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Biomedical subjects

A Porter

Publications and source records attributed to A Porter.

At least 73 records · Page 4Linked to original sources
PubMed1995

12(S)-HETE is a mitogenic factor for microvascular endothelial cells: its potential role in angiogenesis.

12(S)-HETE [12(S)-hydroxyeicosatetraenoic acid] is a lipoxygenase metabolite of arachidonic acid. Treatment of murine-lung-derived microvascular endothelial cells (CD clone 4) with exogenous 12(S)-HETE promoted wound healing of injured endothelial cell monolayers. 12(S)-HETE, in a time- and dose-dependent manner, enhanced the growth of CD clone 4 cells. Thymidine incorporation assays demonstrated that 12(S)-HETE increased the DNA synthesis by > 4 fold. In addition, normal endothelial cell growth stimulated by serum could be dose-dependently inhibited by a select 12-lipoxygenase inhibitor (BHPP), suggesting that 12(S)-HETE is a physiological mitogenic factor for microvascular endothelial cells.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1995

Quality-adjusted survival analysis of malignant glioma. Patients treated with twice-daily radiation (RT) and carmustine: a report of Radiation Therapy Oncology Group (RTOG) 83-02.

PURPOSE: To quantify the quality of life of malignant glioma patients treated on a randomized Phase I/II trial of twice-daily radiation therapy (RT) and carmustine, using a modified quality adjusted survival (QAS) model, and to compare the QAS among assigned treatment arms. MATERIALS AND METHODS: The Radiation Therapy Oncology Group (RTOG) accrued 786 malignant glioma patients to a Phase I/II randomized dose escalation trial of twice-daily RT with carmustine from 1983 to 1989. Patients were randomized to one of four arms of hyperfractionated RT in 1.2 Gy twice daily (BID) fractions (64.8 Gy, 72.0 Gy, 76.8 Gy, or 81.6 Gy) or to either of two accelerated hyperfractionated RT arms in 1.6 Gy BID fractions (48.0 or 54.4 Gy). Although preliminary toxicity and survival data have been published, little information is available regarding the quality of these patients' lives during and following such therapy. QAS is a refinement of the methodology for assessing survival quality among breast cancer patients receiving adjuvant chemotherapy. The QAS method allows for inclusion of both improvement and decline in neurologic functional status. Patients were scored by the presence or absence of 15 neurologic signs and symptoms at on-study and at every follow-up. Within each category were gradations of severity, with the quality survival time (Q-TIME) adjusted according to any changes in these neurologic findings. The summation of all changes in signs and symptoms were weighted by 1/15th and incorporated into the QAS model as QAS = Q-TIME-TOX-RRX. TOX was the time spent with treatment-related toxicities, and RRX was the time spent in recovery from subsequent therapy. RESULTS: Of 747 evaluable patients, the average QAS time was 18.5 months. The average QAS for the hyperfractionated arms of 64.8 Gy, 72.0 Gy, 76.8 Gy, and 81.6 Gy were 15.6, 20.8, 10.0, and 13.7 months, respectively. For the accelerated hyperfractionated RT arms of 48.0 and 54.4 Gy, the average QAS times were 13.1 and 13.4 months. The QAS time of the 72.0 Gy arm was significantly longer than that of all other groups, except the 64.8 Gy arm. As expected, the QAS times were strongly discriminated by both age and Karnofsky Performance Scores (KPS) (p < 0.001). Younger patients and patients with high KPS benefited most from assignment to the 72.0 Gy arm; QAS time was not significantly longer in any treatment arm among patients over age 50 or with KPS scores of 80 or less. CONCLUSIONS: This quality-adjusted survival methodology can be successfully applied to malignant glioma patients and permits a quantitative assessment of the influence of investigational therapies on patient quality of life. This analysis confirms the potential benefit of intermediate dose (72.0 Gy) hyperfractionated RT for selected malignant glioma patients.

Adult↗
PubMed1995

Survey of brachytherapy practice in the United States: a report of the Clinical Research Committee of the American Endocurietherapy Society.

