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Biomedical subjects

M J Higgins

Publications and source records attributed to M J Higgins.

At least 73 records · Page 4Linked to original sources
PubMed1994

Localization of Beckwith-Wiedemann and rhabdoid tumor chromosome rearrangements to a defined interval in chromosome band 11p15.5.

Chromosome rearrangements have provided useful landmarks to identify disease loci and have served as starting points for positional cloning strategies for candidate genes. We have used fluorescence in situ hybridization (FISH) and pulsed-field gel electrophoresis (PFGE) to map three Beckwith-Wiedemann syndrome (BWS) breakpoints and a rhabdoid tumor breakpoint more precisely. These breakpoints mapped to the interval between D11S679 and the insulin-like growth factor 2 (IGF2) gene on 11p15.5. A cosmid (c15-2) was identified that mapped centromeric to the BWS t(11;16) and the rhabdoid tumor-associated t(11;22), telomeric to the BWS t(11;22), and was found to span the BWS-associated inv(11) breakpoint. Pulsed-field gel analysis placed all four breakpoints into a 250-675 kb interval distal to D11S679 and at least 270 kb centromeric to the IGF2 and H19 loci. These data locate all three BWS rearrangements and the rhabdoid tumor t(11;22) breakpoint in the same region of 11p15.5, suggesting that they may be affecting the same locus or closely linked loci. Cosmid c15-2 provides a well-defined starting point in the search for candidate disease genes.

Beckwith-Wiedemann Syndrome↗
PubMed1994

Traumatic intracranial aneurysms in childhood and adolescence. Case reports and review of the literature.

We report four pediatric traumatic intracranial aneurysms occurring before the age of 10 years. Two of these aneurysms were the result of closed head injury. The remaining two were iatrogenic aneurysms which occurred in unusual circumstances. These four children represent 33% of the pediatric intracranial aneurysms seen at the Children's Hospital of Eastern Ontario from 1974 to 1992. Diagnosis of traumatic intracranial aneurysms requires a high index of suspicion: any head-injured or postoperative child who experiences delayed neurologic deterioration, or who fails to improve as expected following treatment, should promptly undergo diagnostic intracranial imaging. Documented subarachnoid hemorrhage, intracerebral or intraventricular hemorrhage, or subdural haematoma in this clinical setting should be further investigated by cerebral angiography to exclude a traumatic aneurysm or other vascular lesion. Traumatic aneurysms typically arise at the skull base or from distal anterior or middle cerebral arteries or branches consequent to direct mural injury or to acceleration-induced shear. Reported traumatic aneurysms account for 14%-39% of all pediatric aneurysms. Iatrogenic aneurysms also occur with unexpected frequency during childhood and adolescence. Pediatric traumatic cerebral aneurysms may present early or late. Most present early with intracranial hemorrhage. Late presentation occurs infrequently, typically as an aneurysmal mass. Once diagnosed, these aneurysms should be promptly treated by craniotomy employing routine microsurgical techniques, or in some cases, by endovascular detachable balloon techniques. Delay in operative treatment entails significant risks of repeated hemorrhage and death. Outcome in these children is primarily determined by the extent of traumatic cerebral injury and the preoperative clinical status. The latter directly depends upon diagnosis of the aneurysm prior to either initial or repeated hemorrhage.

Adolescent↗
PubMed1994

A new ventricular catheter for the prevention and treatment of proximal obstruction in cerebrospinal fluid shunts.

Ventriculoperitoneal shunt malfunction is most commonly caused by obstruction of the ventricular catheter by choroid plexus. Such ventricular catheter obstructions remain a major unsolved problem, despite improvements in materials, catheter design, new valves, and increased emphasis on precise techniques favoring optimal catheter placement. Shunt malfunction demands elective and often urgent open surgical intervention to revise the shunt system. Such revisions require a general anesthetic in addition to the operative procedure and are followed by a minimum hospitalization of 2 to 3 days. Our experience with hundreds of shunt revisions prompted novel ideas for the development of a new ventricular catheter to treat or prevent this common and previously unresolved difficulty effectively.

Catheters, Indwelling↗
PubMed1993

A human chromosome 11 NotI end clone library.

A NotI end clone library has been constructed from a human-hamster hybrid cell line containing only human chromosome 11. Fifty-one NotI clones were chosen to characterize the library. The majority of NotI clones hybridize to small 15- to 200-kb fragments and have proven to be valuable for chromosome 11 physical mapping by detecting fragments not previously recognized by random probes. These NotI end clones have been used to isolate corresponding NotI linking cosmids which were then used to identify adjacent NotI fragments on pulsed-field gels. The clones were mapped using fluorescence in situ hybridization and a somatic cell hybrid panel. Although these clones were localized over the entirety of chromosome 11, a nonrandom distribution was observed. Northern blot analysis indicated that 57% (17/30) of the NotI clones examined detected poly(A)+ transcripts in HeLa cell RNA.

