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Biomedical subjects

S Nag

Publications and source records attributed to S Nag.

At least 163 records · Page 9Linked to original sources

Cerebrovascular permeability in mechanically induced hypertension.

Our previous studies of cerebrovascular permeability in angiotensin-induced acute hypertension demonstrated that the principal mechanism resulting in increased permeability is enhanced pinocytosis. In order to exclude the possibility that the enhanced pinocytosis was a direct effect of exogenous angiotensin, cerebrovascular permeability alterations were studied in nonpharmacologically induced acute hypertension. Rats receiving horseradish peroxidase (HRP) intravenously, were sacrificed 2 1/2 minutes after the onset of hypertension induced by placing a clip on the abdominal aorta. These animals showed the same pattern of permeability alterations as had been observed previously in animals with angiotensin-induced acute hypertension. Focal segments of penetrating arterioles in the temporal and parietal cortex showed increased permeability to HRP. Permeable vessels showed increased numbers of pinocytotic vesicles and the interendothelial junctions revealed no alterations. Enhanced pinocytosis appears to be the principal mechanism resulting in increased cerebrovascular permeability in this model as well as suggesting that the alterations of cerebrovascular permeability observed previously in angio-tensin-induced acute hypertension occur due to the hypertensive state and are not a direct drug effect of exogenous angiotensin.

Animals↗

Prolactin suppression and spermatogenic developments in maturing rats. A quantitative study.

Prolonged suppression of prolactin (PRL) in immature male rats inhibits the spermatocyte-spermatid conversion process, alters leydig cell morphology, decreases accessory sex organ weight and increases serum LH levels without a significant alteration in serum FSH concentration. Amelioration of these effects by exogenous PRL strongly indicates that in the absence of PRL excess titers of endogenous LH fail to exert an influence on the spermatogenic activity of maturing testes.

Animals↗

Morphological changes in spontaneously hypertensive rats.

Our previous studies of angiotension-induced acute hypertension showed increased intracerebral arteriolar permeability associated with markedly enhanced pinocytosis. This study was performed to determine whether similar findings occurred in spontaneous non-pharmacologically induced chronic hypertension. Cerebrovascular permeability to horseradish peroxidase (HRP) was studied over an 82-week period in spontaneously hypertensive rats (SHR) derived from a strain that originated from Japan. In a few animals increased cerebrovascular permeability to HRP was observed, associated with enhanced pinocytosis. Quantitatively, the number of pinocytotic vesicles in permeable arteriolar segments was significantly increased suggesting that enhanced pinocytosis is the principal mechanism of early cerebrovascular changes in SHR. Light microscopy of renal, ocular and cerebral vessels revealed medial hyperplasia affecting renal vessels at 16 weeks and occurring later in ocular and cerebral vessels. Deposition of fibrin in renal vessels was observed from 64 weeks onwards but was not associated with renal failure.

Animals↗

Quantitative estimate of pinocytosis in experimental acute hypertension.

Cerebral cortical arterioles in focal neocortical areas develop increased permeability to plasma proteins and protein tracers in experimental hypertensive encephalopathy. The mechanism underlying this increased permeability has been the subject of several studies. In our previous studies of angiotensin-induced acute hypertension, pinocytosis appeared to be the principal mechanism for the increased blood-brain barrier (BBB) permeability observed. In the present study pinocytotic activity was assessed quantitatively to determine whether enhanced pinocytosis was confined to the permeable arteriolar segments of hypertensive animals. In addition, the effect of horseradish peroxidase (HRP) itself on the pinocytotic activity of normal cerebral cortical arteriolar endothelium was determined. In 12 rats following administration of HRP, hypertension was induced by an infusion of angiotensin. The animals were perfusion-fixed 90 s after the onset of the infusion. Control animals received saline only or HRP only. The area of arteriolar endothelium in cross section was determined by a planimeter from overlapping electron micrographs taken at a constant magnification around the circumference of the vessel wall. Results indicate a significant (P less than 0.001) increase in the number of pinocytotic vesicles in the permeable arteriolar segments of hypertensive animals as compared with nonpermeable arteriolar segments of the same animals and comparable segments of normotensive rats. In addition, eight times as many vesicles appear to be transporting tracer in the permeable arteriolar segments of hypertensive animals as compared to the nonpermeable segments of the same animals and normotensive animals. HRP alone did not affect the pinocytotic index, there being no difference (P greater than 0.05) in the number of vesicles in normotensive animals receiving saline only and those receiving HRP only. Our previous observation that disruption of endothelial cells or their tight junctions did not occur was confirmed.

