[How much of the GDP should be allocated to health care?]. / Quanto PIL è necessario per proteggere la salute?

Health protection in Italy was allotted 8.9% of the gross domestic product in 2005. This is below the mean of the Organization for Cooperation and Economic Development (OCSE), which averaged 9.5%, as well as below that of France (11.1%), Germany (10.7%) and the United States (15.3%). Public health expenditure was 76% and private health expenditure 24%, whereas for OCSE these percentages averaged 80% and 20%, respectively. When the data are subdivided by area (Northern, Central and Southern Italy), the expenditure was 56.24% in Northern Italy, 56.39% in Central Italy, and 52.05% in Southern Italy. The National Council for Economy and Work (CNEL) has determined that the health expenditure in Italy must be increased to OCSE levels. In addition, structural changes are needed to simplify the administrative process.

[Sequelae of zygomatic-orbito-maxillary fractures. Report of 70 cases and review of literature]. / Esiti a distanza delle fratture zigomatico-orbito-mascellari. Analisi su 70 casi e revisione della letteratura.

Fractures of the zygomatic-orbito-maxillary complex (ZOM) are among the most frequent in maxillo-facial surgery. The study evaluates treatment for this type of fracture in the long-term and the sequelae linked to it. Patients who had been operated between february 1998 and november 1999 to reduce and retain ZOM fractures were subjected to check-up examination at the Maxillo-Facial Surgery Operative Unit, Florence. Cases selected had been operated via trans-oral access with incision of the superior vestibular fornix and where necessary with application of means of retention (Foley balloon and/or wire or plate-and-screw osteosynthesis). In these patients, the presence of residual deformities was evaluated together with enophthalmos, diplopia, compromised mouth opening if present, inflammation of the mucosa of the maxillary sinus, and above all incidence of sensory deficit in the distribution area of the infra-orbital nerves and the dental plexus. Particular attention was paid to evaluating tooth sensitivity on the side involved by the trauma, for any damage of the dental plexus. The most frequent sequela found in our group was lesion of the infra-orbital nerves, and a lower percentage of other sequelae such as residual deformities, enophthalmos or diplopia. Interestingly, in all cases in our series there was a significant reduction in tooth sensitivity on the side of the lesion, above all in the anterior sectors.

[Nodular fasciitis in the zygomatic area. Case report and review of the literature]. / Fascite nodulare in regione zigomatica. Caso clinico e review della Letteratura.

The authors report a clinical case of nodular fasciitis in the zygomatic area. Although this tumor-like proliferation occurs very rarely in the maxillofacial region, careful diagnosis based on histologic examination must distinguish it from neoplastic lesions such as fibrosarcoma with which the disorder shares certain histologic features. The case is compared with others described in the literature. In June 1996 a 12-year-old girl presented at our unit with swelling of the zygomatic region and positive history for trauma to the area. Palpation of the soft tissues detected a nodular formation about 1.5 cm in diameter. Echography and magnetic resonance imaging confirmed the presence of a nodular proliferation above the bone surface. The nodule was surgically removed by skin excision, and histologic examination of the specimen confirmed the diagnosis of nodular fascitis. The etiology of the lesion was thought to be a reaction to trauma, in agreement with data reported in the literature. Nodular fasciitis is a benign, non-recurrent lesion; however, its rapid growth and the histologic features it shares with more aggressive tumors such as fibrosarcoma call for careful differential diagnosis. As in our case, a history of previous trauma to the involved area can aid in establishing a correct diagnosis.

[Deep rotated connective tissue flap for the reconstruction of the interdental papilla]. / Lembo connettivale profondo di rotazione per ricostruire la papilla interdentale.

The LCPR or Rotated Connective Flap is a simple mucogingival surgery technique that permits the to recreate, of an interdental papilla by the contribution of the vascularized connective pedicle. Keeping a good vascularization of the flap by its pedicle and its good recovering by some superficial flaps, seems to insure a long dated stability of the reconstruction.

Bioavailability of isoniazid, rifampicin and pyrazinamide (in free combination or fixed-triple formulation) in intermittent antituberculous chemotherapy.

A study was carried out in six human volunteers, to assess the blood kinetics of isoniazid, rifampicin and pyrazinamide, administered in a fixed-triple combination intended for use in intermittent chemotherapy of tuberculosis. The formulation employed contained 125 mg of isoniazid (H), 100 mg of rifampicin (R) and 375 mg of pyrazinamide (Z) per tablet; six tablets were administered to every subject, giving a total dosage of 750 mg of isoniazid, 600 mg of rifampicin and 2,250 mg of pyrazinamide. In each subject, the same dose of each drug was administered individually in separate sessions and the results compared. The results indicated that, at the level of dose of the intermittent tablet, no negative interactions between the drugs were observed.

