Natural history and treatment of anorectal strictures complicating Crohn's disease

Forty-four patients seen between 1975 and 1985 with anorectal strictures complicating Crohn's disease have been reviewed to determine the natural history and outcome of surgical treatment. Proctitis was present in 98 per cent, and 93 per cent of patients had sever perianal disease. The site of strictures was rectal in 22, anal in 15 and anorectal in 11 (4 patients had a stricture at 2 sites). Initial treatment was by rectal excision alone in 6, dilatation in 33, and 5 needed no treatment at all. Single dilatation was effective in 15, 8 required two dilatations and in 10 repeated dilatation was necessary. Proctocolectomy was eventually required in 19 patients, 2 have a loop ileostomy and 1 has an ileostomy with a rectal stump in situ. Only 21 remain asymptomatic while 3 continue to need dilatation. Perineal wound healing was delayed in 9 of 19 patients having a proctocolectomy and in 3 the perineal wound has never healed.     

Retraction brain ischaemia: mannitol plus nimodipine preserves both cerebral blood flow and evoked potentials during normoventilation and hyperventilation.

In our miniature swine model simulating operating room brain retraction, we investigated the effects of mannitol plus nimodipine on cerebral blood flow (CBF) and evoked potentials (EP) ipsilateral and contralateral to retraction, in comparison with either agent alone, during both normoventilation and hyperventilation. We here report results in 27 animals with intravenous mannitol (2 g kg-1 over 15 min) and/or nimodipine (1 microgram kg-1 min-1 constant infusion). Mannitol plus nimodipine was superior both to controls and to either mannitol alone or nimodipine alone in preserving EP amplitude ipsilateral to retraction during both normoventilation and hyperventilation. Mannitol alone was effective in normoventilation at preserving EP, while nimodipine alone was effective in hyperventilation. No significant asymmetries in CBF or EP were seen with mannitol plus nimodipine in either normoventilation or hyperventilation. By five minutes postretraction CBF had returned to preretraction values for all groups, and EP amplitude had returned also except for hyperventilated controls. In this model of brain retraction, mannitol plus nimodipine is superior to either agent alone in maintaining both CBF and EP when normoventilation and hyperventilation are employed. The results are discussed in terms of the possible mechanisms for the different and complementary effects of mannitol and nimodipine.     

Relative disease severity in siblings with myotonic dystrophy.

Myotonic dystrophy is an autosomal dominant disorder in which an early-onset form is characteristically inherited from the mother. We studied 17 affected sibling pairs from 15 families in which two or more affected children were born to mothers with myotonic dystrophy. Later-born affected children suffered more severe disease than their first-born siblings in 13 of 17 sibling pairs. Later-born affected siblings displayed significantly more neonatal feeding difficulties, later age when first sitting alone, later age when first walking alone, and a higher incidence of scoliosis. The overall difference in disease severity between affected siblings increased as the age difference between them increased, suggesting that increasing maternal age is a factor in the relative disease severity of affected children. These findings may have relevance for genetic counseling.     

Prenatal ultrasound diagnosis of fetal candida infection: a complication of a retained intrauterine contraceptive device.

A 32-year-old woman was referred complaining of abdominal pain and bleeding at 18 weeks' gestation. The striking finding on ultrasound examination was of symmetrically enlarged echogenic fetal lungs. In addition, mediastinal compression, increased echogenicity of the kidneys and bowel, an enlarged liver of decreased echogenicity, and hydrops fetalis, as evidenced by ascites and skin edema, were all present. The differential diagnosis included upper respiratory tract obstruction and cystic kidney disease. The presence of fetal hydrops together with the other findings suggested a poor outcome, and on these grounds therapeutic abortion was recommended and performed. Subsequent postmortem findings explained all the ultrasound abnormalities on the basis of extensive fetal candida infection. The presence of a retained intrauterine contraceptive device was considered to be the likely cause and the implications of this, together with the ultrasound abnormalities and differential diagnoses, are discussed.     

Brain protection at the blood-cerebrospinal fluid interface involves a glutathione-dependent metabolic barrier mechanism.

