Tumor size and prognosis in aggressively treated osteosarcoma

PURPOSE: The aim of this retrospective analysis was to investigate the prognostic significance and optimal measures of tumor size in osteosarcoma treated with intensive neoadjuvant chemotherapy. PATIENTS AND METHODS: Initial anterior-posterior (AP) and lateral x-ray films of 128 patients treated within the trials Cooperative Osteosarcoma Study (COSS)-80, -82, and -86, were evaluated for the following three tumor diameters: length, width, and depth. Metastasis-free survival (MFS) analyses were performed in univariate and multivariate models with one, two, and three dimensions of the tumor as absolute or relative measures (tumor length, referred to bone length, plane and volume to body-surface area). RESULTS: Univariate analyses of MFS showed a high prognostic significance of all absolute measures. Relative measures, at best, showed a comparable predictive value. Cox regression analysis indicated the high prognostic significance of absolute tumor volume (ATV; P < .0001) and histologic response (P < .0001). None of 19 patients with an ATV < or = 70 cm3 and only four of 53 with an ATV < or = 150 cm3 relapsed, while in patients with an ATV more than 150 cm3, the relapse rate remained 40% to 60%, irrespective of further increase in volume. CONCLUSION: Initial tumor size is an important and easily obtainable prognostic factor in osteosarcoma and may serve as a basis for risk-adapted therapy. It is best represented by the absolute three-dimensional measure ATV. There is a cut-off point regarding the incidence of metastases at a tumor volume of approximately 150 cm3 as calculated from two-plane x-ray films.     

A prospective cohort study on the relationship between onion and leek consumption, garlic supplement use and the risk of colorectal carcinoma in The Netherlands

The association between onion and leek consumption, garlic supplement use and colon and rectum carcinoma among men and women was evaluated in the Netherlands Cohort Study, a large-scale prospective cohort study on diet and cancer. Onions, leeks, and garlic belong to the Allium genus and contain large amounts of potentially chemopreventive compounds. The Netherlands Cohort Study was started in 1986 among 120 852 men and women, aged 55-69 years. Dietary intake was measured with a 150-item food frequency questionnaire. After 3.3 years of follow-up, 150 and 143 incident male and female cases of colon carcinoma, and 93 and 57 cases of rectum carcinoma, respectively, with complete dietary data were available for analysis. Dietary data were available for 1525 men and 1598 women of a randomly selected subcohort, that was followed up to estimate person-time in the entire cohort. In men, the adjusted rate ratios (RRs) in multivariable analysis for colon and rectum carcinoma in the highest compared to the lowest onion consumption categories were 0.87 (95% confidence interval [CI] = 0.48-1.65), and 0.66 (95% CI = 0.28-1.52), respectively. The RRs for proximal colon carcinoma were lower than for distal colon carcinoma. Leek consumption was not associated with colon and rectum carcinoma incidence in men. None of the RRs were significantly different from unity and no trends in the RRs were detected. A lower risk was found for rectum carcinoma in women consuming less than 0.25 onions per day (RR=0.36, 95% CI = 0.13-0.99), but the trend in the RRs was not statistically significant (P = 0.25). All other RRs for colon and rectum carcinoma associated with onion consumption were slightly higher than one. Leek consumption was not associated with colon and rectum carcinoma incidence. The use of garlic supplements was not associated with colon and rectum carcinoma in men and women combined. This study does not support an inverse association between the consumption of onions and leeks, or the use of garlic supplements and the incidence of male and female colon and rectum carcinoma.     

Chemical and pharmacological studies of Phyllanthus caroliniensis in mice

We studied retrospectively the effect of long-term treatment with an inhaled corticosteroid on bronchial hyperresponsiveness (BHR) and clinical asthma in moderate-severe asthmatic subjects. Fifty-eight patients who had used beclomethasone dipropionate (BDP) over one year, were enrolled in this study. BHR was measured before and after treatment with BDP by the methods recommended by Japanese Society of Allergology. Moreover we examined the clinical factors and the frequency of acute exacerbations. The results as follows: 1) The mean age was 48.8 years and the mean asthma history was 9.2 years. The mean dose and mean time of BDP administration was 801 micrograms/day and 28.1 months, respectively. 2) Patients during BDP treatment over one year showed about 6-fold mean improvements in BHR, but there were many patients who showed no improvements in BHR. 3) We retrospectively divided all the patients into two groups. Namely, the improved group (n = 25) showed more than 4 fold improvement in BHR and unchanged group (n = 33), less than 4-fold. But there were no significant differences in clinical characteristics and %FEV1 during treatment with BDP. 4) The unchanged group had more near fatal episodes in the past than the improved group. 5) There was significant decrease in acute exacerbation during treatment with BDP, but the unchanged group had more acute exacerbations than the improved group during treatment with BDP. These results indicates that there are many patients who had no improvement on BHR with long term BDP treatment and they have more acute exacerbations due to various stimuli. In conclusion, asthma is recognized chronic inflammatory disease and inhaled corticosteroid therapy has been recommended as the first line therapy. We must further study the clinical problems and underlying mechanisms concerning about treatment with an inhaled corticosteroid.     

