Long-term Results of Through-knee Amputation with Dorsal Musculocutaneous Flap in Patients with End-stage Arterial Occlusive Disease

A modified technique of knee joint disarticulation using a dorsal musculocutaneous flap of the gastrocnemius muscle was first described in 1985. The operative results in 66 patients (33 women, 33 men; mean age 66.7 ± 11.3 years, range 42–93 years) with gangrene due to peripheral vascular disease with 69 knee disarticulations are reported. After a mean survival period of 35.2 months (0–116 months), 88% (n = 58) of the patients had died owing to cardiopulmonary reasons. The in-hospital 48-day mortality was 9%. Nine patients (14%) underwent reamputation at the above-knee level, and five patients underwent operative revision of the soft tissue. After discharge from the hospital, 35 of 60 patients (58%) were able to walk with the aid of a prosthesis. We conclude that knee disarticulation with the use of a myocutaneous gastrocnemius flap is a safe, functionally acceptable operative method in high risk vascular patients.     

Can pre-operative contrast-enhanced dynamic MR imaging for prostate cancer predict microvessel density in prostatectomy specimens?

The aim of this study was to correlate quantitative dynamic contrast-enhanced MRI (DCE MRI) parameters with microvessel density (MVD) in prostate carcinoma. Twenty-eight patients with biopsy-proven prostate carcinoma were examined by endorectal MRI including multiplanar T2- and T1-weighted spin-echo and dynamic T1-weighted turbo-FLASH MRI during and after intravenous Gd-DTPA administration. Microvessels were stained on surgical specimens using a CD31 monoclonal antibody. The MVD was quantified in hot spots by counting (MVC) and determining the area fraction by morphometry (MVAF). The DCE MRI data were analyzed using an open pharmacokinetic two-compartment model. In corresponding anatomic locations the time shift (t) between the beginning of signal enhancement of cancer and adjacent normal prostatic tissue, the degree of contrast enhancement and the contrast exchange rate constant (k₂₁) were calculated. The MVC and MVAF were elevated in carcinoma (p<0.001 and p=0.002, respectively) and correlated to k₂₁ (r=0.62, p<0.001 and r=0.80, p<0.001, respectively). k₂₁-values of carcinoma were significantly higher compared with normal peripheral but not central zone tissue. t was longer in high compared with low-grade tumors (p=0.025). The DCE MRI can provide important information about individual MVD in prostate cancer, which may be helpful for guiding biopsy and assessing individual prognosis.     

Importance of adrenal incidentaloma in patients with a history of malignancy

BACKGROUND: Adrenal incidentaloma presents a frequent finding in patients with a history of malignancy. This study was carried out to determine whether imaging techniques can discriminate between a malignant and a benign adrenal tumor and subsequently select candidates for adrenal surgery. METHODS: Beginning in July 1995, oncologic patients with adrenal incidentaloma underwent abdominal ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and [ 18 ]fluoro-2-deoxy-D-glucose positron emission tomography (18-FDG-PET). Consecutively in all patients adrenalectomy was performed. Histologic findings were compared with the imaging results. RESULTS: In 42 patients, 33 to 79 years old (mean age, 58 years), 44 adrenal lesions were detectable. Two patients presented with bilateral adrenal masses. At operation, 43 adrenal resections and 3 biopsies were performed. Histologic examination revealed 31 metastases (71%) and 13 adrenal adenomas (29%). In metastases the sensitivity of ultrasonography, CT, MRI, and 18-FDG-PET was 66%, 81%, 100%, and 100%, respectively. For adrenal adenoma, the sensitivity of ultrasonography, CT, MRI, and 18-FDG-PET was 46%, 39%, 100%, and 54%, respectively. CONCLUSIONS: In oncologic patients with indeterminate adrenal tumors MRI and 18-FDG-PET provide accurate differentiation between metastases and benign adenomas. Positive results of these 2 imaging modalities are highly suggestive for metastatic disease. In cases of negative MRI and 18-FDG-PET results the adrenal lesion corresponds to a benign adenoma that needs no surgical intervention.     

Rapid identification of preformed alloreactive T cells for use in a clinical setting

BACKGROUND: In clinical practice, HLA matching is generally applied to minimize the incidence of graft rejection after transplantation. Recently, graft rejection has been directly associated with the presence of preformed alloreactive T cells before transplantation. Despite this knowledge, assays to rapidly quantify preformed alloreactivity are not available for use in a clinical setting. In this study, such an assay was developed and evaluated in a large cohort to correlate alloreactive T-cell reactivity with HLA matching. METHODS: Stimulator peripheral blood mononuclear cells were prestained with CD45-fluorescein isothiocyanate antibody and mixed with responder peripheral blood mononuclear cells. Activation-induced cytokine secretion was blocked using brefeldin A. After 6 hr, functionally active alloreactive responder CD4 and CD8 T cells were quantified among fluorescein isothiocyanate-negative cells by their expression of interferon-gamma on flow cytometry. RESULTS: Directly alloreactive CD4 and CD8 T cells among both stimulators and responders were easily distinguished after 6 hr of stimulation without being affected by bystander activation. Among 128 paired combinations, 23.4% of individuals had alloreactive CD8 T cells, 15.7% had alloreactive CD4 T cells, and 12.5% had alloreactivity in both T-cell subpopulations. Alloreactive T cells decreased from circulation within a few days after transplantation. In line with well-known clinical observations that associate HLA matching with graft outcome, the number of HLA-A and -B mismatches correlated with alloreactive CD8 T-cell frequencies in the whole study population, whereas it did not predict alloreactivity on an individual basis. CONCLUSION: Alloreactive T cells may rapidly be quantified after 6 hr of stimulation. Thus, the flow cytometric approach may be applied in a clinical setting to facilitate the individualization of immunosuppressive therapy and studies on the identification of patients who are at increased risk to develop graft rejection.     

