Longitudinal multi-modal muscle-based biomarker assessment in motor neuron disease

Journal of Neurology - Clinical phenotypic heterogeneity represents a major barrier to trials in motor neuron disease (MND) and objective surrogate outcome measures are required, especially for...     

Effects of dexamethasone on selective lymphocyte subpopulations in hypercortisolemic patients with anorexia nervosa and with bulimia nervosa: Preliminary report

The studies reported here describe the effects of intravenous (IV) administration of the synthetic glucocorticoid dexamethasone (DEX) on certain neuroendocrine and immunological measures in hypercortisoiemic patients with anorexia nervosa (AN) and with bulimia nervosa (BN). The results demonstrate that failure to suppress cortisol levels after DEX administration in patients with AN is associated with failure to reduce the level of adrenocorticotropic hormone (ACTH), the ratio of CD4-to-CD8 lymphocytes, the percent and number of circulating CD4 lymphocytes, and the percent and number of virgin CD4 cells (CD4+CD45RA+). Administration of DEX to patients with BN suppressed plasma ACTH and cortisol levels, reduced the CD4/CD8 ratio and the percent and number of CD4 and of CD4 + CD45RA+ lymphocytes, and increased the percent and number of circulating CD8 lymphocytes. Administration of DEX failed to alter other immune measures in either patient population, including circulating populations of B and natural killer cells, the proliferative response to T-cell mitogen, and the number of glucocorticoid receptors in circulating lymphocytes.     

Temporal definition of haematopoietic stem cell niches in a large animal model of in utero stem cell transplantation

The fetal sheep model has served as a biologically relevant and translational model to study in utero haematopoietic stem cell transplantation (IUHSCT), yet little is known about the ontogeny of the bone marrow (BM) niches in this model. Because the BMmicroenvironment plays a critical role in the outcome of haematopoietic engraftment, we have established the correlation between the fetal‐sheep and fetal‐human BM niche ontogeny, so that studies addressing the role of niche development at the time of IUHSCT could be accurately performed. Immunofluorescence confocal microscopic analysis of sheep fetal bone from gestational days (gd) 25–68 showed that the BM microenvironment commences development with formation of the vascular niche between 25 and 36 gd in sheep; correlating with the events at 10–11 gestational weeks (gw) in humans. Subsequently, between 45 and 51 gd in sheep (c. 14 gw in humans), the osteoblastic/endosteal niche started developing, the presence of CD34⁺ CD45⁺ cells were promptly detected, and their number increased with gestational age. IUHSCT, performed in sheep at 45 and 65 gd, showed significant haematopoietic engraftment only at the later time point, indicating that a fully functional BM microenvironment improved engraftment. These studies show that sheep niche ontogeny closely parallels human, validating this model for investigating niche influence/manipulation in IUHSCT engraftment.     

First occurrence of native cymothoids parasites on introduced rabbitfishes in the Mediterranean Sea

This paper presents the first record of two native Mediterranean cymothoid species caught attached to introduced Lessepsian rabbitfishes. This is also the first record of cymothoids from the coastal waters of Libya. Anilocra physodes was collected from Siganus luridus while Nerocila bivittata was found on both Siganus rivulatus and S. luridus. Rabbitfishes in the southern central Mediterranean have acquired native Mediterranean cymothoids but do not seem to be infested along the Levantine coast.     

Treatment of radioulnar synostosis by radical excision and interposition of a radial forearm adipofascial flap

A patient had radical excision of type II diaphyseal radioulnar synostosis and interposition of a radial forearm adipofascial flap. Neither adjuvant nonsteroidal anti-inflammatory medications nor radiation therapy were used. Three years after surgery the patient showed 90 degrees of pronation and 90 degrees of supination without any evidence of recurrence.     

DNR directives are established early in mechanically ventilated intensive care unit patients

Purpose

Setting treatment goals in the intensive care unit (ICU) often involves resuscitation decisions. Our objective was to study the rate of establishing do-not-resuscitate (DNR) directives, determinants, and outcomes of those directives for mechanically ventilated patients.

Methods

In a multicentre observational study, we included consecutive adults with no DNR directives within 24 hr of ICU admission who were mechanically ventilated for at least 48 hr. We identified the rate with which DNR directives were established, and factors associated with these directives.

