Influence of dialysis on the glucose profile in patients with diabetes: usefulness of continuous glucose monitoring.

We sought to investigate the impact of dialysis on glucose profiles of diabetic patients using continuous glucose monitoring (CGM). The study included 33 hemodialyzed patients with diabetes (14 females and 19 males; mean age: 66±8 years; patients with type 2 diabetes: 30; mean duration of dialysis: 3.8±2.6 years) who were under insulin treatment. After a run-in period, CGM was performed for 48 h, including a dialysis session. Three CGM sessions were proposed for each patient over a 3-month period. CGM results were analyzed during and after dialysis at 6 different time points. Moreover, data were analyzed in 7 different day periods according to meals. Of the 99 CGM available, 21 were excluded because of technical issues or patient refusal. The CGM results indicated that mean glucose values (7.5±2.5 mmol/l vs. 9.4±1.9 mmol/l; p<0.001) and variability indices (p<0.001) were lower, whereas the frequency of hypoglycemia (4.4±9.6% vs. 2.1±7.9%; p<0.001) was higher during hemodialysis sessions. Significant differences were observed in glucose values only before and 2 h after breakfast (p<0.001). Compared with other day periods, glucose values were lower during the second half of the night and higher before and after dinner (p<0.001). In summary, CGM allows the identification of a particular glucose profile in hemodialyzed diabetic patients. CGM seems feasible and clinically useful for the analysis of glucose profiles in this group of patients.

Treating diabetes with islet transplantation: lessons from the past decade in Lille.

Type 1 diabetes (T1D) is due to the loss of both beta-cell insulin secretion and glucose sensing, leading to glucose variability and a lack of predictability, a daily issue for patients. Guidelines for the treatment of T1D have become stricter as results from the Diabetes Control and Complications Trial (DCCT) demonstrated the close relationship between microangiopathy and HbA1c levels. In this regard, glucometers, ambulatory continuous glucose monitoring, and subcutaneous and intraperitoneal pumps have been major developments in the management of glucose imbalance. Besides this technological approach, islet transplantation (IT) has emerged as an acceptable safe procedure with results that continue to improve. Research in the last decade of the 20th century focused on the feasibility of islet isolation and transplantation and, since 2000, the success and reproducibility of the Edmonton protocol have been proven, and the mid-term (5-year) benefit-risk ratio evaluated. Currently, a 5-year 50% rate of insulin independence can be expected, with stabilization of microangiopathy and macroangiopathy, but the possible side-effects of immunosuppressants, limited availability of islets and still limited duration of insulin independence restrict the procedure to cases of brittle diabetes in patients who are not overweight or have no associated insulin resistance. However, various prognostic factors have been identified that may extend islet graft survival and reduce the number of islet injections required; these include graft quality, autoimmunity, immunosuppressant regimen and non-specific inflammatory reactions. Finally, alternative injection sites and unlimited sources of islets are likely to make IT a routine procedure in the future.

High prevalence of diabetes mellitus and hospital-related hyperglycaemia in French general wards.

AIM: The study evaluated the in-hospital prevalence of diabetes and hospital-related hyperglycaemia in a variety of French general wards. METHODS: The multicentre cross-sectional study involving nine French hospitals measured venous fasting plasma glucose (FPG) on a single day in patients hospitalized in adult medical and surgical short-term wards. Diabetes status and length of stay were recorded. RESULTS: Of the 2141 inpatients included in the study, 355 (16.5%) had known diabetes, 156 (7.3%) had screened diabetes (FPG ≥7 mmol/L with no diabetes history), 515 (24.1%) had impaired fasting glucose (IFG; FPG 5.5-6.9 mmol/L) and 1115 (52.1%) had normal glucose values (FPG < 5.5 mmol/L). Diabetes prevalence varied from 11% in hospitals in the west of France to 21% in hospitals in northern and eastern regions. The highest known diabetes prevalence was observed in units for cardiovascular surgery (33%), infectious diseases (27%) and kidney disorders (26%). In cancer units, one-fifth of patients had screened diabetes and one-sixth had known diabetes. Among the known diabetes patients, 127 (36%) were already being treated with insulin, while an additional 41 (12%) started insulin therapy during their hospital stay. Patients with known and screened diabetes were older (70.8 ± 12.2 and 71.1 ± 15.6 years, respectively) than the normal-glucose patients (65.6 ± 18.9 years; P<0.001). Average length of stay was no different between known diabetes and normal-glucose patients after adjusting for age (11.3 ± 7.7 vs 10.0 ± 7.4 days; NS). CONCLUSION: Overall, metabolic glucose disorders (known or screened diabetes and IFG) were found in 48% of inpatients in various French hospital general wards.

