PubMed Health⌕ Search

Biomedical subjects

M J Perry

Publications and source records attributed to M J Perry.

At least 37 records · Page 2Linked to original sources
PubMed2001

Pantoprazole therapy in the long-term management of severe acid peptic disease: clinical efficacy, safety, serum gastrin, gastric histology, and endocrine cell studies.

OBJECTIVE: Pantoprazole is the third proton pump inhibitor to become available. When this study was started, there were few data on its long-term use. Our aim was to investigate this aspect and, because powerful inhibitors of acid secretion can cause hypergastrinemia and, in experimental animals, enterochromaffin-like cell hyperplasia, we also monitored serum gastrin and endocrine cell histology. METHODS: One hundred fifty patients refractory to H2-receptor antagonists, running an aggressive course or with complications, were entered into a 5-yr treatment program. We performed serial endoscopy, checked for adverse events, and laboratory values. We also monitored serum gastrin, gastric endocrine cell histology, and antral and corpus gastritis. RESULTS: This report presents results from up to 3 yr of treatment. Cumulative healing on 40-80 mg of pantoprazole was 82% at 4 wk and 92% by 12 wk. Most patients became asymptomatic within 4 wk. Remission on maintenance treatment with 40 mg (n = 111) was 85% at 12 months and 78% at 24 months. Treatment was safe; only four patients had adverse events definitely related to pantoprazole. Elevations in gastrin were modest and there were no significant changes in gastric endocrine cells. The number of enterochromaffin-like cells tended to decrease. CONCLUSION: Pantoprazole is effective, safe, and does not seem to be associated with large increases in serum gastrin or alterations in gastric endocrine cells.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Capsaicin-sensitive afferents are involved in signalling transneuronal effects between cutaneous sensory nerves.

The aim of the present study was to investigate changes in contralateral nerves associated with peripheral nerve injuries. Transection and subsequent regeneration of the saphenous nerve on one side caused a suppression of the ability of the contralateral saphenous nerve to produce a neurogenic plasma extravasation response. This effect was transient, and was first evident two weeks after injury, reaching its maximum at four weeks, but was no longer detectable at eight weeks. This change was paralleled by a decrease in the content of substance P, a neuropeptide involved in neurogenic plasma extravasation, in the contralateral nerve. The neurotoxin capsaicin was used to deplete the nerve of a subclass of C-fibres, namely the polymodal nociceptor afferents. Pretreatment of the nerve to be lesioned with capsaicin was sufficient to significantly attenuate the changes in the plasma extravasation response and substance P content observed on the contralateral side. The effectiveness of the capsaicin treatment was confirmed by histological examination. These results strongly suggest that changes observed at a site distant from the location of the nerve injury are dependent on the integrity of capsaicin-sensitive C-fibre afferents within the injured nerve. Furthermore, given that the contralateral nerve has commonly been used as the control for an injury conducted on the homologous nerve or muscle on the opposite side of the body, the underlying assumption being that the contralateral nerve remained unchanged, the present findings emphasize the need for separate groups of control animals which have undergone no surgical procedures.

Animals↗
PubMed2000

Is high-dose estrogen-induced osteogenesis in the mouse mediated by an estrogen receptor?

Although estrogen is known to induce new bone formation in the long bones of female mice, this response is only thought to occur following administration of high doses, suggesting that it may not be mediated by a conventional estrogen receptor. To address this question further, we first examined the stereospecificity of this response by comparing the potency of 17beta-estradiol (E(2)) in stimulating cancellous bone formation at the proximal tibial metaphysis of intact female mice with that of the relatively inactive stereoisomer, 17alpha-estradiol (alphaE(2)). We found that E(2) was significantly more potent than alphaE(2), as assessed by histomorphometry. To provide further evidence for an estrogen-receptor-mediated process, we examined whether E(2)-induced osteogenesis in intact female mice could be inhibited by the estrogen receptor antagonist, ICI 182,780 (ICI). Although ICI itself had no effect on histomorphometric indices of the proximal tibial metaphysis when given alone, it significantly inhibited the osteogenic response to E(2). Finally, we examined the dose dependency of E(2)-induced osteogenesis at the proximal tibial metaphysis in intact mice. We found that E(2) stimulated cancellous bone formation in a dose-dependent manner over a wide dose range (i. e., 1-4000 microg/kg per day), with significant increases observed at doses of 4 microg/kg per day and beyond. Our results raise the possibility that estrogen-induced osteogenesis in the mouse represents an estrogen-receptor-mediated response that is not confined solely to supraphysiological estrogen levels.

