Biomedical subjects

S M Taylor

Publications and source records attributed to S M Taylor.

At least 19 recordsLinked to original sources

PubMed1992

Biologic activity of synthetic analogues of C5a anaphylatoxin.

The C activation fragment C5a is the most potent plasma-derived chemotactic factor known. This humoral factor induces both neutrophil and macrophage activation at low nanomolar concentrations. We have synthesized a series of C-terminal C5a analogues that exhibit all of the characteristic biologic activities of C5a. These peptides apparently contain the effector site for C5a receptor-mediated cellular activation, but express only a fraction of the potency of intact C5a. We have demonstrated the following in vitro activities for these C5a peptides: 1) ileal (guinea pig) contraction; 2) platelet (guinea pig) activation; and 3) neutrophil (human) polarization and chemotaxis. The effect of C5a peptides in vivo was evaluated by measuring enhancement in vascular permeability. Although potencies of the most effective synthetic C5a analogues were on the order of 0.01 to 0.1% that of the natural factor, our biologic data confirm that the C5a peptides are full agonists of the intact factor and may be useful substitutes for intact C5a. Furthermore, our results indicate that elongation of the C5a analogues from 10 to 19 residues in length contributes little toward enhancing or decreasing potency of the synthetic C5a analogues. Replacement of residues in the effector region by D-amino acids or by introduction of a cyclic group to reduce flexibility of the backbone decreased potency of the analogues. Substitution of His 67 by Phe in the decapeptide C5a 65-74 resulted in a significant increase in potency of the C5a analogue. The marked enhancement in potency from replacing His 67 by Phe in analogue C5a peptides identifies an important hydrophobic subsite. We conclude that site-specific amino acid modifications in or near the C-terminal effector site sequence can diminish or optimize potency of the model C5a peptides. However, there apparently are subsites on folded C5a, from regions other than the C-terminal portion of the molecule, that contribute significant receptor interactions. These subsites must be identified and incorporated into C5a model peptide designs before expression of full potency by synthetic analogues of this factor will be realized.

Amino Acid Sequence↗

PubMed1992

Effects of diet on plasma concentrations of oral anthelmintics for cattle and sheep.

Groups of parasite-free lambs and calves which were either housed and fed hay and concentrates or were grazing on pasture were dosed separately with the oral anthelmintics fenbendazole and ivermectin (lambs only). The plasma concentrations of the drugs and their major metabolites were monitored during the period of their metabolism and excretion. The peak plasma concentrations and the availability of the drugs, as estimated by the areas under the plasma concentration-time curves, were significantly less in the grazing animals. When similar groups of lambs were dosed orally with the inert marker chromium EDTA, which has a particle size similar to the anthelmintics, it was observed that a higher percentage of chromium was excreted by the grazing lambs during the first 40 hours after dosing, suggesting that the extent of absorption in the grazing animals was less than in the housed animals.

Administration, Oral↗

PubMed1992

Inhibition of invasion and metastasis in cells transfected with an inhibitor of metalloproteinases.

The balance between levels of metalloproteinases and their corresponding inhibitors is a critical factor in tumor invasion and metastasis. Down-regulation of the activity of these proteases was achieved by transfection of invasive and metastatic rat cells with the complementary DNA for metalloproteinase inhibitor/tissue inhibitor of metalloproteinase 2 (MI/TIMP-2), a novel inhibitor of metalloproteinases recently described. (Y. A. DeClerck et al., J. Biol. Chem., 264: 17445-17453, 1989; W. G. Stetler-Stevenson et al., J. Biol. Chem., 264: 17374-17378, 1989). Secretion of functional MI/TIMP-2 protein in stably transfected cells resulted in a marked decrease in metalloproteinase activity. Partial suppression of the formation of lung colonies after i.v. injection in nude mice was observed in a transfected clone expressing high levels of MI/TIMP-2. Production of MI/TIMP-2 in four clones markedly reduced tumor growth rate in vivo after s.c. injection and completely suppressed local tissue invasion. Thus, down-regulation of metalloproteinase activity has a striking effect on local invasion and partially suppresses hematogenous metastasis.