Tuberculosis and HIV infection association in a rural district of northern Uganda: epidemiological and clinical considerations.

59 (18.3%) of 323 patients with tuberculosis (TB) tested for HIV-1 antibody by ELISA technique (Wellcozyme) were seropositive. In the control group selected among the health personnel working in the Arua Hospital, 7.7% were found positive for HIV-1 antibody, thus showing a significantly lower prevalence compared with the TB patients (P < 0.005). The prevalence of HIV infection was 50% in the urban TB patients, 7% in TB patients living in rural areas surrounding Arua town and 1.6% in the peripheral rural setting. Of 27 TB patients with clinical AIDS, 18 died during the course of the study. The AIDS patients' survival rate was 46.4% 6 months after diagnosis, and 21.4% after 16 months, the median period of survival being 5.0 months. Risk factors, sputum conversion rate, clinical and radiological findings were analysed. No significant difference was found between seropositive and seronegative TB patients for clinical drug-related toxicity (P > 0.05).

PIP: Between June 1987 and August 1989, physicians enrolled 323 tuberculosis (TB) patients and 116 health employees at the Arua Regional Hospital in a rural district of northern Uganda in a case control study. They wanted to look at the link between TB and HIV infection. TB patients were more likely to be HIV seropositive than the employees (18.3% vs. 7.7%; p .005). HIV seropositive individuals tended to be men (71.2% vs. 54.9% for controls; p .05) whose mean age was 27.69 years. Most HIV/TB patients lived in the town of Arua (50% vs. 7% in rural areas peripheral to Arua and 1.6% in a rural area near the district border; p .0001). HIV seropositive TB patients were more likely to have a sexually transmitted disease (STD) than HIV seronegative TB patients (47.4% vs. 12.5%; odds ratio [OR] = 6.32; p .0001), especially gonorrhea (p .0001). They also tended to have had more than 5 sexual partners in the past 2 years (mean number of partners among HIV seropositive TB patients = 10.6; 35.6% vs. 9.5%; OR = 9.24; p .0001). HIV seropositive TB patients were more likely to have participated in prostitution and to have had a blood transfusion than HIV seronegative TB patients (33.9% vs. 3.8%; OR = 13.03; p .001 and 6.8% vs. 1.1% OR = 6.33; p .05). Skin piercing, widely practiced in rural areas, appeared to have a protective effect against HIV infection (OR = .33; p .0005). HIV seropositive TB patients were significantly more likely to have a persistent cough of more than 4 months duration (p .001), fever lasting for more than 1 month (p .05), oral thrush (p .0001), lymphadenopathy (p .0005), and amenorrhea (fertile women only, p .005). 27 or 28 TB patients had AIDS. At the time of submission of this study for publication, 18 HIV seropositive TB patients died during treatment. The case fatality rate was indeed higher among HIV seropositive TB patients than among HIV seronegative TB patients (30.5% vs. 8.7%; p .0001). The TB-AIDS survival rate was 46.4% at 6 months, 32.1% at 12 months, and 21.4% at 16 months. Median survival time was 5 months.

Proposal of an improved score method for the diagnosis of pulmonary tuberculosis in childhood in developing countries.

210 children aged less than 5 years, referred to the Arua Regional TB Centre (Uganda) for suspected pulmonary tuberculosis (PTB), were examined by anamnesis, clinical examination, Mantoux test, gastric washing, chest X-ray. The response to treatment criterion was applied to the patients treated. According to the score method suggested by Ghidey and Habte, 31 children were diagnosed as PTB patients. 30 of the 31 children with PTB tested positive for alcohol acid-fast bacilli (AAFB) in the aspirated juice. The Mantoux test and X-rays gave a minor contribution to diagnosis. The clinical results are commented. A statistical analysis was carried out to evaluate the role of gastric washing in the diagnosis of PTB in children under 5 years of age (sensitivity, 96.8%; specificity, 92.2%; positive predictive value, 68.2%; negative predictive value, 99.4%). The response to treatment was also evaluated. A modified enlarged score method (based on gastric washing and including response to treatment) is proposed to be applied in developing countries where chest X-ray and other facilities are often lacking.

Comparison of three different regimens in the treatment of acute brucellosis: a multicenter multinational study.

