Application of ruthenium complexes of triazole-containing tridentate ligands to asymmetric transfer hydrogenation of ketones.

The synthesis of a series of tridentate ligands based on a homochiral 1,2-diamine structure attached to a triazole group and their subsequent applications to the asymmetric transfer hydrogenation of ketones are described. In the best cases, alcohols of up to 93% ee were obtained. Although base is not required, the use of Ru(3)(CO)(12) as metal source is essential, indicating a unique mechanism for the formation of the active catalyst.

Camurati-Engelmann disease: unique variant featuring a novel mutation in TGFß1 encoding transforming growth factor beta 1 and a missense change in TNFSF11 encoding RANK ligand.

We report a 32-year-old man and his 59-year-old mother with a unique and extensive variant of Camurati-Engelmann disease (CED) featuring histopathological changes of osteomalacia and alterations within TGFß1 and TNFSF11 encoding TGFß1 and RANKL, respectively. He suffered leg pain and weakness since childhood and reportedly grew until his late 20s, reaching 7 feet in height. He had deafness, perforated nasal septum, torus palatinus, disproportionately long limbs with knock-knees, low muscle mass, and pseudoclubbing. Radiographs revealed generalized skeletal abnormalities, including wide bones and cortical and trabecular bone thickening in keeping with CED, except that long bone ends were also affected. Lumbar spine and hip BMD Z-scores were + 7.7 and + 4.4, respectively. Biochemical markers of bone turnover were elevated. Hypocalciuria accompanied low serum 25-hydroxyvitamin D (25[OH]D) levels. Pituitary hypogonadism and low serum insulin-like growth factor (IGF)-1 were present. Karyotype was normal. Despite vitamin D repletion, iliac crest histology revealed severe osteomalacia. Exon 1 of TNFRSF11A (RANK), exons 2, 3, and 4 of LRP5, and all coding exons and adjacent mRNA splice junctions of TNFRSF11B (OPG), SQSTM1 (sequestosome 1), and TNSALP (tissue nonspecific alkaline phosphatase) were intact. His asymptomatic and less dysmorphic 5'11″ mother, also with low serum 25(OH)D, had milder clinical, radiological, biochemical, and histopathological findings. Both individuals were heterozygous for a novel 12-bp duplication (c.27_38dup, p.L10_L13dup) in exon 1 of TGFß1, predicting four additional leucine residues in the latency-associated-peptide segment of TGFß1, consistent with CED. The son was also homozygous for a single base transversion in TNFSF11, predicting a nonconservative amino acid change (c.107C > G, p.Pro36Arg) in the intracellular domain of RANKL that was heterozygous in his nonconsanguineous parents. This TNFSF11 variant was not found in the SNP Database, nor in published TNFSF11 association studies, but it occurred in four of the 134 TNFSF11 alleles (3.0%) we tested randomly among individuals without CED. Perhaps the unique phenotype of this CED family is conditioned by altered RANKL activity.

Buschke-Ollendorff syndrome: absence of LEMD3 mutation in an affected family.

BACKGROUND: Buschke-Ollendorff syndrome (BOS), an autosomal dominant disorder, features small, acquired, asymptomatic, symmetrical foci of osteosclerosis detected radiographically in epimetaphyseal bone (osteopoikilosis) (OPK) together with connective tissue nevi or juvenile elastomas. Heterozygous, loss-of-function, germline mutation in the LEMD3 gene (which encodes an inner nuclear membrane protein called LEMD3, or MAN1) has been repeatedly documented in patients with BOS or OPK. OBSERVATIONS: We describe a father and son with multiple yellowish papules and nodules coalescing into cobblestone nevoid plaques consistent with nevus elasticus. Radiographs of the father show multiple, small, bone islands within the hands, wrists, distal femurs, proximal tibias, and left distal fibula consistent with OPK. Although the clinical findings are diagnostic of Buschke-Ollendorf syndrome, analysis of the LEMD3 gene showed no exonic mutations. CONCLUSION: Absence of LEMD3 mutation in the exons and splice sites of a family with BOS suggests that there is genetic heterogeneity for this disorder.

