Tumor resection utilizing a minimally invasive spinal retractor with a novel cranial adaptor.

OBJECTIVE: This article describes a method of performing an intracerebral tumor resection utilizing a novel dilator attachment with a system designed for minimally invasive spinal surgery. METHODS: A novel dilator was designed and utilized in conjunction with a retractor system originally designed for minimally invasive spine surgery. Tumor resection was then performed utilizing a method less invasive than a typical cortisectomy but allowing more freedom than could be accomplished with an endoscope. RESULTS: Two patients underwent a standard craniotomy followed by tumor resection using the novel dilator with the Pipeline Minimally Invasive Retractor System (DePuy Spine, Raynham, MA). The dilator was introduced into the tumor cavity followed by sequential insertion of the working ports until a working port of 20 mm had been inserted. Both patients had adequate resection of their tumors with minimal neurological deficit. CONCLUSION: Tumor resection can safely be accomplished using a minimally invasive spine retractor system with a novel dilator adapted for the system. This reduces the size of the cortisectomy and therefore reduces the risk of post-operative neurological damage while still allowing ample room for adequate tumor resection.

Relative predispositional effects of HLA class II DRB1-DQB1 haplotypes and genotypes on type 1 diabetes: a meta-analysis.

The direct involvement of the human leukocyte antigen class II DR-DQ genes in type 1 diabetes (T1D) is well established, and these genes display a complex hierarchy of risk effects at the genotype and haplotype levels. We investigated, using data from 38 studies, whether the DR-DQ haplotypes and genotypes show the same relative predispositional effects across populations and ethnic groups. Significant differences in risk within a population were considered, as well as comparisons across populations using the patient/control (P/C) ratio. Within a population, the ratio of the P/C ratios for two different genotypes or haplotypes is a function only of the absolute penetrance values, allowing ranking of risk effects. Categories of consistent predisposing, intermediate ('neutral'), and protective haplotypes were identified and found to correlate with disease prevalence and the marked ethnic differences in DRB1-DQB1 frequencies. Specific effects were identified, for example for predisposing haplotypes, there was a statistically significant and consistent hierarchy for DR4 DQB1*0302s: DRB1*0405 =*0401 =*0402 > *0404 > *0403, with DRB1*0301 DQB1*0200 (DR3) being significantly less predisposing than DRB1*0402 and more than DRB1*0404. The predisposing DRB1*0401 DQB1*0302 haplotype was relatively increased compared with the protective haplotype DRB1*0401 DQB1*0301 in heterozygotes with DR3 compared with heterozygotes with DRB1*0101 DQB1*0501 (DR1). Our results show that meta-analyses and use of the P/C ratio and rankings thereof can be valuable in determining T1D risk factors at the haplotype and amino acid residue levels.

14th International HLA and Immunogenetics Workshop: report on the HLA component of type 1 diabetes.

The type 1 diabetes (T1D) component of the 13th International Histocompatibility Workshop (IHW) obtained microsatellite (msat) and human leukocyte antigen (HLA)-DR/DQ data on case/control and family samples through an international collaboration. The aim was to detect the effects of susceptibility loci on the HLA complex independent of the primary determinants in the class II region (HLA-DR/DQ). As part of the activity of the 14th International HLA and Immunogenetics Workshop (14th IHIWS), a T1D workshop was held to present analyses of the 13th IHW data and to discuss the current status of knowledge about the genetics of T1D. These data are now available online through dbMHC, a web-based resource established by the National Center for Biotechnology. Continuing work since the 13th IHW has resulted in published work showing heterogeneity of DR3 haplotypes in data sets from the 13th IHW and Human Biological Data Interchange (HBDI). In addition, we identified markers that define DRB1*1501 DQB1*0602 haplotypes conferring reduced protection from diabetes in a Swedish 13th IHW data set. Further analyses of the 13th IHW data set not only showed some significant results but also demonstrated extensive heterogeneity reminiscent of non-HLA genes. The haplotype analysis in HBDI families identified two msats with significant effects on susceptibility and statistically significant age of onset effects at class III markers that are not because of linkage disequilibrium, with class I alleles known to affect age of onset. The above studies underscore the importance of refining our understanding of susceptibility associated with genes in the HLA complex.

