Mucosal and systemic immune responses to plasmid protein pgp3 in patients with genital and ocular Chlamydia trachomatis infection.

The circulating and cervical B cell responses to Chlamydia trachomatis plasmid protein pgp3 were characterized in children and adults with ocular or genital chlamydial infection using the enzyme-linked immunospot assay (ELISPOT) and ELISA. No pgp3-specific ASCs were detected in healthy controls, but predominantly IgA ASCs were detected in UK adults with uncomplicated cervicitis or urethritis (P = 0.03, 0.019). In patients with extragenital complications or pelvic inflammatory disease a mixed response with more IgG and IgM ASCs was evident, suggesting a breach of mucosal immune compartmentalization with more extensive infection. In women with chlamydial cervicitis, ASCs secreting predominantly IgA, but also IgG, to pgp3 were present in cervix at presentation, with a frequency 30-50 times higher than blood. Cervical ASC numbers, especially IgG, fell markedly six weeks after antibiotic treatment. We detected principally IgA pgp3-specific antibody secreting cells (ASCs) in children resident in a Gambian endemic area, with a trend towards suppression of IgA responses during intense trachomatous inflammation (P = 0.06), as previously reported for other chlamydial antigens, and in keeping with the findings in genital disease. These data provide a rationale for further studies of immune responses to pgp3 in humans and animal models of chlamydia-induced disease, and its potential use in diagnostic assays and protective immunization strategies.

Educational level and hypertension: how socioeconomic differences condition health care.

This is the first European study that has evaluated educational level in a large sample of hypertensive outpatients. We established the educational level of the hypertensive outpatients in our unit, and determined whether the awareness of hypertension and its organ damage was education-related. We analysed data from 812 consecutive outpatients (378 men, mean age 50 +/- 10 years) with essential stage I-II hypertension. Subjects were subdivided into two categories: group A subjects were highly educated; group B subjects had a little education. Data were compared with educational level from the 1991 population census for the Campania region (ISTAT data) and with 200 type 2 diabetes patients (96 men, mean age 51 +/- 9 years) from the nearest diabetes unit. For each hypertensive patient we considered clinical, echocardiographic and biochemical parameters. Data from the last census showed a high percentage (80%) of subjects with low education. The percentage of type 2 diabetic patients with little education was high (190 patients, 95%). Conversely, it is somewhat surprising that most hypertensive patients reached high standards of education and worked at sedentary jobs (group A: 736 patients, 91%; P < 0.0001). Multivariate analysis showed that only diastolic blood pressure (P = 0.03) was independently associated with low educational level. Compared to diabetes, hypertension and its risk factors are relatively unknown to people with little education. Education is associated with greater health care and awareness that may overcome the risk related to low physical activity. Thus, we stress the importance of a sound health policy able to reach out to the uneducated and make them aware of hypertension and the health care services available to them.

Left ventricular systolic and diastolic function after anthracycline chemotherapy in childhood.

BACKGROUND: In childhood, late cardiotoxicity is characterized by inappropriately thin wall and consequent increased end-systolic wall stress, but the associations of impaired left ventricular geometry and function occurring under these circumstances need further investigation. HYPOTHESIS: The purpose of this study was to assess anthracycline late effects on the relationships occurring between increased end-systolic stress (ESS) and changes in both M-mode systolic measurements (i.e., endocardial and midwall fractional shortening) and Doppler diastolic indices in the pediatric age. METHODS: The population consisted of 101 children treated with anthracyclines for at least 12 months and 91 healthy children. Using M-mode echocardiography, end-systolic wall stress was calculated as index of afterload, and endocardial and midwall fractional shortening as systolic indices. Doppler transmitral measurements were made as diastolic indices. RESULTS: Patients treated with anthracyclines showed significantly lower relative wall thickness and left ventricular mass index, greater end-systolic wall stress, reduced endocardial and midwall fractional shortening and peak E/A ratio, prolonged deceleration, and isovolumic relaxation times. Direct relationships were found between end-systolic wall stress and both endocardial and midwall shortening. The use of midwall shortening in the relation showed a greater, but not significant increase (from 3 to 6%) in the proportion of patients with depressed systolic function than did endocardial shortening. In the anthracycline group, end-systolic wall stress was also inversely related to relative wall thickness and directly to isovolumic relaxation time. CONCLUSIONS: In childhood, reduced myocardial thickness and increased afterload explain much of systolic and diastolic dysfunction of late anthracycline toxicity. Midwall fractional shortening does not seem to add useful information for identifying subsets of children more prone to the development of heart failure.

