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Biomedical subjects

D N Smith

Publications and source records attributed to D N Smith.

At least 19 recordsLinked to original sources
PubMed1996

Discovery of 1,5-benzodiazepines with peripheral cholecystokinin (CCK-A) receptor agonist activity. 1. Optimization of the agonist "trigger".

Directed screening of compounds selected from the Glaxo registry file for contractile activity on the isolated guinea pig gallbladder (GPGB) identified a series of 1,5-benzodiazepines with peripheral cholecystokinin (CCK) receptor agonist activity. Agonist efficacy within this series was modulated by variation of substituents on the N1-anilinoacetamide moiety. Remarkably, a single methyl group confers agonist activity, with an N-isopropyl substituent providing optimal efficacy. Hydrophilic substituents on the anilino nitrogen abolish agonist activity or produce antagonists of CCK. In contrast, hydrophilic electron-donating groups at the para-position of the anilino ring enhance or maintain in vitro and in vivo agonist activity. Despite decreased affinity for the human CCK-A receptor, relative to CCK-8, some of these compounds are equipotent to CCK as anorectic agents in rats following intraperitoneal administration.

Amino Acid Sequence↗
PubMed1994

Reducing the risk of viral transmission at operation by electronic monitoring of the surgeon-patient barrier.

A new electronic device designed to detect glove holes, wet gowns and glove permeability was assessed during 50 general surgical operations. The cause of each alarm was recorded and the surgeon's awareness of any breach noted. Some 266 alarms were recorded of which 45 were ascribed to glove holes, 86 to wet gowns, 115 to glove porosity and 20 to other causes. Glove holes occurred in 29 of the 50 procedures; the surgeon was unaware of the hole in almost 70 per cent of cases. Holes were more common in laparotomy than in laparoscopic procedures (P = 0.006). In 20 per cent of instances surgeons did not respond immediately to the alarm (median delay 16 min). Six of eight surgeons who used the device indicated that they would do so regularly for major abdominal surgery. The electronic system accurately detects breaches in the surgeon-patient barrier. Its use should improve surgical discipline in acting to restore the barrier, protecting patient and surgeon alike.

Elective Surgical Procedures↗
PubMed1994

A preliminary investigation of temperature distribution in the prostatic urethra during Thermex II thermotherapy.

In a random group of five patients undergoing thermotherapy with Thermex II (Direx Systems), the temperature in the region of the external sphincter was measured using a modified Thermex catheter. In all five patients the measured temperature exceeded 44.5 degrees C for more than half the duration of treatment. Further temperature mapping studies and studies on the assessment of sphincter function after Thermex II thermotherapy are in progress.

Body Temperature↗
PubMed1992

The performance of integrated transconductance amplifiers as variable current sources for bio-electric impedance measurements.

Multiple applied current impedance measurement systems require numbers of current sources which operate simultaneously at the same frequency and within the same phase but at variable amplitudes. Investigations into the performance of some integrated operational transconductance amplifiers as variable current sources are described. Measurements of breakthrough, non-linearity and common-mode output levels for LM13600, NE5517 and CA3280 were carried out. The effects of such errors on the overall performance and stability of multiple current systems when driving floating loads are considered.

Amplifiers, Electronic↗
PubMed1990

Hospitalization decision in patients with community-acquired pneumonia: a prospective cohort study.

PURPOSE: To identify a low-risk subset of patients with community-acquired pneumonia that could safely be treated in the ambulatory setting; and to assess how clinicians make the hospitalization decision. PATIENTS AND METHODS: We performed a prospective, observational study of 280 ambulatory and hospitalized adults with clinical and radiographic evidence of pneumonia. Patients were followed to assess all potential morbid complications and 6-week mortality. Physicians responsible for managing these patients were surveyed to assess the reasons for treating in a hospital or ambulatory setting and the therapies that dictate hospitalization. RESULTS: Sixty-one percent (170 of 280) of patients did not have an indication for admission at presentation using modified Appropriateness Evaluation Protocol criteria (a severe vital sign abnormality, alteration in mental status, suppurative complication, arterial hypoxemia, severe laboratory abnormality, or an acute coexistent medical problem requiring admission independent of the pneumonia). Among these 170 patients, 38% had a complicated course defined as death within 6 weeks, development of a new suppurative or medical complication due to pneumonia, intensive care unit admission, persistent fever or use of intravenous fluids or oxygen beyond 3 days, hospitalization lasting more than 3 days, or subsequent hospitalization in patients initially treated in the ambulatory setting. Five predisposing factors for a complicated course were identified in logistic regression models. The odds ratio for age more than 65 years was 2.7; for comorbid illness, 3.2; for temperature more than 38.3 degrees C (101 degrees F), 4.1; for immunosuppression, 12.0; and for a high-risk etiology, 23.3. The risk of a complicated course increased linearly with the number of risk factors, from 12% with none to 100% with four or more factors (p less than 0.001). Physicians most often relied on the general clinical appearance of the patient when making the triage decision, and most commonly cited intravenous antibiotics and chest physical therapy as treatments requiring hospitalization. CONCLUSIONS: If validated, our findings could improve physicians' assessment of prognosis, and may identify a low-risk subset of patients with community-acquired pneumonia who could safely be managed in the ambulatory setting.

Adult↗
PubMed1989

Identification of cysteine 530 as the covalent attachment site of an affinity-labeling estrogen (ketononestrol aziridine) and antiestrogen (tamoxifen aziridine) in the human estrogen receptor.

