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Biomedical subjects

S Wallace

Publications and source records attributed to S Wallace.

At least 73 records · Page 4Linked to original sources
PubMed1999

The legal and risk management conundrum of telemedicine.

A store-and-forward teledermatology service was established between two general practices and the department of plastic surgery at Derriford Hospital in Plymouth. An academic lawyer and an expert in risk management made an assessment of the service. They looked at the following issues: medicolegal problems; security; confidentiality; and risk. None of them was considered insoluble and there is no reason why such issues should prevent the National Health Service from developing telemedicine services. All organizations considering telemedicine need to ensure that the proposed telemedicine service satisfies the issues raised in this study.

Computer Security↗
PubMed1999

Selective hepatic arterial chemoembolization for liver metastases in patients with carcinoid tumor or islet cell carcinoma.

In many patients with liver metastases from islet cell or carcinoid tumor, vascular occlusion therapy results in prolonged control of symptoms, biochemical response, and also tumor regression. Chemotherapy agents were added to evaluate safety and efficacy. Thirty patients with liver metastases from either carcinoid tumor or islet cell carcinoma underwent sequential vascular occlusion therapy combined with chemotherapeutic agents. In patients with carcinoid tumor, a combination of cisplatin (150 mg) and doxorubicin (50 mg) was used. In patients with islet cell carcinoma, a combination of 5-fluorouracil (350 mg) and streptozotocin (1000-2000 mg) was used. Sixteen patients had carcinoid tumor and 14 had islet cell carcinoma. Biochemical response was observed in 12 of 16 (75%) carcinoid patients and 9 of 10 (90%) islet cell patients. The overall partial response rate was 37% (11/30 patients). Partial response occurred in 4 of 16 (25%) patients with carcinoid tumor and 7 of 14 (50%) with islet cell carcinoma. The median duration of partial responses was 24 months (range, 6-63+ months). The median survival of all patients was 15 months (range, 2-67+ months). No treatment-related deaths occurred. Our data suggest that the addition of these chemotherapeutic agents to vascular occlusion, although safe, has no additional benefit.

Adult↗
PubMed1999

Antitumor activity of poly(L-glutamic acid)-paclitaxel on syngeneic and xenografted tumors.

Poly(L-glutamic acid)-paclitaxel (PG-TXL) is a new water-soluble paclitaxel derivative that has shown remarkable antitumor activity against both ovarian and breast tumors. The purpose of this study was to test whether the antitumor efficacy of PG-TXL depends on tumor type, as is the case for paclitaxel, and to test whether paclitaxel-resistant tumors could be responsive to PG-TXL. We evaluated the therapeutic activity of PG-TXL against four syngeneic murine tumors (MCa-4, MCa-35, HCa-1, and FSa-II) inoculated i.m. into C3Hf/Kam mice, a human SKOV3ip1 ovarian tumor injected i.p. into nude mice, and a human MDA-MB-435Lung2 breast tumor grown in the mammary fat pad of nude mice. Two paclitaxel-responsive murine tumors, MCa-4 and MCa-35, showed significant growth delay with PG-TXL given as a single i.v. injection at its maximum tolerated dose of 160 mg of equivalent paclitaxel/kg or even at a lower dose of 120 mg of equivalent paclitaxel/kg. The other two murine tumors, HCa-1 and FSa-II, did not respond particularly well to either of the two agents, although significant growth delay was observed for both tumors with PG-TXL. In mice with SKOV3ip1 tumors, the median survival times for mice treated with PG alone and PG-TXL at doses of 60 or 120 mg of equivalent paclitaxel/kg were 43, 61, and 75 days, respectively; no survival difference was found between paclitaxel-treated and Cremophor vehicle-treated mice. In mice with MDA-MB-435Lung2 tumor, PG-TXL at a dose of 120 mg of equivalent paclitaxel/kg produced regression of the tumor in 50% of the animals, and in the remaining mice, micrometastases in the lung were found only in 25% of the animals. In comparison, treatment with paclitaxel at 60 mg/kg did not result in tumor regression, and the rate of lung metastases was 42%. These results clearly demonstrate that PG-TXL has significant therapeutic activity against breast and ovarian tumors tested in this study. Future studies to elucidate the mechanism of action of PG-TXL and to assess its clinical applications are warranted.