Animals↗
PubMed2000

Allogeneic whole-tumour cell vaccination in the rat model of prostate cancer.

OBJECTIVE: To investigate cancer immunotherapy using whole allogeneic (differing tissue-type) tumour cells as vaccines in the rat prostate cancer model. Materials and methods Two rat models of prostate cancer were used; MAT-LyLu tumours which grow in Copenhagen rats and PAIII tumours which grow in Lobund-Wistar rats, with crossover of the cell lines to test allogeneic vaccination. The cell lines were immunologically characterized by flow cytometry. Irradiated tumour cells were administered as subcutaneous vaccines either before tumour challenge or after tumour establishment (both subcutaneous). A preparation of heat-killed Mycobacterium vaccae bacilli (SRL172) was used as an adjuvant to increase vaccine efficiency. RESULTS: Flow cytometry analysis of the cell lines showed that the PAIII cells had higher levels of major histocompatibility complex (MHC) class I and intercellular adhesion molecule (ICAM-1) expression than the MAT-LyLu cells. However, both tumour cell lines were rejected in their allogeneic hosts. Prophylactic vaccination with allogeneic MAT-LyLu cells protected against PAIII tumour challenge in Lobund-Wistar rats, with 80% of animals surviving for > 5 months, compared with 40% for animals receiving autologous cells. The immunity was prolonged, as rats were protected when rechallenged 5 months later. In Copenhagen rats allogeneic PAIII cells protected against the more aggressive MAT-LyLu tumour challenge only when the cells were combined with SRL172. Initial therapy experiments showed that vaccination with the cell lines mediated only limited tumour regression in the Lobund-Wistar rats. CONCLUSION: The allogeneic tumour cell vaccination model described is valuable for assessing the principle and efficacy of allogeneic prostate cancer cell vaccines for clinical use.

Animals↗
PubMed2000

Tumor necrosis factor alpha can contribute to focal loss of cartilage in osteoarthritis.

UNLABELLED: OBJECTIVE; To evaluate the potential for tumor necrosis factor alpha (TNFalpha)-induced focal loss of cartilage in osteoarthritic (OA) knee joints. DESIGN: Fresh cartilage from specified regions of OA joints was immunostained for TNF-receptor (R) bearing chondrocytes. Cartilage explants from the same regions were cultured with or without small amounts of TNFalpha and cumulative GAG release into supernatants measured. Concentrations of TNFalpha, p55 and p75 soluble (s) TNF-R in supernatants from cultured OA and non-arthritic (NA) synovium were measured by ELISA. RESULTS: TNF-R bearing chondrocytes were identified in OA cartilage; more specimens contained p55 TNF-R- than p75 TNF-R-bearing chondrocytes and differences in TNF-R distribution were apparent in cartilage from different regions of the same knees. TNFalpha at 5, 1, 0.5 and 0.25 ng/ml (but not 0.1 ng/ml) significantly increased glycosaminoglycans (GAG) release from cartilage explants in a dose-dependent manner. Variation in susceptibility to TNFalpha was observed in explants from different sites. TNFalpha and p75 sTNF-R, but not p55 sTNF-R, concentrations were significantly higher in OA, as compared with NA, supernatants. A significant correlation between TNFalpha and p75 sTNF-R measurements was apparent only in NA supernatants. CONCLUSIONS: Variations in chondrocyte TNF-R expression occur in OA cartilage in vivo. TNFalpha at concentrations produced by OA synovium in vitro, can degrade cartilage matrix. In most OA supernatants sTNF-R concentrations were insufficient to abrogate the effects of TNFalpha. Thus conditions exist in some OA knees for TNFalpha to contribute to focal loss of cartilage.

Aged↗
PubMed2000

Association of pesticide safety knowledge with beliefs and intentions among farm pesticide applicators.

Although a number of health hazards associated with pesticide exposure have been well documented, relatively little is known about the knowledge and health beliefs that may influence pesticide handling. This study measured knowledge levels concerning pesticide safety and precautionary handling among applicators and examined relationships between knowledge scores and intentions to use handling precautions, perceptions of pesticide safety peer norms, and perceived self-efficacy to prevent personal exposure. Telephone interviews were conducted with a randomly selected sample of 164 dairy farmers who were pesticide applicators residing in Wisconsin (response rate = 77.4%). The percentage of correct responses to 18 knowledge items ranged from 100% to 45.7%. Knowledge levels were positively related to intentions, beliefs, and self-efficacy regarding use of personal protective gear but were not significantly related to risk perceptions and peer norms concerning pesticide safety.

