The delta32 deletion of CCR5 receptor in rheumatoid arthritis.
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Arthritis, Rheumatoid↗
Biomedical subjects
G Forrest
Publications and source records attributed to G Forrest.
Maternal autoantibodies and congenital heart block: clues from two consecutive pregnancies, one in which there was congenital complete heart block and one in which the fetus was healthy.
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Adult↗
Factors affecting length of stay and need for rehabilitation after hip and knee arthroplasty.
The purpose of this study was to determine the factors that predict the length of stay on a surgical service after total hip or knee arthroplasty and the factors that predict whether a patient will require admission to a rehabilitation unit before he or she is ready to return home. The authors reviewed the records of all patients admitted to the Albany Medical Center for elective total hip or total knee arthroplasty in 1995. The study looked for correlations of patients' age, sex, marital status, body mass index, and comorbid illnesses with length of stay on the surgical service and need for inpatient rehabilitation. The only factor that correlated with length of stay on the surgical unit was age. The factors that correlated with the need for inpatient rehabilitation were age and diabetes mellitus.
Age Factors↗
High dose gabapentin in refractory partial epilepsy: clinical observations in 50 patients.
Fifty patients with refractory partial seizures took part in a prospective, observational study of adjuvant gabapentin (GBP) in increasing doses. Thirty-three were started on 400 mg GBP daily with further weekly increments of 400 mg until seizures came under control for at least 6 months or to the limit of tolerability. A further 17 patients, not fully controlled on low dose GBP, followed the same regimen. All patients took the drug three times daily. Comparisons were made with seizure numbers during a 3-month baseline during which antiepileptic medication remained unchanged. Overall, 24 of the 50 patients documented a seizure reduction of 50% or more. Fifteen did so at or below 2400 mg GBP daily. Three of these patients became seizure-free. The remaining nine appeared to respond to higher daily doses of GBP (1:2800 mg; 3:3600 mg; 1:4000 mg; 1:4800 mg; 3:6000 mg), with two becoming seizure-free. Side-effects most commonly reported included tiredness, dizziness, headache and diplopia. On GBP doses exceeding 3600 mg daily, three patients developed flatulence and diarrhoea and two more had myoclonic jerks. Mean circulating GBP concentrations (mg/l) at each 1200 mg dose level were as follows: 1200 mg-4.1; 2400 mg-8.6; 3600 mg 13.2; 4800 mg 15.5; 6000 mg-17.2. In six patients, including three taking 6000 mg daily, GBP concentrations continued to rise linearly at each dosage increment. Although limited, our results do not support the suggestion that GBP absorption is saturable. High dose GBP may be effective in controlling seizures in patients with refractory partial epilepsy.
Acetates↗
Neurochemical studies with the novel anticonvulsant levetiracetam in mouse brain.
Levetiracetam is a novel antiepileptic agent with a wide spectrum of activity against experimental and clinical seizures. The mechanism of its anticonvulsant action remains to be determined. We have investigated the effects of levetiracetam on several gamma-aminobutyric acid (GABA)-related neurochemical parameters in mouse brain. Adult male mice were randomised into two groups and administered levetiracetam (0-300 mg/kg) intraperitoneally either as a single dose or twice daily for 5 days. Four hours after the final dose, animals were killed and their brains removed. Brain tissues were analysed for concentrations of GABA, glutamate and glutamine and for the activities of GABA-transaminase and glutamic acid decarboxylase. Single dose and repeated levetiracetam treatments were without effect on all of the parameters investigated. The anticonvulsant action of levetiracetam is unlikely to be mediated via an action on the GABAergic system.
4-Aminobutyrate Transaminase↗
Neurochemical actions of vigabatrin and tiagabine alone and in combination in mouse cortex.
1. The effects of repeated administration of the anticonvulsant compounds, vigabatrin (VGB) and tiagabine (TGB), on gamma-aminobutyric acid (GABA) concentration and the activities of GABA-transaminase (GABA-T) and glutamic acid decarboxylase (GAD) were investigated in mouse cortex. 2. VGB alone increased GABA levels and decreased GABA-T and GAD activities. 3. TGB alone was essentially without effect. 4. Low doses of VGB and TGB in combination increased GABA levels when neither drug had such an effect alone. 5. Despite this observation, this study failed to establish any conclusive evidence for an interaction between VGB and TGB that might help to explain their reported clinical synergism.
4-Aminobutyrate Transaminase↗
Neurochemical actions of gabapentin in mouse brain.