Animals↗
PubMed1998

Complete regression of well-established tumors using a novel water-soluble poly(L-glutamic acid)-paclitaxel conjugate.

Despite an intensive search, few water-soluble paclitaxel derivatives have been shown to have a therapeutic index superior to paclitaxel itself. We now report a water-soluble poly(L-glutamic acid)-paclitaxel conjugate (PG-TXL) that produces striking antitumor effects with diminished toxicity. A single i.v. injection of PG-TXL at its maximum tolerated dose (defined as that dose that produces a maximum 12-15% body weight loss within 2 weeks after a single i.v. injection) equivalent to 60 mg of paclitaxel/kg and at even a lower dose equivalent to 40 mg of paclitaxel/kg resulted in the disappearance of an established implanted 13762F mammary adenocarcinoma (mean size, 2000 mm3) in rats. (An equivalent dose of PG-TXL is the amount of conjugate that contains the stated amount of paclitaxel.) Similarly, mice bearing syngeneic OCA-1 ovarian carcinoma (mean size, 500 mm3) were tumor-free within 2 weeks after a single i.v. injection of the conjugate at a dose equivalent to 160 mg of paclitaxel/kg. The conjugate has little if any intrinsic tubulin polymerization activity in vitro and is >20 times less potent in supporting the growth of a paclitaxel-dependent CHO mutant cell line. PG-TXL has a prolonged half-life in plasma and greater uptake in tumor as compared with paclitaxel. Furthermore, only a small amount of total radioactivity from PG-[3H]TXL was recovered as free [3H]paclitaxel in either the plasma or the tumor tissue within 144 h after drug injection. Histological studies of tumor tissues obtained from mice treated with PG-TXL show fewer apoptotic cells but more extensive tumor necrosis as compared with paclitaxel treatment. These data suggest that in addition to its role as a carrier for selective delivery of paclitaxel to the tumor, PG-TXL exerts distinct pharmacological actions of its own that may contribute to its remarkable antitumor efficacy.

Animals↗
PubMed1998

Role of indium-111 labelled platelet scintigraphy in the management of thrombocytopenic patients with malignant neoplasms.

This study was done to investigate the role of indium-111 labelled platelet scintigraphy in the treatment of thrombocytopenia in patients with malignant neoplasms. The study involved 20 consecutive patients with thrombocytopenia associated with malignant neoplasms of hematological disorders and without evidence of underproduction of megakaryocytes due to chemotherapy or bone marrow infiltration by the malignancy. Splenic sequestration of platelets was evaluated by measuring splenic uptake of 111In-labelled platelets, and findings were correlated with the outcome of splenectomy and medication. Of the 20 patients, 13 had splenic sequestration of platelets. Seven of the 13 patients underwent splenectomy; six of these seven patients experienced a complete response. The other six patients received medication only and showed no response. Of the seven patients without splenic sequestration of platelets, five received medication, and four of them responded to it. 111In-labelled platelet scintigraphy has a role in selecting appropriate therapy and predicting its efficacy in patients with thrombocytopenia associated with malignant neoplasms.

Adult↗
PubMed1998

Standard linear plans in single channel high dose rate brachytherapy: a dosimetric analysis.

The use of standard linear plans is proposed for single channel intraluminal High Dose Rate brachytherapy. This technique employs the optimized dwell times derived from a straight line within a curved geometry. Such standardization of the planning procedure ensures expedient delivery of treatment. The 3-D dose distribution resulting from the use of standard linear plans within various curved geometries is investigated. In this study a comparison is made between the dose delivered to the perimeter of the target volume from both standard linear plans and individually optimized plans. Our results demonstrate that the use of a standard linear plan is acceptable in curved geometries, given the current practice of dose and volume specification for high dose rate intraluminal brachytherapy.

Brachytherapy↗
PubMed1998

Epilepsy needs revisited: a revised epilepsy needs document for the UK.

We revisit epilepsy needs in the United Kingdom, and update our previous publication to take into account new epidemiological data, changes in investigation and treatment and trends in the organization of health and other caring agencies. This document attempts to define and quantify the scope, content and standards of services required, from primary care settings to specialized centres. Reference is also made to the role of other agencies.

Adult↗
PubMed1998

An audit of children referred with suspected epilepsy.