Increasing incidence of type 1 diabetes in population from Santiago of Chile: trends in a period of 18 years (1986-2003).

UNLABELLED: STUDY OBJECTIVE AND SETTING: The aim of this study is to determine the incidence rate of type 1 diabetes in the metropolitan region of Santiago, Chile from 1 January 1986 to 31 December 2003. DESIGN: Population-based incidence study. PARTICIPANTS: A case must fulfill the following requirements to be included in this study: age at onset: 0 to 14 years, diagnosed with diabetes and placed on insulin, diagnosed within the defined time period, and to be a resident of the metropolitan region of Santiago at the time of the diagnosis. The population 'at risk' is the population less than 15 years of age. RESULT: The overall rate of type 1 diabetes was estimated as 4.02 cases per 100 000 children per year (95% confidence interval: 2.98-4.83). CONCLUSION: The incidence of type 1 diabetes in Santiago, Chile has increased during the last years. This data are concordant with the observation that the incidence of type 1 diabetes is increasing in Latin America and worldwide.

D6S265*15 marks a DRB1*15, DQB1*0602 haplotype associated with attenuated protection from type 1 diabetes mellitus.

AIMS/HYPOTHESIS: The HLA class II DQB1*0602 allele confers strong dominant protection against type 1 diabetes but protection is not absolute. The aim of this study was to identify markers within the HLA region that differentiate DQB1*0602 haplotypes and show different associations with disease risk. METHODS: We defined alleles at eight microsatellite markers spanning the HLA region in a case-control cohort from Sweden. RESULTS: We found that allele 15 at marker D6S265 (109 kb centromeric of HLA-A) was over-represented among patients carrying DRB1*15, DQB1*0602. A detailed haplotype analysis showed that DRB1*15, DQB1*0602 haplotypes carrying D6S265*15 have a ten-fold higher odds ratio (OR) than those carrying other alleles and thus confer reduced protection [OR D6S265*15=0.186 (95% CI 0.074, 0.472) vs OR D6S265*15-=0.017 (95% CI 0.005, 0.062), p<0.001]. CONCLUSIONS/INTERPRETATION: Our data support the existence of a locus that modifies the protective effect associated with DQB1*0602. Typing for allele D6S265*15 can identify a less protective DQB1*0602 haplotype, thereby allowing a more accurate prediction of type 1 diabetes risk.

Recurrence rate after laparoscopic repair of recurrent inguinal hernias: have we improved?

Laparoscopic repair of recurrent inguinal hernias is becoming increasingly accepted in surgical practice, using an extraperitoneal or transabdominal approach for the placement of mesh. Previous literature reflects that efforts to perform open repair of recurrent inguinal hernias often result in further recurrences, testicular damage, or nerve injuries. Our study reflects physical examination of 37 patients over 4 years that underwent laparoscopic repair of recurrent inguinal hernia(s). Early and late complications are presented. The re-recurrence rate at this short follow up to 54 months is quite low at 2.5%. The laparoscopic repair of recurrent hernia reflects a very low likelihood of recurrence, low occurrence of testicular damage, and less likelihood of other such complications as nerve or spermatic cord injury (none of these occurred in this study). Seroma was clinically significant in 3 patients and no infections were noted. Our study and ongoing careful follow-up are the subject of this report.

Progression to insulin-requiring diabetes in seronegative prediabetic subjects: the role of two HLA-DQ high-risk haplotypes.

