A tri-modal distribution of age-of-onset in female patients with myasthenia gravis is associated with the gender-related clinical differences

Background: A tri-modal distribution of age-at-onset emerged among females patients with myasthenia gravis (MG) in our database. This finding may be indicative of different gender-based disease mechanisms.

Methods: We retrospectively reviewed the files of 127?MG patients for the clinical, serology and thymus pathology according to their age at disease onset: ≤40 years (early-onset, EOMG), 40–70 years (intermediate-onset, IOMG) and >70 years (late-onset, LOMG).

Results: EOMG was more common among females, and IOMG was more common among males. Ocular MG was more common among the male MG patients with an IOMG. Patients with EOMG had lower rates of positive anti-acetylcholine receptor (anti-AChR). IOMG females, but not IOMG males, had lower rates of positive anti-AChR. IOMG and EOMG females had high rates of thymic hyperplasia, while EOMG males had high rates of thymoma. Comorbidity with autoimmune diseases was common among females with IOMG and LOMG.

Conclusions: The prevalence of IOMG was the reason for the trend reversal of MG prevalence between genders. The clinical features of patients with IOMG differed between genders in the rates of positive anti-AChR, follicular hyperplasia of the thymus and comorbidity with autoimmune diseases. This may suggest a different gender-based mechanism of immune intolerance towards AChR and other antigens.     

Does prenatal nicotine exposure alter the brain's response to nicotine in adolescence? A neuroanatomical analysis

This study examined changes in dendritic morphology and spine density in multiple brain regions [Zilles' areas: (i) the Cg3 region of the anterior cingulate cortex or the medial prefrontal cortex, layer III (Cg3); (ii) the dorsal agranular insular cortex, layer III (AID); (iii) the PAR I region of the parietal cortex, layer III (Par1) and (iv) the nucleus accumbens (NAc)]of Long–Evans rats following exposure to nicotine prenatally, in late adolescence, or both prenatally and in adolescence. Prenatal nicotine exposure induced enduring changes in neuroanatomical organisation that varied between male and female offspring, with males exhibiting increased dendritic complexity of neurons in AID and NAc whereas females experienced increased dendritic complexity in Par1 but decreased dendritic complexity of neurons in NAc. Similarly, nicotine given in late adolescence dramatically reorganised neural circuitry of both male and female offspring, with males exhibiting decreased dendritic complexity of neurons in Par1 and Cg3 but increased dendritic complexity in AID, and females exhibiting decreased dendritic complexity in Cg3 and NAc but increased complexity in AID. Exposure to nicotine both prenatally and in adolescence produced few neuroanatomical parameters that demonstrated a prenatal experience × adolescent drug administration interaction. Females showed additive effects in Par1, Cg3 and NAc whereas males demonstrated additive effects only in AID. Thus, the timing of nicotine exposure produced differential effects on cerebral organisation in a regionally specific manner.     

Does the cement stiffness affect fatigue fracture strength of vertebrae after cement augmentation in osteoporotic patients?

Purpose

Normal progression of osteoporosis or the rigid reinforcement of the fractured vertebral body with polymethyl methacrylate (PMMA) cement is being discussed as a cause for adjacent-level fractures after vertebroplasty. The purpose of this study was to investigate whether augmentation with low stiffness cement can decrease the risk of adjacent-level fractures in low-quality bone.

Methods

Eighteen female osteoporotic lumbar specimens (L1–L5) were harvested and divided into three groups according to bone mineral density: (I) native; (II) PMMA; (III) modified PMMA (lower stiffness). For the PMMA and modified PMMA groups, a compression fracture was first mechanically induced in L3, and then the fracture received vertebroplasty treatment. The cement stiffness reduction of the modified PMMA group was achieved via an addition of 8 mL of serum to the typical PMMA base. All specimens were exposed to cyclic loading (4 Hz) and a stepwise increasing applied peak force. Cement stiffness was tested according to ISO 5833.

Results

A 51 % decrease in cement stiffness was achieved in the modified PMMA group (954 ± 141 vs. 1,937 ± 478 MPa, p < 0.001). Fatigue fracture force (the force level during cyclic loading at which the deformation experienced a sudden increase; FFF) was significantly affected by bone quality (r ² = 0.39, p = 0.006) and by the initial fracture force (the force necessary to create the initial fracture in L3 prior to augmentation; r ² = 0.82, p < 0.001). Using initial fracture force as a covariate, the FFF of the modified PMMA group (1,764 ± 49 N) was significantly higher than in the PMMA group (1,544 ± 55 N; p = 0.03).

Conclusions

A possible method to reduce adjacent-level fractures after vertebroplasty in patients with reduced bone quality could be the use of a lower modulus cement. Therefore, mixing cement with biocompatible fluids could prove useful to tailor cement properties in the operating theater.     

Calcium homeostasis influences radiological fracture healing in postmenopausal women

Introduction

Recent studies suggest that calcium and 25-[OH]-cholecalciferol represent substantial co-factors in fracture healing. However, there still seems to be no sustainable consensus regarding the influence on fracture healing patterns. In this study, the influence of calcium and vitamin D levels on fracture callus formation was prospectively analysed using pQCT scan.

