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Biomedical subjects

S A Allen

Publications and source records attributed to S A Allen.

At least 19 recordsLinked to original sources
PubMed2005

Evaluation of ER, PgR, HER-2 and Ki-67 as predictors of response to neoadjuvant anthracycline chemotherapy for operable breast cancer.

Primary systemic therapy (PST) for operable breast cancer enables the identification of in vivo biological markers that predict response to treatment. A total of 118 patients with T2-4 N0-1 M0 primary breast cancer received six cycles of anthracycline-based PST. Clinical and radiological response was assessed before and after treatment using UICC criteria. A grading system to score pathological response was devised. Diagnostic biopsies and postchemotherapy surgical specimens were stained for oestrogen (ER) and progesterone (PgR) receptor, HER-2 and cell proliferation (Ki-67). Clinical, radiological and pathological response rates were 78, 72 and 38%, respectively. There was a strong correlation between ER and PgR staining (P < 0.0001). Higher Ki-67 proliferation indices were associated with PgR- tumours (median 28.3%, PgR+ 22.9%; P = 0.042). There was no relationship between HER-2 and other biological markers. No single pretreatment or postchemotherapy biological parameter predicted response by any modality of assessment. In all, 10 tumours changed hormone receptor classification after chemotherapy (three ER, seven PgR); HER-2 staining changed in nine cases. Median Ki-67 index was 24.9% before and 18.1% after treatment (P = 0.02); the median reduction in Ki-67 index after treatment was 21.2%. Tumours displaying >75% reduction in Ki-67 after chemotherapy were more likely to achieve a pathological response (77.8 vs 26.7%, P = 0.004).

Adult↗
PubMed2002

Use of implantable cardioverter defibrillator and anti-arrhythmic agents in a parturient.

We describe a case of a 36-yr-old patient who presented at 14 weeks gestation with multifocal dysrrhythmic episodes. Despite treatment with anti-arrythmic agents and an implantable cardioverter defibrillator (ICD) in situ, she continued to experience persistent dysrrhythmic episodes. She was delivered by Caesarean section at 34 weeks under general anaesthesia. We discuss some of the anaesthetic challenges of parturients with ICD devices.

Adult↗
PubMed2001

Virologic and immunologic determinants of heterosexual transmission of human immunodeficiency virus type 1 in Africa.

More than 80% of the world's HIV-infected adults live in sub-Saharan Africa, where heterosexual transmission is the predominant mode of spread. The virologic and immunologic correlates of female-to-male (FTM) and male-to-female (MTF) transmission are not well understood. A total of 1022 heterosexual couples with discordant HIV-1 serology results (one partner HIV infected, the other HIV uninfected) were enrolled in a prospective study in Lusaka, Zambia and monitored at 3-month intervals. A nested case-control design was used to compare 109 transmitters and 208 nontransmitting controls with respect to plasma HIV-1 RNA (viral load, VL), virus isolation, and CD4(+) cell levels. Median plasma VL was significantly higher in transmitters than nontransmitters (123,507 vs. 51,310 copies/ml, p < 0.001). In stratified multivariate Cox regression analyses, the risk ratio (RR) for FTM transmission was 7.6 (95% CI: 2.3, 25.5) for VL > or = 100,000 copies/ml and 4.1 (95% CI: 1.2, 14.1) for VL between 10,000 and 100,000 copies/ml compared with the reference group of <10,000 copies/ml. Corresponding RRs for MTF transmission were 2.1 and 1.2, respectively, with 95% CI both bounding 1. Only 3 of 41 (7%) female transmitters had VL < 10,000 copies/ml compared with 32 of 93 (34%) of female nontransmitters (p < 0.001). The transmission rate within couples was 7.7/100 person-years and did not differ from FTM (61/862 person-years) and MTF (81/978 person-years) transmission. We conclude that the association between increasing plasma viral load was strong for female to male transmission, but was only weakly predictive of male to female transmission in Zambian heterosexual couples. FTM and MTF transmission rates were similar. These data suggest gender-specific differences in the biology of heterosexual transmission.

Adolescent↗
PubMed2001

Pre-operative estimation of primary breast cancer size: a comparison of clinical assessment, mammography and ultrasound.

This prospective study aimed to determine which is the most precise modality for the pre-operative measurement of primary breast cancers: clinical palpation; mammography; or ultrasound. Analysis of the difference between the measurement of the maximum tumour diameter by these three modalities and by the histological measurement was performed in 210 cases. Clinical palpation tended to overestimate tumour size and gave the largest standard deviation of the difference. Ultrasound and mammography both gave a similar standard deviation of the difference, with ultrasound tending to underestimate tumour size. For all modalities, the standard deviation and the 95% confidence intervals of the difference increased with increasing tumour size. There is little difference between the precision of ultrasound and mammography in measuring tumour size. The wide 95% confidence intervals for any method of pre-operative tumour measurement should be considered when planning patient management.

