Severe cardiac toxicity in hematological stem cell transplantation: predictive value of reduced left ventricular ejection fraction.

Eighty patients receiving hematological stem cell transplantation (HCT) with a preparative regimen consisting of total body irradiation (12.5 Gy), cyclophosphamide (4000 or 4500 mg/m2), and thiotepa (400 mg/m2) were evaluated for the development of cardiac toxicity. Patients in whom the pretransplant cumulative dose of anthracycline was more than or equal to 300 mg/m2 showed a lower left ventricular ejection fraction (EF) before HCT compared to patients with less than 300 mg/m2 (0.61 +/- 0.09 vs 0.67 +/- 0.06, P = 0.0010). Patients who had undergone more than or equal to six courses of chemotherapy showed a decreased EF before HCT compared to those after less than six courses (0.67 +/- 0.05 vs 0.63 +/- 0.09, P = 0.03). Three of seven patients (43%) whose pretransplant EF had been less than or equal to 0.55 developed severe cardiac toxicity, characterized by congestive heart failure (CHF) compared with none of 83 patients (0%) whose pretransplant EF had been more than 0.55 (P = 0.00026). Of the three patients who developed severe cardiac toxicity, two were given more than 300 mg/m2 of cumulative anthracycline and underwent 23 courses and six courses of chemotherapy, while the other patient received only two courses of chemotherapy with a total dose of 139 mg/m2 of anthracycline. These results indicate that an increased cumulative dose of anthracycline and number of chemotherapy treatments are correlated with a decrease of the EF and that the EF before HCT is useful for predicting the risk of cardiac complications for recipients who have received chemotherapy.

Homozygosity mapping of the locus responsible for renal tubular dysplasia of cattle on bovine chromosome 1.

Renal tubular dysplasia is a hereditary disease of Japanese black cattle showing renal failure and growth retardation with an autosomal recessive trait. In the present study, we mapped the locus responsible for the disease (RTD) by linkage analysis with an inbred paternal half-sib pedigree obtained from commercial herds. By analyzing segregation of microsatellite markers in the half-sibs, significant linkage was observed between the RTD locus and markers on bovine Chromosome (Chr) 1 with the highest lod score of 11.4. Homozygosity mapping with the inbred pedigree further defined the localization of the RTD locus in a 4-cM region between microsatellite markers BMS4003 and INRA119. Mapping of the RTD locus on bovine Chr 1 will facilitate cloning and characterization of the gene responsible for this disease.

Notchplasty in anterior cruciate ligament reconstruction: an experimental animal study.

The purpose of this study was to evaluate the effects of a notchplasty on the biomechanical and histological properties of the anterior cruciate ligament (ACL) and changes in patellar articular cartilage. We used an in situ freeze-thaw model for the ACL reconstruction performed with or without notchplasty in 36 Japanese white rabbits. The cross-sectional area of the regenerated ACLs without a notchplasty (6.4 +/- 0.4 mm(2)) was statistically smaller than that of the ACLs with a notchplasty (7.0 +/- 0.3 mm(2)), and the cross-sectional area of the normal ACLs (5.4 +/- 0.5 mm(2)) was statistically smaller than that of both other types. However, the mechanical strength of the ACL with the notchplasty was identical to that of the ACL without a notchplasty. Although the notchplasty areas were covered with fibrous scar tissue, caliper measurement and histological examination showed no obvious osteochondral reconstitution in the notchplasty sites of any of the specimens. Regarding the deleterious effect of notchplasty on patellar articular cartilage, the extent of the slight degenerative changes was about the same in the group with a 1-mm notchplasty and in the control group.

The long-term effects of tibial drill hole position on the outcome of anterior cruciate ligament reconstruction.

Fifty-three cases of anterior cruciate ligament reconstruction were classified into two groups depending on the tibial drill hole position: in the anterior group, the center of tibial drill hole was positioned anteriorly to the dome of the intercondylar notch (Blumensaat's line), and in the posterior group, it was positioned posteriorly to the Blumensaat's line. Knee extension loss in the anterior group was significantly greater at 1 and 2 years postoperatively than that of the posterior group. However, there were no differences between the anterior and posterior groups 3 to 5 years postoperatively. No significant differences in anterior laxity were seen from 1 to 4 years postoperatively. After more than 5 years, anteroposterior translation of the anterior group was significantly greater than that of the posterior group. In the anterior group, extension was restricted in the early postoperative period. At latest follow-up more than 5 years postoperatively, anterior laxity in the posterior group was significantly less than that in the anterior group.

[Assessment of ischemic heart disease by dipyridamole stress electrocardiographic gated myocardial single photon emission computed tomography with technetium-99m tetrofosmin].

