Successful and long-lasting treatment of solar urticaria with ultraviolet A rush hardening therapy.

BACKGROUND: Solar urticaria (SU) is a photodermatosis that is thought to be caused through the effects of mast cell mediators released because of an altered chromophore, possibly a photoallergen recognized by IgE. Phototherapy for SU to induce a tolerant state appears to be most effective, but is often time consuming and provides only short-lived remission. Ultraviolet (UV) A rush hardening has been successful and less time consuming in serum factor-negative patients with SU. However, the mechanism of action and long-lasting effects of UVA rush hardening therapy remain unclear. OBJECTIVES: We aimed to evaluate whether UVA rush hardening exhibits long-lasting therapeutic effects in serum factor-positive patients with SU and to examine the action mechanism of tolerance. METHODS: Two serum factor-positive patients with SU were exposed to multiple UVA irradiations at 1-h intervals per day for 2 or 3 days. Intradermal injection of their in vitro-irradiated autologous serum or compound 48/80 and a prick test for histamine were performed before and after UVA rush hardening. RESULTS: The two serum factor-positive patients with SU benefited greatly from UVA rush hardening, as documented by a marked increase in minimal wealing dose, and remained symptom free without using sunscreen in their daily life. Intradermal injection of in vitro-irradiated autologous serum induced wealing before hardening, but not in tolerized skin after hardening. The responses to compound 48/80 and histamine were unaltered. CONCLUSIONS: UVA rush hardening is an effective and long-lasting treatment even in serum factor-positive patients with SU. The mechanism of tolerance may involve continued blockade of photoallergen binding to IgE on mast cells, rather than depletion of mast cell mediators or histamine tachyphylaxis.

Pharmacological brain cooling with indomethacin in acute hemorrhagic stroke: antiinflammatory cytokines and antioxidative effects.

We evaluated the effects of a novel pharmacological brain cooling (PBC) method with indomethacin (IND), a nonselective cyclooxygenase inhibitor, without the use of cooling blankets in patients with hemorrhagic stroke. Forty-six patients with hemorrhagic stroke (subarachnoid hemorrhage; n = 35, intracerebral hemorrhage; n = 11) were enrolled in this study. Brain temperature was measured directly with a temperature sensor. Patients were cooled by administering transrectal IND (100 mg) and a modified nasopharyngeal cooling method (positive selective brain cooling) initially. Brain temperature was controlled with IND 6 mg/kg/day for 14 days. Cerebrospinal fluid concentrations of interleukin-1beta (CSF IL-1beta) and serum bilirubin levels were measured at 1, 2, 4, and 7 days. The incidence of complicating symptomatic vasospasm after subarachnoid hemorrhage was lower than in non-PBC patients. CSF IL-1beta and serum bilirubin levels were suppressed in treated patients. IND has several beneficial effects on damaged brain tissues (anticytokine, free radical scavenger, antiprostaglandin effects, etc.) and prevents initial and secondary brain damage. PBC treatment for hemorrhagic stroke in patients appears to yield favorable results by acting as an antiinflammatory cytokine and reducing oxidative stress.

Positive selective brain cooling method: a novel, simple, and selective nasopharyngeal brain cooling method.

Brain damage is worsened by hyperthermia and prevented by hypothermia. Conventional hypothermia is a non-selective brain cooling method that employs cooling blankets to achieve surface cooling. This complicated method sometimes induces unfavorable systemic complications. We have developed a positive selective brain cooling (PSBC) method to control brain temperature quickly and safely following brain injury. Brain temperature was measured in patients with a ventriculostomy CAMINO catheter. A Foley balloon catheter was inserted to direct chilled air (8 to 12 L/min) into each side of the nasal cavity. The chilled air was exhaled through the oral cavity. In most patients, PSBC maintained normal brain temperature. This new technique provides quick induction of brain temperature control and does not require special facilities.

Transient elevation of serum bilirubin (a heme oxygenase-1 metabolite) level in hemorrhagic stroke: bilirubin is a marker of oxidant stress.

Bilirubin (Bil) is the end product of heme catabolism. The production of Bil reflects heme oxygenase-1 expression in response to oxidative stress in various diseases. To assess the role of Bil as a marker of oxidative stress in cases of brain damage, we measured serum Bil concentrations in patients with hemorrhagic stroke. Serum levels of total Bil were measured in 20 subarachnoid hemorrhage patients with symptomatic vasospasms and in 23 patients with intracerebral hemorrhage; concentrations were measured every day for 14 consecutive days. Serum Bil levels were significantly elevated in the early phases in both groups. Moreover, transient elevation was observed on the day prior to the observation of clinical manifestations of symptomatic vasospasm after SAH. Bil, known to be a powerful antioxidant, was induced after hemorrhagic stroke, reflecting the intensity of oxidative stress. Plasma Bil concentrations might serve as a useful marker of oxidative stress in hemorrhagic stroke patients.

