Prevention of transfusion-associated graft-versus-host disease: selection of an adequate dose of gamma radiation

To determine the optimal dose of gamma radiation necessary to inhibit T- lymphocyte function and prevent transfusion-acquired graft-versus-host disease (TA-GVHD), a donor plateletpheresis component was initially divided into ten 20-mL samples. One sample was not irradiated, while the other nine samples were treated with gamma radiation at doses ranging from 500 to 4500 cGy. T-lymphocyte function was subsequently measured by mixed lymphocyte cultures and mitogen stimulation assays. The results were assessed in each test by calculating the percentage of inhibition of each irradiated sample as compared to that of the unirradiated sample. The accuracy of the delivered dose of gamma radiation was measured with thermoluminescent dosimeters. It was concluded that a nominal dose of 3000 cGy (actual dose delivered, 2898 cGy) is the appropriate amount of gamma radiation needed to eliminate T- lymphocyte-mediated graft-versus-host disease.     

Placebo response trajectories in short-term and long-term antipsychotic trials in schizophrenia

Increasing rates of placebo response have eroded placebo-control group differences in randomized controlled trials, although the reasons for this trend remain unclear. Data were extracted from the placebo arms in two identically designed 6-week studies and one 52-week study in the ziprasidone clinical trial database. The objective of this analysis was to identify distinct patterns of placebo response trajectories that could capture individual variability in the time course of change during a 1-year trial using growth mixture latent class analyses. These long-term placebo response patterns were contrasted with two 6-week schizophrenia studies. The placebo response trajectory analysis that showed 58% (Group 4) had gradual improvement in the PANSS negative subscale score (p<0.05), fewer dropouts (p<0.05) and improvement in abnormal movements, contrasted with 3 other trajectory groups that showed worsening on these measures. Almost all subjects (98%) in this symptom improvement group were treated with conventional antipsychotics just prior to placebo treatment. In contrast, the trajectory analyses showed worsening of symptoms based on PANSS total score in the 1-year trial (+15.5, SEM 2.6). Some gradual improvement of symptoms (-14.0, SEM 1.6) was also noted in 67% (n=114) of patients in the 6-week short term trials. Our findings indicate that substantial heterogeneity in placebo response occurs in both short-term and long-term trials. The placebo response trajectories appeared to depend on the efficacy measure of symptom reduction chosen, prior antipsychotic use profile, and trial durations. Further research is warranted to examine the trajectory patterns of placebo responses in independent patient populations.     

Increased expression of TrkB and Capzb2 accompanies preserved cognitive status in early Alzheimer disease pathology

Brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB) may influence brain reserve, the ability of the brain to tolerate pathological changes without significant decline in function. Here, we explore whether a specifically vulnerable population of human neurons shows a compensatory response to the neuropathological changes of Alzheimer disease (AD) and whether that response depends on an upregulation of the BDNF pathway. We observed increased neuronal TrkB expression associated with early-stage AD pathology (Braak and Braak stages I-II) in hippocampal CA1 region samples from cognitively intact Framingham Heart Study subjects (n = 5) when compared with cognitively intact individuals with no neurofibrillary tangles (n = 4). Because BDNF/TrkB signaling affects memory formation and retention through modification of the actin cytoskeleton, we examined the expression of actin capping protein β2 (Capzb2), a marker of actin cytoskeleton reorganization. Capzb2 expression was also significantly increased in CA1 hippocampal neurons of cognitively intact subjects with early-stage AD pathology. Our data suggest that increased expression of TrkB and Capzb2 accompanies adequate brain reserve in the initial stages of AD pathology. In subsequent stages of AD, the higher levels of TrkB and Capzb2 expression achieved may not be sufficient to prevent cognitive decline.     

Intensity of Central Pain: Analysis of Pain Scores in 18 Patients

Abstract: The aim of this clinical study was to investigate the intensity of central pain in 18 patients. Each patient systematically recorded their own pain scores a total of 700 times (ie, 7 times/day for 100 consecutiv e days) using a standard four-point scale. In all 18 patients, the intensity of pain varied considerably (ranging in grade from no pain, mild pain, moderate pain to severe pain). During the 100 days, the average number of times (percentage of total) that each grade of pain intensity was scored was: no pain 7.4 (1.1%); mild pain 570.9 (81.6%); moderate pain 93.4 (13.3%), and severe pain 28.3 (4%). The difference between mild pain and moderate, severe, or no pain was significant. Thus, in our patient group the intensity of central pain was mostly mild, not severe. In contrast to other reports, our data suggest that to state that the intensity of central pain continues to be intolerable and severe throughout the day is an exaggeration. Among our 18 patients, an exacerbation of pain intensity was observed 507 times. Of these 507 events, 392 (77.3%) were due to specifiable factors and 115 (22.7%) were due to unknown factors. The specifiable factors could be attributed to: emotional factors 261 times (66.6%), somatic stimuli 44 times (11.2%), weather 38 times (9.7%), fatigue 29 times (7.4%), visceral activity 20 times (5.1%). Since there is no universally effective treatment for central pain, the strategy to manage central pain should primarily focus (if possible) on prevention of the exacerbating factors of central pain.     

