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Biomedical subjects

D C Brown

Publications and source records attributed to D C Brown.

At least 19 recordsLinked to original sources
PubMed1992

Treatment of refractory familial hypercholesterolemia by low-density lipoprotein apheresis using an automated dextran sulfate cellulose adsorption system. The Liposorber Study Group.

A subgroup of patients with familial hypercholesterolemia (FH) respond inadequately to standard diet and drug therapy, and are therefore at high risk for the premature development or progression of coronary artery disease. This study evaluated low-density lipoprotein (LDL) cholesterol and lipoprotein (a) removal in a multicenter, controlled trial with a new LDL apheresis procedure (Liposorber LA-15 System). The study comprised patients with FH who had not responded adequately to diet and maximal drug therapy. There were 54 patients with heterozygous FH (45 randomized to treatment and 9 control subjects) and 10 with homozygous FH (all of whom received LDL apheresis). The study included three 6-week treatment phases and a 4-week rebound phase. Treatments were administered at 7- to 14-day intervals. Mean acute reductions in LDL cholesterol were 76% in heterozygous FH patients and 81% in homozygous ones. Time-averaged levels of LDL cholesterol were reduced 41% (243 to 143 mg/dl) in heterozygous FH patients and 53% (447 to 210 mg/dl) in homozygous ones. The substantial acute reduction of lipoprotein (a) (means: 65%, heterozygous FH; 68%, homozygous FH) has not been reported with other therapies. The Liposorber LA-15 System represents an important therapeutic option in FH patients who respond inadequately to diet and drug therapy.

Adult↗
PubMed1992

Comparison of proliferation rates assessed using "multiblock" and conventional tissue blocks of lung carcinoma.

AIMS: To compare the proliferative rates, assessed immunohistochemically, of human lung tumours using conventional paraffin wax blocks and the multitumour tissue block (MTTB) technique. METHODS: A multiblock containing 20 lung tumours (eight adenocarcinomas, five squamous cell, five small cell and two carcinoid tumours) was constructed. Sections were also cut from the original blocks of formalin fixed, paraffin wax embedded tissue used to construct the multiblock. Sections were stained with the monoclonal antibody PC10, which recognises a proliferating cell nuclear antigen, using the three stage immunoperoxidase technique. RESULTS: The proliferation rates of the lung tumours obtained using both techniques were, overall, significantly different (p = 0.05), although most cases showed good correlation. Some tumours displayed a high degree of intratumoral variation in PC10 staining. The degree of PC10 staining was in keeping with the known proliferative state of particular histological subtypes--that is, carcinoid tumours showed little staining and small cell carcinomas showed extensive positivity. CONCLUSION: The MTTB technique is a less suitable means of assessing proliferation rate in lung carcinomas than conventional tissue blocks. It should be restricted to qualitative antibody studies or quantitative studies using tumours with little intratumoral variation.

Adenocarcinoma↗
PubMed1991

Dihydroorotase from Escherichia coli. Substitution of Co(II) for the active site Zn(II).

Treatment of Escherichia coli dihydroorotase (a homodimer of subunit molecular weight 38,729) containing only the 1 active site Zn(II) ion per subunit with the sulfhydryl reagent N-(ethyl)-maleimide (NEM) blocks the two external Zn(II) sites per subunit and dramatically lessens the precipitation caused by high concentrations of Zn(II); stabilizes the enzyme partially against air oxidation and dilution inactivation; makes the active site Zn(II) easier to remove; and lowers Km and increases kcat. Treatment of NEM-blocked dihydroorotase ((NEM)dihydroorotase) with the chelator 2,6-pyridinedicarboxylic acid at pH 5.0 in the absence of oxygen and trace metal ions removes the active site Zn(II) with a half-life of 15 min, allowing the production of milligram amounts of moderately stable apo-(NEM)dihydroorotase in about 80% yield. Treatment of apo-(NEM)dihydroorotase with Co(II) at pH 7.0 produces (NEM)dihydroorotase completely substituted at the active site with Co(II) in 100% yield: analysis gives 0.95-1.1 g atoms of Co(II) per active site and 0.03-0.05 g atoms of Zn(II) per active site. This Co(II)-(NEM)dihydroorotase is hyperactive at pH 8. The electronic absorption spectrum of Co(II)-(NEM)dihydroorotase at pH 6.5 implicates an active site thiol group as a ligand to the metal ion. The spectrum is inconsistent with tetrahedral coordination of the active site metal ion and is most consistent with a pentacoordinate structure.

