Combining a dipeptidyl peptidase-4 inhibitor, alogliptin, with pioglitazone improves glycaemic control, lipid profiles and beta-cell function in db/db mice.

BACKGROUND AND PURPOSE: Alogliptin, a highly selective dipeptidyl peptidase-4 (DPP-4) inhibitor, enhances incretin action and pioglitazone enhances hepatic and peripheral insulin actions. Here, we have evaluated the effects of combining these agents in diabetic mice. EXPERIMENTAL APPROACH: Effects of short-term treatment with alogliptin alone (0.01%-0.1% in diet), and chronic combination treatment with alogliptin (0.03% in diet) and pioglitazone (0.0075% in diet) were evaluated in db/db mice exhibiting early stages of diabetes. KEY RESULTS: Alogliptin inhibited plasma DPP-4 activity up to 84% and increased plasma active glucagon-like peptide-1 by 4.4- to 4.9-fold. Unexpectedly, alogliptin alone lacked clear efficacy for improving glucose levels. However, alogliptin in combination with pioglitazone clearly enhanced the effects of pioglitazone alone. After 3-4 weeks of treatment, combination treatment increased plasma insulin by 3.8-fold, decreased plasma glucagon by 41%, both of which were greater than each drug alone, and increased plasma adiponectin by 2.4-fold. In addition, combination treatment decreased glycosylated haemoglobin by 2.2%, plasma glucose by 52%, plasma triglycerides by 77% and non-esterified fatty acids by 48%, all of which were greater than each drug alone. Combination treatment also increased expression of insulin and pancreatic and duodenal homeobox 1 (PDX1), maintained normal beta-cell/alpha-cell distribution in islets and restored pancreatic insulin content to levels comparable to non-diabetic mice. CONCLUSIONS AND IMPLICATIONS: These results indicate that combination treatment with alogliptin and pioglitazone at an early stage of diabetes improved metabolic profiles and indices that measure beta-cell function, and maintained islet structure in db/db mice, compared with either alogliptin or pioglitazone monotherapy.

Traumatic spondylolisthesis of the lumbosacral spine with multiple fractures of the posterior elements.

We describe a patient with a traumatic spondylolisthesis of L5 and multiple, bilateral pedicle fractures from L2 to L5. Conservative treatment was chosen, with eventual neurological recovery and bony union. We are not aware of previous reports of this pattern of injury.

Developmental and dynamic canal stenosis as radiologic factors affecting surgical results of anterior cervical fusion for myelopathy.

STUDY DESIGN: The correlation between preoperative and postoperative lateral functional radiograms and clinical results was analyzed in 74 cases of myelopathy treated by anterior cervical fusion. OBJECTIVES: To clarify the correlation between clinical results and radiologic findings (developmental and dynamic stenosis). SUMMARY OF BACKGROUND DATA: Although radiologic changes have been reported at the disc level adjacent to anterior cervical fusion, the question of whether these radiologic findings affect the clinical results of anterior fusion has not been resolved. METHODS: The "deteriorated" results group (28 cases) was composed of cases with deterioration of 2 points or more in the Japan Orthopedic Association score at follow-up compared with the postoperative best score. The "good" results group (46 cases) exhibited a recovery rate of > or = 50%. The two groups were compared in lateral functional roentgenograms on which the sagittal canal diameter in each vertebra and the diameter between the inferoposterior lip of the vertebral body and the anterior margin of the lamina of the distal vertebra in the extended neck were measured. A diameter of less than 12 mm was defined as developmental canal stenosis or dynamic canal stenosis. RESULTS: Fifty-four percent of the cases in the deteriorated results group had developmental canal stenosis, whereas the same findings were identified in only 2% of the cases in the good results group (P < 0.01). Preoperative dynamic canal stenosis at the disc level adjacent to the fusion was found in 64% of the patients in the deteriorated results group and in only 4% of the patients in the good results group (P < 0.01). CONCLUSIONS: Patients in the deteriorated results group showed a higher incidence of preoperative developmental and/or dynamic canal stenosis at the adjacent disc level than those in the the good results group. These results indicate that patients with preoperative developmental canal stenosis are not suitable candidates for anterior cervical fusion. When dynamic canal stenosis is found below or above the level of fusion, simultaneous fusion is recommended to avoid deterioration of the myelopathy.

A case of cervical myelopathy with developmental canal stenosis at the level of the atlas. A case report.

