A 6 day course of liposomal amphotericin B in the treatment of infantile visceral leishmaniasis: the Italian experience

OBJECTIVES: To evaluate in a retrospective analysis the efficacy and safety of a 6 day course of liposomal amphotericin B (L-AmB) in infantile cases of Mediterranean visceral leishmaniasis (VL) diagnosed over a 10 year period in Italy. PATIENTS AND METHODS: Patients included were diagnosed as having VL consecutively admitted from December 1992 to December 2001 at four main referral children's hospitals in Italy and treated with six intravenous doses of 3 mg/kg L-AmB given on days 1-5 and 10 (a total dose of 18 mg/kg). Demographic data, nutritional status, underlying diseases, clinical and laboratory findings, and therapy outcome were considered. RESULTS: A total of 164 HIV-negative children (median age 1.6 years; range 4 months to 14 years) were enrolled. All patients were initially cured by the given treatment, and did not present adverse events related to drug infusion. Seven patients (4.3%) had a clinical and parasitological relapse 3-15 months after therapy. All relapses were successfully retreated with 3 mg/kg L-AmB for 10 consecutive days (a total dose of 30 mg/kg). CONCLUSIONS: This study highlights the efficacy (>95%) and safety of the six dose L-AmB regimen and validates it as a first-line treatment for Mediterranean VL in children.     

HBV-DNA-related hepatocellular carcinoma occurring in childhood report of three cases

In a series of 325 HBV chronically infected children observed over an 18-year period, three developed HCC. These three children were born in southern Italy, a region characterized by a high endemic HBV infection rate; each had been infected perinatally, developed an acute hepatitis, and became a chronic carrier. Two of the three with cirrhosis were HB_sAg positive at the time their HCC was detected. The remaining case had seroconverted to HB_sAb but HBV-DNA integration could be demonstrated in the absence of cirrhosis; moreover HBV antigens were not expressed in the tissue of this case. The interval between HBV infection and HCC appearance in these three cases ranged from six to 11 years. A similarity between these three Italian cases and the majority of HCC, arising in chronically infected children in the Far East is noted.Presented at the Proceedings of the International Meeting on Normal and Neoplastic Growth in Hepatology, Bari, Italy, June 1989     

Effect of p-chlorophenylalanine on thermoregulation in unrestrained rats

p-Chlorophenylalanine (PCPA), a serotonin depletor, was used to investigate thermoregulation of unrestrained unanesthetized rats exposed to warm (approximately 32 degrees C) and cold (approximately 3 degrees C) environments. PCPA (300 mg/kg, ip) was administered approximately 48-96 h prior to the experimental trials. After 60 min of warm exposure, PCPA-treated rats had a significantly smaller increase in mean tail temperature (3.05 degrees C) and a greater increase in mean core temperature (1.47 degrees C) than did the control rats (6.13 and 1.20 degrees C, respectively) as measured via chronically implanted thermistors. A noninvasive method, infrared photography, was also used to monitor skin temperatures following heat exposure. Changes were qualitatively similar to those seen with thermistors, although differences between control and PCPA-treated groups were not statistically significant. During cold exposure, thermistor measurements indicated that the decrease in mean core temperature of the PCPA-treated rats (0.62 degrees C) did significantly differ from that of the controls (1.11 degrees C), whereas tail temperatures did not. These data confirm other studies implicating serotonin in the thermoregulation of rats. In particular, these results show that in a warm environment, PCPA may alter, albeit subtly, peripheral vasodilation in unrestrained rats.     

