Combined electric field and ultrasound therapy as a novel anti-tumour treatment.

The permeabilising effects of electric pulses on cell membranes and the use of ultrasound energy of various intensities, for both thermal effects and enhancement of drug and gene delivery, have led to extensive research into the potential applications of these systems in the development of novel anti-cancer treatments. In the present study we have demonstrated for the first time that the application of brief electric pulses 'sensitises' tumour cells to the effects of low intensity ultrasound. The studies were conducted in human tumours established in athymic nude mice and in many instances resulted in the reduction of tumour mass. The combined electric field and ultrasound approach (CEFUS) was applied in vivo to a murine colon adenocarcinoma (C26) and a human oesophageal adenocarcinoma (OE19). The experiments performed demonstrated the anti-tumour effects of the combined therapy. Varying the electrosensitisation parameters used (voltage, waveform, electrode type) contributed to optimise the procedure. Exponential electric pulses with a peak of 1000 V/cm were initially used, but square wave pulses (1000 V/cm, 1 ms, x2, 1 Hz) were found to be just as effective. All ultrasound application parameters were kept constant during the study. The growth rate of C26 tumours treated with CEFUS was significantly reduced with respect to untreated controls at day 7 (96% of average initial tumour volume in CEFUS group versus 615% for controls, P < 0.05). Similar reduction was observed in OE19 tumours treated with CEFUS by day 4 (82% versus 232%, P < 0.032). Our preliminary data suggest that this novel technology could potentially be of wide application in clinical practice for the treatment of solid tumours and is worth further investigation.

Donor-related secondary haemorrhage complicating renal transplantation.

We report two cases of secondary haemorrhage in renal transplant recipients that would appear to relate to their common donor. Our experience confirms the inadequacy of arterial repair in this setting. One patient, a middle aged diabetic male, required excision of his external iliac artery, but recovered without reconstructive surgery. In the second case nephrectomy was performed on day 8 because of accelerated rejection. This was followed by recurrent sepsis due to E. coli, which was implicated in the previous case. Haemorrhage from the donor aortic wall patch occurred 3 weeks later. We now recommend that if secondary haemorrhage occurs, recipients of other organs from the donor should be carefully monitored for evidence of infection. If this is found and a similar organism cultured, consideration to transplant nephrectomy should be made with removal of all donor tissue to avoid the risk of subsequent secondary haemorrhage.

Nematode burdens and productivity of grazing cattle treated with a prototype sustained-release bolus containing ivermectin.

One hundred and twenty four-month-old Hereford-Friesian cross heifers weighing from 88 to 130 kg were divided into two equal groups. One group acted as a control with each animal receiving one placebo bolus, the other animals received one prototype intraruminal sustained-release bolus designed to deliver approximately 8 mg ivermectin/day for 100 to 120 days. The boluses were administered the day before turnout in mid-May. Each group was grazed separately for 167 days on pastures contaminated with parasitic nematode larvae including the lungworm Dictyocaulus viviparus, and the gastrointestinal worms Ostertagia ostertagi, Cooperia oncophora and Nematodirus helvetianus. Parasitic disease did not occur in the ivermectin-bolus group, but the control group required anthelmintic treatment to control parasitic gastroenteritis at 111 and 154 days after turnout. Up to the 111th day after turnout, the peak mean nematode egg and larval counts per gram of faeces in controls was, respectively, 564 epg and 0.5 lpg. Based on faecal nematode egg counts and worm burdens in bolus-treated cattle removed from pasture at 119 days after turnout and bolus function studies, it was concluded that ivermectin delivery from the prototype bolus ceased between 95 and 98 days after administration. However, unlike the controls, the treated cattle did not develop parasitic gastroenteritis at any time. Their faecal nematode egg output was significantly (P < 0.01) lower (< 1 epg) compared to the controls and lungworm larval output zero during the functional life of the bolus. The faecal egg and larval outputs continued low until the end of the trial.(ABSTRACT TRUNCATED AT 250 WORDS)

Trypanosoma congolense: erythrocyte indices, plasma iron turnover and effects of treatment in infected cattle.

