The metabolic rate of the fetus per tissue weight is relatively high when compared to that of an adult. Moreover, heat is transferred to the fetus via the placenta and the uterus, resulting in a 0.3C° to 0.5C° higher temperature than that of the mother. Therefore, fetal temperature is maternally dependent until birth. At birth, the neonate rapidly cools in response to the relatively cold extrauterine environment. Thus, the neonatal temperature rapidly drops soon after birth. In order to survive, the neonate must accelerate heat production via nonshivering thermogenesis (NST), which is coupled to lypolysis in brown adipose tissue. Heat is produced by uncoupling ATP synthesis via the oxidation of fatty acids in the mitochondria, utilizing uncoupled protein. Thermogenesis must begin shortly after birth and continue for several hours. Since thermogenesis requires adequate oxygenation, a distressed neonate with hypoxemia cannot produce an adequate amount of heat to increase its temperature. In contrast to the neonate, the fetus cannot produce extra heat production. This is because the fetus is exposed to inhibitors to NST, which are produced in the placenta and then enter the fetal circulation. The important inhibitors include adenosine and prostaglandin E2, both of which have strong anti-lypolytic actions. The inhibitors play an important role in the metabolic adaptation of a physiological hypoxic fetus because NST requires adequate oxygenation. Furthermore, the presence of NST inhibitors allows the fetus to accumulate an adequate amount of brown adipose tissue before birth. The umbilical circulation transfers 85% of the heat produced by the fetus to the maternal circulation. The remaining 15% is dissipated through the fetal skin to the amnion, and is then transferred through the uterine wall to the maternal abdomen. As long as fetal heat production and loss are appropriately balanced, the temperature differential between the fetus and the mother remains constant (heat clump). However, when the umbilical circulation is occluded for any reason, the fetal temperature will rise in relation to the extent of the occlusion. The fetal temperature may elevate to the hyperthermic range in cases of acute cord occlusion; if this occurs, fetal growth, including brain development, may be impacted. Experimentally induced cord occlusion, which is recognized as a significant cause of brain damage, results in a rapid elevation of body temperature; however, the brain temperature tends to remain constant. This is considered to be a cerebral thermoregulatory adaptation to hypoxemia, which has the physiologic advantage of protecting the fetus from hyperthermia, a condition that predisposes the fetus to hypoxic injury (cerebral hypometabolism). A number of thermoregularatory mechanisms are in place to maintain normal fetal and neonatal growth. Data has primarily been collected from animal studies; aside from the strict thermal control provided in the newborn nursery, little information exists concerning these mechanisms in the human fetus and neonate. Probably further information on thermoregulation is necessary specially to improve perinatal management for hypoxic fetuses.

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Education, resident training, guidelines, and evaluation are necessary to improve health care quality. Changing the resident system, re-organizing medical associations and Evidenced-Based Medicine (EBM) are becoming popular, and clinical practice using guidelines has been stressed in recent years in Japan. However, clinical evaluation is generally not so popular, except within internal conferences, and during short discussions at medical societies, although evaluation of the hospital services is on going by the Japanese Council for Quality Health Care (JCQHC). In contrast, the Joint Commission on Healthcare Accreditation Organization (JCAHO) is generally used for evaluation of hospitals in the US. The TRISS (Trauma and Injury Severity Score) method has offered a standardized approach to the evaluation of the outcome of trauma care. All trauma cases admitted to emergency centers in Japan were reviewed using the TRISS methodology in 2001 to assess preventable trauma death (PTD). There are big discrepancies regarding PTD among hospitals. The Emergency Medicine Study Group for Quality (EMSQ), organized by 14 emergency centers in the Kanto area, has developed a peer review (PR) system using explicit standards together with the TRISS methodology, in order to promote accuracy in the evaluation of PTD. Definitions of trauma, PTD, and a set of standards consisting of 20 items for determining PTD, were proposed. The optimal quality level of medical care for the patients was the criterion against which decisions regarding PTD were made. All death cases whose probability of survival (Ps) value exceeded 50% were reviewed using a PR method based on explicit standards. The PR process found that only 11.2% of all deaths were preventable, although 25.3% were considered preventable by the TRISS method. The PR process, using explicit standards, provided an excellent method of evaluation of PTD. The PR process also serves an educational purpose in improving the quality of care in emergency trauma cases. PR, by applying uniform standards at the optimal level of quality for the patients, offers not only more precise assessment, but also a means of case identification for quality assurance review on a local basis. Outcome reviews will offer the opportunity to assess comparability with national standards and norms. Trauma registry and evaluation are recommended for all emergency centers in Japan. These evaluation processes may be useful for systematic improvement of the emergency medical field.

