The Effect of Extensor Tendon Adhesions on Finger Motion.

PURPOSE: To quantify the amount and pattern of finger range of motion loss at the metacarpophalangeal (MCP), proximal interphalangeal (PIP), and distal interphalangeal (DIP) joints with a simulated extensor tendon adhesion at the level of the proximal phalanx or metacarpal. METHODS: In 10 cadaveric specimens, traction sutures were placed in the forearm extensor digitorum communis and flexor digitorum profundus tendons of the middle and ring fingers. Active motion was simulated by suspending weights from the traction sutures via pulleys. The angles of the MCP, PIP, and DIP joints were measured at the position of maximum flexion and extension. Extensor tendon adhesions were simulated alternately at the proximal phalanx and metacarpal levels of the middle and ring fingers, using suture anchors. Repeat measurements were taken using the same amount of force. RESULTS: There was an average total loss of flexion of 38° and of extension of 6° with a proximal phalanx adhesion, with a greater contribution of flexion loss at the PIP joint. The loss of flexion was 17° and of extension was 50° with a metacarpal adhesion, with a loss of extension mostly at the MCP joint. CONCLUSIONS: The results of this study identified clear patterns of motion loss that are associated with isolated simulated adhesions in different locations along the extensor mechanism. The greatest motion loss occurred at the joint immediately distal to the simulated adhesion. CLINICAL RELEVANCE: Although extrapolation of these findings to clinical relevance remains unclear, the ability to predict the level of adhesion by the pattern of motion restriction may allow for a targeted tenolysis procedure. This would reduce the amount of soft tissue dissection required, which in turn, could be expected to reduce the degree of repeat adhesion formation.

The effect of lunate morphology on the 3-dimensional kinematics of the carpus.

PURPOSE: To assess carpal kinematics in various ranges of motion in 3 dimensions with respect to lunate morphology. METHODS: Eight cadaveric wrists (4 type I lunates, 4 type II lunates) were mounted into a customized platform that allowed controlled motion with 6 degrees of freedom. The wrists were moved through flexion-extension (15°-15°) and radioulnar deviation (RUD; 20°-20°). The relative motion of the radius, carpus, and third metacarpal were recorded using optical motion capture methods. RESULTS: Clear patterns of carpal motion were identified. Significantly greater motion occurred at the radiocarpal joint during flexion-extension of type I wrist than a type II wrist. The relative contributions of the midcarpal and radiocarpal articulations to movement of the wrist differed between the radial, the central, and the ulnar columns. During wrist flexion and extension, these contributions were determined by the lunate morphology, whereas during RUD, they were determined by the direction of wrist motion. The midcarpal articulations were relatively restricted during flexion and extension of a type II wrist. However, during RUD, the midcarpal joint of the central column became the dominant articulation. CONCLUSIONS: This study describes the effect of lunate morphology on 3-dimensional carpal kinematics during wrist flexion and extension. Despite the limited size of the motion arcs tested, the results represent an advance on the current understanding of this topic. CLINICAL RELEVANCE: Differences in carpal kinematics may explain the effect of lunate morphology on pathological changes within the carpus. Differences in carpal kinematics due to lunate morphology may have implications for the management of certain wrist conditions.

Association between screw prominence and vascular complications after clavicle fixation.

CONTEXT: Fixation of clavicle fractures has become more common to prevent symptomatic malunion and nonunion. The subclavian and axillary vessels are in close proximity to the medial two-thirds of the clavicle, placing them at risk from prominent metalware. Injury to these major vessels has the potential to be life or limb-threatening. Despite this anatomical risk, iatrogenic vascular injury associated with clavicle fixation is rare. AIMS: The aim of this study was to identify risk factors associated with modern fixation techniques in reported cases of vascular injury after clavicle fixation. MATERIALS AND METHODS: A literature search was performed, and all identified cases of iatrogenic vascular injury associated with prominent clavicle fixation were analyzed. Clinical details, the total length of the prominent screws and the distance that they protruded from the far cortex were recorded. RESULTS: Five cases were identified; there were four pseudoaneurysms and one arteriovenous fistula. The total length of the offending screw was identifiable in two cases, measuring 26 and 30 mm. The length of screw prominence was identifiable in 3 cases (8, 10 and 10 mm). The pseudoaneurysms presented at 2-10 years following clavicle fixation. Three of these cases developed limb-threatening ischemia. CONCLUSIONS: Vascular complications associated with clavicle fixation are uncommon but potentially limb-threatening. Several associated factors are identified. The authors provide a number of detailed recommendations aimed at preventing these complications.

