Ofloxacin penetration into bile and pancreatic juice.
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Adult↗
Biomedical subjects
A Messori
Publications and source records attributed to A Messori.
Primary cutaneous follicular centre-cell lymphoma--a lymphoproliferative disease with favourable prognosis.
In this study the clinico-pathological and immuno-histological features, the methods of treatment and follow-up data of 11 patients with follicular centre-cell (B-cell) lymphoma primarily presenting in the skin are reported. All the patients had nodular, tumorous and/or papulonodular skin lesions on the trunk. In nine patients the disease was confined to a circumscribed area of the back. Small papulonodular or plaque-like lesions, as well as large nodules or tumours, were biopsied in six of 11 patients. No clear-cut correlation between the age and clinical morphology of the lesions and their histological growth pattern was found. Interestingly, however, a different immuno-architectural pattern was observed in large, late lesions compared to small, early lesions. Initial treatment consisted of orthovolt radiotherapy (in two patients associated with surgical excision), resulting in complete remission in all patients. Only one patient developed extracutaneous disease, which was limited to a single drainage lymph node appearing simultaneously with a cutaneous relapse. Five other patients had recurrent disease in the skin close to the initial site. The median disease-free period was 15.5 months. On relapse, radiotherapy alone or in combination with short courses of chemotherapy was performed. This resulted in a second complete remission. All the patients are still alive and in complete remission, with a median survival of 37 months. These results confirm the favourable prognosis of patients affected with primary cutaneous follicular centre-cell lymphoma limited to the trunk. Orthovolt radiotherapy proved to be the most suitable treatment for both initial lesions and relapses limited to the skin.
Combined Modality Therapy↗
Long-term immunogenicity of a plasma-derived hepatitis B vaccine in HIV seropositive and HIV seronegative hemophiliacs.
Short-term studies indicate that hepatitis B vaccines are safe and satisfactorily immunogenic in hemophiliacs. The duration of immunity in these immunocompromised patients, however, is not known. To determine this, we studied 78 hemophiliacs prospectively 2, 3, and 4 years after the initial vaccination with a plasma-derived vaccine given as three monthly injections followed by a fourth booster injection at month 14. The duration of immunity clearly depended on whether the patients were infected with the human immunodeficiency virus (HIV). In HIV seronegative hemophiliacs (n = 67), there was a progressive decline in titers of antibody to the hepatitis B surface antigen (anti-HBs), but antibody was still detectable 4 years later in all of them. From the curves of decline of antibody titers, it appears that there is no need to revaccinate patients for at least 5 to 6 years. The HIV seropositive hemophiliacs (n = 11) not only started from much lower anti-HBs titers, but 5 of 11 lost anti-HBs. None of the 45 patients treated with concentrates during the postvaccination period developed serologic signs of hepatitis B, even though 6 of them had come into contact with live or inactivated hepatitis B virus as shown by the occurrence of spontaneous anamnestic antibody responses. This vaccine and schedule of vaccination afford a prolonged duration of immunity in HIV seronegative hemophiliacs, but HIV seropositive hemophiliacs have a risk of losing immunity early.
Adolescent↗
Theophylline levels after single daily and divided dosing of a once-a-day theophylline preparation in asthmatic children.
Twelve children with chronic asthma were treated with a single dose of sustained-release theophylline once-a-day taken after supper at 9 PM. During the steady-state period after 15 days of treatment, serum theophylline levels were measured one and two hours after dosing and then every two hours until 9 PM the following day. The peak concentration (mean +/- SD) of serum theophylline (20.9 +/- 6.5 micrograms/mL) was observed eight hours after dosing while the through concentration (4.34 +/- 2.62 micrograms/mL) was measured 24 hours after dosing; the percent fluctuation (mean +/- SD) was 966.45 +/- 1105.55%. Another 15 children were treated with the same preparation administered at 8 AM after breakfast and at 8 PM after supper. Serum samples for theophylline concentration were obtained immediately before dosing at 8 AM and then every two hours for the following 12 hours. The mean theophylline level observed immediately before dosing at 8 AM was 10.16 +/- 3.84 micrograms/mL while the mean level at 8 PM was 9.39 +/- 4.77 micrograms/mL. The peak serum level was 13.07 +/- 5.13 micrograms/mL at 2 PM, while the trough was 9.31 +/- 3.71 micrograms/mL at 10 AM, with a percent fluctuation of 155.21 +/- 147.95%. Few side effects were seen in both groups. The results of our study clearly demonstrated that in children the percent fluctuation and peak-trough differences are far greater with once daily than with twice daily dosing and this should be considered when planning theophylline treatment in asthmatic children. The administration of a once-a-day preparation every 8-12 hours can however result in overlapping absorption patterns.
