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Biomedical subjects

J H Smith

Publications and source records attributed to J H Smith.

At least 55 records · Page 3Linked to original sources

Interassay differences in growth hormone measurement in acromegaly.

We measured plasma growth hormone concentrations by three different two-site immunometric assays (Pharmacia hGH RIA, IDS Gamma-BCT and Delfia 22 kDa hGH) to determine whether there are GH isoforms secreted by acromegalic patients that are under-recognized by some assays. There was a fairly good agreement between assays with the IDS Gamma-BCT and Delfia 22 kDa assays giving lower results than the Pharmacia IRMA. GH was measured on stored plasma samples from 24 patients with proven acromegaly. There was a consistent difference between the three assays of approximately 20% of the mean value for each patient.

Acromegaly↗

Skin appendage involvement in anal intraepithelial neoplasia.

BACKGROUND: High-grade anal intraepithelial neoplasia (AIN III) may be premalignant. Surgical excision of large areas of anal epithelium carries significant morbidity. Ablation treatments may carry less morbidity; however, the depth of ablation is uncertain and failure to ablate dysplasia in hair shafts and other skin appendages may lead to early recurrence. METHODS: This study assesses morphometric aspects of skin appendages in perianal skin and anal canal mucosa in tissues from 30 patients with AIN III. Both normal and dysplastic epithelium was assessed in each patient. The depth to which AIN III involved skin appendages was measured using computerized image analysis. RESULTS: Both the perianal epidermis and anal canal mucosa affected by AIN III were significantly thicker than normal. Nineteen of 30 patients with AIN III had skin appendage involvement. Some 57 per cent of hair follicles (79 of 138), 16 per cent of sebaceous glands (11 of 69) and 25 per cent of sweat glands (24 of 96) observed beneath an abnormal epithelium had evidence of AIN. The median depth of AIN involvement of the hair follicle was 1.14 (range 0.44-1.67) mm, sebaceous glands 1.44 (range 0.96-1.90) mm, and sweat glands 0.94 (range 0.50-2.20) mm. These figures do not take into account tissue shrinkage due to histological processing. CONCLUSION: AIN III involvement of epithelial appendages is a significant problem. For disease eradication, tissue destruction or removal to a depth of at least 2.2 mm below the adjacent basement membrane is required. Surgical excision of high-grade AIN remains the treatment of choice.

Adult↗

Detection of rRNA from four respiratory pathogens using an automated Q beta replicase assay.

Ribosomal RNA targets from Mycobacterium avium complex (23S), Mycoplasma pneumoniae (16S), Pneumocystis carinii (18S) and Legionella pneumophila (16S) were detected in four separate assays on a model automated Q-beta amplification instrument. Sandwich hybridization, reversible target capture, detector probe amplification and fluorescent signal detection occurred in closed, disposable packs at 38 degrees C. Packs were injected with 0.5 ml samples in 3.06 M guanidine thiocyanate. Ten samples per run were read after 7 h, requiring only 4 min loading time. Synthetic RNA transcripts and purified, natural RNAs from up to four different strains per assay were diluted to 10(6) or fewer molecules per sample (approximately 100 cells for prokaryotes, 10 cells for Pneumocystis). All analytes were detected at 10(6) targets. The limits of detection were found at 10(5) to 10(4). Discrimination against competitor RNA was tested using up to 10(9) molecules (1000 X excess) of appropriate test strains. Samples containing either zero targets or 10(7) competitors produced negative results in 95 to 100% of the samples, depending on the assay. Closely related Legionella and Mycoplasma species cross-reacted at high challenge levels of 10(9) molecules as a result of sequence similarities in the target regions. These results demonstrate the utility and versatility of an automated, high sensitivity, closed system for amplified analysis of direct-from-sample testing of respiratory pathogens.

Bacteria↗

Variable responses of species and strains to white mineral oils and paraffin waxes.

