Immunology

A selection of interesting papers that were published in the two months before our press date in major journals most likely to report significant results in immunology.     

Neuroendocrine and clinical effects of transdermal 17β-estradiol in postmenopausal women

The neuroendocrine and clinical effects of transdermal 17β-estradiol (rated at 50 μg/day; TTS 50) were studied in 40 postmenopausal women; ten additional postmenopausal women did not receive any drugs. The changes in LH and rectal temperature induced by the infusion of the opioid antagonist naloxone (10 mg i.v. bolus plus 10 mg/h for 4 h) were used to evaluate the central activity of endogenous opioid peptides. TTS 50 increased opioid activity, as evidenced by the restoration of the LH response (P < 0.01) and the enhancement of the hypothermic effect (P < 0.05) of naloxone. A greater reduction in hot flushes was observed in TTS 50-treated subjects than in untreated women, with the maximal effect of TTS 50 achieved after 3 months of therapy. TTS 50 did not modify the concentrations of circulating lipids, glucose or liver enzymes but reduced the biochemical parameters indicative of bone reabsorption. Bone density of the distal radius significantly increased during TTS 50 (P < 0.02), reaching its maximum value after 6 months of therapy. Thereafter bone density declined, but more slowly than in untreated women.

Our data suggest that TTS 50 has marked neuroendocrine effects, that it diminishes the incidence of hot flushes and reduces bone demineralization. By contrast, it has a very little, if any, metabolic impact on the liver or on glucose and lipid metabolism.     

Bicycle Helmet Wearing in Children: A Seven-Year, Observational Study in Broward County, Florida

We evaluated the effectiveness of statewide bicycle legislation using direct observation of the number of elementary and middle school children riding bicycles with and without helmets to or from school over a 7-year period. The percentage of children wearing helmets increased dramatically over the past 7 years (to a high of 81%) due to the passage of state law that required helmet usage. Rates for elementary school children were consistently higher than rates of middle school children. Numerous children still do not wear helmets, particularly older children. Further interventions are needed to promote helmet wearing.     

Effects of posts on dentin stress distribution in pulpless teeth.

A finite element analysis was carried out to study the roles of posts in reducing dentin stress in pulpless teeth. Two-dimensional plane strain models of the midlabiolingual section of a human maxillary central incisor were first analyzed. The results showed that the gold alloy post reduced maximal dentin stress by as much as 30%. However, the integrity of the dentin was compromised and the effects of the post were likely to be exaggerated in such models. In an effort to correct for these problems, plane stress models with side plates and axisymmetric models were analyzed. Posts were found to reduce maximal dentin stress by only 3% to 8% when the teeth were subjected to masticatory and traumatic loadings in these latter models. Although posts reduced maximal dentin stress by as much as 20% when the teeth were loaded vertically, teeth such as incisors and canines normally are not subjected to vertical loadings. Thus the reinforcement effects of posts seem to be doubtful in these teeth.     

Corticotropin-Releasing Factor Reduces Lipopolysaccharide-Induced Pulmonary Vascular Leak

Previous studies have suggested that corticotropin-releasing factor (CRF) has immunoregulatory effects in addition to its neuroendocrine role. We examined the ability of CRF to inhibit lipopolysaccharide (LPS)-induced pulmonary vascular leak in vivo. Female BALB/C mice were treated with either normal saline (NS) or CRF prior to injection with LPS. Pulmonary vascular leak was inhibited by CRF as assessed by measurement of lung wet-to-dry ratios. The stress-induced increase in serum corticosterone levels in mice injected with LPS alone was not further increased by treatment with CRF. This indicates that the effect of CRF was not mediated centrally by stimulation of endogenous steroid release. Histologic examination of the lungs revealed that leukocyte infiltration was significantly depressed in CRF-treated mice thus confirming the protective effect of CRF. In addition, a modest prolongation of survival was demonstrated in CRF-treated mice following challenge with LPS (p=.08). These data indicate the potential utility of CRF as a modulator of pulmonary vascular leak.     

Executive cognitive deficits in primary dystonia.

Primary dystonia is a disorder of movement for which no consistent pathophysiology has been identified; in the absence of evidence to the contrary, it is assumed to be cognitively benign. We have studied a clinically heterogeneous group of 14 patients with primary dystonia on a battery of neuropsychological tests. Despite well-preserved speed of information processing, language, spatial, memory and general intellectual skills relative to normal controls, we have identified a constellation of attentional-executive cognitive deficits on the Cambridge Neuropsychological Test Automated Battery (CANTAB). Specifically, patients demonstrated significant difficulties negotiating the extra-dimensional set-shifting phase of the IED task. The implications of these findings for the pathophysiology of primary dystonia are discussed. This is, to the best of our knowledge, the first report of a significant cognitive deficit in patients with primary dystonia.     

Laparoscopic nephrectomy in a porcine model.

Laparoscopic nephrectomy was performed in 15 male pigs, the procedure was successful in 14. Extraction of the intact kidney through a 5-cm lower abdomen incision was done in 7 animals; complete destruction and evacuation of the kidney was accomplished by a round-knife suction device through a 1-cm port in another 7 pigs. Grossly, the specimen consisted of sausage-like tubular renal tissue and a small amount of tissue debris. Pathology revealed that the glomerular and tubular structures were well preserved, no interstitial hematoma could be found. Four ports were usually used, one 1-cm umbilical camera port, one 0.5-cm port for ureter traction, and two 1-cm working ports along the midclavicular line. All the pigs recovered uneventfully. The average operation time was 3 h 20 min. The application of endo-GIA (United States Surgical Corporation) for renal hilum reduced the operative time to 2 h 20 min. Complications included renal vein tear during endoclip application and cutting in the first case, mild subcutaneous emphysema in 2 cases. This first pig received exploratory laparotomy for the repair and ligation of the renal vein. No more major complications occurred with increasing experience. From this porcine experiment, we conclude that the combination of laparoscopy, a tissue destroyer and an endobag for the entrapment of kidney seem to be a promising technique for clinical nephrectomy.     

Dystonia gravidarum: a new case with a long follow-up.

We report a case of cervical dystonia occurring in a 33-year-old without personal history of movement disorder but with family history of essential tremor, primigravid, primiparous woman at 1 weeks' amenorrhea, resolved completely after delivery in the course of 3 months. Dystonia never recurred in the following 5 years. Several neurological disorders are known to occur or worsen during pregnancy. As far as we know, this is the second reported case of dystonia occurring during pregnancy, thus confirming that dystonia gravidarum represents a new entity and should be considered in women of reproductive age affected by dystonia, especially when presenting with rapid-onset cervical dystonia.     

Management of status dystonicus: our experience and review of the literature.

Status dystonicus (SD) is a life threatening disorder that develops in patients with both primary and secondary dystonia, characterized by acute worsening of symptoms with generalized and severe muscle contractions. To date, no information is available on the best way to treat this disorder. We review the previously described cases of SD and two new cases are reported, one of which occurring in a child with static encephalopathy, and the other one in a patient with pantothenate kinase-associated neurodegeneration. Both patients were admitted to an intensive care unit and treated with midazolam and propofol. This approach proved to be useful in the former while the progressive nature of the dystonia of the second patient required the combination of intrathecal baclofen infusion and bilateral pallidal deep brain stimulation. We believe that a rapid and aggressive approach is justified to avoid the great morbidity and mortality which characterize SD. Our experience, combined with the data available in the literature, might permit to establish the best strategies in managing this rare and severe condition.