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Biomedical subjects

G Graham

Publications and source records attributed to G Graham.

At least 55 records · Page 3Linked to original sources
PubMed1994

New dominant syndrome of pterygium colli, mental retardation, and digital anomalies.

We describe a proband and his mother who appear to have a new dominant syndrome of mental retardation: pterygium colli, unusual features, and digital anomalies. The craniofacial abnormalities include brachycephaly, epicanthus inversus, angulated eyebrows, upward slanting of the palpebral fissures, ptosis, hypertelorism, and prominent low set, posteriorly rotated ears. The digits are remarkable for proximally displaced small thumbs, widened interphalangeal joints, and broad terminal phalanges.

Abnormalities, Multiple↗
PubMed1994

In-vitro interaction between H2 antagonists and vecuronium.

The interaction between histamine H2 antagonists and the neuromuscular blocking drug vecuronium was investigated in the rat phrenic nerve-hemidiaphragm preparation. Cimetidine alone, in the concentration range 800-4000 microM produced between 14 and 74% neuromuscular paralysis with an EC50 (mean +/- s.e.) of 2900 +/- 100 microM. Ranitidine augmented the indirectly-evoked muscle response at concentrations between 30 and 160 microM but at higher concentrations, between 300 and 1800 microM, produced neuromuscular paralysis. Famotidine produced negligible and statistically insignificant (0-5%) neuromuscular paralysis at concentrations between 0.3 and 300 microM. Cimetidine (800 microM) shifted the neuromuscular concentration-effect curve of vecuronium to the left in a parallel manner, while ranitidine (160 microM) shifted it to the right. The potentiation ratio was 1.90 +/- 0.14 for cimetidine and 0.62 +/- 0.05 for ranitidine. Famotidine (30 microM) did not alter the response to vecuronium. These data indicate that higher than clinically relevant concentrations of cimetidine and ranitidine produce neuromuscular paralysis and may potentiate the action of vecuronium. Low concentrations of ranitidine may antagonize the action of vecuronium. Famotidine, in contrast, lacks significant neuromuscular effects.

Animals↗
PubMed1994

The kinetics of effect of neuromuscular blocking drugs.

In attempts to derive pharmacokinetic constants from effect data three methods were explored, using non-depolarizing neuromuscular blocking drugs as the paradigm for obtaining effect data. The first method, based on the simple assumption that following two doses, the drug concentrations at times of equal effect during recovery, were equal. Provided that recovery took place in the log-linear drug elimination phase, the elimination rate constant (beta) could be calculated. This method proved rather inaccurate, a second method, again dependent on recovery in the log-linear phase yielded a constant which was the product of beta and the exponent of the Hill equation (s). This method yielded results within 20% of values calculated from plasma drug assays, and it was demonstrated that the time-effect curve could be described from knowledge of this constant. The third method, using non-linear curve fitting technique, derived values for the rate constants of plasma redistribution (alpha) and elimination (beta) as well as for the rate constant of elimination from an effect compartment (keo). If the values were derived from the effect of two doses of a drug, the intensity and duration of effect of a third dose could be predicted with reasonable accuracy. The dose dependent constants of the usual compartmental equations for the plasma concentration of a drug (A and B) could be derived in terms of the EC50. The method can be applied to any drug whose effect can be measured and whose maximal effect can be defined. We believe that the method may be useful in rapidly and inexpensively estimating population kinetic parameters, and in screening drugs.

Humans↗
PubMed1994

Tourniquet-induced rhabdomyolysis after total knee replacement.

A case is described of a patient who developed rhabdomyolysis and acute renal failure after the use of an intraoperative tourniquet for elective orthopaedic surgery. A review of the literature revealed four similar cases in the last 20 years. The clinical features and management of such patients are discussed.

Acute Disease↗
PubMed1994

The high incidence of foot deformity in patients with high-level spina bifida.

In a consecutive series of 124 children with spina bifida we found that 220 (89%) of the 248 feet were deformed: 70 had a calcaneus deformity; 126 were in equinus; 16 were in valgus; 3 were in varus; and 5 had convex pes valgus. Operations were performed on 171 (78%) of the deformed feet. Spasticity of the muscles controlling the foot was detected in 36 (51%) of the 70 calcaneus feet and in 22 (17%) of the 126 equinus feet. The deformities were symmetrical in 94 children. There is a high incidence of foot deformity in patients with spina bifida who have no voluntary activity in the motors of the feet.

Child, Preschool↗
PubMed1992

Isolated diffusing capacity reduction in systemic sclerosis.

