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Background: Juvenile systemic lupus erythematosus (JSLE) is diagnosed in children younger than 18 years of age. Depression and anxiety are common, but not well understood in JSLE. We investigated the clinical and psychological factors associated with the psychological manifestations of JSLE. Methods: Twenty-nine JSLE patients were recruited for the study. They responded to surveys testing their psychological status and perceptions about their health, including the Hospital Anxiety and Depression scale, the Fatigue Severity Scale, and a Medical outcomes questionnaire (the SF-36). Clinical lab results were obtained from the patients’ medical records. Univariate and multivariate analyses were used to compare the patient populations with adult-onset SLE (ASLE) patients and unaffected controls, finding indicators that correlated with depression and anxiety in JSLE patients. Results: Kidney disease was associated with depression in the JSLE patients. The BUN levels, BUN/creatinine ratio, and leukocyturia were all significantly associated with depressive symptoms. The BUN/creatinine ratio was the most predictive laboratory value for both depression and anxiety. The JSLE patients had less depression than the ASLE, although not less anxiety. JSLE patients had comparable levels of fatigue and pain to the adult-onset SLE patients. Age and education were protective against depression in the JSLE patients. Conclusions: Kidney function correlated with symptoms of depression and anxiety. This may mean that symptomatology is an important indicator of whether the patient needs psychiatric care. Age and education were likely protective against depression in the JSLE population.

Introduction: New York City is one of the areas most affected by the COVID-19 pandemic in the United States. Healthcare workers are among those at high risk of contracting the virus, and a vital source of information and trust in vaccines to the community. Methods: This study was conducted about attitudes towards COVID-19 vaccination among healthcare workers at a public hospital in New York City during the beginning of COVID-19 vaccination. 428 hospital employees responded. Results: Several factors were significantly associated with vaccine attitudes, including demographics such as gender (p = 0.002), age (p = 0.005), race (p &lt, 0.001) and home location (p &lt, 0.001), role within the hospital (p &lt, 0.001), knowledge about the virus (p &lt, 0.001) and confidence in and expectations about personal protective equipment and behaviors (p &lt, 0.001). Structural equation modeling revealed that the most predictive factors were prior vaccine attitudes and concern with the speed of testing and approval of the vaccines (p &lt, 0.001). Multivariate analysis reinforced these, while also identifying perceived personal risk as significant (p = 0.033). Conclusions: Several modifiable factors that reflect confidence in science, scientific knowledge, personal risk perception, experience and medical authority are correlated with vaccine attitudes, indicating that a holistic educational approach to improve trust in science is likely to be effective in long-term reduction in vaccine hesitancy.

Background and purposeNon-traditional risk factors such as chronic inflammation, oxidative stress and thrombogenic factors are believed to contribute to the excess stroke risk in chronic kidney disease (CKD) by triggering vascular injury and endothelial dysfunction. We aimed to determine how well a panel of biomarkers representative of these factors would correlate with estimated glomerular filtration rate (eGFR) in patients with recent transient ischaemic attack (TIA) or stroke. We also investigated whether eGFR would confound previously reported associations between biomarkers and mortality.MethodsWe studied a panel of 16 blood biomarkers related to inflammation, thrombosis, atherogenesis and cardiac or neuronal cell damage in TIA or ischaemic stroke in a population-based study (Oxford Vascular Study). Biomarker levels were log-transformed and correlated with eGFR, adjusted for age. Cox proportional hazard models were used for survival analysis.ResultsAmong 1297 patients with TIA or stroke, 52.7% (n=684) of patients had CKD (eGFR 2). There was a moderate correlation between log-eGFR and the log-transformed soluble tumour necrosis factor receptor-1 (R2=0.21), attenuating with adjustment for age (R2=0.12). There were moderate-to-strong correlations with markers of cardiac injury, N-terminal pro-brain natriuretic peptide and heart-type fatty acid binding protein (hFABP, R2=0.14 and 0.34, respectively). The strongest correlation after adjustment for age was between hFABP and eGFR (R2=0.20). Adjusting for eGFR did not impact any biomarker associations with mortality.ConclusionsCorrelations between biomarkers related to inflammation and thrombosis with renal dysfunction in the setting of cerebrovascular events were generally modest after adjustment for age, suggesting that putative risk factors such as chronic inflammation or coagulopathy are unlikely to be important stroke mechanisms in patients with CKD.

Summary Background SARS-CoV-2 is the virus responsible for the current global pandemic, COVID-19. Because this virus is novel, little is known about its sensitivity to disinfection. Methods We performed suspension tests against SARS-CoV-2 using three commercially available quaternary ammonium compound (Quat) disinfectants and one laboratory-made 0.2% benzalkonium chloride solution. Findings Three of the four formulations completely inactivated the virus within 15 s of contact, even in the presence of a soil load or when diluted in hard water. Conclusion Quats rapidly inactivate SARS-CoV-2, making them potentially useful for controlling SARS-CoV-2 spread in hospitals and the community.

Patients with autoimmune disorders (AD) have altered cancer risks compared to the general population. Systemic lupus erythematosus and multiple sclerosis lead to a heightened risk for hematological malignancies and decreased risk for breast, ovarian, and prostate malignancies. Often patients with autoimmune disease have dysregulated antiviral immune responses, including against oncogenic viruses. To uncover the relationship between viral incidence and cancer risk in the context of autoimmune disease, we extracted electronic health records (EHR) from Vanderbilt University. ICD-9/10 codes and laboratory values were collected for hematological, lung, anal-vaginal, thyroid, hepatobiliary, bladder, prostate, and breast cancers; and viruses including Epstein Barr virus (EBV), Human papilloma virus (HPV), and Hepatitis A/B/C (Hep). Only viral infections that led to a physician visit or laboratory test were entered into the EMR; therefore, only clinically relevant cases were noted and considered positive in this study. The relationship between virus infection and cancer in an SLE cohort (SLE-cases n = 2,313, and SLE-controls n = 5,702) and an MS cohort (MS-case n = 7,277, MS-control n = 7,277) was examined by multilinear logistic regression. Viral infection was strongly associated with increased risk for cancer overall. SLE and MS patients were more susceptible to all viral infections. MS patients trended toward increased risk for cancers overall, while decreased risk for hormone-based cancers in SLE patients non-significantly reduced their risk for overall cancer. Both SLE and MS patients had increased clinically relevant EBV infection, which was associated with risk for hematological cancers. Preventing viral infections by vaccination may be especially helpful in controlling risk for cancer in SLE and MS patients.

