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D Israeli

Publications and source records attributed to D Israeli.

27 records · Page 2Linked to original sources

Evaluation of a continuous systemic infusion of iloprost, a stable PGI-2 analog, on the survival of experimental skin flaps.

Numerous investigators have attempted to enhance the survival of ischemic experimental skin flaps using various pharmacologic manipulations. Recently, the authors' laboratory demonstrated the beneficial effect of iloprost, a stable PGI2 analogue, as a post-ischemic perfusion washout, in improving the survival of ischemic skin flaps. The rat unilateral abdominal skin flap, based on the superficial epigastric vessels, was utilized in this study involving 30 animals. The animals were divided into three different treatment groups, with ischemic periods of 16 and 18 hr. Perfusion washouts were performed at the completion of the various ischemic periods. Alzet osmotic pumps were used to deliver a continuous systemic infusion of iloprost for 7 days postoperatively. The groups consisted of the following: Group 1 (single ILO)--perfusion washout with iloprost only; Group 2 (continuous LD ILO)--low-dose systemic iloprost infusion (0.066 mcg/kg/min) and perfusion washout with iloprost; and Group 3 (continuous HD ILO)--high-dose systemic iloprost infusion (0.1 mcg/kg/min) and perfusion washout with iloprost. The percentage of flap survival was assessed on postoperative day 7. Skin flaps of the animals receiving the continuous systemic infusion of iloprost were noted to have varying percentages of survival, while skin flaps undergoing perfusion washout only were found to have either complete survival using a continuous systemic infusion of iloprost, compared to iloprost perfusion washout alone. In addition, the hypotensive side effects of systemic iloprost infusion limit its use in the rat skin-flap model.

Animals↗

Use of urokinase during secondary ischemia in experimental skin flaps.

The ability of urokinase to salvage experimental flaps after a secondary ischemic insult was investigated in a rat model. Unilateral abdominal island skin flaps based on the superficial inferior epigastric vessels were raised and subjected to either 4 or 6 hours of primary ischemia followed by 12 hours of reperfusion and varying lengths of secondary ischemia. At the conclusion of secondary ischemia, the flaps were perfused with either lactated Ringer's solution or urokinase. One group of flaps served as a control and received no postischemic perfusion washout. The secondary critical ischemia time at which 50% of the flaps failed clinically was greater for flaps perfused with urokinase. Furthermore, the survival rates for all flaps perfused with urokinase were significantly greater than either control flaps or flaps perfused with lactated Ringer's solution (p < 0.05). Flap survival decreased significantly in all groups with increasing primary and/or secondary ischemia time (p < 0.05).

Animals↗

Iloprost improves survival of ischemic experimental skin flaps.

The ability of the prostacyclin analogue iloprost to improve survival of ischemic experimental skin flaps was investigated. Unilateral island skin flaps based on the superficial inferior epigastric vessels were raised in 70 rats and subjected to varying lengths of primary ischemia. The flaps were divided into the following four groups: group I, no perfusion washout; group II, postischemic washout with lactated Ringer's solution; group III, postischemic washout with urokinase; and group IV, postischemic washout with iloprost. Flap survival rates for group IV were significantly higher than all other groups (p < 0.05). The primary ischemia time at which 50% of the flaps failed was 8.9 hours for group I, 9.5 hours for group II, 13.3 hours for group III, and 15.3 hours for group IV. This is the first study to investigate the effect of iloprost on skin flap survival. Iloprost was found to be significantly more effective than urokinase in salvaging ischemic experimental skin flaps.

Animals↗

The significance of family history for patients with carcinoma of the breast.

