Biomedical subjects
T To
Publications and source records attributed to T To.
NG-monomethyl-L-arginine does not restore loss of hypoxic pulmonary vasoconstriction induced by TNF-alpha.
Tumor necrosis factor-alpha (TNF-alpha) causes systemic hypotension, pulmonary vasodilation, and loss of hypoxic pulmonary vasoconstriction. NG-monomethyl-L-arginine (L-NMMA) inhibits nitric oxide (NO) production and prevents some systemic manifestations of TNF-alpha. We tested using an isolated perfused canine lobe whether NO also mediates the pulmonary vascular effects of TNF-alpha. Total resistance (RT) was measured during control and hypoxic ventilation over a 90-min period in six control lobes, five lobes treated with TNF-alpha (250 micrograms), six lobes treated with L-NMMA (200 mg), and five lobes treated with L-NMMA (200 mg) + TNF-alpha (250 micrograms). In the control lobes RT increased (P < 0.02) from 0.0474 +/- 0.0105 to 0.0677 +/- 0.0133 cmH2O.ml-1 x min during normoxic and hypoxic ventilation, respectively. RT decreased (P < 0.05) from a baseline of 0.0593 +/- 0.0133 to 0.0449 +/- 0.0176 cmH2O.ml-1 x min 30 min after TNF-alpha administration and did not further change during hypoxic ventilation (0.0475 +/- 0.0107 cmH2O.ml-1 x min). L-NMMA pretreatment did not prevent the TNF-alpha-induced loss of hypoxic pulmonary vasoconstriction, with values of RT unchanged from normoxic (0.0541 +/- 0.0067 cmH2O.ml-1 x min) to hypoxic (0.0545 +/- 0.0078 cmH2O.ml-1.min) ventilation (P > 0.10) in the L-NMMA + TNF-alpha group after TNF-alpha administration. We conclude that NO is not the mediator responsible for the acute pulmonary vascular effects of TNF-alpha.
Canadian National Breast Screening Study: 1. Breast cancer detection and death rates among women aged 40 to 49 years.
OBJECTIVES: To evaluate the efficacy of the combination of annual screening with mammography, physical examination of the breasts and the teaching of breast self-examination in reducing the rate of death from breast cancer among women aged 40 to 49 years on entry. DESIGN: Individually randomized controlled trial. SETTING: Fifteen urban centres in Canada with expertise in the diagnosis and treatment of breast cancer. PARTICIPANTS: Women with no history of breast cancer and no mammography in the previous 12 months were randomly assigned to undergo either annual mammography and physical examination (MP group) or usual care after an initial physical examination (UC group). The 50,430 women enrolled from January 1980 through March 1985 were followed for a mean of 8.5 years. DATA COLLECTION: Derived from the participants by initial and annual self-administered questionnaires, from the screening examinations, from the patients' physicians, from the provincial cancer registries and by record linkage to the Canadian National Mortality Data Base. Expert panels evaluated histologic and death data. MAIN OUTCOME MEASURES: Rates of referral from screening, rates of detection of breast cancer from screening and from community care, nodal status, tumour size, and rates of death from all causes and from breast cancer. RESULTS: Over 90% of the women in each group attended the screening sessions or returned the annual questionnaires, or both, over years 2 to 5. The characteristics of the women in the two groups were similar. Compared with the Canadian population, the participants were more likely to be married, have fewer children, have more education, be in a professional occupation, smoke less and have been born in North America. The rate of screen-detected breast cancer on first examination was 3.89 per 1000 in the MP group and 2.46 per 1000 in the UC group; more node-positive tumours were found in the MP group than in the UC group. During years 2 through 5 the ratios of observed to expected cases of invasive breast cancer were 1.26 in the MP group and 1.02 in the UC group. Of the women with invasive breast cancer through to 7 years, 191 and 157 women in the MP and UC groups respectively had no node involvement, 55 and 43 had one to three nodes involved, 47 and 23 had four or more nodes involved, and 38 and 49 had an unknown nodal status. There were 38 deaths from breast cancer in the MP group and 28 in the UC group. The ratio of the proportions of death from breast cancer in the MP group compared with those in the UC group was 1.36 (95% confidence interval 0.84 to 2.21). The survival rates were similar in the two groups. The highest survival rate occurred among women whose cancer had been detected by mammography alone. CONCLUSION: The study was internally valid, and there was no evidence of randomization bias. Screening with yearly mammography and physical examination of the breasts detected considerably more node-negative, small tumours than usual care, but it had no impact on the rate of death from breast cancer up to 7 years' follow-up from entry.