The National Blood Transfusion Service (NBTS) in England and Wales was established as a single entity in 1946 and operated as such for almost half a century. During those 50 years, the blood service in Wales, as in the rest of the UK, saw many technological and operational changes. The automation of donation testing, the introduction of successive layers of microbiological screening, the creation of the Tissue Typing Laboratory (later renamed the Welsh Transplantation and Immunogenetics Laboratory) and the development of information technology brought - over a relatively long period - highly significant improvements to an organisation that had begun life as an Emergency Medical Service. Differing funding and reporting arrangements for the Welsh and English blood services made little difference in practice, but the devolution of government following the 1997 referendum in Wales would have a profound influence. Four years before the Government of Wales Act (1998) was passed through the UK parliament, the National Blood Authority (NBA) assumed executive control of the English blood services but not the blood service in Wales. The Scottish National Blood Transfusion Service and the Northern Ireland Blood Transfusion Service had been created as independent organisations in 1946; thus, the scene was set for diversification between the four independent blood services, each operating in different political environments with different funding streams. The creation of the UK Blood Services Forum and its Joint Professional Advisory Committee in 1999 has, however, ensured consistency in professional matters. The blood transfusion service in Wales, in its new headquarters in Talbot Green, became known as the Welsh Blood Service (WBS), or Gwasanaeth Gwaed Cymru in Welsh, reporting for most of its life to the Velindre NHS Trust, part of NHS Wales. Considerable changes would impact the WBS in the 21st century. Social changes would mean that the role of recruitment and marketing would become ever more important, although the impact of this was lessened somewhat by a decreasing demand for blood following the Better Blood Transfusion initiatives. The Medicines and Healthcare Products Regulatory Agency found new powers and impetus after the so-called EU Blood Directive was transposed into British law, and the inspection regime became significantly more onerous, requiring more resources to be put in this area. A strategic review found that some parts of the service required extensive modernisation, such as the information technology system in use and the deployment of staff on the blood collection teams, and these matters were attended to. The review also prompted the Welsh Government to consider the question of blood supply to and blood collection in North Wales, which had been the remit of the Liverpool Centre since the establishment of the NBTS in 1946. The Welsh Government duly announced the creation of an all-Wales Blood Service, and finally, in May 2016, 70 years after its creation, the WBS took over responsibility for blood collection and blood provision in the whole of Wales.

In 2019, the World Health Organization (WHO) listed vaccine hesitancy in its top ten threats to global health. Vaccine hesitancy is a &ldquo, delay in acceptance or refusal to vaccinate despite availability of vaccination services&rdquo, Urban areas with large amounts of vaccine hesitancy are at risk for the resurgence of vaccine-preventable diseases (VPDs). Many vaccine-hesitant (VH) parents may be unfamiliar with the consequences of VPDs, and thus might be swayed when confronted with the symptoms and dangers of VPDs. As such, we sought to educate college students (future parents) in an urban vaccine-hesitant hotspot by assigning them to interview family or community members who had experienced a VPD. Student vaccine attitudes were assessed by surveys before and after the interviews. Vaccine-hesitant students who conducted a VPD interview but received no additional vaccine educational materials were significantly more likely (interaction term p &lt, 0.001) to become pro-vaccine (PV) (68%) than students who conducted an autoimmune interview and received no additional educational materials. Additionally, students whose interviewees experienced intense physical suffering or physical limitations or students who were enrolled in a course with intensive VPD and vaccine curriculum had significantly increased vaccine attitudes. This suggests that introducing students to VPDs can decrease vaccine hesitancy.

We describe 2 cases of child maltreatment who presented as common pediatric conditions: preseptal cellulitis and gastroenteritis. The first case is an 8-year-old girl who presented with progressive right eye pain, swelling, and discharge. She was initially treated for preseptal cellulitis, but eye cultures ultimately grew Neisseria gonorrhoeae. Further investigation revealed sexual abuse by a male family member. The second case is a 2-year-old previously healthy girl who presented with 6 hours of emesis, lethargy, and abdominal pain. Initially attributed to viral gastroenteritis, her serum blood urea nitrogen and creatinine were above what was expected for her clinical course, and she later developed signs of peritonitis. She was ultimately found to have a large bladder wall defect secondary to inflicted blunt abdominal trauma. These cases are presented to emphasize the need for pediatricians to consider child abuse even when patients present with common pediatric complaints.

Evan M Pucillo,1 Nancy Christensen-Mayer,2 Shelly D Poole,2 Denise M Whitten,2 Danielle Freeman,3 Blake R Bohe,4 Brandon R Swensen,3 A Gordon Smith,1 Nicholas E Johnson1 1Department of Neurology, School of Medicine, 2Department of Physical Medicine & Rehabilitation, 3Outpatient Neurology, University of Utah Hospitals and Clinics, 4Business Support, University of Utah Information Technology, Salt Lake City, UT, USA Background: Team-based care has been shown to offer more comprehensive benefits to patients when compared to standard physician-based care alone in clinics for chronic conditions. However, apart from grant-funded multidisciplinary clinics, there are no reports on the usage of same-day physical therapy (PT) consults within a daily outpatient neuromuscular disease (NMD) physician clinic.Objective: To determine the impact of same-day PT consults at the University of Utah’s outpatient Clinical Neurosciences Center.Design: A qualitative assessment and survey of patient satisfaction.Methods: An eight question Health Insurance Portability and Accountability Act-compliant patient satisfaction survey using a 5-point Likert scale was administered. Demographic data and Press-Ganey Provider Satisfaction surveys were retrospectively collected from electronic medical records for patients receiving same-day PT encounters in the neuromuscular division over 1 year.Results: Mean (standard deviation) age was 54.22 (19.81) years for 134 patient encounters, median age was 60 years, with 76 male (57%) and 58 female (43%) patients. Mean Likert score for 61 self-reported patient satisfaction surveys for same-day PT consults was 4.87 (97.4%). Press-Ganey Provider Satisfaction scores improved from 89.9% (N=287) for the year prior to 90.8% (N=320) for the corresponding year (P=0.427). A total of 46 (75.4%) patients have either never before received PT care or never before received PT care for their NMD, 67.4% of whom were male.Conclusion: Same-day PT consults in an outpatient NMD physician clinic demonstrated excellent patient satisfaction and improved access to specialty care. This model could potentially be implemented in other academic medical centers to improve access to rehabilitation services for patients with NMD. Keywords: neuromuscular therapy, neuromuscular care, team-based health care, physical therapy consults, same-day physical therapy, physician clinics, patient satisfaction

Use of selective serotonin reuptake inhibitors (SSRIs) is common during pregnancy. Fetal exposure to SSRIs is associated with persistent pulmonary hypertension of the newborn (PPHN); however, a direct link between the two has yet to be established. Conversely, it is well known that PPHN can be caused by premature constriction of the ductus arteriosus (DA), a fetal vessel connecting the pulmonary and systemic circulations. We hypothesized that SSRIs could induce in utero DA constriction. Using isolated vessels and whole-animal models, we sought to determine the effects of two commonly prescribed SSRIs, fluoxetine and sertraline, on the fetal mouse DA. Cannulated vessel myography studies demonstrated that SSRIs caused concentration-dependent DA constriction and made vessels less sensitive to prostaglandin-induced dilation. Moreover, in vivo studies showed that SSRI-exposed mice had inappropriate DA constriction in utero. Taken together, these findings establish that SSRIs promote fetal DA constriction and provide a potential mechanism by which SSRIs could contribute to PPHN.

