Experimental exercise-induced ischemia: drug therapy can eliminate regional dysfunction and oxygen supply-demand imbalance

The purpose of this study was to test the hypothesis that moderately severe exercise-induced regional myocardial ischemia can be prevented by combined pharmacologic intervention. Eight chronically instrumented dogs were studied using an ameroid constrictor to produce critical stenosis of the left circumflex coronary artery. The dogs were studied during steady state treadmill exercise that induced regional myocardial dysfunction (reduced systolic wall thickening; sonomicrometers) and ischemia (reduced subendocardial blood flow; microspheres). During a control exercise run, wall thickening in the ischemic posterior wall decreased from 21.4 to 13.3% whereas subendocardial blood flow failed to increase normally (36% of that in the normal zone). In the control anterior wall, both wall thickening and subendocardial blood flow increased significantly during the control run. Wall thickness-left ventricular pressure loop areas were calculated as an index of regional work; this index increased abruptly with the onset of exercise in both regions but became significantly depressed in the ischemic region during the steady state exercise. Therapy with a combination of atenolol (0.3 mg/kg body weight orally), diltiazem (0.3 mg/kg intravenously) and isosorbide dinitrate (2.0 mg/kg orally) effectively prevented regional myocardial ischemia and regional dysfunction. After drug therapy, wall thickening in the posterior wall increased from 17.3% at rest to 18.8% during exercise, and the regional transmural blood flow pattern was markedly improved. The initial overshoot of the regional work index during exercise was blunted by the drug therapy, and at steady state no differences between the ischemic and control regions were detected. Thus, combined drug therapy can eliminate exercise-induced regional myocardial ischemic dysfunction and appears to normalize the oxygen supply-demand imbalance.     

Falls in the institutionalized elderly in Japan

Falls can be considered a vital factor in impeding successful aging in the elderly. The purpose of the study is to know rates of falls per year among the elderly, to observe the situations when falls occurred, and to clarify the association of falls with physical deterioration. The survey was carried out in 1406 residents aged 65 and over of the Tokyo Metropolitan Home for the Elderly in 1982. The rate of subjects who fell more than once during a one-year period was 14.5%. Females had a higher rate than males. Sixty per cent of all the falls occurred indoors. As for the cause of the falls, extrinsic factors were accounted three times as much as intrinsic factors. Among injuries sustained by the falls, fracture was more frequent in females than in males. Length of time of standing on one leg was shorter for fallers than for non-fallers in both sexes. However, the differences were not significant when age was controlled. Fall is attributed not only to physical factors but also to environmental factors. Therefore, it should be encouraged to design an environment with devices.     

Two-level posterior lumbar interbody fusion for degenerative disc disease: improved clinical outcome with restoration of lumbar lordosis

BACKGROUND CONTEXT: Although posterior lumbar interbody fusion (PLIF) for degenerative lumbar diseases is routine, there are few reports on double-level PLIF. PURPOSE: To evaluate the clinical outcomes of double-level PLIF. STUDY DESIGN/SETTING: A retrospective study of operated cases in Gifu, Japan. PATIENT SAMPLE: Nineteen patients (8 men and 11 women, 59.5+/-10.2 years) who underwent double-level PLIF between 1996 and 2001. OUTCOME MEASURES: Operation time, blood loss, complications, the Japanese Orthopaedic Association (JOA) score for back pain and lumbar sagittal alignment were evaluated. METHODS: Patients were examined retrospectively at follow-ups of 3.6+/-1.7 years. Primary diseases were spondylolisthesis, spinal canal stenosis, degenerative scoliosis and herniated intervertebral disc. Fusion areas were L3 to L5 in 15 cases and L4 to S1 in 4 cases. RESULTS: The mean JOA score increased from an initial score of 12.9+/-3.5 to 21.3+/-4.9 at the final follow-up. There was a positive correlation (R=0.718, p<.001) between the increase in lordotic angle and the increase in the JOA score. Several parameters suggested that the surgical invasiveness was not minimal. CONCLUSION: Double-level PLIF provided satisfactory results and preserved lumbar spine lordosis.     