Canadian National Breast Screening Study: 2. Breast cancer detection and death rates among women aged 50 to 59 years.
OBJECTIVE: To evaluate the efficacy of annual mammography over and above annual physical examination of the breasts and the teaching of breast self-examination among women aged 50 to 59 on entry. DESIGN: Individually randomized controlled trial. SETTING: Fifteen urban centres in Canada with expertise in the diagnosis and treatment of breast cancer. PARTICIPANTS: Women with no history of breast cancer and no mammography in the previous 12 months were randomly assigned to undergo either annual mammography and physical examination (MP group) or annual physical examination only (PO group). The 39,405 women enrolled from January 1980 through March 1985 were followed for a mean of 8.3 years. DATA COLLECTION: Derived from the participants by initial and annual self-administered questionnaires, from the screening examinations, from the patients' physicians, from the provincial cancer registries and by record linkage to the Canadian National Mortality Data Base. Expert panels evaluated histologic and death data. MAIN OUTCOME MEASURES: Rates of referral from screening, rates of detection of breast cancer from screening and from community care, nodal status, tumour size and rates of death from all causes and from breast cancer. RESULTS: Over 85% of the women in each group attended the screening sessions after screen 1. The characteristics of the women in the two groups were similar. Compared with the Canadian population the participants were more likely to be married, have fewer children, have more education, be in a professional occupation, smoke less and have been born in North America. The rate of screen-detected breast cancer on first examination was 7.20 per 1000 in the MP group and 3.45 per 1000 in the PO group, more node-positive tumours were found in the MP group than in the PO group. At subsequent screens the detection rates were a little less than half the rates at screen 1. During years 2 through 5 the ratios of observed to expected cases of invasive breast cancer were 1.28 in the MP group and 1.18 in the PO group. Of the women with invasive breast cancer through to 7 years, 217 in the MP group and 184 in the PO group had no node involvement, 66 and 56 had one to three nodes involved, 32 and 34 had four or more nodes involved, and 55 and 46 had an unknown nodal status. There were 38 deaths from breast cancer in the MP group and 39 in the PO group. The ratio of the proportions of death from breast cancer in the MP group compared with those in the UC group was 0.97 (95% confidence interval 0.62 to 1.52). The survival rates were similar in the two groups. Women whose cancer had been detected by mammography alone had the highest survival rate. CONCLUSION: The study was internally valid, and there was no evidence of randomization bias. Screening with yearly mammography in addition to physical examination of the breasts detected considerably more node-negative, small tumours than screening with physical examination alone, but it had no impact on the rate of death from breast cancer up to 7 years' follow-up from entry.
Risk of breast cancer in women with breast cysts.
OBJECTIVE: To study the occurrence of breast cancer in women with breast cysts. DESIGN: Prospective follow-up study. SETTING: Office surgical practice. PATIENTS: All 742 women referred to the practice with breast cysts diagnosed by means of aspiration or, occasionally, biopsy between 1969 and 1985. MAIN OUTCOME MEASURES: The incidence of breast cancer and the number of years between diagnosis of breast cyst and diagnosis of cancer. The observed number of cases of breast cancer was compared with the expected number, calculated from Ontario rates of breast cancer. RESULTS: Fifteen of the women died but did not have breast cancer. No follow-up information was available for five women. Another 38 were lost to follow-up; they did not have breast cancer at the last contact, after 2 to 17 years of follow-up. These patients were withdrawn from the study in the year in which they died or were last observed. By 1990, 34 (5%) of the women had breast cancer. The overall ratio of observed:expected cases of cancer was 3.04 (95% confidence interval 2.09 to 4.28). Breast cancer developed after 7.5 years, but the average length of follow-up was only 10.1 years. Only 3.8% of 374 women after 10 years and 5.4% of 141 women after 15 years had breast cancer. CONCLUSION: Women who have a gross breast cyst are at moderately increased risk of breast cancer, which usually develops only after many years.
