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Biomedical subjects

B Kavanagh

Publications and source records attributed to B Kavanagh.

At least 19 recordsLinked to original sources
PubMed2002

Normocapnia vs hypercapnia.

Initial Implementation of Mechanical Ventilation was focused on providing adequate oxygenation and relief of work of breathing. Over the last few decades it has become apparent that stretch-induced lung injury, associated with normocapnia or hypocapnia, is a real phenomenon. Attempts to reduce stretch-induced injury led to development of permissive hypercapnia in the neonatal population, and later to its acceptance as a standard of care in adult patients with ARDS. Here, the elevated CO2 was a result of reduced minute ventilation, and was considered to be a by-product of the technique that could be tolerated in most instances. It is now apparent that hypercapnia by itself can be protective. In addition, hypocapnia can be harmful. These observations led to the hypothesis of therapeutic hypercapnia, i.e., deliberate production of high CO2 as a goal in the care of critically ill patients.

Acid-Base Equilibrium↗
PubMed1999

Utilization of intensive care unit days in a Canadian medical-surgical intensive care unit.

OBJECTIVES: To analyze the utilization of intensive care unit (ICU) days in a Canadian medical-surgical ICU and to identify ICU patients with prolonged ICU length of stay (LOS). DESIGN: Prospective descriptive study. SETTING: A Canadian tertiary care medical-surgical ICU. PATIENTS: Consecutive patients admitted to an adult medical-surgical ICU. Neurosurgical, cardiac surgical, and coronary care unit patients were excluded. MEASUREMENTS: For each ICU admission, patient demographics, diagnosis, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, ICU LOS, and hospital mortality were collected. The patients' risk of death was calculated using the APACHE II equation. Admissions were stratified by ICU LOS into four groups: 1 to 2, 3 to 6, 7 to 13, and > or = 14 days. Among the four LOS groups, the number of ICU days and observed and predicted death rates were compared. Admissions were also stratified by risk of death into five probability range quintiles. Among the five risk groups, ICU LOS was compared between survivors and nonsurvivors. RESULTS: A total of 1,960 admissions utilized 9,298 ICU days. ICU LOS (mean +/- SEM) was 4.74 +/- 0.2 (median, 2; range, 1 to 178) days. Short-stay patients (ICU LOS < or = 2 days) accounted for 60.3% of total admissions but consumed only 16.4% of total ICU days. Long-stay patients (ICU LOS > or = 14 days) accounted for 7.3% of total admissions but consumed 43.5% of total ICU days. Among the long-stay patients, the most common reasons for admission were pneumonia, multiple trauma, neuromuscular weakness, and septic shock. The mortality for long-stay patients approached 50%. When analyzed by patients' mortality risks, those with a risk of death >0.8 (predicted to die) or <0.2 (predicted to live) whose outcomes were opposite to that predicted had twice the ICU LOS compared with patients whose outcomes were consistent with prediction. CONCLUSION: In a Canadian medical-surgical ICU, patients with ICU LOS > or = 14 days accounted for 7.3% of total admissions but consumed 43.5% of total ICU days. Identification of patients with prolonged ICU LOS who would ultimately die in the ICU may lead to earlier withdrawal of therapy in these patients, resulting in a substantial reduction in suffering and cost savings. In our study population, outcome prediction using the APACHE II equation did not provide sufficient power to accurately discriminate between nonsurvivors and survivors.

APACHE↗
PubMed1998

Prolactin is an antagonist of TGF-beta activity and promotes proliferation of murine B cell hybridomas.

Prolactin (PRL) is an immunomodulator that has been demonstrated to enhance immune responses both in vitro and in vivo. Prolactin enhances the proliferative response of lymphoid cells to both nonspecific mitogens and specific antigens and increases their production of IL-2 and interferon-gamma. Studies were performed to examine whether recombinant human prolactin (r-hPRL) also acts as a growth factor for B cell hybridomas. Prolactin was able to stimulate proliferation of murine B cell hybridomas in a dose-dependent manner and enhanced their proliferation in response to IL-4, IL-5, and IL-6. This increase in proliferation resulted in an overall increase in antibody production. Studies were also undertaken to examine the effect of PRL with transforming growth factor beta (TGF-beta), an immunosuppressive cytokine. Hybridoma cell lines incubated with TGF-beta demonstrated a dose-dependent decrease in proliferation. Variability in the degree of inhibition was observed among the various hybridomas in their responsiveness to TGF-beta. The addition of r-hPRL to the cultures reversed the antiproliferative effects of TGF-beta. The mechanism by which PRL can overcome the anti-proliferative effect of TGF-beta is under investigation. These findings provide an additional rationale for using r-hPRL clinically in immunosuppressed patients in certain disease settings such as AIDS and cancer, where overexpression of TGF-beta has been implicated in disease development and progression.