Simultaneous assessment of stress perfusion and rest function is possible with gated single photon emission computed tomography (SPECT) using stress injected technetium-99m (99mTc) tetrofosmin (TF). The feasibility of dipyridamole stress electrocardiographic gated myocardial SPECT (GSPECT) with TF was examined as an alternative to conventional stress/rest imaging. Fifty-one patients underwent stress GSPECT. 740 MBq of TF was administered 3 min after dipyridamole infusion. GSPECT acquisition was performed one hour after the injection. Additional rest SPECT was performed on another day only in patients with abnormal perfusion on stress images. Perfusion and thickening were analyzed visually on 17 segments of the left ventricle. Percentage of wall thickening (%WT) was also calculated in 17 segments of the polar map. Thirty-two of 51 patients (63%) had normal stress perfusion and normal rest thickening. Nineteen of 51 patients (37%) had abnormal perfusion on stress images. Among 157 abnormal perfusion segments of the 19 patients, 139 segments (89%) had thickening and the rest (11%) had no thickening. %WT was higher in the reversible segments with or without thickening. There was better agreement for the identification of normal segments and the presence of reversibility between stress GSPECT and the conventional stress/rest study in patients without previous myocardial infarction than in those with previous myocardial infarction (89% vs 79%). These results suggest that stress GSPECT may substitute for conventional stress/rest perfusion study in patients without previous myocardial infarction, allowing shorter examination time and lower cost. However, stress GSPECT does not replace the need for rest perfusion study in patients with previous myocardial infarction, because of underestimation of viability, but %WT may eliminate this underestimation.

Intermediate-term results of meniscal repair in anterior cruciate ligament-reconstructed knees.

We investigated the incidence of and risk factors for recurrent tears of repaired menisci in anterior cruciate ligament-reconstructed knees. We observed 63 patients whose menisci had been evaluated at second-look arthroscopy as healed (N = 50) or incompletely healed (N = 13) for an average of 4 years (range, 2 to 9.5). Of the 13 patients with incompletely healed menisci, 6 (46%) required additional meniscal surgery and 2 (15%) had recurrence of meniscal symptoms such as catching or locking. Among the 50 patients with healed menisci, 5 (10%) required additional meniscal surgery and 9 (18%) had recurrence of meniscal symptoms after second-look arthroscopy. The timing of the recurrence of these symptoms was from 12 to 28 months after surgical repair. Of the 11 patients who had undergone additional surgery, 6 had sustained second injuries during sports activities and the other 5 had no identifiable cause of injury. When comparing age, tear sites, rim width, side-to-side differences with KT-1000 arthrometer testing, and the pivot shift test, there were no differences between the group requiring additional surgery, the symptomatic group, and the asymptomatic group. However, the postoperative Tegner activity score of the group requiring additional surgery was statistically significantly higher than the others.

Malignant insulinoma with extensive liver metastases presenting as disturbance of consciousness.

A 56-year-old man was referred to our hospital for evaluation of episodic disturbance of consciousness. Hypoglycemic symptoms were noted and Whipple's triad was satisfied. The 75 g OGTT and the glucagon test revealed a high baseline insulin level and hyperreactivity to glucagon. A pancreatic tumor and liver metastases were found by abdominal computed tomography (CT). Based on the finding of liver biopsy, the final diagnosis was malignant insulinoma with liver metastasis. He selected conservative treatment and no hypoglycemic crisis has occurred for one year since discharge. Early diagnosis and long-term follow-up is necessary since this tumor is slow growing.

Arthroscopic meniscal repair in conjunction with anterior cruciate ligament reconstruction: factors affecting the healing rate.

Ninety-eight of 121 consecutive patients who underwent arthroscopy-assisted meniscal repair in combination with anterior cruciate ligament reconstruction were evaluated by second-look arthroscopy with an average interval of 16 months (range, 6 to 63 months). Of the 98 meniscal repairs, 73 had completely healed, 13 had incompletely healed, and 12 had not healed. Six possible factors that may have affected the healing of the repaired menisci were statistically analyzed. There were no statistically significant differences between the three groups with respect to sex, age, tear site on the medial or lateral meniscus, or residual anterior laxity as measured using the KT-1000. The factors that had a statistically significant impact on healing rate were the rim width and meniscal locking. Negative correlations with the healing rate were observed in menisci that were repaired in the central third zone and that had been locked or could be locked by probing at the time of surgery.

Forefoot pressures during walking in feet afficted with hallux valgus.

Forefoot pressures during walking in feet with hallux valgus were recorded using pressure-sensitive film, and the relationships between deformities and foot pressures were analyzed. There were 32 female subjects comprising 50 feet with hallux valgus, of which 20 feet underwent surgery. As in normal feet, the pressure patterns of feet with hallux valgus were varied: peak pressures were under the first metatarsal head, under the second and/or third metatarsal heads, and first, second, and/or third metatarsal heads. Peak pressures of hallux valgus feet were larger in each type than those of the normal foot. In feet with hallux valgus showing peak pressures under the first metatarsal heads, the hallux valgus angle and the intermetatarsal angle were larger than those in feet showing peak pressures on the second and/or third metatarsal heads. After surgery, peak pressures were under the second and/or third metatarsal heads and they decreased.