Background Although studies involving preterm infants ≤34 weeks gestation report a decreased incidence of patent ductus arteriosus after antenatal betamethasone, studies involving younger gestation infants report conflicting results. Methods We used preterm baboons, mice and humans (≤276/7 weeks gestation) to examine betamethasone’s effects on ductus gene expression and constriction both in vitro and in vivo. Results In mice, betamethasone increased the sensitivity of the premature ductus to the contractile effects of oxygen without altering the effects of other contractile or vasodilatory stimuli. Betamethasone’s effects on oxygen sensitivity could be eliminated by inhibiting endogenous prostaglandin/nitric oxide signaling. In mice and baboons, betamethasone increased the expression of several developmentally-regulated genes that mediate oxygen-induced constriction (K+ channels) and inhibit vasodilator signaling (phosphodiesterases). In human infants, betamethasone increased the rate of ductus constriction at all gestational ages. However, in infants born ≤256/7 weeks gestation, betamethasone’s contractile effects were only apparent when prostaglandin signaling was inhibited, whereas, at 26-27 weeks gestation betamethasone’s contractile effects were apparent even in the absence of prostaglandin inhibitors. Conclusions We speculate that betamethasone’s contractile effects may be mediated through genes that are developmentally regulated. This could explain why betamethasone’s effects vary according to the infant’s developmental age at birth.

Depression and anxiety cause severe loss of quality of life for patients with systemic lupus erythematosus. The causes and factors that contribute to these psychological manifestations in lupus are difficult to disentangle. This study compared clinical, psychological, and demographic factors between lupus patients, depressed patients, and rheumatoid arthritis patients to discover lupus-specific contributors to depression. Lupus-specific manifestations of depression were also investigated. Physiological, clinical, and psychosocial data were collected from 77 patients. ELISA was used to measure cytokine levels. Univariate and Multivariate analyses were used to compare the patient populations and identify correlations between key physical and psychological indicators. The prevalence of depression in the SLE cohort was 6 times greater than the healthy control subjects. Pain, IL-6, and Pittsburgh Sleep Quality index values were all significantly higher in SLE patients compared with the healthy control group (P < .001, P = .038, and P = .005, respectively). Anxiety levels were significantly higher in SLE patients compared to healthy and RA control patients (P = .020 and .011, respectively). Serum IL-10 concentrations, relationship assessment scale, and fatigue severity scale values were found to be correlated with depression among the SLE patients (P = .036, P = .007, and P = .001, respectively). Relationship assessment and fatigue severity scale scores were found to be the best indicators of depression for the SLE patients (P = .042 and .028, respectively). Fatigue Severity, relationship satisfaction, and IL-10 concentrations are indicators of depression in lupus patients. Despite also suffering from the pain and disability that accompanies chronic autoimmune disease, the rheumatoid arthritis patients had less anxiety and better relationship scores. The authors thank the Portugal Fulbright Commission for funding Dr. Poole

All relevant data are within the paper and its Supporting information files., Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects a large number of people throughout the world. Anxiety, depression and fatigue are common symptoms of SLE that substantially contribute to decreased quality of life. This study investigates the interplay between physical and psychiatric manifestations of lupus. To this end, an SLE patient cohort was examined for correlations between clinical presentation, laboratory tests, and psychological indicators., BDP was funded by the Fulbright commission: Portugal, scholar program. Funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Purpose. Rheumatoid arthritis (RA) is an often debilitating autoinflammatory disease. Patients with rheumatoid arthritis are often troubled by co-occurring depression or other psychological manifestations. RA patients have a variety of treatment options available, including biologicals that inhibit cytokines or immune cells. If these cytokines influence the psychological symptoms, then the use of cytokine inhibitors should modulate these symptoms. Methods. A cohort of 209 individuals was recruited. This group included 82 RA patients, 22 healthy subjects, 32 depressed control subjects, and 73 subjects with systemic lupus erythematosus. Of the RA patients, 51% were on a biological therapeutic. ELISA was used to measure cytokine levels. A variety of psychological assessments were used to evaluate depression, anxiety, sleep, fatigue, and relationship status. Clinical values were obtained from medical records. Results. IL-10 concentration was associated with depressive symptoms in the RA patients, healthy controls, and the lupus patients. In the patients with primary depression, depressive symptoms were associated with IL-6 and TNF-alpha. In RA patients, Tocilizumab use was associated with decreased depressive symptoms. 14 RA patients who were not using biologicals began using them by a one-month follow-up. In these patients, there was no significant change to any value except for fatigue. Conclusions. A variety of both biological and social factors influences depressive symptoms in RA. IL-10 and IL-6 are likely to be involved, since IL-10 concentration was associated with depression and Tocilizumab decreased depressive symptoms in the RA patients. The roles of these cytokines are different in RA and lupus, as high IL-10 in RA is associated with increased depressive symptoms, but high IL-10 in the lupus patients is associated with decreased depression. IL-6 was also associated with depressive symptoms in the patients with primary depression. These results strongly indicate that disease activity, including cytokine levels, has a strong impact on depressive symptoms.

INTRODUCTION Pachyonychia congenita (PC) is a rare skin disorder caused by an autosomal dominant mutation in one of five genes encoding keratin (K6a, K6b, K6c, K16 or K17; each defining one PC subtype). Pain is a prominent symptom, but its severity and type are poorly characterized. METHODS In total, 35 genotyped US patients with PC consented to clinical assessment including the quality of life (QoL) questionnaire EQ-5D-3L, the Brief Pain Inventory (BPI) and painDETECT. Abbreviated quantitative sensory testing (QST) was also performed, and included mechanical detection threshold (MDT), mechanical pain threshold (MPT), wind-up pain ratio (WUR) and vibration detection threshold (VDT). RESULTS Significant pain in patients with PC was confirmed, as indicated by mean BPI severity and interference of 4.2 ± 1.7 and 4.4 ± 2.2, respectively, as well as QoL impairment, as indicated by mean EQ-5D index of 0.69 ± 0.18. PD identified neuropathic pain in 62% of patients, the remainder being nociceptive. The painDETECT score was most significantly related to EQ-5D index (R(2) = 0.26, P = 0.02). The K17 and K6a subtypes exhibited significantly worse QoL (0.584 and 0.613 respectively) than the K16 and K6b subtypes (P = 0.02). In QST analysis, abnormal pressure pain (assessed as MPT) was frequently observed, with more than half of patients with PC affected (54%), and 57% of patients with K17 also exhibiting abnormality in minimum touch threshold (assessed as MDT, P