Effect of glenoid cementation on total shoulder arthroplasty for degenerative arthritis of the shoulder: a review of the New Zealand National Joint Registry.

BACKGROUND: Despite the lack of literature showing improved results compared with cemented designs, uncemented glenoid components are still commonly used in total shoulder arthroplasty (TSA). Most studies comparing cemented with uncemented glenoids involve small numbers or include patients with inflammatory arthritis. METHODS: New Zealand National Joint Registry data was used to compare the outcomes of uncemented and cemented glenoids in TSA performed for degenerative arthritis. Measured variables were the revision rate and the Oxford Shoulder Score (OSS). RESULTS: Data were retrieved on 1596 patients, with a mean follow-up 3.5 years (range 2-10.7 years), 1065 of whom had a cemented glenoid. There were no significant differences in any preoperative factors between the 2 groups. The revision rate for uncemented glenoids was 4.4 times higher than for cemented glenoids (1.92 vs. 0.44 revisions per 100 component-years, P < .001). Age <55 years was an independent risk factor for revision (P < .001). The most common reason for revision was rotator cuff wear (35.5%) in the uncemented glenoids and loosening (36.3%) in the cemented glenoids. The difference in the mean OSS between the 2 groups was less than 1 point at 6 months (P = .109) and at 5 years (P = .377). CONCLUSION: Uncemented glenoids had a markedly higher revision rate. Patients aged <55 years have the highest revision rate regardless of glenoid fixation method. The higher revision rate in the uncemented glenoid group persisted when the effect of young age was corrected for. There was no clinically or statistically significant difference in the OSS results for clinical outcome between the two groups. LEVEL OF EVIDENCE: Level III, retrospective cohort, treatment study.

Characterization and potential uses of rabbit polyclonal antibodies against human plasma lecithin-cholesterol acyltransferase.

Familial and secondary deficiency of plasma lecithin-cholesterol acyltransferase (LCAT) produce circulating lipoprotein particles with gross structural and compositional abnormalities; these have adverse effects on a variety of cellular functions. Factors affecting hepatic synthesis and secretion of this plasma enzyme are largely unknown but, potentially, some of them can be investigated with monospecific antibodies. In the present study, enzymically active LCAT was purified 40,000-fold from human plasma and then used to raise polyclonal antibodies in New Zealand White rabbits. Addition of this antiserum (1 microliter) to human plasma (25 microlitres) completely inhibited LCAT activity, although it was less effective against plasma from other species. The antibodies appeared to be monospecific to plasma LCAT. They gave a single precipitin arc by crossed immunoelectrophoresis, while immunodiffusion established that there was no cross-reactivity with several apolipoproteins or with serum albumin. Moreover, the antiserum was successfully used to detect LCAT in normal human plasma by Laurell rocket immunoelectrophoresis. By contrast, Western blotting of plasma proteins using whole LCAT antiserum was largely unsuccessful because of high background staining, although this could be substantially reduced by use of an IgG fraction. However, the whole antiserum readily immunoprecipitated LCAT secreted into the culture medium of HepG2 cells, a human hepatoblastoma cell line, pre-labelled with [35S]methionine, the [35S]-labelled LCAT appearing as a narrow 65-kDa protein band by electrophoresis and fluorography. We conclude that polyclonal antibodies may be an important tool to investigate the characteristics and underlying mechanisms of secondary LCAT deficiencies, including those associated with hepatic cirrhosis and schistosomiasis.

