Pharmacokinetics of arginine butyrate in patients with hemoglobinopathy

Recent reports have demonstrated improvement in the clinical status and hemoglobin levels with use of intravenous arginine butyrate in patients with homozygous β-thalassemia and sickle cell disease.

To allow optimalization of therapy, we conducted pharmacokinetic studies in nine patients, five with sickle cell disease and four with β-thalassemia, treated with continuous intravenous infusion of arginine butyrate.

The disappearance of the drug after discontinuation was characterized by a biphasic elimination with an initial rapid phase followed by a slower phase. Redistribution was noted in five of the patients after 11.2 ± 4.0 min. The short half life was the result of both rapid clearance rate of 93.6 ± 31.9 ml/kg/min and small Vc (0.21 ± 0.26 l/kg) and Vss (0.31 ± 0.37 l/kg).

While preliminary results of the effectiveness of arginine butyrate are encouraging with a rise of γ-globin mRNA and F reticulocytes in some patients, the rapid elimination of this agent will probably limit its current use to administration by continuous infusion.     

Immunological comparison between prostate-specific antigen and γ-seminoprotein

Summary Prostate-specific antigen (PA) and -seminoprotein (-Sm) were compared by immunocytochemical, immunodiffusion and immunoblotting methods using rabbit anti-PA antibody and rabbit anti--Sm antibody. Enzyme immunoassys (EIAs) were developed for measurements of PA and -Sm to determine a correlation between serum PA and -Sm levels in patients with prostate cancer. The patterns of localization and distribution of PA and -Sm were identical in prostate tissue sections, including benign and cancerous human prostacs. The immunodiffusion study showed that the antigens with which anti-PA antibody and anti--Sm antibody reacted in seminal plasma and prostate tissue homogenates were identical to each other. In the immunoblotting study, anti-PA antibody and anti--Sm antibody recognized a single antigen corresponding to a molecular weight of approximately 33,000 both in seminal plasma and prostate tissue homogenates. The EIAs developed in this study were sensitive, specific, and reproducible, and the correlation between serum PA and -Sm values determined by these EIAs was highly significant (r=0.99, P(0.001). These results indicated that PA and -Sm were immunologically identical and that serum PA and -Sm determined by immunoassays using anti-PA antibody and anti--Sm antibody should be evaluated as identical tumor markers for serodiagnosis of prostate cancer.     

Histochemical and ultrastructural observations on brown degeneration of human intervertebral disc

Thirty-eight fresh human intervertebral discs collected during anterior interbody fusion surgery were histochemically and ultrastructurally analyzed for pigments. Macroscopically, five stages of degeneration were classified according to the color, fibrosis, and fragility of the nucleus pulposus of the discs. In order to demonstrate lipofuscin granules, specimens were subjected to special staining procedures, including carbol fuchsin lipofuscin stain, the Schmorl's reaction, and autofluorescence. Lipofuscin granules were distributed from the inner layer of the annulus fibrosus to the nucleus pulposus. Such granules were numerous in cases of slight or severe degeneration, whereas fewer granules were found in cases of moderate degeneration. However, the stage of macroscopic degeneration of the intervertebral disc did not necessarily correlate with the incidence of lipofuscin granules. By ultrastructural observation, the morphological features of the components of the intervertebral disc and the ultrastructure of the lipofuscin granule were clarified. The ultrastructure of the "brown degeneration" disc exhibited markedly increased amorphous electron-dense bodies located among collagen fibrils in the matrix.     

A Japanese patient with frontotemporal dementia and parkinsonism by a tau P301S mutation

The authors report a patient carrying a missense mutation in exon 10 of tau that causes a substitution at codon 301 (P301S). Although the patient shares the rapidly progressive frontotemporal dementia of the other reported pedigrees with P301S, the clinical phenotype is unique in that parkinsonism was a major symptom in the early stage and because behavioral symptoms with dementia became prominent 2 years after the onset of the disease. This study substantiates the notion that tau mutations at codon 301 can show various phenotypes.     

Magnetic resonance imaging and histologic evidence of postoperative back muscle injury in rats

STUDY DESIGN: Postoperative back muscle injury was evaluated in rats by magnetic resonance imaging and histologic analyses. OBJECTIVE: To compare the magnetic resonance imaging manifestation of back muscle injury with the histologic findings in rats and to subsequently clarify the histopathologic appearance of the high intensity regions on T2-weighted images in human postoperative back muscles. SUMMARY OF BACKGROUND DATA: In a previous study, it was found that the signal intensity on T2-weighted images of the postoperative back muscles was increased in patients who had postsurgical lumbar muscle impairment, especially in those with a prolonged surgery duration. However, the specific histopathologic changes that cause the high signal intensity on T2-weighted images remain unclear. METHODS: Rats were divided into three groups: sham operation group, 1-hour retraction group, and 2-hour retraction group. Magnetic resonance imaging and histology of the multifidus muscles were examined before surgery and at 2, 7, and 21 days after surgery. RESULTS: T2-weighted imaging was more useful than T1-weighted imaging to estimate back muscle injury. The high signal intensity of the multifidus muscles on T2-weighted images remained 21 days after surgery only in the 2-hour retraction group. Histologically, the regeneration of the multifidus muscles was complete at 21 days after surgery in the 1-hour retraction group, but the regenerated muscle fibers in the 2-hour retraction group had a small diameter, and the extracellular fluid space remained large. CONCLUSION: The high signal intensity on T2-weighted images of the postoperative multifidus muscles in the regenerative phase may be due to an increased extracellular space and incomplete muscle fiber regeneration.     

A new fibular osteotomy in association with high tibial osteotomy (a comparative study with conventional mid-third fibular osteotomy)

A new technique for dividing the fibula when performing a high tibial osteotomy is described. The head of the fibula is enucleated and morselized. The technique is simple and safe with a low complication rate.

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Résumé  En cas d’ostéotomie supérieure du tibia, nous décrivons une nouvelle technique d’ostéotomie péronière avec énucléation et morcellement de la tête du péroné. On peut employer pour ce faire la même incision cutanée que pour l’ostéotomie du tibia. L’incidence de complications est faible.

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Accepted: 17 March 2000     

Treatment of ununited fracture of the hook of hamate by low-intensity pulsed ultrasound: a case report

A patient presented 4 months after sustaining a fracture of the hook of hamate. X-rays and computed tomography scanning of the carpal tunnel confirmed the presence of an ununited fracture. Low-intensity ultrasound was applied to the fracture site. After 4.5 months of exposure to ultrasound, union was confirmed by both x-rays and computed tomography scanning of the carpal tunnel. (J Hand Surg 2000; 25A:77-79.