OBJECTIVES: We hypothesized that common variants in the collagen genes COL4A1/COL4A2 are associated with sporadic forms of cerebral small vessel disease. METHODS: We conducted meta-analyses of existing genotype data among individuals of European ancestry to determine associations of 1,070 common single nucleotide polymorphisms (SNPs) in the COL4A1/COL4A2 genomic region with the following: intracerebral hemorrhage and its subtypes (deep, lobar) (1,545 cases, 1,485 controls); ischemic stroke and its subtypes (cardioembolic, large vessel disease, lacunar) (12,389 cases, 62,004 controls); and white matter hyperintensities (2,733 individuals with ischemic stroke and 9,361 from population-based cohorts with brain MRI data). We calculated a statistical significance threshold that accounted for multiple testing and linkage disequilibrium between SNPs (p < 0.000084). RESULTS: Three intronic SNPs in COL4A2 were significantly associated with deep intracerebral hemorrhage (lead SNP odds ratio [OR] 1.29, 95% confidence interval [CI] 1.14-1.46, p = 0.00003; r(2) > 0.9 between SNPs). Although SNPs associated with deep intracerebral hemorrhage did not reach our significance threshold for association with lacunar ischemic stroke (lead SNP OR 1.10, 95% CI 1.03-1.18, p = 0.0073), and with white matter hyperintensity volume in symptomatic ischemic stroke patients (lead SNP OR 1.07, 95% CI 1.01-1.13, p = 0.016), the direction of association was the same. There was no convincing evidence of association with white matter hyperintensities in population-based studies or with non-small vessel disease cerebrovascular phenotypes. CONCLUSIONS: Our results indicate an association between common variation in the COL4A2 gene and symptomatic small vessel disease, particularly deep intracerebral hemorrhage. These findings merit replication studies, including in ethnic groups of non-European ancestry./n© 2015 American Academy of Neurology. Kristiina Rannikmäe is supported by the Edinburgh and Lothians Health Foundation REMIND Fund and Stroke Research and Amenities Endowments Fund; Cathie Sudlow is supported by the Scottish Funding Council; Gail Davies is supported by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1), BBSRC and Medical Research Council (MSRC). Tom Van Agtmael is supported by the Kidney Research UK project grant RP19/2012. Details of funding for the studies contributing to the ICH GWAS can be found in: Woo D, Falcone GJ, Devan WJ, et al. Meta-analysis of genome-wide association studies identifies 1q22 as a novel susceptibility locus for intracerebral hemorrhage. American Journal of Human Genetics 2014;pii: S0002-9297(14)00070-6. doi:10.1016/j.ajhg.2014.02.012. [Epub ahead of print]. Details of funding for the studies contributing to the ischaemic stroke GWAS can be found in: Traylor M, Farrall M, Holliday EG, et al. Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE Collaboration): a meta-analysis of genome-wide association studies. Lancet Neurology 2012;11:951-962. Details of funding for the studies contributing to the WMH in ischaemic stroke GWAS can be found in: Adib-Samii P, Rost N, Traylor M, et al. 17q25 Locus Is Associated With White Matter Hyperintensity Volume in Ischaemic Stroke, But Not With Lacunar Stroke Status. Stroke 2013;44:1609-1615. Details of funding for the studies contributing to the WMH in population GWAS can be found in: Fornage M, Debette S, Bis JC, et al. Genome-Wide Association Studies of Cerebral White Matter Lesion Burden: The CHARGE Consortium. Annals of Neurology 2011;69:928-939. Martin Dichgans is supported by the Fondation Leducq (Transatlantic Network of Excellence on the Pathogenesis of Small Vessel Disease of the Brain); Guido J Falcone is supported by the NIH / NINDS grant P50NS061343; Chistopher D Anderson is supported by the American Brain Foundation Clinical Research Training Fellowship, NIH-NINDS K23NS086873, Massachusetts General Hospital Institute for Heart, Vascular, and Stroke Care SPARK award; Jonathan Rosand is supported by the NIH / NINDS grant R01NS059727.

Sepsis is strongly associated with patency of the ductus arteriosus (PDA) in critically ill newborns. Inflammation and the aminoglycoside antibiotics used to treat neonatal sepsis cause smooth muscle relaxation, but their contribution to PDA is unknown. We examined whether: 1) lipopolysaccharide (LPS) or inflammatory cytokines cause relaxation of the ex vivo mouse DA; 2) the aminoglycosides gentamicin, tobramycin, or amikacin causes DA relaxation; and 3) newborn infants treated with aminoglycosides have an increased risk of symptomatic PDA (sPDA). Changes in fetal mouse DA tone were measured by pressure myography in response to LPS, TNF-α, IFN-γ, macrophage-inflammatory protein 2, IL-15, IL-13, CXC chemokine ligand 12, or three aminoglycosides. A clinical database of inborn patients of all gestations was analyzed for association between sPDA and aminoglycoside treatment. Contrary to expectation, neither LPS nor any of the inflammatory mediators caused DA relaxation. However, each of the aminoglycosides caused concentration-dependent vasodilation in term and preterm mouse DAs. Pretreatment with indomethacin and N-(G)-nitro-L-arginine methyl ester did not prevent gentamicin-induced DA relaxation. Gentamicin-exposed DAs developed less oxygen-induced constriction than unexposed DAs. Among 488,349 infants who met the study criteria, 40,472 (8.3%) had sPDA. Confounder-adjusted odds of sPDA were higher in gentamicin-exposed infants, 32 wk. Together, these findings suggest that factors other than inflammation contribute to PDA. Aminoglycoside-induced vasorelaxation and inhibition of oxygen-induced DA constriction support the paradox that antibiotic treatment of sepsis may contribute to DA relaxation. This association was also found in newborn infants, suggesting that antibiotic selection may be an important consideration in efforts to reduce sepsis-associated PDA.

Background Fabry disease (FD) is an X-linked lysosomal storage disorder frequently associated with cerebrovascular disease. In recent years, the prevalence of FD has been reported to be up to 4% in cryptogenic young stroke patients. However, there have been no population-based studies in unselected patients with transient ischaemic attack (TIA) or stroke across the full range of ages. Methods We determined the prevalence of FD mutations in consecutive patients from a population-based study of acute TIA or ischaemic stroke (Oxford Vascular Study). Analysis included amplifying of the α-galactosidase A gene by polymerase chain reaction, denaturing high-performance liquid chromatography (dHPLC) analysis and sequencing using standard automated sequencing protocols [Mutation Surveyor software (Softgenetics)] where the dHPLC indicated a possible mutation. Results Samples of 1046 consecutive patients (52% women; mean age 73.2 years; 15% age