Gabapentin (GBP) is a recently licensed antiepileptic, drug whose mode of action remains to be fully elucidated. The following studies were designed to investigate the effects of GBP on several gamma-aminobutyric acid (GABA) related neurochemical parameters in mouse brain. GBP (0-75 mg/kg) was administered by intraperitoneal injection either as a single dose or twice daily for 8 days. Animals were sacrificed 4 h after the final administration and their brains removed and analysed for concentrations of GABA, glutamate and glutamine and the activities of GABA-transaminase (GABA-T) and glutamic acid decarboxylase (GAD). Single dose GBP increased brain GABA-T activity and glutamine concentration but was without effect on GAD activity or the concentrations of GABA and glutamate. Following repeated treatment with GBP, brain GABA-T activity was consistently decreased and there was also a decrease in brain glutamate concentration. Repeated drug treatment was without effect on the activity of GAD or on the concentrations of GABA and glutamine. These results suggest that GBP has effects on the GABAergic system which may contribute to its antiepileptic and/or neuroprotective actions.
Acetates↗
Neurochemical actions of the desglycinyl metabolite of remacemide hydrochloride (ARL 12495AA) in mouse brain.
1. Remacemide hydrochloride, a recently developed antiepileptic drug, is believed to exert its effects, at least in part, via its desglycinyl metabolite, ARL 12495AA. 2. We have investigated the effects of ARL 12495AA on several neurochemical parameters in mouse brain. Adult male ICR mice were randomized into two groups and administered ARL 12495AA (0-75 mg kg-1) intraperitoneally, either as a single dose or once daily for 5 days. 3. Six hours after the final dose, animals were killed and their brains removed. Brain tissues were analysed for concentrations of gamma-aminobutyric acid (GABA), glutamine and glutamate and for the activities of GABA-transaminase (GABA-T) and glutamic acid decarboxylase (GAD). 4. Single dose ARL 12495AA was without effect on any of the parameters investigated. 5. Repeated ARL 12495AA treatment did not alter brain concentrations of GABA and glutamine, but at a high dose there was a trend toward reduced brain glutamate concentrations (P = 0.10). 6. Repeated administration of ARL 12495AA at a high dose significantly increased GABA-T activity (P < 0.05) and decreased that of GAD (P < 0.05). 7. These findings may have relevance to the clinical use of remacemide hydrochloride in human epilepsy.
4-Aminobutyrate Transaminase↗
Determination of gabapentin in plasma by high-performance liquid chromatography.
A rapid and simple method for determination of the novel antiepileptic compound gabapentin [1-(aminomethyl)cyclohexaneacetic acid] in plasma is described. Blank human plasma was spiked with gabapentin (1.0-10.0 micrograms/ml) and internal standard [1-(aminomethyl)-cycloheptaneacetic acid; 5.0 micrograms/ml]. Individual samples were treated with 2 M perchloric acid, centrifuged and then derivatised with o-phthalaldehyde-3-mercaptopropionic acid. Separation was achieved on a Beckman Ultrasphere 5 microns reversed-phase column with mobile phase consisting of 0.33 M acetate buffer (pH 3.7; containing 100 mg/l EDTA)-methanol-acetonitrile (40:30:30, v/v). Eluents were monitored by fluorescence spectroscopy with excitation and emission wavelengths of 330 and 440 nm, respectively. The calibration curve for gabapentin in plasma was linear (r = 0.9997) over the concentration range 1.0-10.0 micrograms/ml. Recovery was seen to be > or = 90%. The inter- and intra-assay variations for three different gabapentin concentrations were < or = 10% throughout. The lower limit of quantitation was found to be 0.5 microgram/ml. Chromatography was unaffected by a range of commonly employed antiepileptic drugs or selected amino acids.
Acetates↗
Subacute sclerosing panencephalitis presenting with psychosis and possible sexual abuse.
A previously healthy 8-year-old girl began to experience nightmares, soon followed by sleeplessness and perceptual abnormalities including visual hallucinations. She also complained that she had been attacked and possibly assaulted sexually. Physical investigations were considered to have provided no relevant abnormality and psychiatric enquiries were begun directed towards possible sexual abuse. However, the child's mental and physical state continued to deteriorate and evidence of a progressive organic process was then obtained from past school reports, review of the initial EEG findings and further EEG investigations. The latter in particular indicated a diagnosis of SSPE which was confirmed immunologically. Treatment was ineffective and the child died 7 months after the onset of the illness. The details of the psychological changes at the onset of SSPE are ill-defined. This case illustrates that they can include psychotic phenomena but also that the basic nature of the disorder may be misconstrued as psychological depending on the circumstances.
