Phosphorylated neurofilament subunit NF-H as a biomarker for evaluating the severity of spinal cord injury patients, a pilot study.

STUDY DESIGN: A pilot cross-sectional study of patients with acute cervical spinal cord injury (SCI). OBJECTIVES: The precise evaluation of the severity of SCI is important for developing novel therapies. Although several biomarkers in cerebrospinal fluid have been tested, few analyses of blood samples have been reported. A novel biomarker for axonal injury, phosphorylated form of the high-molecular-weight neurofilament subunit NF-H (pNF-H), has been reported to be elevated in blood from rodent SCI model. The aim of this study is to investigate whether pNF-H values in blood can serve as a biomarker to evaluate the severity of patients with SCI. SETTING: Tokyo Metropolitan Bokutoh Hospital and National Rehabilitation Center, Japan. METHODS: This study enrolled 14 patients with acute cervical SCI. Sequential plasma samples were obtained from 6 h to 21 days after injury. Patients were classified according to American Spinal Injury Association impairment scale (AIS) at the end of the follow-up (average, 229.1 days). Plasma pNF-H values were compared between different AIS grades. RESULTS: In patients with complete SCI, pNF-H became detectable at 12 h after injury and remained elevated at 21 days after injury. There was a statistically significant difference between AIS A (complete paralysis) patients and AIS C (incomplete paralysis) patients. CONCLUSIONS: Plasma pNF-H was elevated in accordance with the severity of SCI and reflected a greater magnitude of axonal damage. Therefore, pNF-H is a potential biomarker to independently distinguish AIS A patients (complete SCI) from AIS C-E patients (incomplete SCI). However, further studies are required to evaluate its utility in predicting prognosis of patients in the incomplete category.

Microdose study of 14C-acetaminophen with accelerator mass spectrometry to examine pharmacokinetics of parent drug and metabolites in healthy subjects.

A study of the pharmacokinetics of (14)C-labeled acetaminophen (AAP) was performed in healthy Japanese subjects receiving an oral microdose of the drug. After separation by high-performance liquid chromatography (HPLC), the levels of AAP and its metabolites in the pooled plasma specimens were quantified using accelerator mass spectrometry (AMS). The total body clearance (CL(tot))/bioavailability (F) of AAP was within the variation in the reported values at therapeutic doses, indicating the linearity of AAP pharmacokinetics. AAP-glucuronide (Glu) and AAP-4-O-sulfate satisfied the criteria of safety testing of drug metabolites. AMS could detect AAP-Cys, the active metabolite of AAP conjugated with cysteine, in the urine. Probenecid prolonged the systemic elimination of total radioactivity and caused a marked decrease in AAP-Glu levels in plasma. Probenecid likely inhibited the glucuronidation of AAP and the renal elimination of AAP-4-O-sulfate. Microdosing of (14)C-labeled drug followed by AMS is a powerful tool that can be used in the early phase of drug development for pharmacokinetic analysis of drugs and their metabolites and for detecting the formation of active metabolites in humans.

Epidemiological and outcome characteristics of major burns in Tokyo.

The Tokyo Burn Unit Association (TBUA) was established in 1983 funded by the Tokyo Metropolitan Government, and is organized by 13 burn units in Tokyo. TBUA covers more than 90% of severe burn patients occurring in Tokyo, and all of the cases are registered according to the burn injury registration format. The purpose of this study is to analyze the registered data and to elucidate epidemiological and outcome characteristics of major burn injuries in Tokyo. The total of 6988 hospitalized patients had data for epidemiological analysis, and 6401 patients had complete data for outcome analysis as well, and were included in this study. The characteristic profiles for the analysis included age, sex, cause of burns, inhalation injury, %BSA, burn index (BI), length of burn unit stay, and outcome, and were analyzed by age groups. The mean age of the patients was 40.4 years, and 63% of them were male. It was noteworthy that 25% of the total patients were elderly patients over 60 years of age. Flame was the most common cause making up 45.6% followed by scalding (32.0%). The overall mortality rate was 15.4%. Inhalation injury was accompanied in 27.3% of burn patients. The mortality rate was 34.6% with inhalation injury, and 8.2% without inhalation injury. Causes of death showed that multiple organ failure made up 36.9% of total mortality, followed by sepsis 25.2 and shock 19.0%. The burn size (%BSA and BI) and inhalation injury were the factors for high mortality rate in all age groups whereas age was a predictor for high mortality in the patients older than 16 years of age. Gender was not a factor for high mortality in any age group. The mortality rate showed mildly decreasing tendency since 1995 for which implementation of skin bank was thought to be responsible.