Periodic metastable structures in the discrete straight phi4 model.

For the discrete straight phi(4) model a class of metastable periodic solutions is given in the form of Fourier series. From the symmetry consideration, we eliminate the harmonics with zero amplitudes and thus, reduce the number of degrees of freedom. For the rest of harmonics we establish the hierarchy of their significance. For solutions with a small period we give the exact expression of energy density in terms of amplitudes of harmonics. Conditions of existence and stability of the solutions are discussed. For some limiting cases the approximate solutions of different kinds are given. The analytical results are compared with the results of numerical study. We also discuss a mechanism of transition from a metastable periodic structure into the ground state and apply the results to the lock-in transition in dielectric crystals supporting incommensurate phase.

Direct superoxide scavenging activity of nonsteroidal anti-inflammatory drugs: determination by electron spin resonance using the spin trap method.

Nonsteroidal anti-inflammatory drugs (NSAIDs), which are used widely to manage pain, are known to inhibit cyclooxygenase, but details of the mechanisms of NSAID action remain unclear. We investigated the ability of three NSAIDs (indomethacin, loxoprofen, and etodolac) to eliminate and inhibit free radicals. Superoxide scavenging activity of these NSAIDs was measured in vitro by electron spin resonance spectrometry using 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) as a spin trap. Electron spin resonance demonstrated that formation of superoxide-DMPO spin adduct was completely inhibited by two nonselective cyclooxygenase inhibitors, indomethacin (3 mmol) and loxoprofen (3 mmol). The electron spin resonance study also demonstrated that the formation of superoxide-DMPO spin adduct was strongly inhibited by a selective cyclooxygenase-2 inhibitor, etodolac, in a concentration-dependent manner. These results indicate that NSAIDs, including indomethacin, loxoprofen, and etodolac, have direct superoxide scavenging activity.

Prevalence of endometriosis in ovarian cancer.

Endometriosis may be the precursor of clear cell or endometrioid ovarian cancer. In this review, we focus on the prevalence of endometriosis in ovarian cancer and related clinical and epidemiological issues. According to 15 published reports, the rank order of the prevalence of endometriosis in each histologic type was clear cell (39.2%) > endometrioid (21.2%) > serous (3.3%) > mucinous type (3.0%). The high prevalence of endometriosis in clear cell and endometrioid types is a consistent finding in Japan and western countries. However, the incidence of the clear cell type is much higher (15-20% vs. 7-8%), and that of the endometrioid type is lower (7-16% vs. 18-26%), in Japan compared with western countries. This review is also concerned with the relationship between the presence of ovarian endometriosis and clinical features such as age, parity, menopausal status, clinical stage, and survival in ovarian cancer patients.

Fatal severe vasospasm due to rewarming following hypothermia--case report.

A 37-year-old female died of cerebral vasospasm as a complication of rewarming following hypothermia therapy for severe head injury. She presented with severe consciousness disturbance and anisocoria after falling down a flight of stairs. Computed tomography (CT) revealed a right acute subdural hematoma and temporal contusion. Following surgery, mild hypothermia was started and rewarming was completed by the 11th day. Neurological examination showed no abnormalities, but intracranial pressure (ICP) suddenly increased and she manifested anisocoria on the 13th day. Repeat CT revealed a low density area in the right middle cerebral artery region and cerebral angiography showed diffuse narrowing of the main arterial trunks. A cerebrospinal fluid (CSF) sample was collected using an intraventricular ICP monitoring catheter. The CSF level of 8-hydroxy-2'-deoxyguanosine was elevated during the rewarming period, indicating substantial deoxyribonucleic acid (DNA) oxidation. She died on the 15th day due to uncontrollable ICP. Histological examination at autopsy of the narrowed artery found the waving phenomenon in the internal elastic lamina and invasion of inflammatory cells into the adventitia. These findings constitute the possible evidence that free-radical-mediated oxidative DNA damage may be important in the genesis of severe vasospasm due to rewarming following hypothermia.

A clinicopathological study of postoperatively upgraded early squamous-cell carcinoma of the uterine cervix.