Effects of knee flexion angle at graft fixation on the outcome of anterior cruciate ligament reconstruction.

Clinical outcome in 44 patients who underwent anterior cruciate ligament (ACL) reconstruction with hamstring tendons augmented by the ligament augmentation device for chronic ACL deficiency was studied; average follow-up was 38 months (range, 24 to 52 months). In 19 patients, grafts were fixed with the knees at full extension (group 1), whereas in 25 patients, the grafts were fixed with the knees at 30 degrees of flexion (group 2). The results of subjective testing (Lysholm score), the Lachman test, the pivot-shift test, muscle strength testing, angle of extension loss, and follow-up arthroscopy were compared to assess the effects of flexion angle at fixation on stability and function. The range of motion in group 1 was significantly better than that in group 2. The stability of the knees and the arthroscopic appearance of the grafts in group 1 were, however, significantly worse than those in Group 2.

The effects of tibial tunnel placement and roofplasty on reconstructed anterior cruciate ligament knees.

Seventy-five anterior cruciate ligament (ACL) reconstructions augmented with the Kennedy Ligament Augmentation Device were evaluated according to classification of tibial drill-hole position on the basis of the anatomic landmarks of the ACL by two-dimensional radiographic imaging of the fully extended knee. The effects of roofplasty to avoid graft impingement were also assessed. The tibial drill-hole position was classified in relation to the medial intercondylar tubercle on anterior-posterior (AP) view, and in relation to Blumensaat's line (B-line) on lateral view. Arthroscopic evaluation of the ACL and incidence of chronic synovitis as well as Lysholm knee score, manual knee tests, knee extension and flexion angles, and knee tester measurements were performed. The results indicated that the knee joints in which the tibial drill hole was positioned laterally from the medial intercondylar tubercle or in which the tibial drill hole was positioned anteriorly to the B-line showed a tendency to develop more postoperative chronic synovitis. The knees in which the tibial drill hole was positioned anteriorly to the B-line also showed larger AP laxity. There was no difference between the non-roofplasty and roofplasty groups.

Lower leg fracture with Parkes-Weber syndrome complicated by disseminated intravascular coagulation.

Reports of Parkes-Weber syndrome complicated by disseminated intravascular coagulation (DIC) are rare in the orthopaedic literature. This is a case report of a 23-year-old man who had this syndrome and who sustained a lower-leg fracture complicated by the DIC. Open reduction was not attempted because the DIC worsened after manual reduction. Amputation was rejected by the patient. Three months of continuous infusion of heparin and replacement therapy with fresh frozen plasma was done. Cast immobilization without further reductions was continued. The DIC improved and union of the fractures was observed at 2 years and 3 months after injury.

Evaluation of anterior cruciate reconstruction reinforced by the Kennedy ligament augmentation device. An arthroscopic and histological study.

Fifty anterior cruciate ligament reconstructions with the Kennedy ligament augmentation device were examined arthroscopically and histologically 6 to 61 months after operation. The autogenous segments used were the quadriceps tendon in 13 and the semitendinosus tendon, with or without gracilis, in 37. The arthroscopic findings were rated as good in 31, fair in 15 and poor in 4, and there was correlation between these grades and KT-1000 measurements. The histological findings were graded as good in 17, fair in 26 and poor in 4; these did not correlate with the arthroscopic grades but with the time interval after reconstruction. Maturation of the autogenous augmented segment was found to progress with time, but took more than 3 years to become complete.

Computerized tomographic analysis of tibial tubercle position in the painful female patellofemoral joint.

We used computerized tomography to evaluate the position of the tibial tubercle and to determine if the tibial tubercle is positioned more laterally in female patients with patellofemoral pain. We also wanted to determine the relationship of the tibial tubercle to tibial external rotation and patellar tilt. Sixty female patients and 19 healthy female controls were evaluated. To evaluate the position of the tibial tubercle, the tibial tubercle rotation angle (the angle formed by the line between the posteriormost edges of the medial and lateral femoral condyle and the line between the central point of the intercondylar space and the central point of the patellar tendon at the level of the tibial tubercle) was measured by superimposing the images from the level of the distal femoral condyle and the tibial tubercle. The relationship between the tibial tubercle rotation angle and patellar tilt was then assessed by dividing the patients into 3 subgroups according to the patellar tilt. The tibial tubercle rotation angle was significantly different between the patellofemoral pain patients and the controls. There were also significant differences between the patients with moderate patellar tilt (10 degrees to 20 degrees) and the controls, and between the patients with high patellar tilt (> 20 degrees) and the controls.

