The use of autologous platelet-rich plasma (PRP) versus no intervention in women with low ovarian reserve undergoing fertility treatment: a non-randomized interventional study.

PURPOSE: To investigate the impact of a 3-month course of intracortical injections of autologous platelet-rich plasma (PRP) upon ovarian reserve markers versus no intervention in women with low ovarian reserve prior to undergoing assisted reproductive technology (ART). METHODS: Prospective controlled, non-randomized comparative study conducted in a private fertility clinic, in Venezuela. Women with abnormal ovarian reserve markers (FSH, AMH and AFC) who declined oocyte donation were allocated to one of the following groups according to patient choice: monthly intracortical ovarian PRP injections for three cycles, or no intervention. Primary outcomes were the change in FSH, AMH and AFC pre- and post-treatment. Secondary outcomes included the number of oocytes collected and fertilized, biochemical/clinical pregnancy rates and miscarriage and live birth rates. RESULTS: Eighty-three women were included, of which 46 received PRP treatment and 37 underwent no intervention. Overall median age was 41 years (IQR 39-44). There were no demographic differences between the study groups. At the 3-month follow-up, women treated with PRP experienced a significant improvement in FSH, AMH and AFC, whereas there was no change in the control group. Furthermore, overall rates of biochemical (26.1% versus 5.4%, P = 0.02) and clinical pregnancy (23.9% versus 5.4%, P = 0.03) were higher in the PRP group, while there was no difference in the rates of first trimester miscarriage and live birth between groups. CONCLUSION: PRP injections are effective and safe to improve markers of low ovarian reserve prior to ART, although further evidence is required to evaluate the impact of PRP on pregnancy outcomes.

The relationship between childhood BMI and adult serum cholesterol, LDL, and ankle brachial index.

OBJECTIVE: Effects of childhood overweight may persist into adulthood. We assessed the effect of childhood overweight on cardiovascular disease high risk factor levels in the same participants as adults, after controlling for adult body mass index (BMI) status. DESIGN: A subset of participants in an observational study (Heartwatch) were contacted approximately 26-27 years after initial enrollment to participate in a follow-up study on the long-term effects of childhood overweight. During follow-up, BMI, waist:hip circumference (WHC), blood pressure (BP), serum lipids, and ankle brachial index (ABI) were measured; additional BMI measures throughout childhood were obtained as available from the electronic medical record. Primary outcomes were ABI and serum low density lipoprotein (LDL). SETTING: The 1982 Heartwatch study was conducted with children participants living in Marshfield, Wisconsin; follow-up included original participants who were re-contacted and agreed to be enrolled. PARTICIPANTS: Participants were a stratified random sample of eligible participants in the original 1982 Heartwatch study. Of the original 3106 participants, 647 adult participants completed follow-up exams. RESULTS: Among males with 1982 BMI ≥ 85(th) percentile, adult BMI, WHC, (both P ≤ 0.001), ABI (P = 0.001), total cholesterol (P = 0.01), LDL (P = 0.003) and BP (P < 0.02) were higher in 2008-2009 as compared to males with 1982 BMI < 85(th) percentile. Among females, BMI, BP and WHC (all P < 0.001) were higher in 2008-2009. BMI in 1982 and 2008-2009 were correlated [r = 0.56 (males); 0.58 (females), P < 0.001]. 2008-2009 BMI was more strongly correlated with 2008-2009 measures of ABI (r = 0.16, P = 0.006, males) and high LDL [r = 0.18, P = 0.002 (males); r = 0.11, P = 0.046 (females)]. 1982 BMI was not independently associated with ABI or LDL after adjusting for adult BMI. CONCLUSION: In a cohort studying childhood and adult overweight, childhood BMI was associated with health outcomes relating to cardiovascular disease in adulthood. However, childhood BMI was not independently related to LDL-C or ABI levels in adulthood after accounting for adult BMI. Longitudinal measurements of BMI and other health risk factors were not found to improve accuracy of models for high cardiovascular disease risk factor levels.

Understanding the needs of smokers who work as routine and manual workers on building sites: results from a qualitative study on workplace smoking cessation.