OBJECTIVE: To investigate the clinicopathological backgrounds and diagnostic problems of postoperatively upgraded early squamous-cell carcinomas of the uterine cervix. PATIENTS AND METHODS: A total of 23 patients with postoperatively upgraded early squamous-cell carcinomas who were treated at the Saitama Cancer Center during the period of January 1, 1976, through December 31, 1991, were analyzed clinicopathologically. We reexamined the Pap smears (ectocervix, endocervix), colposcopic findings, punch biopsies, and histological findings of the operative specimens. All patients were divided into one of 3 groups based on each patient's main location of the carcinoma of the cervix: Type A: ectocervical type; Type B: endocervical type; or Type C: combined (ectocervical and endocervical) type. Clinical staging of the uterine cervical carcinomas was done in accordance with the 1994 FIGO rules. RESULTS: The numbers of patients were: Type A, 2; Type B, 10; Type C, 11. Of the 23 patients, 21 (91.3%) had lesions in the endocervical portion at least. Fifteen patients (65.2%) complained of atypical vaginal bleeding. Colposcopic findings suggesting an invasive carcinoma appeared for only 6 patients (26.1%). A cytological reevaluation revealed that the endocervical findings were much stronger than the ectocervical ones in 10 (66.7%) of 15 patients whose smears of both sites could be rechecked. CONCLUSIONS: Even if the preoperative diagnosis was early cervical carcinoma, CIS or Stage Ia1, the signs of atypical vaginal bleeding suggested that the final clinical stage would be upgraded after an operation. Furthermore, when the endocervical cytological findings were much more exaggerated than the ectocervical ones, the possibility of deeply invaded endocervical lesions should be considered.

Neuropsychological changes after surgery for anterior communicating artery aneurysm.

Neuropsychological disturbances following surgery for anterior communicating artery aneurysms were analyzed in 26 patients (11 males, 15 females) using the Hasegawa dementia scale-revised (HDS-R) over a 3-year period. The patients were aged from 34 to 76 years (mean 54.1 years). Lesions in the frontal lobe were evaluated using computed tomography (CT). Twenty-three patients had symptoms over the course. Four patients had basal forebrain lesion, five had ventral frontal lesion, and 12 had no lesion. Patients with basal forebrain lesion and no lesion tended to show disorientation. The mean HDS-R score was 10.2 points in the patients with ventral frontal lesion, and 13.5 points in the patients with no lesion. These scores are within the range for dementia. The mean HDS-R score in patients with basal forebrain and striate lesions was over 25 points and beyond the range for dementia. Significant differences were observed in the HDS-R score between patients with ventral frontal lesion and basal forebrain lesion, and between patients with no lesion and basal forebrain lesion (p < 0.05). Recovery from neuropsychological disturbances was poorer in patients with ventral frontal lesion and no lesion compared to those with basal forebrain and striate lesions, and their symptoms tended to persist.

Considerations on surgical treatment for elderly patients with intracranial aneurysms.

BACKGROUND: The purpose of this study was to investigate why elderly patients have poorer outcomes and to determine indications for surgery in elderly patients. METHODS: One hundred fifty-four patients with intracranial aneurysms admitted to the Department of Neurosurgery, Showa University School of Medicine, from 1990 through 1996 were reviewed. The patients were classified by age into three groups (young group, middle-aged group, elderly group). RESULTS: Forty-four patients (28.6%) were in the elderly group (mean age, 73 years). No difference in outcome was found between middle-aged and elderly patients if patients were stratified according to clinical grade. In addition, the main factors related to unfavorable outcomes in elderly patients were infection, organ failure, aneurysm rerupture before operation, and delayed ischemic deterioration. Elderly patients were more likely to experience rebleeding and have poor outcomes. CONCLUSIONS: Our results suggest that elderly patients should have early surgery. Furthermore, we found that the presence of hypertension or atherosclerosis had no significant effect on outcome. We conclude that early surgical treatment of aneurysms is indicated for elderly patients with good clinical grades in the absence of organ failure.

L-histidine but not D-histidine attenuates brain edema following cryogenic injury in rats.