Adjuvants, Immunologic↗
PubMed1998

Admissions, length of stay, and discharge barriers at the Hawaii State Hospital.

Based on data gathered from patients, psychiatrists, and social workers at the Hawaii State Hospital, it was determined that the majority of patients had been in the hospital for more than one year, were committed for forensic reasons, and did not need continued hospitalization. An inter-agency systems approach is needed to address the issue of length of patient stay.

Adult↗
PubMed1995

Heuristically derived tumor burden score as a prognostic factor for stage IIIB carcinoma of the cervix.

PURPOSE: A retrospective analysis of radiotherapeutic management of locally advanced carcinoma of the uterine cervix was performed to evaluate the effect of various treatment parameters and disease extent upon treat outcome. METHODS AND MATERIALS: Between 1976 and 1989, 89 patients with Stage IIIB disease were treated with external beam radiotherapy and brachytherapy. Treatment outcomes were evaluated by dose to Point A, the proportion of Point A dose delivered by brachytherapy, clinical response at 3 months, and a newly developed tumor burden scoring system that quantifies the anatomical extent of disease. Kaplan-Meier estimates of tumor control and survival parameters were determined. RESULTS: Loco-regional control (LRC), disease-free survival (DFS), and overall survival (OVS) at 5 years were 52.9%, 45.5%, and 50.3%, respectively. Clinical response at 3 months was highly predictive of local and distant tumor control. There was no correlation between proportion of brachytherapy dose and treatment outcome. The tumor burden scoring system demonstrates that FIGO Stage IIIB disease can be clinically divided into two prognostic groups of low and high tumor burden. Five year LRC was 62.9% and 40.2% for the low and high tumor burden groups, respectively (p = 0.024). Within the high tumor burden group the LRC was 53.0% and 22.5% when the point A dose given was > 78 Gy and < or = 78 Gy, respectively (p = 0.047). This correlated with improved DFS and OVS. CONCLUSION: The tumor burden scoring system subdivides FIGO Stage IIIB cervical carcinoma into two prognostic groups, predicting for overall survival and demonstrating a dose response in the high tumor burden group. This system may serve to improve future comparison of treatment outcome and to guide selection of patients who may benefit from a more aggressive treatment approach.

Adult↗
PubMed1994

Late complications of postoperative radiation therapy for cancer of the rectum and rectosigmoid.

PURPOSE: We retrospectively examined the surgical, medical, radiotherapeutic and technical factors associated with late small bowel and nonsmall bowel morbidity. METHODS AND MATERIALS: The medical records of 224 patients with cancer of the rectum and rectosigmoid treated mainly with abdominoperineal resection or anterior resection and postoperative radiotherapy at the University of Texas M.D. Anderson Cancer Center from 1973 to 1990 were reviewed. The median dose was 54 Gy (range 34-66 Gy) at 1.8-2 Gy per fraction using various techniques (23 had extended fields to L1 or L2; pelvic fields were treated with anterior-posterior in 85, 83 had a 3-field plan and 33 had a 4-field "box"). A positioning technique that treats patients on an open table-top device was used in 78 patients to move the small intestine out of the pelvis. Bladder distension was used in eight. Forty-seven patients received concomitant 5-fluorouracil. Small bowel series were performed in 122 patients to assess the volume of small bowel inside the pelvis below the conjugate line. RESULTS: In 29 patients, the median time to the development of small bowel obstruction was 7 months (range 0-69 months); 18 patients required reoperations. The small bowel obstruction rate was 30% in patients treated with daily extended field radiotherapy, 21% in those with a single pelvic field and 9% with multiple pelvic fields. Small bowel obstruction was positively correlated with postsurgical adhesions prior to radiotherapy and absence of reperitonealization at the time of initial surgery (p < 0.05). There was no correlation of small bowel obstruction with a history of hypertension, diabetes, prior surgery, history of abdominal infections, postoperative infections, wound healing, pathologic tumor stage, types of surgical procedures, sites of primary tumor, age, or sex. Patients developing small bowel obstruction had larger amounts of small bowel assessed radiologically below the conjugate line than those without complications. With the open table-top device, the small bowel obstruction rate was 3%. In 47 patients treated with radiation and chemotherapy on the open table-top device, the small bowel obstruction rate was 15%, but these patients had more small bowel inside the pelvis than those without the complication. The median time to the development of nonsmall bowel obstruction in 29 patients was 8 months (range 0-85 months), and the nonsmall bowel obstruction complications were significantly correlated with postoperative infection. Most nonsmall bowel obstruction complications were in the genitourinary tract and occurred in patients who had abdominoperineal resection. CONCLUSION: The open table-top device, by moving the small bowel out of the treatment field, reduces small bowel obstruction in patients treated with radical surgery and postoperative radiotherapy for cancer of the rectum and rectosigmoid. This technique is facile, reproducible, and does not require patient compliance.

