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Biomedical subjects

D Kirsch

Publications and source records attributed to D Kirsch.

At least 19 recordsLinked to original sources
PubMed2003

External reinforcement of varicose veins with PTFE prosthesis in infrainguinal bypass surgery -- clinical results.

OBJECTIVE: Segmental varicose degeneration of the autogenous greater saphenous vein may limit its use in infrainguinal bypass surgery. Wrapping a PTFE prosthesis around dilated veins has emerged as an option to create externally reinforced vein bypasses. Results regarding graft patency and limb salvage were analyzed. METHODS: Between September 1995 and January 2001, 35 infrainguinal bypass operations in 33 patients were performed with greater saphenous veins exhibiting segmental varicose dilatation. Grafts were followed by duplex scan and retrospective analysis of graft patency and limb salvage was performed. RESULTS: One bypass prompted successful revision for early occlusion. Four bypasses required additional reintervention during follow-up. 48 months primary, primary assisted and secondary patency rates were 66%, 82% and 82%, respectively, with a limb salvage rate of 97%. Duplex scan failed to demonstrate stenosis of the reinforced vein segments or aneurysmal degeneration of the residual vein. CONCLUSION: External reinforcement with a PTFE prosthesis allows the use of autogenous greater saphenous veins with varicose dilatation and enables the construction of all autogenous bypasses with promising graft patency and limb salvage.

Aged↗
PubMed2001

[Status of discontinuity resection in septic diverticular complications. History or a still current procedure?].

Primary anastomosis is becoming increasingly favoured because of the shorter hospital stay even in emergency operations on the colon and rectum. This appears entirely justified when an objective of cost-effective medicine has been set. At our hospital between September 1985 and February 1999, 365 patients were operated on because of diverticular disease. The data from 346 of these patients were evaluated. 202 of these cases were elective; 144 were carried out on an emergency or urgent basis. In 223 cases, a primary anastomosis (Stage I and II according to Hinchey) and in 56 patients a double-barreled colostomy with a distal mucus fistula were performed. 57 patients had a too short rectum-sigma stump and were operated in two stages, according to Hartmann. Of 223 patients with a primary anastomosis, 6 (2.7%) developed an insufficiency of the anastomosis, whereby 3 (1.3%) of these patients subsequently died. Of the patients with Hartmann operation, 11 (19.3%) died due to the sequelae of peritonitis and only 2 patients died following insufficiency of the Hartmann's stump. Of the patients with a mucus fistula, 10 patients (17.9%) died as a result of complications of peritonitis. Of the 113 patients (21 died) with a discontinuity resection, 66 (71%) had their colostomy closed. There were no cases of anastomosis insufficiency and no patient died as a result of the colostomy closure. In the interest of the patients in septic diverticulitis the safest surgical procedure, the discontinuity resection, should be chosen.

Adult↗
PubMed2001

[Hereditary pancreatitis - a clinically relevant cause of pancreatic adenocarcinoma?].

UNLABELLED: Hereditary pancreatitis is an autosomal dominant disease. Recently, the genetic defect has been mapped to chromosome 7q35 and consists mainly of a point mutation in exon 3 of the cationic trypsinogen gene which causes an Arg(CGC)-His(CAC) substitution at residue 117. In patients with hereditary pancreatitis the estimated cumulative risk for pancreatic carcinoma to age 70 approaches 40 %. Thus, the role of hereditary pancreatitis in the pathogenesis of pancreatic carcinoma is of interest. PATIENTS AND METHODS: DNA was extracted from peripheral blood (n = 16), fresh tumor tissue (n = 29) and formalin fixed and paraffin embedded tumor tissue (n = 5) of 50 patients with ductal adenocarcinoma of the pancreas. We specifically amplified exon 3 and the intronic flanking sequences of the cationic trypsinogen gene by nested PCR and performed restriction fragment length polymorphism analysis using the restriction enzyme Afl III. In patients with hereditary pancreatitis the G : A point mutation creates a recognition site for Afl III which is not present in unaffected individuals. RESULTS: None of the 50 patients with ductal adenocarcinoma of the pancreas revealed the G : A point mutation in exon 3 of the cationic trypsinogen gene which is characteristic of hereditary pancreatitis. In addition sequencing of exon 3 did not reveal any other mutations in the DNA of patients with pancreatic adenocarcinoma. CONCLUSION: Although hereditary pancreatitis markedly increases the risk for pancreatic cancer, it is rare and probably of little significance with respect to the pathogenesis of the majority of pancreatic adenocarcinomas.

