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Biomedical subjects

P Hall

Publications and source records attributed to P Hall.

At least 163 records · Page 9Linked to original sources

Detection of intratumoral aromatase in breast carcinomas. An immunohistochemical study with clinicopathologic correlation.

The expression of aromatase was evaluated in 38 breast carcinomas by an immunohistochemical method (ABC) using an specific polyclonal antibody against human placental aromatase. Fifteen tumors (40%) showed significant immunoreactivity, as defined by cytoplasmic positivity of moderate intensity present in at least 15% of the cells. The results were correlated with the estrogen and progesterone hormone receptor status and several clinicopathologic parameters such as age, tumor size, lymph node status, and stage of the disease. There was a significant, but inverse, correlation between the aromatase activity and the estrogen receptor status (P = 0.04), indicating the likelihood of negative estrogen if substantial aromatase activity was present. No statistically significant correlation was found between the presence of intratumoral aromatase and the rest of the parameters studied (P greater than 0.7). Nor was there a correlation between the aromatase content of the tumors and the menopausal status. The degree of intratumoral heterogeneity of the aromatase content was minimal in six cases where multiple samples from each tumor were analyzed. This is the first study reporting the detection of aromatase in archival material from breast carcinomas using immunohistochemical techniques. The lack of biologic significance of its presence in breast cancer reported here and by others using biochemical assays should be validated in larger series with longer follow-up. The method described can be readily used for that objective.

Aromatase↗

The Salmonella typhimurium locus mviA regulates virulence in Itys but not Ityr mice: functional mviA results in avirulence; mutant (nonfunctional) mviA results in virulence.

The virulent Salmonella typhimurium strain WB600 carries the mviA allele of the gene mouse virulence A. As shown here, the virulent phenotype of WB600 is the result of a nonfunctional mviA gene. As compared to the functional allele mviA+, mviA increases virulence in Itys mice, but not in Ityr mice. A specific BglII site, mviA4185, between osmZ and galU, located at approximately 35 min on the salmonella chromosome, was within mviA. Insertion of an antibiotic cassette in the mviA4185 site of mviA+ or the homologous mviA4093 site of mviA DNA resulted in virulence when either cassette was recombined into the chromosome. When mviA and mviA+ were both expressed in the same strain with one carried in the chromosome and the other on a plasmid, avirulence was dominant. Replacement of the mviA allele of strain WB600 using P22 transductions of linked antibiotic cassettes cloned into the chromosome of virulent S. typhimurium strains (SR-11, TML, SL1344, C5, ATCC14028, W118-2, and WB600) showed that all but WB600 contained the avirulent mviA+ allele. Southern hybridizations provided no evidence for a second mviA allele anywhere in the genome of the six non-WB600 strains.

Alleles↗

Cancer risk after iodine-131 therapy for hyperthyroidism.

Cancer incidence was studied in 10,552 patients (mean age, 57 years) who received 131I therapy (mean dose, 506 MBq) for hyperthyroidism between 1950 and 1975. Follow-up on these patients was continued for an average of 15 years. Record linkage with the Swedish Cancer Register for the period 1958-1985 identified 1543 cancers occurring 1 year or more after 131I treatment, and the standardized incidence ratio (SIR) was 1.06 (95% confidence interval = 1.01-1.11). Significantly increased SIRs were observed for cancers of the lung (SIR = 1.32; n = 105) and kidney (SIR = 1.39; n = 66). Among 10-year survivors, significantly elevated risks were seen for cancers of the stomach (SIR = 1.33; n = 58), kidney (SIR = 1.51; n = 37), and brain (SIR = 1.63; n = 30). Only the risk for stomach cancer, however, increased over time (P less than .05) and with increasing activity administered (P = not significant). The risk for malignant lymphoma was significantly below expectation (SIR = 0.53; n = 11). Overall cancer risk did not increase with administered 131I dose or with time since exposure. The absence of any increase in leukemia adds further support to the view that a radiation dose delivered gradually over time is less carcinogenic than the same total dose received over a short time. Only for stomach cancer was a possible radiogenic excess suggested.

Adolescent↗

Brachial approach to management of an abdominal aortic occlusion with prolonged lysis and subsequent angioplasty.

