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Biomedical subjects

R S Martin

Publications and source records attributed to R S Martin.

At least 19 recordsLinked to original sources

Estimation of intra-abdominal pressure by bladder pressure measurement: validity and methodology.

BACKGROUND: Increased intra-abdominal pressure (IAP) is an adverse complication seen in critically ill, injured, and postoperative patients. IAP is estimated via the measurement of bladder pressure. Few studies have been performed to establish the actual relationship between IAP and bladder pressure. The purpose of this study was to confirm the association between intravesicular pressure and IAP and to determine the bladder volume that best approximates IAP. METHODS: Thirty-seven patients undergoing laparoscopy had intravesicular pressures measured with bladder volumes of 0, 50, 100, 150, and 200 mL at directly measured intra-abdominal pressures of 0, 5, 10, 15, 20, and 25 mm Hg. Correlation coefficients and differences were then determined. RESULTS: Across the IAP range of 0 to 25 mm Hg using all of the tested bladder volumes, the difference between IAP and intravesicular pressures (bias) was -3.8 +/- 0.29 mm Hg (95% confidence interval) and measurements were well correlated (R2 = 0.68). Assessing all IAPs tested, a bladder volume of 0 mL demonstrated the lowest bias (-0.79 +/- 0.73 mm Hg). When considering only elevated IAPs (25 mm Hg), a bladder volume of 50 mL revealed the lowest bias (-1.5 +/- 1.36 mm Hg). A bladder volume of 50 mL in patients with elevated IAP resulted in an intravesicular pressure 1 to 3 mm Hg higher than IAP (95% confidence interval). CONCLUSION: Intravesicular pressure closely approximates IAP. Instillation of 50 mL of liquid into the bladder improves the accuracy of the intravesicular pressure in measuring elevated IAPs.

Abdomen↗

Identification of a locus for autosomal dominant polycystic liver disease, on chromosome 19p13.2-13.1.

Polycystic liver disease (PCLD) is characterized by the growth of fluid-filled cysts of biliary epithelial origin in the liver. Although the disease is often asymptomatic, it can, when severe, lead to complications requiring surgical therapy. PCLD is most often associated with autosomal dominant polycystic kidney disease (ADPKD); however, families with an isolated polycystic liver phenotype without kidney involvement have been described. The clinical presentation and histological features of polycystic liver disease in the presence or absence of ADPKD are indistinguishable, raising the possibility that the pathogenetic mechanisms in the diseases are interrelated. We ascertained two large families with polycystic liver disease without kidney cysts and performed a genomewide scan for genetic linkage. A causative gene, PCLD, was mapped to chromosome 19p13.2-13.1, with a maximum LOD score of 10.3. Haplotype analysis refined the PCLD interval to 12.5 cM flanked by D19S586/D19S583 and D19S593/D19S579. The discovery of genetic linkage will facilitate diagnosis and study of this underdiagnosed disease entity. Identification of PCLD will be instrumental to an understanding of the pathogenesis of cyst formation in the liver in isolated PCLD and in ADPKD.

Adult↗

Dual-electrode electrochemical detection for poly(dimethylsiloxane)-fabricated capillary electrophoresis microchips.

The development of a poly(dimethylsiloxane)-based (PDMS-based) microchip electrophoresis system employing dual-electrode electrochemical detection is described. This is the first report of dual-electrode electrochemical detection in a microchip format and of electrochemical detection on chips fabricated from PDMS. The device described in this paper consists of a top layer of PDMS containing the separation and injection channels and a bottom glass layer onto which gold detection electrodes have been deposited. The two layers form a tight reversible seal, eliminating the need for high-temperature bonding, which can be detrimental to electrode stability. The channels can also be temporarily removed for cleaning, significantly extending the lifetime of the chip. The performance of the chip was evaluated using catechol as a test compound. The response was linear from 10 to 500 microM with an LOD (S/N = 3) of 4 microM and a sensitivity of 45.9 pA/microM. Collection efficiencies for catechol ranged from 28.7 to 25.9% at field strengths between 200 and 400 V/cm. Dual-electrode detection in the series configuration was shown to be useful for the selective monitoring of species undergoing chemically reversible redox reactions and for peak identification in the electropherogram of an unresolved mixture.