Sustained potential shifts and paroxysmal discharges in hippocampal formation

Paroxysmal firing was provoked by electric stimulation of afferent pathways in hippocampal formation of intact, urethan-anesthetized rats, of freely moving unanesthetized rats, and in hippocampal tissue slices in vitro. The electric responses of fascia dentata and CA3 zone of the hippocampus of urethan-anesthetized rats were recorded with extracellular microelectrodes. Paroxysmal discharges were provoked by stimulating the ipsilateral angular bundle. During repetitive stimulation, intercurrent paroxysmal discharges (IPaD) took the form of compound action potentials (population spikes) of large amplitude, provoked by but not locked in time to the stimulus pulses. IPaD was often but not always followed by paroxysmal after-discharge (PaAD), usually consisting of bursts of population spikes, sometimes superimposed on a slow wave. Stimulus pulses that were not strong enough to evoke population spikes when applied singly could provoke the paroxysmal firing of large amplitude spikes when applied repetitively. The liminal frequency to provoke paroxysmal firing, with 10-s train duration and with pulses evoking 60 to 80% of maximal amplitude focal postsynaptic potential (PSP) waves, varied between 6 and 15 Hz in urethan-anesthetized rats. The outbreak of IPaD was always accompanied by a marked sustained potential (SP) shift. The polarity of the paroxysmal SP shift was the opposite of the polarity of the PSP waves. We conclude that the extracellular paroxysmal SP shifts in fascia dentata are probably generated mainly by current flowing from the dendritic trees toward the cell somata of granule cells. The amplitude of the population spikes fired during paroxysmal discharges could reach 30-40 mV, indicating the precise coincidence of the impulses fired by many neurons. These spikes often arose without a detectable preceding synaptic potential. We conclude that the synchronization of the action potentials fired by granule and pyramidal cells during paroxysmal discharge is probably due to electric interaction among the neurons. In unanesthetized freely moving rats IPaD and PaAD consisting of bursts of population spikes were provoked. These were similar to those observed in urethan-anesthetized rats. Motor seizures provoked in kindled rats were associated with intense and prolonged spike bursts followed by spikeless positive waves recorded in the granule cell layer of fascia dentata. In hippocampal tissue slices maintained in vitro, paroxysmal firing could be provoked in CA1 zone by repetitive stimulation of Schaffer collaterals. IPaD and PaAD could be provoked in some slices exposed to normal (3.5 mM) [K+] and in all slices exposed to elevated (5.5 or 7.0 mM) [K+].(ABSTRACT TRUNCATED AT 400 WORDS)     

The leukemia-lymphoma syndrome with gastrointestinal involvement in childhood. A case report]

The gastrointestinal tract is an uncommon site of presentation for acute lymphoblastic leukemia in children. We report a child who developed a leukemia-lymphoma syndrome with central nervous system and gastrointestinal tract involvement at the diagnosis. The patient received an intensive combination chemotherapy and is currently off-therapy in continuous complete remission 29 months after the diagnosis.     

Pharmacokinetic variability and strategy for therapeutic drug monitoring of saquinavir (SQV) in HIV-1 infected individuals

AIMS: To investigate the pharmacokinetic profile of the protease inhibitor saquinavir (SQV) after multiple doses in HIV-positive patients and to evaluate the possibility of predicting total body exposure of SQV from concentrations determined at single time points. METHODS: Twenty HIV-positive patients on steady-state treatment with SQV (Hard-Gel-Capsule, Invirase(R)) were enrolled in this study. Serial blood samples were obtained during a dosing interval. SQV plasma concentrations were determined by high performance liquid chromatography (h.p.l.c.) and pharmacokinetic parameters were determined by noncompartmental techniques. RESULTS: There was a marked interindividual variability in SQV pharmacokinetic parameters with a 11-fold variability in total systemic exposure to SQV, as expressed by AUC(0,8h) values (range: 268-3009 ng ml-1 h, CV: 69%). The oral clearance shows an interindividual CV of 75%. A strong correlation (r=0.94) was found between SQV plasma concentration at 3 h (C3 h ) and AUC(0,8h). CONCLUSIONS: This study shows that C3 h is a good predictor for total body exposure of SQV and might be useful to predict SQV disposition in HIV-positive patients on steady-state treatment.