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Biomedical subjects

G Mackay

Publications and source records attributed to G Mackay.

15 recordsLinked to original sources

Is pre-operative radiotherapy necessary in T-T rectal cancer with TME?

OBJECTIVE: The indications for pre-operative radiotherapy in rectal cancer are still unclear with the exception of T4 tumours. The aim of this study was to assess local and overall recurrence in patients with T1-T3 rectal cancers undergoing total mesorectal excision (TME). METHODS: Prospective data was collected from 150 patients with rectal cancer treated in one surgical centre between July 1997 and July 2002. One hundred and twenty-nine primary resections were carried of which 102 were with curative intent. Seventy-nine patients with T1-T3 tumours were included in the analysis. Nine had local resections and 70 underwent TME; 19 of the 70 patients were node positive and 51 were node negative. RESULTS: At a median follow-up of 37 months (range 19-79 months) there were 3 (4.3%) isolated local recurrences. One node positive patient developed isolated local recurrence compared with 2 node negative patients. The node positive patient died from a myocardial infarction while the two node negative patients died as a consequence of local recurrence. Three (4.3%) of 70 patients developed systemic relapse all of whom were node positive. The cancer specific mortality rate over the same follow-up period was 3/19 for node positive patients and 2/51 for node negative patients. Of 9 patients who had local resections, none developed local recurrence or systemic relapse. CONCLUSIONS: With TME the rate of local recurrence in T1-T3 tumours is low. Our results do not support the use of pre-operative radiotherapy for these patients.

Adult↗

Antibodies that neutralize SIV(mac)251 in T lymphocytes cause interruption of the viral life cycle in macrophages by preventing nuclear import of viral DNA.

Previous reports from our lab had shown that sera obtained from SIV(mac)-infected animals neutralized SIV(mac) infectivity in CD4(+) T cells but failed to protect monkey primary macrophages from infection with the virus. However, the antibodies could inhibit completion of the viral life cycle in the macrophages at the postentry stage(s). In this report we examined the mechanisms of the late effect of the antibodies. Using monoclonal antibodies (MAbs), we demonstrated that only antibodies to the SIV envelope protein (KK17 and KK42) but not antibody to the viral core protein (FA2) had the same inhibitory effect as that of the anti-SIV sera. To identify the stage of the viral replication cycle that was inhibited by anti-SIV antibodies in macrophages, we used various PCR techniques to study viral entry/reverse transcription (by amplifying the viral gag gene), viral genome nuclear transport (by amplifying 2-LTR circular forms), viral integration (by Alu-PCR assay), and viral protein expression (by RIPA). We found that in macrophage cultures inoculated with SIV(mac)251 that were preincubated with antienvelope MAbs, viral DNA was detected at 8 h postinoculation but the 2-LTR circular forms and integrated viral DNAs were undetectable, and viral proteins were not expressed in these infected macrophages. These results strongly suggested that anti-SIV antibodies inhibited SIV(mac) replication in macrophages by blocking nuclear transport of viral genomes since viral DNA could not be detected in the nuclei of treated cultures. Furthermore, we showed that although viral replication in macrophages was interrupted by the antibodies, when cocultured with permissive T cells, the viral genomes presented in the cytoplasm of the macrophages could readily transfer to T cells during cell-cell contact. Importantly, this transfer could not be prevented by the antibodies. These results might explain the failure of passive antibody immunization against SIV(mac)251--a critical obstacle in AIDS vaccine development.

Active Transport, Cell Nucleus↗

Neuropathogenesis of chimeric simian human immunodeficiency virus infection in rhesus macaques.

