Preventative effect of exercise against falls in the elderly: a randomized controlled trial.

SUMMARY: The present study was conducted to determine the effect of 5-month exercise program on the prevention of falls in the elderly. The exercise training, which consisted of calisthenics, body balance training, muscle power training, and walking ability training 3 days/week improved the indices of the flexibility, body balance, muscle power, and walking ability and reduced the incidence of falls compared with non-exercise controls. The present study showed the beneficial effect of the exercise program aimed at improving flexibility, body balance, muscle power, and walking ability in preventing falls in the elderly. INTRODUCTION: The present study was conducted to determine the effect of exercise on the prevention of falls in the elderly. METHODS: Sixty-eight elderly ambulatory volunteers were randomly divided into two groups: the exercise and control groups. The daily exercise, which consisted of calisthenics, body balance training (tandem standing, tandem gait, and unipedal standing), muscle power training (chair-rising training), and walking ability training (stepping), were performed 3 days/week only in the exercise group. No exercise was performed in the control group. RESULTS: After the 5-month exercise program, the indices of the flexibility, body balance, muscle power, and walking ability significantly improved in the exercise group compared with the control group. The incidence of falls was significantly lower in the exercise group than in the control group (0.0% vs. 12.1%, P = 0.0363). The exercise program was safe and well tolerated in the elderly. CONCLUSIONS: The present study showed the beneficial effect of the exercise program aimed at improving flexibility, body balance, muscle power, and walking ability in preventing falls in the elderly.

Very long baseline interferometric observations made with an orbiting radio telescope.

An orbiting spacecraft and ground observatories have been used to obtain interferometric observations of cosmic radio sources. The Tracking and Data Relay Satellite System (TDRSS) was used as the orbiting observatory in conjunction with two 64- meter radio telescopes at ground observatories, one in Australia and one in Japan. The quasars 1730-130 (NRAO 530), 1510-089, and 1741-038 were observed at a frequency of 2.3 gigahertz, and a maximum projected baseline of 1.4 earth diameters was achieved. All quasar observations for which valid data were acquired resulted in detected fringes. Many of the techniques proposed for a dedicated very long baseline interferometry observatory in space were used successfully in this experiment.

Immunotherapy of liver metastases of human gastric carcinoma with interleukin 2-activated natural killer cells.

To better understand the events occurring during immunotherapy of liver metastases with effector cells, we have developed a clinically relevant animal model in which both effector-tumor cell interactions and survival can be evaluated. A cell line of human gastric carcinoma (HR) metastatic to the liver has been established from a patient's liver biopsy. HR cells (10 x 10(6)) injected intrasplenically metastasize into the liver of immunosuppressed nude mice, with micrometastases detectable histologically by day 4 and macrometastases by day 7. The animals subsequently develop ascites and die between days 30 and 40 after tumor injection. To investigate early metastatic events in the liver, HR cells were transduced with a plasmid containing both the lacZ gene under the control of the CMV promoter and NeoR gene. Transfectants selected for neomycin resistance were lacZ gene positive and stained blue in the presence of a beta-galactosidase substrate, 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-Gal). These transfectants (HRLZ) remained lacZ gene positive for at least 25 passages in vitro. Injected intrasplenically, an HRLZ clone grew invasively in nude mice and formed liver metastases comparably to parental tumor cells. The number and localization of blue X-Gal-positive tumor cells were followed in liver tissues of animals sacrificed at various times, from 1 h to 28 days postinjection of HRLZ cells. HRLZ cells were seen in liver blood vessels and sinusoids within 1 h after injection, and the progressive growth of micrometastases and macrometastases could be followed with precision by X-Gal staining. On day 3 after injection of HRLZ cells, numerous micrometastases were established containing 12-16 tumor cells. When these 3-day established HRLZ micrometastases were treated by the intrasplenic infusion of interleukin 2 (IL2)-activated human natural killer (NK) cells selected by IL2-induced adherence to plastic (A-NK) and systemic IL2, nearly all liver micrometastases were eliminated within 24 h after a single transfer of A-NK cells (P < 0.001). This xenogeneic model was also used for adoptive immunotherapy of 7-day established liver macrometastases with human A-NK cells injected intrasplenically and exogenous IL2 given i.p. A significant decrease in the number of hepatic metastases and the weight of livers (P < 0.003) in comparison with those of control mice was observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Evidence for local and systemic activation of immune cells by peritumoral injections of interleukin 2 in patients with advanced squamous cell carcinoma of the head and neck.