Dimethylpolysiloxanes↗

Characterization of human recombinant alpha(2A)-adrenoceptors expressed in Chinese hamster lung cells using extracellular acidification rate changes.

1. Human alpha(2A)-adrenoceptors heterologously expressed in Chinese hamster lung (CHL) fibroblasts have been characterized pharmacologically using a cytosensor microphysiometer to measure ligand-induced extracellular acidification rate changes. 2. In untransfected CHL cells, noradrenaline had no effect at concentrations up to 100 microM. In alpha(2A)-adrenoceptor transfected cells the rank order of agonist potency was A-54741 (mean pEC(50)=8.96)>dexmedetomidine (8.88)>UK-14304 (8.42)>B-HT 920 (7.05)>noradrenaline (6.92). A-54741, UK-14304 and noradrenaline had the same maximum response while dexmedetomidine and B-HT 920 behaved as partial agonists. 3. The selective alpha(2)-adrenoceptor ligand rauwolscine antagonized acidification rate changes with an affinity independent of the agonist used; the affinity (mean pK(B)) against noradrenaline was 8.43. 4. The selective alpha(1)-adrenoceptor ligands prazosin and doxazosin (each 3 microM) had no effect on noradrenaline responses. 5. Acidification rate changes induced by each agonist were abolished by pre-treatment of cells with pertussis toxin. 6. These data suggest that agonist-induced acidification rate responses in CHL cells transfected with the human alpha(2A)-adrenoceptor are mediated exclusively by the recombinant protein, via pertussis toxin sensitive G(i/o) proteins.

Adrenergic alpha-Agonists↗

Effects of cannabinoid receptor agonists on neuronally-evoked contractions of urinary bladder tissues isolated from rat, mouse, pig, dog, monkey and human.

This study investigated the cannabinoid receptor, known to inhibit neuronally-evoked contractions of the mouse isolated urinary bladder, in bladder sections isolated from mouse, rat, dog, pig non-human primate or human. The CB(1)-like pharmacology of the cannabinoid receptor in mouse isolated bladder observed previously was confirmed in this study by the rank order of agonist potencies: CP 55940>/=WIN 55212-2>HU 210>JWH 015>anandamide, the high affinity of the CB(1) selective antagonist, SR 141716A (apparent pK(B) 8.7), and the low affinity of the CB(2) antagonist, SR 144528 (apparent pK(B)<6.5). In these studies, SR 141716A (10-100 nM) significantly potentiated electrically-evoked contractions in this tissue by an undetermined mechanism. A similar rank order of agonist potencies was determined in rat isolated bladder sections (CP 55, 940> or =WIN 55212-2>JWH 015). In this tissue, the maximal inhibitory effect of all agonists was lower than in the mouse bladder. Indeed, the effects of both HU 210 and anandamide were too modest to quantify potency accurately. In the rat isolated bladder, SR 141716A (30 nM) or SR 144528 (100 nM), reversed the inhibitory effect of WIN 55212-2 (apparent pK(B) = 8.4 and 8.0, respectively) or JWH 015 (apparent pK(B) = 8.2 and 7.4, respectively). These findings may demonstrate pharmacological differences between the rat and mouse orthologues of the CB(1) receptor. Alternatively, they may be attributed to a mixed population of CB(1) and CB(2) receptors that jointly influence neurogenic contraction of the rat bladder, but cannot be differentiated without more selective ligands. WIN 55212-2 had no effect on electrically-evoked contractions of bladder sections isolated from dog, pig, cynomolgus monkey and human. These findings suggest that the effect of cannabinoid agonists to inhibit neurogenic contraction of the mouse and rat bladder is not conserved across all mammalian species.

