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Biomedical subjects

R A James

Publications and source records attributed to R A James.

At least 73 records · Page 4Linked to original sources
PubMed1996

Design and evaluation of an olfactometer for the assessment of 3-methylindole-induced hyposmia.

Few studies objectively evaluate olfactory function in animals following exposure to chemicals that induce nasal toxicity. An olfactometer capable of generating a reproducible olfactory stimulus and measuring an odorant-cued behavioral response was developed for rats from a commercially available two-way shuttle box. The box was modified to deliver the test odorant, acetaldehyde, to either of two chambers separated by a physical barrier consisting of a downward-directed airwall sandwiched between two exhaust panels. Male Fisher 344 rats were trained with either a coupled odorant- or tone-cued active avoidance paradigm in order to compare auditory-cued versus olfactory-cued learning and memory. Odorant-cued animals had faster acquisition and longer retention of the avoidance behavior than tone-cued animals. Animals given the model olfactory toxicant 3-methylindole (3-MI, 400 mg/kg, ip) had reduced odorant-cued avoidance, while no effect on tone-cued behavior was observed. In a follow-up study, additional odorant-trained rats were dosed with 0, 100, 200, or 300 mg/kg of 3-MI ip and olfactory function reassessed 6 days later. Histopathologic evidence of moderate to severe olfactory epithelial damage was observed in all rats 7 days after 3-MI administration. Only the highest 3-MI dose (300 mg/kg) was associated with a significant reduction in odor-cued avoidance behavior as compared to that seen in control. These results indicate that use of this olfactometer can provide a functional assessment of chemically induced olfactory toxicity and complements more routine nasal pathology.

Animals↗
PubMed1995

Two-year inhalation exposure of female and male B6C3F1 mice and F344 rats to chlorine gas induces lesions confined to the nose.

Chlorine gas is a respiratory irritant in both animals and humans that produces concentration-dependent responses ranging from minor irritation to death. Female and male B6C3F1 mice and F344 rats were exposed to chlorine gas for up to 2 years to determine chronic toxicity and carcinogenicity. Groups of approximately 70 each of female and male mice and rats were exposed to 0, 0.4, 1.0, or 2.5 ppm chlorine gas for 6 hr/day, 5 days/week (mice and male rats), or 3 alternate days/week (female rats) for 2 years, with an interim necropsy of rats at 12 months (10 rats/sex/concentration group). A complete necropsy was performed on all animals. Histological examination was performed on all organs from high-concentration and control animals and selected target organs from mid- and low-concentration groups. Exposure-dependent lesions were confined to the nasal passages in all sex and species groups. Chlorine-induced lesions, which were most severe in the anterior nasal cavity, included respiratory and olfactory epithelial degeneration, septal fenestration, mucosal inflammation, respiratory epithelial hyperplasia, squamous metaplasia and goblet cell hypertrophy and hyperplasia, and secretory metaplasia of the transitional epithelium of the lateral meatus. Intracellular accumulation of eosinophilic proteinaceous material was also a prominent response involving the respiratory, transitional, and olfactory epithelia, and in some cases the squamous epithelium of the nasal vestibule. Many of these nasal lesions exhibited an increase in incidence and/or severity that was related to chlorine exposure concentration and were statistically significantly increased at all chlorine concentrations studied. Male mice and female rats appeared more sensitive to chlorine than female mice and male rats, respectively. The reasons for the sex differences within a species were not determined. Interspecies differences in regional dosimetry and site-specific tissue susceptibility to chlorine exposure should be taken into account when using these data for accurate assessment of potential human health risks. The incidence of neoplasia was not increased by exposure, indicating that inhaled chlorine in rats and mice is an upper respiratory tract toxicant but not a carcinogen.

Administration, Inhalation↗
PubMed1994

Effects of thermocycling, load-cycling, and blood contamination on cemented implant abutments.

This study compared the effects of thermocycling, load-cycling, and human blood contamination on the retentive strength of five different cements for luting posts to root-form implants. For each cement, 10 specimens (controls) were stored in an incubator, 10 specimens were thermocycled, 10 specimens were subjected to cyclic compressive loading, 10 specimens were subjected to a combination of thermocycling and cyclic compressive loading, and 10 specimens were contaminated with blood before cementation, then exposed to a combination of thermocycling and compressive loading. After 70 hours, retentive tests were performed on the Instron machine, and data were recorded in kilograms. Significant retentive differences were identified among the cements and with load-cycling, but minimal effect on the retentive strength was demonstrated from thermocycling. Blood contamination in combination with thermocycling and load-cycling adversely affected the retentive strengths of all of the cements and could be a major cause of abutment failure in dental implants.

