was highly correlated with the number of diabetic students (r = 0.87, P = 0.011). CONCLUSIONS: Genetic susceptibility to type 2 diabetes, when coupled with obesity, can produce type 2 diabetes in Mexican-American children. This diagnosis should be considered in young Hispanic patients, who might otherwise be assumed to have type 1 diabetes, and also when caring for overweight Hispanic youth with a family history of type 2 diabetes, in whom intervention may prevent or delay diabetes onset.

Different HLA haplotypes in Mexican Americans with IDDM.

The study of HLA histocompatibility antigens and insulin-dependent diabetes mellitus (IDDM) in non-White populations may provide a unique opportunity to more accurately define the diabetes susceptibility gene(s) located within the HLA region. To determine whether HLA haplotypes differ between ethnic groups, we compared 105 HLA haplotypes from 55 Mexican-American IDDM patients with 272 haplotypes from 136 IDDM patients of non-Hispanic White descent. The accurate determination of genotypes and haplotypes requires the study of family units. Therefore, all diabetic patients in this study were from studies of families having one or more siblings with IDDM. In the Mexican-American group, HLA-DR3 and -DR4 were the most common HLA-DR alleles and were present in comparable frequencies in the non-Hispanic White group (HLA-DR3, 27% of Mexican-American and 29% of non-Hispanic White haplotypes; DR4, 46% of Mexican-American and 43% of non-Hispanic White haplotypes). However, the HLA-B/DR-containing haplotypes and haplotype frequencies differed between the two groups. Several common haplotypes (B8/DR3, B15/DR4) in the non-Hispanic White group occurred less frequently in the Mexican-American group. In contrast, uncommon haplotypes in the non-Hispanic White group comprised nearly 50% of the DR4-containing haplotypes (B35/DR4, B40/DR4, B44/DR4) in the Mexican-American group. Although both DR3- and DR4-haplotype frequencies differed significantly between the two groups, the relative frequency of DR3- but not DR4-containing haplotypes was similar in both ethnic groups. This adds to the evidence suggesting that different susceptibilities are provided by the haplotypes carrying the DR3 and DR4 alleles.

Insulin and islet cell autoantibodies as time-dependent covariates in the development of insulin-dependent diabetes: a prospective study in relatives.

Using time-dependent methods, the temporal relationships between the detection of insulin and islet cell autoantibodies and the onset of insulin dependent diabetes (IDDM) were analyzed in a prospective study of 4694 nondiabetic relatives of 1929 patients with IDDM who had been followed for a median of 4 yr. Insulin autoantibodies were detected in 1.5% of relatives at their initial test whereas an additional 1.0% subsequently became positive for these antibodies during follow-up. Islet cell autoantibodies were detected in 2.6% of the relatives at the time of their first test and an additional 0.9% were observed to develop them during the follow-up period. The risk of developing IDDM was significantly higher (P = 0.0001) among those who were found to have one of these antibodies, but was highest among those under the age of 20 yr at inception of this study who tested positive for both. Among older relatives, the detection of insulin autoantibodies among those who were islet cell antibody positive did not convey an additional risk of IDDM. In a subset of relatives, the presence of either antibody was associated with a higher frequency (P < 0.001) of diabetes associated human leukocyte antigen-DR 3/4 heterozygotes. Islet cell autoantibodies were highly associated with elevated fasting and 60-min glucose concentrations (P = 0.0001) as well as decreased early phase (1 and 3 min) insulin response to an iv glucose tolerance test (P = 0.0001). Insulin antibodies were significantly associated with decreased early phase insulin response to iv glucose (P = 0.0003). These data confirm independent risks associated with each antibody and suggest that their temporal relationship may be an important reflection of the pathogenic process underlying IDDM observations which facilitate its predictability.

Effectiveness and safety of an Haemophilus influenzae type b conjugate vaccine (PRP-T) in young infants. Kaiser-UCLA Vaccine Study Group.