Acetylcholine↗

A novel frameshift mutation (2436insT) produces an immediate stop codon in the autosomal dominant polycystic kidney disease 2 (PKD2) gene.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disorder that can be caused by mutations in at least three different genes. Several mutations have been identified in PKD1 and PKD2 genes. Most of the mutations found in PKD2 gene are predicted to cause premature termination of the protein. METHODS: We analysed an Argentinian family characterized previously as PKD2. The PKD2 gene was amplified from genomic DNA using 17 primer pairs and the products were analysed by heteroduplex analysis. PCR products that showed a variation by heteroduplex analysis were sequenced directly. The mutation was confirmed by sequencing relatives. The segregation of the mutation in this family was verified by restriction endonuclease digestion of PCR products obtained from genomic DNA of all family members. Results and conclusions. Here, we report a novel mutation present in an Argentinian family characterized as PKD2 by linkage analysis. The mutation, shared by all affected members of the family, is a thymidine insertion at position 2436 of the gene, which results in a translation frameshift and creates an immediate stop codon. This mutation is expected to lead to a truncated protein that lacks the interacting domain with the PKD1 gene product. The thymidine insertion abolished a Ddel restriction site, allowing a rapid test for detection of PKD2 carriers in the family.

Adult↗

Somatostatin receptor scintigraphy: the definitive technique for characterizing vasoactive intestinal peptide-secreting tumors.

Vasoactive intestinal peptide-secreting tumors (VIPomas) are extremely rare and difficult to diagnose. The authors describe a patient who was found to have a VIPoma after 3 years of symptoms. Somatostatin receptor scintigraphy using indium-labeled octreotide localized her tumor and prompted a surgical resection. This is the preferred imaging study for the earliest, most accurate, and cost-effective identification of VIPomas and their metastases.

Female↗

Isolated polycystic liver disease not linked to polycystic kidney disease 1 and 2.

Autosomal dominant polycystic liver disease occurs commonly in association with autosomal dominant polycystic kidney disease, types 1 and 2. It may also exist as a separate entity, genetically distinct from autosomal dominant polycystic kidney disease types 1 and 2, as has been recently established to exist in a Belgian family. We report here a large Argentinian family of Spanish-Belgian ancestry with autosomal dominant polycystic liver disease, where proximal and distal markers for both polycystic kidney disease 1 and 2 failed to demonstrate genetic linkage. The data support the notion that polycystic liver disease and autosomal dominant polycystic kidney disease may have separate chromosomal loci.

Adult↗

Methamphetamine-induced alterations in dopamine transporter function.

Repeated methamphetamine (METH) administration has been shown to produce differing neurochemical as well as behavioral effects in rats. This study was designed to examine the effects of acute and chronic METH exposure on uptake and release of [3H]dopamine (DA) in cultured midbrain dopamine neurons to determine if persistent neuronal adaptations ensue. In addition, we have assessed DA D2 receptor function to determine if chronic METH alters this receptor. Fetal midbrain cultures were exposed to METH (1, 10 microM) for 5 days and dopaminergic function examined 1 or 7 days after drug removal. The ability of METH to release [3H]DA was compared to other releasing agents as well as several potent uptake inhibitors. Chronic exposure to a release-promoting concentration of METH resulted in either no change or a reduction in [3H]DA release upon subsequent METH challenge. Pretreatment with METH was also found to cause a decrease in the Bmax for [3H]raclopride binding, suggesting that persistently elevated DA levels cause a downregulation of DA D2 receptors. Examination of transporter kinetics utilizing initial velocity of uptake revealed that METH treatment caused a significant decrease in affinity (K(m)) for the substrate (DA), while not altering the maximal velocity of uptake (Vmax). Binding studies with [125I]RTI-55 revealed that there was no alteration in either the Bmax or Kd for this ligand, suggesting that the changes induced by METH treatment are due to alterations in K(m) and not in the number of DA transport sites. The results from these studies indicate that METH treatment produces a modification in transporter function which may be associated with both the altered uptake and release of [3H]DA. These changes have broad implications for the regulation of transporter activity not only because of the relevance to pre-synaptic mechanisms controlling neurotransmission, but also to the importance of the neuronal adaptation that occurs in response to chronic METH exposure.