Characterization and potential uses of rabbit polyclonal antibodies against human plasma lecithin-cholesterol acyltransferase

Familial and secondary deficiency of plasma lecithin-cholesterol acyltransferase (LCAT) produce circulating lipoprotein particles with gross structural and compositional abnormalities; these have adverse effects on a variety of cellular functions. Factors affecting hepatic synthesis and secretion of this plasma enzyme are largely unknown but, potentially, some of them can be investigated with monospecific antibodies. In the present study, enzymically active LCAT was purified 40,000-fold from human plasma and then used to raise polyclonal antibodies in New Zealand White rabbits. Addition of this antiserum (1 mul) to human plasma (25 mul) completely inhibited LCAT activity, although it was less effective against plasma from other species. The antibodies appeared to be monospecific to plasma LCAT. They gave a single precipitin arc by crossed immunoelectrophoresis, while immunodiffusion established that there was no cross-reactivity with several apolipoproteins or with serum albumin. Moreover, the antiserum was successfully used to detect LCAT in normal human plasma by Laurell rocket immunoelectrophoresis. By contrast, Western blotting of plasma proteins using whole LCAT antiserum was largely unsuccessful because of high background staining, although this could be substantially reduced by use of an IgG fraction. However, the whole antiserum readily immunoprecipitated LCAT secreted into the culture medium of HepG2 cells, a human hepatoblastoma cell line, pre-labelled with [35S]methionine, the [(35)S]-labelled LCAT appearing as a narrow 65-kDa protein band by electrophoresis and fluorography. We conclude that polyclonal antibodies may be an important tool to investigate the characteristics and underlying mechanisms of secondary LCAT deficiencies, including those associated with hepatic cirrhosis and schistosomiasis.

The contribution of proinsulin and des-31,32 proinsulin to the hyperinsulinemia of diabetic and nondiabetic cirrhotic patients.

We used specific, monoclonal antibody-based, two-site immunoradiometric assays to test the hypothesis that serum levels of proinsulin and des-31,32 proinsulin would be increased in cirrhosis, particularly in those with overt diabetes. A 75-g oral glucose tolerance test was performed after an overnight fast in eight cirrhotic patients with diabetes (fasting blood glucose, 7.8 +/- 2.2 [SE] mmol/L), seven nondiabetic cirrhotic patients, and eight normal control subjects. Fasting serum immunoreactive insulin levels were approximately six times higher in cirrhotics than in controls, but were not different between diabetic and nondiabetic cirrhotic patients. After oral glucose, the incremental area under the serum insulin concentration curve was 3,475 +/- 1,009 pmol.L-1.h in nondiabetic cirrhotic patients, significantly higher than in controls (761 +/- 48, P < .001) or diabetic cirrhotic patients (881 +/- 186, P < .05). Fasting serum proinsulin levels in diabetic cirrhotic patients (24.0 +/- 5.7 pmol/L) were higher than in controls (2.3 +/- .05, P < .001) or nondiabetic cirrhotic patients (4.4 +/- 0.8, P < .005). Fasting serum levels of des-31,32 proinsulin were also much higher in diabetic cirrhotic patients than in nondiabetic cirrhotic patients or controls (P < .02 and P < .005, respectively). Fasting proinsulin plus des-31,32 proinsulin constituted 12.5% +/- 1.4% of serum immunoreactive insulin in diabetic cirrhotics, higher than in nondiabetic cirrhotics (3.7% +/- 0.5%, P < .001) and normal controls (7.8% +/- 1.5%, P = .035).(ABSTRACT TRUNCATED AT 250 WORDS)

Lipid metabolism and substrate oxidation during intravenous fructose administration in cirrhosis.

