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An assessment of the incidence of iron deficiency in paediatric otolaryngology inpatients.

The aims of this study were: to determine whether there is an increased incidence of iron deficiency in paediatric otolaryngology inpatients compared with other surgical controls; and to establish whether preoperative screening of haemoglobin level is warranted in such patients. Children aged 1-10 years admitted electively for ENT surgery or for general surgical procedures had blood taken for haemoglobin level, mean cell volume and serum ferritin. Their age, weight, socioeconomic class and ethnic background were recorded. A total of 100 patients entered the study, in a six-month period. The mean ages and weights for the two groups were statistically different, so allowance was made for this in calculations. Social class was not significantly different. No relationship could be established between haemoglobin level and ferritin level for individual patients. Multiple regression analysis for haemoglobin level, mean cell volume and for ferritin level showed that allowing for the age and weight differences these variables were not significantly different for the two groups. This study has therefore shown no increased incidence of iron deficiency in paediatric ENT inpatients. Each Department should formulate its own policy on pre-operative haemoglobin screening, based on local considerations.

Child↗

Dietary and plasma phosphorus in hens with fatty liver syndrome.

Plasma inorganic phosphorus was determined in two experiments in hens that had fatty liver syndrome. In Experiment 1, plasma inorganic phosphorus was determined in twelve strains of hens all fed the same diet. Plasma inorganic phosphorus immediately following oviposition was elevated in all strains. The two strains in the first experiment with the highest as well as the two strains with the lowest plasma inorganic phosphorus were used in the second experiment. Each of the four strains were subdivided into three groups of 60 hens each and fed a practical layer diet containing either .30, .75, or 1.40% total phosphorus and 3.4% calcium. Significant differences were found in plasma inorganic phosphorus between strains fed the three dietary phosphorus levels. Results indicated that plasma inorganic phosphorus is related to dietary phosphorus in hens with an elevated plasma inorganic phosphorus level associated with fatty liver syndrome.

Animals↗

Animal models of depression: navigating through the clinical fog.

Animal models of human disease have proven of considerable value in elucidating basic pathophysiological mechanisms and in developing novel treatments. However, modelling human mental disorders in experimental animals is fraught with difficulties. Depression models generally lack both clinical and scientific credibility and have, thus far, failed to inform treatment strategies previously acquired through serendipity. The complexity and heterogeneity of the clinical states labelled 'depression' dictate that we continue to work with a crude and uninformative taxonomy within which 'core' clinical and pathophysiological features of depression are not clearly identified. Consequently, much of the neuroscience of animal modelling is framed around physiological and neurobiological phenomena that may be of relevance to only a minority of patients. Additionally, inferring pathophysiology from apparent treatment responses overestimates the efficacy of existing treatments and tends to ignore reliable demonstrations of the 'antidepressant effects' of non-pharmacological interventions. Whilst animal modelling remains a potentially important approach towards understanding neurobiological mechanisms in depression, we need to address the poverty of reliable clinical science that should inform model development.

Animals↗

Studies on the purification of antihemophilic factor (factor VIII). II. Separation of partially purified antihemophilic factor by gel filtration of plasma.

A high degree of purification of antihemophilic factor was achieved by filtration of chylomicronpoor human plasma through columns of agarose. The final product contained, on the average, 67 units of antihemophilic activity per mg of protein, and was 3360-fold purified compared with the filtered plasma. The molecular weight of antihemophilic factor appeared to be at least two million. Preparations separated by gel filtration were contaminated with appreciable amounts of plasma thromboplastin antecedent (PTA), and traces of Christmas factor and Hageman factor, but no detectable fibrinogen was present. Similar fractions of plasma prepared from the blood of patients with classic hemophilia, von Willebrand's disease, or a circulating anticoagulant directed against antihemophilic factor contained, on the average, somewhat less protein than normal plasma; whether this difference was significant is not yet known. The purified fractions were partially stabilized by the addition of 1% gelatin. Adaptation of the technique of gel filtration to purification of antihemophilic factor for clinical use remains to be explored.

Anticoagulants↗

Both soluble and membrane-bound forms of Flt3 ligand enhance tumor immunity following "suicide" gene therapy in a murine colon carcinoma model.

