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Biomedical subjects

J J Ferrara

Publications and source records attributed to J J Ferrara.

At least 55 records · Page 3Linked to original sources

Serotonin receptors regulate canine regional vasodilator responses to burn.

OBJECTIVE: To determine which serotoninergic receptor subtype(s) mediates the regional vasodilator response to scald injury. DESIGN: Prospective, randomized trial. SETTING: Microcirculation research laboratory. SUBJECTS: Anesthetized dogs. INTERVENTIONS: Mechanically ventilated dogs underwent cannulation of a brachial artery and placement of an ultrasonic flow probe around one femoral artery. All animals received a 2% to 3% body surface area partial thickness scald injury by immersing the paw ipsilateral to the instrumented femoral artery into 100 degrees C water for 5 secs. In one group of dogs, BMY 7378 (a serotoninergic1A receptor antagonist) was given by the peripheral intravenous route before burn. These results were compared with those findings obtained from a group of animals that received a burn only, and groups of animals given a peripheral intravenous injection of methysergide (a serotoninergic receptor antagonist) or ritanserin (a serotoninergic2 receptor blocking agent) before burn. Experiments were conducted for two postburn hours. MEASUREMENTS AND MAIN RESULTS: Burn injury caused a marked and persistent increase in regional (e.g., femoral artery) blood flow, an effect that was significantly blunted by preburn administration of the serotoninergic receptor antagonist, methysergide. Preburn administration of BMY 7378 increased baseline femoral blood flow by 13%, reflecting its known serotonin agonist properties. However, when compared with the mean postscald increases in femoral blood flow over baseline seen in scald only dogs and in animals given the serotoninergic2 receptor blocking agent, ritanserin (before scald), the BMY 7378-treated group demonstrated a significant (p < .001 by analysis of variance) 2-hr-postscald blunting of this femoral vasodilator response. CONCLUSION: These data suggest that serotoninergic1A-like receptors play an integral, albeit not an exclusive, role in blood flow regulation to the site of burn injury.

Animals↗

Effects of methysergide administration on edema formation at the site of scald.

Femoral blood flow (Qa), hind paw lymph flow (Qlym), and lymph-to-plasma protein concentration ratio (Clym/Cp) were monitored before and 4 h after 1) 5-s 100 degrees C paw scald, 2) methysergide (1 mg/kg iv) 20 min before scald, 3) methysergide 30 min after scald, and 4) methysergide only. Before experimentation, hind paw venous pressure was elevated and maintained until steady-state Qa, Qlym, and minimal Clym/Cp levels were reached. The reflection coefficient (sigma d) was determined as 1 - minimal Clym/Cp; the filtration coefficient (Kf) was calculated. Methysergide alone caused no changes. Increases in Qa, Qlym, Clym/Cp, and Kf were identified in all scald groups. Compared with scald only animals, pre- and postscald methysergide blunted the increases in Qa, Qlym, Kf, and paw weight gain without an effect on sigma d. These data demonstrate that methysergide reduces edema formation at the site of scald, perhaps by modulating the burn-induced vasodilator response and/or by limiting the burn-induced increase in microvascular surface area.

Animals↗

Effects of graded thermal injury on microvascular permeability at the site of injury.

To define whether capillary permeability traits at the site of a burn differ according to injury severity, a canine hind leg lymphatic was cannulated to measure macromolecular permeability in response to three different scalding solutions. Leg venous pressure was raised to approximately 40 mm Hg and maintained until a minimal lymph-to-plasma total protein ratio (CL/CP)min and steady-state lymph flow (QL; microliter/min/100 g) was attained. The protein reflection coefficient (1-CL/CP), fluid filtration coefficient (Kf; microliter/min/mm Hg/100 g), and QL were determined before and for 6 hr after a 5-sec hind paw immersion in either 100 degrees C (n = 7), 80 degrees C (n = 7), or 70 degrees C (n = 7) water. A group of five animals served as controls. In the absence of any systemic hemodynamic alterations, the 100 and 80 degrees C scald groups experienced significant (P < 0.05, ANOVA) increases in QL, CL/CP, and Kf as compared to respective preburn values and time-matched unburned control values. Most monitored parameters were significantly higher following 100 degrees C injury vs 80 degrees C injury. Parameters in the 70 degrees C group did change after scald, but were not significantly different from preburn values or from the control group. Alterations in capillary permeability to protein and fluid flux measured at the burn site are graded, not all or none phenomena, being dependent upon the severity of injury.