We used isotope dilution techniques (constant intravenous [IV] infusion of 2-3H-glycerol and 1-14C-palmitate) and indirect calorimetry to measure lipid kinetics and substrate oxidation rates during IV fructose administration at 200 and then 500 mg/kg/h in eight cirrhotic patients and seven normal control subjects. Fasting plasma glucose, glycerol, and glycerol appearance rate (Ra) were similar in both groups, but insulin levels were fourfold higher in cirrhotics (P < .01). Fasting serum nonesterified fatty acid (NEFA) levels (cirrhotics, 869 +/- 124, controls, 717 +/- 90 mumol/L) and NEFA Ra (7.1 +/- 0.8 v 5.5 +/- 0.9 mumol/min/kg) were higher in cirrhotics, but the differences were not significant. Plasma fructose was similar in both groups at both fructose infusion rates. Fructose appeared to stimulate insulin secretion. With i.v. fructose, serum NEFA levels decreased, reaching similar low levels when 500 mg/kg/h was infused, due to a reduction in NEFA Ra and an increase in the NEFA metabolic clearance rate (MCR). Glycerol levels showed little change. As glycerol Ra decreased by less than 20% in both groups, the decrease in serum NEFA was primarily due to enhanced reesterification of fatty acids both within adipose tissue (preventing their release) and in other tissues (enhancing their removal from plasma). Although total fructose utilization was normal in cirrhotics, they oxidized more of the infused fructose; nonoxidative disposal was reduced (first step, 242 +/- 12 v 318 +/- 16 mg/kg in 2 hours, P < .002; second step, 657 +/- 32 v 786 +/- 21 mg/kg in 2 hours, P < .005). Although tissue fructose uptake is insulin-independent, insulin resistance in cirrhosis may influence the intracellular metabolism of fructose.

Lipid metabolism and insulin resistance in cirrhosis.

Fasting patients with cirrhosis have high plasma non-esterified fatty acids, and a high turnover and oxidation of non-esterified fatty acids, despite high plasma insulin levels. To assess whether increased non-esterified fatty acid availability impairs utilisation of circulating glucose, and contributes to the insulin insensitivity in cirrhosis, we measured glucose, non-esterified fatty acid and glycerol flux rates, in patients with cirrhosis and controls, in the basal state and during a 0.05 U.kg-1.h-1 hyperinsulinaemic euglycaemic clamp. After an overnight fast, basal blood glucose and glucose turnover were similar in both groups. Basal plasma glycerol and non-esterified fatty acid levels were higher in patients with cirrhosis as were 1-14C-nonesterified fatty acid turnover (4.48 +/- 0.53 vs 2.54 +/- 0.45 mumol.kg-1.min-1, p < 0.05) and 2H5-glycerol turnover (3.27 +/- 0.34 vs 2.24 +/- 0.15 mumol.kg-1.min-1, p < 0.05), indicating increased lipolysis in patients with cirrhosis; metabolic clearance rate of non-esterified fatty acids and glycerol were similar in both groups, suggesting no impairment of tissue uptake in patients. The euglycaemic clamp showed patients with cirrhosis to be markedly insensitive to insulin. The glucose metabolic clearance rate increased during the clamp in controls (p < 0.005) but not in patients with cirrhosis, indicating that infused insulin had little or no effect on glucose disposal in the patients. Clamp glucose turnover in controls was higher than in the basal state (p < 0.001); in patients with cirrhosis it was lower. The profound insulin insensitivity and the clamping of blood glucose below fasting levels explains the fall in glucose turnover in patients with cirrhosis during the clamp. In both groups serum non-esterified fatty acid and glycerol levels, and their appearance rates, were suppressed during the clamp, but levels remained significantly higher in patients with cirrhosis (non-esterified fatty acids, 0.20 +/- 0.4 vs 0.10 +/- 0.01 mmol/l, p < 0.05; glycerol 74 +/- 9 vs 46 +/- 4 mumol/l, p < 0.05). This, with the high basal non-esterified fatty acid and glycerol levels seen in patients with cirrhosis, despite high insulin levels, suggests resistance of adipose tissue lipolysis to insulin. There was no correlation between glucose infusion requirements and non-esterified fatty acid turnover. The normal turnover of blood glucose in fasting patients with cirrhosis, despite increased non-esterified fatty acid turnover, suggests utilisation mainly by tissues with an obligatory requirement for glucose, which may be similar in patients with cirrhosis and controls.(ABSTRACT TRUNCATED AT 400 WORDS)

Antiestrogenic potency of toremifene and tamoxifen in postmenopausal women.

