GLUT4 is reduced in slow muscle fibers of type 2 diabetic patients: is insulin resistance in type 2 diabetes a slow, type 1 fiber disease?

To gain further insight into the mechanisms underlying muscle insulin resistance, the influence of obesity and type 2 diabetes on GLUT4 immunoreactivity in slow and fast skeletal muscle fibers was studied. Through a newly developed, very sensitive method using immunohistochemistry combined with morphometry, GLUT4 density was found to be significantly higher in slow compared with fast fibers in biopsy specimens from lean and obese subjects. In contrast, in type 2 diabetic subjects, GLUT4 density was significantly lower in slow compared with fast fibers. GLUT4 density in slow fibers from diabetic patients was reduced by 9% compared with the weight-matched obese subjects and by 18% compared with the lean control group. The slow-fiber fraction was reduced to 86% in the obese subjects and to 75% in the diabetic subjects compared with the control group. Estimated GLUT4 contribution from slow fibers was reduced to 77% in the obese subjects and to 61% in type 2 diabetic patients compared with the control subjects. We propose that a reduction in the fraction of slow-twitch fibers, combined with a reduction in GLUT4 expression in slow fibers, may reduce the insulin-sensitive GLUT4 pool in type 2 diabetes and thus contribute to skeletal muscle insulin resistance.     

Anti-sliding plating for Letenneur type Ⅰ Hoffa fractures

Objective To explore the anti-sliding plating for Hoffa fractures by comparing the me-chanical properties of anti-sliding plates and cancellous bone screws. Methods Twenty cases of the same type of Hoffa fracture in the model femur were randomly divided into 4 even groups. Group A used 2 antegrade cancellous bone screws; Group B used 2 retrograde cancellous bone screws forwards; Group C used anti-sliding plate and locking screw fixation; Group D used anti-sliding plate and cancellous bone screw fixation. All the samples were subjected to the cycle fatigue and the maximum failure load tests. Results The fatigue test revealed no significant difference in the mean maximum displacements at the 10, 100, 1000, 10 000 cycles between the 4 groups. In the maximum failure load test, there were significant differences between Group A [(1224±72) N] and Groups C and D [(2183±227) N and (2124±235) N], as well as between Groups B [(1405±235) N] and Groups C and D; there was no significant difference between Group A and Group B, neither between Group C and Group D, Conclusions In the initial period after secure fixation for Hoffa fractures, anti-sliding plates and cancellous bone screws can all provide satisfactory mechanical stability and strength. But anti-sliding plating is recommended for cases of long healing expected, patients with great body mass index, and patients with poor compliance.     

Clinical evaluation of the hip joint after implantation of cementless Mittelmeier type and Parhofer-M?nch type hip prosthesis]

Total hip replacement is the most common procedure in the treatment of severe degenerative changes in the hip joint. The authors present clinical evaluation of 129 patients (151 hips) who underwent total hip replacement using either the Mittelmeier type or the Parhofer-M?nch type hip prothesis. The age of the patients ranged at the time of the operation between 17 and 74 years (average 44.9). The follow-up ranged from 24 to 143 months (average 61.2 months). The P-M prothesis was implanted in 53 hips, the P-M "Plasmapore" prothesis in 42 patients, Mittelmeier Autophor 900 prothesis in 49 patients and the Mittelmeier Autophor 900S prothesis in 7 patients. Clinical evaluation was performed according to the d'Aubigne-Postel method with the Charnley modification. The results were graded as very good in 17 cases, good in 64 cases, satisfactory in 53 cases and poor in 17 cases. Very good and good results were mainly observed after implantation of the P-M type prothesis and P-M "Plasmapore" type prothesis. Worse results were observed in patients, who at the time of the operation were aged 45 years or less and who had congenital hip dysplasia. P-M type prothesis gives better clinical results in the treatment of degenerative changes of the hip joint.     

Molecular profile of grade 3 endometrioid endometrial carcinoma: is it a type I or type II endometrial carcinoma?

