Control of respiratory pattern in conscious dog: effects of heat and CO2

We measured tidal volume (VT) and inspiratory (TI) and expiratory (TE) durations in five conscious tracheostomized dogs breathing air or 5% CO2 in air either at normal (20 degrees C) or elevated (30 degrees C) ambient temperatures. Respiratory frequency ranged between 16 and 333/min due to changes in both TI and TE. During panting TI exceeded TE. During air inhalation instantaneous ventilation (V) spontaneously ranged from 100 to 1,600 ml . kg-1 . min-1. Hypercapnia, heat stress, or both, increased this range of V by increasing maximum V, primarily due to increases in mean inspiratory flow. Under these conditions, changes in TI accounted for more of the spontaneous changes in breath duration. During inhalation of air and 5% CO2, a positive correlation between VT and TI was obtained for TI between 0.13 and 1.05 s; above 1.05 s VT decreased. Heat stress increased VT at a given TI. We suggest that either the decay rate or position of the inspiratory off-switch threshold curve (Clark and von Euler, J. Physiol. London 222: 267, 1972) varies in conscious dogs. Shifts in either the reset (onset) value or decay rate of the curve yield a positive correlation between VT and TI. This modification to the Clark-von Euler model implies that the primary effect of anesthesia on respiratory control is fixation of the inspiratory off-switch threshold curve.     

Direct effect of Pa(CO2) on respiratory sinus arrhythmia in conscious humans

Respiratory sinus arrhythmia (RSA) may improve the efficiency of pulmonary gas exchange by matching the pulmonary blood flow to lung volume during each respiratory cycle. If so, an increased demand for pulmonary gas exchange may enhance RSA magnitude. We therefore tested the hypothesis that CO2 directly affects RSA in conscious humans even when changes in tidal volume (V(T)) and breathing frequency (F(B)), which indirectly affect RSA, are prevented. In seven healthy subjects, we adjusted end-tidal PCO2 (PET(CO2)) to 30, 40, or 50 mmHg in random order at constant V(T) and F(B). The mean amplitude of the high-frequency component of R-R interval variation was used as a quantitative assessment of RSA magnitude. RSA magnitude increased progressively with PET(CO2) (P < 0.001). Mean R-R interval did not differ at PET(CO2) of 40 and 50 mmHg but was less at 30 mmHg (P < 0.05). Because V(T) and F(B) were constant, these results support our hypothesis that increased CO2 directly increases RSA magnitude, probably via a direct effect on medullary mechanisms generating RSA.     

Prostate-specific antigen testing in Ontario: reasons for testing patients without diagnosed prostate cancer

BACKGROUND: The use of the prostate-specific antigen (PSA) test has been increasing rapidly in Canada since its introduction in 1988. The reasons for using the PSA test in patients without known prostate cancer are unclear. This paper reports on the first study in Canada to use physician records to assess the use of PSA testing. METHODS: A questionnaire was mailed to physicians attending 475 patients without diagnosed prostate cancer. The patients were randomly selected from 2 laboratory databases of PSA test records in the greater Toronto area during 1995. The physicians were asked to consult their patient records to avoid recall bias. Information obtained included physician''s specialty, patient''s age at time of PSA test and reason(s) for the test. RESULTS: There were 264 responses (56%), of which 240 (91%) were usable. Of these 240, 63% (95% confidence interval [Cl] 58%-70%) indicated that the test was conducted to screen for prostate cancer, 40% (95% Cl 34%-47%) said it was to investigate urinary symptoms, and 33% (95% Cl 27%-40%) responded that it was a follow-up to a medical procedure or drug therapy. More than one reason was permitted. Of 151 responses indicating screening as one reason for testing, 64% (95% Cl 56%-72%) stated that it was initiated by the patient, and 73% (95% Cl 65%-80%) stated that it was part of a routine examination. For 19%, both investigation of symptoms and screening asymptomatic patients were given as reasons for testing, and for another 19% both follow-up of a medical procedure and screening were given as reasons. Screening was recorded as a reason for testing far more commonly for patients seen by family physicians and general practitioners than for patients seen by urologists (67% v. 29%, p < 0.001). In contrast, the use of PSA testing to diagnose urinary symptoms was more common for patients seen by urologists than for those seen by family physicians and general practitioners (52% v. 37%, p = 0.044). No significant difference was found between physician groups in the use of PSA testing as a follow-up of a medical procedure (42% for urologists and 31% for family physicians and general practitioners). About 24% of the PSA test records were for patients younger than 50 and older than 70 years. PSA testing initiated by patients was more common in the practices of family physicians and general practitioners than in the practices of urologists (44% v. 13%, p < 0.001). INTERPRETATION: Screening for prostate cancer was the most common reason for PSA testing in our study group; it occurred most commonly in the family and general practice setting and was usually initiated by the patient. Differences in reasons for testing were identified by practice specialty. Although PSA screening for prostate cancer is sometimes recommended for men between 50 and 70 years of age, it is being conducted in men outside this age group.     

Temporal trends in breast cancer surgery in Ontario: can one randomized trial make a difference?