Amino Acid Sequence↗
PubMed1991

Clinical use of the 193-nm excimer laser in the treatment of corneal scars.

Phototherapeutic keratectomy using a 193-nm excimer laser was performed at four centers on 33 sighted patients with corneal opacity and/or irregular astigmatism. Pathologic conditions included anterior stromal and superficial scarring from postinfectious and posttraumatic causes, including inactive herpes simplex virus, anterior corneal dystrophies, recurrent erosions, granular dystrophy, and band keratopathy. Most patients received peribulbar anesthesia and underwent removal of the epithelium prior to laser ablation. A majority of patients had a reduction in the amount of corneal scarring and approximately half had improved visual acuity. No intraocular reaction or changes in endothelial counts were seen, and some patients avoided the need for penetrating keratoplasty. Reepithelialization usually occurred within 4 or 5 days and we noted no significant scarring secondary to use of the laser. It was difficult to eliminate preexisting irregular astigmatism despite the use of surface modulators, such as methylcellulose. A hyperopic shift secondary to corneal flattening was encountered in approximately 50% of the patients. A combination of myopic ablation, followed immediately by a secondary hyperopic steepening, may minimize this refractive change. The 193-nm excimer laser is an effective new tool in the treatment of selected patients with superficial corneal opacity from a variety of conditions.

Adult↗
PubMed1991

The use of the 193-nm excimer laser for myopic photorefractive keratectomy in sighted eyes. A multicenter study.

Photorefractive keratectomy was performed at three centers using the 193-nm excimer laser on 31 sighted myopic eyes. Preoperative refractive errors (spherical equivalent) ranged from -12.00 to -4.00 diopters (D) (mean, -6.49 +/- 1.75 D). Peribulbar anesthesia, a 5.2- to 6.0-mm beam diameter, and topical corticosteroids were used for up to 6 months after surgery. The epithelium healed within 3 to 4 days, and all patients returned to their best corrected visual acuity within 1 line of their preoperative acuity. There was minimal subepithelial reticular haze, peaking at 3 weeks and diminishing over the next 3 to 4 months, which was not felt to be visually significant. At 6 months, the average residual refractive error was -1.85 +/- 2.5 D. Sixty-eight percent of eyes were corrected within 2 D and 55% within 1 D of attempted correction. There was no significant change in astigmatism, contrast sensitivity, corneal sensation, or endothelial cell counts. This preliminary work shows that photorefractive keratectomy has promise in the reduction of moderate myopia.

Adult↗
PubMed1991

Height and glucose tolerance in adult subjects.

In a prospective study concerning the pathogenesis of impaired glucose tolerance and Type 2 (non-insulin-dependent) diabetes mellitus, 346 subjects with no clinical history of diabetes were given a standard 75 g oral glucose tolerance test. The expected positive associations between 120-min plasma glucose concentration and age and body mass index were observed in both sexes and between 120-min plasma glucose and waist/hip ratio in male subjects. An unexpected negative correlation was found between 120-min plasma glucose and height in both sexes (r = -0.23, (95% confidence interval, -0.38 - -0.07) p less than 0.007 for male subjects and r = -0.24, (-0.37 - -0.11) p less than 0.006 for female subjects). These negative associations with height remained significant after controlling for age and body mass index in male subjects but not in female subjects. In the latter a highly significant negative relationship of height with age was recorded (r = -0.33, (-0.45 - -0.20) p less than 0.0001). Comparison between individuals with impaired glucose tolerance and control subjects matched for sex, age and body mass index showed that subjects with impaired glucose tolerance are significantly shorter. Mean (+/- SEM) height in the male subjects with impaired glucose tolerance (n = 29) was 173.4 +/- 1.1 cm vs 176.9 +/- 1.3 cm in control subjects, p = 0.02. In the female subjects (n = 39) mean (+/- SEM) height was 159.4 +/- 1.0 cm vs 162.4 +/- 1.0 cm in control subjects, p = 0.02. The negative relationship between height and glucose tolerance is a new epidemiological observation which has not been previously reported.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Life threatening 'epilepsy'.