IntroductionDepression is a common companion of systemic lupus erythematosus that substantially contribute to patient's suffering and a decreased quality of life. The relationship between depressive symptoms and disease immune processes is not well understood.ObjectivesTo further understand the relationship between lupus and depression, a patient cohort was examined for correlations between clinical presentation, biological parameters and psychosocial evaluation.MethodsSeventy-two lupus patients were screened for depressive symptoms, clinically and psychologically characterized using a battery of instruments, including assessments for depression, anxiety, fatigue, pain and overall health. Scores from these assessments were correlated with lupus clinical profile and biological parameters namely the immune profile.ResultsForty-two percent of the patients had scores indicative of depression using the HADS Depression scale. Strong correlation was found between pain and depression. Moderate correlation was found between several lupus symptoms, such as mouth ulcers, rash, and arthritis, and psychological evaluation. There was low to moderate correlation between complement levels, C-reactive protein and psychological indicators, but no other lab tests correlated well with the psychological tests.ConclusionThe correlation of depressive symptoms, complement and C-reactive protein with depressive symptoms suggests that these may be mediated by disease activity and share pathophysiological mechanisms. The overall weakness of correlations with biological markers demonstrates that more specific tests need to be developed. The study of lupus associated depression may, furthermore clarify the role of immune dysfunction in the pathophysiology of this psychiatric disorder.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Objectives. The primary aim of this study was to estimate annual health care costs for biologic-naive patients with PsA in the UK. The relationship between disease severity, defined by physical limitations, and costs was also explored. Methods. This study utilized data from the British Society of Rheumatology Biologics Register (BSRBR) to develop a multivariate model estimating disease severity from parameters available in routine primary care data. The HAQ Disability Index was used to determine disease severity. This algorithm was then applied to routine data from The Health Improvement Network (THIN). Annual costs were estimated for drugs, contacts with a general practitioner and other health care professionals, tests, hospital outpatient attendances and inpatient admissions from a National Health Service perspective using official tariffs. The relationship between disease severity and health care costs was estimated using a generalized linear model. Results. Three hundred and fifty-six cases with PsA were identified in the BSRBR and 4492 in THIN. Total mean annual health care costs ranged from £11 to £20 782 with a mean of £1446 (S.D. £1756). When costs were sub-grouped by the predicted HAQ score, the mean annual observed costs ranged from £548 per person for the least severely affected (HAQ ≤1.2) to £4832 for the most severely affected (HAQ >2.6). Prescription costs and secondary care episodes accounted for more than a third of total care costs each (38 and 34%, respectively). When the relationship between disease severity and costs was examined, estimated HAQ was found to be a significant predictor of total health care costs. Conclusions. Treatment of people with PsA resulted in considerable financial costs and these costs varied markedly by disease severity.

To evaluate the association between systemic inflammation, as measured by CRP, and all-cause mortality. To also evaluate the association between change in CRP status (sub-acute,or =10 mg/l and acute10 mg/l) and all-cause mortality.A cohort of patients was selected from The Health Improvement Network (THIN) data set of anonymized patient-level data from UK general practice. Patients were selected if they had a diagnosis of RA, psoriasis, AS or PsA. Survival was evaluated using Cox proportional hazards regression models (CPHMs).A total of 11 362 cases had at least one CRP measurement. Analysis grouped by each additional unit increase in log-CRP (range 1-6) across the observed range was associated with a 21% increase in the hazard ratio (HR) of death, after controlling for cardiovascular risk factors (P0.001). This observation was consistent in separate analysis of cases with either RA or psoriasis. Repeated CRP observations around 1 yr apart were recorded in 2802 subjects. After controlling for confounding factors, in cases whose CRP changed from sub-acute (or =10 mg/l) to acute (10 mg/l), the HR for death increased 2-fold (P0.001) relative to cases whose CRP remained sub-acute. In comparison, among those subjects whose CRP was reduced from acute to sub-acute, the HR was virtually identical to those who stayed sub-acute (P = 0.571).CRP level predicted all-cause mortality after standardization for traditional risk factors, as did change in CRP status from sub-acute to acute observed over 1 yr.

We evaluated the efficacy of a new pharmacokinetically enhanced formulation of amoxicillin/clavulanate (2,000/125 mg) twice daily for the treatment of acute bacterial rhinosinusitis (ABRS) caused by Streptococcus pneumoniae, particularly penicillin-resistant S pneumoniae (PRSP; penicillin minimum inhibitory concentrations [MICs]: ≥2 μ/ml. A total of 2,482 patients received study medication (safety population). Of these, 2,324 were clinically evaluable (efficacy population), and 1,156 of them had at least one pathogen isolated at screening (bacteriology population). S pneumoniae was isolated from 371 patients in the bacteriology population, including 37 with PRSP. Follow-up in the bacteriology population on days 17 through 28 revealed that amoxicillin/clavulanate therapy was successful in 345 of 371 patients with S pneumoniae infection (93.0%) and in 36 of 37 patients with PRSP infection (97.3%), including 7 of 8 patients (87.5%) whose amoxicillin/clavulanic acid MICs were 4/2 μg/ml or higher. Pharmacokinetically enhanced amoxicillin/clavulanate was generally well tolerated, as only 2.2% of patients withdrew because of adverse events. This agent represents a valuable new therapeutic option for the empiric treatment of ABRS, particularly in areas where antimicrobial-resistant pathogens (including β- lactamase–positive organisms) are prevalent, and for the treatment of patients who are at increased risk of infection with PRSP.

A helical tomotherapy system is used in our clinic to deliver intensity-modulated radiation therapy (IMRT) treatments. Since this machine is designed to deliver IMRT treatments, the traditional field flatness requirements are no longer applicable. This allows the unit to operate without a field flatness filter and consequently the 400 mm wide fan beam is highly inhomogeneous in intensity. The shape of this beam profile is mapped during machine commissioning and for quality assurance purposes the shape of the beam profile needs to be monitored. The use of a commercial diode array for quality assurance measurements is investigated. Central axis beam profiles were acquired at different depths using solid water built-up material. These profiles were compared with ion chamber scans taken in a water tank to test the accuracy of the diode array measurements. The sensitivity of the diode array to variations in the beam profile was checked. Over a seven week period, beam profiles were repeatedly measured. The observed variations are compared with those observed with an on-board beam profile monitor. The diode measurements were in agreement with the ion chamber scans. In the high dose, low gradient region the average ratio between the diode and ion chamber readings was 1.000 +/- 0.005 (+/- 1 standard deviation). In the penumbra region the agreement was poorer but all diodes passed the distance to agreement (DTA) requirement of 2 mm. The trend in the beam profile variations that was measured with the diode array device was in agreement with the on-board monitor. While the calculated amount of variation differs between the devices, both were sensitive to subtle variations in the beam profile. The diode array is a valuable tool to quickly and accurately monitor the beam profile on a helical tomotherapy unit.

