Salicylic acid disposition in children with rheumatoid arthritis.

The plasma level profile of SA and SUA after a single oral dose of ASA was studied in 8 children with juvenile rheumatoid arthritis, aged 3.5-15.0 years. Pharmacokinetic parameters were on average similar to those reported in the literature for adult subjects, although a somewhat larger intersubject variability was found.

A new glucose clamp algorithm: clinical validation.

A new glucose clamp technique for in vivo studies of insulin sensitivity was validated clinically. Eighteen patients (10 males, 8 females, age 35-80 years, body mass index 34.6-17.04) were connected to a computer-assisted artificial pancreas "Betalike R", using a new algorithm based on a "minimal model", to carry out the glucose clamp technique automatically and especially to overcome the well-known problems of its priming phase. We performed the euglycemic hyperinsulinemic clamp in four patients and the hyperglycemic hyperinsulinemic clamp in 14. In one patient both clamps were done. The mean priming time to reach steady-state glycemia was 20 min. Plasma insulin concentrations were measured every 20 min. This new automatic glucose clamp technique enables the priming phase to be run without any significant overshoot, and accidental variations of glycemia in steady state were reduced to a minimum. The system showed satisfactory safety and stability in controlling the patient's glycemia and assured high speed of the priming phase.

[Clinical heterogeneity in fructose intolerance]. / Eterogeneità clinica nell'intolleranza al fruttosio.

We observed eight infants with hereditary fructose intolerance which had been diagnosed by the fructose tolerance test and an aldolase assay on biopsied liver. None of these had been diagnosed before their admission to our department. The most frequent symptoms were vomiting and failure to thrive. All the patients had hepatomegaly. Laboratory findings were indicative of disturbed hepatic function. Hypoglycemia was found in only 3 out of 8 patients. The course was lethal in 2 patients; the 6 survivors are doing well following a fructose-free diet. The importance of practising paediatricians having the detailed nutritional history of the patient and precise knowledge of infant food formulae is stressed. The danger of using fructose continuing solutions for infusion therapy is pointed out. We also report a case of F-1,6-diphosphatase deficiency.

[Isoniazid therapy and monitoring plasma levels]. / Terapia con isoniazide e monitoraggio dei livelli plasmatici.

Plasma levels of isoniazid (INH) have been monitored in fifteen children, aged 1 to 13 years, who were under chronic therapy with INH plus rifampin for tuberculosis. The pharmacokinetic parameters of children were not significantly different from those found in adults by other authors. It is necessary to check two plasma concentrations at the 3rd h. versus different doses (5 mg/kg and 10 mg/kg) of INH, in order to determine the optimal dose to be given. In subjects with external ventricular drainage, the concentrations of INH in cerebro-spinal fluid are lower than in plasma. The latter finding should be stressed for its importance in the therapy of tuberculous meningitis.

[Neuroblastoma at the Giannina Gaslini Institute. Analysis of 94 cases diagnosed 1972-1981]. / Neuroblastoma all'Istituto Giannina Gaslini. Analisi di 94 casi diagnosticati nel periodo 1972-1981.

The authors have analysed 94 consecutive previously untreated children affected by NB diagnosed at the Giannina Gaslini Children's Hospital in the period January 1972 - December 1981. Age at diagnosis ranged between 1 month - 16 years (median 2 years). Diagnosis was made on histological grounds in 82 cases, on clinical, instrumental and laboratory data in the remaining 12 cases. Evans' staging system was adopted for classifying the disease extent. Patient recruitment was 9.4 cases for year. Female sex slightly prevailed in our series. 17 patients had localized disease (stage I and II), all surviving since 27 - 90 months. 28 children had regional disease (stage III) half of whom are presently alive. Five of the 47 cases with disseminated disease are alive at the time of this study; only one of these 5 can be considered cured, having been followed since more than 4 years. One of the two IV-s stage children survives disease-free at 89 months. 49% of patients were 2-year old or less at diagnosis while only 2 patients were older than 10. Survival was best in children diagnosed under one year of age, lowest in the 2 - 6 year age group. 74% of patients had their primary located in the abdomen (36 in the adrenal, 16 in sympathetic ganglia, 18 in un unidentifable site). Prognosis was worse in these patients compared with those with primary in the thorax, neck and pelvis. The clinical presentation of the disease has been extremely various: most patients had a diagnosis different from the definitive one, and were accordingly treated usually for several weeks or even months. Among laboratory data, urinary catecholamine metabolites, serum LDH and serum ferritin represented the most suitable indices of disease activity. Among immunological studies, none has shown a good correlation with the extent of the disease, nor with the clinical course. Stage I children had only surgery as treatment, while in stage II surgical ablation was followed by short-lasting chemotherapy and radiotherapy in few cases. In stage III and IV more complex multidisciplinary approach was utilized in the attempt to achieve a complete tumor regression. While about a half stage III cases appears curable by these treatment modalities, little impact has been demonstrated by this therapy in widespread disease, although the use of well-designed protocols seems have improved the complete remission rate and the median length of survival.