In prodrug-activated ("suicide") gene therapy, tumor cells are transfected with the gene for an enzyme that converts an inactive prodrug, such as ganciclovir (GCV), to a toxic compound. Transfected cells are killed on administration of GCV, as also are untransfected "bystander" cells. The ability of the dendritic cell stimulatory cytokine Flt3 ligand (Flt3-L) to modulate prodrug-activated gene therapy has been investigated. Transfectants of the murine colon carcinoma MC26 were generated expressing soluble (FLS) and membrane-bound forms of Flt3-L. They were inoculated together with wild-type MC26 cells and cells expressing herpes simplex virus-1 (HSV1) thymidine kinase into BALB/c mice, which were then administered GCV. Expression of Flt3-L or FLS prevented regrowth of tumor in most mice, which was comparable to the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF), while tumors recurred in all mice receiving "suicide" gene therapy alone. Recurring tumor cells were resistant to direct killing by GCV but sensitive to "bystander" killing in vitro. Mice without tumor recurrence were rechallenged with unmodified MC26 cells. Of those mice given transfectants expressing GM-CSF, Flt3-L, or FLS, approximately 50% were immune to rechallenge. These mice also showed cytotoxic and proliferative responses to MC26 cells. These experiments show that both soluble and membrane-bound forms of Flt3-L were able to induce a protective immune response to colon carcinoma cells in a fashion similar to GM-CSF.

Animals↗

Oedemerid blister beetle dermatosis: a review.

Blister beetle dermatosis is a distinctive vesiculobullous eruption that occurs after contact with three major groups of beetles (Order: Coleoptera). It is caused by a vesicant chemical contained in the body fluids of the beetles. The smallest and least known family is the Oedemeridae. Although there are few references in the medical literature, blister beetle dermatosis caused by oedemerids may be more common and widespread than currently recognized. The best known family is the Meloidae with numerous species worldwide causing blistering. The vesicant chemical in both Oedemeridae and Meloidae is cantharidin. The third group of blister beetles includes species of the genus Paederus (Family: Staphylinidae). The clinicopathologic picture differs because this genus contains a different vesicant agent, pederin. The clinicopathologic features of oedemerid blister beetle dermatosis are described. The world medical and relevant entomologic literature is reviewed.

Animals↗

Pityriasis rosea with palmoplantar plaque lesions.

Pityriasis rosea is a skin disease characterized by sharply defined pruritic red patches covered by fine scales. It affects mostly adolescent and young adults. Typical lesions usually affect the trunk in a Christmas-tree pattern. The eruption usually resolves after 6 weeks but symptomatic treatment may be needed. Two patients are reported with classic presentation of pityriasis rosea except for the unusual associated palmoplantar lesions; both patients had negative RPR (with dilutions) and MHA-TP. They responded to 2-week courses of either oral erythromycin or Clarithromycin with complete resolution.

Adult↗

The carvedilol hibernation reversible ischaemia trial, marker of success (CHRISTMAS) study. Methodology of a randomised, placebo controlled, multicentre study of carvedilol in hibernation and heart failure.

BACKGROUND: Carvedilol reduces mortality and improves symptoms and ejection fraction in ischemic heart failure, but its mode of action is not well defined and not all patients respond to treatment. The aim of the CHRISTMAS (Carvedilol Hibernation Reversible Ischaemia Trial, Marker of Success) study is to examine whether hibernation may be a significant factor determining this response. This paper describes the methodology and the rationale for the choice of the nuclear cardiology and echocardiography imaging techniques used in the study. METHODS AND RESULTS: The CHRISTMAS study is a double-blind, randomised, parallel group, multinational study of oral carvedilol versus placebo in patients with chronic stable heart failure due to left ventricular systolic dysfunction from coronary artery disease. The study aims to randomise 400 patients who are on optimal treatment. Two parallel groups will be randomised to carvedilol or placebo, namely 200 with hibernating myocardium at baseline and 200 matched patients without. The presence of hibernation is defined from a mismatch between regional contractile function and regional viability, measured by echocardiography (severe segmental asynergy) and nitrate prepared resting Tc99m-MIBI myocardial perfusion imaging (segmental activity >60%). The primary treatment-related end-point of the study is the comparison of the mean change, from baseline to the final visit, in radionuclide-determined left ventricular ejection fraction in patients on placebo with those on carvedilol, between the groups designated as hibernating and non-hibernating. Other end-points being examined include the prevalence of hibernation in heart failure, the relationship between the volume of hibernating myocardium and the ejection fraction response, the prevalence of reversible ischemia in heart failure, and the comparison of echo with gated SPECT. To date, 303 patients have been screened and 251 patients randomised in the study. The study aims to report in 2000. CONCLUSIONS: The CHRISTMAS study addresses the issue of whether the presence of hibernation is a predictor of the ejection fraction response to carvedilol in heart failure. It also examines the potential role of medical therapy in hibernation as well as a number of other end-points. The study may potentially lead to an important new role for nuclear cardiology in heart failure, and demonstrates important synergy between cardiac imaging and the pharmaceutical industry.

