Intensive retreatment of adults and children with acute lymphoblastic leukemia.

Twenty-three patients (16 adults) failing their first or subsequent (n = 8) intensive treatment for de novo acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia lymphoid blast phase (n = 2) were managed with protocol POG 8201, originally introduced in relapsed ALL of childhood. In this programme, a four-drug induction phase is followed by early consolidation with teniposide-cytarabine, intrathecal chemotherapy, continuation weekly chemotherapy alternating teniposide-cytarabine with vincristine-cyclophosphamide, and periodic reinduction courses. Fourteen adults and five children with ALL achieved a complete response (CR) (86 per cent). The highest response rate (100 per cent) was obtained in 12 patients treated at first relapse after an initial CR of greater than 18 months (p = 0.07). Median duration of CR was 8 months in adults and 11 months in children. A longer than previous one CR (inversion) was obtained in four cases. Four ALL patients were successfully transplanted from a matched sibling after 3-11 months from achievement of CR. Median overall survival in adults with ALL was 11 months, significantly longer than for 40 comparable cases treated intensively but without rotational continuation therapy in previous years (p less than 0.001). This regimen is applicable to adults with relapsed ALL, where prolongation of survival may allow time for effective salvage with bone marrow transplantation.     

Renal effect of anti-hypertensive drugs depends on sodium diet in the excision remnant kidney model.

Angiotensin converting enzyme inhibitors (ACEI) are believed to protect remnant kidney, but all previous studies used the ligation model which causes severe hypertension, and very few have compared drugs in rats having similar control of blood pressure (BP). We compared rats with uremia obtained by 70% excision of total renal mass, a model which causes mild, late hypertension. Study I compared the effects of enalapril (E), cicletanine (C) and placebo (P) in uremic (U) rats fed a 0.50% (normal-high) Na diet. Study II compared the effects of E, C, P, and guanfacine (G) in U rats fed a diet restricted to 0.25% Na (normal-low). In study I, UP rats developed progressive hypertension (140, 146, 160 and 166 mm Hg at 3, 6, 9 and 12 weeks), proteinuria (240 mg/day at 9 and 12 weeks) which were not affected by E or C. The occurrence of end-stage renal disease (ESRD) led to the sacrifice of all rats after three months. All three groups had similar severe renal lesions (over 25% sclerosed glomeruli in 5 of 10 UP, 9 of 14 UE, 7 of 14 UC rats, with huge cystic tubular dilatations). In study II, rats could be sacrificed later (6 months) and had evidence of less severe renal disease. All the drugs tested prevented hypertension throughout the study (P less than 0.001), with lowest values in UE rats. E and G, but not C, reduced proteinuria. Renal damage was reduced with E and G, but not with C, despite similar BP in C and G rats. Thus, in contrast with what was obtained in the ligation model, ACEI affected neither the BP nor the renal lesions of rats made uremic by renal excision and fed a 0.50% Na diet. Moderate Na restriction improved the consequences of nephron loss and restored the anti-hypertensive effect of drugs. However, these drugs had a different effect on renal preservation: it was dramatic with E, good with G, and undetectable with C.     

Differential distribution of aldolase A and C in the human central nervous system

We have analyzed the distribution of aldolase A and C mRNAs and proteins in various areas of the human brain using Northern blot analyses and immunohistochemistry. Aldolase A mRNA expression was higher than aldolase C mRNA expression in all areas of the brain examined. Aldolase C mRNA expression was highest in the cerebellum. Aldolase C protein was present in well-delimited regions of the CNS, and was distributed in stripes in the Purkinje cell layer of the cerebellum, in the inferior olives and in the sensory neurons of the posterior horn of the spinal cord. The novel finding of aldolase C in well-delimited cell compartments of the human cerebellum and in several other areas of the CNS lends weight to the hypothesis that this protein exerts other functions (e.g. sensory transmission) besides those characteristic of a glycolytic enzyme.     

Intracranial tuberculomas in a child: regression on the CT scan under conservative therapy

The case of a four-year-old boy is reported in whom the diagnosis of multiple cerebral and cerebellar focal tuberculous infections ("tuberculomas") was made. The diagnosis was based on a positive skin test, a history of contact, typical x-ray findings in the lung, CSF findings, and CT scan. The patient was treated during a three-year-period with antituberculous therapy. Sequential CT scans showed a relatively slow modification of the lesions, during a period of at least eighteen months, and thereafter their almost complete regression.     

Increased sodium requirement following early postnatal surgical correction of congenital uropathies in infants

Serum electrolyte equilibrium and plasma aldosterone concentrations were monitored in 19 infants who had severe obstructive uropathy or grade 5 vesico-ureteral reflux and were undergoing surgical correction in the first 2 months of life. Before surgery high plasma aldosterone levels were observed in 8 patients, but serum sodium and potassium concentrations were normal. Plasma concentrations of aldosterone were elevated in all patients during the week following surgery and 7 patients developed severe hyponatraemia, hyperkalaemia and weight loss despite very high plasma aldosterone concentrations. As a consequence 5 infants were infused with sodium chloride (4 mEq/kg per day) before and for 36h after surgery; this prevented metabolic imbalance. We conclude that infants undergoing surgical correction of uropathies may require a high sodium intake to maintain electrolyte balance and adequate growth.     

The Impact of Mitral Stenosis on Left Atrial Function Assessed by Two‐Dimensional Speckle Tracking Echocardiography

Aims: The aim of this study is to investigate the effect of mitral stenosis (MS) on left atrial (LA) function using two‐dimensional speckle tracking echocardiography (2DSTE). Methods and Results: The study subjects consisted of 52 patients with asymptomatic MS and 52 control subjects. LA function was assessed using prototype speckle tracking software and manual tracking method. Maximal LA volume (LAVmax) and minimal LA volume (LAVmin) and LA volume before atrial contraction (LAVpre‐a) were measured. Using these volumes, LA reservoir, conduit and booster pump fuction parameters were calculated. Indexed LAVmax, LAVmin, and LAVpre‐a measurements via speckle tracking were highly correlated with manual tracing methods in both groups. Expansion index (67.8 ± 36.4 vs. 148.3 ± 44.2), diastolic emptying index (37.7 ± 12.9 vs. 58.0 ± 8.5), passive emptying (37.3 ± 14.1 vs. 70.4 ± 10.4) and passive emptying index (13.3 ± 6.3 vs. 41.3 ± 10.6) were decreased significantly in MS patients (P < 0.001). In contrast active emptying index (62.6 ± 4.1 vs. 29.5 ± 10.1) increased in MS group (P < 0.001) while active emptying (28.1 ± 13.0 vs. 28.3 ± 6.9) remained same among both groups. Conclusions: This is the first study relating LA volumes and function assessed by 2DSTE to MS. 2D speckle tracking analysis of LA volume is relatively easy and provides more detailed information regarding the changes in LA volumes during the cardiac cycle.