Comparative studies were performed to determine the neuropathogenesis of infection in macaques with simian human immunodeficiency virus (SHIV)89.6P and SHIV(KU). Both viruses utilize the CD4 receptor and CXCR4 co-receptor. However, in addition, SHIV89.6P uses the CCR5 co-receptor. Both agents are dual tropic for CD4+ T cells and blood-derived macrophages of rhesus macaques. Following inoculation into macaques, both caused rapid elimination of CD4+ T cells but they varied greatly in mechanisms of neuropathogenesis. Two animals infected with SHIV89.6P developed typical lentiviral encephalitis in which multinucleated giant cell formation, nodular accumulations of microglial cells, activated macrophages and astrocytes, and perivascular accumulations of mononuclear cells were present in the brain. Many of the macrophages in these lesions contained viral RNA. Three macaques infected with SHIV(KU) and killed on days 6, 11 and 18, respectively, developed a slowly progressive infection in the CNS but macrophages were not productively infected and there were no pathological changes in the brain. Two other animals infected with this virus and killed several months later showed minimal infection in the brain even though one of the two developed encephalitis of unknown etiology. The basic difference in the mechanisms of neuropathogenesis by the two viruses may be related to co-receptor usage. SHIV89.6P, in utilizing the CCR5 co-receptor, caused neuropathogenic effects that are similar to other neurovirulent primate lentiviruses.

AIDS Dementia Complex↗

The effects of radiation treatment after TRAM flap breast reconstruction.

A subgroup of mastectomy patients receives adjuvant radiation therapy after autogenous breast reconstruction for locoregional control of cancer. The effects of radiation therapy on pedicled transverse rectus abdominis musculocutaneous (TRAM) flaps were determined to evaluate complication rates and aesthetic results. Nineteen patients from 1981 to 1994 receiving radiation therapy after a pedicled TRAM flap reconstruction were compared with 108 patients who received radiation prior to reconstruction and 572 patients who underwent breast reconstruction without radiation. Retrospective reviews of patient charts were completed. Adjuvant radiation therapy was given for chest-wall recurrence in 13 of 19 patients. With a mean follow-up of 47.6 months from the time of reconstruction, 10 patients (52.6 percent) demonstrated postradiation changes in the TRAM flap reconstruction, and 6 required surgical intervention (31.6 percent). Overall complication rates were increased but were not found to be statistically significant between the radiated TRAM flap group and patients with preoperative radiation followed by TRAM flap reconstruction (31 versus 25 percent). Fibrosis was not found in patients with pre-TRAM flap radiation or in patients without radiation but was seen in 31.6 percent of patients who received radiation after the reconstruction. Fat necrosis was not significantly increased between the two groups of radiated patients. The complication rate does not change whether a patient receives radiation before or after her reconstruction; only the nature of the complication changes (fat necrosis to fibrosis).

Breast Neoplasms↗

TRAM flap breast reconstruction after radiation treatment.

OBJECTIVE: Patients with and without radiation treatment before their breast reconstruction were compared to study the relationship of radiation to flap-related complications. SUMMARY BACKGROUND DATA: The transverse rectus abdominis muscle (TRAM) flap for breast reconstruction involves a a vascular pedicle and recipient bed, both included in the radiated field of patients undergoing adjunctive therapy. Detailed reviews of flap-related complications in this subgroup of patients have been limited. METHODS: One hundred eight patients with radiation treatment who subsequently underwent a TRAM flap breast reconstruction were compared with 572 patients with no radiation treatment before similar reconstruction. Flap-related complications, radiation dosage, time, fields, relationships between risk factors, and complications were studied. RESULTS: Overall complication rates were comparable between the two groups. Only fat necrosis (> 10% of total reconstruction) was found to be statistically significant (17.6% vs. 10.1%, p = 0.03228). No difference was found for fat necrosis in unipedicled vs. bipedicled flaps controlled for radiation (17.7% vs. 17.4%). Obesity and radiation therapy were associated with fat necrosis and major infection in a logistic regression. Significant abdominal scarring was also associated with major infection (p = 0.0044). CONCLUSIONS: In this, the largest reported series, radiation therapy was associated with increased fat necrosis and major infection. The use of the TRAM flap was not found to be prohibitive in radiated patients and should still be the first choice in this subgroup of patients.

Breast Neoplasms↗

Evaluation of a dual bias dual metal oxide-silicon semiconductor field effect transistor detector as radiation dosimeter.

A new type of direct reading semiconductor dosimeter has been investigated as a radiation detector for photon and electron therapy beams of various energies. The operation of this device is based on the measurement of the threshold voltage shift in a custom-built metal oxide-silicon semiconductor field effect transistor (MOSFET). This voltage is a linear function of absorbed dose. The extent of the linearity region is dependent on the voltage controlled operation during irradiation. Operating two MOSFETS at two different biases simultaneously during irradiation will result in sensitivity (V/Gy) reproducibility better than +/- 3% over a range in dose of 100 Gy and at a dose per fraction greater than 20 x 10(-2) Gy. The modes of operation give this device many advantages, such as continuous monitoring during irradiation, immediate reading, and permanent storage of total dose after irradiation. The availability and ease of use of these MOSFET detectors make them very promising in clinical dosimetry.

