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Biomedical subjects

R Brown

Publications and source records attributed to R Brown.

At least 631 records · Page 35Linked to original sources

Pathologic findings from the National Surgical Adjuvant Breast Project (protocol 6). II. Relation of local breast recurrence to multicentricity.

One hundred ten local breast recurrences were observed in 1108 pathologically evaluable patients enrolled in NSABP protocol 6 who were treated by lumpectomy and followed for 5 to 95 months (average, 39 months). Eighty-six percent and 95% of all local breast recurrences were noted within 4 and 5 years, respectively, following lumpectomy. Life table analysis revealed their incidence to be 24% for those not and 6% for those receiving lumpectomy and breast irradiation. One hundred four (95%) of the breast recurrences involved the mammary parenchyma and the remaining 6 (5%) involved the skin and/or nipple only. Eleven (10%) of the former were noninvasive. The most common (86%) presentation of breast recurrence appeared to be a localized mass within or close to the quadrant of the index cancer. In 14% the recurrence not only involved the same quadrant, but was more diffuse within the breast extending to remote areas as well. This type was characterized pathologically by marked intralymphatic extension as well as involvement of the overlying skin and/or nipple after the fashion of so-called inflammatory or occult inflammatory breast cancer. The recurrences noted in the skin and/or nipple only were also pathologically characterized by intralymphatic involvement at these sites in the majority of instances. These two forms of breast recurrences appear to reflect the localized growth of highly aggressive invasive breast cancers. The concordance of histologic types and grades of the index and recurrent cancers implies that such events represent growth of overlooked tumor, a deficiency attendant with lumpectomy due to the extreme multifocal nature (not multicentricity) of some breast cancers and/or inadequacies in evaluating the lines of resection of lumpectomy specimens. Sources of error in regard to this latter are identified and guidelines for the examination of such specimens, as well as the assessment of margins, are presented. The observation that local breast recurrences noted following lumpectomy occurred within or close to the same quadrant as the index cancer, despite the presence of multicentric noninvasive cancers in 10% of the patients treated by total mastectomy, minimizes the biological and clinical significance of multicentric foci of cancer present in some breast cancers. Cancer measuring greater than or equal to 2.0 cm, having high histologic and nuclear grades, or intralymphatic extension, were found to have a statistically significant association with local breast recurrence in all patients following lumpectomy. A converse relationship was noted with tubular and scar cancers of types 1 and 4.(ABSTRACT TRUNCATED AT 400 WORDS)

Actuarial Analysis↗

Postmortem evidence of structural brain changes in schizophrenia. Differences in brain weight, temporal horn area, and parahippocampal gyrus compared with affective disorder.

The brains of 232 patients with a case-note diagnosis of schizophrenia or affective disorder who died in one mental hospital over a period of 22 years were weighed, and were assessed in a coronal section at the level of the interventricular foramina. From this sample were eliminated the brains of patients whose illnesses did not meet the Washington University criteria for a diagnosis of definite schizophrenia or primary affective disorder and those brains that showed significant histopathologic evidence of Alzheimer's-type change or cerebrovascular disease. This left a sample of 41 patients with schizophrenia and 29 patients with affective disorder. With age, sex, and year of birth controlled for, the brains of the patients with schizophrenia were 6% lighter, had lateral ventricles that were larger in the anterior (by 19%), and particularly in the temporal, (by 97%) horn cross section, and had significantly thinner parahippocampal cortices (by 11%). The findings provide postmortem confirmation of reports of ventricular enlargement in radiological studies and suggest that such enlargement is associated with tissue loss in the temporal lobe. The changes in schizophrenia were of a lesser degree than those seen in a sample of brains of patients with Alzheimer's-type dementia and Huntington's chorea.

Aged↗

Yersinia colitis masquerading as pseudomembranous colitis.

We describe a 15-month-old male who presented with fever and diarrhea 24 hr after receiving antibiotics for otitis media. A flexible sigmoidoscopy was initially interpreted endoscopically as antibiotic-associated pseudomembranous colitis, and the patient was treated with vancomycin. The diagnosis of antibiotic-associated colitis was excluded in our patient by the negative stool examination for Clostridium difficile toxin, the failure to obtain supportive features on rectal biopsy, and the failure to demonstrate sigmoidoscopic improvement with vancomycin therapy. Thirteen days later, Y. enterocolitica was cultured from the initial stool specimens. In this case, the raised central whitish area on an erythematous base was misinterpreted as pseudomembranous colitis.

Colitis↗

Factors influencing mortality in rheumatoid arthritis.

The prognosis in rheumatoid arthritis respecting mortality was studied in a consecutive series of 489 hospital patients over a period of 18 years. The relative risk of mortality was raised in both men (2.6; p less than 0.001) and women (3.4; p less than 0.001). In the women the relative risk was also influenced by prior duration of RA and was characterised by a diminution in risk 5-9 years after first presentation. Relative risks for men were more uniformly distributed over time. Annual excess mortality rates were strongly associated with age at first presentation in women, the rate increasing with increasing age in both the group seen within 5 years of onset of disease (chi 2(1) for trend = 30.4; p less than 0.001) and in the later referral group (chi 2(1) = 34.0; p less than 0.001). A similar but much less marked effect was observed in men in the early referral group (chi 2(1) = 13.7; p less than 0.001) only. These results suggest that initially women may have a milder form of disease and that hormonal status may affect prognosis. Future long-term therapeutic studies in RA should take into account the prognostic factors of age, sex and duration of disease.

