Effect of Free-Volume Hole Fraction on Dynamic Mechanical Properties of Epoxy Resins Investigated by Pressure-Volume-Temperature Technique.

Dynamic mechanical analysis experiments were carried out to investigate the mechanical properties of four types of chemically different epoxy resins. Pressure-volume-temperature (PVT) experiments were performed to determine the free-volume hole fraction (hPVT) of each epoxy resin using the Simha-Somcynsky lattice-hole theory. Using the Williams-Landel-Ferry equation, the correlations between the relative hole fraction (1 - hPVTTr/hPVT, where hPVTTr is the hole fraction at a reference temperature Tr) and four typical parameters reflecting dynamic mechanical properties [storage modulus (E'), loss modulus (E″), damping factor (tanδ), and complex viscosity (|η*|)] were studied in the temperature range from Tg(PVT) (the glass transition temperature determined by PVT data) to Tg(PVT) + 100 °C. In the temperature range from Tg(Eonset') (temperature corresponding to the intersection of the two tangent fitting lines in the E'(T) curve indicating the glassy-state and glass-transition stages) to Tg(PVT) + 100 °C, the variations in the four dynamic mechanical parameters with a relative hole fraction could be separated into two distinct categories: (i) log[E'(T)] and log[|η*|(T)] decreased linearly to their minimum values and then remained nearly unchanged with increasing relative hole fraction, and (ii) log[E″(T)] and log[tanδ(T)] first increased monotonically to their maximum values and then decreased linearly with the increasing relative hole fraction. This study demonstrates that the PVT technique is a feasible and reliable experimental method to determine the hole fractions of thermoset polymers.

Salting-out taste-masking system generates lag time with subsequent immediate release.

Salting-out effects were utilized for developing a multiparticulate system balancing numbness masking and high bioavailability. A "salting-out taste-masking system" consisting of a drug core containing acetaminophen as a model drug, a salting-out layer containing sodium carbonate (Na(2)CO(3)) and hydroxypropylmethylcellulose (HPMC), and a water-penetration-control layer consisting of cetanol was designed and prepared. The system successfully generated a long lag time while achieving immediate drug release. In the system, the Na(2)CO(3) release rate was slower and the lag time was longer than when the water-penetration-control layer was not present. During the release of Na(2)CO(3) from the system, the release of HPMC and drug was suppressed. These results indicated that the water-penetration-control layer maintained a high concentration of Na(2)CO(3), prevented HPMC's dissolution, and generated a long lag time of drug release. The system generated longer lag time and released drug more immediately than formulation containing the water-penetration-control layer of same thickness without the salting-out layers. These results indicated the salting-out layers were necessary for obtain a long lag time and subsequent immediate drug release. This novel taste-masking system has the potential to be a useful multiparticulate dosage form for effective, safe, and user-friendly drug therapy.

Pharmacokinetics of positron-labeled 1,3-bis(2-chloroethyl)nitrosourea in human brain tumors using positron emission tomography.

The nitrosoureas are widely used in the chemotherapy of brain tumors, two of the most common being 1,3-bis(2-chloroethyl)nitrosourea and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea. However, we do not understand how these compounds work, nor do we know which part of the molecule has antitumor activity. In six patients with brain tumor, we measured the kinetic behavior of positron-labeled 1,3-bis(2-chloroethyl)nitrosourea in both the tumor and the normal brain with the aid of positron emission tomography; we also analyzed the distribution of radioactivity in plasma. We found the clearance of total radioactivity from the tumor to be significantly slower than from the contralateral brain and plasma, indicating a different rate of 1,3-bis(2-chloroethyl)nitrosourea decomposition in the tumor than in normal brain.

Evaluation of [18F]-4-fluoroantipyrine as a new blood flow tracer for multiradionuclide autoradiography.

This article reports the evaluation of [18F]-4- fluoroantipyrine (FAP) as a quantitative blood flow tracer by comparing blood flow measured with [18F]FAP to that determined simultaneously with [14C]-4-iodoantipyrine (IAP), a standard blood flow tracer, by means of double-tracer autoradiography. The single-pass extraction value (m), which indicates diffusibility of a tracer, was determined according to the procedure described by Crone . The diffusibility of FAP was essentially the same as that of IAP. The brain-blood partition coefficient for FAP was found to be similar to that for IAP, 0.89 +/- 0.01. Values of local cerebral blood flow obtained with FAP agree with those determined with IAP. From these results, we concluded that FAP is indeed as good a blood flow tracer as IAP. Since 18F is a positron-emitting radionuclide, it might be a useful tracer for blood flow measurement by positron emission tomography.

