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Biomedical subjects

D M Rose

Publications and source records attributed to D M Rose.

At least 55 records · Page 3Linked to original sources

Elevation of glutathione and related enzyme activities in high-grade and metastatic extremity soft tissue sarcoma.

BACKGROUND: Glutathione is a free radical scavenger implicated in the chemoresistance of certain tumors. As treatment with chemotherapy has added little to improved survival in adult soft tissue sarcoma and little is known concerning the mechanisms of chemoresistance in sarcoma, we studied concentrations of glutathione (nmol/mg protein) and activities of gamma-glutamylcysteine synthetase (GCS; nmol/mg protein/h) and gamma-glutamyl transpeptidase (GGTP; U/mg protein) in extremity soft tissue sarcoma. METHODS AND RESULTS: Tumor specimens (n = 65) were frozen in liquid nitrogen at the time of resection. Fourteen low-grade tumors, 40 high-grade tumors, and 11 pulmonary metastases were analyzed. Glutathione concentrations and GGTP activity were significantly lower in low-grade (3.97 +/- 0.7 nmol/mg protein and 1.07 +/- 0.2 U/mg protein) than in high-grade (8.98 +/- 1.2 nmol/mg protein, p < 0.001; 2.10 +/- 0.4 U/mg protein, p < 0.002) tumors and pulmonary metastases (10.05 +/- 1.8 nmol/mg protein, p < 0.008; 3.14 +/- 2.8 U/mg protein, p < 0.04). While GCS activity was lower in low-grade (0.81 +/- 0.3 nmol/mg protein/h) than high-grade (1.49 +/- 0.5 nmol/mg protein/h) tumors and pulmonary metastases (1.03 +/- 0.2 nmol/mg protein/h), these differences were not significant. In those patients with a high-grade tumor presenting with a local recurrence, glutathione levels were higher in those patients who had received preoperative doxorubicin-based chemotherapy (9.25 +/- 1.7 nmol/mg protein; n = 7) than in those who had no preoperative chemotherapy (4.71 +/- 3.1 nmol/mg protein; n = 4, p = 0.08). CONCLUSIONS: In extremity soft tissue sarcoma, glutathione concentration and GGTP activity are significantly elevated in patients with high-grade and metastatic sarcomas. In addition, there is a trend for increased glutathione levels in tumors previously exposed to doxorubicin-based chemotherapy. Glutathione may play a role in soft tissue sarcoma chemoresistance.

Adolescent↗

gamma-Glutamyl transpeptidase mediation of tumor glutathione utilization in vivo.

BACKGROUND: Glutathione is a tripeptide used by cells to protect against oxidative and free radical damage. It may also be involved in biochemical mechanisms that cause some tumors to become resistant to anticancer drugs. gamma-Glutamyl transpeptidase (GGTP) is a membrane-bound enzyme that cleaves extracellular glutathione, providing cells with amino acids necessary for intracellular synthesis of this compound. Increased expression of GGTP has been found in a number of human tumors; however, few studies have examined the contribution of GGTP to tumor glutathione metabolism in vivo. PURPOSE: Our goals were to study the utilization of host glutathione by 3-methylcholanthrene (MCA)-induced sarcomas grown in rats and to evaluate the involvement of tumor GGTP in this process. METHODS: The left ovaries of 21 female Fischer 344 rats were isolated by laparotomy and placed in subcutaneous positions through stab wounds in the abdominal wall. A 3-mm cube of MCA sarcoma was then sutured to each of the isolated ovaries. The MCA implants obliterated the ovarian tissue, yielding isolated tumors with one arterial supply (the ovarian artery) and one draining vein (the ovarian vein, referred to as the tumor vein). After 2 weeks of tumor growth, blood was drawn from the tumor vein, the inferior vena cava (IVC), and the aorta of 16 animals. Glutathione and cysteine concentrations in plasma samples from this blood were determined by high-performance liquid chromatography and used to calculate glutathione and cysteine utilization ratios for the tumor and the systemic circulations ([(concentration aorta-concentration tumor vein)/concentration aorta] x 100 and [(concentration aorta-concentration IVC)/concentration aorta ] x 100, respectively). The utilization ratios from these control animals were compared with those from acivicin (AT-125; an irreversible GGTP inhibitor)-treated rats (the remaining five animals). Data are presented as mean +/- standard deviation; reported P values are from two-tailed tests of statistical significance. RESULTS: In the control animals, glutathione and cysteine concentrations were significantly lower in the tumor vein (3.55 +/- 1.9 and 5.69 +/- 2.8 microM, respectively) and in the IVC (5.65 +/- 2.3 and 7.17 +/- 2.4 microM, respectively) than in the artery (12.48 +/- 5.7 and 12.33 +/- 5.9 microM, respectively; all P values < .05). In addition, the glutathione utilization ratio was significantly higher for the tumor circulation than for the systemic circulation (69% +/- 14% versus 52% +/- 14%; P < .003). The combined glutathione and cysteine utilization ratio was also significantly higher for the tumor circulation than for the systemic circulation (116% +/- 35% versus 88% +/- 28%; P < .02). Treatment with AT-125 lowered the tumor glutathione utilization ratio significantly (45% +/- 12% for treated animals versus 69% +/- 14% for control animals; P < .005). CONCLUSIONS: Our results show that glutathione and cysteine in the host circulation are used by MCA sarcomas. The significant reduction in tumor utilization of serum glutathione after treatment with AT-125, a GGTP inhibitor, indicates that GGTP is important in tumor glutathione metabolism.