In this nonblinded, controlled multicenter trial, postmenopausal women were randomly assigned to receive graded doses of toremifene and tamoxifen or no antiestrogen to assess dose-response levels and evaluation methodology. For standardization, transdermal estradiol (Estraderm-Ciba Geigy) was applied to all women for 38 days. The antiestrogens were added on days 29-38. For control and all treatment groups, there were no significant changes in serum chemistries or serum hormone levels, nor were there differences in adverse effects. The use of continuous estradiol precluded any meaningful assessment of the estrogenicity of tamoxifen or toremifene. As measured by vaginal superficial cytologic cell count changes, the antiestrogenic activity of toremifene doses ranging from 20 to 200 mg/day could not be distinguished from that of 20 mg/day of tamoxifen, the clinically recommended dose in North America.

Insulin sensitivity, insulin secretion and glucose effectiveness in diabetic and non-diabetic cirrhotic patients.

In cirrhotic patients with normal fasting glucose levels both insulin insensitivity and a blunted early insulin response to oral glucose are important determinants of the degree of intolerance to oral glucose. It is not known whether the ability of hyperglycaemia per se to enhance glucose disposal (glucose effectiveness) is also impaired. It is also unclear whether overt diabetes is due to: (1) more marked insulin insensitivity; (2) impaired insulin secretion; (3) reduced glucose effectiveness; or (4) a combination of these mechanisms. We used the "minimal model" to analyse the results of a 3-h intravenous glucose tolerance test to assess glucose effectiveness, insulin sensitivity and insulin responses in 12 non-diabetic cirrhotic patients, 8 diabetic cirrhotic patients and 10 normal control subjects. Fasting blood glucose levels were 4.8 +/- 0.2, 7.5 +/- 0.6 and 4.7 +/- 0.1 mmol/l, respectively. Fasting insulin and C-peptide levels were higher in both cirrhotic patient groups compared with control subjects. The glucose clearance between 6 and 19 min after i.v. glucose was lower in both cirrhotic groups (non-diabetic, 1.56 +/- 0.14, diabetic, 0.76 +/- 0.06, control subjects, 2.49 +/- 0.16 min-1%, both p < 0.001 vs control subjects). Serum insulin peaked at 3 and 23 min in the non-diabetic cirrhotic patients and control subjects; both peaks were higher in the non-diabetic cirrhotic patients and showed a delayed return to basal levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Randomized comparison of cisplatin plus epirubicin or doxorubicin for advanced epithelial ovarian carcinoma. A multicenter trial.

Stage III and IV epithelial ovarian cancer patients were prospectively randomized to receive eight courses of 60 mg/m2 of cisplatin plus either 75 mg/m2 of epirubicin (62 patients) or 60 mg/m2 of doxorubicin (54 patients). Clinical response rates for cisplatin/epirubicin of 42% [15% complete response (CR) and 27% partial response (PR)] and for cisplatin/doxorubicin of 55% (24% CR and 31% PR) were not statistically different (p = 0.14). The negative second look rate was 35% (10/29) for cisplatin/doxorubicin and 17% (5/30) for cisplatin/epirubicin (p = 0.12). The progression-free interval for cisplatin/epirubicin (13 months) was not statistically different (p = 0.09) from that for cisplatin/doxorubicin (19 months). The median survivals for cisplatin/epirubicin (756 days) and cisplatin/doxorubicin (739 days) were similar (p = 0.70). Cardiotoxicity was greater for the cisplatin/doxorubicin group (p = 0.0003). With similar survival and less cardiotoxicity, the cisplatin/epirubicin regimen had the more favorable therapeutic index.

Plasma lipid and lipoprotein response to carbohydrate feeding in cirrhotic patients.

Serum lipids and lipoproteins, and glucose and insulin, were measured after an overnight fast, and during 3 days of a eucaloric diet rich in carbohydrate, in 15 patients with cirrhosis and seven normal subjects. Following the high-carbohydrate diet triglyceride rose in all groups but the increase in cirrhotics was lower than in normals. In normals and in cirrhotics with good liver function most of the triglyceride increment was carried in VLDL; in cirrhotics with poor liver function only 31% of the increment was found in VLDL, and 56% in triglyceride-rich LDL. In an earlier study on fat feeding, our cirrhotic patients with poor liver function had an impaired chylomicron and VLDL response; they also carried most of the triglyceride increment in triglyceride-rich LDL. The markedly impaired response of triglyceride-rich lipoproteins to both carbohydrate and fat feeding suggests that sick cirrhotics may have a problem with storage of dietary energy and that this contributes to loss of their adipose tissue.