Animals↗

Cytoplasmic filaments in intracerebral cortical vessels.

Actin filaments measuring 5 nm in diameter are present in the endothelium of systemic vessels and presumably have a contractile function that may be related to vascular permeability. Little attention has been directed to the presence of similar cytoplasmic filaments in the endothelium of cerebral vessels. This study was undertaken to determine whether filaments are present in the endothelial cells of intracerebral cortical vessels of rats and humans. Ultrastructural studies revealed two populations of endothelial cytoplasmic filaments 5 nm and 10 nm in diameter, respectively. The 5-nm filaments were abundant in the endothelium of penetrating cortical arterioles, being grouped near the cytoplasmic margins in proximity to cell junctions and along the abluminal side of the endothelial cells. The filaments were scant in capillaries and venules.

Animals↗

Cerebral cortical changes in acute experimental hypertension: An ultrastructural study.

Multiple focal cortical areas of increased vascular permeability to tracer substances occur in experimental hypertensive encephalopathy. In this study, rats with angiotensin-induced acute hypertension were used to determine whether increased permeability was associated with focal cerebral edema and if so, the tissue component involved. In addition, the mechanism of increased permeability and the types of vessels involved were investigated using horseradish peroxidase as a tracer. Quantitative morphometric studies 8 minutes after the onset of hypertension demonstrated significant perivascular glial swelling around arterioles, venules, and capillaries; the swelling was confirmed to the permeable areas and absent in the nonpermeable areas of the same animals. Ninety seconds after the onset of hypertension, horseradish peroxidase reaction product was present in focal superficial segments of the walls of penetrating arterioles but rarely in venular and capillary walls. At this time period endothelial cells showed prominent pinocytotic uptake of tracer. Eight minutes after the onset of hypertension, reaction product was again found in arteriolar walls and had extravasated into the surrounding extracellular space of the neuropil as well. Extravasation also occurred through capillary and venular walls but was less frequent. At this time interval endothelial pinocytotic activity was still prominent. There was no mechanical damage of vessel walls in the form of endothelial discontinuities or disruption of interendothelial spaces. Tracer was not found in interendothelial jundtions in continuity from lumen to base. The principle mechanism of increased permeability was enhanced pinocytosis, which occurred rapidly, being demonstrable 90 seconds after the onset of hypertension; it was observed principally in permeable arteriolar segments.

Acute Disease↗

Radiotherapy and brachytherapy for recurrent colorectal cancer.

Radical surgical excision of locoregional recurrence of colorectal carcinoma usually produces the best survival and should be attempted whenever possible. However, recurrences are often unresectable; hence palliative local therapy may be indicated. There are several options for the radiation therapy of local, unresectable, recurrent, or metastatic colorectal cancer. Whole pelvis irradiation of 4,000-5,000 cGy followed by a coned-down boost of 1,000-1,500 cGy generally provides good symptomatic palliation in 80-90% of patients, but long-term control or cure is rarely achieved. External beam irradiation of 2,000-3,000 cGy to the whole liver with or without concurrent chemotherapy may be used for palliation of metastatic disease to the liver. A combination of intraoperative radiation therapy applied directly to the tumor bed and external beam irradiation may improve local control and survival rates. Multiple options are available for the intraoperative use of brachytherapy which can deliver high radiation doses to the residual tumor, or tumor bed, sparing normal tissue.

Brachytherapy↗

Intraoperative high dose rate brachytherapy in recurrent or metastatic colorectal carcinoma.

