Non-tuberculous mycobacteria: epidemiological pattern in a reference laboratory and risk factors associated with pulmonary disease.

The diseases caused by non-tuberculous mycobacteria (NTM), in both AIDS and non-AIDS populations, are increasingly recognized worldwide. Although the American Thoracic Society published the guidelines for diagnosis of NTM pulmonary disease (NTM-PD), the diagnosis is still difficult. In the first part of the study, we collected data on NTM isolates in the Mycobacteriology Laboratory of Careggi Hospital (Florence, Italy) and analysed the epidemiological data of NTM isolates. Then, to analyse the risk factors associated to NTM-PD, we studied the presence of ATS/IDSA criteria for NTM-PD in patients who had at least one positive respiratory sample for NTM and were admitted to the Infectious Disease Unit and the Section of Respiratory Medicine. We selected 88 patients with available full clinical data and, according to ATS/IDSA criteria, classified 15 patients (17%) as NTM-PD cases and 73 as colonized patients (83%). When comparing colonized and NTM-PD patients we did not find significant differences of age, gender and comorbidity. We observed that Mycobacterium avium and M. intracellulare were statistically associated with NTM-PD (P = 0·001) whereas M. xenopi was statistically associated with colonization. Although the number of studied patients is limited, our study did not identify risk factors for NTM-PD that could help clinicians to discriminate between colonization and disease. We underline the need of close monitoring of NTM-infected patients until the diagnosis is reasonably excluded. Further larger prospective studies and new biological markers are needed to identify new useful tools for the diagnosis of NTM-PD.

Infection due to a novel mycobacterium, mimicking multidrug-resistant Mycobacterium tuberculosis.

The treatment of multidrug-resistant tuberculosis (TB) requires the use, for long periods, of drugs liable to cause significant side effects. In the case of misdiagnosis of multidrug-resistant TB, the patient is exposed to toxic substances without any benefit. In low-income countries, where the microbiological diagnosis of TB relies on microscopy only, the misdiagnosis of multidrug-resistant TB is very frequent in patients persistently smear-positive despite anti-TB treatment, with the possibility of an infection due to non-tuberculous mycobacteria (NTM) being neglected. The isolation of a mycobacterium from the sputum of a Somali patient apparently confirmed the previous diagnosis of cavitary pulmonary disease. Preliminary investigations led, at first, to the strain being identified as multidrug-resistant Mycobacterium tuberculosis, with findings fully in agreement with the patient's history, which was characterized by repeated interruptions of anti-TB treatment. Thorough phenotypic and genotypic analyses led subsequently to the recognition that the strain was a previously unreported non-tuberculous mycobacterium. The patient, who was unresponsive to the anti-TB treatment, dramatically improved once a drug combination active against NTM was used. A major objective of this article is to alert the medical community to the risk, present also in settings in which sophisticated diagnostic techniques are used, that a cavitary infection due to NTM, and consequently not responding to the anti-TB standard regimen, will be mistaken for multidrug-resistant TB.

Disseminated Scedosporium apiospermum infection in renal transplant recipient: long-term successful treatment with voriconazole: a case report.

Scedosporium apiospermum, the asexual form of Pseudallescheria boydii, is a ubiquitous fungus that represents an unfrequent complication of immune suppression. It accounts for 20% of all non-Aspergillus mold infections in organ transplant recipients. The infection can be localized or disseminated in multiple organs, including lungs, brain, joints, tendons, and skin, and is difficult to treat, due to resistance of S apiospermum to amphotericin B and other antifungal agents. The mortality rate is about 50%. To our knowledge, there are no prospective studies or registries of transplant recipients to guide diagnosis and there are no evidence-based recommendations for the optimal management of this infection. We report a case of S apiospermum infection in a woman with renal transplantation. The first occurrence of infection was a solitary nodule on the forearm, which was surgically excised. Two following relapses were disseminated to the knee, the Achilles tendon, and the skin of the left leg. The infection was successfully treated with voriconazole, but due to the severe iatrogenic immune suppression, a strong reduction in immunosuppressant drugs was needed.

Lactobacillus casei pneumonia and sepsis in a patient with AIDS. Case report and review of the literature.