Prostacyclin (not nitroprusside) preserves venous admixture in the injured canine lung.
OBJECTIVE: To compare the effects of a prostaglandin vasodilator (prostaglandin I2 [PGI2]) with that of sodium nitroprusside in the isolated lung during 3% and 35% oxygen ventilation. BACKGROUND AND METHODS: Pulmonary vascular resistance was divided into arterial, middle, and venous segmental resistances. Left lower lobes were injured in a patchy (atelectasis) or diffuse (oleic acid-induced edema) manner. RESULTS: Nitroprusside diminished, but PGI2 ablated, the usual increase in middle segment resistance observed during 3% oxygen ventilation in atelectatic lobes. In the oleic acid-treated lobes, both nitroprusside and PGI2 ablated the increase in middle segment resistance during 3% oxygen ventilation. During nitroprusside administration, as pulmonary vascular resistance decreased, venous admixture proportionately increased, but this correlation was lost during PGI2 administration. CONCLUSIONS: We hypothesize that exogenous PGI2 dilates the vessels most constricted by hypoxia but to a lesser degree than does nitroprusside. Therefore, increases in venous admixture may be reduced during PGI2 administration, compared with nitroprusside administration.
Interactions of endotoxin, prostaglandins, and circulating cells upon pulmonary vascular resistance.
We studied the effects of endotoxin on total pulmonary vascular resistance (PVR) and hypoxic pulmonary vasoconstriction (HPV) in 24 isolated canine lung lobes. Group 1 lobes were perfused with whole blood; group 2 lobes with granulocyte/platelet depleted blood; group 3 lobes with whole blood and ibuprofen (12.5 mg/kg); group 4 lobes with granulocyte/platelet depleted blood and ibuprofen (12.5 mg/kg). All groups were otherwise treated in a similar manner and all received endotoxin (1 mg/kg) after baseline periods of normoxic and hypoxic ventilation. We found endotoxin increased PVR by 18% in group 1 and by 41% in group 2. Endotoxin administration inhibited HPV in group 1 but did not inhibit HPV in group 2. Ibuprofen administration prevented the increase in PVR and the loss of HPV caused by endotoxin. We conclude that endotoxin administration causes release of a lung-derived vasoconstrictor, but this is obscured by concomitant release of a granulocyte/platelet associated vasodilator. Our data also suggest that granulocytes or platelets may modulate baseline PVR by producing a nonprostaglandin vasodilator.
Pesticide concentrations in Arkansas breast milk.
During an episode of pesticide dairy product contamination in Arkansas in 1986, breast milk samples from 942 women were analyzed for concentrations of chlorinated pesticides. The pesticides found most frequently in quantifiable concentrations were p,p'-DDE (100%), oxychlordane (84%), trans-nonachlor (77%), heptachlor epoxide (74%) and beta-HCH, an isomer of lindane (27%). The pesticides present in highest mean concentrations of all samples analyzed (reported as ppm in milk fat) were p,p'-DDE (0.952 ppm), trans-nonachlor (0.062 ppm), oxychlordane (0.051 ppm), heptachlor epoxide (0.045 ppm), p,p'-DDT (0.039 ppm), and beta-HCH (0.032 ppm). These concentrations are lower than previous reports from similar regions of the US. However, continued persistence in human breast milk is of concern due to potential adverse health effects from these chemicals.
A study of acne treatments as risk factors for skin cancer of the head and neck.
