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Biomedical subjects

R Harrison

Publications and source records attributed to R Harrison.

At least 199 records · Page 11Linked to original sources
PubMed1985

Microscale syntheses of anti-tumour platinum compounds labelled with 191Pt.

Several compounds of platinum have been found to have significant anti-tumour activity and are in various stages of clinical trials. Four such compounds: cis-PtCl2(NH3)2, cis PtCl2(cyclopropylamine)2, cis,trans-PtCl2(OH)2(isopropylamine)2 and cis-Pt(1,1-cyclobutanedicarboxylate) (NH3)2 were synthesised with radioactive platinum-191 as a label for the study of animal organ distribution, patient blood clearance, urinary excretion and renal uptake and clearance. This paper describes the microscale synthesis of these compounds. Purification and quality control procedures are also described.

Antineoplastic Agents↗
PubMed1985

Prosthodontic rehabilitation of midfacial defects.

A definition and classification of midfacial defects has been presented with a systematic approach to the prosthetic restoration of these defects. Patient factors, prognostic and diagnostic considerations, clinical procedures, fabrication, materials, and retention have been discussed. Patients with complex orofacial defects can be provided with prosthodontic treatment that results in an acceptable appearance and function consistent with the deficits encountered (Figs. 14 and 15).

Denture Design↗
PubMed1985

Complement-dependent toxicity of serum from myasthenic patients to muscle cells in culture.

The toxicity of myasthenic sera to rat myotubes in monolayer culture was examined by measuring the release of [Me-3H]carnitine from pre-loaded cells. In the presence of guinea pig complement, heat-inactivated serum samples from 9 out of 13 myasthenic patients showed clear myotoxicity, in contrast to 0 out of 11 normal controls and 0 out of 6 polymyositis patients. Neither heat-inactivated sera alone nor guinea pig complement sera alone showed myotoxicity. Removal of anti-acetylcholine receptor (anti-AChR) antibodies from a myasthenic serum sample by affinity absorption led to loss of myotoxicity. Myotoxicity of myasthenic sera could, in most cases, be confirmed by light microscopy. These results support the idea that complement-mediated cell damage, initiated by anti-AChR antibodies, contributes to post-synaptic membrane degeneration in myasthenia gravis.

Animals↗
PubMed1985

Preparatory clinical studies of Pi-mesons at TRIUMF.

Eighty patients have been treated with Pi-mesons (pions) at TRIUMF between 1979-1984. The patients had tumors rarely curable by standard methods and had no prior radiotherapy. The distribution by site included skin, metastatic nodules (13), brain, glioblastoma multiforme (32), pelvis, rectosigmoid (15), prostate (12), bladder (7), and ovary (1). The studies involve serial escalations of pion dose until maximum tissue tolerance is reached, monitoring the response at each dose increment. Sites were chosen for study where lack of local control is a significant cause of treatment failure with conventional radiation therapy. The low dose rate and the available beam access at TRIUMF limit the number of patients treated and the volume treatable. A 3-D treatment planning program is in use, and a 3-D display of the dose distribution delivered in brain tumor treatments has been developed using the PET scanner. In practice, new methods introduced for measurement of tissue response include tumor growth delay curves, fine-needle biopsy mapping, and PET scanning of brain tumors. The use of endoscopic assessment of the rectosigmoid region is emphasized. Treatment results of glioblastoma multiforme show that the median survival for patients treated to 125 pion cGy/fx is in the range of 187-198 days; for patients receiving 170 cGy per dose/fraction (fx) the range is 290-315 days, and for those receiving 200-220 cGy/fx the median survival is in excess of 290 days. For pelvic malignancies the local control obtained with doses of 2500 cGy or less was 50% in 12 assessable patients; it was 75% in 20 patients who had 3000 cGy or more.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

Complement factor adsorption on solid surfaces--an ellipsometric method for investigation of quantitative aspects.

An optical method, ellipsometry, has been used for quantification of organic material adsorbed from complement sufficient sera on antibody coated solid surfaces. Maximal adsorption of organic material from complement sufficient human sera occurred at about 0.5 micrograms/cm2 of IgG. C3 but not C5, C8 or C9 was detected on the antibody surface incubated with complement sufficient sera. This may indicate that IgG adsorbed on methylized silicon surfaces lack binding sites for complement factors beyond C3. A modification of the method was also used for quantification of migration inhibition of human polymorphonuclear leucocytes (PMNL). Locomotion inhibition fell in a sharp interval from 0.2 to 0.5 micrograms/cm2 of IgG on the surface. We believe that the suggested type of measurements is important for understanding the quantitative relationships between humoral effects such as antibody dependent complement activation and cellular effects such as migration of PMNL.

Adsorption↗
PubMed1984

Prenatal diagnosis of lysosomal storage diseases. Review of experience in 145 patient referrals over a period of eight years.

