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Biomedical subjects

D Nicholson

Publications and source records attributed to D Nicholson.

At least 55 records · Page 3Linked to original sources

Automated quantitation of immunocytochemically localized estrogen receptors in human breast cancer.

Frozen sections of breast tumor tissue have been stained using an immunoperoxidase [estrogen receptor (ER)-immunocytochemistry] kit incorporating a monoclonal antiserum [H222] to visualize nuclear human ERs. Quantitation of specific staining has been performed by manual procedures using optical microscopy and by a computer-assisted image analysis system (CAS 100). Initial investigations with a test panel of ER-immunocytochemistry-positive tumors revealed a good qualitative agreement between CAS and manual assessments. Reduced variance was, however, observed between quantified ER-immunocytochemistry results from four experienced investigators using the CAS analysis. An extended study confirmed the relationships between CAS and manual methods of assessment. These findings were evident when studies were scored either by assessment of the percentage of positively stained cells (n = 92; r = 0.919; P less than 0.01) or by H-score calculations (n = 92; r = 0.913; P less than 0.01). A good correlation was also found between CAS quantification and the results of an ER enzyme immunoassay of 48 primary breast cancer specimens (r = 0.715; P less than 0.05). In 49 cases it was possible to relate CAS-defined ER status and levels to the subsequent response of patients to endocrine therapy. ER was assessed on specimens obtained prior to commencement of treatments for recurrent breast cancer. Presuming the presence of ER to be a prerequisite for successful therapy, very good correlations between response and both status and levels of positivity were recorded. None of 16 patients with CAS-ER-negative tumors responded to treatment, while 16 of 33 (48.4%) CAS-ER-positive patients achieved an objective response according to International Union Against Cancer criteria. A relationship between response and the degree of CAS-ER positivity was obtained when the CAS score divisions of 0, 1-100, and greater than 100 (response rates, 0, 41, and 64%, respectively) were used. These data demonstrate that automated image analysis offers a reliable, reproducible procedure for quantifying ER in immunocytochemically stained sections. It has potential advantages over manual procedures, providing less opportunity for subjective influences in scoring sections. Future advances in software design should further reduce elements of subjectivity and increase both the speed and reliability of results. We anticipate image analysis becoming a valuable tool in investigations concerning, for example, the influence of heterogeneity of steroid receptor distribution on the rate of recurrence of breast cancer after mastectomy and in the clinical course of the disease.

Breast↗

Chronic cor pulmonale.

Chronic cor pulmonale is defined as right heart hypertrophy and/or chronic right heart failure. There are many etiologies, but the common cause is increased right heart work from pulmonary hypertension. Etiology can be conveniently discussed by assuming two prototypes, the asphyxial or hypoxic type and the vascular obliterative type. A common cause of the asphyxial type is chronic obstructive pulmonary disease, and the obliterative type is represented by chronic pulmonary thromboembolic disease or primary pulmonary hypertension. Pathology is discussed, emphasizing the cardiac manifestations of chronic cor pulmonale including data of specific cardiac chamber size. An overview of hemodynamics is given, and the use and limitation of electrocardiography and chest x-rays are discussed. The exciting potential use of echocardiography for the serial non-invasive measurement of anatomical and pathophysiological features is outlined, along with the value of a careful physical examination and the proper utilization of laboratory tests in the diagnosis of chronic cor pulmonale. In the patient with the asphyxial type, the treatment of pulmonary infectious exacerbations, the role of corticosteroids, digoxin, diuretics, phlebotomy, bronchodilators (theophylline, beta adrenergic agonists, and anticholinergics), and long-term oxygen therapy is noted. The controversy surrounding the use of vasodilators and calcium blockers in these patients is discussed. Treatment aspects of the vascular obliterative type, including the role of vasodilators, calcium blockers, prostacyclin, anticoagulants, and overall strategy are discussed. A brief note is mentioned of the promising role of surgical therapy in chronic thromboembolic disease causing chronic cor pulmonale.

Adult↗

Pulmonary embolism: an internist's perspective.

Forty years ago there was less interest in thromboembolism than there is now, although it was apparent even at that time that many episodes of embolization were being missed. Retrospective autopsy studies had indicated a 40% to 60% incidence of pulmonary emboli. Such studies were reviewed in a prospective study of 263 right lungs taken from every fourth autopsy performed on patients older than 10 years of age who died in United Oxford Hospitals from 1964 to 1965. Pulmonary emboli were present in 136 autopsies (51.7%) and were judged to be the main cause of death in 37 of those with emboli (27%). This high incidence of embolization was certainly not fully appreciated in the 1940s and 1950s, nor was the frequent absence of clinical signs in these cases.