Child↗
The Albany Medical College Ventilator Walker.
This report describes the design and use of a wheeled walker that can accommodate a ventilator and oxygen tanks. It is constructed of aluminum tubing. The front of the walker has receptacles to support a Mark 7 Bird Ventilator and oxygen tanks. The back end of the walker has a bench seat that is lifted to allow entry into the walker. The seat provides rigidity and stability to the frame of the walker. The walker has been used in the Medical Intensive Care Unit of the Albany Medical Center to facilitate early ambulation of patients who are ventilator dependent or who require a portable source of oxygen to begin ambulation training.
Aged↗
Concentration--effect and concentration--toxicity relations with lamotrigine: a prospective study.
This prospective study was designed to ascertain whether measurement of lamotrigine (LTG) concentrations in the epilepsy clinic could be used to predict the onset of complete seizure control or the emergence of adverse effects. LTG was initiated in doses of 25 or 50 mg daily in 69 patients with newly diagnosed or poorly controlled epilepsy and was increased monthly in 50-mg increments until the patient became seizure-free for at least 6 months or developed adverse effects that abated after a reduction in dosage. LTG and other antiepileptic drug (AED) concentrations were measured at each clinic visit but were not supplied to the investigator examining the patients. Overall, 19 patients either withdrew due to lack of efficacy or defaulted from the clinic. Of the remaining 50 patients, 32 (19 monotherapy, 13 polytherapy) became seizure-free at widely varying daily LTG doses (median 200 mg, range 25-850 mg) and concentrations (median 3.8 mg/L, range 1.4-18.7 mg/L). Likewise, the 18 patients (5 monotherapy, 13 polytherapy) who experienced intolerable side effects showed substantial variations in daily LTG doses (median 300 mg, range 100-900 mg) and concentrations (median 4.0 mg/L, range 0.4-18.5 mg/L). No useful concentration-effect or concentration-toxicity relation with LTG could be demonstrated in this study; therefore, we believe that routine therapeutic drug monitoring with this new AED is not currently indicated.
Adolescent↗
Wheelchair-accessible housing: its role in cost containment in spinal cord injury.
OBJECTIVE: To determine frequency with which the need to find accessible housing delays discharge from an inpatient rehabilitation unit. DESIGN: Retrospective review of the records of all patients (122) admitted with a diagnosis of acute spinal cord injury to the Inpatient Rehabilitation Unit of a teaching hospital between January 1986 and December 1993. SETTING: Tertiary care center's inpatient rehabilitation unit. MAIN OUTCOME MEASURE: A determination of whether each patient was discharged at the time that he or she was ready to leave the Rehabilitation Unit or whether discharge had to be delayed because the patient did not have an accessible home to which he or she could return. RESULTS: Ten percent of the patients had to stay in the hospital beyond the planned date of discharge while their families or representatives of the hospital looked for accessible housing. The delays ranged from 6 to 210 days, with an average delay of 60 days. The hospital's average charge for this time was $29,280. The average savings, had the patient been transferred to a transitional living unit when they were ready for hospital discharge, would have been $27,660. CONCLUSION: The need to find accessible housing should be included in the list of factors that can affect the length of stay of patients admitted to a rehabilitation unit and increase charge for service provided to those patients.
Adult↗
A novel intrachromosomal rearrangement in the beta-globin gene found in an African-American family.
We describe here a deletion of 34 nucleotides from the 3' end of the first intervening sequence of the beta-globin gene covering the AGGC splice junction, and the insertion of 32 nucleotides of the delta-globin gene at the same location. This gene rearrangement was detected in three members of an African-American family. The proband, a 28-year-old female, and her mother had a history of chronic anemia. One of her two brothers, who inherited the same gene defect, was apparently healthy with no symptoms of hemolytic anemia. The proband, her father, and her two brothers, including the one who carried the beta-globin gene rearrangement, were found to be heterozygous for alpha-thalassemia-2 (-alpha 3.7). Although the AGGC splice junction is disrupted (AGGC-->AGAT), the invariant AG has remained intact after this gene rearrangement. Our investigations could not detect any defect in RNA processing in the affected beta-globin genes. The discrepancies between the phenotypes and the globin chain synthesis ratios of the mother, her daughter, and her son who inherited the same gene defect at their beta-globin genes, remain unexplained.
