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Biomedical subjects

J M Malone

Publications and source records attributed to J M Malone.

At least 19 recordsLinked to original sources

Receptors for 1,25-dihydroxyvitamin D3 in gynecologic neoplasms.

To determine if gynecologic malignancies are candidates for 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) therapy we measured vitamin D receptor (VDR) levels in 11 tumor specimens using a radiolabeled ligand-binding assay. VDR was demonstrated in 3 of 6 ovarian tumors and 1 of 1 uterine sarcomas, but not in endometrial tumors (2), cervical tumors (1), or Krukenberg tumors (1). Scatchard plots revealed that [3H]1,25(OH)2D3 was bound to a single class of high-affinity (Kd = 0.3 to 0.6 nM), saturable sites characteristic of authentic 1,25(OH)2D3 receptors. Specificity of binding activity for 1,25(OH)2D3, the active vitamin D3 metabolite, was demonstrated by failure of 25-hydroxy- and 24,25-dihydroxyvitamin D3 to compete effectively against 1,25(OH)2D3 binding in total cellular tumor extracts. The ovarian carcinoma cell line NIH:OVCAR3 was shown to possess VDR (binding capacity = 137 fmol/mg protein, Kd = 0.48 nM). A 3-day incubation of NIH:OVCAR3 cells with 100 nM 1,25(OH)2D3 resulted in 49% inhibition of cell growth. The growth inhibition of an ovarian carcinoma line and the observation that 36% of gynecologic tumors assayed were shown to be VDR-positive suggest that further study is warranted to delineate the mechanism and possible therapeutic aspects of 1,25(OH)2D3 action in gynecologic tumors.

Calcitriol

Management of small artery vascular trauma.

This 11-year retrospective study reviewed 99 arterial injuries distal to the brachial bifurcation or popliteal trifurcation in 89 extremities in 88 patients. Associated injuries occurred in 78 of 88 (89%) patients, including 10 fractures or dislocations, 66 nerve injuries, and 59 single or multiple tendon injuries. Fasciotomy was performed in 9 upper extremities and 11 lower extremities (23% of patients). The selection of operative treatment by arterial repair or ligation was by surgeon choice (52% repair and 48% ligation). Postoperative patency was found in 45 of 47 (96%) repaired arteries. In cases of isolated single arterial injuries (10), there were excellent results, and there was no difference in the results between repair and ligation. In cases of nonisolated single arterial injuries (69), there were 46% and 36% nonvascular complications in the repaired and ligated groups, respectively. In 10 patients with nonisolated multiple arterial injuries in the same extremity, the results of repair of one artery with ligation of the other artery versus repair of both arteries were identical, and there were no vascular complications. Operative exploration was the key to complete evaluation of vascular and neuro/musculoskeletal injuries. The data suggest that one functional artery distal to the elbow or knee is sufficient for limb viability and vascular function (follow-up range: 0 to 110 months; mean: 12 months). Nerve injury was the single most important factor of extremity injury in terms of the degree of functional loss.

Adolescent

Major complications of angioaccess surgery.

Angioaccess procedures at one institution over a 4-year period were retrospectively reviewed to ascertain the frequency of major limb- or life-threatening complications. A total of 435 angioaccess procedures were performed, including 81 Cimino-Brescia fistulas, 166 polytetrafluoroethylene grafts, and 111 thrombectomy/revisions. There were 77 operations for major complications in 53 patients. In addition, five patients required major vascular repair or emergency thoracotomy for complications of central hemodialysis line placement. A significant portion (18% of this series) of the total angioaccess caseload of a vascular surgeon will be utilized in the repair of major complications. The in-hospital (6 patients, or 11%) and long-term (12 patients, or 23%) mortality rates are significant. Although most complications can be repaired without limb loss and with shunt salvage, a small percentage (in our study three patients, or 4%) will have debilitating long-term symptoms.

Adult

The use of medicinal leeches in the salvage of flaps with venous congestion.

The use of medicinal leeches (Hirudo medicinalis) for the salvage of tissues with venous congestion has been intermittent over the last two centuries. During the last decade, interest in leech therapy has undergone a resurgence. Hirudo's tricuspid bite injects a highly potent anticoagulant. The site usually bleeds for 1 to 2 hours and under special circumstances may bleed for up to 24 hours. This collective series presents four patients in whom immediate postoperative venous congestion threatened the survival of three tissue replants and one latissimus dorsi flap. Two of the replants were completely salvaged; the other two failed due to infection. Hirudo medicinalis is an important adjunct in preventing flap or replant failure secondary to venous congestion, but its use is associated with significant risks.