A genome-wide scan for childhood obesity-associated traits in French families shows significant linkage on chromosome 6q22.31-q23.2

We conducted a genome-wide search for childhood obesity-associated traits, including BMI >/==" BORDER="0">95th percentile (PCT95), 97th percentile (PCT97), and 99th percentile (PCT99) as well as age of adiposity rebound (AAR), which corresponds to the beginning of the second rise in childhood adiposity. A set of 431 microsatellite markers was genotyped in 506 subjects from 115 multiplex French Caucasian families, with at least one child with a BMI >/==" BORDER="0">95th percentile. Among these 115 pedigrees, 97 had at least two sibs with a BMI >/==" BORDER="0">95th percentile. Fine-mapping was performed in the seven most positive loci. Nonparametric multipoint analyses revealed six regions of significant or suggestive linkage on chromosomes 2q33.2-q36.3, 6q22.31-q23.2, and 17p13 for PCT95, PCT97, or PCT99 and 15q12-q15.1, 16q22.1-q24.1, and 19p13.3-p13.11 for AAR. The strongest evidence of linkage was detected on chromosome 6q22.31 for PCT97 (maximum likelihood score: 4.06) at the marker D6S287. This logarithm of odds score meets genome-wide significance tested through simulation (empirical genome-wide P = 0.01 [0.0027-0.0254]). Six independent ge-nome scans in adults have reported quantitative trait loci on 6q linked to energy or glucose homeostasis-associated phenotypes. Possible candidate genes in this region include SIM1, MCHR2, and PC-1.     

Fetoscopic placement of a transurethral stent for intrauterine obstructive uropathy

PURPOSE: Fetal urinary obstructive uropathy and consecutive oligohydramnios result in a poor outcome. Usually renal insufficiency and life threatening lung hypoplasia have developed at term. We report a case of in utero fetal cystoscopy and successful placement of a transurethral vesico-amniotic Double-J (Medical Engineering Corp., New York, New York) stent. Indications, results and the potential benefits of different techniques are discussed. MATERIAL AND METHODS: A 36-year-old woman (primipara) was evaluated at week 26 due to a male fetus with bilateral hydronephrosis, massive distended bladder and an open posterior urethra. Using local anesthesia the fetal bladder was punctured, a 2.6 mm endoscope was inserted and a wire was advanced antegrade through the penis. A 2.8Fr Double-J stent was then placed between the bladder and amniotic cavity. RESULTS: The bladder drained into the amnion, hydronephrosis disappeared and the lung developed normally. At week 37 a healthy infant was delivered who voided spontaneously. CONCLUSIONS: After careful selection of candidates for fetal intervention in obstructive uropathy direct vision fetoscopy and transurethral stent placement can be performed in patients with oligohydramnios, favorable urinary electrolytes and normal appearing kidneys.     

The pharmacokinetics of equoral versus neoral in stable renal transplant patients: a multinational multicenter study

We studied the pharmacokinetics (PKs) of the new generic cyclosporine formulation, Equoral capsules, after the switch from original formulation Neoral capsules in stable renal transplant patients. The study was carried out in accordance with the basic principles defined in the US 21 CFR Part 312.20 and the principles of the Declaration of Helsinki. The study included clinically stable first renal transplant patients maintained on cyclosporine with no rejection episode during the past 6 months. Hematology, biochemistry, and urine chemistry were determined on day 7, and day 21. The patients were all switched to Neoral (lot number 416MFD0601) on day 0 when the first sparse sampling PK was performed. On day 14 a 12-hour PK profile included predose, 30 minutes; 1 hour; 1 hour 30 minutes; 2 hours; 3 hours; 4 hours; 5 hours; 6 hours; 8 hours; 10-hours and 12-hour samples. Cyclosporine levels were determined using a CYA kit (Abbott TDx). On day 15 the patients were switched from Neoral capsules to Equoral capsules (lot 5T111014) at an equivalent dosage (mg/mg). The second sparse sampling PK was performed on day 21 and a 12-hour PK was performed on day 28. On the morning of day 29 patients were switched from Equoral capsules to Neoral capsules at an equivalent dosage (mg/mg). Additional concentrations were measured on days -7, 18, and 35. Safety parameters were monitored at each visit. The pharmacokinetics of both formulations were equivalent. The mean AUC for Neoral and Equoral was 2856 and 2892, respectively. The ratios of LSM and the 90% confidence intervals for the in-transformed parameters (AUC o-t, AUC inf, and Cmax) of Equoral and Neoral SGC were 98% and 95%, respectively, suggesting that Equoral and Neoral SGC are bioequivalent.     

