Risk factors,clinical course and outcomes of pregnancy-related group A streptococcal infections: retrospective 13-year cohort study

Objectives

To investigate the incidence, risk factors, clinical course and outcomes of pregnancy-related group A streptococcus (GAS) infection.

Outcomes of unrelated umbilical cord blood transplantation for X-linked adrenoleukodystrophy.

Adrenoleukodystrophy (ALD) is an X-linked disorder caused by a defect in the metabolism of long chain fatty acids leading to demyelination, neurodegeneration, and death. The disease typically presents in young boys and adolescent boys. Allogeneic bone marrow transplantation has been used to halt progression of the disease. However, many patients lack suitable HLA- matched related donors and must rely on unmatched donors for a source of stem cells. The purpose of this study was to evaluate outcomes of unrelated donor umbilical cord blood transplantation after chemotherapy-based myeloablative conditioning and retrospectively determine if baseline studies correlate and help predict outcome. Between November 22, 1996, and November 3, 2005, 12 boys with X-linked ALD who lacked HL- matched related donors were referred to Duke University Medical Center for transplantation. These children were conditioned with myeloablative therapy including busulfan, cyclophosphamide, and antithymocyte globulin before receiving umbilical cord-blood transplants from unrelated donors. Baseline studies of neurophysiologic, neuroimaging, and neurodevelopmental status were performed and patients were subsequently evaluated for survival, engraftment, graft-versus-host disease, and neurodevelopmental outcomes. A substudy evaluated whether baseline neuroimaging and neurophysiologic studies correlated with cognitive and motor function and if these studies were predictive of posttransplantation outcomes. The umbilical cord blood grafts had normal levels of very long chain fatty acids. They delivered a median of 6.98 x 10(7) nucleated cells per kilogram of recipient body weight and were discordant for up to 4 of 6 HLA markers. Neutrophil engraftment occurred at a median of 22.9 days after transplantation. Three patients had grade II-IV acute graft-versus-host disease; 2 had extensive chronic graft-versus-host disease. Cumulative incidence of overall survival of the group at 6 months is 66.7% (95% confidence interval 39.9-93.3%). Median follow-up was 3.3 years (range 12 days to 6.3 years). As previously reported with bone marrow transplantation, symptomatic patients faired poorly with lower survival and rapid deterioration of neurologic function. This study included 3 patients transplanted at a very young age (2.6-3.5 years) before the onset of clinical symptoms who continue to develop at a normal rate for 3-5 years posttransplant. Although baseline Loes scores correlated with cognitive and motor outcome, neurophysiologic studies failed to show statistically significant differences. Transplantation of boys with X-linked ALD using partial HLA-matched umbilical cord blood yields similar results to those previously reported after bone marrow transplantation. Superior outcomes were seen in neurologically asymptomatic boys less than 3.5 years of age at the time of transplantation. Baseline Loes scores were a strong predictor of cognitive and motor outcome.     

Jejunal angiomatoses causing small bowel obstruction in a patient with Down syndrome: a case report

Gastrointestinal vascular anomalies are extremely uncommon. We describe a patient with Down syndrome who presented with acute abdominal pain due to a mixed capillary and venous vascular malformation involving the proximal jejunum.     

Stress-induced analgesia: adaptive pain suppression

In this paper we have examined the phenomenon of stress-induced analgesia. We have described the procedures used to measure analgesia and have suggested that the tests can be designed not only to indicate changes in pain threshold but also to allow for the determination of the capacity to execute adaptive behavior. Aside from enabling the analysis of responses, tests that induce reflexive as well as nonreflexive behavior may have the capacity to separate the more complex aspects of pain such as the possible presence of two components of pain, sensory/discriminative and motivational/affective. These components may be of fundamental importance for any attempt to understand the biological significance of SIA. Our examination of the neurotransmitter and neuropeptide systems has revealed that they are affected by the same manipulations that induce SIA. These amines and perhaps peptides play an integral role in learning, motivation, and performance. We conclude that the functional advantage of a reduction of pain during stressful situations is significant because it allows the animal to react in threatening and perhaps critical situations as if there were no pain. Once the pain system is inhibited, other systems modulate and mediate adaptive responses that expedite the survival of the animal.     