PURPOSE: To obtain reliable data on the extent of the brachytherapy practice in the United States by conducting a comprehensive survey of all facilities. METHODS AND MATERIALS: The Clinical Research Committee of the AES surveyed all 1321 radiation oncology facilities identified in the Patterns of Care Study (PCS) of the American College of Radiology (ACR). Multiple mailings and follow-up were made to obtain a high response rate. Survey responders and nonresponders were compared using chi-square tests. Summary statistics were reported. RESULTS: Of the 1321 facilities, 1054 responded (80%). Hospital-based and larger facilities had a statistically significant higher rate of response. Brachytherapy was being performed at 819 facilities (the median number of procedures = 21-50). Two hundred and two facilities did no brachytherapy. The common isotopes used were 137Cs (705 facilities), 192Ir (585 facilities), 125I (236 facilities), and 131I (194 facilities). The common brachytherapy techniques used were intracavitary (751 facilities), interstitial (536 facilities), intraluminal (310 facilities), and plaques (148 facilities). Remote afterloaded brachytherapy was used at 205 centers as follows: high dose rate (HDR) (164), medium dose rate (MDR) (5), and low dose rate (LDR) (36). Computerized dosimetry was most commonly used (790 facilities), followed by Patterson-Parker (104 facilities) and Quimby (72 facilities). The common sites treated were cervix (701 facilities), endometrium (565 facilities), head and neck (354 facilities), and lung (344 facilities). CONCLUSION: Data regarding brachytherapy practice has been obtained from a large percentage (80%) of all facilities in the United States. The majority (78-81%) of radiation oncology facilities perform brachytherapy; however, its use is restricted to gynecological implants in many of these centers. The results from this survey will be used to develop a pattern of care study and data registry in brachytherapy.

Brachytherapy↗
PubMed1995

Functional discrepancies between tumor necrosis factor and lymphotoxin alpha explained by trimer stability and distinct receptor interactions.

Tumor necrosis factor (TNF) and lymphotoxin alpha (LT alpha) are closely related cytokines which bind with nearly identical affinities to the same pair of cell surface receptors, p55 and p75TNFR. Therefore it is assumed that TNF and LT alpha are redundant cytokines. This study, however, demonstrates that TNF and LT alpha differ significantly with regard to their mitogenic and cytotoxic potentials. LT alpha's superior mitogenic effect could be explained by its formation of a more stable trimer. In contrast to the TNF trimer, which disintegrated under physiological conditions into biologically inactive monomers, the LT alpha trimer remained stable for several days. Accordingly, LT alpha more effectively induced fibroblast growth which demands long-term presence of the cytokine. TNF's superior cytotoxicity, which requires only short-term impact of the cytokine, could be attributed to a distinct interaction with the human p55TNFR. This was demonstrated in NIH 3T3 cells transfected with the human p55TNFR, where cytotoxicity is mediated exclusively by the transfected receptor. Although the p55ATNFR had virtually identical affinities for TNF and LT alpha, as defined by Scatchard analysis, it nevertheless discriminated between binding of each cytokine and showed a 200-fold enhanced cytotoxicity mediated by TNF.

3T3 Cells↗
PubMed1995

Atypical skeletal tuberculosis.

Tuberculosis remains a major cause of skeletal infection in many parts of the world. With the advent of acquired immune deficiency syndrome (AIDS) and mass emigration from underdeveloped to industrialized nations this past decade, a new patient population is being encountered in which extrapulmonary tuberculosis is not uncommon and atypical presentations may confuse the diagnosis. Our recent experience with an unusual presentation has prompted this report.

Adult↗
PubMed1995

Cephalad sacral resection with a combined extended ilioinguinal and posterior approach.