Analysis of Variance↗

Redistribution of organ blood flow after hemorrhage and resuscitation in full-term piglets.

Newborn piglets (aged 1 to 2 days and 7 to 14 days) were used to study (1) the redistribution of organ blood flow after a 25% acute blood loss and (2) the response to resuscitation with shed blood (20 mL/kg), crystalloid (normal saline [NS] or lactated Ringer's [LR]; 60 mL/kg), and colloid (Dextran-40, 20 mL/kg). Hemodynamic parameters showed little differences in the response to hemorrhage and resuscitation. The two age groups had no significant differences in parameters or blood flow (results combined). The animals maintained flow to the heart and central nervous system (CNS) and had significantly decreased flow to the kidneys and splanchnic organs. In the gastrointestinal tract, the small intestine was affected most severely, with a significant decrease in blood flow, especially to the mucosa. In all organ systems, Dextran 40 restored blood flow to levels significantly above the baseline. Shed blood and crystalloid restored flow to organs sustaining decreased flow, but crystalloid did not restore flow to the baseline level in the kidney and all segments of the gastrointestinal tract.

Animals↗

The effects of albumin administration on microvascular permeability at the site of burn injury.

In a canine hind leg model, lymph flow (QL), lymph (CL), and plasma (CP) total protein concentrations, the reflection coefficient for total proteins (sigma d), and the filtration coefficient (Kf) were determined before and for 6 hours after a 5-second 100 degrees C hind paw scald (3% total body surface area, TBSA). Before injury, hind leg venous pressure was elevated and maintained by outflow restriction until a minimal, steady-state CL/CP ratio was achieved. Albumin (5%) was infused 30 minutes after the scald at low (0.4 mL/kg/% TBSA) or high (2 mL/kg/% TBSA) doses. Scald uniformly increased QL, CL/CP, Kf, and paw weight gain (PWG). Whereas postburn infusion of low-dose albumin mildly attenuated increases in CL/CP and PWG noted in scald-alone animals, no differences were noted between the scald and scald/high-dose albumin groups.

Albumins↗

Laparoscopic cholecystectomy: what's so special?

One hundred seventy-one laparoscopic cholecystectomies were done by senior surgery residents who received only traditional "hands-on" training. Eight patients (5%) required conversion to open cholecystectomy, and two had complications requiring immediate celiotomy (one common bile duct injury, one "dropped" gallbladder). The average operative time was 91 minutes (range, 30 to 245 minutes). There were no deaths and only five postoperative complications related to the procedure (retained common bile duct stone in four cases, intra-abdominal hemorrhage in one). There were three complications unrelated to the procedure. Data acquired from recent resident training program graduates show that these practicing surgeons are doing laparoscopic cholecystectomy with a 95% success rate and have yet to encounter appreciable complications. We concluded that a large-volume general surgery resident training program provides adequate opportunity for training surgeons in the techniques of laparoscopic cholecystectomy; there is no need to attend an expensive and time-consuming classroom and animal laboratory course.

Adolescent↗

Analysis of regional hemodynamic regulation in response to scald injury.