AIMS/HYPOTHESIS: Most Caucasians with Type I (insulin-dependent) diabetes mellitus develop an autoimmune form of diabetes known as Type IA diabetes, based on the presence of humoral responses to islet autoantigens. Alleles at the HLA locus account for the strongest susceptibility to this form of diabetes, which requires insulin therapy. Because a number of patients who develop insulin-requiring diabetes are islet autoantibody negative, the HLA class II haplotypes, DQA1*0501-DQB1*0201 and DQA1*0301-DQB1*0302, were evaluated to assess whether they are an independent risk factor for progression to insulin requirement in first-degree relatives of Type I diabetic patients. METHODS: Both HLA-DQ genotyping and islet cell autoantibody assessment (insulin, GAD65, IA-2 autoantibodies and cytoplasmic islet cell antibodies) were evaluated prospectively in 74 relatives of Type I diabetic patients who developed diabetes treated with insulin (prediabetics) and in 426 control subjects who did not develop insulin-requiring diabetes. Based on the presence of DQA1*0501-DQB1*0201 and/or DQA1*0301-DQB1*0302, the number of HLA-DQ high-risk haplotypes was assigned as 0, 1 or 2. RESULTS: A higher prevalence of 2 HLA-DQ high-risk haplotypes was present in seronegative prediabetic subjects as compared to non-diabetic autoantibody negative first-degree relatives (33.3 % vs 10.1 % respectively; p < 0.05). Moreover, in seronegative relatives who developed insulin-requiring diabetes, the presence of 2 HLA-DQ high-risk haplotypes conferred an increased cumulative risk of developing insulin requirement of 27 % at 12.5 years of follow-up, compared to a risk of 6 % for non-diabetic relatives who were antibody-negative and had 0 or 1 HLA-DQ high-risk haplotypes (Log rank p = 0.01). CONCLUSION/INTERPRETATION: These data provide evidence for a phenotype, which is associated with the absence of conventional islet autoantibodies at initial screening, while usually remaining seronegative, and the presence of 2 HLA-DQ high-risk haplotypes with progression to clinical Type I diabetes after a prolonged follow-up. Given the fact that in humans the highest risk-conferring locus associated and linked to the disease is the HLA cluster, and that HLA-DQ molecules play a key role in the development of autoimmune diabetes, our observations imply that as yet unidentified immunologic abnormalities could well exist in seronegative relatives at risk of developing clinical diabetes and carrying 2 HLA-DQ high-risk haplotypes.

Menopause in type 1 diabetic women: is it premature?

Women with type 1 diabetes have a delayed menarche and a greater prevalence of menstrual disorders than women without diabetes. However, little is known about the menopause transition among type 1 diabetic women. The Familial Autoimmune and Diabetes (FAD) Study recruited both adult individuals who were identified from the Children's Hospital of Pittsburgh Type 1 Diabetes Registry for the years 1950-1964 and their family members. Unrelated nondiabetic control probands and their relatives were also evaluated. Women with type 1 diabetes (n = 143) compared with nondiabetic sisters (n = 186) or unrelated control subjects (n = 160) were more likely to have an older age at menarche (13.5, 12.5, and 12.6 years, respectively, P < 0.001), more menstrual irregularities before 30 years of age (45.7, 33.3, and 33.1%, respectively, P = 0.04), and a younger age at menopause (41.6, 49.9, and 48.0 years, respectively, P = 0.05). This resulted in a 6-year reduction in the number of reproductive years (30.0, 37.0, and 35.2 years, respectively, P = 0.05) for women with type 1 diabetes. Risk factors univariately associated with earlier menopause included type 1 diabetes (hazard ratio [HR] 1.99, P = 0.04), menstrual irregularities before 30 years of age (HR 1.87, P = 0.04), nulliparity (HR 2.14, P = 0.01), and unilateral oophorectomy (HR 6.51, P < 0.0001). Multivariate analysis confirmed that type 1 diabetes (HR 1.98, P = 0.056), menstrual irregularities by 30 years of age (HR 2.36, P = 0.01), and unilateral oophorectomy (HR 9.76, P < 0.0001) were independent determinants of earlier menopause in our cohort. We hypothesize that an earlier menopause, which resulted in a 17% decrease in reproductive years, is a major unstudied complication of type 1 diabetes.

Mortality trends in type 1 diabetes. The Allegheny County (Pennsylvania) Registry 1965-1999.

