Sodium-lithium countertransport and family history of hypertension in childhood

We have studied the relationship between sodium-lithium countertransport, determined in childhood, and family history of hypertension. Countertransport was measured in healthy children and those with secondary hypertension. There was no significant difference in countertransport between these two groups. In the normal children ( n = 52, median age 6.8 years), there was a positive relationship between body mass index and countertransport (r_s= 0.34, p <0.02). A positive relationship between family history of hypertension using a ranked scoring system, and countertransport, not related to age, body mass or blood pressure (n = 34, r_s= 0.63, p<0.001 ) was also found. There was no significant relationship between intraccllular sodium concentration and countertransport. These data confirm that countertransport in normal children is related to body mass index and indicate that a genetic predisposition to primary hypertension marked by sodium-lithium countertransport is identifiable in childhood.     

A radiation hybrid map of the human genome

We have developed a panel of whole-genome radiation hybrids by fusing irradiated diploid human fibroblasts with recipient hamster cells. This panel of 168 cell lines has been typed with microsatellite markers of known genetic location. Of 711 AFM genetic markers 404 were selected to construct a robust framework map that spans all the autosomes and the X chromosome. To demonstrate the utility of the panel, 374 expressed sequence tags (ESTs) previously assigned to chromosomes 1, 2, 14 and 16 were localized on this map. All of these ESTs could be positioned by pairwise linkage to one of the framework markers with a LOD score of greater than 8. The whole genome radiation hybrid panel described here has been used as the starting material for the Genebridge4 panel that is being made widely available for genome mapping projects.      

Dural ectasia in individuals with Marfan‐like features but exclusion of mutations in the genes FBN1, TGFBR1 and TGFBR2

Sheikhzadeh S, Rybczynski M, Habermann CR, Bernhardt AMJ, Arslan‐Kirchner M, Keyser B, Kaemmerer H, Mir TS, Staebler A, Oezdal N, Robinson PN, Berger J, Meinertz T, von Kodolitsch Y. Dural ectasia in individuals with Marfan‐like features but exclusion of mutations in the genes FBN1, TGFBR1 and TGFBR2. Mutations in the genes FBN1, TGFBR1, and TGFBR2 can result in heritable connective tissue disorders comprising the Marfan syndrome and the Loeys‐Dietz syndrome. Dural ectasia is a characteristic manifestation of both syndromes. However, dural ectasia has not yet been investigated in connective tissue disorders that are unrelated to mutations in the FBN1, TGFBR1 or TGFBR2 genes. Here, we assessed dural ectasia in 33 individuals both with typical manifestations of heritable connective tissue disease and in whom mutations in all three genes had been excluded. We identified 19 individuals with dural ectasia (58%), who exhibited major skeletal manifestations of the Marfan syndrome more frequently than the remaining 14 persons without dural ectasia (p = 0.06). Moreover, only persons with dural ectasia fulfilled clinical criteria of the Marfan syndrome (p = 0.01). Conversely, aortic aneurysm (12 patients; p = 0.8), aortic dissection (five patients; p = 0.1), spontaneous dissection of the carotid arteries (five patients; p = 1), and mitral valve prolapse (13 patients; p = 0.4) were similarly frequent irrespective of dural ectasia. We conclude that dural ectasia is a marker for connective tissue disease which coincides with skeletal rather than with cardiovascular manifestations, and which may involve currently uncharacterized pathogenetic mechanisms and syndromes.     

Perceived prevalence of peanut allergy in Great Britain and its association with other atopic conditions and with peanut allergy in other household members

BACKGROUND: Despite increasing awareness of peanut allergy, little is known of its prevalence. We report on a two-stage interview survey conducted in Great Britain. METHODS: A total of 16434 adults (aged 15+ years) reported their own allergies and atopies and named cohabitants with peanut allergy (stage 1). Follow-up interviews were conducted with identified sufferers from peanut allergy (stage 2). RESULTS: At stage 1, peanut allergy was reported in 58 respondents and 205 other household members. When we accounted for cases where peanut allergy was unconfirmed or newly reported at stage 2, the prevalence, based on 124 confirmed sufferers, was estimated as 0.48% (95% confidence interval 0.40%-0.55%). The prevalence in children (0.61%, 0.41%-0.82%) was slightly higher than in adults; age-of-onset was strikingly earlier. Prevalence was strongly associated with other atopies, particularly tree-nut allergy. Cases tended significantly to cluster in households. Half of cases had never consulted a doctor. Exactly 7.4% reported being hospitalized after a reaction. CONCLUSIONS: Peanut allergy is reported by 1 in 200 of the population and is commoner in those reporting other atopies. The fact of similar rates in children and adults argues against a recent marked rise in prevalence. The frequency and potential lethality of this disorder emphasize the need for sufferers to demographic factors, other food allergies, atopic conditions, and allergy in family/household members. Our study comprised a screening survey and detailed interviews with sufferers identified. The frequency and potential lethality of this disorder emphasize the need for sufferers to receive correct medical advice on management [corrected].     