A quantitative anatomic characterization of the quadrilateral surface for periacetabular osteotomy

The periacetabular osteotomy described by Ganz et al is used widely, and includes an outward osteotomy from the quadrilateral surface. Because intraarticular extension of the osteotomy can complicate the Ganz osteotomy, it is important to image the margin of the hip. To prevent this complication, and to do this procedure more safely, 32 hemipelves from cadavers were used in the current study. Some landmarks were selected that can be clarified on the quadrilateral surface during the periacetabular osteotomy. The acetabulum was hollowed out using an acetabular reamer of the same size as each femoral head, and the margin of the penetrated hole through the acetabulum was determined using these landmarks. The posterior margin of the hip is located approximately 2 cm anterior to the sciatic notch. The anatomic guidepoint for the osteotomy of the ischium averaged 14 mm inferior to the distal margin of the hip. By clarifying the margin of the hip presumed on the quadrilateral surface in this way, the periacetabular osteotomy can be done more safely, without causing complications such as intraarticular chisel penetration.     

Nonviable Burkholderia mallei induces a mixed Th1- and Th2-like cytokine response in BALB/c mice

Nonviable cell preparations of Burkholderia mallei, the causative agent of glanders, were evaluated as potential vaccine candidates in a BALB/c murine model. Three different B. mallei cell preparations plus Alhydrogel were evaluated: a heat-killed preparation, an irradiation-inactivated preparation, and a preparation of a capsule-negative mutant strain which had been irradiation inactivated. BALB/c mice were vaccinated twice with the different B. mallei preparations, and spleens and sera were collected to determine their cellular and humoral immune responses. All three bacterial cell preparations had essentially the same results in two cellular immune response assays. In a splenocyte proliferation assay, the amount of cell proliferation in response to the homologous immunogen, concanavalin A, or lipopolysaccharide was similar for all the cell preparations. Also, splenocytes from the inoculated mice expressed interleukin 2 (IL-2), gamma interferon, and small amounts of IL-4 and IL-5, and more IL-10 cytokine in the presence of the homologous antigen. When the immunoglobulin subclasses from these mice were examined, they all produced higher levels of IgG1 than IgG2a subclasses. The higher ratio of IgG1 to IgG2a was not due to the amount of the immunogen or the adjuvant (Alhydrogel) used in the BALB/c mice. The cell preparations did not protect the vaccinated mice from a live challenge (>300 50% lethal doses). Our results suggest that in BALB/c mice, a mixed T-helper-cell-like response to nonviable B. mallei is obtained, as demonstrated by a Th1- and Th2-like cytokine response and a Th2-like subclass immunoglobulin response. This may be the reason for the inability of the B. mallei cells that were examined as candidate vaccines to protect the mice from a live challenge.     

Granulocytapheresis (GCAP) for severe alcoholic hepatitis-A preliminary report.

AIM: To evaluate the efficacy of granulocytapheresis therapy in alcoholic hepatitis. METHODS: We attempted to trap leukocytes in the peripheral circulation using the granulocytapheresis (GCAP) technique in patients with severe alcoholic hepatitis who showed a marked elevation of peripheral leukocytes. Corticosteroids were co-administered. RESULTS: The Maddrey's indices for these patients varied between 42 and 117 and MELD scores for alcoholic hepatitis (Mayo) ranged from 20 to 44. Survival rate was 50% (3/6), which is better than the results reported recently for similar patients in a national survey (29%). The effect of GCAP was reflected in decreases in interleukin-6 and interleukin-8 levels as well as in serum concentrations of soluble intercellular adhesion molecule. White blood cell counts were not affected. In the surviving patients, the Maddrey's indices and MELD scores for alcoholic hepatitis varied between 49 and 67, and 20 and 22, respectively, showing that GCAP is effective in patients with disease of moderate severity. Hemolytic anemia occurred in one patient after GCAP therapy. Other events such as pancreatitis, pneumonia, and cerebral hemorrhage were considered to be related to the alcoholic hepatitis itself. CONCLUSION: GCAP therapy deserves further evaluation as a new therapeutic modality for a moderately severe alcoholic hepatitis.     

