Prognostic value of C-reactive protein in HIV-infected patients with Pneumocystis jirovecii pneumonia.

C-reactive protein (CRP) is a sensitive marker of inflammation and tissue damage. We aimed to describe CRP responses in HIV-infected patients presenting with Pneumocystis pneumonia (PCP), bacterial pneumonia (BP) and pulmonary tuberculosis (TB) and, in patients with PCP, to identify if elevated CRP has prognostic significance. Data obtained by case-note review of consecutive HIV-infected adults with acute respiratory episodes included admission CRP (elevated >5 mg/L), haemoglobin, white blood count, CD4 count and partial pressure of oxygen in the blood (PaO(2)), presence of pulmonary co-pathology/intercurrent infection and outcome (survival). Median (range) CRP in patients with BP = 120 mg/L (<5-620 mg/L), TB = 44 mg/L (<5-256.3 mg/L) and PCP = 35 mg/L (<5-254 mg/L). CRP was elevated in 93/103 (90.3%) patients with PCP; six patients died; and all had an elevated CRP. PaO(2) and CRP values were associated as follows: average CRP levels declined by 10% (95% confidence interval [CI] 0.20%) per kPa increase in PaO(2) = 0.002. Factors associated with death were higher CRP, odds ratio (OR) (95% CI) = 5.30 (1.61 to 17.51) per 100 mg/L increase, P = 0.006 and haemoglobin, OR (95% CI) = 0.52 (0.29 to 0.93) per g/dL, P = 0.033. CRP is elevated in the majority of HIV-infected patients with PCP, BP and TB. Admission CRP measurement lacks specificity, but in PCP elevations of CRP are associated with disease severity (PaO(2)) and poor outcome and might be used prognostically, together with other mortality risk factors; further prospective evaluation is needed.

Trends in HIV testing and recording of HIV status in the UK primary care setting: a retrospective cohort study 1995-2005.

OBJECTIVES: To provide nationally representative data on trends in HIV testing in primary care and to estimate the proportion of diagnosed HIV positive individuals known to general practitioners (GPs). METHODS: We undertook a retrospective cohort study between 1995 and 2005 of all general practices contributing data to the UK General Practice Research Database (GPRD), and data on persons accessing HIV care (Survey of Prevalent HIV Infections Diagnosed). We identified all practice-registered patients where an HIV test or HIV positive status is recorded in their general practice records. HIV testing in primary care and prevalence of recorded HIV positive status in primary care were estimated. RESULTS: Despite 11-fold increases in male testing and 19-fold increases in non-pregnant female testing between 1995 and 2005, HIV testing rates remained low in 2005 at 71.3 and 61.2 tests per 100,000 person years for males and females, respectively, peaking at 162.5 and 173.8 per 100,000 person years at 25-34 years of age. Inclusion of antenatal tests yielded a 129-fold increase in women over the 10-year period. In 2005, 50.7% of HIV positive individuals had their diagnosis recorded with a lower proportion in London (41.8%) than outside the capital (60.1%). CONCLUSION: HIV testing rates in primary care remain low. Normalisation of HIV testing and recording in primary care in antenatal testing has not been accompanied by a step change in wider HIV testing practice. Recording of HIV positive status by GPs remains low and GPs may be unaware of HIV-related morbidity or potential drug interactions.

Primary care consultations and costs among HIV-positive individuals in UK primary care 1995-2005: a cohort study.

