Sporadic and MEN1‐Related Primary Hyperparathyroidism: Differences in Clinical Expression and Severity

Primary hyperparathyroidism (PHPT) is a common endocrine disease that is associated with multiple endocrine neoplasia type 1 (MEN1) in ～2% of PHPT cases. Lack of a family history and other specific expressions may lead to underestimated MEN1 prevalence in PHPT. The aim of this study was to identify clinical or biochemical features predictive of MEN1 and to compare the severity of the disease in MEN1‐related versus sporadic PHPT (sPHPT). We performed a 36‐mo cross‐sectional observational study in three tertiary referral centers on an outpatient basis on 469 consecutive patients with sporadic PHPT and 64 with MEN1‐related PHPT. Serum calcium, phosphate, PTH, 25(OH)D₃, and creatinine clearance were measured, and ultrasound examination of the urinary tract/urography was performed in all patients. In 432 patients, BMD was measured at the lumbar spine (LS) and femoral neck (FN). MEN1 patients showed lower BMD Z‐scores at the LS (?1.33 ± 1.23 versus ?0.74 ± 1.4, p = 0.008) and FN (?1.13 ± 0.96 versus ?0.6 ± 1.07, p = 0.002) and lower phosphate (2.38 ± 0.52 versus 2.56 ± 0.45 mg/dl, p = 0.003) and PTH (113.8 ± 69.5 versus 173.7 ± 135 pg/ml, p = 0.001) levels than sPHPT patients. Considering probands only, the presence of MEN1 was more frequently associated with PTH values in the normal range (OR, 3.01; 95% CI, 1.07–8.50; p = 0.037) and younger age (OR, 1.61; 95% CI, 1.28–2.02; p = 0.0001). A combination of PTH values in the normal range plus age <50 yr was strongly associated with MEN1 presence (OR, 13.51; 95% CI, 3.62–50.00; p = 0.0001). In conclusion, MEN1‐related PHPT patients show more severe bone but similar kidney involvement despite a milder biochemical presentation compared with their sPHPT counterparts. Normal PTH levels and young age are associated with MEN1 presence.     

安氏Ⅱ类1分类患者拔牙或非拔牙矫治后长期面形变换

通常认为Ⅱ1错拔除4个第一前磨牙后,面形会变平或凹陷,但有些研究不支持这种观点.本实验目的就是评价拔牙与非拔牙治疗后和长期保持期间的面部软组织变化. 材料和方法63名美国白人,23名拔牙者(男11,女12),平均年龄12.6岁,40名非拔牙者(男19,女21),平均年龄11.3岁,牙列完整,均采用方丝弓矫治器治疗.开始时采用颈牵引抑制上颌生长,内收切牙.拍摄治疗前(T1)、治疗后(T2)和长期保持后(T3)13～14年期间的颅颌定位X线侧位片,进行有关测量比较各个时期治疗和生长的关系、切牙和唇的变化、拔牙与否的影响. 结果治疗前拔牙与非拔牙组LI-APg、LI-NB(mm)、LI-NB、NAPg有显著差异,显示拔牙组下切牙位置更靠前,颏部更突出.治疗期间以关节点位置变化表示的下颌生长,T1-T2期间6.24 mm,T2-T3期间4.62 mm. 矫治前后拔牙与非拔牙组比较,LI-APg、LI-NB(mm)、LI-NB、LL-E、LL-S等指标两组间差异有显著性,说明拔牙组治疗期间下唇及下切牙更向后移动,而上唇后移、下颌及鼻部生长、颏部向前,两组间差异无显著性. 矫治保持阶段,拔牙与非拔牙组均显示上下唇位置后移,软组织颏部更向前,两组间比较差异无显著性;鼻部生长、下颌生长两组间测量也无差异. 结论经拔牙或不拔牙成功治疗的安氏Ⅱ类1分类患者治疗后及保持期间面形持续变平,面部软组织突度进一步减小,这是由于下颌和鼻部生长所致,而不是拔牙与否的影响.长期保持后,唇的位置比Ricketts等倡导的理想位更后移,但与未治疗的同年龄组成人相似,治疗前下唇位置和厚度及上下颌骨关系可作为预测治疗后及长期保持期间下唇位置的因素. [蔡留意摘 丁寅校]     

Pharmacokinetics in obese patients

One of the many problems in providing anaesthesia for morbidlyobese patients is the influence of obesity on pharmacokineticsand pharmacodynamics. Drug administration in obese patientsis difficult because recommended doses are based on pharmacokineticdata obtained from individuals with normal weights; therefore,mistakes in the determination of the appropriate dose are oftenmade. Because of comorbidity in these patients, the functionof organs involved in drug elimination (e.g. kidney, liver)can be affected making pharmacokinetics more difficult and complex.     