Left atrial size in 164 hypertensive patients: an echocardiographic and ambulatory blood pressure study.

BACKGROUND: Left atrial enlargement (LAE) is associated with an increased risk of death and cardiovascular (CV) hospitalization. Whether or not LAE reflects early structural change from hypertension is unclear. HYPOTHESIS: The aim of this study was to evaluate the relationship between LA size, 24-h blood pressure measurements, age, body mass index (BMI), and left ventricular mass index (LVMI) in hypertensive patients. METHODS: We studied 164 outpatients (age range 30-76 years, 73 men and 91 women) with mild to moderate hypertension. Physical examination, electrocardiogram, noninvasive blood pressure monitoring (ABPM), Doppler echocardiogram were performed. Left ventricular mass index and LA dimensions were calculated. The sample was divided by age (< 60 and > or = 60 years). RESULTS: Left ventricular hypertrophy (LVH) was present in 45% of patients aged < 60 years and in 70% of patients aged > or = 60 years (p = 0.002). Left atrial enlargement (> 4 cm) was present in 35% of elderly and in 24% of young patients (p = 0.31), and in 36% of patients with and 21% of patients without LVH (p = 0.0057). There was no significant difference in the younger patients with and without LVH. The incidence of obesity was low (31%) in the whole sample. The percentage of overweight in the elderly patients with LVH and higher LA size was equally low. Multivariate analysis showed age (p = 0.044) and LVMI (p = 0.002) as the only significant predictors of LA enlargement. CONCLUSION: Since LAE is associated with a high risk of death and CV hospitalization, we emphasize the importance of development and use of drugs that inhibit LVH.

Atrial natriuretic factor and mitral valve prolapse syndrome.

Mitral valve prolapse (MVP), is the most frequent valvulopathy, although it is difficult to evaluate its incidence since this pathology is often asymptomatic. However, in some patients a rich variety of symptoms such as chest pain, dyspnea, palpitations, syncope, dizziness, panic attacks and autonomic dysfunctions have been found. The pathogenesis of these symptoms, incompletely understood, appears to be multifactorial, related to altered autonomic function, adrenergic responsiveness and to combinations of these factors. In patients with MVP a variety of neuroendocrine anomalies has been found: high epinephrine and norepinephrine plasma levels, altered rennin-angiotensin-aldosteron (RAA) response to volume depletion and orthostatic stimulation, and high plasma levels of atrial natriuretic factor (ANF) especially in hypovolaemic individuals. The role of ANF could be important in the genesis of MVP syndrome, it could contribute to determine: the imbalance between the sympathetic and parasympathetic system, the altered RAA response to orthostatic stimulus, the volemic and venous flow reductions (with a direct action, other than diuretic and natriuretic action). Factors that can determine ANF secretion abnormality in MVP could be: 1) Mitral regurgitation; 2) increased heart rate and the high incidence, in MVP syndrome, of arrhythmias; 3) central nervous system neuroendocrine imbalance; 4) increased catecholamines secretion.

Arterial distensibility and ambulatory blood pressure monitoring in young patients with neurofibromatosis type 1.

Vascular disease is an underestimated complication of neurofibromatosis type 1 (NF1). The few studies available on this disease are based on case reports. The purpose of this study was to evaluate the relationship between 24-h systolic blood pressure (SBP) and 24-h heart rate obtained by ambulatory blood pressure monitoring and the carotid femoral pulse wave velocity, a widely used index of arterial distensibility, evaluated with Complior. We studied 64 young NF1 patients and 30 healthy subjects. There was no difference in pulse wave velocity between NF1 patients and healthy subjects. Ten of the NF1 patients showed 24-h SBP or 24-h diastolic blood pressure (DBP) >95th percentile for age and sex. We divided the NF1 group into subgroups: NF1 patients with 24-h SBP and 24-h DBP < or = 95th percentile for age and sex (NF1A group) and NF1 patients with mean SBP or DBP >95th percentile for age and sex (NF1B group). The pulse wave velocity of NF1A and NF1B patients were 6.3 +/- 1 m/sec and 6.4 +/- 1 m/sec, respectively (P = not significant). A significant relationship was found between 24-h SBP, 24-h heart rate, and pulse wave velocity in healthy subjects, but not in all NF1 patients and also between the NF1A and NF1B groups. Distensibility of the central arteries may be altered by various environmental or genetic factors. Thus, genetic determinants may play a role in the response of the large arteries to blood pressure. The recent discovery of neurofibromin in aortic smooth muscle may explain the vascular abnormalities present in NF1 patients. We emphasize the importance of a careful vascular evaluation using a noninvasive method, such as Complior and a periodic ambulatory blood pressure monitoring to detect NF1 patients at high risk of vascular complications.