Ultrasonic probes were placed around dog femoral arteries to record blood flow. Hind paw scalding with boiling water (5 s) caused a marked increase in ipsilateral femoral blood flow that persisted for the 2-h observation period. Contralateral femoral blood flow and systemic and pulmonary vascular resistances were unchanged. Compared to scald only animals, methysergide pretreatment diminished and shortened the femoral vasodilator response to scald (109 +/- 14 vs 243 +/- 27 ml/min at 5 min; 59 +/- 14 vs 191 +/- 31 ml/min at 2 h). Pretreatment with ritanserin, BW A1433U83, atropine, ICI 118551, diphenhydramine, ranitidine, meclofenamate, L-nitro-arginine methyl ester, 3-amino-1,2,4-triazine, and U 37883A had no effect on the increased femoral blood flow response to scald, suggesting this vasodilator response is not dependent upon activation of serotonergic2, adenosineA1, muscarinic, beta 2-adrenergic, histaminergic1 or histaminergic2 receptors, on cyclooxygenase products, endothelium-derived relaxing factor derived from nitric oxide (NO) synthase III, NO derived from NO synthase II, or KATP channels, respectively. Methysergide given after burn immediately reduced the augmented femoral blood flow to preburn levels, suggesting the vasodilator response to scald is mediated through continual activation of local serotonergic1-like receptors, which may be target site(s) for therapeutic interventions to influence burn-induced hemodynamic alterations.

Adamantane↗

Effects of pentafraction administration on microvascular permeability alterations induced by graded thermal injury.

BACKGROUND: Pentafraction is a pentastarch derivative hypothesized to limit burn edema by "sealing" damaged capillaries, restoring a barrier to fluid translocation and macromolecular (protein) flux. METHODS: Canine hind paw lymph flow (QL) and lymph (CL) and plasma (CP) protein concentrations were measured before and for 6 hours after (1) 5-second 100 degrees C (n = 6) or 80 degrees C (n = 6) foot paw scald, (2) 100 degrees C (n = 5) or 80 degrees C (n = 5) foot paw scald followed 30 minutes later by a 4 cc/kg bolus of 6% pentafraction, or (3) pentafraction infusion without scald (n = 5). Before scald or pentafraction infusion, hind paw venous pressure was elevated and maintained by outflow restriction until a steady state, minimal CL/CP was reached. The reflection coefficient, sigma d, was determined as 1-CL/CP, and the (fluid) filtration coefficient (Kf) was calculated. RESULTS: Scalding uniformly produced statistical (p < 0.05, ANOVA) increases in QL, CL/CP, sigma d, Kf, and paw weight gain. Postburn pentafraction infusion produced no enduring alterations in any measured parameter as compared with those of animals who received a matched severity scald without pentafraction. CONCLUSIONS: Pentafraction does not appreciably ameliorate the adverse microcirculatory consequences observed at the site of burn injury.

Animals↗

Utility of the biofragmentable anastomotic ring in traumatic small bowel injury.

OBJECTIVE: To evaluate the use of the 25 mm Biofragmentable Anastomotic Ring (BAR) in traumatic small bowel injury. METHODS: In a one year prospective, nonrandomized study, 18 patients (x age = 25 yrs) with penetrating small bowel injury had 25 BAR devices placed to restore intestinal continuity. Using one-way analysis of variance, this group was compared to 63 historical controls (x age = 27 yrs) with small bowel trauma who had either sutured or stapled anastomoses (SSA), with regard to Penetrating Abdominal Trauma Index (PATI) score, time until return of bowel function, and postoperative morbidity. RESULTS: PATI scores for the two groups were not significantly different (P = 0.099). No deaths in the SSA group (n = 8) or in the BAR group (n = 1) were related to the anastomotic technique. There was no significant difference (P = 0.991) in the rate of post-operative intestinal obstruction between BAR (n = 3) and SSA (n = 8) groups; none of the BAR patients required re-operation. The average length of time for return of bowel function was not significantly different (P = 0.197) between BAR (4.3 days) and SSA (5.8 days) groups. CONCLUSIONS: The 25 mm BAR may be used in the repair of traumatic small bowel injury, based upon comparable outcomes when compared with sutured and stapled anastomoses.

Adolescent↗

A convincing case for primary repair of penetrating colon injuries.