OBJECTIVE: To study the safety, immunogenicity, and protective efficacy of the Haemophilus influenzae capsular polysaccharide tetanus conjugate vaccine (PRP-T). DESIGN: Randomized, double-blind, controlled clinical trial. SETTING: Southern California Kaiser-Permanente Health Plan. PARTICIPANTS: 10,317 infants 6 to 15 weeks of age, with no known immune dysfunction, exposure to hepatitis B, or contraindication to diphtheria-tetanus-pertussis (DTP) vaccination were enrolled between August 1989 and September 1990. INTERVENTION: Infants were randomized to receive either PRP-T or a recombinant hepatitis B control vaccine (in addition to DTP) at approximately 2, 4, and 6 months of age. OUTCOME MEASURES: Adverse reactions occurring during the first 72 hours and between doses (including hospitalizations and outpatient visits) were measured using parental reporting/interviews and review of records. Invasive disease caused by H influenzae was ascertained from the time of enrollment until December 31, 1990. RESULTS: In October 1990, the study was prematurely terminated because of licensure of other H influenzae vaccines recommended for routine infant use. The rates of systemic and local reactions occurring within 72 hours of each vaccine dose were generally similar for infants given PRP-T and hepatitis B, but some reaction rates (local reactions, fever > or = 102 degrees F, irritability, crying) were significantly higher in the PRP-T group. In the month following receipt of vaccine, PRP-T-vaccinated infants experienced five definite seizures compared with three in the hepatitis B control group. Within 48 hours of vaccination, three seizures (two definite and one possible), which were thought to be related to vaccination, occurred in the PRP-T group, compared with none in the control group (P < .13). Overall morbidity, mortality, and hospitalization rates were similar in the two vaccine groups. Three cases of invasive disease caused by H influenzae occurred in the control group; none occurred in the PRP-T group. CONCLUSIONS: The PRP-T vaccine is safe and appears to be effective in preventing invasive disease caused by H influenzae type b.

Application of synthetic oligonucleotides to detect DQ beta genes transmission within insulin-dependent diabetes families.

Class II antigen genes encoded by the major histocompatibility complex region (HLA-D region) in man play an important role in susceptibility to insulin dependent diabetes mellitus (IDDM). Evidence suggests that the DQ subregion within the HLA-D region is more directly responsible for susceptibility to IDDM. Therefore, we designed a synthetic oligonucleotide specific for the DQ beta gene to further the understanding of the disease association with HLA-D region genes at the molecular level. Restriction fragment length polymorphism (RFLP) analysis was carried out using DNA isolated from nine families, each including at least two affected siblings (a total of 37 siblings). The segregation pattern of hybridizing fragments showed that: (1) for each of the DR2, DR3, and DR4 specificities, two different alleles can be identified by the DQ beta probe; (2) a 1.9 kb-Taq 1 fragment with the DR4 specificity and a 6.0 kb-Taq-1 fragment within the DR2 specificity tend to cosegregate with IDDM; (3) there was no preferential segregation of the two alleles detected within the DR3 specificity (one allele identified by a 4.7 kb-Taq 1 fragment is quite common among individuals with the DR3 specificity). The results from this study add to the evidence that certain DQ alleles appear to be more directly associated with the diabetogenic gene (or genes) in certain DR specificities.

Safety evaluation of PRP-D Haemophilus influenzae type b conjugate vaccine in children immunized at 18 months of age and older: follow-up study of 30,000 children.

We evaluated the safety of the PRP-D conjugate Hib vaccine (ProHIBit, Connaught) in 29,309 children vaccinated at 18-60 months of age in the Southern California Kaiser Permanente medical clinics during the period April 1, 1988, to July 31, 1989. Surveillance for potential reactions involved postcard questionnaires, telephone surveys, reports of Kaiser staff and review of hospitalizations and covered two periods following immunization: (1) the first 48 hours and (2) days 2 through 30. Surveillance for invasive Hib disease involved the above methods in addition to systematic reviews of laboratory and hospital records through January 31, 1990. Rates of local and systemic reactions within 48 hours of vaccination with PRP-D alone were low (less than or equal to 2% for fever greater than 102 degrees F, local redness or swelling) and similar to those previously reported after vaccination with PRP. Hospitalization and seizures (0.15% and 0.09% of vaccinated children, respectively) occurring within 1 month of immunization appeared to be unrelated to vaccination. One 29-month-old child had onset of a fatal episode of Hib sepsis/meningitis within 48 hours of vaccination. Also, a 30-month-old child developed Hib meningitis 10 months after PRP-D vaccination. We conclude that PRP-D is safe when given alone or in combination with other childhood vaccines between 18 and 60 months of age.

Protection provided by Haemophilus influenzae type b conjugate vaccines in Los Angeles County: a case-control study.

