The persistent problem of late HIV diagnosis in people with AIDS: a population-based study in Italy, 1999-2013.

OBJECTIVES: Despite the wide accessibility to free human immunodeficiency virus (HIV) testing and combined antiretroviral therapy (cART), late HIV diagnosis remains common with severe consequences at individual and population level. This study aimed to describe trends of late HIV testing and to identify their determinants in the late cART era in Italy. STUDY DESIGN: We conducted a population-based, nationwide analysis of the Italian National AIDS Registry data (AIDS - acquired immune deficiency syndrome) for the years 1999-2013. METHODS: Late testers (LTs) were defined as people with AIDS (PWA) whose first HIV-positive test preceded AIDS diagnosis by 3 months or less. Odds ratios (ORs) with the corresponding 95% confidence intervals (CIs) were estimated to examine factors associated with being LTs. Joinpoint analysis was used to estimate annual percent changes (APCs) of LTs' proportion over time. RESULTS: Among 20,753 adult PWA, 50.8% were LTs. Italian PWA showed a lower proportion of LTs than non-Italian PWA (46.5% vs 68.2%). Among Italian PWA, the odds of being LTs was higher in men than in women (OR = 2.62, 95% CI: 2.38-2.90); in the age groups below 35 years and over 49 years at diagnosis (OR = 1.24, 95% CI: 1.12-1.37 and OR = 1.51, 95% CI: 1.38-1.67, respectively) vs PWA aged 35-49 years; and in those infected through sexual contact as compared with injecting drug use (OR = 13.34, 95% CI: 12.06-14.76 for heterosexual contact and OR = 8.13, 95% CI: 7.30-9.06 for male-to-male sexual contact). The proportion of LTs increased over time among Italians, especially in the latest period (APC2006-2013 = 5.3, 95% CI: 3.8-6.9). The LTs' proportion resulted higher, though stable, among PWA aged ≥50 years. Conversely, an increasing trend was observed among PWA aged 18-34 years (APC = 5.3, 95% CI: 4.5-6.1). The LTs' proportion was persistently higher among PWA who acquired HIV infection through sexual contact, even if a marked increase among injecting drug users was observed after 2005 (APC = 11.4, 95% CI: 5.7-17.5). CONCLUSIONS: The increasing trend of LTs' proportion in the late cART era highlights the need of new strategies tailored to groups who may not consider themselves to be at a high risk of infection. Active promotion of early testing and continuous education of infection, especially among young people, need to be implemented.

Clinical predictors and microbiology of ventilator-associated pneumonia in the intensive care unit: a retrospective analysis in six Italian hospitals.

The purpose of this study was to assess the main clinical predictors and microbiological features of ventilator-associated pneumonia (VAP) in the Intensive Care Unit (ICU) environment. This work is a retrospective analysis over one year from September 2010 to September 2011. Patients' risk factors, causes of admission, comorbidities and respiratory specimens collected in six Italian ICUs were reviewed. Incidence and case fatality rate of VAP were evaluated. After stratification for VAP development, univariate and multivariate analyses were performed to assess the impact of patients' conditions on the onset of this infection. A total of 1,647 ICU patients (pts) were considered. Overall, 115 patients (6.9 %) experienced at least one episode of VAP. The incidence rate for VAP was 5.82/1,000 pts-days, with a case fatality rate of 44.3 %. Multivariate analysis showed that admission for neurological disorders (aIRR 4.12, CI 1.24-13.68, p = 0.02) and emergency referral to ICU from other hospitals (aIRR 2.11, CI 1.03-4.31, p = 0.04) were associated with higher risk of VAP, whereas a tendency to a higher risk of infection was detected for admission due to respiratory disease, cardiac disease, trauma and for having obesity or renal failure. A total of 372 microbiological isolates from respiratory specimens were collected in VAP patients. The most common species were Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa, showing high resistance rates to carbapenems. Neurological disorders and emergency referral at the admission into the ICU are significantly associated with the onset of VAP. A high incidence of multi-drug resistant Gram- species was detected in the respiratory specimens.

Molecular surveillance of pandemic influenza A(H1N1) viruses circulating in Italy from May 2009 to February 2010: association between haemagglutinin mutations and clinical outcome.