Noninvasive evaluation of arterial abnormalities in young patients with neurofibromatosis type 1.

Neurofibromatosis regroups at least two different autosomal dominant genetic disorders: neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2). Vascular disease is an underestimated complication of NF1. Few studies are available on this, all based on case reports. Neurofibromin, NF1 protein product, has also been detected in aortic smooth muscle. The purpose of this study was to evaluate the physical properties of the vessels, by measuring the carotid-femoral pulse wave velocity (PWV). This parameter was assessed by the Complior, a new noninvasive, validated device, used to screen a large population. The authors studied 64 neurofibromatosis patients (34 boys and 30 girls) with a mean age of 12 years (range 5-25 years). To investigate the presence of vascular lesions, aortic stiffness was evaluated by carotid-femoral PWV by using an automatic processor (Complior). They compared data from the PWV with a control group (30 healthy children, 17 boys and 13 girls, mean age 11 years, range 5-23 years). The calculated mean PWV in the control group was 6.5 +/- 1.15 m/s. The mean PWV of the 64 young patients with NF1 was 6.3 +/- 1.02 m/s. There was no difference between the two groups (p=0.39). Nevertheless, analysis of the linear regression has shown a linear relationship between systolic blood pressure (SBP) and PWV in the control group, while in NF1 patients this relationship is not present. The authors suggest that the coexistence of different factors, such as intimal proliferation, thinning media, fragmentation of the elastic tissue, irregularity, stenosis and tortuosity of the vessels, dysplasia of the small vessels, that counterbalance PWV, normalize the mean value. They emphasize the importance of a careful vascular evaluation, using noninvasive method, such as Complior. This device is well accepted by NF1 patients.

Ivermectin alone or in combination with benzyl benzoate in the treatment of human immunodeficiency virus-associated scabies.

In order to establish a safe and reliable treatment for human immunodeficiency virus (HIV)-associated scabies, we have treated 60 episodes of scabies in this setting, occurring in 39 patients, with one of the following regimens: (i) topical treatment with benzyl benzoate solution; (ii) single-dose oral treatment with ivermectin alone; and (iii) combination therapy with benzyl benzoate solution and oral ivermectin, employing the same regimens as single-agent therapy. Patients were stratified according to the severity score of the disease and the outcome (eradication, relapse, failure). We found that both benzyl benzoate and ivermectin alone were quite effective in mild to moderate scabies, but they were both associated with an unacceptable rate of relapse and failure in severe or crusted scabies. In contrast, combined treatment produced an optimal rate of success, without significant treatment-related side-effects. Therefore, we consider that combination treatment with benzyl benzoate solution and oral ivermectin is preferable to single-agent therapy in crusted scabies occurring in HIV/acquired immune deficiency syndrome patients.

Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing.

Neisseria meningitidis is a major cause of bacterial septicemia and meningitis. Sequence variation of surface-exposed proteins and cross-reactivity of the serogroup B capsular polysaccharide with human tissues have hampered efforts to develop a successful vaccine. To overcome these obstacles, the entire genome sequence of a virulent serogroup B strain (MC58) was used to identify vaccine candidates. A total of 350 candidate antigens were expressed in Escherichia coli, purified, and used to immunize mice. The sera allowed the identification of proteins that are surface exposed, that are conserved in sequence across a range of strains, and that induce a bactericidal antibody response, a property known to correlate with vaccine efficacy in humans.

Comparison of losartan and hydrochlorothiazide on cognitive function and quality of life in hypertensive patients.

