Phase II trial of piroxantrone in patients with recurrent and metastatic squamous cell carcinoma of the head and neck

Summary Twenty-two patients with recurrent or metastatic squamous cell carcinoma of the head and neck were treated with piroxantrone 150 mg/m² intravenously every 21 days. There were no objective responses. The 95% upper confidence bound for response is 15%. Primary toxicity was hematologic.     

Response to foot-and-mouth disease vaccines in newborn calves. Influence of age, colostral antibodies and adjuvants

Oil-emulsified (OE) and aqueous (Aq) vaccines were prepared with the same batch of inactivated A24 8345 foot and mouth disease virus (FMDV). Calves born to vaccinated dams did not respond to the Aq vaccine 30 or 90 days post partum. When the OE vaccine was used on a similar group of calves, no responses were elicited up to 21 days post partum. However, calves 30 or more days old responded like adult cattle to the OE vaccine. When the OE vaccine was used in colostral antibody-free calves 3-30 days old, all animals showed good antibody responses but, in calves vaccinated 3 or 7 days post partum, antibodies were detectable only after a considerable period of time. Our results show that both passively acquired colostral antibodies and age are important in the response of very young calves to FMDV oil vaccines. From a practical point of view, in endemic areas where adult cattle are periodically vaccinated, vaccination of calves between 30 and 60 days post partum with OE vaccines would lead to high levels of herd protection.     

Relation between energy expenditure and body composition in man: specific energy expenditure in vivo of fat and fat-free tissue

The relationship between energy expenditure and body composition, in terms of fat and fat-free masses, has previously been described by a variety of predictive regression equations with parameters devoid of physiological content. We present here results obtained by calculating the specific energy expenditure, ie, the energy expenditure per unit of mass, of fat and fat-free tissue on the basis of measurements of the total energy expenditure (EE), the masses of fat (FM), and fat-free (FFM) tissue using the following simple model: EE = k1.FM + k2.FFM where k1 and k2 are the specific energy expenditures of fat and fat-free tissue, respectively. The results of observations on 104 women at rest yielded values for k1 and k2 of 0.31 and 1.35 watts/kg of fat and fat-free mass, respectively, with standard errors of estimate of 0.074 and 0.052 watts/kg, respectively. Analysis of several series of measurements, from other sources and on smaller samples of subjects, yielded similar values at rest but with larger standard errors of estimate. Data from subjects performing varying amounts of work in 24-h measurements showed, as expected, larger values for both tissues. The results explain to a very large extent the well-established relation between resting metabolic rate and body weight, ie, a linear relation with a non-zero intercept. The results also offer a clear-cut explanation for the well known difference in energy expenditure between men and women with the same body weight.     

The origin and nature of stromal osteoclast-like multinucleated giant cells in breast carcinoma: implications for tumour osteolysis and macrophage biology

The origin and nature of osteoclast-like multinucleated giant cells (OMGCs), in extraskeletal neoplasms, is uncertain. The ultrastructure, antigenic phenotype and function of OMGCsm in a breast carcinoma were studied in order to clarify the relationship between OMGCs, osteoclasts and other cells of the mononuclear phagocyte system (MPS). OMGCs resorbed cortical bone in a manner similar to osteoclasts. However, unlike osteoclasts, OMGCs did not possess a ruffled border or clear zone, and expressed HLA-DR and Fc receptors and CD14, CD16, CD18 and CD11 (p150,95) antigens. In addition, OMGCs failed to respond morphologically to calcitonin and were directly stimulated by parathyroid hormone (PTH) to increase bone resorption. These findings suggest that OMGCs are a specific type of macrophage polykaryon distinct from both osteoclasts and other types of inflammatory polykaryon. Occasional smaller (20-25 microns) macrophage-like cells were also associated with resorption pits. Bone resorption by OMGCs isolated from the breast indicates that a cell of the MPS can be transplanted to a new tissue location and perform a highly specialised function appropriate to an MPS cell of that tissue (i.e. the osteoclast). PTH stimulation of bone resorption by OMGCs suggests that PTH or a PTH-like protein, may be involved in the bone resorption and consequent hypercalcaemia associated with metastatic breast cancer.     

Percutaneous Endovascular Treatment for Stenoses and Occlusions of Infrarenal Aorta and Aortoiliac Bifurcation: Midterm Results

OBJECTIVE: evaluation and comparison of the endovascular treatment of isolated aortic and aortoiliac atherosclerotic lesions (stenoses and occlusions). METHODS: a percutaneous endovascular procedure was performed in 52 patients (38 men and 14 women) with a mean age of 52 years (range, 25-85 years). The baseline angiogram showed 35 aortic lesions (31 stenoses, 4 occlusions) and 17 aortoiliac lesions (14 stenoses, 3 occlusions). Percutaneous techniques used in this series included variable combinations of transluminal angioplasty and stenting. All stents placements were performed over-the-wire using the transfemoral route (most often bilateral approach). Clinical examination and Duplex-scan were performed at discharge, 1 month, 6 months, 12 months, and then yearly. RESULTS: technical success was 100% for aortic and aortoiliac lesions. Angiographic success rates were comparable for aortic (91%) and aortoiliac (94%) lesions. No death occurred during or early after the endovascular intervention. Duplex-scan confirmed 100% patency rate at discharge. There was no significant difference between the aortic (94%) and aortoiliac (96%) groups regarding immediate clinical improvement. Mean follow-up was 34+/-31 months (range, 0-130 months). The cumulative primary patency rate at 36 months was 85% in the aortic group and 86% in the aortoiliac group. Clinical success, defined as a symptom-free status at the end of follow-up, was also similar in both groups. CONCLUSION: endovascular treatment of isolated aortic lesions of the infra-renal aorta has favorable outcomes comparable to those of aortoiliac lesions.     