Gene therapy has been investigated in many aspects of plastic and reconstructive surgery. These areas ultimately involve various forms of tissue healing and the manipulation of bony and soft tissues to reconstruct defects secondary to neoplastic and congenital disorders and trauma. Most research has been limited to animal studies with the exception of clinical trials on the use of gene therapy in lower leg ulcer healing and as an adjunct to advanced recurrent squamous cell carcinoma of the head and neck. Overall, these preliminary studies have produced optimistic results. With the development of more efficient and safer delivery systems, the application of gene therapy in plastic surgery could become more widespread, especially in combination with tissue engineering technology.

The therapeutic outcomes model (TOM) provides a logical and consistent manner in which bacteriologic and clinical efficacy can be predicted and calculated. It not only allows antibiotics to be ranked in efficacy, it gives precise estimates of the magnitude of differences in efficacy, which is typically lacking in older antimicrobial guidelines. The TOM identifies the major variables that need to be considered in accurately estimating outcome and places those variables into the appropriate relationships and formulas so that outcomes will be automatically calculated. In the case of rhinosinusitis, the major variables are (1) likelihood of spontaneously resolving nonbacterial cause, (2) likelihood of nonresolving nonbacterial cause, (3) prevalence of subcauses (eg, different species of bacteria), (4) the spontaneous resolution rates of each subcause, (5) the antibacterial efficacy of the treatment (eg, antibiotic) against each of the subcauses, and (6) the compliance rate of the treatment recommended. Minor variables, such as prior antibiotic use, patient age, or bacterial vaccination status, affect the efficacy of a given agent by modifying the value of one or more of the major variables. The TOM is a superior mechanism for ranking and evaluating relative antibiotic efficacy than previous methodologies.

OBJECTIVE: The primary objective of this study was to demonstrate the clinical and radiologic efficacy of 5 days compared with 7 days of gemifloxacin therapy in the treatment of acute bacterial rhinosinusitis (ABRS).STUDY DESIGN: In this prospective, double-blind, multicenter, parallel-group study, adult patients presenting with ABRS were randomized to receive gemifloxacin 320 mg once daily for either 5 days (n = 218) or 7 days (n = 203).RESULTS: For the primary efficacy end point, clinical response to therapy at follow-up, 5 days of therapy with gemifloxacin was as effective as 7 days of therapy (per-protocol population; treatment difference 0.44%; 95% confidence interval (CI), −6.54 to 7.41). Five and 7 days of treatment with gemifloxacin were well tolerated.CONCLUSION AND SIGNIFICANCE: The clinical efficacy of gemifloxacin 320 mg daily for 5 days is at least as good as the efficacy of gemifloxacin 320 mg daily for 7 days in the treatment of ABRS.

We evaluated the clinical effectiveness of variable courses of paracetamol on patent ductus arteriosus (PDA) closure and examined its effect on the in vitro term and preterm murine ductus arteriosus (DA).Neonates received one of the following three paracetamol regimens: short course of oral paracetamol (SCOP), long course of oral paracetamol (LCOP), and intravenous paracetamol (IVP) for 2-6 d. Pressure myography was used to examine changes in vasomotor tone of the preterm and term mouse DA in response to paracetamol or indomethacin. Their effect on prostaglandin synthesis by DA explants was measured by mass spectroscopy.Twenty-one preterm infants were included. No changes in PDA hemodynamics were seen in SCOP infants (n = 5). The PDA became less significant and eventually closed in six LCOP infants (n = 7). PDA closure was achieved in eight IVP infants (n = 9). On pressure myograph, paracetamol induced a concentration-dependent constriction of the term mouse DA, up to 30% of baseline (P0.01), but required1 µmol/l. Indomethacin induced greater DA constriction and suppression of prostaglandin synthesis (P0.05).The clinical efficacy of paracetamol on PDA closure may depend on the duration of treatment and the mode of administration. Paracetamol is less potent than indomethacin for constriction of the mouse DA in vitro.

The use of exogenous agents to stimulate the growth of new blood vessels into ischaemic tissue is a potentially revolutionary therapy in a wide variety of clinical specialties. Therapeutic angiogenesis research has been mostly confined to ischaemia of the heart and the lower limb. There has been relatively little research into the potential applications of the technique to plastic, reconstructive and burns surgery. In this paper, relevant published work is reviewed and potential applications of therapeutic angiogenesis to our specialty are considered.

The impact of modern medical techniques has given rise to an increasing survival of persons with disorders of consciousness including coma, the vegetative state, and the minimally conscious state. The numbers of pediatric and adolescent survivors of brain injury who remain vegetative or minimally conscious are not definitively known, and while these patients have received growing professional consideration, no specific standards of care exist. Pediatric and adolescent treatment recommendations are not differentiated from adult populations although some questions linger regarding the progression and outcome of the disorders in adults as compared to those in children. Kluge Children's Rehabilitation Center has initiated a Low Response and Treatment Protocol for Children Following Acquired Brain Injury to provide structure for diagnostic and therapeutic initiatives. Its single subject design is literature based, empirically driven, and peer recognized. Clinical classifications label a patient's emergence from coma as uncomplicated, complicated by confounding medical conditions, or neuropathic complicated emergence. Patients receiving the neuropathic designation are considered for pharmacological intervention. Beyond optimizing care for the enrolled patient, the protocol is established to provide (Giacino, 1995) an ongoing data store for future group analysis. Case 1 presents the course of treatment and recovery for a 16-year-old male, severely disabled due to an automobile accident. Medical complications are addressed and his failure to progress is deemed complicated neuropathic at 14 weeks post-injury. At 15 weeks post-injury, administration of Amantadine 100 mg bid shows improvements, with almost complete emergence after two weeks at an increased dose of 200 gm bid. Discontinuation at the family's request, approximately a year post-injury, is followed by a measurable loss of functional ability. The patient regained functioning after returning to the Amantadine schedule. Case 2 outlines the course of treatment and recovery for a nine-year-old boy, the victim of a near drowning. Investigation considerations influence the structure of the protocol and analysis of its results. While first a therapeutic tool based on single subject design, the protocol attempts to qualitatively manage various threats to establishing causal relationships between drug interventions and the noted outcomes. Systematic consideration of the single subject design for therapeutic benefit, as well as making a meaningful contribution to the existing evidence base, is suggested until class I evidence is compiled to produce well supported standards of care. Copyright © 2000 John Wiley & Sons, Ltd.

Sinusitis is a prevalent and costly disease that affects >14% of the population and accounts for >$2 billion in yearly healthcare costs. It is one of the most common conditions treated by primary care physicians. The multiple host and environmental factors that contribute to the pathogenesis of the disease and the lack of clear guidelines for diagnosis and treatment pose a challenge to effective management of the problem. The diagnosis of uncomplicated cases rests mainly on the history and clinical examination; attempts have been made to identify the most useful clinical predictors of acute bacterial sinusitis. Microbiologic and imaging studies are rarely performed during the initial assessment and are usually reserved for recurrent or refractory disease. Treatment involves drainage of the congested sinuses and elimination of pathogenic organisms. Although antimicrobial therapy hastens the resolution of symptoms of acute sinusitis, the need for antimicrobial therapy remains questionable, and its judicious use is challenged by the increase in antibiotic-resistant Haemophilus influenzae and Streptococcus pneumoniae, the organisms most commonly implicated in acute sinusitis. A lack of resolution or frequent recurrence of sinusitis warrants evaluation by a specialist.