Results

Among 765 patients, DNR directives were established for 231 (30.2%) patients; 143 (62.1%) of these were established within the first week. Factors independently associated with a DNR directive were: patient age [> 75 yr (hazard ratio [HR] 2.3, 95% confidence interval 1.5–3.4], 65 to 74yr(HR 1.8, 1.2–2.7), 50 to 64 yr (HR 1.4, 1.0–2.2) relative to < 50 yr); medical rather than surgical diagnosis (HR 1.8, 1.3–2.5); multiple organ dysfunction score (HR 1.7 for each five-point increment, 1.4–2.0); physician prediction of ICU survival [< 10% (HR 15.0, 6.7–33.6)], 10 to 40% [(HR 5.0, 2.3–11.2), 41 to 60% (HR 4.0, 1.8–9.0) relative to > 90%]; and physician perception of patient preference to limit life support (no advanced life support [(HR 5.8, 3.6–9.4) or partial advanced life support (HR 3.2, 2.2–4.6) compared to full measures].

Conclusion

One third of mechanically ventilated patients had DNR directives established early during their ICU stay after the first 24 hr of admission. The strongest predictors of DNR directives were physician prediction of low probability of survival, physician perception of patient preference to limit life support, organ dysfunction, medical diagnosis and age.     

Modification of the peritoneoscopic technique of peritoneal dialysis catheter insertion: experience of an interventional nephrology program

Bowel perforation is a well-recognized complication of peritoneal dialysis catheter insertion and is associated with increased morbidity and cost of medical care. In this article we describe our 2-year experience (August 2001-October 2003) with a modified peritoneoscopic technique of peritoneal dialysis catheter insertion to minimize the incidence of bowel perforation. Seventy patients underwent 82 consecutive peritoneal dialysis catheter insertions using the innovative technique. The modified technique is very similar to the traditional peritoneoscopic procedure except for the following differences. To gain access to the peritoneal cavity, a Veress insufflation needle (Ethicon Endo-Surgery Inc., Cincinnati, OH) is utilized instead of the trocar. In contrast to the sharp tip of the trocar, the Veress needle has a blunt, self-retracting end. In addition, the Veress needle is only 14 gauge as opposed to the 2.2 mm diameter of the trocar. Upon introduction of the Veress needle into the abdominal cavity, two "pops" are discerned similar to the trocar. After introduction, 400-500 cc of air are infused and the needle is removed. The infusion of air creates a space between the peritoneal surface of the anterior abdominal wall and the bowel loops. At this point, the cannula with trocar is inserted into the space created. The rest of the steps of the procedure are the same as the traditional peritoneoscopic technique. Utilizing the innovative technique, all 82 catheter insertions were performed successfully without a single bowel perforation. No other complications except for catheter migration (n = 2) were noted. The extra cost of the needle (35 USD) should be viewed in the context of the costs associated with management of a bowel perforation. Large-scale studies are needed to confirm the superiority of this innovative technique over the traditional peritoneoscopic insertion found in our case series. In the interim, however, the increased morbidity and cost associated with bowel perforation calls for logical measures to be taken to avoid this dreaded complication.     

Comparing the effects of 8-week treatment with fluoxetine and imipramine on fasting blood glucose of patients with major depressive disorder

This study was designed to compare the effects of fluoxetine and imipramine on fasting blood glucose (FBG) in patients with major depressive disorder. Sixty nondiabetic patients with major depressive disorder (based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) entered this randomized, double-blind study. Patients did not receive any medication affecting serum FBG levels for at least 2 weeks before the initiation of the study. Patients were assigned to receive 20 to 40 mg/d of fluoxetine or 75 to 200 mg/d of imipramine for 8 weeks. Pregnant women and patients with diabetes mellitus and a history of any major heart disease were excluded from this study. Additionally, none of the patients should have received electroconvulsive therapy within 6 months before the initiation of the antidepressants. FBG levels were measured at the initiation, as well as 4 and 8 weeks after starting antidepressants. Nineteen patients in the fluoxetine and 24 patients in the imipramine groups completed the study. In the fluoxetine group, FBG level was decreased from 88.5 mg/dL (baseline) to 85.0 mg/dL at week 4 (P = 0.73), and to 79.8 mg/dL at week 8 (P < 0.001). On the other hand, in the imipramine group, FBG level was increased from 86.96 mg/dL (baseline) to 89.71 mg/dL at week 4 (P = 0.079), and to 96.90 mg/dL at week 8 (P < 0.001). This 8-week study showed that FBG levels may decrease in depressive patients receiving fluoxetine and may increase in those patients treated with imipramine. Therefore, it is suggested to measure and monitor FBG before initiation and during treatment with fluoxetine and imipramine.