Hereditary lymphedema: evidence for linkage and genetic heterogeneity

Hereditary or primary lymphedema is a developmental disorder of the lymphatic system which leads to a disabling and disfiguring swelling of the extremities. Hereditary lymphedema generally shows an autosomal dominant pattern of inheritance with reduced penetrance, variable expression and variable age at onset. Three multigeneration families demonstrating the phenotype of hereditary lymphedema segregating as an autosomal dominant trait with incomplete penetrance were genotyped for 366 autosomal markers. Linkage analysis yielded a two-point LOD score of 6.1 at straight theta = 0. 0 for marker D5S1354 and a maximum multipoint LOD score of 8.8 at marker D5S1354 located at chromosome 5q34-q35. Linkage analysis in two additional families using markers from the linked region showed one family consistent for linkage to distal chromosome 5. In the second family, linkage to 5q was excluded for all markers in the region with LOD scores Z < -2.0. The vascular endothelial growth factor C receptor ( FLT4 ) was mapped to the linked region, and partial sequence analysis identified a G-->A transition at nucleotide position 3360 of the FLT4 cDNA, predicting a leucine for proline substitution at residue 1126 of the mature receptor in one nuclear family. This study localizes a gene for primary lymphedema to distal chromosome 5q, identifies a plausible candidate gene in the linked region, and provides evidence for a second, unlinked locus for primary lymphedema.      

Information domain analysis of cardiovascular variability signals: Evaluation of regularity, synchronisation and co-ordination

A unifying general approach to measure regularity, synchronisation and co-ordination is proposed. This approach is based on conditional entropy and is specifically designed to deal with a small amount of data (a few hundred samples). Quantitative and reliable indexes of regularity, synchronisation and co-ordination (ranging from 0 to 1) are derived in a domain (i.e. the information domain) different from time and frequency domains. The method is applied to evaluate regularity, synchronisation and co-ordination among cardiovascular beat-to-beat variability signals during sympathetic activation induced by head-up tilt (T), during the perturbing action produced by controlled respiration at 10, 15 and 20 breaths/min (CR10, CR15 and CR20), and after peripheral muscarinic blockade provoked by the administration of low and high doses of atropine (LD and HD). It is found that: (1) regularity of the RR interval series is around 0.209; (2) this increases during T, CR10 and HD; (3) the systolic arterial pressure (SAP) series is more regular (0.406) and its regularity is not affected by the specified experimental conditions; (4) the muscle sympathetic (MS) series is a complex signal (0.093) and its regularity is not influenced by HD and LD; (5) the RR interval and SAP series are significantly, though weakly, synchronised (0.093) and their coupling increases during T, CR10 and CR15; (6) the RR interval and respiration are coupled (0.152) and their coupling increases during CR10; (7) SAP and respiration are significantly synchronised (0.108) and synchronisation increases during CR10; (8) MS and respiration are uncoupled and become coupled (0.119) after HD; (9) the RR interval, SAP and respiration are significantly co-ordinated (0.118) and co-ordination increases during CR10 and CR15; (10) during HD the co-ordination among SAP, MS and the respiratory signal is larger than that among the RR interval, SAP, MS and the respiratory signal, thus indicating that the RR interval contributes towards reducing co-ordination.     

Quantifying electrocardiogram RT-RR variability interactions

A dynamic linear parametric model is designed to quantify the dependence of ventricular repolarisation duration variability on heart period changes and other immeasurable factors. The model analyses the beat-to-beat series of the RR duration and of the interval between R- and T-wave apexes (RT period). Directly from these two signals, a parametric identification procedure and spectral decomposition techniques allow RT variability to be divided into RR-related and RR-unrelated parts and allow the RT-RR transfer function to be calculated. RT variability is driven by RR changes at low frequency (LF, around 0.1 Hz) and high frequency (HF, at the respiratory rate), whereas, at very low frequencies, the RR-unrelated contribution to the total RT variability is remarkable. During tilt at LF the RR-related RT percentage power increases (p<0.02), the RR-unrelated RT percentage power remains unchanged, the gain of the RT-RR relationship largely increases (p<0.001), and the phase is not significantly modified. Both the RR-related and the RR-unrelated RT percentage powers at LF are not affected by controlled respiration, and an increase in the RT-RR gain at HF is observed (p<0.02). The proposed analysis may help to describe the regulation of the ventricular repolarisation process and to extract indexes quantifying the coupling between heart period and ventricular repolarisation interval changes.     

Causal relationship between heart rate and arterial blood pressure variability signals

A method is described which allows the determination of the causal relationship existing between two biological signals (heart rate and arterial blood pressure variability signals) which carry information about the role of control elicited by the autonomic nervous system. This method assumes an autoregressive (AR) model for the two signals to check the cross-correlation of the two residuals after AR identification. This information, together with the classical parameters of the spectral analysis (mean, variance, frequency and power in two typical bands, gain, phase and coherence) may provide a more precise evaluation of the complex mechanisms involved in the control of heart rate and blood pressure in numerous physiopathological situations.