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P Malone

Publications and source records attributed to P Malone.

At least 19 recordsLinked to original sources
PubMed2005

Long-term activation of c-Fos and c-Jun in optic nerve head astrocytes in experimental ocular hypertension in monkeys and after exposure to elevated pressure in vitro.

This study investigates whether the immediate early gene (IEG) products c-Fos and c-Jun are activated in vivo in monkeys with experimental glaucoma, and in vitro in cultured human ONH astrocytes exposed to hydrostatic pressure (HP). Three Rhesus monkeys with mild glaucomatous damage (mean intraocular pressure (IOP) 27 +/- 1.3 mm Hg approximately 42 weeks) and three with moderate glaucomatous damage (mean IOP 44 +/- 6.7% mm Hg approximately 11 weeks) were used for this study; the contralateral eye served as normal control (mean IOP 18.6 +/- 1.7 mm Hg). ONH tissues were stained with GFAP, DAPI, and c-Jun or c-Fos, and transcription factor positive and negative nuclei were counted to determine nuclear localization. Cultured human normal and glaucomatous ONH astrocytes exposed to elevated HP served as the in vitro model of elevated pressure. Activation and nuclear localization of c-Fos and c-Jun increased significantly in the monkeys with elevated IOP. These data correlated with axonal loss, reactive astrocytes, and remodeling of the optic disc. Cultured human ONH astrocytes showed increased nuclear localization of c-Fos and c-Jun under exposure to HP. Immunohistochemistry demonstrated that the upstream regulators of c-Fos and c-Jun, ERK-MAPK and MAPKp38 localized to the nuclei of ONH astrocytes in monkeys with experimental glaucoma. Taken together, these results demonstrate c-Fos and c-Jun activation in ONH astrocytes in vivo and in vitro, and that activation of both transcription factors is associated with ERK and MAPKp38 activation in experimental glaucoma, suggesting that activation of transcription factors may participate in the induction and maintenance of the reactive astrocyte phenotype in glaucomatous optic neuropathy.

Animals↗
PubMed2000

Pediatric office emergencies and emergency preparedness in a small rural state.

OBJECTIVE: Although the frequency of pediatric office medical emergencies has been investigated in a retrospective manner, there have been no prospective studies. We examined how often pediatricians in a small rural state encountered medical emergencies in the office setting. This study included an in-office educational program and the donation of resuscitation equipment to study participants. DESIGN AND INTERVENTION: Thirty-eight of the 40 active primary care pediatric practices in the state of Vermont participated in this study. Thirty-seven sites were surveyed retrospectively regarding office preparedness for emergencies and frequency of office emergencies. At each practice site, an educational session was provided and an office resuscitation kit was donated. Thirty-seven sites were followed prospectively for a 12-month period evaluating the incidence of office medical emergencies and the adequacy of the donated resuscitation kit. RESULTS: Three hundred twenty-seven individuals from 38 Vermont pediatric practice sites participated. Forty-nine percent had basic life support training and 26% had pediatric advanced life support training. Sixty-seven percent of practices had a plan for office medical emergencies. Forty-six percent of practices had called local emergency medical services providers to their offices in the past year. Emergency preparedness ranged from a high of 95% of sites with oxygen to a low of 27% of sites with intraosseous needles. The estimate of the frequency of medical emergencies was.9 (standard deviation =.8) per office in the previous 12 months. In the 12-month study, there were 28 medical emergencies reported, averaging.8 (standard deviation = 1.5) emergencies per office per year. Sixty-five percent of participating sites had no emergencies in the study. Of the emergencies reported, 75% were respiratory in origin. The donated resuscitation kits proved sufficient for all of the emergencies reported. CONCLUSIONS: Serious medical emergencies are rare events in the primary care pediatric office, occurring less than once per office per year. The most common emergency situations encountered are respiratory. All of the emergencies in this study were managed effectively using a simple and relatively inexpensive resuscitation kit. We provided an emergency preparedness program for pediatric practices in a small rural state.

Certification↗
PubMed1998

Lower moiety heminephroureterectomy in the duplex refluxing kidney: the accuracy of isotopic scintigraphy in functional assessment.

