Serum itraconazole and hydroxyitraconazole concentrations and interaction with digoxin in a case of chronic hypertrophic pachymenigitis caused by Aspergillus flavus.

A patient treated with itraconazole (ITCZ) under the diagnosis of Aspergillus flavus-induced chronic hypertrophic pachymeningitis is presented. The reason for the successful cure of this patient was investigated by the pharmacokinetic analysis of serum levels of ITCZ. Concurrently administered digoxin was also investigated for its drug-drug interaction. The patient (a 75-year-old male) developed ophthalmopathy, and was diagnosed as having A. flavus hypertrophic pachymeningitis by pachymeninx biopsy. After admission, he was treated with FLCZ, AMPH, 5-FC and MCZ. The infection tended to subside with the AMPH administration. Since renal insufficiency was induced by AMPH and the other antifungal drugs were ineffective, daily administration of 200 mg of ITCZ was initiated, and the inflammatory signs and symptoms gradually subsided. The symptoms did not recur during the 36 months of itraconazole treatment after discharge, and it was concluded that ITCZ was effective for A. flavus hypertrophic pachymeningitis. Pharmacokinetic parameters of ITCZ and OH-ITCZ as follows: ITCZ: Cmax 93.2 ng/ml, T1/2 beta 11 hours, AUC0-24 999 ng.h/ml, OH-ITCZ: Cmax 159.4 ng/ml, T1/2 beta 16. 2 hours, AUC0-24 of 1391 ng.h/ml. Both ITCZ and OH-ITCZ reached steady states seven days after administration began. The ITCZ and OH-ITCZ levels in serum collected 36 months after the initiation of administration were 452.9 ng/ml and 1233.6 ng/ml, respectively. Cmax and AUC0-24 of ITCZ and OH-ITCZ on the second day were markedly lower than those in healthy adults reported by Oguchi et al., and hypoalbuminemia observed at administration on that day was considered the most probable cause. It was assumed that the most plausible reason for a successful cure even at a low dose of ITCZ was the increase of distribution to tissue by the increase of the unbound form. Digoxin was concurrently given to this patient at 0. 125 mg/day, but the blood digoxin level was not elevated. Consideration of the blood level of albumin is believed to be important for evaluating the blood concentration of ITCZ.     

Long-term results of bipolar hemiarthroplasty for osteoarthritis of the hip and idiopathic osteonecrosis of the femoral head

BACKGROUND: Satisfactory results have been reported from long-term studies on bipolar hemiarthroplasty for femoral neck fracture. However, long-term results of this procedure for osteoarthritis of the hip (OA) and idiopathic necrosis of the femoral head (ION) have given rise to pessimism. These poor results have often reported migration of the bipolar head, but few had described the direction of this migration. The purpose of the present study was to conduct a long-term follow-up analysis of bipolar hemiarthroplasty for OA and ION, including the direction of migration. METHODS: We retrospectively reviewed a consecutive series of 64 patients (76 hips) who underwent primary bipolar hemiarthroplasty for symptomatic OA and ION with a cementless femoral component between 1976 and 1995. Of these 64 patients, 35 patients (40 hips) were available for clinical and radiographic review at a minimum follow-up duration of 10 years. RESULTS: The Japanese Orthopaedic Association score significantly improved and pain relief was high following surgery; however, preservation of acetabular bone stock could not be achieved because of migration. The survival rate declined 10 years after surgery. Superomedial migration was found to be a risk factor for revision, and one factor affecting superomedial migration was the postoperative center edge angle. CONCLUSIONS: The long-term results of bipolar hemiarthroplasty for OA and ION are not favorable. If a sufficient centripetal position is obtained with reaming, the bipolar head tends to migrate superomedially, subsequently requiring revision.     

Age-dependent changes in DNA polymerase fidelity and proofreading activity during cellular aging.

DNA polymerase alpha and the 3'-->5' exonuclease involved in the proofreading of DNA synthesis were isolated from human diploid fetal lung fibroblast (TIG-1) cells at various population doubling levels (PDL). The final PDL of the TIG-1 cells used in these experiments was 70. The fidelity of DNA polymerase alpha remained high until late passage and fell suddenly just before the end of the life span between 65 and 69 PDL. The activities of the 3'-->5' exonuclease related to proofreading remained unchanged from 21 to 61 PDL, but the activity decreased rapidly in more aged cells. The 3'-->5' exonuclease activity at 69 PDL was about 50% of that in TIG cells at 21 PDL. In vitro DNA synthesis by DNA polymerase alpha from TIG-1 cells harvested at 69 PDL showed the amount of non-complementary nucleotides incorporated to be decreased by the addition of the 3'-->5' exonuclease from the same cells. However, not all errors were edited out since the ratio of DNA polymerase activity to 3'-->5' exonuclease activity was adjusted to reflect that in vivo and the infidelity of DNA synthesis by error-prone DNA polymerase alpha from aged cells was improved by the addition of the highly active 3'-->5' exonuclease from cells at 41 PDL. These results suggested that the mutation frequency rises just before the end of the life span of TIG-1 cells.     