The objective was to assess the degree of disease control and to evaluate the protective efficacy of licensed Haemophilus influenzae type b (Hib) conjugate vaccines (HbOC, PRP-OMP, PRP-D) used routinely in children 2 to 35 months of age. We conducted a case-control study in Los Angeles County between January 1, 1991, and December 31, 1992, and a cohort analysis of Hib cases between 1983 and 1992. For the case-control study 105 cases of invasive Hib disease were identified and 767 geographically and age-matched controls were selected by random digit telephone dialing. Sixteen HbOC vaccine failures occurred > 14 days after a single dose of vaccine, 6 vaccine failures after 2 doses and 3 failures after 3 doses; 2 cases occurred 6 and 12 days, respectively, after an initial dose of HbOC. The protective efficacy of a single HbOC vaccine dose was 71.1% (95% confidence interval (CI), 37.5 to 87.2%). After 2 doses the efficacy was 88.8% (95% CI, 59.5 to 96.9%) and after 3 doses it was 94.4% (95% CI, 68.0% to 99.0%). Similar 95% CIs were seen for 1 and 2 doses of PRP-OMP vaccine. Adjustment of efficacy estimates for potential confounding variables did not significantly alter the results. Despite relatively low rates of immunization (20 to 60%) the rates of Hib disease decreased strikingly between 1990 and 1992 (from 24.2 to 4.4/100,000 children < 5 years of age). The HbOC conjugate vaccine, used predominantly but incompletely during this period, provided substantial protection against invasive Hib disease in children immunized between 2 and 35 months of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative safety and immunogenicity of two recombinant hepatitis B vaccines given to infants at two, four and six months of age.

OBJECTIVES: To evaluate the relative safety and immunogenicity of the two recombinant hepatitis B vaccines licensed in the United States with doses recommended for routine immunization of low risk infants and a schedule that corresponds with routine pediatric visits. METHODS: Healthy infants were immunized at 2, 4 and 6 months of age with hepatitis B vaccine manufactured by either SmithKline Beecham (Engerix-B, 10 micrograms/dose, n = 228) or Merck and Co. (Recombivax HB, 2.5 micrograms/dose, n = 200). Adverse reactions were ascertained by parental reports and interviews and by review of medical records. Antibody concentrations to hepatitis B surface antigen (anti-HBs) were measured in sequential serum specimens by enzyme immunoassay. RESULTS: Adverse reactions were mild and the rates were not significantly different between the two groups. After the first and second doses the rates of seropositivity (> or = 10 mIU/ml) and seroprotection (> or = 10 mIU/ml) were significantly higher in infants given SmithKline Beecham vaccine (P < 0.01). After the second and third doses infants given SmithKline Beecham vaccine also had significantly higher geometric mean anti-HBs concentrations compared with those given Merck vaccine (348.0 mIU/ml vs. 66.9 and 1914.8 mIU/ml vs. 514.8 mIU/ml, respectively, P < 0.001). Nevertheless after the third dose 99% of infants in both vaccine groups achieved seroprotective antibody concentrations. CONCLUSIONS: Both recombinant hepatitis B vaccines were safe and immunogenic when administered concurrently with other pediatric vaccines at 2, 4 and 6 months of age, but earlier protective responses were observed with the SmithKline Beecham vaccine than with the Merck vaccine.

Epidemiology of diarrheal disease among children enrolled in four West Coast health maintenance organizations. Vaccine Safety Datalink Team.

BACKGROUND: We used information from the Vaccine Safety Datalink (VSD) about approximately 1 million children enrolled in four health maintenance organizations to assess the morbidity from diarrhea and estimate the disease burden of rotavirus. METHODS: We examined trends of diarrhea-associated hospitalizations and emergency room (ER) visits among VSD children ages 1 month through 4 years during October, 1992, through September, 1994 (two rotavirus seasons) and estimated the morbidity from rotavirus on the basis of characteristic patterns of age and seasonality. RESULTS: Overall diarrhea was associated with 6.3% of hospitalizations and 4% of ER visits. During a child's first 5 years of life, we estimated that 1 in 57 was hospitalized and 1 in 21 required an ER visit because of diarrhea. Each year the number of diarrhea-associated hospitalizations and ER visits was greatest in winter among children ages 4 to 23 months and peaked in November in California and during February in Oregon and Washington. The winter seasonality of diarrhea-associated hospitalizations reflected the trends for diarrhea of presumed noninfectious and viral etiologies, which together accounted for most (92.9%) hospitalizations. CONCLUSIONS: Diarrhea is an important cause of morbidity among VSD children. The epidemiologic patterns of diarrhea-associated hospitalizations and ER visits resembled those reported previously for rotavirus diarrhea, suggesting that rotavirus may be a major contributor to the overall morbidity from diarrhea. Enhanced surveillance by screening for rotavirus in a sample of children with diarrhea will permit a more accurate assessment of the disease burden of this pathogen and the cost effectiveness of a rotavirus immunization program.