Analysis of Variance↗
PubMed1994

Oncoprotein immunoreactivity in human pituitary tumours.

OBJECTIVE AND DESIGN: The immediate early gene locus AP-1, incorporating the cellular oncogenes c-fos and c-jun (and their oncoprotein products Fos and Jun respectively) play a key role in regulating cell growth and differentiation. The myc-gene is also known to promote cell growth. In order to investigate the possible role of these oncogenes in human pituitary adenomas, Fos, Jun and Myc oncoprotein immunoreactivities were assessed in surgically resected pituitary adenomas in relation to in-vivo characteristics (hormone secretion, size and invasiveness) and an in-vitro index of cell proliferation (Ki-67 immunoreactivity). Thirty-three human pituitary adenomas and 16 normal pituitary glands were examined. MEASUREMENTS: Oncoprotein immunoreactivity was recorded as present (+) or absent (-), and Ki-67 labelling indices were scored quantitatively. Tumour size was scored from CT scan appearances and radiographic evidence of bone erosion was noted. RESULTS: Oncoprotein immunoreactivity was present in a total of 32/33 cases. Myc immunoreactivity was restricted to the only ACTH-secreting tumour in the series (1/33). Ki-67 immunoreactivity was present in 24/32 cases and labelling indices varied from 0.1 to 3.2%. CONCLUSIONS: Oncoprotein immunoreactivity did not correlate with hormonal profile, bone erosion or the size of the proliferating compartment estimated by Ki-67 labelling indices. Although oncoprotein expression is common in human pituitary adenomas, its significance remains to be elucidated.

Adenoma↗
PubMed1994

Production of bioactive and immunoreactive interleukin-6 (IL-6) and expression of IL-6 messenger ribonucleic acid by human pituitary adenomas.

Preliminary studies have demonstrated that some pituitary adenomas secrete immunoreactive interleukin-6 (irIL-6) when cultured in vitro. We have extended these studies by investigating 100 pituitary adenomas of different types measuring immunoreactive and bioactive IL-6. Tumors were cultured either as explants without fetal calf serum or as dispersed cells with 10% total calf serum. Fifty-three of the 100 (53%) pituitary cultures were found to release irIL-6 and in 44 adenomas examined, 32 (72.7%) secreted bioactive IL-6. In 61 explant cultures, 30 adenomas released IL-6, indicating autonomous secretion. The amount of IL-6 released by adenomas in cell culture was generally higher, although the incidence was similar to explant cultures. IrIL-6 was released by 7 of 14 prolactinomas, 15 of 27 somatotrophinomas, 5 of 7 corticotrophinomas (including 2 Nelson's adenomas), 1 of 1 thyrotrophinomas, 2 of 2 gonadotrophinomas, and 23 of 49 clinically non-functioning adenomas. Periadenomatous tissue removed from a patient with a corticotrophinoma was found to secrete IL-6 but in much lower concentration than from the adenoma tissue. Tumor necrosis factor-alpha and -gamma-interferon were not detected in the conditioned media. Four IL-6-secreting adenomas were examined by in situ hybridization for IL-6 messenger RNA, and three of these were positive with fluorescence present throughout the tissue examined. We have provided evidence that over half of pituitary adenomas secrete IL-6 which is bioactive and that IL-6 is synthesized within the tumor by the adenoma cells.

Adenoma↗
PubMed1994

Comparative three-dimensional analysis of two finite-element endosseous implant designs.

The finite-element method was used to assess force distribution to the cortical and cancellous bone surrounding two HA-coated, cylindrical implant designs, one grooved, the other smooth-sided. It was shown that, with both designs, large compressional stresses occurred in a small volume of bone at the coronal portion of the mandibular ridge. The stresses produced gave rise to a large stress gradient in the interface area. Significant differences were noted between the two designs in this area. It was also noted that the majority of the loading occurred in the cortical region of the mandibular ridge.

Dental Implants↗
PubMed1994

Factors determining the long-term outcome of surgery for acromegaly.

