A case of aspergilloma detected after surgery for pneumothorax.

We report a case of aspergilloma in an 80-year-old male patient who had no identifiable underlying disease before surgery for pneumothorax. He was hospitalized for left pneumothorax. A chest CT revealed a large bulla in the left lung apex with a nodule (diameter; 1.5 cm) at the edge of the bulla. After thoracodocesis, air leakage persisted and a large bulla and nodule were resected. Aspergillus was detected histopathologically in the nodule. Treatment with itraconazole 200 mg a day followed, and 4 months later he had no recurrent pneumothorax or Aspergillus infection.     

Accelerated Loss of Islet β Cells in Sucrose-Fed Goto-Kakizaki Rats, a Genetic Model of Non-Insulin-Dependent Diabetes Mellitus

The Goto-Kakizaki (GK) rat is a spontaneously diabetic animal model of non-insulin-dependent diabetes mellitus, which is characterized by progressive loss of β cells in the pancreatic islets with fibrosis. In the present study, we examined the effects of sucrose feeding on the islet pathology in this model. Six-week-old GK rats were fed with 30% sucrose for 6 weeks to induce severe hyperglycemia, and their condition was compared with that of nontreated rats. Age-matched normal Wistar rats were also given sucrose for the same periods and used for comparison. The sucrose-treated GK rats showed elevated blood glucose levels on oral glucose tolerance tests at 60 minutes and 120 minutes, representing 123% and 127% of values in untreated GK rats, respectively. At the end of the study, the mean β-cell volume density in GK rats was 50% less than that in untreated Wistar rats. Sucrose feeding further reduced the volume densities of β cells to only 50% of the levels of age-matched GK rats. Apoptotic cells were found in islet β cells only in GK rats fed sucrose (mean 0.067%). There appeared to be more islets that immunohistochemically stained strongly positive with 8-hydroxy-deoxyguanosine as a marker of oxidative damage of DNA in GK rats fed sucrose compared with those not given sucrose. GK rats not fed sucrose showed significantly lower proliferative activity of β cells measured by 5-bromo-2′-deoxyuridine uptake and intensified expression of Bcl-2 immunoreactivities at 6 weeks of age compared with those in age-matched Wistar rats. These two indices were reduced in both GK and Wistar rats with increasing age and were not affected by sucrose feeding in either group. The present study thus indicated that sucrose feeding promoted the apoptosis of β cells in GK rats through increased oxidative stress without altering their proliferative activity.     

Novel missense mutations in the human lysosomal sialidase gene in sialidosis patients and prediction of structural alterations of mutant enzymes

Three novel missense mutations in the human lysosomal sialidase gene causing amino acid substitutions (P80L, W240R, and P316S) in the coding region were identified in two Japanese sialidosis patients. One patient with a severe, congenital form of type 2 sialidosis was a compound heterozygote for 239C-to-T (P80L) and 718T-to-C (W240R). The other patient with a mild juvenile-onset phenotype (type 1) was a homozygote for the base substitution of 946C-to-T (P316S). None of these mutant cDNA products showed enzymatic activity toward an artificial substrate when coexpressed in galactosialidosis fibroblastic cells together with protective protein/cathepsin A (PPCA). All mutants showed a reticular immunofluorescence distribution when coexpressed with the PPCA gene in COS-1 cells, suggesting that the gene products were retained in the endoplasmic reticulum/Golgi area or rapidly degraded in the lysosomes. Homology modeling of the structural changes introduced by the mutations predicted that the P80L and P316S transversions cause large conformational changes including the active site residues responsible for binding the sialic acid carboxylate group. The W240R substitution was deduced to influence the molecular surface structure of a limited region of the constructed models, which was also influenced by previously identified V217M and G243R transversions. Received: Stptember 21, 2001 / Accepted: November 2, 2001     

Molecular interaction of imino sugars with human α-galactosidase: Insight into the mechanism of complex formation and pharmacological chaperone action in Fabry disease