[Acute isoniazid poisoning presenting convulsion and liver dysfunction].

A-19-year-old girl ingested 7.4 g of Isoniazid (INH) and 14.5 g of Ethambutol (EB) intentionally. She presented repetitive generalized convulsions with metabolic acidosis, treated with diazepam and 7.5 g of Pyridoxine (Vitamin B6). During day 4 and 5, liver dysfunction worsened and prothrombin time declined below 5%. She was treated with infusion of fresh frozen plasma and fully recovered on day 13. Serum concentration of INH and EB at 5 hours after ingestion was 7.6, 0.94 micrograms/ml respectively.

Production of iron nanoparticles by laser irradiation in a simulation of lunar-like space weathering.

'Space weathering' is the term applied to the darkening and reddening of planetary surface materials with time, along with the changes to the depths of absorption bands in their optical spectra. It has been invoked to explain the mismatched spectra of lunar rocks and regolith, and between those of asteroids and meteorites. The formation of nanophase iron particles on regolith grains as a result of micrometeorite impacts or irradiation by the solar wind has been proposed as the main cause of the change in the optical properties. But laboratory simulations have not revealed the presence of these particles, although nano-second-pulse laser irradiation did reproduce the optical changes. Here we report observations by transmission electron microscopy of olivine samples subjected to pulse laser irradiation. We find within the amorphous vapour-deposited rims of olivine grains nanophase iron particles similar to those observed in the rims of space-weathered lunar regolith grains. Reduction by hydrogen atoms implanted by the solar wind is therefore not necessary to form the particles. Moreover, the results support the idea that ordinary chondrites came from S-type asteroids, and thereby provides some constraints on the surface exposure ages of those asteroids.

Experimental study on paratumoral injection of cisplatin-loaded microspheres for gastric cancer.

Microspheres from glycolide-L-lactide copolymers incorporating cisplatin (CDDP-MS) were prepared to evaluate the sustained release and anticancer effect by paratumoral injection on the gastric cancer with regional lymphnode metastases induced by VX2 tumor in rabbits. In the first set of experiment, the rabbits were divided into three groups subjected to treatment and compared the tissue cisplatin distribution. In the first group (CDDP-MS pt group), 1 mg/kg of cisplatin was administered by the method of paratumoral injection in the form of CDDP-MS. In the second group (CDDP solution pt group), the same dose was given in the form of CDDP aqueous solution in the same way and in the third group (CDDP solution i.v. group), the same dose was intravenously administered. In the second set of experiment, after twice of each therapy the anticancer effects were compared between CDDP-MS pt and CDDP solution i.v. groups. In results, the platinum concentrations of the tumor and regional lymphnodes were 3.14 +/- 6.22, 0.65 +/- 0.79 micrograms/g in the first group, 0.43 +/- 0.39, 0.16 +/- 0.16 microgram/g in the second group and 0.03 +/- 0.01, 0.07 +/- 0.05 microgram/g in the third group, respectively.

Clinicopathological features of esophageal cancer simultaneously associated with gastric cancer.

