Unusual kinetics of white cell clearance in transfused mice

BACKGROUND: Donor white cells (WBCs) in blood transfusions are responsible for complications in recipients, including alloimmunization, graft-versus-host disease (GVHD), and virus transmission and reactivation. The recent use of sequence-specific polymerase chain reaction assays to monitor the kinetics of clearance of donor WBCs in transfused humans and dogs found transient recirculation of donor lymphocytes on Days 3 to 5 after transfusion; this presumably reflected an abortive GVHD reaction to major histocompatibility complex-incompatible recipient cells, after which donor WBCs were cleared to undetectable levels. STUDY DESIGN AND METHODS: This study sought to develop a murine model to further characterize the kinetics and major histocompatibility complex restriction of donor WBC clearance. A sensitive murine Y chromosome- specific polymerase chain reaction assay was developed and applied to serial blood samples collected after transfusions of allogeneic blood to naive inbred, primed inbred, and outbred mice, as well as after transfusions of gamma-radiated blood to naive inbred mice. RESULTS: In inbred mice, both naive and primed to the allogeneic blood donor, transfused WBCs were not cleared to undetectable levels for more than 1 month after transfusion. Transfused outbred mice also showed prolonged donor WBC survival, although at lower levels than inbred mice. There was no evidence of GVHD in either inbred or outbred mice, and gamma radiation had no significant impact on donor WBC persistence. CONCLUSION: These results contrast with the rapid clearance of donor WBCs observed in humans and dogs. The immunologic basis for this discrepancy remains unclear. Caution should be exercised in any extrapolation to humans of conclusions drawn from results in transfused mice.     

The MG-QOL15 for following the health-related quality of life of patients with myasthenia gravis

The MG-QOL15 is helpful in informing the clinician about the patient's perception of the extent of and dissatisfaction with myasthenia gravis (MG)-related dysfunction. The aims of this study were to determine the usefulness of the MG-QOL15 for following individuals with MG and to guide clinical researchers who plan to use the MG-QOL15. We assessed sensitivity and specificity for detecting clinical change and evaluated test-retest reliability. Sensitivities and specificities of various cut-points of change in scores are presented. Also presented are means and standard deviations of MG-QOL15 scores for all patients and for subgroups of patients. The test-retest reliability coefficient was 98.6%. The MG-QOL15 has an acceptable longitudinal construct validity. We consider this instrument to be most useful for informing the clinician about the patient's perception and tolerance of MG-related dysfunction. More objective measures, such as the MG Composite, should also be used to follow disease severity.     

Cannabidiolic acid prevents vomiting in Suncus murinus and nausea-induced behaviour in rats by enhancing 5-HT1A receptor activation

Background and Purpose

To evaluate the ability of cannabidiolic acid (CBDA) to reduce nausea and vomiting and enhance 5-HT_1A receptor activation in animal models.

Experimental Approach

We investigated the effect of CBDA on (i) lithium chloride (LiCl)-induced conditioned gaping to a flavour (nausea-induced behaviour) or a context (model of anticipatory nausea) in rats; (ii) saccharin palatability in rats; (iii) motion-, LiCl- or cisplatin-induced vomiting in house musk shrews (Suncus murinus); and (iv) rat brainstem 5-HT_1A receptor activation by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and mouse whole brain CB₁ receptor activation by CP55940, using [³⁵S]GTPγS-binding assays.

Key Results

In shrews, CBDA (0.1 and/or 0.5 mg·kg⁻¹ i.p.) reduced toxin- and motion-induced vomiting, and increased the onset latency of the first motion-induced emetic episode. In rats, CBDA (0.01 and 0.1 mg·kg⁻¹ i.p.) suppressed LiCl- and context-induced conditioned gaping, effects that were blocked by the 5-HT_1A receptor antagonist, WAY100635 (0.1 mg·kg⁻¹ i.p.), and, at 0.01 mg·kg⁻¹ i.p., enhanced saccharin palatability. CBDA-induced suppression of LiCl-induced conditioned gaping was unaffected by the CB₁ receptor antagonist, SR141716A (1 mg·kg⁻¹ i.p.). In vitro, CBDA (0.1–100 nM) increased the E_max of 8-OH-DPAT.

Conclusions and Implications

Compared with cannabidiol, CBDA displays significantly greater potency at inhibiting vomiting in shrews and nausea in rats, and at enhancing 5-HT_1A receptor activation, an action that accounts for its ability to attenuate conditioned gaping in rats. Consequently, CBDA shows promise as a treatment for nausea and vomiting, including anticipatory nausea for which no specific therapy is currently available.     

Unopposed appetite (orexigenic) mechanisms in the near-term ovine fetus: central leptin does not inhibit sucrose ingestion

Objective: Leptin is produced in adipocytes and is present in the term fetus. In the adult, leptin acts centrally to inhibit neuropeptide Y-induced carbohydrate intake. We sought to examine if central leptin alters fetal ingestion of oral sucrose in the near-term ovine fetus.