Enzyme enhancement therapy (EET) for Fabry disease involving imino sugars has been developed and attracted interest. It is thought that imino sugars act as pharmacological chaperones for wild-type and mutant α-galactosidases (GLAs) in cells, but the mechanisms underlying the molecular interactions between the imino sugars and the enzyme have not been clarified yet. We examined various kinds of imino sugars and found that galactostatin bisulfite (GBS) inhibited GLA in vitro and increased the enzyme activity in cultured Fabry fibroblasts as in the case of 1-deoxygalactonojirimycin (DGJ). Then, we analyzed the molecular interactions between the imino sugars and recombinant human GLA by means of isothermal titration calorimetry and surface plasmon resonance biosensor assays, and first determined the thermodynamic and binding-kinetics parameters of imino sugar and GLA complex formation. The results revealed that DGJ bound to the enzyme more strongly than GBS, the binding of DGJ to the enzyme protein being enthalpy-driven. In the case of GBS, the reaction was mainly enthalpy-driven, but there was a possibility that entropy-driven factors were involved in the binding. Structural analysis in silico revealed that both the chemicals fit into the active-site pocket and undergo hydrogen bonding with residues comprising the active-site pocket including the catalytic ones. The side chain of GBS was oriented towards the entrance of the active-site pocket, and thus it could be in contact with residues comprising the wall of the active-site pocket. Thermodynamic, kinetic and structural studies should provide us with a lot of information for improving EET for Fabry disease.     

Accompanying artery of sciatic nerve as recipient vessel for free‐flap transfer: A computed tomographic angiography study and case reports

Suitable recipient vessels for free‐flap transfer are hard to find in the posterior thigh. To investigate the versatility of accompanying artery of sciatic nerve as a recipient vessel in this region, we performed computed tomographic angiographic study of 20 consecutive healthy thighs in 10 patients. The presence and internal diameter of the accompanying artery were studied. The accompanying artery of the sciatic nerve was present in 11 thighs (55%) and the internal diameter of the artery at the mid‐thigh level ranged from 2.1 to 3.2 mm. We used this artery as a recipient vessel for free flaps transferred to reconstruct extensive thigh defects in three patients with sarcomas. In all patients the flaps survived without vascular compromise. No sensory or motor dysfunction in the sciatic nerve distribution occurred in any patients. We believe that the accompanying artery of the sciatic nerve may be a recipient vessel for free‐flap transfer in selected patients. © 2014 Wiley Periodicals, Inc. Microsurgery 35:284–289, 2015.     

The use of infliximab in the prevention of postsurgical recurrence in polysurgery Crohn's disease patients: a pilot open-labeled prospective study

Purpose

Crohn's disease (CD) commonly recurs after surgery, and a number of patients need repeated surgery, especially smokers and those with repeated surgeries or penetrating disease. Whether infliximab prevents postsurgical recurrence in high-risk CD remains unknown. In the present pilot open-labeled study, we investigated the safety and efficacy of scheduled infliximab, which was started early after surgery, in maintaining remission of CD patients who have undergone multiple surgeries due to penetrating disease.

Methods

Eleven patients (nine male, two female; age range, 26–48?years) who had undergone repeated surgeries (median, 4; range, 2–5) for penetrating disease were enrolled. Two to 4?weeks after surgery, the patients were started on intravenous infliximab (5?mg/kg) at an 8-week interval. The primary end points were the proportion of patients in clinical remission at the end of the study, the rate of endoscopic/radiologic remission at 24?months, and the rate of adverse effects.

Results

One patient dropped out due to non-compliance, and ten patients were eligible for analysis. Clinical remission was maintained in six of ten patients (60.0%) at the end of the study. At 24?months, four out of ten patients were in endoscopic or radiological remission (40.0%). Two patients experienced adverse effects (18.2%), one of whom elected to withdraw from the study.

Conclusion

The findings of no major safety concern and possible clinical benefit in our study suggest that further investigation of infliximab as a treatment for prevention of postsurgical recurrence in high-risk CD is warranted.     

Flow‐through fibula flap using soleus branch as distal runoff: A case report

The flow‐through fibula flap utilizing the soleus branch as a distal runoff has not yet been reported. We herein present a patient with left tibial adamantimoma in whom wide resection of the tumor resulted in a segmental tibial defect 22 cm in length. The defect was successfully reconstructed with a flow‐through free fibula osteocutaneous flap using the soleus branch of the peroneal artery as a distal runoff. The short T‐segment of the peroneal artery was interposed to the transected posterior tibial artery. The soleus branch has a constant anatomy and a larger diameter than the distal stump of the peroneal artery. Short interposed flow‐through anastomosis to the major vessels is much easier and more reliable than the conventional methods. We believe that our method represents a versatile option for vascularized fibula bone grafting for extremity reconstruction. © 2012 Wiley Periodicals, Inc. Microsurgery, 2013