Decreased CD11b expression, phagocytosis, and oxidative burst in urban particulate pollution-exposed human monocytes and alveolar macrophages

Elevated levels of air pollution particulates < or = 10 microm in diameter (PM10) have been associated with an increase in mortality and morbidity due to pulmonary complications, including pneumonia. Impairment of inflammatory and host defense functions of the alveolar macrophage (AM) may be a precipitating factor. The present study was undertaken to determine whether human AM and blood derived monocytes (MO) modulate the expression of receptors important for phagocytosis of opsonized microbes (CD11b, CD11c), gram-negative bacteria (CD14), extracellular matrix interaction (CD29), and immune responses (CD11a, CD54, HLA-DR) when exposed to particulates obtained from urban air (UAP). Furthermore, phagocytosis of and oxidant generation by opsonized yeast were investigated in particle-exposed cells. AM and MO exposed to UAP for 18 h expressed significantly lower levels of CD11b and CD29. CD14 expression was markedly decreased in MO but not in AM, and CD11c was reduced in AM but not in MO. CD11a, CD54, and HLA-DR were unaltered in both phagocyte populations. Decreased receptor expression was not dependent on particle load in the cells. Phagocytosis of Saccharomyces cerevisiae and the chemiluminescence response were also significantly inhibited by UAP. Time-course studies revealed that decreased oxidant generation was evident already at 3 h postexposure, while significant effects on phagocytosis and CD11b expression were found at 18 h. These data indicate that exposure to particulate pollution is likely to impair host defense functions of AM and MO, which are important in elimination of a variety of pathogens in the lung.     

Tolerance, compliance and psychological consequences of post-exposure prophylaxis in health-care workers

We have cloned, from an oribatid mite, a gene homologous to the zerknült (zen) genes of insects and the Hox 3 genes of vertebrates. Hox genes specify cell fates in specific regions of the body in all metazoans studied and are expressed in antero-posteriorly restricted regions of the embryo. This is true of the vertebrate Hox 3 but not of the zen genes, the insect homologs, and it has been proposed that the zen genes have lost their Hox-like function in the ancestor of the insects. We studied expression of a mite Hox 3/zen homolog and found that it is expressed in a discrete antero-posterior region of the body with an anterior boundary coinciding with that of the chelicerate homolog of the Drosophila Hox gene, proboscipedia, and propose that its loss of Hox function in insects is due to functional redundancy due to this overlap with another Hox gene.     

Narrow complex tachycardia with VA block: diagnostic and therapeutic implications

To review our experience with cases of narrow complex tachycardia with VA block, highlighting the difficulties in the differential diagnosis, and the therapeutic implications. Prior reports of patients with narrow complex tachycardia with VA block consist of isolated case reports. The differential diagnosis of this disorder includes: automatic junctional tachycardia, AV nodal reentry with final upper common pathway block, concealed nodofascicular (ventricular) pathway, and intra-Hissian reentry. Between June 1994 and January 1996, six patients with narrow complex tachycardia with episodes of ventriculoatrial block were referred for evaluation. All six patients underwent attempted radiofrequency ablation of the putative arrhythmic site. Three of six patients had evidence suggestive of a nodofascicular tract. Intermittent antegrade conduction over a left-sided nodofascicular tract was present in two patients and the diagnosis of a concealed nodofascicular was made in the third patient after ruling out other tachycardia mechanisms. Two patients had automatic junctional tachycardia, and one patient had atrioventricular nodal reentry with proximal common pathway block. Attempted ablation in the posterior and mid-septum was unsuccessful in patients with nodofascicular tachycardia. In contrast, those with atrioventricular nodal reentry and automatic junctional tachycardia readily responded to ablation. The presence of a nodofascicular tachycardia should be suspected if: (1) intermittent antegrade preexcitation is recorded, (2) the tachycardia can be initiated with a single atrial premature producing two ventricular complexes, and (3) a single ventricular extrastimulus initiates SVT without a retrograde His deflection. The presence of a nodofascicular pathway is common in patients with narrow complex tachycardia and VA block. Unlike AV nodal reentry and automatic junctional tachycardia, the response to ablation is poor.     

Override of spontaneous respiratory pattern generator reduces cardiovascular parasympathetic influence

We investigated the effects of voluntary control of breathing on autonomic function in cardiovascular regulation. Variability in heart rate was compared between 5 min of spontaneous and controlled breathing. During controlled breathing, for 5 min, subjects voluntarily reproduced their own spontaneous breathing pattern (both rate and volume on a breath-by-breath basis). With the use of this experimental design, we could unmask the effects of voluntary override of the spontaneous respiratory pattern generator on autonomic function in cardiovascular regulation without the confounding effects of altered respiratory pattern. Results from 10 subjects showed that during voluntary control of breathing, mean values of heart rate and blood pressure increased, whereas fractal and spectral powers in heart rate in the respiratory frequency region decreased. End-tidal PCO2 was similar during spontaneous and controlled breathing. These results indicate that the act of voluntary control of breathing decreases the influence of the vagal component, which is the principal parasympathetic influence in cardiovascular regulation.     