OBJECTIVE: To determine the long-term outcome of patients with systemic sclerosis (SSc) and an isolated reduction in the diffusing capacity for carbon monoxide (DLCO) at the time of initial evaluation. METHODS: Patients with an isolated reduction in DLCO (i.e., normal forced vital capacity [FVC] and normal ratio of the forced expiratory volume in one second [FEV1] to the FVC) on initial evaluation were identified from among 815 patients with SSc who were carefully followed up throughout their illness. We requested that patients have repeat pulmonary function testing (PFT), and the outcomes of these tests, as well as cardiopulmonary and survival outcomes, were determined. RESULTS: An isolated reduction in DLCO, with a normal FVC was detected in 152 (19%) of the 815 patients. A subset of those with an isolated reduction in DLCO (11%) developed isolated pulmonary hypertension and had severely reduced survival rates. Pulmonary hypertension was strongly associated with an initial DLCO of less than 55% of predicted normal and a FVC (% predicted)/DLCO (% predicted) ratio of greater than 1.4. Among all patients in whom this ratio was greater than 1.4, 22% developed isolated pulmonary hypertension, compared with only 2% of those whose ratio was less than 1.4 (P less than 0.01). Of the 152 patients with isolated DLCO reduction, 73 (48%) underwent PFTs a mean of 5.4 years (range 2.0-13.2) after the initial PFT. Only 6 (8%) of these 73 patients ever had serious pulmonary disease: 5 had isolated pulmonary hypertension, and 1 had severe pulmonary fibrosis. Half of the patients with a low initial DLCO demonstrated a significant improvement (greater than 20%) at followup testing that could not be explained by the demographic, clinical, or laboratory findings at the first visit. CONCLUSION: Isolated reduction in DLCO is a frequent abnormality in SSc. Overall, it is associated with a good prognosis for survival and for pulmonary morbidity. A small subset of patients (11%) who have a very low DLCO (less than 55% of predicted) have developed isolated pulmonary hypertension, all of whom had limited scleroderma.

Carbon Monoxide↗
PubMed1992

Multidisciplinary preoperative assessment and late function in dysvascular amputees.

During a three-year period, 95 adults were treated by lower-extremity amputations for peripheral vascular insufficiency. A multidisciplinary team for presurgical evaluation determined all to be potentially independent walkers with a prosthesis. Patients were graded for level of independent walking before amputation and again at a minimum two-year follow-up examination using a seven-level functional grading system. Seventy-six of 90 patients (84%) ambulated within one functional level of their preamputation status. This return to preamputation level of function was maintained whether comparing preamputation functional level or surgical amputation level. Prosthetic use increased and the use of walking aids decreased with increased functional ambulation levels, but did not correlate with surgical levels. Peripheral vascular insufficiency patients can maintain walking independence. Multidisciplinary presurgical evaluation helps selection of the amputation level and correct prosthetic limb fitting.

Adult↗
PubMed1991

Investigation of varicella-zoster virus infection by polymerase chain reaction in the immunocompetent host with acute varicella.

A polymerase chain reaction (PCR) method developed to detect varicella zoster virus (VZV) in clinical samples is based on amplifying sequences of viral gene 31, the coding region for glycoprotein II. Its sensitivity was evaluated by amplification from plasmid VZV DNA containing VZV gene 31; 45 copies were detected in 1 microgram of human DNA. In testing within 24 h after the onset of varicella exanthem, 21 (75%) of 28 lesion samples were positive by VZV PCR, whereas VZV was isolated from only 21% by a standard tissue culture method. Only 1 (3.3%) of 30 samples of oropharyngeal secretions but peripheral blood mononuclear cells from 8 (67%) of 12 patients were positive. The sensitivity and specificity of the VZV PCR method indicates its usefulness for investigating the pathogenesis of VZV infection. Direct contact with cutaneous lesions rather than respiratory secretions may be the most important route of VZV transmission from healthy individuals with acute varicella.

Acute Disease↗
PubMed1991

Differential effect of interleukin 3 on the metabolism of high-dose cytosine arabinoside in normal versus leukemic human bone marrow cells.

We have examined the effect of recombinant interleukin 3 (rIL-3) on the metabolism of high-dose cytosine arabinoside (Ara-C), an S-phase-specific agent, in normal human bone marrow mononuclear cells (BMMC) and leukemic blasts from patients with acute myeloid leukemia (AML). Exposure to rIL-3 for 24 h significantly increased the percentage of cycling S-phase cells in normal BMMC as well as leukemic cells. A concomitant expansion of intracellular deoxycytidine triphosphate (dCTP) levels occurred to a significantly greater extent in normal BMMC. Compared to treatment with Ara-C (10 mumol/liter) alone, prior and coadministration of rIL-3 with Ara-C increased Ara-CTP levels in leukemic blasts. However, an identical treatment produced significantly higher dCTP levels in normal BMMC, resulting in a significantly lower mean Ara-CTP to dCTP pool ratio in normal BMMC compared to that observed in each of the samples of AML blasts. Following treatment with Ara-C plus rIL-3 versus Ara-C alone, the alteration in Ara-C DNA incorporation corresponded with the change in Ara-CTP to dCTP ratio observed in normal BMMC and AML blasts. The differential effect of rIL-3 on the metabolism of high-dose Ara-C in normal versus leukemic cells may indicate a role for rIL-3 in enhancing the selectivity of Ara-C toward leukemic myeloblasts.

