Teratologic and postnatal evaluation of aniline hydrochloride in the Fischer 344 rat

Timed-pregnant Fischer 344 rats were dosed by gavage with aniline hydrochloride (10, 30, or 100 mg/kg/day), a positive control agent (hydroxyurea, 200 mg/kg/day), or vehicle (distilled water) on gestational days (gd) 7 through 20 or gd 7 through parturition. At termination on gd 20 confirmed-pregnant dams exhibited characteristic signs of aniline HCl toxicity, i.e., methemoglobinemia, increased relative spleen weight, decreased red blood cell (RBC) count, and hematological changes indicative of increased hematopoietic activity. High-dose dams exhibited mild methemoglobinemia, increased relative spleen weight, and increased RBC size at termination on postnatal day (pnd) 30. At termination on gd 20, fetuses from aniline-treated dams exhibited increased relative liver weight and enhanced hematopoietic activity, but no evidence of an embryolethal or teratogenic effect was observed. Postnatal signs of toxicity in litters from aniline-treated dams (i.e., decreased body weight, elevated relative liver weight, and elevated relative spleen weight) were transient, and no evidence of toxicity was observed in pups surviving to pnd 60. Hydroxyurea (200 mg/kg/day) administered by gavage proved to be an excellent positive control for embryotoxicity, maternal toxicity, teratogenicity, and postnatal maturational deficits in the Fischer 344 rat. In conclusion, aniline hydrochloride was not teratogenic to Fischer 344 rats, even at maternally toxic doses; transient signs of toxicity were observed postnatally in the offspring in conjunction with mild, but persistent signs of maternal toxicity through pnd 30.     

Clinical biomechanics of the peritalar joint

The peritalar joint includes the articulations between the talus and calcaneus and the talus and navicular. Motion between the talus and calcaneus is described most often as rotation about an axis that points medially, anteriorly, and superiorly. This motion is considered to be triplanar, with inversion, plantar flexion, and adduction occurring together, whereas eversion, dorsiflexion, and abduction are associated. Similar motions have been described between the talus and navicular. Foot deformity, such as a pes planus or a pes cavus foot type, and hindfoot or midfoot joint fusion can alter the biomechanics of the peritalar joint.     

Airway intervention in adult supraglottitis

Background The timing of aggressive airway intervention in adult epiglottitis is controversial. Aims To correlate Friedman’s staging of epiglottitis on admission with the airway interventions undertaken. Methods A retrospective study of 23 adult patients, mean age 51 years (range 29–81 years), who had been admitted with acute supraglottitis between March 1988 and December 2000 was undertaken. Results Three patients (13%) had airway interventions; two with tracheostomy and one with tracheal intubation. All were Friedman stage III and had rapid symptom progression during the 24 hours prior to admission. Three other stage III patients with symptom progression longer than 24 hours and all the remaining patients (stage II or less) were managed with observation and intravenous therapy. Conclusions Friedman originally advocated airway intervention in any patient stage II or worse, but this intubation threshold should probably be lowered to those patients with rapid-onset stage III (moderate respiratory distress, stridor, respiratory rate >30 per minute, pCO₂ >45mmHg) disease.     

Biomechanical differences among pes cavus, neutrally aligned, and pes planus feet in subjects with diabetes

The purpose of this study was to quantify differences in joint range of motion, foot deformity, and foot morphology among pes cavus, neutrally aligned, pes planus rigid, and pes planus flexible feet. A cohort of 1047 veterans with diabetes (contributing 2047 feet) was enrolled in a prospective study of diabetic ulcer risk factors (the Seattle Diabetic Foot Study). Significant differences between foot types were found. Pes cavus feet had an increased percentage of prominent metatarsal heads, bony prominences, and hammer/claw toes (p < .0001), as well as significantly increased amounts of hallux dorsiflexion and decreased amounts of hallux plantarflexion (p < .0001) with a total range of motion equal to the other foot types (p = .3). Neutrally aligned feet had a lower percentage of intrinsic muscle atrophy, bony prominences, and hammer/claw toes (p < .0001). Pes planus feet had an increased lateral talometatarsal angle (p < .0001) and an increased second metatarsal length. These data demonstrate structural differences between foot types in a population with diabetes.     

Targeting human 8-oxoguanine glycosylase to mitochondria of oligodendrocytes protects against menadione-induced oxidative stress

Within the central nervous system (CNS), there is a differential susceptibility among cell types to certain pathological conditions believed to involve oxidative stress. Oligodendrocytes are extremely sensitive to oxidative stress, which correlates with a decreased ability to repair damage in mitochondrial DNA (mtDNA), as we have shown previously. To determine whether there is a causal relationship, studies were carried out to correct the deficit in repair of the oxidative damage in mtDNA in cultured oligodendrocytes. A vector containing a mitochondrial transport sequence (MTS) upstream of the sequence for human 8-oxoguanine-DNA glycosylase (OGG) was transfected into the cells. The efficiency of transfection and the localization of recombinant protein were determined by fluorescence microscopy and by Western blot analysis. Subsequent mtDNA repair studies, employing 100 micro M menadione to produce reactive oxygen species, showed a significant enhancement in repair of oxidative lesions in mtDNA of MTS-OGG transfected oligodendrocytes compared with cells transfected with vector only. Experiments were also conducted to determine the effect of changing mtDNA repair capacity on menadione-induced apoptosis in oligodendrocytes. These experiments show that targeting the OGG repair enzyme to mitochondria reduces the release of cytochrome c from the intermitochondrial space and the activation of caspase 9 in oligodendrocytes after exposure to menadione. Therefore, targeting of DNA repair enzymes to mitochondria appears to be a viable approach for the protection of cells against some of the deleterious effects of oxidative stress.     

1,25-dihydroxycholecalciferol in renal osteodystrophy. Epiphysiolysis--anticonvulsant therapy

Three children with azotaemic renal osteodystrophy were treated with 1,25-dihydroxycholecalciferol (1,25(OH)2D3). All showed clinical, biochemical, and radiological improvement within 6 months of starting treatment. There were no complications. The dose of 1,25(OH)2D3 required was 0-5 microgram per day for 2 children aged 22 and 30 months, and 2 microgram per day for a 15-year-old boy. 2 of the patients were receiving phenobarbitone and phenytoin and in one of them prior treatment with dihydrotachysterol 0-5 mg daily and 6 microgram 1alpha-hydroxycholecalciferol (1alphaOHD3) daily had failed to induce improvement. In one patient, in whom serial iliac bone samples were available, 2 microgram 1,25(OH)2D3 resulted in histological improvement in previously severe osteomalacia. 1,25(OH)2D3 appears to be an effective and safe drug in the treatment of uraemic osteodystrophy.