Adult↗
PubMed2000

Effects of high-dose estrogen on murine hematopoietic bone marrow precede those on osteogenesis.

High-dose estrogen both stimulates new medullary bone formation and suppresses hematopoiesis in mouse long bones. To determine whether the latter response is a direct consequence of the former, we compared the time course of estrogen's effects on osteogenesis and hematopoietic bone marrow. Flow cytometry was employed to measure hematopoietic subpopulations in bone marrow from femurs of female mice killed at different times after commencing 0.5 mg estradiol/wk to each animal. Estrogen markedly reduced the number of leucocytes (CD11a positive), which had already diminished by 75% after 4 days and had virtually disappeared by 18 days. Specific populations showed a similar pattern of decline after estrogen, including B lymphocytes, monocytes, and endothelial cells. In contrast, the osteogenic precursor population showed a marked increase after estrogen treatment, as assessed by assaying alkaline phosphatase-positive colony-forming units (fibroblastic) ex vivo. However, this rise did not reach significance until 8 days after estrogen administration, suggesting that it follows rather than precedes estrogen's effects on hematopoiesis. We conclude that estrogen does not suppress hematopoiesis in mouse long bones as a direct consequence of its effects on osteogenesis.

Animals↗
PubMed2000

Urinalysis of atrazine exposure in farm pesticide applicators.

This study compared three relatively common laboratory methods for the detection of atrazine (a triazine herbicide commonly used in US agriculture), and related metabolites in urine. Ninety-nine samples collected from atrazine applicators within 8 h post application were analyzed. Thirty-seven percent of applicators showed detectable levels (minimum = 1.0 ng/ml) of deethylatrazine (an atrazine metabolite typically found in environmental samples) in their urine, based on gas chromatography-mass spectrometry (GC-MS) analysis (mean = 14.2 ng/ml). Fifty applicator samples were tested using an enzyme-linked immunosorbent assay (ELISA) designed for the mercapturate metabolic product. Most of these samples (80%) had detectable levels of the mercapturate product. A triazine in water ELISA was also used to test several diluted urine samples from atrazine applicators, and all samples were positive for triazines. Mediocre agreements between the three methods indicated that each detected distinct atrazine exposure products. The results indicate that single field applications of atrazine result in measurable pesticide doses to applicators and that the choice of field assay should depend on the exposure product to be evaluated.

Agriculture↗
PubMed2000

Changes in the proportions of peripheral blood lymphocytes in patients with worn implants.

We compared the peripheral blood and periprosthetic tissues of 53 patients at revision arthroplasty with those of 30 patients at primary arthroplasty to determine whether there is a systemic difference in lymphocytes in patients with worn hip implants. The absolute number and relative proportion of lymphocytes bearing CD2, CD3, CD4, CD8, CD16, CD19, HLA-DR, kappa and lambda antigens were compared with the levels of IL-1beta, IL-6 and PGE2 in the pseudosynovial membrane as well as with a semiquantitative estimate of metal and polyethylene particles, necrosis and chronic inflammation and the total concentration of metals within the periprosthetic tissues. There was a significant increase in the relative proportion of CD2-positive T-cells and CD16-positive natural killer cells in the peripheral blood at revision arthroplasty compared with primary arthroplasty and an increased proportion of CD8-positive T-cells and a decreased ratio of CD4 to CD8 (helper inducer/suppressor cytotoxic cells). Three control patients, who went on to have revision surgery, had values at primary arthroplasty which were similar to those of patients at the time of revision surgery. These differences did not correlate with the local concentration of metal, plastic or cement or inflammatory response or the type of prosthesis. An inverse correlation was noted between the necrosis in the periprosthetic tissue and both the local production of IL-6 and the absolute numbers of T-cells in peripheral blood. We conclude that there may be several cell-mediated systemic immune responses to aseptic loosening, at least one of which may be directly related to events in the periprosthetic tissues. We cannot exclude the possibility that the changes in the proportion of CD8-positive cells reflected a predisposition, rather than a reaction, to loosening of the implant.

Aged↗
PubMed2000

Outcomes of a randomized community-level HIV prevention intervention for women living in 18 low-income housing developments.