Two types of endometrial carcinoma (EC) have been delineated on the basis of clinicopathologic studies. Low-grade endometrioid carcinoma (EEC) is the prototype of type I EC and is characterized by microsatellite instability and PTEN, K-ras, and/or β-catenin gene mutations, whereas type II EC is typically represented by serous and clear cell carcinomas (SCs/CCCs), the former frequently showing p53 mutations and c-erb-2 overexpression; however, the molecular profile of grade 3 EEC has not yet been well characterized. The goal of this study was to define the immunohistochemical and molecular profile of grade 3 EEC. We studied 25 patients with grade 3 EEC ranging in age from 35 to 87 (mean 61) years. At the time of initial diagnosis, 16 patients had stage I tumors, whereas 3, 5, and 1 had stages II, III, and IV tumors, respectively. Only 1 patient with stage IV tumor had disease in the peritoneum because of direct extend of tumor through the uterine wall. Two tissue microarrays were constructed from paraffin-embedded blocks and stained for MLH-1, MSH-2, p16, cyclin D1, C-erb-B2, WT-1, and p53. Loss of MLH-1 and MSH-2 was seen in 3 of 25 and 1 of 24 tumors, respectively; none showed loss of both. Diffuse p16 nuclear expression was found in 7 of 23 cases; diffuse and strong nuclear immunostaining for p53, cyclin D1, and Her-2 was seen in 9 of 24 neoplasms, 9 of 25, and 3 of 25 carcinomas, respectively. WT-1 was negative in all 25 tumors. One of the 3 grade 3 EECs with Her-2 overexpression showed gene amplification by fluorescence in situ hybridization analysis. No gene amplification for cyclin D1 was found. Follow-up information was available for all patients. Sixteen had stage I tumors. Of these patients, 11 were alive and well (AW), 3 died of disease (DOD), and 2 died of unrelated causes (DUC), with a mean follow-up time of 56 months (range, 24 to 96 mo); 2 of 3 patients with stage II tumors DOD, and 1 was AW with a mean follow-up time of 81 months (range, 6 to 66 mo); of the 5 patients with stage III tumors, 2 DOD, 1 was AW, 1 was alive with lung metastases, and 1 DUC [mean follow-up of 29 months (range, 12 to 74 mo)]; the only patient who had a stage IV tumor DOD 12 months later. Interestingly, patients with grade 3 EECs showing loss of MLH-1/MSH-2 had stage I tumors, and all were AW (60 to 84 mo). Seventy-seven percent (7 of 9) of patients with tumors showing cyclin D1 overexpression were stage I, and none died of disease, whereas 85% (6 of 7) of patients with p16-positive tumors were high stage (2 stage II, 3 stage III, and 1 stage IV), and 5 DOD. All but one of these patients had tumors that also had p53 overexpression. All 3 patients with Her-2 overexpression DOD (stages I, III, and IV). In conclusion, this study shows that grade 3 EEC shares with low-grade EEC the overexpression but not amplification of cyclin D1 and low frequency of Her-2 overexpression and amplification. Grade 3 EEC shares with SC the relatively common p53 and p16 overexpression and low frequency of loss of mismatch repair genes. However, in contrast to SC ECs, which often show WT-1, cyclin D1 amplification, and Her-2 overexpression and/or amplification, grade 3 EECs rarely overexpressed any of these markers. Moreover, in this study, patients with tumors showing loss of MLH-1/MSH-2 or cyclin D1 overexpression were more likely to have low-stage tumors (stage I), whereas patients with tumors that overexpressed p53, p16, or Her-2 were frequently associated with high-stage tumors.     

Alzheimer type dementia: is early diagnosis significant?

ADVANTAGES OF EARLY DIAGNOSIS: Better prognosis and quality of life for patients with Alzheimer's disease and their caregivers depends on early diagnosis as specific treatment (anticholinesterase drugs) early in the disease process can have a beneficial effect on cognition and psychiatric or behavioral disorders. In addition early diagnosis gives the physician the opportunity to provide adapted advice for the patient and caregivers especially important in preventing complications and helping the family cope with the inevitable disruption of the family pattern caused by the disease, a situation which is particularly for the "designated caregiver". PREDEMENTIA STATES: The question of early diagnosis raises several types of problems. Defining the limits of the disease is particularly difficult: when does Alzheimer type dementia start? what is the definition of predementia? A growing body of work suggests that it is warranted to identify patients at risk of developing Alzheimer type dementia since, according to certain authors, they can benefit from specific treatment. RISK FACTORS: The only fully recognized risk factors are age, family history of dementia and presence of the allele epsilon 4 of the apolipoprotein E gene. There are probably several other risk factors. Their identification is a current subject of debate. TOOLS FOR EARLY DIAGNOSIS: Psychometric tests have been shown to provide specific information useful for interpreting the clinical assessment which must focus on detecting early signs and exploring even minimal memory deficiencies.     