Interleukin 2 (IL2) was injected peritumorally and intranodally in 36 patients with unresectable squamous cell carcinoma of the head and neck enrolled in an Eastern Cooperative Oncology Group-sponsored phase Ib trial (EST P-Z388). Groups of 6 patients received escalating doses(200, 2 x 10(3), 2 x 10(4), 2 x 10(5), 2 x 10(6), and 4 x 10(6) units) of IL2 daily 5 times/week for 2 weeks. Tumor biopsies were obtained before and after IL2 therapy. Tumor tissue was provided for histology, and the remaining fresh tissue was divided for snap-freezing in -75 degrees C and for separation of tumor-infiltrating lymphocytes (TIL) and tumor cells. Immunophenotyping of TIL performed on cryostat sections of paired pre- and post-IL2 biopsy tissues showed increases after IL2 therapy in the number of T-cells (P = 0.005), natural killer (NK; CD16+) cells (P = 0.0001), CD25+ cells (P = 0.004), and HLA-DR+ cells (P = 0.001) accumulating in the tumor stroma. In the tumor parenchyma, NK cells (P = 0.0001) and HLA-DR+ cells (P = 0.003) were increased after IL2 therapy. The T:NK cell ratios in the tumor stroma and parenchyma were decreased after therapy, suggesting selective accumulation of NK cells. By flow cytometry, TIL recovered from post-IL2 biopsy tissues were enriched (P < 0.05) in CD3-CD56+ (NK) cells. In situ hybridization with [35S] cDNA probes for cytokines and IL2 receptors indicated that the numbers of cells expressing mRNA for IL2, tumor necrosis factor alpha, IL1-beta, gamma-interferon, transforming growth factor beta, and IL2 receptor p55 or p70 were increased in post-IL2 biopsy tissues as compared to pre-IL2 tissues. Cytolytic activity of TIL isolated from post-IL2 tissues was also increased, as determined in 4-h 51Cr release assays against K562 targets (12 +/- 3 mean lytic units/10(7) cells +/- SEM pre-IL2 versus 46 +/- 13 post-IL2; n = 16) and against autologous tumor (13 +/- 8 versus 68 +/- 26; n = 9). Fresh TIL of one clinical responder showed relatively high levels (195 lytic units) of autotumor cytotoxicity after IL2 therapy versus no activity prior to therapy. In the blood, NK and lymphokine-activated killer cell activity, and percentages of CD3-CD56+ NK cells and of activated (CD25+) T-lymphocytes were increased for all doses of IL2.(ABSTRACT TRUNCATED AT 400 WORDS)

Human cytotoxic T-cell lines with restricted specificity for squamous cell carcinoma of the head and neck.

Human cytotoxic T-lymphocyte (CTL) lines with specificity restricted for autologous squamous cell carcinoma of the head and neck (SCCHN) were established from peripheral blood lymphocytes obtained at the time of surgery and again at two different times after surgery from a patient with cancer of the tongue. The CTL lines were cultured in the presence of interleukin (IL) 2, IL4, and autologous tumor (AuTu) cell monolayers. All three lines were CD3+CD8+CD11b-HLA-DR+ T-cell receptor alpha/beta+. They were tested in 4-h51Cr release assays against SCCHN cell lines (n = 5) and a variety of nonsquamous human tumor (n = 5) and normal (n = 5) cell targets and was found to lyse only AuTu (PCI-50) and three allogenic SCCHN cell lines. Lysis of AuTu and the three allogenic SCCHN targets by the established CTL lines appeared to be major histocompatibility complex class I restricted, since it was blocked by monoclonal antibodies to class I histocompatibility complex antigens. The CTL lines proliferated in vitro in response to autologous PCI-50 or an allogenic SCCHN cell line (PCI-1). The lines have been maintained in culture in the presence of AuTu monolayers and retained cytotoxicity against AuTu for over 20 weeks. The AuTu (PCI-50) cell line was tested for in vitro sensitivity to cytotoxic or cytostatic effects of various effector cells, including the CTL lines. PCI-50 targets were resistant to lysis by resting human mononuclear cells but sensitive to IL2-activated natural killer cells in 4-h 51Cr release assays. In comparison with IL2-activated natural killer cells, the CTL line mediated lower levels of lysis against AuTu. Growth of PCI-50 cells in culture was significantly inhibited by a combination of gamma-interferon and IL2 or by high concentrations of tumor necrosis factor alpha. While supernants of IL2-activated natural killer cells were growth inhibitory, those of the CTL line were not. On the other hand, lysis of AuTu targets by the CTL line was increased by preincubation of the tumor cells with tumor necrosis factor alpha or gamma-interferon. These cytokines augmented expression of HLA-class I, HLA-class II, and intercellular adhesion molecule I, but not squamous cell carcinoma-associated antigens, E7 and A9, on PCI-50 cells. The CTL lines described are the first with restricted specificity for autologous SCCHN ever reported and their availability will facilitate studies of the AuTu T-cell response in head and neck cancer.

