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Biomedical subjects

M Gennaro

Publications and source records attributed to M Gennaro.

33 records · Page 2Linked to original sources

Acute mesenteric ischemia after cardiopulmonary bypass.

Three thousand sixty-six patients underwent cardiopulmonary bypass at the Maimonides Medical Center over a 5-year period from January 1, 1987, to January 1, 1992. Of these patients, 1,890 (62%) were less than 70 years of age, 969 (32%) ranged from 70 to 79 years of age, and 207 (7%) were 80 years of age or older. The overall 30-day mortality rate was 8%. Eleven patients developed acute mesenteric ischemia from 24 hours to 12 days postoperatively. At the time of diagnosis, the majority of patients presented with late classical signs and symptoms of acute mesenteric ischemia including abdominal distension, respiratory distress, hypotension, oliguria, and sepsis. All patients underwent immediate laparotomy. Extensive bowel necrosis was found in all, and resection was possible in eight patients. All patients died as a result of this complication. Using the exact trend test, we found a statistically significant increase in the incidence of deaths due to acute mesenteric ischemia after cardiopulmonary bypass in older compared with younger patients. This fatal complication after cardiopulmonary bypass occurs more often than previously believed and is a relatively common cause of death in the elderly.

Acute Disease↗

Unilateral renal artery revascularization can salvage renal function and terminate dialysis in selected patients with uremia.

Revascularization of renal arteries to salvage glomerular function in patients with chronic renal failure is performed infrequently. However, during the past 12 months we have encountered three patients over 60 years of age known to have chronic renal failure who were on dialysis for 2 weeks, 3 weeks, and 2 months, respectively. All three patients were hypertensive, requiring between four and five antihypertensive medications. One patient was ventilator dependent in intractable cardiac failure with pulmonary artery systolic pressures ranging from 60 to 70 mm Hg. Standard biplanar arteriography revealed occlusion of the left renal artery with distal reconstitution in two patients and a 99% stenosis of the right renal artery in the remaining patient. The contralateral renal artery was totally occluded in two patients and diffusely stenotic in one. The recipient kidneys measured 8, 10, and 11 cm in length. Kidney function was assessed by renal scintigraphy and creatinine clearance. Two splenorenal bypasses and one hepatorenal bypass with 6 mm polytetrafluoroethylene graft were performed successfully. After surgery, renal function improved in all patients with two of three patients resuming normal function as evidenced by reduction of serum creatinine levels to 0.9 and 1.3 mg/dl. The third patient recovered to have a creatinine level of 3.2 mg/dl. All patients were discharged home within 1 month with a daily urine output greater than 1500 ml. At discharge, each patient required only two antihypertensive medications to control blood pressure. Duplex scanning 3, 6, and 12 months after surgery confirmed patency of all reconstructions.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Association of intra-abdominal pathologies and vascular anomalies with infrarenal aortic aneurysm: a computed tomographic study.

The prevalence of potentially significant intra-abdominal pathologies or vascular anomalies in candidates for infrarenal aortic aneurysm repair remains unclear. This study retrospectively reviewed 130 consecutive patients with aortic aneurysms (4.5-10.0 cm in largest diameter) who had undergone contrast-enhanced abdominal computed tomography. The overall incidence of potentially significant pathologies was 31.5%. Gallstones were detected in 25 patients (19.2%), adrenal masses in six (4.6%), pancreatic tumors in two (1.5%), renal stones in two (1.5%), liver metastases in one (0.8%), retroperitoneal lymphoma in one (0.8%) and left gastric artery aneurysm in one (0.8%). Other pathologies included renal cysts in 42 patients (32.3%), colonic diverticulosis in nine (6.9%) and hepatic cysts in three (2.3%). Major vascular anomalies were encountered in only three of the 130 patients (2.3%) and these included two with a left-sided inferior vena cava and one case of retroaortic left renal vein. This study emphasizes the high incidence of potentially significant intra-abdominal pathologies and the low incidence of major vascular anomalies associated with infrarenal aortic aneurysm. The impact of such findings on the management of aortic aneurysms is discussed.

Abdomen↗

The preferential use of the external iliac artery as an inflow source for redo femoropopliteal and infrapopliteal bypass.