The femoral head/neck offset and hip resurfacing.

Because the femoral head/neck junction is preserved in hip resurfacing, patients may be at greater risk of impingement, leading to abnormal wear patterns and pain. We assessed femoral head/neck offset in 63 hips undergoing metal-on-metal hip resurfacing and in 56 hips presenting with non-arthritic pain secondary to femoroacetabular impingement. Most hips undergoing resurfacing (57%; 36) had an offset ratio or= 50.5 degrees. Most hips undergoing resurfacing have an abnormal femoral head/neck offset, which is best assessed in the sagittal plane.

Notching of the femoral neck during resurfacing arthroplasty of the hip: a vascular study.

During hip resurfacing arthroplasty, excessive valgus positioning or surgical technique can result in notching of the femoral neck. Although mechanical weakening and subsequent fracture of the femoral neck are well described, the potential damage to the retinacular vessels leading to an ischaemic event is relatively unknown. Using laser Doppler flowmetry, we measured the blood flow in 14 osteoarthritic femoral heads during routine total hip replacement surgery, before and after notching of the femoral neck. In ten hips there was a reduction in blood flow of more than 50% from the baseline value after simulated notching of the femoral neck. Our results suggest that femoral head vascularity in the osteoarthritic state is similar to the non-arthritic state, where damage to the extraosseous vessels can predispose to avascular necrosis. Surgeons who perform resurfacing arthroplasty of the hip should pay careful attention to these vessels by avoiding excessive dissection around the femoral neck and/or notching.

Polyethylene wear characteristics in vivo and in a knee stimulator.

Validation of a wear simulator requires that the device produce a similar type and amount of wear and particles of a comparable morphology as occurs clinically. Using techniques previously established to compare polyethylene particles from hip simulators to those from retrieved tissues, particles isolated from six revised posterior stabilized knee replacements were characterized and compared to particles generated from the same knee design worn in a knee simulator. The particles produced in the knee simulator were of comparable size but had less variability in their form factor compared to the particles produced in vivo. Comparable wear features were seen on the articulating surfaces in both groups. These results indicate that this knee joint simulator is able to reproduce a baseline type of wear that is similar to that in vivo and should encourage further use of this device to better understand knee component wear and function.

Quality of life assessment in elite collegiate athletes.

The objectives of this study were to establish baseline Medical Outcomes Study Short Form Health Survey (SF-36) data for Division I collegiate athletes and to determine the effects of injury severity and training time. All participating athletes (N = 562) at a major university were evaluated with the SF-36. Regression analysis was performed to identify predictive factors. When the men without injury were compared with a previously established norm group, there was a significant increase in the role emotional score. In the women without injury there were significant increases in mental component summary, physical function, role emotional, mental health, and vitality scores when compared with the norm group. Serious injury was a predictor of lower scores in all domains, whereas minimal injury was predictive of lower physical component summary, role physical, bodily pain, social function, and general health scores. Increased training time was predictive of higher mental component summary, role physical, vitality, and general health scores. Elite collegiate athletes scored differently from previously established age-matched norms, and injury was a strong predictor of lower scores.

