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Biomedical subjects

A Goetz

Publications and source records attributed to A Goetz.

At least 19 recordsLinked to original sources
PubMed2006

Association between vasopressor dependence and early outcome in patients after cardiac surgery.

Arterial hypotension with vasopressor dependence is a major problem after cardiac surgery. We evaluated the early postoperative course of 1558 consecutive patients scheduled for cardiac surgery, and compared the outcome of patients with and without vasopressor dependence (defined as the need for > 0.1 microg x kg(-1) x h(-1) noradrenaline for > 3 h in the face of normovolaemia). Vasopressor dependence was diagnosed in 424 patients (27%) and was associated with a higher incidence of postoperative renal failure (67 (15.7%) vs 7 (0.6%), respectively; p < 0.0001), a longer duration of ventilation (median IQR [range]) 14 (8-26 [6-39]) h vs 8 (5-11 [4-32]) h; p < 0.0001), a greater need for red cell transfusion (3 (1-5 [0-10]) units vs 1 (0-2 [0-4]) units; p < 0.001) and a longer length of stay in the ICU (4 (2-6 [2-9] days) vs 2 (1-3 [1-6] days; p < 0.001). Vasopressor dependence could be predicted from a combination of factors, including pre-operative ejection fraction < 37%, cardiopulmonary bypass lasting > 94 min, and postoperative interleukin-6 > 837 pg x ml(-1).

Aged↗
PubMed2001

A phase I and pharmacokinetic study of 1843U89, a noncompetitive inhibitor of thymidylate synthase, in patients with advanced solid malignancies.

This study was performed to assess the feasibility of administering 1843U89, a potent, noncompetitive inhibitor of thymidylate synthase that does not require polyglutamation for activity, as a 2-min i.v. infusion daily for 5 days every 3 weeks, to determine whether folic acid supplementation ameliorates the toxic effects of 1843U89 and permits further dose escalation, and to recommend doses of 1843U89 administered without and with folic acid for further clinical evaluations. The study also sought to characterize the pharmacokinetic behavior of 1843U89 and to seek preliminary evidence of anticancer activity. Patients with advanced solid malignancies were treated with escalating doses of 1843U89 as a 2-min i.v. infusion daily for 5 days every 3 weeks. Initially, patients were treated in the absence of high-dose folic acid until dose-limiting toxicity was consistently noted. Next, patients were treated with escalating doses of 1843U89 preceded by 1000 mg of folic acid administered p.o. 30 min before each of the 5 daily doses of 1843U89. Patients (32) received 101 total courses of 1843U89 at doses ranging from 1 to 6 mg/m(2)/day with and without folic acid. At the 2 mg/m(2)/day dose level without folic acid, 2 of 7 new patients experienced dose-limiting toxicity, principally neutropenia, mucositis, and malaise in 3 of 11 courses. 1843U89 doses were further increased with folic acid to 6 mg/m(2)/day, but repetitive treatment was not feasible at this dose level because of an unacceptable high incidence of severe neutropenia and mucositis. Other toxicities included thrombocytopenia, rash, and fever. In contrast, repetitive treatment at the 5 mg/m(2)/day dose level was feasible. The pharmacokinetics of 1843U89 were neither dose dependent nor affected by folic acid. On day 1, clearance, terminal half-life, and steady-state volume of distribution values averaged 47.1 +/- 21.7 ml/min/m(2), 7.72 +/- 4.09 h, and 16.7 +/- 8.8 liter/m(2)/h, respectively. The results of the study indicate that the administration of 1843U89 as a 2-min infusion daily for 5 days every 3 weeks without and with folic acid is feasible at 1843U89 doses as high as 2 and 5 mg/m(2)/day, respectively. Because folic acid pretreatment results in no diminution of the antitumor activity of 1843U89 in preclinical studies and ameliorates the toxic effects of 1843U89 in both preclinical models and cancer patients, the therapeutic index of 1843U89 may be enhanced by folic acid pretreatment and, therefore, the development of 1843U89 with folic acid is warranted. However, the question of whether to administer 1843U89 at a dose of 2 mg/m(2)/day with folic acid, which is associated with negligible toxicity, or at its highest feasible dose with folic acid, 5 mg/m(2)/day, should be addressed in appropriately designed trials.

Adult↗
PubMed2000

Markers of myocardial ischemia after minimally invasive and conventional coronary operation.