Humans↗

Shopping for the best purchasing group.

As hospitals seek horizontal and vertical linkages to enhance their chances for survival, they are frequently join group purchasing organizations. Prior to joining any of these organizations, the hospital should carefully evaluate bow the linkage will benefit the organization not just on the basis of price, so this author contends. In this article, the author reviews the various selection criteria that should be reviewed.

Decision Making↗

Chronic suppurative otitis media in the Solomon Islands: a prospective, microbiological, audiometric and therapeutic survey.

Chronic suppurative otitis media affected 3.8% of 3500 Solomon Island children under 15 years (and 6.1% under 5 years) and was the sole cause of conductive hearing loss recorded in 265 children tested audiometrically. It was characterised by early onset (65% under 18 months) male preponderance and large central tubotympanic perforations. Measles, respiratory infections, swimming and malnutrition were identified as aetiological factors amenable to intervention. Proteus and pseudomonas were the principle aerobes isolated from ear pus and gentamicin the only antibiotic tested to be effective against them. However although a prospective therapeutic trial demonstrated a significantly improved outcome after aural toilet, no additional benefit was imparted by concurrent ototopical boric acid or aminoglycoside solution or oral antianaerobic clindamycin. Parental tuition in aural cleaning, avoidance of ear water entry, nose blowing and breathing will yield a good result in up to 60% of children in half of whom tympanic healing occurred.

Adolescent↗

Characterization of 5'-flanking region of heart myosin light chain 2A gene. Structural and functional evidence for promoter activity.

Two recombinant clones, lambda LC5 and lambda LC13, encompassing the entire regulatory myosin light chain 2 (MLC2A) gene of chicken heart muscle were isolated. Of these, lambda LC5 which contains a large 5'-flanking sequence of about 7.0 kb, was characterized by a partial nucleotide sequence analysis. A TATA-like sequence (TATTTTTA) and a CAAT-box (CAAAAGT) are located at positions -32 and -59, respectively, which most likely constitute the functional promoter region in the gene. Based on primer extension reaction with a synthetic 20-mer corresponding to the 5'-leader sequence and total poly(A+) RNA, the probable transcription initiation site in the gene was located. The gene promoter activity was demonstrated following transient expression of recombinant genomes containing the chicken upstream sequence fused to the bacterial chloramphenicol acetyltransferase (CAT) or to the rat preproinsulin II genes. The extracts from a Quail fibroblast cell line (QT35) transfected with the construct (pLCo5.2iCat) containing the putative chicken promoter, and the CAT gene promoted the formation of 3'-acetate chloramphenicol. Another construct (pBC12LC5.2f) contains the rat preproinsulin II gene placed under the control of chicken promoter and a simian virus 40 origin of replication. Transfection of COS cell line with pBC12LC5.2f DNA resulted in an efficient expression of rat preproinsulin mRNA initiating from the chicken promoter. The transfection assay also allowed detection of chicken MLC2A gene transcripts by S1-nuclease protection of end-labeled DNA probes. A comparison of the MLC2A upstream gene sequence with those available for skeletal myosin light chains revealed no common sequence elements, suggesting that cardiac MLC2A gene promoter region has diverged considerably from its counterparts in skeletal muscle.

Amino Acid Sequence↗

Rheumatoid rigor: gold induced myokymia. A report and review of the literature.

Myokymia is a spontaneous movement disorder characterized by slow, undulating, persistent movement of the involved muscles. It is an unusual manifestation of gold neurotoxicity, rarely reported in the rheumatologic literature. We report a case of gold induced myokymia associated with gold-induced dermatitis and nephropathy.

Adult↗

Progressive systemic sclerosis and Graves' disease. Report of three cases.

Progressive systemic sclerosis (PSS) is associated with a broad spectrum of autoimmune thyroid diseases. While an association between PSS and hypothyroidism is well established, a relationship between PSS and hyperthyroidism is less well defined. We treated three patients with PSS whose course was complicated by Graves' disease. Because hyperthyroidism can simulate many of the symptoms of PSS progression and treatment of hyperthyroidism can lead to resolution of clinical deterioration in such patients, it is important to recognize the simultaneous occurrence of these diseases.

Adult↗