SARS incubation and quarantine times: when is an exposed individual known to be disease free?

The setting of a quarantine time for an emerging infectious disease will depend on current knowledge concerning incubation times. Methods for the analysis of information on incubation times are investigated with a particular focus on inference regarding a possible maximum incubation time, after which an exposed individual would be known to be disease free. Data from the Hong Kong SARS epidemic are used for illustration. The incorporation of interval-censored data is considered and comparison is made with percentile estimation. Results suggest that a wide class of models for incubation times should be considered because the apparent informativeness of a likelihood depends on the choice and generalizability of a model. There will usually remain a probability of releasing from quarantine some infected individuals and the impact of early release will depend on the size of the epidemic.

Short-lived orogenic cycles and the eclogitization of cold crust by spasmodic hot fluids.

Collision tectonics and the associated transformation of continental crust to high-pressure rocks (eclogites) are generally well-understood processes, but important contradictions remain between tectonothermal models and petrological-isotopic data obtained from such rocks. Here we use 40Ar-39Ar data coupled with a thermal model to constrain the time-integrated duration of an orogenic cycle (the burial and exhumation of a particular segment of the crust) to be less than 13 Myr. We also determine the total duration of associated metamorphic events to be approximately 20 kyr, and of individual heat pulses experienced by the rocks to be as short as 10 years. Such short timescales are indicative of rapid tectonic processes associated with catastrophic deformation events (earthquakes). Such events triggered transient heat advection by hot fluid along deformation (shear) zones, which cut relatively cool and dry subducted crust. In contrast to current thermal models that assume thermal equilibrium and invoke high ambient temperatures in the thickened crust, our non-steady-state cold-crust model satisfactorily explains several otherwise contradictory geological observations.

Thermodynamic analysis of water interaction with excipient films.

The interaction of water with excipients that can form moisture-protective coatings was examined earlier by the application of theoretical models. In this study, thermodynamic analysis of water-excipient film systems has been performed to elucidate the mechanistic details of the water-excipient interaction. Partial molal free energies, enthalpies, and entropies were computed for films of lipidic (glyceryl behenate, GB) and polymeric (polyvinyl alcohol, PVA) coating excipients using the temperature dependence of the adsorption process. The analysis of free energy changes showed that excipient films were not inert participants in the water sorption process. The isoteric heats of adsorption confirmed that water formed hydrogen bonds with the excipient films and allowed estimation of number of hydrogen bonds per water molecule. This result also provided the reason for hysteresis during drying. A comparative evaluation of the application of theoretical models and thermodynamic analysis revealed that results obtained from both approaches were not always complementary. An exponential relationship was found to exist between sorption microrate constants and water activity for the PVA films at all temperatures.

Hot-melt coating: water sorption behavior of excipient films.

Hot-melt coating allows encapsulation of water-labile, drug-laden substrates to form a barrier that resists moisture ingress. To understand the interaction of water with excipients that can form moisture-protective coatings, sorption behavior of films of lipidic (glyceryl behenate) and polymeric (polyvinyl alcohol) coating excipients was investigated. A simple and rapid method using a new, fully automated instrumental technique to investigate the sorption/desorption behavior of excipient films is reported. Further, the influence of temperature and film thickness on the sorption behavior of films is examined. Both excipient films displayed sorption isotherms that were classified as type III and demonstrated hysteresis during desorption. The sorption data for both films did not follow the Langmuir model, and the BET model could only be used restrictively. The GAB model fitted the sorption data at all conditions and over the entire range of water activity studied. The ability of the Young and Nelson model to explain the hysteresis behavior, from analytical and mechanistic perspectives, is evaluated. Temperature and film thickness were found to profoundly influence the nature of moisture interaction and distribution of moisture in the excipient films. An Arrhenius-type relationship was observed between equilibrium moisture content of excipient films and temperature at constant water activity.