OBJECTIVES: The number of adults who smoke is decreasing, yet this decreasing trend is not spread evenly across the population, with the greatest number of smokers in the routine/manual worker (R/M) population. This study aimed to gain insight into the beliefs, behaviours and cessation needs of R/M smokers working on construction sites to inform the potential development of a work-based smoking cessation service. STUDY DESIGN: A qualitative study in a work-based setting in the UK. METHODS: Semi-structured focus group discussions and individual interviews (n = 23) with R/M employees on two development sites in London and seven employers. Data were analysed using a framework approach. RESULTS: Key motivations for smoking continuance within this group were evident: physical effects, habit and routine, opportunity and social factors. Employees were knowledgeable about the negative health impacts of smoking, but showed limited awareness of smoking cessation services and aids available. Intentions to give up smoking were common, with favourable attitudes towards the development of a work-based smoking cessation service. CONCLUSION: The milieu of construction sites means that tailored approaches to work-based smoking cessation programmes are needed to maximize potential benefits for both employees and employers. Reconsideration of current Smokefree legislation as it applies to the construction industry is also required.

Association between obesity and vulnerability and serologic response to influenza vaccination in older adults.

BACKGROUND: Serologic response to influenza vaccination declines with age. Few other host factors are known to be associated with serologic response. Our objective was to determine whether obesity and vulnerability independently predicted serologic response to influenza vaccination. METHODS: Adults ≥ 50 years were recruited during the 2008-2009 influenza season. Subjects provided pre- and post-vaccination sera for measuring antibody titers to 2008-2009 vaccine components. Body mass index (BMI) was calculated as weight (kg)/height (m(2)). Data were collected on vulnerability using the vulnerable elders survey (VES13). Logistic regression evaluated the associations between obesity and vulnerability and the serologic response to vaccination (both seroprotection and seroconversion), adjusting for gender, age, comorbidities, pre-vaccination titer, and site. RESULTS: Mean (± standard deviation) age of 415 study subjects was 65 ± 10 years; 40% were obese. Mean BMI was 29 ± 5.6 kg/m(2); mean VES13 was 1.6 ± 1.8. The proportions of subjects who seroconverted and had seroprotective titers were 40% and 49%, respectively, for A/Brisbane/59 (H1N1); 73% and 80% for A/Brisbane/10 (H3N2); and 34% and 94% for B/Florida. Modified VES-13 (score 0-10, with 10 being most vulnerable) was not associated with seroprotection against H1N1 or H3N2, and VES-13 was directly associated with seroconversion to H1N1 but not H3N2 or B. Obesity (BMI ≥ 30 kg/m(2) vs. BMI 18.5-30 kg/m(2)) was not associated with seroprotection for H1N1 or H3N2; obesity was directly associated with seroconversion to H3N2 but not H1N1 or B. Age was inversely associated with seroprotection and seroconversion against H1N1 and with seroconversion to influenza B. CONCLUSION: Based on this sample of older healthy subjects, there were no consistent relationships between VES 13 or obesity and either seroprotection or seroconversion to three influenza vaccine antigens.

Dural infantile hemangioma masquerading as a skull vault lesion.

We describe a case of intracranial dural IH initially diagnosed as a primary skull vault lesion hemangioma due to associated focal hyperostosis. Histopathologic examination of the dural component confirmed IH. The case is discussed in the context of IH within the neural axis.

TNF receptor-associated factor 4 (TRAF4) is a novel binding partner of glycoprotein Ib and glycoprotein VI in human platelets.

BACKGROUND: Reactive oxygen species generation is one consequence of ligand engagement of platelet glycoprotein (GP) receptors GPIb-IX-V and GPVI, which bind VWF/collagen and initiate thrombosis at arterial shear; however, the precise molecular mechanism coupling redox pathway activation to engagement of these receptors is unknown. OBJECTIVE: The objective of this study was to identify novel binding partners for GPIb-IX-V and GPVI that could provide a potential link between redox pathways and early platelet signaling events. METHODS AND RESULTS: Using protein array analysis and affinity-binding assays, we demonstrated that the orphan TNF receptor-associated factor (TRAF) family member, TRAF4, selectively binds cytoplasmic sequences of GPIbß and GPVI. TRAF4, p47(phox) [of the NADPH oxidase (Nox2) enzyme complex] and other redox relevant signaling proteins such as Hic-5, co-immunoprecipitate with GPIb/GPVI from human platelet lysates whilst MBP-TRAF4 or MBP-p47(phox) fusion proteins specifically pull-down GPIb/GPVI. GPIb- or GPVI-selective agonists induce phosphorylation of the TRAF4-associated proteins, Hic-5 and Pyk2, with phosphorylation attenuated by Nox2 inhibition. CONCLUSION: These results describe the first direct association of TRAF4 with a receptor, and identify a novel binding partner for GPIb-IX-V and GPVI, providing a potential link between these platelet receptors and downstream TRAF4/Nox2-dependent redox pathways.