PURPOSE: It is believed that secondary operations involving the inguinal region are associated with a significant morbidity that includes infection, lymphatic obstruction, lymphorrhea, and neurovascular injury. To prevent these potentially important complications we have avoided a redo groin incision in 38 patients with severely symptomatic disease who had primary (23 cases) or secondary (15 cases) femoropopliteal bypass thrombosis during the past 3 years. METHODS: All patients were candidates for prosthetic bypasses because of lack of a suitable vein. Twenty-nine external iliac-to-popliteal bypasses (18 above-knee; 11 below-knee) and nine external iliac-to-infrapopliteal bypasses (five anterior tibial; two posterior tibial; two peroneal) were performed with 6 mm polytetrafluoroethylene ringed grafts in 38 patients. Adjunctive distal arteriovenous fistulas were constructed in all infrapopliteal bypasses. The external iliac artery was exposed via a retroperitoneal approach. The second incision was placed just below the scarred area and deepened to the level of the medial border of the sartorius muscle. A tunnel that connected both incisions was easily created by blunt dissection alongside the anterolateral border of the femoral artery. RESULTS: Four popliteal bypasses occluded at 4, 6, 10, and 28 months after operation. The remaining 25 grafts are patent (mean 14 months). Three of the infrapopliteal bypasses occluded at 0, 2, and 3 months after operation. The remaining six grafts are patent with follow-up from 4 to 18 months (mean 12 months). Only one patient had a superficial wound infection at the below-knee popliteal incision, which healed with local treatment. All other patients had an uneventful postoperative course. CONCLUSIONS: Thus we believe this approach to be simple, safe, and durable and should be used preferentially to avoid the difficult and hazardous dissection of a previously operated groin.

Aged↗

Interleukin-1 and thromboxane release after skeletal muscle ischemia and reperfusion.

Interleukin-1 and thromboxane are known to mediate the host response to sepsis, trauma, and myocardial ischemia. A well-established model of canine isolated gracilis muscle was used to evaluate whether cytokine (interleukin-1) played a role in skeletal muscle ischemia-reperfusion injury. Six adult mongrel dogs (25-30 kg) were subjected to six hours of muscle ischemia followed by reperfusion. Gracilis venous samples were collected pre-ischemia and at one hour of reperfusion. Systemic (arterial) blood samples were taken at one hour of reperfusion. Sera were analyzed for interleukin-1 by bioassay and thromboxane (B2) by radio-immunoassay. The gracilis muscle of the operated limb was harvested in all the animals for assessment of the percentage of muscle necrosis. This was found to be 56.2 +/- 14.8% by serial transections, nitroblue tetrazolium staining, and computerized planimetry. Interleukin-1 levels in the gracilis venous effluent increased from 21.88 +/- 7.13 units/ml during pre-ischemic baseline to 50.42 +/- 9.12 units/ml after six hours of ischemia followed by one hour of reperfusion (p less than 0.04). Thromboxane B2 levels were 2983 +/- 1083 pg/ml and 9483 +/- 2218 pg/ml at pre-ischemia and at one hour of reperfusion respectively (p less than 0.04). Systemic levels of both interleukin-1 and thromboxane B2 at one hour of reperfusion were 0 units/ml and 1584 +/- 520 pg/ml respectively, which were significantly lower than the one hour reperfusion gracilis venous effluent levels (p less than 0.04). This is the first report in which cytokines have been implicated in skeletal muscle ischemia-reperfusion injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Reduction of the extent of ischemic skeletal muscle necrosis by perfusion with oxygenated perfluorocarbon.

Oxygenated perfluorocarbon emulsion has been shown to preserve feline cerebral function after ischemia. The postulated protective effects of perfluorocarbons include improvement of blood rheology and prevention of neutrophil adherence by nonchemical inhibition of surface receptors. In this study, we used a well-described gracilis muscle model to investigate whether oxygenated perfluorocarbon can minimize skeletal muscle necrosis by mitigating the degree of leuko-sequestration. In eight adult mongrel dogs, both gracilis muscles were weighed and then subjected to 6 hours of normothermic ischemia followed by 48 hours of normothermic reperfusion. However, one randomly selected side (experimental side) was infused with oxygen (O2) Fluosol-DA 20% (4.4 +/- 0.2 mL O2/100 mL) intra-arterially at 12 mL/min for 40 minutes immediately after ischemia. Muscle biopsy specimens were obtained before ischemia and after 1 hour and 48 hours of reperfusion to estimate myeloperoxidase (MPO) activity, a marker of neutrophil infiltration. After 48 hours, both gracilis muscles were harvested and weighed in all animals. Muscle necrosis was measured by serial transections, nitroblue tetrazolium staining, and computerized planimetry. The transmuscular oxygen tension (pO2) of the gracilis muscle on the experimental side increased from 2 to 4 mm Hg during ischemia to 315 +/- 50 mm Hg during O2 Fluosol-DA 20% infusion. The percentage of muscle necrosis on the control side was 48.08% +/- 8.46%, compared with 27.62% +/- 6.96% on the experimental side (p less than 0.001). MPO activity was significantly higher at 48 hours of reperfusion compared with pre-ischemic and 1-hour reperfusion values (5.46 +/- 1.52 U/mg tissue protein versus 0.06 +/- 0.01 U/mg tissue protein and 0.16 +/- 0.06 U/mg tissue protein, respectively, in the control group; 1.78 +/- 0.60 U/mg tissue protein versus 0.16 +/- 0.08 U/mg tissue protein and 0.27 +/- 0.10 U/mg tissue protein, respectively, in the experimental group, p less than 0.05). However, MPO activity at 48 hours of reperfusion in the experimental group was significantly lower than in the control group (p less than 0.05). There was no difference in the percentage of weight gain between the control and the experimental groups (38.31% +/- 9.36% and 28.34% +/- 7.35%, respectively, p greater than 0.05). These data show that perfluorocarbons minimize the extent of skeletal muscle necrosis in this canine model. Based on our data on MPO activity, we believe t hat the protective effect of perfluorocarbons is in part due to th e decreased leuko-sequestration in the muscle during the the periods of ischemia and reperfusion.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The value and limitation of iloprost infusion in decreasing skeletal muscle necrosis.