OBJECTIVES: Women in impoverished inner-city neighborhoods are at high risk for contracting HIV. A randomized, multisite community-level HIV prevention trial was undertaken with women living in 18 low-income housing developments in 5 US cities. METHODS: Baseline and 12-month follow-up population risk characteristics were assessed by surveying 690 women at both time points. In the 9 intervention condition housing developments, a community-level intervention was undertaken that included HIV risk reduction workshops and community HIV prevention events implemented by women who were popular opinion leaders among their peers. RESULTS: The proportion of women in the intervention developments who had any unprotected intercourse in the past 2 months declined from 50% to 37.6%, and the percentage of women's acts of intercourse protected by condoms increased from 30.2% to 47.2%. Among women exposed to intervention activities, the mean frequency of unprotected acts of intercourse in the past 2 months tended to be lower at follow-up (mean = 4.0) than at baseline (mean = 6.0). These changes were corroborated by changes in other risk indicators. CONCLUSIONS: Community-level interventions that involve and engage women in neighborhood-based HIV prevention activities can bring about reductions in high-risk sexual behaviors.

Adult↗
PubMed2000

Prospects for vaccination in prostate cancer.

Prostate cancer continues to be a major cause of morbidity and mortality. Surgical and medical management of the disease has improved but there is little effect upon overall survival. Novel therapies such as immunotherapy offer the potential of treating the disease by stimulating the immune system to mount a response to the cancer systemically. This review highlights the pitfalls and progress in the understanding of the role of the immune system in malignancy and also explains the theory behind prostate cancer vaccine trials.

Antigen Presentation↗
PubMed2000

Modeling access, cost, and perceived quality: computer simulation benefits orthodontic clinic staffing decisions.

Given limited financial resources, simulation permits a financial analysis of the optimum staffing levels for orthodontists and dental assistants in an orthodontic clinic. A computer simulation provides the information for managerial review. This study, by building a computer simulation of an orthodontic service, set out to determine the most efficient mix between providers and support staff to maximize access, maximize perceived quality, and minimize expenditures. Six combinations of providers and support staff were compared during an animated, computer-generated what-if analysis. Based on the clinic workload and size, on the cost per patient, and on the cost per quality point, the research team recommended a staffing mix of one orthodontist and three assistants. This study shows that computer simulation is an enormous asset as a decision support tool for management.

Ambulatory Care↗
PubMed1999

Development of a recombinant cell-based system for the characterisation of phosphodiesterase 4 isoforms and evaluation of inhibitors.

We described the development of a recombinant cell-based system for the characterisation of phosphodiesterase (PDE) 4 isoforms and the evaluation of inhibitors. The Chinese hamster ovary (CHO) cell, which was found to have a low endogenous PDE4 background and no beta-adrenergic receptors (beta-AR), was transiently transfected with beta-AR and various PDE4 isoforms which were expressed as functionally coupled molecules. From correlations of elevation of adenosine 3',5'-cyclic monophosphate in situ and the inhibition of catalytic activity in vitro with the various PDE4 isoforms, it was apparent that PDE4A4, 4B2, 4C2, 4D2, and 4D3 all adopted a high-affinity binding conformation (i.e. expressed the high-affinity rolipram binding site) in the CHO cell, whereas PDE4A330 was expressed in a low-affinity conformation in situ. This gives the opportunity of using this system to screen and optimise inhibitors against a low-affinity conformation of PDE4 in situ and use a high-affinity conformation of PDE4 as a counterscreen, as inhibitor activity against this conformer has been linked with undesirable side effects. This system could also be utilised to screen inhibitors against various PDE4 isoforms in isolation against a low endogenous PDE background in situ for isoform-selective inhibitors.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1999

Matrix metalloproteinase levels are elevated in inflammatory bowel disease.

BACKGROUND & AIMS: The expression of matrix metalloproteinases 1, 2, 3, and 9 was examined in biopsy specimens removed from adult and pediatric patients with ulcerative colitis and Crohn's disease. The aim of this study was to determine if the expression of these enzymes was altered between areas of actively inflamed vs. noninvolved mucosa in the same patient and between patients with diseased bowel vs. a control group of patients. METHODS: Proteolytic activity was quantified by zymography using image analysis. The identity of the matrix metalloproteinases was confirmed by using inhibitors, by comparison with purified standards, and by Western immunoblotting with specific antibodies. RESULTS: In patients with ulcerative colitis (n = 21), a significant increase (P = 0.0051) in metalloproteinase activity was found in inflamed areas of mucosa compared with noninvolved regions. The levels of activity also were significantly greater (P < 0.001) in noninvolved areas of the bowel (n = 21) compared with levels in control patients (n = 9). In Crohn's disease (n = 8), differences between ulcerated and nonulcerated sites were not significantly different but levels of protease activity at both of these sites were significantly elevated compared with levels in control patients (P < 0.03). Of the proteases detected, matrix metalloproteinase 9 was the most abundantly expressed in the inflamed bowel; neutrophils were confirmed as the likely origin of this protease. CONCLUSIONS: The abundance and activation of matrix metalloproteinases significantly increases in ulcerative colitis and Crohn's mucosa. Inhibitors of these proteolytic enzymes may therefore be of therapeutic value in the treatment of inflammatory bowel disease.

