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Biomedical subjects

E Dvir

Publications and source records attributed to E Dvir.

At least 19 recordsLinked to original sources

A novel phospholipid derivative of indomethacin, DP-155 [mixture of 1-steroyl and 1-palmitoyl-2-{6-[1-(p-chlorobenzoyl)-5-methoxy-2-methyl-3-indolyl acetamido]hexanoyl}-sn-glycero-3-phosophatidyl [corrected] choline], shows superior safety and similar efficacy in reducing brain amyloid beta in an Alzheimer's disease model.

Indomethacin has been suggested for the treatment of Alzheimer's disease (AD), but its use is limited by gastrointestinal and renal toxicity. To overcome this limitation, D-Pharm Ltd. (Rehovot, Israel) developed DP-155 (mixture of 1-steroyl and 1-palmitoyl-2-{6-[1-(p-chlorobenzoyl)-5-methoxy-2-methyl-3-indolyl acetamido] hexanoyl}-Sn-glycero-3-phosophatidyl [corrected] choline), a lecithin derivative of indomethacin. Safety was tested by daily oral administration of DP-155 or indomethacin to rats in a dose range of 0.007 to 0.28 mmol/kg. The prevalence of gastrointestinal ulceration was significantly lower (10-fold) for DP-155 than for indomethacin, and the ulcerations were delayed. Signs of renal toxicity, namely reduced urine output and increased urine N-acetyl glycosaminidase to creatinine ratio, were 5-fold lower for DP-155. Indomethacin, but not an equimolar dose of DP-155, reduced urine bicyclo-prostaglandin E(2). An equimolar oral dose of DP-155 or indomethacin, administered every 4 h for 3 days, was equally efficacious in reducing the levels of Abeta42 in the brains of Tg2576 mice. Indomethacin was the principal metabolite of DP-155 in the serum. After DP-155 oral administration, indomethacin's half-life in the serum and the brain was 22 and 93 h, respectively, compared with 10 and 24 h following indomethacin oral administration. The brain to serum ratio was 3.5 times higher for DP-155 than indomethacin. This finding explains the efficacy of DP-155 in reducing Abeta42 brain levels, despite the low systemic blood concentrations of indomethacin derived from DP-155. In conclusion, compared with indomethacin, DP-155 has significantly lower toxicity in the gut and kidney while maintaining similar efficacy to indomethacin in lowering Abeta42 in the brains of Tg2576 mice. This superior safety profile highlights DP-155's potential as an improved indomethacin-based therapy for AD.

Alzheimer Disease↗

Congenital narrowing of the intrapharyngeal opening in a dog with concurrent oesophageal hiatal hernia.

A one-year-old, male, smooth-haired standard dachshund was presented with a history of chronic hypersalivation, dysphagia, puffing of the cheeks on expiration, and inspiratory stridor. Oral examination revealed a moderately thickened tongue radix and that the normal intrapharyngeal opening was obliterated. A 7 mm long, midline palatal slit was the only communication between the naso- and oropharynx. The soft palate was fused to the caudal pharyngeal wall. A concurrent hiatal hernia was diagnosed on thoracic radiographs. The soft palate abnormality was surgically corrected and the hiatal hernia was managed medically. On follow-up evaluations, the clinical signs had markedly improved, and the hiatal hernia was no longer visible on survey thoracic radiographs.

Animals↗

Effect of electrocardiographic filters on the R-amplitude of canine electrocardiograms.

Lead II electrocardiograms (ECGs) were recorded in 88 dogs ranging in weight from 3 to 50 kg. A commercial direct-writing electrocardiograph was used to record the ECGs, first with manual HUM filter (notch filter at 50/60 Hz) and EMG filter (cut-off frequency of -3 dB at 35 Hz) on, immediately followed by a recording with both filters off. The mean (sd) reduction in R-amplitude with the filters on was 53(18) per cent with a range from 22 to 100 per cent and a median value of 51 per cent. The R-amplitude with the filters off was related to the R-amplitude with the filters on, making it possible to correct for the effect of the filters. The reduction in R-amplitude was inversely correlated with the weight of the dog and with the duration of the QRS-complex. Other known changes induced by filters, such as the elimination of notches and the slurring of the junction between the QRS-complex and the ST-interval were also observed. The inverse relationship between the weight of the dog and the magnitude of the reduction in R-amplitude by the filters indicates that ECG machines with different characteristics should ideally be used to record ECGs in dogs of different sizes.

Animals↗

Chronic idiopathic intestinal pseudo-obstruction in an English bulldog.