Drop episodes improved after tracheotomy: a case of Coffin-Lowry syndrome associated with obstructive sleep apnea syndrome.

Some cases of Coffin-Lowry syndrome recognized episodic drops and it tended to be intractable for medical treatment. We reported here a patient with the Coffin-Lowry syndrome associated with obstructive sleep apnea syndrome (OSAS). The patient had epileptic seizures and drop attacks only during night-time and it was not recognized during the daytime. His sleep-induced electroencephalogram was normal. At 12-years old of his age, his OSAS was worse, so we performed a tracheotomy. Notably after the operation, his epileptic episodes were disappeared.

Long-term survival of full trisomy 13 in a 14 year old male: a case report.

Long term survival for the cases of trisomy 13 into over a first decade is very rare. We reported here the case of a 14-year-old male karyotype with full type of trisomy 13. In this clinical phenomenon, the case had typical facial, finger and limb anomalies for trisomy 13. Arterial septal defect and patent ductus arteriosus were recognized using ultrasonography after birth. Major cerebral malformation such as holoprosencephaly or cerebellar hypoplasia were also not revealed. After 5 months of his age, artificial ventilation therapy for dyspnea associated with laryngomalacia was required. A tracheotomy was performed at 6 months of his age. After 12 years old, intractable partial epilepsy was recognized. For his partial seizures, a treatment with a combination of two anti-epileptic drugs, valproic acid and levetiracetam, were advised. Now he is alive for 14-years-old and he is the 4th longest surviving patient with full karyotype of trisomy 13.

Growth stimulation of human head and neck squamous cell carcinoma cell lines by interleukin 4.

Interleukin 4 (IL-4) has been reported recently to inhibit growth of acute lymphoblastic lymphoma, non-Hodgkin's lymphoma, melanoma, sarcoma, breast, gastric, colon, and renal tumor cell lines, and treatment of murine tumors with IL-4 gene-transduced cells has been therapeutically successful. Therefore, we sought to determine the effect of IL-4 on the growth of human squamous cell carcinoma of the head and neck (SCCHN) cell lines. Growth of SCCHN cell lines incubated in the presence of various concentrations of IL-4 was measured in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assays and by cell counts. Specific binding of IL-4 to SCCHN cells was demonstrated by flow cytometry with phycoerythrin-labeled IL-4, blocking studies with antibodies to IL-4, and using the radiolabeled ligand 125I-labeled IL-4. Reverse transcription PCR for IL-4 and IL-4 receptor (IL-4R) mRNA was performed. SCCHN tissue biopsies were examined by immunohistology and in situ hybridization for the presence of IL-4 protein and IL-4 mRNA in the tumor, respectively. In contrast to earlier reports, we observed growth stimulatory effects of IL-4 consistently in 6 of 13 SCCHN cell lines tested. Growth stimulation by IL-4 ranged from 20 to 200% of control (P < 0.05) and was IL-4 dose dependent. The growth-promoting effect of IL-4 was inhibited completely by incubation of tumor cells in the presence of antibodies specific for IL-4. Reverse transcription PCR analysis of mRNA obtained from the SCCHN cell lines and ELISA performed with SCCHN cell supernatants respectively indicated that the tumor cells did not transcribe or secrete IL-4 actively. The SCCHN cell lines expressed 260-540 IL-4Rs/cell with a dissociation constant of 100 +/- 8 pM. SCCHN cell lines also contained IL-4R mRNA. Immunostaining of SCCHN tissue biopsies indicated that IL-4 may be produced and secreted within these tumors by tumor-infiltrating lymphocytes. In situ hybridization for IL-4 mRNA indicated the presence of positive cells in the tumor stroma. Our data suggest that IL-4 may regulate the growth of SCCHN cells by a paracrine mechanism. These data also indicate that immunotherapy with exogenous IL-4 or IL-4 gene therapy to treat head and neck cancer may not be effective, given the potential tumor growth-stimulatory effects of this cytokine.