OBJECTIVES: To investigate the role of primary care in the management of HIV and estimate primary care-associated costs at a time of rising prevalence. METHODS: Retrospective cohort study between 1995 and 2005, using data from general practices contributing data to the UK General Practice Research Database. Patterns of consultation and morbidity and associated consultation costs were analysed among all practice-registered patients for whom HIV-positive status was recorded in the general practice record. RESULTS: 348 practices yielded 5504 person-years (py) of follow-up for known HIV-positive patients, who consult in general practice frequently (4.2 consultations/py by men, 5.2 consultations/py by women, in 2005) for a range of conditions. Consultation rates declined in the late 1990s from 5.0 and 7.3 consultations/py in 1995 in men and women, respectively, converging to rates similar to the wider population. Costs of consultation (general practitioner and nurse, combined) reflect these changes, at pound100.27 for male patients and pound117.08 for female patients in 2005. Approximately one in six medications prescribed in primary care for HIV-positive individuals has the potential for major interaction with antiretroviral medications. CONCLUSION: HIV-positive individuals known in general practice now consult on a similar scale to the wider population. Further research should be undertaken to explore how primary care can best contribute to improving the health outcomes of this group with chronic illness. Their substantial use of primary care suggests there may be potential to develop effective integrated care pathways.

Development and evaluation of a real-time PCR assay for detection of Pneumocystis jirovecii DNA in bronchoalveolar lavage fluid of HIV-infected patients.

BACKGROUND: Pneumocystis pneumonia (PCP) is conventionally diagnosed by identifying Pneumocystis jirovecii in lower respiratory tract samples using cytochemical stains. Molecular diagnosis of PCP is potentially more sensitive. METHODS: A study was undertaken to use an extensively optimised real-time polymerase chain reaction (PCR) using primers designed to hybridise with the P. jirovecii heat shock protein 70 (HSP70) gene to quantify P. jirovecii DNA in bronchoalveolar lavage (BAL) fluid from HIV-infected patients with and without PCP, and to compare this assay with conventional PCR targeting the P. jirovecii mitochondrial large subunit rRNA gene sequence (mt LSU rRNA). RESULTS: Sixty-one patients had 62 episodes of PCP (defined by detection of P. jirovecii in BAL fluid by cytochemical stains and typical clinical presentation). Quantifiable HSP70 DNA was detected in 61/62 (range approximately 13-18,608 copies/reaction; median approximately 332) and was detectable but below the limit of quantification (approximately 5 copies/reaction) in 1/62. Seventy-one other patients had 74 episodes with alternative diagnoses. Quantifiable HSP70 DNA was detectable in 6/74 (8%) episodes (range approximately 6-590 copies/reaction; median approximately 14) and detectable but below the limit of quantification in 34/74 (46%). Receiver-operator curve analysis (cut-off >10 copies/reaction) showed a clinical sensitivity of 98% (95% 91% to 100%) and specificity of 96% (95% CI 87% to 99%) for diagnosis of PCP. By contrast, clinical sensitivity of mt LSU rRNA PCR was 97% (95% CI 89% to 99%) and specificity was 68% (95% CI 56% to 78%). CONCLUSION: The HSP70 real-time PCR assay detects P. jirovecii DNA in BAL fluid and may have a diagnostic application. Quantification of P. jirovecii DNA by real-time PCR may also discriminate between colonisation with P. jirovecii and infection.

Lung tissue elastin composition in newborn infants with the respiratory distress syndrome and other diseases.

Amino acid analysis of human fetal lung elastin was undertaken in 49 instances of live-born neonates, ranging from 380 g to full term, and in 3 abortuses of 12-14 wk gestation. The data suggest that formation of the cross-linking agents, desmosine and isodesmosine, occurs early, between 14 and 22 wk. The ratio of neutral to charged amino acids remains low until the 36th wk when it attains adult levels. The composition of elastin was independent of sex and duration of survival. In three neonatal pulmonary diseases (respiratory distress syndrome, atelectasis, and hemorrhage) ratios were significantly lower than those found in nondiseased lungs. This may be a reflection of immaturity or may be a predisposing factor in neonatal lung disease. The latter hypothesis is attractive and receives indirect support from the association of a more polar elastin with other diseases, including adult emphysema and atheromatous aortic change.Our finding of relatively high polarity in elastin from human fetal lung is consistent with previous observations in a variety of fetal organs of other species.

Climate and genotypes of Pneumocystis jirovecii.