Over the past 14 years, 146 patients with penetrating colon trauma were managed by primary repair with/without resection (PR, n = 55), and by diverting colostomy (DC, n = 91). These groups did not differ in terms of age, ISS (Injury Severity Scale), PATI (Penetrating Abdominal Trauma Index), a-AIS (abdominal Abbreviated Injury Scale), or preoperative hypotension. No intergroup differences were manifested in intra-abdominal complications (fistula/leak, abscess, pancreatitis, intestinal obstruction, wound dehiscence). The percentage of patients who experienced at least one major intra-abdominal complication did not differ statistically when the two groups were compared--12.7% in PR versus 11% in DC--although risk in both groups increased with the additional number of organs injured. Wound infection was significantly higher (p < 0.05) in the PR group (19.6%) compared with the DC group (9.4%). Mortality in the PR and DC groups was 0% and 3.6%, respectively. One hundred and ten patients who underwent elective colostomy closure following trauma had a 9.1% intra-abdominal complication rate and a 3.6% wound infection rate. These risks should be considered when colostomy is selected to manage patients with penetrating colon injury. These data support primary repair of all colon injuries, reserving skin closure for patients with limited collateral damage.

Adult↗

Indomethacin-induced blood flow distribution in premature and full-term piglets.

Indomethacin (IND), widely used in premature infants to effect nonoperative closure of patent ductus arteriosus (PDA), has been implicated in gastrointestinal tract (GI) perforations and necrotizing enterocolitis (NEC). The vasoactive effects of IND could simultaneously affect regional blood flow distribution, specifically a decrease in intestinal blood flow. This study determined blood pressure (BP), heart rate (HR), cardiac output (CO), total peripheral resistance (TPR) and regional blood flows (mL/min/g) at baseline, 15, 60, and 120 minutes after intravenous infusion of IND (0.4 mg/kg) in three groups: preterm piglets delivered 7 to 10 days before term; 1- to 2-day-old piglets; and 7- to 14-day-old piglets. IND did not significantly affect hemodynamic parameters (BP, HR, CO, TPR) or regional blood flows to the heart, central nervous system, kidney or GI tract in the premature animals. In 1- to 2-day-old animals, a significant increase in BP and TPR occurred at 120 minutes, with significant decreases in blood flow to the GI tract in the esophagus, stomach, and rectosigmoid. In the 7- to 14-day group CO significantly decreased while TPR increased. Significant decreases in blood flow occurred throughout the GI tract, most pronounced in the small intestine and colon, essentially due to decreased mucosal blood flow. Our study indicates that indomethacin can cause selective GI tract mucosal ischemia, and that the effect is increased in the more developed animal. This effect on mucosal blood flow suggests the GI tract disturbances seen after IND administration are due to an ischemic injury to mucosa previously affected by ischemia-reperfusion injury from other stresses.

Aging↗

Breast cancer after mammary augmentation.

Augmentation mammoplasty has been said to reduce the risk for subsequent development of mammary gland carcinoma, but it may confer a worse prognosis should breast cancer develop. Nine patients who had breast cancer after augmentation mammoplasty were treated at the Ochsner Foundation Hospital and Clinic. The mean interval between augmentation and the development of a palpable mass was 6.8 years (range, 2 to 20 years). Four patients were treated with modified radical mastectomy, one was treated with radical mastectomy, and four were treated with tylectomy, axillary dissection, and radiotherapy. One of the four treated with tylectomy required salvage mastectomy. Reconstructions were done in all except one mastectomy patient. Five patients had stage I disease and four had stage II disease at the time of diagnosis. Over a mean follow-up of 4.75 years from the time of diagnosis of carcinoma of the breast, three of the four patients with stage II disease have either had recurrent disease or died of breast cancer, and one of the patients with stage I disease died with hepatic metastases. Mammography was not found to be useful for the detection of masses after augmentation mammoplasty. Needle aspirations were useful for diagnosis of nodal disease outside the breast, but not helpful in diagnosis of the breast lesion proper. Our analysis suggests that breast augmentation and the patient's psychologic considerations may delay the diagnosis of breast cancer. Additionally, patients may fare worse when breast cancer develops after mammary augmentation. We recommend preoperative mammography in most patients before mammary augmentation, particularly in those over the age of 30 years and those with a family history of breast cancer.