Uncoupling of local blood flow and metabolism in the hippocampal CA3 in kainic acid-induced limbic seizure status.

Limbic seizure status was induced by microinjection of kainic acid into a unilateral amygdala in rats. Two hours after kainic acid injection, distant neuronal cell damage was produced, especially in the hippocampal CA3 on the kainic acid-injected side. In order to elucidate the mechanism of this neuronal cell damage, local cerebral glucose utilization and local cerebral blood flow were studied by means of an autoradiographic method using [14C]2-deoxyglucose and [14C]iodoantipyrine during kainic acid-induced limbic seizure status. These studies were performed 2 h after kainic acid microinjection into a unilateral amygdala. Both local cerebral glucose utilization and local cerebral blood flow were remarkably increased in the limbic system, ventrobasal complex of the thalamus, septal nucleus, nucleus accumbens, caudate nucleus, substantia nigra and hypothalamus on the kainic acid-injected side. In the hippocampus, local cerebral glucose utilization increased 2.6 times control in CA1 and 4.1 times in CA3, whereas the rates of increase in local cerebral blood flow were similarly low in CA1 and CA3: 1.2 and 1.4 times control, respectively. The results demonstrated that the degree of uncoupling of local cerebral glucose utilization and local cerebral blood flow were higher in CA3 than in CA1, and also suggested that relative hypoxia occurred in CA3 in this high degree of uncoupling, resulting in pyramidal cell damage in CA3 in kainic acid-induced limbic seizure status.

Sequential changes in cerebrovascular reserve capacity in three-vessel occlusion rats.

To understand the pathophysiology of hemodynamic compromise, we evaluated the cerebrovascular reserve capacity of a cerebral hemisphere in rats with 3-vessel occlusion (3VO). The bilateral vertebral and left common carotid arteries were occluded in Wistar rats. Sequential changes in local cerebral blood flow (LCBF) and local cerebral plasma volume (LCPV) were measured by [14C]iodoantipyrine and [14C]dextran autoradiography, respectively. There was no significant difference in LCBF between 3VO and control rats at rest. After acetazolamide administration, however, an increase of LCBF in the left hemisphere was less significant compared to that in the right side in the 3VO rats. The left and right ratio was 0.67 +/- 0.15 (P < 0.05) in the parietal cortex and 0.70 +/- 0.10 (P < 0.01) in the caudate nucleus. This asymmetrical response to acetazolamide administration gradually corrected by 7 days after 3VO. A significant increase of the LCPV in the ischemic side was observed between day 0 and the 5th day. The 3VO rat is a useful model for studies on the pathophysiology of a hemodynamically compromised state.

Protein kinase C in focal ischemic rat brain: dual autoradiographic analysis of [14C]iodoantipyrine (IAP) and [3H]phorbol-12,13-dibutyrate (PDBu).

Protein kinase C (PKC) activity was measured in rat brain with 2 h of middle cerebral artery (MCA) and common carotid artery (CCA) occlusion, using dual autoradiography of [14C]iodoantipyrine (IAP) and [3H]phorbol-12,13-dibutyrate (PDBu). In the ischemic brain, it required more than 120 min of incubation to obtain a plateau in PDBu binding. In contrast, the binding of PDBu in non-ischemic brain reached a plateau with incubation for 60 min. This delay of PDBu binding in the ischemic brain suggests that the affinity of this ligand is reduced due to a change in structure of the cell membrane caused by ischemia. PDBu binding in the ischemic brain increased significantly compared to the non-ischemic brain. This finding provides further evidence that excessive activation of PKC in the ischemic brain may play an important role in ischemic neuronal damage.

Effects of intracarotid infusion of neuropeptide Y on cerebral blood flow in rats.