Induction of heme oxygenase protein protects neurons in cortex and striatum, but not in hippocampus, against transient forebrain ischemia.

To clarify whether heme oxygenase-1 (HO-1) protein plays a protective role against cerebral ischemia, we investigated the effects of an HO inhibitor (tin mesoporphyrin IX [SnMP] three doses of 30 micromol/kg, intraperitoneally) and an HO inducer (hemin, three doses of 30 micromol/kg, intraperitoneally) on the pathologic outcome and on the immunohistochemical reaction for HO-1 after 20-minute transient forebrain ischemia followed by 3-day reperfusion in rats. Hemin significantly increased viable neurons in the cortex (compared to the SnMP-treated group, P < .05) and striatum (compared to the saline-treated group at P < .01 and SnMP-treated group at P < .05), and intense HO-1 immunoreactivity was observed in cortex and striatum, whereas the administration of SnMP tended to decrease viable neurons in the parietal cortex. In contrast, neither hemin nor SnMP affected the pathologic outcome in the CA1 and CA3 hippocampi, in which HO-1 immunoreactivity was weak. These results suggest that induction of HO-1 protein may contribute to cellular defense against ischemic damage in brain regions where potential ability to synthesize HO-1 is retained in ischemia.

Dynamics of nitrotyrosine formation and decay in rat brain during focal ischemia-reperfusion.

The purpose of this study was to establish the dynamics of nitrotyrosine (NO2-Tyr) formation and decay during the rise of NO2-Tyr in rat brain subjected to 2-hour focal ischemia-reperfusion, and to evaluate the role of inducible nitric oxide synthase in the rise. The authors first determined the half life of NO2-Tyr in rat brain at 24 hours after the start of reperfusion by blocking NO2-Tyr formation with N(G)-monomethyl-L-arginine and after the decay of NO2-Tyr by means of a hydrolysis/HPLC procedure. The values obtained were approximately 2 hours in both peri-infarct and core-of-infarct regions. Using the same hydrolysis/HPLC procedure, the ratio of nitrotyrosine to tyrosine from the 2-hour occlusion to as much as 72 hours after the start of reperfusion was measured in the presence and absence of aminoguanidine (100 mg/kg intraperitoneally twice a day). In the absence of aminoguanidine, the ratio of NO2-Tyr in the peri-infarct and core-of-infarct regions reached 0.95% +/- 0.34% and 0.52% +/- 0.34%, respectively, at 1 hour after the start of reperfusion. The elevated levels persisted until 48 hours, then declined. The peri-infarct region showed the highest percent NO2-Tyr level, followed by the core of infarct, then the caudoputamen. Aminoguanidine significantly reduced NO2-Tyr formation (up to 90% inhibition) during 24 to 48 hours. The authors conclude that inducible nitric oxide synthase is predominantly responsible for NO2-Tyr formation, at least in the late phase of reperfusion. These results have important implications for the therapeutic time window and choice of nitric oxide synthase inhibitors in patients with cerebral infarction.

Why are some patients with severe neglect able to copy a cube? The significance of verbal intelligence.