Comparison of Na+-Ca2+ exchange current elicited from isolated rabbit ventricular myocytes by voltage ramp and step protocols

 In this study, the effects of three different voltage protocols on the Na⁺-Ca²⁺ exchange current (I _Na-Ca) of rabbit right ventricular myocytes were studied. Whole-cell patch-clamp recordings were made using a Cs⁺-based internal dialysis solution and external solutions designed to block major interfering currents. I _Na-Ca was measured at 35–37°C as (5 mM) Ni-sensitive current elicited by: a 2 s descending ramp (DR: +80 to –120 mV); a 2 s ascending ramp (AR: –120 to +80 mV) and 500 ms voltage steps (VS) between –120 and +80 mV. DR and AR were applied from –40 mV and elicited I _Na-Ca with reversal potentials (E _rev) of –17.6±2.5 mV (mean±SEM; n=16) and –46.2±4.1 mV (n=10; P=0.0001) respectively. This difference was maintained when the holding potential was –80 mV (–44.0±2.1 mV, n=24 and –86.3±4.8 mV, n=10; P=0.0001), when the internal Ca chelator (EGTA) was replaced with BAPTA (–19.5±1.8 mV and –46.3±1.6 mV, n=6; P=0.0003) and when DR and AR were applied alternately to the same cell. Experiments using modified ramp waveforms suggested a possible mechanism for these differences. Increases in subsarcolemmal Ca caused by Ca entry (coupled to Na extrusion) during the initial positive potential phase of the DR might have induced I _Na-Ca reversal at less negative potentials than observed with AR, during the initial phase of which subsarcolemmal Ca would not have accumulated. These data suggest that I _Na-Ca during voltage-clamp experiments can be significantly influenced by the type of voltage protocol chosen, as the protocol appears to induce subsarcolemmal changes in Ca and Na concentration that are independent of Ca buffering in the bulk cytosol and can occur on a pulse-to-pulse basis. Received: 23 October 1998 / Received after revision: 8 January 1999 / Accepted: 11 January 1999     

Interdependency of CEACAM-1, -3, -6, and -8 induced human neutrophil adhesion to endothelial cells

Members of the carcinoembryonic antigen family (CEACAMs) are widely expressed, and, depending on the tissue, capable of regulating diverse functions including tumor promotion, tumor suppression, angiogenesis, and neutrophil activation. Four members of this family, CEACAM1, CEACAM8, CEACAM6, and CEACAM3 (recognized by CD66a, CD66b, CD66c, and CD66d mAbs, respectively), are expressed on human neutrophils. CD66a, CD66b, CD66c, and CD66d antibodies each increase neutrophil adhesion to human umbilical vein endothelial cell monolayers. This increase in neutrophil adhesion caused by CD66 antibodies is blocked by CD18 mAbs and is associated with upregulation of CD11/CD18 on the neutrophil surface. To examine potential interactions of CEACAMs in neutrophil signaling, the effects on neutrophil adhesion to human umbilical vein endothelial cells of a set of CD66 mAbs was tested following desensitization to stimulation by various combinations of these mAbs. Addition of a CD66 mAb in the absence of calcium results in desensitization of neutrophils to stimulation by that CD66 mAb. The current data show that desensitization of neutrophils to any two CEACAMs results in selective desensitization to those two CEACAMs, while the cells remain responsive to the other two neutrophil CEACAMs. In addition, cells desensitized to CEACAM-3, -6, and -8 were still responsive to stimulation of CEACAM1 by CD66a mAbs. In contrast, desensitization of cells to CEACAM1 and any two of the other CEACAMs left the cells unresponsive to all CD66 mAbs. Cells desensitized to any combination of CEACAMs remained responsive to the unrelated control protein CD63. Thus, while there is significant independence of the four neutrophil CEACAMs in signaling, CEACAM1 appears to play a unique role among the neutrophil CEACAMs. A model in which CEACAMs dimerize to form signaling complexes could accommodate the observations. Similar interactions may occur in other cells expressing CEACAMs.     

