Peripheral nerve structure and function in long-term galactosemic dogs: morphometric and electron microscopic analyses

Experimental galactosemia for activating the polyol pathway is used extensively to explore the pathogenesis of diabetic complications. However, despite the presence of severe neuropathy in galactosemic rats, changes in the peripheral nerve have not been well established in galactosemic dogs. We therefore conducted biochemical, electrophysiological, and morphometric studies on peripheral nervous systems (PNS) in dogs given a 30% galactose diet for 44 months. Age- and sex-matched dogs given a 30% cellulose diet were used as control. Chronic galactosemia resulted in accumulation of galactitol and decrease in myo-inositol in the sciatic nerve. Electrophysiological and teased fiber analyses demonstrated no significant abnormalities in the ulnar and peroneal nerves in galactosemic dogs. Morphometric analyses revealed a tendency of myelinated fiber atrophy (24% reduction of average fiber size) associated with 20% decrease (P < 0.05 vs control) in mean myelinated fiber occupancy rate in the peroneal nerve in galactosemic dogs. In the anterior mesenteric ganglion, there was a slight but significant increase (8%) in mean neuronal cell size in galactosemic dogs (P < 0.05 vs control). Electron microscopy revealed that galactosemia did not produce dystrophic and degenerative changes in the autonomic ganglion in dogs. We conclude that structural and functional changes in the PNS of galactosemic dogs are mild and different from those of the rat model. These findings suggest that the severity of peripheral neuropathy induced by chronic galactosemia may be species dependent. Received: 10 July 1998 / Revised: 10 October 1998 / Accepted: 21 October 1998     

The effect of feeding carrots on immunoglobulin E production and anaphylactic response in mice.

Carrot juice was administered orally to BALB/c mice immunized intraperitoneally with dinitrophenylated (DNP)-OVA for about 1 month. The titers of DNP-specific IgE, DNP-specific IgG, and the levels of total IgE in mouse sera were determined. The DNP-specific IgE production by mice fed carrot juice was significantly inhibited. On the other hand, the DNP-specific IgG production and the level of total IgE in mice fed carrot juice were not significantly different from those in control mice. We also examined the effect of feeding carrots on immediate-type hypersensitivity. One hour after antigen stimulation, the ears of mice fed carrots swelled less than those of control mice. Furthermore, the rise in serum histamine in the mice fed carrots under active systemic anaphylaxis was lower than in controls. We then examined the pattern of cytokine production by spleen cells from mice followed by restimulation with DNP-OVA in vitro. The spleen cells from the mice fed carrots produced more interferon-gamma than those from the control group. In contrast, the spleen cells from the mice fed carrots produced less interleukin-4 than those from the control group. Furthermore, the interleukin-12 production of the spleen cells from mice fed carrots was also higher than that of the control group. These findings suggest that feeding carrots improves the helper T cell (Th)1/Th2 balance, inhibiting specific IgE production and antigen-induced anaphylactic response.     

Malignant adenomyoepithelioma of the breast: a case with distant metastases

Adenomyoepithelioma is thought to be a low-grade malignancy, and cases showing malignant behavior are rare. A massive breast tumor with skin invasion in a 60-year-old woman was diagnosed as malignant adenomyoepithelioma. Despite the tumor size and skin invasion, no axillary lymph node metastases were detected. Light microscopy showed proliferation of tubular structures composed of atypical epithelial and myoepithelial cells and occasional anaplastic cells with mitotic figures extending to the epidermis of the skin. Twenty-four months after the surgery the patient complained of dull pain in the right thigh, and was found to have bone, lung and mediastinal lymph node metastases. There was neither local recurrence nor axillary lymph node metastasis. Subsequent femur fracture was treated by osteotomy. Despite additional chemoradiotherapy, the patient died 43 months after the first operation. Our case and literature review indicated that this tumor tends to show hematogenous metastasis.     

Correlation of Clinicopathologic Features of Resected Hepatocellular Carcinoma with Hepatitis C Virus Genotype

Clinicopathologic findings in patients with hepatocellular carcinoma complicating hepatitis C virus and outcomes after liver resection were compared between different viral genotypes. One hundred and forty-seven patients with both anti-hepatitis C virus antibody and hepatitis C virus RNA in their sera underwent curative resection for hepatocellular carcinoma in our department between 1991 and 1997. Of these patients, 115 were infected with hepatitis C virus genotype 1b (group 1), and 32 were infected with 2a or 2b (group 2). Clinicopathologic findings and outcomes after operation were compared between the two groups. Alanine aminotransferase activity was significantly higher in group 2 than in group 1. Genotypes did not differ concomitantly with histopathologic features of the carcinoma or adjacent hepatic tissue. Although the tumor-free survival rate did not differ significantly between the two groups, recurrence was not detected during the period beyond 3 years following operation in group 2, while recurrences arose during that period in 16 group 1 patients, most of whom continued to manifest active hepatitis. In 7 of these 16 patients, the recurrent tumors were histologically multicentric in origin. The cumulative survival rate was significantly lower in group 1 than 2. Multivariate analysis indicated that genotype 1b was an independent risk factor for short survival. Patients infected with genotype 1b may have a relatively high risk of ongoing hepatocarcinogenesis and more aggressive progression of associated liver dysfunction, resulting in a poorer outcome than with other genotypes.     