The R620W C/T polymorphism of the gene PTPN22 is associated with SLE independently of the association of PDCD1

The gene PTPN22 is located on chromosome 1p13 and encodes a protein tyrosine phosphatase called the lymphoid-specific phosphatase (Lyp). Lyp is expressed in lymphocytes, where it physically associates through its proline-rich motif (called P1) with the SH3 domain of the protein tyrosine kinase Csk, an important suppressor of the Src family of kinases Lck and Fyn, which mediate TCR signaling. Therefore, it is said that interaction between Lyp and Csk enables these effectors to inhibit T-cell activation synergistically. It was reported that a missense single nucleotide polymorphism , R620W (rs2476601), 1858C->T encodes an amino-acid change in the P1 proline-rich motif of the gene PTPN22 and is associated with SLE in North American white individuals. PTPN22 gene polymorphisms were genotyped in 571 Swedish SLE patients and 1042 healthy controls using TaqMan SNP Genotyping Assay. Differences were observed between cases and control subjects at both the allele (chi(2)=11.2895;P=0.0007,1df) and genotype (chi(2)=10.2243;P=0.0013, 1df) levels. We also found evidence of a genetic association between PTPN22 and renal disorder (chi(2)=9.5660;P=0.0019). We then analyzed if in patients with renal disorder associations with PDCD1 and PTPN22 were independent. Our data suggest that this appears to be the case although we observed some degree of interaction.     

Molecular cloning and characterization of a novel gene of Candida albicans,CDR1, conferring multiple resistance to drugs and antifungals

By functional complementation of a PDR5 null mutant of Saccharomyces cervisiae, we have cloned and sequenced the multidrug-resistance gene CDR1 of Candida albicans. Transformation by CDR1 of a PDR5-disrupted host hypersensitive to cycloheximide and chloramphenicol resulted in resistance to cycloheximide, chloramphenicol and other drugs, such as the antifungal miconazole, with collateral hypersensitivity to oligomycin, nystatin and 2,4 dinitrophenol. Our results also demonstrate the presence of several PDR5 complementing genes in C. albicans, displaying multidrug-resistance patterns different from PDR5 and CDR1. The nucleotide sequence of CDR1 revealed that, like PDR5, it encodes a putative membrane pump belonging to the ABC (ATP-binding cassette) superfamily. CDR1 encodes a 1501-residue protein of 169.9 kDa whose predicted structural organization is characterized by two homologous halves, each comprising a hydrophobic region with a set of six transmembrane stretches, preceded by a hydrophilic nucleotide binding fold.     

Dehydroepiandrosterone-mediated decrease in caloric intake by obese Zucker rats is not due to changes in serum entrostatin-like immunoreactivity

To understand the mechanism(s) of appetite modulation by DHEA, we have undertaken a series of studies to examine the effects of DHEA on neurotransmitters and neuropeptides known to affect appetitive behavior. Here, we report the effect of DHEA on serum enterostatin-VPDPR or E, a pentapeptide known to cause selective diminution in fat intake. Four-week-old lean (fa/+) and obese (fa/fa) Zucker rats were divided into control and treatment groups. DHEA-treated groups received powdered chow containing 0.6% DHEA ad lib for 16 weeks. Another group of obese rats was pair fed to match the intake of the obese DHEA-treated rats. At the end of this period, trunk blood was collected from fasted rats for assay of E-like immunoreactivity (E-LI) by ELISA. DHEA treatment caused a significant diminution in circulating E-LI in both lean (control: 2030 +/- 226; treated: 752 +/- 145 ng/mL; n = 10, p < 0.0001) and obese (control: 2489 +/- 391, n = 6; treated: 1123 +/- 185 ng/mL, n = 7; p = 0.0003) rats. Because DHEA treatment decreases caloric intake and body weight, we examined the effect of caloric intake and body weight on E-LI levels. Serum ELI levels were lower in the obese DHEA-treated group compared to that of obese pair fed (pair fed: 1589 +/- 313, n = 6; DHEA: 1123 +/- 185 ng/mL, n = 7), but the differences were statistically insignificant (p = 0.185). Also, both weight-matched lean and obese control rats had significantly (p < 0.008) higher E-LI than their DHEA-treated counterparts. To examine whether the decrease in serum E-LI following DHEA treatment could be due to increased peptide metabolism, the rate of disappearance of endogenous E-LI from serum (obese control and DHEA-treated) at 37 degrees C was evaluated. The results show an attenuation of peptide metabolism in serum from DHEA-treated rats, a finding contrary to our expectations. In summary, DHEA treatment lowers serum E-LI levels both in lean and obese Zucker rats. This decrement in peptide level is not secondary to changes in body weight or caloric intake due to DHEA, or due to altered serum peptide metabolism. Although DHEA appears to be a potent modulator of E-LI levels, the relationship between DHEA and E-LI in relation to appetitive behavior remains to be clarified.