Hazard analysis of Escherichia coli O157:H7 contamination during beef slaughtering in Calvados, France.

To identify hazard points and critical points during beef slaughtering, which is a necessary first step toward developing a hazard analysis and critical control point system to control meat contamination by Escherichia coli O157:H7, samples (n = 192) from surfaces, work tops, worker's hands, and beef carcasses were collected from a slaughterhouse in Calvados, France. Five strains of E. coli O157:H7 were isolated from a footbridge and a worker's apron at the preevisceration post and from a worker's hand at the defatting post. Three isolates carried stx2c, eae, and EHEC-hlyA genes and showed similar molecular types by random amplified polymorphic DNA, polymerase chain reaction IS3, and XbaI pulsed-field gel electrophoresis. Thus, this study has shown that preevisceration and defatting post and associated worker's materials are critical points for carcasses contamination by E. coli O157:H7 during beef slaughtering.

Growth and development of the pediatric cervical spine documented radiographically.

BACKGROUND: The radiographic anatomy of the cervical spine in children is complex and can be difficult to interpret. The present study was undertaken to document radiographically the growth and development of the cervical spine in a prospective, longitudinal manner and to establish standard radiographic measurements on the basis of findings in patients who were followed serially from the age of three months until skeletal maturity. METHODS: The radiographic resources of the Cleveland Study of Normal Growth and Development (Bolton-Brush Collection, Cleveland, Ohio) were reviewed. From this large database, we identified fifty boys and forty-six girls who had a sufficient number of radiographs of the cervical spine for inclusion in our study. With use of a computerized image analyzer, the growth and development of the atlantodens interval, the diameter of the spinal canal, the Torg ratio, the height and width of the second through fifth cervical vertebral bodies, the height of the dens, and the ossification of the first cervical vertebra were assessed on serial radiographs made from the age of three months until skeletal maturity. RESULTS: Serial measurements of the atlantodens interval, the anteroposterior diameter of the cervical canal, the height and anteroposterior width of the cervical vertebral bodies, and the height of the dens, made in normal, healthy children from the age of three months to fifteen years, are presented in tabular and graphic forms. The median Torg ratio was 1.47 for both males and females primarily, and it reached values of 1.06 for males and 1.10 for females by maturity. The anterior arch of the first cervical vertebra had ossified in 33% of the children by the age of three months and in 81% of the children by the age of one year. Closure of the synchondroses was completed in all children by the age of three years. CONCLUSIONS: The measurements presented in the current study are important because they are the first, as far as we know, to document the radiographic parameters of the cervical spine in children who were followed longitudinally from before the age of three years through the course of growth and development until skeletal maturity.

Efficacy of nonoperative treatment for lateral epicondylitis.

One hundred cases of lateral epicondylitis among 97 patients were reviewed, and 84 patients were contacted for long-term follow-up. Patients participated in a structured nonoperative treatment regimen. Mean age of contacted patients was 49 years; mean follow-up was 2.8 years. Surgery was averted in 65 (75%) of 87 cases. Patients who achieved pain control after only 1 cortisone injection successfully avoided surgery 88% of the time, whereas those requiring multiple injections avoided surgery only 44% of the time. Eventual outcomes were similar, regardless of treatment type. Patients requiring multiple cortisone injections to alleviate acute pain have a guarded prognosis for continued nonoperative management.

Reevaluation of the 1997 TNM classification for renal cell carcinoma: T1 and T2 cutoff point at 4.5 rather than 7 cm. better correlates with clinical outcome.

