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Biomedical subjects

D B Hood

Publications and source records attributed to D B Hood.

At least 19 recordsLinked to original sources

Metabolism, bioavailability, and toxicokinetics of benzo(alpha)pyrene in F-344 rats following oral administration.

The objective of this study was to evaluate the bioavailability of Benzo(a)pyrene [B(a)p], subsequent to oral exposure. Eight-week-old F-344 rats were dosed orally with 100 mg/kg body weight B(a)p and sacrificed at 0, 0.5, 1.0, 2.0, 4.0. 8.0, 24, 48 and 72 hours post exposure. Blood, liver, reproductive tissues, urine and fecal samples were collected at necropsy and were analyzed for parent B(a)p and metabolites by HPLC with fluorescence detection. Peak levels of B(a)p in plasma occurred 8 hours after exposure (67%) followed by a gradual decrease. Liver retained 10% of the administered B(a)p up to 24 hours following, which the levels dropped during the remaining time periods studied. Twenty-four hours after administration, 45% of the dose was excreted in feces and urine. Metabolite levels in plasma peaked at 24 hours (10%) and decreased to 1% at 72 hours. In the liver, metabolite levels were higher at 8 hours (10%) but were only 3% at 72 hours. Benzo(a)pyrene levels increased after 24 hours in the reproductive organs and constituted 10% of the administered dose at 72 hours. Blood showed high levels of 7,8-diol than 9,10 and 4,5-diols which were high in liver and reproductive organs. Compared to diols, the hydroxy metabolites were detected at high levels in urine and fecal samples. Among the aqueous phase metabolites, glucuronides were at higher levels compared to glutathiones and sulfates. The slow release of unmetabolized B(a)p from reproductive organs and the presence of reactive metabolites in these organs is a matter of concern as they could interfere with gonadal steroid synthesis and release and its regulatory role in gamete production, maturation and function of male animals in a continuous exposure paradigm.

Administration, Oral↗

Toxicokinetics of inhaled benzo[a]pyrene: plasma and lung bioavailability.

Bioavailability and toxicokinetic studies are essential in order to establish dose-response relationships of widely distributed environmental toxicants such as benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon. Fischer 344 rats were exposed for 4 h (via nose-only inhalation) to aerosol exposure concentrations of 0.1, 1.0, and 2.5 mg/m(3) of BaP absorbed onto carbon black particles using a state-of-the-art model aerosol generation system. Nominal and chamber concentrations of the particulate aerosol were determined gravimetrically with a seven-stage cascade impactor. The average aerosol for the 3 exposure concentrations used in this study exhibited a trimodal distribution with 93% cumulative mass less than 15.85 microm, 89% cumulative mass less than 10 microm, 55.3% cumulative mass less than 2.5 microm, and 38% less than 1 microm. Fifty-five percent of the aerosol had a cumulative mass less than PM(2.5) and the mass median aerodynamic diameter (MMAD) -/+ geometric standard deviation (GSD) for this mode was 1.7 -/+ 0.085 microm. Plasma and lung samples were collected at 30, 60, 120, and 240 min postexposure. The concentrations of BaP parent compound and metabolites were determined by high-performance liquid chromatography. The toxicokinetic parameters were computed from the time course of plasma BaP concentration. The bioavailability of BaP increased as a function of exposure concentration, and toxicokinetic analysis indicates first-order pharmacokinetics for BaP. However, some toxicokinetic parameters such as clearance and volume of distribution remained constant throughout the duration of the postexposure period. BaP and its metabolite concentrations in plasma peaked at 1 h postexposure. At 240 min postexposure, only trace levels of BaP remained in the plasma. The BaP metabolites in the lung showed an identical trend where no parent compound was detected. Among the metabolites detected, BaP 4,5-, 7,8-, and 9,10-dihydrodiols, 3-OH-BaP, and 9-OH-BaP were predominant.

Administration, Inhalation↗

Aryl hydrocarbon hydroxylase activity in F-344 rats subchronically exposed to benzo(a)pyrene and fluoranthene through diet.