Animals↗

PubMed1992

Elimination of apolipoprotein B48 formation in rat hepatoma cell lines transfected with mutant human apolipoprotein B cDNA constructs.

Rat hepatoma McA-RH7777 cell lines transfected with full-length human apolipoprotein (apo) B constructs produce mostly human apoB48 and only small amounts of apoB100, as a result of mRNA editing at codon 2153 (C to U conversion at nucleotide 6666). To abolish the formation of apoB48 and increase the yield of apoB100 and other forms of apoB longer than apoB48, site-specific mutations were introduced at or near the site of apoB mRNA editing. Among four mutations examined, only that in which codon 2153 was converted from CAA (Gln) to CTA (Leu) effectively precluded the formation of apoB48. In this mutant, a stop codon would not be generated even if the C to U conversion occurred. The three other mutations were introduced to disrupt the proposed stem-loop structure encompassing the editing site. Changes made in the third positions of five codons on the 5' side of the edited base or of four codons 3' of the edited base failed to eliminate the production of a protein with the approximate size of apoB48. A construct in which codon 2153 was changed from CAA to GAT (Asp) also failed to eliminate the production of a protein the size of apoB48. Analysis of the region between nucleotides 6200 and 6900 of the cDNA did not detect any prevalent alternate editing sites. Immunoblot analysis using polyclonal antibodies raised against synthetic peptides of human apoB100 indicated that the carboxyl terminus of the apoB48-like proteins probably resides between amino acid residues 2068 and 2129 of apoB100. These results provide some insight into the mechanism of apoB mRNA editing and will facilitate further studies on apoB-containing lipoproteins.

Amino Acid Sequence↗

PubMed1992

The influence of groin sepsis on extraanatomic bypass patency in patients with prosthetic graft infection.

Twenty-seven vascular prosthetic graft infections in 25 patients were managed from 1981 through 1990 using the principles of extraanatomic bypass through uncontaminated fields and removal of the infected prosthesis. This experience included 18 aortic, three femoral-femoral, three femoral-popliteal, two axillofemoral grafts, and one popliteal endarterectomy patch. The predominant organism was Staphylococcus epidermidis (26%). Mean follow-up was 36 months. There was only one early and one late death, with two late amputations. Extraanatomic bypass grafts were placed in 21 of 25 patients including all 18 infected aortic grafts. Of these 21 patients, 11 (52%) experienced at least one extraanatomic bypass failure within 15 months, resulting directly in two major lower extremity amputations and two graft reinfections. Axillounifemoral bypass had a higher incidence of failure than axillobifemoral bypass (54% versus 29%). More importantly, however, extraanatomic graft failure was also associated with the presence of groin sepsis. The revision rate was 63% when the graft required circuitous tunneling to avoid groin sepsis, in contrast to a revision rate of only 17% when the graft could be anastomosed directly to the common femoral artery. Of extraanatomic bypass grafts that failed once, 63% had multiple failures. Graft removal and extraanatomic revascularization produced excellent overall results when not involving the groin. Late complications occurred more frequently when groin sepsis was present. These results suggest that, to reduce the incidence of late graft failure and amputation, more aggressive early direct reconstruction should be performed in lieu of atypical graft tunneling, especially if the extraanatomic graft has failed once and the causative organism is Staphylococcus epidermidis.

Bacterial Infections↗

PubMed1992

Contribution of routine intraoperative completion arteriography to early infrainguinal bypass patency.