Iloprost has been shown to minimize skeletal muscle necrosis when administered before the onset of ischemia in animal experiments, possibly by preventing neutrophil activation. Since patients with acute limb ischemia are seen after the process has begun, we investigated whether iloprost can be protective when given only during reperfusion. After anesthesia, 18 adult mongrel dogs underwent a standard isolated gracilis muscle preparation. In six control animals (group I) the gracilis muscle was subjected to 6 hours of ischemia followed by 48 hours of reperfusion. Group II animals (n = 6) received intravenous infusion of iloprost at a dose of 0.45 microgram/kg/hr beginning 1 hour before the onset of muscle ischemia and throughout the experiment (6 hours of ischemia and 1 hour of reperfusion). In addition to the continuous infusion, they received 0.45 microgram/kg intravenous boluses of iloprost 10 minutes before the induction of ischemia and 10 minutes before reperfusion. Group III animals (n = 6) had a similar ischemic interval, but were given a bolus of iloprost of 0.45 microgram/kg at end ischemia followed by continuous infusion of 0.45 microgram/kg/hr for 48 hours during reperfusion. Muscle biopsies were obtained at baseline and after 1 hour of reperfusion in all groups. Additional biopsies were obtained at 48 hours of reperfusion in groups I and III. Myeloperoxidase activity, a marker of neutrophil activation, was measured in all muscle biopsies. At the end of reperfusion, the gracilis muscle was harvested in all animals and weighed. Muscle necrosis was estimated by serial transection, nitroblue tetrazolium histochemical staining followed by computerized planimetry.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Minipump clorgyline administration and CSF amine metabolites in unrestrained monkeys.

The irreversible MAO-A inhibitor clorgyline was administered in doses of 0.5 mg/kg (N = 1), 1 mg/kg (N = 3), and 2 mg/kg (N = 1) to 5 young (age 5.5 to 23.9 months) pigtail (M. nemestrina) monkeys using a 28-day (Alza 2ML4) osmotic minipump. CSF MHPG, 5-HIAA, HVA, and plasma MHPG were measured before and at approximately weekly intervals after pump implantation. Implants were well tolerated. CSF MHPG decreased about 75%, 5-HIAA 30%, and HVA from 30-50% with a tendency to plateau by the second week. Plasma MHPG decreased to undetectable levels. The findings demonstrate that long-term inhibition of MAO-A can be produced in unrestrained monkeys by minipump administered clorgyline. There is an apparently greater effect on the norepinephrine system relative to the serotonin and dopamine systems.

Animals↗

A comparison of CO2 laser-assisted venous anastomoses and conventional suture techniques: patency, aneurysm formation, and histologic differences.