Genetic polymorphisms and prostate cancer risk

The identification of common genetic polymorphisms that influence susceptibility to PC would allow an early risk assessment with earlier and therefore potentially more effective intervention by chemopreventive means. In this review we focus on published case-control studies and meta-analyses of the following polymorphic genes that may play a role in etiology of the androgen receptor (AR), the prostate-specific antigen (PSA), 5-reductase type II gene (SRD5A2), cytochrome P450c17 (CYP17), cytochrome P4503A4 (CYP3A4) and a putative hereditary PC susceptibility gene, ELAC2.Abbreviations PC Prostate cancer - BPH Benign prostatic hyperplasia - SNP Single nucleotide polymorphism - AR Androgen receptor - PSA Prostate-specific antigen - ARE Androgen responsive element - SRD5A2 5-reductase type II gene - CYP17 Cytochrome P450c17 - CYP3A4 Cytochrome P4503A4 - DHT Dihydrotestosterone - CL Confidence limit - OR Odds ratio - SD Standard deviation     

Analysis of renal function after aneurysm repair with a device using suprarenal fixation (Zenith AAA Endovascular Graft) in contrast to open surgical repair

PURPOSE: This study was undertaken to assess the effect on renal function of open surgery and endovascular abdominal aortic aneurysm (AAA) repair with suprarenal fixation with the Zenith device. METHODS: Data for 279 patients with similar preoperative comorbid conditions were prospectively analyzed after AAA repair. One hundred ninety-nine patients underwent endografting with the Zenith AAA Endovascular Graft, which incorporates suprarenal fixation (Zenith standard risk group, ZSR), and 80 patients underwent open surgery (standard surgical risk group, SSR). Endovascular repair was also performed in 100 patients considered poor candidates for open repair (Zenith high risk group, ZHR). Serum creatinine concentration (SCr) and anatomic defects were assessed before the procedure, before discharge, and at 1, 6, 12, and 24 months in all patients who underwent endovascular repair, and before the procedure and at 1 and 12 months in patients who underwent open surgical repair (only SCr was measured before discharge). Renal function was also analyzed, with a creatinine clearance calculation (Cockcraft-Gault). Renal insufficiency was defined as an increase in SCr greater than 30% from a preoperative baseline value, any SCr concentration in excess of 2.0 mg/dL, or any need for dialysis. Cumulative renal infarction and arterial occlusion rates were calculated with computed tomographic, ultrasonographic, and angiographic data, and reported as cumulative values. RESULTS: Despite the initially superior renal function in the ZSR group at the pre-discharge evaluation (P =.01), there were no differences at 12 months with respect to rise in SCr greater than 30% (ZSR, 16%, vs SSR, 12%; P =.67), SCr rise greater than 2.0 mg/dL (ZSR, 2.5%, vs SSR, 3.4%; P =.66), incidence of renal artery occlusion (ZSR, 1%, vs SSR, 1.4%; P >.99), or infarction (ZSR, 1.5%, vs SSR, 1.4%; P >.99). Only one patient in each group required hemodialysis. Of note, both groups of patients demonstrated a reduction in creatinine clearance over 12 months, which then stabilized or improved by 24 months for ZSR patients. CONCLUSIONS: Renal dysfunction occurs in a subset of patients regardless of type of repair (open or endovascular with suprarenal fixation). The cause of renal dysfunction after open or endovascular repair with a suprarenal stent is probably multifactorial. The observed dysfunction occurs in a small number of patients, and the effect in the endovascular group (no data for the surgical group at 24 months) appears to be transient. The initial dysfunction, apparent in both groups over 12 months of follow-up, stabilizes or improves at 12 to 24 months.     

Parieto-premotor areas mediate directional interference during bimanual movements

In bimanual movements, interference emerges when limbs are moved simultaneously along incompatible directions. The neural substrate and mechanisms underlying this phenomenon are largely unknown. We used functional magnetic resonance imaging to compare brain activation during directional incompatible versus compatible bimanual movements. Our main results were that directional interference emerges primarily within superior parietal, intraparietal and dorsal premotor areas of the right hemisphere. The same areas were also activated when the unimanual subtasks were executed in isolation. In light of previous findings in monkeys and humans, we conclude that directional interference activates a parieto-premotor circuit that is involved in the control of goal-directed movements under somatosensory guidance. Moreover, our data suggest that the parietal cortex might represent an important locus for integrating spatial aspects of the limbs' movements into a common action. It is hypothesized to be the candidate structure from where interference arises when directionally incompatible movements are performed. We discuss the possibility that interference emerges when computational resources in these parietal areas are insufficient to code two incompatible movement directions independently from each other.