Biomedical subjects

T M Sullivan

Publications and source records attributed to T M Sullivan.

At least 19 recordsLinked to original sources

PubMed2002

Effect of saline acclimation on body water and sodium compartmentalization in Pekin ducks (Anas platyrhynchos).

The compartmentalization of body fluids was measured in individual Pekin ducks ( Anas platyrhynchos) drinking freshwater and after sequential acclimation to 300 mM NaCl and 400 mM NaCl. Total body water, extracellular fluid volume, plasma volume and exchangeable sodium pool were measured using (3)H(2)O, [(14)C]-polyethylene glycol, Evans Blue dye, and (22)Na dilution, respectively. Following acclimation to 300 mM NaCl, body mass decreased, but total body water and total exchangeable sodium pool were unaltered. Na and water were redistributed from the extracellular fluid (interstitial fluid) compartment into the intracellular fluid compartment. Following further acclimation to 400 mM NaCl, body mass, total body water and intracellular fluid volume decreased, but exchangeable sodium pool and extracellular fluid volume were unchanged. Our results suggested that, when Pekin ducks drink high but tolerable salinities, they maintain total body water, but redistribute Na(+) and water from interstitial fluid to the intracellular fluid compartment. When stressed beyond their ability to maintain total body water, they lose water from the intracellular fluid.

Acclimatization↗

PubMed2001

A reappraisal of a modified through-knee amputation in patients with peripheral vascular disease.

BACKGROUND: Through-knee amputation provides a longer lever arm and improved muscle control of the limb compared with above-knee amputation. Through-knee amputation also allows use of a total end-bearing prosthesis, which avoids the ischial pressure and suspension belts required of the above-knee amputation prosthesis. Several reports in the European literature tout the superiority of the through-knee amputation over the above-knee amputation in the patient with vascular disease. Through-knee amputation has received little attention in the United States, however, owing to the belief that the long flaps necessary to close a standard through-knee amputation are associated with an unacceptable rate of wound problems and offer no functional ambulatory advantage to above-knee amputation. We reviewed our experience with a modified technique of through-knee amputation in a group of patients with severe lower extremity ischemia who were not candidates for below-knee amputation to determine the incidence of wound complications and their functional outcome. METHODS: Since 1996, 12 patients with severe lower extremity arterial insufficiency have undergone through-knee amputation utilizing a technique designed to limit flap length and facilitate the fit of a suction prosthesis. Two patients died of myocardial infarction in the immediate postoperative period and were excluded from the study. In the remaining 10 patients (1 man, 9 women; mean age 63 years (range 40 to 86), the below-knee amputation level was precluded because of gangrene or nonhealing wounds of the mid leg in 5 patients, failure of a previous below-knee amputation attempt in 4 patients, and severe ischemia that would compromise below-knee amputation healing in 1 patient. Nine patients had at least one failed vascular reconstruction procedure. RESULTS: Mean follow-up is 25 months (range 6 to 41). Six (60%) patients had primary healing of their amputations. Two (20%) patients had delayed healing (6 weeks and 8 weeks). Two (20%) patients developed wound infections, which required amputation revision to the above-knee level. Seven (70%) patients were fitted with a suction socket prosthesis and are fully ambulatory. One patient healed but has not ambulated because of ischemia and subsequent ulceration of the contralateral limb. CONCLUSIONS: These data show that through-knee amputation is associated with an acceptable primary healing rate (80%) and satisfactory functional outcomes (70% ambulation) in a high-risk vascular population. The functional advantages of through-knee amputation over above-knee amputation make it the preferred alternative for patients with vascular disease.

Adult↗

PubMed2000

Isolated arteriovenous dialysis access graft segment infection: the results of segmental bypass and partial graft excision.

