Biomedical subjects

P Maher

Publications and source records attributed to P Maher.

At least 37 records · Page 2Linked to original sources

PubMed1998

Endoscopic treatment of uterine fibroids.

Endoscopic surgery is able to replace most abdominal operations in the surgical treatment of uterine leiomyomas. The use of gonadotrophin hormone-releasing hormone analogues, arterial embolization, hysteroscopy, new techniques of morcellation, laparo-vaginal gasless laparoscopy and laparoscopic mini-laparotomy have enabled the avoidance of laparotomy incisions in most patients. The previous disadvantages of laparoscopy, namely a prolonged operating time, excessive bleeding and inadequate closure, have been overcome. Case and controlled studies have demonstrated the effectiveness of endoscopy in fibroid treatment. The surgical techniques require advanced endoscopic training.

Electrocoagulation↗

PubMed1998

Oxidative stress induces a form of programmed cell death with characteristics of both apoptosis and necrosis in neuronal cells.

Oxidative stress is implicated in a number of neurological disorders including stroke, Parkinson's disease, and Alzheimer's disease. To study the effects of oxidative stress on neuronal cells, we have used an immortalized mouse hippocampal cell line (HT-22) that is particularly sensitive to glutamate. In these cells, glutamate competes for cystine uptake, leading to a reduction in glutathione and, ultimately, cell death. As it has been reported that protein kinase C activation inhibits glutamate toxicity in these cells and is also associated with the inhibition of apoptosis in other cell types, we asked if glutamate toxicity was via apoptosis. Morphologically, glutamate-treated cells underwent plasma membrane blebbing and cell shrinkage, but no DNA fragmentation was observed. At the ultrastructural level, there was damage to mitochondria and other organelles although the nuclei remained intact. Protein and RNA synthesis inhibitors as well as certain protease inhibitors protected the cells from glutamate toxicity. Both the macromolecular synthesis inhibitors and the protease inhibitors had to be added relatively soon after the addition of glutamate, suggesting that protein synthesis and protease activation are early and distinct steps in the cell death pathway. Thus, the oxidative stress brought about by treatment with glutamate initiates a series of events that lead to a form of cell death distinct from either necrosis or apoptosis.

Amino Acid Chloromethyl Ketones↗

PubMed1998

Factors associated with pain following operative laparoscopy: a prospective observational study.

An open prospective observational study was performed, aiming to measure symptom severity following operative gynaecological laparoscopy and explore any associated factors. Women having concomitant procedures were excluded. Each woman had standardized analgesia, completed a symptom diary for 7 days postoperation, and had a standardized form completed by the surgeon detailing the operation. Back pain, nausea and vaginal pain were found to not be of clinical significance. Cutting major vessels, ligaments, vagina or ovary had major impacts on postoperative symptoms. In the presence of a standardized analgesic regimen, symptoms did not resolve for at least 5 days.

Abdominal Pain↗

PubMed1998

The place of laparoscopic surgery in surgical gynaecology.

This review was undertaken to ascertain whether the low usage of laparoscopic surgery in gynaecology resulted from unacceptable complication rates and long operating times. The safety and efficacy of laparoscopic surgery has been compared to that of laparotomy. Reports of controlled or comparative trials of laparoscopic gynaecological surgery for adhesions, infertility, ectopic pregnancy, oophorectomy, myomectomy and laparoscopically-assisted vaginal hysterectomy (LAVH) have been reviewed between 1984 and 1997. Although further multicentre controlled trials may improve the assessment of complication rates for both laparotomy and laparoscopy procedures, laparoscopy appears to be as safe as laparotomy and generally has the advantage of shorter hospital stay and earlier return to normal activities. Except for LAVH, operating times of laparoscopic surgery are similar to that of laparotomy.

Clinical Trials as Topic↗

PubMed1997

Requirement for cGMP in nerve cell death caused by glutathione depletion.