Haemagglutinin sequences of pandemic influenza A(H1N1) viruses circulating in Italy were examined, focusing on amino acid changes at position 222 because of its suggested pathogenic relevance. Among 169 patients, the D222G substitution was detected in three of 52 (5.8%) severe cases and in one of 117 (0.9%) mild cases, whereas the D222E mutation was more frequent and evenly distributed in mild (31.6%) and severe cases (38.4%). A cluster of D222E viruses among school children confirms reported human-to-human transmission of viruses mutated at amino acid position 222.

Infection with chikungunya virus in Italy: an outbreak in a temperate region.

BACKGROUND: Chikungunya virus (CHIKV), which is transmitted by Aedes spp mosquitoes, has recently caused several outbreaks on islands in the Indian Ocean and on the Indian subcontinent. We report on an outbreak in Italy. METHODS: After reports of a large number of cases of febrile illness of unknown origin in two contiguous villages in northeastern Italy, an outbreak investigation was done to identify the primary source of infection and modes of transmission. An active surveillance system was also implemented. The clinical case definition was presentation with fever and joint pain. Blood samples were gathered and analysed by PCR and serological assays to identify the causal agent. Locally captured mosquitoes were also tested by PCR. Phylogenetic analysis of the CHIKV E1 region was done. FINDINGS: Analysis of samples from human beings and from mosquitoes showed that the outbreak was caused by CHIKV. We identified 205 cases of infection with CHIKV between July 4 and Sept 27, 2007. The presumed index case was a man from India who developed symptoms while visiting relatives in one of the villages. Phylogenetic analysis showed a high similarity between the strains found in Italy and those identified during an earlier outbreak on islands in the Indian Ocean. The disease was fairly mild in nearly all cases, with only one reported death. INTERPRETATION: This outbreak of CHIKV disease in a non-tropical area was to some extent unexpected and emphasises the need for preparedness and response to emerging infectious threats in the era of globalisation.

Bacterial isolates from severe infections and their antibiotic susceptibility patterns in Italy: a nationwide study in the hospital setting.

The most frequent agents of severe bacterial infections and their antibiotic susceptibility patterns were determined in patients admitted to 45 Italian hospitals over the years 2002-2003. The most common diagnoses were: sepsis (33.8%), pneumonia (9.4%), intravascular catheter-associated infections (9.3%) and ventilator-associated pneumonia (8.1%). Overall, 5115 bacterial isolates were identified from 4228 patients. Three bacterial species, Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli, accounted for more than 50% of the isolates. Other prevalent bacterial isolates were Staphylococcus epidermidis and Enterococcus faecalis, while Acinetobacter baumanii ranked third among all Intensive Care Unit (ICU) isolates. 7% of S. aureus had intermediate resistance to vancomycin. Although E. faecalis displayed no vancomycin resistance, 34% of vancomycin-resistant isolates were found among Enterococcus faecium, one of the highest rates found to date, emphasizing the difference between these two enterococcal species. All the Gram-positive pathogens were susceptible to linezolid, with the exception of approximately 2% of the enterococcal isolates that were intermediate with a minimum inhibitory concentration (MIC)=4 microg/ml. Almost 10% of Escherichia coli, 14% of Klebsiella pneumoniae, 22% of Serratia marcescens and 50% of Enterobacter cloacae were non-susceptible to cefotaxime. Amikacin was the most active antibiotic against P. aeruginosa that showed lack of susceptibility to ceftazidime, gentamicin, piperacillin and ciprofloxacin ranging from 20 to 35%. Finally, Acinetobacter baumanii showed a high level of resistance to all the antibiotics tested including imipenem (58%). The results obtained in this study, the first of its kind in Italy, offer indications for guiding empirical therapy and implementing specific interventions to fight antibiotic-resistant bacterial infections and their transmission in the hospital setting in Italy.

Infection with human immunodeficiency virus, herpes simplex virus type 2, and human herpes virus 8 in remote villages of southwestern Papua New Guinea.

