Marshall R. Urist, 1914–2001

This biographical sketch of Marshall R. Urist corresponds to the historic texts, The Classic: Bone Morphogenetic Protein, available at DOI  10.1007/s11999-009-1068-3; The Classic: A Morphogenetic Matrix for Differentiation of Cartilage in Tissue Culture, available at DOI  10.1007/s11999-009-1069-2; and The Classic: A Morphogenetic Matrix for Differentiation of Bone Tissue, available at DOI  10.1007/s11999-009-1070-9.     

Prognostic significance of persistent mediastinal metastasis following induction therapy in large (> or = 2cm) N2 or N3 non-small cell lung cancer

Objective: It is controversial whether or not surgery is beneficial for patients with non-small cell lung cancer accompanied by persistent lymph node metastasis in the mediastinum following induction therapy. We have therefore conducted a retrospective study to assess this issue Methods: Eligibility criteria were defined as follows: 1) the period of treatment was between January 1991 and April 1998, 2) the clinical stages were IIIA (N2) or IIIB (N3) with large lymph nodes (> or = 2 cm), 3) induction therapy had been administered, 4) tumor was resected completely, 5) at least one mediastinal lymph node had necrosis or scar if the pathological N status was p-N0 or p-N1 and 6) the p-stage was not IV. Dichotomous variables included the radiographic response of the tumor, the T status, and the N status. Results: Thirty-nine patients were eligible. There were 29 males and 10 females aged from 27 to 74 years, and involved 20 cases of adenocarcinoma. The pathological N status was as follows: p-N0 in 18 patients, p-N1 in 3, p-N2 in 16, and p-N3 in the other 2. In overall survival, the median survival time (MST) was 34 months and the actuarial 5-year-survival rate (5-YSR) was 28%. The group of patients with either N0 or N1 (n-21) had a 71-month MST and a 54% 5-YSR, and the group of patients with either N2 or N3 (n=18) had a 13-month MST and a 5-YSR of 0% (p<0.0001). On multivariate analysis, the pathological N factor was confirmed as an independently significant. Conclusions: Our retrospective study found that the survival rate of patients with persistent mediastinal nodal metastasis was very poor. A prospective study is needed to investigate whether or not surgery is beneficial for these patients.     

Giant cell tumor of the rib

We experienced a rare case of giant cell tumor (GCT) arising in the 5^th rib involving the 5^th vertebral body and transverse process. A 57-year-old man presented with a well-defined mass in the left thoracic cavity on chest x ray examination. Chest computed tomography showed a heterogeneous 7cm-diameter mass originating in the posterior segment of the left 5^th rib. The tumor had spread to the 5^th thoracic vertebra destroying the left half of the body and transverse process. Magnetic resonance imaging showed a heterogeneous-intensity mass involving the 4^th to 6^th ribs. A radical excision of the tumor followed by a 50 Gy radiotherapy was performed after embolization of the feeding arteries. The pathological diagnosis was a GCT. The patient remains well without evidence of recurrence for 6 years following surgery. The present case is only the 14^th case of GCT arising in the rib to have been reported in Japan.     

Lateral J-plate fixation in comminuted intercondylar fracture of the humerus

BACKGROUND: Anatomical reduction and rigid internal fixation of the articular surface is key for functional recovery in types C2 and C3 (AO classification) fractures of the distal humerus. Since these fractures are associated with varying degrees of comminution in both the medial and lateral columns, rigid fixation of both columns is necessary for early mobilization of the elbow joint. METHODS: We performed a prospective study of the lateral J-plating technique in 17 patients with comminuted intercondylar fracture of the humerus. There were 9 type C2 and 8 type C3 fractures by the AO/ASIF classification. A lateral J-plate was applied along the lateral aspect of lateral column, and the lag screws were inserted into the medial column through the plate hole. A medial reconstruction plate was selectively applied on the posterior aspect of medial column. RESULTS: All fractures united by 18.7 weeks on average (range 10-28 weeks). Seven patients presented with limitation of motion of the elbow joint, and 5 of them underwent arthrolysis and excision of the heterotopic ossification. The final range of motion of the elbow joint was flexion contracture of 16 deg to further flexion of 121 deg on average. Functional results were excellent in 9 cases, good in 6, fair in 1, and poor in 1 according to Murray's criteria. CONCLUSION: Lateral J-plating with selective augmentation of the medial column provided sufficient rigidity and good clinical results.     

