Post-traumatic female urethral reconstruction

Post-traumatic urethral damage resulting in urethrovaginal fistulas or strictures, though rare, should be suspected in patients who have unexpected urinary incontinence or lower urinary tract symptoms after pelvic surgery, pelvic fracture, a long-term indwelling urethral catheter, or pelvic radiation. Careful physical examination and cystourethroscopy are critical to diagnose and assess the extent of the fistula. A concomitant vesicovaginal or ureterovaginal fistula should also be ruled out. The two main indications for reconstruction are sphincteric incontinence and urethral obstruction. Surgical correction intends to create a continent urethra that permits volitional, painless, and unobstructed passage of urine. An autologous pubovaginal sling, with or without a Martius flap at time of reconstruction, should be considered. The three approaches to urethral reconstruction are anterior bladder flaps, posterior bladder flaps, and vaginal wall flaps. We believe vaginal flaps are usually the best option. Options for vaginal repair of fistula include primary closure, peninsula flaps, bilateral labial pedicle flaps, and labial island flaps. Outcomes are optimized by using exacting surgical principles during repair and careful postoperative management by an experienced reconstructive surgeon.     

Safety, tolerability, and pharmacokinetics of PTC124, a nonaminoglycoside nonsense mutation suppressor, following single- and multiple-dose administration to healthy male and female adult volunteers

Nonsense (premature stop codon) mutations are causative in 5% to 15% of patients with monogenetic inherited disorders. PTC124, a 284-Dalton 1,2,4-oxadiazole, promotes ribosomal readthrough of premature stop codons in mRNA and offers therapeutic potential for multiple genetic diseases. The authors conducted 2 phase I studies of PTC124 in 62 healthy adult volunteers. The initial, single-dose study evaluated doses of 3 to 200 mg/kg and assessed fed-fasting status on pharmacokinetics following a dose of 50 mg/kg. The subsequent multiple-dose study evaluated doses from 10 to 50 mg/kg/dose twice per day (bid) for up to 14 days. PTC124 administered orally as a liquid suspension was palatable and well tolerated through single doses of 100 mg/kg. At 150 and 200 mg/kg, PTC124 induced mild headache, dizziness, and gastrointestinal events. With repeated doses through 50 mg/kg/dose bid, reversible transaminase elevations <2 times the upper limit of normal were sometimes observed. Immunoblot analyses of peripheral blood mononuclear cell extracts revealed no protein elongation due to nonspecific ribosomal readthrough of normal stop codons. PTC124 plasma concentrations exceeding the 2- to 10-microg/mL values associated with activity in preclinical genetic disease models were safely achieved. No sex-related differences in pharmacokinetics were seen. No drug accumulation with repeated dosing was apparent. Diurnal variation was observed, with greater PTC124 exposures after evening doses. PTC124 excretion in the urine was <2%. PTC124 pharmacokinetics were described by a 1-compartment model. Collectively, the data support initiation of phase II studies of PTC124 in patients with nonsense mutation-mediated cystic fibrosis and Duchenne muscular dystrophy.     

Similar rapid onset of action and magnitude of effect of fexofenadine and cetirizine as assessed by inhibition of histamine-induced wheal-and-flare reaction.

BACKGROUND: Histamine-induced wheal-and-flare studies are useful, objective tests for determining differences in the peripheral H1-receptor blockade activities of antihistamines. OBJECTIVE: To evaluate the time of occurrence of 95% inhibition of histamine-induced wheal and flare after administration of fexofenadine hydrochloride, 180 mg, or cetirizine, 10 mg. METHODS: Forty-two volunteers (aged 18-60 years) were included in a randomized, double-blind, crossover study. Skin prick tests were undertaken using histamine (100 mg/mL) before treatment and 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, and 4.0 hours after treatment. Wheal and flare areas were evaluated, and the time to occurrence of 95% inhibition and the frequency of subjects exhibiting 95% inhibition before median time to 95% inhibition were calculated. RESULTS: Mean +/- SD time to 95% wheal inhibition was 2.46 +/- 0.71 hours with fexofenadine and 2.55 +/- 0.57 hours with cetirizine. The estimated mean difference between fexofenadine and cetirizine (-7 minutes in favor of fexofenadine; 2-sided 95% confidence interval, -21 to +7 minutes) was not statistically significant (P = .34). For wheal, 29% of subjects receiving fexofenadine and 24% receiving cetirizine achieved 95% inhibition before the median time of inhibition (2.5 hours). An exact permutation test yielded a P = .37. For flare, 26% of subjects receiving fexofenadine and 10% receiving cetirizine achieved 95% inhibition before the median time of inhibition (3 hours; P = .12 by exact permutation test). CONCLUSIONS: Fexofenadine and cetirizine have comparable onset of action times and similar frequencies of inhibition, as evaluated by the occurrence of 95% inhibition of histamine-induced wheal and flare.     

