Renal thorium deposition associated with transitional cell carcinoma: radiologic demonstration in two patients

Abdominal radiography, excretory urography, retrograde pyelography, and computed tomography were performed in two patients who had undergone retrograde pyelography with thorium dioxide (Thorotrast) approximately 40 years ago. Both patients developed a transitional cell carcinoma due to suburothelial thorium deposition. Typical thorium densities were demonstrated at CT in the peripelvicalyceal area as well as in retroperitoneal lymph nodes. Elderly patients in whom radiographic examination reveals retained Thorotrast in the kidney should be followed up because of the high risk of renal carcinoma.     

Associations of 25‐Hydroxyvitamin D and 1,25‐Dihydroxyvitamin D With Bone Mineral Density,Bone Mineral Density Change,and Incident Nonvertebral Fracture

Relationships between 1,25‐dihydroxyvitamin D (1,25(OH)₂D) and skeletal outcomes are uncertain. We examined the associations of 1,25(OH)₂D with bone mineral density (BMD), BMD change, and incident non‐vertebral fractures in a cohort of older men and compared them with those of 25‐hydroxyvitamin D (25OHD). The study population included 1000 men (aged 74.6 ± 6.2 years) in the Osteoporotic Fractures in Men (MrOS) study, of which 537 men had longitudinal dual‐energy X‐ray absorptiometry (DXA) data (4.5 years of follow‐up). A case‐cohort design and Cox proportional hazards models were used to test the association between vitamin D metabolite levels and incident nonvertebral and hip fractures. Linear regression models were used to estimate the association between vitamin D measures and baseline BMD and BMD change. Interactions between 25OHD and 1,25(OH)₂D were tested for each outcome. Over an average follow‐up of 5.1 years, 432 men experienced incident nonvertebral fractures, including 81 hip fractures. Higher 25OHD was associated with higher baseline BMD, slower BMD loss, and lower hip fracture risk. Conversely, men with higher 1,25(OH)₂D had lower baseline BMD. 1,25(OH)₂D was not associated with BMD loss or nonvertebral fracture. Compared with higher levels of calcitriol, the risk of hip fracture was higher in men with the lowest 1,25(OH)₂D levels (8.70 to 51.60 pg/mL) after adjustment for baseline hip BMD (hazard ratio [HR] = 1.99, 95% confidence interval [CI] 1.19–3.33). Adjustment of 1,25(OH)₂D data for 25OHD (and vice versa) had little effect on the associations observed but did attenuate the hip fracture association of both vitamin D metabolites. In older men, higher 1,25(OH)₂D was associated with lower baseline BMD but was not related to the rate of bone loss or nonvertebral fracture risk. However, with BMD adjustment, a protective association for hip fracture was found with higher 1,25(OH)₂D. The associations of 25OHD with skeletal outcomes were generally stronger than those for 1,25(OH)₂D. These results do not support the hypothesis that measures of 1,25(OH)₂D improve the ability to predict adverse skeletal outcomes when 25OHD measures are available. © 2015 American Society for Bone and Mineral Research.     

In vitro killing of neuroblastoma cells by neutrophils derived from granulocyte colony-stimulating factor-treated cancer patients using an anti-disialoganglioside/anti-Fc gamma RI bispecific antibody

Neutrophils isolated from cancer patients treated with granulocyte colony-stimulating factor (G-CSF) express high levels of Fc gamma RI. They exhibited an efficient killing of GD2+ neuroblastoma cells in the presence of an antidisialoganglioside (GD2) mouse monoclonal antibody (MoAb; 7A4, IgG3 kappa). However, this cytotoxicity was totally blocked by human monomeric IgG. In contrast, a bispecific antibody (7A4 bis 22/MDX-260), prepared by chemically linking an F(ab') fragment of 7A4 with an F(ab') fragment of an anti-Fc gamma RI MoAb, 22, which binds outside the Fc binding domain, triggered antibody-dependent cell cytotoxicity, even when neutrophils were preincubated with human monomeric IgG. F(ab')2 22 MoAb abrogated the MDX-260 killing without affecting that of 7A4. The 3G8 MoAb, directed against the Fc gamma RIII binding site, did not inhibit the cytotoxicity induced by either antibody. Thus, these results indicate that G-CSF-activated neutrophils exert their cytotoxic effect against neuroblastoma cells through Fc gamma RI and not Fc gamma RIII, and that the saturation of the high affinity Fc gamma RI by monomeric IgG can be overcome by the use of bispecific antibodies binding epitopes outside the IgG Fc gamma RI binding site. A combined administration of such bispecific antibodies and G-CSF may be, therefore, an efficient therapeutic approach to trigger tumor lysis by cytotoxic neutrophils in vivo.     