Seventy-nine patients with acromegaly were investigated before and after transsphenoidal adenomectomy, to determine the immediate and late outcome, the pre-operative features associated with a good result, and the accuracy of post-operative testing in predicting outcome. Pre-operative evaluation included basal growth hormone (GH), GH response to oral glucose tolerance test (OGTT), GH response to thyrotrophin-releasing hormone (TRH), tests of pituitary reserve, and pituitary scanning to assess tumour size. A few weeks after surgery, these tests were repeated. The patients were recalled for late assessment 1-13 years (median 86 months) after the operation. At the immediate postoperative testing, minimum GH after oral glucose was < or = 2 mU/l in 48.7%, < 5 mU/l in 76.3% and < 10 mU/l in 84.2%. Only 12 patients had GH > 10 mU/l. Basal GH was < or = 2 mU/l in 21%, < 5 in 59.2%, < 10 in 73.6% and < 20 in 90.8%. A minimum GH of < or = 2 mU/l during an OGTT was achieved in 67.4% of patients with intrasellar tumours, compared with 27.3% with extrasellar tumours. Basal GH and post-glucose GH correlated with the late outcome. GH response to TRH showed no correlation with outcome. IGF-1, which could not be assessed in detail, correlated with GH but was not a reliable indicator of outcome. Transsphenoidal adenomectomy is thus a very satisfactory treatment for acromegaly. Postoperative levels of basal growth hormone < 5 mU/l and post-glucose GH < or = 2 mU/l can be regarded as a biochemical cure. Postoperative radiotherapy is not required in patients who achieve a good result. The preoperative factors which significantly influenced the final outcome were basal GH, post-glucose minimum GH, tumour size and impaired pituitary reserve.

Acromegaly↗
PubMed1993

Effects of recombinant human activin A on growth hormone secretion by human somatotrophinomas in vitro.

Activin A is a homodimer of inhibin beta A subunits, and was first isolated from gonadal fluids on the basis of its ability to stimulate FSH secretion by rat pituitary cells in vitro. The beta A subunits of activin and their mRNAs have been found in many cell types, in several species and at different stages of development, suggesting that activin A has a wide range of diverse biological roles. Apart from the modulation of gonadotroph function, in-vitro studies have demonstrated inhibitory effects of activin A on GH synthesis, GH secretion and possibly somatotroph proliferation. We have therefore investigated the potential role of activin A in the pathophysiological regulation of GH secretion by human somatotrophinoma cells using in-vitro techniques. Cell cultures were established by enzyme dispersion of adenoma tissue obtained from six patients with acromegaly, and treated for 72 h with 0.01-10 nmol recombinant human activin A/l followed by a 2-h stimulation test with 10 nmol GH-releasing factor (GRF)/l. Medium was collected at 24, 48 and 72 h, as well as after GRF treatment, and GH concentrations were measured by immunoradiometric assay. Basal GH secretion from the cells of two tumours was significantly stimulated 12-63% above control values during treatment with 0.01-10 nmol activin A/l, whereas the peptide had no effect on GH release from cells of the remainder of the tumours. GRF significantly stimulated GH release from the cells of two different adenomas, and pretreatment with 0.01-1 nmol activin A/1 partially but significantly blocked GRF-stimulated GH release from the cells of one of these.(ABSTRACT TRUNCATED AT 250 WORDS)

Activins↗
PubMed1993

Root-form implants placed in subantral grafted sites.

Life-table analysis of survival data of implants placed in subantral grafts reveals a high rate of survival, particularly in comparison with implants placed in non-grafted subantral sites. However, sample size (158 grafted, 140 non-grafted, in a total of 120 patients) and follow-up time remain insufficient to reach a definite conclusion. Results also appear improved over other reports in which the sinus was penetrated by the implants, possibly because the procedure has become more standard over the years.

Adult↗
PubMed1993

HA-coated implants: warranted or not?

Despite anecdotal reports that challenge hydroxyapatite (HA)-coated implant survivability, the experience in the placement of these implants over 9 years at Loma Linda University School of Dentistry has been favorable. The results of these implant placements are presented and analyzed in this article. After 7 years, the survival rate of HA-coated custom and stock blade-form implants is 97%. At 5 years, the survival rate for all upper HA-coated root form implants is 98%, and for all HA-coated implants placed in the lower jaw it is 99%. For implants placed in maxillary type 4 bone, there was a 32.6% failure rate among uncoated implants, but a rate of 14.9% in HA-coated implants. The causes of implant failure are often related to factors other than the type of implant, such as iatrogenic factors and poor oral hygiene.