A combined anterior and posterior approach was used for the resection of a large tumor (a chordoma, a giant-cell tumor, an osteosarcoma, or a chondrosarcoma) of the cephalad part of the sacrum in twelve patients. The anterior aspect of the sacrum was exposed through an extended ilioinguinal approach, and the posterior aspect, through a midline approach. This widely extensile procedure permitted simultaneous visualization of the anterior, posterior, and circumferential aspects of the sacrum at the time of the osteotomy and facilitated the resection of these difficult lesions. At the time of follow-up (average duration for the eleven surviving patients, thirty-seven months; median, thirty months; range, twenty to sixty-nine months), ten patients were able to walk independently (four with the use of a cane) and one was confined to a wheelchair. One patient had died immediately postoperatively. The results of the present study indicate that a combined extended ilioinguinal and posterior approach can be used effectively for the wide resection of a tumor arising in the cephalad part of the sacrum.

Adult↗
PubMed1994

God's fools.

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Biological Evolution↗
PubMed1994

Helicobacter pullorum sp. nov.-genotype and phenotype of a new species isolated from poultry and from human patients with gastroenteritis.

Campylobacter-like organisms were isolated from the liver, duodenum and caecum of broiler and layer chickens, and from humans with gastroenteritis. They formed a unique DNA homology group and a polyphasic taxonomic analysis was made of 16 strains. Analysis of the nucleotide sequence of the 16S rRNA gene from seven of the strains identified them as belonging to a single species, within the genus Helicobacter. This conclusion was supported by the studies of relative DNA homology and of total protein electrophoretic patterns. The new species could be biochemically differentiated from other helicobacters and its ultrastructure in the electron microscope was typical of the genus except that the flagellum was not sheathed. We propose the name Helicobacter pullorum sp. nov. for this group. Like H. fennelliae or H. cinaedi it represents another non-gastric urease-negative Helicobacter species colonizing the lower bowel. Its isolation from the livers of chickens with vibrionic hepatitis is significant. We describe a species-specific PCR assay for H. pullorum sp. nov. which will facilitate its identification and further studies of its epidemiology.

Animals↗
PubMed1994

Nazi doctors.

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Anthropology, Cultural↗
PubMed1993

Identification of a new receptor subtype for tumor necrosis factor-alpha.

Two distinct receptors, which bind both tumor necrosis factor-alpha and tumor necrosis factor-beta (TNF-alpha and TNF-beta), have been previously identified and cloned from transformed cells. The present study identifies a novel receptor subtype in normal human liver which binds TNF-alpha but not TNF-beta. TNF-alpha but not TNF-beta competes for 125I-TNF-alpha binding and incorporation into affinity-labeled complexes in human liver plasma membranes (HLPM). Antisera to the cloned receptors competed for 125I-TNF-alpha binding to plasma membranes isolated from various transformed cell lines but not to HLPM. However, mRNAs corresponding in size to both known TNF receptors were detected in liver RNA, making it likely that post-transcriptional modifications account for the TNF-alpha specificity of HLPM. These observations suggest that the effects of TNF-alpha and TNF-beta on some normal tissues may be more distinct than previously realized.

Antibodies, Monoclonal↗
PubMed1993

Combined modality program with possible organ preservation for invasive bladder carcinoma: results of RTOG protocol 85-12.

PURPOSE: This Phase II study was designed to test the tolerance and effectiveness of concurrent cisplatin-radiotherapy in the treatment of invasive bladder cancer. Objectives were to determine toxicity, complete response rate, bladder preservation rate, and survival. METHODS AND MATERIALS: Patients with invasive bladder cancer, clinical Stages T2-4, NO-2 or NX, MO were treated with pelvic radiotherapy 40 Gy in 4 weeks and cisplatin 100 mg/m2 on days 1 and 22. Complete responders were given an additional 24 Gy bladder boost plus a third dose of cisplatin; patients with residual tumor after 40 Gy were assigned radical cystectomy. RESULTS: The complete remission rate following cisplatin and 40 Gy for evaluable cases was 31/47 (66%). Acute toxicity was acceptable with only two patients not completing induction therapy. Patients with poorly differentiated tumors were more likely to achieve complete remission. Of fully evaluable patients, 28/42 (67%) achieved complete remission with induction therapy, 11 remain continuously in remission, and eight have relapsed with bladder as the only site of failure. Five of these eight cases relapsed with noninvasive tumor. Of the 14 patients who failed to achieve complete remission, only three remain disease-free. Median survival is not reached, with 17/42 (19/48) deaths reported. Actuarial survival is 64% at 3 years. CONCLUSION: This combined cisplatin-radiotherapy regimen was moderately well-tolerated and associated with tumor clearance in 66% of patients treated. Isolated bladder recurrences with invasive carcinoma are infrequent. Better definition of pretreatment selection criteria is needed if combined modality treatment is to achieve disease control and organ preservation for patients with bladder cancer.