Adenocarcinoma↗
PubMed2000

[Primary varicose veins--changes in the venous wall and elastic behavior].

The aetiology of varicosis is still unclear. Investigation of changes in normal veins which result in the formation of varicosis led to examination of elastic properties and histomorphological alterations in the region of the extracellular matrix in the vessel wall of the long saphenous vein in normal and varicose veins. The rigidity of varicose veins was higher than that of normal veins; there was no difference between the varicose vein above a competent valve and the "normal" vein below this competent valve. The matrix proteins demonstrated an increase in total fibres, whereas the elastic fibres were reduced and fragmented, explained the rigidity of varices. These results suggest that the role of the venous valves in the development of varicose veins is secondary to changes of the vein wall.

Animals↗
PubMed2000

Developing outpatient mental health services for managed care.

One of the characteristics of the best outpatient treaters is their capacity to manage their own anxieties so as not to interfere with their patients' progress. This does not mean "sitting on," shutting out, or otherwise ignoring those signals to prevent their intruding into the therapeutic space. On the contrary, this requires that a clinician be acutely aware of his or her internal dialogue and be able to listen to use it to facilitate the treatment. This has meant simultaneously listening to oneself while paying complete attention to one's patient. This paradox is part of the nature of this work and remains one of its important features. Today, those who choose to treat psychiatric patients in this setting are presented with many more such paradoxes, including the necessity of being aware of (1) populations needing to be served while providing the best care for individual patients; (2) limited resources; and (3) balancing ethical, fiscal, legal, and clinical concerns. This article demonstrates that the successful development of outpatient services in a managed care environment requires attention to these same tensions on a larger scale. It also shows that understanding the evolution of managed care and the myriad competing interests involved are necessary to be able to care successfully for psychiatric patients.

Ambulatory Care↗
PubMed2000

Changes in the extracellular matrix of the vein wall--the cause of primary varicosis?

BACKGROUND: Conflicting theories on the development of primary varicosis have led to the molecular biological investigation of the vein wall or, more accurately, of the extracellular matrix. It was the aim of this study to quantify matrix expression and to compare pathological changes in the vein wall with valve-orientated staging of varicosis, in order to determine indicators of the primary cause of varicosis. MATERIALS AND METHODS: Three hundred seventy-two tissue specimens of greater saphenous veins were obtained from 17 patients with varicosities and categorised according to Hach stage and procurement site. The specimens were compared with 36 specimens collected from six patients without varicosities, incubated with fluorescence-stained antibodies for collagen 4, laminin, fibronectin and tenascin prior to being assessed with confocal laser scan microscopy. In addition, 22 vein specimens (16 varicose, 6 normal veins) serving as negative controls were investigated. RESULTS: Image analysis and statistical evaluation showed that compared with normal veins, varicose veins are associated with a significant increase in matrix protein expression for collagen 4, laminin and tenascin. A trend towards an increase in matrix expression was further observed for fibronectin. There was, however, no difference between varicose veins and clinically healthy vein segments inferior to a varicose segment. CONCLUSION: If the findings of the present investigation can be confirmed by other studies, alterations in the vein wall may be regarded as the primary cause of varicosis and valvular insufficiency as the result of these changes.

Extracellular Matrix↗
PubMed1999

Analysis of cyclic and acyclic analogs of retinol, retinoic acid, and retinal by laser desorption ionization-, matrix-assisted laser desorption ionization-mass spectrometry, and UV/Vis spectroscopy.

Laser desorption ionization (LDI)- and matrix-assisted laser desorption ionization (MALDI)-mass spectrometry (LDI-MS, MALDI-MS) at 337-nm laser wavelength were used to analyze retinol (vitamin A), retinoic acid, and retinal and their analogs 3-hydroxyretinol, 3-hydroxyretinoic acid, 3-hydroxyretinal, 4-oxoretinol, 4-oxoretinoic acid, 4-oxoretinal, 3,4-didehydroretinol (vitamin A(2)), 3,4-didehydroretinoic acid, 3,4-didehydroretinal, acycloretinol, acycloretinoic acid, and acycloretinal. The compounds exhibit sufficient ionizability which allows to obtain mass spectra by LDI which are similar in quality to those obtained by MALDI. Mass spectra were recorded with a linear time-of-flight (TOF) instrument or a reflectron-type (RETOF) instrument in positive-ion mode. Under the conditions of LDI-MS the compounds form abundant radical molecular ions (M+*), whereas in the MALDI mass spectra abundant protonated molecular ions ([M + H]+) are observed. Characteristic fragment ions provide additional structural information. High-performance liquid chromatography (HPLC) coupled with UV/Vis photodiode detection was used to assist in retinoid characterization. Synthesis of 3-hydroxyretinal, 4-oxoretinal, and acycloretinal was performed by oxidative cleavage of the all-trans-carotenoids of zeaxanthin, canthaxanthin, and lycopene.