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Purpose: We investigated whether urine survivin, an inhibitor of the apoptosis protein, is useful for diagnosing bladder tumor. Method: We measured urine survivin levels in 40 patients with bladder tumors and 9 healthy volunteers. Results: The average urine survivin levels in the 40 patients and 9 healthy controls were not significantly different (3.802±8.669 and 1.127±1.529, respectively (p=0.3646) ). However, significantly high urine survivin levels were observed in 3 of the 40 patients, but not in healthy volunteers. Urine Cyfra 21-1 was not elevated (1.3 ng/ml) in one patient with a significantly elevated urine survivin level (33.54 ng/ml), while in two patients with elevated Cyfra (320 ng/ml and 240 ng/ml), the urine survivin level was not detectable. Conclusion: With improvements in the sensitivity of our Elisa system for urine survivin and combined use of urine Cyfra 21-1, it is possible that urine survivin will be a useful tumor marker in detecting both new-onset and recurrent bladder tumors.

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Objective: To assess the potential usefulness of Ki-67 antigen expression as a predictor of outcome in ovarian cancer through the analysis of MIB-1 monoclonal antibody reactivity. Methods: Cell proliferation and clinicopathologic variables were assessed in 26 patients with primary epithelial ovarian cancer who had undergone exploratory laparotomy. The expression of primary tumor proliferation related to Ki-67 antigen was immunohistochemically evaluated by MIB-1 monoclonal antibody. Results: The value of Ki-67 labeling index (LI) ranged between 0 and 92.6% with a mean of 48.9%. Ki-67 LI correlated well with the mitotic index, but not the histological subtype. Ki-67 LI of more than 40%was defined as a higher proliferating tumor by a receiver operating characteristic curve analysis. Higher proliferating tumors were identified in 14 patients (54% of all subjects). The patients with higher proliferating tumors had a statistically significantly worse prognosis compared with those with lower proliferating tumors (p<0.001). Conclusions: The present study demonstrates that the proliferating index detected by Ki-67 antigen immunostaining is a useful factor for predicting the survival of patients with ovarian cancer.

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Background: Laparoscopic partial nephrectomy has been recently applied as a minimally invasive procedure. Several non-ischemic operation devices in partial nephrectomy have been developed. However, the problem related to maintenance of renal homeostasis remains. We investigated the efficacy and safety of a microwave tissue coagulator in laparoscopic partial nephrectomy. Methods: Between April 2001 and February 2003, eleven patients with small renal tumors underwent laparoscopic partial nephrectomy using a microwave tissue coagulator. Seven patients underwent hand-assisted laparoscopic procedure and 4 pure laparoscopic procedure. Results: The mean tumor size on preoperative CT scan was 2.5 cm (range: 2.0 to 4.0 cm), the mean operative time was 307 minutes (range: 160 to 580 minutes), and the mean estimated blood loss was 154.4 ml (range: 50 to 1,140 ml). The microwave tissue coagulator well controlled the renal bleeding and maintained renal function. All patients safely underwent partial nephrectomy without inducing renal ischemia. A complication of urine leakage was recognized in only one patient with hypoproteinemia caused by nephrotic syndrome. Conclusions: Laparoscopic partial nephrectomy using a microwave tissue coagulator was a useful method for achieving homeostasis, and was less invasive for treating small renal tumors.

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Partial peripheral nerve injury produces a persistent neuropathic pain which is difficult to relieve. In order to determine whether different degrees of peripheral nerve injury are related with the severity of neuropathic pain, we examined pain-related behaviors, histological changes and NGF in the skin in rats treated with different types of spinal nerve injury: tight ligation of the left L5 spinal nerve, incomplete ligation of the left L4 and L5 spinal nerves and incomplete crush of the left L4 and L5 spinal nerves. In all model rats, the thresholds of paw withdrawal in response to mechanical and heat stimuli began to decrease on the injured side 1 day after the operation, and the decreases in the thresholds persisted for more than 1 month. Incomplete ligation and incomplete crush of the left L4 and L5 spinal nerves caused more severe allodynia and hyperalgesia than tight ligation of the left L5 spinal nerve on the injured side. In rats treated with incomplete crush, the threshold of withdrawal response to mechanical or heat stimuli was improved on day 32 after the operation as compared with that on day 15. Histological analysis revealed that about 80% of the fibers in the sciatic nerve were injured after incomplete ligation and incomplete crush of the left L4 and L5 spinal nerves on day 15, while about 50% of the fibers were damaged by tight ligation of the left L5 spinal nerve. In accordance with pain-relieving, the sciatic nerve fibers regenerated to about 50% of the number of the intact sciatic nerve fibers on day 32 in the crush model. Nerve growth factor (NGF) in the skin of the hindpaw on the injured side was accumulated after incomplete ligation and incomplete crush of the left L4 and L5 spinal nerves, but not tight ligation of the left L5 spinal nerve, on day 15 after the operation, possibly due to impairment of transport via unmyelinated primary afferents. Regeneration of the sciatic nerve alleviated the accumulation of NGF in the injured side hindpaw skin on day 32. The present results suggested that the severity of neuropathic pain was related with the degrees of both degeneration and/or regeneration of myelinated fibers and of functional damage of unmyelinated fibers.