The expected patency and the potential complications of CO2 laser-welded end-to-end venous anastomoses have not been well established despite increasing clinical interest in the subject. To further study this relatively new technique we used the internal jugular veins (1.0 to 1.4 mm diameter) of 15 New Zealand White rabbits weighing 2.5 to 3.5 kg. On one randomly selected side, a laser-welded end-to-end anastomosis was performed in all animals by placing three equidistant stay sutures followed by welding the vein edges with a CO2 laser (spot size of 0.27 mm, power of 100 mW, and power density of 175 W/cm2). On the contralateral side, the vein was anastomosed with interrupted 10-0 nylon sutures in 10 animals, and in the remaining five animals a continuous 10-0 nylon suture technique was used. All anastomoses were surgically assessed at 30 days after operation. A significantly lower 30-day patency rate (p less than 0.05, Fisher's Exact Test) was found in anastomoses constructed by use of the continuous technique (20%) compared with either interrupted (90%) or the laser-assisted technique (87%). No significant difference was observed in 30-day patency between laser-assisted and conventional interrupted anastomoses. Anastomoses performed with the continuous and the laser-assisted technique required 12.5 +/- 1.3 and 12.9 +/- 3.0 minutes, respectively, whereas those constructed with interrupted technique required 19.1 +/- 4.5 minutes (p less than 0.05, Student-Neuman-Keuls' Test). No evidence of false or true aneurysm was noted in any of the animals. Histologic evaluation of laser-assisted anastomoses demonstrated early full-thickness coagulation necrosis of the wall with reendothelialization by 7 days and complete healing by 30 days after the procedure. Conventional anastomoses showed reendothelialization and minimal necrosis near the sutures at 7 days, but healing was complete by 30 days after the procedure. The patency rate of vein anastomoses performed with the CO2 laser is excellent and superior to the one obtained with continuous sutures, and except for less operating time, the former technique does not appear to offer any significant advantage over the conventional interrupted suture technique for small vein anastomosis in this animal model up to 1 month of follow-up.

Anastomosis, Surgical↗

The clinical significance of gastric epithelial dysplasia.

Six-hundred-and-ninety-four patients with localized gastric lesions (ulcers, polyps, enlarged or irregular folds, erosions and tumors) underwent endoscopic examination and multiple biopsies. Twenty-nine proved to have severe or moderate gastric epithelial dysplasia. Another group of 123 patients were submitted to endoscopic examination and multiple biopsies, but showed no evidence of localized gastric lesions. Only one case of mild dysplasia was observed in this group. Of the 29 patients with dysplasia, 8 (27.5%) had a carcinoma in the surgical specimen. The endoscopic follow-up carried out in non-operated patients with dysplasia did not show any development of malignancy. This study shows dysplastic changes significantly associated with prominent or depressed lesions of the gastric mucosa at endoscopy. In operated patients a synchronous carcinoma is often detected in the surgical specimen.

Adult↗

[Anti-GM1 and anti-sulphatide antibodies in systemic idiopathic vasculitis, systemic lupus erythematosus and mixed cryoglobulinaemia: Serum detection and clinical and electrophysiologic correlations].

BACKGROUND: In the last two decades increasing interest has been focused on the association between autoimmune polyneuropathies and high titers of anti-nervous serum autoantibodies. High titer of IgG anti-GM1 antibody could be detected in Guillain Barre' syndrome and in chronic painful axonal sensory immune-mediated polyneuropathy. The possible occurrence of anti-nervous autoantibodies in autoimmune diseases not limited to the nervous system is still under study. METHODS: We evaluated 29 patients with systemic lupus erythematosus (SLE), 19 with biopsy-proven renal involvement, 28 patients with mixed IgM-K/IgG polyclonal cryoglobulinaemia (18 with glomerulonephritis) and 19 with small-sized vessel ANCA-associated vasculitis (12 with renal involvement) by using a sensitive immunoenzyme method of autoantibody detection. RESULTS: Compared to controls (1/176+/-1/205; 1:204+/-1:103), we found a significant increase in plasma IgM and IgG anti-GM1 titers (1:643+/-1:531; 1:444+/-1:309) in SLE patients (p<0.0001). We also found IgM (1:3032+/-1:2844) and IgG (1:1560) anti-sulphatide titers to be higher than the control group (p<0.0001). Mean plasma IgM and IgG anti-GM1 titers of the cryoglobulinaemic patients were 1:524+/-1:403 and 1:501+/-1:415, respectively, once again higher than the controls (p<0.0001). Mean plasma IgM and IgG anti-sulphatide titers in this group were 1:1864+/-1:1189 and 1:1350 (p<0.0001). We found idiopathic systemic vasculitis patients to have significantly increased levels of anti-sulphatides IgG class autoantibodies (1:1400; p<0.0001). We found no correlation with the serologic markers for vasculitis or the clinical or histologic extent of renal involvement. Electrophysiologic studies revealed that in 38% of SLE patients (p<0.005), 61% of cryoglobulinaemic patients (p<0.01) and 42% of ANCA-related vasculitic patients (p<0.01) the abnormal titers of antineuronal antibodies were associated with clinical or subclinical evidence of neuropathy. CONCLUSIONS: In patients with systemic idiopathic or secondary vasculitis anti-GM1 and anti-sulphatide antibodies can frequently be found. Their presence should prompt an accurate neurological examination because these serologic abnormalities are significantly associated with neurologic, often subclinical, involvement. Antineuronal reactivity might be the epiphenomenon of primary phylogistic damage, which exposes normally segregated neuronal epitopes or be directly involved in triggering neurological injury.

