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Biomedical subjects

R Bourne

Publications and source records attributed to R Bourne.

At least 19 recordsLinked to original sources

Sequence and structure requirements for Drosophila tRNA 5'- and 3'-end processing.

Eukaryotic tRNAs are processed at their 5'- and 3'- ends by endonucleases RNase P and 3'-tRNase, respectively. We have prepared substrates for both enzymes, separated the activities from a Drosophila extract, and designed variant tRNAs to assess the effects of sequence and structure on processing. Mutations affect these reactions in similar ways; thus, RNase P and 3'-tRNase probably require similar substrate structures to maintain the catalytic fit. RNase P is more sensitive to substrate substitutions than 3'-tRNase. In three of the four stems, one substitution prevents both processing reactions while the opposite one has less effect; anticodon stem substitutions hardly affect processing, and double substitution intended to restore base pairing also restore processing to the wild type rate. Structure probing suggests that tRNA misfolding sometimes coincides with reduced processing. In other cases, processing inhibition probably results from specific unfavorable stem appositions leading to local helix deformation. A single T loop substitution disrupts the tertiary D-T loop interaction and reduces processing. We have thus begun mapping tRNA processing determinants on the global, local, and tertiary structure levels.

Animals

Costs of elective total hip arthroplasty during the first year. Cemented versus noncemented.

The cost-effectiveness of the Mallory Head (Biomet, Warsaw, IN) cemented versus noncemented total hip arthroplasty was determined as part of a randomized trial. Costs were assessed during the first postoperative year. In-hospital resource use was determined using a chart review of 60 randomly selected patients. Costs were determined using a fully allocated costing model. Outpatient resource use was determined using patient diaries, and appropriate costs were allocated for outpatient visits, admissions to hospital, and patient-borne costs. There was no difference in costs between the cemented and noncemented prostheses. The average cost of the initial hospitalization was $9,990 (1988 Canadian dollars), and outpatient costs during the first year were $1,137 (total cost during the first year was $11,127). The cost per quality adjusted life year was $27,139 during the first year and $8,031 during the first 3 years.

Ambulatory Care

Increased damage to type II collagen in osteoarthritic articular cartilage detected by a new immunoassay.

A new immunoassay was developed to detect denaturation of type II collagen in osteoarthritis (OA). A peptide, alpha 1 (II)-CB11B, located in the CB11 peptide of type II collagen, was synthesized and used to produce a monoclonal antibody (COL2-3/4m) of the IgG1 (kappa) isotype. This reacts with a defined epitope in denatured but not native type II collagen and the alpha 3 chain of type XI collagen. The latter is present in very small amounts (about 1% wt/wt) in cartilage relative to the alpha 1 (II) chain. By using an enzyme-linked immunosorbent assay, type II collagen denaturation and total type II collagen content were determined. The epitope recognized by the antibody was resistant to cleavage by alpha-chymotrypsin and proteinase K which were used to extract alpha 1 (II)-CB11B from the denatured (alpha-chymotrypsin soluble) and residual native (proteinase K soluble) collagen alpha-chains, respectively, present in human femoral articular cartilage. Type II collagen content was significantly reduced from a mean (range) of 14% (9.2-20.8%) of wet weight in 8 normal cartilages to 10.3% (7.4-15.0%) in 16 OA cartilages. This decrease, which may result in part from an increased hydration, was accompanied by an increase in the percent denaturation of type II collagen in OA to 6.0% of total type II collagen compared with 1.1% in normal tissue. The percent denaturation was ordinarily greater in the more superficial zone than in the deep zone of OA cartilage.

Adult

Cancer of the cervix--old and young, now and then.

A study of two 5-year periods, 1960-1964 and 1982-1986, in Queensland is made. Changing patterns of preinvasive and invasive cervical carcinoma in the world literature are discussed. The age of presentation, stage, histology, and results in Queensland for cervical carcinoma are analyzed. There are over 500 patients in each quinquennium. While the total female population has increased 86%, the maximum increase is in patients under 35 years and over 65. There has been a 50% decrease in the incidence of cervical carcinoma, but a doubling under the age of 30. The stage at diagnosis has markedly improved with 88% stage Ib in the young as opposed to 50% formerly. Late-stage disease remains a problem of the aged. The mortality in both time spans increases with age. Histologic patterns show an increase in nonsquamous patterns and increased mortality in the rare patterns. We have no evidence of the emergence of a rapidly progressive carcinoma in the young. Papanicolaou smear and education programs appear to be preventing cervical carcinoma and allowing diagnosis of the disease at an earlier stage and age. This is reflected in a decrease in mortality from 9.6 per 100,000 (1960-1964) to 4 per 100,000 (1982-1986).

