低危险度流行病学和好的流行病学研究方法

本文对低危险度的流行病学研究方法上存在的困难进行了讨论，如确定暴露估计时可能犯的错误，特别是与疾病有关的几种因子的剂量描述。对如何建立好的流行病学研究方法也进行了讨论。研究者必需注意到他的解释将对公共卫生实践产生重要影响，因此对数据的解释应持慎重态度     

Volume and length changes in outer hair cells of the guinea pig after potassium-induced shortening

Summary Measurements of volume and length were made on isolated guinea pig cochlear outer hair cells (OHCs) in an attempt to establish whether OHC shortening was accompanied by changes in cell volume. A sustained shortening in response to an isotonic 100 mM KCl solution was found to be accompanied by a significant increase in OHC volume. The application of hypotonic solutions had a similar effect. When testing solutions with unchanged or reduced [K⁺] [Cl^–] products in order to avoid loading the cells with chloride ions and producing concomitant water influx, the most frequent response was a rapid shortening followed by an elongation beyond the original cell length. These findings of a sustained and a spontaneously reversible shortening suggest that the potassium-induced response may consist of two components: a rapid one, which may be reversible in the presence of the stimulus, and a second, slower, component resulting in sustained shortening.     

Low-grade pure and mixed cerebral astrocytomas treated in the CT scan era

Summary From 1974 to 1992, 63 patients diagnosed with low-grade pure or mixed oligo-astrocytoma were seen and treated at our institution. All patients underwent CT scan pre-operatively. There were 20 female and 43 males ranging in age from 12 to 73 years (median age of 33 years). 15 patients had a stereotactic biopsy as the only surgical procedure. 34 had a partial tumor resection and 14 a gross total tumor resection.43 patients were treated with post-operative radiotherapy whereas 20 patients underwent surgery only as part of the initial management. 50 to 60 Gy (median 59.4 Gy) were given with daily fractions of 1.8 to 2 Gy. Tumor volume ranged from 3.4 to 441 cm³. Median tumor volume was larger for radiotherapy treated patients.Median follow-up was 54 months (range of 4 to 240 months). The overall 10 and 15 actuarial survival rates were 37% and 25% respectively. The 5 year survival rate for patients treated at initial diagnosis with surgery alone was 66% and it was 67.3% for patients treated with radiation therapy (P = NS). Prognostic factors having independant significant impact on survival were: extent of surgery, age, gender and tumor volume.As well, survival for patients with low-grade astrocytoma in the CT scan era appears to be improved compared to historical controls in the literature.     

Usefulness of tumor volumetry by magnetic resonance imaging in assessing response to radiation therapy in carcinoma of the uterine cervix

: Clinical evaluation of tumor size in cervical cancer is often difficult, and clinical signs of radiation therapy failure may not be present until well after completion of treatment. The purpose of this study is to investigate early indicators of treatment response using magnetic resonance (MR) imaging for quantitative assessment of tumor volume and tumor regression rate before, during, and after radiation therapy.

: Thirty-four patients with cervical cancer Stages IB [5], IIB [8], IIIA [1], IIIB [14], IVA [3], IVB [1], and recurrent [2] were studied prospectively with four serial MR examinations obtained at the start of radiation therapy, at 2-2.5 weeks (20–24 Gy), at 4–5 weeks (40–50 Gy), and 1–2 months after treatment completion. Tumor volume was assessed by three-dimensional volumetric measurements using T₂-weighted images of each MR examination. The volume regression rate was generated based on the four sequential MR studies. These findings were correlated with local control, metastasis rate, and disease-free survival. Median follow-up was 18 months (range: 9–43 months).

: The tumor regression rate after a dose of 40–50 Gy correlated significantly with treatment outcome. The actuarial 2-year disease-free survival was 88.4% in patients with tumors regressing to <20% of the initial volume compared with 45.4% in those with ≥20% residual (p = 0.007). The incidence of local recurrence was 9.5% (2 out of 21) and 76.9% (10 out of 13), respectively (p < 0.001). Analysis by initial tumor volume showed that this observation was valid in patients with initial volumes between 40 and 100 cm³. Analysis by FIGO stage confirmed this observation in all patients except those with Stage IB.

