Identification of the murine beige gene by YAC complementation and positional cloning.

The beige mutation is a murine autosomal recessive disorder, resulting in hypopigmentation, bleeding and immune cell dysfunction. The gene defective in beige is thought to be a homologue of the gene for the human disorder Chediak-Higashi syndrome. We have identified the murine beige gene by in vitro complementation and positional cloning, and confirmed its identification by defining mutations in two independent mutant alleles. The sequence of the beige gene message shows strong nucleotide homology to multiple human ESTs, one or more of which may be associated with the Chediak-Higashi syndrome gene. The amino acid sequence of the Beige protein revealed a novel protein with significant amino acid homology to orphan proteins identified in Saccharomyces cerevisiae, Caenorhabditis elegans and humans.

A comparison of treatment outcomes for moxifloxacin versus ofloxacin/metronidazole for first-line treatment of uncomplicated non-gonococcal pelvic inflammatory disease.

Large randomized controlled trials support the efficacy of moxifloxacin for the treatment of uncomplicated pelvic inflammatory disease (PID). This study compares the clinical outcome and tolerability of treatment with moxifloxacin 400 mg once a day or ofloxacin 400 mg plus metronidazole 400 mg both twice daily in patients diagnosed with PID. A retrospective case-notes review was performed on patients diagnosed clinically with PID before and after local guidelines were changed to recommend moxifloxacin as first-line treatment for uncomplicated PID. Before the guidelines changed, 114/134 (85%) patients received the recommended first-line therapy versus 206/257 (80%) after the change, P = 0.3. There was no difference in the clinical outcomes between the two groups; significant improvement/resolved 77% versus 70%; marginal improvement 3% versus 11%; no change/worse 20% versus 18%, P = 0.14. Moxifloxacin is confirmed to be an effective alternative to ofloxacin/metronidazole for the treatment of PID in a large urban genitourinary clinic setting.

Immunosuppressive human anti-CD83 monoclonal antibody depletion of activated dendritic cells in transplantation.

Current immunosuppressive/anti-inflammatory agents target the responding effector arm of the immune response and their nonspecific action increases the risk of infection and malignancy. These effects impact on their use in allogeneic haematopoietic cell transplantation and other forms of transplantation. Interventions that target activated dendritic cells (DCs) have the potential to suppress the induction of undesired immune responses (for example, graft versus host disease (GVHD) or transplant rejection) and to leave protective T-cell immune responses intact (for example, cytomegalovirus (CMV) immunity). We developed a human IgG1 monoclonal antibody (mAb), 3C12, specific for CD83, which is expressed on activated but not resting DC. The 3C12 mAb and an affinity improved version, 3C12C, depleted CD83(+) cells by CD16(+) NK cell-mediated antibody-dependent cellular cytotoxicity, and inhibited allogeneic T-cell proliferation in vitro. A single dose of 3C12C prevented human peripheral blood mononuclear cell-induced acute GVHD in SCID mouse recipients. The mAb 3C12C depleted CMRF-44(+)CD83(bright) activated DC but spared CD83(dim/-) DC in vivo. It reduced human T-cell activation in vivo and maintained the proportion of CD4(+) FoxP3(+) CD25(+) Treg cells and also viral-specific CD8(+) T cells. The anti-CD83 mAb, 3C12C, merits further evaluation as a new immunosuppressive agent in transplantation.

Delayed detection of coarctation in infancy: implications for timing of newborn follow-up.

During a recent 5-year period, 74 patients younger than 6 months of age were diagnosed with coarctation of the aorta. Coarctation was correctly diagnosed in only 22% of patients prior to referral despite readily apparent femoral pulse abnormalities in 86%. Infants whose symptoms were detected between 5 and 14 days of age were significantly more ill than infants outside this age range and had a high mortality rate (25%). The number of associated cardiac defects was not related to the severity of clinical illness in this group, suggesting that closure of the ductus arteriosus is the primary determinate of disease severity. Observations in two patients suggested that a detectable pulse discrepancy occurs between 3 and 5 days postnatally. Upper extremity hypertension was found commonly in infants after 5 days of age despite the presence of congestive heart failure. Earlier detection of coarctation in the newborn requires a diligent cardiovascular and peripheral pulse examination between 3 and 7 days of life, upper extremity and lower extremity blood pressure measurement, and a high index of suspicion.

Pseudo left axis deviation and the S1S2S3 syndrome in chronic airway obstruction.

Pseudo left axis deviation (not true left axis deviation and the S1S2S3 syndrome are infrequently reported electrocardiographic findings in chronic airway obstruction. One hundred fifty-eight patients with severe chronic airway obstruction documented by pulmonary function testing were evaluated for these electrocardiographic findings. Pseudo left axis deviation was found in 23 patients (15 percent), and the S1S2S3 syndrome was found in 14 patients (9 percent). The electrocardiographic and vectorcardiographic findings are illustrated.

Left stellectomy in the long QT syndrome.

Recent investigations have reaffirmed the role of autonomic innervation of the heart in the genesis of certain cardiac arrhythmias. The long QT syndrome (LQTS) has been described for years, but only recently has evidence of its link to autonomic imbalance been established. A case of LQTS is presented with intraoperative evidence at the time of left stellectomy of life-threatening arrhythmias triggered by stimulation of this neural body. Removal of the left stellate ganglion normalized the electrocardiographic (ECG) abnormalities and has rendered the patient asymptomatic since surgery. Left stellectomy may become definitive therapy for selected patients with the LQTS.

The heritable syndrome of prolonged Q-T interval, syncope, and sudden death. Electron microscopic observation.

A family with the heritable syndrome of prolonged Q-T interval is reported. Three members died suddenly. Six had a prolonged Q-T interval. One had syncopal episodes for four years but has had no syncope since therapy with propranolol was initiated two years ago. The inheritance appears to be autosomal dominant. There was no evidence of hearing defects. Histologic and electron microscopic studies were performed on cardiac tissue from one patient. This is the first report of electron microscopic studies, and the findings suggest a possible defect of calcium metabolism in the myofiber.

Adnexal infarction after conservative surgical management of torsion of a hyperstimulated ovary.

OBJECTIVE: To report a case of postoperative necrosis after conservative management of torsion of a hyperstimulated ovary. DESIGN: Case report and literature review. SETTING: Tertiary care center. PATIENT: Infertility patient undergoing IVF-ET. INTERVENTIONS: Detorsion followed by unilateral salpingo-oophorectomy 2 days later. MAIN OUTCOME MEASURE: Postoperative course. RESULTS: Postoperative necrosis after detorsion. CONCLUSIONS: Postoperative necrosis is an uncommon but serious complication of conservative surgical management of adnexal torsion.

Real-time echocardiography: a new technique to facilitate Swan-Ganz catheter insertion.

Real-time echocardiography was used to position a pulmonary artery catheter in a septic child in whom the usual placement methods were not successful. This technique to facilitate pulmonary artery catheter placement avoids radiation, is portable and allows direct visualization of intracardiac catheter orientation. When smaller children and infants undergo pulmonary artery catheterization at the bedside, real-time echocardiography may allow catheter insertion when the usual techniques have failed.