Newly discovered mutations in the GALNT3 gene causing autosomal recessive hyperostosis-hyperphosphatemia syndrome

Background and purpose Periosteal new bone formation and cortical hyperostosis often suggest an initial diagnosis of bone malignancy or osteomyelitis. In the present study, we investigated the cause of persistent bone hyperostosis in the offspring of two consanguineous parents.Methods Clinical assessment, imaging, and direct sequencing were used to elucidate the etiology of the condition seen in the patient.Results Radiological examination revealed periosteal reaction, diaphysitis, and cortical hyperostosis, suggesting osteomyelitis or a bone neoplasm. The clinical and radiological features were also reminiscent of hyperostosis with hyperphosphatemia (HHS), a rare autosomal recessive disease manifesting with recurrent, transient, and painful swelling of the long bones. The identification of two novel heterozygous pathogenic mutations in the GALNT3 gene confirmed a diagnosis of HHS.Interpretation Molecular analysis represents an invaluable tool in the differential diagnosis of persistent cortical hyperostosis.     

Reference charts for the relationships between dual-energy X-ray absorptiometry-assessed bone mineral content and lean mass in 3,063 healthy men and premenopausal and postmenopausal women

Correlations between dual-energy X-ray absorptiometry (DXA)-assessed bone mineral content and lean mass (BMC-LM curves), and between BMC/LM ratio and age ([BMC/LM]–age curves), were analyzed in the whole body (WB), the upper limbs (ULs) and the lower limbs (LLs) of 3,063 healthy Hispanic adults. Groups of 472 men aged 25–87years, 1,035 premenopausal (pre-MP) women aged 27–54 years, and 1,556 post-menopausal (post-MP) women aged 48–93 years were studied with a GE-Lunar DPX-Plus device. BMC-LM curves confirmed previous observations that BMC and LM masses always correlate linearly, with similar slopes within each region, but differing in intercepts according to gender and hormonal status. Multiple regression tests showed little or no independent interaction of body weight or height with those relationships. [BMC/LM]–age curves were flat in men but showed the positive influence of estrogens throughout the age range in women. Z-scored graphs of all the corresponding relationships were compiled, showing the confidence intervals for means ±1, ±2, and ±3 SDs of the data (±1, ±2, ±3 z-scores) along BMC-LM and [BMC/LM]–age curves. These charts are proposed as references for assessing how well bone mass (as assessed by BMC) and muscle mass (assumed proportional to LM) follow the natural anthropometric/biomechanical proportionality in Hispanic men and women within the age range studied, employing similar devices. Charts for LLs, showing the lowest variance amongst the studied correlations and approaching the origin as an exclusive feature, could provide the most accurate reference curves. Differences between data from ULs and LLs may provide information about any eventual interaction of body-weight bearing with the general results. The proposed analysis may provide useful information for approaching a differential diagnosis between disuse-related and other types of osteopenias employing only DXA.     

Laboratory evaluation of modern plastic brackets

The aim of the study was to evaluate some properties of modern orthodontic plastic brackets. Seven bracket brands [Aesthetik-Line (AL), Avalon (AV), Brillant (BR), Elegance (EL), OrthoFlex (OF), Silkon Plus (SL), and Spirit MB (SP)] were included in the study. The properties tested were chemical composition, base morphology, slot roughness, Vickers hardness (VH), and shear bond strength (SBS) with enamel.According to the results, the brackets were composed of polyurethane (AV and OF), polyoxymethylene (BR), and Ca-Al-silicate fibre glass-reinforced polycarbonate (AL, EL, SL, and SP). Metallic slots were composed of austenitic stainless steel (EL and SP) and Ag-Cu alloy (AV). The base morphology exhibited distinct designs, employing parallel retentive canals (AV, EL, and OF) or round-angled square protrusions with major retentive elements (AL, BR, and SP) or a combination of both (SL). The SP metallic slot demonstrated the lowest Sz values. No significant differences were found in VH among the brackets before water immersion (19.6-16.9 VH). After 12 weeks immersion, the brackets showed a significant hardness reduction (16.6-12.9 HV). SBS ranged between 111 and 193 N (8-14 MPa) for all brackets, except from SP (59 N/5 MPa). The predominant failure mode was mixed adhesive and cohesive. Most of the plastic brackets presented a base structure capable of adequate bonding to enamel, regardless of their differences in composition. Slot roughness showed differences among groups. All the brackets demonstrated plasticization after prolonged water storage.     