Neuropeptide Y (NPY) was continuously administered to Wistar rats intracarotidly via the external carotid artery and local cerebral blood flow (LCBF) was measured by a quantitative autoradiography using [14C]iodoantipyrine. A remarkable reduction in LCBF was observed in the NPY infused hemisphere. This depression was irregular and was particularly evident in the hippocampus, selective thalamic nuclei and the cerebral cortex.

Hypothermia attenuates the activation of protein kinase C in focal ischemic rat brain: dual autoradiographic study of [3H]phorbol 12,13-dibutyrate and iodo[14C]antipyrine.

Using phorbol 12,13-dibutyrate (PDBu) autoradiography, we investigated the effect of hypothermia or protein kinase C (PKC) activation in rat brain 2 h after focal ischemia. In normothermia, a significant increase of PDBu binding was observed in ischemic brain. Hypothermia suppressed the increase of PDBu binding in degree and extent. These observations suggest that intraischemic hypothermia attenuates the activation of PKC, and this may in part be participate in the protective effect of hypothermia.

Regional calcium accumulation and kainic acid (KA)-induced limbic seizure status in rats.

The sites of calcium accumulation were studied by 45Ca autoradiography during kainic acid (KA)-induced limbic seizure in rats. Two hours after KA injection into unilateral amygdala, calcium accumulated in CA3 of the hippocampus, lateral septal nucleus and thalamic reticular nucleus on KA-injected side. Those sites coincided with the sites where neuronal cell damage appeared 4 h after KA injection. These results suggested that regional calcium accumulation might be responsible for neuronal cell loss induced by seizures.

Consecutive in vivo measurement of nitric oxide in transient forebrain ischemic rat under normothermia and hypothermia.

The effects of hypothermia on production of nitric oxide (NO) in ischemic brain were investigated by using in vivo microdialysis. Male Wistar rats were randomly divided into three groups; saline-treated normothermic group (37 degreesC, n=6), 30 mg/kg N-nitro-l-arginine methyl ester(l-NAME)-treated normothermic group (n=6), and saline-treated hypothermic group (30 degreesC, n=6). Transient forebrain ischemia was produced by bilateral common carotid artery occlusion combined with hypotension (MABP=50 mmHg). Saline-treated normothermic animals resulted in a reduction of LCBF to 9% of baseline. Saline-treated hypothermic rats revealed the similar changes of LCBF. In contrast, l-NAME administration reduced the basal CBF to 85% of saline-treated group and to 8% after ischemia. NO products were decreased during ischemia and transiently increased after reperfusion in saline-treated groups. However, the increase of NO products after reperfusion was less significant in the hypothermia. l-NAME-treated group showed a constant reduction of NO production during ischemia and after reperfusion.

HA1077, a novel calcium antagonistic antivasospasm drug, increases both cerebral blood flow and glucose metabolism in conscious rats.

The effects of a novel calcium antagonistic antivasospasm drug, HA1077, on local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) were studied in 33 anatomically discrete regions of the brain in conscious rats, using the quantitative autoradiographic [14C]iodoantipyrine and [14C]2-deoxyglucose techniques. HA1077 was infused i.v. over a 30-min period (1 or 3 mg/kg). HA1077 significantly increased LCBF in 9 of 33 sites in rats given 1 mg/kg, and in 14 of 33 sites in rats given 3 mg/kg compared to the control group given vehicle. Significant increases in LCGU were also noted in 16 of 33 sites in rats given 3 mg/kg. HA1077 increased both cerebral blood flow and glucose metabolism in conscious rats.

Radiation and thyroid carcinoma: radiotherapy, head and neck regions, thyroid carcinoma.

Radiotherapy for benign conditions of the head and neck area was first linked to thyroid carcinoma in 1950. All the salivary glands, the parathyroids, and the facial skin can also develop neoplastic lesions in this setting. Thyroid carcinoma is most commonly papillary or mixed papillary and follicular. It is very often multifocal and can be detected by hand palpation, nuclear scanning, high resolution sonography, and needle aspiration. Each test has its limitations and appropriate protocols for screening and detection should be adapted to different medical centers. The surgical management is controversial and ranges from simple lobectomy to total thyroidectomy with adjuvant 131I treatment and thyroid suppression. We prefer total thyroidectomy if it can be performed safely. With adequate treatment the survival should be good. Prevention by administration of iodine at the time of exposure to radiation seems feasible and deserves further clinical trial.

