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Biomedical subjects

D C Brown

Publications and source records attributed to D C Brown.

At least 73 records · Page 4Linked to original sources

An in vitro study of apical extrusion of sodium hypochlorite during endodontic canal preparation.

One hundred fifty-three single rooted teeth were divided into four groups. Canals were cleaned and shaped using the balanced forces technique. In one group of 50 teeth, irrigation was delivered with the irrigation needle deep within the root canal. In the other group of 51 teeth, the needle was placed passively in the coronal access cavity and the irrigation carried into the root canal during filing. The remaining 52 teeth in the control groups were treated in the same manner using distilled water as the irrigation solution. The concentration of sodium extruded apically was measured by means of atomic emission spectrophotometry, and the volume of sodium hypochlorite extruded was calculated. Significantly more sodium hypochlorite was extruded apically during deep delivery of the irrigation (p<0.05). It is concluded that the use of a reservoir of irrigation in the coronal access cavity results in significantly less apical extrusion of irrigation solution than with deep delivery.

Analysis of Variance↗

Undiagnosed glucose intolerance in the community: the Isle of Ely Diabetes Project.

The Isle of Ely Diabetes Project is a prospective population-based study of the aetiology and pathogenesis of Type 2 diabetes mellitus. Between 1990 and 1992, 1156 subjects aged between 40 and 65 years underwent a standard 75 g oral glucose tolerance test (OGTT). A total of 1122 individuals who were not known to have diabetes completed the test and were classified according to WHO criteria; 51 subjects (4.5%) had previously undiagnosed diabetes and 188 (16.7%) had impaired glucose tolerance. The subjects with newly diagnosed glucose intolerance were significantly older, more obese, and shorter than those with normal glucose tolerance. Blood pressure, cholesterol, triglyceride, and LDL-cholesterol concentrations were elevated and HDL-cholesterol levels were lower among those with abnormal rather than normal glucose tolerance. In multiple regression analyses stratified by gender and including age, body mass index, and the waist-hip ratio as covariates, there were significant differences between those with normal and abnormal glucose intolerance in blood pressure, triglyceride, and HDL-cholesterol, but not total or LDL-cholesterol. In both male and female subjects, height had a significant independent negative association with the plasma glucose at 120 min after administration of oral glucose (standardized beta coefficient = -0.12, p < 0.01).

Adult↗

A double blind, placebo controlled study of the effects of low dose testosterone undecanoate on the growth of small for age, prepubertal boys.

OBJECTIVE: To assess whether very low doses of testosterone can accelerate growth without an undue advance in bone age in prepubertal boys with constitutional delay of growth. SUBJECTS: 23 prepubertal boys aged 11-14 years with height at or below the third centile for chronological age. DESIGN: Randomised, double blind trial comparing oral testosterone undecanoate 20 mg once daily versus placebo for six months. The 18 months' observation period of each subject comprised a six month pretreatment period, followed by a six month treatment (testosterone undecanoate or placebo) period, and a six month period after termination of treatment. OUTCOME MEASURES: At intervals of six months standing and sitting height were measured. Bone age, pubertal stage, weight, and lean body mass were also determined. Growth hormone, luteinising hormone, and follicle stimulating hormone secretion and testosterone concentration were measured before, after, and six months after treatment. RESULTS: Boys taking testosterone undecanoate (n = 11) showed a significantly greater height velocity (mean (SEM) 5.84 (0.53) cm/year) and sitting height velocity (3.54 (0.57) cm/year) during treatment than the placebo treated boys (n = 12, height velocity = 3.38 (0.22) cm/year, sitting height velocity = 1.58 (0.19) cm/year. There were no significant differences between the groups regarding changes in growth hormone, gonadotrophins, testosterone, or dihydrotestosterone concentrations. Bone age was not advanced significantly more rapidly in either group. CONCLUSIONS: There is accelerated gain in height during six months of treatment with low dose testosterone undecanoate, without a significantly greater rise in bone age compared with controls. Testosterone undecanoate is a safe, well tolerated, and effective treatment in the management of constitutional delay of growth.

Adolescent↗

An audit of medical paediatric out-patient appointments and letters.