Arteriovenous (AV) access graft infection results in disruption of dialysis and usually necessitates graft removal when the entire graft is involved. The management of an isolated infected segment of an otherwise noninfected AV access graft, however, remains controversial. To evaluate the utility of segmental bypass and partial graft excision for the treatment of an isolated infected AV access graft segment, 17 consecutive cases in 12 patients (7 females/5 males; 14 arm grafts/3 leg grafts; median age = 69 years) were analyzed on a vascular teaching service that performed 1244 total access procedures from January 1995 through February 1999. Infections presented as a draining sinus or a sinus with hemorrhage emanating from an area over the graft. At operation, the infected sinus was covered by a transparent occlusive dressing and the graft was explored through clean incisions proximal and distal to the infected segment. If the graft was incorporated and free of infection, a piece of expanded polytetrafluoroethylene (ePTFE) was anastomosed proximally end-to-end and tunneled through noninfected tissues around the infected sinus. After the distal anastomosis was performed, the skin incisions were closed and covered with occlusive dressings. The infected graft segment was then removed through the infected sinus wound. The technique of segmental bypass and partial graft excision results in predictable eradication of infection, graft salvage, and maintenance of uninterrupted dialysis in patients presenting with an isolated AV dialysis access infection.

Aged↗

PubMed2000

Intravascular ultrasound assessment of iliac stent procedures.

PURPOSE: To determine whether intravascular ultrasound (IVUS) is more sensitive in identifying incomplete stent deployment or mechanical disruption compared to angiography. METHODS: Over a 9-month period, 44 patients (25 men; mean age 63 years, range 36-88) treated for common or external iliac artery stenoses with balloon angioplasty and stenting underwent IVUS interrogation following completion arteriography. RESULTS: One hundred nine stents were deployed in the 44 patients. Of these, 29 (27%) stents (in 45% of patients) were found by IVUS to be incompletely deployed or to have an associated mechanical disruption despite a normal completion arteriogram. Further treatment (repeat dilation or additional stenting) was performed in 28 cases; 1 hemodynamically insignificant dissection was not treated. Twenty-six (93%) of these interventions were successful as determined by IVUS; 2 underexpanded stents did not respond to redilation. CONCLUSIONS: Incomplete stent deployment or mechanical problems associated with stenting were common in this study, occurring in nearly half of the patients. IVUS has clinical utility in identifying incomplete deployment or mechanical problems in stents with an increased sensitivity compared to contrast angiography.

Adult↗

PubMed2000

Concomitant renal revascularization with aortic surgery: are the risks of combined procedures justified?

Indications for concomitant renal revascularization during aortic surgery are not well established. Higher mortality and poorer results are often cited. To examine this, all combined aortic and renal revascularization procedures from August 1992 until May 1998 were reviewed. Of 2003 major arterial reconstructions performed on the Vascular Teaching Service, 45 patients (2%) underwent renal revascularization. Of these 31 patients (69%) had combined aortic and renal procedures. Aortic pathology in these 31 patients (54% male, 94% white, median age 64 years) included arterial occlusive disease (n = 21; 47%), abdominal aortic aneurysm (n = 6; 13%), and thoracoabdominal aortic aneurysm (n = 4; 9%). In all 31 cases the patient presented because of the aortic pathology. Indications for concomitant renal revascularization included renovascular hypertension (n = 21; 68%) and preservation of renal function (n = 10; 32%). Renal revascularization procedures included transaortic endarterectomy (n = 23; 74%), renal bypass (n = 7; 23%), and both bypass and endarterectomy (n = 1; 3%). Seven (22%) complications and two (6%) deaths (both patients operated on for renal salvage) occurred perioperatively. Complications included wound infection (n = 2; 6%), postoperative bleeding (n = 1; 3%), respiratory failure (n = 1; 3%), deep venous thrombosis (n = 1; 3%), cerebrovascular accident (n = 1; 3%), and pseudomembranous enterocolitis (n = 1; 3%). All patients either were cured of their hypertension (n = 5; 24%) or were improved (n = 16; 76%) at 3 months. No patient to date operated on for renal salvage progressed to chronic hemodialysis, but mortality was higher after renal revascularization for renal salvage versus hypertension (20% vs. 0; P = 0.034). There was no significant difference in mortality between the combined aortic/renal procedures versus aortic procedures alone. Despite adding complexity, renal revascularization in patients undergoing aortic surgery appears relatively safe and effective. These data favor an aggressive approach toward renal revascularization in selected patients needing aortic surgery.