The present study was undertaken to evaluate efficacy, safety and patient acceptability of three antibiotic regimens for the treatment of acute brucellosis. Six different centres were involved: three in France, one in Greece and two in Spain. The regimens were: oral rifampicin 900 mg/day plus oral doxycycline 200 mg/day for 45 days (A), oral doxycycline 200 mg/day for 45 days plus im streptomycin 1 g/day for 21 days (regimen B) [corrected] and the WHO regimen (C) combining oral tetracycline 2 g/day for 21 days plus im streptomycin, 1 g/day, for 14 days. Regimens A and B were randomly allocated in all centres, while regimen C was allocated only in two centres. All patients were suffering from acute brucellosis clinically and biologically proven. 143 patients were allocated for treatment and analysed. Their mean age was 41 years (range 13-70), 49 were female and 94 male, and their mean weight was 64 kg (range 35-98). Among these patients, 14% had localized disease (nine orchitis, eight osteo-articular involvement and one pleural effusion), but there was no statistical difference between the three regimens in regard to this localized disease. Forty-five per cent of the patients had positive blood cultures. The cure rate with regimen A was 95%, 96% with regimen B and 59% with regimen C. Thus regimen A presented the same efficacy rate as regimen B, but regimen C cannot be regarded as the treatment of choice for acute brucellosis.

Past, present and future trends in tuberculosis epidemiology in a region of northern Italy. An analysis carried out through the application of a simulation model (Eskimo).

The epidemiological model Eskimo has been utilized to simulate some epidemiological parameters relative to tuberculosis in a restricted geographical area of northern Italy. After having identified a series of features relative to the regimens applied in the area in the period 1982-86 and which were found to be compatible with the observed data, this hypothesis has been utilized to project data on tuberculosis for the period 1986-1996. The results have indicated that the incidence in the area should stabilize around values of 20 new cases per year (per 100,000 population). A decrease in the incidence can be expected to occur only if the regimens so far employed are brought to a greater part of the patients' population (increasing coverage). The effects of importing the disease from developing countries through immigration and of the AIDS epidemic are likely to negatively affect the trend of tuberculosis incidence in the future.

Eskimo: an epidemiological simulation kinetic model for tuberculosis.

A simple, easy to use, kinetic model allowing the simulation of the main epidemiological parameters of tuberculosis and of the financial costs associated with the implementation of different anti-tuberculous policies, has been developed and described. The model, which has been denominated "ESKIMO" (Epidemiological Simulation Kinetic Model) can be utilized on a personal computer and requires, for its use, the knowledge of a series of easily available census data relative to a given country or geographical area, an essential epidemiological profile of the disease in the same area and data which characterize one or more antituberculous treatments in therapeutic and financial terms. The rationale of the model, which is a multicompartemental system, derive from an analysis of the relationships (transfer rates) between sub-populations of individuals in relation to tuberculosis either when the dynamic state of the system is governed by "natural forces" (no treatment) or when an external action is applied to it with an aim to alter its internal pathways in a favourable sense (vaccination, long-term hospitalization, chemotherapy). The model is based on the assumption that the main objective of any antituberculous program is the reduction in size of the subpopulation of patients who can infect other individuals and therefore perpetuate the disease. Validation and projection tests carried out through Eskimo seem to indicate that concentrating the analysis on the effect of various treatments on this group of patients simplifies the calculations while the relative precision of the estimates of other parameters is very satisfactory. The results of several simulations substantiate and quantify the opinions expressed by several experts in the past that the policy of applying cheap regimens of low efficacy to a relatively small fraction of the patients' population, as frequently done in developing countries, not only does not alter the trend of the disease but produces essentially negative results (increase in the number of new cases and in the frequency of resistant M. tuberculosis). Treatment with highly effective regimens of the same number of patients as those treated now (constant coverage) and therefore without the extra costs resulting from the improvement of the available sanitary infrastructures, produces much better results in clinical terms and overall saving of financial resources.

Comparative bioavailability of isoniazid, rifampin, and pyrazinamide administered in free combination and in a fixed triple formulation designed for daily use in antituberculosis chemotherapy. I. Single-dose study.

A comparative bioavailability study of the antituberculosis drugs isoniazid, rifampin, and pyrazinamide was carried out in a group of 10 healthy volunteers after administration of the three compounds, once in individual association and once in a combined, fixed preparation. The investigation was designed as an open, crossover study where each subject received five tablets of a preparation containing 50 mg isoniazid, 120 mg rifampin, and 300 mg pyrazinamide (corresponding to a total dose of 250 mg isoniazid, 600 mg rifampin, and 1,500 mg pyrazinamide). The same doses were administered in the session where the drugs were combined using the individual formulations. For each subject and experimental session, 15 blood samples were collected over a period of 24 h, and the plasma concentrations of the three drugs were assessed. The results indicated the absence of negative pharmacokinetic interactions between the drugs when administered in both free and this new, fixed combination.