Molecular Structure↗
PubMed1999

Alterations of the extracellular matrix of venous walls in varicous veins.

BACKGROUND: Investigation of changes in normal veins which result in the formation of varicosis led to examination of the histological organisation of the vessel wall and to histomorphological alterations in the region of the extracellular matrix. PATIENTS AND METHODS: The expression pattern of the matrix proteins collagen IV, fibronectin, laminin, tenascin, and undulin as well as the structure and orientation of elastic fibres were determined by means of immunohistochemical staining. RESULTS: All varices exhibited an increased expression pattern in comparison to healthy veins. The venous vessel wall was often non-homogeneously enlarged. The intima was always more involved than the media and showed enhanced accumulation, whereas, the adventitia was not influenced by the pathological process. Collagen IV exhibited an early accumulation, especially in the subendothelial region. The other matrix proteins demonstrated an increase in fibre propagation parallel to the enlargement of the vessel wall. Essentially, an augmented de novo synthesis of fibres with an irregular arrangement and the formation of local plaques was found. Elastic fibres were enhanced by slight involvement of the vessel wall and were reduced and fragmented during increased involvement of the venous wall which explained the rigidity of varices in contrast to normal veins.

Elastic Tissue↗
PubMed1999

[Amputation due to chronic peripheral vascular disease. Risks and prognosis].

A series of 181 amputations in 156 patients treated between 1985 and 1996 because of chronic peripheral vascular disease was reviewed. 107 major amputations (above- and below-knee) and 74 minor amputations (foot and forefoot) were performed. 81% of the patient population had previous vascular operations. Complications, revisions and mortality of all patients were retrospectively analyzed. The operative mortality rate of major amputations was 20% and the operative mortality rate of minor amputations was 9%. By a vessel-reconstruction before amputation the complication- (wound healing) and revision-rate could be reduced. By examination of the family-doctors, the survival times of the patients and the rehabilitation status of 69 living patients were recorded. Minor amputations, below-knee amputations and knee-disarticulations had the best results of rehabilitation.

Adult↗
PubMed1998

A government purchaser perspective: TennCare--strengthening the safety net.

BACKGROUND: On January 1, 1994, in response to escalating Medicaid costs, the State of Tennessee implemented TennCare, a statewide managed health care system for three population groups: Medicaid eligibles, uninsurable individuals, and people who lacked access to insurance through their place of employment. METHODS: Under the TennCare program, the State contracts with ten managed care organizations to provide a comprehensive benefit package to each enrollee. Preventive services are exempt from copayment or deductible requirements. Each patient is assigned to a primary care provider who is responsible for assuring that the enrollee receives preventive services. RESULTS: More than 400,000 previously uninsured and uninsurable persons now receive health care coverage through the TennCare program. An extensive quality assurance program monitors managed care organization service delivery, with particular emphasis on prevention and access. Effective case management, combined with an enrollment cap, have enabled the program to grow at a predictable rate, without exceeding the annual rate of growth of state revenues. CONCLUSIONS: The TennCare program has been successful in using the savings experienced during the shift from a fee-for-service to a managed care Medicaid program to expand coverage to previously uninsured populations.

Humans↗
PubMed1998

Identification of phosphorylated proteins from thrombin-activated human platelets isolated by two-dimensional gel electrophoresis by electrospray ionization-tandem mass spectrometry (ESI-MS/MS) and liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS).

Two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) is a powerful tool to separate complex protein mixtures including whole cell lysates. In combination with immunoblotting techniques or radioactive labeling techniques it is a fast and convenient way to demonstrate the presence of certain proteins or protein modifications. With the development of extremely sensitive analytical techniques such as matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) or electrospray ionization (ESI)-MS, it has become possible to use 2-D gels not only as an analytical but also as a preparative tool. Starting with a number of spots excised from 2-D gels, a protein can be identified using different strategies involving enzymatic cleavage of the protein in the gel matrix, elution of the resulting peptides and analysis of these peptides by mass spectrometry. The obtained peptide mass fingerprint or fragment ion spectra from peptides can be used to screen protein or nucleic acid databases in order to identify the protein. We have used the techniques described above to identify proteins from human platelets which change their phosphorylation state following activation of platelets by thrombin. Platelets were radioactively labeled with [32P]orthophosphate and stimulated. Several protein spots in the observed range of 10-80 kDa and an isoelectric point of 3-10 showed a significant increase or decrease in phosphorylation. We present the results from the investigation of a spot group representing different isoforms and phosphorylation states of myosin light chain.