The precise role of maxillary constriction in the pathophysiology of obstructive sleep apnea (OSA) is unclear. However, it is known that subjects with maxillary constriction have increased nasal resistance and resultant mouth-breathing, features typically seen in OSA patients. Maxillary constriction is also associated with alterations in tongue posture which could result in retroglossal airway narrowing, another feature of OSA. Rapid maxillary expansion (RME) is an orthodontic treatment for maxillary constriction which increases the width of the maxilla and reduces nasal resistance. The aim of this pilot study was to investigate the effect of rapid maxillary expansion in OSA. We studied 10 young adults (8 male, 2 female, mean age 27 +/- 2 [sem] years) with mild to moderate OSA (apnea/hypopnea index-AHI 19 +/- 4 and minimum SaO2 89 +/- 1%), and evidence of maxillary constriction on orthodontic evaluation. All patients underwent treatment with RME, six cases requiring elective surgical assistance. Polysomnography was repeated at the completion of treatment. Nine of the 10 patients reported improvements in snoring and hypersomnolence. There was a significant reduction in AHI (19 +/- 4 vs 7 +/- 4, p < 0.05) in the entire group. In seven patients, the AHI returned to normal (i.e., = < 5); only one patient showed no improvement. These preliminary data suggest that RME may be a useful treatment alternative for selected patients with OSA.

To the Editor .— In his commentary, “Why Don't Those Ear Drops Work for My Patients?”1 Isaacson presented his argument against the use of ototopical fluoroquinolones alone or in combination with a steroid as the first line of defense for the treatment of acute tube otorrhea in infants. He made several points to discount the use of these agents in pediatric patients with acute otitis media with tympanostomy tubes. However, rooted in the first sentence of the commentary was the fact that seems to lie at the epicenter of his concerns: “‘Topical Ciprofloxacin/Dexamethasone Is Superior to Oral Amoxicillin/Clavulanic Acid in Acute Otitis Media With Otorrhea Through Tympanostomy Tubes,’ [is] the latest in a series of pharmaceutical industry–funded articles… .” Isaacson's first critique of this article2 pertains to the study population. He stated that “[i]f one were trying to design a study to demonstrate the superiority of ototopical drops over oral antibiotics, the ideal population would be older children.” This statement directly contradicted his other criticism that “more than half of their subjects were >22 months of age.” In fact, 58% of the subjects in the study were

Distraction osteogenesis is a technique of new bone formation by the gradual separation of bony fragments. The method, although initially developed for limb lengthening, is now being applied in the treatment of craniofacial deformities. A number of principles have been established through careful scientific study to guide clinical practice, such as the ideal rate and rhythm of distraction, the need for periosteal preservation during bone division, a "latent period" of neutral fixation before, and a "consolidation period" after distraction. The technique is being applied in craniofacial surgery particularly for mandibular deformities and offers considerable advantages over previous methods such as osteotomy and inlay bone grafting. Donor site morbidity is avoided, the investing soft tissue envelope is concurrently expanded, and the magnitude of the procedure is less. However, the technique is still in its infancy and requires further modification and refinement before widespread acceptance as a treatment in mainstream craniofacial surgery. Problems with cutaneous scarring and socially undesirable external hardware, particularly in the pediatric population, have led to the emergence of intraoral miniature devices, with the ultimate goal of development of a multiplanar internal autodistractor. Furthermore, many principles well established in leg lengthening, such as the rate and rhythm of distraction, need to be reexamined and the parameters redefined with particular reference to the craniofacial skeleton. Distraction osteogenesis has an expanding role in craniofacial surgery.

Rational antibiotic therapy for sinusitis is a difficult goal, made difficult by few satisfactory comparative trials with sufficient clinical power, the large numbers of therapeutic options, prescribing pressures from the pharmaceutical industry, and rapid changes in bacterial resistance patterns. Controversies exist about the relative need of antibiotics for uncomplicated disease, duration of therapy, and relative efficacy of various agents. Nonetheless, limited data support the notion of superior efficacy of more potent antimicrobials, and an analysis of in vitro activity versus tissue concentrations of the various antibiotics can predict efficacy of eradication of causative bacteria. Multidrug-resistant pneumococci render any algorithm for empiric antibiotic use problematic and prone to fail.

The controversy about timing of cleft palate surgical procedures is focused on early palatoplasty for improved speech versus delayed hard palate repair for undisturbed facial growth. Timing and technique of palate repair are the most important influences on speech and facial growth, yet there is no consensus on the age or technique for surgery. The Oxford Cleft Palate Study was initiated to evaluate critically the long-term follow-up of 44 patients with early versus late closure of the hard palate. A multidisciplinary approach was used to determine the incidence of speech deficiencies, palatal fistulas, maxillofacial growth disturbances, and hearing abnormalities and to assess objectively the long-term effects of two different treatment modalities on the cleft palate patient. The 44 patients were selected randomly, interviewed, and examined by the multidisciplinary Oxford Cleft Palate Study team. The average age at follow-up in the early closure group was 17.0 years versus 18.2 years in the late closure group. There was a similar number of unilateral and bilateral clefts in both the early and late closure groups. The hard palate was closed in the early group at an average age of 10.8 months versus 48.6 months in the late closure group. All operative procedures in each group were performed by the same senior plastic surgery consultant. Both consultants have since retired and did not participate in the study. Each patient was evaluated by the same plastic surgeon, speech pathologist, orthodontist, and otologist. All examiners were blinded in that they were unaware of the type or timing of the surgical technique and had no prior knowledge of or access to the patient's medical records. Furthermore, none of the examiners participated in the initial care and surgery of these patients. Statistically significant greater speech deficiencies were noted with delayed hard palate closure, especially in articulation, nasal resonance, intelligibility, and substitution pattern assessment (overall intelligibility, p < 0.01). Likewise, the persistent palatal fistula rate in the late closure group was 35 percent in comparison with 5 percent for the early closure group (p

Many pathologic processes may lead to vertical orbital dystopia. We reviewed 47 consecutive cases seen over a 13-year period. Twenty-nine patients underwent eye leveling procedures to improve cosmesis, 2 of these by camouflage procedures and 27 by orbital translocation. Ten patients had 16 secondary operations. There was one death, serious complications occurred in 3 patients, and nuisance complications occurred in 20 others. Seven patients developed diplopia postoperatively, and in 6 patients it was troublesome. In these, it resolved fully in 2 patients, improved to be of no consequence in 2, and in the remaining 2 troublesome symptoms persisted requiring inferior oblique muscle recession in 1. Binocular vision was never restored when not present preoperatively, and in 3 patients temporary loss occurred. There was an overall modest but significant improvement in appearance after surgery. It is concluded that vertical orbital translocation is rewarding and worthwhile.