Ancestral origin of insulin-dependent diabetes in Mexican-Americans.

To test the hypothesis that insulin-dependent diabetes mellitus in the Mexican-American population is due to Spanish genetic admixture, we obtained ancestral information on 106 Mexican-American families with an insulin-dependent diabetic index case and 80 Mexican-American control families from 1987 to 1991. The Mexican states of origin were available on 395 grandparents of the insulin-dependent diabetic index cases and 291 grandparents of the controls. Analysis of the individual states of origin revealed that there were significantly more Mexican-American grandparents of diabetic index cases from the states of Jalisco and Michoacan when compared to the control families (31% and 16% diabetic versus 22% and 11% controls respectively, P less than 0.01). The states of Zacatecas and Durango had a lower frequency of diabetic grandparents as compared to controls (6% diabetic versus 12% controls, P less than 0.001). Analysis of the origin by Northern and Southern states of México revealed a significant decrease in the number of grandparents of the insulin-dependent diabetic cases from the Northern regions of México, 19.5%, versus 32% in controls, (P less than 0.001). These data indicate that the grandparents of the insulin-dependent diabetic index cases originate from states and regions of México which were those of the early entry of the Europeans. These data thus support the hypothesis that insulin-dependent diabetes mellitus in the Mexican-American population may be due in significant part to an original genetic contribution from the Spanish-European population.

HLA-DR and the 5' insulin gene polymorphism in insulin-dependent diabetes.

While the human leukocyte antigen (HLA) region provides the major susceptibility for insulin-dependent (type I) diabetes mellitus (IDDM), other (non-HLA) genes must also play a role. Population studies have shown an increased frequency of small insertions (class I alleles) 5' to the insulin gene in individuals with IDDM, suggesting that this region may account for part, if not all, of the non-HLA genetic predisposition. However, no data are available as to whether the relation of the insulin gene polymorphism is to a DR-defined subset of IDDM or with all of IDDM. To test the hypothesis that specific combinations of HLA and insulin gene polymorphism alleles may interact in providing susceptibility for IDDM, HLA-DR and 5' insulin gene insertion size have been determined in 300 individuals with IDDM. The frequency of class 1 insulin gene alleles in the entire sample is 0.79 and the frequency of class 3 alleles (large inserts) is 0.20. The frequencies of class 1 alleles were equal across all DR classes: 0.79 in the DR3/X IDDM subjects, 0.80 in the DR4/X, 0.79 in the DR3/4, and 0.78 in those with DRX/X. Additionally, the frequencies of class 1/1 homozygotes and 1/3 heterozygotes were similar between HLA-DR types. These results suggest that the HLA region and the region 5' to the insulin gene provide independent and nonsynergistic genetic risks for IDDM.

Eradication of Haemophilus influenzae type b disease in southern California. Kaiser-UCLA Vaccine Study Group.

OBJECTIVE: To assess the effects of Haemophilus influenzae vaccination of infants. RESEARCH DESIGN: We evaluated H influenzae type b (Hib) disease rates in Los Angeles County, California (population, 9 million; 1983 through 1992), and in the Southern California Kaiser Health Plan (2.5 million enrollees; 1988 through 1992) during the past decade. Cases were obtained through active and passive disease surveillance in the two populations. The following vaccines were used during the study period (1983 through 1992): (1) Hib polysaccharide vaccine (polyribosyl ribitol phosphate) (used from 1985 through 1987 for children 24 through 60 months of age); (2) Hib polysaccharide-diphtheria toxoid conjugate, Hib polysaccharide CRM197 mutant diphtheria toxoid conjugate vaccine, and Hib polysaccharide outer-membrane protein of group B meningococcus conjugate vaccine in older children (1988 through 1990; ages 15 through 60 months); and (3) Hib polysaccharide CRM197 mutant diphtheria toxoid conjugate vaccine and Hib polysaccharide outer-membrane protein of group B meningococcus conjugate vaccine used in infants (1991 through 1992). MEASUREMENTS AND RESULTS: Between 1983 and 1988, the Hib disease incidence in Los Angeles County was unchanged (32.7 to 42.5/100,000 person-years in children younger than 5 years). In 1989 through 1990, before Hib conjugate licensure for infant use, Hib disease rates in all age groups declined. After licensure of Hib vaccines for infants in 1990, there was a further fivefold decrease in infants. More dramatic decreases occurred in the better-immunized Kaiser Health Plan children aged 0 through 60 months (53 cases in 1989, only two cases in 1992). CONCLUSIONS: The Hib disease has been nearly eradicated in a fully immunized population (Kaiser Health Plan), and significant reductions have also occurred in Los Angeles County.