OBJECTIVE: To determine the accuracy of dimercaptosuccinic acid (DMSA) scintigraphy in assessing the differential function between upper and lower moieties of a refluxing duplex system. PATIENTS AND METHODS: Between 1990 and 1996, 20 patients underwent lower moiety heminephroureterectomy. All patients had their differential renal function assessed by DMSA scintigraphy before and after surgery, the results being assessed by comparing the predicted and actual loss of renal function. RESULTS: The mean (SD, range) function attributed to the scarred lower moiety (predicted loss of function) was 4.3 (4.9, 0-14)%, which compared with an actual mean loss of function of 6.8 (5.1, +4 to -16)%. Thus the mean (SD, range) difference between the predicted and actual loss of renal function was -2.1 (3.2, +4 to -8)%. CONCLUSION: DMSA scintigraphy provides an accurate assessment of the differential renal function between upper and lower moieties in a duplex system. The decision to proceed to lower moiety heminephroureterectomy can be logically based on the information gained from DMSA scintigraphy.

Adolescent↗
PubMed1998

Differential effects of estrogen metabolites on bone and reproductive tissues of ovariectomized rats.

The effects of 17 beta-estradiol and the important estrogen metabolites, 2-hydroxyestrone (2-OHE1) and 16 alpha-hydroxyestrone (16 alpha-OHE1) on bone, mammary gland, and uterine histology, and on blood cholesterol were investigated in ovariectomized growing rats. Rats were treated with 200 micrograms/kg of body weight/day of each of the test compounds for 3 weeks. Ovariectomy resulted in uterine and mammary gland atrophy, increased body weight, bone turnover and tibia growth, and hypercholesterolemia. 17 beta-estradiol treatment prevented these changes, with the exception that this high dose of estrogen did not prevent hypercholesterolemia. 2-OHE1 had no effect on any of the measurements. 16 alpha-OHE1 resulted in bone measurements that did not differ from the 17 beta-estradiol-treated rats and prevented the increase in serum cholesterol. In contrast, 16 alpha-OHE1 resulted in increases in uterine weight, uterine epithelial cell height, and mammary gland cell proliferation that were significantly less than the 17 beta-estradiol treatment. These findings demonstrate that 16 alpha-hydroxylation of estrone results in tissue-selective estrogen agonistic activity, whereas 2-hydroxylation resulted in no measured activity. Furthermore, they suggest that factors that modulate the synthesis of these metabolites could selectively influence estrogen target tissues.

Animals↗
PubMed1997

Immunohistochemical analysis of the proapoptotic protein Par-4 in normal rat tissues.

Prostate apoptosis response 4 (par-4) is a recently identified gene that encodes a transcription factor, Par-4, with a leucine zipper domain. Par-4 protein is constitutively expressed in various cell lines and is functionally required but not sufficient for apoptosis. Induction of Par-4 in cultured cells is found exclusively during apoptosis, and ectopic overexpression of Par-4 enhances the potency of apoptotic stimuli. Western or Northern blot analysis on mRNA or protein extracts, respectively, from rat organs revealed that the expression of Par-4 was ubiquitous and was not restricted to any specific organ(s). To further identify specific cell types that expressed Par-4, we performed an immunohistochemical analysis of the protein in paraffin-embedded sections of various organs from rats. Our findings indicated that consistent with its proapoptotic role, Par-4 is expressed in apoptotic granulosa cells of atretic ovarian follicles and in terminally differentiated cells, such as the cardiomyocytes, cerebellar Purkinje cells, and pyramidal cells of the hypothalamus. Moreover, testosterone ablation by castration of rats caused an early and transient induction of Par-4 in the ductal cells of the prostate that undergo apoptosis. By contrast, in tissues in which the cells could be visually differentiated from their mature counterparts, Par-4 expression was lowest in the mature cells. This was the case for epithelia of the mammary and the prostate gland in which the basal cells maintained higher protein levels of Par-4 than did the terminally differentiated ductal cells. Similarly, cells of the stratum corneum of the skin and cells on top of the duodenal villi stained less intensely for Par-4 as compared to the stem cells in the stratum basale and at the bottom of the crypts of Lieberkühn, respectively. It is possible that Par-4 has to be down-regulated for successful differentiation in these tissues. Taken together, the widespread expression of Par-4 in various adult cell types underscores the physiological importance of the protein. The observation of constitutive Par-4 expression in the stem cell compartments is inconsistent with the probability of apoptosis per se and can be extended to determine whether Par-4 plays a role in other cellular processes.

