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BACKGROUND Obesity has been associated with attenuated vaccine responses and an increased risk of contracting pneumococcal pneumonia, but no study to our knowledge has assessed the impact of obesity and genetics on 23-valent pneumococcal vaccine (PPSV23) efficacy. We assessed the relationship of obesity (primary analysis) and stimulator of interferon genes (STING1) genotype (secondary analysis) on PPSV23 efficacy. METHODS Nonobese (BMI 22–25 kg/m2) and obese participants (BMI ≥30 kg/m2) were given a single dose of PPSV23. Blood was drawn immediately prior to and 4–6 weeks after vaccination. Serum samples were used to assess PPSV23-specific antibodies. STING1 genotypes were identified using PCR on DNA extracted from peripheral blood samples. RESULTS Forty-six participants were categorized as nonobese (n = 23; 56.5% women; mean BMI 23.3 kg/m2) or obese (n = 23; 65.2% women; mean BMI 36.3 kg/m2). Obese participants had an elevated fold change in vaccine-specific responses compared with nonobese participants (P < 0.0001). The WT STING1 group (R232/R232) had a significantly higher PPSV23 response than individuals with a single copy of HAQ-STING1 regardless of BMI (P = 0.0025). When WT was assessed alone, obese participants had a higher fold serotype-specific response compared with nonobese participants (P < 0.0001), but no difference was observed between obese and nonobese individuals with 1 HAQ allele (P = 0.693). CONCLUSIONS These observations demonstrate a positive association between obesity and PPSV23 efficacy specifically in participants with the WT STING1 genotype. TRIAL REGISTRATION ClinicalTrials.gov NCT02471014. FUNDING This research was supported by the NIH and the University of Florida MD-PhD Training Program., Obesity and a WT STING1 genotype are positively associated with efficacy of the 23-valent pneumococcal vaccine in a small cohort of subjects.

Systemic lupus erythematosus is an autoimmune disease characterized by autoantibodies and systemic inflammation that results in part from dendritic cell activation by nucleic acid containing immune complexes. There are many mouse models of lupus, some spontaneous and some induced. We have been interested in an induced model in which estrogen is the trigger for development of a lupus-like serology. The R4A transgenic mouse expresses a transgene-encoded H chain of an anti-DNA Ab. This mouse maintains normal B cell tolerance with deletion of high-affinity DNA-reactive B cells and maturation to immunocompetence of B cells making nonglomerulotropic, low-affinity DNA-reactive Abs. When this mouse is given estradiol, normal tolerance mechanisms are altered; high-affinity DNA-reactive B cells mature to a marginal zone phenotype, and the mice are induced to make high titers of anti-DNA Abs. We now show that estradiol administration also leads to systemic inflammation with increased B cell-activating factor and IFN levels and induction of an IFN signature. DNA must be accessible to B cells for both the production of high-affinity anti-DNA Abs and the generation of the proinflammatory milieu. When DNase is delivered to the mice at the same time as estradiol, there is no evidence for an abrogation of tolerance, no increased B cell-activating factor and IFN, and no IFN signature. Thus, the presence of autoantigen is required for positive selection of autoreactive B cells and for the subsequent positive feedback loop that occurs secondary to dendritic cell activation by DNA-containing immune complexes.

International Journal of Paediatric Dentistry 2010; 20: 179–185 Objectives. This study examined caries level, amount of calculus, and oral microbial environment in gastrostomy tube (GT)-fed children compared with healthy children and children with disabilities orally fed (PO). Study design. The study group consisted of 12 GT-fed children and the two control groups consisted of 16 children with disabilities orally fed and 17 healthy children. DMF-T/dmf-t index, calculus index, Mutans Streptococci (MS), Lactobacilli (LB) levels and salivary buffer capacity were examined. Results. DMF-T/dmf-t index was significantly lower in the tube-fed group. Calculus index was highest in the tube-fed group. MS and LB levels were the lowest in the tube-fed children. Correlation was found between MS and DMF-T/dmf-t. Conclusions. Tube-fed children demonstrated significantly higher calculus levels and less caries, MS, and LB levels then healthy children or children with disabilities eating PO.

PURPOSE: To summarize evidence on the costs of treating patients in clinical trials and to describe the Cost of Cancer Treatment Study, an ongoing effort to produce generalizable estimates of the incremental costs of government-sponsored cancer trials. METHODS: A retrospective study of costs will be conducted with 1,500 cancer patients recruited from a randomly selected sample of institutions in the United States. Patients accrued to either phase II or phase III National Cancer Institute–sponsored clinical trials during a 15-month period will be asked to participate in a study of their health care utilization (n = 750). Costs will be measured approximately 1 year after their trial enrollment from a combination of billing records, medical records, and an in-person survey questionnaire. Similar data will be collected for a comparable group of cancer patients not in trials (n = 750) to provide an estimate of the incremental cost. RESULTS: Evidence suggests insurers limit access to trials because of cost concerns. Public and private efforts are underway to change these policies, but their permanent status is unclear. Previous studies found that treatment costs in clinical trials are similar to costs of standard therapy. However, it is difficult to generalize from these studies because of the unique practice settings, insufficient sample sizes, and the exclusion of potentially important costs. CONCLUSION: Denials of coverage for treatment in a clinical trial limit patient access to trials and could impede clinical research. Preliminary estimates suggest changes to these policies would not be expensive, but these results are not generalizable. The Cost of Cancer Treatment Study is an ongoing effort to provide generalizable estimates of the incremental treatment cost of phase II and phase III cancer trials. The results should be of great interest to insurers and the research community as they consider permanent ways to finance cancer trials.