Adolescent↗
PubMed1999

High-dose estrogen-induced osteogenesis in the mouse is partially suppressed by indomethacin.

We recently found that high-dose estrogen induces the formation of new sites of cancellous bone formation within the long bones of intact female mice. To examine whether prostaglandins play a role in mediating this response, we studied whether this is inhibited by coadministration of the cyclooxygenase inhibitor, indomethacin. Eight-week-old intact female mice were divided into four groups of ten, and administered vehicle, 17beta-estradiol (E2), at 500 microg/animal per week and/or indomethacin at 2 mg/kg per day. Animals were killed after treatment for 24 days, and histomorphometric indices subsequently analyzed on longitudinal sections of the proximal tibial metaphysis. As found previously, E2 treatment caused a striking increase in cancellous bone volume, associated with an equivalent increase in the extent of cancellous double-labeled surfaces. In mice treated with both indomethacin and E2, significant reductions in cancellous bone volume and cancellous double-labeled surfaces were observed as compared with animals treated with E2 alone. In contrast, indomethacin did not significantly influence these parameters when given alone. Subregional analysis within the proximal tibial metaphysis revealed that this inhibitory effect of indomethacin was more marked distally as compared with proximally, with the estrogen-induced gain in cancellous bone volume at these sites being reduced by 50% and 25%, respectively. We conclude that estrogen-induced osteogenesis in female mice is partially suppressed by treatment with indomethacin, suggesting that prostaglandin synthesis plays a significant role in mediating this response.

Animals↗
PubMed1999

High-dose estrogen induces de novo medullary bone formation in female mice.

It is well recognized that, in the mouse, high-dose estrogen induces sclerosis within the shaft of long bones, an action that is largely thought to reflect increased osteoblastic cellular activity. We undertook to characterize this response in more detail, by performing a histologic analysis of the early changes induced by high-dose estrogen in the tibial cavity of young intact female mice. Female mice were sacrificed immediately before or 4, 8, 12, or 24 days after commencing subcutaneous injections of 17beta-estradiol (500 microg/animal/week), and longitudinal tibial sections were subsequently examined. Estrogen was found to cause a rapid gain in cancellous bone, with cancellous bone volume increasing by approximately 50% after 8 days, and by 5-fold after 24 days. Analysis of cancellous double-labeled surfaces revealed that this gain in bone reflected the emergence of new cancellous bone formation sites within the medullary cavity, rather than the reactivation and extension of formation over pre-existing bone surfaces. Comparison of the time course of these changes between proximal and distal regions of the proximal tibial metaphysis suggested that these new cancellous formation sites appear as a rapid wave extending distally from the secondary spongiosa. Alkaline phosphatase (ALP) immunocytochemistry revealed that, by 12 days after estrogen administration, a population of strongly ALP positive cells had appeared throughout the marrow cavity. We conclude that, at the proximal tibial metaphysis of female mice, estrogen-induced medullary sclerosis largely reflects a process of de novo medullary bone formation, possibly mediated by the generation of osteoblasts from bone marrow osteoprogenitor cells.

Alkaline Phosphatase↗
PubMed1999

The role of herpes simplex virus thymidine kinase in the treatment of solid tumours.

Suicide gene therapy is the approach whereby the genetic alteration of a cell renders it susceptible to an otherwise non-toxic prodrug. Suicide gene therapy for solid tumours has progressed rapidly since the concept was originally described: nearly all tumour types have been explored, with some, such as glioma, melanoma and colon cancer frequently used experimentally. The exciting aspect of suicide gene therapy is the bystander effect, the phenomenon whereby there is extended tumour death when only a small fraction is transfected with the suicide gene. This phenomenon implies that there is a reduced need to target specifically all tumour cells, as the effect mechanism itself carries out this function. The bystander effect mode of action has not yet been fully characterised, but the role of gap junctions and the immune system are implicated as the main instruments in its potentiation. This approach is also amenable to pharmacological intervention, which may help to optimise parameters prior to commencing suicide gene therapy. Clinical trails have already commenced using this form of treatment and results are eagerly awaited.

Journal Article↗