We examined long-term changes in cognitive function and quality of life (QL) in hypertensive patients by comparing the antihypertensive effect of hydrochlorothiazide (HCTZ) and losartan. We studied 69 patients (age range, 30 to 73 years) with mild-to-moderate hypertension. All patients, in a double-blind study, were randomly allocated to either treatment with 50 mg losartan once daily or 25 mg HCTZ once daily. The sample in each treatment group was divided by age (younger than 60 years or 60 years or older). At baseline and after 26 months, a QL questionnaire appropriate for the hypertensive patients was given. Cognitive function was evaluated, at baseline and after 26 months, by psychometric tests consisting of items from the Mini-Mental State Examination (MMSE) and the Sandoz Clinical Assessment Geriatric (SCAG). A score of less than 24 on the MMSE and more than 40 on the SCAG was predictive of cognitive impairment. The losartan group had a significant improvement in SCAG (P<.001) and MMSE (P<.001). No significant changes were observed in the HCTZ group (SCAG, P = .1; MMSE, P = .2). Sixty-five percent of the elderly had a MMSE score less than 24 and 70% had a SCAG score greater than 40, v. 35% and 48%, respectively, in younger patients. The health state index of QL improved significantly in both groups (losartan group, P<.01; HCTZ group, P<.02); the improvement in QL scores in patients using HCTZ was significant only in subjects aged 60 years and older (P<.04). These results suggest that losartan can have a positive effect not only on blood pressure but also on impaired cognitive function, reversing even minimal cognitive deficits induced by hypertension. The elderly patients in our sample had worse scores and cognitive performance was lower than in younger patients, even if in the losartan group the score improvement was the same at all ages. The same could not be said for HCTZ.

Identification of immunoreactive proteins of Chlamydia trachomatis by Western blot analysis of a two-dimensional electrophoresis map with patient sera.

Western blots of two-dimensional electrophoretic maps of proteins from Chlamydia trachomatis were probed with sera from 17 seropositive patients with genital inflammatory disease. Immunoblot patterns (comprising 28 to 2 spots, average 14.8) were different for each patient; however, antibodies against a spot-cluster due to the chlamydia-specific antigen outer membrane protein-2 (OMP2) were observed in all sera. The next most frequent group of antibodies (15/17; 88%) recognized the hsp60 GroEL-like protein, described as immunopathogenic in chlamydial infections. Reactivity to the major surface-exposed and variable antigen major outer membrane protein (MOMP) was observed at a relatively lower frequency (13/17; 76%). The hsp70 DnaK-like protein was also frequently recognized (11/17; 64.7%) in this patient group. Besides the above confirmatory findings, the study detected several new immunoreactive proteins, with frequencies ranging from 11/17 to 1/17. Some were characterized also by N-terminal amino acid sequencing and homology searches. Amongst these were a novel outer membrane protein (OmpB) and, interestingly, five conserved bacterial proteins: four (23%) sera reacted with the RNA polymerase alpha-subunit, five (29%) recognized the ribosomal protein S1, eight (47%) the protein elongation factor EF-Tu, seven (41%) a putative stress-induced protease of the HtrA family, and seven sera (41%) the ribosomal protein L7/L12. Homologs of the last two proteins were shown to confer protective immunity in other bacterial infections. The data show that immunological sensitization processes commonly thought to play a role in chlamydial pathogenicity may be sustained not only by the hsp60 GroEl-like protein, but also by other conserved bacterial antigens, some of which may be also considered as potential vaccine candidates.

Effects of losartan on hypertension and left ventricular mass: a long-term study.

This study evaluated the anti-hypertensive efficacy, tolerability and effects on left ventricular mass of losartan, a selective angiotensin II receptor antagonist, after 22 months in patients with essential hypertension. The study included 77 hypertensive patients who were randomised at baseline to 22 months double-blind once-daily treatment with losartan 50 mg (L group n = 44 patients, mean age 54+/-9 years) or hydrochlorothiazide 25 mg (HCTZ group, n = 33 patients, mean age 56+/-7 years). Routine haematology, blood chemistry, standard electrocardiography, echocardiography and ambulatory non-invasive 24-h blood pressure (BP) monitoring were performed at baseline and after 10 and 22 months. The results showed good tolerability and a significant mean systolic and diastolic BP reduction in all groups (L group: 22 mm Hg and 11 mm Hg; HCTZ group: 11 mm Hg and 7 mm Hg, respectively for systolic and diastolic mean BP). Moreover, a remarkable reduction in left ventricular mass index was reached after 10 and 22 months only in the L group (L group: delta = -11 g/m2, P<0.02; HCTZ group: delta = -5 g/m2, P= 0.38). In conclusion, losartan was well tolerated and produced a significant reduction in BP and left ventricular mass in hypertensive patients

[The effectiveness and tolerability of losartan and effect on left ventricular mass in patients with essential hypertension]. / Efficacia e tollerabilità del losartan ed effetto sulla massa ventricolare sinistra in pazienti con ipertensione essenziale.

