A model to refine the selection of children with otitis media with effusion for adenoidectomy

The selection of children with otitis media with effusion for adenoidectomy has been criticized on a number of grounds. In spite of the widespread popularity of the procedure there are few objective guidelines to help the otolaryngologist make a decision which is therfore usually subjective. We present a scientifically derived model using a Generalized Linear Interactive Modelling (GLIM) technique from a population of 122 children who underwent either adenoidectomy or no pharyngeal surgery. The outcome parameter studied was otoscopic clearance in an unoperated ear 1 year after treatment. This was related principally to the operation type (P < 0.001) and to the age at which the operation was performed (P < 0.005). Using a probability of clearance threshold of 50% the model was tested on a prospective population of 166 children and outcome was correctly predicted in over 72%. This model enables the surgeon to determine the probability of clearance of effusion following adenoidectomy in an individual child. At a probability threshold of 50% adenoidectomy would be offered to children with bilateral otitis media with effusion aged between 4.33 and 8.00 years. Over the age of 8 years the probability of clearance occurence spontaneously increases beyond 50%. By careful selection of the probability of clearance thresholds it was possible to produce otoscopic resolution in over 80% of those selected undergo adenoidectomy. The model also enables the otolaryngologist to determine the proportion of children with established disease that require adenoidectomy at his own chosen probability thresholds which will ensure that a more effective resource allocation is achieved.     

Evaluation of biological activities of new LH-RH antagonists (T-series) in male and female rats

A series of new highly potent LH-RH antagonists (T-series) has been synthesized in our laboratory. Among these analogs, antagonists [Ac-d -Nal(2), d -Phe(4Cl)². d -Pal(3)³, d -Lys(A₂pr(Car)₂)⁶, d -Ala¹⁰LH-RH (T-140); [Ac-d -Nal(2)¹, d -Phe(4Cl)², d -Pal(3)³, d -Lys(A₂pr(Ac)₂)⁶, d -Ala¹⁰]LH-RH (T-148); [Ac-d -Nal(2)¹, d -Phe(4Cl)², d -Pal(3)³, d -Lys(A₂pr(For)₂)⁶, d -Ala¹⁰)]LH-RH (T-151) and [Ac-d -Nal(2)¹, d -Phe(4cl)², d -Pal(3)³, d -Lys(A₂bu(For)₂)⁶, d -Ala¹⁰]LH-RH (T-159) were the most powerful. Antagonists T-140, T-148 and T-151 produced a complete blockade of ovulation in normal cycling rats at a dose of 1.5 μg/rat and antagonist T-159 at a dose of only 0.75 μg/rat. The inhibitory effects of compounds T-148, T-151 and T-159 on gonadotropin and sex steroid secretion were investigated in male and female rats. To determine their effect on LH levels in castrated male and ovariectomized female rats, T-148, T-151 and T-159 were injected subcutaneously in doses of 0.625 and 2.5 μg/rat. Blood samples were taken at different intervals for 48 h. All three compounds at either dose caused a significant (P< 0.01) decrease in LH levels for more than 6 h. Significant (P <0.01) inhibition of LH lasted for more than 24 h following a dose of 2.5 μg sc of all 3 antagonists in both male and female rats. Serum FSH levels were also suppressed significantly for more than 48 h in castrated male rats by all three antagonists at a dose of 5 μg/rat sc. Serum testosterone levels were measured in intact male rates injected with antagonists T-148, T-151 and T-159 in doses of 50 and 100 pg sc. Both doses produced a dramatic fall in testosterone (P<0.01) to castration levels 6 h after injection. The inhibition of serum testosterone lasted for more than 48 h, but only 100 μg of T-148 maintained testosterone in the castration range for more than 48 h. Antagonists T-148, T-151 and T-159 injected at a dose of 100 μg to intact female rats reduced serum estradiol levels significantly (P<0.01) for more than 48 h, as compared to control animals. In the cutaneous anaphylactoid test (CAT), T-148, T-151 and T-159 proved to have very low histamine releasing activities. These data demonstrate a high efficacy of these new LH-RH antagonists in suppressing the pituitary-gonadal axis in male and female rats. These LH-RH antagonists could possibly be used for treatment of sex-hormone sensitive cancers and other disorders and conditions, in which a reduction in circulating sex steroids would be beneficial.     

