Adenovirus-mediated p53 gene transfer in patients with advanced recurrent head and neck squamous cell carcinoma

PURPOSE: Standard therapies of head and neck squamous cell carcinoma (HNSCC) often cause profound morbidity and have not significantly improved survival over the last 30 years. Preclinical studies showed that adenoviral vector delivery of the wild-type p53 gene reduced tumor growth in mouse xenograft models. Our purpose was to ascertain the safety and therapeutic potential of adenoviral (Ad)-p53 in advanced HNSCC. PATIENTS AND METHODS: Patients with incurable recurrent local or regionally metastatic HNSCC received multiple intratumoral injections of Ad-p53, either with or without tumor resection. Patients were monitored for adverse events and antiadenoviral antibodies, tumors were monitored for response and p53 expression, and body fluids were analyzed for Ad-p53. RESULTS: Tumors of 33 patients were injected with doses of up to 1 x 10(11) plaque-forming units (pfu). No dose-limiting toxicity or serious adverse events were noted. p53 expression was detected in tumor biopsies despite antibody responses after Ad-p53 injections. Clinical efficacy could be evaluated in 17 patients with nonresectable tumors: two patients showed objective tumor regressions of greater than 50%, six patients showed stable disease for up to 3.5 months, and nine patients showed progressive disease. One resectable patient was considered a complete pathologic response. Ad-p53 was detected in blood and urine in a dose-dependent fashion, and in sputum. CONCLUSION: Patients were safely injected intratumorally with Ad-p53. Objective antitumor activity was detected in several patients. The infectious Ad-p53 in body fluids was asymptomatic, and suggests that systemic or regional treatment may be tolerable. These results suggest the further investigation of Ad-p53 as a therapeutic agent for patients with HNSCC.     

Maternal N-Acetyl-Cysteine Prevents Neonatal Hypoxia-Induced Brain Injury in a Rat Model

Perinatal hypoxia is a major cause of infant brain damage, lifelong neurological disability, and infant mortality. N-Acetyl-Cysteine (NAC) is a powerful antioxidant that acts directly as a scavenger of free radicals. We hypothesized that maternal-antenatal and offspring-postnatal NAC can protect offspring brains from hypoxic brain damage.Sixty six newborn rats were randomized into four study groups. Group 1: Control (CON) received no hypoxic intervention. Group 2: Hypoxia (HYP)-received hypoxia protocol. Group 3: Hypoxia-NAC (HYP-NAC). received hypoxia protocol and treated with NAC following each hypoxia episode. Group 4: NAC Hypoxia (NAC-HYP) treated with NAC during pregnancy, pups subject to hypoxia protocol. Each group was evaluated for: neurological function (Righting reflex), serum proinflammatory IL-6 protein levels (ELISA), brain protein levels: NF-κB p65, neuronal nitric oxide synthase (nNOS), TNF-α, and IL-6 (Western blot) and neuronal apoptosis (histology evaluation with TUNEL stain). Hypoxia significantly increased pups brain protein levels compared to controls. NAC administration to dams or offspring demonstrated lower brain NF-κB p65, nNOS, TNF-α and IL-6 protein levels compared to hypoxia alone. Hypoxia significantly increased brain apoptosis as evidenced by higher grade of brain TUNEL reaction. NAC administration to dams or offspring significantly reduce this effect. Hypoxia induced acute sensorimotor dysfunction. NAC treatment to dams significantly attenuated hypoxia-induced acute sensorimotor dysfunction. Prophylactic NAC treatment of dams during pregnancy confers long-term protection to offspring with hypoxia associated brain injury, measured by several pathways of injury and correlated markers with pathology and behavior. This implies we may consider prophylactic NAC treatment for patients at risk for hypoxia during labor.     

Parallel Computation and Control Problems: A Review

The reports submitted at the International Conference on Parallel Computation and Control Problems (PACO'2001) held in Moscow on October 2–4, 2001, are reviewed.     

4-Defect repair of grade 4 cystocele

PURPOSE: The 4-defect repair of grade 4 cystocele corrects discrete and severe deficiencies of vesicourethral support. We describe this technique used during pelvic reconstruction in 130 women. MATERIALS AND METHODS: During a 3-year period 130 patients (age range 35 to 96 years) underwent repair of grade 4 cystocele using the 4-defect repair technique. Cystocele repair had been performed in 60 patients (46%) and hysterectomy had been performed in 85 (65%). A "goalpost incision" is used in the vaginal wall to facilitate separation of the wall from underlying perivesical fascia, entry into the retropubic space, and exposure of the urethropelvic ligament, cardinal ligament and perivesical fascia. The 4 polypropylene sutures are used to provide an anterior vaginal wall sling which is modified to incorporate perivesical fascia and cardinal ligaments. Central defect repair is achieved by approximation of the cardinal ligaments and midline plication of the perivesical fascia over absorbable mesh. RESULTS: A total of 112 patients were available for followup which ranged from 6 to 42 months (mean 21). Repair of grade 4 cystocele was accompanied by other transvaginal repairs in 94 patients (83%), including rectocele repair in 81, hysterectomy in 22 and enterocele repair in 31. Of the patients 92% had excellent objective and subjective results for anatomical cystocele repair. Of the patients with preoperative stress urinary incontinence 90% had excellent or good subjective results. De novo urge incontinence was seen in 7% of patients. CONCLUSIONS: The 4-defect repair technique relies on anatomical restoration of 4 distinct deficiencies of pelvic support and is highly effective for relief of symptoms of grade 4 cystocele.     