To determine the clinical utility of routine intraoperative completion arteriography, we prospectively evaluated 214 consecutive infrainguinal bypass grafts (209 reversed-vein and 5 polytetrafluoroethylene grafts) performed from July 1987 to August 1991. Visual inspection, pulse palpation, and continuous-wave Doppler examination were performed in all cases. At least 1 completion arteriogram was obtained in 213 cases (99%). The bypasses were to the popliteal artery in 130 cases and to the tibial or pedal arteries in 84 cases. Graft patency was confirmed at 30 days in all patients by ankle-brachial index determinations (greater than 0.2 increase) and duplex scan-derived peak-systolic flow velocities (greater than 45 cm/s). Significant technical problems requiring revision were identified in 18 grafts (8%), including 6% of popliteal grafts and 12% of tibial/pedal grafts. Only three of these problems were suspected by pulse palpation or continuous-wave Doppler examination. The intraoperative angiographic findings leading to revision included distal anastomotic stenoses (n = 6), distal arterial disease requiring sequential bypass (n = 4), mid-graft valvular or branch ligature stenoses (n = 4), distal arterial thrombosis (n = 2), and graft kink or twist (n = 2). Thirty-day primary patency was 99% (129 of 130) for femoropopliteal grafts and 93% (78 of 84) for femorodistal grafts. Secondary patency was 100% (130 of 130) and 96% (81 of 84), respectively. Primary patency was 89% (16 of 18) for those grafts that required intraoperative revision based on arteriographic findings. We conclude that routine completion arteriography is an excellent method of ensuring the intraoperative technical adequacy of infrainguinal bypass. The test is easy to perform, reproducible, and should be considered the "gold standard" for intraoperative bypass assessment. Prior to adopting angioscopy or duplex scanning for intraoperative surveillance, randomized, controlled validation studies against angiography should be performed.

Aged↗

PubMed1992

Diminished arachidonic acid metabolite release by bovine alveolar macrophages exposed to surface-modified silica.

Modification of the silica surface has been shown to reduce its cytotoxicity in vitro and its fibrogenic activity in vivo. We have shown silica to be a potent stimulator of arachidonic acid (AA) metabolism in bovine alveolar macrophages (BAM). To determine the effect of surface-modified silica on AA metabolism in BAM, we exposed BAM in vitro to silica treated with aluminum lactate or polyvinylpyridine-N-oxide (PVPNO). BAM were prelabeled with [3H]AA and incubated with 3 and 5 mg of silica. Unmodified silica at these doses elicited maximal AA metabolite release from BAM. AA metabolites were analyzed by high performance liquid chromatography. Lactate dehydrogenase release was quantitated to determine the cytotoxicity of treated and untreated silica on BAM. Treating silica with aluminum lactate or PVPNO significantly (P less than or equal to 0.05) reduced 5-lipoxygenase metabolite release and significantly (P less than or equal to 0.05) increased cyclooxygenase metabolite release. These changes in AA metabolite release were accompanied by a significant (P less than or equal to 0.05) reduction in the cytotoxicities of the treated silicas compared with untreated silica. Our results suggest that the reduced inflammatory and fibrogenic activity of surface-modified silica may in part be due to reduced AA metabolite release from exposed macrophages.

Animals↗

PubMed1992

The effect of unilateral internal carotid arterial occlusion upon contralateral duplex study: criteria for accurate interpretation.

To determine the influence of unilateral internal carotid arterial occlusion (ICO) on Doppler frequency spectral analysis (DFSA) of the patent contralateral carotid artery, a retrospective review of 154 patients between July 1987 and December 1991 with angiographically confirmed ICO was performed, correlating duplex and arteriographic findings in a blinded fashion. Biplane arteriograms and bilateral carotid artery duplex studies that used a 5.0 MHz Doppler probe with a 1.5 mm3 sample volume at a 60 degree angle of insonation were performed on all patients. Each carotid artery was categorized by the severity of stenosis as quantified by arteriography: 1% to 15% (n = 41); 16% to 49% (n = 48), 50% to 79% (n = 21), 80% to 99% (n = 34), and bilateral occlusion (n = 10). DFSA peak systolic frequencies were commonly exaggerated in the presence of contralateral ICO and use of standard criteria for DFSA interpretation overestimated bifurcation stenoses in 43 of 89 lesions (48.3%) when determining nonhemodynamically significant lesions (less than 50% diameter reduction) with a sensitivity of only 57.3% and specificity of 96.9%. Conversely, prediction of hemodynamically significant lesions (greater than 50% diameter reduction) with standard criteria had 96.9% sensitivity but only 57.3% specificity. Modification of these criteria to account for the velocity increase or "jet effect" in the ipsilateral carotid artery system increased the sensitivity and specificity to 97.8% in predicting nonhemodynamically and hemodynamically significant stenoses respectively. A Doppler frequency spectrum with a peak systolic frequency (PSF) greater than 4.0 kHz and end-diastolic frequency (EDF) less than 5 kHz with an "open window" distinguished lesions with less than 50% diameter reduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Flow Velocity↗

