A mild case of nesidioblastosis with diagnostic and therapeutic difficulty

A female infant with nesidioblastosis who showed mild clinical symptoms is reported. In this patient, insulin levels and insulin to glucose ratios (IRI/G) were often normal. Regular milk feedings supplemented with continuous glucose infusion (0.7-2 mg/kg per min) or oral glucose feedings (4.5 mg/kg per min) prevented hypoglycemia. As leucine-sensitivity was diagnosed at 2 months of age, she was started on diazoxide. This was, however, ineffective, and adverse effects appeared. Subtotal pancreatectomy (95%) was therefore attempted at 5 months of age, and persistent normoglycemia as well as normal growth and development followed up to 3 years after the operation. The pancreas showed characteristic signs of nesidioblastosis. The above clinical observation suggests that a patient with nesidioblastosis whose blood glucose level is easily controllable may develop an unexpected episode of hypoglycemia in the presence of a leucine sensitivity. In such a patient, diazoxide or, when it is of no avail, surgical intervention should promptly be instituted to prevent possible neurologic sequelae induced by hypoglycemia.     

Coexistence of renal replacement lipomatosis with xanthogranulomatous pyelonephritis

We report on a case of coexistence of replacement lipomatosis with xanthogranulomatous pyelonephritis (XGP) in the same kidney associated with staghorn calculi. A 63-year-old man was admitted to hospital complaining of a right abdominal mass. Computed tomography (CT) showed renal parenchymal atrophy with extremely increased perirenal fat. Right nephrectomy was performed. Postoperative diagnosis was renal replacement lipomatosis with XGP. Renal replacement lipomatosis and XGP have several similarities in terms of clinical background and CT findings. Sometimes it is difficult to differentiate them from malignant diseases. It is extremely rare that both conditions coexist in the same kidney. To our knowledge, only one such case has been reported.     

Successful treatment for squamous cell carcinoma of the female urethra with combined radio- and chemotherapy

We report on two cases of women with locally advanced squamous cell carcinoma of the urethra. Patient 1 also displayed regional lymph node metastasis. Treatment comprised combined radiotherapy to 60 Gy and chemotherapy with 5-fluorouracil and cisplatin. Complete response was obtained in both patients, including the inguinal lymph nodes of Patient 1. Patient 1 experienced recurrent inguinal lymph node metastasis on the contralateral side at 42 months after initial treatment, and the same treatment was performed followed by surgical excision. Both patients remain alive with no evidence of disease, at 12 months after recurrence in Patient 1, and at 27 months after treatment in Patient 2.     

Long-term survival after bilateral adrenalectomy for metachronous adrenocortical cancer

We report the case of a female patient with bilateral metachronous adrenocortical cancer who survived long-term after adrenalectomy. In 1991, the patient underwent left adrenalectomy to remove a huge adrenal mass (10 x 9 cm) displaying no hormonal abnormality. Histological diagnosis was adrenocortical cancer. A right adrenal mass (7 x 6 cm) was found 4 years after left adrenalectomy. Right adrenalectomy was performed, and histological diagnosis was again adrenocortical cancer. The patient remains alive with no evidence of disease 8 years after last surgery.     

HtrA2 is up-regulated in the rat testis after experimental cryptorchidism

AIM: The aim of the present study was to elucidate the role of high temperature requirement A2 (HtrA2) in germ cell loss in the heat-stressed testis. METHODS: We examined the expression of HtrA2, caspase-9 activity and proteolytic activity of HtrA2 in the rat testis, and their in vivo responses to experimental cryptorchid treatment. RESULTS: Northern analysis revealed the expression of HtrA2 mRNA peaked at days 1 and 7 after cryptorchid treatment. While expression of HtrA2 mRNA was seen in the spermatogonium, spermatocytes and some spermatids in normal adult rat testis, experimental cryptorchidism treatment resulted in a marked increase in its signal intensity in spermatocytes and some spermatids, and the layers of spermatogonium and early primary spermatocytes became negative at days 1 and 7 after the treatment. However, the spermatogonium, Sertoli cells and interstitial cells appeared to have strong intensities at days 14, 28 and 56 after the treatment. Western analysis revealed the expression of HtrA2 protein peaked at day 2 coinciding with the increase of positive spermatogonium, the appearance of protein-positive interstitial cells, and day 28 coinciding with the reappearance of protein-positive interstitial cells. Caspase-9 activity peaked at day 2 and HtrA2 proteolytic activity peaked at day 28. Consequently, the first peak of HtrA2 mRNA expression was followed by the peak of caspase-9 activity and the second peak was followed by the peak of proteolytic activity; however, the second peak of mRNA expression had considerable chronological difference from that of the protein. CONCLUSION: These findings suggest the probabilities that the heat stress results in germ cell death by a caspase-independent manner with the elevation of HtrA2 proteolytic activity, as well as a caspase-dependent manner with the elevation of caspase-9 activity.     