Glutathione depletion occurs in several forms of apoptosis and is associated with Parkinson's disease and HIV toxicity. The neurotransmitter glutamate kills immature cortical neurons and a hippocampal nerve cell line via an oxidative pathway associated with glutathione depletion. It is shown here that soluble guanylyl cyclase (sGC) activity is required for nerve cell death caused by glutathione depletion. Inhibitors of sGC block glutamate toxicity and a cGMP analogue potentiates cell death. Glutamate also induces an elevation of cGMP that occurs late in the cell death pathway. The resultant cGMP modulates the increase in intracellular calcium that precedes cell death because sGC inhibitors prevent calcium elevation and the cGMP analogue potentiates the increase in intracellular calcium. These results suggest that the final pathway of glutamate induced nerve cell death is through a cGMP-modulated calcium channel.

Animals↗

PubMed1997

The role of protein phosphorylation in beta amyloid toxicity.

Recent evidence suggests that amyloid beta protein (A beta) mediates the neurotoxicity observed in Alzheimer's disease (AD). Little is known, however, about the cytotoxic pathway leading to nerve cell death. Using a rat brain cell line which is sensitive to A beta, it is shown that a 50-60 kDa protein becomes more phosphorylated when cells are exposed to A beta. Several kinase and phosphatase inhibitors block both the increase in phosphorylation of the 50-60 kDa protein and A beta toxicity. In contrast, a tyrosine kinase inhibitor blocks toxicity at a step which is distinct from the phosphorylation of this protein. A beta also causes a general increase in overall phosphatase activity. It is therefore likely that a protein phosphorylation cascade is involved in A beta toxicity.

Amyloid beta-Peptides↗

PubMed1997

Growth factor regulation of cell growth and proliferation in the nervous system. A new intracrine nuclear mechanism.

This article discusses a novel intracrine mechanism of growth-factor action in the nervous system whereby fibroblast growth factor-2 (FGF-2) and its receptor accumulate in the cell nucleus and act as mediators in the control of cell growth and proliferation. In human and rat brain the levels and subcellular localization of FGF-2 differ between quiescent and reactive astrocytes. Quiescent cells express a low level of FGF-2, which is located predominantly within the cytoplasm. In reactive astrocytes, the expression of FGF-2 increases and the proteins are found in both the cytoplasm and nucleus. In glioma tumors, FGF-2 is overexpressed in the nuclei of neoplastic cells. Similar changes in FGF-2 expression and localization are found in vitro. The nuclear accumulation of FGF-2 reflects a transient activation of the FGF-2 gene by potentially novel transactivating factors interacting with an upstream regulatory promoter region. In parallel with FGF-2, the nuclei of astrocytes contain the high-affinity FGF-2 receptor, FGFR1. Nuclear FGFR1 is full length, retains kinase activity, and is localized within the nuclear interior in association with the nuclear matrix. Transfection of either FGF-2 or FGFR1 into cells that do not normally express these proteins results in their nuclear accumulation and concomitant increases in cell proliferation. A similar regulation of nuclear FGF-2 and FGFR1 is observed in neural crestderived adrenal medullary cells and of FGF-2 in the nuclei of cerebellar neurons. Thus, the regulation of the nuclear content of FGF-2 and FGFR1 could serve as a novel mechanism controlling growth and proliferation of glial and neuronal cells.

Animals↗

PubMed1997

A role for 12-lipoxygenase in nerve cell death caused by glutathione depletion.

An early and highly specific decrease in glutathione (GSH) in the substantia nigra is associated with Parkinson's disease, and low levels of GSH lead to the degeneration of cultured dopaminergic neurons. Using immature cortical neurons and a clonal nerve cell line, it is shown that a decrease in GSH triggers the activation of neuronal 12-lipoxygenase (12-LOX), which leads to the production of peroxides, the influx of Ca2+, and ultimately to cell death. The supporting evidence includes: 1) inhibitors of arachidonate metabolism and 12-LOX block cell death induced by GSH depletion; 2) there is an increase in 12-LOX activity and a membrane translocation in HT22 cells, and an induction of the enzyme in primary cortical neurons following the reduction of GSH; 3) 12-LOX is directly inhibited by GSH; and 4) exogenous arachidonic acid potentiates cell death. These data show that the LOX pathway is a critical intermediate in at least some forms of neuronal degeneration.