BACKGROUND AND OBJECTIVES: We usually use the stomach for esophageal substitution in the surgical treatment of esophageal cancer, although it is often associated with gastric cancer. In order to improve the likelihood of safe and curative surgery of esophageal cancer, we investigated the clinicopathological characteristics of synchronous esophageal and gastric cancer. METHODS: Among 288 patients with primary esophageal cancer who had undergone esophageal resection, this cancer was associated with gastric cancer in 11 cases, and 1,416 gastric cancer patients operated on during the same period, were analyzed. The clinicopathological characteristics and surgical procedures of the 11 patients were compared with those of the other esophageal cancer patients and with those with the gastric cancer only. RESULTS: There were significant differences between the synchronous double cancer and the gastric cancer only in sex (P < 0.01) and location of the gastric cancer (P < 0.05). All of the patients with the synchronous double cancer were men, and the incidence of patients with cardiac cancer was high. CONCLUSIONS: Our findings suggest that, in cases of synchronous esophageal and gastric cancer, an adequate surgical procedure must be chosen in terms of the stage, location, and operative burden.

A case of esophagectomy for corrosive esophageal stricture caused by swallowing strong alkali. A case report.

We report herein the case of a 22-year old woman who underwent esophagectomy for corrosive esophageal stricture. This patient with mental disturbance swallowed a strong alkali in a suicide attempt and suffered from esophageal stenosis instead of steroid therapy. Because the stiffness and stricture of the esophagus proved to be refractory, transhiatal esophagectomy by blunt finger with gastroesophagostomy was performed four months after injury. Operative findings revealed severe stiffness and inflammation of the esophagus which had spread to the adjacent organs, especially the carina. As for pathological findings, most of the esophageal mucosa showed defects resulting from infiltration of inflammatory cells and capillary vascularization from the lamina propria to the extra-esophageal wall. The postoperative course was uneventful and perioperative psychological state had been stable leading to a decrease in tranquilizer dosage. This experience indicates that esophagectomy is the treatment of choice for such mental disturbed patients with severe stenosis.

A study of patients having survived curative operation for esophageal cancer for five years or more.

In order to analyze the prognostic factors for curatively resected esophageal cancer, 42 patients who had survived their operation more than 5 years (long-term survivors) were compared for clinicopathologic items with 30 recurrent patients who had died within 5 years postoperatively (recurrent cases). Moreover, to estimate the prognosis for the current survivors, we investigated the cause of death of long-term survivors who had died. This comparison showed that the rate of lymphatic invasion was 36.4% and of blood vessel invasion 19.4% for the survivors, much lower than those of the recurrent cases which were respectively 62.1% and 31.0%. It was found that the significantly unfavorable prognosis-determinant factors was lymphatic invasion (p < 0.05). Ten out of 12 n (+) survivors (83.3%) had single metastasing region, one in the neck, three in the mediastinum and six in the abdomen. This was not significantly different from the recurrent cases, of whom, ten out of 14 n (+) cases had a single metastasing region, six in in the mediastinum and four in the abdomen. As for the number of metastatic lymph nodes, nine out of 12 n (+) survivors (75%) had only one matastatic lymph node, and none of them had more than three. On the other hand, two of the recurrent cases had more than three. Of the 42 long-term survivors, 21 patients are still alive (current survivors' average age: 70.1 +/- 7.9) and 21 have died. The cause of death was recurrence in six cases, metachronous primary malignant tumor in three, other disease in six and unknown in six. The average age of death was 62.1 +/- 10.3 in cases of recurrence or double cancer, and 71.8 +/- 9.5 in others. The former were thus significantly younger than the latter (p < 0.05).

[An experimental study on radiotherapy for esophageal cancer using intraluminal administration of radiosensitizer].

