The prognostic value of quantitative angiogenesis in breast cancer and role of adhesion molecule expression in tumor endothelium

Summary Angiogenesis is the formation of new capillaries from the existing vascular network and is essential for tumor growth and metastases. Increased microvessel density in breast cancer is associated with lymph node metastasis and reduced survival. We have assessed tumor vascularity in 211 breast carcinomas using a more rapid technique based on a Chalkley point eyepiece graticule. We confirmed using this method a significant reduction in overall survival between patients stratified by Chalkley count in both a univariate (p=0.02) and multivariate (p=0.05) analysis.Since studies have suggested that cell adhesion molecules (CAMs) might be important in the angiogenic process, and interaction of neoplastic cells with this neovasculature is a significant step in tumor metastasis, we have also examined the expression of CAMs in a subset of these tumors (n=64). Using immunohistochemistry we observed widespread and intense staining on the endothelium of tumor-associated vessels for PECAM (100%), ICAM 1 (69%), and E- and P-selectins (52% and 59% of cases respectively). Endothelial expression of the selectins was more prominent at the tumor periphery. Immunoreactivity of ICAM-1 (34%), PECAM (1.6%), and E- and P-selectins (7% and 37% of cases respectively) was also observed on the neoplastic element of the tumors.     

Transfer of telemedical support to Cornwall from a national telemedicine network during a solar eclipse

During late 1998 and early 1999, planning officers in Cornwall predicted a huge increase in summer visitors to the county to observe the August solar eclipse. There was the possibility that a mass gathering in Cornwall could overload existing arrangements for handling accident and emergency patients. We therefore set up a telemedicine system to support the county's minor injury units (MIUs) from hospitals throughout the UK. Six main hospital accident and emergency departments outside Cornwall with existing links to their own MIUs were twinned with 10 of the 11 MIUs in Cornwall before the expected date of the gathering. The network was live for nine days, starting four days before the eclipse, and 2045 patients were seen in the 10 MIUs. There were 93 telemedicine calls from the 10 MIUs, involving 91 patients. Overall, 4.6% of the patients required a telemedicine consultation. Fifty-seven calls were made during working hours. Thirty-four patients were referred for further management, of whom 18 were referred on the same day. The transfer of telemedical support to a national network was successful.     

The origin of the initial heat associated with a single impulse in mammalian non-myelinated nerve fibres

1. A study has been made of the temperature changes associated with the passage of a single impulse in rabbit desheated vagus nerves.2. The initial changes consist of an evolution of positive heat followed by a reabsorption of most of it; i.e. there is a phase of positive and a phase of negative heat production.3. The size of the positive heat, its time of onset, and the time of onset of the negative heat have been measured by an analogue method of analysis. In addition, these parameters, together with the size of the negative heat and the duration of both phases of initial heat, have been studied with the aid of a computer, and also by conventional heat block analysis.4. At about 5 degrees C the measured positive heat is 7.2 mucal/g. impulse. It starts as soon as the compound action potential reaches the thermopile and lasts for about 107 msec.5. This positive heat decreases with increasing temperature, the ratio of heat at 4 degrees C to that at 14 degrees C being 1.86.6. The measured negative heat at about 5 degrees C is 4.9 mucal/g. impulse. It starts 102 msec after the onset of positive heat, and lasts for about 240 msec.7. When the sodium of Locke solution is replaced by lithium the positive heat is reduced by 19%, but the negative heat is increased by 22%.8. In potassium-free solutions the positive heat is hardly affected (increase of 5%), but the negative heat is more than doubled. As a result the nerve may become briefly colder than its initial temperature by about 2 mu degrees C.9. The effect of sodium-deficient solutions on the positive heat is somewhat variable, but the negative heat is consistently diminished.10. Replacement of the chloride of Locke solution by sulphate or nitrate has little effect on the positive heat. The negative heat is reduced in size by 26% and in duration by 22%.11. Replacement of most of the sodium of Locke solution by barium reduces or abolishes the negative heat, and increases the measured size of the positive heat nearly threefold.12. Veratrine (10(-5) g/ml.) produces a nearly tenfold increase in the net positive heat.13. Ouabain (1 mM) and antimycin A (1 mug/ml.) applied for 30-60 min have little effect on the initial heat production.14. Over the temperature range 5-15 degrees C, and for the ionic solution changes described above, there is close agreement in timing between the positive heat and the rising phase of the action potential, and between the negative heat and the falling phase.15. Because of the inevitable temporal dispersion of the action potential over the face of the thermopile, the observed temperature changes are smaller than those which occur at a single point in the nerve close to a stimulating electrode. The corrected value of the positive heat at 5 degrees C is 24.5 mucal/g. impulse, while that of the negative heat is 22.2 mucal/g. impulse.16. The heats of mixing of the ions in solution that interchange during the action potential are much too small to account for the observed initial heats, but an exchange of ions associated with fixed charges might make a significant contribution to the heats.17. The condenser theory, according to which the positive heat represents the dissipation of electrical energy stored in the membrane capacity, while the negative heat results from the recharging of the capacity, appears unable to account for more than half of the observed temperature changes.18. It seems probable that the greater part of the initial heat results from changes in the entropy of the nerve membrane when it is depolarized and repolarized.     