Comparative bioavailability of isoniazid, rifampin, and pyrazinamide administered in free combination and in a fixed triple formulation designed for daily use in antituberculosis chemotherapy. II. Two-month, daily administration study.

The time course of the plasma concentrations of isoniazid, rifampin, and pyrazinamide was assessed in a group of 13 patients with lung tuberculosis treated over a period of 2 months on a continuous daily basis with a fixed triple combination of the same drugs. The blood kinetics of the three antituberculosis drugs were determined on Days 1, 15, 30, and 60 of treatment. The triple combination employed in this study contained 50 mg isoniazid, 120 mg rifampin, and 300 mg pyrazinamide per tablet, the number of tablets ranging from four to seven per day according to the body weight of the patients. Almost superimposable plasma concentration curves for isoniazid were observed during the 4 days of the study. For rifampin, a fall in the plasma concentrations at the time intervals after the peak was observed comparing the data on Day 1 with those on Days 15, 30, and 60, which did not differ from each other. This finding is thought to be due to the well-known phenomenon of self-induction, which leads to an increased rate of disposal of the antibiotic from the blood compartment within the first and second weeks of continuous treatment. For pyrazinamide, an equilibrium in the opposite sense as that of rifampin seemed to take place within the 2 months of the study. Because of the relatively high plasma levels observed 24 h after each administration, an increase in plasma concentrations with respect to those observed on Day 1 was found on Days 15, 30, and 60, the levels on these days no differing from each other.(ABSTRACT TRUNCATED AT 250 WORDS)

Short-course chemotherapy of pulmonary tuberculosis: a new approach to drug dosage in the initial intensive phase.

An analysis carried out on the dosage schemes adopted in several controlled clinical trials in tuberculosis has indicated that preestablishing the daily doses of isoniazid, rifampicin, and pyrazinamide in the initial intensive phase results in large deviations of the doses administered from those considered appropriate in mg/kg body weight. This is due partly to the variations in the patients' body weight and partly to the restrictions in terms of fine adjustments of dosage imposed by the unitary content of active principle in the available individual preparations of the drugs. The availability of a fixed-triple combination of the same 3 drugs where the content of each component is established multiplying the mg/kg requirement of each drug by 10, allows a complete coincidence between the appropriate and the administered dose simply administering 1 tablet every 10 kg of body weight. The implications of the large overdosing in light patients if the conventional approach is followed are discussed in terms of toxicity and drug purchasing cost, both being of great relevance for Third World countries where the majority of patients are of low body weight.

Killing of macrophage-ingested mycobacteria by rifampicin, pyrazinamide, and pyrazinoic acid alone and in combination.

A study was undertaken with the aim of assessing the killing capacity of rifampicin, pyrazinamide, and pyrazinoic acid on macrophage-ingested, live Mycobacterium tuberculosis. The 3 drugs were used at concentrations corresponding to the average peak levels observed in humans after administration of therapeutic doses that had been found to penetrate into macrophages in a previous study. The degree of killing was studied after exposure of the cell cultures to the individual drugs and their combinations for 3, 18, 24, 48, and 72 h. Comparing the degree of killing in the control, drug-free cultures with that observed in the drug-containing systems, over a period of 3 to 24 h, indicated that in these a greater, more rapid, although not statistically significant, killing of intracellular mycobacteria took place. At 48 h the degree of killing was similar in the control and in the drug-containing cell cultures. Between 48 and 72 h, however, a marked growth of intracellular mycobacteria was observed in the control cultures. This phenomenon was much less evident in the drug-containing cultures. No major increase in the killing effect with respect to that observed with the individual drugs was found after exposure of the macrophages to all possible combinations of the 3 drugs.

The penetration of rifampicin, pyrazinamide, and pyrazinoic acid into mouse macrophages.

The degree of penetration of rifampicin, pyrazinamide, and its metabolite pyrazinoic acid in mouse macrophages was evaluated over a period of 24 h. Cell cultures were exposed to 14C-labeled drugs at concentrations corresponding to peak, trough, and intermediate serum concentrations observed in humans after administration of therapeutic doses. The study was carried out with dead, resident, and stimulated peritoneal macrophages. The results indicated that the 3 compounds penetrate macrophages rapidly. At the lower concentrations, uptake of the 3 drugs is practically complete. With increasing concentrations, the absolute amount in the intracellular compartment increased. Comparison of the degree of penetration of the 3 drugs into dead, resident, and stimulated macrophages seems to suggest that the process of transfer through the macrophage wall is of a passive nature and not related to the metabolic state of the cells. Analysis of the binding of the 3 drugs to intracellular proteins indicated that more binding sites are probably available for rifampicin than for the other 2 drugs.