Adult

A technology assessment study design.

Randomized controlled trials of drug therapies are now required before the licensing and use of almost all medications. Other health care technologies should be similarly evaluated. The area of competing technologies requires more research, and cemented and noncemented hip prostheses have recently been identified as an important example of such a technology. Although trials such as ours require considerable care in their planning and execution, they can be conducted on a busy clinical teaching ward without adversely affecting the quality and quantity of clinical care.

Bone Cements

Hemispheric asymmetry of synapses in chick medial hyperstriatum ventrale following passive avoidance training: a stereological investigation.

A stereological analysis was made of synapses in the left and right hemispheres of chick medial hyperstriatum ventrale (MHV) 24h after passive avoidance training (PAL) and in water trained controls (W-control). The synaptic parameters examined were (D), the mean length of the postsynaptic thickening; (NV.syn), the number of synapses per unit volume of neuropil; (VV.syn), the volume density of the pre-synaptic bouton; (NV.ves), the number of synaptic vesicles per unit volume of neuropil and (ves.syn), the mean number of synaptic vesicles per pre-synaptic bouton. No significant differences exist in NV.syn between the left or right hemispheres of W-control and trained chicks, nor is NV.syn influenced by training. However, in W-control chicks D in the right MHV is significantly greater (12%) than in the left MHV and this difference disappears on training. There are no differences in VV.syn between left and right hemispheres of W-control chicks but following training VV.syn is 22.7% greater in the left MHV than in the right MHV. Training als influences the number of synaptic vesicles; in W-control chicks NV.ves in the right MHV is 12.25% greater than in the left MHV but following training these differences are reversed. When the data are expressed as numbers of vesicles per synapse (ves.syn), values for the left hemisphere of trained chicks exceed those in the right hemisphere by a staggering 61.38%. These results are discussed in the context of biochemical and electrophysiological studies which suggest that there is lateralization of the memory trace.

Animals

Primary carcinoid tumor of the mesentery.

A primary carcinoid tumor of the mesentery was associated with intestinal obstruction in a 74-year-old man. Increased levels of plasma pancreatic polypeptide were subsequently demonstrated. An autopsy performed four years later showed carcinoid metastatic dissemination and confirmed the primary mesenteric origin of the carcinoid tumor initially resected at surgery.

Aged

Interaction between oral hydralazine and propranolol. I. Changes in absorption, presystemic clearance and splanchnic blood flow.

A study was undertaken of propranolol pharmacokinetics in dogs before and after oral coadministration of hydralazine to determine whether interactions described in humans could be reproduced in an animal model. Additionally, physiological parameters considered to be relevant to the pharmacokinetic handling (absorption rate and splanchnic hemodynamics) were studied. Coadministration of oral hydralazine and propranolol in conscious dogs caused an increase in peak plasma concentration ( Cpmax ) and area under the oral plasma concentration-time curve (AUC) of propranolol ( Cpmax = 19.2 +/- 5.8 ng/ml, control; Cpmax = 91.5 +/- 12.8 ng/ml, posthydralazine : AUC = 65.7 +/- 14.6 ng X hr/ml, control; AUC = 152.4 +/- 23.9 ng X hr/ml, posthydralazine : mean +/- S.E.M., n = 5; P less than .01 and P less than .01), without change either in the peak plasma level, time to peak or plasma AUC of [14C] propranolol and metabolites (P greater than .70, P greater than .90 and P greater than .60, respectively) or in urinary recovery (urinary recovery = 39.7 +/- 4.3% dose, control; urinary recovery = 41.8 +/- 6.2% dose, posthydralazine ). When propranolol was administered i.v., hydralazine caused a small (42.3 +/- 18%), but significant (P less than .025), increase in systemic clearance. Oral bioavailability increased from 7.3 +/- 2.1 to 23.6 +/- 5.1% (mean +/- S.E.M., n = 5, P less than .025), hepatic extraction showed correspondingly inverse changes and estimated hepatic blood flow increased from 34.9 +/- 3.8 to 63.3 +/- 10.8 ml/min/kg (P less than .025).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral

Paired cervical smears: a method of reducing the false-negative rate in population screening.

Cervical smears taken by the wooden Ayre spatula (widely used in the United Kingdom) and by a plastic spatula (Armovical) were compared for their ability to detect dysplastic cervical epithelium and endocervical cells. At the same time, the value of taking duplicate smears was assessed. Paired cervical smears were obtained at a single attendance from 21,352 women, using the 2 types of spatulas in 4 different sequences. Although individually the Armovical proved superior to the Ayre spatula for the collection of endocervical epithelial material, this advantage was not complemented by any marked improvement in its detection of cervical dysplasia. Paired smear sampling, however, was clearly more rewarding in this respect and also allowed the introduction of laboratory quality control, as each preparation of any given pair was examined by a different screener. The false-negative rate was 18.5%: it comprised 11.1% sampling error and 7.4% screening error. It is concluded that paired smear sampling in population screening would significantly reduce the false-negative rate.