Adult↗
PubMed1993

Helicobacter canis sp. nov., a new species from dogs: an integrated study of phenotype and genotype.

A group of Campylobacter-like organisms (CLOs) were isolated from the faeces of diarrhoeic or healthy dogs, constituting 4% of all CLOs from this source. Since they formed a unique DNA homology group within the genus Helicobacter, and exhibited distinctive phenotypic properties, they were collectively termed the HC group. A polyphasic taxonomic analysis was made of this group. The phenotype of four dog isolates and a single human isolate was unique and could be distinguished bacteriologically from other helicobacters. Electron microscopic ultrastructure revealed defining characteristics of Helicobacter. The 16S rRNA gene of the nominated type strain NCTC 12739T was sequenced, and its analysis delineated the group as a new species of Helicobacter. This conclusion was supported by relative DNA homology and whole-cell protein electrophoretic patterns. We therefore propose the name Helicobacter canis sp. nov. for this group. The species most closely related to H. canis sp. nov. were H. cinaedi, 'Flexispira rappini' and H. fennelliae. A species-specific recombinant DNA probe was cloned from NCTC 12739T for use in routine laboratory identification and epidemiological studies. The faecal source, bile tolerance and lack of urease activity of H. canis sp. nov. suggest that this new Helicobacter species colonizes the lower bowel rather than the stomach.

Animals↗
PubMed1992

Effects of amiodarone on erect and supine exercise haemodynamics and exercise capacity in patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a primary heart muscle disease associated with a high incidence of sudden death. Amiodarone is of benefit in those patients with a high risk profile for sudden death. Amiodarone has also been reported to improve symptoms dramatically in some patients with HCM but to cause functional deterioration in others. In the acute phase of oral amiodarone therapy there are few discernable changes in cardiovascular haemodynamics and the mechanisms of any beneficial effects on symptoms remain unclear. To determine the effect of amiodarone on exercise responses we measured haemodynamic indices in 10 patients during maximal supine- and symptom-limited erect treadmill exercise before and 6 weeks after amiodarone therapy. Following amiodarone therapy there was a significant reduction in resting and peak heart rate during erect exercise (76 +/- 13 vs 97 +/- 19 b.min-1; P = 0.001 and 114 +/- 26 vs 146 +/- 21 b.min-1; P = 0.001 respectively). Despite increases in peak pulmonary and systemic artery pressures with amiodarone therapy there was no difference in the peak left ventricular filling pressure or maximum cardiac output achieved. Similarly, during supine exercise the resting and peak heart rates were less following the 6 weeks amiodarone therapy. Comparison of supine and erect exercise haemodynamic indices demonstrated higher peak LV filling and higher peak systolic and pulmonary artery pressures during supine than during erect exercise (29 +/- 10 vs 25 +/- 12; P less than 0.04; 151 +/- 42 vs 126 +/- 48; P = 0.01 and 66 +/- 27 vs 62 +/- 21; P = 0.08 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

HIV-1 and HIV-2 infection in children in Abidjan, Côte d'Ivoire.

