Surgical treatment of recurrent tracheo-esophageal fistula using a latissimus dorsi pedicled muscle flap —Report of a case—

We report herein, a case of a child in whom a prepared latissimus dorsi muscle flap was successfully utilized in the treatment of recurrent tracheo-esophageal fistula (TEF). A 12-month-old girl who had undergone a primary repair of Gross’s type C esophageal atresia at 6 days of age and a secondary repair of recurrent TEF at 4 months of age experienced, postoperatively, repeated episodes of aspiration pneumonia caused by recurrence of the fistula. Thus, we performed a reoperation in which the fistula was excised, and a latissimus dorsi muscle pedicled flap was interposed between the tracheal and esophageal suture lines. Viability of the muscle flap was adequately achieved by means of a three-stage delayed operation. Although a minor anastomotic leakage of the esophagus was found postoperatively, it healed spontaneously, and the patient was commenced on a normal diet orally without any problems at 26 months of age.     

Magnetic resonance imaging of skeletal muscle in patients with Duchenne muscular dystrophy--serial axial and sagittal section studies

Magnetic resonance imaging of skeletal muscles in thirteen patients with Duchenne muscular dystrophy was performed to estimate pathological changes. Serial axial and sagittal sections of the right lower extremity were recorded. In the early stage, the T1 values of gastrocnemius and soleus muscles were slightly lower than the control values, and in the late stage, the values were much lower in all muscles examined. In sagittal sections, the gastrocnemius muscles in the early stage showed a high density area at the distal region adjacent to soleus muscle, and the soleus muscle showed a high density area adjacent to the gestrocnemius muscle. In serial axial sections, high density areas of the anterior and posterior tibialis muscles appeared first at their proximal and peripheral regions. It was concluded that the sequence of appearance of pathological changes was different not only among individual muscles but also among various regions of each muscle; the high density changes appeared first at myotendon junctions.     

Distorted control of feeding behavior induced by abnormally regulated peripheral energy metabolism

To regulate feeding behavior and energy metabolism, a variety of neuronal and hormonal messages are integrated by glucose sensing system located in peripheral organ and central nervous system. Among them, a hepatoportal glucose sensor plays a major role in perception of peripheral humoral information such as brain-gut peptides and cytokines. These signals are transmitted to the hypothalamus through the hepatic afferent vagus nerve and the nucleus of the solitary tract. Recent molecular approaches using knock out or transgenic mice have indicated important effects of peripheral energy metabolism on feeding control. Particularly, fatty acid metabolism in the liver and functions of uncoupling protein family in the brown adipose tissue and the muscle play an essential role as detector for energy storage, and in turn may be contributable to regulation of feeding behavior.     

Bactericidal activity of the nitroimidazopyran PA-824 in a murine model of tuberculosis

The nitroimidazopyran PA-824 has potent in vitro activity against Mycobacterium tuberculosis, a narrow spectrum of activity limited primarily to the M. tuberculosis complex, and no demonstrable cross-resistance to a variety of antituberculosis drugs. In a series of experiments, we sequentially characterized the activity of PA-824 in an experimental murine model of tuberculosis. The minimal effective dose was 12.5 mg/kg of body weight/day. The minimal bactericidal dose (MBD) was 100 mg/kg/day. When PA-824 was used as monotherapy at the MBD, it exhibited promising bactericidal activity during the initial intensive phase of therapy that was similar to that of the equipotent dose of isoniazid in humans. In combination with isoniazid, PA-824 prevented the selection of isoniazid-resistant mutants. Perhaps more importantly, PA-824 also demonstrated potent activity during the continuation phase of therapy, during which it targeted bacilli that had persisted through an initial 2-month intensive phase of treatment with rifampin, isoniazid, and pyrazinamide. Together, these data strongly support further evaluation of PA-824 in combination with first- or second-line antituberculosis drugs to determine its potential contribution to the treatment of drug-susceptible or multidrug-resistant tuberculosis, respectively.     