Adult↗

The role of endoscopic retrograde cholangiopancreatography: sphincterotomy versus common bile duct exploration as a primary technique in the management of choledocholithiasis.

253 patients underwent diagnostic or therapeutic intervention for a presumed diagnosis of choledocholithiasis. In 104 (mean age, 60 years) the diagnosis was confirmed by endoscopic retrograde cholangiopancreatography (ERCP) or common bile duct exploration (CBDE). Of this group, 70 patients first underwent a total of 102 attempts at endoscopic sphincterotomy (ERCP-S). Success (clearing the common duct of stones) was achieved in 43 patients (61%), though an average of 1.5 ERCP-S/patient was required (maximum of four per patient). Of the 27 in whom ERCP-S failed, 20 went on to CBDE, which was successful in 18. Significant morbidity occurred in 12 (17%) ERCP-S patients, including hemorrhage. There were no deaths. Of the 34 patients who first underwent CBDE, 30 were cleared of common duct stones (88%). ERCP-S was subsequently employed to retrieve retained stones in three patients. Significant morbidity was documented in three (9%). No patients required perioperative blood transfusion. There were no deaths. While there is, as expected, a lower initial success rate with ERCP-S than with CBDE, the fact that ERCP-S is a less invasive procedure than is CBDE justifies its preferential utilization. However, patients must be informed that successful ERCP-S may require multiple visits to the endoscopy suite. Furthermore, the morbid consequences of ERCP-S, particularly hemorrhage, cannot be understated.

Cholangiopancreatography, Endoscopic Retrograde↗

Irrigation of the abdominal cavity in the treatment of experimentally induced microbial peritonitis: efficacy of ozonated saline.

Ozone is an oxidizing agent possessing potent in vitro microbicidal capacity. This study was designed to address the extent to which irrigation of the contaminated abdominal cavity using a saline solution primed with ozone is effective in reducing morbidity and mortality. Gelatin capsules containing different quantities of a premixed slurry of filtered human fecal material were implanted in the peritoneal cavities of a preliminary series of rats. Three inocula concentrations were selected for later experiments, based upon their ability to produce morbid consequences: (1) high (100% 1-day mortality), (2) medium (70% 3-day mortality, 100% abscess rate in survivors), and (3) low (100% 10-day survival, 100% abscess rate). Fecal and abscess bacteriology were similar in all rats. The peritoneal cavities of 240 rats then underwent fecal-capsule implantation (three groups of 80 rats/inoculum concentration). At celiotomy 4 hours later, equal numbers of rats from each group were randomly assigned to one of four protocols: (1) no irrigation, (2) normal saline irrigation, (3) saline-cephalothin irrigation, and (4) ozonated saline irrigation. Each treatment lasted 5 minutes, using 100 ml of irrigation fluid. Mortality was significantly reduced when, in lieu of no irrigation, any of the irrigation solutions were used. Additionally, ozonated saline statistically proved the most effective irrigating solution for reducing abscess formation in survivors.

Abscess↗

Effects of hypertonic saline and dextran 70 resuscitation on microvascular permeability after burn.