Adolescent↗
Prognostic factors in Hodgkin's disease.
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Analysis of Variance↗
Multi-variate analysis of factors governing the pharmacokinetics of exogenous factor VIII in haemophiliacs.
The pharmacokinetics of Factor VIII was evaluated by mathematical modeling in a large-scale study in 62 haemophilia-A subjects, in whom 137 plasma Factor VIII-time curves were measured during single dose (n = 87) and repeated-dose (n = 47) treatments for prophylaxis or minor bleeding episodes. The pharmacokinetic parameters [mean (SD)] estimated from single-dose curves were: clearance 3.85 ml.h-1.kg-1, volume of distribution 58.2 ml.kg-1, mean residence time 15.9 h. Parameters calculated from repeated-dose curves were: clearance 3.93 ml.h-1.kg-1, volume of distribution 61.8 ml.kg-1, and half-life 12.2 h. In patients with mild haemophilia, pharmaco-statistical analysis revealed that the endogenous synthesis of Factor VIII was constant and was not influenced by the administration of exogenous Factor VIII. The coefficient of variation for intra-individual variability of Factor VIII kinetics (estimated according to the Standard Two-Stage method) was 20.7% in single-dose curves and 23.2% in repeated-dose curves.
Adolescent↗
Effect of increased haemoglobin levels on growth hormone (GH) secretion in beta-thalassaemia major: differences between prepubertal subjects and patients with delayed puberty.
Basal and L-dopa-stimulated secretion of growth hormone (GH) was investigated in 10 patients with beta-thalassaemia major. Five patients were prepubertal (chronological age 8 to 12 years), whereas 5 patients had delayed puberty (chronological age 15 to 19 years). Ten normal prepubertal subjects (chronological age 8 to 11 years) served as the control group. Each thalassaemic patient was subjected to two L-dopa tests (0.5 g L-dopa plus 0.7 mg/Kg body weight propranolol, orally): one was performed under conditions of low haemoglobin (Hb) levels (30 days after the last blood transfusion), and the second in the presence of increased Hb concentrations (10 days after the transfusion of packed red blood cells). Before the transfusion of packed red blood cells, basal GH concentrations were significantly higher in the patients with delayed puberty (4.3 +/- 1.6 ng/ml), than in prepubertal thalassaemic (1.8 +/- 0.9 ng/ml, p less than 0.05) and control (1.9 +/- 1.0 ng/ml, p less than 0.02) subjects. In contrast, the pituitary responsiveness to L-dopa, expressed as the relative maximum response for GH (GH delta %), was significantly higher in the latter two groups (8.5-fold, p less than 0.05, and 10.9-fold, p less than 0.02, respectively). The transfusion of packed red blood cells increased significantly Hb concentrations in both groups of thalassaemic patients (prepubertal +27%, p less than 0.05, delayed puberty +33%, p less than 0.025, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Effect of food on the bioavailability of a slow-release theophylline formulation.
A study was conducted in two groups of healthy volunteers to assess whether the time of administration (10 min before the meal versus 60 min after the meal) influences the pharmacokinetics and absorption kinetics of a slow-release theophylline product (Teonova). In the first group (Group A, n = 10), the drug was given in a paired-sample design as a single dose of 600 mg before and after breakfast with an interval of at least 1 week between the two administrations. In the second group (Group B, n = 10), Teonova was given by the same study design before and after dinner. In all cases, time curves of theophylline plasma levels were determined by collecting serial blood samples 24 h after dosing and analysed pharmacokinetically through model-independent methods. In Group A, curves obtained before and after the meal were fully superimposable, and no difference was found between the pharmacokinetic parameters determined in either condition. The same result was obtained in Group B. Our results indicate that, after single dose, the two different times of administration that we tested were equivalent in pharmacokinetic terms.