Simultaneous detection and quantitation of drugs commonly involved in self-administered overdoses.

The system described here is designed for ease of detection and quantitation of tricyclic antidepressants, benzodiazepines, and other tranquilizers now commonly found in self poisoning. An ether extract of serum is purified by acid transfer, back-extracted into ether, dried, and evaporated. The residue is run on a thin-layer plate against standards and inspected under 254-nm light. Depending on requirements, the amount of unknown may then be estimated or further chromatography performed in a different solvent. Quantitation and further confirmation of identity by staining follow. The equipment needed is very simple and many samples can be handled simultaneously and completed within a working day.     

Haemostatic factors in human peripheral afferent lymph

Peripheral afferent lymph was obtained by cannulation of a collecting vessel in 17 healthy men (mean age 26 years). Lymph/plasma ratios of all vitamin K-dependent factors were lower than expected from molecular weight. Factor VII, factor IX and tissue factor pathway inhibitor (TFPI) lymph/plasma activity ratios were higher than antigen ratios. Activated factor VII (FVIIa) and TFPI-Xa complex concentrations were higher in lymph than plasma, and the raised FVIIa did not appear to be due to cannulation. The fibrinogen lymph/plasma activity (Clauss) ratio averaged about 20% of the antigen ratio. The result of an ELISA for D-dimer was higher in lymph than plasma, often more than five-fold. This high level in lymph was not explored but may indicate proteolysis of fibrinogen and fibrin with release of D-like and D-dimer-like fragments in interstitial fluid.     

T3 blood levels and treatment outcome in depression

OBJECTIVE: We examined the correlation between the basal triiodothyronine resin uptake (T3-RU) levels in depressed subjects and the response to anti-depressant treatment. METHOD: We treated with fluoxetine 235 outpatients meeting DSM-IV criteria for major depression. We measured T3 resin uptake (T3-RU) levels before the onset of treatment. The 17-item Hamilton Rating Scale for Depression (Ham-D-17) was administered before, during and after the eight weeks of treatment to assess changes in depressive symptoms. RESULTS: 16 patients (6.8 percent) had low T3-RU levels (range 16.5-21), and 7 patients (3.0 percent) had high T3-RU levels (range 36-38). No relationship was found between T3-RU levels and clinical improvement, defined as either total Ham-D-17 score change or Ham-D-17 score < or = 7 in the last 3 weeks of treatment, even after adjusting for baseline severity of depression. CONCLUSION: Abnormal T3-RU levels are rather uncommon in outpatient depression and do not correlate with the response to antidepressant treatment or lack thereof.     

Family perceptions of medication administration at school: errors, risk factors, and consequences

Medications are administered every day in schools across the country. Researchers and clinicians have studied school nurses' and educators' experiences with medication administration, but not the experiences of children or their parents. This study examined medication administration from the child and parent perspectives to (a) determine problems children experience with medicines at school, (b) clarify risk factors for medication errors, and (c) examine the perceived impact of medication errors on school performance and social relationships. Participants included children ages 8 to 18 years (n=157) being treated at a large Midwestern Children's Hospital in diabetes, asthma, and Attention Deficit Hyperactivity Disorder (ADHD) clinics. Findings suggest that forgetting a dose and running out of medication were the most common problems. Missing a dose was more frequent in students with ADHD than in students with diabetes or asthma. Medication nonadherence at school, which includes medication administration errors such as missing a dose, may potentially lead to a variety of educational, social/emotional, and physical consequences. These results indicate that the impact of missing medication on children with ADHD appeared to have a greater effect on schoolwork and friendships, while the physical consequences appeared to vary widely based on health condition. Interestingly, children with more self-responsibility for medications were less likely to report medication errors. School nurses will want to include students when planning for medication management at school.