PURPOSE: We analyzed the effects of the change in TNM classification from the 1987 to the 1997 version and suggest a modified tumor size cutoff point between T stages 1 and 2 for renal cell carcinoma. MATERIALS AND METHODS: We evaluated a database containing the records of 661 patients who underwent nephrectomy between 1989 and 1999. The effect of the change in TNM classification on the distribution of patients between stages, the rates of M+ and N+ disease, and the local and distant recurrence rates were outlined for 280 patients with T stages 1 and 2 disease. The Cox model was used to identify the optimal cutoff point between T1 and T2 disease, and the resulting effect of adopting this cutoff was outlined. RESULTS: A total of 174 and 128 cases were down staged from 1987 version stage T2 to 1997 version stage T1 and from 1987 TNM stage II to 1997 TNM stage I, respectively. Survival was not significantly different in patients with 1997 TNM stages I and II disease due to a lack of survival difference during the first 2 years of followup. Stage shift also caused an increase in average tumor size, the proportion of patients with high grade cancer, and M+ and N+ disease at diagnosis in 1997 stages T1 and T2 as well as an increase in the proportion of 1997 stage T2N0M0 cases at diagnosis with systemic failure. Analysis of 11 potential cutoff points between 1 and 10 cm. revealed that 4.5 cm. was most predictive of patients survival (hazards ratio 4.99, p = 0.0001). Using this cutoff resulted in improved discriminatory power of the TNM classification and a moderating effect on the distribution of patients, average tumor size, high grade disease, M+ and N+ disease at diagnosis, and systemic failure between T(14.5) and T(24.5) compared with 1997 T1 and T2. CONCLUSIONS: Our data imply that the current cutoff point of 7 cm. between stages T1 and T2 tumors is too high. Lowering the cutoff to 4.5 cm. resulted in better discriminatory power of the TNM classification in our dataset. This observation should be further validated by external data.

Treatment-induced pathologic necrosis: a predictor of local recurrence and survival in patients receiving neoadjuvant therapy for high-grade extremity soft tissue sarcomas.

PURPOSE: To determine whether treatment-induced pathologic necrosis correlates with local recurrence and overall survival in patients who receive neoadjuvant therapy for high-grade extremity soft tissue sarcomas. PATIENTS AND METHODS: Four hundred ninety-six patients with intermediate- to high-grade extremity soft tissue sarcomas received protocol neoadjuvant therapy. All patients underwent surgical resection after neoadjuvant therapy and had pathologic assessment of tumor necrosis in the resected specimens. RESULTS: The 5- and 10-year local recurrence rates for patients with > or = 95% pathologic necrosis were significantly lower (6% and 11%, respectively) than the local recurrence rates for patients with less than 95% pathologic necrosis (17% and 23%, respectively). The 5- and 10-year survival rates for the patients with > or = 95% pathologic necrosis were significantly higher (80% and 71%, respectively) than the survival rates for the patients with less than 95% pathologic necrosis (62% and 55%, respectively). Patients with less than 95% pathologic necrosis were 2.51 times more likely to develop a local recurrence and 1.86 times more likely to die of their disease as compared with patients with > or = 95% pathologic necrosis. The percentage of patients who achieved > or /= 95% pathologic necrosis increased to 48% with the addition of ifosfamide as compared with 13% of the patients in all the other protocols combined. CONCLUSION: Treatment-induced pathologic necrosis is an independent predictor of both local recurrence and overall survival in patients who receive neoadjuvant therapy for high-grade extremity soft tissue sarcomas. A complete pathologic response (> or = 95% pathologic necrosis) correlated with a significantly lower rate of local recurrence and improved overall survival.

Prostate stem cell antigen is overexpressed in human transitional cell carcinoma.

