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Biomedical subjects

R Squires

Publications and source records attributed to R Squires.

10 recordsLinked to original sources
PubMed2006

Elective liver transplantation for the treatment of classical maple syrup urine disease.

An 8.5-year-old girl with classical maple syrup urine disease (MSUD) required liver transplantation for hypervitaminosis A and was effectively cured of MSUD over an 8-year clinical follow-up period. We developed a collaborative multidisciplinary effort to evaluate the effects of elective liver transplantation in 10 additional children (age range 1.9-20.5 years) with classical MSUD. Patients were transplanted with whole cadaveric livers under a protocol designed to optimize safe pre- and post-transplant management of MSUD. All patients are alive and well with normal allograft function after 106 months of follow-up in the index patient and a median follow-up period of 14 months (range 4-18 months) in the 10 remaining patients. Leucine, isoleucine and valine levels stabilized within 6 hours post-transplant and remained so on an unrestricted protein intake in all patients. Metabolic cure was documented as a sustained increase in weight-adjusted leucine tolerance, normalization of plasma concentration relationships among branched-chain and other essential and nonessential amino acids, and metabolic and clinical stability during protein loading and intercurrent illnesses. Costs and risks associated with surgery and immune suppression were similar to other pediatric liver transplant populations.

Adolescent↗
PubMed2000

Predictive value of quantitative PCR-based viral burden analysis for eight human herpesviruses in pediatric solid organ transplant patients.

Human herpesviruses can cause significant morbidity and mortality in pediatric solid organ transplant recipients. It was hypothesized that viral burden quantification by polymerase chain reaction using an internal calibration standard could aid in distinguishing between viral disease and latency. Here we report the results of a 2-year prospective study of 27 pediatric solid organ (liver, kidney, or heart) transplant recipients in which multiple samples were analyzed for levels of all eight human herpesviruses by internal calibration standard-polymerase chain reaction. Herpes simplex viruses 1 and 2, varicella-zoster virus, and Kaposi's sarcoma-associated herpesvirus were not detected in any of these samples. Human herpesvirus types 6 and 7 were detected in half of the patients, but were present at low levels, similar to those found in reference populations. Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were detected in 89% and 56% of the patients, respectively. Viral burden analysis suggested distinct patient populations for CMV, with a natural cutoff of 10,000 viral targets/ml blood strongly associated with disease. In some cases, a dramatic increase in CMV levels preceded clinical evidence of disease by several weeks. EBV viral burden was relatively high in the only patient presenting with an EBV syndrome. However, two other patients without evidence of EBV disease had single samples with high EBV burden. Rapid reduction in both EBV and CMV burden occurred with antiviral treatment. These data suggest that viral burden analysis using internal calibration standard-polymerase chain reaction for CMV, and possibly other herpesviruses, is an effective method for monitoring pediatric transplant patients for significant herpesvirus infection and response to therapy.

Adolescent↗
PubMed1985

Are the toxicities of pentobarbital and ethanol mediated by the GABA-benzodiazepine receptor-chloride ionophore complex?

Both barbiturates and ethanol have been reported to interact with the GABA-benzodiazepine receptor-chloride ionophore 'supramolecular complex'. These observations raise the possibility that some of the pharmacologic actions of barbiturates and ethanol may be mediated through this complex. In this study we have administered a series of drugs which bind to various components of the complex in an attempt to antagonize the lethality of sodium pentobarbital, and ethanol-induced loss of righting reflex in mice. It was found that isopropylbicyclophosphate (IPPO), a cage convulsant which binds at or near the chloride ionophore, greatly reduces the overall mortality (and increases latency to death) of animals pretreated with a lethal dose of pentobarbital. Picrotoxin also decreases pentobarbital lethality, but only at doses which were usually lethal when given alone. Picrotoxin shortened, rather than increased, latency to death. Strychnine did not prevent pentobarbital lethality, suggesting that the IPPO effect is not shared by convulsants in general. IPPO did not prevent ketamine-induced deaths, which supports the notion that the protective actions of IPPO are specific for depressant drugs which act at the chloride ionophore. IPPO also significantly reduced the duration of loss of righting reflex induced by ethanol. These observations suggest that the use of compounds which have a high affinity for the chloride ionophore in vitro might be fruitful in developing a clinical treatment for barbiturate or ethanol toxicity.

Animals↗
PubMed1979

Increased thermolability of benzodiazepine receptors in cerebral cortex of a baboon with spontaneous seizures: a case report.

The benzodiazepine receptor in the cortex of 1 spontaneously epileptic baboon exhibited an increased rate of thermal inactivation at 65 degrees C when compared with those from 3 other baboons. In other respects (receptor concentration, affinities for flunitrazepam and diazepam, and response to changing pH), the benzodiazepine receptor from this animal was very similar to the receptors in the cortex of 3 other baboons. The 3H-QNB (muscarinic) and 3H-naloxone (opiate) binding sites in the brain of all 4 baboons appeared very similar with respect to all parameters studied (thermal stability, concentration, regional distribution, and affinities for respective ligands). An endogenous factor stabilizing the benzodiazepine receptor could be lacking in the spontaneously epileptic baboon.

Animals↗