Animals↗

Prolonged dopamine and serotonin transporter inhibition after exposure to tropanes.

Cocaine and tropane analogs are known to interact with biogenic monoamine transporters by inhibiting amine uptake. Previous in vivo studies have demonstrated that some of these tropanes produce a longer lasting behavioral effect compared with cocaine. We have previously examined several tropane analogs and found a difference in their relative affinities for dopamine (DA) and serotonin (5-HT) transporters. The purpose of this study was to determine the recovery time of transporter function in vitro and in vivo comparing cocaine with the tropane analogs WF-11 (PTT, selective for DA transporters), WF-31 (selective for 5-HT transporters) and WF-23 (highly potent at both DA and 5-HT transporters). In vitro, using primary rat brain cultures of either midbrain or raphe regions, the recovery of the ability to transport either [3H]dopamine or [3H]serotonin, respectively was evaluated at 0, 3, 24, 48, 120 and 240 h after a 1 h exposure to cocaine and tropane analogs. The tropanes exhibited clearance half-lives ranging from 12 to 69 h, while cocaine, on the other hand, exhibited a clearance half-life of approximately 6 h. In studies utilizing [125I]RTI-55 binding, intraperitoneal injections of cocaine and WF-23 into the rat resulted in striatal clearance half-lives ex vivo that were almost identical to those obtained in vitro. These data suggest that the tropanes bind to and reduce transporter function for prolonged periods of time (up to 10-fold longer than cocaine) and those compounds with the highest affinity may produce a pseudo-irreversible inhibition of transporter function.

Animals↗

Regulation of cell cyclic AMP in medullary thick ascending limb of Henle in a rat model of chronic renal failure.

Chronic renal failure (CRF) is accompanied by adaptive changes in electrolyte reabsorption in the thick ascending limb of Henle of surviving nephrons. To study the cellular mechanism of this adaptation, we measured intracellular cAMP in micro-dissected medullary thick ascending limb (mTAL) segments in rats with CRF. mTAL exhibited in CRF an increase of basal cAMP from 25.6 +/- 10.0 in controls to 65.8 +/- 11.3 fmol mm-1 tubule in CRF (P < 0.05). Vasopressin and calcitonin stimulated mTAL adenylate-cyclase in a dose-dependent manner in controls but failed to stimulate in CRF. Likewise, maximal stimulation with 10(-3) M 3-isobutyl-1-methylxanthine (IBMX) plus 10(-5) M forskolin increased cAMP in controls to 63.0 +/- 16.0 but not in CRF, where maximal stimulated values remained at 63.1 +/- 18.8 fmol mm-1 tubule (P NS). Alpha2-adrenoreceptor activation with clonidine at concentrations ranging from 10(-8) to 10(-6) M diminished cAMP production by 37% in CRF (P < 0.05), whereas no differences were found in controls. Thus, the basal intracellular cAMP is increased in rat mTAL in CRF. The finding that neither forskolin nor vasopressin were able to further augment intracellular cAMP would suggest that stimulatory pathways of the adenylate-cyclase system are activated in the basal state. However, mTAL cells in CRF seem to retain the response of normal epithelium to inhibitory pathways such as the one mediated by alpha2-adrenoreceptors.

1-Methyl-3-isobutylxanthine↗

Technical complications of endovascular abdominal aortic aneurysm repair.