Prostate stem cell antigen (PSCA), a homologue of the Ly-6/Thy-1 family of cell surface antigens, is expressed by a majority of human prostate cancers and is a promising target for prostate cancer immunotherapy. In addition to its expression in normal and malignant prostate, we recently reported that PSCA is expressed at low levels in the transitional epithelium of normal bladder. In the present study, we compared the expression of PSCA in normal and malignant urothelial tissues to assess its potential as an immunotherapeutic target in transitional cell carcinoma (TCC). Immunohistochemical analysis of PSCA protein expression was performed on tissue sections from 32 normal bladder specimens, as well as 11 cases of low-grade transitional cell dysplasia, 21 cases of carcinoma in situ (CIS), 38 superficial transitional cell tumors (STCC, stages T(a)-T(1)), 65 muscle-invasive TCCs (ITCCs, stages T(2)-T(4)), and 7 bladder cancer metastases. The level of PSCA protein expression was scored semiquantitatively by assessing both the intensity and frequency (i.e., percentage of positive tumor cells) of staining. We also examined PSCA mRNA expression in a representative sample of normal and malignant human transitional cell tissues. In normal bladder, PSCA immunostaining was weak and confined almost exclusively to the superficial umbrella cell layer. Staining in CIS and STCC was more intense and uniform than that seen in normal bladder epithelium (P < 0.001), with staining detected in 21 (100%) of 21 cases of CIS and 37 (97%) of 38 superficial tumors. PSCA protein was also detected in 42 (65%) of 65 of muscle-invasive and 4 (57%) of 7 metastatic cancers, with the highest levels of PSCA expression (i.e., moderate-strong staining in >50% of tumor cells) seen in 32% of invasive and 43% of metastatic samples. Higher levels of PSCA expression correlated with increasing tumor grade for both STCCs and ITCCs (P < 0.001). Northern blot analysis confirmed the immunohistochemical data, showing a dramatic increase in PSCA mRNA expression in two of five muscle-invasive transitional cell tumors when compared with normal samples. Confocal microscopy demonstrated that PSCA expression in TCC is confined to the cell surface. These data demonstrate that PSCA is overexpressed in a majority of human TCCs, particularly CIS and superficial tumors, and may be a useful target for bladder cancer diagnosis and therapy.

Tissue effects of saw palmetto and finasteride: use of biopsy cores for in situ quantification of prostatic androgens.

OBJECTIVES: To determine the effects of a saw palmetto herbal blend (SPHB) compared with finasteride on prostatic tissue androgen levels and to evaluate needle biopsies as a source of tissue for such determinations. METHODS: Prostate levels of testosterone and dihydrotestosterone (DHT) were measured on 5 to 10-mg biopsy specimens (18-gauge needle cores) in three groups of men with symptomatic benign prostatic hyperplasia: 15 men receiving chronic finasteride therapy versus 7 untreated controls; 4 men undergoing prostate adenomectomy to determine sampling variability (10 specimens each); and 40 men participating in a 6-month randomized trial of SPHB versus placebo, before and after treatment. RESULTS: Prostatic tissue DHT levels were found to be several times higher than the levels of testosterone (5.01 versus 1.51 ng/g), that ratio becoming reversed (1.05 versus 3.63 ng/g) with chronic finasteride therapy. The finasteride effect was statistically significant for both androgens (P <0.01), and little overlap of individual values between finasteride-treated and control patients was seen. In the randomized trial, tissue DHT levels were reduced by 32% from 6.49 to 4.40 ng/g in the SPHB group (P <0.005), with no significant change in the placebo group. CONCLUSIONS: For control versus finasteride-treated men, the tissue androgen values obtained with needle biopsy specimens were similar-both for absolute values and the percentage of change-to those previously reported using surgically excised volumes of prostatic tissue. The quantification of prostatic androgens by assay of needle biopsies is thus feasible and offers the possibility of serial studies in individual patients. The SPHB-induced suppression of prostatic DHT levels, modest but significant in a randomized trial, lends an element of support to the hypothesis that inhibition of the enzyme 5-alpha reductase is a mechanism of action of this substance.

The effect of quadriceps femoris muscle strengthening exercises on spasticity in children with cerebral palsy.