Severe intrahepatic cholestasis and rapidly progressive renal failure in a patient with immunocyte-related amyloidosis.

A woman developed severe cholestatic jaundice and progressive renal failure secondary to amyloid deposition. The amyloid protein was of AL type, consisting of IgG-related kappa chains. This form of amyloidosis is classified as immunocyte-related, not associated with myeloma.

Erythrocyte echinocytosis in liver disease. Role of abnormal plasma high density lipoproteins.

Echinocytes were frequently found in patients with liver disease when their blood was examined in wet films, but rarely detected in dried, stained smears. When normal erythrocytes (discocytes) were incubated with physiologic concentrations of the abnormal high density lipoproteins (HDL) from some jaundiced patients, echinocytosis developed within seconds. Other plasma fractions were not echinocytogenic. There was a close correlation between the number of echinocytes found in vivo and the ability of the corresponding HDL to induce discocyte-echinocyte transformation. On incubation with normal HDL, echinocytes generated in vitro rapidly reverted to a normal shape, and echinocytes from patients showed a similar trend. Echinocytosis occurred without change in membrane cholesterol content, as did its reversal, and was not caused by membrane uptake of lysolecithin or bile acids. Abnormal, echinocytogenic HDL showed saturable binding to approximately 5,000 sites per normal erythrocyte with an association constant of 10(8) M-1. Nonechinocytogenic patient HDL and normal HDL showed only nonsaturable binding. Several minor components of electrophoretically separated erythrocyte membrane proteins bound the abnormal HDL; pretreatment of the cells with trypsin or pronase reduced or eliminated binding. Echinocytosis by abnormal HDL required receptor occupancy, rather than transfer of constituents to or from the membrane, because cells reversibly prefixed in the discoid shape by wheat germ agglutinin, and then exposed to abnormal HDL, did not become echinocytes when the HDL and lectin were successively removed. Binding did not cause dephosphorylation of spectrin. We conclude that the echinocytes of liver disease are generated from discocytes by abnormal HDL, and we infer that the shape change is mediated by cell-surface receptors for abnormal HDL molecules.

Extramedullary transformation of chronic myeloid leukaemia with a unique chromosome pattern.

A case of extramedullary myeloblastic transformation of chronic myeloid leukaemia is reported. This was characterised by an unusual clinical and haematological course and showed a unique cytogenetic pattern.

Abnormal high density lipoproteins from patients with liver disease regulate cholesterol metabolism in cultured human skin fibroblasts.

Apolipoprotein B (apoB) of plasma low density lipoproteins (LDL) binds to high affinity receptors on many cell types. A minor subclass of high density lipoproteins (HDL), termed HDL1, which contains apoE but lacks apoB, binds to the same receptor. Bound lipoproteins are engulfed, degraded, and regulate intracellular cholesterol metabolism and receptor activity. The HDL of many patients with liver disease is rich in apoE. We tested the hypothesis that such patient HDL would reduce LDL binding and would themselves regulate cellular cholesterol metabolism. Normal HDL had little effect on binding, uptake, and degradation of 125I-labeled LDL by cultured human skin fibroblasts. Patient HDL (d 1.063-1.21 g/ml) inhibited these processes, and in 15 of the 25 samples studied there was more than 50% inhibition at 125I-labeled LDL and HDL protein concentrations of 10 micrograms/ml and 25 micrograms/ml, respectively. There was a significant negative correlation between the percentage of 125I-labeled LDL bound and the apoE content of the competing HDL (r = -0.54, P less than 0.01). Patient 125I-labeled HDL was also taken up and degraded by the fibroblasts, apparently through the LDL-receptor pathway, stimulated cellular cholesterol esterification, increased cell cholesteryl ester content, and suppressed cholesterol synthesis and receptor activity. We conclude that LDL catabolism by the receptor-mediated pathway may be impaired in liver disease and that patient HDL may deliver cholesterol to cells.