A 5 year old girl presenting with episodes of sudden loss of consciousness was found to have intermittent ventricular tachycardia and, on one occasion, self limiting fibrillation. Corrected QT interval was normal. After several therapeutic measures clinical and electrocardiographic improvement was achieved by administration of sotalol.

Child, Preschool↗
PubMed1991

Cholestasis in a neonatal intensive care unit.

A retrospective study of 17 babies admitted to the neonatal intensive care unit of the Royal Maternity Hospital, Belfast, was undertaken to determine the causes and prognosis of conjugated hyperbilirubinaemia (direct fraction greater than 20% of total) over a five year period. Mean gestational age was 29 weeks and mean birth weight was 1,240g with a 2:1 male preponderance. All babies had a complicated clinical course involving prolonged periods of parenteral nutrition and many episodes of sepsis. Liver damage was not found to be a contributory factor to death in any baby who died before the age of one year. Bilirubin levels in the survivors had returned to normal within one year. No permanent pathological cause of cholestasis, such as biliary atresia, was ascribable to any of the cases, indicating that extensive investigation to exclude anatomical causes in this population is unlikely to prove rewarding.

Bacterial Infections↗
PubMed1990

CD30 expression in non-Hodgkin's lymphoma.

The CD30 antigen has been reported as the immunophenotypic hallmark of a recently described category of non-Hodgkin's lymphoma, termed anaplastic large cell lymphoma. From a series of approximately 500 lymphomas, 17 cases showing typical anaplastic features have been identified. They were strongly labelled by monoclonal antibodies recognizing CD30 (Ki-1 or BerH2). However, 36 other lymphomas, mainly high-grade, of non-anaplastic cytology also expressed CD30, either diffusely or focally, with a staining pattern identical to that seen in anaplastic large cell lymphomas. This clearly suggests that such lymphomas cannot be identified solely on the basis of being high-grade non-Hodgkin's lymphomas showing CD30 positivity. From the present results, the distinction between the anaplastic and non-anaplastic types would be better made with antibodies to epithelial membrane antigen than to CD30. Clinical data, available for 48 of the patients (16 with anaplastic large cell lymphomas and 32 with non-anaplastic) revealed no significant differences with regard to age at presentation, sex or clinical signs. A short-term follow-up study of 25 patients revealed that for the first 2 years after diagnosis there were no significant differences in patient survival between anaplastic large cell lymphoma, other CD30+ high-grade lymphomas and all high-grade non-Hodgkin's lymphomas considered together. These findings, which must be confirmed by larger studies, suggest that in a general lymphoma clinic there is probably little justification for differentiating anaplastic large cell lymphomas or CD30+ lymphomas from other high-grade non-Hodgkin's lymphomas.

Adolescent↗
PubMed1990

Monoclonal antibody Ki-67: its use in histopathology.

Monoclonal antibody Ki-67 is a reliable and easy means of accurately assessing the growth fraction of human neoplasms. Although the number of long-term follow-up studies is limited, it does appear to provide valuable prognostic information particularly in lymphoproliferative disease. Since the estimation of growth fraction is only one factor influencing tumour behaviour it would be naive to believe that measurement of this parameter alone, no matter how accurately, would provide the clinician with definitive prognostic information for all tumours. The antibody is also of use in research, providing a means of measuring proliferative activity in a variety of conditions besides malignancy, and may prove of value in monitoring tumour response to established and trial therapies.

Antibodies, Monoclonal↗
PubMed1990

Proliferation in non-Hodgkin's lymphoma: a comparison of Ki-67 staining on fine needle aspiration and cryostat sections.

