Importance of locoregional chemotherapy by anthracyclines

With loco-regional chemotherapy high local concentration of antineoplastic products can be achieved without systemic toxicity. However local toxicity and technical problems are frequent and limit its use. Intra arterial chemotherapy (IAC) is interesting when the drugs used have a high total body clearance. One of the best indication of IAC is the intra-hepatic chemotherapy with anthracyclin for hepatocellularcarcinoma (40-60% objective response) and metastatic carcinoid. Among other IAC the IA limbs perfusions for soft tissue sarcoma have given interesting results. Chemoembolization with lipiodol and/or gelfoam mixed with anthracyclin is an interesting field of investigation in liver tumor and metastases. Intraperitoneal chemotherapy is used essentially for peritoneal carcinomatosis from ovarian origin and gives some positive results. However, intra peritoneal Adriamycin is not well tolerated and other anthracyclines are to be investigated.     

Surgical Treatment of an Early Epileptic Encephalopathy with Suppression-Bursts and Focal Cortical Dysplasia

Summary: A case of early epileptic encephalopathy (EIEE) with suppression-bursts or Ohtahara's syndrome, associated with focal cortical dysplasia is reported. Infantile spasms and brief tonic unilateral seizures began on the fifth day of life. Interictal EEG demonstrated an asymmetrical "suppression-burst" pattern with no wake or sleep cycling. Seizures were refractory to all antiepileptic drug (AED) and steroid therapy. Magnetic resonance imaging (MRI) showed right frontotemporal cortical thickening. After three weeks of an ineffective medical treatment a preoperative evaluation with single photon emission computed tomography (SPECT) and electrocorticography (ECoG) was performed to characterize epileptogenic focus. Surgical resection of the precentral area was performed at age 1 month. Neuropathologic examinations confirmed diagnosis of focal cortical dysplasia by identifying cytoarchitectural disarray and ectopic neurons located deep in subcortical white matter. During follow-up, 1-year postoperative the child had a single febrile seizure. Neurologic examination showed minor developmental delay and slight left-sided weak ness.     

PK/PD modeling of aminoglycoside nephrotoxicity

Aminoglycosides are bactericidial antibiotics with a serum concentration-dependent activity. They are mainly eliminated by the kidneys and the main difficulty arising in clinical use is their uptake by the renal cortex which leads to nephrotoxicity. An ototoxicity is also reported. We propose a PK/PD modelling of aminoglycoside nephrotoxicity which unifies more fourty years of physiological knowledge. This deterministic model successively describes the pharmacokinetics of aminoglycosides, their storage into renal cortex, their effect on renal cells, their consequences on the renal function through tubuloglomerular feedback and the changes in the serum concentrations of creatinine that is considered as a toxicity marker. The simulation of the model displays the leading effect of the shape and daily-time of administration schedule on the search for minimizing toxicity.     

Cowden disease: report of 8 cases in 2 families (author's transl)]

These 8 cases of multiple hamartoma syndrome are the first reported in Switzerland. Two men aged respectively of 65 and 28 years presented a cobblestone appearance of the gingiva and of the tongue ("pebbly tongue"), which suggested Cowden disease. This diagnosis was confirmed by the discovery of numberous skin lesions, a thyroid goiter, gastrointestinal polyposis, and a mild skelettal dysmorphosis. The older patient had a grade one carcinoma of the bladder; his son and his daughter presented the syndrome, which was also discovered in the family of the second patient (his father, his brother, his sister and one of her daughters). The ultrastructural study of two skin biopsies demonstrated anomalies of the fibroblasts and collagen fibers.     

Accelerated fractionation in esophageal cancers: A multivariate analysis on 88 patients

: Accelerated fractionation was used to shorten overall treatment time to increase locoregional control and cause-specific survival.

: Eighty-eight patients with cancer of the esophagus ineligible for surgery were entered in the study between 1986 and 1993. Neoadjuvant chemotherapy was given to 64% of patients. Accelerated radiotherapy using the concomitant boost technique delivered a median dose of 65 Gy in a median overall treatment time of 32 days.

: The 3-year acturial local control rate in patients with T1, T2, and T3 tumors was 71%, 42%,and 33%, respectively. The 3-year cause-specific survival rates were 40%, 22%, and 6%, respectively. Sixteen percent of patients experienced Grafe 3 esophagitis. Late toxicity included esophageal stenosis and pulmonary fibrosis in 8% and 9% of the patients, respectively. Multivariate analysis demonstrated that T stage and overall treatment time were prognostic factors for cause-specific survival. T stage and neoadjuvant chemotherapy were independent prognostic factors for locoregional control.

: These findings suggest that accelerated giben in an overall treatment time of <35 days might be beneficial for easy-stage cancer of the esophagus. Neoadjuvant chemotherapy is not recommended, as it was a significant adverse prognostic factor in the multivariate analysis for local control. Accelerated fractionation can be carried out with modeate acure and late toxicity.     

