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In this paper, we study flow through thin porous media as in, e.g. seals or fractures. It is often useful to know the permeability of such systems. In the context of incompressible and iso-viscous fluids, the permeability is the constant of proportionality relating the total flow through the media to the pressure drop. In this work, we show that it is also relevant to define a constant permeability when compressible and/or piezo-viscous fluids are considered. More precisely, we show that the corresponding nonlinear equation describing the flow of any compressible and piezo-viscous fluid can be transformed into a single linear equation. Indeed, this linear equation is the same as the one describing the flow of an incompressible and iso-viscous fluid. By this transformation, the total flow can be expressed as the product of the permeability and a nonlinear function of pressure, which represents a generalized pressure drop.

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A randomised multicentre study was conducted among patients over 65 yr of age with newly diagnosed acute myeloid leukaemia (AML) to compare oral treatment with etoposide 80 mg/m(2) and thioguanine 100 mg/m(2) twice daily on 5 d and idarubicin 15 mg/m(2) on 3 d (ETI) to a mainly i.v. combination of cytarabine 100 mg/m(2) twice daily on 5 d, idarubicin 12 mg/m(2) x 1, and thioguanine (TAI). Ninety-two patients were enrolled. Their median age was 72 yr, range 65-84 yr. Sixty-five patients had de novo AML, 21 AML subsequent to myelodysplastic syndrome, and six treatment-related AML. They received at first a 6-d i.v. treatment with cytarabine and idarubicin. After the first treatment, 68 patients were randomised to receive two cycles of ETI (n = 36) or TAI (n = 32) and thereafter maintenance with mercaptopurine and methotrexate. Of the 92 patients, 52 (57%) achieved remission at some stage. The median survival was 10 months. There were no significant differences between the patients randomised to ETI or TAI in the remission rate (67% vs. 72%), survival (12 months from randomisation in both arms), event-free survival or relapse rate. The patients randomised to receive ETI spent significantly fewer days at hospital during the two randomised cycles (20 vs. 41 d, P = 0.010), and they had fewer days with infusions, shorter neutropenias and thrombocytopenias and fewer and less severe infections. In conclusion, treatment with oral ETI resulted in a similar antileukaemic effect as obtained with mainly i.v. TAI, with less toxicity and reduced need for hospitalisation.

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In acute myelogenous leukemia (AML) intensive postremission treatment is needed for an optimal result. However, it is not known how long the treatment should last and how many courses are necessary. The object of this prospective study was to compare four and eight intensive chemotherapy cycles in the treatment of adult de novo AML. In a multicenter study, 248 consecutive patients, aged from 16 to 65 years, were treated with intensive induction treatment. The patients in remission after two courses were randomized to receive either two (short arm) or six (long arm) additional intensive cycles of chemotherapy. The median follow-up time of the living patients is 68 months. Of the patients, 77% achieved complete remission, and 36% of all patients survived for 5 years. Seventy-three patients were randomized to the short arm and 66 to the long arm. There was no significant difference in the relapse-free survival (median 21 months vs 17 months) or overall survival (43 months vs 39 months) between the short and long arms, respectively. Treatment-related deaths occurred in 31 patients (13%), 11 of them in first remission. More than one-third of the patients survived for 5 years. It seems probable that the first few months after diagnosis are decisive for the prognosis if the chemotherapy is intensive, and further treatment cannot markedly influence the outcome.

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In order to study the efficacy of an oral induction and consolidation regimen in the treatment of acute myeloid leukemia (AML) in elderly patients assessed not to tolerate full-scale intensive chemotherapy, 51 patients over 65 years of age with newly diagnosed AML were randomized to receive two cycles of either totally oral ETI (25 patients) or conventional 5-day TAD (26 patients). The median age of the patients was 73 years, range 65-87 years. Thirty-eight patients had de novo AML and the remaining patients AML subsequent to myelodysplastic syndrome ((n = 11) or treatment related AML (n = 2)). ETI consisted of etoposide 80 mg/m2 and thioguanine 100 mg/m2 twice a day on days 1-5, and idarubicin 15 mg/m2 on days 1-3, all given orally. TAD consisted of oral thioguanine and i.v. cytarabine, both in the dose of 100 mg/m2 twice a day on days 1-5, and daunorubicin 60 mg/m2 on day 5. The maintenance treatment was daily oral mercaptopurine 70 mg/m2 and weekly oral methotrexate 12 mg/m2. In the ETI group complete remission (CR) was achieved in six patients after the first cycle and in nine more patients after the second cycle. The CR rate was 15/25 = 60%. The corresponding figures for the TAD group were four and two remissions, CR rate 6/26 = 23% (p = 0.007). The survival was significantly longer in the ETI arm (p = 0.042). The median survival was 9.9 months in the ETI group and 3.7 months in the TAD group. There were no significant differences in the side effects between the two arms. In conclusion, the totally oral ETI regimen resulted in a significantly higher remission rate and longer survival than the 5-day TAD regimen in elderly patients with AML, with no more toxicity.