The craniocervical junction is one of the most common sites of malformations. Only three cases of myelopathy due to hypoplasia of atlas have been reported previously. Among these malformations, the hypoplasia of atlas was first described by Wackenheim in 1974. Although developmental canal stenosis due to the hypoplasia of atlas seems to have a tendency of causing the cervical myelopathy, only three cases of cervical myelopathy due to this condition have been reported previously. A 77-year-old man with severe canal stenosis at the level of the atlas is reported. The clinical manifestations were 20-year history of progressive gait disturbance and paresis of both upper and lower extremities. The spinal cord was markedly compressed at the level of the atlas. The clinical manifestations improved after a resection of posterior arch of the atlas.

Atlantoaxial dislocation. A follow-up study of surgical results.

STUDY DESIGN: The cases of 47 patients with atlantoaxial dislocation exclusive of rheumatoid arthritis, cerebral palsy, and tumors as causative pathologies were reviewed after surgical treatment, which was performed between 1979 and 1993. OBJECTIVES: To investigate the surgical results of atlantoaxial dislocation itself without any systemic factors affected by rheumatoid arthritis, cerebral palsy, and tumors. METHODS: Neck pain (or occipitalgia) and extent of myelopathy at follow-up evaluation were compared with that present before surgery. The results were classified into four groups: excellent (no pain or recovery rate in myelopathy of more than 50%), good (decreased pain or recovery rate of 25% to 50%), fair (no improvement of pain or recovery rate of zero to 25%), and poor (aggravation of pain or recovery rate less than zero). The average follow-up period was 4 years and 2 months. RESULTS: Of the patients evaluated, 51% were assessed as excellent, 23% as good, 7% as fair, and 19% as poor. Pain relief was achieved in 95% of patients with non myelopathy. Extent of myelopathy, pathology of atlantoaxial dislocation (ligamentous or osseous instability), loss of reduction after surgery, and surgical procedures were recognized as the major factors affecting surgical results. Better surgical results were obtained in mild myelopathy cases (> 10 points in Japan Orthopaedic Association scoring), ligamentous instability, and cases without loss of reduction. The incidence of pseudarthrosis and loss of reduction was low in Brooks' method for atlantoaxial fusion and in Luque's segmental sublaminal wiring method for occipitocervical fusion. CONCLUSION: The best results occurred in patients with no myelopathy, and the worst results occurred in patients with severe myelopathy; therefore, surgery is best indicated for atlantoaxial dislocation with intractable pain or with mild myelopathy. To avoid pseudarthrosis and loss of reduction, a strong fixation method, such as Brooks' or Luque's segmental sublaminal wiring method, should be selected.

Occipitoatlantal and occipitoaxial hypermobility in Down syndrome.

STUDY DESIGN: In this study, the authors evaluated upper cervical spine in 75 children and adolescents with Down syndrome on the basis of lateral flexion-extension radiographs. OBJECTIVE: To assess occipitoatlantal motion and occipitoaxial motion in children and adolescents with Down syndrome compared with age-matched control subjects. SUMMARY OF BACKGROUND DATA: Although previous studies have described a high prevalence of occipitoatlantal hypermobility in Down syndrome, there have been no comparisons with age-matched control subjects. Only a few reports have mentioned the physiologic relation between the occiput and axis other than basilar impression. Moreover, there have been no reports examining anteroposterior mobility in abnormal conditions. METHODS: Seventy-five children and adolescents with Down syndrome and 30 age-matched control subjects were examined. Lateral radiographs of the upper cervical spine in flexion and extension were taken, and anteroposterior translation of the occiput in relation to the atlas and axis was measured. RESULTS: Anteroposterior occipitoatlantal hypermobility was found to be present in children and adolescents with Down syndrome even when compared with age-matched control subjects. Occipitoaxial hypermobility was observed only when atlantoaxial instability was present. CONCLUSION: In evaluating the upper cervical spine in Down syndrome, it is necessary to pay attention to the relation between the occiput, atlas, and axis.

Postoperative lumbar spinal instability occurring or progressing secondary to laminectomy.

