An Autopsy Case of Tracheal Agenesis with Broncho-esophageal Fistula

Abstract True incidence of this malformation is probably greater than that reported since the definitive diagnosis has been made at autopsy in most cases. Various hypotheses on the pathogenesis of tracheal agenesis have been proposed but they are still controversial.
In this report, we present a case of tracheal agenesis with a broncho-esophageal fistula and discuss the formal genesis.     

Neural connections between the hypothalamus and the liver

After receiving information from afferent nerves, the hypothalamus sends signals to peripheral organs, including the liver, to keep homeostasis. There are two ways for the hypothalamus to signal to the peripheral organs: by stimulating the autonomic nerves and by releasing hormones from the pituitary gland. In order to reveal the involvement of the autonomic nervous system in liver function, we focus in this study on autonomic nerves and neuroendocrine connections between the hypothalamus and the liver. The hypothalamus consists of three major areas: lateral, medial, and periventricular. Each area has some nuclei. There are two important nuclei and one area in the hypothalamus that send out the neural autonomic information to the peripheral organs: the ventromedial hypothalamic nucleus (VMH) in the medial area, the lateral hypothalamic area (LHA), and the periventricular hypothalamic nucleus (PVN) in the periventricular area. VMH sends sympathetic signals to the liver via the celiac ganglia, the LHA sends parasympathetic signals to the liver via the vagal nerve, and the PVN integrates information from other areas of the hypothalamus and sends both autonomic signals to the liver. As for the afferent nerves, there are two pathways: a vagal afferent and a dorsal afferent nerve pathway. Vagal afferent nerves are thought to play a role as sensors in the peripheral organs and to send signals to the brain, including the hypothalamus, via nodosa ganglia of the vagal nerve. On the other hand, dorsal afferent nerves are primary sensory nerves that send signals to the brain via lower thoracic dorsal root ganglia. In the liver, many nerves contain classical neurotransmitters (noradrenaline and acetylcholine) and neuropeptides (substance P, calcitonin gene-related peptide, neuropeptide Y, vasoactive intestinal polypeptide, somatostatin, glucagon, glucagon-like peptide, neurotensin, serotonin, and galanin). Their distribution in the liver is species-dependent. Some of these nerves are thought to be involved in the regulation of hepatic function as well as of hemodynamics. In addition to direct neural connections, the hypothalamus can affect metabolic functions by neuroendocrine connections: the hypothalamus-pancreas axis, the hypothalamus-adrenal axis, and the hypothalamus-pituitary axis. In the hypothalamus-pancreas axis, autonomic nerves release glucagon and insulin, which directly enter the liver and affect liver metabolism. In the hypothalamus-adrenal axis, autonomic nerves release catecholamines such as adrenaline and noradrenaline from the adrenal medulla, which also affects liver metabolism. In the hypothalamus-pituitary axis, release of glucocorticoids and thyroid hormones is stimulated by pituitary hormones. Both groups of hormones modulate hepatic metabolism. Taken together, the hypothalamus controls liver functions by neural and neuroendocrine connections.     

Clinical experience with ceftizoxime suppositories in bacterial infections in children

A clinical trial of ceftizoxime suppositories (CZX-S) was performed to evaluate the therapeutic effectiveness in children with bacterial infection. The subjects were 10 children comprising 4 with pneumonia, 3 with lacunar tonsillitis, 2 with pharyngitis, and 1 with UTI. They were given 1 suppository containing either 125 mg or 250 mg of CZX 2 to 4 times a day. The daily per kg body weight dose ranged from 17.1 to 60.0 mg. The result was "markedly effective" in 3, "effective" in 6, and "failure" was recorded in 1. Bacteriologically, successful eradication of causative organisms was confirmed in all the 4 children who underwent the test. No clinical side effects were observed. The only laboratory test abnormality recorded in a single patient was eosinophilia, which was not definitely ascribable to CZX-S. In conclusion, CZX-S have proved to be a clinically safe and effective antibiotic preparation in infantile infection, even in children whose treatment with conventional antibiotics is associated with difficulties.     

Destruction of anionic sites in blood-retinal barrier after retinal photocoagulation

The retinal pigment epithelial cells (RPE) have "tight junctions" at the apical side of the lateral wall between neighbouring cells and form physiological blood-retinal barriers. Recently, in addition to physiological barriers, charged barriers, consisting of anionic sites of cell membrane and its basement membrane, have been discussed. We performed weak retinal photocoagulation in rabbit eyes in order to break their charged barriers, and examined the repair process using a cationic probe, polyethyleneimine (PEI). Two days after photocoagulation, RPE cells were broken down and choriocapillaries were occluded with thrombi, and their anionic sites were lost. At one week after photocoagulation, structural reconstruction started from the edge of the photocoagulation area. In this area, proliferated RPE cells covered Bruch's membrane, but their charged barrier did not recover. Two weeks after photocoagulation, proliferated RPE cells covered Bruch's membrane over the entire photocoagulated area, and they obtained anionic charge. The present study revealed that retinal damage induced by weak laser photocoagulation was repaired within two weeks after photocoagulation with respect to the charged barrier.     

Novel chloride channel gene mutations in two unrelated Japanese families with Becker's autosomal recessive generalized myotonia

We investigated the skeletal muscle voltage-gated chloride channel gene (CLCN1) in two unrelated Japanese patients with Becker's myotonia congenita. The non-myotonic parents of each patient were consanguineous. The proband of each family shares generalized myotonia, transient weakness after rest, and leg muscle hypertrophy. However, the disease severity related to the degree of myotonia differed, even in view of the response to long train nerve stimulation tests. CLCN1 gene analysis revealed a novel Ala659Val missense mutation identified to be homozygous in the more severe patient, while a novel Gln445Stop nonsense mutation was present in the other patient. Both mutations were absent in 90 Japanese normal controls. This is the first report of Japanese cases of Becker's myotonia congenita with CLCN1 gene mutations.     

Identification of a Notch3 mutation in a Japanese CADASIL family. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary disease that is characterized by recurrent stroke episodes and focal neurologic deficits progressing to pseudobulbar palsy and dementia. The causative gene is the Notch3 gene on chromosome 19, and 22 missense mutations have been identified in Caucasian patients to date. To perform mutational analysis of the Notch3 gene, we identified its exon intron boundaries and prepared sets of primers for amplification of each exon. Using these primers, we determined the Notch3 gene in a Japanese family with CADASIL symptoms and found a missense mutation (Arg133Cys) in exon 4. The mutation was heterozygous and cosegregated with the disease. Thus, the Notch3 gene is responsible for CADASIL in patients across different ethnic groups.