Animals↗
PubMed1993

The role of the Mathieu repair as a salvage procedure.

Conceived as a primary single-stage procedure for coronal and subcoronal hypospadias, the Mathieu repair has not been previously described as a salvage operation in situations where other forms of hypospadias surgery have failed to give an adequate functional or cosmetic result. We describe the use of the operation as a planned salvage procedure.

Child↗
PubMed1989

Long-term results of amiodarone therapy in patients with recurrent sustained ventricular tachycardia or ventricular fibrillation.

Four hundred sixty-two patients, all with either documented spontaneous sustained ventricular tachycardia or cardiac arrest unresponsive to other antiarrhythmic drugs (2.6/patient), were treated with amiodarone. Thirty-five patients (7.6%) failed to respond or died during the initial oral or intravenous loading phase. The remaining 427 patients were discharged on treatment with oral amiodarone and followed up for up to 98 months. Recurrence of ventricular tachycardia or sudden cardiac death at 1, 3 and 5 years by life-table analysis was 19%, 33% and 43%, respectively, for patients discharged on amiodarone therapy. The sudden cardiac death rate was 9%, 15% and 21%, respectively, at 1, 3 and 5 years. Side effects were reported by 45% of patients after 1 year, by 61% after 2 years and by 86% after 5 years. Amiodarone was discontinued because of side effects in 14%, 26% and 37% of patients after 1, 3 and 5 years, respectively. Incidence rates of recurrence of arrhythmia, sudden cardiac death and side effects were highest in the early months and then decreased. By multivariate analysis, advanced age, low ejection fraction and a history of cardiac arrest were independent risk factors for sudden cardiac death during amiodarone therapy.

Aged↗
PubMed1989

The ovarian remnant syndrome presenting with acute urinary retention.

The case of a woman presenting with acute urinary retention, which, on investigation, proved to be due to the ovarian remnant syndrome, is reported. This syndrome is rare, with only 36 previously published cases. To our knowledge none has so far presented in this manner.

Acute Disease↗
PubMed1988

Use of intravenous amiodarone for emergency treatment of life-threatening ventricular arrhythmias.

Efficacy, side effects and predictors of response for intravenous amiodarone were evaluated in 46 patients with recurrent drug-refractory sustained ventricular tachycardia or ventricular fibrillation, or both, who were treated with intravenous amiodarone. Of the 46 patients, 27 (58.5%) responded early to intravenous amiodarone and 6 (13%) showed a late response to amiodarone. The majority of patients who responded to intravenous amiodarone did so within the first 2 h of therapy, and all responded within 84 h. Patients with an ejection fraction greater than 25% were more likely to respond (p less than 0.05). Major side effects occurred in 13% of patients. The cumulative 2 year mortality rate due to arrhythmia recurrence or sudden death for responders discharged from the hospital was 23% and the cumulative overall 2 year mortality rate was 46%. In conclusion, intravenous amiodarone is rapidly effective in the majority of patients with recurrent ventricular tachycardia or ventricular fibrillation refractory to other drugs. The poor long-term outcome of patients who require this therapy, respond to it and are discharged on long-term oral amiodarone therapy warrants consideration of other long-term treatment of these patients. Use of intravenous amiodarone is an important new modality in the treatment of drug-refractory malignant ventricular arrhythmias.

Amiodarone↗
PubMed1988

Renin in mesoblastic nephroma: an immunohistochemical study.