OBJECTIVES: To investigate long-term mortality and its temporal trends as of 1 January 1999 among the 1,075 patients with type 1 diabetes (onset age <18 years, diagnosed between 1965 and 1979) who comprise the Allegheny County population-based registry. RESEARCH DESIGN AND METHODS: Overall, sex- and race-specific mortality rates per person-year of follow-up were determined. Standardized mortality ratios were also calculated. Survival analyses and Cox proportional hazard model were also used. Temporal trends were examined by dividing the cohort into three groups by year of diagnosis (1965-1969, 1970-1974, and 1975-1979). RESULTS: Living status of 972 cases was ascertained as of January 1, 1999 (ascertainment rate 90.4%). The mean duration of diabetes was 25.2 +/- 5.8 (SD) years. Overall, 170 deaths were observed. The crude mortality rate was 627 per 100,000 person-years (95% CI 532-728) and standardized mortality ratio was 519 (440-602). Life-table analyses by the Kaplan-Meier method indicated cumulative survival rates of 98.0% at 10 years, 92.1% at 20 years, and 79.6% at 30 years duration of diabetes. There was a significant improvement in the survival rate between the cohort diagnosed during 1965-1969 and that diagnosed during 1975-1979 by the log-rank test (P = 0.03). Mortality was higher in African-Americans than in Caucasians, but there were no differences seen by sex. The improvement in recent years was seen in both ethnic groups and sexes. CONCLUSIONS: An improvement in long-term survival was observed in the more recently diagnosed cohort. This improvement is consistent with the introduction of HbA1 testing, home blood glucose monitoring, and improved blood pressure therapy in the 1980s.

Treatment of acute cholecystitis in non-critically ill patients at high surgical risk: comparison of clinical outcomes after gallbladder aspiration and after percutaneous cholecystostomy.

OBJECTIVE: This study was performed to compare the clinical outcome after gallbladder aspiration with that after percutaneous cholecystostomy in non-critically ill patients with acute cholecystitis who were at high risk from surgery. MATERIALS AND METHODS: Medical records of 53 consecutive non-critically ill, high-surgical-risk patients admitted with acute cholecystitis between July 1995 and July 1999 were reviewed. Thirty-one had gallbladder aspiration and 22 had percutaneous cholecystostomy. The primary outcome measure of clinical response within 72 hr and the secondary outcome measures of overall positive response rate, complication rate, time to resolution, and rate of recurrence of acute cholecystitis were compared between the two groups. RESULTS: Gallbladder aspiration and percutaneous cholecystostomy were technically successful in 30 (97%) and 21 (97%) patients, respectively; of these, 23 (77%) and 19 (90%) patients responded clinically within 72 hr (p > 0.2). Complications occurred in three patients (12%) after percutaneous cholecystostomy and in none after gallbladder aspiration (p < 0.05). No significant difference was noted in the other secondary outcome measures of the two groups. CONCLUSION: We found no significant difference in the clinical outcomes of gallbladder aspiration and percutaneous cholecystostomy in the treatment of acute cholecystitis in high-surgical-risk patients who are not critically ill. However, we found gallbladder aspiration to be significantly safer. Therefore, gallbladder aspiration should be the procedure of choice in high-risk patients with acute cholecystitis who are not critically ill, and percutaneous cholecystectomy should be reserved as a salvage procedure if gallbladder aspiration is technically or clinically unsuccessful.

Associations between religious behavior and attitude to Christianity among Australian Catholic adolescents: scale validation.

In a sample of 1,166 Catholic high school students (age = 13-18 years), the author used confirmatory factor analysis to validate a 30-item instrument that assesses 6 dimensions of attitude to Christianity (viz., attitude to prayer, attitude to God, attitude to Jesus, attitude to the Bible, attitude to Christian practice, attitude to social justice). Goodness-of-fit indices for the proposed measurement model revealed that the model fitted the data very well, thus confirming the instrument's structure. A correlation analysis revealed associations between religious behavior and attitude to Christianity.

Contagious diseases in competitive sport: what are the risks?

Great concern is often expressed over the possibility of contagion among athletes in competitive sports, particularly sports with much person-to-person contact. Human immunodeficiency virus (HIV) is only the most notorious of infectious agents; potentially, other viruses, bacteria, and even fungi may be involved. Because of the concern, however, special attention is paid to HIV and hepatitis B infections. For most of the infections considered, the athlete is more at risk during activities off the playing field than while competing. Inclusion of immunizations against measles and hepatitis B among prematriculation immunization requirements (PIRs) for colleges and universities would eliminate these two diseases from the list of dangers to college athletes and all students. Education, rather than regulations, should remain the cornerstone in considering the risks to athletes from contagious diseases.

Action potential waveform voltage clamp shows significance of different Ca2+ channel types in developing ascidian muscle.

