Variants of fractionation of irradiation in intracavitary gamma-therapy

Under study was the efficacy of three schedules of dose fractionation in intracavitary gamma-therapy in cervical cancer patients treated on the machine "AGAT-B". Single doses were 1000, 700 and 500 rad, while total dosage at point A depending on the stage of the disease was within the range of 4000-5000 rad. The survival during the first, second and third years following termination of the radiotherapy was found to be identical for patients of all the groups under examination. No differences were noted in them also in the character of early radiation reactions on the part of the adjacent organs. The frequency and severity of late radiation injuries of the urinary bladder, rectum and vagina were related to the dose fractionation regimen.     

Bypass surgery for vascular disease of the carotid system

A series of 58 operations on 56 patients, in whom a branch of the superficial temporal artery was anastomosed to a branch of the middle cerebral artery (STA-MCA bypass or Yasargil procedure), is reviewed. These operations were performed chiefly for occlussions or for inaccessible stenotic lesions of the internal carotid or middle cerebral arteries. Patency in eight patients operated on from April 1971 through November 1973 was low (25%). Patency in patients operated on since July 1974 has been high (95%). There have been no deaths and no major ischemic strokes attributable to the surgery. The rationale for this procedure is considered in relationship to the anatomy and physiology of the cerebral circulation and the pathogenesis of syndromes of cerebral ischemia. The operation appears to have a low morbidity in good-risk patients. The role of this operation in managing common manifestations of cerebral vascular disease such as focal transient cerebral ischemic attacks (TIAs) and amaurosis fugax, although not fully established, appears encouraging. The procedure seems useful for orthostatic cerebral ischemia caused by multiple occlusions of major extracranial (and intracranial) vessels and, occasionally, for progressing strokes related to internal carotid artery occlusion, both of which are relatively uncommon manifestations of cerebral vascular occlusive disease. It may have application in the rare "slow stroke." The procedure is probably of limited value, if any, in the management of large completed infarcts but may be indicated in selected patients with small infarctions who have preserved most of their cerebral function and who have had evidence of subsequent focal ischemic events. The procedure is useful for bypassing giant aneurysms or basofrontal tumors invading major vessels. It may have a role in the management of fibromuscular disease of the internal carotid artery.     

Decreased resistance to intravenous tumour-cell challenge during reticuloendothelial depression following surgery

The influence of surgical stress on resistance to i.v. challenge with Walker 256 tumour cells was investigated in rats, with respect to the functional state of the reticuloendothelial system (RES). Phagocytic activity of the RES was evaluated by colloid (gelatinized [131I] "RE test lipid emulsion") clearance, and opsonin levels were determined by bioassay. Reticuloendothelial clearance capacity was significantly (P less than 0-05) depressed 60 min following surgery (coeliotomy plus jejunal enterotomy) as quantified by both humoral and cellular parameters of RE function. Phagocytic depression was primarily due to impaired hepatic Kupffer cell function and related to a deficiency in the phagocytic supporting capacity of plasma, also referred to as opsonic or recognition factor (RF) capacity. During the postoperative period of RES colloid clearance depression, pulmonary localization of the blood-borne test particulate matter increased. Rats challenged with 51Cr-labelled viable tumour cells at a dose of 1-0 X 106 i.v., either prior to or during the postoperative period of RE depression, manifested a significant (P less than 0-05) increment in pulmonary localization of the viable tumour cells, and a decrease (P less than 0-05) in hepatic clearance. Evaluation of survival patterns demonstrated a significant (P less than 0-01) decrease in host resistance to i.v. tumour cell challenge (2 X 103 cells) during the postoperative period of RE depression and hypo-opsonaemia. Sham-anaesthetized control animals survived 17-9 +/- 0-8 days, while animals challenged during the period of RE depression survived 7-9 +/- 0-4 days. An increased incidence of respiratory distress and nasal discharge was observed in the animals with impaired survival. Thus, surgical manipulation may transiently compromise RES systemic host defence and may be reflected in an increment in the pulmonary localization of blood-borne tumour cells. The relationship of this altered pattern of tumour cell distribution to the impaired survival remains to be determined, and warrants investigations.     

Comparison of calcium lactate with chlorine as a washing treatment for fresh‐cut lettuce and carrots: quality and nutritional parameters

The efficacies of calcium lactate and chlorine washing treatments of fresh‐cut lettuce and carrots were compared during storage at 4 °C over 10 days. The gas composition of packages, colour, enzyme activity, texture, sensory attributes, microflora and levels of ascorbic acid and carotenoids were evaluated at 1, 3, 7 and 10 days. Calcium lactate treatment was not significantly different to chlorine treatment (p < 0.05) in terms of maintaining colour, texture and acceptability of fresh‐cut lettuce and carrots during the entire storage period. The washing treatments did not affect levels of ascorbic acid of fresh‐cut lettuce or carrots. Carotenoid levels were higher in calcium lactate‐treated carrots than chlorine‐treated samples at the end of storage. Mesophilic, psychrotrophic and lactic acid bacteria counts were not significantly different between treatments for both vegetables. Copyright © 2005 Society of Chemical Industry     

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.     

Transplantation of stromal cells transduced with the human IL3 gene to stimulate hematopoiesis in human fetal bone grafts in non-obese, diabetic-severe combined immunodeficiency mice

The non-obese diabetic-severe combined immunodeficiency (NOD-SCID) mouse is a convenient host for human hematopoietic tissues and cells. Human fetal bone fragments engrafted subcutaneously in NOD-SCID mice sustain human hematopoiesis for several months. MS5 murine bone marrow stromal cells were transfected by electroporation with a plasmid containing the human interleukin-3 gene. As expected, stably transfected hu-IL3-MS5 cells supported human hematopoiesis in vitro more efficiently than MS5 cells. hu-IL3-MS5 cells were then injected intravenously into hu-NOD-SCID mice to test their ability to home to the mouse and/or human bone marrow, and to evaluate the role of hu-IL3 secretion on human hematopoiesis in vivo. hu-IL3 was detected in the mouse serum for up to an observation time of 8 weeks. hu-IL3-MS5 cells engrafted the bone marrow, spleen, liver and lungs of the mice but also the human bone graft. The presence of hu-IL3-MS5 cells in the human bone significantly stimulated local human hematopoiesis. This setting could be used to model the bone marrow homing of intravenously injected stromal cells or stromal cell precursors. The same experimental principle could also be applied in a therapeutic perspective to malignant human bone marrow hematopoiesis.