Identification and parameter estimation of the mechanical ventilatory system.

Oesophageal pressure and mouth volume were measured by oesophageal balloon and pneumotachography, respectively, in 10 men (both normal and diseases) under different experimental conditions, i.e. spontaneous ventilation, quasi-static manoeuvres and respiration at high frequencies. The recorded data were then analyzed by an identification and parameter estimation computer programme, to determine a mathematical model for the process. Contrary to other recently published papers dealing with frequency analysis, we studied a time-dependent model, represented by a linear time-invariant differential equation. The results were quite satisfactory since a relatively second-order model seems to be adequate for describing the process. Differences in the parameter values between normal and diseased subjects were characterized by increases in the patients' lung viscous component. In conclusion, our identification test results in the mechanical ventilatory system seem to indicate that a simple second-order mathematical model is consistent with the experimental data.

Analysis of nitrogen multibreath washout curves through a statistical approach.

A new method for analyzing nitrogen multibreath washout curves, founded on a statistical multicompartment model is presented. This method consists of two phases: (i) the preliminary conversion by mathematical means of the nitrogen end-tidal concentration curves - as usually available in routine practice - into the corresponding lung nitrogen decay curves normalized for ventilation rate and function al residual capacity and (ii) the determination of distribution function G(k) in the Laplace integral y(t) = integral of infinity,G(k)e-ktdk (where y(t) represents the experimental curve, k is the compartmental rate constant and the random variable of the statistical set). G(k) values are approximated by an accurate calculation of the distribution moments and the use of Edgeworth-Cramér series expansion. The clinical usefulness of the method was verified in normal subjects and in patients with chronic obstructive pulmonary disease. An excellent separation of the two groups was achieved by calculating the following parameters: the first moment (m1), the standard deviation (sigma) and the coefficient of dispersion (sigma/m). Besides, further information about the lung ventilation pattern could be obtained by a skillful inspection of the approximated distribution function curves of the rate constant k.

Partial deficiency of red cell 6-phosphogluconate dehydrogenase: a family study.

A family with partial deficiency of erythrocytic 6PGD is described. Biochemical and electrophoretic analysis suggest that the partial deficiency is due to a silent PGD0 allele. Chromosomal analysis and assay of closely linked markers do not reveal a grossly detectable deletion.

[Spectrum analysis of the r-r interval using a PC]. / L'analisi spettrale degli intèrvalli r-r mediante PC.

Spectral analysis of r-r variability has been recently proposed as a clinical tool to assess the autonomic nervous system function. In this article we present the results obtained using an equipment and an analysis software (based on Maximum Entropy Method) developed in our laboratory. Analyzing the tachograms derived from prolonged ECG registrations of 12 young healthy subjects, 24 to 36 years old (mean 31 +/- 4), we observed the two classic components of the signal: a low frequency component (0.7 +/- 0.2 Hz) and a high frequency component (0.21 +/- 16.6 Hz). As expected, standing, a simple manoeuvre augmenting sympathetic activity, caused a stronger predominance of the low frequency component. We conclude that our method is reliable to evaluate, by means of spectral analysis, rhythmical oscillations of r-r variability.