Adaptative effects of loss of vision on upright undisturbed stance

In order to evaluate the long term effect of blindness on an undisturbed postural task, seven blind individuals (BLI) were compared to twelve healthy individuals (REF) who were required to close their eyes. To this aim, centre of pressure (CP) trajectories were recorded through a force platform on which the subjects remained upright. Through a low-pass filter, the vertical projection of the centre of gravity (CG(v)) and consequently the difference CP-CG(v) were estimated. The former represents the controlled variable whilst the latter is assumed to express the resultant joint stiffness. A first analysis consisted in studying the frequency distribution of these motions. Increased mean amplitudes in both elementary motions and no difference between frequency distributions were observed for the BLI when compared to the REF group. These trajectories were then modelled as a fractional Brownian motion process in order to gain insight about the nature of the control mechanisms called into play and their spatio-temporal organisation. Moreover, the main characteristic observed in the BLI group is a decreased in CP-CG(v) motions, which, according to Winter's model, may be related to joint stiffness. In addition, reduced spatial transition point co-ordinates and more deterministic control mechanisms aimed at returning the estimated CG to an equilibrium point during the longest Deltat were observed. This phenomenon is more pronounced in the antero-posterior direction and also allows the blind subject to significantly diminish their CG sways. Finally, these features are discussed in relation to other similarly analysed investigations.     

Enzyme-replacement therapy in perinatal hypophosphatasia: Case report and review of the literature

Hypophosphatasia (HPP) is a rare disease resulting from alterations of the ALPL gene encoding tissue-nonspecific alkaline phosphatase (TNSALP). Perinatal HPP is mainly characterized by bone hypomineralization and severe respiratory insufficiency. We describe a full-term boy diagnosed with perinatal HPP after birth, showing dramatic improvement after treatment with Asfotase Alfa, an enzyme-replacement therapy (ERT) prescribed in HPP cases. He initially presented with respiratory insufficiency due to bone hypomineralization, and severe pulmonary hypoplasia that required tracheostomy and invasive ventilation for 8 months. He was taken off ventilation at 41 weeks of age. He also presented complications including hypercalcemia, craniosynostosis, nephrocalcinosis, hypotonia, and a severe feeding disorder. He is still alive at 30 months of age, and his respiratory status and tonus is steadily improving. This case reflects the progression of HPP patients with specific therapy added to symptomatic management. Some aspects of the disease are now well known, such as nephrocalcinosis and craniosynostosis, related to the natural course of the disease, which persisted despite the ERT. The long-term prognosis and outcome for this newborn child remain unknown.     

Value and limitations of Holter monitoring and electrophysiologic testing in the evaluation of the treatment of sustained monomorphic ventricular tachycardia

The authors studied the value and limitations of Holter monitoring and electrophysiological investigation in the evaluation of treatment of sustained monomorphic ventricular tachycardia (VT). One hundred and twenty-four consecutive patients were included in the study from January 1981 to February 1988. The etiologies were chronic myocardial infarction (N = 54), dilated cardiomyopathy (N = 24), right ventricular dysplasia (N = 31), and idiopathic VT (N = 15). All the tachycardias could be induced during baseline electrophysiological investigations and presented as complex ventricular arrhythmias on the Holter recordings. The investigations were repeated after treatment which was maintained irrespective of the results, unless the tachycardia which was induced or recorded was over 130 cycles/min and/or poorly tolerated. Recurrence was defined as the recording of VT in the absence of a change of treatment and/or the occurrence of sudden death. The follow-up period averaged 29 +/- 21 months. The Kaplan-Meier method was used to study the prevalence of absence of recurrence and survival rates. We observed 28 recurrences of VT and there were 21 deaths. Eighty-five per cent of patients had normal Holter monitoring after treatment. The prevalence of absence of recurrence was 0.751 when the Holter was normal and 0.485 when an arrhythmia was recorded (p = 0.03). The sensitivity was 25 per cent and the specificity 88 per cent. The survival rates were 0.66 and 0.585 respectively (p = 0.008). Fifty-three per cent of patients remained inducible after treatment with a prevalence of absence of recurrence of 0.572. This value rose to 0.877 when VT could not be induced (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Carcinomas of the colon with multidirectional differentiation

Summary Two cases of colonic carcinomas with multidirectional differentiation are presented. Both tumors showed light microscopic and immunohistochemical evidence of areas of adenocarcinomatous, squamous cell carcinomatous, and neuroendocrine differentiation. Only six similar cases have been previously reported. These highly malignant tumors support the recent concept of a multipotential stem cell within the mucosa of the gastrointestinal tract capable of differentiation in several directions.