Warburg (HARD +/- E) syndrome without retinal dysplasia: case report and review.

Warburg syndrome is a recently defined autosomal recessive oculocerebral syndrome. It was previously given the acronym HARD +/- E, indicating what were regarded as the pathognomonic features, namely hydrocephalus, agyria, and retinal dysplasia with or without encephalocele. We report the case of a male infant with the typical cerebral features of hydrocephalus, agyria, and pseudoencephalocele, but without retinal dysplasia. Peters' anomaly and optic nerve hypoplasia were the main ocular defects. We believe that anterior chamber defects and optic nerve hypoplasia are the ocular defects more directly related developmentally to the cerebral defects. Definition of ocular defects is important, since diagnosis and counselling rely heavily on ocular signs, which help to distinguish this syndrome from neural tube defects in general.     

Postmortem assessment of thalamic nuclear volumes in subjects with schizophrenia.

OBJECTIVE: The authors assessed schizophrenia-associated changes in volume and neuronal number in the mediodorsal nucleus and the pulvinar regions of the thalamus. METHOD: Right-hemisphere thalami obtained at autopsy from 14 schizophrenic and eight comparison subjects were examined. Computer-assisted morphometric techniques were used to determine volumes for the mediodorsal nucleus, pulvinar, and the anterior and centromedian nuclei as well as the parvocellular, magnocellular, and caudodorsal subdivisions of the mediodorsal nucleus. Neurons in the mediodorsal nucleus and pulvinar were counted and measured by using a stereology-based sampling strategy. RESULTS: Four schizophrenic and three comparison subjects had Alzheimer's type pathology, leaving 10 schizophrenic and five comparison subjects without other documented neuropathological changes. In analyses that included either the full cohort or only the subjects without Alzheimer's type pathology, volumes of the mediodorsal nucleus and pulvinar, but not the anterior or centromedian nuclei, were significantly smaller in the schizophrenic subjects. For the schizophrenic subjects, neuronal number in the mediodorsal nucleus, parvocellular subdivision, and pulvinar was significantly lower, and neuronal size in the mediodorsal nucleus, caudodorsal subdivision, and pulvinar was significantly smaller. CONCLUSIONS: Schizophrenia is associated with volume and neuronal changes in the mediodorsal nucleus and pulvinar, the major association nuclei of the thalamus, whereas total thalamic volume and the volumes of anterior and centromedian nuclei were not significantly altered.     

Eubacterial diversity of activated biomass from a common effluent treatment plant

A common effluent treatment plant (CETP) is a biological wastewater treatment facility that receives wastewater from different industries. The activated biomass in the CETP survives on a wide range of chemicals with no fixed wastewater characteristics. We carried out a diversity analysis of this activated biomass using culture as well as culture-independent techniques. Using culture-based techniques, strains belonging to 26 different genera from the phyla Proteobacteria, Actinobacteria and Firmicutes were isolated. The gamma-proteobacteria was the best represented class, with 36.5% of the isolates. Bacterial diversity was also analyzed culture-independently by means of sequence determination of cloned 16S rRNA genes. Twenty-one different genera from the phyla Proteobacteria, Firmicutes, Planctomycetes and Bacteroidetes were identified. The total diversity of the activated biomass was composed of members of five known phyla, represented by 37 genera, with the Proteobacteria constituting the most abundant phylum detected. However, a very large fraction of the diversity represented a hitherto unidentified bacterial population. More than half (50.2%) of the 16S rDNA clones represented unidentified non-culturable bacteria, underlining the vast untapped diversity of CETP communities. Our results also indicate that both culture-based and culture-independent techniques should be combined to cover the microbial diversity of complex ecosystems.     

Quantification of reduction in forced vital capacity of sand stone quarry workers

This study assessed the reduction in forced vital capacity of lungs of sand stone quarry workers exposed to high respirable suspended particulate concentration. The sand stone quarry workers are engaged in different type of activities like drilling, loading and dressing. These different working places have different concentration of RSPM and these workers are exposed to different concentration of RSPM. It is found that exposure duration and exposure concentrations are main factors responsible to damage respiratory tract of worker. It is also revealed from the study that most of the workers are suffering from silicosis if the exposure duration is more than 15 years.