Beeinflussung humaner Osteoblasten durch verschiedene Analgetika

In der Behandlung von Frakturen spielt die Analgesie eine wesentliche Rolle. Es stellt sich daher die Frage, ob in der Klinik h?ufig eingesetzte Analgetika wie Tramadol oder Diclofenac negative Wirkungen auf die Knochenbruchheilung haben.     

Stereoselectivity of actions of the calcium sensitizer [+]-EMD 60263 and its enantiomer [-]-EMD 60264

The thiadiazinone derivative [+]-EMD 60263 ((+)-5-(1-(α-ethylimino-3,4-dimethoxybenzyl)-1,2,3,4- tetrahydroquinoline-6-yl)-6-methyl-3,6-dihydro-2H-1,3,4 -thiadiazine-2-on) is a Ca²⁺-sensitizing agent with only minor phosphodiesterase inhibitory activity. Our aim was to characterize the inotropic and electrophysiological effects of [+]-EMD 60263 and its enantiomer [-]-EMD 60264 in several cardiac muscle preparations. The Ca²⁺-sensitizing activity resided in the [+]-enantiomer only. [+]-EMD 60263 (3 μM) shifted the EC₅₀ of Ca²⁺ for contractile activation of skinned fibers of pig heart from 2.41 μM to 0.73 μM, whereas [-]-EMD 60264 (30 μM) was ineffective. In Langendorff-perfused guinea pig hearts, [+]-EMD 60263 and [-]-EMD 60264 induced concentration-dependent positive and negative inotropic effects, respectively; both enantiomers reduced spontaneous heart rate but did not influence perfusion pressure. The maximum increase in force of human atrial trabeculae was 35 % of pre-drug control with [+]-EMD 60263 in comparison to 113 % with forskolin. In guinea-pig papillary muscles, [+]-EMD 60263 and [-]-EMD 60264 had opposite inotropic responses, however, both agents similarly prolonged action potential duration. Both enantiomers concentration-dependently blocked the rapidly activating component I_Kr of the delayed rectifier in guinea-pig myocytes. The block saturated at potentials positive to +30 mV, closely resembling the effects of the antiarrhythmic agent E-4031 which had been originally used to define I_Kr. It is concluded, that the positive inotropic action of [+]-EMD 60263 can be explained by prevalence of the Ca²⁺-sensitizing effect. The accompanying prolongation in action potential duration is caused by block of the I_Kr component of the delayed rectifier. While the inotropic effects are stereoselective, most of the electrophysiological actions are clearly independent of sterical configuration. The combination of Ca²⁺-sensitizing with class-III antiarrhythmic action may provide an interesting pharmacological profile of potential therapeutic use. Received: 7 January 1997 / Accepted: 25 February 1997     

Is colonic electrical activity a similar phenomena to small-bowel electrical activity?

PURPOSE: This study was designed to investigate colonic spike bursts regarding 1) their migration behavior, 2) their pressure correlates, and 3) comparing colonic short spike bursts with spike bursts from migrating myoelectric complex from the small bowel. METHODS: Rectosigmoid electromyography and manometry were recorded simultaneously in seven normal volunteers and electromyography alone in five others during two hours of fasting and for two hours after one 2,100-kJ meal. One patient with an ileostomy was also studied by the same method to record the migrating myoelectric complex from the terminal ileum during fasting. RESULTS: Three kinds of spike bursts were observed in the pelvic colon: rhythmic short spike bursts, migrating long spike bursts, and nonmigrating long spike bursts. The meal significantly increased the number of migrating and nonmigrating long spike bursts (from 25 to 38.7 percent of the recording time; P <0.01). These bursts of potentials showed a peak 15 minutes after the meal, which may be caused by the gastrocolic reflex. Migrating long spike bursts started anywhere along the rectosigmoid and migrated from there aborad 82 percent of the time and orad or in both directions in 10 or 7 percent of the time, respectively. They originated pressure waves 99 percent of the time. Short spike bursts were more frequent before the meal (15.1 percent before and 9.6 percent after the meal), but the difference was not significant; they neither propagated nor initiated pressure waves detected by the miniballoon. CONCLUSIONS: Migrating long spike bursts were the only potentials that migrated, sometimes for short distances. Short spike bursts are a different phenomenon from the small-bowel migrating myoelectric complex because they do not migrate; they can occur during the postprandial period and never originated intraluminal pressure waves.Supported by a grant from the Instituto Nacional de Investigação Científica, Proc. DBI-22086.Presented at the meeting of the Portuguese Congress of Gastrenterology, Vila Moura, Portugal, June 2 to 5, 1993.