To investigate the spread of human immunodeficiency virus (HIV) and other sexually transmitted viruses, two serosurveys (the first in 1999 among 56 adults and the second in 2001 among 351 adults) were conducted in remote villages of the southwestern part of Papua New Guinea. Only one individual was positive for antibodies to HIV. In 2001, the seroprevalence of human herpes virus 8 (HHV-8) was 32.2%, and the seroprevalence of herpes simplex virus type 2 (HSV-2) was 27.4%. Both prevalence rates increased with age, and were lower in the villages near the Bensbach River. The seropositivity of HSV-2 was independently correlated with HHV-8 infection. Our data show that the inhabitants of the southwestern region of Papua New Guinea currently experience an extremely low circulation of HIV. However, the high prevalence of infectious agents that can be sexually transmitted, such as HSV-2 and to a lesser extent HHV-8, indicates the presence of behavioral patterns that may facilitate the spread of HIV in this area of currently low endemicity.

Incidence and consequences of pregnancy in women with known duration of HIV infection. Italian Seroconversion Study Group.

BACKGROUND: The increasing incidence of human immunodeficiency virus (HIV) infection in women of childbearing age led us to evaluate whether pregnancy affects the natural history of this disease. OBJECTIVES: To conduct a prospective study of women with known dates of HIV seroconversion to describe the incidence and outcome of pregnancy and to assess differences according to age and exposure group. To compare the rate of disease progression between pregnant and nonpregnant women. PATIENTS: All participants, recruited from 14 clinical centers in Italy, had documented HIV-seronegative test results followed by confirmed positive test results within 2 years. RESULTS: A total of 331 women, who had seroconversion between 1981 and 1994, were followed up for a median of 5.5 years from seroconversion; 94 developed HIV-related diseases, 47 developed acquired immunodeficiency syndrome, and 53 had at least 1 CD4 cell count lower than 0.10 x 10(9)/L (< 100 cells/mm3). Thirty-eight women (11.5%) were pregnant at the time of HIV seroconversion and 31 (9.4%) became pregnant after HIV seroconversion (cumulative incidence of pregnancy within 8 years of seroconversion, 28.9%; 95% confidence interval, 21.6%-36.2%). Forty-five (65.2%) of the 69 pregnancies were carried to term. There were no discernible differences in these findings by age or exposure group. Pregnant women did not experience a more rapid rate of progression of disease, even when adjusting for age, exposure group, CD4 cell count, or use of treatment (adjusted relative hazards: HIV-related diseases, 0.72; acquired immunodeficiency syndrome, 0.69; CD4 cell count <0.10 x 10(9)/L, 1.24). CONCLUSION: Women infected with HIV continue to become pregnant after seroconversion, yet pregnancy does not appear to influence the rate of progression of HIV disease.

Changing epidemiology of Infant Meningococcal Disease after the introduction of meningococcal serogroup C vaccine in Italy, 2006-2014.

BACKGROUND: In Italy, the incidence of Invasive Meningococcal Disease (IMD) was around 0.28 per 100,000 over the last years. Since the risk IMD is usually high among infants aged less than 1 year, we decided to evaluate the trend of IMD cases reported between 2006 and 2014 in this age group. In particular, the study aim was to describe the main characteristics of IMD cases in infants following the introduction of MCC vaccine (2005) and to estimate the number of cases which are potentially preventable through early vaccination. METHODS: The National Surveillance System of Bacterial Meningitis was established in 1994 and in 2007 was extended to all invasive bacterial diseases. Clinical data and isolates and/or clinical samples are collected from hospitalized patients throughout the country. IMD cases are reported by clinicians to the local health authorities, and samples are sent to the Reference Laboratory at the Istituto Superiore di Sanità for further characterization and storage at -80°C. In particular, serogroup identification is obtained by agglutination with commercial antisera or by multiplex PCR. RESULTS: The annual incidence for infants <1 year old remained rather stable of 3.6 per 100,000, with several upward and downward oscillations and a peak in 2010. The incidence of IMD among infants was more than 10 times higher than the overall rate of IMD observed in Italy. Finally, serogroup B was more frequently detected among infants aged <1 year, accounting for 65% of the total (p<0.01). CONCLUSIONS: During the study period, IMD incidence reported among infants aged less than one year old was 10 times higher than the overall rate, and serogroup B was the most commonly detected over time. The long-term impact of meningococcal C conjugate vaccine and the effect of the introduction of meningococcal B vaccination among infants need to be evaluated.