A case of chronic idiopathic intestinal pseudo-obstruction in an English bulldog is described. The dog was presented with chronic weight loss and vomiting. An intestinal obstruction was suspected based on clinical and radiological findings. A diagnosis of chronic idiopathic intestinal pseudo-obstruction was made on the basis of full thickness intestinal biopsies. The dog was refractory to any antiemetic therapy. Necropsy revealed marked atrophy and fibrosis of the tunica muscularis, together with a mononuclear cell infiltrate extending from the duodenum to the colon. This case was presented with clinical findings consistent with visceral myopathy in humans--namely, atony and dilatation of the whole gut--but the histological findings resembled sclerosis limited to the gastrointestinal tract.

Animals↗

A histological and carbon perfusion study of cephalic and saphenous venous flaps in the dog.

A histological and carbon-infusion study of cephalic and saphenous venous flaps in the dog shows that cephalic flaps survive significantly better than saphenous flaps, their mean viability at 5-14 days being 50-60% compared to 23.8% for saphenous flaps. Venous drainage is essential for flap survival but perfusion of the cephalic vein with arterial blood does not alter flap viability. The findings indicate that cephalic flaps survive better because they are thinner and contain a more extensive venous plexus. A cephalic flap is a suitable model for in vivo study of the circulation within a venous flap.

Animals↗

Biochemical analysis of the venous flap in the dog.

There has been great interest stimulated by reports on factors influencing the survival of skin flaps which possess only venous inflow and outflow, i.e., venous flaps. The present study serially (Days 1, 2, and 4 postoperatively) observed several biochemical factors which might affect flap survival. ATP levels were measured to assess endogenous energy stores, malonyldialdehyde (MDA) and xanthine oxidase (XO) to estimate free radical production, superoxide dismutase (SOD) to quantify antioxidant defenses, and edema to measure inflammatory changes. Eighteen thighs on nine dogs were assigned randomly to one of three groups: full-thickness skin grafts, flaps based solely on the saphenous artery and vein (AV flaps), or flaps based solely on the saphenous vein (venous flaps). These were regarded as being mostly ischemic, totally perfused, and partially ischemic, respectively. Control skin biopsies were obtained adjacent to surgical sites. AV flaps and control skin were similar in all respects. Venous flaps compared with skin grafts were significantly less edematous (P less than 0.01) had less MDA and XO (P less than 0.05), but no significant differences in SOD and ATP levels. However venous flaps had significantly less ATP than AV flaps (P less than 0.01). Thus venous flaps survive despite depletion of ATP levels. These results suggest that decreased free radical production and lessened edema may be important factors in promoting ultimate survival of venous flaps.

Adenosine Triphosphate↗

Microsurgical transfer of the greater omentum in the treatment of canine obstructive lymphoedema.

In 13 dogs, experimental obstructive lymphoedema of the lower limb was created by combined radiotherapy and radical groin dissection. Six months later, when the degree of lymphoedema was stable, the lymphatic obstruction was bridged by microvascular insertion of a free omental graft. Six months after grafting, circumferential measurements indicated a statistically significant 38% reduction in the magnitude of lymphoedema. Biopsies showed the omental grafts were alive but contained much fibrous tissue. Lymphatic vessels were identified in 10 of 11 biopsies but connections between these lymphatics and lymphatics proximal to the graft could not be demonstrated by either lymphangiography or dye-injection techniques. The findings indicate that experimental obstructive lymphoedema in the dog can be reduced significantly by insertion of a vascularised omental graft. However, it could not be established that improvement was due to union of graft lymphatics with those of the lymphoedematous limb, although this union may have consisted of lymphatics too small to be demonstrated.

Animals↗

Prefabrication of thin transferable axial-pattern skin flaps: an experimental study in rabbits.

The arteriovenous pedicle of all known axial-pattern skin flaps enters from the deep aspect and consequently the flap must contain fat and/or muscle and be of considerable thickness. In an attempt to fabricate a thinner axial-pattern flap the femoral artery and vein of rabbits were implanted, in various vascular configurations, directly into the subdermal layer of the skin. Implantation was found to provoke an extensive outgrowth of new vessels from the implanted artery and vein, and the progress and pattern of this neovascularisation was studied by carbon gelatine perfusion and histology. Neovascularisation begins within a few days of implantation and progresses rapidly. By 8 to 12 weeks it is possible to elevate regularly a viable, large skin flap based on the implanted pedicle.

Animals↗

Long-term results after microlymphaticovenous anastomoses for the treatment of obstructive lymphedema.