All medical out-patient appointments of a firm of three consultants at the Royal Hospital for Sick Children were reviewed over a four week period. Of 758 appointments initially offered, 490 (64%) patients attended; 19% of patients cancelled and 17% did not attend without cancelling. Delay from referral to attendance ranged from 0 to 9 weeks. The characteristics of those patients experiencing prolonged registrar-only follow-up are described. The content of subsequent letters to family practitioners was usually adequate compared to accepted standards. Delays in dictation of letters were usually short in comparison to delays in typing. Such delays and the intervals between consultant review of out-patients may prove costly to providers. Potential improvement strategies are discussed.

Appointments and Schedules↗

Advances in endodontic surgery: Part 2.

As practitioners have increased their knowledge and skills in the art of saving teeth, periradicular surgery has increased in importance. This article, the second in a short series, considers how the practitioner should incorporate the many advances in endodontic surgical techniques and materials into their practice in order to ensure more predictable results.

Apicoectomy↗

Advances in endodontic surgery: Part 1.

It is generally accepted that non-surgical endodontic therapy eliminates periapical inflammation or infection and allows teeth to be restored that previously might have been extracted. However, failure does occur in a small percentage of cases. When confronted with such cases the clinician should be prepared to initiate alternative procedures, including surgery, to enhance the rate of success. This, the first of two articles, describes refinements in endodontic surgical techniques and introduces the research that has been used to develop new materials and devices.

Anesthesia, Dental↗

Inhibition of pulmonary tumor seeding by antiplatelet and fibrinolytic therapy in an animal experimental model.

Fibrin and platelets contribute to the development of blood borne metastases by facilitating the arrest of tumor cell emboli in the microcirculation. We have previously demonstrated that the fibrinolytic agent streptokinase inhibits pulmonary tumor cell seeding in an animal model. To determine whether this effect was potentiated by antiplatelet therapy, a further study was performed to assess the effect of streptokinase in combination with aspirin in a similar model. The results demonstrated that aspirin did not significantly enhance the antimetastatic effect of streptokinase (median: streptokinase = 60, streptokinase + aspirin = 60.5, P = 0.79, Mann Whitney). In a second series of experiments, the antimetastatic effect of streptokinase was compared with another fibrinolytic agent, human recombinant tissue plasminogen activator (rt-PA). Fibrinolytic doses of streptokinase (30,000 units/kg) and rt-PA (5 mg/kg) significantly reduced pulmonary tumor seeding when compared with controls (median: control = 48, streptokinase = 23, P < 0.01, rt-PA = 29, P < 0.001). There was no significant difference in pulmonary tumor seeding between the groups treated with streptokinase and rt-PA (P = 0.56). The clinical implications of these findings are discussed.

Animals↗

Streptokinase inhibits pulmonary tumor seeding in an animal experimental model.

One aspect of the metastatic process involves entrapment of tumor cells within the microcirculation of organs in a "fibrin-platelet mesh." We postulate that destruction of this mesh by fibrinolysis might discourage tumor seeding, thereby inhibiting metastasis. To study this hypothesis, the effect of intravenous streptokinase on pulmonary tumor seeding was examined in a rodent model. In vitro experiments demonstrated that streptokinase had no cytotoxic or cytostatic effect on the Mtln3 cell line. Pharmacokinetic studies showed that at 30,000 U/kg, streptokinase caused systemic fibrinolysis in the Fischer rat, as demonstrated by the thrombin time and fibrin plate lysis assay. Streptokinase administered at this dose, 30 min after tumor cell injection, caused a significant decrease in pulmonary tumor seeding (median 23.0 in the streptokinase-treated group vs. 67.5 in untreated controls, P < 0.0001, Mann-Whitney U-test). Analysis of fibrin degradation products in the streptokinase-treated group suggested that this effect might be secondary to fibrinolysis. The implications of these findings are discussed.

Adenocarcinoma↗

Hypertriglyceridaemia in subjects with normal and abnormal glucose tolerance: relative contributions of insulin secretion, insulin resistance and suppression of plasma non-esterified fatty acids.