The choroid plexuses (CPs) form a protective interface between the blood and the ventricular cerebrospinal fluid (CSF). To probe into the pathways by which CPs provide brain protection, we sought to evaluate the efficiency of glutathione conjugation in this barrier as a mechanism to prevent the entry of blood-borne electrophilic, potentially toxic compounds into the CSF, and we investigated the fate of the resulting metabolites. Rat CPs, as well as human CPs from both fetal and adult brains, displayed high glutathione-S-transferase activities. Using an in vitro model of the blood-CSF barrier consisting of choroidal epithelial cells cultured in a two-chambered device, we showed that glutathione conjugation can efficiently prevent the entry of 1-chloro-2,4-dinitrobenzene (CDNB) into the CSF, a model for electrophilic compounds. The duration of this enzymatic protection was set by the concentration of CDNB to which the epithelium was exposed, and this barrier effect was impaired only on severe epithelial intracellular glutathione and cysteine depletion. The conjugate was excreted from the choroidal cells in a polarized manner, mostly at the blood-facing membrane, via a high-capacity transport process, which is not a rate-limiting step in this detoxification pathway, and which may involve transporters of the ATP-binding cassette c(Abcc) and/or solute carrier 21 (Slc21) families. Supplying the choroidal epithelium at the blood-facing membrane with a therapeutically relevant concentration of N-acetylcysteine sustained this neuroprotective effect. Thus, glutathione conjugation at the CP epithelium coupled with the basolateral efflux of the resulting metabolites form an efficient blood-CSF enzymatic barrier, which can be enhanced by pharmacologically increasing glutathione synthesis within the epithelial cells.     

Computerized cortical surface electroencephalography after temporary middle cerebral artery occlusion in rabbits

The sensitivity and regional specificity of intraoperative electroencephalographic (EEG) monitoring in cerebral ischemia was evaluated in a new experimental model of temporary focal cerebral ischemia in rabbits. EEG potentials were recorded directly from the cortical surface using a bipolar disc electrode grid and were analyzed by computer. Groups of 5 animals each underwent temporary occlusion of the left middle cerebral arterial trunk for 5, 10, 20, 30, 45, or 60 minutes. EEG data were recorded from the cortex proximal (temporal site) and distal (parasagittal site) to the middle cerebral arterial trunk during occlusion and 2 hours of reperfusion. EEG suppression was detected immediately after occlusion at the temporal site by analysis of power spectra in 29 of 30 rabbits (mean power, 32% of base line), by compressed spectral array (CSA) edge analysis in 23, and by analysis of the conventional EEG wave form in 24. Within 5 minutes after the start of occlusion, all 30 rabbits showed EEG power suppression and 26 showed decrease in the CSA edge frequency or in the routine EEG wave form. By the end of the occlusion period, EEG power at the temporal site had decreased to 20.5% of base line. At the parasagittal site, a lesser degree of EEG suppression was detected; 20 rabbits had an initial loss of EEG power (mean, 85.7% of base line), 13 had decrease in the CSA edge, and 7 had suppression of the EEG wave form. By the end of the occlusion period, spectral power at the parasagittal site had decreased in 25 of 30 rabbits to a mean of 86.9% of base line.(ABSTRACT TRUNCATED AT 250 WORDS)     

Construction and validation of a Parkinson's disease mutation genotyping array for the Parkin gene.

Parkin mutations account for the majority of familial and sporadic early onset Parkinson's disease (EOPD) cases with a known genetic association. More than 100 mutations have been described in the Parkin gene that includes homozygous, compound heterozygous, and single heterozygous mutations. We have designed a Parkin mutation genotyping array (gene chip) that includes published Parkin sequence variants and allows their simultaneous detection. The chip was validated by screening 85 PD cases and 47 controls previously tested for Parkin mutations. Similar genotyping microarrays have been developed for other genetically heterogeneous diseases including age-related macular degeneration. Here, we show the utility of a genotyping array for Parkinson's disease by analysis of 60 subjects from the Genetic Epidemiology of Parkinson Disease (GEPD) study that includes 15 early-onset PD case probands and 45 relatives.