Planning for children whose parents are dying of HIV/AIDS. American Academy of Pediatrics. Committee on Pediatric AIDS, 1998-1999

Although the character of acquired immunodeficiency syndrome is changing into a chronic illness, it is estimated that by the end of this century, 80 000 children and adolescents in the United States will be orphaned by parental death caused by human immunodeficiency virus infection. Plans for these children need to be made to ensure not only a stable, consistent environment that provides love and nurturing, but also the medical and social interventions necessary to cope with the tragic loss. Pediatricians should become aware of local laws and community resources and initiate discussion early in the course of parental illness to facilitate planning for the future care and custody of the children. States need to adopt laws and regulations that provide flexible approaches to guardianship and placement of children orphaned by acquired immunodeficiency syndrome.     

Total knee replacement: a comparison of ropivacaine and bupivacaine in combined femoral and sciatic block

BACKGROUND: Femoral and sciatic nerve block may improve post-operative analgesia following total knee replacement. OBJECTIVES: To compare the post-operative analgesia following primary total knee replacement provided by spinal anaesthesia alone or in combination with femoral and sciatic nerve block with bupivacaine or ropivacaine. METHODS: Seventy-five patients were randomised into one of three groups: spinal anaesthesia only; spinal anaesthesia and combined femoral and sciatic nerve block with 1 mg x kg(-1) bupivacaine 7.5 mg x ml(-1) to each nerve; spinal anaesthesia and combined femoral and sciatic nerve block with 1 mg x kg(-1) ropivacaine 7.5 mg x ml(-1) to each nerve. RESULTS: The mean (SD) time to first morphine request was significantly prolonged for both groups receiving combined femoral and sciatic block, 912 (489) min for the bupivacaine group and 781 (394) min for the ropivacaine group (P<0.001) compared with 413 (208) min for the group receiving spinal anaesthesia alone. Morphine consumption was significantly reduced in both groups receiving combined femoral and sciatic block. There were no systemic or neurological sequelae in any of the groups. CONCLUSIONS: Femoral and sciatic blockade following intrathecal bupivacaine/diamorphine provided superior analgesia when compared with intrathecal bupivacaine/diamorphine alone. There were no significant clinical differences between the group receiving bupivacaine 7.5 mg x ml(-1) and the group receiving ropivacaine 7.5 mg x ml(-1).     

Computed tomography for cervical spine trauma. The impact of MDCT on fracture detection and dose deposition

A multidetector computed tomography (MDCT) was installed in our department. Referral rates, examination protocols and detection rates of abnormal findings in CT examinations for cervical spine trauma 6 months before and 6 months after MDCT installation were compared to look for changes in practice. Retrospective analysis of all CT cervical spine examinations in patients with multiple trauma over two contiguous 6-month periods: from July 2003 to December 2003 (helical CT) and from January 2004 to June 2004 (MDCT). Variables recorded were number of CT examinations performed, scan plane coverage and traumatic abnormalities detected. Phantom dosimetry measurements for cervical spine examination in both helical CT and MDCT were compared. One hundred and fifty four patients underwent cervical spine CT during these periods. Helical CT period: of 91 patients undergoing CT cervical spine examination for trauma, 65 (71%) were complete cervical examinations and 26 (29%) were level-specific examinations. Eight patients (9%) had cervical spine fracture, six of which were apparent on radiographs. Dose estimations for thyroid, lens and breast were 24.76, 1.86 and 0.21 mGy, respectively, for complete cervical spine examinations. MDCT period: of 63 patients who underwent CT cervical spine examination for trauma, 61 (97%) were complete examinations and 2 (3%) were level-specific examinations. Six patients (11%) had cervical spine fracture, three of which were apparent on radiographs. Dose estimations for thyroid, lens and breast were 75.8, 9.7 and 0.7 mGy, respectively, for complete cervical spine examinations, which were notably higher than those for helical CT. After installation of MDCT, clinical requests for complete examination of the cervical spine following trauma increased. This changing trend resulted in a significantly higher radiation dose to thyroid, lens and breast.