PubMed1992

Metabolic effects of ritodrine in the fetal lamb.

Ritodrine infusion to fetal lambs causes numerous metabolic perturbations including hypoxemia. To investigate these changes further and to elucidate a mechanism for the development of hypoxemia, ritodrine was infused at rate of 2.6 micrograms/min into nine chronically catheterized fetal lambs for 8, 12 or 24 hr. Plasma levels of ritodrine (20.0 +/- 2.7 ng/ml) were within the range of those reported in human fetuses exposed to ritodrine tocolysis. Fetal arterial glucose levels nearly doubled (0.72 +/- 0.07 to 1.29 +/- 0.18 mM), whereas lactate levels rose more than 5-fold (1.54 +/- 0.11 to 8.67 +/- 1.12 mM), with the latter change leading to a decline in fetal arterial pH from 7.370 +/- 0.004 to 7.273 +/- 0.033. Fetal oxygen consumption (VO2) rose from 342 +/- 35 to 407 +/- 30 mumol/min.kg via an increase in fetal fractional O2 extraction (32.0 +/- 1.1 to 49.0 +/- 1.7%). The rise in fetal O2 extraction contributed to concurrent declines in fetal arterial PO2 (21.9 +/- 0.6 to 17.0 +/- 0.5 mm Hg) and O2 content (3.7 +/- 0.2 to 2.1 +/- 0.1 mM). Umbilical venous PO2 and O2 content also fell resulting in a decline in fetal O2 delivery (DO2) from 1115 +/- 97 to 838 +/- 68 mumol/min.kg. The rise in fetal VO2 was reflected by a similar rise uterine VO2 (not significant), with the latter being accompanied by a significant increase in uterine O2 extraction and decrease in uterine venous PO2 and O2 content, perhaps contributing to the fall in fetal DO2. In conclusion, fetal hypoxemia during the infusion of ritodrine results from an increase in fetal VO2 that is not compensated for by a similar increase in umbilical or uterine DO2. These metabolic effects may put the fetus at risk, particularly in situations in which fetal DO2 is already reduced, as may occur in compromised pregnancies.

Animals↗

PubMed1991

Determination of ritodrine in biological fluids of the pregnant sheep by fused-silica capillary gas chromatography using electron-capture detection.

A sensitive and selective gas chromatographic assay method employing splitless injection, fused-silica capillary columns and electron-capture detection is reported for the quantitation of the tocolytic drug, ritodrine, in a variety of biological fluids obtained from the pregnant ewe and fetus. This method has improved sensitivity and selectivity over previously published assay procedures. A 25 m x 0.31 mm I.D., cross-linked 5% phenylmethylsilicone, fused-silica capillary column was employed for all analyses. Linearity of response was observed over the range 2.5-75 ng of ritodrine base per 0.05-0.5 ml of biological fluid, representing approximately 1-75 pg at the detector. The coefficient of variation was less than 10% over the range 2.5-75 ng of added ritodrine. The minimum quantifiable amount is approximately 2.5 ng from a 0.5-ml biological fluid sample. Applicability of this method to biological fluids, obtained from ovine subjects, is demonstrated by the analysis of samples obtained during the course of ritodrine placental transfer studies.

Amniotic Fluid↗

PubMed1991

Expression of carboxyl-terminally truncated forms of human apolipoprotein B in rat hepatoma cells. Evidence that the length of apolipoprotein B has a major effect on the buoyant density of the secreted lipoproteins.