Over the past eight years, 145 patients from Australia and New Zealand were referred to the Department of Chemical Pathology, The Adelaide Children's Hospital, for the prenatal assessment of a variety of lysosomal storage diseases. This group comprised 65 patients at risk for a glycosphingolipidosis, 50 for a mucopolysaccharidosis, five for mucolipidosis, 15 for glycogen storage disease, and 10 for cystinosis. In three cases, amniotic cells failed to establish in culture; in one of these cases, cell-free amniotic fluid was used to make the prenatal diagnosis; the fetus spontaneously aborted in another; only in one case could the prenatal assessment not be completed. Of the 143 cases of successful assessment, 40 fetuses (28%) were predicted to be homozygous affected by the disease for which they were at risk, and 38 pregnancies were subsequently terminated. Follow-up biochemical tests in the affected fetuses and in the newborn children were performed in 82% of cases and confirmed the prenatal assessment to have been correct in all cases. There were no known false positive or false negative diagnoses. It is concluded that the prenatal diagnosis of a range of lysosomal storage diseases can be performed accurately and reliably, provided that cultured amniotic cells are used for enzymatic assay and that a strict protocol, related to each individual prenatal assessment, is followed.

Amniocentesis↗
PubMed1984

Congenital ectropion uveae with glaucoma.

Congenital ectropion uveae (CEU) is a rare, nonprogressive anomaly characterized by the presence of iris pigment epithelium on the anterior surface of the iris stroma, often associated with neurofibromatosis and occasionally with other ocular anomalies. We present eight patients with unilateral CEU. Seven patients had glaucoma in the involved eye, while the eighth was a 10-week-old infant. In the two patients with bilateral glaucoma, the second eye was similar to the first, but without CEU. Three patients had neurofibromatosis, two had facial hemihypertrophy, one had Rieger's anomaly, one had Prader-Willi syndrome, and one had no systemic anomalies. Two had initially been misdiagnosed as having a large pupil in the involved eye and one as having a Horner's syndrome in the uninvolved eye. The finding of CEU in an infant warrants continued observation for the development of glaucoma and disorders of neural crest origin.

Abnormalities, Multiple↗
PubMed1984

Experimental Schistosoma mansoni infection in vervet monkeys (Cercopithecus aethiops) in Kenya: I. Susceptibility to a primary infection.

Groups of five 3-kg Kenyan monkeys, Cercopithecus aethiops, were exposed individually to 150,600 or 1500 Schistosoma mansoni cercariae per monkey. Three monkeys died soon after the infections became patent and the survivors were autopsied 4 months after exposure. Mortality and most haematological, parasitological and pathological sequelae of infection were dose-related, but not the white cell response or changes in the levels of serum proteins or fibrinogen. No gross liver fibrosis was seen. Comparison of this study with earlier ones on related cercopithecine monkeys suggests that the vervet closely resembles the baboon in its response to S. mansoni infections. Difficulties in managing and maintaining vervets can be overcome by using colony-bred or properly adapted feral animals. Thus, the vervet provides a cheaper, more readily available primate model for experimental S. mansoni studies. A prolonged infection, sufficiently heavy to permit reliable parasitological monitoring without undue mortality, should be provided by 150 S. mansoni cercariae per kg body-weight, using the Kenyan strains of vervet and parasite.

Animals↗
PubMed1984

The influence of early malnutrition on subsequent behavioral development. IV. Soft neurologic signs.

Soft neurologic signs were evaluated in 101 Barbadian school children, ages 4-11 years, who were malnourished in the first year of life, and 101 comparison children matched for age, sex, and handedness, but who had no history of malnutrition. Previously malnourished children performed significantly slower than comparison children on several timed motor tasks when using the nondominant hand only. Boys were found to perform significantly slower than girls, and younger (4-7 years of age) children performed slower than older (8-11 years of age) children. A model is presented that displays interrelationships among previous malnutrition, soft neurologic signs, classroom behavior, intelligence, and physical growth. In summary, slow motor performance was associated with lower verbal and performance IQ and the presence of attention deficit disorder, as assessed by the child's teacher. The time to perform the motor tests was unrelated to measures of physical growth.

Body Height↗
PubMed1984

Is low salt dietary advice a useful therapy in hypertensive patients with poorly controlled blood pressure?

In order to decide whether or not to advise a low Na trial routinely in a hypertension clinic, a randomised controlled 'management' trial was conducted to assess dietary compliance, well-being and changes in antihypertensive medication as a result of such a diet. Sixty-five out-patients on drug treatment for hypertension but with diastolic blood pressures greater than 95 mm Hg on two successive occasions were randomly allocated either to an index group on a 1 g Na (44 mmol) daily diet or to a reference group. Dietary advice was given in detail and repeated as necessary to ensure there was no misunderstanding. After three months 28% of the index group still added salt to their cooking and 13% sometimes added salt at the table. The difference between the groups in 24-hour Na excretion averaged 59 mmol at the end of the trial but 55% of the index group had a 24-hour Na excretion greater than 80 mmol. The average blood pressure at the end of the trial was only a 4 mm Hg systolic and 3 mm Hg diastolic lower in the index group. However, this modest benefit was achieved without any obvious deterioration in the quality of the lives of the patients on the low Na diet. The index group enjoyed their food as much as before and tended to require less drug treatment. On the debit side the index group complained more of transient unsteadiness (p less than 0.05) suggestive of postural hypotension. Low salt dietary advice is only marginally effective in patients poorly controlled on drug treatment. Non-compliance limits the usefulness of the advice.