In order to investigate the relationship between aryl hydrocarbon hydroxylase (AHH) activity and exposure to benzo[a]pyrene [B(a)p] and fluoranthene (FLA), AHH activities in liver tissues of male and female F-344 rats were determined. Based on a range-finding study, doses of 0, 5, 50, and 100 mg/kg B(a)p or 0, 150, 750, and 1500 mg/kg FLA were administered in the animal diet over a 90-day period. After dosing, animals were sacrificed, liver tissues were removed, and microsomes were isolated. AHH activities were determined by reverse-phase HPLC coupled with fluorescence detection using 3-hydroxy B(a)p, and trans-2,3-dihydroxy-1,10-epoxy-1,2,3,10b tetrahydrofluoranthene as the standards. A dose-dependent increase in enzyme activity was observed with increased B(a)p or FLA exposure in both males and females. Our results also demonstrate that B(a)p-exposed females possess a higher AHH activity than males, but there is no significant sex difference with regard to enzyme activity in the case of FLA at higher doses. Overall, our findings suggest that long-term exposure to the parent compound results in elevated levels of AHH activity, which may contribute to the formation of toxic reactive metabolites and subsequent symptoms in target organs.

Animals↗

The use of colorflow duplex scanning to detect significant renal artery stenosis.

The purpose of this study was to review our institutional experience with colorflow duplex scanning in detecting significant renal artery stenosis and to validate the criteria used: renal artery peak systolic velocity (PSV) >/=200 cm/sec and renal-to-aortic peak systolic ratio (RAR) >/=3.5. The results of renal artery duplex and arteriography in 58 patients (107 kidneys) who underwent both exams were reviewed. Arteriography revealed 32 main renal arteries with >/=60% stenosis. The PSV criterion detected 29, for a sensitivity of 91%, specificity of 75%, positive predictive value (PPV) of 60%, negative predictive value (NPV) of 95%, and accuracy of 79%. Using RAR >/=3.5 provided a sensitivity of 72%, specificity of 92%, PPV of 79%, NPV of 88%, and accuracy of 86%. In a subset of 36 kidneys that had hilar scans, the criteria of acceleration time (AT) >/=100 cm/sec and index (AI) </=3.78 kHz/sec were evaluated. The AT and AI yielded sensitivity of 50% and 36%, specificity of 86% and 100%, PPV of 70% and 100%, NPV of 73% and 71%, and accuracy of 72% and 75%, respectively. Colorflow duplex scanning is clinically useful in screening for hemodynamically significant renal artery stenosis. The renal artery PSV criterion is highly sensitive, with a high NPV that obviates the need for arteriography in most cases of a negative duplex. The criteria of RAR, AT, and AI are of less value.

Adult↗

The standardized vascular clinic: an alternative to the traditional ambulatory setting.

PURPOSE: To investigate the effectiveness of a standardized vascular clinic (SVC) in teaching diagnostic and management skills for common vascular problems, as compared with that of the traditional ambulatory setting. METHODS: Third-year medical students participating in the required surgical clerkship participated in this study. Students were randomly assigned to attend either a 4-hour SVC experience (group 1, n = 64) or a 4-hour traditional ambulatory experience (group 2, n = 60). Students completed a satisfaction rating scale and a preencounter and postencounter self-efficacy rating scale at the end of the experience. Student t tests were used to compare the groups in the areas of knowledge acquisition, problem solving, clinical skills and satisfaction with the encounter. Analysis of covariance was used to compare the change between pre and post self-efficacy ratings. RESULTS: Students in group 1 performed significantly higher than students in group 2 in the areas of problem solving, clinical skills, and student satisfaction. They also demonstrated a higher level of confidence in their vascular skills than students assigned to the traditional setting. CONCLUSION: The SVC may be more effective in teaching problem-solving and clinical skills. It also may promote more student satisfaction with the experience and confidence in clinical skills than the traditional ambulatory setting.

Ambulatory Care↗

Modulation in the developmental expression profile of Sp1 subsequent to transplacental exposure of fetal rats to desorbed benzo[a]pyrene following maternal inhalation.