Adult↗
PubMed1994

Is hypoxic pulmonary vasoconstriction important during single lung ventilation in the lateral decubitus position?

Hypoxic pulmonary vasoconstriction (HPV) has not been demonstrated in human single lung anaesthesia in the lateral decubitus position (LDP). The purpose of this study was to determine whether (1) HPV occurs in the non-dependent, non-ventilated lung, and (2) if the infusion of sodium nitroprusside (SNP) inhibits HPV. During intravenous anaesthesia the tracheas of seven patients were intubated with double lumen endotracheal tubes. Standard monitors plus radial and pulmonary arterial catheters were placed. Patients were positioned in the LDP and haemodynamic and gas exchange data were recorded for each of three stages; I: two-lung ventilation, II: single, dependent lung ventilation (1 LV) and III: 1LV with infusion of SNP. In stage II the PaO2 decreased from 531 +/- 42 mmHg to 285 +/- 42 mmHg (P < 0.05) and Qs/Qt increased from 12.3 +/- 2.7 to 29.0 +/- 6.3% (P < 0.05). With SNP infusion there was a 30% increase in cardiac index (CI) (P < 0.05). The SNP infusion was not associated with changes in Qs/Qt or PaO2. This model demonstrates changes in Qs/Qt and PaO2 associated with single-lung ventilation in ASA I and II patients in the LDP but we were unable to demonstrate inhibition of HPV by SNP.

Anesthesia, Intravenous↗
PubMed1992

Patterns of failure following combined modality therapy for esophageal cancer, 1984-1990.

From 1984-1990, 143 patients with squamous cell or adenocarcinoma of the esophagus were enrolled in a Phase I/II study of neoadjuvant chemotherapy followed by concurrent chemotherapy plus radiotherapy with or without subsequent esophagectomy. Patients received one cycle of Cisplatin or Carboplatin plus Etoposide for squamous cell carcinoma, or Cisplatin or Carboplatin plus 5FU for adenocarcinoma, followed by two cycles of the same chemotherapy given concurrently with 44-46 Gy over 5 weeks. Operable patients then underwent esophagectomy. Inoperable patients and those with positive surgical margins received additional irradiation (16-18 Gy). Twelve percent of the surgical group received preoperative radiotherapy doses > or = 50 Gy. Seventy-two percent (103) had clinical Stage I-III tumors and 28% (40) were clinical Stage IV (1983 American Joint Committee on Cancer criteria). Only clinical Stage I-III patients were analyzed with respect to patterns of failure. Isolated local failure occurred in 19/103 (18%) of clinical Stage I-III patients. Both local and distant relapse occurred in 15/103 (15%), and distant metastases alone occurred in 25/103 (24%). The 3-year actuarial rates of local and distant failures were 45% and 60%, respectively. Among the clinical Stage I-III patients who underwent surgery (n = 58) versus those who did not (n = 45), the 3-year actuarial local and distant failure rates were 30% versus 60% and 45% versus 45%, respectively. Multivariate analysis was performed to identify significant predictors of local control. For all clinical Stage I-III patients, treatment with surgery (p = 0.001) and with three or more cycles of chemotherapy (p = 0.02) were significant predictors of improved local control. Patients who underwent surgery were significantly younger and had a better performance status than those who did not. The improvement in local control with surgery did not translate into better survival, likely on account of a high operative mortality rate in older patients and those receiving > or = 50 Gy preoperatively. We conclude that local control remains poor with concurrent chemotherapy + radiotherapy for esophageal cancer. The addition of surgery improved local control, but distant metastases remain a problem both in this group of patients as well as those treated without esophagectomy. Efforts to improve local control appear warranted, but it remains to be demonstrated that improved local control translates into improved survival in esophageal cancer because of a high rate of distant metastases in patients whose disease is controlled in the esophagus.