Basicervical fracture – a rare type of hip fracture

Basicervical fracture is a controversial type of hip fracture, which can be regarded as either extracapsular or intracapsular. It is seldom mentioned in the authorized orthopaedic textbooks, and it lacks an exact definition in the most commonly used classifications. The aim of this study was to evaluate the rate of basicervical hip fractures and the methods of treating them in a prospective series of 1624 consecutive hip fractures. Standardized forms were used to collect information, including the classification of fracture types. Initially, 108 fractures were classified as basicervical, but a careful second-look check revealed that 51 were transcervical fractures, while 27 fractures had a trochanteric extension. Thus, 30 of the fractures fulfilled the criteria of basicervical fracture (rate 1.8%). The 14 fractures treated as extracapsular fractures (dynamic hip screw, DHS, or gamma nail) showed a better outcome than the 16 treated as intracapsular fractures (hemiarthroplasty or screw osteosynthesis). We conclude that basicervical fracture of the hip is a very uncommon entity, but it is worth considering and should be treated as a trochanteric fracture.     

Rotationplasty type BI versus type BIIIa in children under the age of ten years. Should the knee be preserved?

Type BI rotationplasty is currently indicated for children with tumours of the proximal femur whereas type BIIIa rotationplasty is reserved for those in which the entire femur has to be removed. Our aim was to compare these two types of rotationplasty and determine whether the knee should be preserved in children with tumours of the proximal femur. We compared the post-operative complications, oncological outcome, range of movement, Enneking score and radiographs of six children, who had undergone type BI rotationplasty with those of 12 who had undergone type BIIIa rotationplasty. Patients with type BI rotationplasty had a mean Enneking score of 21.6 compared with 24.4 in those with type BIIIa rotationplasty, and worse mean results in all of the parameters investigated. We conclude that type BI rotationplasty has a worse functional outcome and more complications than type BIIIa rotationplasty in children under the age of ten years.     

Total hip arthroplasty for crowe type ⅳ developmental dysplasia

The purposes of this study were to evaluate the midterm clinical and radiographic results of total hip arthroplasty (THA) in patients with Crowe type IV developmental dysplasia and to evaluate whether low back pain would improve after THA. Eighteen consecutive patients (20 hips) were included in this study. The average age at the time of surgery was 58.5 years. The average follow-up was 10.2 years. The socket was placed at the level of the true acetabulum, and a femoral shortening osteotomy was performed. The average Harris hip score before surgery was improved from 56 to 85 points at the final follow-up. Revision was performed in 4 hips due to loosening of the femoral component in 1 hip and osteolysis in 3 hips. The midterm outcomes of THA in patients with Crowe type IV developmental dysplasia were satisfactory. The severity of low back pain was significantly reduced after THA.     

Is latent autoimmune diabetes in adults distinct from type 1 diabetes or just type 1 diabetes at an older age?

Diabetes is classified clinically into two types: type 1 and type 2 diabetes. Type 1 diabetes is an autoimmune diabetes, whereas, in contrast, type 2 diabetes is nonautoimmune. However, there is a group of phenotypic adult type 2 diabetic patients ( approximately 10%) who have islet autoantibodies similar to type 1 diabetes. These patients are said to have latent autoimmune diabetes in adults (LADA) or type 1.5 diabetes. T-cells reacting with islet proteins have been demonstrated in type 1 and type 1.5 diabetic patients. In contrast, classic autoantibody-negative type 2 diabetic patients are also negative for T-cell responses to islet proteins. Therefore, we questioned whether type 1 and type 1.5 diabetes are similar or different autoimmune diseases. We have investigated the immunological and metabolic differences between type 1, type 1.5, and classic type 2 diabetic patients. We have identified autoantibody differences, differences in islet proteins recognized by T-cells, and differences in insulin resistance. We have also identified a small group of patients who have T-cells responsive to islet proteins but who are autoantibody negative. These patients appear to be similar to type 1.5 patients in having decreased stimulated C-peptide values. These immunological differences between type 1 and type 1.5 diabetes suggest at least partially distinct disease processes.     