Adolescent↗

The nature of mutants induced by ionizing radiation in cultured hamster cells. II. Antigenic response and reverse mutation of HPRT-deficient mutants induced by gamma-rays or ethyl methanesulphonate.

A large series of independent mutants deficient in HPRT enzyme activity, isolated from V79-4 hamster cells (Brown and Thacker, 1984), were assessed for properties which reflect the nature of the genetic changes induced. A total of 88 mutants were screened, 43 isolated from gamma-ray-treated cultures and 45 induced by ethyl methanesulphonate (EMS). Firstly, each mutant was assayed for the presence of protein with the antigenic response of HPRT (cross-reacting material, CRM), using an antibody raised against partially purified V79-4 HPRT enzyme. In a competitive inhibition assay, 31% of EMS-induced mutants were CRM-positive compared to 7% of the gamma-ray series. Secondly, each mutant was tested for ability to revert to HPRT proficiency, either spontaneously or after treatment with the powerful mutagen ethyl nitrosourea (ENU). All except 2 of the EMS-induced mutants reverted with ENU, and many reverted spontaneously, under the given conditions. However reversion was not detected in about 80% of gamma-ray-induced mutants, suggesting that the types of forward mutation caused by ionizing radiation differ qualitatively from those caused by EMS. The EMS-induced mutations are likely to be mostly point mutations, with at least 40% of the missense type, while gamma-ray-induced mutations may arise mostly through larger genetic changes.

Animals↗

Nucleotide and deduced amino acid sequence of the influenza neuraminidase genes of two equine serotypes.

Equine influenza is caused by two serotypes of type A influenza virus, EIV-A1 and EIV-A2. The complete nucleotide sequence of the neuraminidase (NA) genes of both the A1 (N7 subtype) and A2 (N8 subtype) serotype has been determined following cloning of full-length viral NA cDNAs into pBR322. Analysis of the deduced amino acid sequences reveals that the N7 and N8 genes share expected extensive homologies with the previously sequenced N1, N2, and N9 NA subtypes. These homologies include conservation of basic NA gene and protein structure, cysteine residues, potential glycosylation sites, and residues known to reside in the enzyme active site of the NA molecule. Additionally, the N1 and N8 molecules and the N7 and N9 molecules are more related by total amino acid homology than any other combination of two subtypes. The area of homology in both cases is particularly strong in the region of residues 100-205, an area roughly corresponding to the amino terminal one-third of the "head" of the NA protein.

Amino Acid Sequence↗

A possible role for oxytocin in the response to a psychological stressor.

Recent evidence suggests that oxytocin (OXT) potentiates corticotropin releasing factor-induced secretion of ACTH. The present study was therefore designed to investigate the possible role of oxytocin in the response to predictable and unpredictable novelty stress. The results clearly demonstrate that oxytocin produced a significant increase in corticosterone in all OXT treated animals. Repeated unpredictable exposure also produced a more substantial increase in corticosterone than predictable exposure to the same stressor. However, a significant interaction between stress and oxytocin was not obtained. It was concluded that whereas corticosterone is released in response to most types of stress, administration of oxytocin does not potentiate the corticosterone response to psychological stress.

11-Hydroxycorticosteroids↗

An evaluated programme of rheumatology training for general practitioners.

The management of painful, upper-limb disorders by 34 general practitioners (GPs) was examined 3 months before and 3 months after personal instruction of GPs by a consultant rheumatologist. Tuition was conducted either in GP surgeries or a hospital out-patient department. Following instruction there were significant increases in the application of appropriate treatments (p less than 0.0005) and of local corticosteroid injections by GPs (p less than 0.005), fewer requests for investigations and less-frequent hospital referrals for consultant rheumatology opinions. Hospital out-patient instruction was associated with a significant reduction of patients' time off work (p less than 0.005) and, in general, differences of management appeared to be more pronounced amongst those GPs instructed in the hospital than in GP surgeries. The study showed that personal instruction of GPs by a consultant rheumatologist may result in modifications of practice, at least in the short term. The evidence indicates that such alterations of GP management may significantly reduce patient morbidity.

Arm↗

Effects of high doses of celiprolol in asthmatic patients.

Sixteen normotensive asthmatic patients received single doses of 400 and 600 mg of celiprolol and 100 mg of atenolol in this placebo-controlled, double-blind crossover study. Pulmonary function was assessed by spirometry. Changes in forced one-second expiratory volume (FEV1) and mid-maximal expiratory flow (MMEF) following both doses of celiprolol were indistinguishable from the effects of placebo, whereas atenolol caused a significant reduction in both measurements of pulmonary function. Graded doses of albuterol, a beta 2-selective sympathomimetic administered at 15-min intervals starting 3 h after each treatment, as expected, caused bronchodilation. The overall bronchodilatory effects of this combined, beta-blocker plus albuterol treatment on pulmonary function were greatest after celiprolol 600 mg, followed in order by celiprolol 400 mg, placebo, and atenolol. Celiprolol 400 mg and 600 mg neither caused bronchoconstriction nor antagonized albuterol in this acute study. Because of its bronchosparing properties, even at high doses, celiprolol may offer an advantage over other, similar agents in the treatment of hypertension and angina in asthmatics.