Lactobacilli are ubiquitous gram-positive anaerobic rods present in the normal bacterial flora of the mouth, vagina and gastrointestinal tract. Although they are usually non pathogenic, serious infections have occasionally been described in transplant recipients or severely ill patients. Only 4 cases have been reported involving AIDS: one had predisposing conditions other than AIDS, and none of the others had pure growth of lactobacilli. We report a case of community-acquired Lactobacillus casei pneumonia in a CD4 lymphocyte-depleted AIDS patient. Lactobacillus was isolated in pure growth in repeated blood cultures in an outpatient with no preexisting lung diseases and no known risk factors for Lactobacillus infections (dental procedures, complicated deliveries, gastrointestinal diseases, cardiac prosthetic valves) or consumption of unusual dairy products. Although uncommon, lactobacilli are possible pathogens in HIV-infected patients with very low CD4 counts, and their isolation in clinical specimens must not be neglected. Susceptibility tests are essential because of the variable antibiotic-resistance patterns of these bacteria.

Human parvovirus B19 infection within a family and risk for pregnant women.

During an outbreak of parvovirus B19 infection among four related families at least 70% of the household contacts, including a woman at the 33rd week of pregnancy, became infected. Twins were born at the 39th week of pregnancy, both with B19 infection. B19 DNA was detected in their sera by a nested PCR, anti-B19 IgM was detectable only by an immunofluorescence assay, and low levels of maternal anti-B19 IgG were demonstrable by an immunoenzymatic test in the serum of both children. All the haematological parameters were normal at birth and 6 months later, when B19 DNA and anti-B19 antibody were no longer detectable in serum samples. This observation emphasizes the high risk of B19 infection among household contacts and the possibility of a favourable outcome of the foetal infection, possibly related to infection late in the pregnancy.

[Therapy of tuberculosis today: to prescribe is not enough. A case report]. / La terapia della tubercolosis oggi: prescrivere non è curare. Descrizione di un caso.

Tuberculosis is a re-emerging disease not only in developing but also in industrialized countries. The multidrug resistance of Mycobacterium tuberculosis is an increasing problem, mainly due to the poor compliance of the patients on drug regimens. The authors discuss the case of a 28-year-old male affected by pulmonary tuberculosis who did not improve after a 3-month period of oral tuberculosis treatment. The switch to intravenous therapy was rapidly followed by clinical and microbiological improvement. The patient subsequently admitted that he had not complied with oral treatment because after healing he would be sent back to prison. This case demonstrates that, even in the hospital setting, noncompliance to antitubercular therapy is not unfrequent, as demonstrated by other case reports. The authors discuss a great amount of literature that strongly supports the introduction of directly observed therapy for the treatment of all tuberculosis patients.

[Isosporiasis and sarcocystosis. The current findings]. / Isosporiasi e sarcocistosi. Acquisizioni attuali.

A review on infections by Isospora belli and Sarcocystis spp. both in healthy and in AIDS patients is done on the basis of literature and personal data. In this view a special focus is made on isospora belli infection in AIDS because of its high recurrence after successful attack therapy. Consequently the most recent protocols for maintenance and attack therapy in these patients are reported. At the end, concerning ultrastructural pathology, the features of some Isospora belli developing stages are described by means of electron microscopy on duodenal biopsy specimens from a patient.

Age-related changes in red blood cell lipids.

Red blood cell (RBC) lipid composition was investigated in 81 healthy subjects aged twenty to sixty-nine years, having similar dietary habits, and living in the same geographic area in order to search for changes referable to aging. A significant increase in RBC cholesterol and total phospholipid content with aging was found (p less than 0.001), whereas no differences were observed in cholesterol/phospholipid molar ratio. Significant increases in palmitic acid 16:0 esterified in phosphatidylcholine and in stearic acid 18:0 esterified in phosphatidylethanolamine (p less than 0.001) were observed with aging. Moreover, a decrease in 18:2 n6 was observed in all three phosphoglyceride fractions investigated (p less than 0.001). These results suggest that modifications in RBC lipid composition occur with aging, possibly causing a reduction of membrane fluidity.

Red blood cell lipid alterations in type II diabetes mellitus.

Alterations in blood rheological properties have been reported in diabetes mellitus. Changes in lipid composition of red blood cell (RBC) membranes resulting in an impairment of RBC deformability may play a role in the altered blood rheological pattern. The aim of this study was to investigate the lipid composition of RBC membrane in a group of patients affected by type II diabetes (age 21-45 years), selected on the basis of the absence of complications and good metabolic control, and in a group of suitable control subjects. Saturated fatty acid amounts in the different phospholipid fractions were significantly higher in diabetics than in controls (p less than 0.05), whereas polyunsaturated fatty acids were decreased (p less than 0.05). Cholesterol/phospholipid molar ratio was not altered. On the contrary, sphingomyelin/phosphatidylcholine ratio was higher in diabetics than in controls (1.10 +/- 0.08 vs 0.96 +/- 0.10, p less than 0.01) due specially to high levels of sphingomyelin. These alterations could account for the impairement of RBC deformability frequently reported in diabetes mellitus, independently of metabolic control and the presence of severe atherosclerotic lesions.