Cube-copying is often used to assess constructional ability of brain-damaged patients and the influence of unilateral spatial neglect is often pointed out in patients with right hemisphere lesions. However, some patients with severe neglect perform cube-copying satisfactorily. The aim of the present study is to identify the factors that affect the performance of cube-copying in patients with left unilateral spatial neglect. Constructional performance was investigated in 100 patients with unilateral spatial neglect using a task to copy the Necker cube. The relationship of the patients' cube-copying performance to the severity of their neglect, as well as other factors (verbal intelligence, age, duration after onset of the disease, educational level, lesion site, piecemeal approach, and side of starting to copy) was analyzed. Twenty-two normal subjects also participated in this study as controls. Among many factors adopted for analysis, neglect severity and verbal intelligence were found to be primary factors affecting the cube-copying performance of the patients with unilateral spatial neglect. The effect of neglect severity on cube-copying performance was apparent in the patients whose verbal intelligence was deteriorated, but was not observed in the patients with preserved verbal intelligence. Similarly, the effect of verbal intelligence on cube-copying performance was apparent in the patients with severe neglect, but not in the patients with mild neglect. We conclude that constructional ability in the copying of a cube is determined by verbal intelligence, as well as by the severity of unilateral spatial neglect.

Nitrotyrosine generation via inducible nitric oxide synthase in vascular wall in focal ischemia-reperfusion.

Nitrotyrosine produced by NO-mediated reaction is a possible marker for cytotoxicity in brain ischemia. In this study, we aimed to determine whether iNOS is responsible for the nitrotyrosine formation and which type of cell is predominantly nitrated. Fifty-eight wild-type and 28 iNOS knockout male mice were used. Under halothane anesthesia the left middle cerebral artery was occluded for 2 h and reperfused for 0.5 or 15 h. The ratio of nitrotyrosine to total tyrosine (%NO2-Tyr) was measured by means of a hydrolysis/HPLC. After 0.5-h reperfusion, %NO2-Tyr in the ischemic cortex of wild-type and knockout mice amounted to 0.037 +/- 0.040% (n = 8) and 0.064 +/- 0.035% (n = 6), respectively, being significantly higher than that in the sham operation group (n = 7) (P < 0.05). After 15-h reperfusion, nitrotyrosine was detected only in wild-type mice (0.039 +/- 0.025%, n = 7), not in knockout or sham-operated mice (P < 0.05). Immunohistochemical reaction for nitrotyrosine was seen predominantly in the vascular wall in the peri-infarct region of the cerebral cortex in wild-type mice after 15-h reperfusion, but not in corresponding knockout mice. Our data suggest that iNOS is responsible for nitrotyrosine formation in the later phase of reperfusion, and that vascular endothelium is the major site of this reaction, at least in the case of 15-h reperfusion.

Bone-specific delivery and sustained release of diclofenac, a non-steroidal anti-inflammatory drug, via bisphosphonic prodrug based on the Osteotropic Drug Delivery System (ODDS).

We have newly synthesized osteotropic diclofenac with bisphosphonic moiety (DIC-BP) based on the concept of Osteotropic Drug Delivery System (ODDS) and investigated its potency of site-specific and controlled delivery of diclofenac to the bone in rats. After intravenous injection into rats, DIC-BP was predominantly distributed in the skeleton. DIC-BP once incorporated in the bone was gradually eliminated (t(1/2)=9.7 days), releasing diclofenac into the bone compartment. As a result, the bone concentration of regenerated diclofenac was apparently constant over 28 days. Furthermore, we evaluated the anti-inflammatory effects of DIC-BP compared with diclofenac (sodium salt) in adjuvant-induced arthritic rats. The mean effective doses (ED(50)) were 0.55 mg/kg and 1.3 mg/kg for daily oral administration of diclofenac and weekly intravenous injection of DIC-BP, respectively. Considering the frequency of medication of 17 times for diclofenac and 4 times for DIC-BP in the experimental period, ED(50) was corrected to 9.4 and 5.2 mg/kg (per experimental period) for diclofenac and DIC-BP, respectively. Moreover, DIC-BP exhibited no side effects of gastrointestinal damage, typical of non-steroidal anti-inflammatory drugs. Thus, ODDS of diclofenac shows promise as an approach for highly potent and non-toxic therapy of diclofenac, with less frequent medication.

7-Nitroindazole attenuates nitrotyrosine formation in the early phase of cerebral ischemia-reperfusion in mice.