Value and limitations of diffusion-weighted imaging in grading and diagnosis of pediatric posterior fossa tumors.

DWI reportedly accurately differentiates pediatric posterior fossa tumors, but anecdotal experience suggests limitations. In 3 years, medulloblastoma and JPA were differentiated by DWI alone in 23/26 cases (88%). Ependymoma (n = 5) could not be reliably differentiated from medulloblastoma or JPA. A trend toward increased diffusion restriction in higher grade tumors (1/14 grade I, 7%; 9/12 grade IV, 75%) had too much overlap to predict the grade of individual cases. The overlap in ADC between tumor types appeared partly due to technical factors (in small, heterogeneous, calcific, or hemorrhagic tumors) but also likely reflected true histologic variability, given that our 3 overlap cases included a desmoplastic medulloblastoma, an anaplastic ependymoma, and a JPA with restricted diffusion in its nodule. Simple structural features (macrocystic tumor, location off midline) aided in distinguishing JPA from the other tumors in these cases.

Minimum effective bolus dose of oxytocin during elective Caesarean delivery.

BACKGROUND: The aim of this study was to determine the lowest effective bolus dose of oxytocin to produce adequate uterine tone (UT) during elective Caesarean delivery (CD). METHODS: Seventy-five pregnant patients undergoing elective CD under spinal anaesthesia were randomized to receive oxytocin (0.5, 1, 3, 5 units) or placebo. UT was assessed by a blinded obstetrician as either adequate or inadequate, and using a verbal numerical scale score (0-10; 0, no UT; 10, optimal UT) at 2, 3, 6, and 9 min after oxytocin administration. Minimum effective doses of oxytocin were analysed (ED(50) and ED(95)) using logistic regression. Oxytocin-related side-effects (including hypotension) were recorded. RESULTS: There were no significant differences in the prevalence of adequate UT among the study groups at 2 min (73%, 100%, 93%, 100%, and 93% for 0, 0.5, 1, 3, and 5 units oxytocin, respectively). The high prevalence of adequate UT after placebo and low-dose oxytocin precluded determination of the ED(50) and ED(95). UT scores were significantly lower in patients receiving 0 unit oxytocin at 2 and 3 min compared with 3 and 5 units oxytocin (P<0.05, respectively). The prevalence of hypotension was significantly higher after 5 units oxytocin vs 0 unit at 1 min (47% vs 7%; P=0.04). CONCLUSIONS: The routine use of 5 units oxytocin during elective CD can no longer be recommended, as adequate UT can occur with lower doses of oxytocin (0.5-3 units).

Analgesic requirements and postoperative recovery after scheduled compared to unplanned cesarean delivery: a retrospective chart review.

BACKGROUND: Studies examining the effects of various analgesics and anesthetics on postoperative pain following cesarean delivery conventionally use the scheduled cesarean population. This study compares postoperative analgesic requirements and recovery profiles in women undergoing scheduled cesarean compared to unplanned cesarean delivery following labor. We postulated that unplanned cesarean deliveries may increase postoperative analgesic requirements. METHODS: We conducted a retrospective chart review of 200 cesarean deliveries at Lucile Packard Children's Hospital, California. We examined the records of 100 patients who underwent scheduled cesarean delivery under spinal anesthesia (hyperbaric bupivacaine 12 mg with intrathecal fentanyl 10 microg and morphine 200 microg) and 100 patients that following a trail of labor required unplanned cesarean under epidural anesthesia (10-25 mL 2% lidocaine top-up with epidural morphine 4 mg after clamping of the umbilical cord). We recorded pain scores, analgesic consumption, time to first analgesic request, side effects, and length of hospital stay. RESULTS: We found no differences in postoperative pain scores and analgesic consumption between scheduled and unplanned cesarean deliveries for up to five days postoperatively. There were no differences in treatment of side effects such as nausea, vomiting, or pruritus (P>0.05). CONCLUSION: The results indicate that women experience similar pain and analgesic requirements after scheduled compared to unplanned cesarean delivery. This suggests that the non-scheduled cesarean population may be a suitable pain model to study pain management strategies; and that alterations in pain management are not necessary for the unplanned cesarean delivery population.