Antibodies↗

Does iloprost mediate thromboxane activity and polymorphonuclear leukocyte sequestration in ischemic skeletal muscle?

Thromboxane is known to alter the endothelial cytoskeleton, thereby causing increased endothelial permeability and polymorphonuclear leukocyte (PMN) sequestration in the lungs. We investigated whether iloprost (a stable prostacyclin analog) can decrease thromboxane activity and consequently PMN sequestration because of its anti-platelet aggregation effect. This premise was investigated in a canine isolated gracilis muscle model using 18 animals. Six animals (group I) had the gracilis muscle subjected to 6 hours of complete ischemia followed by 48 hours of reperfusion. Group II (n = 6) received intravenous infusion of iloprost (0.45 micrograms/kg/hr) throughout the experiment (1 hour preischemia, 6 hours of ischemia and 1 hour of reperfusion) and boluses of 0.45 micrograms/kg 10 minutes before ischemia and reperfusion. Group III (n = 6) underwent a similar ischemic interval, but were given iloprost bolus of 0.45 micrograms/kg followed by intravenous infusion of 0.45 micrograms/kg/hr during 48 hours of reperfusion. Gracilis venous samples were obtained at preischemia (PI) and 1 hour of reperfusion (all 3 groups) and at 48 hours of reperfusion (groups I and III) to measure thromboxane (TXB2) levels. Muscle biopsies were taken at the same time to measure myeloperoxidase (MPO) activity, a marker of PMN infiltration. In group I, TXB2 level increased from a pre-ischemic value of 2983 +/- 1083 pg/ml to 9483 +/- 2218 pg/ml at 1 hour of reperfusion (p < 0.05) and then decreased to 2386 +/- 1533 pg/ml at 48 hours of reperfusion (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Do cytokines play a role in skeletal muscle ischemia and reperfusion?

Cytokines, interleukin-1 (IL-1) and tumor necrosis factor (TNF) are known to mediate host cell response to sepsis, trauma, and myocardial ischemia. We have previously found increased levels of IL-1 in the venous effluent during the reperfusion phase of skeletal muscle ischemia in a canine model. This study was done to evaluate whether TNF also played a role in skeletal muscle ischemia-reperfusion injury since IL-1 and TNF have inter-related functions. In twelve adult mongrel dogs (28-32 kg) one gracilis muscle was subjected to six hours of normothermic ischemia followed by normothermic reperfusion. The contralateral side served as a control and remained normally perfused throughout the experiment. Gracilis venous samples were collected at pre-ischemia and one hour of reperfusion. Systemic (arterial) blood samples were taken simultaneously with the venous samples at one hour of reperfusion. At the end of the experiment the muscles were harvested and amount of necrosis quantitated by serial transections, nitroblue tetrazolium staining and computerized planimetry. Muscle necrosis on the experimental side was found to be 48.86 +/- 5.37%. Sera were analyzed for TNF activity using a bioassay. TNF levels in the gracilis venous effluent at one hour of reperfusion were not significantly different from the simultaneous systemic (arterial) levels (27.15 +/- 5.05 pg/ml vs 18.23 +/- 4.27 pg/ml). Pre-ischemic levels of TNF were 96.50 +/- 20.12 pg/ml, which was significantly higher than either venous or arterial levels obtained after one hour of reperfusion (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Laser welding and irradiation in alcohol preserved homografts.

This experiment examined the effect of laser welding and irradiation on the patency rate of microvascular anastomoses done with alcohol preserved homografts. The carotid arteries from Sprague-Dawley rats were freshly harvested and preserved in 70% ethyl alcohol for at least 3 weeks. The homografts were interposed into the carotid arteries with one of the following techniques: Group I, grafts were anastomosed with three stay sutures and laser welding (carbon dioxide laser, 90 mW); Group II, anastomoses were completed with eight to nine interrupted sutures (10-0 nylon); or Group III, the same technique used in Group II, but followed by laser irradiation (90 mW for 1 min) of the grafts. These results showed that patency at 2 weeks was 73% in Group I, 71% in Group II, and 82% in Group III, respectively. The patency at 12 weeks was 67% in Group I and unchanged in Groups II and III. In conclusion, laser irradiation and laser welding did not increase the patency rate of microvascular anastomoses done with alcohol preserved homografts. Thrombotic occlusion in microvascular homografts usually occurs before the second week postoperatively.

Anastomosis, Surgical↗