Animals↗

Selective glutathione repletion with oral oxothiazolidine carboxylate (OTZ) in the radiated tumor-bearing rat.

Oxothiazolidine carboxylate (OTZ) is a cysteine prodrug which augments intracellular glutathione (GSH) levels. We examined the effects of oral OTZ on tumor and host tissue reduced GSH levels in fasting and radiated models of GSH depletion. In addition, we studied the tumor's ability to utilize OTZ via the enzyme, oxoprolinase. Fischer 344 rats (n = 40) were implanted with MCA sarcoma and studied at 10% tumor burden. Treatment consisted of 10 mmol/kg OTZ or buffer orally. After a 24-hr fast, 16 animals were treated and tumor, kidney, jejunal, and colonic mucosa were collected after 4 hr. Significant increases in GSH with OTZ (n = 8) vs buffer (n = 8) were seen in kidney (5.6 +/- 0.4 vs 4.3 +/- 0.9; P < 0.01), jejunum (13.8 +/- 1.3 vs 12.1 +/- 1.1; P < 0.05), and colon (6.7 +/- 1.2 vs 5.3 +/- 0.6; P < 0.05), but not tumor (8.9 +/- 2.4 vs 10.6 +/- 1.4; P = 0.12). Sixteen animals were treated 4 hr before and 18 hr following 1100 cGy of abdominal radiation and at 4 days, tumor, jejunal, and colonic mucosa were collected. Significant increases in GSH with OTZ (n = 8) vs buffer (n = 8) were noted in jejunum (9.3 +/- 1.1 vs 7.5 +/- 1.8; P < 0.05) and colon (5.6 +/- 1.1 vs 4.3 +/- 0.9; P < 0.05) but not tumor (8.4 +/- 1.6 vs 7.6 +/- 1.4; P = 0.34). To determine tissue oxoprolinase activity, tumor, kidney, liver, jejunal, and colonic mucosa were collected from 8 animals. Oxoprolinase activity was highest in the kidney (814 +/- 145) with no difference noted between liver and tumor (280 +/- 117 and 324 +/- 137, respectively). Oral OTZ selectively increases reduced GSH levels in normal tissues compared to tumor following fasting and whole abdominal radiation. This increase does not appear to be due to a differential activity of oxoprolinase. OTZ may have a role in protection against toxicity associated with oxidative injury by selective repletion of normal host tissue GSH levels.

Administration, Oral↗

Oral L-2-oxo-4-thiazolidine reduces bacterial translocation after radiation in the Fischer rat.