Adrenergic beta-Antagonists↗

Chemotherapy for small cell lung carcinoma: the Greenlane Hospital experience 1993-1995.

AIMS: 1. To compare treatment response and survival of patients with small cell lung carcinoma managed at Greenlane Hospital with published results. 2. To compare the outcome of patients with extensive disease treated with oral etoposide with those who received combination chemotherapy. METHODS: Case notes of all new patients assessed for small cell lung carcinoma between 1993 and 1995 were reviewed. RESULTS: Seventy-eight cases were identified. Sixty-three patients (81%) underwent chemotherapy, of whom 32 had limited disease, 28 extensive disease and three were inadequately staged. Twenty-six patients (81%) with limited disease received combination treatment (carboplatin, etoposide +/- vincristine) compared with 16 (57%) in the extensive disease group. Response rate was significantly higher in those with limited disease (87.5%) than with extensive disease (50%), (p = 0.006). Overall median survival was 56 weeks in the limited disease group and 32 weeks for extensive disease (p = 0.007). Of patients with limited disease who achieved complete or partial response, 41% (n = 9) developed cerebral metastases as the first sign of disease relapse. These patients relapsed late (mean = 56 weeks) compared with those who relapsed at other sites (31 weeks) (p = 0.002). Patients with extensive disease, who received more than one drug (n = 16), had better median survival than those treated with etoposide only (n = 8), 35 vs 12 weeks, respectively (p = 0.6). Severe treatment complications were uncommon in either group. Four patients required admissions for infection although none were neutropenic. Only one patient (12.5%) treated with etoposide and three (18%) with combination chemotherapy developed grade IV neutropenia. CONCLUSIONS: 1. The survival in our series was comparable with published data on other treatment regimes. 2. Patients with extensive disease who received etoposide only had poorer median survival compared with those treated with more than one drug. This is likely a result of selection bias and the role of etoposide in palliation needs to be further assessed. 3. In spite of achieving good local control in patients with limited disease, late relapse with cerebral metastases was common. Prophylactic cranial irradiation, particularly in responders, needs to be considered in planning future treatment strategies. Small cell lung carcinoma (SCLC) accounts for 15-20% of all primary lung carcinomas and has an aggressive natural history because of its short tumour-doubling time and early metastatic potential. Chemotherapy has been used as the primary treatment modality for SCLC at Greenlane Hospital since 1979. Carboplatin, etoposide and vincristine (CEV) is an effective combination for patients with limited disease and has been adopted as the standard regime at Greenlane Hospital since 1993. Oral etoposide has attracted attention as a single agent for palliation in patients with advanced small cell lung carcinoma. Aggressive chemotherapy may not be appropriate in these patients whose prognosis is poor in spite of treatment. Etoposide offers the advantage of being an active oral agent and avoids the need for repeated venous access. It has been perceived as less toxic than other regimes and thus a preferred option for frail patients with extensive disease. The aims of this study were to compare treatment response and survival of patients with small cell lung carcinoma treated in our service since the introduction of the CEV regime with published data and to compare the outcome of patients with extensive disease treated with combination chemotherapy with those who receive oral etoposide only.

Actuarial Analysis↗