Journal Article↗
PubMed2001

Chest wall thickness measurements and the dosimetric implications for male workers in the uranium industry.

The Human Monitoring Laboratory has measured the chest wall thickness and adipose mass fraction of a group of workers at a Canadian uranium refinery, a conversion plant, and a fuel fabrication site using ultrasound. A site-specific biometric equation has been developed for these workers, who seem to be somewhat larger than other workers reported in the literature. Chest wall thickness is a very important modifier on lung counting efficiency and these data have been put into the perspective of the impending Canadian dose limits that will reduce the limit of occupationally exposed workers to 100 mSv in a 5-y period with a maximum of 50 mSv in any one year. The sensitivity of the germanium and phoswich based lung counting systems have been compared. Over a range of chest wall thickness of 1.6 cm to 6.0 cm and using a 30-min counting time, the achievable MDA's lie in the range of 6.7 mg to 19.1 mg or 6.7 mg to 30 mg with a two-phoswich-detector array or a germanium lung counting system, respectively. Depending on chest wall thickness, these achievable MDA's are close to, or exceed, the predicted amounts of natural uranium that will remain in the lung (absorption type M and S) after an intake equivalent to the Annual Limit on Intake that corresponds to 20 mSv. Neither system is sufficiently sensitive to detect an intake of Type S natural uranium in a worker with a chest wall thickness that corresponds to the average (3.73 cm) if it occurred more than 7 d prior to the lung count.

Adult↗
PubMed2000

Electrophysiological mapping and ablation of intra-atrial reentry tachycardia after Fontan surgery with the use of a noncontact mapping system.

BACKGROUND: Atrial tachyarrhythmias are a complication of Fontan surgery. Conventional electrophysiological mapping and ablation techniques are limited by the complex anatomic and surgical substrate and a high arrhythmia recurrence rate. This study investigates the use of noncontact mapping to identify arrhythmia circuits and guide ablation in Fontan patients. METHODS AND RESULTS: Eleven arrhythmias were recorded in 6 patients. Noncontact mapping improved recognition of the anatomic and surgical substrate and identified exit sites from zones of slow conduction in all clinical arrhythmias. Radiofrequency linear lesions were targeted across these critical zones in 5 patients. One patient underwent surgical cryotherapy. Although immediate success was achieved in 3 of 5 patients with radiofrequency ablation, 2 patients had a recurrence after a mean of 6.4 months of follow-up. The patient who underwent cryoablation remains free of arrhythmias. CONCLUSIONS: Noncontact mapping can identify arrhythmia circuits in the Fontan atrium and guide placement of ablation lesions. Arrhythmia recurrence is high, possibly because of inadequate lesion creation rather than inaccurate mapping and lesion targeting.

Adolescent↗
PubMed2000

Radiofrequency ablation of idiopathic left ventricular tachycardia at the site of earliest activation as determined by noncontact mapping.

INTRODUCTION: The most effective method for guiding radiofrequency (RF) ablation of idiopathic left ventricular tachycardia (ILVT) has yet to be determined. We investigated the use of noncontact mapping in five patients with this condition. METHODS AND RESULTS: The multielectrode array was positioned in the left ventricular apex via the retrograde approach. Isopotential color maps of ILVT were examined to determine the site of earliest endocardial activation. The ablation catheter was steered to the target site using the locator signal. Pace mapping was performed and contact electrograms examined for diastolic potentials. RF energy was applied to the target site. Sustained ventricular tachycardia was induced in 2 patients and nonsustained ventricular tachycardia in 3. The site of earliest activation was at the apical septum in 3, the inferior apex in 1, and the base of the inferior wall in 1. Mean timing was 21 +/- 10 msec before onset of the surface QRS. Diastolic activity was visualized with noncontact mapping at the base of the septum in 1 patient. A Purkinje potential was seen at the ablation site in only 1 patient. No diastolic activity was seen in the remaining 3 patients. Tachycardia was successfully terminated in all 5 patients with a median of four RF applications. No patient suffered a recurrence after 9.6 +/- 4.7 months of follow-up. CONCLUSION: By identifying the precise site of earliest activation during ILVT, noncontact mapping has been shown to be an effective and safe method for guiding RF ablation.

Adult↗
PubMed1999

Description and outcomes of a Medicare case management program by nurses.