Genetics of common diseases of adulthood. Implications for prenatal counseling and diagnosis.

Genetic factors play an important role in the development of many common diseases of adulthood that result in early morbidity and mortality. Prevention of these disorders and their sequelae is best established through early detection and early intervention. Although it may be feasible to screen the entire population for some disorders (e.g., hypertension), this approach would be expensive and impractical for others (e.g., colon cancer). The family history provides an inexpensive and convenient method of identifying families at risk for premature diseases of adulthood. Family screening for a disorder should be recommended if there is increased risk for the disorder among family members, if screening methods are available to detect the condition at an early age or preclinical stage, and if early intervention will alter the course of the disease. For many disorders screening and intervention can prevent the occurrence of clinical disease. The prenatal counseling session affords an ideal setting for identifying families at risk for diseases of adulthood with major genetic components. By reviewing the family history, key family members can be identified and investigated, in order to establish a specific genetic diagnosis. At-risk relatives can then be counseled and screened for the disorder preclinically and premorbidly. The screening and intervention available for a disease depends on the nature of the disorder, our understanding of its physiology and etiology, and our current technology. The disorders discussed earlier are typical of conditions of adulthood that are influenced strongly by genetic factors, especially when they appear in younger adults. Atherosclerosis, colon cancer, and diabetes are complex phenotypes. Each can be caused by single-gene defects, but commonly the genetics are more complex. Empiric data help to establish the risk to an individual in the latter cases. In all three examples, early detection should lead to treatment, which can prevent more serious sequelae: by treating the dyslipidemia, coronary artery disease can be prevented; by removing the benign polyp, malignant cancer can be avoided; and when impaired glucose tolerance is detected, diet and exercise can prevent or delay frank diabetes and its complications. The complete evaluation of individuals at risk for disorders such as those in Table 1 and their families can be a complicated task. Referral to a center experienced in the genetics of common diseases often may be necessary.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies in patients with inflammatory bowel disease and the apparent influence of medications.

Patients with inflammatory bowel disease (IBD) are known to have increased antibodies to several food and bacterial antigens. To assess selected isotype contributions in greater detail, we examined the concentrations of IgA, IgG, IgE, and IgG4 antibodies to five selected antigens, two of bacterial and three of food origin. Thirty patients with IBD and thirty matched healthy controls were studied. Most antibodies were increased in IBD patients compared to controls. Statistically significant increases were more frequent in Crohn's disease (CD) than in ulcerative colitis (UC). An unexpected finding was that IBD patients treated with sulfasalazine had statistically higher levels of most IgA antibodies than healthy controls, while steroid treated patients had lower levels. These findings suggest differing effects on the immune systems of IBD patients by each of these commonly used drugs.

Relation between maternal age and serum concentration of IgG antibody to type III group B streptococci.

Coded serum samples collected from healthy obstetric patients at delivery were examined by ELISA for IgG antibody to the purified type III polysaccharide of group B streptococci. When 217 patients were divided into 4 groups according to age (group I =16-20 years, n = 56; group II = 21-25, n = 53; group III = 26-30, n = 54; group IV = 31-35, n = 54), antibody concentrations were significantly lower in group I than in older patients. Fewer subjects in group I had measurable antibody levels (> or = 0.05 microgram/mL) than in groups II-IV (41% vs. 76%, P < .001). The geometric mean in group I (0.09 microgram/mL) was significantly lower (P < .001) than in the older groups (0.23, 0.19, and 0.20 microgram/mL, respectively) with little or no overlap of the 95% confidence limits (1.96 SE) about the means. These findings may be relevant to the observation of a significantly greater risk of both early- and late-onset group B streptococcal disease in infants of teenage mothers.

Crohn's disease among ethnic groups in a large health maintenance organization.