Maternal-fetal transfers: indications, appropriateness, and cost

The objective of this study was to assess the indications, appropriateness, and cost of maternal-fetal transfers to a tertiary care facility in an era of managed care. Our perinatal database was reviewed from January 1, 1996 through June 30, 1997 to determine maternal and fetal indications for transfer, referring institution characteristics, utilization of tertiary level services, and cost of transfer. There were 273 transfers from 53 referring hospitals ranging in distance from <20 miles (n = 102) to >100 miles (n = 41). Thirty-one patients were transferred by air (average cost $7656), 238 by ground (average cost $920), 4 by private car. The referring diagnosis was preterm premature rupture of membranes (PPROM) (n = 80), preterm labor (n = 76), preeclampsia (n = 42), medical complications (n = 25), or other (n = 50). Mean gestational age (GA) at transfer was 28.5+/-5.5 weeks. Patients were referred from hospitals with a self-designated nursery level I (n = 115), II (n = 111), III (n = 45), or none (n = 2). In 42 patients, (15%) no maternal or fetal indication for hospital transfer was identified after evaluation at the tertiary center. The most common referring misdiagnoses were preterm labor (n = 25), PPROM (n = 10) and preeclampsia (n = 3). One hundred and sixty-five patients delivered during transfer admission (mean GA = 29.6+/-4.8 weeks); 79 infants (48%) required admission to a level III, and 52 (31%) to a level II nursery. Most patients require the services of a tertiary facility after maternal fetal transfer. If delivered during transfer admission, the majority of neonates require care in an intermediate or intensive care nursery.     

The use of tricyclic antidepressants in children and adolescents

For children and adolescents, TCAs have proven efficacy in the treatment of enuresis, OCD, and ADHD, with less compelling evidence in anxiety and tic disorders and as-yet unproven efficacy in major depression. The TCAs continue to be a valuable second-line treatment in the previously mentioned conditions. Given the possible adverse effects caused by these medications and the individual variability in plasma levels, effective, responsible use of these medications includes careful monitoring by the prescribing clinician.     

Testing the gonadal regression-cytoprotection hypothesis

Germinal damage is an almost universal accompaniment of cancer treatment as the result of bystander damage to the testis from cytotoxic drugs and/or irradiation. Cancer treatment for the most common cancers of the reproductive age group in men has improved such that most are now treated with curative intent, and many others are treated with likelihood of prolonged survival, so that the preservation of fertility is an important component of posttreatment quality of life. This has led to the consideration of developing adjuvant treatments that may reduce the gonadal toxicity of cancer therapy. One dominant hypothesis has been based on the supposition that the immature testis was resistant to cytotoxin damage. Hence, if hormonal treatment were able to cause spermatogenic regression to an immature state via an effective withdrawal of gonadotrophin secretion, the testis might be maintained temporarily in a protected state during cytotoxin exposure. However, clinical studies have been disappointing but have also been unable to test the hypothesis definitively thus far, due to the inability to completely suppress gonadotrophin secretion. Similarly, experimental models have also given conflicting results and, at best, a modest cytoprotection. To definitively test this hypothesis experimentally, we used the fact that the functionally hpg mouse has complete gonadotrophin deficiency but can undergo the induction of full spermatogenesis by testosterone. Thus, if complete gonadotrophin deficiency were an advantage during cytotoxin exposure, then the hpg mouse should exhibit some degree of germinal protection against cytotoxin-induced damage. We therefore administered three different cytotoxins (200 mg/kg procarbazine, 9 mg/kg doxorubicin, 8 Gy of X irradiation) to produce a range of severity in testicular damage and mechanism of action to either phenotypically normal or hpg mice. Testis weight and homogenization-resistant spermatid numbers were measured to evaluate the potential protective effects on spermatogenesis. Although the three cytotoxins produced a range of severity of spermatogenic damage, there was no evidence of cytoprotection in the hpg mice that were completely gonadotrophin deficient at the time of treatment. These findings cast doubt on the validity of the hypothesis that spermatogenic regression via gonadotrophin withdrawal can protect the mouse testis against cytotoxin-mediated spermatogenic damage.     

Review article: The management of inflammatory bowel disease during pregnancy

The management of inflammatory bowel disease during pregnancy is a particular challenge because adequate disease control before and during gestation is essential for both maternal and foetal health. As a practical problem this situation arises frequently, because a quarter of patients conceive after the diagnosis of their disease. Many of the clinical, biochemical, radiological and endoscopic investigations that are used to monitor and assess disease activity are difficult to use and interpret during pregnancy. Furthermore, patients and clinicians often have concerns about the safety of medical and surgical treatments for the foetus. This review is designed for the practising clinician, to guide the management of patients with inflammatory bowel disease before and during pregnancy. The literature is at times conflicting and data on some issues are scanty, therefore recommendations are based on the balance of evidence including, if necessary, extrapolation from other conditions.     

The poliovirus empty capsid specifically recognizes the poliovirus receptor and undergoes some, but not all, of the transitions associated with cell entry

Experimental results presented here demonstrate that the poliovirus empty capsid binds with saturable character to poliovirus-susceptible cells, binds preferentially to susceptible cells, and competes with mature virus for binding sites on cells. Hence, induced changes in the structure and/or stability of the particle by RNA encapsidation and virus maturation are not necessary for recognition by receptor. In mature virus, heat-induced rearrangements mimic those induced by receptor at physiological temperatures in several important respects, namely, expulsion of VP4 and externalization of the VP1 N-terminal arm. It is shown here that in the empty capsid the VP1 N-terminal arm is externalized but the VP4 portion of VP0 is not. Thus, these two hallmark rearrangements associated with cell entry can be uncoupled.