Glutathione (GSH) is important in protecting rapidly dividing intestinal cells against free radicals generated following radiation. L-2-Oxo-thiazolidine (OTZ) promotes GSH synthesis through increased cysteine delivery. We hypothesize that oral supplementation with OTZ will augment GSH levels and decrease the incidence of bacterial translocation after abdominal radiation, and these effects will be abrogated by treating with a blocker of GSH synthesis, buthionine sulfoximine (BSO). Fischer rats received by oral gavage either OTZ (OTZ/rad), OTZ plus BSO (OTZ/BSO/rad), or saline (sal/rad) 4 hr prior to and 18 hr after radiation. One group underwent saline gavage and no radiation (ctl/sal). On Day 4, animals were sacrificed and mesenteric lymph nodes (MLN) were cultured. Liver and jejunum were removed for GSH analysis by HPLC. Nonradiated, ctl/sal had higher levels of hepatic and jejunal GSH than ctl/rad (13.0 +/- 1.2 vs 9.7 +/- 1.5, 11.2 +/- 1.0 vs 7.8 +/- 2.5 micromol/g dry wt, P < 0.05). Supplementation with OTZ (OTZ/rad) increased hepatic and jejunal GSH levels but treatment with OTZ and BSO (OTZ/BSO/rad) eliminated this benefit (12.0 + 2.6 vs 9.5 + 1.7, 10.1 + 2.4 vs 5.9 + 1.3 micromol/g dry wt, P < 0.05). Ctl/rad had a high rate of positive MLN cultures (80%) compared to ctl/sal and OTZ/rad (10 and 30%, P < 0.05). Treatment with OTZ and BSO (OTZ/BSO/rad vs OTZ/rad, 70 and 30%, P < 0.05) reversed the benefit of OTZ supplementation. This study demonstrated whole abdominal radiation depleted both hepatic and jejunal levels of GSH. Uniquely, OTZ supplementation restored hepatic and jejunal levels of GSH and decreased rate of bacterial translocation.

Administration, Oral↗

Primary duodenal adenocarcinoma: a ten-year experience with 79 patients.

BACKGROUND: Duodenal adenocarcinoma is a rare malignancy with a poorly defined natural history and outcome. The factors that affect management and survival of patients with this disease remain controversial. This study analyzed the ten-year experience at one institution with primary duodenal adenocarcinoma to define factors that have an impact on patient survival. In addition, the outcome of patients with resected duodenal adenocarcinoma was compared with that of patients with gastric and pancreatic adenocarcinoma. STUDY DESIGN: A retrospective review of the prospective database for patients with peripancreatic lesions treated at Memorial Sloan-Kettering Cancer Center between 1983 and 1994 identified 79 patients with a primary duodenal adenocarcinoma. Demographics, presenting symptoms, operative variables, pathologic findings, and survival data were analyzed. Multivariate comparisons and actuarial survival were calculated using these variables. RESULTS: A curative resection was performed in 42 (53 percent) of the 79 patients, including 38 pancreaticoduodenectomies and four duodenal resections. The overall projected five-year survival rate was 31 percent, with resected and nonresected patient survival rates of 60 and zero percent, respectively (p < 0.0001). Nodal metastases, regardless of location, did not have an impact on survival. While stage was a significant factor in survival on univariate analysis, no survival difference was noted between stages I, II, and III. Only resectability and presence of non-nodal metastases predicted outcome on multivariate analysis. CONCLUSIONS: Resectability and presence of distant metastatic disease are the strongest determinants of outcome for patients with duodenal adenocarcinoma. Staging and nodal status offer little prognostic information and nodal positivity should not preclude resection. As patients have symptoms similar to those of pancreatic adenocarcinoma but have an outlook more comparable to gastric adenocarcinoma, a vigorous approach to resection is justified.

Adenocarcinoma↗

Autocrine/paracrine involvement of platelet-activating factor and transforming growth factor-beta in the induction of phosphatidylserine recognition by murine macrophages.