Any alteration of the critical sequence of genes that are required to coordinate the differentiation of cells, the promotion of migration, dendritic arborization, synapse formation, and myelination in the developing nervous system would be expected to have deleterious consequences. The focus of this article is a molecular evaluation of the neurotoxicological effects that result subsequent to the transplacental exposure of fetal rats to desorbed benzo(a)pyrene (BaP) following maternal inhalation. A state-of-the-art, newly designed, fabricated, and tested model aerosol generation system was utilized in these studies. Timed-pregnant Sprague Dawley rats were exposed for 4 h on gestation day 15 of a 21-day gestation period to an acute dose of BaP:carbon black aerosol (100 microg/m(3)). Controls received carbon black only. Nominal and chamber concentrations of the particulate aerosol were determined gravimetrically with a seven-stage cascade impactor. The aerosol exhibited a trimodal distribution with 95% cumulative mass less than 15.85 microm, 90% cumulative mass less than 10 microm, 67. 5% cumulative mass less than 2.5 microm and 66.2% cumulative mass less than 1.0 microm. Time-course bioavailability results indicated that greater than 95% of the parent compound is cleared from blood 240 min postexposure. An Sp1 transcription factor consensus sequence was examined by electrophoretic mobility shift analysis of nuclear extracts from various brain regions of resulting pups on postnatal days 3, 5, 7, 10, and 15. It revealed perturbations in the developmental expression profile of Sp1 abundance as a result of nose-only particulate aerosol exposure to the timed-pregnant dam. The data obtained on the temporal and spatial regulation of gene expression in the brain indicate that (1) Sp1 DNA-binding is developmentally regulated and expressed very highly in actively developing brain regions, and (2) a consequence of the transplacental deposition of desorbed BaP to the fetus is in utero neurotoxicity.

Administration, Inhalation↗

Percutaneous transluminal angioplasty and stenting for iliac artery occlusive disease.

Atherosclerotic iliac artery stenoses respond well to simple balloon angioplasty and have the best results of all of the peripheral vessels. Nonetheless, initial technical failures occur in as many as 20% of patients, most of which can be salvaged with intravascular stenting, as can many of the potential complications; however, even though the initial technical success rates for stenting approach 100%, stenotic recurrences within stents are not infrequent. Whether promising new concepts, such as brachytherapy, gene therapy, and endoluminal grafting, will have a durable impact on the results of iliac angioplasty is yet to be seen. Meanwhile, the excellent results of endoluminal treatment of patients with iliac artery occlusive disease, combined with the relatively low risk for complications compared with surgical revascularization, ensure an enduring role for this modality of treatment and a diminution in the fraction of patients requiring surgery to correct their iliac artery occlusive disease.

Angioplasty, Balloon, Coronary↗

Breast screening: the psychological sequelae of false-positive recall in women with and without a family history of breast cancer.

The psychological effects of false-positive mammography were evaluated in 124 women who had taken part in the U.K. National Health Service Breast Screening Programme. In addition, the effects of recall on women with and without a family history were compared. These women were asked to complete the Hospital Anxiety and Depression Scale (HADS) before being invited to attend for screening, at recall and 5 weeks and 4 months after recall. At screening and at recall, the women were asked to complete the Health Questionnaire (HQ) which measures stress-related behaviour changes in the previous week. In the week before screening, compared with women who did not have a family history of breast cancer, women with a family history had lower scores on HADS depression and reported fewer stress-related behaviour changes. At recall, regardless of family history, the women were more likely to have borderline or clinically significant anxiety than at baseline or screening. Nevertheless, for most women, recall-induced anxiety was relatively transient (less than 5 weeks). Compared with women without a family history, women with a family history were more anxious 4 months after recall, although their anxiety scores tended to be lower (P < 0.06) than at baseline. A strength of the present study is that the initial baseline measure was uncontaminated by the screening process. Women who did not complete questionnaires at one or more of the subsequent time points scored higher on HADS depression at baseline, indicating that the results are likely to have underestimated the effects of recall. Screening appears to be less stressful for women with a family history than for those without a history. However, for both groups recall causes short term distress. Breast screening programmes should ensure that steps are taken to minimise the number of women who are recalled for unnecessary investigations.

Anxiety↗

Combined carotid endarterectomy and coronary artery bypass grafting in asymptomatic carotid artery stenosis.

