Effect of early induction of hypothermia on severe head injury.

Although therapeutic hypothermia for patients with head injury has improved the outcome, the results in the most severe cases (GCS 3-6) have not been satisfactory so far. We induced hypothermia in head injury patients within 3 hours after the trauma, and compared the outcome of the treatment without hypothermia. Fourteen patients with GCS less than 6 were entered into this study (age range 13 to 58, mean 27.0 years). Seven of them were treated by hypothermia and 6 by the conventional method. The patients undergoing hypothermia were cooled to 34 degrees C within 3 hours after injury, kept at 32-34 degrees C for 48 hours, and then rewarmed. The outcome was evaluated at 6 months post-trauma, and the results were compared in the two groups. Therapeutic hypothermia dramatically suppressed brain swelling on CT in 3 of 7 patients. Four patients including these 3 showed a favorable outcome (good or moderate disability) and 3 died in the hypothermia group. In the conventional treatment group, only 1 patient was moderately disabled and 6 exhibited an unfavorable outcome (severely disabled, vegetative, or death). Early induction of hypothermia can improve the outcome in patients with severe head injury by reducing the severe brain swelling.

The conformational study of chitin and chitosan oligomers in solution.

The inter-residual dihedral angles phi and phip of chitin and chitosan oligomers were determined from experimental 3J(C-H) constants and ROESY cross peaks.

The structure and decay dynamics of exciplexes derived from dibenzoyl-methanatoboron difluoride and alkylbenzenes in cyclohexane

Dibenzomethanatoboron difluoride (DBMBF2) interacted with alkylbenzenes from its singlet excited state to form exciplexes ranging from weak polarity up to contact radical ion pairs (CRIP); this exciplex series shows the characteristics in the Marcus "normal" region. In cyclohexane these exciplexes gave intense fluorescence spectra and high quantum yields (phi(infinity)ex). The dipole moment of these exciplexes calculated from the solvatochromic shift of the fluorescence maximums (vmax) was used to estimate the coefficient ("a" and "c") of the CT and LE terms in the exciplex wavefunction. On the basis of the measured lifetimes and phi(infinity)ex of these exciplexes, the radiative (k(ex)f) and nonradiative (k(ex)NR) rate constants were calculated. The former k(ex)f were also computed from a semi-empirical approach based on the assumption that the exciplex wavefunction could be adequately described by CT and LE states, and that *DBMBF2 primarily contributes to the probability of exciplex emission. Two results agree with each other with small systematic deviations for those less polar exciplexes. The plots of k(ex)r and k(ex)NR (or their logarithmic value) against the LE contribution (c2) and transition energy gaps (hvmax) afford better correlation than those against -deltaG(-et). This indicates the role played by the LE contribution in generating the stabilization energy (U(s)) in these exciplexes through the A-D+)<==> *AD) resonance interaction; U(s), in turn, modifies -deltaG(-et) to afford the decay driving force hvmax. Also, those plots from k(ex)f values (being determined directly from experiments) show better correlation than those from k(ex)NR. In contrast to the CRIP type exciplexes in the Marcus "inverted" region, these k(ex)f and k(ex)NR increase in the common trend with increasing transition energy gaps. The k(ex)NR plots show less steep slopes and attains more quickly a minimum toward the CRIP region; the latter is identified as the turning point from the "normal" to "inverted" region. Both the attenuation and reversal of the k(ex)NR value with increasing polarity are believed to be generated by the emerging contribution of the intersystem crossing process as an additional nonradiative process, which is induced by the increased spin-orbit coupling in highly polar exciplexes.

The conformation of alpha-(1-->4)-linked glucose oligomers from maltose to maltoheptaose and short-chain amylose in solution.

The conformation of maltose-type oligomers in water and in dimethylsulfoxide (Me2SO) was studied using two-dimensional NMR spectra. In Me2SO all of the oligomers have a 1a-type conformation. In water, they tend to adopt the same conformation, but the oligomers are looser and more flexible than in Me2SO.

Common bile duct stones: management strategies in the laparoscopic era.

We reviewed our experience with the treatment of common bile duct (CBD) stones in 70 patients by sequential endoscopic-laparoscopic management and single-stage laparoscopic treatment during the past 7 years. The advantages, disadvantages, and feasibility of the two procedures are discussed to elucidate therapeutic strategies for patients harboring gallbladder stones and associated choledocholithiasis. In 44 patients, sequential endoscopic-laparoscopic management was indicatedd, and was successful in 37 of them but, in seven patients endoscopic stone extraction could not be accomplished. Single-stage laparoscopic treatment was attempted in 26 patients. In practice, laparoscopic transcystic common duct exploration or choledochotomy may not always be feasible if the cystic duct or CBD are not dilated; there is a high risk of intraoperative CBD injury in such circumstances. Laparoscopic management was considered to be especially useful for the treatment of numerous, large or difficult stones, because stone removal could be succesfully performed without any injury to the papilla of Vater. This last issue is of particular importance in patients with dilated CBD, because insufficient opening of the ampulla of Vater made by endoscopic sphincterotomy (EST) may lead to stasis and reflux-related complications such as cholangitis and recurrent stones. We conclude that the most rational management of CBD stones should be decided according to the size of the CBD, which depends on the size, number, and location of stones. Patients with dilated CBD are indicated to under-go laparoscopic single-stage treatment and combined endoscopic-laparoscopic treatment may be best for patients with non-dilated CBD.