We examined the relationship between the size of human apolipoprotein (apo) B and the formation and secretion of apoB-containing lipoprotein particles. Stable transformants of the rat hepatoma cell line McA-RH7777 harboring a variety of human apoB cDNA constructs were established, and these produced carboxyl-terminally truncated apoB proteins (apoB18, -B23, -B28, -B31, -B48, and -B53). Immunoblotting of apoB proteins secreted into the culture medium and fractionated by equilibrium density ultracentrifugation revealed that each of the truncated apoB species was secreted from the cells. The peak densities of the apoB-containing particles decreased as the length of the apoB proteins increased. Apolipoproteins B18 and B23 appeared at the bottom of the salt gradient (d = 1.23 g/ml), whereas particles containing apoB28, -B31, -B37, -B48, and -B53 exhibited progressive decreases in density. The density distribution of secreted apolipoproteins was not affected by the expression or secretion of these recombinant apoB species. As determined by nondenaturing gel electrophoresis, apoB28, -B31, -B37, -B48, and -B53 formed their own discrete particles, and there was a direct correlation between the size of the particles and the length of the apoB species. The efficiency and rate of secretion of these truncated forms of apoB were studied by measuring the decrease of immunoprecipitated 35S-labeled apoB proteins in the cells and their accumulation in the medium. Proteins corresponding to apoB28 or larger were rapidly and efficiently secreted, whereas apoB18 and apoB23 were secreted much more slowly. These data imply that the size of these truncated apoB forms governs the lipid content of the apoB-containing lipoproteins formed as well as the kinetics of secretion.

Animals↗

PubMed1991

Characterization of arachidonic acid metabolism, superoxide production, and bacterial killing by bovine alveolar neutrophils elicited with leukotriene B4 and zymosan-activated plasma.

Leukotriene B4 (LTB4) and zymosan-activated plasma (ZAP) were each instilled into the lungs of steers to elicit alveolar neutrophils for subsequent functional analysis. Prior to instillation of either agent, bronchoalveolar lavage cell populations consisted of 95.8 +/- 0.4% macrophages (mean +/- SEM). Four hours after instillation of LTB4 or ZAP, the lavage cell populations consisted of 75.0 +/- 8.8% and 90.7 +/- 0.7% neutrophils, respectively. Alveolar neutrophils elicited with LTB4 and stimulated with the calcium ionophore A23187 released diminished amounts of LTB4 and increased amounts of 5-hydroxyeicosatetraenoic acid (5-HETE) as compared to circulating neutrophils. Release of superoxide anion was decreased for LTB4-elicited alveolar neutrophils as compared to circulating cells, while bacterial killing was unchanged. ZAP-elicited alveolar neutrophils released diminished amounts of LTB4 when stimulated with A23187 as compared to circulating neutrophils. There were no differences observed in 5-HETE levels between the two cell populations. In addition, release of superoxide anion was diminished among ZAP-elicited alveolar cells, while bacterial killing was unchanged. Incubation of circulating neutrophils with LTB4 did not influence the release of arachidonate metabolites, superoxide anion, or bacterial killing. However, incubation of circulating neutrophils with ZAP, followed by A23187 resulted in a reduction in the release of LTB4, as compared to control cells. Prior exposure to ZAP did not influence the release of superoxide anion or bacterial killing by the circulating neutrophils.

Animals↗

PubMed1991

Comparison of arachidonate metabolism by alveolar macrophages from bighorn and domestic sheep.

