A morphometric study of the protective effect of cryotherapy on oral mucositis in cancer patients treated with 5-fluorouracil

We investigated cytological changes in oral mucosa smears from patients treated with cryotherapy to determine whether cryotherapy prevented mucositis caused by 5-fluorouracil (5-FU) therapy. Patients with gastrointestinal malignancies were divided into four groups; control patients before 5-FU therapy, patients after 5-FU therapy without cryotherapy, patients with cryotherapy before 5-FU therapy and patients with cryotherapy after 5-FU therapy. Oral mucosa samples from all patients were assessed at the beginning and on day 14 of chemotherapy. We used exfoliative cytology to evaluate cellular changes in the oral mucosa that were caused by 5-FU. Smears from each patient were stained using the Papanicolaou method and analyzed using stereology. Smears were taken from each group before and after 5-FU infusion. We found that nuclear volume was decreased significantly in cells of the 5-FU therapy after cryotherapy patients compared to the 5-FU therapy before cryotherapy patients. We also found significantly decreased cytoplasmic volumes in the 5-FU therapy after cryotherapy patients compared to the 5-FU therapy before cryotherapy patients. The results of cytomorphometric estimations revealed that cryotherapy may be used to prevent damage to oral tissue and may decrease the frequency and duration of oral mucositis caused by 5-FU.     

Hypohydration does not impair skeletal muscle glycogen resynthesis after exercise

The purpose of this investigation was to examine the effects of moderate hypohydration (HY) on skeletal muscle glycogen resynthesis after exhaustive exercise. On two occasions, eight males completed 2 h of intermittent cycle ergometer exercise (4 bouts of 17 min at 60% and 3 min at 80% of maximal O2 consumption/10 min rest) to reduce muscle glycogen concentrations (control values 711 +/- 41 mumol/g dry wt). During one trial, cycle exercise was followed by several hours of light upper body exercise in the heat without fluid replacement to induce HY (-5% body wt); in the second trial, sufficient water was ingested during the upper body exercise and heat exposure to maintain euhydration (EU). In both trials, 400 g of carbohydrate were ingested at the completion of exercise and followed by 15 h of rest while the desired hydration level was maintained. Muscle biopsy samples were obtained from the vastus lateralis immediately after intermittent cycle exercise (T1) and after 15 h of rest (T2). During the HY trial, the muscle water content was lower (P less than 0.05) at T1 and T2 (288 +/- 9 and 265 +/- 5 ml/100 g dry wt, respectively; NS) than during EU (313 +/- 8 and 301 +/- 4 ml/100 g dry wt, respectively; NS). Muscle glycogen concentration was not significantly different during EU and HY at T1 (200 +/- 35 vs. 251 +/- 50 mumol/g dry wt) or T2 (452 +/- 34 vs. 491 +/- 35 mumol/g dry wt). These data indicate that, despite reduced water content during the first 15 h after heavy exercise, skeletal muscle glycogen resynthesis is not impaired.     

Thermal responses during arm and leg and combined arm-leg exercise in water

Thermal and metabolic responses were examined during exposures in stirred water at approximately 20, 26, and 33 degrees C while subjects were performing 45 min of either arm (A), leg (L), or combined arm-leg (AL) exercise. Eight males immersed to the neck completed a low exercise intensity for A exercise and both a low and high exercise intensity for L and AL exercise. During low-intensity exercise, final metabolic rate (M) for A, L, and AL exercise was not different (P greater than 0.05) between exercise type for each water temperature (Tw). In contrast final rectal temperatures (Tre) for A and AL exercise were significantly lower than L values for each Tw during low-intensity exercise. These findings were supported by both mean weighted skin temperature (Tsk) and mean weighted heat flow (Hc) values, which were greater during A than L for each Tw. During high-intensity exercise, final Tre values were lower (P less than 0.05) during AL compared with L exercise across all Tw. Final Tsk and Hc values were not different between each type of exercise, although M was significantly lower during L exercise in 20 degrees C water. These data suggest a greater conductive and convective heat loss during exercise utilizing the arms when compared with leg-only exercise.     

Plasma volume shifts during progressive arm and leg exercise

Upper and lower body exercise was performed to assess the influence muscle mass has on plasma volume (PV) shifts. Nine male subjects (mean = 28 yr) completed a progressive intensity, discontinuous test with an arm crank (AC) and cycle (CY) ergometer. Power output (PO) levels for the AC were 25, 74, 98, and 133 W. PO levels for the CY were 49, 98, 147, and 263 W. At a given submaximal oxygen uptake (VO2), PV efflux was significantly greater for AC compared with CY exercise. When PV efflux was related to the relative intensity of the exercise (ergometer specific % peak VO2), responses were nearly identical. Maximal PV efflux was 18% for both AC and CY exercise. Mean arterial pressure (MAP) was significantly greater for AC compared with CY exercise for a given VO2. MAP plotted against the relative intensity of exercise, however, was similar for both AC and CY exercise. These results suggest that the amount of plasma efflux during exercise is related to the MAP, which is directly related to the relative intensity of the exercise.     