Animals↗

PubMed1997

Bleeding associated with vaginal hysterectomy.

The increased use of blood transfusion, ultrasound evidence of postsurgical haematoma, the frequency of postoperative febrile morbidity of unknown cause and reports of these complications in large series which contain both abdominal and vaginal hysterectomy over the last 25 years, suggests that bleeding may be more common after vaginal hysterectomy. We performed laparoscopy routinely after vaginal hysterectomy in 50 patients. The frequency of bleeding was 48%, consistent with other studies ranging from 30 to 98%. Arterial bleeding from a branch of the uterine or vaginal artery occurred in 20%. The frequency of bleeding was not related to uterine size, ranging from normal to that equivalent in size to that of a pregnancy of 18 weeks' gestation. The most common site of bleeding was the vaginal vault. Liberal definitions of haemorrhage, possible emphasis in speed in performing hysterectomy, and difficulty in visualizing and ligating major and minor blood vessels, may have contributed to the increased frequency of bleeding reported after vaginal hysterectomy. Haemostasis is more easily obtained at laparoscopic surgery because of magnification, close inspection, routine use of suction irrigation and bipolar electrocoagulation. Routine laparoscopy at the completion of vaginal hysterectomy is recommended. New and improved methods of vessel closure are also required. Attitudes to haemorrhage during hysterectomy require change to further reduce the use of blood transfusion.

Blood Loss, Surgical↗

PubMed1996

The role of monoamine metabolism in oxidative glutamate toxicity.

Glutamate kills neuronal cells by either a receptor-mediated pathway or the inhibition of cystine uptake, the "oxidative pathway." Antioxidants can block cell death initiated by either pathway, suggesting that toxicity is dependent on the production of free radicals. We provide evidence that in a neuronal cell line, glutamate toxicity via the oxidative pathway requires monoamine metabolism as a source of free radicals. Glutamate toxicity is inhibited by monoamine oxidase (MAO) type-A-specific inhibitors, but only at concentrations much higher than those required to inhibit classical type-A MAO. Toxicity is not inhibited by MAO type-B-specific inhibitors at any concentration. Furthermore, treatment of cells with agents that block monoamine uptake inhibits glutamate toxicity. These results suggest that an enzyme distinct from MAO is involved in monoamine metabolism and demonstrate a relationship between glutamate toxicity and monoamine metabolism. These data also have implications for the understanding and treatment of neurodegenerative disorders in which glutamate toxicity is thought to be involved.

Amines↗

PubMed1996

Copper and calcium binding motifs in the extracellular domains of fibroblast growth factor receptors.

High affinity fibroblast growth factor (FGF) receptors contain a cluster of acidic amino acids in their extracellular domains that is reminiscent of the calcium binding domains of some cell adhesion molecules. Based on this observation, we used a calcium blotting technique to show that FGFR-1 binds calcium and that calcium binding is not observed in a mutagenized form of the receptor that lacks the acidic box region. The acidic box also binds other divalent cations, including copper. This latter interaction appears unique since the binding of copper to FGFR-1 mediates the binding of the receptor to immobilized heparin. While this observation may help explain the angiogenic properties of copper, divalent cation binding to FGF receptors may also mediate the interaction between FGF receptors, cell adhesion molecules and other proteoglycan components of the extracellular matrix.

Animals↗

PubMed1996

The role of calmodulin in the gravitropic response of the Arabidopsis thaliana agr-3 mutant.