Adult↗
13-cis-Retinoic acid treatment in patients with myelodysplastic syndrome.
Twenty patients with primary myelodysplastic syndromes (16 refractory anemia without or with ringed sideroblasts, 2 refractory anemia with excess blasts, 2 refractory anemia with excess blasts in transformation) received 13-cis-retinoic acid at a dosage of 50-100 mg/m2/day for a minimum of 4 weeks. Twelve patients obtained an increase of hemoglobin levels greater than 1 g/dl and 7 showed an associated increase of granulocyte count greater than 50% of baseline values. No significant biochemical signs of dyslipidemia or liver damage were noted. A sustained response was noted only in refractory anemia without or with ringed sideroblasts and normal or hypercellular bone marrow. Five patients are still on therapy from 23 to 82 weeks without transfusion requirement and all have shown an improvement in performance status. We conclude that 13-retinoic acid may only be clinically useful in selected patients since in myelodysplastic syndromes with blast excess the drug does not seem to improve the course of the disease.
Aged↗
Clinical pharmacokinetics of valproic acid--1988.
Sodium valproate (valproic acid) has been widely used in the last decade and is now considered a relatively safe and effective anticonvulsant agent. Recently, several investigators have proposed its use in the treatment of anxiety, alcoholism and mood disorders, although these indications require further clinical studies. Valproic acid is available in different oral formulations such as solutions, tablets, enteric-coated capsules and slow-release preparations. For most of these formulations bio-availability approaches 100%, while the absorption half-life varies from less than 30 minutes to 3 or 4 hours depending on the type of preparation used. Once absorbed, valproic acid is largely bound to plasma proteins and has a relatively small volume of distribution (0.1 to 0.4 L/kg). Its concentration in CSF is approximately one-tenth that in plasma and is directly correlated with the concentration found in tears. At therapeutic doses, valproic acid half-life varies from 10 to 20 hours in adults, while it is significantly shorter (6 to 9 hours) in children. Valproic acid undergoes extensive liver metabolism. Numerous metabolites have been positively identified and there is reasonable evidence that several of them contribute to its pharmacological and toxic actions. In fact, several valproic acid metabolites have anti-convulsant properties, while many of the side effects it may cause (e.g. those related to hyperammonaemia or liver damage) are most often observed in patients previously treated with phenobarbitone. This could indicate that induction of liver enzymes is responsible for the formation of toxic valproic acid metabolites.
Administration, Oral↗
Long-term treatment with sodium valproate: monitoring of venous ammonia concentrations and adverse effects.
Adverse effects and venous blood ammonia concentrations were monitored over a period of 7 months in patients with epilepsy treated with valproate (VPA). During the 1st, 4th, 12th, 20th, and 28th weeks of therapy, blood samples for analysis of ammonia and anticonvulsants were taken immediately before the morning dose of VPA as well as 2 h after dosing. In all, 40 patients completed the follow-up; 16 of these (Group 1) received VPA alone, while the remaining 24 (Group 2) were treated simultaneously with VPA and other anticonvulsants (phenobarbital, phenytoin, and/or carbamazepine). In Group 1 patients, a slight though significant increase in ammonia concentrations was found during long-term VPA treatment; this trend was even more pronounced in Group 2 patients. The difference between postdose and predose ammonia levels in Group 2 patients was significant at each of the five follow-up examinations. In contrast, no such difference was demonstrated in patients of Group 1. VPA concentrations were found to be consistently higher in Group 2 patients than in Group 1. Twenty-three patients complained of various long-term adverse effects, while the other 17 remained symptom-free. The adverse effects reported included drowsiness, tremors, weight gain, hair loss, and gastrointestinal symptoms. Our data confirm the previously suggested hypothesis that changes in venous blood ammonia are particularly evident in patients taking VPA in combination with other antiepileptic drugs, such as phenobarbital and phenytoin.
Adolescent↗
Single-dose pharmacokinetics of factor IX evaluated by model-independent methods.