人HCN4通道的滞后现象:影响窦房结起搏的潜在决定因素(英文)

超极化活化环核苷酸门控(hyperpolarization-activated cyclic-nucleotide-gated,HCN)通道参与调制心脏跳动的节律和速率。与HCN1和HCN2有所不同,慢通道HCN4可能不存在电压依赖的滞后现象。本研究采用单细胞膜片钳方法,在稳定转染hHCN4的HEK293细胞上进行电生理记录,观察hHCN4通道是否存在滞后现象,以及cAMP对其的调制作用;同时采用实时定量RT-PCR方法检测窦房结和心房组织中HCNs的表达。电压钳实验结果显示hHCN4电流(Ih)激活随着保持电位超极化的变化而向去极化方向移动。三角电位变化钳(triangular ramp)和动作电位钳的结果也显示了hHCN4的滞后现象。cAMP增加Ih电流幅度,且使电流激活向去极化方向移动,从而改变内源性hHCN4滞后行为。RT-PCR结果显示,人窦房结组织主要表达HCN4,占75%,HCN1占21%,HCN2占3%,HCN3占0.7%。以上结果提示,人窦房结组织主要表达HCN4亚型,hHCN4的Ih存在电压依赖性的滞后现象,且受cAMP调制。由此推断,hHCN4通道的滞后现象可能在窦房结起搏活动中起到了关键作用。     

Efficacy of intermittent, regional microclimate cooling.

The vasomotor response to cold may compromise the capacity for microclimate cooling (MCC) to reduce thermoregulatory strain. This study examined the hypothesis that intermittent, regional MCC (IRC) would abate this response and improve heat loss when compared with constant MCC (CC) during exercise heat stress. In addition, the relative effectiveness of four different IRC regimens was compared. Five heat-acclimated men attempted six experimental trials of treadmill walking ( approximately 225 W/m(2)) in a warm climate (dry bulb temperature = 30 degrees C, dewpoint temperature = 11 degrees C) while wearing chemical protective clothing (insulation = 2.1; moisture permeability = 0.32) with a water-perfused (21 degrees C) cooling undergarment. The six trials conducted were CC (continuous perfusion) of 72% body surface area (BSA), two IRC regimens cooling 36% BSA by using 2:2 (IRC(1)) or 4:4 (IRC(2)) min on-off perfusion ratios, two IRC regimens cooling 18% BSA by using 1:3 (IRC(3)) or 2:6 (IRC(4)) min on-off perfusion ratios, and a no cooling (NC) control. Compared with NC, CC significantly reduced changes in rectal temperature ( approximately 1.2 degrees C) and heart rate ( approximately 60 beats/min) (P < 0.05). The four IRC regimens all provided a similar reduction in exercise heat strain and were 164-215% more efficient than CC because of greater heat flux over a smaller BSA. These findings indicate that the IRC approach to MCC is a more efficient means of cooling when compared with CC paradigms and can improve MCC capacity by reducing power requirements.     

An investigation of cut-points for primary breast cancer oestrogen and progesterone receptor assays

Oestrogen and progesterone receptor (ER and PgR) assay values are frequently used in medical decision-making for breast cancer patients. We have proposed statistical standardization of receptor assay values to improve inter-laboratory comparability, and now report the use of standardized log units (SLU) to investigate the effects of ER and PgR cut-points on time to first recurrence outside the breast (DFS). Between 1980 and 1986, there were 678 primary breast cancer patients treated at the Henrietta Banting Breast Centre (HBBC). The effects of ER and PgR cut-points were examined with multivariate analyses considering the variables: age, tumour size, nodal status, weight and adjuvant treatment. We considered receptor assay cut-points ranging from −1.0 to +1.0 SLU (ER between 7 and 166 fmol/mg protein; PgR between 7 and 181 fmol/mg protein). PgR was included in the multivariate prognostic models more often than ER, although patients had a better prognosis with both larger ER and PgR values. There was no best cut-point for ER or PgR, and there was strong evidence that ER and PgR should be considered as continuous rather than dichotomous (negative, positive) variables. Patient prognosis should also be more comparable with SLU.     

Patterns of initial management of node-negative breast cancer in two Canadian provinces

OBJECTIVE: To describe the patterns of initial management of node-negative breast cancer in Ontario and British Columbia and to compare the characteristics of the patients and tumours and of the physicians and hospitals involved in management. DESIGN: Retrospective, population-based, cohort study. PARTICIPANTS: All 942 newly diagnosed cases of node-negative breast cancer in 1991 in British Columbia and a random sample of 938 newly diagnosed cases in Ontario in the same year. OUTCOME MEASURES: Number and proportion of patients with newly diagnosed node-negative breast cancer who received breast-conserving surgery (BCS) or mastectomy and who received radiation therapy after BCS. RESULTS: BCS was used in 413 cases (43.8%) in British Columbia and in 634 cases (67.6%) in Ontario (p < 0.001). After BCS, radiation therapy was received by 378 patients (91.5% of those who had undergone BCS) in British Columbia and 479 patients (75.6% of those who had undergone BCS) in Ontario (p < 0.001). In both provinces, lower patient age, smaller tumour size, a noncentral unifocal tumour, absence of extensive ductal carcinoma in situ and initial surgery by a surgeon with an academic affiliation were associated with greater use of BCS. Lower patient age and larger tumour size were associated with greater use of radiation therapy after BCS in both provinces. CONCLUSION: Patient, tumour and physician factors are associated with the choice of initial management of breast cancer in these two Canadian provinces. However, the differences in management between the two provinces are only partly explained by these factors. Other possible explanations, such as the presence of provincial guidelines, differences in the organization of the health care system or differences in patient preference, require further research.