Methods

94 postmenopausal females with distal radius fractures and consecutive surgery were included. Calcium, 25-[OH]-cholecalciferol, parathyroid hormone and bone-specific alkaline phosphatase levels were obtained prior surgical treatment and after 6 weeks. A pQCT scan was performed on both sites. Bone mineral density and fracture callus area were determined after detecting the outer border contour at a threshold of 280 mg/ccm. Patients received daily supplements of 1000 mg calcium and 880 IU 25-[OH]-cholecalciferol.

Results

Mean 25-[OH]-cholecalciferol level was 19.61 ± 21.87 ng/ml, mean parathyroid hormone level was 52.6 ± 58.9 ng/l and mean Ca level was 2.23 ± 0.35 mmol/l. After 6 weeks of supplementation a significant increase of calcium (p < 0.001) and 25-[OH]-cholecalciferol (p < 0.001), and a significant decrease of parathyroid hormone (p < 0.001) levels were observed. Sixth week follow-up fracture callus area correlated significantly with postoperative normal range calcium levels on the fractured site (p = 0.006). Bone mineral density correlated with age (p < 0.001), but not with calcium and 25-[OH]-cholecalciferol levels after 6 weeks. All fractures presented timely adequate callus formation.

Conclusion

Calcium and parathyroid hormone serum levels influence fracture callus area interpreted as fracture callus formation patterns. Calcium levels within physiological range accounted for highest fracture callus area. Therefore, a balanced calcium homeostasis is required for appropriate callus formation.     

Corticosteroid treatment exacerbates nephrotic syndrome in a zebrafish model of magi2a knockout

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Heterogeneity of t(4;14) in multiple myeloma. Long-term follow-up of 100 cases treated with tandem transplantation in IFM99 trials.

One hundred de novo multiple myeloma patients with t(4;14) treated with double intensive therapy according to IFM99 protocols were retrospectively analyzed. The median overall survival (OS) and event-free survival (EFS) were 41.4 and 21 months, respectively, as compared to 65 and 37 for patients included in the IFM99 trials without t(4;14) (P<10(-7)). We identified a subgroup of patients presenting at diagnosis with both low beta(2)-microglobulin <4 mg/l and high hemoglobin (Hb) >/=10 g/l (46% of the cases) with a median OS of 54.6 months and a median EFS of 26 months, respectively, which benefits from high-dose therapy (HDT); conversely patients with one or both adverse prognostic factor (high beta(2)-microglobulin and/or low Hb) had a poor outcome. The achievement of either complete response or very good partial response after HDT was also a powerful independent prognostic factor for both OS and EFS.     

Psychometric evaluation of an inpatient psychiatric care consumer satisfaction survey

This study assessed the psychometric properties of a questionnaire designed to measure consumer satisfaction with inpatient psychiatric care. To this end, 37 inpatient psychiatric units from across the United States agreed to participate. The questionnaire was completed by 1,351 individuals, or a responsible party, for an average response rate of 53%. The factor analysis identified six scales: Nonclinical Services, Psychiatric Care, Staff, Medical Outcome, Patient Education, and Program Components/Activities. The internal reliability of the scales was high to moderate (.88 to .74). Results of a stepwise regression model showed good criterion-related validity, explaining 58% of the variance in overall quality ratings. Little shrinkage in this variance occurred when the model was cross-validated. Also, differences in satisfaction levels were noted for select facility and consumer characteristics. Results are interpreted as providing support for the reliability and validity of a newly developed consumer satisfaction survey for use in evaluating inpatient psychiatric care.     

Hemostatic complications in bone marrow transplantation: a retrospective analysis of 447 patients

BACKGROUND: Hemostatic complications are not uncommon after bone marrow transplantation (BMT). However, little is known about the frequency, localization, determinants, and outcome of hemostatic events in autologous and allogeneic BMT. METHODS: Four hundred forty-seven patients (364 allogeneic, 83 autologous transplants) were evaluated retrospectively for the presence of hemostatic complications (bleeding, thrombosis, hepatic veno-occlusive disease [VOD], microangiopathic hemolytic anemia) from the start of conditioning therapy until June 2000. RESULTS: A total of 83.2% of the patients presented with at least one hemostatic complication during the investigational period. Most bleeding episodes occurred within the first 4 weeks after transplantation and were relatively mild. However, 27.1% of the patients hemorrhaged severely, generally doubling the overall mortality of the BMT recipients. Fatal gastrointestinal or intracerebral hemorrhages contributed to 1.1% of the events. Bleeding was strongly associated with prolonged thrombocytopenia and graft-versus-host disease (GVHD). Hemorrhagic cystitis may additionally have been triggered by the preceding conditioning regimens containing cyclophosphamide. Thromboembolic events occurred most frequently in allogeneic transplant recipients, for whom the incidence was 14.6%. Chronic GVHD and treatment with steroids were the major determining factors. The incidence of hepatic VOD in 4.7% of the allogeneic transplant recipients was associated with a high fatality rate. Busulfan conditioning increased the VOD risk 2.6-fold. Moderate or severe microangiopathic hemolytic anemia was associated with GVHD and occurred in 14.6% of the allogeneic transplant recipients, leading to an increased overall mortality. CONCLUSION: Hemostatic disturbances, commonly found in the course of transplantation, are associated with a high transplantation risk and closely related to thrombocytopenia and immunologic complications.