pQCT bone strength index may serve as a better predictor than bone mineral density for long bone breaking strength

Bone mineral density (BMD) is commonly used to predict osteoporotic fracture risk without considering the geometry of the bone. However, geometric parameters are also important in determination of bone strength. An index including both material and geometric properties may be therefore more relevant in prediction of fracture risk. We studied the correlation between parameters measured by noninvasive peripheral quantitative computed tomography (pQCT) and bone bending strength of the diaphysis of 45 fresh goat humeri and 27 femora. Multislice pQCT was used for measuring volumetric diaphyseal cortical BMD, total BMD, diaphyseal and cortical cross-sectional area (CSA), and cross-sectional moment of inertia (CSMI) and their derived bone strength indices (BSIs), including BSI_CSMI (cortical BMD × CSMI) and BSI_CSA (cortical BMD × cortical CSA). Conventional dual-energy absorptiometry (DXA) was also conducted to measure areal BMD of diaphysis for comparison. Ultimate fracture load was obtained via three-point bending test. Results showed that for femora, fracture load was correlated better with BSI_CSA (r = 0.697, P 0.001) than cortical BMD (r = 0.304, P 0.05) and total BMD (r = 0.387, P 0.05) measured using pQCT and areal BMD (r = 0.612, P 0.001) measured using DXA. For humeri, fracture load was also correlated with BSI_CSA (r = 0.579, P 0.001) but not with other pQCT parameters including cortical BMD and total BMD (r = 0.282 and 0.305, respectively; P 0.05, both). The best correlation was found with areal BMD measured by DXA (r = 0.760, P 0.001). In conclusion, pQCT noninvasive BSI_CSA derived from cortical BMD (material) and its cortical CSA (bone geometry or distribution) may serve as an important noninvasive index for predicting long bone bending strength. The bending strength was also predicted by bone mass (areal BMD) measured by DXA, an integration of bone mineral and geometry. Further clinical studies are needed to validate the predictive value of BSI in long bone osteoporotic fracture.     

Impact of a Clinical Pathway and Standardization of Treatment for Acute Appendicitis

Purpose: Acute appendicitis is one of the most common surgical diseases. Simple and precise guidelines for treating acute appendicitis are necessary for improving the treatment outcome of this disease. The purpose of this study was to determine the impact of a clinical pathway and standardization of treatment for acute appendicitis at our hospital. Methods: The clinical pathway and standardization of treatment for acute appendicitis were introduced to our hospital in January 2000. We compared the length of hospitalization, postoperative stay, hospital costs, and operation time during the years before and the years after their introduction. Results: There was no significant difference in the clinical characteristics of the 73 patients in the control group and the 112 patients in the pathway group. There were 6 (8.2%) and 24 (21.4%) cases of perforated appendicitis in the respective groups. The mean length of hospitalization (P < 0.001), postoperative stay (P < 0.001), and hospital costs (P < 0.01) were significantly less in the patients in the pathway group who underwent surgery. Conclusion: Our clinical pathway and standardization of treatment for acute appendicitis proved effective for treating patients with acute appendicitis and minimizing costs without compromising patient care. Received: February 19, 2002 / Accepted: November 19, 2002 Reprint requests to: K. Takegami (address 2)     

Two-dimensional gel electrophoresis of synovial fluid: method for detecting candidate protein markers for osteoarthritis

Synovial fluid (SF) is a dynamic reservoir for proteins originating from serum, synovial tissue, and cartilage. The composition of the SF proteome may reflect the pathophysiological conditions affecting the circulatory system and cartilage. Our long-term goal is to identify reliable protein markers for osteoarthritis (OA) in SF. We first evaluated the pattern of SF proteins on two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) as a function of protein loading, pH range for isoelectric focusing, and concentration of acrylamide in SDS-PAGE. Removal of albumin and -globulins from the samples did not improve the detection of protein spots on 2D-PAGE. The repeatability of protein spot intensity was tested by triplicate 2D-PAGE of a given sample; these experiments showed low intrasample variability (correlation coefficients 0.89–0.95). Differences between multiple samples were tested by comparing the 2D-PAGE of four samples. These experiments showed slightly greater variation between samples (correlation coefficients 0.85–0.93) and a number of differentially expressed proteins. The intensity of 18 protein spots differed more than fivefold, and the intensity of nine protein spots differed more than 100-fold. These results show that 2D-PAGE can be used under standard conditions to screen SF samples and identify a small subset of proteins in SF that are potential markers associated with OA.     