Operative mortality after renal transplantation--does surgeon type matter?

PURPOSE: Currently there are 64 accredited renal transplantation fellowships in Canada and the United States. Only 27% are limited in scope to kidney transplants. In the remaining fellowships the trainee learns to transplant multiple abdominal organs. Given this evolution to the multiorgan transplant surgeon, we evaluated the effect of the current training paradigm on practice patterns and outcomes for kidney transplants. MATERIALS AND METHODS: Using data from the Nationwide Inpatient Sample, discharge records for kidney transplants (6,674) were abstracted (1993 to 2003). Through the Nationwide Inpatient Sample unique surgeon identifier we determined the proportion of kidney transplants performed by multiorgan and kidney only transplant surgeons. We fit multilevel regression models to examine the relationship between surgeon type and transplant outcome. RESULTS: We identified 99 multiorgan and 196 kidney only transplant surgeons who performed 3,255 and 3,419 kidney transplants, respectively. Kidney only transplant surgeons were more likely than multiorgan surgeons to practice in nonteaching, private, for-profit hospitals (p <0.05). Unadjusted operative mortality was higher in patients treated by kidney only vs multiorgan transplant surgeons (1.7% vs 0.9%, p = 0.002). After adjusting for patient and hospital factors, those who underwent renal transplantation performed by multiorgan transplant surgeons had 55% lower odds of inpatient death (OR 0.45, 95% CI 0.26-0.76) vs kidney only transplant surgeons. CONCLUSIONS: Despite the current training paradigm, kidney only transplant surgeons have a prominent role in renal transplantation. However, given the current donor organ shortage and the implications for quality, the observed mortality difference suggests that additional investigation is needed to determine whether this role should be decreased.     

Primary hyperoxaluria type 1: still challenging!

Primary hyperoxaluria type 1, the most common form of primary hyperoxaluria, is an autosomal recessive disorder caused by a deficiency of the liver-specific enzyme alanine: glyoxylate aminotransferase (AGT). This results in increased synthesis and subsequent urinary excretion of the metabolic end product oxalate and the deposition of insoluble calcium oxalate in the kidney and urinary tract. As glomerular filtration rate (GFR) decreases due to progressive renal involvement, oxalate accumulates and results in systemic oxalosis. Diagnosis is still often delayed. It may be established on the basis of clinical and sonographic findings, urinary oxalate ± glycolate assessment, DNA analysis and, sometimes, direct AGT activity measurement in liver biopsy tissue. The initiation of conservative measures, based on hydration, citrate and/or phosphate, and pyridoxine, in responsive cases at an early stage to minimize oxalate crystal formation will help to maintain renal function in compliant subjects. Patients with established urolithiasis may benefit from extracorporeal shock-wave lithotripsy and/or JJ stent insertion. Correction of the enzyme defect by liver transplantation should be planned, before systemic oxalosis develops, to optimize outcomes and may be either sequential (biochemical benefit) or simultaneous (immunological benefit) liver–kidney transplantation, depending on facilities and access to cadaveric or living donors. Aggressive dialysis therapies are required to avoid progressive oxalate deposition in established end-stage renal disease (ESRD), and minimization of the time on dialysis will improve both the patient’s quality of life and survival.     

Mouse models and the genetics of diabetes: is there evidence for genetic overlap between type 1 and type 2 diabetes?

In humans, both type 1 and type 2 diabetes exemplify genetically heterogeneous complex diseases in which epigenetic factors contribute to underlying genetic susceptibility. Extended human pedigrees often show inheritance of both diabetes types. A common pathophysiological denominator in both disease forms is pancreatic beta-cell exposure to proinflammatory cytokines. Hence, it is intuitive that systemically expressed genes regulating beta-cell ability to withstand chronic diabetogenic stress may represent a component of shared susceptibility to both major disease forms. In this review, the authors assemble evidence from genetic experiments using animal models developing clearly distinct diabetes syndromes to inquire whether some degree of overlap in genes contributing susceptibility can be demonstrated. The conclusion is that although overlap exists in the pathophysiological insults leading to beta-cell destruction in the currently studied rodent models, the genetic bases seem quite distinct.