Assessment of the growth fraction of non-Hodgkin's lymphomas may provide useful additional prognostic information to that obtained with conventional histological criteria. The monoclonal antibody Ki-67 has been reported to provide such information immunocytochemically in tissue biopsy specimens from lymphoma as well as other tumours. This study was undertaken to assess whether this approach could be extended to fine needle aspiration (FNA) biopsy specimens which are becoming increasingly important in the diagnosis of lymphoma. In 21 cases of non-Hodgkin's lymphoma the rate of tumour proliferation estimated by Ki-67 immunostaining of FNA material, obtained from surgically removed specimens, was compared with that obtained on tissue biopsy. The correlation between both preparations was excellent, indicating that FNA biopsy material is suitable for the immunocytochemical assessment of the growth fraction of non-Hodgkin's lymphoma.

Antibodies, Monoclonal↗
PubMed1990

The laterally tilted dens: a sign of subtle odontoid fracture on plain radiography.

Type III (low) odontoid fractures may be subtle on initial plain film radiographic examination. We describe a sign on the routine open-mouth view, the laterally tilted dens, which has not been previously stressed in the radiologic literature, and is an important diagnostic sign of type III fractures of the odontoid process of the axis. In a series of 82 nontraumatized patients, no odontoid angle of less than 87 degrees (3 degrees from perpendicular) was observed. In a series of type III odontoid fractures, tilting of the dens in excess of 5 degrees was present in eight (67%) of 12 cases. This may be the only readily apparent finding on the initial cervical spine series. Of eight type III odontoid fractures in which an abnormal odontoid angle was identified, it was the only definite abnormality that could be recognized prospectively in two cases (25%) and that supported very subtle findings in two other cases (25%).

Adolescent↗
PubMed1990

Adverse events reported in association with the use of monoclonal antibody purified factor VIIIC--Monoclate.

In the 2-year period between October 1987 and October 1989, during which an estimated 3,000 to 4,000 hemophiliacs were treated with Monoclate, spontaneous reports were received on 43 patients who experienced 134 adverse events. The symptomatic adverse events reported have been remarkably few in number and similar in nature to those reported with use of other factor VIII preparations. Monoclate has been shown to have an excellent safety profile and there have been no reports of viral transmission or of unexpected adverse events related to its administration.

Adolescent↗
PubMed1989

Characteristics of the in vitro interaction of a small proteoglycan (PG II) of bovine tendon with type I collagen.

Binding of the small dermatan sulfate proteoglycan of bovine tendon (PG II type/decorin-like) to type I collagen was characterized in an in vitro fibril-forming assay, using native collagen prepared from bovine tendon by acid extraction and radiolabeled proteoglycans synthesized by bovine tendon fibroblasts in culture. Substantial binding to collagen was noted for both intact small proteoglycan and core protein from which the glycosaminoglycan chain was removed. However, binding to collagen was minimal for free glycosaminoglycan chains or large proteoglycans. Binding of the small proteoglycan was optimal at approximately physiological conditions of salt concentration and pH. Scatchard analysis showed a binding affinity constant of 3.3 x 10(7) M-1 with 0.054 proteoglycan binding sites/collagen molecule, when about 0.25-6 micrograms proteoglycan was combined with 100 micrograms collagen. Binding to preformed fibrils of native tendon collagen and to pepsin-treated bovine skin collagen was similar to binding to native tendon collagen. Binding occurred in non-ionic detergents at concentrations up to 1% and once bound, the proteoglycan was not released by washing with up to 2 M NaCl. When both PG I and PG II small proteoglycans were added to collagen, only PG II was bound. This difference is not readily explained by differences in disulfide bond position. These studies indicate a strong, specific interaction between type I collagen fibrils and the core protein of the small (PG II) proteoglycan of tendon.

Animals↗
PubMed1989

The prognostic significance of immunophenotype in high-grade non-Hodgkin's lymphoma.

The prognostic value of immunophenotyping lymphomas was assessed by studying 51 cases of high-grade non-Hodgkin's lymphoma for which long term clinical follow-up (14-28 years) was available. Using antibodies which identify T- and B-cell-related antigens in formalin-fixed, paraffin-embedded material, 43 were shown to be of B-cell and eight of T-cell phenotype. In terms of survival, cases of high-grade T-cell lymphoma fared significantly worse (P less than 0.05) than cases of high-grade B-cell subtype. These findings support the belief that T-cell lymphomas have a more aggressive clinical course than their B-cell counterparts.

Antibodies, Monoclonal↗