The specific recognition of phosphatidylserine (PS) by macrophages is believed to be one means by which effete and apoptotic cells expressing PS on their outer membrane leaflet are targeted for phagocytosis. The aim of this study was to better understand the autocrine/paracrine factors involved in beta-glucan induction of PS recognition by macrophages. We provide evidence that both platelet-activating factor (PAF) and TGF-beta are involved in beta-glucan induction of PS recognition. This is based on the observations that the PAF receptor antagonist WEB 2086 and Ab against TGF-beta each could partially inhibit beta-glucan-induced PS recognition when used alone and could completely inhibit induction when used in combination. PAF, like TGF-beta, was found to prime macrophages for PS recognition, which could then be triggered by costimulation with a nonspecific phagocytic stimulus, latex particles. We also provide evidence that the priming by PAF and that by TGF-beta can occur independently of each other. This is based on the observations that 1) PAF priming was not blocked by anti-TGF-beta Ab, nor was TGF-beta priming prevented by WEB 2086; and 2) PAF did not increase the steady state level of TGF-beta mRNA, and TGF-beta did not induce PAF synthesis in these cells.

Animals↗

Divergence in macrophage insulin-like growth factor-I (IGF-I) synthesis induced by TNF-alpha and prostaglandin E2.

Increased synthesis of insulin-like growth factor I (IGF-I), a fibroblast growth factor, is induced in murine macrophages by TNF-alpha. TNF-alpha also induces macrophages to express cytocidal activity, but only during costimulation with IFNs. Since prostaglandin E2 (PGE2) is known to inhibit macrophage cytocidal activity, its possible reciprocal enhancement of IGF-I synthesis was examined. PGE2 or dibutyryl cyclic AMP (dbcAMP) stimulated the synthesis of IGF-I similarly to TNF-alpha in magnitude and time course. TNF-alpha did not increase IGF-I synthesis by first inducing PGE2 synthesis, because indomethacin was unable to block the effect of TNF-alpha. PGE2 did not stimulate IGF-I synthesis by first inducing TNF-alpha production, because 1) anti-TNF-alpha Ab did not block PGE2-induced IGF-I synthesis, and 2) PGE2 down-regulated TNF-alpha mRNA levels and did not affect levels of the cytokine in supernatants. Moreover, the difference in the induction of IGF-I was observed at the level of signal transduction, in that PGE2 and dbcAMP increased cAMP-dependent protein kinase (PKA) activity, whereas TNF-alpha stimulated the mitogen-activated protein (MAP) kinase pathway. Divergence between the two pathways was also noted in the regulation of IGF-I at the mRNA level, and an additive effect on IGF-I synthesis was observed when cells were incubated with the combination of TNF-alpha plus PGE2 or dbcAMP. Collectively, these data suggest that TNF-alpha and PGE2 stimulate IGF-I synthesis in macrophages by two separate pathways, and that PGE2 acts as a positive stimulus for IGF-I synthesis through a cyclic AMP/PKA pathway.

Animals↗

Collision-induced dissociation of F2-isoprostane-containing phospholipids.

Free radical-induced lipid peroxidation results in the production of metabolites of arachidonic acid isomeric with prostaglandin F2 alpha. The formation of these compounds, termed F2-isoprostanes, occurs independent of the enzyme cyclooxygenase. The discovery that F2-isoprostanes can exert potent biological activity has suggested that they may mediate, to some extent, the biological responses to oxidant injury. Collision-induced dissociation of the [M-CH3]- ions from oxidized phospholipids isolated by extraction and normal phase high performance liquid chromatography from livers of rats treated with CCl4 to induce lipid peroxidation revealed several molecular species of phospholipids that had the F2-isoprostane esterified to the glycerophosphocholine backbone. Collision-induced dissociation of the [M-CH2CHN(CH3)3]- ion revealed that the F2-isoprostanes were primarily esterified at the sn-2 position of the glycerophospholipid as expected. Furthermore, tandem mass spectrometry of the carboxylate anion from the F2-isoprostane (m/z 353) resulted in the unique loss of 44 u characteristic of a 1,2-cyclic diol moiety such as that found in the PGF2-ring. These observations indicate that intact phospholipids containing fatty acyl groups of the isoprostane structure can be readily detected with tandem mass spectrometry even when present as minor components in a biological extract. Although no specific isomer identification can be made from the complex mixture, these techniques establish the existence of these novel metabolites of arachidonic acid esterified to glycerophospholipids.