Adult↗

PubMed2000

Ultrasound-guided thrombin injection of iatrogenic femoral pseudoaneurysms: a prospective analysis.

An adverse consequence of the use of the femoral artery for the endovascular evaluation and treatment of arterial disease is the increased incidence of iatrogenic femoral pseudoaneurysms. Although surgical repair has traditionally been used to treat such aneurysms, less invasive modalities have emerged. The purpose of this study is to prospectively evaluate ultrasound-guided thrombin injection (UGTI) for the treatment of iatrogenic femoral pseudoaneurysms. A treatment protocol was approved and 30 stable patients (21 female; age range 43-85 years; mean 67 years) were prospectively enrolled from December 1997 through June 1999 to undergo UGTI on 30 iatrogenic femoral pseudoaneurysms. Pseudoaneurysms occurred after cardiac intervention (n = 22, 73%), peripheral intervention (n = 7, 23%), and after a femoral line placement (n = 1, 3%). They ranged in size from one to 5 cm with a time interval from intervention until UGTI of one to 132 days (median 3 days). Eleven patients (37%) were systematically anticoagulated at the time of UGTI. All pseudoaneurysms were treated using sterile technique and local anesthesia with ultrasound-guided injection via a 20-gauge spinal needle of 0.1 to 2 cm3 (median 0.6 cm3) of 1000 units/cm3 topical thrombin solution administered by one of six physicians. A period of bedrest for 4 to 6 hours after injection was followed by repeat groin duplex scan at 24 hours and a clinical follow-up at 30 days. There were no procedural deaths or nonvascular complications. Twenty-seven (90%) UGTIs resulted in successful pseudoaneurysm ablation with no recurrences at 24 hours or 30 days. Two (7%) UGTIs failed and one (3%) femoral artery embolic complication occurred; all were successfully treated with surgery. Success appeared to be independent of anticoagulation status, pseudoaneurysm age, size, or operator experience. We conclude that UGTI is a safe, easy, well-tolerated and effective noninvasive method for treatment of iatrogenic femoral pseudoaneurysms and should be considered in all stable patients before operative repair.

Adult↗

PubMed1999

The impact of a community-wide vascular access program on the management of graft thromboses in a dialysis population of 495 patients.

BACKGROUND: The unpredictability of prosthetic vascular access thrombosis precludes the scheduling of elective graft thrombectomy. This results in inconsistent dialysis for patients, as well as logistical challenges for dialysis clinics and surgeons, and increased cost. In an effort to solve this problem a community-wide, prospective vascular access program (VAP) was established. This study evaluates the impact of the VAP by comparing the operative procedures and outcomes of vascular access surgery performed in the community before and after establishment of the program. METHODS: All 17 surgeons who perform vascular access, representing five independent practice groups in Greenville, South Carolina, formed a VAP in November 1996. Dialysis patients were pooled, and all graft thrombectomies were managed on a rotational basis by a surgeon assigned daily to a specifically designated access thrombectomy operating room. The hospital records of all patients undergoing vascular access procedures from November 1, 1995, through October 31, 1996 (pre-VAP), and November 1, 1996, through October 31, 1997 (post-VAP), were reviewed. RESULTS: Comparison of the pre-VAP and post-VAP groups showed no significant difference in the number of patients undergoing vascular access procedures (391 versus 378), number of vascular access procedures performed (1034 versus 1,048), or average number of vascular access procedures performed per patient (2.64 versus 2.79). There was no statistical difference in the number of thrombectomies and revisions (786 versus 765; P = 0.114) or thrombectomies alone (248 versus 283; P = 0.114) in the pre-VAP and post-VAP groups. There was a significant increase in the number of procedures performed on an outpatient basis in the post-VAP group (757; 73%) compared with the pre-VAP group (575; 56%); P <0.001. There was also a significant difference in the percentage of cases performed after 6:00 PM in the pre-VAP group (262; 25%) compared with the post-VAP group (48; 4.5%; P = 0.001). CONCLUSIONS: Dialysis graft thrombosis, occurring in 75% of our patients annually, represents a substantial logistical dilemma necessitating the incorporation of 1,000 additional operations into a busy elective surgery schedule. An organized VAP reduces inpatient hospitalization, minimizes expensive after hours surgery, and enhances patient and physician convenience while providing a mechanism to monitor clinical outcomes and assure timely dialysis.