Antihypertensive Agents↗
PubMed1983

Ligand-induced conformational changes in proteins.

The natures and roles of ligand-induced conformational changes are described in terms of the influence of the ligand on the equilibrium distribution of the protein structure among various conformational states. A very commonly observed conformational change is produced by a ligand binding into a cleft that lies between two domains and then closing the cleft through a hinge-like motion. Such a change in hexokinase serves to bring potential catalytic groups into the active site and to provide a binding site for the three phosphates of ATP. Flexibility in gene regulatory proteins such as the Escherichia coli catabolite activator protein and lac repressor may be important in the dual requirement for rapid diffusion of the proteins along the DNA as well as specific recognition of base sequences. A second role for flexibility in this class of proteins is to reduce their affinity for affinity for DNA, without reducing their capacity to discriminate among sequences.

Adenosine Triphosphate↗
PubMed1983

Interaction of foetal and adult human acetylcholine receptors with serum from patients with myasthenia gravis.

Acetylcholine receptors were partially purified from foetal and adult human muscle and their binding to myasthenic serum was compared. No significant differences between the binding characteristics of the two receptor types were detected; indicating the absence, at least in 14-22-week-old foetuses of antigenic sites unique to foetal receptor and recognised by myasthenic sera.

Adult↗
PubMed1983

Behavior in vivo of normal and dysfunctional C1 inhibitor in normal subjects and patients with hereditary angioneurotic edema.

The metabolism of normal C1 inhibitor and two dysfunctional C1 inhibitors (Ta and WeI) was studied in 10 normal subjects and 8 patients with hereditary angioneurotic edema (HANE), 4 with low antigen concentration (type 1) and 4 with dysfunctional protein (type 2). The fractional catabolic rate of the normal C1 inhibitor in normal subjects was 0.025 of the plasma pool/hour, whereas in HANE subjects it was significantly elevated at 0.035 of the plasma pool/hour. The synthesis of normal C1 inhibitor was decreased in patients with type 1 HANE (0.087 mg/ kg per h compared with 0.218 mg/kg per h). The fractional catabolic rate of dysfunctional protein WeI was similar to normal and showed a slightly accelerated catabolism in patients with HANE, whereas the dysfunctional protein Ta had a strikingly decreased fractional catabolic rate in normals and subjects with HANE. The present study is compatible with reduced C1 inhibitor synthesis in patients with type 1 HANE consistent with a single functional C1 inhibitor gene. The lower than anticipated levels of C1 inhibitor in HANE type 1 appears to result from (a) the single functional gene and (b) increased catabolism of the protein, perhaps related to activation of C1 or other proteases.

Adolescent↗
PubMed1982

Blood clearance of three radioactively labelled platinum complexes: cis-dichlorodiammine platinum II, cis, trans-dichlorodihydroxy-bis-(isopropylamine) platinum IV, and cis-dichloro-bis-cyclopropylamine platinum II, in patients with malignant disease.

The blood clearances of three platinum compounds, cis-dichlorodiammine platinum II (DDP), cis, trans-dichloro-dihydroxy-bis-(isopropylamine) platinum IV (CHIP), and cis-dichloro-bis-cyclopropylamine platinum II (CP), were determined in nine patients with malignant disease. The complexes were prepared using radioactive platinum (191Pt and 193Pt). A 10-mu Ci dose of each complex, containing the equivalent of 1-2 mg elemental platinum, was injected IV into groups of three patients. Serial blood and urine samples were collected over 72 h. No obvious difference was found between the three complexes for blood clearance, median t1/2a being 16.8 (range 11.2-23.5) min and median t1/2 beta 89 (range 63.7-127) h. The urinary excretion was greatest for CHIP, 60% of injected dose as against 42.6% for CP and 38.8% for DDP. Differences in renal excretion of DDP analogues could indicate potentially less nephrotoxic agents. The use of radioactive Pt will allow in vivo dynamic imaging of the distribution of platinum compounds in areas of interest.

Aged↗
PubMed1982

Immunological cross-reactivity between the alpha-bungarotoxin-binding component from rat brain and nicotinic acetylcholine receptor.

An alpha-bungarotoxin-binding protein was partially purified from rat brain and, when complexed with [125I] alpha-bungarotoxin, was shown to behave as a single radiolabelled protein that is distinct from the similarly complexed nAChR from Torpedo marmorata. The alpha-bungarotoxin-binding protein was used as antigen in radioimmunoassays for rabbit anti-(rat muscle nAChR) and rabbit anti-(Torpedo nAChR) antibodies, giving titres approximately 5% and 0.5%, respectively, of those obtained by using homologous antigen in the same assay.

Animals↗