Combined analysis of eIF4E and 4E-binding protein expression predicts breast cancer survival and estimates eIF4E activity.

Increased eukaryotic translation initiation factor 4E (eIF4E) expression occurs in many cancers, and makes fundamental contributions to carcinogenesis by stimulating the expression of cancer-related genes at post-transcriptional levels. This key role is highlighted by the facts that eIF4E levels can predict prognosis, and that eIF4E is an established therapeutic target. However, eIF4E activity is a complex function of expression levels and phosphorylation statuses of eIF4E and eIF4E-binding proteins (4E-BPs). Our hypothesis was that the combined analyses of these pathway components would allow insights into eIF4E activity and its influence on cancer. We have determined expression levels of eIF4E, 4E-BP1, 4E-BP2 and phosphorylated 4E-BP1 within 424 breast tumours, and have carried out analyses to combine these and relate the product to patient survival, in order to estimate eIF4E activity. We show that this analysis gives greater prognostic insights than that of eIF4E alone. We show that eIF4E and 4E-BP expression are positively associated, and that 4E-BP2 has a stronger influence on cancer behaviour than 4E-BP1. Finally, we examine eIF4E, estimated eIF4E activity, and phosphorylated 4E-BP1 as potential predictive biomarkers for eIF4E-targeted therapies, and show that each determines selection of different patient groups. We conclude that eIF4E's influence on cancer survival is modulated substantially by 4E-BPs, and that combined pathway analyses can estimate functional eIF4E.

Accidental intrathecal sufentanil overdose during combined spinal-epidural analgesia for labor.

A laboring woman was accidentally given 45 microg of sufentanil intrathecally in the course of combined spinal-epidural analgesia. She experienced intense pruritus and transient swallowing difficulty without respiratory depression, but still had incomplete pain relief, with delivery and episiotomy repair requiring additional analgesia. This case highlights the importance of adding local anesthetic to intrathecal opioids to facilitate effective analgesia during the second stage of labor. The contributory systems issues and multiple factors that allowed this error to occur are examined.

Birth weight and systemic lupus erythematosus.

The fetal environment may be a contributing factor in the etiology of some adult diseases. This study examined whether birth weight, birth length and gestational age are associated with the subsequent development of systemic lupus erythematosus (SLE). The Marshfield Clinic Lupus Registry was searched to identify patients who were born at Saint Joseph's Hospital in Marshfield, Wisconsin, USA. Birth data on each case and five age-, sex-, and race-matched controls were recorded from medical and delivery room register records. Perinatal data were obtained for 23 cases and 115 controls. The unadjusted mean birth weight was similar for cases (3407 +/- 581 g) and controls (3422 +/- 514 g). Birth length was not different between groups. Birth weight adjusted for gestational age, analysed by conditional logistic regression, was not statistically significantly different between groups. We concluded that birth weight and length were similar among SLE cases and controls, suggesting that these perinatal characteristics are not associated with subsequent SLE.

Microsatellite instability in sporadic colon cancer is associated with an improved prognosis at the population level.

Some previous studies have reported an improved prognosis in sporadic colon cancers with microsatellite instability, whereas others have not. In addition, relatively few of those reporting an improved prognosis controlled for tumor stage or were population-based. Therefore, we evaluated the relationship between microsatellite instability and prognosis, tumor stage, and other clinical variables in a population-based study of 1026 individuals. Microsatellite instability was determined by the noncoding mononucleotide repeat BAT-26 and the coding mononucleotide repeat in transforming growth factor-beta receptor type II. Significant relationships were seen between microsatellite instability and proximal tumor location, female gender, young and old age at diagnosis, poor histological differentiation, and low tumor stage (P < 0.01). There was a significant relationship between microsatellite instability and improved prognosis, even after adjusting for stage, with a reduction in the risk of death attributable to colon cancer of approximately 60%. Most of this risk reduction occurred in individuals with American Joint Committee on Cancer stage III tumors, although transforming growth factor-beta receptor type II mutations were associated with a significant reduction in colon cancer death in tumors with distant metastases. We conclude that microsatellite instability in sporadic colon cancer is associated with an improved prognosis at the population level.

Microlissencephaly with cardiac, spinal and urogenital defects.