Adolescent

Randomized prospective double-blind trial in healing chronic diabetic foot ulcers. CT-102 activated platelet supernatant, topical versus placebo.

OBJECTIVE: To assess the efficacy of topically applied CT-102 APST for treating diabetic neurotrophic foot ulcers. RESEARCH DESIGN AND METHODS: Thirteen patients entered a randomized, double-blind trial of topically applied CT-102 APST vs. placebo (normal saline) gauze dressings for the treatment of nonhealing diabetic neurotrophic foot ulcers. CT-102 APST (Curative Technologies, Setauket, NY) was prepared from homologous platelets and contained multiple growth factors including PDGF, PDAF, EGF, PF-4, TGF-beta, aFGF, and bFGF. Inclusion criteria for subjects included diabetes, ulcer of > 8 wk duration, peri-wound transcutaneous oxygen tension > 30 mmHg, platelet count > 100,000/mm3, and no wound infection. Wounds were excised before entry and were > 700 mm3 but < 50,000 mm3 in volume, < 100 cm2 in area, and involved subcutaneous tissue. RESULTS: In the CT-102 group, 5 of 7 ulcers were healed (100% epithelialized) by 15 wk, but only 1 of 6 ulcers was healed by 20 wk with placebo (P < 0.05). Average percent reduction in ulcer area at 20 wk was 94% for CT-102 vs. 73% for placebo. Daily reduction in ulcer volume was 73.8 +/- 42.4 mm3/day (mean +/- SE) for CT-102 vs. 21.8 +/- 8.1 mm3/day for placebo (P < 0.05). Daily reduction in ulcer area was 6.2 +/- 1.8 mm2/day for CT-102 vs. 1.8 +/- 0.4 mm2/day for placebo (P < 0.05). CONCLUSIONS: CT-102 significantly accelerated wound closure in diabetic leg ulcers when administered as part of a comprehensive program for the healing of chronic ulcers.

Chronic Disease

The influence of vascular certification on lower extremity revascularization at one institution.

The potential impact of vascular certification on the practice of vascular surgery at Maricopa Medical Center (Phoenix, AZ) was analyzed by comparison of lower extremity revascularization results over consecutive 2-year periods before (Period I) and after (Period II) institution of vascular surgery service. The overall setting (county hospital, surgical residency) and ancillary services (Anesthesia, Intensive Care Unit, Radiology) were unchanged, except for the authors' use of invasive hemodynamic support. In Period I, there were 49 cases (30 inflow, 19 outflow) with 14 per cent (7/49) mortality, 32 per cent (21/67) limb thrombosis or embolus, and 10 per cent (5/49) graft infection; 80 per cent (39/49) of operations were done for claudication; 20 per cent (10/49) were done for inappropriate indications (P less than 0.005). In Period II, there were 110 cases (47 inflow, 63 outflow). The increase in cases was predominantly due to increased use of extra-anatomic inflow and complex infrapopliteal outflow reconstructions. Seventy per cent (77/110) of operations were done for limb salvage; of 17 aortic cases, 3 were "re-do's" and 5 underwent simultaneous renal revascularization. There was a 3 per cent (4/110) mortality (P less than 0.025), 11 per cent (13/137) limb thrombosis or embolus (P less than 0.005), and no graft infections (P less than 0.001). Lower extremity revascularization delivered by certified vascular surgeons was offered to more patients with lower overall mortality and morbidity rates after more thorough diagnostic work-up and for more appropriate indications, with concomitant use of more refined vascular techniques/procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors

Bilateral traumatic internal carotid artery dissections: case report.

Bilateral internal carotid artery dissections after blunt cervicofacial trauma are rare, with 16 cases being previously published. Management is presumed to be an extension of the dominant therapy for unilateral dissection, that being anticoagulant therapy; however, bilateral stenoses engender questions of threat to total cerebral blood flow. We herein present a patient who suffered bilateral type B dissections and who then had progression of the process on anticoagulant therapy, resulting in an unusual carotid reconstruction.

Adult

Combination chemotherapy for advanced adenocarcinoma of the cervix.

A patient with advanced adenocarcinoma of the cervix was treated only with cisplatin and mitomycin C (MMC). The regimen achieved a complete response, confirmed by chest radiograph and computed axial tomography scan, lasting 50 months. The patient is alive with recurrent disease 59 months after diagnosis. No severe drug-related toxicity occurred.