Animals↗
PubMed1993

A chromosome 11 YAC library.

A targeted yeast artificial chromosome (YAC) library for chromosome 11 has been constructed from the J1 cell line that carries a single human chromosome 11 within a hamster DNA background. Interspecies chimeric clones generated during construction of the library were detected during the screening process and eliminated from the library. Contig assembly becomes much less difficult using such a library as the complexity is decreased and the ends of the clone inserts can be rescued for walking to neighboring clones. The library contains > 1824 clones with an average insert length of 337 kb. This represents a fourfold coverage of chromosome 11 or a > 95% chance of recovering a unique single-copy sequence from the library. Two hundred YAC clones were localized by fluorescence in situ hybridization and found to be randomly distributed along the chromosome. The library has been screened with probes for the chromosome 11 markers HBB, GLUR4, H19, and D11S193. Corresponding YAC clones have been isolated for each locus. This analysis has indicated that the library is unbiased, that cognate YAC clones can be recovered with chromosome 11 markers, and that extensive contig assembly should be feasible.

Animals↗
PubMed1993

Bicuculline-resistant paired-pulse inhibition in the rat hippocampal slice.

1. An initial observation that paired-pulse inhibition in hippocampal slices was increased rather than decreased by bicuculline prompted the present study to explore the mechanism underlying bicuculline-resistant inhibition. 2. In the presence of bicuculline, paired-pulse interactions were dependent on the interpulse interval (i.p.i.) but a medium-latency inhibition was consistently observed at an i.p.i. of 300 to 500 ms. 3. The medium-latency (300 ms) bicuculline-resistant inhibition produced by paired orthodromic stimuli was substantially reduced by 2-hydroxysaclofen and was probably largely mediated by GABAB-receptor activation. Paired-pulse inhibition produced by an orthodromic/antidromic stimulation sequence was not affected by 2-hydroxysaclofen suggesting the possibility that the GABAB-receptors involved in orthodromic inhibition may be located presynaptically on the Schaffer collateral terminals rather than on the postsynaptic surface. The medium latency inhibition was also reduced by baclofen and under some conditions, by adenosine. 4. In addition to the GABAB-component, a hydroxysaclofen-resistant depression of postsynaptic excitability contributed to bicuculline-resistant paired-pulse inhibition at the 300 ms latency.

Adenosine↗
PubMed1993

Complications of epilepsy surgery in children and adolescents.

The Children's Hospital of Eastern Ontario's Epilepsy Surgery Series of 47 medically intractable children and adolescents was reviewed and analyzed to assess complications of surgical treatment. Complications and rates of incidence are discussed, and compared with the existing literature regarding children, adolescents and adults. No deaths or permanent disabling complications were incurred. Minor morbidity was minimal: 2 (4.2%) sustained permanent but nondisabling complications while an additional 3 (6.4%) incurred transient neurologic deficits which resolved rapidly. Epilepsy surgery in children and adolescents is safe, highly effective, and underutilized.

Adolescent↗
PubMed1993

Isolation of new probes in the region of the Wilson disease locus, 13q14.2-->q14.3.

A hybrid panel was used to refine the localizations of eight established markers useful for the diagnosis of Wilson disease. Two of the markers, D13S59 and D13S31, that map very close to the Wilson disease locus (WND) were localized to the region 13q14.2-->q14.3. We report the isolation of seven new probes from this region, using two different approaches. First, 16 clones from a chromosome 13-specific library were mapped using the hybrid panel. Three of the clones mapped to 13q14.2-->q14.3. As a second approach, Alu element-mediated PCR (Alu-PCR) was used to generate clones from a hybrid (ICD) that contains the proximal half of chromosome 13 as the only human component. To select for those that potentially mapped within the region 13q14.2-->q14.3, the clones were screened by differential hybridization using the labeled Alu-PCR products from a hybrid (KSF39) that is similar to ICD but has a deletion in the region 13q14.2-->q14.3. The procedure was successful even though KSF39 contains five additional human chromosomes. Six independent clones were selected. Five of these were found to be nonrepetitive, and four were found to map correctly to 13q14.2-->q14.3 when localized using the hybrid panel.

Chromosomes, Human, Pair 13↗
PubMed1993

Arrested development in a freshwater myxosporean, Myxidium salvelini, following transfer of its host, the sockeye salmon (Oncorhynchus nerka), to sea water.