The epidemiology of Crohn's disease (CD) was investigated among ethnic groups in a 2-million-member health maintenance organization. Between 1982 and 1988 there were 909 hospitalizations for CD. Annual hospitalizations per 100,000 were much lower for Hispanics (0.6) than those for whites (10.2) and blacks (10.2), and rates were higher among women (8.3) than men (6.0) (P less than 0.001). Bimodal age distributions were found for both sexes with peaks identified in the 20-29-year and greater than or equal to 60-year age groups. Annual age-adjusted hospitalizations per 100,000 decreased from 1982 (8.3) through 1988 (5.4) (P less than 0.05). A mail survey and medical records were used to collect data from the 169 CD patients who were identified at two sites within the organization. Prevalence rates per 100,000 for Hispanics (4.1) and Asians (5.6) were much lower than those for whites (43.6), blacks (29.8), and "others" (8.4). The distribution of age at diagnosis was bimodal, and the average age at diagnosis was 36 years. Patients reported an average of 3.7 outpatient visits and 13.3 days lost from work per year. Current cigarette smokers reported significantly more days troubled by symptoms during a one-month period (15.4 days) than nonsmokers (5.0 days) (P less than 0.001).

The 5' insulin gene polymorphism and the genetics of vascular complications in type 1 (insulin-dependent) diabetes mellitus.

Recent data suggest genetic contributions to the microvascular complications of Type 1 (insulin-dependent) diabetes mellitus. Most research has focused on the HLA region, and the potential role of other genetic loci has not been adequately explored. We examined the possible relationship between DNA polymorphisms in the region 5' to the insulin gene on chromosome 11 and diabetic nephropathy. This was done by comparison of those diabetic patients homozygous for class 1 alleles at the 5' insulin gene polymorphism locus to 1/3 heterozygotes in a well-characterized series of 324 insulin-requiring diabetic patients from the Wisconsin Epidemiologic Study of Diabetic Retinopathy. Proteinuria (defined as greater than or equal to 0.3 g protein/l urine), was used as suggestive evidence for diabetic nephropathy. Hypertension, a frequent associated finding in diabetic patients with nephropathy, was defined as a blood pressure greater than 140/90 or a history of previous treatment of hypertension. The two genotypically defined groups did not differ from each other in regard to sex ratio, age at diagnosis, age at examination, duration of diabetes, body mass, HbAlc or C-peptide. The 1+1 group had a higher prevalence of proteinuria, 29% as compared to 16.2% in other genotypes (p less than 0.05). There was no significant difference in the frequency of hypertension between the two genotypic groups. This finding suggests that the 5' insulin gene polymorphism may be associated with risk for nephropathy, but the pathophysiologic mechanism remains unclear.

Protective efficacy of Haemophilus influenzae type b polysaccharide and conjugate vaccines in children 18 months of age and older.

To evaluate the protective efficacy of polyribosylribitol phosphate (PRP) and polyribosylribitol phosphate-diphtheria toxoid (PRP-D) vaccines in children 18 to 59 months of age, we conducted a case-control study in Los Angeles (Calif) County between July 1, 1988, and July 31, 1989. Seventy-nine children with invasive Haemophilus influenzae type b disease 18 to 59 months of age were identified, and 212 controls were selected by random-digit telephone dialing methods. Cases and controls were stratified by age and month of disease onset of the case. Seventeen PRP vaccine failures and two PRP-D vaccine failures occurred more than 2 weeks after vaccination. The PRP vaccine was shown not to be effective (point estimate--47%; 95% confidence interval,--307% to 47%), but the PRP-D vaccine was 88% protective (95% confidence interval, 42% to 97%). Adjustment of the efficacy estimates for potential confounding variables did not change the results significantly. The PRP-D vaccine provided significantly better protection than the PRP vaccine against invasive H influenzae type b disease in this population.

Polymorphic gene markers in Mexican-Americans residing in southern California.

The gene frequencies of nine different genetic polymorphic markers [ABO, MNS and P blood groups; haptoglobin, transferrin, Gc protein, complement (C3), properdin factor B and alpha 1-antitrypsin] were determined in 94 Mexican-Americans residing in the Los Angeles, California area. Comparisons with published data on Mexican-Americans living in other areas of the United States or in Mexico itself revealed no significant differences in the gene frequencies between this and previous studies. However, data from the current study demonstrated significant differences in ABO and haptoglobin allele frequencies compared to published non-Hispanic Caucasian data. These data suggest a large degree of genetic homogeneity in the Mexican-American population residing in the United States. Additional gene marker studies will be important to test this hypothesis and further define the degree of non-Hispanic Caucasian admixture in this population.