During the current environment of cost-cutting and restructuring, case management is viewed as a means of providing comprehensive, coordinated care while reducing costs. Studies of community-based case management have been disappointing. This study evaluates a Medicare service, Management and Evaluation of the Care Plan (MAE), as a model of nurses providing case management in the home. Three groups were compared: MAE (N = 176), non-MAE (N = 187) and newly discharged (N = 93). Utilization data was collected over one year. Overall, subjects were unmarried older women with three functional limitations, four medical diagnoses and averaged 43 home care visits and one hospitalization. MAE patients were older, had more functional and environmental limitations, less ADL independence, and a worse prognosis, yet used significantly less health care than non-MAE recipients did. Regression analysis was performed using group membership and hospital and home care utilization as dependent variables. Although the project was conducted at one site, overall the sample was similar to the national Medicare population.

Aged↗
PubMed1998

Comparison of the LLNL and JAERI torso phantoms using Ge detectors and phoswich detectors.

The Human Monitoring Laboratory has compared the LLNL and JAERI torso phantoms using its germanium detector lung counting system by measuring the counting efficiencies for radioactive materials in the phantoms at photon energies of 17.7 keV, 59.5 keV, 121.8 keV, and 344 keV to assess the similarity (or differences) in performance characteristics. The counting efficiencies obtained from the two phantoms were compared by converting the Chest Wall Thickness data and Adipose Mass Fractions of the phantoms to Muscle Equivalent Chest Wall Thicknesses. The counting efficiencies for the two phantoms were found to be within a factor of 1.44 of each other at 17.7 keV, 1.30 at 59.5 keV, 1.25 at 121.8 keV, and 1.17 at 344 keV when using a four detector array (JAERI efficiency divided by LLNL efficiency). However, individual detector responses show that the counting efficiencies from the two phantoms differ considerably in the region of the heart (up to a factor of 6 at 17 keV). Other areas above the lungs give counting efficiencies that are similar to each other. A routine intercomparison exercise with Cameco Corporation has shown that the counting efficiencies derived from the LLNL and JAERI phantoms were found to be within a factor of 1.18 (JAERI/LLNL) when a natural uranium lung set was used to calibrate a lung counter consisting of phoswich detectors. This work has also shown that over the energy range 63 keV-185 keV the LLNL phantom can be used to calibrate phoswich detector systems that are positioned on the back of the subject.

Germanium↗
PubMed1997

Rapid HIV testing and counseling for voluntary testing centers in Africa.

OBJECTIVE: Voluntary HIV testing and counseling (VTC) has been shown to reduce the incidence of HIV in cohabiting couples who now represent the majority of new infections in many African cities. Community and client perceptions of a 1-day voluntary testing and counseling program in Lusaka, Zambia, were assessed, and a rapid HIV-testing algorithm was evaluated for VTC centers. METHODS AND DESIGN: Between May 1995 and June 1996, outreach workers distributed written invitations door to door. The 1-day program was held 6 days/week including weekends. Transport, child care and lunch were provided. Community and client surveys followed in July 1996. RESULTS: Over 3500 couples married for a median of 4-5 years requested testing: 23% were HIV+/+, 57% were HIV-/- and 20% were discordant with one HIV+ and one HIV- partner. Sixty-eight per cent of couples surveyed had made the decision to be tested before attending the 1-day program and 80% had not previously known where to obtain HIV testing. Knowledge that couples could show discordant results rose from 29 before to 88% after pretest counseling. Clients reported high levels of satisfaction with the services and 90 out of 99 (92%) preferred to receive their results the same day. Clients at another center who waited 10 days for their results reported more fear, and 19 out of 31 (61%) would have preferred to get their results the same day. Over 99% of those who attended the program thought active promotion of voluntary HIV testing in the community was a positive thing, as did 90% of those who were invited but did not attend. Sensitivity and specificity of the rapid test algorithm were both 99.4% in this setting. CONCLUSIONS: Active promotion of voluntary HIV testing and counseling in couples is needed to reduce the spread of HIV in high-prevalence areas. The use of rapid, on-site HIV testing allows clients to receive result-specific counseling in a single visit. Ongoing quality control of a subset of samples at an outside laboratory is essential.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Isolation and characterization of mouse Xrcc-1, a DNA repair gene affecting ligation.