A retrospective questionnaire was conducted as to the risk factors for facial skin cancer with emphasis on acne and past treatments for acne, in particular use of benzoyl peroxide preparations. The response rate was 90.9% for 964 cases and 79.9% for 3856 controls. There was no association between acne and the use of any acne medication for the risk of facial skin cancer. Cases of skin cancer were significantly more likely to have used phototherapy or sunbeds than the controls (P = 0.024), and more likely to have had radiotherapy prior to diagnosis (P = 0.001). The major risk factors as determined by generalized linear interactive modelling were family history of skin cancer (odds ratio 2.68; 95% confidence interval 2.15, 3.34), light skin (1.54; 1.25, 1.89), sunburning easily (1.43; 1.16, 1.76) and Irish, Scottish, Scandinavian or German mothers (1.33; 1.11, 1.59).
Interactions of tumor necrosis factor and granulocytes with pulmonary vascular resistance.
We studied the effects of endotoxin and tumor necrosis factor (TNF-alpha) on hypoxic pulmonary vasoconstriction (HPV) in 12 isolated perfused canine lung lobes. Group 1 lobes were perfused with whole blood, and group 2 lobes were perfused with granulocyte-depleted blood. All lobes were sequentially ventilated with control (35% O2) and hypoxic (3% O2) gas mixtures before and after receiving TNF-alpha. After TNF-alpha, group 2 lost HPV but group 1 retained HPV. After TNF-alpha, total pulmonary vascular resistance decreased in group 2 from 0.085 +/- 0.013 to 0.049 +/- 0.016 cmH2O.ml-1.min (P less than 0.05). We conclude that TNF-alpha acts as a pulmonary vascular vasodilator. In lobes perfused with whole blood, HPV is paradoxically preserved. We speculate that in the presence of cells rich in TNF-alpha receptors, i.e., granulocytes, the circulating levels of TNF-alpha are depressed and full expression of its vascular effects is blunted.
Clinical use of immunoperoxidase markers in excluding ectopic gestation.
Ectopic pregnancy is suspected when a pregnancy test is positive and an Arias-Stella phenomenon with decidua is seen on endometrial curettings in the absence of chorionic villi and trophoblast. We performed immunoperoxidase stains for beta-hCG, hPL, placental alkaline phosphatase, and keratin (AE1/AE3) on endometrial curettings of 72 patients with first-trimester bleeding in whom ectopic pregnancy was suspected based on routine hematoxylin and eosin (H&E) stain. Negative immunoperoxidase stains correlated with a retrospective patient chart review identified only ten patients with extrauterine pregnancy, a prevalence of 14%. The sensitivity of hCG, hPL, placental alkaline phosphatase, and keratin markers in detecting trophoblastic cells in the curettings was 42, 48, 24, and 69%, respectively. Each marker had a specificity of 100%. When both keratin and hPL were used, the sensitivity improved to 73%; however, there was no advantage in using three or more markers. We conclude that 73% of patients suspected to have ectopic pregnancy would be spared additional diagnostic techniques when immunoperoxidase markers for keratin and hPL are used on endometrial curettings without trophoblast on routine H&E stain. The procedure requires only 3 hours of laboratory time.
Relative roles of prostaglandins and leukotrienes in canine hypoxic pulmonary vasoconstriction.
We indirectly examined the role of prostaglandins and leukotrienes in modulation of hypoxic pulmonary vasoconstriction. We used a cyclo-oxygenase inhibitor (indomethacin) and a lipoxygenase inhibitor (diethylcarbamazine) in an in-situ canine lung lobe preparation. We measured total resistance in two control groups ventilated with either 35% O2 or 3% O2 (groups CC and HC respectively). Two additional groups treated with indomethacin (groups CI and HI), and two groups treated with the combination of indomethacin and diethylcarbamazine (groups CID and HID), were also ventilated with either 35% O2 or 3% O2 respectively. Total resistance was significantly greater in hypoxic groups compared with their respective control oxygen groups. Total resistance was greatest in group HI (0.288 +/- 0.103 cm H2O.ml-1 min-1), intermediate in group HID (0.153 +/- 0.016 cm H2O.ml-1 min-1) and lowest in group HC (0.066 +/- 0.017 cm H2O.ml-1 min-1). We concluded that cyclo-oxygenase blockade augments hypoxic pulmonary vasoconstriction by decreasing production of a vasodilating prostaglandin. Hypoxia also increases production of a vasoconstricting leukotriene in the presence of cyclo-oxygenase blockade with indomethacin.