p53 Status Predicts the Efficacy of Postoperative Oral Administration of Tegafur for Completely Resected Non-small Cell Lung Cancer†

Although postoperative adjuvant therapy for non-small cell lung cancer (NSCLC) had not been reported to be effective, it has been reported recently that oral administration of tegafur (1-[2-tetrahydrofuryl]-5-fluorouracil, FT) may improve the postoperative prognosis. In the present paper, to examine whether p53 status affects the efficacy of FT as postoperative adjuvant chemotherapy for NSCLC, a total of 236 consecutive patients with completely resected pathologic stage I–IIIa NSCLC were retrospectively reviewed. p53 status was determined by immunohistochemical staining. For all patients, the 5-year survival rate of patients with FT administration (FT group) was 78.1%, being significantly higher than that (69.1%) of patients without FT administration (control group) (P=0.046). For patients without immunohistochemical evidence of p53 overexpression, the 5-year survival rate in the FT group was 87.1%, being significantly higher than that (74.0%) in the control group (P=0.036). This demonstrates an improvement of postoperative prognosis by FT administration. On the other hand, for patients with p53 overexpression, there was no significant difference in the postoperative prognosis between the FT group and the control group (5-year survival rate 63.2% and 60.1%, respectively; P=0.514), demonstrating that FT administration was not effective for these patients. In conclusion, p53 status may be useful for predicting the efficacy of postoperative adjuvant chemotherapy using FT. A prospective randomized study stratified by p53 status is needed to clarify the effect of postoperative FT administration.     

Treatment of seven cases of chronic granulomatous disease with sulfamethoxazole-trimethoprim (SMX-TMP)

Seven male Japanese children with chronic granulomatous disease were given sulfamethoxazole-trimethoprim (SMX-TMP) for recurrent pyogenic infections, most of which had proved difficult to control with other antibiotics. With continuous treatment the children remained free of infections severe enough to necessitate hospitalization, except on one occasion. Serious complications, including hematological disorders, never occurred during therapy and there were no changes in leukocyte function during therapy. These results indicate that SMX-TMP should be considered in the treatment of bacterial infections associated with chronic granulomatous disease.     

Resection of a mediastinal mature teratoma diagnosed owing to sudden chest pain with elevated preoperative serum CA19-9

Mediastinal teratomas are typically benign and asymptomatic, but they undergo sudden enlargement or rupture into neighboring organs in some patients owing to intratumoral hemorrhage, leading to serious complications. We report the case of a mediastinal mature teratoma that was discovered because of the sudden onset of chest pain accompanied by elevated preoperative serum CA19-9 levels. The patient was a 43-year-old man who experienced sudden chest pain and was brought to hospital in an ambulance. Chest radiography and computed tomography revealed a mediastinal tumor and a serum CA19-9 level that was elevated to 4377 U/ml. The tumor comprised soft tissue, fluid, and cystic components. The histological diagnosis was mature teratoma with peritumoral bleeding. Most epithelial components, including squamous epithelium and similar components in the bronchi, showed positive results for CA19-9 on immunohistological examination. The postoperative course was uneventful, and serum CA19-9 levels normalized.     

Porcine enamel matrix derivative enhances trabecular bone regeneration during wound healing of injured rat femur

To elucidate the effects of enamel matrix derivative (EMD: Emdogain®) on bone regeneration in rat femurs after drill‐hole injury, defects in bone were filled with either EMD or its carrier, PGA, as control. On postoperative days 4 to 28, dissected femurs were examined by means of various morphological approaches. In both experimental groups, formation of trabecular bone, which was immunostained for bone sialoproteins (BSP), had occurred in the medullary cavities at cylindrical bone defects on Day 7 postoperatively. Cuboidal osteoblasts were clearly observed on these newly‐formed BSP‐positive bone trabeculae. On Days 7 and 14, many multinucleated giant cells, which strongly expressed cathepsin K, had appeared on these bone trabeculae, indicating active bone remodeling. In these bone trabeculae, Ca and P weight % and Ca/P ratio were similar to those of cortical bone, and there was no significant difference between the PGA‐ and EMD‐applied groups. Bone volume fraction of newly‐formed bone trabeculae on Day 7 postoperatively was significantly higher in the EMD‐applied group than in the PGA‐applied controls. Because of active bone remodeling and the marked decrease of bone volume, on Days 14 and 28 postoperatively, however, there was no longer a significant difference in trabecular bone volume fraction between the experimental groups. Our results suggest that EMD possesses an osteo‐promotive effect on bone and medullary regeneration during wound healing of injured long bones. Anat Rec 264:438–446, 2001. © 2001 Wiley‐Liss, Inc.