Antitumor activity of recombinant human tumor necrosis factor-alpha (rH-TNF alpha) and liposome-entrapped rH-TNF alpha.

The antitumor activities of recombinant human tumor necrosis factor-alpha (rH-TNF alpha) and liposome-entrapped rH-TNF alpha were evaluated in various glioma cell lines and a rat brain T9 gliosarcoma model. rH-TNF alpha had a direct cytotoxic activity against various glioma cell lines in vitro, and indirect cytotoxic activity against gliosarcoma (T9) in vivo. Liposome-entrapped rH-TNF alpha had increased direct cytotoxic activity in vitro, and against experimentally induced brain tumors in vivo. The effects in vivo were probably due to vascular damage of the tumor vessels as shown by histological examination and activation of cytotoxic macrophages as shown in vitro. These results indicate that the general or local administration of liposome-entrapped rH-TNF alpha may become a useful adjunct treatment for malignant brain tumor.

[A case report of far advanced gastric cancer with multiple liver metastasis (H3) treated with transarterial intermittent chemotherapy and intradermal administration of low molecular lipopolysaccharide (LPSp) extracted from Pantoea agglomerans].

A case of far advanced gastric cancer with multiple liver metastasis (H3) was treated with transarterial intermittent chemotherapy (5-FU: 250 mg/week, Farmorubicin: 10 mg/4 weeks, MMC: 4 mg/2 weeks) and intradermal administration of low molecular lipopolysaccharide (LPSp) extracted from Pantoea agglomerans. The CT examination and endoscopy showed regression of the tumor and the patient was discharged from the hospital. LPSp was given at the concentration of 0.1 microgram initially, and the dose was gradually increased. Finally, the dose of LPSp was increased up to 70 micrograms. No serious side effect except fever was observed. The serum TNF-alpha levels were elevated and, histologically, CD 8(+) lymphocyte dominantly infiltrated around the tumor. These findings clearly indicated the immunological anticancer effect of LPSp. Intradermal administration of LPSp is a promising new adjuvant therapy to improve QOL without serious side effect.

Emetic responses of Sorex unguiculatus.

We have shown previously that Suncus murinus, a species of the insectivore, can vomit in response to various emetogenic stimuli. In the present study we investigated whether or not Sorex unguiculatus, which belongs to different subfamily (Soricinae) of insectivore, vomits in response to emetogenic drugs. Subcutaneous injection of veratrine and oral administration of copper sulfate caused emesis in the animal. Histological study showed that bilateral structure of the area postrema was not important for the emetic reflex. Therefore, the capability of emesis may be common to the family of soricidae of the insectivore, and the Sorex unguiculatus is the smallest known mammal which can vomit.

Effects of epidermal growth factor and basic fibroblast growth factor on generation of long-term potentiation in the dentate gyrus of fimbria-fornix-lesioned rats.

The effects of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) on long-term potentiation (LTP) in the dentate gyrus in vivo were investigated in fimbria-fornix (FF)-lesioned rats. Transection of FF resulted in decreased frequency of LTP generation. Intracerebroventricular injection of EGF (50 ng) and bFGF (50 ng) significantly facilitated LTP generation in the FF-lesioned rats. These results suggest that EGF and bFGF can promote the hippocampal LTP impaired by loss of subcortical afferents.

Angiographically occult arteriovenous malformation in the septal region--case report.

An occult arteriovenous malformation (AVM) in the septal region occurred in a 14-year-old boy, manifesting as headache and vomiting. Computed tomography showed a high-density mass in the septal region, faintly enhanced postcontrast. Mild hydrocephalus was also seen. Angiography revealed no abnormalities other than hydrocephalic signs. The lesion was totally removed by the transventricular approach after corticotomy of the left frontal lobe. The histological diagnosis was AVM. He was discharged without neurological or endocrinological deficits.

Epidermal growth factor and basic fibroblast growth factor promote the generation of long-term potentiation in the dentate gyrus of anaesthetized rats.

The effects of epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) on long-term potentiation (LTP) of evoked potential were investigated in the dentate gyrus of anaesthetised rats. Tetanic stimulation of 100 pulses at 100 Hz was applied to induce complete LTP, and stimulation of 20 pulses at 60 Hz was used as a subthreshold stimulation in inducing LTP. Injection of 50 ng EGF, bFGF or NGF into the contralateral ventricle influenced neither the basal amplitude of the population spike nor the LTP induced by the tetanus of 100 pulses at 100 Hz. However, EGF or bFGF, but not NGF, significantly augmented the potentiation induced by the tetanus of 20 pulses at 60 Hz and facilitated the generation of LTP. Moreover, the effect of EGF was dose-dependent in the range 5-500 ng. These results suggest that EGF and bFGF promote the generation process of LTP.