Changes in breast self-examination behavior achieved by 89,835 participants in the Canadian National Breast Screening Study.
Breast self-examination (BSE) behavior was analyzed in 89,835 participants in the National Breast Screening Study (NBSS) of whom 64,619 were eligible for annual rescreening and 25,216 were followed by mail after a single screen exam. Among those eligible for rescreening, BSE competence scores based on seven BSE criteria significantly improved over time and correlated directly with reported BSE frequencies. Among all participants, the proportion reporting BSE frequencies of greater than or equal to 12/year increased over time from approximately 20% on entry to 50% to 64% at final screen. Similarly, reports of zero frequency diminished from 50% to 10% to 15%. Variables such as educational status, age (fifth versus sixth decades), eligibility for mammography, smoking history, and ethnic origin had negligible or no influence on BSE competence. However, women with first-degree relatives with breast cancer had significantly higher BSE scores. NBSS experience suggests that most women who enter screening programs will upgrade their BSE skills if subjected to brief episodes of repeated BSE instruction.
Women's attitudes to screening after participation in the National Breast Screening Study. A questionnaire survey.
A self-administered questionnaire study exploring women's attitudes to breast screening after participation in the Canadian National Breast Screening Study (NBSS) achieved an 82% response rate. Of active respondents (AR) attending two to five screening examinations, 1582 had received annual mammography (MA) and physical examination (PE) of the breasts and 548 received annual PE alone. Of 139 dropouts after the first screening, 105 received MA and PE and 34 received PE alone. Dropout respondents (DR) were significantly less likely than AR to report receiving very prompt (46% versus 66%), very courteous (73% versus 92%), or very competent examinations (74% versus 95%). Although 35% of those allocated to PE expressed disappointment with PE allocation compared with 9% of those allocated to MA, fewer of those allocated PE were prepared to accept MA in the future than those allocated MA (59% versus 73%). Of those who had MA, 36% reported moderate and 9% extreme discomfort from mammography. Almost half of each subgroup--MA allocations, PE allocations, and DR--preferred mammography every 2 to 3 years and 30% preferred mammography restricted to diagnostic purposes. Only 5% of AR reported anxiety after screening. National Breast Screening Study participation was a positive experience for 93%. An intention to do breast self-examination (BSE) was reported by 89% of AR and 79% of DR. Forgetfulness was a major impediment to BSE. Disincentives for screening were excessive distance to center, painful mammography, fear of radiation, lack of time, and preference for own physician. Convenient location, punctual appointments, and courteous and supportive staff should enhance screening compliance.
The effects of halothane in hypoxic pulmonary vasoconstriction.
Human and animal experiments have not consistently shown halothane to inhibit hypoxic pulmonary vasoconstriction (HPV). The authors used a canine lung lobe perfused in situ to more precisely characterize the effects of halothane on HPV. The pulmonary vasculature can be divided into inflow, middle, and outflow segments by sequentially occluding the lobar inflow and outflow of blood. The lobes were ventilated with four different gas mixtures (normoxia, hypoxia, normoxia/halothane, hypoxia/halothane) and measured inflow, outflow, and middle segment (Rm) resistances using this stop-flow technique. All values are shown as means +/- standard deviation. The authors found that hypoxia increased Rm from normoxia values of .006 +/- .005 cmH2O.ml-1.min-1 to .025 +/- .008 cmH2O.ml-1.min-1 (P less than 0.05). During hypoxia/halothane Rm returned to .005 +/- .004 cmH2O.ml-1.min-1. The relationship between pressure and flow (P-Q) for the lobes for each gas mixture was also determined. The slopes of the P-Q lines by linear regression were all similar. The zero-flow pressure intercepts of the P-Q lines for normoxia (3.2 +/- .9 cmH2O) and hypoxia (4.4 +/- 1.1 cmH2O) were significantly decreased after the administration of halothane (1.7 +/- 1.0 cmH2O and 2.6 +/- 1.0 cmH2O, respectively). Since the zero-flow intercept likely reflects the tone at alveolar vessel level, the authors conclude that halothane inhibits HPV by decreasing the tone in the middle vascular segment.
