Upper thoracic myelopathy caused by vertebral collapse and subluxation in rheumatoid arthritis: report of two cases

We report two cases of rheumatoid arthritis (RA) with upper thoracic myelopathy and a review of the literature. Clinical data of a 47-year-old woman (case 1) and a 54-year-old woman (case 2) are described. Case 1 showed a transverse-type myelopathy at the T2 segment level of the spinal cord and case 2 had the same type of myelopathy at the T4 segment level. Case 1 had anterior vertebral subluxation of C7 due to marked vertebral collapse and Case 2 had subluxation of T2 with vertebral destruction. These two patients had the mutilating type of RA with multilevel spontaneous fusion in the cervical spine. The lesions in the thoracic spine might be caused by the severe destructive inflammation that is characteristic in mutilating disease. The vertebral collapse might lead to subluxation of the upper thoracic vertebra, resulting in spinal cord compression. Upper thoracic subluxation might be caused by vertebral collapse due to RA and the increased motion as a compensation for decreased mobility caused by spontaneous fusion in the cervical spine.     

Ontogenesis of the cerebellofugal projection in the rat.

Ontogenesis of the cerebellofugal projection was studied in the rat by the tract-tracing method with WGA-HRP. The projection, forming a uniform front of compact fibre bundle tipped by growth cones, began entering the brainstem on embryonic day 17 (E17), grew rapidly and orderly with no random extension of fibers, and arrived at the most rostral part of the thalamus already by E18, distributing dense terminals to various brainstem and thalamic nuclei. The course and termination of this projection in prenatal animals was largely similar to normal adult projection although differences were found. Some projections increased postnatally, whereas some projections which were existent in embryos regressed with age and finally disappeared completely. The adult pattern of the projection was attained by 3 weeks of age. It is worth noting that the projections which appeared transiently are similar to those reported as aberrantly regenerated projections in kittens which are born in more mature state than rats and have no such projections at birth.     

Development and Intrauterine Fate of Normal and Abnormal Human Conceptuses

Using the data from the Kyoto Collection of Human Embryos, three main topics related to normal and abnormal development of human embryos are discussed. 1) Wide variability was noted in developmental stage of human embryos at any given gestational age. This was true not only for the estimated ovulation age but also for ‘coital’ age in single coital cases. Such diversity in human prenatal development may be, at least in part, ‘normal’ biological variability and it should be taken into account when assessing the teratogenic risk of environmental agents to human embryos. 2) At the early postimplantation period prior to major organogenesis, the percentage of morphologically abnormal embryos is high (> 30%), which supports the clinical finding that a substantially large proportion of human conceptuses are eliminated at an early stage of pregnancy, often without the knowledge of the mother. The fate of undifferentiated abnormal embryos is not certain and should be studied. 3) Life-table estimates for normal and abnormal human conceptuses showed that more than 10% of all embryos recognizable at 5 weeks gestation are malformed or ‘potentially’ malformed. Because of selective intrauterine death of malformed embryos and fetuses, the proportion of the malformed drops to 2.4% by age 8 weeks and 1% at term. The cumulative intrauterine mortality rate of malformed conceptuses was estimated to be 93%, while the corresponding rate for normal conceptuses was 18%.     

Objective definition and measurement method of ground-glass opacity for planning limited resection in patients with clinical stage IA adenocarcinoma of the lung

Objective: The standard operation for patients with stage IA lung adenocarcinoma is considered to be a lobectomy. Recently, some researchers have reported that patients with tumors showing greater proportions of ground-glass opacity (GGO) at computed tomography (CT) could be candidates for limited resection, because of its less aggressive nature. However, the lack of a precise definition or standard measuring method of GGO prevents its general use as an index for planning limited resection. Therefore, we attempted to define GGO based on CT number and measured it more objectively. Methods: Between 1998 and 2001, 90 patients with clinical stage IA adenocarcinoma, who underwent standard or intentional limited resection and whose images of chest high-resolution CT were preserved in Digital Imaging and Communications in Medicine (DICOM) format, constituted the study population. The tumor shadow seen on the solid window (WL, −160 HU; WW, 2 HU) was regarded as the central solid area of the tumor seen on the lung window, and GGO was defined as the whole tumor area with the exception of the central solid area. Each area was measured using Scion Image (Scion Corp., Frederick, MD). We analyzed the relationship between the proportion of GGO and both of pathologic findings and recurrence. Results: Among the 90 tumors, 31 (34.4%) were calculated to have a GGO area greater than or equal to 50%. Of these, 27 (87%) tumors were bronchioloalveolar carcinoma. Lymphatic and vascular invasions, or nodal involvement were found only in patients with a smaller proportion of GGO (<50%) (P<0.05). During the follow-up period (median 36 months), recurrences occurred in eight patients who were diagnosed as having tumors showing smaller proportion of GGO (<50%). Conclusions: Tumors with a greater proportion of GGO measured by our method are thought to have a less invasive nature. Our objective measuring method of GGO could be useful for future multicenter trials to elucidate the value of limited resection for clinical stage IA adenocarcinoma based on the proportion of GGO.     

