Development of an animal model for neuroleptic malignant syndrome: heat-exposed rabbits with haloperidol and atropine administration exhibit increased muscle activity, hyperthermia, and high serum creatine phosphokinase level

The neuroleptic malignant syndrome (NMS) is a life-threatening complication of neuroleptic treatment. To elucidate the pathogenesis of NMS, an animal model has been developed. Experimental rabbits treated with haloperidol (1 mg/kg) by intramuscular injection, were studied for the diagnostic symptoms of increased muscle rigidity, elevated body temperature, and high serum creatine phosphokinase (CPK) level. Administration of haloperidol (1 mg/kg) and atropine (0.4 mg/kg), and exposure to high ambient temperature (35°C) induced a significant increase in electromyographic activity with muscle rigidity similar to that observed in patients with NMS. Such rabbits also showed elevated body temperature and serum CPK value. In addition to the similarity of the signs and symptoms, all parameters measured (muscle rigidity, body temperature, and serum CPK level) were normalized by dantrolene treatment. The effectiveness of dantrolene in the experimental animal partially confirms the validity of this animal model for NMS. This experimental animal model for NMS may be useful to elucidate the pathogenesis of NMS.     

The use of frame fixation in the management of open distal extensor mechanism avulsion fracture in a dislocated knee

An avulsion fracture of the tibial tubercle is a common injury in traffic accident. If the fracture is closed, then a comparatively good prognosis can be expected through reinforcement of the bone via osteosynthesis and the use of artificial ligaments. In this case, an open wound was observed in the tibial tubercle, and the wound was so polluted that the healing process was significantly delayed. It was therefore difficult to provide simultaneous surgical treatment and so three operations were required to perform the reconstruction of the extensor mechanism. The reconstruction of extensor mechanism and the frame fixation between the patella and tibia was performed. Six months after the injury, the patient was able to walk without aid, had a range of movement from 5°to 130°, and did not show any indications of ADL disorder. Using this method of frame fixation between the patella and tibia proved to be an effective technique for the reconstruction of the open knee extension mechanism injury.     

Off-pump resection of a coronary arterial fistula using the Harmonic Scalpel

Off-pump surgery was performed in a patient with post-infarction angina complicated with aneurysmal coronary-pulmonary arterial fistula. Epicardial echocardiography localized the artery feeding the fistula in the myocardium, which had not been revealed by visual inspection, palpation, or transesophageal echocardiography. The patient underwent off-pump coronary artery bypass grafting concomitant with aneurysmectomy. The feeding arteries were dissected easily using a Harmonic Scalpel and ligated. The flow in the aneurysm disappeared immediately and aneurysmectomy was performed without bleeding.     

Action of Isoflurane on the Substantia Gelatinosa Neurons of the Adult Rat Spinal Cord

Background: Although isoflurane, a volatile anesthetic, can block the motor response to noxious stimulation (immobility and analgesia) and suppress autonomic responsiveness, how it exerts these effects at the neuronal level in the spinal cord is not fully understood.

Methods: The effects of a clinically relevant concentration (1 rat minimum alveolar concentration [MAC]) of isoflurane on electrically evoked and spontaneous excitatory/inhibitory transmission and on the response to exogenous administration of the [gamma]-aminobutyric acid type A receptor agonist muscimol were examined in lamina II neurons of adult rat spinal cord slices using the whole cell patch clamp technique. The effect of isoflurane on the action potential-generating membrane property was also examined.

Results: Bath-applied isoflurane (1.5%, 1 rat MAC) diminished dorsal root-evoked polysynaptic but not monosynaptic excitatory postsynaptic currents. Glutamatergic miniature excitatory postsynaptic currents were also unaffected by isoflurane. In contrast, isoflurane prolonged the decay phase of evoked and miniature [gamma]-aminobutyric acid type A receptor-mediated inhibitory postsynaptic currents and increased the amplitude of the muscimol-induced current. Isoflurane had little effect on action potential discharge activity.     

Characterization of a highly polymorphic marker adjacent to the SLC4A1 gene and of kidney immunostaining in a family with distal renal tubular acidosis.