Haemodynamic effects of the crude venom from nematocysts of the box-jellyfish Chiropsalmus quadrigatus (Habu-kurage) in anaesthetized rabbits.

Haemodynamic effects of saline-extracted venom from nematocysts isolated from tentacles of the box-jellyfish Chiropsalmus quadrigatus (Habu-kurage) were investigated. In anaesthetized rabbits, i.v. injections of the venom produced hypotension following a transient hypertension. Mean femoral arterial blood flow markedly decreased immediately after the injection and femoral vascular resistance increased. Left ventricular dP/dt remarkably decreased after a transient and small increase, and heart rate decreased. Left ventricular end-diastolic pressure markedly elevated. All of the above changes by 0.2-5 microg/kg of the venom expressed as the amount of protein were seen dose-dependently and occurred without tachyphylaxis. In five of seven animals received an injection of the venom at 10 microg/kg, irreversible cardiac arrest occurred. Changes produced by 1 or 2 microg/kg of the venom were significantly attenuated either by heating the venom at 40 degrees C for 10min or by pretreatment with diltiazem. These results indicate that the venom from Habu-kurage has both vasoconstrictor and cardiodepressive effects, and suggest that these thermolabile actions may be due partly to activation of voltage-dependent calcium channels and probably subsequent calcium-overload.     

Problems and solutions of pedicle screw plate fixation of lumbar spine

Fifty-seven patients with low back pain and sciatica of various causes were reviewed with reference to problems associated with pedicle plate fixation of the lumbar spine. Eleven percent of patients had neurologic problems postoperatively and 3.5% (two patients) had severe sensory impairments. All patients had this complication in the early phases of the study. Of 297 screws, 17 broke, ie, 5.7%. These breakages occurred in 12 of 57 patients (21%). In patients with spondylolisthesis, the degree of slip correction averaged 53% postoperatively, which decreased to 35% at the 1-year follow-up. Slip angle was maintained after correction. Pedicle screw plate fixation is an effective form of immobilization of the lumbar spine used in achieving arthrodesis. The surgeon must be fully trained in methodology. It is recommended that screw and plate materials be improved to prevent screw breakage.     

Hypoxia-induced renal epithelial cell death through caspase-dependent pathway: role of Bcl-2, Bcl-xL and Bax in tubular injury

Although injury of epithelial cells has been reported to be responsible for renal disease such as acute renal failure, its molecular mechanisms are largely unknown. As hypoxia has been postulated as the initial trigger of epithelial injury, we studied the molecular mechanisms of apoptosis induced by hypoxia in human renal epithelial cells. Severe hypoxia caused epithelial cell death, accompanied by a significant increase in LDH release (p<0.01). In addition, hypoxic treatment of epithelial cells resulted in a significant increase in apoptotic cells as assessed by cell morphology (p<0.01). The apoptotic change in epithelial cells under hypoxic condition was also confirmed by a significant increase in caspase-3-like activity and release of cytochrome c (p<0.01). The decrease in epithelial cell number was completely abolished by addition of a wide-spectrum caspase inhibitor, Z-VAD, rather than Z-DEVD, a specific caspase-3 inhibitor (p<0.01). Thus, we further studied the molecular mechanisms of apoptosis induced by hypoxia. Anti-apoptotic factors, Bcl-2 and Bcl-xL, were significantly decreased in epithelial cells under a hypoxic condition as assessed by Western blotting (p<0.01). In contrast, hypoxia did not alter their location. Of particular importance, translocation of a proapoptotic factor, Bax, from the cytoplasm to the mitochondrial membrane was observed in response to hypoxia, whereas total Bax protein was not changed by hypoxia. Overall, this study demonstrated that hypoxia caused epithelial cell death induced by caspase-3-like activity-dependent apoptosis. The pro-apoptotic mechanisms of hypoxia in epithelial cells largely depend on a significant decrease in Bcl-2 and Bcl-xL. In addition, the present results demonstrate that translocation of Bax from the cytosol to the mitochondrial membrane occurred under hypoxia, thereby leading to pathological tissue destruction.