The role of combined carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG) in patients with severe asymptomatic carotid artery disease and concurrent symptomatic coronary artery disease is controversial. The objective of this report is to investigate the safety of combined CEA/CABG. The medical records of 30 patients who underwent combined CEA/CABG for coexistent asymptomatic carotid and symptomatic coronary artery occlusive disease were reviewed. All patients were scheduled for either elective or urgent myocardial revascularization due to their symptomatic coronary artery disease. Color-flow duplex scanning identified internal carotid artery stenosis of 80 to 99 per cent in 28 patients (93%) and 50 to 79 per cent in 2 patients (7%). Seventeen patients (57%) were male. The mean age was 64 +/- 10 years (range, 42-84 years). Contralateral internal carotid artery occlusion was present in four patients. Severe left main coronary artery disease was present in 12 patients (40%) and 7 patients (23%) had an ejection fraction of less than 50 per cent. There were no perioperative deaths or strokes. One patient suffered a myocardial infarction on postoperative day 1. This study demonstrates the safety of combined CEA/CABG for coexistent coronary and asymptomatic carotid disease. Using this surgical approach for critical coexistent disease may minimize the incidence of perioperative cerebrovascular complications in patients undergoing CABG.

Adult↗

Changing perspectives in the diagnosis of peripheral vascular trauma.

The diagnosis of peripheral vascular trauma has undergone significant evolution in the last two decades. A minority of patients with arterial trauma present with classic findings that make the diagnosis obvious. However, the diagnosis of occult arterial injuries is more challenging, and it is for this group that the diagnostic algorithm has changed most significantly. Because of the low yield of routine operative exploration and routine arteriography to evaluate potential injury to vessels in proximity to penetrating wounds, many authors now recommend the selective use of arteriography or other diagnostic modalities based on the results of clinical examination and noninvasive pressure determinations. This article reviews the evidence in support of such a selective approach to the diagnosis of arterial injuries.

Algorithms↗

Local anesthesia for infrainguinal arterial reconstruction.

PURPOSE: Perioperative cardiac complications occur in 4% to 6% of patients undergoing infrainguinal revascularization under general, spinal, or epidural anesthesia. The risk may be even greater in patients whose cardiac disease cannot be fully evaluated or treated before urgent limb salvage operations. Prompted by these considerations, we investigated the feasibility and results of using local anesthesia in these high-risk patients. METHODS: From January 1, 1994, through August 30, 1996, 86 infrainguinal reconstructions were performed under local infiltration anesthesia (0.5% or 1.0% lidocaine). Supplementary intravenous sedation with propofol or other agents was given as needed for patients comfort. Most patients had arterial lines but Swan Ganz catheters were used infrequently. Postoperatively, continuous electrocardiographic monitoring was continued in the intermediate or intensive care units. Patients ranged in age from 37 to 86 years (mean 68 +/- 12); 47% were diabetic, 69% had severe coronary artery disease, and 14% had end-stage renal disease. RESULTS: Operations included 7 femoral-femoral, 21 femoral-popliteal, 16 femoral-tibial and 13 popliteal-tibial bypass grafts, 9 pseudoaneurysms, and 20 distal graft revisions (+/- thrombectomy). Autogenous vein was used in eight of the femoral-popliteal and all of the femoral-tibial and popliteal-tibial bypass grafts. There were two postoperative deaths. One patient died of a stroke (1.2%) on postoperative day (POD) 2 and one died on POD 27 of unknown cause. Two other (2%) patients had nonfatal subendocardial myocardial infarctions. Conversion to general anesthesia was required in four (5%) operations, three because patients became agitated and one because a long segment of vein had to be harvested from the opposite leg. Otherwise, patients tolerated the procedures well and postanesthetic recovery problems were minimized. CONCLUSIONS: Limb salvage operations can be done under local anesthesia with acceptable complication rates. In selected patients with high-risk coronary artery disease, local anesthesia has theoretic and practical advantages and should be considered an alternative to general or regional anesthesia.

Adult↗

Vascular complications of thoracic outlet syndrome.