Adenocarcinoma↗
PubMed1992

Simplified enrollment for autologous transfusion: automatic referral of presurgical patients for assessment for autologous blood collections.

We implemented a pilot program at our institution for automatic referral of patients for presurgical assessment for preoperative and intraoperative collection of autologous blood. Although patients and clinicians support the use of autologous transfusion, often a request for collection of autologous blood is not initiated. During 11 months, 269 patients (82%) of three orthopedic surgeons entered the program, and 218 underwent operation and were dismissed from the hospital. A total of 940 units of autologous blood (675 preoperatively and 265 intraoperatively) was collected from these 218 patients, and 84% of the units were transfused. Throughout hospitalization, 86% of the patients received only autologous blood, whereas 14% received various proportions of homologous and autologous blood. In contrast, only 26% of a concomitant control group of 220 consecutive orthopedic surgical patients not participating in the automatic-referral program received only autologous blood. Thus, the automatic-referral program increased the percentage of elective orthopedic surgical patients who received only autologous blood from 26% to 86% (P less than 0.001). This study also showed that the same amount of blood was used for autologous transfusions as was routinely used for homologous transfusions in similar cases. The automatic-referral system was convenient for physicians and patients and offered the benefits of reduction of transfusion-associated risks and amelioration of patient anxieties.

Blood Transfusion, Autologous↗
PubMed1992

Effects of the calcium channel blocker flunarizine on the hemodynamics and oxygenation of tumor microvasculature.

Flunarizine is a diphenylpiperazine calcium entry blocker that has been shown previously to increase tumor blood flow and sensitivity to radiotherapy via reduction in the radiobiologically significant hypoxic fraction. Two mechanisms of action have been proposed previously (vasodilation, altered blood viscosity), but no studies have been performed to examine its mechanisms of action in vivo. Such information would be invaluable in determining the role of flunarizine in multimodality approaches to reduce tumor hypoxia. Fisher-344 rats bearing R3230Ac tumors transplanted into dorsal flap window chambers were used to examine microcirculatory changes after administration of flunarizine (1.0 mg/kg, iv). The drug increased the diameters of the microvasculature and red cell velocities specifically in central tumor regions (producing an average increase in vessel flow by a factor of 1.96), which was accompanied by an increase in perivascular pO2 of 12 mm Hg, on the average. The drug did not change the diameters of tumor "feeding" vessels, nor did it change vascular length densities. Thus the improvement in central tumor blood flow and oxygenation could not be attributed to dilation of feeding vessels. The oxygen-carrying capacity of the blood was not altered either since hemoglobin saturation (measured in vitro) and the hematocrits of the microvasculature were unchanged after drug administration. Therefore, by a process of elimination, the most likely explanation for the effect of the drug is modification of blood viscosity. Additional studies are under way in this laboratory to examine whether changes in viscosity occur after flunarizine administration.

Adenocarcinoma↗
PubMed1991

Aminoglycoside induced ototoxicity in patients with cystic fibrosis.

The improved survival of cystic fibrosis (CF) patients is partly due to intensive treatment for their chronic infections. Treatment usually includes intravenous and nebulised aminoglycoside antibiotics and they receive a large cumulative dose of these antibiotics over their lifetime. There is little information in the literature on the prevalence of ototoxicity due to aminoglycoside in these patients. We performed pure tone audiometry on 43 CF patients aged 14-42 years. Seven (16%) had bilateral sensorineural hearing loss (SNHL) for high frequency sounds, consistent with aminoglycoside induced ototoxicity. However, only 2 of these patients had documented toxic serum levels in the past. The identification of bilateral SNHL in one in six adult CF patients is a cause for concern. It may be that the high cumulative dose of aminoglycosides received by these patients may be causing inner ear injury in the absence of specific episodes of toxic serum levels.

Adolescent↗
PubMed1987

Vinyl chloride monomer and other contaminants in PVC welding fumes.

An investigation into the nature of fumes produced during thermal welding of plasticized PVC sheeting has been carried out with the objective of determining if the known carcinogen vinyl chloride monomer (VCM) is formed and to assess the level of exposure to the operator. The results show that the atmospheric concentrations of VCM are well below accepted occupational exposure limits. This finding is consistent with reports in the technical literature which suggest that VCM is produced during thermal degradation of PVC only at temperatures considerably higher than those encountered during plastic welding.

Air Pollutants, Occupational↗