The purpose of our study was to evaluate the antihypertensive efficacy, tolerability and effects on left ventricular mass of losartan over 10 months in patients with essential hypertension. Losartan is a selective angiotensin II receptor-antagonist. The whole study comprised 89 hypertensive patients who were randomized, at baseline, to 10 months of double-blind once daily treatment with losartan 50 mg (L Group, n = 49, mean age 55 +/- 13 years) or hydrochlorothiazide 25 mg (HCTZ Group, n = 40, mean age 56 +/- 10 years). Routine hematology, blood chemistry and urinalysis were performed before and after 5 and 10 months; standard electrocardiography, ambulatory non invasive 24-hours blood pressure monitoring, M-mode echocardiography, psychometric test and quality of life evaluation were obtained from all the patients before and after 10 months. In patients non responding after 4 weeks, hydrochlorothiazide 25 mg or losartan 50 mg was added in the L Group and in the HCTZ Group, respectively (L-HCTZ Group). The results showed good tolerability and a significant mean systolic and diastolic blood pressure reduction in all groups (L Group from 157/96 +/- 9/7 to 137/85 +/- 9/5 mmHg, p < 0.001; HCTZ Group from 158/97 +/- 11/8 to 150/91 +/- 9/7 mmHg, p < 0.003; L-HCTZ Group from 159/98 +/- 9/5 to 141/88 +/- 6/4 mmHg, p < 0.001), although L and L-HCTZ treatment were more effective during 24 hours than HCTZ. Moreover, a remarkable reduction in left ventricular mass index was obtained after 10 months only in the L Group (from 138.4 +/- 26.2 to 127.2 +/- 23.1 g/m2, p < 0.04) and in the L-HCTZ Group (from 140 +/- 20.3 to 125.5 +/- 20.1 g/m2, p = 0.126). Finally, in patients treated with losartan the results of psychometric test significantly improved (L Group: p < 0.05; L-HCTZ Group: p < 0.05) and a positive remarkable change in the quality of life was observed (L Group: p < 0.05; L-HCTZ Group: p = 0.083). In conclusion, losartan in monotherapy or in association with hydrochlorothiazide, was well tolerated, respected the quality of life, and produced a significant and remarkable reduction in blood pressure and left ventricular mass in hypertensive patients.

Characterization of a new isolate of Chlamydia trachomatis which lacks the common plasmid and has properties of biovar trachoma.

A Chlamydia trachomatis urethral isolate, alpha/95, yielding pgp3-negative but otherwise normal inclusions by immunofluorescence also gave negative results when pCT-homologous DNA was searched by PCR and Southern blotting. omp-1 sequence analysis identified alpha/95 as a new genotype B variant. These findings confirm that pCT is not required for chlamydial growth in vitro.

[Diagnostic imaging and therapeutic implications in lung infections in patients with HIV-1 infection]. / L'imaging diagnostico e le implicazioni terapeutiche nelle infezioni polmonari del paziente affetto da HIV1.

We studied retrospectively 132 episodes of infectious pneumonias in 89 patients examined from 1990 to 1995. Pneumocystis carinii was found to be the most common cause of pneumonia (33 patients). The other causes were: Streptococcus pneumoniae (15), Mycobacterium tuberculosis (14), Pseudomonas aeruginosa (8), Staphylococcus aureus (5), Cytomegalovirus (4), Haemophilus influentiae (4), Mycobacterium avium intracellulare (2), Klebsiella pneumoniae (2), E. coli (2), Serratia marcescens (1). No etiologic agent was found in 40 cases. We stress the need of a more frequent use of invasive diagnostic procedures in the study of focal lung consolidations because this radiologic sign is highly aspecific and may be caused by too many different pathogenic agents, needing different therapies-i.e., Streptococcus pneumoniae (15 cases), Pseudomonas aeruginosa (8), Staphylococcus aureus (5), Klebsiella pneumoniae (2), Escherichia coli (2), Pneumocystis carinii, Serratia marcescens and Haemophilus influentiae (1). Since there is an increase in mortality among patients treated with empiric antibiotic therapy, we stress the need of the routinary use of bronchoalveolar lavage in HIV+ patients with lung consolidation to perform specific therapy. Moreover, Pneumocystis carinii is by far the most frequent cause of diffuse interstitial infiltrates, and PCP has very suggestive clinical (dyspnea), radiologic (diffuse perihilar interstitial infiltrates; ground glass opacities; pneumatoceles) and laboratory (CD3+CD4 < 200/mcl; LDH > 600 UI/dl; PO2 < 70 mmHg) patterns, always related to the discovery of Pneumocystis carinii in escreatum. Thus, we decided to treat 15 patients with specific therapy for Pneumocystis carinii pneumonia with the above diagnostic algorithm, obtaining in all of them complete clinical and radiologic recovery. To conclude, in critical patients, invasive procedures should be performed only in the cases in which PCP is clinically improbable.