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We report four patients on maintenance hemodialysis (HD) with transitional cell carcinoma (TCC) of the bladder. Three patients underwent transurethral resection (TUR) of their tumors, which were grade 2 or 3, stage pT1 TCC. Among them, one patient underwent repeat TUR for recurrent superficial TCC. The remaining one patient underwent total cystectomy for grade 3, stage pT4 TCC and squamous cell carcinoma of the bladder. Subsequently, he died suddenly without evidence of local recurrence or systemic metastasis. We discuss the relationship between the duration of HD and the tumor grade and stage of primary bladder TCC in maintenance HD patients.

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In case a pre-senile patient presented subacutely progressive dementia, secondary dementia, such as paraneoplastic neurological syndrome (PNS), hypothyroidism, confusion, early phase of primary degenerative dementia and prion diseases are to be considered. It is a case of pathologically confirmed, and clinico-pathologically assessed limbic encephalitis with cerebellar degeneration. The patient was a 63-year old male, with a well followed up medical history of gastric cancer 8 years earlier. Four weeks after he presented himself at our hospital his memory and disorientation progressively declined. A neurological examination revealed gaze nystagmus, with potential secondary dementia. However, no abnormal findings were detected from systemic radiological examination, or from chemical analyses. Two months later, after the onset of the disease, he presented additional symptoms, including seizure, gait disturbance, and insomnia. On admission, neurological examinations revealed gaze nystagmus and progression of dementia; however, his thought process was relatively preserved. No paroxysmal synchronized discharge was seen on electroencephalogram. Chest X-rays showed an inflammatory infiltration. In spite of anti-biotic medication, he died due to respiratory failure. The autopsy was limited to the brain. Histologically, limited lymphocytic infiltration into the hippocampus through the entorhinal cortex, with marked neuronal loss and gliosis was observed. Neuronophagia, microglial nodules, and perivascular lymphocytic infiltration were also seen. Additionally, most of the Purkinje cells in the cerebellum were lost, with Bergmann's gliosis and sparse lymphocytic infiltration. No tumor was observed in the brain. Pathological findings of the brain were compatible with paraneoplastic limbic encephalitis and cerebellar degeneration, though no neoplasm, clinically or pathologically, was detected in this patient. Consequently, it is suggested that when a senile patient presents sub-acute onset of progressive dementia, with a variety of neurological symptoms, paraneoplastic syndrome is to be taken into consideration, even if a tumor or an auto-antibody is not detected since the resection of the tumor is still the best therapeutic means. Otherwise immuno-suppressive and steroid therapies should be used.

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Adenocarcinoma is the most common malignant neoplasm of the gallbladder, but squamous cell carcinoma (SCC) is rare with an incidence of 1.4∼3.3%. We present a recent case of a 63-year-old man complaining of abdominal distention. Preoperative US and CT revealed a large tumor of the gallbladder infiltrating the liver and transverse colon. Cholecystectomy, subsegmental resection of the liver, lymph node dissection, and partial resection of the transverse colon were performed. The resected specimen was histologically diagnosed as SCC without nodal metastases.

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The present paper reviews the pathophysiology and therapeutic strategies in heart failure based on clinical investigations performed in our institute, and also recently reported large-scale double-blind clinical trials for the medical treatments of heart failure. Careful introduction of beta-blocker therapy along with RAAS inhibitors (ACE inhibitor, ARB, and/or aldosterone antagonist) should bring about marked improvement in mortality and morbidity in all subgroups of patients with heart failure.

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Acute heart failure has recently become a very common syndrome. Therefore, even if you are not a cardiologist, you should know how to diagnose and treat it. A basic technique is here summarized. Diagnosis of heart failure can be performed from a simple criteria including coarse crackles, an extra-sound (S3), a distention of the cervical vein, cardiomegaly, pulmonary edema, and serum levels of B-type natriuretic peptide (100 pg/ml<). After diagnosis, the severity should be assessed by the degrees of both pulmonary edema and cardiac output. For these evaluations, a Swan-Ganz catheter might not be needed, since we can evaluate them clinically, i.e., physical examinations and auscultation. We can then treat the patient with heart failure with a vasodilator and/or diuretics. If the blood pressure is low, we can administer a low dose of an inotropic agent. But an inotropic agent should be withdrawn as early as possible, because they can occasionally have deleterious effects. Finally, please bear in mind that the elimination of several triggers, e.g., infection, transient cessation of medication, and physical or metal stress, and also the detection of early symptoms of heart failure, e.g., shortness of breath on exertion, fatigue, increase in body weight, and appetite loss, are very important for the prevention of acute heart failure.

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