: Sequential tumor volumetry using MR imaging appears to be a sensitive measure of the responsiveness of cervical cancer to irradiation. Treatment response can be assessed as early as during the course of radiation therapy by measurement of initial tumor volume and regression rate at 40–50 Gy. In patients with large (>40 cm³) and advanced (Stage ≥ IIIA) tumors, this technique may be helpful in supplementing the clinical examination for response assessment. The identification of patients at high risk for treatment failure may ultimately lead to improved clinical outcome.     

Erythropoietin and granulocyte-macrophage colony-stimulating factor allow acceleration and dose escalation of cyclophosphamide/epidoxorubicin/5-fluorouracil chemotherapy: a dose-finding study in patients with advanced breast cancer

 To verify whether the association of granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (EPO) would allow both the acceleration and the dose escalation of the cyclophosphamide/epidoxorubicin/5-fluorouracil (CEF) regimen as first-line therapy in advanced breast cancer patients, we conducted a dose-finding study. Cohorts of three consecutive patients received cyclophosphamide (Ctx, dose range 800 –1400 mg/m²), epidoxorubicin (Epidx, dose range 70–100 mg/m²), and 5-fluorouracil (5-Fu, 600 mg/m², fixed dose) given as an intravenous bolus on day 1 every 14 days; GM-CSF at 5 μg/kg given as a subcutaneous injection from day 4 to day 11; and EPO at 150 IU/kg given as a subcutaneous injection three times a week. In no single patient was any dose escalation allowed. A total of 14 patients entered the study. At the 4th dose level (Ctx 1400 mg/m², Epidx 100 mg/m², 5-Fu 600 mg/m²), two patients had dose-limiting mucositis and one patient developed dose-limiting neutropenia. Therefore, the 3rd cohort received the maximum tolerated dose, i.e. Ctx at 1200 mg/m², Epidx at 90 mg/m², and 5-Fu at 600 mg/m², given every 18.5 (±2.5) days. Toxicity was moderate and manageable in an outpatient setting. Only 1 admission at the 4th dose level was required. Throughout the 4 dose levels there was no toxicity-related death; grade IV leukopenia ranged from 24% to 75% of cycles and grade IV thrombocytopenia ranged from 6% to 8%. No grade IV anemia was recorded. Increasing the doses of Ctx and Epidx while maintaining a fixed dose of 5-Fu with the support of both EPO and GM-CSF allows safe acceleration and dose escalation of CEF chemotherapy. Further controlled studies will evaluate the activity and efficacy of this strategy. Received: 8 October 1995/Accepted: 1 March 1996     

Prediction of timed vital capacity from height and weight in children in the age group of 5 to 12 years

In the present study 350 school boys and 350 school girls in the age group of 5 to 12 yr were studied. It was observed that there is parallel progressive increase in physical growth and pulmonary function in this age group. There was positive significant correlation of FEV₁ with height and weight.     

Hypovolemic pregnant women and their risk determinants

Among hypovolemic pregnant women there is a high risk of premature labor, fetal growth retardation, and/or hypertension. Arterial wave velocity was determined and Evan's blue disappearance rates measured in hypovolemic gravidas with complications. It appeared that those hypovolemic gravidas without increased cardiac performance are more likely to give birth prematurely, while those with increased cardiac performance and delayed in vivo mixing of Evan's blue dye develop hypertension.     

Characterization of lymphocyte beta 2-adrenoceptor signalling in patients with left ventricular volume overload disease

