Experimental Animal Models for Studying Antimicrobial Pharmacokinetics in Otitis Media

Antimicrobial treatment of otitis media, especially drug dosing considerations, is largely empiric, with few reported pharmacologic studies of drug distribution into the middle ear. A chinchilla animal model of serous and purulent otitis media has been used for some time to investigate mechanisms of disease pathogenesis. This model was adapted to investigate the penetration of amoxicillin, trimethoprim, and sulfamethoxazole into middle ear effusion. Purulent otitis media was produced by direct middle ear inoculation with type 7F Streptococcus pneumoniae. Serous otitis media was produced by eustachian tube obstruction using silastic sponge or Coeflex cement, but the Coeflex caused an undesirable local inflammatory response. The three antibiotics were administered to chinchillas with serous and purulent middle ear effusion. Plasma and ear fluid drug concentrations were measured by liquid chromatography and demonstrated the value of this model in assessing antibiotic penetration.     

Effect of decreased levels of intrinsic tetrahydrobiopterin on endothelial function in anesthetized rats

Tetrahydrobiopterin (BH4) deficiency has been suggested to be an important factor in vascular endothelial dysfunction. In this study, we investigated the influence of decreased BH4 level produced by administration of 2,4-diamino-6-hydroxypyrimidine (DAHP), a specific inhibitor of the rate-limiting enzyme of BH4 synthesis, on vascular endothelial function in anesthetized rats. Wistar rats were given DAHP (0.1 - 1.0 g/kg, i.p.) or the vehicle 5 h before the experiment. Depressor responses to the endothelium-dependent vasodilator acetylcholine and the endothelium-independent vasodilator sodium nitroprusside were tested. After the experiment, blood and thoracic aorta were taken for estimating their BH4 levels and plasma concentrations of nitrite plus nitrate. DAHP produced marked decreases in BH4 levels in plasma and aorta in a dose-related manner. Baseline values for hemodynamics were not affected by DAHP. Depressor responses to acetylcholine were attenuated with the highest dose of DAHP (1.0 g/kg) but not with DAHP (0.3 g/kg), although similar decreases in BH4 levels were seen with these two doses of DAHP. Treatment with DAHP at each dose did not decrease plasma concentrations of nitrite plus nitrate. These findings suggest that a decrease in BH4 levels by acute inhibition of de novo BH4 synthesis does not necessarily cause endothelial dysfunction.     

Increase in spinal longitudinal length by correction surgery for adolescent idiopathic scoliosis

Purpose

One of the downsides of spinal correction surgery for adolescent idiopathic scoliosis (AIS) is the cessation of spinal longitudinal growth within the fused levels in growing children. However, the surgery itself has the potential to increase spinal longitudinal length by correcting the curvature. The purpose of this study was to evaluate the correlation between curve correction and increased spinal longitudinal length by corrective surgery for AIS.

Methods

This study included 208 consecutive patients (14 male, 194 female) with AIS who underwent posterior or anterior correction and fusion surgeries. Mean age at the time of surgery was 15.7 ± 3.3 years (range 10–20 years). Patients with hyperkyphosis of more than 40° were excluded. All patients had main curves in the thoracic spine (Lenke type 1 or 2). Forty-three patients underwent anterior spinal correction and fusion (ASF) and 164 underwent posterior spinal correction and fusion (PSF). The mean preoperative height was 154.7 ± 6.9 cm (range 133–173 cm). Pre and postoperative PA standing X-ray films were used to measure the Cobb angle and spinal length between the end vertebrae of the main thoracic curve, and between T1 and L5. The patients were divided into ASF and PSF groups, within which correlations between the Cobb angle correction and spinal length increase were evaluated.

Results

In the ASF group, the mean preoperative Cobb angle of the main thoracic curve was 54.9 ± 8.3° (range 41–83°) and it was corrected to 19.7 ± 9.5° (range 0–47°) with a mean correction of 35.2 ± 11.1° (range 10–74°) after surgery. The mean increase in the length of the main thoracic curve was 1.5 ± 4.6 mm (range ?8 to 13 mm), and the mean increase in T1–L5 length was 16.6 ± 7.7 mm (range ?3 to 51 mm). Significant correlation between the correction of the Cobb angle and increase in T1–L5 length was observed, with a correlation coefficient of 0.44. In the PSF group, the mean preoperative Cobb angle of the main thoracic curve was 58.8 ± 11.6° (range 36–107°) and it was corrected to 17.1 ± 7.6° (range 10–49°), with a mean correction of 41.7 ± 10.2° (range 21–73°) after surgery. The mean increase in the length of the main thoracic curve was 14.0 ± 5.2 mm (range 0–42 mm), and the mean increase in T1–L5 length was 32.4 ± 10.8 mm (10–61 mm). Correlation between the correction of the Cobb angle and increase in T1–L5 length was high, with a correlation coefficient of 0.64. The increase in T1–L5 length could be calculated by the following formula based on linear regression analysis: increase in T1–L5 length (mm) = correction of the Cobb angle (º) × 0.77.