Although plasma insulin and triglyceride concentrations are positively correlated in many studies, the relationships between insulin resistance, insulin secretion and hypertriglyceridaemia remain unclear. To study these associations, subjects between the ages of 40 and 64 were randomly selected from a general practice register and invited to attend for a standard oral glucose tolerance test for measurement of insulin, triglyceride and non-esterified fatty acid concentrations. The study comprised 1122 subjects who were not previously known to have diabetes and who completed the test. Using the World Health Organisation criteria, 51 subjects were classified to have non-insulin-dependent diabetes mellitus, 188 had impaired glucose tolerance and 883 subjects had normal glucose tolerance. Triglyceride concentrations in subjects with glucose intolerance were elevated compared to those in control subjects, even after adjustment for age, obesity and gender (p < 0.001 for subjects with diabetes and p < 0.01 for those with impaired glucose tolerance compared to normal subjects). In separate multiple regression analyses for males and females, the most important determinants of the plasma triglyceride concentration were the area under the non-esterified fatty acid suppression curve (p < 0.001 in both genders) and the waist-hip ratio (p < 0.001 for men and < 0.01 for women). The fasting insulin concentration was independently associated with triglyceride concentration in women only (p < 0.01). The most important determinant of the area under the non-esterified fatty acid suppression curve in men was the 30-min insulin increment, a measure of insulin secretion, (p < 0.001) whereas for women age (p < 0.001) and the body mass index (p < 0.01) were the most important.

Adult↗

Clonal heterogeneity in the progeny of HeLa cells which survive X-irradiation.

Clones of HeLa cells that had survived 9 Gy X-rays were investigated for plating efficiency, radiosensitivity, the proportion of giant cells, and chromosome numbers. A significant decrease in plating efficiency was observed that persisted for > 20 population doublings. The reduced plating efficiency was associated with an increased proportion of giant cells in the colonies. There was pronounced clonal heterogeneity in the progeny of irradiated surviving cells with respect to plating efficiency, proportion of giant cells, and chromosome numbers. The radiosensitivity of progeny from irradiated cells did not change compared with controls.

Cell Survival↗

Multiblock slides: a useful technique for teaching.

Data on the quality of a modified method for producing multiblocks from conventional blocks of paraffin wax embedded histological material are reported. Originally devised as a way of assessing antibodies for immunohistology, the technique is particularly suited to producing a set of reference and teaching material for use by trainee and senior pathologists.

Audiovisual Aids↗

Which proliferation markers for routine immunohistology? A comparison of five antibodies.

AIMS: To determine the best of five antibodies for immunohistochemical assessment of growth fraction in formalin fixed, paraffin wax embedded tissues. METHODS: Sections from 100 recent, and 17 ten year old or over wax embedded blocks of normal and malignant tissues were immunostained with monoclonal Ki67, polyclonal Ki67, PC10, MIB1, and JC1. The antibodies were evaluated for specificity of nuclear versus cytoplasmic staining, cleanliness of background, and compared with the expected pattern of staining in normal tissues, defined immunohistochemically by monoclonal Ki67 antibody in frozen tissues or by tritiated thymidine uptake. RESULTS: No marker was ideal, but best results were obtained with MIB1 and polyclonal Ki67, followed by JC1, PC10, and monoclonal Ki67. CONCLUSIONS: For routine use, MIB1 or polyclonal Ki67 are the best proliferation markers in conventional histological preparations. The other markers tested cannot be recommended.

Antibodies, Monoclonal↗

An audit of autopsy rates in an inner London general hospital.

Low autopsy rates are of continuing concern to pathologists. The aim of this study was to investigate the reasons why autopsy did not happen, and to determine whether carrying out the investigation and providing some feedback of the results would have any effect on autopsy rates. The main reasons why autopsy did not happen were that junior doctors considered it unnecessary because the diagnosis and cause of death appeared to be well established, and that patients' relatives declined to give permission for autopsy. No increase in autopsy rates was demonstrated, but possible avenues of approach were suggested and these are being implemented.

Attitude of Health Personnel↗

Neurogenic orthostatic hypotension: a double-blind, placebo-controlled study with midodrine.