Members of the British Paediatric Neurology Association were invited to participate in a national audit of children presenting with a possible diagnosis of epilepsy. The audit was based on a 'standard' or set of pre-determined questions drawn up by an advisory audit group. The audit form comprised a total of 30 questions divided into four sections addressing history, examination, investigation, treatment and communication. Information for the audit was obtained retrospectively from the child's case notes. Each participating centre or consultant was asked to audit the case notes of 20 children. At the end of the 12-month recruitment period three centres responded, contributing audit forms on 50 children. The required information was provided for the majority of the questions in each of the four sections, thereby meeting the audit 'standard'. Within the history section, only 32 of the 50 (64%) case notes had recorded whether or not there was 'any obvious provoking factor or circumstance to the episodes'. Communication was the least satisfactorily completed section with between none and 48% of the case notes documenting that the child's family had been informed of the existence of a voluntary epilepsy organization. Despite the simplicity of the audit form, the response for this national audit was considerably lower than anticipated.

Adolescent↗
PubMed1998

Ultrastructure, immunofluorescence, western blot, and PCR analysis of eight isolates of Encephalitozoon (Septata) intestinalis established in culture from sputum and urine samples and duodenal aspirates of five patients with AIDS.

Microsporidia are ancient, intracellular, eukaryotic protozoan parasites that form spores and that lack mitochondria. Currently, as many as eight species included under six genera are known to infect humans, mostly patients with AIDS. Among these, Enterocytozoon bieneusi, the agent of gastrointestinal (GI) disease, is the most frequently identified microsporidian in clinical laboratories in the United States. Encephalitozoon (Septata) intestinalis, the agent that causes a disseminated infection including infection of the GI tract, is the second most frequently identified microsporidian parasite. In spite of this, not many isolates of E. intestinalis have been established in culture. We describe here the continuous cultivation of eight isolates of E. intestinalis obtained from different samples including the urine, sputum, and duodenal aspirate or biopsy specimens from five AIDS patients originating from California, Colorado, and Georgia. The specific identification was made on the bases of ultrastructural, antigenic, and PCR analyses.

AIDS-Related Opportunistic Infections↗
PubMed1998

Telemedicine in the NHS for the millennium and beyond.

This article defines telemedicine, discusses evidence of its effectiveness, looks at its advantages and disadvantages (and barriers to implementation), and considers its role in the NHS for the millennium and beyond.

Diffusion of Innovation↗
PubMed1998

Idiopathic progressive hyalinizing and calcifying CNS vasculopathy.

We present a female adolescent with intermittently progressive neurologic deficits over a period of 7 years. Serial imaging studies showed a calcifying lesion with increasing enhancement, signal abnormalities from the subcortex to the medulla, and hemispheric volume loss. Stereotactic biopsies disclosed a hyalinizing and calcifying vasculopathy involving the penetrating vessels. The vasculopathy may result in ischemic lesions responsible for the severe deficits.

Adolescent↗
PubMed1998

Two-phase study of hepatic artery vascular occlusion with microencapsulated cisplatin in patients with liver metastases from neuroendocrine tumors.