Bone Marrow↗
PubMed1990

A generalized information function applied to the genetic code.

The problem of the partitioning of the degeneracy of the codons in the genetic code is considered in the framework of a generalized information function IG = c sigma kpk(ln pk + G(Ek] where k represents the number of codons in a specific degeneracy class and G(Ek) is an arbitrary real valued function. For G(Ek) = 0 the Shannon information function is recovered. For a particular choice of G(Ek) that takes the dominance of even degeneracies into account, it is found by direct numerical calculations that the correct degeneracy partitioning appears as optimal values of the Ig function. This results is also supported by optimization calculations in which the generalized information function is regarded as a continuous function in the degeneracy variables.

Amino Acids↗
PubMed1989

2'-Deoxycytidine protects normal human bone marrow progenitor cells in vitro against the cytotoxicity of 3'-azido-3'-deoxythymidine with preservation of antiretroviral activity.

Bone marrow cytotoxicity of 3'-azido-3'-deoxythymidine (AZT), an anti-human immunodeficiency virus (anti-HIV) drug, has been attributed to deoxyribonucleotide pool perturbations that might result in impaired DNA synthesis in normal bone marrow elements. We examined, in vitro, the effect of high, but clinically achievable and nontoxic, concentrations of 2'-deoxycytidine (dCyd) (greater than or equal to 100 mumol/L) on high-dose AZT mediated growth inhibition and intracellular biochemical perturbations in normal bone marrow progenitor cells. Colony formation by bone marrow progenitor cells in semisolid medium was significantly protected by dCyd against the inhibitory effects of co-administered, high concentrations of AZT (10 mumol/L). Also, dCyd significantly corrected AZT mediated depletion of intracellular thymidine triphosphate (dTTP) and dCyd triphosphate (dCTP) levels in normal bone marrow mononuclear cells (BMMC). Moreover, dCyd reduced the intracellular accumulation of AZT triphosphate (AZT-TP) and its DNA incorporation in BMMC. In contrast, co-administration of dCyd (100 mumol/L to 1 mmol/L) did not reverse AZT (10 mumol/L) mediated suppression of HIV infectivity in HUT-102 cells in culture, although a partial reduction in intracellular AZT-TP pools and its DNA incorporation as well as a correction of AZT mediated depletion of dTTP and dCTP pools was observed in these cells. These studies suggest that dCyd at high concentrations might ameliorate the bone marrow cytotoxicity of high-dose AZT without impairing its anti-HIV effect.

Bone Marrow↗
PubMed1989

On the information content of the genetic code.

In living organisms 20 amino acids along with the terminator value(s) are encoded by 64 codons giving a degeneracy of the codons as described by the genetic code. A basic theoretical problem of genetic codes is to explain the particular distribution of degeneracies of partitions involved in the codes. In this work the degeneracy problem is considered in the framework of information theory. It is shown by direct numerical evaluation of a certain degeneracy information function associated with the genetic code that the degeneracy of the codes is observed to be related to the optimization of this function.

Amino Acids↗
PubMed1989

The effect of recombinant human granulocyte-macrophage colony-stimulating factor (rGM-CSF) on 3'-azido-3'-deoxythymidine (AZT)-mediated biochemical and cytotoxic effects on normal human myeloid progenitor cells.

Administration of 3'-azido-3'-deoxythymidine (AZT) to patients with acquired immunodeficiency syndrome (AIDS) causes significant anemia and neutropenia. The bone marrow cytotoxicity of AZT has been attributed to deoxyribonucleotide pool perturbations that might result in impaired DNA synthesis in normal bone marrow elements. We examined the effect of human recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) on AZT-mediated biochemical perturbations and in vitro growth inhibition of normal bone marrow myeloid progenitor cells. Exposure of nonadherent, bone marrow mononuclear cells (BMMC) to 100 ng/ml of rGM-CSF for 6 h resulted in approximately twofold increments in the mean intracellular deoxycytidine triphosphate (dCTP) and thymidine triphosphate (dTTP) levels. Administration of 10 microM AZT alone to BMMC for 6 h markedly reduced dCTP and dTTP levels and generated significant levels of AZT triphosphate (AZT-TP). Coadministration of rGM-CSF (100 ng/ml) along with AZT (10 microM) partly restored dCTP and dTTP levels and significantly reduced AZT-TP levels. Furthermore, simultaneous exposure of BMMC for 4 h to 100 ng/ml of rGM-CSF reduced the mean DNA incorporation of [3H]AZT (10 microM) from 27.2 to 19.1 pmol/micrograms of DNA. Additionally, the inhibitory effects of AZT (10 microM) on granulocyte-macrophage colony-forming unit (CFU-GM) colony growth were significantly reduced in the presence of 100 ng/ml of rGM-CSF. These in vitro studies suggest that rGM-CSF partly corrects AZT-mediated biochemical perturbations as well as reduces the cytotoxicity of AZT in normal human bone marrow myeloid progenitor cells.

Cell Division↗