Cytolytic activities of IL-2 activated NK cells from MMTV/v-Ha-ras transgenic oncomice during tumor progression

IL-2 activated natural killer (A-NK) cells have the capacity to infiltrate metastatic tumors and lyse tumor cells. Nevertheless, adoptive immunotherapy with lymphokine-activated killer cells has been only modestly effective in the clinic and has not routinely provided long-term survival in patients with established cancer metastases. This may indicate the need for more carefully investigating the role of effector cells of the immune response, including A-NK cells, in models of tumor progression. Herein we describe the use of the MMTV/v-Ha-ras transgenic mouse model as a system for exploring the role of NK cells during tumor progression. We have examined the lytic capacity of A-NK cells generated from tumor-free and tumor-bearing transgenic oncomice against standard A-NK cell targets (YAC-1 and P815) in addition to tumor cells isolated from these animals. A-NK cells generated from mice without obvious tumor burden show higher lytic activity than A-NK cells generated from mice with evident tumors, i.e., those at a more advanced stage of tumor progression. Only long term (8-day) cultures of late passage A-NK cells generated from tumor-bearing mice showed significant increases in lytic activity over those generated from tumor-free mice. These results suggest that experimental protocols using transgenic oncomice at various stages of tumor growth may constitute a novel model for testing the role of A-NK cells for their capacity to interfere with cancer progression.     

Four years' experience of intravenous colomycin in an adult cystic fibrosis unit

Nearly all strains of Pseudomonas aeruginosa are sensitive to colomycin sulphomethate, but studies in the 1970s using large doses demonstrated significant renal and neurotoxic side-effects and it is not now commonly used. In this study colomycin (2 megaunits i.v. t.d.s.) has been used extensively in adult cystic fibrosis (CF) patients and its use reviewed to determine its efficacy and safety profile. Fifty-two CF patients (28 male, 24 female; mean age 26 yrs, range 17-39 yrs) received 135 courses (mean two courses each, range 1-7, median length 14 days) of i.v. colomycin (2,414 patient days in total). It was used in combination with one other i.v. antibiotic in 114 courses (85%) and with two others in 18 (13%). In all cases there was significant improvement in spirometry (pretreatment forced expiratory volume in one second (FEV1) % predicted mean 44.4, range 10-101; post-treatment mean 51.3, range 14-108; p<0.0001). No patient had any neurotoxicity but one developed a skin rash and myositis. There was no change in renal function (urea mean pretreatment 4.1 mmol x L(-1) (sD 1.4), mean post-treatment 43 (2.2), p=NS; creatinine mean pretreatment 77.9 mmol x L(-1) (15.3), mean post-treatment 803 (21.6), p=NS). In the authors' experience intravenous colomycin sulphomethate in moderate doses is an effective and safe antipseudomonal antibiotic which is easy to administer. Other clinicians should consider its use in patients with cystic fibrosis.     

Initial cervical exploration for parathyroidectomy is not benefited by preoperative localization studies

Published data is controversial as to the ability of preoperative localization studies (PLS) to enhance the outcome of initial cervical exploration in patients with primary hyperparathyroidism (PHPT). One surgeon's experience was reviewed to compare surgical success, operative time, and morbidity of initial cervical exploration for PHPT in patients who had undergone PLS versus those who had not. From August 1991 to September 1997, 95 patients who had not undergone prior central cervical exploration presented for surgical management of PHPT. Sixty-seven patients underwent initial cervical exploration without any PLS having been performed (Group A). Twenty-eight patients underwent PLS, either alone or in combination, before surgical intervention (Group B). Analysis of intergroup variability was conducted upon the data available using a two-tailed t test for independent samples. In addition, the sensitivities and positive predictive values of the PLS were calculated using study reports and operative and histologic findings. There was no statistically significant difference in surgical success between those patients who had PLS and those that did not undergo PLS. Sixty-four of 67 patients (95.5%) not having PLS were cured with initial surgery, while 27 of 28 patients (96.4%) who had PLS were surgically cured. Mean postoperative calcium and intact parathormone levels were similar between the two groups, and the mean operative time did not differ. Permanent hypocalcemia occurred in one patient, and five patients had transient hoarseness. Thirty-six total PLS were obtained at an average cost of $752.68/patient, and seven patients underwent multiple tests. Overall, sestamibi scan had the highest positive predictive value (81%). For adenomatous disease alone, sestamibi scan was the most sensitive (83%). Our study shows that for matched groups limited to age, sex, and clinical diagnosis, the use of PLS did not shorten operative time, decrease complication frequency, nor alter the success of the operation as measured by postoperative calcium and parathormone levels. Therefore, routine use of preoperative localization studies before initial cervical exploration for PHPT cannot be recommended.     

