Murine cytokine patterns following rubella vaccination

Although thorough studies on the immune reponse to rubella have been performed, less attention has been given to the cellular mechanism and mediators that shape the process. Specifically, information concerning the nature ofcytokine patterns involved in the immune response to Rubella vaccination is not avaliable. This study deals with cytokine production patterns of spleen cells from Balb/c mice following vaccination with the Takahashi strain of Rubella vaccine. Mice were injected intraperitonealy with Rubella virus and PBS and 7, 10 or 14 days later, spleen cells were separated and cultured with varying doses of virus, con A or only the medium. ELISA assays were performed on supernatants for measurement of IL-4, INF-gamma and IL-5. LTT (Lymphocyte Transformation Test) was also performed. The data indicate variation in cytokine patterns during the time periods after vaccination. On day 7 a type 1 pattern was observed. The LTT response was also indicative of CMI (Cell Mediated Immunity) response on the 7th and 14th days while a transient suppression on day 10 was observed. These results indicate a time dependent cytokine response with variation ultimately leading o a dominant type 1 (Ti) cytokine response.     

Can cure in patients with osteosarcoma be achieved exclusively with chemotherapy and abrogation of surgery?

BACKGROUND: Contemporary therapy for osteosarcoma is comprised of initial treatment with chemotherapy and surgical extirpation of the primary tumor in the affected bone. In view of the major advances forged by chemotherapy in the treatment of the primary tumor, an attempt was made to destroy the tumor exclusively with this therapeutic modality and abrogate surgery. METHODS: Thirty-one consecutive patients were treated. All had localized disease (absence of metastases) at the time of diagnosis. Initial treatment with chemotherapy was comprised of high-dose methotrexate and leucovorin rescue (MTX-LF) in 3 patients and intraarterial cisplatin in 28 patients. Clinical, radiologic, angiographic, radionuclide, and histologic investigations were utilized to assess the efficacy of treatment. After a response at 3 months, entry into the study was permitted and treatment was maintained for a total of 18-21 months with a combination of agents comprised of MTX-LF, intraarterial cisplatin, and doxorubicin. Patients were monitored closely for disease recurrence with the investigations outlined earlier. Two informed consents were required: one at the time of diagnosis and another at 3 months after the initial response had been attained. RESULTS: Only 3 of 31 patients were cured with the administration of chemotherapy alone. Local recurrence and pulmonary metastases were not reported to develop in these 3 patients during a follow-up period of 204+ to 225+ months. Four other patients also possibly were cured with chemotherapy alone. At their request, several months after the cessation of chemotherapy, they underwent surgical extirpation of the tumor. No evidence of viable tumor was found. These patients remained free of disease for 192+ to 216+ months. Thus, only seven patients did not develop local recurrence and/or pulmonary metastases. Among the remaining 24 patients, 9 developed local recurrences without pulmonary metastases 14-74 months (median, 30 months) after the initial response. Eight of the nine patients were rendered tumor free by extirpation of the local recurrence. Two of these eight patients subsequently died, one of the acquired immunodeficiency syndrome (AIDS) and the other of varicella septicemia. The ninth patient refused amputation and died of metabolic complications. Three other patients developed local recurrences 20-69 months and pulmonary metastases 10-98 months after achievement of the initial response. These patients were rendered tumor free by extirpation of the local recurrence and metastasectomy. One of these patients also later died of AIDS. In the remaining 12 patients, local recurrences developed 5-29 months (median, 14 months) after the initial response was achieved. The patients also developed pulmonary metastases 11-60 months after the initial response. In eight patients the local recurrences were extirpated and metastasectomy was performed; however, these patients later died of recurrent pulmonary metastases. The remaining four patients refused to undergo extirpation of the local recurrence. The pulmonary metastases were not resected. They failed to respond to alternate therapy. Thus, the tumor-free survival rate was 23% (7 of 31 patients): 3 patients who were treated with chemotherapy only and 4 patients who were treated with chemotherapy plus surgery. The overall survival rate (patients who remained free of disease and those who underwent resection for local recurrence and metastasectomy) was 48% (15 of 31 patients). Prior to the deaths from AIDS and varicella septicemia, the overall survival was 58% (18 of 31 patients). CONCLUSIONS: Utilizing the regimen employed in the current study, only 3 of 31 patients with osteosarcoma (10%) were cured exclusively with chemotherapy. Four additional patients who underwent extirpation of the primary tumor without disease recurrence and in whom no viable tumor was found in the resected specimens possibly could increase the number of patients who potentially were cured with chemotherapy to 7 (23%). With an overall expected cure rate of 50-65% with "conventional" sin whom no viable tumor was found in the resected specimens possibly could increase the number of patients who potentially were cured with chemotherapy to 7 (23%). With an overall expected cure rate of 50-65% with "conventional" strategies, the results of the current study do not justify the adoption of current forms of chemotherapy as exclusive treatments for osteosarcoma.     

Antidepressant-like effect of harmane and other beta-carbolines in the mouse forced swim test.

The purpose of the present study was to determine the effects of harmane, norharmane and harmine on the immobility time in the mouse forced swim test (FST) - an animal model of depression. After 30 min of the beta-carbolines injections, mice were placed individually in a vertical glass cylinder (height, 25 cm; diameter, 12 cm) containing water about 15 cm deep at 22+/-1 degrees C and forced to swim. Treatment of animals with harmane (5-15 mg/kg, i.p.), norharmane (2.5-10 mg/kg, i.p.) and harmine (5-15 mg/kg, i.p.) reduced dose-dependently the time of immobility. Their antidepressant-like effects were not affected by pretreatment with reserpine at the dose of 5 mg/kg, i.p., 18 h before the test, which did not modify the immobility time. Conversely, when flumazenil (5 mg/kg, i.p.) was administered 30 min before the test, it was able to antagonize completely the antidepressant-like effects of harmane, norharmane and harmine. It was concluded that harmane, norharmane and harmine reduce the immobility time in this test, suggesting an antidepressant-like effect, via an inverse-agonistic mechanism located in the benzodiazepine receptors.     