Adenocarcinoma, Mucinous

Combined effects of 1,25-dihydroxyvitamin D3 and platinum drugs on the growth of MCF-7 cells.

The effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and platinum treatments (both singly and combined) on the growth inhibition of MCF-7 cells, an epithelial cell line shown to possess specific receptors for 1,25(OH)2D3, were evaluated. The inhibitory effects of 1,25(OH)2D3 and platinum on MCF-7 cell proliferation in vitro were time and dose related. The data showed that 10 nM and 100 nM 1,25(OH)2D3 inhibited MCF-7 cell growth by 10.8 +/- 2.4% and 34.9 +/- 0.5% (mean +/- SE), respectively. The degrees of growth inhibition induced by 0.2 to 200 micrograms/ml of cis-diammine-1,1-cyclobutane dicarboxylatoplatinum(II) (carboplatin) were slightly less than those induced by 0.02 to 20 micrograms/ml of cis-diamminedichloroplatinum(II) (cisplatin). The combined administration of 10 nM and 100 nM 1,25(OH)2D3 with either carboplatin (200 to 0.2 micrograms/ml) or cisplatin (20 to 0.02 micrograms/ml) was evaluated. Addition of 1,25(OH)2D3 to the platinum resulted in marginal to marked enhancement of growth inhibition over that observed with either platinum alone. The strength of these interactions varied inversely with the dose of the platinum drugs. Evaluation of drug interactions with isobolograms showed that at near-serum levels, carboplatin or cisplatin interacted synergistically with 1,25(OH)2D3 to inhibit MCF-7 cell growth. Our findings suggest potential usefulness in combining 1,25(OH)2D3, a biological modifier, with cytotoxic agents for the treatment of malignant disease.

Ascites

Cervical dysplasia in the postmenopausal female: diagnosis and treatment.

Thirty-two postmenopausal women, age 50 years or older, were colposcoped for abnormal Papanicolaou (PAP) smears. Sixteen had mild to moderate dysplasia, six severe dysplasia and the remainder had no dysplasia. Treatment included observation, topical estrogen, cryotherapy, conization or hysterectomy. Based upon our observations, satisfactory colposcopy can be performed in the majority of postmenopausal women. Oral or topical estrogen is a valuable adjunct in the initial evaluation and treatment of abnormal PAP smears in postmenopausal women. Criteria for adequate colposcopy in postmenopausal women are discussed and a management scheme is proposed.

Aged

A preliminary report of combination chemotherapy with cisplatin and mitomycin-C followed by radical hysterectomy or radiation therapy in patients with locally advanced cervical cancer.

Neoadjuvant chemotherapy with cisplatin and mitomycin-C was used in the primary treatment of 17 patients with locally advanced cervical cancer (stages Ib-IIIb; tumor diameter greater than 5 cm) prior to definitive local treatment with radical hysterectomy or radiotherapy. Thirteen of the seventeen patients (76.5%) responded to initial chemotherapy, permitting a radical hysterectomy in ten patients. At histologic examination of the surgically resected primary tumor and lymph nodes, complete pathologic responses were found in 2 patients and partial pathologic responses in 8 patients. The median follow-up time is 14.5 months with a median survival for all patients of 52 weeks. All responders are alive. No therapy-related deaths, major complications, or delay in treatment occurred. Neoadjuvant chemotherapy with mitomycin-C and cisplatin is feasible and may be of benefit for patients with locally advanced cervical cancer.

Adult

High-dose-rate afterloading brachytherapy, external radiation therapy, and combination chemotherapy in poor-prognosis cancer of the cervix.

Fourteen patients with poor-prognosis cervical cancer were treated with concurrent chemotherapy (cisplatin and mitomycin-C), external radiation therapy (RT), and high-dose-rate (HDR) brachytherapy. Pelvic RT was delivered as (a) external-beam radiation (four-field box technique, 40.0 Gy), (b) brachytherapy using HDR 60Co or 192Ir (3.80 Gy/fraction, thrice weekly; total dose, 46.83 Gy) with intrauterine stent, and (c) parametrial boost using an AP field with custom-fabricated step wedges. Post-radical-hysterectomy patients received 50.40 Gy external RT and 3.23 Gy/day vaginal cylinder HDR at 1/2-cm depth (total dose, 16.15 Gy). Complete clinical and radiographic response was noted in all evaluable patients who are alive with no evidence of disease, 3 to 27 months after completion of therapy (median, 9 months). Toxicity consisted of grade 2 to 3 hematologic toxicity (4 patients) and nausea and vomiting in all, but grade 3 in only 2 patients. One patient had grade 2 diarrhea. The only major complication (small bowel obstruction) occurred in a patient with lupus vasculitis. This pilot study demonstrates the feasibility of this regimen in an outpatient setting with acceptable toxicity. More prolonged follow-up of our patients is required to determine its impact on long-term survival.

