Fracture risk in monoclonal gammopathy of undetermined significance.

To assess fractures in monoclonal gammopathy of undetermined significance (MGUS), the precursor of multiple myeloma, we followed 488 Olmsted County, MN, residents with MGUS in a retrospective cohort study. There was a 2.7-fold increase in the risk of axial fractures but no increase in limb fractures. The pathophysiologic basis for the increased axial fractures should be determined. INTRODUCTION: Multiple myeloma is often preceded by monoclonal gammopathy of undetermined significance (MGUS). Fractures are common in myeloma as a result of lytic bone lesions, generalized bone loss, and elevated bone turnover from excessive cytokine production. Whether fractures are also increased in MGUS is unknown. MATERIALS AND METHODS: In a population-based retrospective cohort study, 488 Olmsted County, MN, residents with MGUS first diagnosed in 1960-1994 (52% men; mean age, 71.4 +/- 12.8 years) were followed for 3901 person-years; follow-up was censored at progression to myeloma. The relative risk of fractures was assessed by standardized incidence ratios (SIRs), and risk factors were evaluated in proportional hazards models. RESULTS AND CONCLUSIONS: Altogether, 200 patients experienced 385 fractures. Compared with expected rates in the community, statistically significant increases were seen for fractures at most axial sites, for example, vertebrae (SIR, 6.3; 95% CI, 5.2-7.5). There was a slight increase in hip (SIR, 1.6; 95% CI, 1.2-2.2) but not distal forearm fractures (SIR, 0.8; 95% CI, 0.4-1.5). The relative risk (SIR) of any axial fracture was 2.7 (95% CI, 2.3-3.1) compared with only 1.1 (95% CI, 0.9-1.4) for all limb fractures combined. In a multivariate analysis, the independent predictors of any subsequent fracture were age (hazard ratio [HR] per 10-year increase, 1.4; 95% CI, 1.2-1.6) and corticosteroid use (HR, 1.8; 95% CI, 1.2-2.6); greater weight at diagnosis (HR per 10 kg, 0.8; 95% CI, 0.8-0.9), and IgG monoclonal protein (HR, 0.7; 95% CI, 0.5-0.97) were protective. Baseline monoclonal protein level, a determinant of myeloma progression, did not predict fracture risk. Thus, the risk of axial, but not peripheral, fractures is increased among MGUS patients even before progression to myeloma. The pathophysiologic basis for this should be determined because elevated bone turnover, for example, might be treatable.     

Distinct osteogenic mechanisms of bones of distinct origins

Mammalian bones have three distinct origins (paraxial mesoderm, lateral plate mesoderm, and neural crest) and undergo two different modes of formation (intra-membranous and endochondral). Bones derived from the paraxial mesoderm and lateral plate mesoderm mainly form through the endochondral process. During this process, hypertrophic chondrocytes play a vital role in inducing both osteogenesis and angiogenesis. One of the essential osteogenic factors secreted from hypertrophic chondrocytes is Indian hedgehog (Ihh). In contrast, bones derived from the neural crest mainly form through the intramembranous pro-cess and do not require Ihh. Thus, depending on their origin, bones have distinct signaling properties, which need to be considered in the research and application of bone biology.Presented at the 18th Annual Research Meeting of the Japanese Orthopaedic Association, Kitakyushu, Japan, October 17, 2003     

Right Hepatic Lobectomy Using the Staple Technique in 101 Patients

Background Application of linear stapling devices for extrahepatic vascular control in liver surgery has been well-established. However, the technique for use of stapling devices in hepatic parenchymal transection is not well defined. Purpose To describe the safety and efficacy of our technique for use of vascular stapling devices in hepatic parenchymal transection during open right hepatic lobectomy is the purpose of this study. Methodology We reviewed our experience with 101 consecutive open right hepatic lobectomies performed by a single surgeon between January 2003 and July 2006, in which vascular staplers were utilized for the parenchymal transection phase. Results Of the 101 patients who underwent resection, 53 (52%) were female. The mean age was 58 years. Malignant disease was the indication for resection in the majority of patients (88%). Of those with cancer, 78% (69 of 89) had metastatic colorectal cancer, 6% (5 of 89) had metastatic neuroendocrine tumor, 4% (4 of 89) had hepatocellular carcinoma, 4% (4 of 89) had cholangiocarcinoma, and the remaining 8% were other metastatic cancers. Twelve patients (12%) underwent resection for hepatic adenoma or symptomatic benign disease (FNH or hemangioma). Forty-eight patients (48%) underwent a major ancillary procedure at the time of hepatic resection. Thirty-nine patients (39%) had a nonanatomic wedge resection of a left lobe lesion, 27 patients (27%) had one or more lesions treated with radiofrequency ablation (RFA), and 6 patients (6%) were treated with a synchronous bowel resection. The median total operative time was 336 min (range 155–620 min). A Pringle maneuver for temporary vascular inflow occlusion was utilized in all cases, with a median time of 9 min (range 4–17 min). Ten patients (10%) required blood transfusion during surgery or in the postoperative period. The maximum transfusion was 2 U of packed red blood cells (PRBC) in seven patients and 1 U of PRBC in three patients. The mean nadir postoperative hematocrit was 28.2. All patients with malignant disease had tumor-free margins at the completion of the procedure. The average hospital length of stay was 6.0 days. One patient (1%) developed a clinically significant bile leak requiring a postoperative endoscopic retrograde cholangiography (ERCP). No patient required reoperation. The 30 and 60-day postoperative survival was 100%. Conclusion These findings indicate that application of vascular stapling devices for parenchymal transection in major hepatic resection is a safe technique, with low transfusion requirements and minimal postoperative bile leak. The technique allows for rapid transection of the entire right hepatic lobe in under 10 min. Short video clips of the technique will be demonstrated. Presented at the 2007 American Hepato–Pancreato–Biliary Association, Las Vegas, Nevada, April 19–22, 2007 (oral presentation/video presentation).     