Ambulatory Surgical Procedures↗

PubMed1999

Splenic artery aneurysms: methods of laparoscopic repair.

PURPOSE: Surgical therapy for splenic artery aneurysms (SAAs) has traditionally consisted of a laparotomy with resection of the aneurysm and possibly a splenectomy. Our early experience with the laparoscopic approach to treat SAAs is reported. METHODS: A retrospective review of medical records was conducted on all patients who underwent laparoscopic resection of SAAs at the Cleveland Clinic Foundation from May 1996 to August 1997. RESULTS: Four patients with SAAs, three women and one man, with an average age of 55 years (range, 37 to 63 years), underwent successful laparoscopic SAA repair. The average size of the aneurysm was 3.2 cm (range, 2.5 to 5.0 cm). Three patients underwent an aneurysm resection, whereas one patient underwent simple ligation. Intraoperative ultrasound scanning with Doppler was used in three cases as a means of localizing the aneurysm and identifying all feeding vessels; the complete cessation of flow within the aneurysm in the case in which the feeding vessels were simply ligated was also documented. The average intraoperative time was 150 minutes (range, 100 to 190 minutes). The mean estimated blood loss was 105 mL (range, 20 to 300 mL). There were no intraoperative complications. The average hospital stay was 2.2 days (range, 1 to 4 days). CONCLUSION: The laparoscopic approach to splenic artery aneurysm by aneurysmectomy or splenic artery ligation can be safe and effective. The laparoscopic approach affords a short hospital stay and an effective result.

Aneurysm↗

PubMed1999

Relationship of dose intensity to the induction of palmar-plantar erythrodysesthia by pegylated liposomal doxorubicin in dogs.

The multiple dose pharmacokinetics of pegylated liposomal doxorubicin (PL-DOX), known as DOXIL (US) and CAELYX (EU), was characterized in dogs and a pharmacokinetic/pharmacodynamic model to identify a relationship between drug exposure and the probability of observing treatment-related palmar-plantar erythrodysesthesia (PPE) was developed. Twenty dogs were assigned to PL-DOX groups (2/sex/ group) that received intravenous PL-DOX doses of 0.5 mg/kg ql, 2, or 4 weeks; 1.0 mg/kg q2weeks; or 1.5 mg/kg q4weeks for 12 weeks. Blood was collected for HPLC analysis of doxorubicin concentration pre-dose and periodically up to 120 h after dosing three times during treatment. Plasma drug concentration was modeled using iterative 2-stage analysis. Dermal lesions (PPE) were scored twice weekly for six regions of each dog using a 0-6 severity scale; maximum severity was 36. PPE score data were modeled using an approach in which the % probability of PPE was related to a hypothetical effect site by a series of Hill-type functions. Pharmacokinetics were best modeled as a one-compartment open model. Vss (ml/kg), CLt (ml/hr/kg) and half-life (h) were 44.1, 1.39 and 23.1, respectively. Cmax increased linearly with dose. CLt decreased with repeated doses. 5 A two-compartment pharmacodynamic model, which correctly predicted 97% of the observed lesion severity, was developed to establish the relationship of lesion severity to dose intensity (a measure of drug exposure incorporating the effect of both dose level and dosing frequency, which can be expressed in units of mg/kg/week). The model demonstrated that maximal PPE was positively correlated with dose intensity, the major factor that affects the incidence and severity of dermal lesions. 6 The model can be used to predict acceptable dose intensities in humans utilizing body surface area conversion factors and comparative AUCs for dogs and humans. It predicts that a dose intensity of 10-12.5 mg/m2 of PL-DOX will be well tolerated in patients. The results of recent clinical studies are consistent with this prediction.