Early during the course of Trypanosoma congolense infection in cattle decreases in PCV occurred and coincided with increases in both MCV and MCH. The indices reached highest levels between eight and 12 weeks post-infection. By week 20 of infection MCV and MCH had decreased to pre-infection levels even though a substantial anemia persisted. Serum iron levels were elevated at eight weeks postinfection. (Infected 271 mg dl-1 v. control 140 mg dl-1) but decreased to low levels in infected animals by Week 28 (63 mg dl-1). At eight weeks post-infection PITR was elevated in infected animals (infected 2.6 mg dl-1 day-1 v. control 0.82 mg dl-1 day-1). By Week 28, however, PITR had fallen in infected animals to 0.62 mg dl-1 day-1 indicating a severe dyshaemopoesis since PCV levels averaged only 22%. Cattle which were treated with Berenil or that self-cured the infection had normal iron parameters when tested 61 weeks post-infection. Cattle treated early during the course of infection showed a significantly greater PCV response that those treated later during infection.

Efficacy of topically administered ivermectin against chorioptic and sarcoptic mange of cattle.

The efficacy of topically administered ivermectin against Chorioptes bovis and Sarcoptes scabiei var bovis on cattle was evaluated in five studies involving a total of 68 cattle. Treatment with ivermectin solution at a dose rate of 500 micrograms/kg bodyweight topically once was fully effective against C bovis and S scabiei when applied to healthy skin. Efficacy against S scabiei was impaired when the formulation was applied over areas of severe lesions caused by this parasite, presumably due to reduced absorption of ivermectin.

Treatment of inhibited Dictyocaulus viviparus in cattle with ivermectin.

Fifteen calves, each infected with approximately 3000 third stage larvae, were used to compare the tendencies of two strains of Dictyocaulus viviparus to inhibit at the fifth larval stage and to evaluate the efficacy of ivermectin. There were notable differences between the strains. While greater than 99% of worms developing from infection with an Alpine strain remained inhibited 42 days after infection, only 0-26% of those recovered following infection with a U.K. laboratory strain were arrested. Neither adult nor immature D. viviparus were present in the lungs of animals treated with ivermectin subcutaneously at 200 micrograms/kg body weight 28 days after infection with the Alpine larvae.

Proton nuclear magnetic resonance studies of soybean lectin-monosaccharide interactions: computer analysis of complex binding behavior.

1H NMR was used to quantify soybean lectin binding to monosaccharides, using presaturation of HOD plus a spin-echo sequence to observe sugar -NHCOCH3 and -OCH3 to below 0.01 mM. Binding is in the very-slow-exchange limit; there is no broadening or shifting and only unbound sugar is observed for pH 5 to 8 and 25 to 75 degrees C. Preliminary results were consistent with those previously reported for methyl 2-acetamido-2-deoxy-alpha-D-galactopyranoside (Me alpha-D-GalNAcp) (K = 3 X 10(4) liters mol-1 with four sites per tetramer). More detailed studies, however, gave concave Scatchard plots for methyl 2-acetamido-2-deoxy-alpha- and beta-D-galactopyranoside, (Me alpha- and Me beta-D-GalNAcp), best fitted using K1 values of (6-12) X 10(4) liters mol-1, K2 values less than or equal to 0.5 X 10(4) liters mol-1, and four sites of each type in D2O or 80% H2O at 25 degrees C and pH 7.2. Data for methyl alpha-D-galactopyranoside were fitted with K = 0.5 X 10(4) liters mol-1 and eight sites of the same K. Monosaccharides may be binding in the recently reported "hydrophobic sites" of soybean lectin. Both methyl 2-acetamido-2-deoxy-beta-D-galactofuranoside (Me beta-D-GalNAcf) and methyl 2-acetamido-2-deoxy-alpha-D-glucopyranoside (Me alpha-D-GlcNAcP) showed some binding by 1H NMR; K's were similar to those for the high-affinity sugars, but the occupancy was much lower. The soybean lectin in this study was saturated in Ca2+ (greater than or equal to 4 mol/tetramer), but low in Mn2+, with Mn2+ plus Mg2+ less than 4. We report new melting points for D-N-acetylgalactosamine, Me alpha-D-GlcNAcp, Me beta-D-GalNAcp, and Me beta-D-GalNAcf, and a fully listed program for fitting curved Scatchard plots using Apple IIc and IIe computers.