BACKGROUND: Mutations in the human SLC4A1 (AE1/band 3) gene are associated with hereditary spherocytic anaemia and with distal renal tubular acidosis (dRTA). The molecular diagnosis of AE1 mutations has been complicated by the absence of highly polymorphic genetic markers, and the pathogenic mechanisms of some dRTA-associated AE1 mutations remain unclear. Here, we characterized a polymorphic dinucleotide repeat close to the human AE1 gene and performed an immunocytochemical study of kidney tissue from a patient with inherited dRTA with a defined AE1 mutation. METHODS: One CA repeat region was identified in a phage P1-derived artificial chromosome (PAC) clone containing most of the human AE1 gene and the upstream flanking region. We determined its heterozygosity value in multiple populations by PCR analysis. Genotyping of one family with dominant dRTA identified the AE1 R589H mutation, and family member genotypes were compared with the CA repeat length. AE1 and vH(+)-ATPase polypeptides in kidney tissue from an AE1 R589H patient were examined by immunocytochemistry for the first time. RESULTS: This CA repeat, previously reported as D17S1183, is approximately 90 kb upstream of the AE1 gene and displayed considerable length polymorphism, with small racial differences, and a heterozygosity value of 0.56. The allele-specific length of this repeat confirmed co-segregation of the AE1 R589H mutation with the disease phenotype in a family with dominant dRTA. Immunostaining of the kidney cortex from one affected member with superimposed chronic pyelonephritis revealed vH(+)-ATPase-positive intercalated cells in which AE1 was undetectable, and proximal tubular epithelial cells with apparently enhanced apical vH(+)-ATPase staining. CONCLUSIONS: The highly polymorphic dinucleotide repeat adjacent to the human AE1 gene may be useful for future studies of disease association and haplotype analysis. Intercalated cells persist in the end-stage kidney of a patient with familial autosomal dominant dRTA associated with the AE1 R589H mutation. The absence of detectable AE1 polypeptide in those intercalated cells supports the genetic prediction that the AE1 R589H mutation indeed causes dominant dRTA.     

Deficiency of insulin receptor substrate-1 impairs skeletal growth through early closure of epiphyseal cartilage.

Morphological analyses in and around the epiphyseal cartilage of mice deficient in insulin receptor substrate-1 (IRS-1) showed IRS-1 signaling to be important for skeletal growth by preventing early closure of the epiphyseal cartilage and maintaining the subsequent bone turnover at the primary spongiosa. Introduction: IRS-1 is an essential molecule for intracellular signaling by IGF-I and insulin, both of which are potent anabolic regulators of cartilage and bone metabolism. To clarify the role of IRS-1 signaling in the skeletal growth, morphological analyses were performed in and around the epiphyseal cartilage of mice deficient in IRS-1 (IRS-1(-/-)), whose limbs and trunk were 20-30% shorter than wildtype (WT) mice. MATERIALS AND METHODS: The epiphyseal cartilage and the primary spongiosa at proximal tibias of homozygous IRS-1(-/-) and WT male littermates were compared using histological, immunohistochemical, enzyme cytohistochemical, ultrastructural, and bone histomorphometrical analyses. RESULTS: In and around the WT epiphyseal cartilage, IRS-1 and insulin-like growth factor (IGF)-1 receptors were widely expressed, whereas IRS-2 was weakly localized in bone cells. Chronological observation revealed that height of the proliferative zone and the size of hypertrophic chondrocytes were decreased in WT mice as a function of age, and these decreases were accelerated in the IRS-1 (-/-) cartilage, whose findings at 12 weeks were similar to those of WT at 24 weeks. In the IRS-1(-/-) cartilage, proliferating chondrocytes with positive proliferating cell nuclear antigen (PCNA) or parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor immunostaining had almost disappeared by 12 weeks. Contrarily, TUNEL+ apoptotic cells were increased in the hypertrophic zone, at the bottom of which most of the chondrocytes were surrounded by the calcified matrix, suggesting the closure of the cartilage. In the primary spongiosa, bone volume, alkaline phosphatase (ALP)+ osteoblasts, TRACP+ osteoclasts, and the osteopontin-positive cement line were markedly decreased. Bone histomorphometrical parameters for both bone formation and resorption were significantly lower in IRS-1(-/-) mice, indicating the suppression of bone turnover. CONCLUSION: The IRS-1(-/-) epiphyseal cartilage exhibited insufficient proliferation of chondrocytes, calcification of hypertrophic chondrocytes, acceleration of apoptosis, and early closure of the growth plate. Thus, the data strongly suggest that IRS-1 signaling is important for the skeletal growth by preventing early closure of the epiphyseal cartilage and by maintaining the subsequent bone turnover at the primary spongiosa.     