Animals↗

PubMed1998

Comparative carcinogenicity in Sprague-Dawley rats of the polychlorinated biphenyl mixtures Aroclors 1016, 1242, 1254, and 1260.

A comprehensive chronic toxicity and carcinogenicity study was conducted on a series of Aroclors (1016, 1242, 1254, and 1260). Each Aroclor was assessed at multiple dietary concentrations, ranging from 25 to 200 ppm, for 24 months in male and female Sprague-Dawley rats. Liver toxicity was indicated by elevated serum enzyme activity (AST, ALT, and GGT), elevated serum cholesterol concentration, decreases in hematologic parameters (RBC, Hb, and Hct), hepatocellular hypertrophy, an increased incidence of altered hepatocellular foci, and an increased incidence of hepatocellular neoplasms (primarily adenomas). Liver toxicity was distinctly more severe in females than in males. The incidence of hepatocellular neoplasms was highly sex-dependent (females >> males), differed between Aroclor mixtures and, for females, increased with dose and followed the general incidence pattern of Aroclor 1254 > Aroclor 1260 approximately Aroclor 1242 > Aroclor 1016. A significant response (p < 0.05) in males was seen only for the high dose of Aroclor 1260. A small increase in the incidence of thyroid gland follicular cell adenomas was noted in males for Aroclors 1242, 1254, and 1260, with the incidence being uniform across dose groups and Aroclor mixtures. For females, increased survival relative to controls was observed for all Aroclor treatment groups. A significantly decreased trend in the incidence of mammary gland neoplasms compared to control was also noted for females receiving Aroclors 1242, 1254, and 1260.

Animals↗

PubMed1998

Epidural versus general anesthesia: does anesthetic management influence early infrainguinal graft thrombosis?

A few contemporary reports have suggested that the use of epidural anesthesia may favorably influence early graft patency in patients undergoing infrainguinal revascularization. In order to test this hypothesis, we have retrospectively reviewed our experience with 303 primary femoropopliteal-tibial bypass procedures in 294 patients from January 1989 through June 1994. A total of 145 of these operations were done under epidural anesthesia (EA) and 158 under general anesthesia (GA); the demographic profiles for the patients in both of these groups were nearly identical. Thirteen patients (4.2%) died during the perioperative period (EA 3.4%, GA 5.0%; p = 0.48). Early graft thrombosis occurred in 35 patients (12%) during the same hospital admission (EA 14%, GA 9.4%; p = 0.28). There were no significant differences in the graft thrombosis rates for EA and GA with respect to surgical indications (claudication versus limb salvage), graft materials (vein versus synthetic), or the extent of revascularization (popliteal versus crural). Most graft failures appeared to be related to such conventional factors as disadvantaged outflow vessels and/or specific technical complications. Therefore, we conclude that the choice between EA and GA should continue to be made selectively on the basis of traditional anesthetic considerations.

Anesthesia, Epidural↗

PubMed1998

Angioplasty and primary stenting of the subclavian, innominate, and common carotid arteries in 83 patients.

PURPOSE: The initial and long-term results of angioplasty and primary stenting for the treatment of occlusive lesions involving the supra-aortic trunks were studied. METHODS: All patients in whom angioplasty and stenting of the supra-aortic trunks was attempted were included in a prospective registry. Results are, therefore, reported on an intent-to-treat basis. The preprocedural and postprocedural clinical records, arteriograms, and noninvasive vascular laboratory examinations of 83 patients (41 men [49.4%] and 42 women [50.6%]; mean age at intervention, 63 years) in whom endovascular repair of the subclavian (66, 75.9%), left common carotid (14, 16.1%), and innominate (7, 8.0%) arteries was attempted were retrospectively reviewed. RESULTS: Initial technical success was achieved in 82 of 87 procedures (94.3%). The inability to cross 4 complete subclavian occlusions and the iatrogenic dissection of 1 common carotid artery lesion accounted for the 5 initial failures. Complications occurred in 17.8% of 73 subclavian and innominate procedures, including access-site bleeding in 6 and distal embolization in 2. Ischemic strokes occurred in 2 of 14 common carotid interventions (14.3%), both of which were performed in conjunction with ipsilateral carotid bifurcation endarterectomy. The 30-day mortality rate was 4.8% for the entire group. By means of life-table analysis, 84% of the subclavian and innominate interventions, including initial failures, remain patent by objective means at 35 months. No patients have required reintervention or surgical conversion for recurrence of symptoms. Of the 11 patients available for follow-up study who underwent common carotid interventions, 10 remain stroke-free at a mean of 14.3 months. CONCLUSION: Angioplasty and primary stenting of the subclavian and innominate arteries can be performed with relative safety and expectations of satisfactory midterm success. Endovascular repair of common carotid artery lesions can be performed with a high degree of technical success, but should be approached with caution when performed in conjunction with ipsilateral bifurcation endarterectomy.