R4A is an anti-DNA antibody derived by hybridomas technology from a BALB/c mouse. The study of its properties has helped to elucidate aspects of the physiopathology of Systemic Lupus Erythematosus (SLE). It has been useful to decipher the mechanisms implicated in breaks in B cell self tolerance by B cell extrinsic or B cell intrinsic factors. Furthermore, it illustrates the importance of molecular mimicry in understanding the cellular and molecular effects relevant to some manifestations of neuropsychiatric lupus, as it cross-reacts with the D/E W D/E YS/G peptide sequence present in subunits of the N-methyl D-aspartate receptor (NMDAR).

Our research, inspired by the pioneering works of Isaac Witz in the 1980s, established that 40% of human metastatic melanomas express ectopically inhibitory Fc gamma receptors (FcgammaRIIB), while they are detected on less than 5% of primary cutaneous melanoma and not on melanocytes. We demonstrated that these tumoral FcgammaRIIB act as decoy receptors that bind the Fc portion of antimelanoma IgG, which may prevent Fc recognition by the effector cells of the immune system and allow the metastatic melanoma to escape the humoral/natural immune response. The FcgammaRIIB is able to inhibit the ADCC (antibody dependent cell cytotoxicity) in vitro. Interestingly, the percentage of melanoma expressing the FcgammaRIIB is high (70%) in organs like the liver, which is rich in patrolling NK (natural killer) cells that exercise their antitumoral activity by ADCC. We found that this tumoral FcgammaRIIB is fully functional and that its inhibitory potential can be triggered depending on the specificity of the anti-tumor antibody with which it interacts. Together these observations elucidate how metastatic melanomas interact with and potentially evade humoral immunity and provide direction for the improvement of anti-melanoma monoclonal antibody therapy.

A 65-year-old woman who had type 2 diabetes mellitus, hypertension and coronary artery disease was admitted with a 4-day history of pain, erythema and swelling of her left toes and adjacent dorsum of her foot associated with high temperature. Pulses were normal and no peripheral neuropathy was found. Bullous erysipelas was diagnosed (Fig. 1). The ESR was 118 mm/h; CRP 54 mg/dl and WBC 10 £ 10/ l with a left shift. Oral antibiotics (clindamycin + oXoxacin) were commenced. At night, she was given a 500 mg dipyrone tablet for leg pain. Three days later a palpable purpuric rash appeared below the knee on her right leg alone (Fig. 1). Biopsy revealed changes characteristic of leukocytoclastic vasculitis (not shown). Mild arthralgia was the only other change observed. Once she improved suYciently at home and started walking, she presented again to the emergency room, alarmed because multiple additional typical lesions now developed on the other leg as well. Bulla formation occurs in about 5% of patients with erysipelas and require longer treatment [1]. The patient’s hypersensitivity vasculitis was most likely associated with the administration of dipyrone: drug therapy is the most common precipitating event in patients with this type of vasculitis [2], no other cause could be identiWed and the purpuric rash later receded spontaneously despite continued antibiotic treatment. The eruption of small vessel vasculitis occurs predominantly in dependent areas such as the lower extremities, below the knees and is characteristically symmetrical [3, 4]. The unilateral development of leukocytoclastic vasculitis in one leg is odd and unexpected. Our explanation is that before the appearance of vasculitis, the infected leg was kept horizontal either in bed or on a chair for most of the day. Once she started walking, lesions developed symmetrically. Thus, increased hydrostatic pressure must have a greater role in the pathogenesis of the immune-mediated purpuric lesions of leukocytoclastic vasculitis than we usually believe.

A 69-year-old man presented with fever and chills of acute onset without any localizing complaints. He was previously generally well, but had a history of dyslipidemia and benign prostatic hypertrophy. The findings of his examination and laboratory tests were normal, and he was discharged. He was

