Reorganization of human cortical maps caused by inherited photoreceptor abnormalities

We describe a compelling demonstration of large-scale developmental reorganization in the human visual pathways. The developmental reorganization was observed in rod monochromats, a rare group of congenitally colorblind individuals who virtually lack cone photoreceptor function. Normal controls had a cortical region, spanning several square centimeters, that responded to signals initiated in the all-cone foveola but was inactive under rod viewing conditions; in rod monochromats this cortical region responded powerfully to rod-initiated signals. The measurements trace a causal pathway that begins with a genetic anomaly that directly influences sensory cells and ultimately results in a substantial central reorganization.     

Lipophosphoglycan expression and virulence in Ricin-resistant variants of Leishmania major

Lipophosphoglycan (LPG) of Leishmania is a polymorphic molecule comprising an alkylglycerol anchor, a conserved oligosaccharide core and a species-specific polymer of oligosaccharide repeats joined by phosphodiester bonds. This molecule, together with the membrane polypeptide gp63, has been implicated as a parasite receptor for host macrophages. To examine the role of LPG in parasite infectivity glycosylation variants of Leishmania major were generated by chemical mutagenesis of a virulent cloned line V121 and variants with modified LPG selected using the galactose-specific lectin Ricinus communis II (RCA II). Twenty RCA II-resistant primary clones were generated. Analysis of LPG profile by immunoblotting using LPG-specific monoclonal and polyclonal antibodies revealed that some of the clones were LPG-deficient. Three clones that did not bind any LPG-specific antibodies but expressed normal levels of the M_r 63 000 glycoprotein (gp63), a second parasite receptor for host, were chosen for detailed studies.All three clones expressed, at least to some extent, a surface molecule which could be labeled by mild periodate oxidation and sodium borotritide and behaved like LPG by hydrophobic interaction chromatography. All clones also bound a well-characterized monoclonal antibody L157 directed to the core oligosaccharide of LPG, but did not bind another monoclonal antibody, CA7AE, to an epitope on a repeating unit shared by Leishmania donovani and L. major LPG. A third monoclonal antibody, 5E6, recognizing LPG on the surface of wild-type V121 promastigotes bound only to RCA II-resistant clone 3A2-C3 and was restricted to an internal structure. The LPG molecule that this clone expressed was a form of LPG by its chromatographic behavior and by its monosaccharide and alkylglycerol composition. Clone 3A2-C3 was the only one to infect mice in vivo and survive in macrophages in vitro, albeit at a much reduced rate compared to wild-type V121 promastigotes. The data suggest that some form of LPG may be necessary to ensure parasite infectivity.     

The effect of the illumination time when treating port-wine stains

This paper reports the electron microscopy results obtained from two patients who were treated with 5 W of yellow (578 nm) light from a copper vapour laser with an illumination time of 3.6 ms and a 0.3 mm spot diameter. The endpoint of treatment was transient blanching. Following treatment, erythema was observed. There was minimal damage to the epidermis and non-vascular tissue such as the nerve fibres. There was severe damage to the endothelial cells of the ectatic vessels. Twenty-four hours after treatment, platelet activation and collagen were present, indicating that these vessels were no longer viable. Theoretical calculations are used to determine the flow of heat within and away from a 50m diameter vessel. From this, heating of the entire vessel is shown to occur with illumination times of 4 ms, with minimal heating of the non-vascular tissue. Shorter illuminations do not heat the entire vessel, while the use of longer illumination times will cause excessive damage to the surrounding non-vascular tissue. Illumination times close to 4 ms must be regarded as optimal.     

Actinomyces and nocardia infections in immunocompromised and nonimmunocompromised patients

A retrospective survey of nocardia and actinomyces infections in five local hospitals was conducted over a 3-year period in El Paso, Texas, a border city, in the southwestern United States. The medical records of 42 patients with suspected nocardiosis or actinomycosis were reviewed. One patient was diagnosed with actinomyces and 12 patients with nocardia. Microbiological data included morphologic characteristics, biochemical profile, and susceptibility testing. Predisposing factors included leukemia, renal insufficiency, renal transplant, and lymphoma. No predisposing factors were found in 67% (n = 8) of patients (including the patient with actinomycosis). Twenty-three percent (n = 3) of patients had disseminated disease without evidence of underlying disease or immunosuppression. The mortality and morbidity of these infections appeared to be low.     