Ester prodrugs of zidovudine

Ten novel ester prodrugs of zidovudine (azidothymidine; AZT) were synthesized with aliphatic acids (acetic-stearic), and the enzymatic regeneration of AZT from the prodrugs was investigated both in vitro and in vivo. The enzymatic hydrolysis rates of the AZT esters in the presence of mouse enzyme systems (plasma, liver, and intestine, and kidney) were highly dependent on the lengths of the acyl chains of the prodrugs. The caprate or caprylate of AZT showed the highest reactivity to three of the four enzyme systems; either the decrease or the increase in the acyl chain length resulted in the decrease of the reactivity to the enzymes. Zidovudine (AZT) and three of the prodrugs (acetate, caprate, and stearate) were administered to mice intraperitoneally, and the plasma concentrations of AZT and a corresponding prodrug were measured. The AZT concentrations in plasma following the acetate administration rapidly decreased with a half-life of 14.5 min. This tendency is similar to that shown in direct AZT administration. On the other hand, the concentrations following the caprate or stearate administration decreased slowly and were maintained for as long as 4 h after dosing. The prodrug concentrations in plasma after the prodrug administration were under the detection limit (0.01 micrograms/mL), except for acetate. The absence of the caprate and stearate in plasma may be attributed to the high hydrophobicity or favorable tissue distribution of the ester derivatives.     

Prostatectomy by transurethral balloon Laserthermia™ (PROSTALASE™) in the canine

Prostatectomy by transurethral balloon Laserthermia (PROSTA-LASE?) was performed in a canine model. This balloon device monitored by transrectal ultrasound can cylindrically irradiate with a laser beam. The treatment was performed in 8 canines using 15 watts for 20 minutes at 60°C at a 5 mm depth of the prostate from the urethral surface. Immediately following the laser therapy, an area of coagulation necrosis was observed around the urethra to a depth of 4–5 mm from the surface. After 1 week, cavitation formation was seen in 3 or 4 canines by ultrasound, and the urethral reepithelialization was shown in 1 of 2 canines. After 2 weeks, cavitation formation was observed in both canines, and the urethra was completely reepithelialized in one canine. There was no tissue damage in the bladder neck of urethral sphincter and no urinary incontinence in any animal. This system is thought to be simple and, satisfactorily performed, is an effective transurethral prostatectomy. © 1994 Wiley-Liss, Inc.     

Disc and condyle translation in patients with temporomandibular disorder.

OBJECTIVE: The purpose of this study was to elucidate causal relationship between disc and condyle range of movement and clinical signs and symptoms in patients with temporomandibular disorders (TMD), using magnetic resonance imaging (MRI). STUDY DESIGN: The subjects comprised of a study group of 191 patients with TMD and a control group of 43 asymptomatic patients. The clinical assessment consisted of range of maximum mouth opening (MMO) and preauricular pain during mandibular function. After clinical and radiographic findings assessment, disc and condyle condition were examined by MRI and the range of movement was accordingly classified. RESULTS: Disc displacement was observed in 156/191 (81.7%) of the study group and 9/43 (20.9%) of the control group. When disc and condyle mobility was presented around the eminence, wider MMO range was maintained, P < .05. Presence of osteoarthrosis (OA) was not correlated with preauricular pain, because OA variables were mild in the study group. CONCLUSION: Maintenance of disc/condyle translation is an important factor in TMJ function, irrespective of disc displacement or arthritis.     

Role of interleukin-17F in chronic inflammatory and allergic lung disease

IL-17 family members belong to a distinct category of cytokines that coordinate local tissue inflammation by inducing the release of pro-inflammatory and neutrophil-mobilizing cytokines. The importance of the IL-17 family in inflammatory and autoimmune disease is becoming increasingly apparent. IL-17F is a recently discovered member of the IL-17 family that has a number of biological activities through induction of various cytokines, chemokines, and mediators. IL-17A, the founding member of the IL-17 family, and IL-17F are produced by several inflammatory cells, including activated T cells, in response to infectious and antigenic stimuli. Overexpression of IL-17A or IL-17F in the lungs results in induction of CXC chemokines and neutrophil recruitment. In a case-control study of 1125 unrelated Japanese subjects, a His161 to Arg161 (H161R) substitution in the third exon of the IL17F gene was shown to be associated with asthma and chronic obstructive pulmonary disease (COPD). Functionally, this variant failed to induce cytokines and chemokines, and interestingly, was able to antagonize the activity of wild-type IL-17F. These results provide an experimental basis for the observed genetic association with chronic inflammatory lung diseases, and also suggest the potential therapeutic utility of this antagonistic variant of IL-17F. Given that asthma and COPD are complex diseases involving a number of genetic and environmental factors, the genetic impact of IL-17F H161R with regard to the development of chronic airway inflammation likely varies among individuals with different genetic backgrounds and environmental exposures.     

Local cerebral blood flow measured by stable xenon CT during fentanyl-diazepam anesthesia

We assessed the local cerebral blood flow (LCBF) in 40 patients under fentanyl-diazepam anesthesia. The measurement of LCBF was made using 50%–70% stable xenon with 20 min of inhalation interval and a shuttle method for computed tomography imaging. All patients were anesthetized with 5.95±1.76 μg·kg⁻¹ fentanyl and 0.22±0.07 mg·kg⁻¹ diazepam under mechanical ventilation during CBF measurement. The values and distribution of LCBF on non-affected hemisphere appeared to be unaltered by fentanyldiazepam anesthesia. We also assessed the cerebral carbon dioxide reactivity in 6 patients. The cerebral carbon dioxide reactivity, expressed as percentage change in LCBF per unit change in arterial carbon dioxide partial pressure, was 5.39±1.07, and there were no significant differences of reactivity among regions studied. In conclusion, we showed reference values of LCBF and carbon dioxide reactivity, measured by stable xenon-enhanced computed tomography, in patients under fentanyl-diazepam anesthesia. Carbon dioxide reactivity was preserved in all regions including gray matter, white matter, and basal ganglia.