Herpes labialis in parturients receiving epidural morphine following cesarean section.
A significant association exists between the use of epidural morphine (EM), reactivation of herpes labialis (HL) commonly known as coldsores, and pruritus in the obstetric population. A randomized prospective study was designed to eliminate previously identified confounding variables. Immediately following delivery, parturients having undergone cesarean section with epidural anesthesia with carbonated lidocaine (Xylocaine CO2, Astra, Mississauga, Ontario, Canada) with 1:200,000 epinephrine were sequentially randomized to receive either EM or im opioids for postoperative analgesia. One blood sample was collected for viral serology and two mouthwashes (day 0 and 2) were collected to determine oral viral shedding. The patients were observed daily for 5 days. Coldsores were cultured for herpes simplex virus (HSV). Of 187 patients, 96 received EM and 91 im opioids; herpes labialis occurred in 14 of 96 (14.6%) of the former but in 0 of 91 of the latter (P = 0.0004). All 14 experienced facial pruritus. The two groups were at equal risk for reactivation (seropositivity 64.6% and 62.6%, respectively). Analysis of data for those with positive HSV serology reveals 14 of 62 (22.5%) had EM and herpes labialis compared with 0 of 57 in the im group (P less than 0.0001). The incidence of oral viral shedding was low. Surgical stress, the local anesthetic solution, and epinephrine addition to the local anesthetic were eliminated as confounders. Stepwise logistic regression analysis revealed that EM and a history of herpes labialis in these patients were predictive for reactivating oral HSV.
Canadian National Breast Screening Study: assessment of technical quality by external review.
Mammograms from the Canadian National Breast Screening Study (NBSS) were reviewed by three external experts to provide an objective evaluation of their technical quality, to establish a model for auditing mammograms in a screening program, and to assess whether NBSS mammograms improved over time. The sample reviewed included 10 randomly chosen mammograms from each of 15 screening centers for each calendar year of their operation between 1980 and 1987. All 830 mammograms were reviewed on two consecutive days in randomized sequence by each reader, and rated 0-3 for each of four criteria including positioning and image quality, with a total possible score of 0-12. Although the mammograms were not in temporal sequence when reviewed, the scores assigned by each reader were significantly higher for mammograms dating from later years. Subjects' ages at entry (40-49 vs 50-59 years) did not affect the score. The largest increase in scores was associated with a 1985 protocol change in which mediolateral oblique positioning replaced straight mediolateral positioning. This study reinforces the importance of monitoring technical quality in screening programs and establishes that the NBSS benefited from technical improvements during its operation. A retrospective review of NBSS mammography by three external reviewers confirmed that technical quality improved from 1980 to 1987. This improvement was associated with improved technology (film, processing, and units) and with the quality assurance programs operating during the NBSS, which identified problems and offered remedies.
Efficacy of chlorhexidine and sanguinarine mouthrinses on selected salivary microflora.
The antibacterial effects of chlorhexidine and sanguinarine on selected salivary microflora were evaluated in 15 healthy young adults. The experiment was performed in a cross-over manner enabling both mouthrinses and the saline control to be tested on all 15 subjects for periods of one week separated by three week intervals. The total bacterial count and selected bacterial genera were followed in saliva samples taken just before the first rinse, and on three occasions after the last rinse. Statistically significant reductions in the salivary levels of S. mutans and S. salivarius were obtained with chlorhexidine but not with sanguinarine, and rinsing twice a day with sanguinarine, according to the manufacturer's instructions, did not significantly reduce the total bacterial count. Additional well controlled, longer-term studies are required before any firm conclusions can be drawn regarding the effect of sanguinarine on salivary microorganisms.