A simulation model for tumor growth controlled by therapeutic agents.

Results obtained in a controlled tumor growth depend on the experimental model used, the agent employed (drugs, ionizing radiations, heat), aw well as the administration scheduling and the host environment. Empirical search and treatment optimization are related to a discrete number of agent combinations and fractioning, and system parameters and dependencies are strictly connected to biological assumptions. A simplified model for the evaluation of the rate of change of tumor volume at the time of cytotoxic agent administration is proposed here, as well as a computer program to perform the simulation of tumor growth controlled by therapeutic agents.

Modeling the HIV/AIDS epidemic via survivor functions.

An original approach to simulation modeling of the HIV/AIDS epidemic is proposed. This approach uses survivor functions estimated from cohort studies conducted with seropositive and AIDS-diagnosed individuals. The model can be considered an alternative to the usual Markov models and accounts for time-dependent HIV progression to AIDS, and AIDS progression to death. By using various forms of survivor functions, it can also easily be extended to accommodate natural history events, as well as long-term survivors and cofactor effects, when appropriate data are available.

The results of radiosurgical management of 72 middle fossa meningiomas.

Of 812 patients with intracranial tumours treated by radiosurgery during the period 1984-1990, 129 had meningiomas. Of these latter, 72 had middle fossa meningiomas. Patients with meningiomas treated by us since March 1990 are not included in this report since we established the investigative principle of a minimum of 30 months follow-up. Seventeen of the 72 patients were treated after incomplete surgical resection, and 21 for tumour regrowth. In 34 patients, radiosurgery was the primary treatment. The tumour volume was calculated by the ellipsoid method. It ranged from 0.588-76.346 ml. Radiosurgery was performed using the non-invasive stereotactic fixation head device (Greitz-Bergström) adapted to the Fixster frame, and dynamic irradiation performed with the linear accelerator, using especially designed collimators. The total tumour dose for each patient ranged from 15-45 Gy. The minimum follow-up was 2 1/2 years and the maximum 8 years. In 50 patients there was tumour shrinkage ranging from 24-91% of the initial tumour volume. Shrinkage was associated with central tumour necrosis in 11 of these 50 patients. In 18 patients the tumour volume remained stable. In 2 patients there was tumour progression and in 2 there was regrowth after initial reduction of tumour volume. There were no significant treatment complications. Radiosurgery is preferable to re-operation in recurrent meningiomas and indicated after incomplete surgical removal. In high risk patients, as well as in "unresectable" meningiomas, it is an obvious alternative to microsurgery.

Linear accelerator and Greitz-Bergstrom's head fixation system in radiosurgery of single cerebral metastases. A report of 86 cases.

Between 1984 and 1991 86 patients with single cerebral metastases underwent linear accelerator radiosurgery using the atraumatic and reproducible Greitz-Bergström head-fixation device. Routine one-month follow-up documented disappearance of the tumour in 16 patients, with resolution of the oedema and ventricular shift. Shrinkage of the metastasis occurred in 51 patients. In 9 patients the tumour remained stable, in 7 there was progression of tumour size. Among the patients showing shrinkage of the tumour or unchanged tumour volume, repeated radiosurgery resulted in disappearance of the metastasis in 5 and further shrinkage in 28. In 14 patients routine stereotactic CT follow-up study led to the detection of a new metastasis, again treated with excellent results. Local recurrence occurred in 2 patients and radiation necrosis in the target area in 5 patients. Radiosurgery thus proves to be an appropriate alternative to surgery. The versatility of our non-invasive and painless method permits CT staging (which we consider essential) without hospitalization of the patient.

Linkage analysis of 6p21 polymorphic markers and the hereditary hemochromatosis: localization of the gene centromeric to HLA-F.

Hereditary Hemochromatosis (HFE) is one of the most common inherited disorders with an estimated frequency of homozygous patients of 0.002-0.0045. The disease is characterized by increased intestinal iron absorption and progressive iron overload. Affected subjects show clinical symptoms of parenchymal organ damage after the third-fourth decade of life and have a 200 fold increased risk of developing hepatocellular carcinoma. Early diagnosis and treatment prevent complications and may normalize life expectancy of patients. The biochemical and genetic defects leading to progressive iron accumulation are still unknown, but the HFE gene is tightly linked to HLA complex on the short arm of chromosome 6. Utilizing HLA serotypes and the study of several polymorphic markers of 6p21, a linkage analysis of the disease locus was performed in a series of Italian hemochromatosis families. The data obtained by linkage analysis and the study of a family with a double recombinant allowed us to better define the HFE gene location with respect to HLA-class I A and F loci.

The gene for spinal cerebellar ataxia 1 (SCA1) is flanked by two closely linked highly polymorphic microsatellite loci.

The gene for one form of autosomal dominant spinal cerebellar ataxia (SCA1), is mapped by linkage to chromosome 6p, very close to the microsatellite locus D6S89. Eight large Italian kindreds segregating SCA1, as defined by very close linkage to D6S89, were genotyped with five microsatellite markers linked closely to D6S89, all mapping within a 6 cM interval on 6p. Multipoint linkage analysis and haplotypes from recombinants map SCA1 between two of these markers, D6S274 and D6S259, 5-6 cM apart. A single rare four marker haplotype within this interval shows linkage disequilibrium with the disease locus in southern Italy and is transmitted with SCA1 in five kindreds originating from this area.

Multivariate analysis of a tissue CEA, TPA, and CA 19.9 quantitative study in colorectal cancer patients. A preliminary finding.

Tissue CEA, TPA, and CA 19.9 concentrations from samples of surgical specimens were measured in 47 evaluable colorectal cancer patients (median follow-up, 20 months, 13 recurrences) and correlated with individual patient follow-up status. The quantitative method appeared to be sensitive, easily reproducible, and standardizable. The tissue marker concentration was analyzed by means of the multivariate discriminant analysis, to evaluate the risk of relapse in each patient; the tumor CEA (CEA T) showed the best discriminant capacity (P = .005). The relative Fisher function provided a reliable prognostic patient index, independently of other recognized prognostic factors (Dukes' stage and cellular differentiation grade). The Cox model showed a statistical significance analyzing the tumor (T) and healthy mucosa (M) CEA values (P = .001 and P = .006, respectively). The combination of these two variables allowed for identification of three classes of patients according to CEA T and M threshold values of 216 and 85 ng/mg of protein, respectively, and different disease-free curves were obtained for each group. The two-year disease-free rate was 81 percent for patients with low values of both CEA T and M, and 21.4 percent for the group with both values above these thresholds (P = .0008). In the third class (CEA T or M higher than the reported cut-off levels), the two-year disease-free rate was 65.9 percent.