Treatment failure in intracranial primary germinomas

Object A radiation dose of 40–50 Gy is able to produce a cure rate of more than 90% in intracranial pure germinoma. However, many attempts have been made to reduce the dose and volume of radiation without compromising the disease control rate because of the toxicity of irradiation. This retrospective study is intended to provide the physician with an appropriate therapeutic strategy. Materials and methods We reviewed a series of 10 recurrent germinomas among 117 germinomas diagnosed histologically or clinically between 1979 and 2002. These patients involved underwent three different treatment modalities; radiation alone (N = 71), chemotherapy alone (N = 9), and combined therapy (N = 37). The 10-year overall and relapse-free survival rates were 97 and 93% in the radiation alone group, 89 and 67% in the chemotherapy alone group, and 92 and 92% in the combined therapy group, respectively. As expected, both radiation therapy and combined therapy were effective in controlling the disease. Tumor recurrence was closely related to the volume of radiation but not to the dose of radiation. If the tumor bed and craniospinal axis were fully covered, the radiation dose might be reduced. Chemotherapy alone showed earlier recurrence and a higher tumor recurrence rate. In the case of combined therapy, chemotherapy was useful in reducing the radiation dose but revealed some toxicity (death of two patients). Conclusions The investigation of a possible further dose reduction seems worthwhile. Radiation therapy alone with a dose of less than 40 Gy should be compared with ongoing chemotherapeutic protocols combined with low-dose irradiation.     

Quantification of nuclear cardiac images: The Yale approach

Conclusion  Quantification of nuclear cardiac images provides a secondary support in reading myocardial perfusion images and improves the reproducibility in the diagnosis of cardiovascular diseases. The technology for the remote Web reading of nuclear cardiac images and the quantitative data allows for an easy and secured access to patient studies without the limitations of time and space. The recent increasing interests and applications in molecular targeted imaging have opened a new field in nuclear cardiology, and absolute image quantification of the focal tracer uptake in the myocardium is exceedingly critical for the quantitative analysis of molecular targeted images.     

Ruptured pediatric posterior cerebral artery aneurysm 9 years after the onset of Kawasaki disease: a case report

CASE REPORT: A 12-year-old boy who had a history of Kawasaki disease 9 years ago experienced a subarachnoid hemorrhage by ruptured right posterior cerebral artery aneurysm. On day 1 operation, as the aneurysm was very fragile and bled easily, two intraoperative ruptures, including a very premature rupture, were encountered. As a result, a left hemiparesis especially severe in the left hand was caused by the right anterior thalamic infarction due to the occlusion of a thalamo-perforating artery arising near the neck of the aneurysm. DISCUSSION: The histopathological examination of the intraoperative excised aneurysmal dome disclosed the thickening of the endothelial inner due to the endothelial hypertrophy and the invasion of inflammatory cells. This finding of the aneurysm was partially mimicking the finding of the coronary artery of the patients with Kawasaki disease. The combination of cerebral aneurysm and Kawasaki disease has never been reported until now, and the etiology of the aneurysm of this patient is unclear.     

Seasonal variation in the content of a febrifugine and isofebrifugine alkaloid mixture in aerial parts of <Emphasis Type="Italic">Hydrangea macrophylla</Emphasis> var. <Emphasis Type="Italic">Otaksa</Emphasis>, with special reference to its antimalarial activity

Febrifugine and isofebrifugine alkaloid mixtures extracted from the leaves and buds of Hydrangea macrophylla var. Otaksa, collected during different months, in Japan, were quantified using high-performance liquid chromatography. Leaves collected during the flowering season, namely from June to August, contained 0.16–0.31 mg/g of the alkaloid mixture, whereas those collected from September to December had less than 0.03 mg/g of the mixture. However, extracts of buds harvested from October to February contained a consistently larger amount (more than 0.49 mg/g) of the alkaloids. Hot-water extracts from the leaves and buds collected during different seasons were evaluated for antimalarial activity against Plasmodium yoelii 17XL in mice. The extract of leaves collected in August demonstrated high antimalarial activity, and all mice that received the extract survived the infection. In contrast, the extract of leaves collected in December showed little activity. The extract of buds collected in December cleared parasites, but with subsequent mortality to mouse. The present results show that the amount of antimalarial agent—febrifugine and isofebrifugine mixture—in H. macrophylla var. Otaksa is both part- and season-dependent, suggesting that the choice of plant parts and their harvesting season are important factors worth considering in the pharmacological use of medicinal plants.     

<Emphasis Type="Italic">Bcl11b</Emphasis>mutations identified in murine lymphomas increase the proliferation rate of hematopoietic progenitor cells

Background  

The telomeric region of mouse chromosome 12 has previously shown frequent allelic loss in murine lymphoma. The Bcl11b gene has been identified and suggested as a candidate tumor suppressor gene within this region. In this study, we aimed to elucidate whether Bcl11b is mutated in lymphomas with allelic loss, and whether the mutations we detected conferred any effect on cell proliferation and apoptosis.