The purpose of this study was to evaluate the role of neuronal nitric oxide synthase (nNOS) in nitrotyrosine (NO2-Tyr) formation in the early phase of ischemia-reperfusion in mouse brain. Using a hydrolysis/high pressure liquid chromatography (HPLC) procedure (0.6 microM detection limit), we measured %NO2-Tyr (ratio of NO2-Tyr to total tyrosine) in 23 male C57Black/6J mice subjected to 2-h middle cerebral artery occlusion followed by 0.5-h reperfusion, in the presence (25 or 50 mg/kg) and absence of 7-nitroindazole (7-NI), a relatively specific nNOS inhibitor. At 25 mg/kg, 7-NI reduced NO2-Tyr formation to about a half of that in the vehicle-treated group (0.10 +/- 0.07 vs. 0.18 +/- 0.05%), while 50 mg/kg suppressed NO2-Tyr formation to below the limit of detection, indicating that nNOS is responsible for most of the NO2-Tyr formation in the early phase after reperfusion.

N-methyl-D-aspartate receptor antagonist reduces nitrotyrosine formation in caudate-putamen in rat focal cerebral ischemia-reperfusion.

The aim of this study is to determine experimentally whether N-methyl-D-aspartate (NMDA) receptor is involved in nitrotyrosine formation in rat brain subjected to focal ischemia-reperfusion, by using the NMDA receptor antagonist MK-801. Halothane-anesthetized and artificially ventilated rats were given MK-801 (5 mg/kg, i.p.) or vehicle prior to 2 h of focal cerebral ischemia followed by 0.5 h of reperfusion. The brain was then removed and divided into four sections, cortical ischemic core, peri-ischemic cortex, lateral caudate-putamen and non-ischemic cortex. Tissue nitrotyrosine was measured by means of hydrolysis/HPLC. MK-801 significantly attenuated nitrotyrosine formation in the lateral caudate-putamen. We conclude that nitrotyrosine formation required activation of NMDA receptors, at least in part.

Spinal cord blood flow and pathophysiological changes after transient spinal cord ischemia in cats.

OBJECTIVE: The goal was to study the hemodynamics and regional pathophysiological changes in the spinal cord after transient vascular occlusion in cats. METHODS: We measured spinal cord blood flow (SCBF) continuously in the lumbar region with a laser-doppler flowmeter, before, during, and after spinal cord ischemia induced by balloon occlusion of the thoracic aorta, in 24 cats (divided into three groups) and simultaneously recorded the evoked spinal cord potentials (ESPs). In each group (n = 8), 10-, 20-, and 30-minute ischemic loading was performed. All animals were evaluated neurologically 36 hours later, and then their spinal cords were examined histologically. RESULTS: The amplitude of ESPs decreased 10 minutes and disappeared 20 minutes after occlusion. SCBF increased to as much as 2 times the control values after reperfusion and decreased gradually in all groups. Then, in all animals in the 10-minute group and six animals in the 20-minute group, SCBF returned to the control values, which were subsequently maintained throughout the experiment, and ESPs returned to normal patterns within 1 hour. For all animals in the 30-minute group and two in the 20-minute group, hypoperfusion after recirculation, irreversible amplitude changes in ESPs, postischemic paraparesis, and pathological ischemic changes in the lower thoracic and lumbar spinal segments were recognized. CONCLUSION: Our results showed that > 20-minute occlusion of the thoracic aorta in cats resulted in irreversible spinal perfusion disorders and that the monitoring of SCBF and ESPs could be useful for predicting potential neurological deficits. Furthermore, postischemic hypoperfusion may have an important role in the development of secondary spinal cord ischemia, resulting in severe neurological dysfunction. This observation suggested the possibility of therapeutic modification of the secondary processes inducing hypoperfusion after spinal ischemia.

Middle cranial fossa arachnoid cyst developing in infancy. Case report.

The pathophysiology of primary arachnoid cysts of the middle cranial fossa is still unclear, and no widely accepted therapeutic criteria for this condition have been established. The authors present the case of a 7-year-old boy with this cyst accompanied by temporal lobe hypoplasia. On the basis of computerized tomography taken on the 2nd day after birth and magnetic resonance imaging upon admission, the arachnoid cyst in this case was attributed to brain hypoplasia secondary to abnormal arachnoid development and was confirmed to have developed primarily during infancy. Experience with this case yielded new findings useful in clarifying the pathophysiology of this condition and establishing therapeutic criteria for such a case.