Amino Acid Sequence↗
PubMed1998

Inhibition of avian osteoclast bone resorption by monoclonal antibody 121F: a mechanism involving the osteoclast free radical system.

Osteoclasts generate high levels of superoxide anions during bone resorption that contribute to the degradative process, although excessive levels of this free radical may be damaging. One mechanism for their removal is via superoxide dismutase (SOD), a protective superoxide scavenging enzyme. We have previously described a novel developmentally regulated 150 kDa plasma membrane glycoprotein of avian osteoclasts which is reactive with the osteoclast-specific monoclonal antibody (Mab) 121F and is related immunologically, biochemically, and in protein sequence to mitochondrial Mn2+/Fe2+ SOD. We hypothesized that this unusual osteoclast surface component may be involved in protection against superoxides generated during active bone resorption. Increasing concentrations of monovalent Fab fragments prepared from Mab 121F, but not those from another antiosteoclast Mab designated 29C, markedly inhibited both bone particle and bone pit resorption by avian osteoclasts, while reducing tartrate-resistant acid phosphatase activity and causing the morphological contraction of osteoclasts on bone. Thus, the SOD-related membrane antigen may be essential for osteoclast bone resorption. Osteoclast superoxide production, monitored kinetically by cytochrome c reduction and histochemically by nitroblue tetrazolium reduction staining, was significantly greater in the presence of 121F, but not 29C, Fab treatment. Furthermore, the release of another free radical known as nitric oxide, which is produced by osteoclasts, can scavenge superoxides, and acts to potently inhibit osteoclast bone resorption, was dose-dependently increased by 121F Fab in resorbing osteoclast cultures. Therefore, Mab 121F binding may block the potential protective function of the osteoclast plasma membrane SOD-related glycoprotein, leading to a rapid elevation of superoxide levels and a subsequent rise in osteoclast nitric oxide release, feedback messages which may be sensed by the osteoclast as signals to cease active bone resorption.

Acid Phosphatase↗
PubMed1998

Rapid acquisition of beta-sheet structure in the prion protein prior to multimer formation.

The N-terminally truncated form of the prion protein, PrP 27-30, and the corresponding recombinant protein, rPrP, were solubilized in 0.2% SDS, and the transitions induced by changing the conditions from 0.2% SDS to physiological conditions, i.e. removing SDS, were characterized with respect to solubility, resistance to proteolysis, secondary structure and multimerization. Circular dichroism, electron microscopy and fluorescence correlation spectroscopy were used to study the structural transitions of PrP. Within one minute the alpha-helical structure of PrP was transformed into one that was enriched in beta-sheets and consisted mainly of dimers. Larger oligomers were found after 20 minutes and larger multimers exhibiting resistance to proteolysis were found after several hours. It was concluded that the monomeric alpha-helical conformation was stable in SDS or when attached to the membrane; however, the state of lowest free energy in aqueous solution at neutral pH seems to be the multimeric, beta-sheet enriched conformation.

Animals↗
PubMed1998

Prion rods contain small amounts of two host sphingolipids as revealed by thin-layer chromatography and mass spectrometry.

Sphingolipids were detected in prions, the agents of transmissible spongiform encephalopathies. The analysis was carried out on highly purified, infectious prion rods, which are composed mainly of insoluble aggregates of the N-terminally truncated prion protein, so-called PrP 27-30. Lipid classes were quantified by high performance thin-layer chromatography with a detection limit of 25-50 ng per lipid class. Matrix-assisted laser desorption/ionization mass spectrometry was applied for the first time to lipid analysis in complex biological samples. A newly developed preparation technique improved the sensitivity to 1-20 pg per molecular species. Only the sphingolipids, galactosylceramide and sphingomyelin, were consistently observed in chloroform/methanol (2:1 v/v) extracts of prion rods. The molar ratio of PrP to the sphingolipids was between 2:1 and 40:1, depending on the purity of the prion preparation. The same lipids were also present in the low density fraction of a gradient centrifugation of prion-rods after sonication in 0.2% SDS. From the two alternatives, that the sphingolipids are either required for prion function or are relics from the cellular location of PrP in caveolae, the second alternative appears more plausible since the preparation of highest specific infectivity contained the lowest amount of sphingolipids.