Recent dietary studies on mineral hydrocarbon (MHC) white oils and waxes have shown inflammatory effects in Fischer 344 (F-344) rats, but not in other rat strains or dogs. Histopathologic effects seen in F-344 rats include mesenteric lymph node histiocytosis, liver granulomas, and inflammation of the mitral valve (only seen with paraffin waxes). Human ingestion of MHC can result in noninflammatory lipogranulomas (oil droplets) in tissues which are regarded as clinically unimportant. It is speculated that inherent interspecies differences in pharmacokinetics and/or immune function may contribute to the differential response to MHC seen in F-344 rats. The F-344 rat retains greater amounts of MHC in target tissues compared to other rat strains and dogs and appears to be more sensitive immunologically to MHC than other species, including humans. This strain may be predisposed to these effects as indicated by a high background incidence of inflammatory granulomatous lesions in control female F-344 rats. Because of its apparently unique sensitivity, relevance of effects seen in F-344 rat to human health is questionable and requires further investigation.

Animals↗

The application of an artificial neural network to Doppler ultrasound waveforms for the classification of arterial disease.

In this study we have investigated the application of an Artificial Neural Net classifier to the diagnosis of vascular disease using Doppler ultrasound blood-velocity/time waveforms. A multi-layer perceptron network was trained with waveforms from control subjects and from patients with arterial disease. The diseased cases were confirmed by angiography and allocated to three groups according to the location of the stenosis: proximal or distal to the site of measurement or multi-segmental. We compared network classification results with a Bayesian classifier following a Principal Component Analysis of the waveforms. Versions of both classifiers were trained to discriminate two classes (normal v. abnormal) and four classes. In both cases the neural networks gave superior discrimination to the Bayesian classifier. While the four-class network was unable to provide useful discrimination among the stenosis sites, discrimination between abnormal classes was obtained which is comparable to that achieved by a human expert observer.

Adult↗

Postmortem diagnosis of autochthonous acute chagasic myocarditis by polymerase chain reaction amplification of a species-specific DNA sequence of Trypanosoma cruzi.

We report a fatal case of vector-transmitted acute Chagas' myocarditis in a seven-month-old child in south Texas. This diagnosis was not suspected during the three days of hospitalization that preceded the child's death, which was caused by heart failure. A diagnosis of acute myocarditis, probably of viral origin, was listed as the cause of death after cardiac tissue was examined microscopically at autopsy. One year after the death of the patient, a diagnosis of Trypanosoma cruzi myocarditis, based solely on morphological grounds, was made after newly prepared slides of cardiac tissue were examined. Seven years later, we confirmed the diagnosis of T. cruzi infection by using the polymerase chain reaction to amplify a species-specific genomic repetitive DNA sequence of the parasite from fixed cardiac tissue.

Acute Disease↗

Gas plasma sterilization--application of space-age technology.

Gas plasma sterilization is new to the healthcare field. The first such sterilizer has been manufactured by Advanced Sterilization Products (J&J, Irvine, CA). The system uses hydrogen peroxide as the substrate gas and radio frequency emissions to generate plasma. This system is a low-temperature, quick-acting process with no toxic residues. It appears that this sterilizer system holds promise in the healthcare field and could help to reduce the use of ethylene oxide.

Hydrogen Peroxide↗

The pathology of hysterectomy specimens following trans-cervical resection of the endometrium.

The pathological findings in 29 hysterectomy specimens from a series of 175 patients undergoing trans-cervical resection of the endometrium are presented. In all but one case endometrium was present. Although all phases of the normal menstrual cycle were represented, in nine (28%) cases the endometrium appeared inactive, sometimes showing appearances similar to those in Asherman's syndrome. Adenomyosis was present in five (17%) cases and simple hyperplasia in one case. Haematocolpos was present in two cases. Inflammation was uncommon, usually mild in degree and present in the superficial myometrium. Four (14%) cases contained epithelioid or foreign body granulomas in the superficial myometrium. Deposits of haemosiderin and amorphous brown and/or particulate black pigment were seen in a total of 20 (69%) cases. A combination of transmission electronmicroscopy and energy dispersive analysis of X-rays showed these pigments to be a combination of charred organic material and metals, the latter corresponding to the composition of the diathermy cutting loop and electrocautery rollerball used in the ablative surgery.