Carcinoma in Situ

The value of the electromagnetic flow probe in experimental and clinical microvascular anastomosis.

The Gould Statham Blood Flowmeter Model SP 2204 has been used to assess microanastomosis in 25 superficial femoral arteries of rabbits. When a pulsatile wave form has been achieved this correlates with a satisfactory anastomosis and vice versa. The digital read out of estimated volume flow past the anastomosis made by this instrument will need further evaluation. We are persisting with the electromagnetic flow probe in the assessment of our clinical microvascular anastomoses at operation.

Animals

The medicalization and legalization of child abuse.

Certain symptoms of family crisis and childhood injury are being "medicalized," "legalized," and called "child abuse"--to be processed and dealt with by a range of professionals who derive their social legitimacy and support in the process. Professional conflicts are considered, and the effects of the system on treatment interventions are discussed. Guidelines are offered to minimize the abuse of power of the professional definers.

Battered Child Syndrome

Trial of new cervical spatula.

A trial comparing the relative values of the 'Armovical' and Ayre's spatulae showed a significant improvement of the former over the latter in sampling endocervical epithelium. No such difference was found in their ability to detect epithelial atypia. However, it was confirmed that if (at each attendance of a patient) the cervix was sampled twice instead of once the incidence of atypical smears was increased.

Adult

Platelet monamine oxidase in schizophrenia. An investigation in drug-free chronic hospitalized patients.

Platelet monoamine oxidase (MAO) activity was investigated in a series of 60 patients with chronic schizophrenic illnesses free from neuroleptic medication, and 70 normal controls. No significant differences in platelet MAO activity or in substrate preference were detected between patients and controls, using tryptamine and tyramine as substrates. Platelet MAO activity did not distinguish patients with positive symptoms from those with negative symptoms alone and did not show any relationship with severity of disease or with a number of clinical features. These findings suggest that low platelet MAO activity cannot be regarded as a genetic marker for schizophrenia. Important determinants of platelet MAO activity yet to be discovered may have contributed to the discrepancies in recent observations of platelet MAO activity in schizophrenia.

Adult

Innervation of the muscle of the bladder in the rat.

A quantitative ultrastructural analysis of the organisation and terminal density of the nerves associated with the muscle of the body of the bladder was undertaken in the rat. The results obtained were suggestive of the organisation of the intramuscular plexuses into 2 separate and possibly functionally distinct networks. The nerves ramifying within the muscle fascicles mostly contained between 1 and 3 axons and on the basis of counts made in 12 animals, appeared to provide the muscle with only a moderate level of innervation. Although adrenergic terminals were frequently seen in the perivascular plexuses, they were rarely encountered in the nerves within the muscle fascicles. The majority of the terminals in the intrafascicular nerves were similar to those normally classified as cholinergic and, in many, the exposed parts of the axonal membrane were closely related to that of adjacent muscle cells. In addition to clear vesicles and large dense-cored vesicles, many of these terminals contained scattered small dense-cored vesicles. It was suggested that the involvement of the material present in the small dense-cored vesicles with acetylcholine in impulse transmission might account for the atypical features of such transmission in the bladder and in particular its resistance to blockade by atropine. The nerves forming the interfascicular networks contained few axons with cholinergic terminals, and were characterised by much larger numbers of a morphologically distinctive type of terminal. Some of these were indistinguishable from those recently defined as the terminals of purinergic axons but their distribution in the nerves suggests that they represent the terminals of afferent axons and is consistent with the concept that, together with those observed in other tissues, such axons are involved in pain perception.

Adult

Ureteric vascular and muscle coat innervation in the rat. A quantitative ultrastructural study.

The application of a quantitative ultrastructural approach to the study of the innervation of the smooth muscle in the wall of the ureter of the rat has revealed major differences in the structure of the nerves in the muscle coat and in the walls of the arterioles. The high density of adrenergic terminals in the periarteriolar nerves is consistent with the distribution of many of the postganglionic sympathetic axons that run in the ureteric nerves to blood vessels and the low density of both adrenergic and cholinergic terminals in the intramuscular nerves implies that the autonomic nervous system plays only a secondary role in controlling the activity of the muscle. The mean size of the intramuscular nerves corresponds to that of the nerves in the submucosa and terminals of the kind that occur in the submucosal nerves are numerous. The function of axons with such terminals and their possible involvement in the transmission to the central nervous system of pain impulses is discussed.

Animals