OBJECTIVE: We conducted a two-phase trial in which 100-micron polylactic acid microcapsules with a cisplatin payload (manufactured at our institution [the M. D. Anderson Cancer Center]) were used for hepatic artery occlusion therapy for symptomatic patients who had liver metastases from neuroendocrine tumors. SUBJECTS AND METHODS: Between January 1993 and December 1995, 20 patients with advanced, unresectable, symptomatic neuroendocrine tumors with liver metastases received repeated hepatic artery occlusion therapy using encapsulated cisplatin. The dose of encapsulated cisplatin was increased in a stepwise fashion. Selective angiography was used to occlude the portion of the hepatic vasculature that had the most metastases with encapsulated cisplatin microcapsules. In each patient, hepatic artery occlusion therapy was repeated in 6-8 weeks and responses were evaluated. Subsequent vascular occlusions were performed on the basis of the level of palliation achieved and the persistence of symptoms. RESULTS: Of the 20 patients, 17 patients had carcinoid tumors and three had islet cell tumors. The median percentage of liver replacement was approximately 50%. Fifteen of the 20 patients had received prior therapy and 17 patients had hormonal syndrome at the beginning of therapy. One patient had tumor bulk-related symptoms. Nineteen patients had elevated peptides markers that could be followed serially Six patients received encapsulated cisplatin at 50 mg/m2, four patients at 75 mg/m2, and 10 patients at 100 mg/m2 of body surface area. The median number of vascular occlusive procedures per patient was three. All patients were assessable for toxicity and 18 were assessable for response (the other two patients were not assessable because of loss of follow-up). The median follow-up time was 14 months. Twelve (67%) of 18 patients had a median reduction in symptoms of 50%. Eleven (73%) of 15 patients with elevated 24-hr-urine levels of 5-hydroxyindoleacetic acid had a median reduction of 64% for this symptom. We observed objective reduction in the tumors of 14 of the 18 patients. In six of the 14 patients, we noted a partial response. In eight, we observed a minor response. In four of the 18 patients, we noted no response. One treatment-related death resulted from hepatorenal syndrome. Other major complications included hepatic pain (100%), fever (100%), nausea (100%), and vomiting (95%). Also all patients had a transient elevation of liver enzymes. Five of the 20 patients died of disease during our study. CONCLUSION: Hepatic artery vascular occlusion therapy using encapsulated cisplatin is feasible, can palliate symptoms, and can produce biochemical and objective responses in liver metastases from neuroendocrine tumors. The maximum tolerated dose appears to be 100 mg/m2 of body surface area per treatment. Polylactic acid capsules have potential because they can incorporate multiple agents. With surface coating, such capsules can also be used to target specific receptors.

Adenoma, Islet Cell↗
PubMed1998

Identification of the microsporidian Encephalitozoon hellem using immunoglobulin G monoclonal antibodies.

OBJECTIVE: Microsporidia isolated from clinical specimens so far have been identified to level of species by electron microscopy, indirect immunofluorescence (IIF), western blot (WB), and genetic analysis. Recent studies, however, indicate extensive serologic cross-reactions among microsporidian species involved in human disease. DESIGN AND SETTING: In this study, we used IIF and WB techniques to evaluate the reactivity of six different immunoglobulin G monoclonal antibodies (MAbs) raised against Encephalitozoon hellem with six isolates of E hellem that originated from patients with acquired immunodeficiency syndrome. A rabbit isolate of Encephalitozoon cuniculi, and an isolate of Encephalitozoon intestinalis, which was established in cultures from the urine of a patient with acquired immunodeficiency syndrome were also used for comparison. RESULTS: Five of the six antibodies, when analyzed by both IIF and WB assays, specifically identified six isolates of E hellem originating from three patients with acquired immunodeficiency syndrome. The sixth MAb, however, reacted with all of the E hellem isolates in the WB assay, but failed to react with them in the IIF assay. Using the IIF test, five of the six MAbs failed to react with E cuniculi and E intestinalis, even at a dilution of 1:50. The MAbs also did not react in the IIF test with Enterocytozoon bieneusi, Giardia, and Cryptosporidium. These MAbs did react with E cuniculi and E intestinalis in the WB assay, but the banding patterns were very different from those of E hellem, thus facilitating the identification of E hellem from the other microsporidia. The MAbs also reacted, in the IIF test, with E hellem spores in formalin-fixed tissue sections that were heated in a microwave oven. CONCLUSIONS: Identification of microsporidian agents to the species level is important. Since certain therapeutic agents (eg, fumagillin, albendazole) are efficacious in treating E hellem infections of the cornea, as well as urogenital and respiratory infections caused by E hellem, a quick and definitive identification of the organism is important so that successful therapy may be instituted. An IIF test using the MAbs described here would therefore be invaluable in the quick identification of this parasite.

Animals↗
PubMed1998

Monte Carlo dosimetry of the microselectron HDR 192Ir brachytherapy source using MCNP4A.

