Contribution of known and unknown susceptibility genes to early-onset diabetes in scandinavia: evidence for heterogeneity

In an attempt to identify novel susceptibility genes predisposing to early-onset diabetes (EOD), we performed a genome-wide scan using 433 markers in 222 individuals (119 with diabetes) from 29 Scandinavian families with > or =2 members with onset of diabetes < or =45 years. The highest nonparametric linkage (NPL) score, 2.7 (P < 0.01), was observed on chromosome 1p (D1S473/D1S438). Six other regions on chromosomes 3p, 7q, 11q, 18q, 20q, and 21q showed a nominal P value <0.05. Of the EOD subjects in these 29 families, 20% were GAD antibody positive and 68% displayed type 1 diabetes HLA risk alleles (DQB*02 or 0302). Mutations in maturity-onset diabetes of the young (MODY) 1-5 genes and the A3243G mitochondrial DNA mutation were detected by single-strand conformation polymorphism and direct sequencing. To increase homogeneity, we analyzed a subsample of five families with autosomal dominant inheritance of EOD (greater than or equal to two members with age at diagnosis < or =35 years). The highest NPL scores were found on chromosome 1p (D1S438-D1S1665; NPL 3.0; P < 0.01) and 16q (D16S419; NPL 2.9; P < 0.01). After exclusion of three families with MODY1, MODY3, and mitochondrial mutations, the highest NPL scores were observed on chromosomes 1p (D1S438; NPL 2.6; P < 0.01), 3p (D3S1620; NPL 2.2; P < 0.03), 5q (D5S1465; NPL 2.1; P < 0.03), 7q (D7S820; NPL 2.0; P < 0.03), 18q (D18S535; NPL 1.9; P < 0.04), 20q (D20S195; NPL 2.5; P < 0.02), and 21q (D21S1446; NPL 2.2; P < 0.03). We conclude that considerable heterogeneity exists in Scandinavian subjects with EOD; 24% had MODY or maternally inherited diabetes and deafness, and approximately 60% were GAD antibody positive or had type 1 diabetes-associated HLA genotypes. Our data also point at putative chromosomal regions, which could harbor novel genes that contribute to EOD.     

Establishing primary angioplasty as the preferred treatment for acute myocardial infarction

OBJECTIVE: To report procedural results and mortality rates from the first 4 years after establishing primary angioplasty as the preferred treatment for acute myocardial infarction in a single Scandinavian centre. DESIGN AND RESULTS: From August 1995 to October 1999 all patients with the diagnosis of suspected acute myocardial infarction (n = 529, mean age 62 +/- 13 years, 72% men), either transferred (73%) or directly admitted to our institution for coronary angiography with the intention of performing primary percutaneous coronary intervention (primary PCI), were prospectively registered. Procedural success in terms of residual stenosis < or = 30% and a final Thrombolysis in Myocardial Infarction (TIMI) 3 flow was achieved in 94 and 85% of patients treated, respectively. In-hospital delay and procedure times decreased significantly during the 4-year study period. A low in-hospital mortality was observed in each of the 4 years studied (8.7, 8.7, 7.7 and 6.0%). CONCLUSION: In a centre with both directly admitted and transferred patients primary angioplasty can be established as the preferred treatment for acute myocardial infarction with an initially low complication and mortality rate. During the first years after implementing the primary angioplasty programme a learning effect can be anticipated with reductions in procedural times.     

Laparoscopic radical prostatectomy: published series

Next to the retropubic and perineal approaches, laparoscopic radical prostatectomy has become the third most common technique in the surgical treatment of localized prostate cancer. Although long-term oncologic data are still lacking, based on several contemporary series, it seems likely that oncologic results will fulfill expectations. Over the past decade, quality-of-life issues have come into the spotlight in oncologic surgery in particular. In this regard, the aim of the laparoscopic technique is to become the best in terms of operative stress, postoperative morbidity, catheterization time, and return to normal activities. The unique intraoperative visibility and magnification of the operative field allow ultraprecise dissection and suturing of vital neural and sphincteric structures. Will the use of this new kind of surgery translate into better functional results? The goal of this review is to analyze the published results of laparoscopic radical prostatectomy in the context of its rapidly evolving open surgical counterpart.     