Congenital mesoblastic nephroma (CMN) is the most common renal tumor of early infancy. It is usually evident at birth as an abdominal mass and is composed of spindle-shaped cells resembling smooth muscle cells and fibroblasts. There is macroscopic and microscopic infiltration of the surrounding kidney and entrapped tubules and glomeruli are common at the edge of the tumor. In this report, we describe a case of CMN associated with hyperreninaemia and hypertension. We examined the tumor from this case and 11 other cases for the presence of renin using a polyclonal antibody to human kidney renin. Hypertension was present in three of four additional cases for which records were available. Immunoreactive renin was present in ten of the 12 cases studied. In all of these cases, intense staining was present in vessels within the areas of the trapped cortex. In seven cases, renin was identified in the walls of vessels within the tumor itself without identifiable adjacent cortical structures. These findings indicate that CMN may often be associated with primary reninism in early infancy.

Humans↗
PubMed1988

The effects of aminoglutethimide and hydrocortisone, alone and combined, on androgen levels in post-orchiectomy prostatic cancer patients.

Aminoglutethimide has been used in combination with hydrocortisone in patients with advanced prostatic cancer with the rationale that it causes a 'medical adrenalectomy'. Both objective and subjective responses have been recorded. We have examined the effect of AG and HC alone and in combination on plasma androgen levels throughout the day in two studies on 11 such patients. Whilst AG combined with HC led to a significant suppression of both testosterone and androstenedione levels, the suppression with HC alone was significantly greater, indicating that any beneficial clinical effects of AG in these patients is not due to its suppression of adrenal androgen secretion.

Aged↗
PubMed1986

Altered growth properties and cell surface changes in ras transformed mouse bladder epithelium.

Transfection of the c-Ha-ras-1 oncogene, cloned from EJ/T24 cells, into different mouse bladder epithelial cell lines resulted in the acquisition of tumorigenic potential and, in all but one cell line (MB33I), anchorage-independent growth. Sera from syngeneic mice bearing tumours immunoprecipitated an 18 kDa protein from ras-transfected urothelial cells which was not detectable in their parental counterparts. Screening of a limited panel of mouse cell lines showed this protein to be urothelium-specific and associated with the expression of an activated ras gene. Polyoma middle T and v-myc-transfected bladder epithelial cells did not express this 18 kDa protein. Localization of this protein to the cell surface was demonstrated by immunofluorescence and absorption studies.

Animals↗
PubMed1986

Malignant transformation of murine fibroblasts by a human c-Ha-ras-1 oncogene does not require a functional epidermal growth factor receptor.

Although mutations in ras genes are thought to be important for the development of about 20% of human tumors, almost nothing is known about the way in which these mutations lead to cellular transformation. The known biochemical properties of the 21-kilodalton ras proteins suggest that they may behave as G proteins, regulating the proliferation of cells in response to growth factor stimulation of a receptor. Although the putative receptor(s) has not been identified, several lines of evidence, in particular the fact that rodent cell lines containing ras oncogenes produce transforming growth factor alpha, have suggested that the epidermal growth factor (EGF) receptor is involved in ras transformation. Here we show that murine fibroblasts with no EGF receptors can be transformed to a completely malignant phenotype with a mutated ras gene. It appears, therefore, that the EGF receptor is not required for ras-mediated transformation of these cells.

Animals↗
PubMed1985

Possible mechanism of the synergistic effect of heparin and dihydroergotamine.

A combination of heparin and dihydroergotamine mesylate (Heparin-Dihydergot) has been shown to be more effective than either of these drugs alone in preventing postoperative venous thromboembolism. The possible mechanism for the synergistic effect of heparin and dihydroergotamine was assessed. Phlebograms obtained after administration of 0.5 mg of dihydroergotamine showed marked constriction of the tibial and soleal veins with a significant reduction in the mean diameter of the femoral vein. The effect on the coagulation mechanism was assessed in 28 patients. Blood samples were withdrawn from the femoral vein during varicose vein operations. A significant difference was observed in antithrombin III activity, kaolin-cephalin clotting time, beta-thromboglobulin, and fibrino-peptide levels between the control, dihydroergotamine, heparin, and the combination groups.

Antithrombin III↗