Altered membrane fatty acid composition and increased thromboxane A2 generation in platelets from patients with diabetes.

Lipid composition of platelet membranes and thromboxane A2 (TxA2) generation by platelets were investigated in 42 diabetic patients (14 with macroangiopathic complications, 10 with microangiopathy and 18 without vascular complications) and in 42 clinically healthy subjects of similar age. All subjects were on a similar dietary regimen and the adherence to diet was checked by analysis of red blood cell lipids. Platelets from all groups of diabetic patients produced increased amounts of TxA2 than platelets from controls (at least p less than 0.01) and patients with macroangiopathy (p less than 0.01). Platelet cholesterol and total platelet phospholipids were higher in patients with macroangiopathy, while the relative percentage of the different phospholipid fractions in platelet membrane and their saturated and unsaturated fatty acids were similar in the different groups. Arachidonic acid (AA) content in phosphatidylcholine (PC) was found to be significantly higher in diabetic patients than in controls (at least p less than 0.005). Moreover patients with macroangiopathy had higher AA (p less than 0.001) and lower eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) levels in PC (p less than 0.001) than the other groups of patients and controls.

Radioimmunoassay of thromboxane B2 in plasma: methodological modifications.

Thromboxane B2 (TxB2) determination is usually performed by using commercial 3H-RIA kits. However, the low amounts of TxB2 present in plasma are not detectable without previous extraction. The aim of this study is the evaluation of 1) plasma protein interferences on the binding and separation steps of bound from free analyte and 2) charcoal efficacy in different experimental conditions. Our results indicate that plasma proteins do not influence the antibody binding, but significantly reduce the efficacy of precipitation of kit dextran-charcoal, so that the supernate radioactivity rises with the protein amount increase (r = 0.99 p less than 0.001). Such greater number of counts in the samples determines a lower estimation of TxB2 concentration in plasma when the calibration curve is set up in buffer. Our findings suggest that, in order to measure low amounts of plasma TxB2 without extraction, it is useful: 1) to refer to a calibration curve set up in buffer-diluted plasma, 2) to use the uncoated charcoal concentration allowing the lowest stripping and 3) to perform all steps at 4 degrees C.

Altered lipid composition and thromboxane A2 formation in platelets from patients affected by IIa hyperlipoproteinemia.

Platelets from patients with familial hypercholesterolemia (type IIa hyperlipoproteinemia), a condition associated with high prevalence of atherosclerosis and of its thrombotic complications, are known to be hyperresponsive to aggregating stimuli and to synthesize increased amounts of thromboxane A2 (TxA2) in comparison to platelets from normal subjects. In order to search if these functional alterations are linked to a different platelet lipid composition, we studied a group of young patients affected by IIa hyperlipoproteinemia and a group of suitable controls with similar dietary habits. Both cholesterol and phospholipid content of platelets were higher in patients than in controls with a significant increase of cholesterol/phospholipid molar ratio (at least p less than 0.05). The percent contents of the main platelet phospholipid fractions were not altered, while an increase in saturated fatty acids, both unesterified and esterified in different lipid fractions, was observed. Moreover, an increased TxA2 production by platelets and a significantly increased number of megathrombocytes occur in patients with respect to controls (p less than 0.001). Our results indicates that platelets from patients with IIa hyperlipoproteinemia have an altered lipid composition which could explain, at least in part, the enhanced platelet reactivity reported in these patients.

Decrease in frequency of anginal episodes by control of thrombin generation with low-dose heparin: a controlled cross-over randomized study.