Squamous cell carcinoma of the pyriform sinus.

At the Roswell Park Memorial Institute, 111 patients were treated for squamous cell carcinoma of the pyriform sinus over a 15-year period. Treatment modalities included surgery, radiation therapy, or a combination of both. A retrospective study was carried out to determine how these treatments, used singly or in combination, affected the cure rate. TNM clinical staging and recurrence patterns were studied, and a high tendency for distant metastases was documented. The five-year survival figure in this study was 29% (28/97).

Nonsimultaneous bilateral radical neck dissection.

From January 1963 to December 1977, 63 patients underwent a therapeutic second (staged) neck dissection at our institute. The mean interval between the first neck dissection and the second neck dissection was 13.2 months; 58.7% of the second neck dissections were performed between 6 and 12 months after the first. Forty-six patients had histologically positive and 17 patients had histologically negative nodes in the first neck clearance; 57 patients had histologically positive and 6 patients had histologically negative nodes in the second neck clearance. Forty-two of the 63 patients had bilateral nodal disease, while 2 patients had no disease in either side of the neck. Fifty-four percent of the patients had postoperative complications; 30% developed immediate postoperative edema, and 14% had wound infection. The overall three-year and five-year survival rates were 60% and 38%, respectively. Patients who had bilateral histologically positive nodes had a 16% five-year survival rate, while those who had histologically positive nodes in one side of the neck only had a 26% five-year survival rate.

Reconstruction of massive orbito-maxillary-cheek defects.

The problem of soft-tissue reconstruction in patients who must undergo radical resection of the maxilla, orbit, and cheek is discussed. This problem is greatly complicated by previous radiation therapy or by the need for postoperative radiation therapy. Restoration of oral competence is of primary importance and usually cannot be satisfactorily accomplished with prosthetic appliances when a stable support base is lacking. An orderly reconstructive plan with a high success rate is of the utmost help to the surgeon facing this problem. A multistaged procedure utilizing a deltopectoral flap that has been successful in 7 patients is presented.

Lipoma involving the skull. Case report.

The case of an intraosseous lipoma involving the left frontal bone is reported. Lipomas of the bone are rare; only three cases of lipomas involving the skull have previously been reported. The differential diagnosis includes a healing bone infarction or fracture, meningioma, hemangioma, and fibrous dysplasia. Diagnosis prior to surgery is difficult.

Preoperative irradiation for squamous cell carcinoma of the head and neck. Does it improve five year survival or control figures?

1. A well defined group of patients have been studied. 2. Composite operation resulted in a 56 per cent five year disease-free survival rate. 3. Treatment of recurrent disease with irradiation increased the five year survival to 61 per cent. 4. Preoperative irradiation for squamous cell carcinoma of the intraoral cavity, stage III, is unwarranted unless this treatment plan can produce five year end results better than 61 per cent.

The diagnosis of thyroid carcinoma during the postoperative period after less than total thyroidectomy.

In clinical practice, small or localized thyroid cancer is often missed at the time of surgery and is diagnosed only later after the pathologist has been able to study multiple sections. Our data suggest that patients with early or localized thyroid cancer can be controlled with less than total thyroidectomy. If the nodule is completely excised without fracture (preferably lobectomy) or not cut into, if there is no evidence of metastatic disease either by palpation or frozen section, and if gross examination of the surgical specimen and frozen sections is negative for carcinoma, it is our policy to place these individuals on a regimen of observation only. Additional surgery is performed only if clinical evidence of recurrent cancer develops. Long-term follow-up of forty-four patients supports this treatment policy. Of these, seven had clinical recurrences: three benign; four (9 per cent) malignant. (The 2 patients with metastatic periglandular lymph nodes in the surgical specimen would not meet our present criteria.) We have in our files several additional patients who seem to support the same conclusions but will be reported on only after longer follow-up.

Epstein-Barr Virus antibodies in patients with carcinoma of the nasopharynx and carcinoma of other sites in the head and neck.

Serum antibody titers to Epstein-Barr virus were significantly elevated in a group of twenty-three patients with nasopharyngeal carcinoma as compared with eighty-six patients with cancer of other sites in the head and neck and 222 age-matched controls. Our findings in this group of patients support the suggestion of an association between the Epstein-Barr virus and nasopharyngeal carcinoma.