Human DNA repair gene XRCC1 complements the strand-break rejoining defect in Chinese hamster mutant EM9 and encodes a protein that is apparently required for optimal activity of DNA ligase III. Toward the goal of producing transgenic mice that carry a mutation in the Xrcc-1 locus, the murine homolog of XRCC1 was cloned from both cosmid genomic and cDNA libraries. Upon transfection into EM9 cells, cosmids containing the functional mouse gene efficiently corrected (94-100%) the high sister-chromatid-exchange defect. Mouse Xrcc-1 is 26 kb in length, contains 17 exons, and maps by metaphase in situ hybridization to the 7A3-7B2 region of mouse chromosome 7. Isolated cDNA clones were highly truncated and were extended by anchored polymerase chain reactions. The 1893-bp open reading frame of mouse Xrcc-1 encodes 631 amino acids, compared with 633 for the human homolog. The predicted mouse Xrcc-1 protein of 69.1 kDa and pI of 5.95 is 86% identical and 93% similar to human XRCC1.

Amino Acid Sequence↗
PubMed1990

Sequence and expression of two regulated transcription units during Drosophila melanogaster development: Deb-A and Deb-B.

Two transcription units, Deb-A and Deb-B (developmental embryonic), are present in a recombinant bacteriophage clone containing a DNA insert from Drosophila melanogaster. The insert maps cytologically to chromosome 2R at 48EF. Sequence analysis of the open reading frames indicates that both are putative membrane proteins with similar hydropathy profiles. The expression of the encoded poly(A)+ RNAs is regulated during oocyte embryonic and larval development. The 600 base Deb-A RNA is present in oocytes and increases in abundance until 15 h of embryogenesis. Its abundance level drops dramatically between 15 and 19 h and is modulated at a low level in the three larval instars and pupae. The 525 base Deb-B RNA is present in oocytes at a 10-fold lower level than the Deb-A transcript. Its abundance increases until a maximum level is reached at 9-12 h. After this time the transcript is undetectable on Northern transfers. Both RNAs are present in greater than 95% polyadenylated form in the cytoplasm. Deb-B RNA is found on polysomes in proportions similar to the bulk of poly(A)+ RNA populations. Deb-A RNA, on the other hand is mostly nonpolysomal during embryogenesis. The RNAs from both Deb-A and Deb-B are found uniformly distributed throughout the embryo during development.

Amino Acid Sequence↗
PubMed1990

Molecular cloning of the human XRCC1 gene, which corrects defective DNA strand break repair and sister chromatid exchange.

We describe the cloning and function of the human XRCC1 gene, which is the first mammalian gene isolated that affects cellular sensitivity to ionizing radiation. The CHO mutant EM9 has 10-fold-higher sensitivity to ethyl methanesulfonate, 1.8-fold-higher sensitivity to ionizing radiation, a reduced capacity to rejoin single-strand DNA breaks, and a 10-fold-elevated level of sister chromatid exchange compared with the CHO parental cells. The complementing human gene was cloned from a cosmid library of a tertiary transformant. Two cosmid clones produced transformants that showed approximately 100% correction of the repair defect in EM9 cells, as determined by the kinetics of strand break repair, cell survival, and the level of sister chromatid exchange. A nearly full-length clone obtained from the pcD2 human cDNA expression library gave approximately 80% correction of EM9, as determined by the level of sister chromatid exchange. Based on an analysis of the nucleotide sequence of the cDNA insert compared with that of the 5' end of the gene from a cosmid clone, the cDNA clone appeared to be missing approximately 100 bp of transcribed sequence, including 26 nucleotides of coding sequence. The cDNA probe detected a single transcript of approximately 2.2 kb in HeLa polyadenylated RNA by Northern (RNA) blot hybridization. From the open reading frame and the positions of likely start sites for transcription and translation, the size of the putative XRCC1 protein is 633 amino acids (69.5 kDa). The size of the XRCC1 gene is 33 kb, as determined by localizing the endpoints on a restriction endonuclease site map of one cosmid clone. The deduced amino acid sequence did not show significant homology with any protein in the protein sequence data bases examined.

Amino Acid Sequence↗
PubMed1980

Prevention of pneumocystis pneumonia. Use of continuous sulfamethoxazole-trimethroprim therapy.

Owing to a 15% attack rate of Pneumocystis carinii pneumonitis (PCP) among the leukemic population of Riley Hospital, Indianapolis, a two-year study using continuous low-dosage sulfamethoxazole-trimethoprim to prevent PCP was started in January 1977. A total of 229 pediatric cancer patients considered at high risk for getting PCP received prophylaxis, while 19 additonal low-risk cancer patients did not receive sulfamethoxazole-trimethoprim. None of these 248 patients contracted PCP. However, five cases of PCP did occur among ten additional high-risk patients who failed to receive this preparation for a variety of reasons. Complications of the continuous prophylaxis program included neutropenia, rash, and gastrointestinal complaints. This study confirms that continuous, low-dosage sulfamethoxazole-trimethoprim prophylaxis is effective in preventing PCP in susceptible immunosuppressed patients but is ineffective in eradicating the organism from the population at risk.

Administration, Oral↗