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.     

High-resolution real-time ultrasonography of thyroid nodules

High-resolution real-time ultrasonography was used to evaluate 98 patients with palpable abnormalities of the thyroid and positive isotopic studies. It confirmed 37 of 73 (51%) suspected solitary nodules. Of 25 patients thought to have multinodular goiter, sonography was supportive in 21 (84%). In patients with adenoma or adenomatous nodules, characteristic features included a sonolucent "halo". Colloid nodules tended to be more sonolucent than normal thyroid tissue, whereas Hashimoto thyroiditis was characterized by an enlarged gland and decreased echogenicity.     

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.      

Effect of ozone and Tooth MousseTM on the efficacy of peroxide bleaching

Background:  The aim of this in vitro study was to investigate the effect of Tooth Mousse™ (TM) and ozone on the bleaching effectiveness of peroxide (P).
Methods:  Sixty enamel specimens were stained by tea infusion. P (8% carbamide peroxide solution) and the P/TM (50:50) blend were prepared freshly as required. The specimens were divided randomly into six groups: Group A – ozone followed by P; Group B – ozone concurrently with P; Group C – P alone; Group D – ozone followed by P/TM; Group E – ozone concurrently with P/TM; and Group F – P/TM alone. Ozone exposure was of 40 seconds duration. Digital photographic images were recorded at baseline and endpoint under standardized lighting and desiccation conditions. CIELAB L*a*b* values were determined.
Results:  The addition of TM to P or the application of ozone with P did not significantly affect bleaching effectiveness compared with P alone. The application of ozone prior to P significantly decreased bleaching effectiveness as indicated by the ΔL*, Δa*, ΔE and %L* values. The addition of TM to the P did enhance the aesthetic by increasing the lustre and translucency of the treated enamel.
Conclusions:  The results of this study suggest that Tooth Mousse may be applied concurrently with the bleach, and not reduce bleaching effectiveness.     

Chemical and biomechanical characterization of hyperhomocysteinemic bone disease in an animal model

Background

Classical homocystinuria is an autosomal recessive disorder caused by cystathionine β-synthase (CBS) deficiency and characterized by distinctive alterations of bone growth and skeletal development. Skeletal changes include a reduction in bone density, making it a potentially attractive model for the study of idiopathic osteoporosis.

Methods

To investigate this aspect of hyperhomocysteinemia, we supplemented developing chicks (n = 8) with 0.6% dl-homocysteine (hCySH) for the first 8 weeks of life in comparison to controls (n = 10), and studied biochemical, biomechanical and morphologic effects of this nutritional intervention.

Results

hCySH-fed animals grew faster and had longer tibiae at the end of the study. Plasma levels of hCySH, methionine, cystathionine, and inorganic sulfate were higher, but calcium, phosphate, and other indices of osteoblast metabolism were not different. Radiographs of the lower limbs showed generalized osteopenia and accelerated epiphyseal ossification with distinct metaphyseal and suprametaphyseal lucencies similar to those found in human homocystinurics. Although biomechanical testing of the tibiae, including maximal load to failure and bone stiffness, indicated stronger bone, strength was proportional to the increased length and cortical thickness in the hCySH-supplemented group. Bone ash weights and IR-spectroscopy of cortical bone showed no difference in mineral content, but there were higher Ca²⁺/PO₄^3- and lower Ca²⁺/CO₃^2- molar ratios than in controls. Mineral crystallization was unchanged.

Conclusion

In this chick model, hyperhomocysteinemia causes greater radial and longitudinal bone growth, despite normal indices of bone formation. Although there is also evidence for an abnormal matrix and altered bone composition, our finding of normal biomechanical bone strength, once corrected for altered morphometry, suggests that any increase in the risk of long bone fracture in human hyperhomocysteinemic disease is small. We also conclude that the hCySH-supplemented chick is a promising model for study of the connective tissue abnormalities associated with homocystinuria and an important alternative model to the CBS knock-out mouse.