[An autopsy case of Paget's disease of the scrotum with general metastasis].

An autopsy case of genital Paget's disease with a widespread metastases is reported. A 69-year-old man with redness, itching and swelling of the scrotum obtained dermatological consultation and underwent tumor resection for Paget's disease. At 8 months after discharge, he suffered from a costal fracture because of carcinomatosis of the bone marrow. In laboratory data the serum level of alkaline phosphatase and carcinoembryonic antigen was shown to be high. Four months later, he died of severe congestive edema of the lung with diffuse micrometastases. An autopsy revealed a widespread metastases in various organs and lymph nodes. The Paget cells were positive in carcinoembryonic antigen.

Effect of ramipril on 24-hour variability of blood pressure and heart rate in essential hypertension.

Nonrestricted blood pressure recording was performed invasively or noninvasively, using new portable devices, for a period of 24 hours in 4 patients with essential hypertension before and after 6- to 17-day treatment with ramipril at an initial dosage of 1.25 mg daily. Ramipril produced a steady decrease in blood pressure without changing heart rate. Before initiation of ramipril treatment, the blood pressure was lower during the night than during the day. This day to night difference was not affected by ramipril. In addition, analysis of the standard deviation of the mean for each time point examined during 24 hours revealed no effect of ramipril on circadian variation of blood pressure.

The effects of twice daily captopril and once daily enalapril on ambulatory intraarterial blood pressure in essential hypertension.

Intraarterial ambulatory pressure (AP) was recorded before and during therapy with captopril or enalapril in two groups with hypertension. Seven patients were admitted during the study. The monitoring of AP and heart rate (HR) was performed during placebo therapy and following a minimum period of 7 days of 25 mg twice daily captopril or 2.5 to 10 mg once daily enalapril. The AP and HR following percutaneous insertion of a cannula into the brachial artery were sampled then data were analyzed as reported previously. After the cannula was inserted, examinations of tilt-up, handgrip and ergometer were performed. Both drugs produced a significant reduction of ambulatory AP throughout 24 hours with preservation of the overall shape of the circadian curve. The results also demonstrated that both drugs had not affected normal daily activities. Thus, twice daily captopril and once daily enalapril can be used as the first-line therapy of hypertension.

Long-term in vivo carcinogenicity tests of potassium bromate, sodium hypochlorite, and sodium chlorite conducted in Japan.

Long-term in vivo carcinogenicity tests of potassium bromate (KBrO3), sodium hypochlorite (NaClO), and sodium chlorite (NaClO2) have been conducted in Japan from 1977 to 1985. In these investigations, groups of approximately 50 male and 50 female F344 rats or B6C3F1 mice were given solutions of the compounds as their drinking water ad libitum at two dose levels determined on the basis of preliminary 13-week tests. Control animals were given distilled water. The carcinogenic potential of KBrO3 was tested by administering doses of 500 or 250 ppm to rats for 110 weeks. Significantly elevated incidences of renal cell tumors in males and females and mesotheliomas of the peritoneum in males as compared to controls were observed. When female mice were given KBrO3 at doses of 1000 or 500 ppm for 78 weeks, no significant differences in tumor incidences between experimental and control groups were apparent. NaClO was administered to male and female rats, respectively, at doses of 1000 or 500 ppm and 2000 or 1000 ppm for 104 weeks. In mice, NaClO was given at doses of 1000 or 500 ppm to either sex for 103 weeks. The incidences of tumors in NaClO-treated and control animals of both sexes were not significantly different in both rat and mouse studies. NaClO2 was given to rats of both sexes at a dose of 600 or 300 ppm for 85 weeks. No statistically significant differences were observed in the incidences of tumor formation between NaClO2-treated and control groups of both sexes. NaClO2 was administered to mice at a concentration of 500 or 250 ppm for 85 weeks. In males, the combined incidences of hyperplastic nodules and hepatocellular carcinomas of the liver in a low-dose group, and adenomas and adenocarcinomas of the lung in a high-dose group, were marginally increased compared to controls (p less than 0.05). However, these incidences in treated males were within the range of values of historical control data in our program. We concluded that KBrO3 was carcinogenic in rats of both sexes. NaClO was not carcinogenic in either rats and or mice under the conditions of the present studies. Although NaClO2 was shown to be noncarcinogenic in rats, the results for mice were evaluated as inconclusive. Also the results of two-stage mouse skin carcinogenesis using KBrO3, NaClO, and NaClO2 are presented. The necessity for further testing of oxidant chemicals to determine potential carcinogenic and/or promoting effects is suggested in view of the recently proposed role of active oxygen species in carcinogenesis.