This study was undertaken to evaluate the efficacy of intraluminal administration of 5-bromo-2'-deoxyuridine (BUdR) as a radiosensitizer during radiotherapy for esophageal cancer. Lipid-surfactant mixed micelles (MM) was used as an absorption promoter. VX2 carcinoma cells were endoscopically injected into the esophageal wall of rabbits. Two weeks after tumor inoculation, BUdR (100 mg/body) with MM was administered into the esophageal lumen and kept for 3 hours. Subsequently, animals were irradiated with 60Co at dosages of either 5 or 10 Gy. Twelve days after, animals were sacrificed to determine tumor diameter and to evaluate histological effect of radiation. BUdR uptake rates of tumor tissue were determined two weeks after tumor inoculation. Tumor diameters in control animals and those treated with simple irradiation at a dose of 5 Gy were similar. In contrast, irradiation at a dose of 5 Gy significantly reduced tumor diameters when combined with intraluminal administration of BUdR with MM. In cancer bearing animals receiving irradiation under intraluminal injection of BUdR with MM, the histological effect were apparently enhanced as compared to animals receiving simple irradiation. BUdR uptake rates of primary tumors showed a significant increase in animals with the intraluminal administration of the drug as compared the those with intravenous one shot bolus and intravenous drip infusion. Based on those results, we conclude that preoperative radiotherapy combined with intraluminal administration of radiosensitizer could be an effective method.

[Nocturnal infusion of 5-fluorouracil in advanced digestive tract cancer--two case reports].

Two patients, with terminal stage digestive tract carcinoma, are presented who received continuous nocturnal administration of intravenous 5-FU (300 mg/m2/day), between 9:00 pm and 8:00 am for more than 45 consecutive days. They showed improvement in general physical and functional status, and no side effects were observed. The first case is that of a patient with not only an early gastric cancer, but also a nonresectable esophageal cancer. After therapy, complete disappearance of the gastric cancer was noted by endoscopy. The second patient had advanced gastric cancer with carcinomatosis. He received intraperitoneal cisplatinum for intractable ascites without improvement. But after continuous nocturnal 5-FU therapy, a significant reduction in ascites was noted. Two cases did not experience leukopenia and no significant side effects were noted, even in the second patient who received nocturnal 5-FU for 122 days. The therapeutic effects of continuous nocturnal 5-FU administration generally appeared after 20 days, so a prolonged period of time seems to be important.

Fatal and near fatal asthma.

Despite the recent development of apparently effective asthma drugs, the number of deaths from asthma has not declined. The authors tried to establish an optimal strategy for the prevention of acute asthmatic death by analyzing the circumstances of acute fatal or near-fatal asthma. Data were collected from 51 adult patients admitted to Bokutoh Tertiary Emergency Center due to acute asthma between November 1985 and May 1990 and 38 asthmatic patients admitted to Yokohama City Hospital in 1990. Pre-admission data were obtained through interviews with the patients, their families, or doctors who had seen them. A total of 89 patients were classified into three subgroups: group 1 consisted of patients dead-on-arrival (DOA); group 2, non-DOA patients with disturbed consciousness; and group 3, patients with less severe episodes. Little background information was significantly different among groups, but symptomatic episodes in group 1 patients tended to occur more rapidly. The speed of onset of the episodes was also dependent on the asthma control status. Prehospital care of groups 1 and 2 patients was very poor despite severity of the symptoms. All patients in groups 2 and 3 were successfully treated and discharged, but five of the 26 patients in group 2 died during follow-up periods. Prognosis of patients after discharge appeared to be dependent upon asthma control status before the acute episodes. It was concluded that acute fatal or near fatal asthma could occur in apparently low-risk patients as well as high-risk ones. It was also suggested that the optimal strategy for preventing asthma deaths might be variable.

[A case of complete remission of lymph nodes metastasis from esophageal cancer with combination treatment of UFT and radiation].

A 65 year old female patient, who had developed left atelectasis because of mediastinal lymph nodes metastasis after esophageal resection for esophageal cancer, underwent the combination treatment with UFT (300 mg/day) and radiation (1.5 Gy/day, total dosage: 70.2 Gy). The symptoms soon subsided, and mediastinal CT and bronchoscopy revealed a complete disappearance of metastatic lymph nodes after one month. During one year of CR she enjoyed her daily life, however the relapse occurred. It is suggested that the combination treatment is an effective and safe way even in a patient who went through a lot of invasive surgeries.