PURPOSE: Results from 34 endovascular repairs of abdominal aortic aneurysms are reviewed to identify technical complications and relate them to anatomic and technical features of the operation. METHODS: Twenty-one patients underwent attempted tube graft repair (mean follow-up, 13 months). Thirteen patients underwent placement of a bifurcated graft (mean follow-up, 7.2 months). RESULTS: Twenty-five patients (74%) underwent repair without technical complication (16 tube graft and nine bifurcated graft). Of five patients who had tube graft complications, two involved small iliac arteries and resulted in arterial injury. One of these patients needed a femorofemoral bypass procedure, and the other required conversion to standard operation. Two patients had distal leaks associated with the attachment system, and one patient had misplacement of the distal attachment system. The two patients who had leaks were followed-up; one required operation after 7 months, whereas the other leak sealed. The patient who had distal attachment system misplacement had a second endograft placed within the first to provide a distal seal. The four patients who had bifurcated graft complications involved two graft limb stenoses, one managed with a Palmaz stent and the other with balloon angioplasty. The patient treated with balloon angioplasty had graft thrombosis 1 week after the operation, which resulted in the need for a femorofemoral bypass procedure. Another bifurcated graft patient had a graft limb twist, which has resulted in chronic claudication. One patient had placement of a limb too proximal in the common iliac artery with chronic leak, and an open operation was performed 18 months later. CONCLUSIONS: Technical complications in this series seem to be associated with short distal necks, small iliac arteries, tortuous iliac arteries, and atherosclerosis at the aortic bifurcation. We believe that experience and understanding of these issues will reduce the risk of these complications in the future.

Aged↗

Limb ischemia: surgical therapy in acute arterial occlusion.

Mortality and amputation rates from acute arterial occlusion are reported from 7 to 37 per cent and 10 to 30 per cent, respectively. Recent data from thrombolysis or peripheral arterial surgery suggest no significant differences between initial management with surgical or thrombolytic therapy. Mortality and amputation rates were in the above ranges. The last 230 procedures (216 patients) over 10 years were reviewed. All graft occlusions, cardiac catheterization injuries, and aortic balloon-related thromboses were excluded. Immediate and delayed amputation rates were 6.5 and 0.9 per cent. Death occurred in 21 patients (9.7%), with only 6 deaths over the last 6 years (3.8%). Except for transesophageal echocardiography, perioperative studies were of limited value. Long-term anticoagulation was also not effective in preventing recurrent episodes. A mortality rate of 9.7 per cent and amputation rate of 7.4 per cent justifies an early aggressive surgical approach. Limited perioperative studies and less prolonged anticoagulation may also improve cost containment.

Acute Disease↗

Resource utilization and pathways: meeting the challenge of cost containment.

The 1990s will bring sweeping changes with managed care and capitation. To address this cost/quality paradox, selective intensive care utilization is coupled with clinical pathways as an innovative change for all patients having cerebral revascularization (CVR) or femoral revascularization (FR). From January 1, 1991 through June 30, 1995, data were accumulated on 2023 procedures in 1524 patients. The study was based on 848 CVRs and 1175 FRs. Intensive care unit (ICU) observation was necessary in 73 patients (3.6%) for cardiac or hypertensive management. Twenty-six patients (1.2%) transported to a vascular surgical floor from the postanesthesia recovery room required return to an ICU for complications during hospitalization. There were nine strokes or transient ischemic attacks (0.4%) in the CVR group, four myocardial infarctions (0.2%), and five perioperative deaths (0.3%). In the FR group, there were 14 deaths (0.9%). Readmission during the perioperative period, 30 days, was necessary in 46 patients (3.1%). Financial cost analysis revealed the mean adjusted cost for CVR in 1990 adjusted to 1995 dollars was $7223. The institution of case management reduced this to $4490 (37.8 per cent reduction in total hospital costs). The cost for FR in 1990 dollars adjusted to 1995 was $14,332 reduced to $5541 (a 59 per cent reduction in total hospital costs). This study suggests the use of clinical pathways does not impair quality of care, leads to no higher morbidity or mortality, and can produce significant cost savings to a hospital.

Aged↗

Case management in cerebral revascularization.