Vascular complications of thoracic outlet syndrome are uncommon but may result in significant long-term disability. This report documents a retrospective review of 17 such patients. Ten patients presented with acute onset of upper extremity swelling and axillosubclavian vein thrombosis. One patient presented with chronic, intermittent arm swelling and subclavian vein stenosis. Three patients presented with acute symptoms of upper extremity emboli, and three presented with chronic arm claudication. Cervical ribs were discovered in four patients with arterial symptoms and in no patients with venous symptoms. All ten patients with acute venous thrombosis underwent successful thrombolysis, with venous stenosis uncovered in 8. Thrombolysis was also performed for two patients with arterial emboli. All 17 patients underwent surgical decompression of the thoracic outlet, 16 via a supraclavicular approach and one via a transaxillary approach. One subclavian arteriotomy with endarterectomy and one resection of a subclavian artery aneurysm were performed at the time of decompression. Repeat venography after decompression demonstrated persistent venous stenosis in one patient that was treated with balloon angioplasty and stenting. After a mean of 22 months' follow-up, 12 patients had no residual symptoms, and 5 had experienced significant improvement of symptoms. In conclusion, a combined approach of thrombolysis and surgical decompression of the thoracic outlet provides a salutary outcome in a majority of patients.

Acute Disease↗

Cardiac evaluation of the diabetic patient prior to peripheral vascular surgery.

The benefit of preoperative cardiac evaluation in the diabetic patient undergoing peripheral vascular surgery is uncertain. To investigate this issue we performed a retrospective review of 192 procedures performed in diabetic patients for chronic lower extremity arterial occlusive disease. The incidence of adverse postoperative cardiac events was determined, as well as its association with several preoperative factors including symptoms of coronary artery disease (CAD), extent and results of preoperative noninvasive cardiac evaluation, and operative site (aorta vs. lower extremity). The overall death and cardiac complication rates were 10.2% for lower extremity and 25.7% for aortic procedures (p = 0.02). For myocardial infarction and cardiac death alone, the rates were 5.1% and 5.7%, respectively (p > 0.10). Although a history of symptomatic CAD predicted the occurrence of any cardiac complication (28.3% vs. 8.2% [p < 0.01] for the aortic and lower extremity revascularization groups combined), no factor was found to be associated with the occurrence of myocardial infarction and cardiac death alone. In patients with a history of symptomatic CAD, there was no significant difference in the incidence of complications whether or not preoperative noninvasive cardiac testing was performed (28.1% vs. 28.6%, p > 0.10) or, if testing was performed, if the results were abnormal or normal (35.3% vs. 20.0%, p > 0.10). Similar results were obtained in patients with no history of symptomatic CAD. In summary, this retrospective review of our experience with noninvasive evaluation to detect CAD in diabetic patients undergoing peripheral vascular surgery failed to show any benefit in terms of reducing the incidence of postoperative cardiac events.

Aged↗

Determinants of success of color-flow duplex-guided compression repair of femoral pseudoaneurysms.

BACKGROUND: Ultrasonography-guided compression repair is reported to be effective therapy for femoral pseudoaneurysms that develop after catheterization procedures. This study summarizes our experience with color-flow duplex-guided repair of these lesions. METHODS: A retrospective chart review of all patients who underwent this procedure was undertaken, with statistical analysis to identify factors associated with success. RESULTS: Compression repair of 69 pseudoaneurysms was attempted. Pseudoaneurysms developed after therapeutic catheterization in 48 patients and after diagnostic procedures in 21. Sites of arterial puncture were the common femoral artery in 59 patients and the superficial femoral or profunda femoris arteries in 10. Diameters of the pseudoaneurysms ranged from 3 to 60 mm (mean, 28 mm). Compression was attempted at a mean of 5 days (range, 1 to 21 days) after catheterization. Compression produced complete thrombosis of the pseudoaneurysm at the initial attempt in 43 (62%) of 69 patients. With repeated attempts the ultimate success was 47 (68%) of 69. Success was achieved in 44 (75%) of 59 common femoral pseudoaneurysms but in only 3 (30%) of 10 superficial femoral or profunda femoris lesions (p = 0.009). Anticoagulation, sheath size, pseudoaneurysm chamber size, and time between catheterization and compression were not significantly different between lesions that were successfully compressed and those that were not. No ischemic or embolic complications were observed. CONCLUSIONS: Color-flow duplex-guided compression repair can be safely attempted as the initial therapy for all uncomplicated pseudoaneurysms arising from the common femoral artery after catheterization, with the expectation of success in most.