Efficacy of ivermectin against somatic Strongyloides ransomi larvae.

The efficacy of ivermectin against the somatic larval stages of Strongyloides ransomi was evaluated in three trials involving 35 pregnant gilts harbouring induced infections. Treatment at a rate of 300 micrograms/kg bodyweight subcutaneously, four to 16 days before farrowing, was highly effective as judged by counts of larvae in milk and worm burdens of piglets.

Efficacy of ivermectin against Dictyocaulus arnfieldi in ponies.

The efficacy of orally administered ivermectin against induced Dictyocaulus arnfieldi infection was evaluated in a controlled study comprising 12 yearling ponies. Treatment with ivermectin paste, at a dose rate of 200 micrograms/kg bodyweight orally once, was 100 per cent effective against both adult and immature or inhibited stages of the horse lungworm. Similar control of second and third instars of Gastrophilus intestinalis was observed and no nematode eggs were present in faeces from seven to 15 days after treatment when the study was terminated.

The pathogenesis of experimentally induced Trypanosoma brucei infection in the dog. I. Tissue and organ damage.

Inoculation of dogs with Trypanosoma brucei produced an acute fetal disease similar to that seen following natural infection. The disease was characterised by high levels of parasitaemia, moderately severe anemia, and marked changes in the lymphoid system. Extravascular invasion by large numbers of trypanosomes was widespread throughout the body and was accompanied by severe tissue damage. Tissue invasion by trypanosomes was associated with marked cellular infiltration involving lymphoid cells and plasma cells followed by macrophages and polymorphonuclear leukocytes. Associated with these reactions, severe cellular degeneration and focal necrosis occurred. While these changes were widespread and were found in the majority of tissues examined, consistently severe lesions were found in the heart, eyes and central nervous system. In many organs, lymphatic vessels were distended with fluid, trypanosomes, and a cell population similar to that in the surrounding tissue; fibrin deposition and thrombus formation was sometimes observed within the lymphatic lumens. Thrombosis was also found in the blood vessels of the pampiniform plexus, the venous plexus of the ovary, and branches of the renal vein. A severe necrotizing vasculitis affecting only the coronary vessels was a prominent feature in some animals.

The pathogenesis of experimentally induced Trypanosoma brucei infection in the dog. II. Change in the lymphoid organs.

Marked changes were found in the spleen and lymph nodes of dogs experimentally infected with Trypanosoma brucei. These changes were considered to occur in two phases. First, in animals examined on Days 8 and 16 after inoculation, there was an intense proliferative response; this involved particularly the B-dependent follicular areas and was accompanied by a dramatic increase in the number of plasma cells in the splenic red pulp and medullary cords of the lymph nodes. Although numerous large proliferating lymphoblasts were found in the periarteriolar regions of the spleen and in the peripheral part of the paracortical areas of the lymph nodes, the presence of cells containing Ig in these regions made it difficult to evaluate the degree of involvement of thymus-derived cells. The plasma cell response involved both IgM and IgG, although the increase in IgM-containing cells was most striking. During this initial phase there was focal hemorrhage, deposition of fibrin, necrosis, and infiltration of polymorphonuclear leukocytes in the spleen, these changes being most severe in the peripheral follicular areas. Following the initial proliferative phase and prior to the death of the host during the fourth week of the infection, the spleen and lymph nodes became less reactive, and there was marked disorganization and disruption of their architecture. Compared with characteristics earlier in the infection there was greatly decreased proliferative activity and a reduction in size of the splenic white pulp and lymph node cortices. Germinal centers were reduced in number, size, and activity, had a disorganized appearance, and, by immunofluorescence, showed a reduction of immunoglobulin on the dendritic reticular cells. The lymph node sinuses exhibited a decrease in content of lymphocytes and contained massive numbers of macrophages, including numerous multinucleated giant cells. There was also severe disruption of the reticulum cell network of the sinuses; and accumulations of polymorphonuclear leukocytes, along with extensive deposition of fibrin, were commonly found in the subcapsular sinuses. During this period, foci of erythropoietic cells were present throughout the red pulp of the spleen.