PURPOSE: We examined the clinical and financial outcomes of case management coupled with the initiation of selective use of the intensive care unit (ICU) in all cerebral revascularization procedures. METHODS: Three hundred eighty-four procedures in 331 patients were retrospectively reviewed. Morbidity and mortality rates, hospital length of stay, cost, and ICU or hospital readmissions were examined. Hypertension was examined as an independent variable for its effect on patient outcome. RESULTS: Cerebral revascularization, including carotid endarterectomy, vertebral-carotid artery transposition, and subclavian-carotid artery transposition, yielded a 0.78% stroke rate and 0.26% perioperative death rate in this series. ICU admission was necessary in nine patients (2.3%) for cardiac or respiratory instability. Three patients (0.78%) required transfer to the ICU for management of hypertension or hypotension. The mean hospital length of stay after institution of case management was reduced by 2.1 days, and the mean cost was decreased by $1987, a savings of 28.9% of total hospital cost. CONCLUSION: The dual approach of case management and selective use of the ICU promotes quality patient care, conserves financial resources without adversely affecting morbidity or mortality rates, enhances physician/nurse collaboration, and improves patient satisfaction.

Aged↗

Cryopreserved saphenous vein allografts for below-knee lower extremity revascularization.

OBJECTIVE: Cryopreserved saphenous vein allografts have been offered as an alternative conduit for bypass in ischemic limbs. The authors examined the efficacy of this conduit for arterial bypass to the distal popliteal and tibial arteries in patients in whom autogenous vein was not available. SUMMARY BACKGROUND DATA: Previous experience with arterial and venous allografts has been unsatisfactory because of aneurysmal degeneration and poor patency. Endothelial loss and host rejection have been suggested as mechanisms of graft failure. Cryopreservation by modern techniques with rate controlled freezing, dimethyl sulfoxide (DMSO), and other cryopreservants, has addressed these issues and rekindled interest in vein allografts. METHODS: Over a period of more than 5 years, 115 cryopreserved vein allografts were implanted in 87 limbs to the distal popliteal (14) or tibial (101) arteries. The indication for surgery was rest pain in 56 procedures (49%), gangrene in 36 (31%), claudication in 21 (18%), and replacement of aneurysmal allografts in 2. Follow-up was 1 to 61 months (mean 25 months). RESULTS: There was no significant difference in patency related to site of proximal or distal anastomosis, patency of runoff vessels, use of anticoagulation, age, sex, diabetes, hypertension, smoking, indication, source of graft, or use of multiple segments. Revision was required in six grafts for aneurysmal dilatation. Histologic examination of explanted sections of allografts showed no immune response, and immunosuppressive drugs were not used. CONCLUSIONS: Although limb salvage has been satisfactory, long-term patency rates for cryopreserved vein allografts are poor when compared with autogenous vein. The cost of cryopreserved allografts far exceeds that of prosthetic grafts, for which comparable and superior results have been reported. Use of cryopreserved vein allografts should be reserved for situations in which adequate lengths of autogenous vein do not exist and the risk of infection of prosthetic grafts is high.

Adult↗

Subclavian revascularization. A quarter century experience.

OBJECTIVE: Twenty-five years of experience with subclavian revascularizations were reviewed to determine the long-term patency rates of different extrathoracic approaches. SUMMARY BACKGROUND DATA: Although it is generally agreed that proximal subclavian stenosis should be treated by an extrathoracic route whenever possible, the optimum procedure is debated. Alternatives include subclavian carotid bypass, subclavian-to-subclavian or axillo-axillary bypasses, and the authors' preferred technique of subclavian carotid transposition (SCT). METHODS: Records were researched for the past 25 years in a single specialty surgical clinic for extrathoracic subclavian revascularizations. One hundred ninety such procedures were identified, and hospital charts and office medical records were reviewed for procedure, preoperative symptoms, blood pressure differentials, and postoperative complications. Patency was determined by physical examination, differential blood pressures, Doppler spectral analysis, duplex examinations, and arteriography. RESULTS: Bypass procedures were used infrequently, and although the results are reported, they are excluded from any analysis. Subclavian carotid transposition was used in 178 procedures. All anastomoses were found to be patient at follow-up, except for one, which failed at 26 months. Mean follow-up was 46 months, with five patients lost to follow-up. Overall mortality rate was 2.2%, with the mortality falling to 1.1% if only subclavian carotid transposition patients are included. CONCLUSIONS: Subclavian carotid transposition should be the treatment of choice for routine subclavian carotid occlusive disease because of its exceptional long-term patency and low morbidity.

Adult↗