BACKGROUND: The survival of patients with recurrent or metastatic colorectal cancer usually is less than 12 months. In an attempt to improve this dismal prognosis, we investigated the role of intraoperative high dose rate brachytherapy (IOHDR) in the management of these patients. METHODS: From April 1992 to December 1996, 26 patients with locally recurrent or metastatic colorectal carcinoma were treated with maximal surgical resection and IOHDR. Intraoperative radiation dose ranged from 10 to 20 Gy, prescribed at 0.5 cm depth. The residual tumor irradiated was microscopic in 16 patients (62%) and gross residual in 10 patients (38%). Six patients received postoperative external beam radiation therapy. RESULTS: After a median follow-up of 28 months (range 6 to 54 months), seven of 15 evaluable patients (47%) failed in the area treated with IOHDR. The median time to local failure was 21 months (range 4 to 52 months). The median survival was 23 months (microscopic 24 months; gross 17 months), with a 4-year actuarial survival rate of 36%. Major morbidity was observed in 7 patients (47%) and usually was surgery-related. CONCLUSION: The use of IOHDR in association with radical resection increases local control in patients with recurrent or metastatic colorectal cancer. Patients with microscopic residual disease achieved a better result than do those with gross residual disease. Future strategies include the addition of limited EBRT dose to IOHDR, even for previously irradiated patients.

Actuarial Analysis↗

Brachytherapy for solid tumors in children.

The standard treatment after surgery and chemotherapy in pediatric solid tumors is external beam to the tumor with a generous (5 cm) margin for local control. This treatment is given over a five to six-week period, requires use of repeated deep sedation, and leads to unacceptable morbidity (especially organ and bone-growth retardation) in infants and younger children. Limited volume irradiation by brachytherapy over a few days may be sufficient therapy for children treated with aggressive chemotherapy. Brachytherapy allows high doses of radiation to be limited accurately to the tumor bed, spares the surrounding normal tissues, and thus minimizes late sequelae. Manually afterloaded removable iridium-192, iodine-125, and cesium-137 have been used with good results. The major disadvantages of LDR brachytherapy are: the necessary sedation and immobilization of younger children to prevent accidental removal of the implants during the entire period, radiation exposure to the medical personnel and the parents, and the psychological effect of separating parents from their child. Using a low energy radionuclide such as iodine-125, or remote afterloading technology with LDR and PDR reduces radiation exposure hazards, but prolonged sedation and immobilization are still required. HDR brachytherapy not only eliminates the radiation exposure hazards but, in addition, eliminates the other disadvantages of brachytherapy thereby extending treatment to the infants and younger children. The long term effects of brachytherapy need further study.

Brachytherapy↗

Mortality and morbidity with intraoperative radiotherapy for head and neck cancer.

OBJECTIVE: To critically evaluate the morbidity and mortality associated with intraoperative radiation therapy (IORT). IORT allows the delivery of large single-doses of radiation to a visible tumor bed with exclusion (or shielding) of critical normal structures from the treatment field. Morbidity and mortality associated with IORT has been directly studied in abdominal malignancies, but only briefly mentioned in the head and neck literature. PATIENTS AND METHODS: At the Arthur G. James Cancer Hospital, The Ohio State University Medical Center, 53 patients with advanced head and neck cancer were treated with surgical resection and IORT. Twenty of these patients had intraoperative high-dose-rate (HDR) brachytherapy, whereas the remaining 33 received intraoperative electron beam therapy. All patients received 7.5 to 20 Gy of radiation. Those treated were reviewed evaluating perioperative mortality, major and minor complications, and length of hospital stay. All patients have been followed at least 3 months postoperatively. RESULTS: There were no perioperative deaths. Additionally, there was no increase in the number of complications or length of hospital stay associated with the use of IORT. The mean length of hospital stay was 13.0 days. The major complication rate was 16.8%. Of the major complications, 9% were medical and not related to the surgical site. The minor complication rate was 8%. CONCLUSION: As we strive to increase control of advanced head and neck cancer, IORT may play an exciting role for intensifying the therapy. At this institution, IORT did not add to the mortality or morbidity of an aggressive multimodality treatment schema.

Head and Neck Neoplasms↗