Adult↗

PubMed1998

Carotid endarterectomy in octogenarians: early results and late outcome.

PURPOSE: This study was undertaken to determine the safety and efficacy of carotid endarterectomy (CEA) in the octogenarian population at the Cleveland Clinic. METHODS: From 1989 to 1995, 182 CEAs were performed among 167 octogenarians (98 men, 69 women) with a mean age of 83 years (median, 83 years; range, 80 to 93 years). One hundred procedures (55%) were performed for severe asymptomatic stenosis, whereas 48 (26%) were performed for hemispheric transient ischemic attacks (TIAs) or amaurosis fugax, 24 (13%) for prior stroke, and 10 (5%) for vertebrobasilar symptoms. Thirteen CEAs (7%) were combined with myocardial revascularization, and another five (3%) represented carotid reoperations. Nine arteriotomies (5%) were closed primarily, whereas the remaining 173 (95%) were repaired using either vein patch angioplasty (141, 77%) or synthetic patches (32, 18%). Two patients were lost to follow-up, but late information was available for 165 patients (180 operations) at a mean interval of 2.7 years (median, 2.4 years; maximum, 7.4 years). RESULTS: Considering all 182 procedures, there were five early (<30 days) postoperative neurologic events (2.7%), including three strokes (1.6%) and two TIAs (1.1%). An additional 15 neurologic events occurred during the late follow-up period, consisting of 11 strokes (6.1%) and four TIAs (2.2%). The Kaplan-Meier estimated 5-year rate of freedom from stroke was 85% (95% confidence interval [CI], 77% to 93%). There was one early postoperative death (0.6%) of cardiac complications 9 days after CEA. The estimated 5-year survival rate was 45% (95% CI, 33% to 57%), and the 5-year stroke-free survival rate was 42% (95% CI, 30% to 53%). Multivariable analysis yielded age at operation (p = 0.001), abnormal creatinine level (p = 0.025), and chronic obstructive pulmonary disease (p = 0.019) as variables that significantly influenced the survival rate. The presence of chronic obstructive pulmonary disease (p = 0.009) and, surprisingly, a lesser degree of contralateral internal carotid stenosis (p = 0.003) were found to be significantly associated with stroke after CEA. Causes of late death were cardiovascular in 16 patients (30%), unknown in 13 (24%), carcinoma in six (11%), stroke in six (11%), and miscellaneous in 13 (24%). CONCLUSIONS: We conclude that CEA may be safely performed in selected octogenarians with carotid stenosis, and that the majority of these patients live the rest of their lives free from stroke. Therefore, age alone should not exclude otherwise-qualified candidates from consideration for CEA.

Age Factors↗

PubMed1998

Management of isolated common iliac artery aneurysms.