The Role of the Biopsy in Diagnosis of Early Gastric Cancer

In order to determine the reliability of endoscopic biopsy indiagnosis of early gastric cancer, and to clarify the problemswith biopsies, preoperative endoscopic biopsies from 771 earlygastric cancer cases were reviewed and analyzed clinicopathologicallyin comparison with surgically resected specimens. The 771 cancerswere surgically resected at the National Cancer Center Hospitalduring the period from 1972 to 1982. Definite histological diagnosiswas obtained in 87.4% of the carcinomas at the initial biopsies.Repeated biopsy raised the percentage of correct definite diagnosesto 96.1%. False-negative (including suspicion of cancer) diagnosiswas most frequent in the case of depressed lesions (50 lesions).Half of the false negatives were found to be due to samplingerrors by the endoscopists. The other half of these 50 lesionswere diagnosed as "suspicious of malignancy" because of thehistological difficulty in differentiating early gastric cancerfrom regenerative atypia with intestinal metaplasia, or becausethere was not enough information, or for the other reasons.Most of the 31 false-negative diagnoses at the initial biopsyfrom elevated lesions were reported as adenoma (group III) orsuspicious of carcinoma (group IV), indicating that differentialdiagnosis between well-differentiated adenocarcinoma and adenomais very difficult. The result of the present study suggeststhat repeated biopsy from correct sites and discussion of thelesions between clinicians and pathologists are very important. ^**Present affiliation: Toranomon Hospital, Toranomon 2-2-2,Minato-ku, Tokyo 105, Japan.     

The Preclinical Safety Evaluation of Human Monoclonal Antibody against Cytomegalovirus

The human monoclonal antibody against cytomegalovinis (Mab C23)was examined pharmacokinetically and toxicologically as partof the preclinical studies prior to approval for human use.Rats given repeated intravenous administrations of Mab C23 producedno antibodies against Mab C23 and maintained a blood Mab C23level in a dose-dependent manner. However, pregnant rabbitsproduced antibodies against Mab C23. The half-life of Mab C23in plasma was 15.9 days in rats, which was similar to that ofnormal human serum -globulin (NHSG). Neither behavioral effectsnor circulatory disturbance was found in mice, rats, and dogseven after a single intravenous injection of 100 or 200 mg/kg,which corresponds to 50 or 100 times the intended clinical dosage.The repeated doses of 2, 10, or 20 mg/kg of Mab C23 on six occasionswith 1- or 2-week intervals elicited a transient decrease inleukocyte counts in rats given 10 or 20 mg/kg, but no adverseeffects in cynomolgus monkeys. Mab C23 did not cause any reproductiveor developmental toxicity when administered to rats and rabbitsat dose levels of 20 mg/kg or less. However, pregnant animalsshowed lower plasma levels of Mab C23 than non-pregnant animals.The chromosomal aberration test disclosed no clastogenicityin human lymphocytes. An immunostaining for Mab C23 revealedno localizations in several tissues of cynomolgus monkeys givenintravenous doses of Mab C23. The preclinical safety evaluationin animals other than rabbits, which produced no antibodiesagainst Mab C23, showed that the behavior of Mab C23 is pharmacokineticallysimilar to that of NHSG and is as safe as NHSG, which has longbeen used as a biological agent. However, because there wasa difference in blood levels of Mab C23 between pregnant andnonpregnant animals, its clinical administration to pregnantpatients should differ from that to non-pregnant patients.     

Physiological and psychological responses induced by expressing empathy with others

Aim: To assess the physical and mental burdens associated with expressing empathy with another person's stress. Methods: Nine female subjects listened to their partner's negative emotions aroused by a stress task (Stroop color‐word test) under two conditions. In the first, the subject reacted empathetically to their partner (“with empathy”); in the second, the subject offered no response (control). Electroencephalograms and skin temperature of the second finger were recorded during the test. Subjective stress was estimated using a visual analog scale, whereas the level of cognition was expressed on a five‐point ranking. Responses during and after expressions of empathy were examined by comparisons with control or by correlation. Results: Sympathetic nerve tone increased under both conditions (i.e. the skin temperature of the second finger fell). Subjective stress was not recognized by the subject while listening “with empathy”, although it did increase significantly after the subject has listened “with empathy”. Subjective stress was not felt under the control conditions. Right temporal activity while listening showed a significantly positive correlation with the level of cognition of feeling the same emotion as the stressed partner, whereas bilateral frontal activity after listening was significantly negative correlated with the level of cognition of understanding the emotions of the stressed partner. Conclusion: Expressing empathy with another person's negative emotion led to increased physiological activity and subjective stress. Physiological responses to empathy depended on cognition of the different subjective factors. Cognition of sharing negative emotions activated the right temporal region of the brain, whereas cognition of understanding negative emotions inhibited bilateral frontal activities.