BACKGROUND: Since the risk of carcinoma of the breast is increased in women with a family history of the disease, new primary carcinomas of the breast may be increased after treatment. Women with several relatives with carcinoma of the breast are thought to be at higher risk of having a second primary carcinoma of the breast develop and mastectomy is more frequently recommended. STUDY DESIGN: The computerized registry of the Mount Sinai Medical Center Breast Service was used to identify 1,337 patients with complete information concerning family history. Three hundred fifty-nine patients with a family history of carcinoma of the breast were compared with women with no family history. RESULTS: Compared with patients with no family history of carcinoma of the breast, patients with a family history of carcinoma of the breast were significantly younger (54.0 versus 55.8 years of age, p < 0.01), were significantly more likely to have used oral contraceptives (26 versus 13 percent, p < 0.001), had significantly more ductal carcinoma in situ (10 versus 4 percent, p < 0.01), and were significantly more often treated with breast conservation (42 versus 31 percent, p < 0.001). Simultaneous contralateral carcinoma of the breast was diagnosed more frequently in patients with a family history (3 versus 1 percent, p < 0.025), but metachronous contralateral carcinomas were not increased. In comparing the two groups, there were no significant differences in proportion premenopausal, parity, use of postmenopausal hormones, tumor size, tumor differentiation, nodal involvement, TNM stage, estrogen receptor status, or use of adjuvant radiation, chemotherapy, or tamoxifen. Complete five-year follow-up evaluation for 748 patients, 179 with a family history, found no differences in local, distant, or disease-free survival rates for mastectomy or breast conservation in relation to family history. Outcome for patients with first-degree affected relatives and those with more than one affected relative was the same as those with no family history. CONCLUSIONS: These results indicate that women with a family history of carcinoma of the breast should be treated no differently than women with no family history.

Breast Neoplasms↗

Numerous candidate plasticity-related genes revealed by differential cDNA cloning.

Plasticity is a property of the nervous system that allows it to modify its response to an altered input. This capacity for change suggests that there are molecular mechanisms in neurons that can couple stimuli to long-term alterations in phenotype. Neuronal excitation elicits rapid transcriptional activation of several immediate-early genes, for example c-fos, c-jun and zif268. Many immediate-early genes encode transcription factors that control expression of downstream genes whose products are believed to bring about long-term plastic changes. Here we use a highly sensitive differential complementary DNA cloning procedure to identify genes that may participate in long-term plasticity. We cloned 52 cDNAs of genes induced by the glutamate analogue kainate in the hippocampus dentate gyrus. The number of these candidate plasticity-related genes (CPGs) is estimated to be 500-1,000. One of the cloned CPGs (16C8), encoding a protease inhibitor, is induced by a stimulus producing long-term potentiation and during dentate gyrus development; a second, cpg1, is dependent on activation of the NMDA (N-methyl-D-aspartate) receptor for induction and encodes a new small, dentate-gyrus-specific protein. Seventeen of the cloned CPGs encode known proteins, including six suggesting that strong neuronal activation leads to de novo synthesis of vesicular and other synaptic components.

Amino Acid Sequence↗

The additive beneficial effect of UW solution and urokinase on experimental microvascular free-flap survival.

Pharmacologic manipulation of free flaps to enhance tolerance to ischemia has become a subject of great interest in the research literature. In an effort to improve survival, perfusion washout of experimental free flaps was performed following an episode of primary ischemia. The perfusates utilized were lactated Ringer's solution (LR), University of Wisconsin solution (UW), a high-molecular-weight medium used in organ preservation, and urokinase, a thrombolytic agent. Seventy-five rats were used in this study and divided into groups of 5 each. A 3 x 6-cm abdominal free flap based on the superficial inferior epigastric vessels was raised in each rat. The free flaps were subjected to either 12 or 18 hr of primary ischemia. Following the period of ischemia, perfusion washout was performed with either LR, UW solution, or urokinase at increasing concentrations alone or in combination with UW solution. Urokinase was first evaluated as a perfusate alone at increasing concentrations. In the 12-hr ischemia group, free-flap survival was shown to increase from 0 percent in the LR-perfused flaps to 20 percent, 60 percent, and 80 percent in flaps perfused with 12,500, 25,000, and 100,000 U of urokinase, respectively (p < 0.05). A similar increase in survival was demonstrated in the 18-hr ischemia group, where 0 percent, 20 percent, and 40 percent of flaps survived following perfusion with 12,500, 25,000, and 100,000 U of urokinase, respectively (p < 0.05). Urokinase was then perfused along with UW solution to evaluate the combined effect on flap survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

Enhancement of fluorescein perfusion in experimental skin flaps following postischemic washout with iloprost, urokinase, verapamil, and University of Wisconsin solution.