PURPOSE: Since isolated common iliac artery aneurysms are rare and there is no consensus regarding some aspects of their management, we reviewed our recorded experience with common iliac artery aneurysms from 1977 through 1993. METHODS: We were able to identify 25 patients having a total of 33 common iliac artery aneurysms on the basis of information maintained by our medical records staff, old surgical logs and a departmental registry that was implemented in 1989. Follow-up data were collected from outpatient charts and by telephone contact. New imaging studies were obtained for 14 patients who either underwent common iliac artery aneurysm repair without aortic replacement (aortic ultrasound scans, n = 7) or had no surgical treatment whatsoever (computerized tomography of the abdomen and pelvis, n = 7). RESULTS: All 25 patients were men (mean age, 71 years). Eighteen patients (72%) had elective (n = 14) or urgent (n = 4) operations to repair common iliac artery aneurysms with mean diameters of 3.8 cm and 5.8 cm, respectively. There was one postoperative death (5.5%) in conjunction with complementary renal revascularization in a patient with pre-operative renal insufficiency. During a mean follow-up period of 50 months, two (29%) of the seven patients who had not received bifurcation grafts at the time of their common iliac artery aneurysm procedures had developed infrarenal aortic aneurysms. Seven (28%) of the original 25 patients were observed without intervention for common iliac artery aneurysms measuring 2-2.5 cm in diameter. No common iliac artery aneurysm enlargement or new aortic aneurysms have been documented in any of these patients at a mean follow-up interval of 57 months. CONCLUSIONS: In our limited experience, the risk for spontaneous rupture appears to be concentrated among common iliac artery aneurysms exceeding 5 cm in diameter, while those that are less than 3 cm in diameter may fail even to enlarge under observation. Therefore, common iliac artery aneurysms measuring > or = 3 cm in size probably warrant surgical treatment, at which time simultaneous aortic replacement also should be a serious consideration.

Adolescent↗

PubMed1998

Human milk as a potential enteral source of erythropoietin.

In addition to its content of traditional nutrients, milk is a rich source of hormones and peptides, which survive digestion in the neonatal gastrointestinal tract secondary to lower proteolytic activity and increased protein permeability. Previous studies have shown accelerated erythropoiesis or elevated serum erythropoietin (Epo) levels in neonatal (suckling) animals after maternal phlebotomy or maternal hypoxia exposure. We sought to determine whether significant quantities of Epo are present in human milk and whether Epo remains intact under physiologic digestion conditions. Immunoreactive Epo concentrations were determined in 409 human milk samples obtained from mothers of term and premature infants. Samples collected between birth and postpartum d 134 were divided into 11 postpartum day groups. Mean milk-borne Epo concentrations were within the normal range for plasma Epo concentrations and rose with postpartum day (F10,398 = 5.82, p < 0.0001). No differences were observed between milk collected from mothers of premature versus term infants. Estimated weekly human milk-borne Epo intakes approximated the lower range of published parenteral therapeutic doses. In simulated digestion at physiologic pH levels of 3.2, 5.8, and 7.4, milk-borne Epo resisted degradation at 1 and 2 h, compared with baseline. Therefore, we conclude that human milk contains considerable amounts of Epo which resist degradation after exposure to gastric juices at physiologic pH levels. These results support continued investigation into the fate and developmental roles of Epo in human milk.

Cross-Sectional Studies↗

PubMed1998

Stenting of the renal artery to improve renal function prior to thoracoabdominal aneurysm repair.

PURPOSE: To report the successful staged treatment of a patient with a thoracoabdominal aortic aneurysm (TAA), who presented with renal insufficiency attributable to renal artery stenosis. METHODS AND RESULTS: A 66-year-old woman with a 6-cm Crawford type IV TAA presented with uncontrolled hypertension (240/130 mmHg), worsening congestive heart failure, and progressive renal insufficiency (serum creatinine 3.8 mg/dL) caused by renal artery stenosis to a solitary functioning kidney. Renal artery stenting restored normal renal and pulmonary function, and elective TAA repair 6 weeks after percutaneous stenting was uneventful. Restenosis (50% diameter reduction) in the renal artery was found 10 months later and treated with repeat dilation. Secondary patency was maintained at follow-up 21 months after redilation. CONCLUSIONS: It appears feasible to use preliminary renal artery stenting to reduce operative risk in TAA surgical candidates with renal insufficiency secondary to renal artery stenosis.