Antineoplastic Combined Chemotherapy Protocols

Ureteroinguinal hernia: a rare companion of sliding inguinal hernias.

Ureteroinguinal herniation is a rare occurrence with only 54 reported cases in the English literature. This article reviews the literature and reports on a case that typifies the problems posed by ureteroinguinal herniation. General surgeons should be aware of the potential of this condition so that they can prevent ligation or severance of the involved ureter.

Aged

Detoxifying enzymes in human ovarian tissues: comparison of normal and tumor tissues and effects of chemotherapy.

Many anticancer drugs exert their cytotoxic effects via formation of oxygen free radicals. Cellular thiols, glutathione (GSH)-dependent enzymes and other redox enzymes are involved in the metabolism of these anticancer drugs and of the oxygen free radicals that may be generated during their metabolism. We quantified these biochemical parameters in cytosol from human ovarian tissues. We compared non-protein thiol levels, GSH transferase, GSH peroxidase, superoxide dismutase, catalase, DT diaphorase and aldehyde dehydrogenase activity in serous ovarian tumors (n = 15), other malignant ovarian tumors (n = 12), benign ovarian tissue (n = 10) and histologically normal ovarian tissue (n = 12). Mean GSH transferase and DT diaphorase activities were similar in serous and other malignant ovarian tumors. GSH transferase activity was decreased in malignant tissues relative to normal and benign tissues. Mean DT diaphorase and superoxide dismutase activities were increased in the malignant tissues, although this was not statistically significant. The mean levels of all enzymes except superoxide dismutase and aldehyde dehydrogenase in benign tissues were fairly similar to the mean levels found in normal tissue samples. Tissues from patients with serous ovarian tumors, who had received cyclophosphamide and cisplatin prior to surgery, also were analyzed (n = 7). Except for aldehyde dehydrogenase, all the parameters measured were decreased in these samples relative to serous tissue from untreated patients. These biochemical analyses may be useful in understanding the mechanisms involved in the response to chemotherapy.

Adult

Frequency of vascular injury with blunt trauma-induced extremity injury.

Vascular injury associated with select blunt trauma-induced orthopedic injuries is thought to occur frequently enough to require angiography in most cases. We sought to establish the actual frequency of such vascular injuries by reviewing all orthopedic and vascular patients seen during 4 years at one institution. A total of 569 at-risk parajoint fractures or dislocations were seen with a 1.5% incidence of vascular injury; all were recognized on clinical examination and vascular consultation then obtained. Vascular injury in this setting is uncommon, associated with particular clinical presentations, and recognized by the orthopedic surgeon, without need for routine angiography or vascular consultation.

Arm Injuries

AIDS/HIV infection and employment.

It is now emerging that most large employment sectors have HIV carriers on their staff. Usually occupation has not contributed to the aetiology of the employee acquiring HIV infection. Pre-employment HIV screening has been rejected, although there have been exceptions to this generally accepted position. Having known or suspected HIV carriers in an organisation poses major challenges for occupational health departments, which can have a major influence on management attitudes. Health promotion, training and education have an important role to play in ensuring an informed and non-emotive response occurs at all levels in the work setting.

Acquired Immunodeficiency Syndrome

Debulking of pelvic and para-aortic lymph node metastases in ovarian cancer with the cavitron ultrasonic surgical aspirator.

Six patients with metastatic ovarian cancer with extensive involvement of the pelvic and/or para-aortic lymph nodes underwent surgical debulking with the Cavitron Ultrasonic Surgical Aspirator. Intraoperative and postoperative morbidity was minimal. It is suggested that this technique may be used for cytoreductive surgery in combination with standard surgical techniques.

Adult

Gastric outlet obstruction caused by traumatic pseudoaneurysm of superior mesenteric artery.

Traumatic pseudoaneurysms of the superior mesenteric artery (SMA) are extremely rare. We describe two cases of posttraumatic proximal SMA pseudoaneurysms with symptoms of gastric outlet obstruction. Repair was accomplished by aorta-SMA bypass with saphenous vein. Injuries to the proximal SMA are easily missed at laparotomy, especially if intestinal ischemia or hematomas are absent. Recognition and repair are stressed to avoid the complications associated with pseudoaneurysm formation.

Adult