Medical treatment of multinodular goiter

Thyroid nodules are among the most common clinical problems in endocrinology. Among several factors responsible for the development of goiter, circulating TSH plays a major role because of its direct growth-promoting effects on the thyroid cells; moreover TSH may enhance the effects of other local growth factors which act in a paracrine mode in the thyroid gland. In addition, autoimmune thyroiditis can clinically appear as thyroid nodules frequently with the functional aspect of a subclinical hypothyroidism. For these reasons a therapeutical approach based on the thyroxine suppression of TSH secretion has become largely used by 1970s and is correctly employed in 75% of the patients with thyroid nodules whose biopsies result benign.     

Continuous hyperfractionated accelerated radiotherapy with/without mitomycin C in head and neck cancer

PURPOSE: To evaluate the effect of mitomycin C to an accelerated hyperfractionated radiation therapy. The aim was to test a very short schedule with/without mitomycin C (MMC) with conventional fractionation in histologically verified squamous cell carcinoma of the head and neck region. METHODS AND MATERIALS: From October 1990 to December 1996, 188 patients entered the trial. Tumors originated in the oral cavity in 54, oropharynx in 82, larynx in 20, and hypopharynx in 32 cases, respectively. Patients' stages were predominantly T3 and T4 (158/188, 84%) and most patients had lymph node metastases (144/188, 77%) at diagnosis. Only 22 patients were female, 166 were male, the median age of patients was 57 years (range 34 to 76 years). Patients were randomized to one of the following three treatment options: conventional fractionation (CF) consisting of 70 Gy in 35 fractions over 7 weeks (65 patients) or continuous hyperfractionated accelerated radiation therapy (V-CHART; 62 patients) or continuous hyperfractionated accelerated radiation therapy with 20 mg/sqm MMC on day 5 (V-CHART + MMC; 61 patients). By the accelerated regimens, the total dose of 55.3 Gy was delivered within 17 consecutive days, by 33 fractions. On day 1, a single dose of 2.5 Gy was given, from day 2 to 17 a dose of 1.65 Gy was delivered twice: the interfraction interval was 6 hours or more. RESULTS: Mucositis was very intense after accelerated therapy, most patients experiencing a grade III/IV reaction. The mucosal reaction did not differ whether MMC was administered or not. Patients treated by accelerated fractionation experienced a confluent mucosal reaction 12-14 days following start of therapy and recovered (no reaction) within 6 weeks. The skin reaction was not considered different in the three treatment groups. Those patients treated with additional chemotherapy experienced a grade III/IV hematologic toxicity in 12/61 patients. Initial complete response (CR) was recorded in 43% following CF, 58% after V-CHART, and 67% after V-CHART + MMC, respectively (p < 0.05). Actuarial survival (Kaplan-Meier) was significantly improved in the combined treated patients. Local tumor control was 28%, 32%, and 56% following CF, V-CHART, and V-CHART + MMC, respectively (p < 0.05). CONCLUSION: We conclude that our continuous hyperfractionated accelerated radiation therapy regimen is equal to conventional fractionation, suggesting that by shortening the overall treatment time from 7 weeks to 17 days a reduction in dose from 70 Gy to 55.3 Gy is possible, with maintenance of local tumor control rates. The administration of MMC to the accelerated regimen is tolerable and improves the outcome for patients significantly.     

Influence of flow pattern on the parameter estimates of a simplebreathing mechanics model

The first-order model of breathing mechanics is widely used in clinical practice to assess the viscoelastic properties of the respiratory system. Although simple, this model takes the predominant features of the pressure-flow relationship into account but gives highly systematic residuals between measured and model-predicted variables. To achieve a better fit of the entire data set, an approach hypothesizing deterministic time-variations of model parameters, summarized by information-weighted histograms was recently proposed by Bates and Lauzon (1992). The present study uses flow and pressure data measured in intensive care patients to evaluate the real potential of this approach in clinical practice. Information-weighted histograms of the model parameters, estimated by an on-line identification algorithm, were first constructed by taking into account the parameter percentage standard deviations. Then, the influence of the respiratory flow pattern on the calculated histograms was evaluated by the Kolmogorov-Smirnov statistical test. The results show that the method gives good reproducibility under stable experimental conditions. In addition, for a given airflow waveform; an increase in respiratory frequency shifts the histograms representing time-varying viscous properties strongly versus lower values, whereas it shifts the histograms representing time-varying elastic properties slightly versus higher values. On the other hand, the same histograms were highly dependent on the airflow waveform, especially for the viscous properties. Even in a limited experimental work, in all the conditions considered, the method provides results which agree well with the physiological knowledge of nonlinear and multicompartment behavior of respiratory mechanics     

Hepatoblastoma in an adult associated with c-met proto-oncogene imbalance

A rare case of hepatoblastoma in a 61-year-old Japanese housewife is described. This liver tumor mainly consisted of two tissue components: embryonal hepatocytes and primitive mesenchymal tissue. Fetal hepatocytes with alpha-fetoprotein production, gland formation, cartilage and osteoid were also found in a small portion. Molecular analysis by slot blot method revealed increased copy numbers of c-met and K-sam proto-oncogenes and cyclin D1 genes. These findings suggest that alterations of these oncogenes might play a role in the development of adult hepatoblastoma.     

Application of HUMF13A01 (AAAG)n STR polymorphism to the genetic diagnosis of coagulation factor XIII deficiency

Deficiency of the A subunit of coagulation factor XIII causes a severe bleeding disorder requiring life long replacement therapy. The mutations causing A subunit deficiency appear to be very heterogeneous, and it is impractical to identify each mutation before genetic counselling or prenatal diagnosis can be attempted. In this study we have shown that a highly polymorphic short tandem repeat element, HUMF13A01 (AAAG)n that occurs in the 5' flanking sequence of the factor XIII A subunit gene, can be used to follow the segregation of deficiency causing mutations. We studied 6 families with factor XIII A subunit deficiency from 5 different ethnic groups. All parents were heterozygous for the repetitive element and therefore all the families were informative. The linked polymorphism was used to carry out the first prenatal diagnosis of factor XIII A subunit deficiency. The analysis of this polymorphism by the polymerase chain reaction is rapid, reliable, requires little DNA and is ideal for the genetic analysis of factor XIII A subunit deficiency.