We have defined the metabolites of arachidonic acid (AA) secreted by alveolar macrophages (AMs) of bighorn sheep and domestic sheep in response to three agents: calcium ionophore A23187, phorbol myristate acetate (PMA), and opsonized zymosan. Cells were labeled with [3H]AA prior to stimulation and 11 tritiated metabolites, including prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs), and hydroxyeicosatetraenoic acids (HETEs), were detected and quantitated by high-performance liquid chromotography and radiometry. Zymosan stimulation resulted in the release of significantly elevated quantities (P less than 0.05), of LTB4, [5(S), 12(R)-dihydroxy-6,14-cis-8,10-trans-eicosatetraenoic acid], 5-HETE, [5(S)-hydroxyeicosatetraenoic acid], and the nonenzymatic isomers of LTB4, [LTB I, 5(S),12(R)-6-trans-LTB4] and LTB II, [5(S), 12(S)-6-trans-LTB4], from domestic sheep AM when compared to bighorn sheep AM. Phorbol myristate acetate (PMA) stimulation released significantly elevated quantities (P less than 0.04), of TXB2, (thromboxane B2), HHT, [12(S)-12-hydroxy-5,8,10-heptadecaenoic acid], LTB I, LTB II, and 15-HETE, [15(S)-hydroxyeicosatetraenoic acid] from domestic sheep AMs when compared to bighorn sheep AMs. However, after A23187 challenge, only 15-HETE was significantly elevated (P less than 0.04) in domestic sheep AMs when compared to bighorn sheep AMs. These clear differences in AA metabolism of AMs obtained from bighorn and domestic sheep in response to three different agonists suggest not only different control mechanisms for lung metabolism of AA in the two species, but also suggest that differences in the metabolites released may lead to quite different regulation of lung defense mechanisms in the two sheep species.

Animals↗

PubMed1991

Results of infrainguinal revascularization with reversed vein conduits: a modern control series.

To determine the outcome of infrainguinal reversed vein bypasses in the modern era, we reviewed the results of 120 consecutive reversed vein grafts performed from March, 1986 to March, 1990. Forty-nine bypasses were to tibial, peroneal, or pedal arteries, 46 grafts to the below-knee popliteal artery, and 25 grafts to the above-knee popliteal artery. Limb salvage was the indication for revascularization in 70% of patients. All grafts were followed with serial, duplex scan, peak-systolic graft flow velocity measurements every three months for one year and every six months thereafter. The primary life table patency rate at 36 months was 67.6% for the entire series; the secondary patency rate was 92.5%. The secondary patency rate reflects the impact of graft revisions resulting from the detection of failing grafts by duplex scanning. Patency rates of reversed vein grafts to the tibial arteries at 36 months (73.8% primary and 89.8% secondary) were equivalent to those performed to the popliteal artery. Our current patency rates with reversed vein grafts are comparable or superior to those reported for in-situ vein conduits and suggest that operative technique and meticulous follow-up are more important with respect to long-term graft durability than whether the vein is used in the in-situ or reversed configuration.

Arterial Occlusive Diseases↗

PubMed1991

The retroperitoneal, left flank approach to the supraceliac aorta for difficult and repeat aortic reconstructions.

Between 1986 and 1990, 11 patients with relative or absolute contraindications to standard infrarenal reconstructions underwent supraceliac aortofemoral bypass. The operation was performed through a left-flank incision extended into the eleventh intercostal space with retroperitoneal and extrapleural dissection. Indications included multiple failed infrarenal reconstructions in four patients, previous removal of infected aortofemoral bypass graft with failure of extra-anatomic bypass in five patients, prior para-aortic lymph node dissection and radiotherapy in one patient, and aortic aneurysmal disease proximal to the renal arteries in one patient. Bypass conduits included either a bifurcated Dacron graft or a tube graft to the left femoral artery with a femorofemoral cross-over graft; concomitant left renal artery reconstruction was performed in three patients. The mean supraceliac cross-clamp time was 24 minutes, and only one patient experienced transient postoperative acute tubular necrosis. There was no operative mortality. The graft limb patency was 95% after mean follow-up extending to 17 months (range: 5 months to 5 years). We conclude that the supraceliac aorta is a useful inflow source for aortofemoral reconstruction in difficult repeat cases. It can be approached easily without thoracotomy and avoids difficult infrarenal aortic dissection in a scarred field. The tunneling is easier than with descending thoracic aorta or ascending aorta inflow sources. In addition, this bypass is likely to be more durable than inflow reconstructions based on the axillary artery.