Effect of stimulation of the dorsal aspect of the cervical spinal cord on local cerebral blood flow and EEG in the cat.

Currently there is considerable interest in electrical stimulation of the dorsal aspect of the cervical spinal cord as a potentially effective therapy for persistent vegetative patients. The authors assessed change in the local cerebral blood flow (LCBF) and electroencephalogram (EEG) in the cat following spinal cord stimulation (SCS). In 31 adult cats under isoflurane anesthesia, an electrode for SCS was introduced epidurally to the midline of the C2-C3 segment. Stimulation was performed at 25 Hz and 0.1 msec for 30 min. These animals were divided into five groups by the voltage: (1) 2V (n = 7), (2) 4V (n = 7), (3) 6V (n = 7), (4) 4V with intravenous injection of muscarinic cholinergic agents--atropine sulfate (n = 5), and (5) sham-operated control (n = 5) without stimulation. LCBF was measured by laser Doppler flowmetry through bilateral small burr holes at the parietal area during and 60 min after stimulation. At 2V, LCBF increased only during SCS, then returned to the pre-stimulated level, while the increase continued until the end of the experiment at 4V and 6V. The increase in LCBF was not affected by atropine sulfate. EEG showed spike and wave or polyspikes after SCS in two animals of the 6V group, but not in the 2V and 4V groups, and moreover a moderate increase of the background activity at only 4V. The present data suggested that SCS at 4V can provide the appropriate microcirculatory enhancement with less harmful influence which continues to increase 30 min after SCS, although the exact mechanism should be elucidated continuously. Within the limitation of animal experiments, this study could provide the logical basis for determining the condition of SCS.

Extracapsular spread of squamous cell carcinoma in neck lymph nodes: prognostic factor of laryngeal cancer.

Fifty-two patients with laryngeal cancer who underwent radical neck dissections were studied to provide further information on the prognosis of various clinical and histopathological parameters. Extracapsular spread (ECS) was found in 31% of patients with N1 nodes, and in 60% of patients with histopathologically positive nodes. The 5-year survival rate of histopathological findings was as follows: patients with no pathological evidence of neck metastasis (81%), patients with neck metastasis confined to the lymph node (no ECS) (76%), and patients with ECS (17%). The difference in survival rate between patients with no ECS and patients with ECS was statistically significant (P = .001). Staging classification, T-stage classification, the number of malignant nodes, the diameter of malignant nodes, and combined therapy had no prognostic importance. The most significant factor was the presence of extracapsular spread.

Production by human squamous cell carcinoma of a factor inducing activation and proliferation of immune cells.

OBJECTIVE: To examine supernatants (SNs) of human squamous cell carcinoma of the head and neck cell lines for soluble tumor-derived factors capable of inducing activation and proliferation of human immune cells. DESIGN: The SN of squamous cell carcinoma of the head and neck cell line PCI-50 was cultured in serum-free medium and tested for the ability to induce expression of activation antigens, proliferation, cytotoxicity against tumor cell targets and cytokine production by purified human natural killer (NK) and CD4+ T cells. RESULTS: Supernatant of PCI-50 promoted expression of the following activation markers on NK and T cells: CD25 (interleukin-2R-alpha), HLA-DR (major histocompatibility complex class II), CD54 (ICAM-1), CD71 (transferrin receptor), and CD69 (activation-inducing molecule). In addition, SN induced and significantly sustained (P < .01) proliferation of human unseparated peripheral blood lymphocytes and NK or T cells in culture. Purified human NK or T cells cultured in the presence of the SN and IL-2 (120 IU/mL) had significantly higher antitumor cytotoxicity than that mediated by NK or T cells cultured in AIM-V medium and IL-2. The SN induced cytokine (interferon gamma, tumor necrosis factor alpha, interleukin-6) production in purified NK or T cells. When the SN was fractionated by molecular weight-based filtration into fractions greater and less than 30 kd, the growth- and cytotoxicity-promoting activities were consistently detectable in the greater than 30-kd fraction. CONCLUSIONS: Culture SN of squamous cell carcinoma of the head and neck cell lines contain a soluble factor(s) capable of activating NK and CD4+ T cells and of promoting growth and antitumor cytotoxicity of these lymphocyte subsets in vitro.