Ability of poly-L-arginine to enhance drug absorption into aqueous humor and vitreous body after instillation in rabbits

The effect of poly-L-arginine with a molecular weight of 35.5 kDa (PLA) on the ocular absorption of hydrophilic molecules after instillation was examined in rabbits in vivo. FITC-labeled dextran (3.8 kDa, FD-4) and pyridoxamine were used as model hyprophilic molecules for absorption. The potential toxicity of PLA was evaluated by microscopic observation of the cornea, production of TNF-alpha, and the thickness of the corneal epithelia and stroma. The concentration of pyridoxamine and FD-4 in aqueous humor 30 min after a single instillation of a solution of PLA was 29- and 16-fold higher than that without PLA, respectively, but the drug concentrations were not determined in the vitreous body. Repetitive instillation of PLA every 30 min for 150 min achieved 31.1- and 13.3-fold increases in pyridoxamine and FD-4 in aqueous humor, respectively. Furthermore, significant amounts of pyridoxamine and FD-4 were detected in the vitreous body after the repetitive instillation of PLA, even although very little of these drugs was detected in the vitreous body in the control eye without PLA. On the other hand, repetitive instillation of PLA did not induce any alteration of corneal epithelial and stromal thickness, production of TNF-alpha, and disruption of the epithelial and stromal morphologies and neutrophil infiltration. Our findings suggest that PLA may be useful in promoting drug delivery of hydrophilic drugs to the ocular tissues without producing any significant corneal damage and inflammation.     

Flexible hinge toe implant arthroplasty for rheumatoid arthritis of the first metatarsophalangeal joint: long-term results

We report the long-term clinical results and survival rate of the implant in flexible hinge toe implant arthroplasty of the first metatarsophalangeal joint, combined with a shortening oblique osteotomy of the metatarsal neck in the lateral toes, in patients with rheumatoid arthritis. Between 1983 and 1990, arthroplasty was performed on 97 feet in 66 patients. Twenty-seven patients died; follow-up information was available for 60 feet in the remaining 39 patients, who were followed for an average of 12 years. Twenty-nine patients (74%) were satisfied with the outcome after surgery, 7 were satisfied but had some pain or recurrent deformities, and 3 were unsatisfied. Radiologically, visible fracture was identified in nine implants. Four implants were removed because of infection (n = 2) or recurrent deformity (n = 2); no implant was removed because silicone synovitis developed. With revision as the endpoint, the implant survival rate was 93% at 10 years, and with radiographic implant fracture as the endpoint, the implant survival rate was 87% at 10 years. Shortening oblique osteotomy of the lateral toes appeared to decrease the rate of implant fracture and should be performed concomitantly with implantation when rheumatoid forefoot deformities are being reconstructed. Received: July 27, 2000 / Accepted: October 2, 2000     

Evaluation of undiagnosed solitary lung nodules according to the probability of malignancy in the American College of Chest Physicians (ACCP) evidence-based clinical practice guidelines

Background

This study retrospectively investigated the clinical significance of undiagnosed solitary lung nodules removed by surgical resection.

Patients and methods

We retrospectively collected data on the age, smoking, cancer history, nodule size, location and spiculation of 241 patients who had nodules measuring 7 mm to 30 mm and a final diagnosis established by histopathology. We compared the final diagnosis of each patient with the probability of malignancy (POM) which was proposed by the American College of Chest Physicians (ACCP) guidelines.

Results

Of the 241 patients, 203 patients were diagnosed to have a malignant lung tumor, while 38 patients were diagnosed with benign disease. There were significant differences in the patients with malignant and benign disease in terms of their age, smoking history, nodule size and spiculation. The mean value and the standard deviation of the POM in patients with malignant tumors were 51.7 + 26.1%, and that of patients with benign lesions was 34.6 + 26.7%. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.67. The best cut-off value provided from the ROC curve was 22.6. When the cut-off value was set at 22.6, the sensitivity was 83%, specificity 52%, positive predictive value 90%, negative predictive value 36% and accuracy 77%, respectively.

Conclusions

The clinical prediction model proposed in the ACCP guidelines showed unsatisfactory results in terms of the differential diagnosis between malignant disease and benign disease of solitary lung nodules in our study, because the specificity, negative predictive value and AUC were relatively low.     

Clinical analysis of esophageal cancer associated with other primary cancers

This study aims to investigate the therapeutic and prognostic implications of esophageal cancer in patients with other primary cancer. Between April 1992 and December 2008, in 83 patients underwent surgery for esophageal cancer at our department. Among them, 24 patients (28.9%) had medical history of additional primary cancer. There were 16 metachronous cancers and 8 synchronous cancers. Six patients had antecedent other primary cancers, and subsequent primary cancers developed in 10 patients. The other primary cancers included head and neck cancer in 8 patients, gastric cancer in 8, lung cancer in 6, colorectal cancer in 3, and other cancer in 3. The patients with other primary cancers were both heavy smokers and heavy drinkers in comparison to those without other primary cancers. The post-operative 5-year survival rate in patients with subsequent cancers, antecedent cancers, and synchronous cancers were 100%, 70.0%, and 46.9%. The 5-year survival rate was 33.4% in patients without other primary cancers. A high incidence of multiple primary cancers was observed in patients with esophageal carcinoma but the prognosis of these patients with metachronous cancers are better than that of patient with synchronous cancers and patients without other primary cancers. Post-operative follow up is considered to be necessary for early detection of multiple occurrences of carcinoma, especially in the upper aerodigestive tract.     

Temporary tracheotomy for post-intubation laryngeal edema after lung cancer surgery: a case report

We compare the early and late outcomes of a modified aortic root remodelling (ARR) technique for aortic root replacement without mobilisation or reimplantation of the coronary ostia, with those of the modified Bentall-de Bono procedure. A retrospective observational study was performed comprising 181 consecutive patients who underwent aortic root replacement with a modified Bentall-de Bono procedure (104 patients) or ARR (77 patients) between January 2013 and December 2019. Primary endpoints included hospital mortality and late survival. Secondary endpoints included incidence of post-operative complications and freedom from late re-operation. ARR procedures were performed with shorter cross-clamp times and comparable cardiopulmonary bypass times to modified Bentall-de Bono procedures. The incidence of early post-complications was comparable between groups. 30-day mortality was numerically lower with ARR than the modified Bentall-de Bono procedure. Over 7-year follow-up, 4 patients (3.8%) required repeat aortic surgery after a modified Bentall-de Bono procedure, and none after ARR. Long-term mortality after ARR and after modified Bentall-de Bono procedures was 17.1% and 22.7%, respectively. The cumulative incidence of reintervention on the aortic root/valve was 3.2% after a modified Bentall-de Bono procedure and 0% after ARR. When adjusted for other independent risk factors, late mortality was not influenced by the procedure performed, although competing risk adjusted for age showed that the modified Bentall-de Bono procedure was associated with an increased risk of aortic root/aortic valve re-operation. The modified ARR technique is associated with reduced myocardial ischaemia time, lower post-operative mortality and aortic re-intervention rates compared to a modified Bentall-de Bono procedure. It may be considered a safe and feasible procedure for aortic root/ascending aortic replacement offering good long-term outcomes.