Increasing survival time after AIDS in Italy: the role of new combination antiretroviral therapies. Tuscany AIDS Study Group.

BACKGROUND: In Italy, antiretroviral combination therapy was adopted in mid-1995 and protease inhibitors in mid-1996. OBJECTIVE: To conduct a prospective, population-based, observational study to evaluate the effect of these therapies on the survival of persons with AIDS (PWA). METHODS: PWA living in the Tuscany region diagnosed between 1985 and 31 March 1997 (National AIDS Registry) were studied. Information on antiretroviral drugs, prophylactic treatment, CD4 cell count, and AIDS-defining illnesses was collected for PWA still alive at 1 January 1996 and those diagnosed thereafter (analysis cut-off date, 30 November 1997). Kaplan-Meier curves were calculated by year of diagnosis. A Cox model was then used to estimate the adjusted (by sex, age, HIV exposure category, CD4 cell count, type and number of AIDS-defining illnesses) relative hazard (RH) of death by year of diagnosis and calendar date (considered as a time-dependent variable). Similar analyses were repeated for PWA diagnosed after 1989, having been stratified by disease-specific AIDS condition. A final analysis was performed for PWA still alive at 1 January 1996 or diagnosed thereafter for estimating the effect of single, double and triple combination therapy (time-dependent variables), having adjusted for the above variables and for prophylactic treatment. RESULTS: A total of 1683 (79.5%) out of 2118 PWA died before 1 December 1997. Use of more potent combination therapies, including protease inhibitors, greatly increased during 1997. Median survival was 2.9, 12.3, 13.4, 11.4 and 17.6 months for diagnoses before 1987, in 1987-1990, 1991-1993, 1994 and 1995, respectively; an estimated 62% of those diagnosed in 1996-1997 had survived 15 months after diagnosis. The Cox model showed a trend of decrease of RH for calendar time starting in the first half of 1996, compared with 1994. When stratifying by specific AIDS-defining disease there was no statistically significant evidence that the improved overall survival was due to increased survival only for certain diseases. The final multivariate analysis for the 771 PWA still alive at 1 January 1996 or diagnosed thereafter estimated significant RH < 1.0 for double and triple therapy (RH, 0.61 and 0.36, respectively) compared with no therapy. CONCLUSIONS: A significant reduction in risk of death after AIDS was observed from the second half of 1996, apparently due to the widespread use of antiretroviral combination therapies.

Hyaline membrane disease treated with early nasal end-expiratory pressure: one year's experience.

This report describes one year's experience treating hyaline membrane disease (HMD) with nasal end-expiratory pressure (NEEP). During the 12 months from July 1, 1973 through June 30, 1974, 119 children with HMD were admitted to the Intensive Care Unit of St. Paul Children's Hospital. Sixty-nine infants were treated early in the course of their disease with NEEP. The survival, incidence of complications, and the number of endotracheal intubations are reported and compared to our experience during a similar time period prior to the use of NEEP (1971-1972). Since the advent of the early application of modest amounts of end-expiratory pressure by nasopharyngeal tube, there has been an increase in the survival of all admissions with HMD, but the increase was statistically significant (P less than .01) only in those weighing 1,501 to 2,000 gm. There was a significant decrease (P less than .025) in the total number of children with HMD requiring endotracheal intubation. There was no change in the incidence of pneumothoraces or bronchopulmonary dysplasia. NEEP is a simple and effective technique for creating continuous airway distending pressure. Its effectiveness and ready availability make the routine endotracheal intubation of infants requiring only continuous airway distending pressure no longer justifiable.

Surface morphology of polyvinyl chloride and silicone elastomer umbilical artery catheters by scanning electron microscopy.

The surface features of a new silicone elastomer umbilical artery catheter have been defined by scanning electron microscopy and compared with those of a standard polyvinyl chloride catheter. Little difference was noted in the surfaces of the catheter materials themselves, but the radiopaque material used to render the catheters visible by x-ray resulted in a considerable difference in the overall smoothness. The polyvinyl chloride catheter's marker was in the form of a wide, rough band extending the length of the tubing whereas the marker particles of the silicone elastomer were dispersed, more uniform in size, and resulted in less overall irregularity of the surface.