FcgammaRs are a family of heterogeneous molecules that play opposite roles in immune response and control the effector functions of IgG antibodies. In many cancers, IgG antibodies are produced that recognize cancer cells, form immune complexes and therefore, activate FcgammaR. The therapeutic efficacy of monoclonal IgG antibodies against hematopoietic and epithelial tumors also argue for an important role of IgG antibodies in anti-tumor defenses. Since the 1980s, a series of lines of evidence in experimental models and in humans strongly suggest that FcgammaR are involved in the therapeutic activity of monoclonal IgG antibodies by activating the cytotoxic activity of FcgammaR-positive cells such as NK cells, monocytes, macrophages and neutrophils and by increasing antigen presentation by dendritic cells. Since many cell types co-express activating and inhibitory FcgammaR, the FcgammaR-dependent effector functions of IgG anti-tumor antibodies are counterbalanced by the inhibitory FcgammaRIIB. In addition, some tumor cells express FcgammaR either constitutively, such as B cell lymphomas or ectopically, such as 40% of human metastatic melanoma. The tumor FcgammaR isoform is preferentially FcgammaRIIB, which is functional at least in human metastatic melanoma. This review summarizes these data and discusses how FcgammaRIIB expression may influence the anti-tumor immune reaction and how beneficial or deleterious this expression could be for the efficiency of therapeutics based on monoclonal anti-tumor antibodies.

Classic immunologic teaching describes the brain as an immunologically privileged site. Studies of neuroimmunology have focused for many years almost exclusively on multiple sclerosis, a disease in which inflammatory cells actually infiltrate brain tissue, and the rodent model of this disease, experimental allergic encephalitis. Over the past decade, however, increasingly, brain‐reactive antibodies have been demonstrated in the serum of patients with numerous neurological diseases. The contribution these antibodies make to neuronal dysfunction has, in general, not been determined. Here, we describe recent studies showing that serum antibodies to the N‐methyl D‐asparate receptor occur frequently in patients with systemic lupus erythematosus and can cause alterations in cognition and behavior following a breach in the blood–brain barrier.

Three weeks after receiving a prosthetic aortic valve because of severe aortic stenosis, a 71-year-old man was admitted to hospital with a 3-day history of gradually increasing temperature. His temperature was 38.3οC, but the results of a physical examination were unremarkable. After 4 sets of

The use of biological dressing techniques accelerates recovery from radical vulvectomy combined with lymphadenectomy. Our earliest interest in the field arose as a result of the morbidity rate which ensued subsequent to surgical therapy of cancer of the vulva. The technique involved in 8 such procedures is described, and its applicability illustrated with photographic plates and review of the literature.

An adolescent girl, had a grade 1 immature teratoma combined with a rare manifestation of glial peritoneal implants of grade 0. A unilateral salpingo-oophorectomy was performed. Alpha-fetoprotein levels, which were elevated before the operation, returned to normal. The patient has been symptom-free for more than three years after the surgical treatment. Repeated normal assays for alpha-fetoproteins can serve as a guide to a projected favorable course. The World Health Organization grading of the teratoma is listed and pertinent medical literature is briefly discussed.

A combination of propranolol and hydrallazine was administered to 13 patients with longstanding hypertension during 15 pregnancies. Hydrallazine was continued through labour and delivery in all patients, while in eight patients propranolol was discontinued 2 to 15 days before delivery. Blood pressure control was uniformly good and superimposed pre-eclampsia did not occur during combined therapy. There were 14 livebirths and one unexplained stillbirth. Except for two cases of milk hypoglycemia, there were no neonatal complications.

(i) A case of hydrops fœtalis diagnosed by radiological means pre-natally is described. (ii) The radiological signs of hydrops-fœtalis are described. (iii) Experimental investigation was undertaken to investigate the means of production of the osteo-petrosis of the skeleton, noted in this case. (iv) The relative value of the serological studies and the X-ray findings in the case recorded are discussed.

A case of severe foetal distress is recorded and the rationale and use of a beta-sympathomimetic drug are described.

Since diagnostic ultrasound was introduced into obstetrics and gynaecology (Donald et al., 1958), it has become an invaluable aid in localization of the placenta and assessment of fetal maturity, growth rate, multiple gestation and presentation. In addition, ultrasonography has been useful in the diagnosis of anencephalus, hydrocephalus, meningocoele, omphalocoele, hydrops, ovarian cysts, polycystic kidneys, hydronephrosis and megaureter.

Periodic sleep apnea, a chronic sleep deprivation state, in which marked changes in the arterial PO2 and PCO2 tensions have been recorded, is a relatively new syndrome not previously reported in pregnancy. It is characterized by episodes of apnea, prevalently obstructive, during sleep. The majority of patients with this syndrome have snored heavily for years, suggesting a causal relationship between snoring and periodic sleep apnea. The effects of prolonged snoring on alveolar ventilation and systemic pressure(s) suggest that this snoring has physiopathological implications on maternal cardio-respiratory reserve and indirectly upon the fetus, especially as there are recordable changes in fetal heart rate and also a change in the acid-base status of the fetus. The possibility that this syndrome may have an adverse effect upon the fetus is stressed.

The individual states have many options in designing Medicaid reimbursement systems for nursing homes. Each option has a differential effect on incentives--and outcomes--for containing costs, providing quality care, and maintaining access to care. The mix and consequences of specific choices are analyzed in a framework that disaggregates costs into three components. Tradeoffs among competing elements will be inevitable, but reimbursement policy can maximize both efficiency and equity.