We conducted a study of 1,003 well and hospitalized children, birth to 5 years old, in Abidjan, Côte d'Ivoire, to determine the prevalence of HIV-1 and HIV-2 infection, evaluate risk factors for infection, and describe associated clinical characteristics. The overall seroprevalence was significantly higher for children in the hospital (10.8%) than for those attending the clinic (3.6%). HIV-1 was the predominant virus in both populations, comprising 87% (hospital) and 77% (clinic) of the seroreactive blood specimens. Ninety-two percent of seroreactive children of all ages had a mother who was HIV positive; 77% of seroreactive children greater than or equal to 15 months old had an HIV-infected mother. The remaining seropositive children had a history of receiving blood transfusions. Hospitalized children who were HIV-1 positive or dually seroreactive were more likely to have HIV-related clinical signs and symptoms than HIV-negative children. These findings suggest that HIV infection is an important cause of morbidity for children in Abidjan and that maternal infection is the primary risk factor for both HIV-1 and HIV-2 infection in children. Further evaluation and attention should be given to transmission, clinical characteristics, and the impact of HIV infection in children in West Africa, where both HIV-1 and HIV-2 are present.

Child, Preschool↗
PubMed1992

The long-term effects of 5-fluorouracil and sodium butyrate on human Tenon's fibroblasts.

The use of subconjunctival 5-fluorouracil (5-FU) in the first weeks after filtration surgery may ensure long-term bleb survival despite a continuing proliferative stimulus such as in eyes with neovascular glaucoma. In addition, long-term side effects may occur, such as increasing bleb thinning. To ascertain the long-term effects of 5-FU and sodium butyrate, an agent with differentiating and antiproliferative properties, we exposed proliferating human Tenon's capsule fibroblasts to different concentrations of the drugs. The cells were exposed to 5-FU for 1-12 d. The cells were subsequently observed for up to 30 d. Cell proliferation was assessed using cell counting and bromodeoxyuridine uptake, and cell viability was assessed with trypan blue uptake. 5-FU and sodium butyrate inhibited fibroblast proliferation during the treatment period. Higher concentrations of 5-FU (100 and 1000 micrograms/ml) for as little as 1 d resulted in no significant increase in the number of fibroblasts for at least 29 d after treatment was stopped, despite continued stimulation with serum. When treatment with sodium butyrate was stopped, there was greater recovery of proliferation. At a constant concentration of 1000 micrograms/ml of 5-FU for 3 or more days, or a concentration of 100 mmol/l sodium butyrate for 12 d, the entire fibroblast population gradually died over the 30 d period. Thus, short-term treatment with 5-FU may result in long-term inhibition of proliferation of fibroblasts. Long-term inhibition depends on the duration of treatment or on the concentration of 5-FU. Short-term treatment may be affecting the ability of the tissues at the bleb site to heal in the long term. Different dosage regimens may have advantages and are discussed.

Adolescent↗
PubMed1991

Cross-reactivity on western blots in HIV-1 and HIV-2 infections.

To examine cross-reactivity of antibodies to heterologous antigens, on HIV-1 and HIV-2 Western blots, we tested sera from 1362 consecutive tuberculosis (TB) patients and 2127 consecutive blood donors. Specimens positive on enzyme-linked immunosorbent assay (ELISA) for HIV-1 or HIV-2 were further characterized by synthetic peptide-based tests, and tested by HIV-1- and HIV-2-specific Western blots. Dual serologic reactivity on synthetic peptide tests was proportionately more frequent in HIV-positive TB patients than in blood donors, and HIV-2 reactivity less frequent. Positive HIV-1 Western blots were seen in 73-83% of specimens specifically characterized as positive for HIV-2 on synthetic peptide tests. Cross-reactivity to HIV-2 Western blots by HIV-1-positive specimens was significantly more frequent in TB patients (35%) than in asymptomatic donors (9%; P less than 0.001). Using recently recommended criteria for HIV-2 Western blot interpretation (presence of two env bands) reduced the overall proportion of HIV-1-positive specimens having a positive HIV-2 Western blot from 27.5 to 16.4%, with [corrected] minimal effect on sensitivity in the diagnosis of HIV-2 reactivity on specimens positive on synthetic peptide tests.

Blotting, Western↗