Animals↗

[Cholesterol--a marker for multiple risk factors? A comparison between coronary disease and coronary health].

Comparison was made in a cross-sectional study between 658 patients in whom coronary arteriography had shown (n = 304) or excluded coronary artery disease (CHD) (n = 354) and a clinically healthy group as controls (n = 1658), to assess possible risk factors. Patients aged 31-40 years with CHD had the highest total cholesterol levels (286 +/- 43 mg/dl) and the highest number of risk factors (3.6 +/- 0.9) compared to patients without CHD of the same age (204 +/- 30 mg/dl; 2.0 +/- 0.5) and healthy controls (216 +/- 45 mg/dl; 1.7 +/- 0.5) (P less than 0.001). In older patients with CHD, total cholesterol levels were lower (age group 61-70 years: 231 +/- 49 mg/dl), reaching about the same level as that of patients without CHD (232 +/- 54 mg/dl) or healthy controls of the same age (228 +/- 55 mg/dl). Furthermore, it was demonstrated that increased total cholesterol concentration can indicate the presence of other risk factors. It would thus appear that the level of total cholesterol in patients with CHD is decisively influenced by age and the presence of other risk factors.

Adult↗

The combined use of lipoxygenase and cyclooxygenase inhibitors in Klebsiella pneumoniae-induced bovine mastitis.

The effect of combined administration of flunixin meglumine (FM) and nordihydroguaiaretic acid (NDGA) on milk prostaglandin F2 alpha (PGF2 alpha) and leukotriene B4 (LTB4) concentrations, and inflammatory indicators of bovine mastitis was examined. Mastitis was induced in six Holstein cows by the inoculation of Klebsiella pneumoniae via the teat canal. Four cows were intravenously treated with FM (1.1 mg/kg) and NDGA (10 mg/kg) 1 hour prior to bacterial inoculation and again at post inoculation hour (PIH) 11. Two control cows were intravenously treated with equivalent volume doses of sterile isotonic saline solution at the same post inoculation time points. Combined use of FM and NDGA was effective in reducing elevations in milk PGF2 alpha levels and slightly effective in reducing elevations in milk LTB4 levels in the mastitic cows. Elevations in milk bovine serum albumin (BSA) levels were partially reduced during the early post inoculation time period in the FM and NDGA treated cows as compared to the saline treated control cows. Milk somatic cell counts from inoculated quarters were not significantly altered by FM and NDGA treatment. Elevations in rectal temperature were not reduced by FM and NDGA treatment, but clinical signs of quarter inflammation (warmth and swelling) were reduced by FM and NDGA treatment.

Animals↗

Dynamics of uptake and channeling of arachidonic acid in hamster alveolar macrophages and the effect of bleomycin on arachidonyl distribution.

The uptake and distribution of [14C]-arachidonic acid (AA) by primary culture hamster alveolar macrophages (AM) were examined. The macrophages were incubated for 2 to 18 hrs in RPMI-1640 medium containing 0.1% BSA and [14C]-AA. The uptake of [14C]-AA by AM was rapid with 71% and 83% of exogenous [14C]-AA taken up after 2 and 4 hrs of incubation, respectively. Initially, the uptaken [14C]-AA was equally distributed between phospholipids (PL) and neutral lipids (NL). However, by 8 hrs, 86% and 14% of [14C]-AA was found in PL and NL, respectively. This distribution pattern remained constant through 18 hrs. Within the PL pool, most of the [14C]-AA was initially incorporated into phosphatidylcholine (PC). However, with time, as the percent of [14C]-AA incorporated in PC declined, the percent incorporated in phosphatidylethanolamine increased. The incorporation of [14C]-AA into sphingomyelin, phosphatidylinositol, and phosphatidylserine remained constant with time. Within the NL, most of the [14C)-AA was initially found incorporated into triacylglycerols (TG). After 4 hrs, the percent of [14C]-AA found in TG decreased markedly, while the percent found in cholesterol esters markedly increased. Incubation of AM prelabeled with [14C]-AA with bleomycin at 0.5, 5, 50 and 500 microM for 2 and 8 hrs failed to have any effect on the distribution of [14C]-AA in PL and NL pools.