Increased thrombin generation is frequently associated with an increase in anginal activity. A cross-over, single-blind, completely randomized study was planned in order to evaluate whether the control of thrombin generation affected the increase in anginal activity. After discharge from the hospital, 24 patients (18 men and 6 women, aged 40 to 69 years) suffering from spontaneous angina were followed up to 12 months and were alternatively treated during two consecutive 6-month periods with calcium heparin, 12,500 IU by the subcutaneous route, or with placebo by the intramuscular route, in addition to the usual antianginal medications. Thrombin generation and clinical activity of angina were assessed every 15 days by measuring fibrinopeptide A (FPA) plasma levels and by grading in three classes (symptomless, mildly symptomatic, and severely symptomatic) the anginal activity on the basis of the number and the time concentration of the ischemic attacks and ECG changes. Low-dose heparin treatment significantly reduced both the FPA plasma level (from 4.1 +/- 3.7 to 2.3 +/- 1.8 ng/ml, p less than 0.001) and the clinical activity of angina. During heparin treatment, the frequency of the observations in the severely and mildly symptomatic classes decreased, respectively, by 53% and by 30%, whereas that in the symptomless class increased by 23% (p less than 0.001) in comparison with the period on placebo. Present results indicate that the control of thrombin generation obtained by low-dose heparin treatment favorably affects the degree of anginal activity in patients with spontaneous angina.

Blood velocity in the coronary artery circulation: relation to thromboxane A2 levels in coronary sinus in patients with angiographically normal coronary arteries.

In the present study, we report the finding that some patients with spontaneous typical angina and angiographically normal coronary arteries present an abnormal cardiocoronary capacity to produce thromboxane A2, both in basal conditions and after sympathetic stimulation. The levels of thromboxane A2 in coronary sinus are significantly correlated to the rate of clearance of contrast medium in coronary circulation. Such a finding might be useful in better understanding the interesting syndrome of angina with normal coronary arteries.

Effect of oral treatment with pantethine on platelet and plasma phospholipids in IIa hyperlipoproteinemia.

In a single-blind, crossover, completely randomized study, the effects of oral treatment with pantethine or placebo on fatty acid composition of plasma and platelet phospholipids were investigated in 10 IIa hyperlipoproteinemic patients. A significant decrease of total cholesterol and total phospholipids was observed both in plasma and in platelets after a twenty-eight-day treatment. In plasma, pantethine induced a decrease of the ratio sphingomyelin/phosphatidylcholine. Moreover, a relative increase of n3-polyunsaturated fatty acids both in plasma and in platelet phospholipids and a decrease of arachidonic acid in plasma phospholipids were observed. These results indicate that pantethine can affect plasma and platelet lipid composition with possibly favorable influences on the determinants of cell membrane fluidity.

Association between time of increased fibrinopeptide A levels in plasma and episodes of spontaneous angina: a controlled prospective study.

Thirty-seven patients affected by spontaneous angina and 15 comparable control subjects were enrolled in a 12-month prospective study to evaluate the relationship between blood clotting activation (assessed by fibrinopeptide A [FPA] plasma concentration) and the occurrence of myocardial ischemic attacks. FPA measurements and clinical examinations in patients were performed every 2 weeks. In control subjects blood sampling was performed every 4 weeks. Data from 28 patients who completed the study and from the 15 control subjects were analyzed. The clinical activity of angina was divided into three classes (asymptomatic, mildly symptomatic, and severely symptomatic) on the basis of the number and time-concentration of the ischemic attacks and ECG changes during the 15 days preceding each clinical examination. In all but one patient, a cyclic pattern of activity of coronary artery disease was observed. During follow-up studies, 624 FPA measurements were performed in patients and 173 in control subjects. Mean values were 4.68 +/- 4.53 and 1.32 +/- 0.60 ng/ml, respectively (p less than 0.001). FPA levels differed markedly in relation to the activity of angina. A relationship between FPA levels and activity of disease (r = 0.54, p less than 0.01) was found in time course. Bolus heparin administration (100 IU/kg) during the active phase of angina sharply but incompletely lowered FPA plasma levels, indicating thrombin formation both intravascularly and extravascularly. Present results indicate that a marked blood clotting activation occurs simultaneously with the outbursts of clinical activity of spontaneous angina.

Age related changes in platelet lipid composition.

Platelet lipid composition was investigated in 52 healthy subjects aged 20 to 68 years with similar dietary habits and living in a narrow geographic area in order to search possible changes referrable to aging. No significant variations were observed when platelet cholesterol, total phospholipids and different phospholipid fractions were considered, whereas cholesterol/phospholipid (C/PL) molar ratio significantly increased with aging (p less than 0.01). Moreover, a significant increase in 16:0 + 16:1 fatty acids was found in phosphatidylcholine (PC) and in sphingomyelin (SP) (r = 0.62, p less than 0.001 and r = 0.30, p less than 0.05 respectively) and a decrease in 18:2 n6 in the phospholipid fractions considered (at least p less than 0.05). These results indicate that modifications in platelet lipid composition occur with aging and that they could affect platelet functions so playing a role in the onset of atherosclerosis and in thrombotic phenomena occurring with increasing frequency in the elderly.