Skeletal fluorosis from instant tea.

INTRODUCTION: Skeletal fluorosis (SF) can result from prolonged consumption of well water with >4 ppm fluoride ion (F(-); i.e., >4 mg/liter). Black and green teas can contain significant amounts of F(-). In 2005, SF caused by drinking 1-2 gallons of double-strength instant tea daily throughout adult life was reported in a 52-yr-old woman. MATERIALS AND METHODS: A 49-yr-old woman developed widespread musculoskeletal pains, considered fibromyalgia, in her mid-30s. Additionally, she had unexplained, increasing, axial osteosclerosis. She reported drinking 2 gallons of instant tea each day since 12 yr of age. Fluoxetine had been taken intermittently for 5 yr. Ion-selective electrode methodology quantitated F(-) in her blood, urine, fingernail and toenail clippings, tap water, and beverage. RESULTS: Radiographs showed marked uniform osteosclerosis involving the axial skeleton without calcification of the paraspinal, intraspinal, sacrotuberous, or iliolumbar ligaments. Minimal bone excrescences affected ligamentous attachments in her forearms and tibias. DXA Z-scores were +10.3 in the lumbar spine and +2.8 in the total hip. Her serum F(-) level was 120 microg/liter (reference range, 20-80 microg/liter), and a 24-h urine collection contained 18 mg F(-)/g creatinine (reference value, <3). Fingernail and toenail clippings showed 3.50 and 5.58 mg F(-)/kg (control means, 1.61 and 2.02, respectively; p(s) < 0.001). The instant tea beverage, prepared as usual extra strength using tap water with approximately 1.2 ppm F(-), contained 5.8 ppm F(-). Therefore, the tea powder contributed approximately 35 mg of the 44 mg daily F(-) exposure from her beverage. Fluoxetine provided at most 3.3 mg of F(-) daily. CONCLUSIONS: SF from habitual consumption of large volumes of extra strength instant tea calls for recognition and better understanding of a skeletal safety limit for this modern preparation of the world's most popular beverage.

Juvenile Paget's disease: the second reported, oldest patient is homozygous for the TNFRSF11B "Balkan" mutation (966_969delTGACinsCTT), which elevates circulating immunoreactive osteoprotegerin levels.

UNLABELLED: The oldest person (60 yr) with juvenile Paget's disease is homozygous for the TNFRSF11B mutation 966_969delTGACinsCTT. Elevated circulating levels of immunoreactive OPG and soluble RANKL accompany this genetic defect that truncates the OPG monomer, preventing formation of OPG homodimers. INTRODUCTION: Juvenile Paget's disease (JPD), a rare autosomal recessive disorder, features skeletal pain, fracture, and deformity from extremely rapid bone turnover. Deafness and sometimes retinopathy also occur. Most patients have diminished osteoprotegerin (OPG) inhibition of osteoclastogenesis caused by homozygous loss-of-function defects in TNFRSF11B, the gene that encodes OPG. Circulating immunoreactive OPG (iOPG) is undetectable with complete deletion of TNFRSF11B but normal with a 3-bp in-frame deletion. MATERIALS AND METHODS: We summarize the clinical course of a 60-yr-old Greek man who is the second reported, oldest JPD patient, including his response to two decades of bisphosphonate therapy. Mutation analysis involved sequencing all exons and adjacent mRNA splice sites of TNFRSF11B. Over the past 4 yr, we used ELISAs to quantitate his serum iOPG and soluble RANKL (sRANKL) levels. RESULTS: Our patient suffered progressive deafness and became legally blind, although elevated markers of bone turnover have been normal for 6 yr. He carries the same homozygous mutation in TNFRSF11B (966_969delTGACinsCTT) reported in a seemingly unrelated Greek boy and Croatian man who also have relatively mild JPD. This frame-shift deletes 79 carboxyterminal amino acids from the OPG monomer, including a cysteine residue necessary for homodimerization. Nevertheless, serum iOPG and sRANKL levels are persistently elevated. CONCLUSIONS: Homozygosity for the TNFRSF11B "Balkan" mutation (966_969delTGACinsCTT) causes JPD in the second reported, oldest patient. Elevated circulating iOPG and sRANKL levels complement evidence that this deletion/insertion omits a cysteine residue at the carboxyterminus needed for OPG homodimerization.