Aorta, Abdominal↗

PubMed1991

Psychosocial impacts in populations exposed to solid waste facilities.

This interdisciplinary study uses a parallel case study design to investigate psychosocial impacts in populations exposed to three solid waste facilities in Southern Ontario. Impacts are examined at three social scales: individual, social network and community levels. The objectives and design derive from a feasibility study recently completed by the same research team. A two stage approach is adopted. The first is an epidemiologic survey to determine the prevalence of psychosocial impacts in the populations within a prescribed area around each site. A disproportionate stratified (by distance) random sample of 250 households is surveyed at each site. Data on awareness, knowledge, concern and action regarding the site are also obtained. Scores on pre-validated health measurement scales will be compared with population norms to determine the frequency distribution above, within and below the range of normal. The second stage involves the use of qualitative methodologies to provide an in-depth analysis of the individual, social network and community level factors affecting psychosocial impacts and reactions to the situation. Depth interviews with a sub-sample of survey respondents explore individual perceptions, attitudes and actions. Focus groups composed of members of relevant organizations and discussion groups comprising non-members uncover social network and community perspectives in an interactional setting. Interviews and group sessions are taped and transcribed for content analysis of salient themes. Textual analysis of media reports and other relevant documentation provide insights regarding the informational environment and the community context of the issues.

Adaptation, Psychological↗

PubMed1991

The diabetic foot: consequences of delayed treatment and referral.

The pathophysiology of foot problems in diabetic patients is poorly understood by many physicians. Two major factors that frequently lead to a delay in appropriate treatment with subsequent limb loss are failure to appreciate the presence and severity of underlying infection and attribution of gangrene of the toe and forefoot to microvascular disease. To evaluate the consequences of delayed recognition and treatment, we reviewed the records of 55 diabetic patients with localized gangrene or infection of the forefoot in 62 limbs, treated consecutively on a single vascular surgical service over a 2-year period using a standard protocol. All appropriately treated neuropathic ulcers and forefoot infections healed in patients with palpable pedal pulses. If foot pulses were absent and arteriography confirmed large-vessel occlusive disease, foot lesions and infections likewise healed if concomitant revascularization was done. In our series, 33 bypasses were required because of severe atherosclerotic occlusive disease. Only one patient had "unreconstructable" arterial disease. Limb salvage was 86% at a mean follow-up of 12.4 months. In 16 of the patients (29%), there was a prolonged delay between initial treatment and referral for definitive care. The specific causes of delay were underestimation of the severity of foot infection in 10 patients, and lack of recognition of ischemia due to large-vessel occlusive disease in six. These delays led to more proximal levels of amputation in six patients, including three below-knee amputations in patients with limbs that were initially salvageable.

Adult↗

PubMed1991

Clearance and disposition of ritodrine in the fluid compartments of the fetal lamb during and after constant rate fetal intravenous infusion.

The disposition of the beta-2 adrenoreceptor agonist, ritodrine, has been examined in the fetal lamb during and after constant rate fetal intravenous infusion (8-24 h). Samples were collected from the fetal femoral artery, umbilical vein, maternal femoral artery, uterine vein, fetal trachea and the amniotic activity for ritodrine quantitation. The amniotic fluid was also analyzed for conjugated metabolites of ritodrine. Ritodrine appears to be cleared across the sheep placenta only to a limited extent (placental clearance 9.2 +/- 2 ml/min/kg; mean +/- S.E.M.). There is, however, significant fetal nonplacental clearance of ritodrine (fetal nonplacental clearance 52.8 +/- 8.0 ml/min/kg). At least part of this clearance appears to be due to fetal drug metabolism, as evidenced by the accumulation of glucuronide conjugates of ritodrine in the amniotic fluid. Ritodrine was also shown to accumulate in the amniotic and fetal tracheal fluids and persist after fetal arterial plasma ritodrine concentrations became undetectable. The accumulation of ritodrine in the tracheal fluid may be of pharmacologic significance, given the well documented, potent effects of beta-2 agonists on fetal lung function and development.

Animals↗