Adult↗

Wide diversity in measurements of growth hormone after stimulation tests in short children are due to assay variability.

A comparison of three commercially available assays for growth hormone (Pharmacia hGH RIA, IDS Gamma-BCT GH and Delfia 22 kDa hGH) were used to measure growth hormone (GH) secretion in 26 short children after pharmacological stimulation. The IDS Gamma-BCT assay was compared with Pharmacia assay in 15 provocative tests (13 children; n = 94). The Pharmacia assay showed a strong positive proportional bias and this was particularly marked at GH > 20 mU/L; the mean difference between the assays at GH < 10 mU/L was 12%. The IDS Gamma-BCT assay was also compared with the Delfia 22 kDa assay in 18 provocative tests (13 children; n = 100). Results from the IDS assay was higher throughout the range 0-90 mU/L with a mean difference of 11.4% in the range 10-90 mU/L; the mean difference between the assays at GH < 10 mU/L was -39%.

Child↗

Subchronic feeding study of four white mineral oils in dogs and rats.

Subchronic 90-day feeding studies were conducted on four highly refined white mineral oils to determine any potential for toxicity in Long-Evans rats (20 per sex per dose level) and beagle dogs (4 per sex per dose level). Each oil was fed at dietary dose levels of 300 ppm and 1500 ppm (w/w). No treatment-related effects of toxicological importance were detected in daily observations of general health or in periodic assessments of food consumption and body weight, hematology, serum clinical chemistry, and urinalysis. Observations in dogs suggested that the white oils produced mild laxative effects. Gross and histopathologic examinations, as well as measurements of organ weights, did not reveal any macroscopic or microscopic changes which could be due to treatment. In addition, special staining by Oil Red O of liver, mesenteric lymph nodes, spleen, gastrointestinal tract, stomach, and kidneys indicated no evidence of oil or lipid deposition. A special re-examination of tissues from female and male rats, in response to more recent conflicting data from the Fischer 344 strain, found no histopathologic signs of macrophage accumulation and/or microgranuloma formation in liver, spleen, or mesenteric lymph nodes. These data indicate that repeated exposure to relatively high levels of white mineral oils in the diets does not produce significant subchronic toxicity in Long-Evans rats or beagle dogs.

Animals↗

From clinical ladders to a professional recognition program.

A three-year process involving the redesign of clinical ladders led to a professional recognition program. After one year, a self-initiating credentialing ladder was established. The second year, one job description/performance evaluation was developed for bedside nurses--a professional ladder with system-wide and unit-specific requirements. Finally, during the third year, a professional recognition program emerged, recognizing expertise and experience.

Awards and Prizes↗

Synthesis and biological evaluation of imidazole based compounds as cytochrome P-450 inhibitors.