Value of magnetic resonance imaging in muscle trauma.

While most muscle injuries are recognized clinically, magnetic resonance imaging (MRI) is the ideal noninvasive test to assess their extent and severity, which impacts therapy and influences prognosis. Typical examples of these injuries include muscle contusions, lacerations, sprains, and delayed onset muscle soreness. For other less common traumatic muscle conditions (exertional compartment syndrome, muscle herniation, and traumatic denervation), the clinical findings are often subtle or ambiguous and MRI will indicate the correct diagnosis. In patients with known muscle trauma, MRI can detect complications such as hematoma or seroma development, scarring and fibrosis, and myositis ossificans. This article illustrates the spectrum of muscle injuries, emphasizing the value of MRI in their diagnosis.

Proximity of the popliteal artery to the PCL during simulated knee arthroscopy: implications for establishing the posterior trans-septal portal.

This study defines the sagittal distance from the posterior cruciate ligament (PCL) to the popliteal artery under simulated arthroscopic conditions. This information is relevant for posterior knee arthroscopy, particularly for the safe establishment of the posterior trans-septal portal. Measurements from the PCL to the popliteal artery were made on sagittal magnetic resonance images obtained in a previous study of 10 fresh-frozen cadaveric knees. The mean sagittal distance from the mid-PCL to the popliteal artery was 29.1 +/- 11 mm (range: 18-55 mm). The mean sagittal distance from the proximal PCL fovea to the popliteal artery was 9.7 +/- 5 mm (range: 3-16 mm). The results of this study provide the arthroscopist working in the posterior compartments of the knee with a more detailed knowledge of the anatomic relationship between the PCL and popliteal artery. This knowledge will help minimize the risk of iatrogenic vascular injury during arthroscopic knee surgery.

Postoperative radiographic assessment of acetabular fractures: a comparison of plain radiographs and CT scans.

OBJECTIVES: This investigation was designed to compare computerized tomography (CT) and plain radiography for detection of articular step and gap deformity after healing of operatively treated acetabular fractures. DESIGN: Retrospective review of CT and plain radiographic images of 15 patients treated operatively for a displaced acetabular fracture. SETTING: Level I trauma center. MAIN OUTCOME MEASURES: Ability of CT scans and plain radiographs to detect residual articular steps and gaps after healing of acetabular fractures managed by open reduction and internal fixation. RESULTS: Using standardized evaluation techniques, more patients were found to have residual articular incongruities on CT scans (8 with step and 7 with gap) than on plain radiographs (1 with step and 6 with gap). In addition, a step deformity on CT scan correlated with a gap deformity, and as the size of the step deformity increased, so too did the size of the gap deformity. CONCLUSIONS: Based on our data, computerized tomography is more likely than plain radiographs to allow detection of residual articular incongruities in healed acetabular fractures. The authors believe that CT scans improve the evaluation of articular reduction and that this information can be used to further evaluate surgical technique and provide insight as to the impact of residual articular incongruity on the development of hip arthrosis.

Giant vertebral notochordal rest: a lesion distinct from chordoma: discussion of an evolving concept.

A 14-year-old boy with severe back pain for several years is described. Roentgenograms, bone scans, and computed tomographic scans of the spine were normal, but magnetic resonance imaging studies showed a lumbar vertebral body lesion, confined to the bone, with low T1- and high T2-weighted signal intensities. Histologically, the lesion consisted of sheet-like notochordal-type tissue, containing physaliphorous cells but lacking the usual features of chordoma. A diagnosis of giant notochordal rest was made. A review of prior possible examples of this recently described and controversial entity is made with a discussion of its embryologic foundations and distinction from chordoma.