Adult↗
A double-blind, placebo-controlled interaction study between oxcarbazepine and carbamazepine, sodium valproate and phenytoin in epileptic patients.
1. The effect of carbamazepine (CBZ), sodium valproate (VPA) and phenytoin (PHT) on the pharmacokinetics of oxcarbazepine (OXC) was explored in three groups of 12 epileptic patients taking one of these drug as monotherapy. 2. Each patient took a single 600 mg dose of OXC followed 7 days later by 3 weeks' treatment with OXC 300 mg thrice daily and matched placebo in random order. 3. Seven untreated patients, acting as controls, were prescribed the single OXC dose and 3 weeks' active treatment only. 4. In those patients completing the study, the area under the concentration-time curve (AUC) at steady-state for hydroxycarbazepine (OHCZ), the active metabolite of OXC, was significantly lower in the CBZ-treated group than in controls (P < 0.05). 5. No other differences in AUCs or elimination half-lives for OHCZ were found between treated and untreated patients following single or multiple OXC dosing. 6. Median AUCs of CBZ, VPA and PHT during a dosage interval did not differ significantly after treatment with OXC and placebo. 7. Ten patients completing the study complained of side-effects during treatment with OXC compared with one taking placebo (P < 0.01). 8. There were no important changes in cognitive function testing during administration of OXC compared with placebo. 9. Standard doses of OXC can be given as add-on therapy in epileptic patients receiving CBZ, VPA or PHT without producing a clinically relevant pharmacokinetic interaction.
Adult↗
Vigabatrin and lamotrigine in refractory epilepsy.
Epilepsy arises from an imbalance of inhibitory and excitatory influences in the brain. Vigabatrin (VIG) decreases the breakdown of the inhibitory neurotransmitter gamma-aminobutyric acid, whereas lamotrigine (LTG) reduces presynaptic excitatory amino acid release. 22 patients with refractory epilepsy, treated with an anticonvulsant regimen containing VIG, entered a balanced, double blind, placebo controlled, crossover trial of additional LTG. Treatment periods of 12 weeks (25 mg, 50 mg, 100 mg LTG twice daily for four weeks at each dose, and matched placebo) were followed by wash out intervals of four weeks. 14 of the 20 patients completing the study improved, resulting in a significant fall in seizure days and numbers. Analysis of seizure type confirmed a beneficial effect on partial and secondary generalised tonic-clonic seizures. At the highest LTG dose (200 mg daily) there was a median fall of 37% in seizure count with nine (45%) patients reporting > 50% reduction. Three of these patients were seizure free during this month of treatment. Side effects were minimal throughout the study. Concentrations of other antiepileptic drugs, including those of carbamazepine 10,11-epoxide, were not modified by LTG. This study suggests a substantial efficacy for a regimen containing VIG and LTG. Combinations of drugs with complementary modes of action may provide a rational pharmacological approach to the management of refractory epilepsy.
Anticonvulsants↗
A comparison of the potassium and magnesium-sparing properties of amiloride and spironolactone in diuretic-treated normal subjects.
1. The relative potencies of amiloride (5 and 20 mg) and spironolactone (25 and 100 mg) for plasma and erythrocyte electrolytes were investigated in a double-blind, randomised, balanced, crossover study in 12 normal men treated concomitantly with hydrochlorothiazide 100 mg daily for 1 week. 2. Participants satisfied an a priori requirement for a fall in plasma potassium concentration of at least 0.5 mmol l-1 after 7 days of treatment with hydrochlorothiazide alone. 3. After hydrochlorothiazide alone, plasma potassium and sodium concentrations fell (P < 0.001). There were associated reductions in erythrocyte sodium (P < 0.01). Plasma magnesium concentration did not change, although erythrocyte magnesium decreased (P < 0.001). 4. Both amiloride and spironolactone attenuated the thiazide-induced fall in plasma potassium (relative potency, amiloride:spironolactone 10:1, 95% confidence interval 6.3-16.2:1). Amiloride but not spironolactone was associated with a dose-related increase in plasma magnesium; a relative potency estimation was precluded. There was little evidence of influences of amiloride or spironolactone on erythrocyte electrolytes. 5. On a weight basis, amiloride is ten times more potent than spironolactone as a potassium-sparing agent in diuretic-treated subjects but neither agent had major effects on erythrocyte potassium. The drugs may have divergent actions on magnesium handling; hydrochlorothiazide alone had no influence on plasma magnesium.
Adult↗
Double boards--another view.
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Curriculum↗