Administration of hyperosmolar fluids to burn patients has been proposed as a means of decreasing resuscitative fluid volume and, subsequently, wound edema accumulation. To test this hypothesis, canine hindpaw lymph flow (QL) and lymph (CL) and plasma (CP) total protein concentrations were measured, and capillary filtration coefficient (Kf) was calculated before and for 6 h after a 5-s 100 degrees C footpaw scald. Scald was followed 30 min later by bolus infusion (4 ml/kg) of 7% saline or 6% Dextran 70 or the two in combination. Before scald, venous pressure was elevated until a minimal CL/CP was reached. The reflection coefficient (sigma d) was calculated by the formula: 1-minimal CL/CP. Scald increased QL, CL/CP, and Kf, but sigma d was decreased (P less than 0.05). Compared with burn alone, 7% saline exacerbated burn-induced increases in QL and Kf. In contrast, infusion of Dextran 70 did not exacerbate these changes in QL or Kf. Perhaps more importantly, Dextran 70 may have attenuated the increase in CL/CP and reduced edema formation in the burned hindpaw. However, the addition of 7% saline to the dextran eliminated these beneficial effects.

Animals↗

Selective nonoperative management of solid breast masses.

A prospective study evaluated the hypothesis that, following consistent clinical and mammographic guidelines, many women with breast masses can be nonoperatively managed. One hundred eighty women with solid breast masses were assigned both a clinical and mammographic diagnosis by each a surgeon and radiologist. Immediate biopsy (n = 78) was recommended when either clinician thought that the mass was malignant (52 cancers). The remainder were offered a trial of observation, with interval biopsy performed upon patient preference or for increased clinical/mammographic concern. Of the 89 who consented to this, 70 received long-term follow-up (X = 22 months) with improvement in the characteristics of the mass. The diagnosis of invasive cancer was delayed in two women initially observed, with no apparent impact on survival. It is concluded that many women with solid breast masses can be safely observed. Biopsy remains warranted for any mass suspicious for malignancy on clinical/mammographic grounds, or if follow-up cannot be assured.

Biopsy↗

Increased hyaluronan flux from skin following burn injury.

Hyaluronan (formerly hyaluronic acid) is an important constituent of the interstitial matrix in skin. Following major burn injury in animal models, plasma hyaluronan can increase to levels 10-fold greater than normal. The present experiments were designed to determine whether this is a result of the increased lymph flow (QL) accompanying the injury or of an increased release of hyaluronan from the burned skin and subcutaneous tissue. The lateral saphenous vein and a prenodal lymphatic were cannulated in the hindpaw of five anesthetized canines. Hindpaw venous pressure was elevated until the total protein concentration in lymph declined to steady-state levels, and QL and hyaluronan flux (QL X [hyaluronan]) was measured. A minor burn was inflicted by immersion of the paw into 100 degrees C water for five sec, and measurements were repeated at regular intervals for a minimum of 4 hr. Burn injury resulted in significant and persistent increases in QL (154 +/- 61 microliters/min versus 562 +/- 105 microliters/min 4 hr postburn) and lymph total protein concentration (1.34 +/- 0.04 g/dl versus 4.08 +/- 0.18 g/dl 4 hr postburn), while lymph hyaluronan concentration fell (3.01 +/- 0.20 micrograms/ml versus 2.1 +/- 0.16 micrograms/ml 4 hr postburn). The resultant increase in hyaluronan flux (0.42 +/- 0.13 microgram/min versus 1.17 +/- 0.22 microgram/min 4 hr postburn) appears to be a function of lymph flow rather than burn-induced release of skin hyaluronan. Hence, the increased plasma concentration of hyaluronan following major burns is likely a consequence of increased lymph flow from the site of injury.

Animals↗

Intraoperative evaluation of intestinal ischemia: a comparison of methods.

Methods for evaluating intestinal ischemia include standard clinical criteria, Doppler ultrasonography, and intravenous fluorescein injection. Each has disadvantages, and a combination of methods is often used. The purpose of this study was to determine whether surface oximetry could be used to assess perfusion in an animal whose intestinal diameter approximates that of infants. Reversible arterial, venous, and arteriovenous occlusion was studied in rabbit intestines. After 6 to 8 hours of occlusion, intestinal vascularity was evaluated by the four methods listed. Doppler ultrasonography and surface oximetry were found to be unreliable tools for assessing perfusion in this animal model. We conclude that standard clinical criteria and fluorescein remain the standards for intraoperative evaluation of intestinal perfusion.

Animals↗