We studied the pharmacokinetic data of 13 subjects with hemophilia B treated with a single-dose of a Factor IX concentrate (Bebulin TIM2, N = 9; Preconativ, N = 4). The decay curves of Factor IX were evaluated by model-independent methods and the following pharmacokinetic parameters (mean +/- SD) were estimated: clearance (ml/h/kg) = 4.99 +/- 2.01; mean residence time (h) = 22.9 +/- 10.6; volume of distribution (ml/kg) = 99.9 +/- 35.5. The in vivo recovery (59.8% +/- 16.9%) was found to be inversely correlated with the volume of distribution. No significant difference in the pharmacokinetic parameters was found between patients treated with Preconativ and those treated with Bebulin. A model-dependent compartmental evaluation of the 13 decay curves showed that the two-compartment model was better than the one-compartment model in 7 cases (53.8%), but the improvement of fit resulting from the two-compartment model was statistically significant in only 2 cases (15.4%).
Factor IX↗
Hodgkin's disease in the elderly: a retrospective clinicopathologic study of 61 patients aged over 60 years.
61 cases of Hodgkin's disease (HD) with age over sixty years were diagnosed in a series of 387 patients. Mixed cellularity (57.4%) and nodular sclerosis (14.7%) were the most common histologic subtypes. Clinical presentation was characterized by superficial lymphadenopathy (92%) and/or general symptoms (57.4%). Mediastinal involvement was observed in 24.6% of cases, and 24.6% of patients had a primitive infradiaphragmatic presentation. Stage II was the most frequent (47.5%). At the onset of the disease, normal values of hemoglobin and white cells were observed while the platelet count was more variable. Only 3 patients (5%) were given radiotherapy (RT), 3 received chemotherapy (CH) plus RT, and 55 (90%) CH. Severe hematologic toxicity was observed in only 11.1% of cases. Complete remission (CR) was obtained in 37 patients (61%), 10 of whom relapsed. Elderly patients had a 5-year survival rate of 54.9%, while in younger ones it was 76.4% (p less than 0.001). Survival was strongly influenced by the achievement of CR (p less than 0.001), whereas stage, histopathology, systemic symptoms and therapeutic modalities did not correlate significantly.
Age Factors↗
Ciprofloxacin penetration in pancreatic juice.
The penetration of ciprofloxacin in pancreatic juice was investigated in 5 patients with pancreatic fistula. The drug was administered as a single oral dose of 500 mg after which serial samples of pancreatic juice and serum were collected for ciprofloxacin assay. The following pharmacokinetic parameters (mean +/- SD) were estimated from the serum level versus time curves: clearance 11.51 +/- 2.85 (ml/min/kg); Vd area 3.08 +/- 1.20 ml/kg; terminal half-life 3.10 +/- 0.92 h; mean residence time 5.64 +/- 1.40 h. Ciprofloxacin serum levels declined rapidly after the third hour, whereas concentrations in pancreatic juice remained elevated (above 1 mg/1) for nearly 12 h. The pancreatic juice/serum ciprofloxacin concentration ratio increased gradually fom 0.63 +/- 0.45 after 0.5 h to 6.18 +/- 4.59 after 12 h (mean +/- SD). Our data indicate that while the drug elimination half-life from the serum is short, the time-course of ciprofloxacin levels in the pancreatic juice conforms to a much slower disappearance rate. In particular, the ciprofloxacin levels achieved in pancreatic juice are constantly greater than the MICs of the bacteria generally responsible for pancreatic infections.
Adult↗
Clinical pharmacokinetics of factor VIII in patients with classic haemophilia.
Studies of Factor VIII pharmacokinetics in haemophiliacs can be classified into 2 groups depending on whether single-dose or multiple-dose Factor VIII curves are used. This review analyses information published so far in both these areas, with particular emphasis on the choice of appropriate models for pharmacokinetic analysis. Single-dose studies of Factor VIII kinetics have previously used a wide variety of methods for pharmacokinetic analysis (empirical methods of Factor VIII level prediction, graphical techniques for semilog analysis, 1-compartment and 2-compartment models). However, Factor VIII poses unique problems to the pharmacokineticist because decay curves can be either monophasic (monoexponential) or biphasic (biexponential) for unknown reasons, and because Factor VIII concentrations are generally subject to significant assay error. Problems of compartmental analysis that occurred in previous studies are highlighted, and a model-independent non-compartmental approach for analysing Factor VIII curves is proposed. To date, fewer data have been published on multiple-dose kinetics of Factor VIII. From a clinical point of view, repeated-dose regimens are most commonly required in patients undergoing surgery and in patients with severe bleeding. A fairly well defined 'therapeutic window' of optimal Factor VIII plasma concentrations has been identified, particularly in surgical patients. This fact has spurred research aimed at applying to haemophilia patients the pharmacokinetic dosing methods commonly used for therapeutic monitoring of drugs (e.g. Bayesian method for dosage individualization). A few papers have already been published in this field, and this review summarises problems encountered by previous investigators, and evaluates comparatively the pharmacokinetic methods used.