The brachial approach for recanalizing an abdominal aortic occlusion utilizing a combination of thrombolysis and balloon angioplasty is described. The patient was deemed too ill to permit any surgical intervention. The unique aspects of the procedure are described including angioplasty of the unmasked (by lytic therapy) aortoiliac bifurcation stenoses utilizing double wires and double balloons through a single arteriotomy site. The advantages of the brachial approach in managing this unusual entity are outlined.

Aged↗

Successful rotational coronary ablation following failed balloon angioplasty.

Rotational coronary ablation was utilized in two cases in which balloon angioplasty initially failed. In both cases, the balloon could not be fully expanded despite using high (18 Bar) inflation pressure. Rotational coronary ablation debulked the lesion, in each instance, and permitted successful balloon angioplasty to be accomplished without difficulty. These cases illustrate the point that complementary deployment of devices may not only improve the primary success of percutaneous coronary interventions, but also may widen its scope.

Aged↗

Urokinase infusion of chronically occluded femoropopliteal Gortex bypass grafts via the popliteal approach.

Thrombolysis of two occluded above-knee femoropopliteal Gortex bypass grafts utilizing the popliteal approach for catheter placement was successfully performed without complication. In both cases, the proximal anastomoses of the graft could not be identified. A percutaneous popliteal approach was used for catheter placement and delivery of urokinase. Angioplasty was performed on the unveiled stenoses that, presumptively, led to graft closure. Selective thrombolysis via catheter placed from popliteal approach is a new technique for recanalization of occluded femoropopliteal bypass grafts and warrants further investigation.

Aged↗

National High Blood Pressure Education Program (NHBPEP) review paper on complications of shock wave lithotripsy for urinary calculi.

This decade has witnessed dramatic advances in the surgical management of urinary calculi. Today, most stones can be removed by minimally invasive means. In fact, the treatment of choice in 60% to 90% of patients with renal and ureteral calculi that need to be surgically removed is extracorporeal shock wave lithotripsy (ESWL). This article reviews indications for ESWL and discusses deleterious effects of ESWL.

Animals↗

A hemA mutation renders Salmonella typhimurium avirulent in mice, yet capable of eliciting protection against intravenous infection with S. typhimurium.

The hemA mutation reduces the virulence of Salmonella typhimurium for mice by at least 10(7)-fold, as measured by change in LD50. The hemA mutation does not appear to affect killing of salmonella in mice. The salmonella with the hemA mutation persist in the spleen and liver for 2 to 3 weeks following intravenous injection. The most likely effect of the hemA mutation is to block, or retard, growth of S. typhimurium in an aerobic in vivo environment. Intravenous vaccination of susceptible ltys mice with hemA salmonella was able to elicit about 4 logs of protection against invasive infection with wild-type S. typhimurium 78 days after vaccination, at a time when the vaccine strain was no longer detectable in the spleen and liver.

Aldehyde Oxidoreductases↗

Cancer risks in thyroid cancer patients.

Cancer risks were studied in 834 thyroid cancer patients given 131I (4,551 MBq, average) and in 1,121 patients treated by other means in Sweden between 1950 and 1975. Record-linkage with the Swedish Cancer Register identified 99 new cancers more than 2 years after 131I therapy [standardised incidence ratio (SIR) = 1.43; 95% confidence interval (CI) 1.17-1.75] vs 122 (SIR = 1.19; 95% CI 0.88-1.42) in patients not receiving 131I. In females treated with 131I overall SIR was 1.45 (95% CI 1.14-1.83) and significantly elevated were noted for tumours of the salivary glands, genital organs, kidney and adrenal gland. No elevated risk of a subsequent breast cancer or leukaemia was noted. SIR did not change over time, arguing against a strong radiation effect of 131I. Organs that were estimated to have received more than 1.0 Gy had together a significantly increased risk of a subsequent cancer following 131I treatment (SIR = 2.59; n = 18). A significant trend was seen for increasing activities of 131I with highest risk for patients exposed to greater than or equal to 3,664 MBq (SIR = 1.80; 95% CI 1.20-2.58). No specific cancer or group of cancers could be convincingly linked to high-dose 131I exposures since SIR did not increase after 10 years of observation. However, upper confidence intervals could not exclude levels of risk that would be predicted based on data from the study of atomic bomb survivors. We conclude that the current practice of extrapolating the effects of high-dose exposures to lower-dose situations is unlikely to seriously underestimate radiation hazards for low LET radiation.