The duration of infections with Myxidium salvelini, a freshwater myxosporean, in the kidneys of anadromous sockeye salmon (Oncorhynchus nerka) smolts from Cultus Lake, Fraser River system, British Columbia, was followed both in fresh water (FW) and in sea water (SW). The smolts were collected at the outlet of the lake as they migrated seaward, were subsequently held captive in M. salvelini-free FW or SW, and were sampled for presence of the parasite biweekly. Initial prevalence of infection was 80% or higher. In FW-held fish, spores were detectable over the 28-wk period of sampling, but the prevalence of infection with spores and prespore forms declined sharply after 22 wk. Nine weeks after the fish were transferred to SW, spores no longer were present but prespore forms continued to be present at high prevalences for up to 25 wk. SW-held fish were reacclimated to FW 4 wk after the last detection of spores. Spore production was resumed in this group of fish within 8 wk and continued for the next 5 wk, when the study was terminated. This indicates that M. salvelini persisted in an arrested prespore form during the SW holding period. This is the first report of arrested development in a prespore stage of a myxosporean. The physiological changes in the kidney that accompany migration of anadromous salmon from fresh to sea water likely inhibit spore production in M. salvelini. In FW salmonids, M. salvelini appears to have an annual life cycle.

Animals↗
PubMed1992

Prenatal demonstration of a cervical myelocystocele.

Myelocystocele is a rare spinal cord disorder and has not been described prenatally. We report a case in which prenatal ultrasound and magnetic resonance imaging (MRI) demonstrated a posterior cervical mass which was initially thought to be a meningocele or an atypical cystic hygroma. Surgery performed at 1 day of age showed this to be a myelocystocele. Therefore, the differential diagnosis of an extracranial cystic mass in the posterior cervical region should be expanded to include myelocystoceles.

Adult↗
PubMed1992

The human ribonuclease/angiogenin inhibitor is encoded by a gene mapped to chromosome 11p15.5, within 90 kb of the HRAS protooncogene.

Ribonuclease/angiogenin inhibitor (RAI) is a tight-binding inhibitor of ribonucleolytic and angiogenic activities involved in tumor progression. It is translated from various mRNAs differing in their 5 regions and originating from a single gene locus. Recently, this gene (RNH) has been assigned to 11p15.5, the terminal part of the short arm of chromosome 11. The regional chromosomal localization was confirmed by somatic cell and in situ hybridization and further refined by long-range restriction mapping. The data place RNH within 90 kb of the Harvey-ras protooncogene (HRAS), so far the most telomeric gene on 11p, in a region involved in growth regulation and tumor development.

Chromosome Mapping↗
PubMed1992

Drug-induced hepatic microgranulomatosis in cynomolgus monkeys.

This report discusses a unique drug-induced hepatotoxicity in cynomolgus monkeys treated orally with a novel potassium sparing experimental diuretic, [2,6-bis(4-chlorophenyl)-4-pyridinecarboxylic acid]. Groups of 6 adult male and female monkeys were treated orally with vehicle diluent, modified vehicle #122 or a suspension of the drug at 5.0, 12.5, or 32.0 mg/kg/day for 2 weeks. Another group of 5 monkeys were treated orally with 25.0 mg/kg/day of the drug for 2 weeks. Disposition of the drugs was evaluated in 2 monkeys in the later group that received 27.4 mg/kg of radiolabelled drug on the 1st and last day of dosing. Hepatic toxicity was characterized biochemically, light and electron microscopically, histochemically, immunocytochemically, and toxico-kinetically. Conjugated serum bilirubin, alanine transaminase, and aspartate transaminase levels were increased in monkeys treated with over 12.5 mg/kg/day of the diuretic. The periacinar hepatic plates of monkeys treated with 25.0 or 32.0 mg/kg/day were distorted by accumulation of PAS and oil red-O positive multinucleated Kupffer cells. The cytosol of these cells was expanded by phagolysosomes containing granular materials of varying electron densities. Granular electron dense materials were also in endothelial cells and bile canaliculi. Fatty change, cholestasis, and rare piecemeal hepatic necrosis were minimal. The drug was primarily excreted through urine. Plasma concentration and half life of the drug were increased with multiple dosing. The highest concentration of unexcreted parent drug was in the liver. Drug-induced noninflammatory hepatic microgranulomatosis, apparently caused by sequestered drug-lipid/mucopolysaccharide complex in the phagocytic cells of the liver, can occur in any species, including humans, if orally administered xenobiotics are presented to the liver in particulate form.

Animals↗
PubMed1991

Inhaled nebulised fentanyl for postoperative analgesia.

The effects of three concentrations of inhaled nebulised fentanyl citrate solution given for postoperative pain relief were studied. Each of 30 patients inhaled one dose of 3 ml of solution nebulised over 9 min. A combined analysis of pain relief, time to further analgesia and effect on respiratory frequency showed the highest concentration (318 micrograms/ml fentanyl base) to be more effective (p less than 0.01) than the two lower concentrations (159 micrograms/ml and 64 micrograms/ml) which were indistinguishable from each other. There were no major side effects. This study provides evidence for the efficacy and safety of inhaled fentanyl for postoperative analgesia. Estimation of the delivered doses did not support the hypothesis that fentanyl is more effective by this route compared with other parenteral routes. Further studies are required to improve the method of delivery and investigate the pharmacodynamic features of this technique.

Adult↗