Adult↗

Immunochemistry of the surface carbohydrate antigens of Bacteroides fragilis and definition of a common antigen.

The components extracted by aqueous phenol from whole cells of Bacteroides fragilis were analysed by SDS-PAGE and immunoblotting and shown to consist of a series of strain-specific, cross-reactive and common antigens. Regularly-spaced ladder patterns on silver-stained gels indicated that in most strains the LPS was present as a predominantly smooth type, but with chain lengths of varying molecular mass, ranging within each particular strain from essentially rough forms to long chain-length smooth forms. The rough form of the LPS at the gel front possessed an antigen common to most of the strains investigated. Another antigen, which migrated behind the rough LPS on SDS gels, was common to all strains of the species. The smooth LPS forms and the other high molecular mass components were strain-specific antigens. Previously published methods are not capable of producing pure LPS or capsular polysaccharide for this organism.

Antigens, Bacterial↗

Role of sphincterotomy in extracapsular cataract surgery.

Forty patients subjected to extracapsular cataract extraction with posterior chamber intraocular lens implantation in whom a sphincterotomy was required are reported on. This method was used to counter the problems created by a small pupil during surgery. The technique is described and results evaluated.

Cataract Extraction↗

Multiple system atrophy (Shy-Drager syndrome): MR imaging.

The Shy-Drager syndrome (SDS) is a form of progressive autonomic nervous system failure (PAF) with orthostatic hypotension and associated extrapyramidal involvement that is often mistaken for Parkinson disease. SDS includes olivopontocerebellar atrophy and striatonigral degeneration which is attended by PAF. Eight patients with SDS were studied on a 0.5-T superconducting system utilizing T1-weighted inversion recovery (IR) and T2-weighted spin-echo pulse sequences and also on a 1.5-T system using spin-echo sequences. With IR sequences, atrophy of the putamina was demonstrated in patients with SDS that is consistent with findings of neuronal loss in these nuclei reported on postmortem examinations. An abnormal decrease in signal intensity of the putamina, particularly along their lateral and posterior portions, was also detected, predominantly on T2-weighted sequences, and in three cases on T1-weighted spin-echo sequences. Abnormalities were detected on both imagers but were shown with greater clarity on the 1.5-T device. SDS is the first disease in which convincing basal ganglia changes have been shown in vivo exclusively by MR imaging.

Adult↗

Upper and lower rib cage deformation during breathing in quadriplegics.

In quadriplegia, the anteroposterior diameter of the rib cage (RC) decreases during inspiration. Our aim was to characterize this paradoxical motion further and to determine to what extent it was due to a diminished inspiratory effect of the diaphragm on the RC because of abdominal muscle paralysis. In six quadriplegics, upper and lower RC (URC, LRC) displacements were studied in various postures with and without extrinsic abdominal support. LRC was in its relaxed configuration at all lung volumes studied in three subjects before and four subjects during abdominal compression. URC distorted most and, despite improvement during abdominal compression, was never in the relaxed configuration during tidal inspiration. Thoracic distortability was further studied by noting the effect on URC and LRC of a cephalad force applied to the RC at the costal margin. This produced distortion similar to that observed during spontaneous inspiration. It was concluded that during spontaneous inspiration in quadriplegics lack of abdominal support does not entirely explain the RC distortion which occurs, and high abdominal pressure results in diminished RC distortion, an effect which we attribute to an increase in the area of diaphragmatic apposition to the RC.

Abdomen↗

Effect of cardiogenic oscillations on gas mixing during tracheal insufflation of oxygen.

In a previous study using tracheal insufflation of O2 (TRIO) at a rate of 2 l/min, we showed that anesthetized paralyzed dogs could be adequately oxygenated for up to 5 h, albeit with hypercapnia (mean arterial PCO2 approximately 160 Torr). To examine the contribution of cardiogenic oscillations in producing this gas exchange, we studied seven anesthetized paralyzed dogs weighing between 19.6 and 25.5 kg and quantified gas transport by analyzing continuous N2-washout curves in vivo and postmortem. We found that cardiogenic oscillations increase gas mixing roughly fourfold and that this value was independent of insufflation flow rate (0.2-10.0 l/min). Our results lend indirect evidence that, with regard to gas exchange, there are two mechanistically different zones in the lung during TRIO. One zone, located in the more peripheral areas of the lung, is dominated by the effects of cardiac oscillations and molecular diffusion and accounts for the increase in gas mixing found in the alive vs. dead dog. A second zone, close to the insufflated jet of O2, uses convective streaming to produce greater gas mixing at higher flows.

Aerosols↗