Adamantinoma of the proximal femur: a case report

Adamantinoma is a rare low-grade malignant bone tumor with an indolent course. The tibia is involved in 85%–90% of long-bone cases. We encountered a patient with primary adamantinoma of the proximal femur. A 60-year-old woman fell and fractured her proximal left femur in the area of a cystic lesion. She underwent an osteosynthesis procedure, and bone union was obtained. After 3 years she developed pain in the left thigh, and a radiographic abnormality was found at the fracture site. A metastatic bone tumor was suspected, and curettage and cementing were carried out. Histologically, we found an epithelial component but failed to detect any primary cancer. Local recurrence became evident after another 6 years. A marginal excision was performed and a bipolar femoral prosthesis was implanted. We finally diagnosed the patient with adamantinoma. In this report we describe the characteristics of this tumor and discuss the reasoning concerning the differential diagnosis and therapeutic plan.     

Effects of dominant and nondominant eyes in binocular rivalry.

PURPOSE: To investigate the relation between sighting and sensory eye dominance and attempt to quantitatively examine eye dominance using a balance technique based on binocular rivalry. METHODS: The durations of exclusive visibility of the dominant and nondominant eye target in binocular rivalry were measured in 14 subjects. The dominant eye was determined by using the hole-in-card test (sighting dominance). In study 1, contrast of the target in one eye was fixed at 100% and contrast of the target in the other eye was varied from 100% to 80% to 60% to 40% to 20%, when using rectangular gratings of 1, 2, and 4 cycles per degree (cpd) at 2 degrees, 4 degrees , and 8 degrees in size. In study 2, contrast of the target in the nondominant eye was fixed at 100% and contrast of the target in the dominant eye was varied from 100% to 80% to 60% to 40% to 20%, when using a rectangular grating of 2 cpd at 4 degrees in size. RESULTS: In study 1, the total duration of exclusive visibilities of the dominant eye target; that is, the target seen by the eye that had sighting dominance was longer compared with that of the nondominant eye target. When using rectangular gratings of 4 cpd, mean total duration of exclusive visibility of the dominant eye target was statistically longer than that of the nondominant eye target (p < 0.05). In study 2, reversals (in which duration of exclusive visibility of the nondominant eye becomes longer than the dominant eye when the contrast of the dominant eye target is decreased) were observed for all contrasts except for 100%. CONCLUSIONS: The dominant sighting eye identified by the hole-in-card test coincided with the dominant eye as determined by binocular rivalry. The contrast at which reversal occurs indicates the balance point of dominance and seems to be a useful quantitative indicator of eye dominance to clinical applications.     

ENDOSCOPIC PANCREATIC STENTING IN CHRONIC PANCREATITIS WITH DUCTAL DILATION PROXIMAL TO A STRICTURE: A SAFE and EFFECTIVE PROTOCOL

After removal of intraductal stones, a 10‐Fr or 7‐Fr pancreatic stent was placed in 16 patients with upstream ductal dilation proximal to a stricture of the main pancreatic duct. Stents were removed after a mean duration of 52.5 days. Nine patients underwent repeated stenting. About one year after removal of the initial stent, when the remaining upstream ductal dilation was found on follow‐up pancreatograms, the next stent was replaced. Repeated stenting improved outflow of pancreatic juice more effectively than one‐time stenting. Correlation between long‐term pain relief without recurrence of intraductal stones and reduction of duct diameter was also shown. Stent occlusion was observed in 14 of 30 stents. Stent occlusion was frequently associated with recurrence of pancreatitis and intraductal stones, and was also associated with morphologic changes in the pancreatic ductal system. Although there were no significant differences between stent patency of the initial stents and that of the next stents, stent patency of 10‐Fr stents was superior to that of 7‐Fr stents. 10‐Fr stents should be removed within 8 weeks and 7‐Fr stents should be removed within 4 weeks for the prevention of stent occlusion. Repeated stenting with short‐term stenting is therefore considered a safe and effective protocol of endoscopic pancreatic stenting.