We describe two children with a brain defect similar to that described as 'microlissencephaly', as defined in Barkovich et aL [(1998) Neuroped 29: 113-119]. Concomitant malformations (cardiac, spinal, urogenital) may represent components of a wider syndrome complex; alternatively, or additionally, there may have been a valproate teratogenic effect. The inheritance is likely to be autosomal recessive, although X-linkage cannot be excluded.

Immunohistochemical staining for DNA topoisomerase I, DNA topoisomerase II-alpha and p53 in gastric carcinomas.

New anticancer drugs targeting DNA topoisomerase I (topo I) are showing activity against gastric carcinomas. Laboratory studies have indicated that cells responsive to topo I targeted drugs have elevated levels of topo I, require active DNA replication and may require a functional apoptotic pathway. In this study, we evaluated these potential markers of topo I targeted drug sensitivity in 22 cases of primary gastric carcinoma. By immunohistochemical staining, we observed elevated topo I expression in 15 of 22 neoplasms (68%). By immunohistochemical staining for the proliferation marker DNA topoisomerase II-alpha (topo II-alpha), we observed that 16 of 22 neoplasms (73%) had topo II-alpha indices > than 50 indicating a large number of actively cycling tumor cells. Abnormal p53 expression was observed in 7 of the 22 cases (32%). Of the 22 cases of gastric carcinoma, 8 (36%) had high levels of topo I, a large number of cycling tumor cells and normal p53 expression. These are the molecular parameters that might suggest responsiveness to drugs targeting topo I.

Near-total absence of the cerebellum.

We report five cases of near-total absence of the cerebellum with accompanying pontine hypoplasia. The cerebellar remnant in each case comprised only antero-superior masses, the posterior fossa being otherwise fluid filled. Three of these patients, two teenagers and an infant, presented a fairly consistent clinical and neuroradiological phenotype, and a few similar cases are recorded in the literature. The cerebellar remnant was irregular and asymmetrical, and no ventral pontine prominence was discernible. In at least the older two, cerebellar motor functions were not greatly compromised, and intellectual handicap was of a mild degree. We propose that these cases represent a distinct entity of "near-total absence of the cerebellum with flat ventral pons, and relatively mild clinical affection". All cases have been sporadic, implying that the risk of recurrence within a family may be low. Quite different clinical pictures, of considerably greater severity, are demonstrated in the remaining two cases. One had pontocerebellar hypoplasia type 2, while the other had a complex cerebellar and cerebral malformation.

Hydrolysis of an organophosphate ester by manganese dioxide.

Amorphous manganese dioxide facilitates the hydrolysis of p-nitrophenyl phosphate to p-nitrophenol and orthophosphate despite insignificant adsorption of p-nitrophenyl phosphate or p-nitrophenol to the manganese dioxide. At pH 8, the orthophosphate product is released into solution; at pH 4 and pH 6, some remains adsorbed. The rate of hydrolysis is an order of magnitude more rapid than the same reaction facilitated by iron oxides. Because manganese dioxides are ubiquitous components of soils and sediments, this suggests the possibility of significant abiotic pathways for the formation of bioavailable orthophosphate from phosphate ester precursors.

Clinical and neuroradiologic features of acute disseminated encephalomyelitis in children.

OBJECTIVE: To identify the clinical and neuroradiologic features of acute disseminated encephalomyelitis (ADEM) in childhood. METHODS: A retrospective review was conducted of the medical records and MRI of children who presented to the Royal Children's Hospital in Melbourne with ADEM between January 1993 and December 1998. RESULTS: Of the 31 patients included in this study, 22 (71%) experienced a prodromal illness. Two patients (6%) had received hepatitis B vaccine 3 to 6 weeks before developing their illness. Symptoms and signs typically evolved over several days. Ataxia was the most common presenting feature, occurring in 20 patients (65%). MRI findings were variable, but lesions were most commonly seen bilaterally and asymmetrically in the frontal and parietal lobes. The authors found a high incidence of the corpus callosal and periventricular changes more typically associated with MS, but they also found a high rate of deep gray matter involvement (61% of patients). The use of high-dose IV methylprednisolone was usually associated with rapid recovery. Eighty-one percent of patients recovered completely, with only mild sequelae recorded in the remaining children. CONCLUSION: In the absence of a biological marker, the distinction between ADEM and MS cannot be made with certainty at the time of first presentation, but the authors suggest that a viral prodrome, early-onset ataxia, high lesion load on MRI, involvement of the deep gray matter, and absence of oligoclonal bands are more indicative of ADEM.