Mechanism of the action of didecyldimethylammonium chloride (DDAC) against Escherichia coil and morphological changes of the cells

The antibacterial activity of a disinfectant with geminated twin long-chain alkyl groups, didecyldimethylammonium chloride (DDAC), was investigated. The minimum inhibitory concentration (MIC) value of DDAC against Eschrichia coil was revealed to be a small value, 1.3 mg/L, by using the specific growth rates, mu, obtained from the cultivation in a liquid nutrient broth (NB) medium. The relationship between the leakage of proteins or beta-galactosidase and the DDAC concentration showed that the leakage of intracellular macromolecules occurs at around 3 - 4 mg/L DDAC. Furthermore, the effect of DDAC on the enhancement of membrane fluidity was examined by using liposomes labeled with a fluorescent probe. It was shown that the phase transition occurs at around 3 mg/L DDAC. The bleb formation of E. coli cells in the presence of DDAC was also examined by use of scanning electron microscopy (SEM) and transmission electron microscopy (TEM). However, bleb formation was not observed at around 3 mg/L DDAC but at concentrations higher than 50 mg/L. These results suggested that the action of DDAC toward the cell membrane causes the leakage of the intracellular molecules and the subsequent death of the cells. Thus the bleb formation seemed to be a result of the action of the DDAC toward the cell membrane but not to be a reason for the death of the cells.     

Antitumor activity of ER-37328, a novel carbazole topoisomerase II inhibitor

DNA topoisomerase II has been shown to be an important therapeutic target in cancer chemotherapy. Here, we describe studies on the antitumor activity of a novel topoisomerase II inhibitor, ER-37328 [12,13-dihydro-5-[2-(dimethylamino)ethyl]-4H-benzo[c]pyrimido[5,6,1- jk]carbazole-4,6,10(5H,11H)-trione hydrochloride]. ER-37328 inhibited topoisomerase II activity at 10 times lower concentration than etoposide in relaxation assay and induced double-strand DNA cleavage within 1 h in murine leukemia P388 cells, in a bell-shaped manner with respect to drug concentration. The maximum amount of DNA cleavage was obtained at 2 microM. Like etoposide, ER-37328 (2 microM) induced topoisomerase II-DNA cross-linking in P388 cells. A spectroscopic study of ER-37328 mixed with DNA demonstrated that ER-37328 has apparent binding activity to DNA. ER-37328 showed potent growth-inhibitory activity against a panel of 21 human cancer cell lines [mean (50% growth-inhibitory concentration) GI50 = 59 nM]. COMPARE analysis according to the National Cancer Institute screening protocol showed that the pattern of the growth-inhibitory effect of ER-37328 was similar to that of etoposide, but different from that of doxorubicin. Studies on etoposide-, amsacrine [4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA)]-, and camptothecin-resistant P388 cell lines showed that: (a) etoposide- and m-AMSA-resistant P388 cell lines were partially resistant to ER-37328 compared with the parental cell line; and (b) a camptothecin-resistant cell line showed no cross-resistance to ER-37328. In addition, ER-37328 overcame P-glycoprotein-mediated resistance. In vivo, ER-37328 produced potent tumor regression of Colon 38 carcinoma inoculated s.c., and its activity was superior to that of etoposide or doxorubicin. These results indicate that ER-37328 inhibits topoisomerase II activity through the formation of topoisomerase II-DNA cleavable complex and has potent antitumor activity both in vitro and in vivo.     

A case of Gerstmann-Sträussler-Scheinker syndrome with the P105L prion protein gene mutation presenting with ataxia and extrapyramidal signs without spastic paraparesis

We describe the clinical features of a patient with Gerstmann-Sträussler-Scheinker syndrome with a mutation in the prion protein gene at codon 105 (GSS105) who presented with ataxia. Neurologic examination showed memory disturbance, dysarthria, extrapyramidal signs (bradykinesia and resting tremor) and ataxic gait without spasticity. Although GSS105 has been referred to as “spastic paraparesis-type GSS”, the patient did not show spastic paraparesis or pyramidal signs, even 11 years after the onset of symptoms. Thus, the spectrum of the GSS105 phenotype varies among patients and requires further clinicopathologic elucidation.