OBJECTIVE: To assess the effect of a single randomized clinical trial, the National Surgical Adjuvant Breast Project (NSABP) B-06, on the surgical management of breast cancer in women. DESIGN: Retrospective cohort study. SETTING: All hospitals in Ontario. PATIENTS: A consecutive sample of 37,447 women with breast cancer newly diagnosed from Jan. 1, 1980, to Dec. 31, 1989, linked to a surgical procedure record in the Ontario Cancer Registry. MAIN OUTCOME MEASURE: The most invasive surgical procedure used within 90 days of diagnosis. RESULTS: Unilateral breast-ablative surgery (BAS) was performed in 57.3% of the women and breast-conserving surgery (BCS) in 31.6%. The annual rate of BAS declined from 77.5% in 1980 to 44.2% in 1989 and the rate of BCS rose from 12.5% in 1980 to 43.5% in 1989. The decline was linear from 1980 to 1984 and then accelerated significantly in 1985 (p < 0.0001), after the results of the NSABP B-06 trial were published. CONCLUSION: One randomized clinical trial can have an immediate and profound effect on medical practice.     

Control of breathing at elevated lung volumes in anesthetized cats

We monitored the steady-state ventilatory responses of anesthetized cats to increases in lung volume produced by expiratory threshold loads (ETL) to study the roles of peripheral and central neural mechanisms in controlling respiration at elevated lung volumes. Application of an ETL of 5 cmH2O produced a significant decrease in respiratory frequency (-18%) but no change in minute ventilation (VE) due to a significant increase in tidal volume (VT) (19.3%). The drop in frequency was due solely to an increase in expiratory duration. ETL of 10 cmH2O significantly reduced VE (-17.5%) for the same reason. VT was maintained or increased at elevated lung volumes due to both an increase in the rate of rise of phrenic activity and a maintenance of inspiratory duration (TI) despite increases in both chemical drive and pulmonary stretch receptor (PSR) activity. No PSR adapted completely to the maintained change in lung volume. The sensitivity of the inspiratory off-switch mechanism to increases in lung volume, given by the reciprocal of the VT-TI relationship, decreased significantly during breathing on ETL. The results are consistent with the hypothesis that central habituation, not just peripheral adaptation of PSR, determines breathing pattern at elevated lung volumes.     

Fat oxidation rate and the exercise intensity that elicits maximal fat oxidation decreases with pubertal status in young male subjects

The range of exercise intensities that elicit high fat oxidation rates (FOR) in youth and the influence of pubertal status on peak FOR are unknown. In a longitudinal design, we compared FOR over a range of exercise intensities in a small cohort of developing prepubertal male subjects. Five boys all at Tanner stage 1 (ages 11-12 yr) and nine men (ages 20-26 yr) underwent an incremental cycle ergometry test to volitional exhaustion. FOR curves were determined from indirect calorimetry during the final 30 s of each increment. The same protocol was duplicated annually in the boys as they progressed through puberty. The peak FOR was considerably higher (P<0.05) in boys at Tanner 1 (8.6+/-1.5 mg.kg lean body mass(-1).min(-1)) (mean+/-SD) compared with men (4.2+/-1.1 mg.kg lean body mass(-1).min(-1)). FOR dropped as boys developed through puberty (Tanner 2/3 peak rate=7.6+/-0.6 mg.kg lean body mass(-1).min(-1); Tanner 4 peak rate=5.4+/-1.8 mg.kg lean body mass(-1).min(-1), main effect of Tanner stage; P<0.05) to the levels found in men (not significant). The exercise intensity that elicited peak FOR was higher in the boys at Tanner 1 [56+/-6% peak aerobic power (VO2 peak)] than in men (31+/-4% VO2 peak) (P<0.001). This value tended to decrease by Tanner stage 4 (45+/-10% VO2 peak, main effect of Tanner stage; P=0.06). We conclude that, compared with men, prepubertal boys have higher relative FOR throughout a wide range of exercise intensities and that FOR drops as boys develop through puberty.     

Re-evaluating the cost of outpatient cancer chemotherapy.

Chemotherapy for common malignant tumours has historically been considered relatively expensive. An examination of costs at the Toronto-Bayview Regional Cancer Centre and Sunnybrook Medical Centre, Toronto, suggests that this perception is not accurate. The cost of chemotherapeutic agents administered on an outpatient basis over 4 to 6 months in established drug protocols ranged from $260 to $5374 (mean $2224). The total cost of outpatient administration was estimated to be $152.53 per dose, compared with $185.39 for inpatient administration of the same protocol, a difference of 22%. The difference was predominantly due to a higher allocated per-diem charge at the medical centre. The results indicate that outpatient administration reduces the overall cost of chemotherapy.     

Prostate cancer: 1. The descriptive epidemiology in Canada

A 70-year-old woman who experienced a long period of depression after her first husband''s death from prostate cancer at the age of 63 has become increasingly anxious about her own health and that of her close family. A few years ago she married a man her own age; he is in good physical condition. Last year the family spent much of the winter in Florida, where the woman noticed several studies in the media suggesting that an epidemic of prostate cancer is occurring in North America and that because early detection can save lives men of retirement age should be checked by their physicians as soon as possible. In addition, 2 close friends recently diagnosed with prostate cancer. On his latest fishing trip her husband learned from a friend that 1 in 8 men get prostate cancer. He has not seen his family physician for several years, but his wife has booked an appointment for them to discuss their concerns.