Facial nerve neuromas: CT findings

Although neuromas of the facial nerve are rare, they present with uniform clinical and radiological findings. Their pluridirectional tomography findings have been well described; however, the appearance of the intracranial extension of the neuroma which is best visualized by CT has not been emphasized. We report five cases of facial nerve neuromas with particular attention to their intracranial extension. For comparative purposes we also have reviewed 10 cases of acoustic and eight cases of trigeminal neuromas, all involving the cerebellopontine angle (CPA) and the middle cranial fossa. Two of the five facial nerve neuromas affected the second and third segments of the facial canal, and three involved both the CPA and the middle cranial fossa spreading across the midpetrosal bone. This type of tumor extension seems to be characteristic of facial nerve neuromas. In acoustic and trigeminal neuromas the tumor crossing toward the middle fossa takes place via the tentorial hiatus (acoustic) and the petrous apex (trigeminal).     

Glycosphingolipids of lectin-resistant mutants of the highly metastatic mouse tumor cell line, MDAY-D2

Neutral and acidic glycolipids in MDAY-D2, a highly metastatic murine tumor cell line, were examined and compared with glycolipids of MDW4 and D33W25-1, two lectin-resistant mutants of MDAY-D2 from distinct genetic complementation classes. D33W25-1 remained highly metastatic while MDW4 cells were found to be nonmetastatic (Dennis, J. W., Donaghue, T., Florian, M., and Kerbel, R. S., Nature (Lond.), 292: 242-245, 1981 and Dennis, J. W. et al., Cancer Res., 46: 4594-4600, 1986). Glycolipid structures were identified by fast-atom bombardment mass spectrometry, methylation analysis, exoglycosidase treatment, and immunostaining. The metastatic MDAY-D2 was found to contain GM3, GM2, IV3GalNAc-GM1b, and high levels of GM1a, GM1b, and GD1a. MDW4 showed a 3-fold decrease in total ganglioside content compared to MDAY-D2 and a corresponding increase in the precursor, glucosylceramide. MDW4 was deficient in GM1 and accumulated GM2 and NeuNG-GM2, indicating a lack of gangliosides having NeuNAc alpha 2-3Gal beta 1-3 terminal sequence. Neosynthesis of GD3 was also observed in MDW4. The metastatic mutant D33W25-1 had a similar pattern of gangliosides as that found in MDAY-D2 cells with N-glycolyl rather than N-acetyl neuraminic acid. These results suggest that the metastatic property of these cell lines may be related to the level of ganglioside, and that the substitution of N-glycolyl for N-acetyl neuraminic acid does not reduce metastatic capacity.     

Relationship between regurgitant flow dynamics and cardiac physical in tricuspid regurgitation: a phono-, mechano- and Doppler echocardiographic study

To evaluate the relationships between regurgitant flow dynamics of tricuspid regurgitation (TR) and cardiac physical signs, and to clarify the role of atrial function on central venous flow, we investigated physical signs by cardiac auscultation and palpation of the liver. In addition, phonocardiography, jugular venous and hepatic pulse tracings and Doppler echocardiographic recordings were performed. The subjects, 109 patients with Doppler-detected TR, were categorized as an SR group of 42 with sinus rhythm, an Af group of 63 with atrial fibrillation and four with sinus arrest. Thirty-five patients underwent open heart surgery before six months or more. Results were as follows: 1. In the Af group, the maximum systolic flow velocity data in the superior vena cava (SVC) and hepatic vein (HV) correlated well with the maximum tricuspid regurgitant signal area on the color Doppler echocardiogram, and systolic backward flow from the heart was more evident in the HV than in the SVC. In the SR group, however, no correlation was observed between the maximum systolic flow velocity and the TR signal area, and systolic backward flow was not evident even in cases with severe TR. 2. After open heart surgery, systolic flow velocities in the SVC and HV were significantly decreased in the SR group compared to the Af group. 3. There was close correlation between the presence of hepatomegaly and systolic backward flow towards the liver. Hepatomegaly was more marked in the Af group than in the SR group. 4. Jugular venous and hepatic pulse data correlated well with the flow velocity data in the SVC and HV and with the TR signal area. 5. Intensity of the tricuspid regurgitant murmur as estimated by the Levine's classification correlated relatively well with the systolic pressure gradient between the right ventricle and right atrium as calculated by the modified Bernoulli equation, but did not correlate with the TR signal area. From these results, we conclude that the intensity of the tricuspid regurgitant murmur and the jugular venous or hepatic pulse patterns are useful for evaluating tricuspid regurgitant dynamics, when they are applied clinically with precise recognition of their significance and limitations, and that sinus rhythm or atrial fibrillation is also an important factor.