Acute Kidney Injury↗

PubMed1997

Novel nuclear matrix protein HET binds to and influences activity of the HSP27 promoter in human breast cancer cells.

Since the small heat shock protein hsp27 enhances both growth and drug resistance in breast cancer cells, and is a bad prognostic factor in certain subsets of breast cancer patients, we have characterized the transcriptional regulation of hsp27, with the long-term goal of targeting its expression clinically. The majority of the promoter activity resides in the most proximal 200 bp. This region contains an imperfect estrogen response element (ERE) that is separated by a 13-bp spacer that contains a TATA box. Gel-shift analysis revealed the binding of a protein (termed HET for Hsp27-ERE-TATA-binding protein) to this region that was neither the estrogen receptor nor TATA-binding protein. We cloned a complete cDNA (2.9 kb) for HET from an MCF-7 cDNA library. To confirm the identity of the HET clone, we expressed a partial HET clone as a glutathione S-transferase fusion protein, and showed binding to the hsp27 promoter fragment in gel-retardation assays. The HET clone is almost identical to a recently published scaffold attachment factor (SAF-B) cloned from a HeLa cell cDNA library. Scaffold attachment factors are a subset of nuclear matrix proteins (NMP) that interact with matrix attachment regions. Analyzing how HET could act as a regulator of hsp27 transcription and as a SAF/NMP, we studied its subnuclear localization and its effect on hsp27 transcription in human breast cancer cells. We were able to show that HET is localized in the nuclear matrix in various breast cancer cell lines. Furthermore, in transient transfection assays using hsp27 promoter-luciferase reporter constructs, HET overexpression resulted in a dose-dependent decrease of hsp27 promoter activity in several cell lines.

Breast Neoplasms↗

PubMed1997

Score for neonatal acute physiology and phlebotomy blood loss predict erythrocyte transfusions in premature infants.

OBJECTIVE: To test the hypothesis that utilization of a previously described measure of acuity (ie, the score for neonatal acute physiology [SNAP]) during the first 7 postnatal days predicts which infants with a birth weight of 1500 g or less received erythrocyte transfusion during the initial hospitalization. DESIGN: Retrospective chart review. SETTING: A regional tertiary care newborn intensive care unit at the Arizona Health Sciences Center, University Medical Center, Tucson. MATERIALS: Medical records of premature infants (birth weight, < or = 1500 g) who were admitted from October 1993 to January 1995. MAIN OUTCOME MEASURES: Occurrence or nonoccurrence of erythrocyte transfusion was determined in 47 infants who were compared for demographic information, phlebotomy blood loss, diagnoses, medications, and the SNAP at 0, 1, 2, and 7 days of life. RESULTS: Infants with a birth weight of 1500 g or less received a mean +/- SD of 1.9 +/- 2.9 transfusions with 22 (47%) of the infants given transfusions Infants who were given transfusions vs those who were not given transfusions were of a lower mean +/- SD birth weight (971 +/- 238 g vs 1272 +/- 144 g; P < .001) and a lower gestational age (27.7 +/- 1.6 weeks vs 30.7 +/- 2.8 weeks; P < .001), and they had a greater mean phlebotomy blood loss (3.3 +/- 1.6 mL/kg per day vs 1.4 +/- 0.5 mL/kg per day; P < .001) during the first postnatal week. The SNAP indexes in those who received transfusions were higher at 1, 2, and 7 days of life (P = .03, P = .001, and P < .001, respectively). Using stepwise logistic regression, phlebotomy blood loss and the SNAP at 7 days of life were significant predictors of the number of transfusions. The logistic model predicted which infants had been administered transfusions with 86% sensitivity and 88% specificity. CONCLUSIONS: The efficacy and cost-effectiveness of recombinant human erythropoietin therapy in premature infants remain under study. As earlier treatment with recombinant human erythropoietin may be more efficacious, early identification of which infants currently undergo transfusion may identify those who will receive the greatest benefit from recombinant human erythropoietin therapy. The SNAP distinguished those infants who were given transfusions from those who did not receive transfusions, even after adjusting for phlebotomy blood loss.

Birth Weight↗