Over the last 14 years, 134 patients with obstructive lymphedema have been treated with microlymphaticovenous anastomoses. Ninety patients were available for long-term follow-up study. Of these, 52 patients were treated by microlymphatic surgery only and 38 of them also had segmental or radical reduction surgery, either at the same time or secondarily. Objective assessment was undertaken by volume and circumferential measurements. Initially, lymphangiography was used, but a study demonstrated increased edema immediately following the investigation in one-third of the patients and it was abandoned, both preoperatively and postoperatively. In the microlymphaticovenous anastomoses only group (N = 52), subjective improvement occurred in 38 patients (73 percent). Objectively, volume changes showed a significant improvement in 22 patients (42 percent), with an average reduction of 44 percent of the excess volume. In the microlymphaticovenous anastomoses and reduction surgery, usually segmental, group (N = 38), subjective improvement occurred in 30 patients (78 percent) and objective improvement occurred in 23 patients (60 percent), with an average reduction of 44 percent of the excess volume. Of those followed up, 67 patients (74 percent) have been able to discontinue the use of conservative measures, with an average follow-up of 4.0 years and average reduction in excess volume of 26 percent. There was a 58 percent reduction in the incidence of cellulitis following surgery. In those patients who were improved, drainage resulted in increased softness of the limbs. Edema of the hand diminished considerably in most patients, although this was difficult to measure. These long-term results indicate that microlymphaticovenous anastomoses have a valuable place in the treatment of obstructive lymphedema and should be the treatment of choice in these patients. Reduction surgery can be used as an adjunct in some of these patients, especially in the posteromedial aspect of the upper arm. Liposuction has been used in failed cases or in patients in whom no lymphatics could be found. Improved results can be expected with earlier operations because patients referred earlier usually have less lymphatic disruption.

Anastomosis, Surgical↗

Effect of postoperative radiation on the incorporation of tibial bone grafts in the rabbit.

A dose of 48 Gy of X-irradiation given over two to five weeks after grafting caused no significant delay in the rate of healing and only a small and statistically non-significant decrease in the torsional strength of the graft-bone junction of either vascularised or non-vascularised bone grafts of the tibiae of rabbits. Healing was faster and the union between the graft and adjacent bone developed torsional strength significantly more rapidly with vascularised than with non-vascularised grafts. These findings suggest that postoperative radiotherapy is unlikely to have a significantly deleterious effect on the healing of bone grafts used to repair defects produced by excision of malignant bone tumours.

Animals↗

An easy and safe way to dress limb flaps in the dog.

When a flap is elevated in a human, the patient is usually managed with bed rest. The same conditions are impractical in dogs. Sometimes a flap in the dog must be protected from the dog itself by applying a special cast or a bucket on the head. An easy, safe, inexpensive, and quick method to dress the dog, by simply applying hot pepper into the dressing, is described.

Animals↗

Liposuction in the treatment of lymphoedema; a preliminary report.

Liposuction was used in the treatment of primary and secondary lymphoedema in 19 patients. Seven patients had no previous surgical treatment and 12 had previously been treated with microlymphaticovenous anastomoses and/or surgical reduction. There was subjective improvement in 11 of the 13 patients available for follow-up. There was objective improvement in 10 of the 11 patients with unilateral lymphoedema, with an average reduction of 23% of the excess volume. Seven of the 13 patients were on conservative treatment prior to liposuction. The average reduction in this group was 20.5%. The average follow-up time was 9.5 months. From this preliminary report it can be concluded that liposuction, either as a primary procedure or as an adjunct, can be a useful procedure in the treatment of both primary and secondary lymphoedema.

Arm↗

Factors involved in salvaging ischaemic rabbit skin flaps: ATP and free radicals but not thromboxane.

Rabbit epigastric free flaps were subjected to ischaemia at 25 degrees C for 24 hours. At the time of revascularisation the flaps were infused intra-arterially with one of the following: Hanks balanced salt solution (control), the high energy phosphates PEP/ATP, the thromboxane synthetase inhibitor dazoxiben hydrochloride, the free radical scavenger SOD and a combination of all these agents (treated groups). Control ischaemic flap survival at post-ischaemia day 7 was 23.5%, while the other treatments resulted in improved flap survival of 43.5% (p less than 0.025), 23.5% (not significant), 38.6% (p less than 0.05) and 35.7% (p less than 0.05) respectively. None of these agents improved post-ischaemic blood flow significantly. These results would support the use of PEP/ATP or SOD in the clinical treatment of failing ischaemic skin flaps but do not support the use of dazoxiben hydrochloride.

Adenosine Triphosphate↗