Final infarct size after acute stroke: prediction with flow heterogeneity

PURPOSE: To compare acute measurements of flow heterogeneity (FH) and mean transit time (MTT) with follow-up data to determine which method yields better predictive measures of final infarct volumes. MATERIALS AND METHODS: Twenty-three patients with symptoms of stroke underwent magnetic resonance (MR) imaging during the acute stage, and the tissue at risk was estimated from MTT maps and maps generated by means of detecting abnormal FH. Final infarct volumes were calculated from T2-weighted follow-up MR image measurement. The Wilcoxon signed rank test was performed to compare the two predictive maps (MTT and FH) with T2-weighted follow-up maps. RESULTS: Eleven (48%) patients experienced infarct growth. Both the MTT and the FH maps enabled prediction of 10 of these cases. There were five false-positive cases with MTT measurement but three with FH measurement. In terms of predicting final infarct volumes, the final infarct size on the MTT maps was overestimated by 75%. The final infarct size on the FH maps also was overestimated, but by only 15%. MTT map measurements were significantly different from follow-up MR image measurements (P =.005), but FH map measurements were not (P =.059). CONCLUSION: FH maps may enable more precise prediction of final infarct volume in stroke patients.     

Iron-induced susceptibility effect at the globus pallidus causes underestimation of flow and volume on dynamic susceptibility contrast-enhanced MR perfusion images

BACKGROUND AND PURPOSE: Age-related iron accumulation in extrapyramidal nuclei causes T2 shortening, which may result in decreased signal intensity in these areas on MR images. Because the dynamic susceptibility contrast-enhanced technique uses heavily T2*- or T2-weighted images, the iron-induced susceptibility may have direct impact on perfusion imaging. The purpose of this study was to assess the effect of iron-induced susceptibility on the calculated perfusion parameters. The difference of this effect between gradient-echo and spin-echo sequences was also assessed. METHODS: Dynamic susceptibility contrast-enhanced MR perfusion imaging data of 12 patients were used for this study. Perfusion images were obtained using a single shot spin-echo echo-planar imaging sequence in seven patients and a gradient-echo echo-planar imaging sequence in five patients. Region of interest measurements of relative cerebral blood flow, relative cerebral blood volume, and mean transit time were obtained at various parts of the gray matter, including the globus pallidus, putamen, caudate nucleus, thalamus, and cerebral cortex of temporal, frontal, and occipital lobes. The baseline signal intensity on the source images and the magnitude of signal change (DeltaR2* or DeltaR2) were also assessed. RESULTS: The globus pallidus had statistically significantly lower values of relative cerebral blood flow, relative cerebral blood volume, baseline signal intensity, and magnitude of signal change compared with other parts of the gray matter for both gradient-echo and spin-echo sequences (P <.05). Underestimations of these values were more prominent for the gradient-echo than for the spin-echo sequence. Little variance in the measured mean transit time was noted. CONCLUSION: Iron-induced susceptibility effect may lead to underestimation of relative cerebral blood flow and relative cerebral blood volume in the basal ganglia.     

Ultrasonography of the infant hip: the significance of provokable instability with normal morphology

The hips of infants 2- to 4-weeks-old were investigated with ultrasonography. In all cases, ultrasonography verified morphologically normal hips; however, either a bilateral or unilateral instability of the hip could be provoked as demonstrated by ultrasonography. The first series of 27 infants (41 hips) were treated with abduction splint (Frejkas pillow) for 16 weeks. The second series of 28 infants (44 hips) were left untreated. All infants had repeat ultrasonography at 2 and 16 weeks and radiographs at 16 weeks. At 2 weeks, provokable instability was still seen in 10 hips in the treated group and 12 hips in the untreated group. At 16 weeks, all hips were ultrasonographically stable. The morphology was evaluated by alpha and beta angles by ultrasonography and also acetabular index by radiographs at 16 weeks. In all cases, normal hip development was noted with no differences between the two groups. Therefore, sonographically, instability in morphologically normal or immature hips has no clinical significance.     