Oxygen free radicals have been implicated in the genesis of traumatic brain injury and brain edema (BE). Recent studies have suggested that hydroxyl radical can initiate lipid peroxidation, thus producing lipid-free radicals that may become important sources of singlet oxygen. L-histidine, a singlet oxygen scavenger, potentially can be used to treat BE. In this study we investigated the effects of L-histidine and D-histidine on BE following cryogenic injury in rats. Male Wistar rats were anaesthetized with chloral hydrate. Vasogenic BE was produced by a cortical freezing lesion. Generation of singlet oxygen from photoactivation of rose bengal was studied by electron spin resonance (ESR). Animals were separated into four groups: sham rats (n = 5), saline-treated rats (n = 10), L-histidine treated rats (n = 6) and D-histidine treated rats (n = 7). Each agent (100 mg/kg) was administered intravenously at 30 minutes before lesion production. Animals were sacrificed at 24 hours after lesion production and the brain water content was determined by the dry-wet weight method. L-histidine had no effect on rectal and brain temperature. Election Spin Resonance studies demonstrated that L-histidine is a singlet oxygen scavenger. L-histidine but not D-histidine significantly attenuated BE following cryogenic injury (p < 0.05). In conclusion, L-histidine is useful in the treatment of traumatic BE.

Protective effect of a novel vitamin E derivative on experimental traumatic brain edema in rats--preliminary study.

Oxygen free radicals have been proposed to be one of the major mechanisms of secondary brain damage in traumatic brain injury. Protective effect by vitamin E against oxidative damage has attracted much attention. Recent studies have demonstrated a novel vitamin E derivative, 2-(alpha-D-glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol (TMG), has excellent water-solubility and antioxidant activity. The purpose of this study was to investigate protective effects of TMG on experimental traumatic brain edema (BE). Male Wistar rats were anaesthetized with chloral hydrate. Traumatic BE was produced by a cortical freezing lesion. Animals were separated into three groups: saline-treated rats (n = 4), TMG-treated (4 mg/kg) rats (n = 7) and TMG-treated (40 mg/kg) rats (n = 8). Saline or TMG was administered intravenously before lesion production. Animals were sacrificed at 6 hours after lesion production and the brain water content was determined by the dry-wet weight method. Half-life of TMG after intravenous administration of TMG was also investigated. The half life of TMG was approximately 5 minutes. TMG (40 mg/kg) significantly attenuated BE following cryogenic brain injury (p < 0.01). In conclusion, this preliminary study has demonstrated that a novel vitamin E derivative might be promising in the treatment of traumatic BE.

Inhibition of human endometrial cancer cell growth in vitro and in vivo by somatostatin analog RC-160.

OBJECTIVE: Our purpose was to investigate the effect of the somatostatin analog RC-160 on the growth of the HEC-1 human endometrial cancer cell line in vivo and in vitro. STUDY DESIGN: Nude mice bearing subcutaneous implanted HEC-1 tumors were treated for 25 days with RC-160 (100 microgram/d) delivered by osmotic minipumps. In cultured HEC-1 cells radioreceptor assay of somatostatin was performed, and the expression of messenger ribonucleic acid for somatostatin receptor subtypes (somatostatin receptors 1-5) was analyzed by reverse transcription-polymerase chain reaction. The effects of RC-160 on epidermal growth factor-stimulated cell proliferation and tyrosine phosphorylation of epidermal growth factor receptor were examined by colorimetric assay and Western blotting, respectively. RESULTS: The treatment with RC-160 resulted in a significant decrease in tumor volume, tumor weight, and serum insulin-like growth factor I levels compared with those values in control animals. The presence of high-affinity somatostatin binding sites and the expression of somatostatin receptor 2 and somatostatin receptor 3 messenger ribonucleic acid were demonstrated in HEC-1 cells by radioreceptor assay and reverse transcription-polymerase chain reaction, respectively. Epidermal growth factor-stimulated proliferation of HEC-1 cells was inhibited by RC-160 in a dose-dependent manner. Western blotting revealed that epidermal growth factor-induced tyrosine phosphorylation of epidermal growth factor receptor was inhibited by RC-160, which suggests that the direct inhibitory effect of RC-160 on HEC-1 cell growth might be mediated in part by interference with epidermal growth factor receptor phosphorylation. CONCLUSION: These results indicate that somatostatin analog RC-160 inhibits the growth of HEC-1 human endometrial cancer cells, thus implying its potential clinical utility in treating endometrial cancer.

[Metastatic skull tumors from cancers associated with subcutaneous mass lesions].