Increased thromboxane A2 generation and altered membrane fatty acid composition in platelets from patients with active angina pectoris.

Lipid composition of platelet membranes and thromboxane A2 (TxA2) generation by platelets were investigated in eighty-seven anginal patients (forty-two with resting angina in active phase and forty-five with effort stable angina or rest angina in inactive phase) and in forty-five clinically healthy subjects of similar age. All subjects were on the same dietary regimen and the adherence to diet was checked by analysis of red blood cell lipids. Platelets from active angina patients produced more TxA2 than platelets from both inactive patients and controls (p less than 0.001). Moreover patients with active angina had higher arachidonic acid (AA, p less than 0.001) and lower eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) levels in phosphatidylcholine (PC, p less than 0.001), than inactive patients and controls. AA and EPA changes in membrane PC significantly correlated with TxA2 production (p less than 0.001) but not with coronary pathoanatomy. Plasma lipids, content of cholesterol, total phospholipids (and their saturated and unsaturated fatty acids) and the different phospholipid fractions in platelet membrane were not different in the three groups. Present results indicate that in platelets from anginal patients phospholipid fatty acid composition is at least in part independent of plasma composition and that in active angina there are modifications leading to increased TxA2 formation and possibly contributing to the occurrence of ischemic attacks.

Impaired cardiac PGI2 and PGE2 biosynthesis in patients with angina pectoris.

Thirty-four patients with unstable angina and 14 patients with stable effort angina were investigated for cardiac prostacyclin and prostaglandin E2 (PGE2) biosynthesis, under resting conditions and after cold pressor testing. Twenty-seven patients undergoing cardiac catheterization and coronary angiography for congenital or acquired heart diseases other than coronary artery disease were studied as a control group. Prostacyclin (as 6-keto-PGF1 alpha) and PGE2 were measured by specific radioimmunoassay of blood from the coronary sinus and aorta. During resting conditions no significant differences in plasma 6-keto-PGF1 alpha and PGE2 concentrations were found between coronary sinus and aortic blood, and no transcardiac gradient existed either in control subjects or in patients with stable and unstable angina, respectively. In control subjects cold pressor testing induced a significant increase in 6-keto-PGF1 alpha and PGE2 levels in blood from the different sampling sites, and a significant transcardiac gradient occurred (+11.2 +/- 6.4 pg/ml for 6-keto-PGF1 alpha and +5.1 +/- 3.4 pg/ml for PGE2). However, in angina patients no significant increase in 6-keto-PGF1 alpha and PGE2 plasma levels was found and no transcardiac gradient was formed after cold pressor testing. These results indicate impaired cardiac prostacyclin and PGE2 biosynthesis both in patients with stable and unstable effort angina.

Enhanced peripheral vasoconstrictor response and increased thromboxane A2 synthesis after the cold pressor test in patients with angina at rest.

Peripheral vascular resistance (PVR) and thromboxane A2(TxA2) synthesis after the cold pressor test were investigated in different subsets of patients with angina (10 with stable effort angina, 36 with resting angina [24 in an active phase and 12 in an inactive phase], and five with Prinzmetal's variant angina) and in 41 control subjects of equivalent age and risk factors. Left ventricular end-diastolic pressure, ejection fraction, extent of coronary angiographic lesions, and baseline PVR were not significantly different among the various patient groups. In all patient groups, except those with variant angina, the cold pressor test resulted in a higher increase in PVR than in the control subjects (p less than .001 for all groups). In patients with variant angina the vasoconstrictor response was increased only in proximity (about 1 hr) to ischemic attacks. In patients with active resting angina the vasoconstrictor response was on the average four times longer than that in patients with effort angina and with inactive resting angina (p less than .001). This exaggerated vasoconstrictor response was associated with elevated TxA2 resting levels in plasma and with increased TxA2 synthesis after the cold pressor test. A linear relationship was found between the area of the vascular response and the area of TxA2 production after the cold pressor test in patients with active resting angina (r = .87, p less than .001). The increased TxA2 synthesis and the inappropriate increase of peripheral vascular response to sympathetic stimulation revert back to normal in the inactive phase.(ABSTRACT TRUNCATED AT 250 WORDS)