Persistent patency of the ductus arteriosus (PDA) is a common problem in preterm infants. The antacid cimetidine is a potent antagonist of the H2 histamine receptor but it also inhibits certain cytochrome P450 enzymes (CYPs), which may affect DA patency. We examined whether cimetidine contributes to PDA and is mediated by CYP inhibition rather than H2 blockade. Analysis of a clinical trial to prevent lung injury in premature infants revealed a significant association between cimetidine treatment and PDA. Cimetidine and ranitidine, both CYP inhibitors as well as H2 blockers, caused relaxation of the term and preterm mouse DA. CYP enzymes that are inhibited by cimetidine were expressed in DA subendothelial smooth muscle. The selective CYP3A inhibitor ketoconazole induced greater DA relaxation than cimetidine, whereas famotidine and other H2 antagonists with less CYP inhibitory effects caused less dilation. Histamine receptors were developmentally regulated and localized in DA smooth muscle. However, cimetidine caused DA relaxation in histamine-deficient mice, consistent with CYP inhibition, not H2 antagonism, as the mechanism for PDA. Oxygen-induced DA constriction was inhibited by both cimetidine and famotidine. These studies show that antacids and other compounds with CYP inhibitory properties pose a significant and previously unrecognized risk for PDA in critically ill newborn infants.

Two studies were conducted to investigate the relationship between cultural background and certain variables relevant to hospital maternity care. Data were collected in semistructured in-person interviews. In the first study, interviews were conducted with 27 Euro-Canadian and 24 Indo-Canadian patients; in the second study, interviews were conducted with 33 Euro-Canadian and 24 Indo-Canadian patients. Patients' interviews were followed by short interviews with their nurses. The first study revealed significant main effects for cultural background on a number of psychosocial variables but little effect of cultural background on biomedical factors. The second study demonstrated that Indo-Canadian patients had learned fewer baby care and self-care procedures and that nurses believed Indo-Canadian patients to be less likely to use the procedures they had learned. Results are presented as evidence of the need to recognize language and cultural differences in the provision of health care.

The use of prophylactic anti-D to prevent Rh D immunization in Rh D- women and subsequent hemolytic disease in Rh D+ infants is widespread, but has led to shortages of the anti-D Ig. With the aim of substituting monoclonal anti-D for Rh D prophylaxis, we have compared the abilities of monoclonal and polyclonal anti-D to clear Rh D+ red blood cells (RBCs) infused into Rh D- male volunteers and to suppress Rh D immunization. Two human monoclonal antibodies (MoAbs), BRAD-3 (IgG3) and BRAD-5 (IgG1), produced from stable Epstein-Barr virus-transformed B-lymphoblastoid cell lines, were selected because of their proven in vitro activity in promoting RBC lysis in antibody-dependent cell- mediated cytotoxicity assays. RBC clearance was assessed by intravenous injection of 3 mL of 51chromium-labeled D+ RBCs into 27 volunteers 48 hours after intramuscular injection of monoclonal or polyclonal anti-D. Further 3-mL injections of unlabeled D+ cells were administered at 6 and 9 months to induce immunization. Blood samples were taken throughout the 12-month period of study for the serologic detection of anti-D. The mean half-life (t50%) of RBCs in 7 recipients of 300 micrograms BRAD-5 (5.9 hours) was similar to that in 8 recipients of 500 IU polyclonal anti-D (5.0 hours), whereas D+ cells were cleared more slowly in some of the 8 subjects injected with 300 micrograms BRAD- 3 (mean t50% 12.7 hours) and in 1 individual administered 100 micrograms BRAD-3 (t50% 41.0 hours). The rate of RBC clearance in both groups administered 300 micrograms monoclonal anti-D correlated with the amount of antibody bound per cell, determined by flow cytometry. There was no evidence of primary immunization having occurred in any subject after 6 months of follow-up. Five of 24 subjects produced anti- D after one or two further injections of RBCs, confirming that they were responders who had been protected by the monoclonal or polyclonal anti-D administered initially. Four of these responders were recipients of monoclonal anti-D (3 BRAD-3, 1 BRAD-5). One individual who received BRAD-5 produced accelerated clearance of D+ RBCs at the third unprotected RBC challenge but did not seroconvert. This study shows that the human MoAbs BRAD-3 and BRAD-5 can prevent Rh D immunization, and indicates that they may be suitable replacements for the polyclonal anti-D presently used in prophylaxis of Rh D hemolytic disease of the newborn.(ABSTRACT TRUNCATED AT 400 WORDS)

Isolated orbital floor fractures in children before the end of the 7th year of life are said to seldom occur. This is thought to be due to differences in anatomy from adults in that the maxillary sinus is developing and the orbit is still increasing in size. Two cases of isolated orbital floor fractures in children aged less than 8 years are reported, their management discussed, and the literature reviewed.

Cytokines regulate and control the immune system. In systemic lupus erythematosus, several of these cytokines are overexpressed and contribute to the pathogenesis of the disease. Cytokine inhibition has been successfully used to treat other rheumatic and autoimmune diseases, and several cytokines are currently being investigated to determine whether inhibition would be therapeutic in lupus. The cytokines discussed in this review have all undergone clinical trials, and include TNF-α, IL-1, IL-6, IL-10, IL-15, IL-17, IL-18 and IL-23. Inhibition of the majority of these targets was safe and showed some efficacy in treating lupus. Cytokine inhibition strategies have just started to realize their potential for the treatment of this difficult disease, and show great promise for the future.

Aim Chloral hydrate (CH) is the most commonly used sedative for medical procedures and lung function tests in infancy. The aim was to determine whether moderate CH sedation affects airway function, lung volume and ventilation. Methods Thirteen chronically instrumented 7- to 8-week-old lambs were studied both before and after CH sedation (50 mg/kg as intravenous bolus followed by 25 mg/kg/hour as continuous infusion). Nitrogen washout technique and lung mechanics analysis were used to assess functional residual capacity (FRC) and airway function. Moment analysis and lung clearance index were calculated as measures of gas mixing efficiency in distal airways. Respiratory rate, tidal volume, minute ventilation and indices of inspiratory drive were determined together with heart rate, blood pressure and oxygenation. Results No significant CH-induced changes were found for gas mixing efficiency, FRC or lung mechanics. Minute ventilation decreased slightly, but significantly, while indices of inspiratory drive remained unchanged. Heart rate increased significantly, but mean arterial blood pressure was unaffected. Conclusion Moderate CH sedation did not significantly affect airway function or FRC. Although indices of inspiratory drive were not affected, minute ventilation decreased slightly. These findings indicate that reliable results can be obtained from lung function testing when CH is used for sedation.