Neonatal high-frequency jet ventilation.

Ten neonates with intractable respiratory failure were treated with high-frequency jet ventilation (HFJV). Nine had progressive pulmonary air leaks with either bronchopleural fistulas or pulmonary interstitial emphysema as the primary cause of their respiratory failure. Following HFJV, x-ray film evidence of pulmonary air leaks decreased in seven of the nine neonates. PaO2/FIO2 increased in eight of the ten patients (P less than .05), and PaCO2 values decreased in nine of the ten patients (P less than .01). Five patients survived. Three of the six patients exposed to HFJV for more than 20 hours developed significant tracheal obstruction. From this experience, it may be concluded that HFJV can successfully ventilate certain neonates with intractable respiratory failure secondary to progressive pulmonary air leaks. In its present form, long-term neonatal HFJV carries a risk of airway obstruction and/or damage.

Reduced thrombus formation with silicone elastomere (silastic) umbilical artery catheters.

This report describes clinical experience with a radiopaque silicone elastomere (Silastic) umbilical artery catheter. Twenty infants, ten with polyvinyl chloride (PVC) umbilical artery catheters and ten with Silastic umbilical artery catheters, all positioned at the aortic bifurcation, had aortograms performed at the time of catheter removal. Catheter-associated thrombus formation was observed in nine of the ten infants (90%) with PVC umbilical artery catheters and in one of the ten infants(10%) with Silastic catheters. The incidence of lower extremity vasospasm associated with the two catheters was not significantly different. Aortic pressure tracing recorded through Silastic catheters were accurate, but slightly damped. Autopsies were performed on five additional infants who died with indwelling Silastic umbilical artery catheters. None of the catheters, nor their surrounding tissues, showed evidence of thrombus formation on either gross or microscopic examination. It is our experience that radiopaque silicone elastomere tubing can be used as an umbilical artery catheter and appears to have the advantage of being less thrombogenic than the standard PVC tubing currently in general use.

Prediction of digoxin treatment failure in infants with supraventricular tachycardia: role of transesophageal pacing.

Transesophageal atrial pacing was used to initiate and terminate tachycardia in 24 infants (seven female and 17 male, aged 1 to 34 days) with ECG documentation of supraventricular tachycardia. Six infants received no chronic treatment, and chronic oral digoxin prophylaxis was administered to 18 infants in an effort to prevent recurrences of tachycardia. In these 18 infants, the effectiveness of digoxin therapy in preventing the initiation of tachycardia by transesophageal pacing was compared with its ability to prevent spontaneous recurrences of supraventricular tachycardia. While receiving chronic oral digoxin therapy, tachycardia could be reinitiated in 15/18 (83%) infants. In these infants, the cycle length of tachycardia and the atrioventricular interval were the same before and during chronic digoxin treatment. Three infants in whom tachycardia could not be initiated during chronic digoxin therapy had no spontaneous recurrences during 6 months of follow-up, whereas 10/15 (67%) infants in whom tachycardia could be reinitiated had clinically significant recurrences in spite of chronic digoxin therapy. Six infants who received no chronic drug treatment had no documented recurrences during 6 months of follow-up. This study demonstrates that digoxin was effective in preventing significant spontaneous recurrences of supraventricular tachycardia in only 8/18 (44%) infants treated with digoxin. The ability to initiate supraventricular tachycardia with transesophageal pacing may be useful in determining which digoxin-treated infants are at risk for recurrence. Finally, not all infants with supraventricular tachycardia require chronic prophylaxis; six of the untreated infants had no documented recurrences.

Using conventional infant ventilators at unconventional rates.