1. Early in development, ascidian muscle cells generate spontaneous, long-duration action potentials that are mediated by a high-threshold, inactivating Ca2+ current. This spontaneous activity is required for appropriate physiological development. 2. Mature muscle cells generate brief action potentials only in response to motor neuron input. The mature action potential is mediated by a high-threshold sustained Ca2+ current. 3. Action potentials recorded from these two stages were imposed as voltage-clamp commands on cells of the same and different stages from which they were recorded. This strategy allowed us to study how immature and mature Ca2+ currents are optimized to their particular functions. 4. Total Ca2+ entry during an action potential did not change during development. The developmental increase in Ca2+ current density exactly compensated for decreased spike duration. This compensation was a function purely of Ca2+ current density, not of the transition from immature to mature Ca2+ current types. 5. In immature cells, Ca2+ entry was spread out over the entire waveform of spontaneous activity, including the interspike voltage trajectory. This almost continuous Ca2+ entry may be important in triggering Ca2+-dependent developmental programmes, and is a function of the slightly more negative voltage dependence of the immature Ca2+ current. 6. In contrast, Ca2+ entry in mature cells was confined to the action potential itself, because of the slightly more positive voltage dependence of the mature Ca2+ current. This may be important in permitting rapid contraction-relaxation cycles during larval swimming. 7. The inactivation of the immature Ca2+ current serves to limit the frequency and burst duration of spontaneous activity. The sustained kinetics of the mature Ca2+ current permit high-frequency firing during larval swimming.

High frequency of HLA-DQB1 non-Asp(57) alleles in Kuwaiti children with insulin-dependent diabetes mellitus.

The prevalence of polymorphic amino acids at position 57 of the HLA DQB1 in Kuwaiti children with insulin-dependent diabetes mellitus (IDDM) and nondiabetic controls has been determined using a polymerase chain reaction-sequence-specific primers (PCR-SSP) method. Using this approach, 34/55 (62%) IDDM children were found to be homozygous Ala/Ala and 19/55 (35%) were heterozygous with various combinations. Amongst the IDDM children with heterozygous genotype at codon 57 of HLA DQB1, 6/55 (11%) had Asp/Ala, 8/55 (15%) had Ala/Val, 4/55 (7%) had Ala/Ser and 1/55 had Asp/Val allelic combinations. When considered collectively, the nonaspartate (NA) alleles were represented in 87% of the IDDM cases and only 13% cases had Asp(57) allele in different heterozygous combinations, while none of the IDDM subjects had a homozygous Asp genotype. In nondiabetic controls, homozygous non-Asp (NA) alleles were represented in 44% subjects, 37% of the controls were heterozygous (NA/A) and 19% had a homozygous (A/A) genotype. These differences between the IDDM group and the control group were found to be statistically significant. Our data report one of the highest frequency of NA/NA residues at this locus compared with that from different world populations (Sardinians, Norwegians, US Caucasians, US Blacks and Chinese).

Type 1 diabetes in offspring of parents with type 1 diabetes: the tip of an autoimmune iceberg?

The objective of the present study was to examine the prevalence of self-reported autoimmune diseases among offspring of type 1 fathers, type 1 diabetic mothers, and non-diabetic parents. Type 1 diabetic probands (n=265; mean age=42 yr), who were ascertained from the Children's Hospital of Pittsburgh Registry for 1950-1964, recently participated in the Familial Autoimmune and Diabetes Study. Non-diabetic probands (n=96), identified from voter registration lists and matched by age, race, median income, and duration of residence in the Pittsburgh area, were also enrolled. Offspring of type 1 diabetic probands were more likely to have a reported autoimmune disease (5.8% vs. 2.4%; p=0.067) than offspring of non-diabetic probands. Half the cases in the diabetic families were disorders other than type 1 diabetes, (e.g., rheumatoid arthritis, Crohn's disease, etc.). Stratification by parental gender revealed a marginally higher risk for type 1 diabetes among offspring of type 1 diabetic fathers compared to mothers (4.9% vs. 3.4%; p=0.38, respectively, through age 20 yr). However, the risk for other autoimmune disorders was statistically significantly increased among offspring of type 1 diabetic mothers (0% vs. 6.2%; p=0.02, respectively, through age 20 yr). These data suggest that offspring of type 1 diabetic parents may be at high risk of developing other autoimmune disorders during childhood, with pediatric diabetes representing the 'tip of an autoimmune iceberg'. The observed risk differences by parental gender, which have also been reported for other autoimmune disorders, warrant further investigation.