Animals↗
PubMed1997

High-performance liquid chromatography and laser desorption/ionization mass spectrometry of retinyl esters.

Laser desorption/ionization mass spectrometry (LDI-MS) at 337 nm laser wavelength was used to analyze retinol and several long-chain fatty acid esters of retinol. Employing this ionization technique helped to overcome the inherent problems resulting from thermal instability of retinyl esters which render this group of compounds rather difficult for standard ionization techniques. Mass spectra were recorded with a linear time-of-flight instrument in positive ion mode. Under these conditions, retinyl esters formed radical molecular ions (M.+) and in addition fragmented by elimination of the fatty acyl chain to uniformly form a peak at m/z = 269 u. The elimination of carbon dioxide was also observed in the spectra. The method is suitable to identify specific retinyl esters in complex mixtures of these compounds. A gradient reversed-phase high-performance liquid chromatography (HPLC) is described for the separation of retinol and 15 related fatty acid esters within 28 min. HPLC was applied to separate retinyl esters from rat liver extracts. The LDI mass spectrum of the collected HPLC fraction of rat liver extract showed the molecular parent ions of retinyl myristate, pentadecanoate, palmitoleate, palmitate, heptadecanoate, linoleate, oleate, stearate, and 3,4-didehydroretinyl palmitate. LDI-MS was found to be more appropriate than matrix-assisted laser desorption/ionization for the described analytical task.

Animals↗
PubMed1997

Ca2+ or phorbol ester but not inflammatory stimuli elevate inducible nitric oxide synthase messenger ribonucleic acid and nitric oxide (NO) release in avian osteoclasts: autocrine NO mediates Ca2+-inhibited bone resorption.

Osteoclast bone resorption is essential for normal calcium homeostasis and is therefore tightly controlled by calciotropic hormones and local modulatory cytokines and factors. Among these is nitric oxide (NO), a multifunctional free radical that potently inhibits osteoclast bone resorption in vitro and in vivo. Previous findings led us to propose that NO might serve as an autocrine, as well as paracrine, regulator of osteoclast function. This premise was investigated using isolated bone-resorptive avian osteoclasts and focusing on the inducible isoform of NO synthase (iNOS) responsible for inflammatory stimulated high-level NO synthesis in other cells. Avian osteoclasts expressed both iNOS messenger RNA (mRNA) and protein. However, inflammatory cytokines that induce iNOS mRNA, protein, and NO in other cells did not do so in avian osteoclasts, consistent with the known role of inflammatory stimuli in promoting osteoclast resorption and localized bone loss. In searching for potential modulators of osteoclast iNOS, protein kinase C activation [by phorbol 12-myristate 13-acetate (PMA)] and intracellular Ca2+ rises (A23187) were each found to elevate osteoclast iNOS mRNA and protein levels, while increasing NO release and reducing osteoclast bone resorption. The iNOS selective inhibitor aminoguanidine suppressed stimulated osteoclast NO production elicited by either signal, but reversed only the resorption inhibition due to raised Ca2+. Thus, whereas additional inhibitory signals are presumably coproduced in osteoclasts treated with PMA, osteoclast iNOS-derived NO may act as an autocrine signal to mediate Ca2+-inhibited bone resorption. These findings document for the first time an iNOS whose mRNA levels are regulated by Ca2+ or PMA, but not inflammatory stimuli, and the autocrine production of NO as a Ca2+ sensing signal to suppress osteoclast bone resorption. The unusual regulation of osteoclast iNOS makes it a potentially attractive target for designing novel therapeutic agents to alleviate excessive bone loss.

Animals↗
PubMed1997

[Long-term outcome after reconstructive interventions of the aorto-iliac segment].

From September 1985 to February 1994, 183 patients (arterial occlusive disease n = 108, abdominal aneurysm n = 75) underwent reconstruction of the abdominal aorta. In 120 patients an aorto-bi-iliac or aorto-bi-femoral reconstruction was performed and in 63 patients a tube-type reconstruction. The early and late postoperative complications are described. The complications were dependent on the choice of graft, the distal anastomosis and the preoperative risk factors. The mortality from elective repairs was compared with the mortality in emergency repairs. The role of endovascular reconstructive surgery in comparison to conventional reconstructive procedures is discussed.

Aged↗