Hall effect in detwinned single crystals of YBa2(Cu1−x Zn x )3O7 −δin the mixed state

The effect of zinc doping on the mixed-state Hall effect in detwinned single crystals of YBa₂Cu₃O_{7 ?δ} has been studied. We observe a sign reveral of the Hall effect in crystals with a superconducting transition temperature (T _c) as low as 71 K. The Hall conductivity in the mixed state follows theC ₁/H+C ₂ H field dependence. The absolute value of the coefficientC ₁ increases faster than (1–T/T _c) with decreasing temperature.C ₂ increases rapidly asT falls belowT _c. The temperature dependence of the ratioC ₁/C ₂ scales approximately asT/T _c for different levels of zinc doping.     

Extended cervical mediastinoscopy

Organic solvent inhalation is a serious problem among youths in Japan. It induces physical and mental disorders, and is related closely to crime and delinquency. The relationship between solvent inhalation and antisocial behavior was investigated in 75 youths. The subjects were divided into three groups according to the level of violent behavior and the time of appearance: a non-violent group, a late-onset group (violence occurred after the start of inhalation) and an early-onset group (violence had occurred before the start of inhalation). Various parameters were compared among the groups. The late-onset group showed the following characteristics; (i) the frequency of inhalation was high, and many subjects experienced hallucinations and mood changes caused by inhalation; (ii) the family environment was characterized by conflict; and (iii) the subjects had strong psychological conflicts and showed dissociative coping with frustration. The violence, psychological conflict and dissociation in this group were found to be related to the inhalation, with familial conflict as a background. The violence in the early-onset group was considered to be the manifestation of a violent personality as the frequency of inhalation and the incidence of mental symptoms were both low. The subjects in this group showed weak psychological conflict and tended to be demanding of others when attempting to cope with frustration. Two types of violent behaviors in the teenagers who inhaled solvents were identified. The violence of solvent inhalers should be managed according to the type.     

Serum factors releasing serotonin from normal platelets: relation to the manifestations of systemic lupus erythematosus

In 13 patients with systemic lupus erythematosus, globulin fractions of sera from serial bleedings were assayed for the induction of serotonin release from normal platelets. Releasing activity appeared at some time in the sera of seven patients, five of whom had episodes of thrombocytopenia. Conversely, only one patient manifested thrombocytopenia without the occurrence of serotonin releasing activity at any time. In three patients with episodes of thrombocytopenia, increases in serotonin releasing activity temporally coincided with drops in platelet count. These data show that levels of circulating platelet serotonin releasing factor(s) vary in the course of systemic lupus erythematosus and these variations may be inversely related to the platelet count in particular patients.     

Effect of warfarin on activated partial thromboplastin time in patients receiving heparin

BACKGROUND: The activated partial thromboplastin time (APTT) is used to adjust heparin sodium dosage. However, warfarin sodium is often administered concomitantly with heparin and may also affect the APTT and, therefore, heparin dose. We performed a prospective cohort study to quantify the effect of warfarin on the APTT in patients who are being treated with heparin. METHODS: Serial assays of APTT, international normalized ratio, heparin levels, and functional levels of prothrombin (factor II) and factors VII and X were performed in 24 patients with acute venous thromboembolism who were treated with concomitant continuous intravenous heparin and warfarin. The effects of warfarin, as expressed by international normalized ratio and coagulation factor levels, on APTT were determined. RESULTS: Warfarin markedly affected APTT; for each increase of 1.0 in the international normalized ratio, the APTT increased 16 seconds (95% confidence interval, 10-22 seconds). The effects of warfarin and heparin on APTT were additive. Consequently, warfarin markedly altered the relationship between APTT and heparin levels; of the 29 blood samples with supratherapeutic APTT, 13 had a therapeutic heparin level and 10 had a subtherapeutic heparin level. CONCLUSIONS: In patients receiving concomitant heparin and warfarin therapy, APTT reflects the combined effects of both drugs. Because of the marked effect of warfarin on the APTT, decreasing heparin dose in response to a high APTT frequently results in subtherapeutic heparin levels.     

Detection of a metastable magnetic phase in the La1.85Ba0.15CuO4−y system

We have made samples of La_1.85Ba_0.15CuO_4–y with varying heat treatments. We have measured their dc magnetization and electron paramagnetic resonance, and have examined them by electron microscopy and electron diffraction. For samples annealed only a few hours, cooling the material below 5 K causes a magnetic transition and a thermal hysteresis. These observations, taken with the EPR data, suggest a possible spin-glass or ferromagnetic phase. Annealing samples in an oxygen atmosphere appears to remove that magnetic phase. For the phase with the K₂NiF₄ structure, no superlattice spots are seen in electron diffraction at room temperature or at 77 K.