The ageing phenome: caloric restriction and hormones promote neural cell survival, growth, and de-differentiation

The phenome represents the observable properties of an organism that have developed under the continued influences of both genome and environmental factors. Phenotypic properties are expressed through the functions of cells, organs and body systems that operate optimally, close to equilibrium. In complex organisms, maintenance of the equilibrium is achieved by the interplay of several regulatory mechanisms. In the elderly, dynamic instability may lead to progressive loss of normal function, failure of adaptation and increased pathology. Extensive research (reported elsewhere in this journal) has demonstrated that genetic manipulations of endocrine signaling in flies, worms and mice increase longevity. Another effective strategy for prolonging the lifespan is caloric restriction: in data presented here, the persistence of estrogen-sensitive cells in the hypothalamus of caloric restricted 22-month-old female mice, may explain the persistence of reproductive function at an age, when reproductive function has long ceased in ad libitum fed controls. Still another strategy utilizes the effects of epidermal growth factor (EGF) to promote in vitro proliferation of neuroglia, astrocytes and oligodendrocytes. Their subsequent de-differentiation generates immature precursor cells potentially capable of differentiating into neuroblasts and neurons. These and other examples suggest that, in terms of functional outcomes, "the genome proposes but the phenome disposes".     

Treatment outcome in endodontics: the Toronto study. Phases I and II: Orthograde retreatment

The 4- to 6-year outcome of orthograde retreatment was assessed for Phases I and II of the Toronto Study. In total, 523 teeth in 444 patients were retreated. With 395 teeth lost to follow-up and 25 extracted, 103 teeth (34% recall) were examined by two independent, blinded, calibrated examiners for outcome: "healed" (absence of apical periodontitis, signs, or symptoms) or "diseased" (presence of apical periodontitis, signs, or symptoms). The "healed" rate (81%) differed significantly for preoperative apical periodontitis (absent, 97%; present, 78%) and perforation (absent, 89%; present, 42%). Logistic regression revealed an increased risk of disease for preoperative perforation and adequate root filling quality, and postoperative lack of definitive restoration (odds ratios = 26.5, 6.6, and 14.0, respectively). Without perforation, inadequate intraoperative root filling length was also identified (odds ratio = 6.8). This study suggested that apical periodontitis, although a strong predictor, was secondary to preoperative perforation and root filling quality, and to postoperative restoration, in predicting the outcome of retreatment.     

Gypsum-bonded investment and dental precision casting (IV) transformation of III-CaSO4 to II-CaSO4

The degree of III-CaSO4 to II-CaSO4 transition was estimated on wet specimens, 25 mm in diameter and 50 mm high, prepared from a gypsum-bonded investment for quick casting. After 30 min from mixing the specimens were heated in a 700 degrees C furnace until a specimen temperature of 200 degrees C to 700 degrees C was reached. The estimation was made by measuring mass changes of the specimens before and after heating. The transition reached 39% at 350 degrees C. The same estimation method, when applied to a previous study, showed no transition to this temperature in dry specimens heated slowly (5 degrees C/min). The large difference in transition found between the wet and dry specimens was attributed to the formation of alpha- and beta-hemihydrate, respectively. At 350-450 degrees C, the transition was 3% and 48%, respectively. The pronounced latter transition, generally identified by differential thermal analysis of gypsum, appears as the major investment shrinkage demonstrating its dry dehydration process.     

A novel method for the detection of transient myocardial ischaemia using body surface electrocardiac mapping

BACKGROUND: The limitations of the 12-lead ECG in the detection of myocardial ischaemia are well known. This study sought to test the hypothesis that a Body Surface Mapping (BSM) system can detect and localise the transient regional ischaemia induced by elective percutaneous coronary intervention (PCI) in patients with stable angina. METHODS AND RESULTS: 25 patients undergoing elective single vessel PCI were studied: 11 with RCA lesions, 9 with LAD lesions and 5 with circumflex lesions. Patients had BSM readings every 30 s following the inflation of a dilating balloon in the target vessel for 1 min. BSMs were analysed for ST segment change at 60 ms after the J point (ST60). Peak ST changes were analysed and colour map reconstruction made. Characteristic ST segment changes in each arterial domain were observed following inflation of the balloon. Maximal change occurred in a standard V lead on only 2/46 occasions. Statistically significant rapid rise and fall of ST 60 readings were observed indicating the onset recovery and location of the transient ischaemia. A novel method for the presentation of colour map reconstruction that removes baseline noise has been developed. CONCLUSIONS: These data confirm the hypothesis that this BSM system can detect and display transient myocardial ischaemia. BSM may represent a novel clinical tool for the assessment of clinical ischaemia.     

Patient and family attitudes toward schizophrenia treatment

Patient and family member attitudes toward illness, psychopharmacologic and nonpharmacologic treatments in schizophrenia, as well as their attitudes toward psychiatric research are reviewed here. The authors’ recent work investigating patient and family member attitudes toward illness, medication, and a new method of receiving medication via surgical implants is also presented. The authors highlight the importance of understanding patient attitudes so that individual treatment plans and new treatments for schizophrenia can be facilitated. The important contribution of family members in caring for their loved ones is also emphasized. Patient participation in biomedical research is also discussed in the context of guiding the treatment of schizophrenia.