Cerebral vasculitis in a case of Sydenham's chorea

A 10-year-old girl with acute-onset hemichorea had multiple areas of abnormal signal seen on magnetic resonance imaging of the brain, associated with middle and anterior cerebral artery vasculitis seen on cerebral angiography. Her serology and clinical course were supportive of the diagnosis of Sydenham's chorea. Other causes of cerebral vasculitis were excluded. Follow-up studies revealed resolution of changes seen on magnetic resonance imaging and partial resolution of angiographic abnormalities. This is the first report of abnormal cerebral angiography in Sydenham's chorea.     

Neonatal herpesvirus sepsis following internal monitoring

The use of internal monitoring, in which an electrode is attached to the fetal scalp, may be associated with serious complications. The authors present a case of fetal neonatal sepsis due to herpesvirus arising at the electrode site.     

Maternal and neonatal morbidity after elective repeat Cesarean delivery versus a trial of labor after previous Cesarean delivery in a community teaching hospital.

OBJECTIVE: To compare maternal and fetal outcomes after elective repeat Cesarean section versus a trial of labor in women after one prior uterine scar. STUDY DESIGN: All women with a previous single low transverse Cesarean section delivered at term with no contraindications to vaginal delivery were retrospectively identified in our database from January 1995 to October 1998. Outcomes were first analyzed by comparing mother-neonate dyads delivered by elective repeat Cesarean section to those undergoing a trial of labor. Secondarily, outcomes of mother-neonatal dyads who achieved a vaginal delivery or failed a trial of labor were compared to those who had elective repeat Cesarean delivery. RESULTS: Of 1408 deliveries, 749/927 (81%) had a successful vaginal birth after a prior Cesarean delivery. There were no differences in the rates of transfusion, infection, uterine rupture and operative injury when comparing trial of labor versus elective repeat Cesarean delivery. Neonates delivered by elective repeat Cesarean delivery were of earlier gestation and had higher rates of respiratory complications (p < 0.05). Mother-neonatal dyads with a failed trial of labor sustained the greatest risk of complications. CONCLUSION: Overall, neonatal and maternal outcomes compared favorably among women undergoing a trial of labor versus elective repeat Cesarean delivery. The majority of morbidity was associated with a failed trial of labor. Better selection of women likely to have a successful vaginal birth after a prior Cesarean delivery would be expected to decrease the risks of trial of labor.     

Treatment of human tumor xenografts with monoclonal antibody 806 in combination with a prototypical epidermal growth factor receptor-specific antibody generates enhanced antitumor activity.

Monoclonal antibody (mAb) 806 is a novel epidermal growth factor receptor (EGFR) antibody with significant antitumor activity that recognizes a mutant EGFR commonly expressed in glioma known as delta2-7 EGFR (de2-7 EGFR or EGFRvIII) and a subset of the wild-type (wt) EGFR found in cells that overexpress the receptor. We have used two human xenograft mouse models to examine the efficacy of mAb 806 in combination with mAb 528, a prototypical anti-EGFR antibody with similar specificity to cetuximab. Treatment of nude mice, bearing s.c. or i.c. tumor human xenografts expressing the wt or de2-7 EGFR, with mAbs 806 and 528 in combination resulted in additive and in some cases synergistic, antitumor activity. Interestingly, mAb 528 was also effective against xenografts expressing the ligand independent de2-7 EGFR when used as a single agent, showing that its antitumor activity is not merely mediated through inhibition of ligand binding. When used as single agents, neither mAbs 806 or 528 induced down-regulation of the de2-7 EGFR either in vitro or in vivo. In contrast, the combination of antibodies produced a rapid and dramatic decrease in the total cell surface de2-7 EGFR both in vitro and in xenografts. Consistent with this decrease in total cell surface de2-7 EGFR, we observed up-regulation of the cell cycle inhibitor p27(KIP1) and a decrease in tumor cell proliferation as measured by Ki-67 immunostaining when the antibodies were used in combination in vivo. Thus, mAb 806 can synergize with other EGFR-specific antibodies thereby providing a rationale for its translation into the clinic.