This study explored whether seasonal and/or climatic factors influenced detection of specific genotypes of Pneumocystis jirovecii. Between 1989 and 2001, 155 isolates of P. jirovecii were obtained from patients undergoing bronchoscopic alveolar lavage. For each isolate, the month and climatic conditions were noted. Genotypes of P. jirovecii were distinguished by polymorphisms in the mitochondrial large-subunit rRNA gene. There were monthly and seasonal variations in the frequency of detection of mixed genotypes (p 0.018 and p 0.031, respectively) and genotype 2 (p 0.029 and p 0.086, respectively). There was no association between month/season and genotypes 1, 3 and 4, or between monthly temperature or rainfall and any genotype.

Uptake of selenium and mercury by captive mink: Results of a controlled feeding experiment.

Captive, juvenile, ranch-bred, male mink (Neovison vison) were fed diets containing various concentrations of methyl-mercury (MeHg) and selenium (Se) for a period of 13 weeks and then sacrificed to determine total Hg levels in fur, blood, brain, liver and kidneys and total Se concentrations in brain tissue. As MeHg concentrations in the diet increased, concentrations of total Hg in the tissues also increased with the highest level occurring in the fur > liver = kidney > brain > blood. Concentrations of Hg in the fur were correlated (r(2) > 0.97) with liver, kidney, blood and brain concentrations. The addition of Se to the mink diet did not appear to affect most tissue concentrations of total Hg nor did it affect the partitioning of Hg between the liver:blood, kidney:blood and brain:blood; however, partitioning of Hg between fur and blood was apparently affected.

Reversible defect of neutrophil chemotaxis and random migration in primary hyperparathyroidism.

Chemotactic and random migrations of neutrophils derived from four patients with primary hyperparathyroidism were found to be defective. These abnormalities improved significantly in parallel with the decrease in serum calcium and parathormone and with the increase in serum phosphorus concentration after surgical removal of the adenoma. These observation suggest a possible role for parathormone phosphorus and calcium in the motility of neutrophils.

Amino acid concentrations in cerebrospinal fluid: effects of aging, depression, and probenecid.

Cerebrospinal fluid (CSF) amino acid concentrations were measured in six Bipolar I, eight Bipolar II, eight Unipolar, and four other and control patients. All but four were also studied after administration of probenecid. Fourteen amino acids showed significant correlations of concentrations with age of subjects. Significant diagnostic group differences were found for five amino acids; only that of tyrosine persisted after taking subject's age into account. Following probenecid administration, there were statistically significant changes in CSF concentration of several amino acids, but these changes were small and likely indicative of diurnal changes.

Child neurology: Amino acid concentrations in cerebrospinal fluid.

Cerebrospinal fluid amino acid concentrations were measured in 16 pediatric patients with febrile convulsions, in 9 with bacterial meningitis, and in 8 noninfected newborn infants. Most CSF amino acids are present in greater concentration in patients with bacterial meningitis than in those without CNS infection. Newborn infants have elevated CNS amino acid concentrations similar to those found in older patients with bacterial meningitis. The reason for increased amino acid concentration in the meningitis group may be due to alterations in brain metabolism, changes in the kinetics of CSF formation, alterations in the removal of amino acids by active transport mechanisms, or a combination of factors. Delayed maturation of transport mechanisms may explain the high levels found in newborn infants.

Effect of CSF on bacterial growth.

The growth patterns of five potentially pathogenic bacteria (Staphylococcus aureus, Escherichia coli, Listeria monocytogenes, group B beta-hemolytic streptococcus, and Klebsiella pneumoniae) and a commonly encountered, nonpathogenic microorganism (S epidermidis) were compared using CSF, trypticase soy broth (TSB), and a phosphate buffer. Each grew less in CSF than in TSB. Escherichia coli was least affected with a median difference of 2 logarithms between CSF and TSB at 24 hours of growth, whereas S epidermidis was markedly inhibited, with a median difference of 6.85 logarithms. The differences among the remaining four organisms ranged from 3.86 to 5.94 logarithms, all significantly greater than that for E. coli. Similar results were obtained at 48 hours of growth. The non-support of bacterial growth by CSF may constitute a host defense mechanism. The basis of these observations may be the presence of inhibitors or the absence of nutrients required for bacterial growth in the CSF.