Patient Barriers to Accessing Surgical Cleft Care in Vietnam: A Multi-site,Cross-Sectional Outcomes Study

Background

Most people who lack adequate access to surgical care reside in low- and lower–middle-income countries. Few studies have analyzed the barriers that determine the ability to access surgical treatment. We seek to determine which barriers prevent access to cleft care in a resource-limited country to potentially enable barrier mitigation and improve surgical program design.

Methods

A cross-sectional, multi-site study of families accessing care for cleft lip and palate deformities was performed in Vietnam. A survey instrument containing validated demographic, healthcare service accessibility, and medical/surgical components was administered. The main patient outcome of interest was receipt of initial surgical treatment prior to 18 months of age.

Results

Among 453 subjects enrolled in the study, 216 (48%) accessed surgical care prior to 18 months of age. In adjusted regression models, education status of the patient’s father (OR 1.64; 95% CI 1.1–2.5) and male sex (OR 1.61; 95% CI 1.1–2.4) were both associated with timely access to care. Distance and associated cost of travel, to either the nearest district hospital or to the cleft surgical mission site, were not associated with timing of access. In a sensitivity analysis considering care received prior to 24 months of age, cost to attend the surgical mission was additionally associated with timely access to care.

Conclusions

Half of the Vietnamese children in our cohort were not able to access timely surgical cleft care. Barriers to accessing care appear to be socioeconomic as much as geographical or financial. This has implications for policies aimed at reaching vulnerable patients earlier.

     

Tuberous sclerosis: characteristics at CT and MR imaging

Computed tomography (CT) and magnetic resonance (MR) imaging findings were reviewed in 26 patients with tuberous sclerosis. All patients underwent CT; 16 patients underwent both. The CT features included subependymal nodules in 25 of 26 patients (96%) and calcifications in 23 of 26 (88%). Parenchymal hamartomas (cortical tubers) were seen in 23 of 26 patients (88%). These lesions had less attenuation than surrounding brain in 16 of 26 patients (62%) and were calcified in 14 of 26 patients (54%). Contrast enhancement of a lesion, indicating a subependymal giant cell astrocytoma, occurred in three of 26 patients (12%). The MR imaging characteristics included subependymal nodules (periventricular nodules) of intermediate signal intensity in ten of the 16 patients (63%). Parenchymal hamartomas, demonstrated in 15 of the 16 patients (94%), usually exhibited long T1 and T2 relaxation characteristics. The pattern was noted to be reversed in the two newborn patients (13%). One parent demonstrated a forme fruste at CT but had a normal MR image.     

Responsiveness of human male volunteers to immunization with ovine follicle stimulating hormone vaccine: results of a pilot study

A study of 140 days duration was performed to examine if human male volunteers (n = 5) respond to ovine follicle stimulating hormone (oFSH) immunization (administered adsorbed on Alugel on days 1, 20, 40 and 70) by producing antibodies capable of both binding and neutralizing bioactivity of human FSH. The kinetics of antibody production for both the immunogen (oFSH) and the cross-reactive antigen (hFSH) were essentially similar. The volunteers responded only to the first two immunizations. The boosters given on days 40 and 70 were ineffective, probably because of the presence of substantial amounts of circulating antibody to oFSH. Of the antibodies generated to oFSH, 25-45% bound hFSH with a mean binding affinity of 0.65 x 10(9) +/- 0.53 M(-1). The binding capacities at the time of high (30-80 days of immunization) and low (>110 days) titres were 346 +/- 185 and 10.5 +/- 5.8 ng hFSH/ml respectively. During the period of high titre, free serum FSH (value in normal males 1-5 ng/ml) was not monitorable. A 50 microl aliquot of the antiserum obtained from different volunteers between days 30 and 80 and on day 140 blocked binding of (125)I-labelled hFSH to its receptor by 82 +/- 9.7 and 53 +/- 12.2% respectively. The antibody produced was specific for FSH, and no significant change in the values of related glycoprotein hormones (luteinizing hormone/testosterone and thyroid stimulating hormone/thyroxine) were recorded. Seminal plasma transferrin, a marker of Sertoli cell as well as of seminiferous tubular function, showed marked reduction (30-90%) following immunization with oFSH. Considering that endogenous FSH remained neutralized for approximately one sperm cycle only (65 days), the reduction in sperm counts (30-74%) exhibited by some volunteers is encouraging. Immunization with oFSH did not result in any significant changes in haematology, serum biochemistry or hormonal profiles. There was no production of antibodies capable of interacting with non- specific tissues. It is concluded that it should be possible to obtain a sustained long-term blockade of endogenous FSH action in men by using oFSH as an immunogen. This is a prerequisite for obtaining significant reduction in the quality and quantity of spermatozoa produced, thus leading to infertility.      

Teenage mothering, admission to hospital, and accidents during the first 5 years

One thousand and thirty-one singleton children of teenage mothers were compared with 10 950 singleton children of older mothers in a national longitudinal cohort study. Children born to teenage mothers and living with them during the first 5 years were more liable to hospital admissions, especially after accidents and for gastroenteritis, than were children born to and living with older mothers. Frequent accidents, poisoning, burns, and superficial injuries or lacerations were more often reported by teenage mothers. The association of teenage mothering with greater likelihood that children would have accidents or be admitted to hospital remained highly significant even after controlling for social and biological confounding influences. Although in part a marker for adverse socioeconomic circumstances, low maternal age appears to be a health hazard for children.