Comparison of GH-stimulation by GH-RH(1-29)NH2 and an agmatine29 GH-RH analog,after intravenous,subcutaneous and intranasal administration and after pulmonary inhalation in rats

Many studies have shown that human GH-RH(1-29)NH₂ possesses full intrinsic activity of GH-RH(1-44)NH₂in vitro and in vivo. This investigation was performed to evaluate the efficacy of GH-RH(1-29)NH₂ given by different routes of administration in stimulating GH release in rats. In each case GH-RH(1-29)NH₂ was administered intravenously, subcutaneously, intranasally and by pulmonary inhalation at two different doses to groups of seven male rats. At a dose of 150 μg/kg GH-RH(1-29)NH₂, the magnitude of GH response was significantly higher for the pulmonary inhalation group (355 ± 33.2 ng GH/mL) than for the subcutaneous group (246 ± 36ng GH/mL) or for the intranasal group (175 ± 30ng GH/mL). The group injected intravenously with GH-RH(1-29)NH₂ at a dose of 2.5 μg/kg showed the highest response, GH levels reaching 877.2 ± 115 ng/mL. A similar pattern of responses was obtained for the superactive GH-RH(1-29) agmatine²⁹ analog, MZ–3-149, at doses that were 50 times lower. Our results indicate a high bioavailability of GH-RH(1-29)NH₂ or analog MZ-3-149 administered by a convenient pulmonary inhalation route. The GH-releasing effect of GH-RH(1-29)NH₂ or analog MZ-3-149 delivered by pulmonary inhalation is superior to subcutaneous and intranasal administration.     

Circulating endothelial cell/leucocyte adhesion molecules in ischaemic heart disease

Increased levels of the endothelial markers soluble E-selectin ( P  = 0.011), soluble thrombomodulin ( P  = 0.0001) and von Willebrand factor (VWF, P  < 0.0001) were found in 116 patients with ischaemic heart disease compared to an equal number of age- and sex-matched asymptomatic controls. In a multivariate analysis of the markers versus the major risk factors for atherosclerosis, VWF correlated with total cholesterol ( P  = 0.002) and E-selectin with sex (lower in women, P  = 0.004) and triglycerides ( P  = 0.007). The data point to profound differences in the release mechanisms of these three endothelial cell products and suggests that further studies into the roles of these molecules in coronary artery disease are warranted.     

Depression in cancer patients: a literature review

It is estimated that 20–25% of cancer patients suffer often unrecognized and untreated long-term depression, a condition that can make life miserable. Symptoms can include: lack of sleep; loss of interest in life; anxiety; irritation; loss of concentration; and, in severe cases, thoughts of suicide; leading to an overall poor quality of life. Given that the majority of patients diagnosed with clinical depression can be effectively treated with one form of treatment or another (psychological, pharmacological or a combination) it is now important that health care professionals routinely assess and offer treatment for depression in cancer patients. Therefore, this article reviews the literature on depression caused by cancer and highlights practical ways in which health care workers can measure and subsequently treat depression using pharmacological and psychological approaches.     

Low Incidence of Cerebrovascular Events in Patients with Incidental Atrial Septal Aneurysm

Objectives: The purpose of our investigation was to describe the echocardiographic characteristics of an atrial septal aneurysm (ASA) and associated cardiac abnormalities, to determine whether any echocardiographic characteristics are associated with cerebrovascular events, and to compare the cerebrovascular risk of ASA when it is an isolated and incidental finding with ASA associated with other cardiac abnormalities and diagnostic indications, including a cardiac source of embolus. Methods: In 1605 consecutive patients referred for transesophageal echocardiography during open heart surgery, we identified 78 patients with ASA as an incidental finding (Group I). During the same period, this anomaly was found in 39 of 8014 consecutive patients referred to the echocardiographic laboratory for various diagnostic reasons (Group II). The frequency of cerebrovascular events and ASA characteristics was compared between these two groups. Results: A total of 117 patients with ASA was included in the study: 60 males and 57 females with a mean age of 66.7 ± 9.1 years. There were no significant differences in the echocardiographic characteristics of ASA or associated cardiac abnormalities between these two groups; no intracardiac or ASA associated thrombi were detected in either group. While only 6.4% of Group I had a clinical event, 23% of patients in Group II had a stroke or transient ischemic abnormality. Conclusions: The morphological characteristics of ASA and associated cardiac abnormalities do not distinguish patients at risk for cerebrovascular events. Although the presence of ASA may be a risk factor for embolic strokes, this risk is lower than previously thought .