This study examines the transverse radial dose distribution around the Nucletron MicroSelectron high dose rate (HDR) 192Ir brachytherapy source using the Monte Carlo radiation transport code MCNP (Monte Carlo N Particle) version 4A. The geometry modeled consisted of an identical simulation of the geometry of the MicroSelectron HDR source within the centre of a cylindrical water phantom of 80 cm diameter and height. Doses were calculated at 0.1 cm intervals in the 1 cm closest to the source, whilst extending to 1 cm intervals 15 cm from the source. Conversion to the clinically relevant unit of air-kerma strength to describe source activity enables absolute comparison of Monte Carlo dose calculations to current treatment planning computer results. Most HDR brachytherapy planning computers utilise algorithms based on a point source with attenuation and scatter corrections based on the Van Kleffen and Starr or Meisberger equations. Significant differences between the planning computer algorithms and the Monte Carlo dose calculations occur in the near field (radius less than 1 cm) and the far field (radius greater than 8 cm) which in some cases may have important clinical consequences. These results are consistent with Monte Carlo calculations of previous authors examining the MicroSelectron HDR 192Ir source and also show that far field uncertainties are increased as the size of the phantom is reduced to a more realistic patient size.

Brachytherapy↗
PubMed1998

CT based 3D Monte Carlo radiation therapy treatment planning.

This paper outlines the "voxel reconstruction" technique used to model the macroscopic human anatomy of the cranial, abdominal and cervical regions directly from CT scans. Tissue composition, density, and radiation transport characteristics were assigned to each individual volume element (voxel) automatically depending on its greyscale number and physical location. Both external beam and brachytherapy treatment techniques were simulated using the Monte Carlo radiation transport code MCNP (Monte Carlo N-Particle) version 3A. To obtain a high resolution dose calculation, yet not overly extend computational times, variable voxel sizes have been introduced. In regions of interest where high attention to anatomical detail and dose calculation was required, the voxel dimensions were reduced to a few millimetres. In less important regions that only influence the region of interest via scattered radiation, the voxel dimensions were increased to the scale of centimetres. With the use of relatively old (1991) supercomputing hardware, dose calculations were performed in under 10 hours to a standard deviation of 5% in each voxel with a resolution of a few millimetres--current hardware should substantially improve these figures. It is envisaged that with coupled photon/electron transport incorporated into MCNP version 4A and 4B, conventional photon and electron treatment planning will be undertaken using this technique, in addition to neutron and associated photon dosimetry presented here.

Abdomen↗
PubMed1997

Transcatheter liver lobar ablation: an experimental trial in an animal model.

Complete embolization of tumor tissue together with surrounding liver sufficiently prevents collateral blood supply to the tumor, offering curative treatment for hepatic malignancies. The present experiment was designed to test the feasibility of hepatic lobar ablation by means of the transcatheter chemoembolization technique. Five groups of rats (n = 6) were treated with a mixture of iodized oil/ethanol in ratios of 5:1, 4:1, 3:1, 1:1, and 1:0, which was injected selectively into the right-lobe artery until saturation during open surgery. Another group (n = 6) was studied using in vivo microscopy to observe the distribution of the mixture in the liver and changes in hepatic microcirculation. Ethiodol/ethanol mixture entered the portal vein after injection into the hepatic artery creating dual, complete arterial and portal venous embolization. Lobar ablation effects were achieved in 2 weeks in the 5:1, 4:1, and 3:1 ratio groups, indicated by the lobe/liver weight measurements (p < 0.001 vs normal liver). Hepatic arterial administration of the Ethiodol/ethanol mixture creates dual hepatic arterial and portal venous embolization, achieving a lobar ablation effect.

Animals↗
PubMed1997

Pulmonary microsporidiosis due to Encephalitozoon hellem in a patient with AIDS.

The microsporidian Encephalitozoon hellem is being reported with increasing frequency in HIV-positive subjects, as an agent of disseminated microsporidiosis without involving the gastrointestinal tract. We describe a case of pulmonary microsporidiosis in a 27-year-old Italian man with AIDS who developed fever, cough, and dyspnea. A chest X-ray showed multiple bilateral pulmonary opacities and mediastinal lymph-node enlargement. Stained smears of bronchoalveolar lavage sediment showed oval structures consistent with microsporidian spores. Viral, bacterial and fungal cultures were repeatedly negative, whereas microsporidia were successfully cultured in human and bovine fibroblast cell lines. Analysis of electron micrographs indicated that the isolate belonged to the genus Encephalitozoon. Based on further immunological, biochemical and molecular studies it was characterized as E. hellem. Even though a temporary improvement with albendazole therapy was noticed, the patient deteriorated clinically and died of severe respiratory distress.

AIDS-Related Opportunistic Infections↗