Molecular epidemiology: the impact of molecular biology in epidemiology research.

Progress in molecular biology and genetics is changing the practice of medicine and public health through the development of molecular diagnostics and targeted interventions for susceptible individuals. The ethical, legal and social issues that are becoming apparent as these important discoveries are introduced into practice will have an enormous impact on society. The accurate translation of this new genetic information from the laboratory to the community is an urgent need. Molecular epidemiology is at the foundation of this important link, and represents the scientific basis of public health for the 21st Century.

A nine-year prospective study on the incidence of childhood type 1 diabetes mellitus in China.

To investigate the epidemiological characteristics of childhood type 1 diabetes mellitus in China, newly diagnosed cases of type 1 diabetes with an onset age under 15 years were retrospectively registered by 23 local centers in China following a standardized protocol on the basis of the nationwide registry established by the WHO DiaMond Project China Participating Center, Chinese Academy of Preventive Medicine (CAPM). A population of about 24 million children were covered in the defined areas. A two-sample capture-recapture method was used to estimate case ascertainment. Between 1988 and 1996, 903 diabetic cases were registered in 9 ethnic groups. The overall ascertainment corrected incidence rate (IR) was 0.59 per 100,000 person-year. The IR was 0.52/100,000 (95% CI: 0.50-0.54) for males and 0.66/100,000 (95% CI: 0.64-0.68) for females. The standardized ascertainment corrected IR by the national age-specific population in 1990 was 0.57 per 100,000 person-year. The incidence among various ethnic groups ranged from 0.25/100,000 to 3. 06/100,000. The IRs increased with northern latitude, and the IR of Han population was significantly higher in North China compared with South China (0.67 versus 0.53 per 100,000 respectively, P < 0.01). A correlation model of incidence and calendar time showed that the IR increased significantly between 1988 and 1996 (r = 0.86, P = 0.0027). The relative risk (RR) of type 1 diabetes mellitus for different age-groups estimated by a Poisson regression model showed that taking RR as 1.00 for age-group from 0 to 4 years, the RR for age-group from 5 to 9 year and from 10 to 14 year was 2.30 and 3.60 respectively. The standardized ascertainment corrected IR of childhood type 1 diabetes mellitus in China in much lower than in other countries. The geographic and ethnic variability of the incidence suggests that both genetic and environmental factors play a role in the development of childhood diabetes in China.

The HLA-DQ associations with Graves' disease in Chinese children.

OBJECTIVE: Graves' disease has been documented to be associated with different HLA genes in Caucasians and Chinese adults. The incidence of childhood Graves' disease has been reported to be high in Hong Kong Chinese. The aims of this study were to examine the HLA-DQA1 and DQB1 associations with Graves' disease in Chinese children. PATIENTS AND DESIGN: Sixty-seven Chinese children with Graves' disease (59 girls and 8 boys) and 51 racially matched healthy controls were recruited for the study. Genomic DNA was extracted from venous blood samples. HLA-DQ typings were determined by sequence-specific oligonucleotide probing of the respective enzymatically amplified gene. Frequencies of HLA-DQ alleles at each locus were compared between patients and controls using the chi 2-test. RESULTS: The frequency of HLA-DQB1.0303 was increased in the combined male and female patient group [53.7%; relative risk (RR) = 4.22; Pc = 0.005] and female patients (50.8%; RR = 3.76; Pc = 0.018) compared with that in the entire control group (21.2%). HLA-DQB1*201 was protective for Graves' disease (10.4%; RR = 0.20; Pc = 0.006). In contrast to studies in Caucasians, DQA1*0501 was not associated with susceptibility for Graves' disease in Chinese children. CONCLUSIONS: This study confirms that DQB1*0303 is a race-specific susceptible allele for Graves' disease in Chinese. Both susceptible and protective HLA-DQ alleles for Graves' disease in Chinese children are different from those in Caucasians.