Factor VIII↗
Pharmacological activity of some pyrrolo and pyrazolo pyrimidine derivatives.
4,7-Dihydro-4-ethyl-2-phenylpyrazolo-[1,5-a]pyrimidin-7-one (FPP028) is the prototype of a class of pyrazolo[1,5-a]pirimidine derivatives that has been shown to possess marked antiinflammatory and analgesic properties; 1,4-dihydro-1-ethyl-7-phenylpyrrolo[1,2-a]pyrimidin-4-one (FPP129) is a new compound belonging to a series of pyrrolo[1,2-a]pirimidine derivatives that has been synthetized in an attempt to reduce certain toxic effects observed with FPP028. To evaluate these two compounds more fully, in the present study we determined the LD50 of FPP129 in mice and assessed its activity in different experimental inflammation models. Ulcerogenic properties of FPP129 were evaluated by the test of stress-induced ulcer in rats. We also studied the in vitro and ex vivo effects of both FPP028 and FPP129 in a series of platelet-aggregation experiments using either arachidonate or collagen as aggregating agents. In the carraggeenan-induced paw edema, FPP129 exerted a marked anti-inflammatory activity with an ED50 of 22.2 mg/kg. FPP129 inhibited also the edema induced by concanavalin-A or Paf-acether. The in vitro anti-aggregatory activity of FPP028 was shown to be much less than that of indomethacin, thus confirming the hypothesis that the compound is a very weak inhibitor of cyclooxygenase. Ex vivo, both FPP028 and FPP129 were shown to exert no antiaggregatory effect in rabbits after administration of doses equal to the ED50. No ulcerogenic activity was found with FPP129, this result being consistent with previous observations on FPP028. Our data show tha FPP028 and FPP129 do not share a typical mechanism of action (cyclooxygenase inhibition) found with the majority of nonsteroidal antiinflammatory drugs. Nonetheless, the antiinflammatory properties of these compounds, together with their lack of ulcerogenic activity, indicate that both FPP028 and FPP129 are potentially interesting for future therapeutic use.
Animals↗
Bioavailability and absorption kinetics of slow-release theophylline.
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Adolescent↗
Hepatitis-free interval after clotting factor therapy in first infused haemophiliacs.
Post-infusion hepatitis is known to occur very frequently in haemophiliacs after treatment with unheated commercial clotting factor concentrates, obtained from large plasma donation pool. On the contrary, single-donor cryoprecipitate is likely to carry a lower risk of transmitting hepatitis. To evaluate this hypothesis, we retrospectively reviewed the medical records of 25 first infused haemophiliacs (from 1981 to 1984) treated with unheated commercial clotting factor concentrates (n = 19) or cryoprecipitate (n = 6). The hepatitis-free interval after the beginning of therapy was expressed as exposure days. The end point of each patient, i.e. the hepatitis occurrence, was defined as an increase of amino-transferases (ALT and AST) and/or the seroconversion of HBV-markers, which were checked every three months. The life-table method and log-rank test showed that cryoprecipitates had a significantly longer hepatitis-free interval (p = 0.0131, log-rank test) and a lower risk of transmitting hepatitis (p = 0.01-0.05, life-table method) than the commercial concentrates. However, the safety of cryoprecipitate therapy was shown to cover only a few exposure days, and so the real advantage of this product depends on the bleeding frequency of the patient concerned. We believe that these methods and our findings may be useful to assess and compare the safety of the new "heat-treated" clotting factor concentrates.
Adolescent↗