Randomized, double-blind, placebo-controlled trial comparing the response rates of carmustine, dacarbazine, and cisplatin with and without tamoxifen in patients with metastatic melanoma. National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: We designed and conducted a randomized, double-blind, placebo-controlled trial to compare the response rates and survival of patients with metastatic melanoma who received carmustine (BCNU), dacarbazine (DTIC), and cisplatin with tamoxifen, or the same chemotherapy with placebo. PATIENTS AND METHODS: Eligible patients with metastatic melanoma received either BCNU 150 mg/m2 intravenously (i.v.) on day 1, DTIC 220 mg/m2 i.v. daily on days 1 to 3 and on days 22 to 24, and cisplatin 25 mg/m2 i.v. daily on days 1 to 3 and on days 22 to 24 with placebo every 6 weeks, or the same chemotherapy with tamoxifen 160 mg orally daily for 7 days before chemotherapy and 40 mg orally daily throughout the remainder of the treatment cycle. Patients were treated on protocol for up to three cycles depending on the type of response. Assuming that a minimum increase in response rate of 20% would be necessary to conclude that tamoxifen conferred a clinically important benefit, we designed the study with an 80% chance of detecting that difference at the 5% level (two-sided). RESULTS: Between February 1992 and January 1995, 211 patients were accrued, 199 of whom were considered assessable for response and toxicity. The overall response rate was 21% in the placebo group and 30% in the tamoxifen group (P = .187). Complete and partial responses were 3% and 27%, respectively, for the tamoxifen group and 6% and 14%, respectively, for the placebo group. Poor performance status and liver involvement were associated with a reduced likelihood to respond to treatment. Major toxicities were similar in both groups with no statistically significant difference in the rates of deep vein thrombosis, pulmonary thromboembolus, grade 4 neutropenia, or grade 4 thrombocytopenia. CONCLUSION: These results demonstrate that the addition of high doses of tamoxifen to this chemotherapy regimen does not increase the response rate compared with chemotherapy alone in unselected patients with metastatic melanoma.

Determination of dietary fiber and carbohydrate composition of foods by a modified version of the Englyst method.

A modified version of the Englyst procedure for determination of dietary fiber and carbohydrate fractions of foods is described. The method is based on hydrolysis of separated fractions and capillary gas chromatographic (GC) analysis of derivatized monomer sugars, UV photometry of uronic acids, gravimetric determination of residue, and analysis of nitrogen content of the residue by using a C, H, N elemental analyzer. Modifications of fractionation, derivatization, and GC procedures are discussed. Rigorous sample preparation is required for reproducibility of 200 mg test portions. Contaminants interfering with chromatography must be minimized. Results for reference samples (wheat bran and Buerre Bosc pears) and white and whole meal bread agree with literature values.

Length of follow-up in teratomas--results of a modification of Einhorn's regime in testicular teratomas.

A modification of Einhorn's original chemotherapy schedule was used to treat 40 patients with metastatic testicular teratomas. Each cycle of chemotherapy consisted of cisplatin (100 mg/m2), bleomycin (30 mg X 3) and vinblastine (5 mg/m2 X 2). Four patients failed to achieve a complete response and died with advanced disease. There was one treatment death. Only two of 14 patients who had residual masses resected still had active tumour. The 2-year actuarial disease free survival for patients in first remission was 85%, but this fell to 77% at 5 years as 3 patients relapsed (34, 36, 37 months). The results are comparable with other series but are associated with less toxicity. The need for continued follow-up is demonstrated in view of relapses occurring after 2 years.

Cisplatin and etoposide alternating with vincristine, doxorubicin and cyclophosphamide in patients with small cell lung cancer.

Fifty-seven patients with small cell lung cancer were treated with cisplatin and etoposide alternating with vincristine, doxorubicin and cyclophosphamide. Seven patients were withdrawn because of drug toxicity. Of 50 evaluable patients 21 had limited and 29 extensive disease of whom 19 and 21 respectively achieved an objective response. Seven patients survived for longer than 2 years of whom 5 remained alive and tumour free 121-167 weeks from the start of treatment. Patients with limited disease and a complete response had a median survival of 72 weeks and the median survival of the whole group was 43 weeks. Seven out of 22 (32%) of patients who obtained a complete response relapsed and died with solitary evidence of cerebral metastases. This indicates the need for reassessment of the role of prophylactic cranial irradiation in patients achieving a complete response with effective systemic chemotherapy.

Resolution after radiotherapy of severe pulmonary damage due to paraquat poisoning.

A 29 year old man was admitted 36 hours after ingesting about 5 g paraquat. His arterial oxygen pressure fell progressively to 3.4 kPa (34 mm Hg), and pulmonary damage induced by paraquat was diagnosed. His condition did not improve after treatment with prednisolone and cyclophosphamide, but after irradiation both lungs cleared and arterial oxygen pressure started to improve. Irradiation of the lungs should be considered in patients who, after surviving the acute phase of poisoning with paraquat, show progressive deterioration of respiratory function.

Treatment of cancer of the cervix with a high-dose-rate afterloading machine (the Cathetron).

Two hundred and ninety-one patients with invasive carcinoma of the cervix uteri were treated by a combination of external beam therapy (telecobalt or 4 Mv Linear accelerator) and a high dose-rate afterloading intracavitary apparatus (the Cathetron). All patients have been followed for a minimum of 3 1/2 years. The five year survival rates are: all patients 55%; Stage I, 81%; Stage IIA, 74%; Stage IIB, 40%; Stage III, 27%. Death was directly attributed to treatment in five patients. We found a serious complication rate of 3% for all patients treated, the major problem being radiation ileitis. It is concluded that high dose-rate treatment offers comparable results to conventional radium therapy; the choice between high and lose dose-rate afterloading systems depends on the number of patients needing treatment and associated economic factors rather than any intrinsic radiobiological advantage of either system.