Penetration of intravesical doxorubicin in human bladders

The bladder wall penetration kinetics of intravesical doxorubicin were examined in radical cystectomy patients, to provide insight into drug concentrations at target tumor sites. The dosing solution (40 mg/20 ml) was instilled just prior to the start of surgery and maintained for 60-115 min until just prior to bladder excision. The data showed considerable inter-patient variability in the peak plasma concentration (24-fold), urine concentration (7- fold), and tissue concentration (28-fold). The urine concentration at the time of tissue harvest was about 17% of the concentration in the dosing solution. This was due to the dilution by post-catheterization residual urine and urine produced during treatment. The doxorubicin concentration dropped by 32-fold across the urothelium, and declined semi-logarithmically with respect to depth in the capillary-perfused tissues beneath the urothelium with a 50% decrease over about 500 micromole. In three of six patients from whom tumor tissue was obtained, the doxorubicin concentration was higher than the adjacent non-tumor-bearing tissues of comparable tissue depth, whereas the reverse was seen in the remaining three tumors. The plasma concentrations were 0.02, 0.03, 0.05, 0.27, and 0.69% of the concentrations in the tumors, urothelium, lamina propria, superficial and deep muscle layers, respectively. These data indicate: (a) a considerable intra- and inter-patient variability in bladder tissue concentrations, in part due to the variability in the urine concentration; (b) the urothelium is an effective barrier to doxorubicin penetration; and (c) a targeting advantage of intravesical therapy for the treatment of superficial bladder cancer yielding superficial bladder tissue concentrations at least 2000-fold higher than in the systemic circulation. A comparison of the data of doxorubicin with our previously published data on mitomycin C shows similar bladder tissue pharmacokinetics for the two drugs, suggesting that there is no pharmacokinetic preference for either drug.     

Congenital enterocyte heparan sulphate deficiency with massive albumin loss, secretory diarrhoea, and malnutrition

BACKGROUND: The molecular basis of protein-losing enteropathy is unknown. However it has been shown that sulphated glycosaminoglycans may be important in regulating vascular and renal albumin loss. METHODS: We describe three baby boys who presented within the first weeks of life with massive enteric protein loss, secretory diarrhoea, and intolerance of enteral feeds. All required total parenteral nutrition and repeated albumin infusions. No cause could be found in any case despite extensive investigations, including small intestinal biopsy sampling, which were repeatedly normal. FINDINGS: By specific histochemistry, we detected gross abnormality in the distribution of small intestinal glycosaminoglycans in all three infants, with complete absence of enterocyte heparan sulphate. The distribution of vascular and lamina propria glycosaminoglycans was, however, normal. INTERPRETATION: The presentation of these infants suggests that enterocyte heparan sulphate is important in normal small intestinal function.     

A long-term outcome study of 170 surgically treated patients with compressive cervical radiculopathy

BACKGROUND: There is a general impression that publications in neuro-surgical journals have comprehensively evaluated the relative merits of various operative techniques with long-term follow-up in patients treated for compressive cervical radiculopathy. However, in some 20,000 neurosurgical papers over the past 50 years, only 74 (0.3%) have addressed this common surgical problem. METHODS: Long-term outcome was assessed by the standardized Functional Economic Outcome Rating Scale of Prolo. Information was obtained primarily by telephone interviews and office visits. No patients were operated upon without a confirmatory neuroradiologic study. Single level soft discs were removed through a posterior-lateral foraminotomy with hemilaminectomy or laminectomy the root was decompressed by the same technique with hard discs. RESULTS: One hundred seventy patients were operated on from 1959-91 with a 96% follow-up. The mean follow-up period was 15 years. Patients who had sedentary occupations and housewives, had statistically higher Economic Prolo scores (p < 0.001) than those who did strenuous work. Of 10 patients with a total Prolo score of 5 or less, seven did strenuous work and had Workers' Compensation claims; the remaining had legal claims or were at psychologic risk for operation. In 86% of patients outcome was good; defined as a Prolo score of 8 in 5%, 9 in 38%, and 10 in 43%. Of 10 recurrences (6%), seven occurred within 3 years after operation and were treated by discectomy and anterior cervical fusion. There were two patients with postoperative deltoid motor weakness who recovered within 1 year. CONCLUSIONS: Although outcome studies must have subjective criteria, the Prolo Scale is more objective and quantitative than currently used methods. The posterior approach to disc lesions causing compressive cervical radiculopathy should be compared to other techniques using the Prolo Outcome Scale.     