The effect of progressive increases in ventilator rate on delivered tidal and minute volumes, and the effect of changing peak inspiratory pressure (Pmax), positive end-expiratory pressure (PEEP), and inspiration to expiration (I:E) ratio at different ventilator rates were examined. Five different continuous-flow, time-cycled, pressure-preset infant ventilators were studied using a pneumotachograph, an airway pressure monitor, and a lung simulator. As rates increased from 10 to 150 breaths per minute, tidal volume stayed constant until 25 to 30 breaths per minute; then progressively decreased. In all, tidal volume began to decrease when proximal airway pressure waves lost inspiratory pressure plateaus. As rates increased, minute volume increased until 75 breaths per minute, then leveled off, then decreased. Substituting helium for O2 increased the ventilator rate at which this minute volume plateau effect occurred. Increasing peak inspiratory pressure consistently increased tidal volume. Increasing positive end-expiratory pressure decreased tidal volume. At rates less than 75 breaths per minute, inspiratory time (inspiration to expiration ratio) had little effect on delivered volume. At rates greater than 75 breaths per minute, inspiratory time became an important determinant of minute volume. For any given combination of lung compliance and airway resistance: there is a maximum ventilator rate beyond which tidal volume progressively decreases and another maximum ventilator rate beyond which minute volume progressively decreases; at slower rates, delivered volumes are determined primarily by changes in proximal airway pressures; at very rapid rates, inspiratory time becomes a key determinant of delivered volume.

High-frequency ventilation and tracheal injuries.

Recent reports linking serious tracheal injuries to various forms of high-frequency ventilation prompted this study. We compared the tracheal histopathology seen following standard-frequency, conventional mechanical ventilation with that seen following high-frequency, conventional mechanical ventilation, and two different forms of high-frequency jet ventilation. Twenty-six adult cats were examined. Each was mechanically ventilated for 16 hours. Seven received standard-frequency, conventional mechanical ventilation at 20 breaths per minute. Seven received high-frequency, conventional mechanical ventilation at 150 breaths per minute. Six received high-frequency jet ventilation at 250 breaths per minute via the Instrument Development Corporation VS600 jet ventilator (IDC). Six received high-frequency jet ventilation at 400 breaths per minute via the Bunnell Life Pulse jet ventilator (BLP). A semiquantitative histopathologic scoring system graded tracheal tissue changes. All forms of high-frequency ventilation produced significant inflammation (erosion, necrosis, and polymorphonuclear leukocyte infiltration) in the trachea in the region of the endotracheal tube tip. Conventional mechanical ventilation produced less histopathology than any form of high-frequency ventilation. Of all of the ventilators examined, the BLP, the ventilator operating at the fastest rate, produced the greatest loss of surface cilia and depletion of intracellular mucus. IDC high-frequency jet ventilation and high-frequency, conventional mechanical ventilation produced nearly identical histologic injuries. In this study, significant tracheal damage occurred with all forms of high-frequency ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Neonatal high-frequency jet ventilation: four years' experience.

During a 4-year period, 34 neonates were treated with high-frequency jet ventilation (HFJV) using two different HFJV systems. Twenty-three of the neonates had severe pulmonary air leaks, five had congenital left-sided diaphragmatic hernias, and six had end-stage respiratory failure without pulmonary air leaks. The two HFJV systems performed similarly in all pathologic conditions. Following HFJV, arterial blood gas values improved in 28 of the 34 patients (82%). Eleven patients (32%) ultimately survived. Of 23 patients with pulmonary air leaks, 17 (74%) improved, nine (39%) survived. One infant with diaphragmatic hernia and one with end-stage respiratory failure survived. Ten of 12 patients (85%) who died following eight or more hours of HFJV had significant tracheal histopathology in the region of the endotracheal tube tip. The lesions ranged from moderate erythema to severe necrotizing tracheobronchitis with total tracheal obstruction. HFJV can be useful in the treatment of severe pulmonary air leaks in neonates and may prove useful in the treatment of congenital diaphragmatic hernias. However, HFJV produces inflammatory injuries in the proximal trachea. More clinical and laboratory studies are needed to define the relative risks and benefits of this new therapy.

Lower respiratory rates without decreases in oxygen consumption during neonatal synchronized intermittent mandatory ventilation.