Endoscopic harvest of four muscle flaps: safe and effective techniques

The recent explosion of endoscopic techniques in plastic surgery has led to the successful harvest of a number of useful muscle flaps. The gracilis, rectus femoris, external oblique, and gastrocnemius muscles can all be harvested safely and reproducibly using endoscopic techniques. The aim of this study was to identify a safe and effective technique for endoscopic muscle flap harvest. Harvesting the gracilis muscle as a free flap and the gastrocnemius as a pedicle flap lends themselves best to the use of endoscopic techniques.     

Rapid down-regulation of thyroid hormones in acute myocardial infarction: is it cardioprotective in patients with angina?

BACKGROUND: In severe illness of any cause, down-regulation of the thyroid hormone system may occur. How this affects patients with acute myocardial infarction (AMI) is largely unknown. OBJECTIVE: To investigate changes in serum levels of the thyroid hormones during AMI and their association with cardiac function and outcome. METHODS: Forty-seven consecutive euthyroid patients with AMI were studied prospectively during the first 5 days and again 6 and 12 weeks later. Time from pain onset was used in all analyses. RESULTS: The thyroid hormone system was rapidly down-regulated with maximal changes 24 to 36 hours after onset of symptoms. The mean level of the hormone total triiodothyronine (T3) decreased 19% (P =.02), the inactive metabolite reverse T3 (rT3) levels increased 22% (P =.01), and thyrotropin levels declined 51% (P<.001) between the first 6-hour and the 24- to 36-hour period. The prohormone free thyroxine was largely unchanged. Patients with poor heart function or more intense inflammatory reaction showed more pronounced down-regulation of the thyroid system. No correlation was found with cardiac enzymes. Patients with prior angina pectoris had lower T(3) levels in early samples, smaller infarctions, and higher levels of C-reactive protein and the proinflammatory cytokine interleukin 6 on admittance. Peak levels of interleukin 6 correlated negatively with T3 (P =.005) and positively with rT3 (P<.05), suggesting that down-regulation before AMI may be cardioprotective. However, mortality was high among patients with the most pronounced thyroid level depression, indicating that down-regulation after AMI may be maladaptive. CONCLUSIONS: The thyroid hormone system is rapidly down-regulated in AMI. This may be beneficial during acute ischemia. Patients with angina had higher levels of interleukin 6 and C-reactive protein and more depressed thyroid hormone system in early samples. Thyroid level depression in patients with angina may possibly have been present before the infarction process started. This novel finding needs further evaluation in large studies to sort out cause-and-effect relationships.     

Nonresponse bias: does it affect measurement of clinician behavior?

BACKGROUND: Previous studies of nonresponders have not assessed the effects of nonresponse on the accuracy of clinician behavior measurements. Knowledge of these effects is critical to both research and quality improvement. OBJECTIVE: To evaluate the hypothesis that nonresponders to a survey would not adversely affect the ability to measure rates of preventive services. RESEARCH DESIGN: Four primary-care medical practices participating in a randomized clinical trial provided an unusual opportunity to compare the medical record-documented care of both responders and nonresponders to a survey of their patients. SUBJECTS: Three hundred forty-five nonresponders and 321 responders to a questionnaire requesting participation in the study. MEASURES: Differences in patient characteristics and diseases and documentation of screening and management of tobacco use, hypertension, and hypercholesterolemia. RESULTS: Although the survey process resulted in a response rate of only 52.5% and some statistically significant differences in responder and nonresponder characteristics, there were no differences in management behavior regarding cardiovascular risk factors. Responders were more likely to have adjusted documentation of tobacco use (OR = 1.4), blood pressure measurement (OR = 9.8), and cholesterol testing (OR = 2.0), but not family history of cardiovascular disease. The most striking difference in subject characteristics was that 22.0% of nonresponders and only 12.1% of responders were tobacco users (P = 0.002). CONCLUSIONS: This study confirms that survey nonresponders may have some different characteristics and risk factor screening rates than responders. However, if confirmed by others, nonresponders who have risk factors identified may not be managed differently than responders.