Dental Implantation, Endosseous↗
PubMed1992

A comparison of octreotide delivered by continuous subcutaneous infusion with intermittent injection in the treatment of acromegaly.

This study was undertaken to evaluate GH, IGF1 and drug levels during incremental continuous subcutaneous infusion of octreotide and compare these parameters following long-term treatment of 300 micrograms 24 h-1 by intermittent injection in a group of acromegalic patients. Ten patients were treated by continuous subcutaneous infusion in increasing dose from 200 micrograms 24 h-1 to 1600 micrograms 24 h-1; this resulted in consistent 24-h growth hormone suppression (less than 5.0 mU l-1), and normalisation of IGF1; the optimum dose was 400 micrograms 24 h-1, the maximum dose was tolerated without any untoward effects. There was no deterioration in carbohydrate tolerance despite a marked decrease in fasting and stimulated insulin levels. After 1 year of maintenance treatment, 300 micrograms 24 h-1 by intermittent injection, patients were re-evaluated; GH levels were not so consistently suppressed over the 24-h period and carbohydrate tolerance had deteriorated. A sub-group of patients with sub-optimal GH suppression on this regimen were identified and reassessed after 6 weeks treatment with an increased dose, 600 micrograms 24 h-1 by intermittent injection; both mean GH suppression and carbohydrate tolerance improved. The dose of drug and method of administration is best adjusted for each patient to achieve optimum GH suppression, thereby minimise compensatory hyperinsuliaemia and hopefully reduce morbidity and mortality. Alterations in pituitary tumour size and acquisition of gallstones during treatment have been observed which substantiate the need to re-evaluate these parameters on routine follow-up of acromegalic patients on long-term octreotide.

Acromegaly↗
PubMed1992

Gallbladder function in acromegalic patients taking long-term octreotide: evidence of rebound hypermotility on cessation of treatment.

Octreotide is increasingly being used in the treatment of acromegaly. It effectively suppresses growth hormone secretion but also has inhibitory effects on gastrointestinal regulatory peptides and induces gallbladder paresis, which may predispose to gallstone formation. In nine acromegalic patients receiving long-term octreotide treatment gallbladder emptying, assessed by 99Tc-EHIDA scintigraphy after a standard fatty meal, was significantly impaired (p less than 0.005) when compared with normal healthy control subjects. Asymptomatic gallstone formation occurred in one patient who had the most severely impaired gallbladder emptying. Between 24 and 96 h after cessation of octreotide, in six of seven patients studied, gallbladder emptying had not only recovered but demonstrated significant rebound hypermotility (p less than 0.005). This finding has important implications for the administration of long-term octreotide therapy and suggests that a drug-free period each week may enable evacuation of gallbladder contents and reduce the risk of gallstone formation.

Acromegaly↗
PubMed1992

Solving the problem of violated intermaxillary space caused by poor pre-planning and improper placement of endosseous implants: a case report.

Every dental implant patient needs thorough evaluation and pre-surgical planning. It is imperative for the practitioner to have absolute knowledge of the implant system to be used. Nevertheless, sometimes we find ourselves in very difficult, almost unrestorable, situations. Often, we cannot rely on the implant manufacturers, and we have to be ready to customize some parts in order to solve difficult clinical situations. This case report shows how customized magnet keepers were fabricated by use of plastic IME's as casting patterns in order to solve the problem of violated intermaxillary space.

Dental Alloys↗
PubMed1991

Actions of L-363,586, a cyclic hexapeptide analogue of somatostatin, on GH secretion by human somatotrophinoma cells in vitro.

L-363,586 is a cyclic, hexapeptide analogue of somatostatin-14 with potent inhibitory actions on rat growth hormone (GH) release in vitro. The studies reported here investigate the direct effects of L-363,586 on basal and growth hormone-releasing factor (GRF)-stimulated GH secretion from 3 human somatotrophinomas in dispersed cell culture. 1nM and 10nM L-363,586 inhibited both basal and GRF-stimulated GH release from cells of all 3 somatotrophinomas during a 2h treatment period, whilst 100nM L-363,586 had a prolonged inhibitory action on basal GH secretion from cells of 2 of the tumours throughout treatment and recovery periods. Rebound release of GH was observed with cells of 1 tumour following treatment with L-363,586 plus GRF. The actions of L-363,586 were similar to those of somatostatin-14. These data suggest that L-363,586 may have a role in the treatment of acromegaly.

Adenoma, Acidophil↗