1. Studies using animal experimental models have suggested that the beta2-adrenoceptor is uncoupled in association with alterations in the expression of G-protein-coupled receptor kinases (GRK) 2/3 in heart failure. However, the functional expression of the components of this pathway in human disease has not been fully elucidated yet. In the present study, we evaluated the possibility that the regulation of beta2-adrenoceptor signalling components in patients with left ventricular volume overload (VOL) depends on the severity of the overload. 2. We characterized the lymphocyte GRK 2-6, beta-arrestins 1 and 2, beta2-adrenoceptor expression at the mRNA and protein levels, as well as the activity of adenylyl cyclase, protein kinases (PK) A and PKC in patients with VOL using healthy blood donors as controls. 3. In the patient group, GRK2 mRNA was increased by 61% (P < 0.001), GRK3 was increased by 54% (P < 0.005), GRK5 was increased fivefold (P < 0.001) and the beta-arrestin 2 mRNA was increased by 40% (P < 0.05). These increases were paralleled with a sixfold increase in GRK2, a twofold increase in GRK3 and a 1.3-fold increase in GRK5 protein levels. These changes were associated with a significant decrease in beta2-adrenoceptor mRNA, the basal, catalytic and receptor-mediated activity of adenylyl cyclase and sensitization of the forskolin-stimulated activity towards augmented inhibition by guanylimidodiphosphate. In general, the increase in GRK2 and 5 mRNA exhibited a positive correlation with the gravity of the haemodynamic load, as determined by changes in left ventricular fractional shortening. 4. The results suggest that VOL induces an increase in the expression of lymphocyte beta2-adrenoceptor-specific GRK and beta-arrestin 2 in association with an attenuation in beta2-adrenoceptor levels. It can be speculated that the cardiac circulatory system adapts itself to altered haemodynamic functional demands partly by altering beta2-adrenoceptor signalling.     

Reassessment of parameters for applying motor-unit triggered stimuli in peri-stimulus time histograms

We reassessed the response properties of peri-stimulus time histograms (PSTHs) in cases when a test stimulus was triggered by a motor-unit discharge with a constant delay time. In this experiment, single motor unit action potentials were recorded from the right tibialis anterior (TA) muscle of five healthy persons. A test stimulus of the common peroneal nerve with low intensity to activate only Ia afferents of the TA was applied through a bipolar stimulating electrode placed distal to the neck of the fibula. We obtained several PSTHs with various delay times and stimulus intensities in the same recording session for maintaining the background property as the same among the test situations. As a result, we confirmed three characteristics of PSTHs from observed data: (1) given the same delay time (the same background firing properties), a weaker stimulus intensity evokes a lessened effect on PSTHs, naturally; (2) delay time alters the induction balance of direct and indirect effects on PSTHs even if the stimulus intensity is the same because the background firing properties are different; and (3) response probabilities do not correspond directly to stimulus intensities when background firing properties are different; it is possible for a relatively strong intensity stimulus to produce a weaker effect than a weak stimulus. We concluded that comparisons of effects taken at different phases in the control distribution (and also effects taken from different control distributions or different motor units) can be misleading. Therefore, such comparisons should only be made within data obtained from the same phase in the same control distribution of the same motor unit.     

Anatomic site evaluation of the zygomatic bone for dental implant placement

Thirty human zygomatic bone specimens (15 females mean age 81.60 +/- 11.38 years, 15 males, mean age 78.47 +/- 6.58 years) were examined by quantitative computed tomography and histomorphometry. The aim of the study was to assess the bone mineral density, the trabecular bone volume and the trabecular bone pattern factor. Moreover, the anterior-posterior and the medio-lateral dimensions and the estimated implant length within the zygomatic bone were determined. For quantitative computed tomography the specimens were scanned together with a bone mimicking anthropomorphic reference phantom. The bone mineral density was calculated for the specimens in the plane of the intended direction of the implant placement. Subsequently, with the sawing and grinding technique, the specimens were prepared in the same plane for histomorphometry. The trabecular bone mineral density was 369.95 +/- 188.80 mg/cm3 for the female and 398.94 +/- 99.11 mg/cm3 for the male specimens (P = 0.23). The male trabecular bone volume showed a value of 27.32 +/- 9.49%, while the female group reached a value of 19.99 +/- 7.60% (P = 0.23). The trabecular bone pattern factor was 1.2 x 10-2 +/- 1.28 mm-1 for the male and 1.02 +/- 0.96 mm-1 for the female specimens (P = 0.045). The study reveals that the zygomatic bone consists of trabecular bone with parameters that are unfavourable for implant placement. However, the success of implants placed in the zygomatic bone is secured by the employment of at least four cortical portions.