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In a randomised multicentre trial a combination of methylprednisolone, vincristine, lomustine, cyclophosphamide and melphalan (MOCCA) was compared with the same regimen omitting methylprednisolone after the first course (COLA) in previously untreated patients with multiple myeloma. The MOCCA arm showed a response rate of 72% among 79 patients and the COLA arm a response rate of 60% among 59 patients. This difference was not statistically significant. The median survival time was 56 months in the MOCCA arm and 61 months in the COLA arm. There was a slight increase of early deaths (within the first 6 months) in the MOCCA arm as compared with the COLA arm. We conclude that, in multidrug therapies, the continuation of corticosteroid at conventional dosage beyond the first course does not improve response rate or survival time in multiple myeloma.

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108 consecutive patients with de novo acute myeloid leukaemia at ages 15 to 59 years were treated in a prospective controlled multicentre trial. Induction with combination TAD resulted in a complete remission in 85 cases (79%). After a cyclic consolidation programme for 6 months, 73% of the remissions continued. The maintenance therapy was at random either nothing, or alpha interferon, or monthly 5 day courses with thioguanine and cytarabine. The median duration of all remissions was 13 months; that of those in the control and interferon arms 15 months each, and in the chemotherapy arm 18 months. The median survival of all the 108 patients was 16 months; that of those in the control arm 20 months, in the interferon arm 33 months and in the chemotherapy arm 26 months. At 5 yr, 31%, 22% and 31%, respectively, were alive. The survival curves did not differ from each other significantly. Maintenance treatment after an intensive induction and a moderately intensive consolidation was of no benefit in this study. Interferon did not improve the prognosis.

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94 patients with refractory multiple myeloma were treated in a multicentre trial with combinations of cytotoxic drugs including anthracyclines. All were refractory to a 5-drug combination containing 3 alkylating agents, vincristine and methylprednisolone (MOCCA). With a combination of epirubicin and iphosphamide a 50% response was achieved in 9% of 22 patients. The response rate after schedule VAP (vincristine, doxorubicin and prednisolone) was 8% of 13 patients and that after schedule VAD (vincristine, doxorubicin and dexamethasone) 20% of 59 patients. The previous chemotherapy had lasted for less than 12 months in 13 cases from among all these patients, and 5 of these (38%) responded. In contrast, there were only 10 responders (12%) among the 81 patients with longer previous chemotherapy.

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The actual use of hospital beds for patients with multiple myeloma was calculated from a randomised trial of primary treatment with either melphalan and prednisone (MP, 66 patients) or intensive combination chemotherapy with vincristine, cyclophosphamide, lomustine, melphalan and methylprednisolone (MOCCA, 64 patients). The survival of the patients was similar in both arms, and the samples, 20 and 32 patients, respectively, were well representative for the whole arms. The average numbers of hospital days were similar fur both arms. For the first year MP 33.2 (SD 27.6) vs. MOCCA 32.1 (SD 19.0), and during the first to 4th years 78.5 (SD 45.9) vs. 67.8 (SD 34.1). For the year of death it was 50.4 (SD 33.1) vii. 36.3 (SD 27.0), respectivelly. Thus the choice of primary chemotherapy whether conventional or more aggressive had no influence on the actual number of in-patient hospital days concerned. When the combination chemotherapy schedule is well tolerated it can be administered just as well on an ambulatory basis or by using it with very short admissions. It seems that the need for inpatient care for patients with multiple myeloma is mostly related to the complications of the disease itself and to intercurrent disorders including infections.

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Patients aged 70 yr or older with multiple myeloma were treated, when suitable, according to concurrent trial protocols for younger patients, with the exception that the cytostatic regimen was not allocated at random. Intermittent melphalan and prednisone (MP) was given as the primary treatment to 42 patients and 5-drug combination MOCCA to 68 patients. The groups were comparable with each other, and the distribution of the clinical stages of the patients was similar to the younger patients in concurrent trials. An at least 50% response was achieved in 33% (SE 7.3) with MP and in 75% (SE 5.3) with MOCCA. The median survival times were 39 and 32 months, the relative age-adjusted survival times 45 and 41 months, respectively. Advanced age as such is thus no contraindication for active treatment of myeloma, and in suitable patients the results compare well with those achieved in younger patients.

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Gel-filtration experiments of mixtures of functionally active and inactive forms of plasminogen activator inhibitor (PAI) with human plasma or bovine serum albumin have provided evidence for the existence of a discrete binding protein of PAI in plasma. Most likely it is a glycoprotein with a molecular weight of approximately 150,000. The data suggest that it forms a very stable complex with functionally active forms of PAI, but not with the inactive or "latent" PAI. However, the PAI activity seems not to be significantly altered by the interaction with the binding protein. Assuming that a stoichiometric complex is formed, titration experiments suggest that a pool of normal human plasma contains about 40-50 mg of PAI-binding protein liter.

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In a randomised multicentre trial a combination of methylprednisolone, vincristine, CCNU, cyclophosphamide and melphalan (MOCCA) was compared with intermittent melphalan and prednisone (MP) as primary treatment in multiple myeloma. In the MP arm the refractory or relapsed patients were treated with regimen MOCCA. The MOCCA arm produced a response rate of 75% among 64 patients and the MP arm a response rate of 54% among 66 patients. The median survival was 41 months in the MOCCA arm and 45 months in the patients primarily randomised to the MP arm. The initial response to MOCCA improved the survival, while this effect was not statistically significant in the MP arm. The results show that the median survival does not increase if aggressive chemotherapy is employed as the first line treatment in multiple myeloma.

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