The enhancement of blood flow in experimental skin flaps following postischemic perfusion washout was investigated in rats. Unilateral island skin flaps based on the superficial epigastric vessels were raised and subjected to 6 hr of primary ischemia. Group 1 was designated as a control and did not undergo postischemic perfusion washout. In the remaining rats, postischemic washout was performed with one of five agents: Group 2--lactated Ringer's solution; Group 3--University of Wisconsin solution, an organ preservation medium; Group 4--verapamil, a calcium channel blocker; Group 5--urokinase, a thrombolytic agent; Group 6--iloprost, a stable prostacyclin analog. Two hours following perfusion washout, fluorometric analysis revealed a statistically significant enhancement of blood flow in Groups 4, 5, and 6, compared to Groups 2 and 3 (p < 0.05). Furthermore, a significant increase in skin surface fluorescence was demonstrated in all the flaps that underwent perfusion washout, compared to the control flaps (p < 0.05). By analyzing skin surface fluorescence, the enhancement of nutritive blood flow in flaps, following postischemic perfusion washout, was evaluated. This is the first study in which the above pharmacologic agents were compared in a quantitative manner.

Adenosine↗

Physician practices in the diagnosis and management of patients with pulmonary embolism.

To examine the diagnostic work-up and subsequent management of patients with pulmonary embolism, we retrospectively reviewed the medical records of 60 patients who had arteriographically proven pulmonary embolism. Ventilation-perfusion scans were utilized in 47 patients and were classified as showing a high (55.3%), moderate (14.9%), low (8.5%), or indeterminate (21.3%) probability of pulmonary embolism. Of the 33 patients treated with anticoagulation, complications occurred in 10 (30.3%). Of the 39 patients treated with inferior vena cava filters, complications occurred in 16 (41.0%) patients, with the most clinically significant complication being recurrent pulmonary embolism, found to occur in one (2.6%) patient. For patients treated with anticoagulation, heparin was started an average of 0.3 (+/- 0.5) days following the initial suspicion of a pulmonary embolism. The average time to reach a therapeutic partial thromboplastin time level was 2.0 (+/- 1.8) days, and warfarin was started an average of 6.2 (+/- 4.1) days after heparin was begun. Among the 60 patients, five (8.3%) died from the pulmonary embolism, and two of these had at least a five day delay before diagnosis was made by pulmonary arteriography. Since the ventilation-perfusion scan had a sensitivity of 70.2% and a false negative rate of 8.5%, it is not always sufficiently accurate in making final treatment decisions, so there should be less hesitation in attaining pulmonary arteriograms. Therapeutic partial thromboplastin time levels should be more aggressively sought. Warfarin should be started within the first few days of heparin therapy. Inferior vena cava filters should be utilized in patients who have a contraindication to anticoagulation therapy or a complication from anticoagulation therapy.

Adult↗

Computerised dystrophic muscle simulator: prospecting potential therapeutic strategies for muscle dystrophies using a virtual experimental model.

Inherited muscle diseases are often characterised by widespread muscle damage in the body, limiting the clinical relevance of cell or gene therapy based upon direct injections into muscles. Recent studies have shown, however, that cells originating from the bone marrow are able to target necrosis-regeneration sites as they occur and, in addition, may also participate in the muscle regeneration after undergoing myogenic differentiation. Here, we present a computerised dystrophic muscle simulator that allows the prospecting of different scenarios of both disease evolution and appropriate employment of blood-borne cells as therapeutic shuttles. It provides the option of examining their use either to transfer a healthy gene into the tissue or to impart substances designed to boost its regeneration. One of the major advantages of this tool is that it offers the opportunity of visualising and composing therapeutic strategies in virtual paradigms in which severe clinical situations, not necessarily available in animal models, can be created. The dystrophic muscle simulator is freely accessible via the Genethon web site (www.genethon.fr), and in the online version via http:@www.wiley.co.uk/genmed.

Algorithms↗