Calmodulin, a primary plant calcium receptor, is known to be intimately involved with gravitropic sensing and transduction. Using the calmodulin-binding inhibitors trifluoperazine, W7 and calmidazolium, gravitropic curvature of Arabidopsis thaliana (L.) Heynh, ecotype Landsberg, roots was separable into two phases. Phase I was detected at very low concentrations (0.01 microM) of trifluoperazine and calmidazolium, did not involve growth changes, accounted for about half the total curvature of the root and may represent the specific contribution of the cap to gravity sensing. Phase II commenced around 1.0 microM and involved inhibition of both growth and curvature. The agr-3 mutant exhibited a reduced gravitropic response and was found to lack phase I curvature, suggesting that the mutation alters either use or expression of calmodulin. The sequences of wild-type and agr-3 calmodulin (CaM-1) cDNAs, which are root specific were completely determined and found to be identical. Upon gravitropic stimulation, wild-type Arabidopsis seedlings increased calmodulin mRNA levels by threefold in 0.5 h. On the other hand, gravitropic stimulation of agr-3 decreased calmodulin mRNA accumulation. The possible basis of the two phases of curvature is discussed and it is concluded that agr-3 has a lesion located in a general gravity transmission sequence, present in many root cells, which involves calmodulin mRNA accumulation.

Arabidopsis↗

PubMed1996

Routine use of ureteric catheters at laparoscopic hysterectomy may cause unnecessary complications.

STUDY OBJECTIVE: To test the use of ureteric catheters in preventing ureteric trauma during laparoscopic hysterectomy. DESIGN: Prospective study of 492 consecutive women. SETTING: Pelosi Women's Medical Center, New Jersey, and Cliveden Hill Private Hospital, Melbourne, Australia. PATIENTS: Four hundred ninety-two consecutive women. INTERVENTIONS: Laparoscopic hysterectomy was performed in all women. Because of the reported increased risk of ureteric trauma during laparoscopic hysterectomy, we passed ureteric catheters in 92 such procedures and ceased the practice with the last 400 when further reports suggested lack of increased risk. MEASUREMENTS AND MAIN RESULTS: Oliguria and anuria occurred in 7 of 92 patients having ureteric catheterization. No ureteric trauma occurred in 400 patients without ureteric catheterization. The injury rate in this series was significantly lower than in three other series of abdominal hysterectomy. CONCLUSIONS: As long as surgical techniques incorporate various procedures to avoid ureteric injury, routine ureteric catheterization during laparoscopic hysterectomy is not indicated and may result in unnecessary complications.

Anuria↗

PubMed1996

Removal of fibromyomas by laparoscopic surgery after preoperative GnRH analogue--an alternative to abdominal hysterectomy or myomectomy.

Nineteen patients with fibromyomas who had been recommended to have a hysterectomy or abdominal myomectomy were referred as they wished to avoid a hysterectomy (14) or laparotomy incision for a myomectomy (5). Following administration of the GnRH analogue goserelin, laparoscopic surgery was performed on all these patients. Hysterectomy was avoided in all but 1 of the 14 patients and laparotomy myomectomy was avoided in 4 of the 5 patients recommended to have these procedures. The combination of a GnRH analogue and laparoscopic-based surgery may be an acceptable alternative to both laparotomy myomectomy and hysterectomy in women with fibromyomas requiring surgery.

Adult↗

PubMed1996

Peritoneal surgery in the treatment of endometriosis--excision or thermal ablation?

Twenty patients with Stage 2 to 4 endometriosis were referred to an Endometriosis Clinic with an average of 3.4 previous medical and surgical treatments. All were treated by peritoneal excision. Follow-up was for 9-36 months and 14 had a further laparoscopy. Seventeen of 20 patients are free of symptoms. In 1 patient recurrence occurred in a separate site and in 2 there were lesions close to the original lesion in the pouch of Douglas and bladder wall. In addition, 1 of the 14 patients having further laparoscopy had mild adhesions. The satisfactory results of the study suggest that a controlled trial comparing peritoneal excision and thermal ablation is worthwhile. There are considerable theoretical advantages in using peritoneal excision rather than peritoneal thermal ablation.