Dual-energy X-ray absorptiometry derived structural geometry for stress fracture prediction in male U.S. Marine Corps recruits

OBJECTIVES: To evaluate the effects of losartan administration on cardiovascular mass, systemic and coronary hemodynamics (rest, maximal treadmill exercise, and dipyridamole infusion) and on resting regional hemodynamics in conscious spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. RESULTS: Although losartan administration (two doses: 10 and 30 mg/kg per day for 3 weeks by gavage) reduced left ventricular mass at the higher dose in WKY rats and with both doses in SHR, only the higher dose reduced arterial pressure in SHR. Losartan administration did not affect cardiac index, myocardial or other organ flows (radiomicrosphere) at rest in both strains. Significant increases in cardiac index and coronary flow and decreases in coronary vascular resistance were observed during exercise in both strains and these responses were not affected by losartan administration. Compared with those in WKY rats, coronary flow and flow reserve (dipyridamole) were decreased and minimal coronary vascular resistance was increased in untreated SHR. Administration of a higher losartan dose increased coronary flow reserve and decreased minimal coronary vascular resistance (measured during dipyridamole infusion) in SHR. CONCLUSIONS: These data demonstrated that losartan administration reduced left ventricular mass, a response that did not seem to be solely dependent on afterload. Furthermore, cardiac and stroke indices and coronary flow reserve were not changed in SHR during maximal treadmill exercise after hypertrophy reversal, even with the lower dose of losartan and when the ventricular afterload was similar to that of untreated SHR.     

Maternal weight gain patterns and birth weight outcome in twin gestation

OBJECTIVE: To evaluate the association between maternal weight gain patterns, based on pregravid body mass index (BMI) and birth weight outcome in twins, and to make specific recommendations for maternal weight gain during twin gestation. METHODS: One hundred eighty-nine twin pregnancies were reviewed retrospectively. Weekly rates of maternal weight gain before 20 weeks, from 20 weeks to delivery, and for total gestation were calculated. Thresholds of weekly maternal weight gain were determined for underweight and normal-weight women. RESULTS: In underweight women, a higher weekly rate of gain before 20 weeks was associated with the birth of both twins weighing at least 2500 g (1.13 versus 0.70 lb/week, P = .017), when compared with mothers of at least one twin weighing less than 2500 g. A higher rate of weight gain from 20 weeks to delivery was associated with the delivery of twins weighing at least 2500 g in both underweight (1.92 versus 1.29 lb/week, P = .031) and normal weight (1.63 versus 1.29 lb/week, P = .046) women. No significant differences in weight gain patterns were found between overweight women delivering twins weighing less than 2500 g or at least 2500 g. A weekly rate of gain from 20 weeks' gestation to delivery of at least 1.75 lb/week in underweight women and at least 1.50 lb/week in normal-weight women was associated with the birth of both twins weighing at least 2500 g. After controlling for other potential determinants of birth weight, the threshold of 1.75 lb/week in underweight women showed a trend toward significance as an independent predictor of both twins weighing at least 2500 g (P = .06). CONCLUSION: Certain maternal weight gain patterns during twin pregnancy are associated with the birth of each twin weighing at least 2500 g. As with singletons, recommendations for maternal weight gain during twin pregnancy can be based on pregravid BMI.     

A new instrument to assess the long-term quality of life effects from migraine: development and psychometric testing of the MSQOL

Quality of life is important to persons experiencing migraine. This study discusses the development of a migraine-specific quality-of-life measure (MSQOL). Participants, who included migraineurs from both tertiary care centers and the community, were screened using the International Headache Society migraine criteria prior to enrollment. Internal consistency of the MSQOL was high (alpha 0.92). Reproducibility over an average of 24 days was high (intraclass correlation 0.90). Construct validity was determined by convergent validity and known groups validity. The MSQOL was compared to two other frequently used health status questionnaires; results indicate that the MSQOL more closely resembles well-being than functional status. Results also indicate that migraineurs with more symptoms, medical appointments per year to treat migraines, and migraine episodes per year have a significantly worse quality of life. The MSQOL proved valid and reliable as a self-administered measure and will be a useful tool in clinical migraine research. The information gained from its use in the clinical environment should provide important additional information about the impact of migraine on quality of life and the potential benefits of therapeutic interventions.