Methods: Five pregnant ewes and fetuses were prepared with fetal vascular, sublingual and intracerebroventricular (ICV) catheters and esophageal electromyogram electrodes, and studied at 132?±?1 days' gestation (term 145–150 days). Following a 2-h baseline period, 10% sucrose was infused sublingually (0.25?ml/min) for the duration of the study. At time 4?h, leptin (0.075?mg/kg) was administered ICV and fetal swallowing was monitored for an additional 6?h.

Results: During the basal period, fetal swallowing averaged 0.7?±?0.1 swallows/min. Fetal swallowing increased significantly in response to 10% sucrose (1.2?±?0.1 swallows/min; p?<?0.05). In response to ICV leptin, fetal swallowing remained significantly elevated at 2, 4 and 6?h (1.3?±?0.4, 1.4?±?0.3 and 1.5 ±?0.2 swallows/min, respectively; p?<?0.05 vs. control).

Conclusions: These results indicate that central leptin inhibition of sucrose ingestion is not functional in the near-term fetus. We speculate that a leptin-mediated anorexigenic response is not present at birth, such that unopposed appetite stimulatory mechanisms in the newborn may facilitate rapid newborn weight gain despite high body fat levels.     

Vaginal birth after Cesarean rates are declining rapidly in the rural state of Maine

Objective: The American College of Obstetricians and Gynecologists (ACOG) revised its practice bulletin on vaginal birth after Cesarean (VBAC) in October 1998 and July 1999 to require the presence of a surgeon, anesthesiologist and operating personnel throughout the trial of labor for patients with prior Cesarean. This study measures the change in VBAC rates from 1998 to 2001 and examines possible reasons for this change.

Study design: We examined birth certificate and hospital data in the State of Maine from 1998 to 2001. Hospital-specific rates for primary Cesareans, total Cesareans, repeat Cesareans and vaginal deliveries after previous Cesarean were obtained. Additionally, we surveyed current obstetric-care providers in Maine regarding reasons for change in VBAC rates at their institutions.

Results: VBAC rates declined by over 50% from 30.1 to 13.1%. The total Cesarean rate climbed from 19.4 to 24.0%. The most commonly reported reason for decrease in VBAC varied depending on whether a practitioner's hospital met ACOG guidelines.

Conclusion: A marked decline in VBAC occurred after the change in ACOG vaginal birth after Cesarean policy. Multiple factors have contributed to this decline, including patients refusing VBAC after counseling and inability of institutions to meet ACOG guidelines.     

Endoscopic innovations to increase the adenoma detection rate during colonoscopy

Up to a quarter of polyps and adenomas are missed during colonoscopy due to poor visualization behind folds and the inner curves of flexures, and the presence of flat lesions that are difficult to detect. These numbers may however be conservative because they mainly come from back-to-back studies performed with standard colonoscopes, which are unable to visualize the entire mucosal surface. In the past several years, new endoscopic techniques have been introduced to improve the detection of polyps and adenomas. The introduction of high definition colonoscopes and visual image enhancement technologies have been suggested to lead to better recognition of flat and small lesions, but the absolute increase in diagnostic yield seems limited. Cap assisted colonoscopy and water-exchange colonoscopy are methods to facilitate cecal intubation and increase patients comfort, but show only a marginal or no benefit on polyp and adenoma detection. Retroflexion is routinely used in the rectum for the inspection of the dentate line, but withdrawal in retroflexion in the colon is in general not recommended due to the risk of perforation. In contrast, colonoscopy with the Third-Eye Retroscope^® may result in considerable lower miss rates compared to standard colonoscopy, but this technique is not practical in case of polypectomy and is more time consuming. The recently introduced Full Spectrum Endoscopy™ colonoscopes maintains the technical capabilities of standard colonoscopes and provides a much wider view of 330 degrees compared to the 170 degrees with standard colonoscopes. Remarkable lower adenoma miss rates with this new technique were recently demonstrated in the first randomized study. Nonetheless, more studies are required to determine the exact additional diagnostic yield in clinical practice. Optimizing the efficacy of colorectal cancer screening and surveillance requires high definition colonoscopes with improved virtual chromoendoscopy technology that visualize the whole colon mucosa while maintaining optimal washing, suction and therapeutic capabilities, and keeping the procedural time as low and patient discomfort as optimal as possible.     

Validity of BMI based on self-reported weight and height in adolescents

Aim:  To assess in a subset of a nationally representative sample of Portuguese adolescents, the validity of Body Mass Index (BMI) based on self-reported weight and height.
Methods:  This study included 462 students in grades 6, 8 and 10 (mean age 14.0 ± 1.9 years) from 12 public schools randomly selected from the list of schools which took part in the 2006 Health Behaviour in School Aged Children Portuguese survey, corresponding to approximately 10% of the sample. Self-reported weight and height were recorded and then measured.
Results:  Prevalence of normal weight, overweight and obesity based on self-report compared with that of measured values was not significantly different for boys and girls, and among age groups. BMI based on measured weight and height was underestimated compared with BMI based on self-reported data, both among girls and boys. Larger limits of agreement were found for boys, indicating a higher variability of self-reported BMI in estimating measured BMI, specifically below the age of 14 years.
Conclusion:  These data suggest that BMI based on self-reported weight and height is not accurate for BMI prediction at an individual level. However, self-reported BMI may be used as a simple and valid tool for BMI estimates of overweight and obesity in epidemiological studies.