Conclusion

Spinal longitudinal length was significantly increased after surgery in both the ASF and PSF groups. Correction of the Cobb angle and increase in T1–L5 length were highly correlated with each other, especially in the PSF group.     

Successful Resection of Hepatocellular Carcinoma with Bronchobiliary Fistula Caused by Repeated Transcatheter Arterial Embolizations: Report of a Case

Bronchobiliary fistula (BBF) is a rare but life-threatening condition. We herein describe a rescued case of a patient with hepatocellular carcinoma (HCC) who developed BBF as a late complication of transcatheter arterial embolization (TAE). A 66-year-old man underwent repeated TAE for a large HCC during a 3-year period. Massive biliptysis developed after the last treatment and bronchoscopy proved the presence of BBF. Radiological studies exhibited a necrotic HCC in the right liver with a tumor thrombus protruding into the common bile duct. Localized pneumonia was also present in the right lung. A right hemihepatectomy with a bile duct tumor thrombectomy and a right lower lobectomy of the lung were performed. He is presently doing well at 6 months after surgery. Increased intraluminal pressure of the biliary system due to obstruction by the tumor thrombus is considered to have led to the rupture of the liver abscess into the bronchus, thus creating a BBF. This is the first successfully resected case of HCC associated with BBF.     

Long-term surgical outcomes of cervical dumbbell neurinomas

Study design

Retrospective case series.

Objective

To evaluate our treatment strategy for cervical dumbbell neurinoma.

Summary of background data

In treating cervical dumbbell neurinoma, possible difficulties include reoperation due to recurrent tumor, denervation due to nerve root resection, and postoperative spinal deformity due to extensive bony removal.

Methods

We reviewed 75 cases of cervical dumbbell neurinoma that were treated surgically between 1985 and 2006. Postoperative neurological deficits, effects of surgical margins on tumor recurrence, and surgical complications were investigated retrospectively.

Results

Sensory and motor deficits due to resection of specific nerve roots appeared temporarily in 33 and 23 % of all cases, and persisted in 8 and 8 % at final evaluation, respectively. Total, subtotal, and partial resection was performed in 57, 13, and 5 cases, respectively. The total resection rate was low in the tumors that had large extraforaminal components. Of the subtotally resected 13 cases, only two cases of high tumor-growth rate required re-operation or showed tumor growth. Among the five partially resected cases, re-operation was necessary in two cases 13 and 15 years later because of aggravated neurological symptoms due to tumor growth. Two patients who underwent C2 laminectomy developed kyphosis, and three patients who underwent facet joint resection and curettage of vertebral body lesions developed scoliosis.

Conclusion

Total resection should be attempted for cervical dumbbell tumors. In cases where total resection was potentially of high risk, however, subtotal resection (within the capsule) was found to be a practical choice yielding favorable long-term outcome when the tumor growth rate (MIB-1 index) was low.     

Surgical lung biopsy for interstitial lung diseases—a single center study of 129 patients

BackgroundAccording to guidelines for the diagnosis and treatment of interstitial lung diseases (ILDs), a diagnostic surgical lung biopsy should be used to obtain the differential diagnosis of an ILD in patients with ILDs, which are difficult to distinguish clinically. However, the risk of developing postoperative complications such as postoperative pulmonary fistula or acute exacerbation is a concern. The purpose of this study was to evaluate the safety of surgical lung biopsy for the differential diagnosis of ILDs.MethodsFrom October 2007 to July 2019, 129 patients thought to have ILD underwent a surgical lung biopsy at Toho University Omori Medical Center. We conducted a retrospective study on the diagnosis and safety of surgical lung biopsy for patients with ILD.ResultsThe 30- and 60-day mortality was 0%. Postoperative complications occurred in 13 of 129 (10.1%) patients. The complications included pneumothorax in 8 (6.2%) patients after removal of the chest tube, postoperative pneumonia in 2 (1.0%), and acute exacerbation in 1 (0.8%). Postoperative pneumothorax was observed in 4 of 13 patients (30.7%) who underwent a biopsy of the apex of the lung (right S1, left S1+2), which was a significantly higher rate of postoperative pneumothorax than seen for patients undergoing biopsy at other sites (P=0.0086).ConclusionsSurgical lung biopsy for the differential diagnosis of an ILD was performed safely. However, biopsy sites for ILDs need to be carefully selected to avoid postoperative complications.