BACKGROUND AND PURPOSE: The Bobath neurodevelopmental treatment approach advised against the use of resistive exercise, as proponents felt that increased effort would increase spasticity. The purpose of this study was to test the premise that the performance of exercises with maximum efforts will increase spasticity in people with cerebral palsy (CP). Spasticity, in the present study, was defined as a velocity-dependent hyperexcitability of the muscle stretch reflex. SUBJECTS: Twenty-four subjects with the spastic diplegic form of CP (mean age=11.4 years, SD=3.0, range=7-17) and 12 subjects without known neurological impairments (mean age=11.6 years, SD=3.5, range=7-17) were assessed. METHODS: Knee muscle spasticity was assessed bilaterally using the pendulum test to elicit a stretch reflex immediately before and after 3 different forms of right quadriceps femoris muscle exercise (isometric, isotonic, and isokinetic) during a single bout of exercise training. Pendulum test outcome measures were: (1) first swing excursion, (2) number of lower leg oscillations, and (3) duration of the oscillations. RESULTS: There were no changes in spasticity following exercise between the 2 groups of subjects. DISCUSSION AND CONCLUSION: These results do not support the premise that exercises with maximum efforts increase spasticity in people with CP.

Duration of symptoms and outcome of hemiresurfacing for hip osteonecrosis.

Thirty-seven hips with Ficat Stage II, III, or early IV osteonecrosis were treated with hemiresurfacing. The purpose of this study is to analyze specifically the clinical and radiographic results of patients who had hemiresurfacing to refine the indications for the procedure and identify factors substantially affecting clinical outcome and survivorship. At an average followup of 6.5 years, the average University of California Los Angeles hip scores for pain, walking, function, and activity improved significantly from 4.3, 6.0, 5.3, and 4.2 to 8.0, 8.8, 7.9, and 5.8. The overall survivorship was 79%, 59%, and 45% at 5, 10, and 15 years. Eleven hips have been converted: 10 hips for acetabular cartilage wear and one hip for femoral loosening. The average time to conversion was 7.5 years. A longer duration of symptoms before surgery (16.6 months versus 12.1 months) was associated with a worse acetabular cartilage grading and suggested a relationship with a shorter time to conversion, although the difference was not statistically significant at the 5% level. Survivorship is better when preoperative symptoms are present for 1 year or less, possibly because the articular cartilage is healthier. When necessary, conversion to total hip replacement can be done without adverse results.

Improved prognostication of renal cell carcinoma using an integrated staging system.

PURPOSE: To integrate stage, grade, and Eastern Cooperative Oncology Group (ECOG) performance status (PS) into a clinically useful tool capable of stratifying the survival of renal cell carcinoma (RCC) patients. PATIENTS AND METHODS: The medical records of 661 patients undergoing nephrectomy at University of California Los Angeles between 1989 and 1999 were evaluated. Median age was 61 years, male-to-female ratio was 2.2:1, and median follow-up was 37 months. Survival time was the primary end point assessed. Sixty-four possible combinations of stage, grade, and ECOG PS were analyzed and collapsed into distinct groups. The internal validity of the categorized was challenged by a univariate analysis and a multivariate analysis testing for the accountability of each UCLA Integrated Staging System (UISS) category against independent variables shown to have impact on survival. RESULTS: Combining and stratifying 1997 tumor-node-metastasis stage, Fuhrman's grade and ECOG PS resulted in five survival stratification groups designated UISS, and numbered I to V. The projected 2- and 5-year survival for the UISS groups are as follows for the groups: I, 96% and 94%; II, 89% and 67%; III, 66% and 39%; IV, 42% and 23%; and V, 9% and 0%, respectively. UISS accounted for the significant variables in the variate analysis. CONCLUSION: A novel system for staging and predicting survival for RCC integrating clinical variables is offered. UISS is simple to use and is superior to stage alone in differentiating patients' survival. Our data suggests that UISS is an important prognostic tool for counseling patients with various stages of kidney cancer. Further prospective large-scale validation with external data is awaited.