The manifestations and pathomechanism of postoperative lumbar spinal instability, occurring or progressing secondary to laminectomy, was clarified by means of functional radiographic analysis in a series of 46 patients over 40 years of age. The relation between instability and the clinical symptoms also is discussed. In patients under 60 years of age, instability at the operated level tended to appear in cases of wide laminectomy more often than in cases of partial laminectomy. Occurrence or progress of instability seems to be promoted by resection of the posterior spinal elements rather than the disc. It is further considered that the postoperative aggravation of clinical symptoms may be influenced not only by instability, but also by the other factors.

Pathomechanism, pathogenesis, and results of treatment in cervical spondylotic myelopathy caused by dynamic canal stenosis.

In this study, the pathomechanism and pathogenesis of dynamic canal stenosis caused by cervical instability in patients with cervical spondylotic myelopathy and the validity of the concept of instability are clarified by analyzing the results of treatment in 53 cases. In cases of cervical spondylotic myelopathy caused by dynamic canal stenosis, the authors found that the posterior slide of the vertebral body occurs as a result of degeneration in the cervical spine due to aging changes, and that the dynamic sagittal diameter of the spinal canal decreases with an increase of the degree of posterior slide. This is followed by gradual aggravation of the clinical symptoms. Continuous cervical traction was found to be the first choice of treatment. Surgical treatment is indicated in cases in which the traction was ineffective, or even when it was effective, in cases in which the Japanese Orthopaedic Association (JOA) score remained low or when there was a tendency toward rapid aggravation of symptoms. It was demonstrated that the shorter the duration of the myelopathy, the better the results of treatment obtained. A limit of the dynamic sagittal diameter of the spinal canal of 12 mm was considered as valid.

Intradural lumbar disc herniation. Report of three cases with a review of the literature.

Intradural lumbar disc herniation (ILDH) is rare. Three new cases of this condition are reported, adding to the 70 previously documented cases. An incidence of ILDH in between 0.04 and 0.33 percent of lumbar disc protrusions has been reported. More than one third of ILDH were observed at L1-2 to L3-4 levels, while only a tenth of cases occurred at L5-S1. The mechanism of ILDH is not known with certainty. Adhesions between the ventral wall of the dura and posterior longitudinal ligament could act as a preconditioning factor. A diagnosis of ILDH may be made with difficulty, and it is seldom suspected preoperatively. Prompt surgery is necessary because the neurologic prognosis appears to be closely linked with preoperative duration of neurologic symptoms.

Spondylolysis of the axis. Report of four cases.

Spondylolysis or spondylolisthesis of the cervical spine, especially of the upper cervical spine, is very rare. The authors report four cases of spondylolysis of the axis and outline its roentgenographic features for differential diagnosis. The clinical course of the cases and the unvarying roentgenographic findings throughout the course strongly suggest that the lesion is congenital in origin.

Lumbar disc herniation in children and adolescents. A review of 70 operated cases and their minimum 5-year follow-up studies.

Seventy cases of surgically documented herniated lumbar disc in children and adolescents were analyzed. Twenty-six of the 70 cases were followed at least five years postoperatively. The incidence of juvenile disc herniation in Japanese patients appear to be much higher than in Caucasians. Repeated trauma may be an important etiological factor of herniated lumbar disc in this age group. The history and physical findings in children and adolescents are not fundamentally different from those in the adult, although abnormal neurological findings are not common. Five-year follow-up studies suggest that interlaminal laminectomy without fusion is the best procedure when surgical treatment of herniated lumbar disc is necessary in children and adolescents.

The surgical treatment of myelopathy secondary to rheumatoid arthritis of the lower cervical spine.

There are few reports in the literature of the surgical treatment of cervical myelopathy secondary to rheumatoid arthritis below the level of the axis. Three cases are presented. All had severe motor and sensory loss in the upper and lower extremities. The cause of myelopathy differed in each case: in the first, the dura mater was infiltrated with rheumatoid material; the second was due to a stenotic spinal canal narrowed by a fixed subluxation of the cervical spine; in the third, traction myelopathy resulted from sub-axial subluxation and posterior angulation combined with cervical instability. Neurological assessment is particularly difficult in patients with rheumatoid arthritis of the cervical spine. Skull or halo traction is useful to gauge neurological improvement, to reduce the dislocation and to immobilise the cervical spine before, during and after surgery. Surgery is considered where conservative treatment is either ineffective or not tolerated, and is indicated if severe myelopathy is evident or progressive. Anterior interbody fusion is the operation of choice for mobile subluxation. Laminectomy is recommended in fixed subluxation where compression of the cord is demonstrated on myelography.