Epidemiology of surgically treated gastric cancer in the United States, 1988-2000

The incidence of gastric cancer and the need for subsequent surgery has been decreasing in the United States. However, very few population-based studies on the magnitude of these changes are available. The objective of the present study was to characterize temporal trends in the use of gastric resection in the treatment of gastric cancer. Patients with a primary diagnosis code for gastric cancer (N = 105,887) and a procedure code for gastric resection (N = 23,690) in the Nationwide Inpatient Sample for 1988–2000 were included. The Nationwide Inpatient Sample represents a 20% stratified random sample representative of all United States hospitals. Outcome variables included the overall incidence, in-hospital mortality rate, and length of stay. Rates of surgery are shown as the number of cases per 100,000 hospital discharges. Hospital volume was defined as follows: low volume (1 to 4 cases per year), medium volume (5 to 8 cases per year), and high volume (9 or more cases per year). Rates of gastric resection have shown a 20% decline from 30 cases per 100,000 (1988-1989) to 24 cases per 100,000 (1999-2000) (P = 0.001). In-hospital mortality has not changed over the 13-year period and remains at 7.4%. There was significant variation in mortality across hospitals, with very low-volume centers having an 8.9% mortality rate, whereas very high-volume centers had a 6.4% mortality rate (P < 0.001). The market share of gastric resections performed at high-volume centers increased a small amount from 43% (1988–1989) to 48% (1999-2000) (P = 0.023). Over the 13-year period, length of stay decreased from 15 days (interquartile range [IQR] 11–23) in 1988 to 11 days (interquartile range [IQR] 8–16) in 2000 (P < 0.001). Rates of gastric resection for cancer have shown a modest decline over the past 13 years in the United States. Although the length of stay for these patients has decreased, no significant changes to in-hospital mortality have occurred. Given the declining rates of gastric cancer surgery, and the superior outcomes at high-volume centers, regionalization of care may improve mortality rates for this high-risk surgical procedure. Presented at the Forty-Fourth Annual Meeting of The Society for Surgery of the Alimentary Tract, Orlando, Florida, May 18-22, 2003 (poster presentation).     

Linkage guide for rotational alignment during total knee arthroplasty

A linkage guide was devised for use in conjunction with knee arthroplasty instruments to achieve proper component rotation. The femoral component was rotationally aligned to the surgical epicondylar axis using one guide. The other guides were used after all bone surfaces were cut and soft tissue balancing was completed. A Kirschner wire was guided into the proximal tibial aspect parallel to the sagittal plane of the femoral component with the patella in its normal position and the knee in full extension. The wire was used as a reference to determine tibial component rotation. The relative rotational alignment of 21 knees in 19 patients who had undergone cruciate-retaining total knee arthroplasty utilizing this guide was assessed using the modified Eckhoff method. The results of radiographic analysis were compared with those in a control group of 25 knees where the guide was not employed. The external rotation of the femoral component relative to the tibial component was 1.3° ± 2.0° (mean ± SD) in the guided group and 1.1° ± 4.4° in the control group. The relative rotational angle was significantly more consistent using the guide. Implant malrotation can be reduced using our technique.     

Influence of spinal cord compression on the C3–C4 propriospinal neurons in cats

The C3-C4 propriospinal neurons (PNs) transmit motor signals to forelimb motoneurons. Stem axons of the PNs bifurcate in the same segments and send ascending axons to the lateral reticular nucleus (LRN) as well as descending axons to the cervical motor nucleus. After laminectomy of decerebrated cats, ascending axons were stimulated by tungsten electrodes placed in the LRN. The N1 descending incoming volleys via axon reflexes with a latency of approximately 1.5 ms (N1 potential) were recorded in the forelimb motoneuron pools at C8 segment. We compressed the spinal cord at C3 or C6 segment by 6 x 5 mm plastic material and analyzed amplitudes of the N1 potentials at C8 motoneuron pools. After spinal compression step by step until 3000 microm from the surface for 30 min at the C3 segment, the amplitude of N1 potentials decreased to approximately 39.7% of the control. On the other hand, the amplitude of N1 potentials changed little after the same compression of the C6 segment. The N1 potentials during compression of the C3 segment did not recover to the initial amplitude of 63.5% after decompression. It is concluded that activities of axons at C3 segment are more sensitive than those at C6 to compression of the spinal cord. We discuss the properties of the bifurcation of the stem axons and the central spinal cord injury.