[Evaluation of the characteristics and performance of an automatic sphygmomanometer (Omega 1400)]. / Valutazione delle caratteristiche e delle prestazioni di uno sfigmomanometro automatico (Omega 1400).

24 hour pressure monitoring is a newly developing technique potentially yielding important informations in hypertensive patients. Numerous automated devices are available whose performance characteristics are poorly documented. To evaluate an automated sphygmomanometer commonly used in our Division (Omega 1400, Invivo Research Laboratories), we performed a series of measurements, simultaneously recording blood pressure in the opposite arm with a common sphygmomanometer. Each measure was then repeated reversing the position of the two devices (manual and automated), thus abolishing possible differences between the two arms. We observed a mean underestimation of 1.90 mmHg of systolic pressure and of 4.82 mmHg of diastolic blood pressure by the automated device. We conclude that the device by us evaluated is not advisable in the basal blood pressure evaluation, but useful in monitoring inpatients.

[Blood pressure monitoring during hospital convalescence]. / Il monitoraggio della pressione arteriosa durante il ricovero ospedaliero.

Blood pressure ambulatory monitoring has provided numerous and interesting informations on the clinical as well as investigational setting of arterial hypertension. The vast majority of data have been obtained registering blood pressure during the normal daily activities of the patients and surprisingly few studies have been undertaken to evaluate blood pressure behaviour in inpatients. We observed the 24 hours pattern of blood pressure in hypertensive and normotensive inpatients, using an automated sphygmomanometer (Omega 1400), whose performance was previously evaluated by us. The results demonstrate that blood pressure monitoring in inpatients could be a useful tool in managing hypertensive patients.

[Cerebrospinal fluid metabolism of biogenic amines in Huntington chorea]. / Rilievi sul metabolismo liquorale delle amine biogene nella Corea di Huntington

CSF metabolites of dopamine (HVA), norepinephrine (MHPG) and serotonine (5HIAA) in 9 patients affected by Huntington's Chorea before and after therapy with phenotiazine derivatives (Fluphenazine) have been studied. A close relationship seems to exist between therapeutical results and CSF HVA modifications: improvement of choreatic movements is associated with marked increase in CSF HVA values. Biochemical bases of Huntington's Chorea are discussed.

Peptichemio in advanced neuroblastoma.

Peptichemio (PTC) is a mixture of six synthetic peptides of m-L-phenylalanine mustard. It acts with both alkylating and antimetabolic effects, interfering with the synthesis of DNA, RNA, and proteins. PTC was administered iv to 18 previously untreated children with advanced neuroblastoma at a dose of 1-1.5 mg/kg/day for one to three cycles of 5-6 consecutive days each. Eleven of 12 patients (92%) experienced both objective and subjective improvement; complete remission was achieved in two of them. In spite of the high remission rate, the median duration of remission has been short (4 months) and the overall survival (median, 6 months) did not seem to be influenced by the use of PTC. The primary toxic effects were, in order of importance, bone marrow depression, phlebosclerosis, nausea and vomiting, and alopecia. Chronic use of PTC seems limited by two major factors: profound long-lasting thrombocytopenia and severe phlebosclerosis.

Resting Energy Expenditure in Long-Term Postobese Subjects after Weight Normalization by Dieting or Biliopancreatic Diversion.

Resting energy expenditure (REE) was measured by Indirect calorimetry in three groups of subjects closely matched for body weight (BW) and body composition. Five subjects had reduced from lO3 kg (129-90) to normal BW by dieting. Fourteen subjects had normalized their weight (preop 120 kg, from 168 to 100) following biliopancreatic diversion (BPD). All subjects in both groups had essentially maintained a stable weight for at least 2 years before the study. Ten healthy volunteers who had never been obese served as controls. No differences in REE were observed between post-BPD and control subjects, while lower (p < 0.05) values of REE were found in post-diet subjects. A long-lasting reduction of REE, in spite of a normal body composition, might partly account for the very poor long-term results of conventional dietary treatment. The unreduced REE following BPD may contribute, along with the permanent intestinal malabsorption, to the excellent long-term weight maintenance caused by this surgical procedure.