PURPOSE: To investigate the efficacy and safety of midodrine for treatment of patients with orthostatic hypotension due to autonomic failure. PATIENTS: Ninety-seven patients with orthostatic hypotension were randomized in a 4-week, double-blinded, placebo-controlled study with a 1-week placebo run-in period. Patients ranged in age from 22 to 86 years (mean: 61 years). METHODS: After a 1-week run-in phase, either placebo or midodrine at a dose of 2.5 mg, 5 mg, or 10 mg was administered three times a day for 4 weeks. Both the placebo group and the 2.5-mg midodrine group received constant doses throughout the double-blind phase. The patients receiving 5 mg or 10 mg of midodrine were given doses that were increased at weekly intervals by 2.5-mg increments until the designated dose was reached. Efficacy evaluations were based on an improvement at 1-hour postdose in standing systolic blood pressure and in symptoms of orthostatic hypotension (syncope, dizziness/lightheadedness, weakness/fatigue, and low energy level). RESULTS: Midodrine (10 mg) increased standing systolic blood pressure by 22 mm Hg (28%, p < 0.001 versus placebo). Midodrine improved (p < 0.05) the following symptoms of orthostatic hypotension compared to placebo: dizziness/lightheadedness, weakness/fatigue, syncope, low energy level, impaired ability to stand, and feelings of depression. The overall side effects were mainly mild to moderate. One or more side effects were reported by 22% of the placebo group compared with 27% of the midodrine-treated group. Scalp pruritus/tingling, which was reported by 10 of 74 (13.5%) of the midodrine-treated patients, was most frequent. Other reported side effects included supine hypertension (8%) and feelings of urinary urgency (4%). CONCLUSION: We conclude that midodrine is an effective and well-tolerated treatment for moderate-to-severe orthostatic hypotension associated with autonomic failure.

Adult↗

The bone marrow trephine biopsy: a review of normal histology.

Bone marrow trephine biopsies are becoming increasingly common in routine surgical pathology. Familiarity with normal marrow histology plays an important part in understanding and interpreting marrow pathology. The aim of this article is to describe the histological features of normal human bone marrow, in particular those features which are relevant to the diagnostic pathologist. The advantages and disadvantages of different technical aspects, such as choice of embedding material and type of stain, are discussed. The use of immunochemistry in identifying different cell types within the marrow is illustrated.

Biopsy↗

Protein C and S deficiency causing childhood stroke.

The annual incidence of cerebrovascular disease in children is 2.5/100,000 and cerebral infarction is being increasingly recognised in neonates. Deficiency of proteins C and S and their roles in thrombosis have only recently been recognised. Immunologic and functional assays of these proteins now make it possible to determine whether deficiency of them is associated in any particular case of childhood cerebrovascular accident (CVA). We describe two patients, both presenting with stroke in childhood, who were found to be deficient, one in protein C and one in protein S.

Cerebrovascular Disorders↗

Early morning plasma testosterone is an accurate predictor of imminent pubertal development in prepubertal boys.

In the management of constitutional delayed growth and/or puberty, there is a need for simple tests which can assess the overall developmental maturity of the hypothalamic-pituitary-testicular axis in clinically prepubertal patients. This would enable the physician to predict the likelihood or otherwise of an individual entering puberty spontaneously within subsequent months. Based on our previous physiological data on the sequential pattern of peripubertal pituitary-testicular activation by hypothalamic GnRH, we hypothesized that the nocturnal secretion of testosterone, in response to sleep-entrained LH secretion, may provide a basis for an in vivo bioassay of neuroendocrine sexual maturity. Overnight testosterone secretion by the testis in clinically prepubertal boys was assessed with respect to their subsequent clinical progress, the target being the attainment of testicular volumes of greater than or equal to 4 mL (a clinical landmark when puberty has assuredly begun and virilization will soon follow). Forty-five prepubertal (Tanner stage G1PH1 testicular volume < or = 2 mL) boys aged 10.0-15.3 yr (mean +/- SEM 11.8 +/- 0.2) with short stature had paired plasma T concentration measured at 2000 h and 0800 h the following morning. After the initial assessment, all patients were reviewed clinically at 3-month intervals for a minimum of 21 months (mean 26.0 +/- 1.1, range 21-50 months). During this period, 38 (84.4%) patients received treatment in the form of sc human GH 2-4 IU daily or oxandrolone 2.5 mg daily by mouth to improve short-term growth although this did not have any significant effect on the subsequent timing of pubertal onset. The patients were divided according to whether 1) there was a demonstrable increase in plasma T between 2000 and 0800 h and 2) morning plasma T concentration was less than or greater than or equal to 0.7 nmol/L at their initial assessment. In those with a significant overnight T increment, 58% and 89% achieved testicular volume of greater than or equal to 4 mL after 12 and 21 months, respectively. In contrast, only 12% and 56% of patients who had not shown a T increase went into puberty by these times. In patients who had morning plasma testosterone concentrations greater than or equal to 0.7 nmol/L, 77% entered puberty within 12 months and 100% within 15 months. However, in those with a morning testosterone of less than 0.7 nmol/L, only 12.5% and 25% entered puberty within 12 and 15 months, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