Adult↗

Prevalence and distribution of calf vein thrombosis in patients with symptomatic deep venous thrombosis: a color-flow duplex study.

PURPOSE: This retrospective study was performed to identify the patterns of calf vein thrombosis in patients in whom deep vein thrombosis (DVT) was suspected and to better define the role of color-flow duplex scanning (CDS) in the evaluation of this patient population. METHODS: Over a recent 9-month period, we reviewed the vascular laboratory charts of 540 symptomatic patients (696 limbs) who underwent CDS for clinically suspected acute DVT. Patients who had a previous episode of DVT were excluded. RESULTS: CDS satisfactorily visualized all three paired calf veins in 655 of the limbs (94%). Inadequate scans (n = 41) were attributed to edema in 29, excessive calf size in eight, and anatomic inaccessibility in four. Peroneal veins were the most difficult to visualize (n = 29), followed by posterior tibial (n = 10) and anterior tibial (n = 9) veins. CDS identified acute DVT in 159 of 655 limbs (24%) that had adequate scans. Calf vein thrombi were detected in 110 of the 655 limbs (17%) and in 69% of the 159 limbs with DVT. Clots were confined to the calf veins in 53 limbs with DVT (33%). Isolated calf vein thrombi were found in 45% of outpatient limbs and in 27% of inpatient limbs with DVT. The peroneal (81%) and posterior tibial veins (69%) were more frequently involved (p < 0.001) than the anterior tibial veins (21%). In limbs with calf DVT, the prevalence of thrombosis isolated to the peroneal and posterior tibial veins was similar (37% and 25%, respectively); no limb had an isolated anterior tibial DVT (p = 0.02). CONCLUSION: CDS is a reliable method for evaluating calf veins for DVT. Calf vein thrombosis is common in patients who have acute DVT and often occurs as an isolated finding. The peroneal and posterior tibial veins are involved in the majority of cases; thrombi occur much less frequently in the anterior tibial veins. We conclude that CDS should be the noninvasive method of choice for the initial evaluation of patients in whom DVT is suspected, and we recommend that calf veins should always be studied but that routine scanning of the anterior tibial veins may not be necessary.

Acute Disease↗

Prospective evaluation of new duplex criteria to identify 70% internal carotid artery stenosis.

PURPOSE: Large multicenter trials (North American Symptomatic Carotid Endarterectomy Trial, European Carotid Surgery Trial) have documented the benefits of carotid endarterectomy for treating symptomatic patients with >or=70% stenosis of the internal carotid artery. Although color-flow duplex scanning has become the preferred method for noninvasive assessment of internal carotid artery disease, no criteria have been generally accepted to identify this subset of patients. We previously reported a retrospective series to establish such criteria. This study details our results when these criteria were applied prospectively. METHODS: Carotid color-flow duplex scans were compared with arteriograms in 457 patients who underwent both studies. Criteria for >or=70% internal carotid artery stenosis were peak systolic velocity >130 cm/sec and end-diastolic velocity >100 cm/sec. Internal carotid arteries with peak systolic velocity <40 cm/sec in which only a trickle of flow could be detected were classified as preocclusive lesions (95% to 99% stenosis). Arteriographic stenosis was determined by comparing the diameter of the internal carotid artery at the site of maximal stenosis to the diameter of the normal distal internal carotid artery. RESULTS: Internal carotid artery stenosis of >or=70% was detected with a sensitivity of 87%, specificity of 97% positive predictive value of 89%, negative predictive value of 96%, and overall accuracy of 95%. Eighty-seven percent of 70% to 99% stenoses were correctly identified. False-positive errors (n=10) were attributed to contralateral internal carotid artery occlusion or high-grade (>90%) stenosis (n=5) and to interpreter error (n=1); no explanation was apparent in the other four. Eleven of 12 false-negative examinations occurred in patients with 70% to 80% internal carotid artery stenosis. CONCLUSIONS: In our laboratories, prospective application of the above velocity criteria identified internal carotid artery stenosis of >or=70% with a reasonably high degree of accuracy. Errors occurred when stenoses were borderline and in patients with severe contralateral disease. With suitably modified velocity criteria, color-flow duplex scanning remains the most reliable noninvasive method for identifying symptomatic patients who are candidates for carotid endarterectomy.

Angiography↗