Radiosequence analysis of peptide fragments of the estrogen receptor (ER) from MCF-7 human breast cancer cells has been used to identify cysteine 530 as the site of covalent attachment of an estrogenic affinity label, ketononestrol aziridine (KNA), and an antiestrogenic affinity label, tamoxifen aziridine (TAZ). ER from MCF-7 cells was covalently labeled with [3H]TAZ or [3H]KNA and purified to greater than 95% homogeneity by immunoadsorbent chromatography. Limit digest peptide fragments, generated by prolonged exposure of the labeled receptor to trypsin, cyanogen bromide, or Staphylococcus aureus V8 protease, were purified to homogeneity by high performance liquid chromatography (HPLC), and the position of the labeled residue was determined by sequential Edman degradation. With both aziridines, the labeled residue was at position 1 in the tryptic peptide, position 2 in the cyanogen bromide peptide, and position 7 in the V8 protease peptide. This localizes the site of labeling to a single cysteine at position 530 in the receptor sequence. The identity of cysteine as the site of labeling was confirmed by HPLC comparison of the TAZ-labeled amino acid (as the phenylthiohydantoin and phenylthiocarbamyl derivatives) and the KNA-labeled amino acid (as the phenylthiocarbamyl derivative) with authentic standards prepared by total synthesis. Cysteine 530 is located in the hormone binding domain of the receptor, near its carboxyl terminus. This location is consistent with earlier studies using sodium dodecyl sulfate-polyacrylamide gel electrophoresis to analyze the size of the proteolytic fragments containing the covalent labeling sites for TAZ and KNA and the antigen recognition sites for monoclonal antibodies. The fact that both the estrogenic and antiestrogenic affinity labeling agents react covalently with the same cysteine indicates that differences in receptor-agonist and receptor-antagonist complexes do not result in differential covalent labeling of amino acid residues in the hormone binding domain.

Affinity Labels↗
PubMed1989

Ultrastructural analysis of leukocytes recruited into the guinea pig lung by LTB4 aerosol.

Two groups of naive guinea pigs were exposed to different LTB4 aerosol solutions: LTB4/saline and LTB4/BSA. Control animals were exposed to saline alone and saline/BSA. The LTB4/BSA aerosol was the most effective in recruiting leukocytes, with the maximal numbers of cells in the lung tissue at 6 hrs. Light microscopy/TEM revealed marked differences in eosinophil morphology in saline/BSA and LTB4/BSA aerosol treated animals. Occasional eosinophils in the submucosa of controls, had few pseudopodia, few cytoplasmic vesicles, and intact granules. In LTB4 treated animals, there were numerous eosinophils in the bronchial mucosa and submucosa with numerous pseudopodia, numerous cytoplasmic vesicles, and light crystalline cores.

Aerosols↗
PubMed1983

Automatic computer processing of digital 2-dimensional echocardiograms.

Quantitative studies of left ventricular function using 2-dimensional echocardiography have been limited because of a lack of computerized methods to automatically analyze the echocardiographic images. Previous computer efforts have been directed at digitizing the video output of the 2-D echocardiogram, but this digitizing method has significant limitations. A direct digitization method that produces improvement in signal-to-noise ratio and, subsequently, improved automatic detection of endocardial and epicardial borders, was developed. With definition of these edges, left ventricular global and regional analysis is possible frame by frame so that dynamic changes in cardiac function may be assessed throughout the cardiac cycle. Further technologic advances in 2-D echocardiographic acquisition and image processing should allow computer processing of 2-D echocardiographic data in real time.

Computers↗
PubMed1979

The correction of angular deformities of long bones by osteotomy-osteoclasis.

The correction of angular deformities of long bones by incomplete osteotomy, followed three weeks later by manual osteoclasis, overcomes the problem of secondary displacement sometimes seen after correction by complete osteotomy and makes internal fixation unnecessary. This paper presents an experience of twenty-six operations in eighteen patients. In all cases the deformity was corrected with excellent cosmetic and functional results. Complete bony union was achieved and there were no problems with displacement at the osteotomy site. Four cases are described in detail to illustrate use of the technique in different clinical situations.

Adolescent↗
PubMed1978

The radiological diagnosis of posttraumatic effusion of the elbow joint and its clinical significance: the 'displaced fat pad' sign.

Alterations occur in the radiological appearance of the soft tissues after injury to the elbow joint. These are due to displacement of the intra-articular fat pads by capsular distension when an effusion is present. A prospective study of 89 consecutive elbow injuries was undertaken in an attempt to assess the usefulness and reliability of these changes in the diagnosis of minor elbow injuries and the assessment of their clinical progress. In 61 elbows (69 per cent) there was no radiological evidence of an effusion and no evidence of bony injury. All quickly returned to normal. In 28 elbows (31 per cent) radiological evidence of an effusion was present. Twenty-three (80 per cent) of these were also found to have a fracture in, or adjacent to the elbow joint. In 9 elbows the fracture could not be seen on the initial radiographs. Because of the presence of an effusion, repeat radiographs were taken and a fracture discovered. The presence of an effusion was associated with an increase in the time required for full recovery.

Adipose Tissue↗
PubMed1975

Continuous electrocardiographic recording during exercise in young male diabetics. A computer study.

Forty selected young patients with diabetes of medium to long duration and 26 control subjects without clinical evidence of ischaemic heart disease were studied using a new and sensitive technique of electrocardiographic recording during exercise with continuous computation of the time course of the ST-T segment changes to detect possible early ST depression indicative of ischaemia. Although no such evidence was found, significant differences in the diabetics were observed in the heart rate and ST-T segment, the latter changes having not been previously reported but which may be attributed to ischaemia or alternatively to autonomic neuropathy in the "presymptomatic" phase.

Adult↗