Female↗

High dose combination chemotherapy with ifosfamide, cyclophosphamide or cisplatin, mitomycin C and mustine with autologous bone marrow support in advanced non-small cell lung cancer. A phase I/II study.

Twenty-three patients with advanced NSCLC were treated with high dose chemotherapy using four agents and autologous bone marrow reinfusion. Ten patients received two bolus doses of cyclophosphamide (maximum tolerated total dose 10 G m-2), ifosfamide as a 24 h infusion (11 G m-2) followed by mitomycin C (70 mg m-2) as a subsequent 24 h infusion and mustine as two boluses (total dose 30 mg m-2). Another 13 patients received the same agents except cisplatin was substituted for cyclophosphamide, two doses (total dose 100 mg m-2) being given in a 24 h period. The median time of recovery to greater than or equal to 20,000 platelets was 21 days and of neutropaenia greater than or equal to 500 was 12-15 days. Unusual non-haematological toxicity e.g. cardiomyopathy, colitis, veno occlusive disease was not noted, all patients being given regular selenium and other trace elements. Three patients died in the first 2 weeks. There were five complete responses (22%) and 12 partial responses (52%) with four patients (2CR, 2PR) still alive at 27, 48, 73 and 82 weeks. The patient's Karnofsky performance in the cisplatin regimen improved over pretreatment values when compared a month after the end of treatment. The high dose regimen was associated with a high (74%) response rate, but with an overall median survival of only 6 months. The regimen has no advantage over conventional doses with the same agents in patients with metastatic NSCLC.

Adult↗

Percutaneous coronary angioplasty in 1,001 multivessel coronary disease patients: an analysis of different patient subsets.

The prospectively collected data of 1,001 multivessel coronary disease patients who underwent percutaneous transluminal angioplasty (PTCA) was analyzed after categorization into single vessel angioplasty (SVA; group I) and multiple vessel angioplasty (MVA; group II) PTCA groups, which were each compartmentalized into "simple" (group A) and "complex" (group B) cohorts. Patients were assigned to the SVA or MVA group according to the physician's pre-PTCA assessment of how many lesions would be attempted (intention to treat) and not the number of lesions actually attempted. A "simple" patient was more likely than a "complex" patient to be clinically improved after PTCA whether or not the patient had a single dilatation (90% vs 78%; P less than 0.05) or multiple dilatations (97% vs 94%; P<0.05). Similarly, a lesion(s) was more likely to be successfully dilated in the "simple" than in the "complex" group (SVA: 90% vs 82%, P less than 0.05; MVA: 97% vs 91%, P<0.05). In addition, occluded vessels in the MVA group were more likely to be recanalized than in the SVA group (73% vs 44%, P less than 0.05). Group I-A patients had a significantly increased (10%) incidence of emergency bypass surgery. Follow-up, at 84 months, showed that "simple" cohorts had a better survival than the "complex" cohorts (MVA: 95% vs 71%, P less than 0.05; SVA: 90% vs 72%, P less than 0.05); and, nearly two thirds of all successful PTCA patients were angina free.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗

The impact of the Healthiest Babies Possible Program on maternal diet and pregnancy outcome in underweight and overweight clients.

The Healthiest Babies Possible Program (HBP) is a prenatal intervention program for the City of Toronto and is designed to reduce the incidence of low birth weight babies. This study was undertaken to assess the impact of the HBP on dietary change and birth outcome for underweight and overweight expectant mothers. Dietary change was measured by the use of food scores applied to 24-hour dietary recalls throughout the pregnancy. Three recalls collected during the early stage of the program were selected to represent early interventions; three of the results collected during the latter stage of the program represent the late stage of intervention. Birth outcome was determined by weight gain and infant birth weight. For both groups, food scores improved throughout the early intervention period and the improvements were sustained through the remainder of the program. During pregnancy the underweight women gained more weight than the overweight women but delivered infants with lower birth weights.

Adult↗

Effects of single-dose infusion of pyridoxalated-hemoglobin-polyoxyethylene conjugate solution on canine renal function.