Adult↗

PubMed1996

Underutilization of laparoscopic oophorectomy.

The objective of this study was to compare the use and effectiveness of laparoscopic and laparotomy oophorectomy in 3 hospitals in Melbourne. A retrospective analysis was made of medical records of 140 patients having laparoscopic or laparotomy oophorectomy in the Mercy Hospital for Women (41), Monash Medical Centre (37), and Cliveden Hill Private Hospital (62). Both public hospitals used the laparoscopic procedure, 12% and 22% respectively, less often than the private hospital, 94%. The average number of hospital days for procedures completed by laparoscopy was 1.3 and for laparotomy 6.9. Fourteen percent of laparoscopic procedures were converted to laparotomy. Adjusting for this the average hospital stay was 1.6 days of procedures started laparoscopically. Assuming 1,000 oophorectomies are performed each year in Australia of which 80% could be performed laparoscopically, there may be cost savings to health care providers of over $1.5 million. Laparoscopic oophorectomy is a safe, effective and cost-efficient method of removing the ovary and gynaecologists should be encouraged to learn and perform this procedure.

Adult↗

PubMed1996

Chemotherapy without irradiation--a novel approach for newly diagnosed CNS germ cell tumors: results of an international cooperative trial. The First International Central Nervous System Germ Cell Tumor Study.

PURPOSE: Radiation therapy for CNS germ cell tumors (GCT) is commonly associated with neurologic sequelae. We designed a therapeutic trial to determine whether irradiation could be avoided. PATIENTS AND METHODS: Patients received four cycles of carboplatin, etoposide, and bleomycin. Those with a complete response (CR) received two further cycles; others received two cycles intensified by cyclophosphamide. RESULTS: Seventy-one patients were enrolled (45 with germinoma and 26 with nongerminomatous GCT [NGGCT]). Sixty-eight were assessable for response. Thirty-nine of 68 (57%) achieved a CR within four cycles. Of 29 patients with less than a CR, 16 achieved CR with intensified chemotherapy or second surgery. Overall, 55 of 71 (78%) achieved a CR without irradiation. The CR rate was 84% for germinomas and 78% for NGGCT. With a median follow-up duration of 31 months, 28 of 71 patients were alive without relapse or progression. Thirty-five showed tumor recurrence (n = 28) or progression (n = 7) at a median of 13 months. Twenty-six of 28 patients (93%) who recurred following remission underwent successful salvage therapy. Pathology was the only variable predictive of survival. The probability of surviving 2 years was .84 for germinoma patients and .62 for NGGCT. Seven of 71 patients died of toxicity associated with study chemotherapy. CONCLUSION: Forty-one percent of surviving patients and 50% of all patients were treated successfully with chemotherapy only without irradiation. Chemotherapy-only regimens for CNS GCT, although encouraging, should continue to be used only in the setting of formal clinical trials.

Adolescent↗

PubMed1995

Excision of endometriosis in the pouch of Douglas by combined laparovaginal surgery using the Maher abdominal elevator.

Twenty-one patients with stage 3 or 4 endometriosis in the pouch of Douglas had combined laparovaginal surgery using the Maher abdominal wall elevator. Opening the pouch of Douglas at the beginning of the operation allowed the combined surgery. Instruments were introduced through both the vagina and accessory laparoscopic incision. And a finger was placed in the vagina to palpate and detect abnormal tissue and assist in blunt dissection. The extent of pathologic tissue in the pouch of Douglas was easily identified. This approach allowed flexibility in maximizing the optimum route, vaginal or laparoscopic, to remove the uterus, and facilitated rectal surgery. The alternatives of laparoscopic and laparotomy surgery have limitations compared with combined laparovaginal surgery, particularly deep in the pelvic cavity.

Abdomen↗