Effects of pretreatment with basic fibroblast growth factor, epidermal growth factor and nerve growth factor on neuron survival and neovascularization of superior cervical ganglion transplanted into the third ventricle in rats.

Effects of short-term treatment with basic fibroblast growth factor (FGF), epidermal growth factor (EGF) and nerve growth factor (NGF) on neurite outgrowth of superior cervical ganglia (SCG) in culture or on neuron survival and neovascularization of SCG in a transplantation system were examined in rats. SCG were preincubated with FGF, EGF and/or NGF for 30 min and cultured with drug-free medium for 2 days. FGF or EGF neither promoted neurite outgrowth of SCG nor potentiated the NGF-induced neurite elongation in culture. In the transplantation study, SCG were exposed to these factors for 30 min and grafted into the third ventricle of adult rats for 14 days. Although pretreatment of NGF, FGF, EGF or the combination of NGF and EGF were not effective, there was better neuron survival in SCG grafts pretreated with 1 micrograms/ml NGF and 1 micrograms/ml FGF together. In addition, density of capillaries in these grafts was significantly greater than in the other group tested. These results suggest that the synergistic interaction between NGF and FGF cause rapid neovascularization, which can prevent neuron death after transplantation.

Isolation of mutants with improved production of cAMP from Microbacterium sp. no. 205 (ATCC 21376).

Mutants were isolated from Microbacterium sp. no. 205 (ATCC 21376) producing 13-30 mM cyclic adenosine 3',5'-monophosphate (cAMP) by salvage biosynthesis, through sequential improvements of the bacterium for the purpose of improving cAMP production. The mutants produced 50-75 mM cAMP on 100 mM inosine 5'-monophosphate as a precursor. Mutants resistant to the inhibition of growth by cAMP at high concentrations were isolated; the resistance was one of four characteristics effective for improved production of cAMP.

Combination chemotherapy with cisplatin and etoposide for malignant intracranial germ-cell tumors. An experimental and clinical study.

Antitumor activity against intracranial malignant teratoma by combination chemotherapy with cisplatin and etoposide was evaluated in experimental and clinical studies. A human teratoma cell line (Tera 2) was exposed in vitro to cisplatin and/or etoposide, after which cell growth inhibition and alterations of deoxyribonucleic acid (DNA) histograms were observed. The results indicated that a synergistic cytotoxic effect was achieved by use of both agents in combination. Four cases of recurrent intracranial germ-cell tumor (three malignant teratomas and one germinoma) were treated with cisplatin and etoposide. With this combination therapy, regression of the tumor was observed in all four cases (three complete and one partial), for a total response rate of 100%. During a follow-up period of 9 to 22 months, no recurrence or progression has been noted in three of these cases.

[Clinical trials of combination chemotherapy using cis-platinum with aclarubicin in intracranial rhabdomyosarcoma].

Combination chemotherapy of Cis-platinum with Aclarubicin was performed in patients with intracranial alveolar rhabdomyosarcoma. These patients were treated with Cis-platinum (20 mg/day) and Aclarubicin (20 mg/day) for 5 days. After two trials with about a four-week interval, complete tumor regression on CT scan was observed. Mild gastrointestinal toxicity was observed in these patients but the symptoms were transient and soon disappeared. No other side effects appeared, on or after treatment. This result demonstrated that combination chemotherapy of Cis-platinum and Aclarubicin is an effective regimen for remission induction chemotherapy in patients with intracranial sarcoma.

[Combination chemotherapy with aclarubicin and cisplatinum against malignant intracranial tumor--an in vitro study].

Augmentation of cytotoxicity against cultured human tumor cell lines (5 gliomas, 2 neuroblastomas, 2 sarcomas) using a combination of Aclarubicin (ACR) and Cisplatinum (CDDP) was analysed in vitro from the viewpoints of cell growth inhibition and alteration of the DNA histogram. Synergistic effects of the combination of the two agents were observed in 7 of the 9 cell lines. In sarcoma cell lines, effects were demonstrated even by a low dose of 0.1 microgram/ml CDDP and 0.01 microgram/ml ACR. Flow cytometry studies of the DNA histogram showed increase of accumulation in the S phase following the G2-M phase and reduction of G1 phase cells in response to the combination. From the present experimental studies in vitro, it is concluded that combination chemotherapy with ACR and CDDP may be effective for sarcoma and ACNU-resistant glioma. The mechanism of the synergistic effect produced by the combination is suggested to be impairment of RNA synthesis by ACR which prevents the repair of DNA damage induced by CDDP.