Pyridoxalated-hemoglobin-polyoxyethylene conjugate (PHP) is an acellular oxygen-carrying red blood cell substitute made from outdated human red blood cells. This study assessed the effect of PHP on renal function when PHP was infused with a clinically relevant dosage. A single dose of PHP that contains 8% wt/vol each of hemoglobin and maltose or an 8% maltose control solution was infused into the intact circulation of eight dogs (five dogs for PHP and three for the control; 20 ml/kg each, at the rate of 2.5 ml/h/kg for 8 h) in the awake state. Serial measurements of glomerular filtration rate (GFR) and renal plasma flow (RPF) were carried out before and after infusion for up to 2 weeks, along with determinations of urine volume flow rate, fractional excretion of sodium (FES), and free water clearance (CH2O). The results showed an elevation of plasma colloid osmotic pressure by an average of 4.4 mm Hg immediately postinfusion with PHP solution. An average 23% decrease in GFR, without notable changes in RPF immediately postinfusion, was observed in the PHP group; the value returned to the preinfusion level by 1 week postinfusion. Increases in parameters such as urine output, FES, and CH2O, which were more pronounced in the PHP group, were observed for 24 h after the infusion in both groups. Light microscopic examination of kidney specimens taken at 2 weeks postinfusion revealed a slight degree of vacuole formation in approximately 80% of the proximal tubules in the PHP group. The tubules were devoid of typical pathologic features of acute renal failure, and the vacuoles did not cause any observable changes in the assessed tubular functions.

Animals↗

The primary effect of the Ity locus is on the rate of growth of Salmonella typhimurium that are relatively protected from killing.

The Ity locus affects the net increase in numbers of Salmonella typhimurium in the liver and spleen of infected mice. There has been controversy, however, about whether the effects of this locus are due to differential killing of S. typhimurium or differential growth rates of S. typhimurium in mice. Our studies using S. typhimurium aroA mutants, which do not grow in vivo, demonstrate that growth of the infecting salmonella is necessary for the observation of the Ity phenotype. To examine the effects of the Ity locus on the growth and killing of fully virulent salmonella, we infected Ity-congenic mice i.v. with stationary phase S. typhimurium containing a single copy of the plasmid pHSG422. This plasmid exhibits defective replication at body temperature and is diluted out during salmonella growth in vivo. Thus, the frequency of plasmid-containing salmonella recovered from mice provides a measure of salmonella cell divisions in vivo. Inasmuch as the numbers of plasmid-containing salmonella are only slightly affected by bacterial division, any decline in the numbers of plasmid-containing salmonella is an unbiased measure of killing. By infecting mice with these plasmid-containing salmonella we observed that: 1) during the first four h post infection (during blood clearance of injected salmonella) there is about 3-fold more killing of salmonella in Ityr mice than in Itys mice; 2) from 4 to 44 h postinfection (after blood clearance is completed) there is little if any additional killing in either Itys or Ityr mice; and 3) during the first 48 h postinfection there is about 18-fold more growth of salmonella in Itys mice than in Ityr mice. Thus, the major effect of the Ity locus on resistance to salmonella, is the regulation of growth within a "safe" (relatively nonbactericidal) site in the liver and spleen.

Animals↗

The effect of complete and incomplete revascularization on exercise variables in patients undergoing coronary angioplasty.

To investigate the effects of complete and incomplete revascularization on the response to exercise, 25 patients underwent symptom-limited exercise testing with continuous assessment of gas exchange a mean of 5 +/- 4 days prior to and 18 +/- 12 days following percutaneous transluminal coronary angioplasty. All antianginal medications were discontinued for testing. Revascularization was considered complete if all stenoses were reduced to less than 50% diameter (13 patients), and incomplete if one or more stenoses remained (12 patients). Consistent improvements in ST-segment depression were observed after angioplasty at matched submaximal exercise levels (mean range 0.5-0.8 mm; p less than 0.05), and were accompanied by a reduction in angina. Significant increases in heart rate and systolic blood pressure were observed at peak exercise following angioplasty in both groups. Gas exchange variables were significantly improved at maximal exercise, with a similar increase in oxygen uptake observed in both groups following angioplasty (mean increase 3.3-3.7 ml/kg/min; p less than 0.01). Thus, incomplete revascularization following coronary angioplasty resulted in hemodynamic, electrocardiographic, symptomatic, and gas exchange responses to exercise that were comparable to complete revascularization.

Adult↗