The incidence of metastatic brain tumors is increasing because of the recent progress in the detection and management of primary cancer. However, metastatic skull tumors from cancers associated with giant subcutaneous mass lesions are rare. We present four patients with metastatic skull tumors: two from hepatic cancer, one from lung cancer, and one from mamma cancer. In these patients, plain skull X-ray and bone CT showed osteolytic lesions. Angiograms revealed a tumor stain fed by abnormal vessels from the external carotid artery. MRI demonstrated masses with marked homogeneous enhancement with the "dural tail sign" in the dura adjacent to the tumors in three skull tumors from hepatic and mamma cancers, and a mass with slightly enhancement without the "dural tail sign" in a skull tumor from lung cancer. At surgery, hemorrhagic well-demarcated tumors were totally removed. The histological diagnosis was skull metastases from cancers in all cases. In cases with the "dural tail sign" on MRI, no tumor cells were seen in the inner layer of the dura and the dura adjacent to the tumors. It is possible that the "dural tail" is due to increased vascular permeability of the dural vessels. The recurrence of these skull tumors was not observed during the follow-up period. Surgical treatment for the metastatic skull tumors from cancers may be indicated to prevent deteriorating neurological symptoms affecting the quality of life.

[Transnasal microsurgery using a micro-pressure-suction-irrigation system for pituitary adenomas].

Micro-pressure-suction-irrigation system (MPSIS), introduced by Luedecke et al, is an instrumentation for the direct transnasal pituitary procedure. We improved this system for use in Japan. The irrigation system can effectively clean the operating field by one-hand manipulation and dissect tumor tissue by its rapid flow. The pressure of suction and irrigation can be adjusted respectively by a device in the handpiece. The MPSIS is applicable to different stages of intervention because it is equipped with separate tips of various diameters, lengths and angles. This system is especially useful in combination with a micromirror or an endoscopy for direct inspection of the eccentric tumor sites such as the cavernous sinus, the upper part of the planum sphenoidale, or the posterior suprasellar regions. The use of the MPSIS helps to avoid injury to normal tissue structures, and prevents tiny soft microadenoma from being lost during preparation. We have proved the suitability and usefulness of the MPSIS in 23 surgical interventions for transnasal microsurgery of pituitary adenomas.

Molecular analysis of clonality in ovarian endometrial cysts.

Ovarian endometrial cysts, one of the typical manifestations of endometriosis, are classified as tumor-like lesions rather than as neoplasms. Clonality analysis provides important information on the histogenesis and progression of neoplastic diseases. It is generally accepted that most neoplasms are monoclonal in origin, while the clonality of endometrial cysts remains uncertain. In our study, the clonality of endometrial cysts was analyzed by means of polymerase chain reaction (PCR) based on restriction fragment length polymorphism of the X chromosome-linked human androgen receptor gene (HUMARA) and on random inactivation of the gene by methylation. We separated 21 fresh epithelial cell samples from 11 endometrial cysts and found that all were monoclonal in the methylation pattern of the human androgen receptor alleles. Moreover, in each of the five cysts where epithelial cells were sampled from multiple areas, the methylation patterns of all samples from a single cyst were identical. These data indicate that endometrial cysts are monoclonal in origin and suggest their neoplastic potential.

Elderly Japanese women with cervical carcinoma show higher proportions of both intermediate-risk human papillomavirus types and p53 mutations.

The p53 mutation has been found only in 0-6% of cervical carcinomas. In light of recent studies demonstrating that mutation of p53 gene was found in over 20% of the patients with vulvar carcinoma, a disease of elderly women and a known human papillomavirus (HPV)-related malignancy, we analysed mutation of the p53 gene in 46 women with cervical carcinomas at the age of 60 or more (mean; 71 years, range; 60-96 years). The presence of HPV and its type were analysed by polymerase chain reaction (PCR)-based assay using the consensus primers for L1 region. Mutation of the p53 gene was analysed by PCR-based single-strand conformation polymorphism and DNA sequencing technique. Point mutation of the p53 gene was detected in 5 out of 46 (11%) cervical carcinomas: 1 of 17 (6%) samples associated with high-risk HPVs (HPV 16 and HPV 18) and 4 of 27 samples (15%) with intermediate-risk HPVs (P= 0.36) whereas no mutation was found in 2 HPV negative cases. The mutated residues resided in the selective sequence known as a DNA-binding domain. The immunohistochemistry revealed the overexpression in cancer tissues positive for p53 mutation. All of the observed mutations of the p53 gene were transition type, suggesting that the mutation may be caused by endogenous mutagenesis. Although falling short of statistical significance reduces the strength of the conclusion, data presented here imply that p53 gene mutation, particularly along with intermediate-risk HPV types, may constitute one pathogenetic factor in cervical carcinoma affecting elderly women.