Several phenyl ethyl and phenyl propyl imidazole based compounds have been synthesised and their biological activity evaluated against human placental Aromatase (AR), rat testicular 17 alpha-hydroxylase/ 17,20-lyase (P450(17) alpha) and bovine cholesterol side chain cleavage (CSCC). The compounds showed good selectivity towards AR with N-[2-(4'-Nitrophenyl) ethyl] imidazole (2) (IC50 = 0.16 +/- 0.01 microM, Ki = 0.09 +/- 0.01 microM), the most potent AR inhibitor, showing some 130 times greater potency over Aminoglutethimide (AG) (IC50 = 20.0 +/- 2.6 microM, Ki = 11.0 +/- 2.0 microM). N-[3-(4'-Fluorophenyl) propyl] imidazole (10) (IC50 = 0.31 +/- 0.01 microM, Ki = 0.34 +/- 0.05 microM), N-(2-(4'-Fluorophenyl ethyl) imidazole (5) (IC50 = 0.74 +/- 0.01 microM, Ki = 0.40 +/- 0.02 microM), N-(3-(4'-Chlorophenyl propyl) imidazole (9) (IC50 = 0.82 +/- 0.02 microM) and N-[3-(4'-Nitrophenyl) propyl] imidazole (7) (IC50 = 0.84 +/- 0.02 microM, Ki = 0.10 microM) were also more potent than AG. Of the compounds tested for P450(17) alpha activity, 7 (IC50 = 25.0 +/- 2.0 microM), N-[2-(4'-Aminophenyl) ethyl] imidazole (3) (IC50 = 27.6 +/- 0.10 microM), 9 (IC50 = 29.0 +/- 4.0 microM) and 2 (IC50 = 30.2 +/- 2.0 microM) showed the highest activity, possessing approximately half the activity of Ketoconazole (IC50 = 12.1 +/- 2.9 microM). Compounds 1, 2, 3, and 7 showed 0% inhibitory activity towards CSCC at 200 microM whilst AG showed 83% inhibition under the same conditions. The compounds proved themselves to be excellent lead compounds and supported the novel models developed by Ahmed for AR and P450(17) alpha.

Animals↗

Synthesis and biological evaluation of novel pyrrolidine-2,5-dione inhibitors as potential anti-tumour agents.

Several novel pyrrolidine-2,5-dione based compounds have been synthesised and evaluated for their biological activity against human placental aromatase (AR), rat testicular 17 alpha-hydroxylase/17,20-lyase (P450(17) alpha) and bovine cholesterol side chain cleavage (CSCC). The compounds showed good inhibition towards AR with 1-cyclohexyl-3-[2'(4"-aminophenyl) ethyl] pyrrolidine-2,5-dione (3) (IC50 = 23.8 +/- 4.6 microM) and 1-octyl-3-[2'(4"-aminophenyl) ethyl] pyrrolidine-2,5-dione (4) (IC50 = 24.6 +/- 1.8 microM) showing equipotent activity with Aminoglutethimide (AG) (IC50 = 20.0 +/- 2.6 microM, Ki = 11.0 +/- 2.0 microM). Of the compounds tested for P450(17) alpha activity, 3 (IC50 = 18.5 +/- 1.9 microM) again showed the highest activity, being equipotent to Ketoconazole (IC50 = 12.1 +/- 2.9 microM). 3 was a poor inhibitor of CSCC with some 22% inhibitory activity at an inhibitor concentration of 200 microM, as compared to AG with 72% inhibitory activity under the same conditions. The compounds proved themselves to be excellent lead compounds and supported the novel models developed by Ahmed for AR and P450(17) alpha.

Adrenal Glands↗

Prevalence of anal human papillomavirus infection and intraepithelial neoplasia in renal allograft recipients.

A study was performed to test the hypothesis that renal allograft recipients are at high risk of developing anal human papillomavirus (HPV) infection and anal intraepithelial neoplasia (AIN). A total of 133 renal allograft recipients and 145 control patients underwent anoscopy and biopsy. A polymerase chain reaction was used to detect HPV16 DNA in biopsy samples. A histological diagnosis of anal HPV infection or AIN was made in 32 allograft recipients (HPV infection, five; AIN I, 20; AIN II, three; AIN III, three; AIN III and anal cancer, one). One subject with AIN was detected in the control group. HPV16 DNA was detected in 47 and 12.4 per cent of anal biopsies in the allograft and control groups respectively. Renal allograft recipients are at high risk of developing anal HPV infection and neoplasia (P < 0.05). Further studies are required to determine whether screening anal examination is required in organ allograft recipients.

Adult↗