15The effect of Lower Esophageal Sphincter (LES) electrical stimulation on LES pressure

Background: Electrical stimulation (ES) of the stomach has been shown to modulate LESP. Electrical stimulation, using neural high frequency stimulation (NGES) can induce contractions of the smooth muscle of the gut. The purpose of this study was to determine if electrical stimulation of the LES can affect LESP. Methods: Four female hound dogs, weight: 20–25 kg, underwent an esophagostomy that allowed the introduction of a sleeve manometry catheter into the esophagus. They were also implanted with a pair of electrodes along the longitudinal axis of the LES. After 3 weeks of recovery, they underwent esophageal manometry recording during control and ES, performed randomly on separate days, using 4 different stimulations: 1‐Low frequency: freq: 6 cycles/min, pulse: 350 milisec, amp: 5 mAmp; 2 High‐frequency: freq: 50 Hz, pulse: 1 milisec, amp: 5 mAmp; 3‐ NGES: freq: 50 Hz, pulse:20 milisec, amp:10 volts; 4‐ High‐frequency, circular: freq: 20 Hz, pulse:1 milisec, amp:5 mAmp. All recordings were performed 1 hour after consumption of 3 ounces of canned dog food, to prevent fluctuations in LESP and under mild sedation (acepromazine 0.5 mg kg^­1). Tests consisted, during ES days, of 3 periods of 20 minutes each: control , stimulation and post stimulation. The effect of NGES was also tested under anesthesia and following administration of L‐NAME 50 mg kg^­1 IV. and also atropine 0.05 mg kg^­1 IV. Analysis: area under the curve (AUC) and pressure were compared among the 3 periods. Data shown as mean ± SD, ANOVA and t‐test, p < 0.05. Results: Sustained increase in LESP was observed during low frequency stimulation, 32.1 ± 12.8 vs. 42.4 ± 18.0 vs. 50.1 ± 23.6, control vs. stimulation vs. post stimulation respectively, p = 0.013. AUC also significantly increased during and after stimulation, 39,320.3 ± 15,722 vs. 51,294 ± 21,826 vs. 59,823.6 ± 28,198.4 mmHgxsec, control vs. stimulation vs. post stimulation respectively, p = 0.01. There was no significant change with other types of ES. NGES induced an initial rise in LESP followed within few seconds by relaxation with slow resumption of pressure over a 1 minute period. L‐NAME increased LESP and augmented the initial rise in LESP following NGES but markedly diminished or abolished the relaxation phase. Atropine lowered LESP and abolished the initial rise in LESP induced by NGES. Conclusions: Low frequency ES of the LES increases LESP in conscious dogs. NGES has dual effect on LESP: an initial stimulation, cholinergically mediated, followed by relaxation mediated by nitric oxide.     

Continuous versus interrupted sutures for repair of episiotomy or second-degree perineal tears: a randomised controlled trial

Objective  To evaluate the repair techniques of continuous and interrupted methods for episiotomy or perineal tears.
Design  A randomised controlled trial.
Setting  The Hospital Universitario Principe de Asturias, a state hospital belonging to the community of Madrid.
Sample  Four hundred forty-five women who had undergone vaginal deliveries with episiotomies or second-grade tearing of the perineum between September 2005 and July 2007.
Methods  One group was repaired with continuous, nonlocking sutures involving the vagina, perineum, and subcutaneous tissues. The other group had continuous, locking sutures of the vagina, interrupted sutures in the perineal muscles, and interrupted transcutaneous sutures. The threads used for stitching were identical in both groups.
Main outcome measures  The participants were questioned regarding the sensation of pain and the use of painkillers on the second and the tenth days, and 3 months postpartum.
Results  When comparing the group with continuous suture to the group with interrupted sutures, the differences included less repair time (1 minute; P = 0.017) and less suture material used (relative risk [RR], 3.2, 95% CI: 2.6–4.0). The comparison of pain on the second and tenth days, and 3 months postpartum were not statistically different between the two techniques (RR, 1.08, 95% CI: 0.74–1.57; RR, 0.96, 95% CI: 0.59–1.55; and RR, 0.68, 95% CI: 0.19–2.46, respectively).
Conclusions  Although we did not demonstrate that one technique was better than the other in the incidence of pain in the short or long term, we showed that episiotomy and perineal tear repairs with continuous suturing were quicker and used less suture material without an increase in complication than interrupted suturing.     

Lipomatous tumors of the liver: evaluation with CT and US

Seven cases of lipomatous masses within the liver parenchyma were demonstrated with computed tomography (CT). Five of these cases were obtained from a retrospective review of 50 cases of renal angiomyolipoma in which the liver was adequately demonstrated. The other two cases were from the files of the Armed Forces Institute of Pathology and had no associated renal lesions. Three of the five cases were associated with tuberous sclerosis. In all seven cases, the fatty tumors appeared on CT scans as a well-defined, 0.8-13-cm mass, with attenuation coefficients of less than -30 HU. On ultrasound studies, the lesions were well circumscribed, highly echogenic, and similar to hemangiomas. While distinctly rare lesions, these lipomatous masses are not as unusual as the literature would indicate. One may anticipate such masses in patients with renal angiomyolipomas and in a relatively high percentage of those with tuberous sclerosis.     

Acute micro-thrombosis after subarachnoid hemorrhage: A new therapeutic target?

Microthrombi formation in the brain following subarachnoid hemorrhage (SAH) has been recognized and suspected to contribute to cerebral ischemia. A recent study found that ultra-early cerebral micro-thrombosis occured four hours after experimental SAH. The number of thrombotic microvessels correlated with brain-blood barrier disruption and neuronal injury. If acute cerebral micro-thrombi also occur in humans, is it time to develop a therapy with systemic thrombolysis for SAH patients?