OBJECTIVE: We tested the hypothesis that synchronization to patient effort during intermittent mandatory ventilation (SIMV), when compared to conventional unsynchronized intermittent mandatory ventilation (IMV), will decrease energy expenditure, as reflected by decreased oxygen consumption (VO2). DESIGN: We used a four-period crossover design. Each patient was studied over four 30-min continuous time intervals. Patients were randomized to receive initially IMV or SIMV, then crossed over such that each patient was treated twice with each modality. Data were analyzed using an analysis of variance technique. SETTING: Patients were receiving treatment in the newborn intensive care unit of Children's Hospital, St. Paul. PATIENTS: We studied 17 patients, who ranged from 23 to 37 weeks gestation, were < or = 14 days old, and had study weights from 623 to 3015 g. All were mechanically ventilated for hyaline membrane disease. MEASUREMENTS AND RESULTS: We measured and compared VO2, carbon dioxide consumption (VCO2), minute ventilation (VE), total respiratory rate, heart rate, arterial blood pressure, and arterial oxygen saturation (SaO2) values during IMV and SIMV. Total respiratory rate fell significantly during SIMV (73 +/- 26 during IMV, 57 +/- 17 during SIMV, p < 0.01) in spite of no significant change in VO2 (0.6 +/- 0.16% fall in VO2 during SIMV) or VCO2 (4.2 +/- 0.19% increase in VCO2 during SIMV) values. Moreover, there were no significant differences in heart rate, blood pressure, VE, or SaO2 values with either form of therapy. CONCLUSIONS: Though total respiratory rate fell, these data do not support the hypothesis that SIMV significantly reduces respiratory rate by decreasing oxygen consumption and carbon dioxide production during infant mechanical ventilation. Rather, the marked fall in respiratory rate may be due to a more efficient respiratory pattern.

Changes in urine 8-hydroxydeoxyguanosine levels of super-marathon runners during a four-day race period.

We have determined the urinary 8-hydroxydeoxyguanosine (8-OHdG) levels of five well trained supra-marathon runners during a four-day race. The daily running distances of the four-day race were the following; 93 km, 120 km, 56 km and 59 km, respectively. Pre-race and post-race urine samples were collected on each day and analyzed by a monoclonal antibody technique. The urinary 8-OHdG content increased significantly on the first day and tended to decrease from the third day. By the fourth day 8-OHdG content was significantly less than measured on the first three days. The serum creatine kinase activity changed in a similar fashion, showing a large increase (P<0.001) up to the third day when it decreased significantly from the peak value (P<0.05). We conclude that extreme physical exercise causes oxidative DNA damage to well trained athletes. However, repeated extreme exercise-induced oxidative stress does not propagate on increase of urinary 8-OHdG, but rather causes an adaptation leading to normalization of oxidative DNA damage.

Hypercarbic ventilatory responses of infants at risk for SIDS.

We examined the hypercarbic ventilatory responses (HVR) of 143 infants at risk for sudden infant death syndrome (SIDS) and 34 normal control infants. Sixty-five of the at-risk infants had experienced apparent life-threatening events (ALTE), and 78 were siblings of SIDS victims. Twenty-three (35%) of the ALTE infants experienced subsequent apnea; one died of SIDS. Seven (9%) of the SIDS siblings experienced subsequent apnea; two ultimately died of SIDS. In the HVR studies, we measured tidal volume (VT), minute ventilation (VE), frequency of breathing (f), and end-tidal PCO2 (PETCO2) at rest and while breathing 2% and 4% CO2. Mean HVR vales for the ALTE, sibling, and control groups were all similar. The mean HVR values for those at-risk infants who experienced subsequent apnea were not different from those who did not experience subsequent apnea. However, those infants experiencing subsequent apnea had higher mean VT/kg values (P less than 0.01) and lower mean PETCO2 values (P less than 0.001) than those who did not. The SIDS siblings had significantly lower resting VT/kg values than either the near-miss infants or normal controls (P less than 0.01). We did not find depressed HVR values in infants at risk for SIDS. On the contrary, those infants who experienced subsequent apnea had evidence suggesting relative hyperventilation. SIDS siblings had evidence suggesting relative hypoventilation. These findings are interesting and thought-provoking. However, HVR studies do not appear to be sensitive, specific, or appropriate for the general screening of infants at risk for SIDS.