Animals↗

Internal mammary artery bypass grafting: influence on recurrent angina and survival in 2,100 patients.

Internal mammary artery (IMA) bypass grafting to the anterior descending coronary artery was performed in 2,100 patients between January 1978 and July 1986. The average number of additional saphenous vein grafts (SVGs) per patient was 1.8. During the same period, 1,753 patients underwent coronary artery bypass grafting using an SVG (average number of grafts per patient, 3.2). The average patient age was similar: 62.3 years for IMA grafts and 64.7 years for SVGs. Men constituted two thirds of each group. Left ventricular function was impaired (ejection fraction less than 45%) in 1,071 (51%) of IMA grafts and 847 (48.3%) of SVGs. Other aggregate risk factors, ie, elevated blood pressure, diabetes mellitus, previous myocardial infarction, and congestive heart failure, were similar in each group. Operative results and postoperative mortality of the IMA and SVG patients were comparable. However, the long-term probability of cumulative survival and occlusion-free survival were significantly greater and the probability of recurrent angina and reoperative coronary artery bypass grafting were significantly less in IMA graft patients (p less than 0.015). The relative risk of occlusion in an SVG was 4 to 5 times greater than that of the IMA graft. These data indicate that a patent IMA graft to the anterior descending coronary artery protects against recurrent angina and death from cardiac-related causes, and that the IMA should be the conduit of choice.

Adult↗

Technique and results with a roller pump left and right heart assist device.

During the last 10 years we have inserted a roller pump-driven left heart assist device in 72 patients and a right heart assist device in 7 patients for profound heart failure after a variety of cardiac surgical procedures. In addition a percutaneous left heart assist device (transseptal insertion of left atrial cannula via a femoral vein) was employed in 5 patients with profound cardiogenic shock after acute myocardial infarction. Thirty patients (41.7%) were weaned from the left heart assist device and 21 (29.2%) were discharged from the hospital. Two patients (40.0%) were weaned from the right heart assist device, but both later died during the postoperative period. Of the 5 patients in whom a percutaneous left heart assist device was inserted, 4 underwent successful emergency percutaneous transluminal coronary angioplasty, but all 5 patients died. Causes of death included severe coagulopathy, irreversible extensive myocardial infarction and cardiac failure, refractory arrhythmias, severe "shock" lung, and multisystem failure. In summary, satisfactory results can be achieved with a roller pump-driven left and right heart assist device for severe postoperative heart failure. Further experience should be obtained with the percutaneous technique to assess its efficacy in treating patients with acute myocardial infarction and cardiogenic shock.

Assisted Circulation↗

Internal mammary artery bypass: effect on longevity and recurrent angina pectoris in 2900 patients.

Internal mammary artery bypass (IMA) to the anterior descending coronary artery was performed in 2900 patients from January 1978 to December 1987. The average age of the patients was 64 years. Males accounted for 68% (1972 patients) and 82% (2378 patients) were in New York Heart Association (NYHA) class III. Left ventricular function was impaired in 51%. The average number of additional saphenous vein grafts per patient was 1.8. The operative mortality was 1.6%. Mediastinitis occurred in 29 patients (1%). Reoperation for bleeding was necessary in 32 patients (1.1%). Perioperative myocardial infarction (MI) was seen in 58 patients (2%) and neurological complications occurred in 32 patients (1.1%). Repeat coronary angiography was performed in 703 patients (25%) and demonstrated a patency rate of 96% in IMA grafts and 81% in saphenous vein grafts (SVG). Survival at 9 years was 90% from all causes and 95% when noncardiac deaths were excluded. Recurrence of angina occurred in 522 patients (18%) and reoperation was performed in 15 patients (0.5%). During the same time period, 1783 patients underwent coronary artery bypass utilizing a SVG. Survival at 9 years was 78% from all causes and 83% when noncardiac deaths were excluded. Recurrent angina was present in 546 patients (39%). These data suggest that a patent-IMA to the anterior descending protects against recurrent angina and death from cardiac causes and should be the conduit of choice.