Biophysical Phenomena↗

The effect of propranolol on portal perfusion in patients with alcoholic cirrhosis having distal splenorenal shunt.

This study tested the hypothesis that reduction in the hyperdynamic systemic circulation with propranolol in patients with alcoholic cirrhosis and distal splenorenal shunt would lead to improved maintenance of portal perfusion. After standard distal splenorenal shunt, 50-75% of patients with alcoholic cirrhosis lose portal flow in 6-12 months: this is associated with an increased hyperdynamic systemic circulation. Twelve patients with alcoholic cirrhosis with distal splenorenal shunt received propranolol in a dose sufficient to provide beta blockade. Pulse was reduced by 25%, cardiac output reduced by 32% and hepatic venous pressure gradient reduced by 15% (p < 0.05). These significant hemodynamic changes with propranolol did not lead to any improvement in the maintenance of portal perfusion: overall, 66% of patients lost prograde portal flow within 1 year. We conclude that the hyperdynamic systemic circulation is not the primary mediator of loss of portal perfusion in this group of patients. Rather, it appears that differences in either intrahepatic resistance or collateral pathway (portal vein to shunt) resistance must account for the different patterns or maintenance of portal perfusion after distal splenorenal shunt.

Female↗

Smooth muscle tumors of the rectum and anus: a collective review of the world literature.

In this collective review, we have compiled all the reported cases of smooth muscle tumors of the rectum/anus in the world literature from 1959 to 1989. Our goal was to increase the data pool of smooth muscle tumors by adding these new data to that previously collected from 1881 to 1959. We increased the pool for leiomyomas from 89 to 148 and that for leiomyosarcomas from 54 to 215. By doing this, we hoped to make more accurate conclusions about smooth muscle tumors based on this increased data pool. Some interesting findings included three cases in small children that were found in our recent review: a 2-year-old with a leiomyoma and two small infants, aged 12 days and 36 days, with leiomyosarcomas. Again, the findings were probably consistent with an increased data pool. We were also able to find several more cases involving the anal region. We found the highest incidence of leiomyomas to have increased by a decade from the 40-49 year age group to the 50-59 year age group, while among leiomyosarcomas, there was about equal incidence among the 50-59 and 60-69 age groups. We doubt that these represent actual changes in the demographics, but rather that these latter findings are more accurate based on the greater quantity of cases available to us. As a further example, we found no appreciable sex difference; however, we did find more cases reported in females. From our increased data pool, we were able to find 16 more cases that were described as dumbbell-shaped, compared to one that was reported before 1959. Palpable mass, hemorrhage, and pain/discomfort continued as the most common symptoms reported at presentation. With regard to size, the majority of leiomyomas were found to be less than 5 cm in diameter, closely followed by those 5-9 cm. The majority of leiomyosarcomas were 5-9 centimeters at discovery. Most cases of leiomyoma were treated by excision, while most cases of leiomyosarcoma were treated by abdominoperineal resection, a finding consistent with old data. We hope that this paper thoroughly reviews pertinent information about leiomyomas and leiomyosarcomas of the rectum/anus and, in doing so, serves to refresh a few memories, stimulate others, and teach a few.

Adolescent↗

Building quality practice settings: an attributes model.

To practice effectively nurses need an environment that supports quality professional practice. This article describes the development of a model identifying seven (7) key system attributes of a quality practice setting. The defined attributes are essential in supporting professional practice and quality care. The Quality Practice Setting Attributes Model developed by the College of Nurses of Ontario in Canada provides the foundational framework for the Practice Setting Consultation Program (PSCP), a unique quality improvement approach to creating quality practice environments.

Focus Groups↗

A nursing model of overdose assessment.

Assessing people following a suicide attempt is an opportunity for therapeutic intervention and for gathering essential information. This article outlines a nursing model for assessing people admitted to hospital following a drug overdose. The model is presented alongside a case study demonstrating its application in practice.

Adaptation, Psychological↗