Distribution of IgG subclasses in antimonial unresponsive Indian kala-azar patients

BACKGROUND: Interleukin 10 (IL-10) decreases the severity of experimental acute pancreatitis. The role of endogenous IL-10 in modulating the course of pancreatitis is currently unknown. AIMS: To examine the systemic release of IL-10 and its messenger RNA production in the pancrease, liver, and lungs and analyse the effects of IL-10 neutralisation in caerulein induced acute pancreatitis in mice. METHODS: Acute necrotising pancreatitis was induced by intraperitoneal caerulein. Serum levels of IL-10 and tumour necrosis factor (TNF), and tissue IL-10 and TNF-alpha gene expression were assessed. After injecting control antibody or after blocking the activity of endogenous IL-10 by a specific monoclonal antibody, the severity of acute pancreatitis was assessed in terms of serum enzyme release, histological changes, and systemic and tissue TNF production. RESULTS: In control conditions, serum IL-10 levels increased and correlated with the course of pancreatitis, with a maximal value eight hours after induction. Both IL-10 and TNF-alpha messengers showed a similar course, and were identified in the pancreas, liver, and lungs. Neutralisation of endogenous IL-10 significantly increased the severity of pancreatitis and associated lung injury as well as serum TNF protein levels (+75%) and pancreatic, pulmonary, and hepatic TNF messenger expression (+33%, +29%, +43%, respectively). CONCLUSIONS: In this non-lethal model, systemic release of IL-10 correlates with the course of acute pancreatitis. This anti-inflammatory response parallels the release of TNF and both cytokines are produced multisystemically. Endogenous IL-10 controls TNF-alpha production and plays a protective role in the local and systemic consequences of the disease.     

Effect of the administration of fish oil by gavage on activities of antioxidant enzymes of rat lymphoid organs

Expression of retinoblastoma (Rb) protein was immunohistochemically examined in laryngeal squamous cell neoplasias from 72 patients. Staining patterns were considered with reference to such prognostic factors as patient's age, histologic grade, tumour size and lymph node status, and 5-year survival rate. Rb protein negativity, either partial or complete, was noted in 28.8% of cases and was associated with a significantly lower 5-year survival rate, as well as with a higher likelihood of lymph node metastasis. This suggests that Rb alteration may be a prognostic indicator in patients with laryngeal carcinoma.     

Treatment of cutaneous Bowen's disease with particular emphasis on the problem of lower leg lesions

Bowen's disease has a particular predilection for the lower leg, especially in women. A review of the literature for treating Bowen's disease is presented and the problems associated with treating the lower leg emphasized. Evidence for the various treatment modalities used to treat Bowen's disease largely comes from studies that lack good methodology in terms of standardized techniques, patient controls and adequate follow-up. In particular the widely accepted recommendation for excision is not supported by evidence that this treatment is superior to other modalities. The choice of treatment for Bowen's disease should take into account the patient's general condition, the site and size of the lesion.     

The unanticipated difficult airway with recommendations for management

PURPOSE: To review the current literature and generate recommendations on the role of newer technology in the management of the unanticipated difficult airway. METHODS: A literature search using key words and filters of English language and English abstracted publications from 1990-96 contained in the Medline, Current Contents and Biological Abstracts databases was carried out. The literature was reviewed and condensed and a series of evidence-based recommendations were evolved. CONCLUSIONS: The unanticipated difficult airway occurs with a low but consistent incidence in anaesthesia practice. Difficult direct laryngoscopy occurs in 1.5-8.5% of general anaesthetics and difficult intubation occurs with a similar incidence. Failed intubation occurs in 0.13-0.3% general anaesthetics. Current techniques for predicting difficulty with laryngoscopy and intubation are sensitive, non-specific and have a low positive predictive value. Assessment techniques which utilize multiple characteristics to derive a risk factor tend to be more accurate predictors. Devices such as the laryngeal mask, lighted stylet and rigid fibreoptic laryngoscopes, in the setting of unanticipated difficult airway, are effective in establishing a patient airway, may reduce morbidity and are occasionally lifesaving. Evidence supports their use in this setting as either alternatives to facemask and bag ventilation, when it is inadequate to support oxygenation, or to the direct laryngoscope, when tracheal intubation has failed. Specifically, the laryngeal mask and Combitube have proved to be effective in establishing and maintaining a patent airway in "cannot ventilate" situations. The lighted stylet and Bullard (rigid) fibreoptic scope are effective in many instances where the direct laryngoscope has failed to facilitate tracheal intubation. The data also support integration of these devices into strategies to manage difficult airway as the new standard of care. Training programmes should ensure graduate physicians are trained in the use of these alternatives. Continuing medical education courses should allow physicians in practice the opportunity to train with these alternative devices.