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Biomedical subjects

P Maher

Publications and source records attributed to P Maher.

At least 19 recordsLinked to original sources
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

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

Laparoscopic minilaparotomy hysterectomy.

A laparoscopic minilaparotomy hysterectomy technique is described. An abdominal elevator allowed the use of an open 2 cm port in the lower abdomen to introduce the finger and instruments used for laparotomy. The technique was developed in 3 patients with moderate to severe endometriosis. The second and third operations were quicker than could be expected by laparovaginal surgery. The use of laparotomy instruments and techniques make the technique easier to learn, cheaper than techniques using disposable products and has the potential to be faster and possibly safer than current techniques. It retains the advantage of laparoscopy surgery, reduced postoperative pain, small incisions and early discharge from hospital.

Female↗
PubMed1994

Protein kinase C activation inhibits glutamate-induced cytotoxicity in a neuronal cell line.

A neuronal cell line, HT-22, is sensitive to glutamate cytotoxicity via a non-receptor mediated oxidative pathway. 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C, blocks this glutamate-induced cell death. Down-regulation of protein kinase C eliminates the protection against glutamate cytotoxicity afforded by TPA. The data suggest that protein kinase C activation blocks an early step in the cytotoxic pathway.

Animals↗
PubMed1994

Laparovaginal hysterectomy.

The technique and complications of 141 patients having laparovaginal hysterectomy in private practice are reported. Abdominal hysterectomy was avoided in the 110 patients having preliminary laparoscopic surgery for pelvic disease, ovarian removal, or a uterus larger than 12cm. Postoperative morbidity included pulmonary embolus (3), vesicovaginal fistula (2) and pelvic haematoma (4). The frequency of complications was less than that reported after abdominal or vaginal hysterectomy. The surgical technique changed during the series; the operative care of the bladder and ureter requires particular attention. A larger number of patients in a variety of centres require study before the laparoscopic procedure can be determined to be as safe as abdominal or vaginal hysterectomy. The laparoscopic procedure has the potential to replace the majority of abdominal hysterectomies.

Evaluation Studies as Topic↗
PubMed1993

Laparoscopic culdotomy.

Laparoscopic culdotomy has been performed in 32 patients. The indications for the procedure included the removal of organs or tissue excised by operative laparoscopy, excision of vaginal endometriosis involving the pouch of Douglas and drainage of a pelvic haematoma. The surgical technique is described and no complications resulted from this technique. Laparoscopic culdotomy has advantages for the removal of lumps exceeding 1 cm, and for the drainage of a pelvic haematoma or pelvic abscess. It is also an integral step in the removal of infiltrating endometriotic lesions in the pouch of Douglas which are attached to the vagina.

Douglas' Pouch↗
PubMed1993

Laparoscopic removal of endometriosis in the pouch of Douglas.

Twenty-six patients with endometriosis in the pouch of Douglas were treated by laparoscopic excisional surgery; previous medical and surgical therapy had failed in 24 of them. Endometriosis in the pouch of Douglas occurred infrequently in association with bladder or ovarian endometriosis. Coital and rectal pain were markedly reduced or cured 6 months after surgery in all except 2 patients. Laparoscopic surgical excision of endometriosis is indicated when drug or other surgical treatments fail and may avoid the need for hysterectomy in some patients.

Adolescent↗
PubMed1993

Biopsy diagnosis and conservative surgical treatment of adenomyosis.

Fifteen patients with dysmenorrhoea and menorrhagia refractory to medical treatment were referred for surgical treatment. Pre-operative diagnosis of adenomyosis was suggested by vaginal ultrasound in 13 patients and was confirmed pre-operatively by myometrial biopsy in 5 and by transcervical myometrial biopsy at the time of endometrial resection in 7. Conservative surgery included endometrial resection (7), myometrial reduction by electrocautery (4), and myometrial excision (3). Marked improvement occurred in 4 of 7 patients after endometrial resection, 3 of 4 after myometrial reduction, and all of 3 having myometrial excision. Diagnosis of adenomyosis is improved by use of vaginal ultrasound and percutaneous or transcervical myometrial biopsy. Conservative surgical procedures including endometrial resection and myometrial reduction or excision may reduce the need for hysterectomy in the presence of adenomyosis.

Adult↗
PubMed1992

Growth factors and vitamin E modify neuronal glutamate toxicity.

The sympathetic nerve cell line PC-12 is killed by glutamate in a concentration-dependent manner. Although glycine and the deletion of magnesium weakly potentiate glutamate toxicity and PC-12 cells express N-methyl-D-aspartate-receptor mRNA, most toxicity is mediated by means of a mechanism independent of typical N-methyl-D-aspartate receptors. Glutamate toxicity is, however, greatly enhanced by prior exposure to nerve growth factor or basic fibroblast growth factor. Glutamate killing is blocked by epidermal growth factor and, to a lesser extent, by vitamin E. These observations show that synergistic interactions between growth factors and excitotoxic amino acids may play critical roles in the developing nervous system and that antioxidants attenuate this toxicity.

Animals↗
PubMed1992

Diagnosis and surgical management of endometriomas.

Fifty two patients with endometriomas greater than 1 cm were treated by surgical excision either with or without ovarian closure. Diagnosis is reliable when clinical features of the pain, vaginal ultrasound, and laparoscopy, including ovarian mobilization and needling, are considered. Fifty of 52 patients were free of pain after 1 year and 26 (50%) became pregnant within 1 year. A second laparoscopy is justified if pain persists or pregnancy does not occur. Adhesive disease was the most common complication (40%), and persistent or recurrent endometriosis occurred in 15%. Surgery by laparoscopy with drainage and excision of the endometrioma without ovarian sutures may be more effective than excision of the endometrioma and ovarian suture.

Endometriosis↗
PubMed1992

Laparoscopic adnexectomy--indications, technique and results.

Laparoscopic adnexectomy was performed successfully in 38 patients in whom the procedure was attempted. Failure may result from inexperience of the surgeon or when preliminary dissection near bowel suggests trauma is likely. The duration of the operation was between 15 and 105 minutes, blood loss was minimal and all but 2 patients were discharged within 24 hours of surgery. Pain was relieved in 33 of 35 patients in whom this was the dominant symptom. In 1 patient a small ovarian remnant implanted on the bladder was removed at subsequent laparoscopy. Preliminary experience of this procedure suggest it may be preferable to laparotomy because of the reduced risk of wound complications, pain, time in hospital and duration of convalescence.

Adolescent↗