Aerosol bag for administration of bronchodilators to young asthmatic children.

An aerosol rebreathing bag was developed by modifying an ordinary freezer bag of 1-qt size. A mouthpiece was inserted in a corner of the bag, and the aerosol canister was actuated inside the bag while an asthmatic child breathed in and out of the bag. Its feasibility was tested in 20 child-parent pairs. Children less than age 7 years easily learned to inhale aerosols from the bag. Bronchodilator efficacy of albuterol aerosol using the bag was compared with that of the canister mouthpiece in 15 children aged 7 to 15 years. The results were nearly identical.

Apparent resurgence of tuberculosis in urban children.

An apparent increase in incidence of pulmonary and extrapulmonary forms of tuberculosis was observed in children in an inner-city community in New York City. This occurred during years in which the case rates of tuberculosis declined in the city and the nation. Two unusual presentations of childhood tuberculosis are described. This experience suggests that physicians should be more aware of the diagnosis of tuberculosis in children and that routine tuberculin skin testing with 5 TU of purified protein derivative (PPD) should be continued, with emphasis on testing in high-risk areas. Adequate funding of detection and treatment programs may prevent reemergence of this disease.

Amikacin pharmacokinetics in the therapy of childhood urinary tract infection.

Amikacin, a new aminoglycoside antibiotic with a spectrum similar to that of gentamicin, has been used mainly in adults. This report summarizes the first use of this drug in children with urinary tract infection. Organisms were eradicated in all cases and recurrent infection occurred in one half after one week. No evidence of ototoxicity or nephrotoxicity was found. Four children developed transient elevation of serum glutamic oxaloacetic transaminase. Serum level (17 mug/ml) of the drug at one hour and its urinary excretion in six hours (60% of the dose) was comparable to those of adults. This antibiotic is potentially valuable and has thus far not shown major toxicity when given for up to 11 days in patients with normal renal and liver functions.

Defects of neutrophil chemotaxis and random migration in thalassemia major.

Chemotactic and random migrations in a group of 11 patients with thalassemia major were found to be defective. This may be partially the basis for the predilection to infection occasionally observed in these patients. These findings may reflect a primary defect of polymorphonuclear leukocytes or may be secondary to associated liver disease and/or diabetes mellitus. Further studies are required to define the mechanisms involved.

Phototherapy effect on the incidence of patent ductus arteriosus in premature infants: prevention with chest shielding.

Patent ductus arteriosus is common among premature neonates, especially those with birth weights less than 1,500 g. In vitro, room light inhibits the contraction of immature piglet's ductal rings. Because phototherapy is used frequently from the first days of life to treat jaundice in preterm neonates, we compared the occurrence of patent ductus arteriosus among premature infants exposed to this intense light source with those whose chests were shielded. Seventy-four babies with respiratory distress syndrome were randomly assigned to either a treatment group (chest shielded with aluminum foil while on phototherapy, 36 babies) or control group (no shield, 38 babies). All were on radiant warmers, received mechanical ventilation for respiratory distress syndrome, and phototherapy (Air Shields model PTU 78-1) from day 1 of life. Irradiance was maintained at greater than 4.0 microW/cm2/nm in all cases. Although both groups had similar birth weights, gestational ages, severity of respiratory distress syndrome, intravenous fluid intake, and duration of phototherapy, the incidence of patent ductus arteriosus was significantly less in the shield group (shield 11/36 v No shield 23/38; P = .009). Patent ductus arteriosus murmurs developed in shielded patients at a later date, they required less vigorous treatment (ie, indomethacin), and they had shorter hospitalizations (74 v 85 days; P less than .05). The significant reduction of patent ductus arteriosus with shielding suggests that phototherapy may play a role in the occurrence of patent ductus arteriosus in premature infants. Shielding may be a practical method to decrease this common complication should this initial observation be confirmed.