A controlled clinical trial in advanced ovarian cancer.

Thirty-eight patients with an advanced ovarian cancer (FIGO stage III and IV) were randomly allocated to treatment, either with melphalan (M) or a combination of adriamycin, 5-fluorouracil and cyclophosphamide (CAF) to determine the effect on survival. Actuarial survival of the two treatment groups was the same but the combination was more toxic.

The investigation and treatment of germ cell tumours of the testis.

Fifty-five per cent of patients presenting with testicular tumours in 1973--78 had teratomata. A history of undescended testis was only found in patients with seminoma. The right testis was the more frequent site of the primary. Radiation doses of 3400 cGy (rad) in 20 fractions for seminoma and 4500 cGy in 25 fractions for teratoma were well tolerated and sterilised microscopic disease in the majority of patients. Forty-two of 44 seminoma patients are alive and free from disease at a median follow-up of three years. Only 15 of 22 Stage I teratoma patients remain disease free, however. A combination of vinblastine and bleomycin produced 12 complete remissions in 30 patients with metastatic teratoma. Survival was significantly longer for patients achieving complete remission. Although six of the complete responders remain alive, only three are in their initial complete remission. Alpha-foeto-protein and/or beta-subunit human chorionic gonadotrophin levels were elevated in almost all cases of advanced teratoma. The biological half-life of alpha-foeto-protein in the serum is less than six days. The value of these markers in predicting relapse was limited in this series. The doubling of complete response rate in metastatic teratomata that can be achieved by adding cis-platinum to the vinblastine/bleomycin combination, together with the propensity for extranodal metastasis shown by testicular teratomata, suggest that adjuvant chemotherapy should be explored in early disease.

Cancer-specific density changes in lymphocytes after stimulation with phytohaemagglutinin.

A fluorescence polarisation technique ("S.C.M. test") for detecting responses to phytohaemagglutinin revealed that the responsive lymphocytes from patients with malignant disease had an abnormal distribution after centrifugation through lymphocyte separation medium. In a small blind series the technique accurately distinguished patients with histologically proven malignancies from those with nonmalignant disease and normal people.

Comparative trial of large and small fractions in the radiotherapy of head and neck cancer.

A random controlled trial was performed to compare long and short fractionation of radiotherapy in patients with head and neck cancer with a poor prognosis. Ninety-eight matched pairs were treated, one member of each pair received 10 fractions in 22 days, the other 30 fractions in 42 days. The same nominal standard dosages were used in each arm of the trial. Mucosal reactions were more severe with 10 fractions, skin reactions more severe with 30 fractions. No difference in survival, local tumour control rates or late normal tissue effects could be demonstrated. It is suggested that any possible therapeutic advantage of prolonged fractionation is minimal and that it is justified to use a small number of large fractions in clinical trials involving hyperbaric oxygen or electron-affinic sensitizers.

Hepatic oil embolism following lymphography.

Lymphograms of 1,000 patients were reviewed with special reference to the occurrence of hepatic oil embolism following the procedure. Oily contrast medium ("Lipiodol" ultra-fluid) was found in the liver in seven cases, five of whom had carcinoma of the cervix uteri. Hepatic oil embolism was not encountered in patients with lymphomas in this series. Complete or partial lymphatic obstruction was present in all seven cases and one patient had almost complete obstruction of the inferior vena cava. Malignant disease need not always be the predisposing factor since hepatic oil embolism occurred in one patient with retroperitoneal fibrosis. The routes through which the contrast medium may reach the liver are discussed and lymphaticoportal communications in the mesentery are thought to play an important role. Contrast was invariably seen in the liver within two hours of commencement of the injection and was still faintly visible in one case three and a half months later. The way in which the contrast-pattern in the liver changes with time is described. An attempt is made to correlate the radiological appearances with the fate of the contrast medium in the liver.

The relationship among motor tasks for preschool children.

The relationship among motor tasks on the Whitener Motor Performance Battery of Tests was determined. The sample included 208 preschool children from white, middle and upper socio-economic class families. Factor analyses revealed relationships among the tasks of the Whitener Motor Performance Battery of Tests for two age groups. Four factors extracted for the 3-and 4-yr. age group were "Total Body Strength and Leg Power," "Arm and Shoulder Power and Gross Coordination," "Rhythmic Coordination," and an "Unknown" factor. For the 5-and 6-yr. age group, five factors were named: "Rhythmic Coordination," "Arm and Total Body Strength," "Speed of Movement and Power," "Gross Motor Coordination" and "Dynamic Balance."