Body composition and newborn birthweight in pregnancies of adolescent and mature women

Teenage pregnancy has been associated with adverse effects for the mother and the newborn (NB). In order to compare body composition (BC) between adolescents (Ad) and mature women (MW) during pregnancy and to determine the difference in birthweight and perinatal morbidity, pregnant Ad (n = 40) and MW (n = 227) were studied. BC changes between the second and third trimesters were determined by multifrequency bioelectrical impedance analysis, and birthweight and NB morbidity were evaluated. During the second and third trimesters of the pregnancy, fat mass was lower in the Ad group [16 kg (13–19)] than in the MW group [22 kg (17–27)] (P < 0.01; median and quartiles 1–3). Fat‐free mass increased by 3.09 kg (2.29–4.20) and 2.20 kg (1.0–3.59) (P ≤ 0.01), and total body water increased by 2.77 L (0.84–4.49) vs. 2.04 L (0.55–3.89) (P = 0.36), in the Ad and MW groups, respectively (median and quartiles 1–3). Birthweight was not significantly different between NBs of Ad (3223 ± 399 g) and NBs of MW (3312 ± 427 g, P = 0.22). The youngest Ad (<18 year old, n = 8) had NB with lower birthweight than MW (3031 ± 503 g, P = 0.06). NBs of Ad mothers showed a non‐significant trend towards a higher rate of morbidity relative to the NBs of MW. In conclusion, the BC of Ad differs from that of MW during pregnancy. In addition, the NB infants of Ad mothers tended to have a lower birthweight than those from MW, a result that suggests that the Ad should be in strict prenatal control.     

Colorectal Cancer Staging: Reappraisal of N/PN Classification

PURPOSE: Current American Joint Committee on Cancer and the Union Internationale Contre le Cancer TNM classification disregards location of positive nodes, discontinuing N3 category, which constitutes a major modification to 1987 version. This study was designed to assess the impact of the recategorization of former N3 cases and the reliability of the current N1-N2 subcategorization of Stage III patients. METHODS: Prospectively collected data from 1,391 patients (55.8 percent males; median age, 64 (range, 21–97) years), operated on with curative intent between 1980 and 1999, were analyzed. The median follow-up was 60 (interquartile range, 27–97) months with 129 cases lost to follow-up. RESULTS: Of positive node cases, 25.3 percent were former N3. Among them, 30.5 percent migrated to the N1 group and 69.5 percent to the N2 group. The proportions of former N3 cases in N1 and N2 groups were 12.5 percent and 46.1 percent, respectively (P < 0.001). Node-positive patients had an actuarial five-year survival rate of 56.7 percent (95 percent confidence interval, 53–59), with a significant difference between N1/N2 categories (63.6 vs. 44.1 percent, respectively; P < 0.001). Although apical node involvement and more than three positive nodes were associated with poorer outcomes in univariate analysis, only the number of positive nodes had independent association (hazard ratio, 1.6 (range, 1.2–2.2); P < 0.001). Integration of former N3 cases did not modify outcomes. CONCLUSIONS: The recategorization of former N3 involved a high proportion of positive node cases. Current N1/N2 categories clearly defined different outcomes and were not modified by the integration of former N3.     

Isolated pituitary granuloma by atypical Mycobacterium in a nonimmunosuppressed woman

A 32-year-old woman presented with a 10-day history of fever (38.0 degrees C), headaches, nausea, vomiting and a 6-month history of diabetes insipidus and amenorrhoea. Two months previously she had undergone a surgical drilling of the right mastoid area because of mastoiditis. Endocrine investigation showed elevated serum prolactin levels, secondary adrenal and gonadal failure and a normal thyroid function. Cranial MRI scan revealed a contrast enhancing intrasellar mass (approximately 2 cm) of heterogeneous appearance with suprasellar extension and thickening of the pituitary stalk. Lumbar puncture was suggestive of aseptic meningitis. The Ziehl-Neelsen stain of cerebrospinal fluid (CSF) and the tuberculin skin test were both negative. The pituitary mass was removed with a transsphenoidal approach. Histological examination demonstrated destruction of the adenohypophysis by epithelioid granulomas with partial caseous necrosis and microabscess formation, suggestive of a mycobacterial infection. A polymerase chain reaction analysis performed on paraffin-embedded tissue was positive for mycobacterial DNA. According to the individual 16S sequence, it was identified as Mycobacterium malmoense, an atypical nontuberculous mycobacterium (NTM). In conclusion, this is the first case of an isolated pituitary granuloma caused by an NTM infection in a nonimmunosuppressed patient.