Angina Pectoris↗

Role of leukotriene B4 in the pathogenesis of Klebsiella pneumoniae-induced bovine mastitis.

Mastitis was induced in 4 lactating cows by inoculation of Klebsiella pneumoniae (10(7) organisms/ml) via the teat canal. Sterile isotonic saline solution (1 ml) was instilled into designated control quarters via the teat canal. Changes in milk leukotriene B4 and C4 (LTB4, LTC4) concentrations, milk somatic cell counts, and milk bovine serum albumin concentration were monitored over a 24-hour postinoculation period. Milk LTB4 concentration before inoculation in control quarters and quarters later to be infected was 376 +/- 45 and 326 +/- 56 pg/ml of milk, respectively. A significant (P less than 0.05) increase in milk LTB4 concentration in the infected quarters was first observed at postinoculation hour 6, and milk LTB4 concentration in infected quarters generally remained significantly high through postinoculation hour 14. Thereafter, milk LTB4 concentration in infected quarters was not significantly different from the concentration in control quarters. Measurable amounts of LTC4 were not detected in the milk of either control or infected quarters. Milk bovine serum albumin concentration in the infected quarters generally was high throughout the study, as were milk somatic cell counts. The results of this study suggested that LTB4 contributes to the pathogenesis of bovine mastitis.

Animals↗

Effect of blood bonding on bursting strength of laser-assisted microvascular anastomoses.

This experiment evaluated the influence of blood on the weld strength of laser-assisted microvascular anastomoses (LAMA). Rat femoral arteries were anastomosed end-to-end by either direct laser welding (group I) or by a blood-bonded technique (group II) whereby fresh blood was applied to the vessel edges before laser exposure. Bursting strength was measured at 0, 1, and 24 hours and at 3 and 7 days by infusing methylene blue into the vessel while pressure was monitored. The results showed significantly increased bursting strength in group II compared with group I at 0 hour and 7 days (P less than 0.05). There was a significant increase in bursting strength in group I from 0 hour to 1 hour (P less than 0.05). It is concluded that blood-bonding enhances the early bursting strength of LAMAs and may facilitate arterial wall healing.

Anastomosis, Surgical↗

Enhancement of CO2 laser microvascular anastomoses by fibrin glue.

Laser-assisted microvascular anastomoses (LAMA) are characterized by low early bursting strength and high aneurysm rates. The effects of fibrin glue on bursting strength (BS), patency, and aneurysm rate of LAMAs were compared to standard suture and laser anastomosis. Rat femoral arteries (0.9-1.1 mm) were anastomosed end-to-end by three methods: (1) conventionally with 8 to 10 interrupted 10-O nylon sutures; (2) 3 stay sutures and CO2 laser (spot size, 0.275 mm; pulse, 0.2 sec, 80 mW); and (3) cryoprecipitated fibrinogen, 35 mg/cc, crystallized thrombin, CaCl, 20 mg/cc, aprotinin (2000 kIU/cc) applied to weld site in conjunction with laser weld as in (2) above. Patency, aneurysms, and histology were evaluated at 3 weeks, and BS (mm Hg) was measured in six additional vessels at 1 and 24 hr. There was no statistically significant difference in patency rates. Both the suture and fibrin glue groups had significantly higher 1 and 24 hr bursting strengths (P less than 0.05) and significantly lower aneurysm rates (P less than 0.001) than standard laser. There was no significant difference in bursting strength between suture and fibrin glue groups. Histology in the fibrin glue group showed medial damage similar to the LAMA and calcification of aneurysmal vessels. Fibrin glue enhancement of LAMAs produces equal patency, higher early bursting strength, and fewer aneurysms at 3 weeks compared to conventional laser.

Anastomosis, Surgical↗