Effects of methadone on thyroid function in mother, fetus, and newborn.

The effects of maternal use of methadone during pregnancy on tests of thyroid function were studied in 14 women and their offspring. Twelve normal nonaddicted women and their infants served as a control group. Concentrations of thyrotropin (TSH), thyroxine (T4), and triiodothyronine (T3) were not significantly different in maternal and cord serum, and in infant serum at age 24 hours. There was no significant difference in infants' TSH concentrations at 2, 3, and 7 days of age. At 2 and 7 days, T3 levels were significantly higher in the methadone than in the control group (P = .01 and less than .01, respectively). At 3 days, differences were of borderline significance (P = .08). Increased T4 levels in the methadone group of infants were statistically significant at 2 days (P less than .01) and at 3 and 7 days (P = .05). The mechanisms responsible for the biochemical evidence of hyperthyroidism were not determined, but may have been related to altered autonomic function and/or increased metabolic activity which occurs during neonatal narcotic withdrawal.

alpha 1-Antitrypsin deficiency and susceptibility to lung disease.

This subject concerns the complex interrelationship of a genetically determined protein deficiency, enzymes which are inhibited by that protein, environmental challenges such as cigarette smoke and industrial pollutants, and the occurrence of obstructive lung disease (Fig. 1). Unequivocal establishment of an etiological role for AAT deficiency, especially of intermediate degree, has proven to be difficult. Confounding variables such as enzyme concentration in PMN and PAMs, duration of exposure to potential environmental hazards, differences in laboratory methods utilized in measuring AAT and in studying pulmonary function all require investigation. The definitive study, incorporating all of these and other factors, has yet to be conducted. No single, clear-cut conclusion can be drawn from analysis of present studies. In those circumstances in which heterozygotes appear to be predisposed to COPD, phenotypic screening of the population at potential risk, such as industrial workers may be appropriate. Conversely, in conditions in which no association is demonstrated, such screening would not be justified. Perhaps, the best one can do is to suggest a "Scotch verdict"; that is, the issue of causation is not proven.

Evaluation of inhalation aids of metered dose inhalers in asthmatic children.

Many patients have incorrect aerosol inhalation technique with metered dose inhalers (MDI). Several inhalation aids have been developed and marketed for these patients. Even those who have correct inhalation technique may benefit from these devices. We compared bronchodilator efficacy of two puffs of albuterol aerosol administered either directly from a MDI mouthpiece, or from an inhalation aid (InspirEase, Aerochamber, Aerosol Bag) in 20 children who had previously demonstrated proper inhalation technique. The children received two puffs of aerosol from a MDI in each of two modalities tested each day on four different days (double blind). One modality contained albuterol aerosol and the other placebo. Pulmonary function was tested before and at 15, 30, 60, 120, and 180 minutes after treatment. Forced expiratory volume in 1 second (FEV1) increased similarly after all four modes of administration. Six patients who had incorrect inhalation technique benefited from the three inhalation aids. The aerosol bag and InspirEase produced slightly greater bronchodilator response than the Aerochamber. The inhalation aids are useful devices for those who have incorrect inhalation technique, but those who have correct technique do not derive any benefit from these devices.

Effect of amniotic fluid on bacterial growth.

The bacteriostatic effect of amniotic fluid was studied using four pathogenic organisms which are encountered in the perinatal period, E. coli, S. aureus, L. monocytogenes, and Group B beta hemolytic streptococci. Amniotic fluid inhibited the growth of all four organisms, with a wide degree of individual variation among specimens. The greatest degree of inhibition was noted for L. monocytogenes and the least for E. coli. The time in gestation in which the amniotic fluid sample was obtained did not appear to be related to its bacteriostatic capacity. The ability of amniotic fluid to inhibit the growth of certain pathogenic organisms may be significant in prevention of perinatal infection.