BACKGROUND: The purpose of this study was to evaluate the course of serum markers of myocardial tissue damage after two different types of minimally invasive coronary surgical procedures (MICS) as compared with conventional coronary artery bypass grafting (CABG). METHODS: We enrolled 87 patients with one- or two-vessel disease scheduled for one of the three procedures: minimally invasive direct coronary artery bypass grafting (MIDCABG) by lateral thoracotomy (n = 29), the OCTOPUS method by median sternotomy (n = 27), and CABG (n = 31). Creatine kinase activity (CK), creatine kinase MB activity (CK-MB act), creatine kinase MB mass concentration (CK-MB mass), myoglobin concentration (MG), and cardiac troponin I concentration (cTnI) were measured perioperatively until the second postoperative day. RESULTS: Creatine kinase-MB, CK-MB mass, and cTnI were significantly higher after CABG and were nearly maintained within the normal range in MICS. Creatine kinase and MG were significantly lower in the OCTOPUS group than in the MIDCABG or CABG groups. CONCLUSIONS: Minimally invasive coronary surgical procedures cause less myocardial injury than CABG as indicated by specific serum markers. However, higher CK and MG reflect more substantial skeletal muscle trauma during MIDCABG operation compared with OCTOPUS procedures.

Adult↗
PubMed1999

Methicillin-resistant Staphylococcus aureus in the community: a hospital-based study.

To determine the proportion of methicillin-resistant Staphylococcus aureus (MRSA) among patients presenting for hospitalization and to assess risk factors for MRSA carriage, we conducted a study for 13 months at five Pittsburgh-area hospitals. Of 504 S aureus identified, 125 (25%) were MRSA. Independent risk factors for MRSA included organ transplantation, employment in a healthcare facility, pressure sores, tube feeding, and hospitalization within the preceding year.

Carrier State↗
PubMed1997

Surgical therapy and follow-up of pancreatitis in children.

BACKGROUND: Acute and chronic pancreatitis in children differ from that in adults both from the etiology and the therapeutic approach. Within the frame of a blunt abdominal trauma-the most frequent cause in children-acute pancreatitis is often detected by emergency laparotomy and external drainage is recommended. Chronic relapsing pancreatitis, and particularly its hereditary form, is very rare in children and requires a different therapeutic concept. The results of surgical therapy for both forms of pancreatitis in childhood were evaluated in the present study. METHODS: Sixteen patients with acute and chronic relapsing pancreatitis were operated on in our facility between 1976 and 1988. Their history and postoperative course were analyzed in a retrospective study, including a final examination at the end of the follow-up period. RESULTS: Eight children with acute pancreatitis were operated on at an average age of 6 years and were followed up for an average of 7.5 years, with good results. The remaining children, aged between 3 and 14 years (average age of 9 years), were operated on for chronic relapsing pancreatitis. Our experience with early operative treatment, on average 2.7 years after onset of symptoms, is presented. Only three patients experienced a mild relapse during the follow-up period of 2-13 years (average of 5.4 years). CONCLUSIONS: For acute pancreatitis in childhood, operative treatment by inner drainage is necessary and effective only in case of complications, should conservative treatment fail. In children with chronic relapsing pancreatitis, the good exocrine and the normal endocrine function of the pancreas in these patients justified the early operation. Timely treatment is recommended in cases with typical changes of the pancreatic duct so as to shorten the relapsing clinical problems of the children and to maintain the function of the pancreas.

Abdominal Injuries↗
PubMed1997

[Surgical treatment of chronic pancreatitis in children].

Chronic relapsing pancreatitis and its hereditary form are very rare in children. Our experience with early operative treatment in nine children is presented. The good exocrine and endocrine function of the pancreas in these patients justifies early operation when typical changes of the pancreatic duct are present since it shortens the relapsing clinical course and maintains good function of the pancreas.

Adolescent↗
PubMed1996

A mathematical model for analysis of pharmacologically induced changes in the kinetics of cardiac muscle.

A mathematical model of the isometric contraction of cardiac muscle is developed and utilized to characterize the inotropic and lusitropic effects of cardioactive compounds in isolated guinea pig left atria. In contrast to metrics that are based on minima and maxima of an isometric twitch and its derivative function, the entire time course of the twitch is used to quantify the kinetics of the contraction-relaxation cycle. The model relates observed tension to a time-dependent activation function that describes generation of internal force and a coupling function that determines mechanical response to the activation function. The model is structured so that it is suitable for nonlinear curve fitting to observed data. Results obtained using the model for fitting experimental data from tissues treated with different classes of cardioactive compounds agree with more qualitative results presented by other authors. Experiments using the model to fit data over an extended (90 min) time course revealed differences in the kinetic profiles of milrinone and forskolin. Computer simulations that demonstrate the effect of each model parameter on twitch kinetics are presented, and the relationships between the model and other theoretical and empirical models of cardiac muscle are discussed. The mathematical model is useful to enable a more quantitative understanding of the kinetics of cardiac muscle contraction and relaxation and identify compounds that may be selective for inotropic or lusitropic effects.

Animals↗
PubMed1996

[Photodynamic diagnosis of neoplasms of the mouth cavity after local administration of 5-aminolevulinic acid].

BACKGROUND: The aim of photodynamic diagnosis (PDD) is the complete visualization of all neoplastic lesions in a tumorous organ after topical or systemic application of a tumor selective photosensitizer. In this investigation we performed semiquantitative fluorescence measurements following topical application of 5-aminolevulinic acid (5-ALA) in 11 patients with neoplastic lesions of the oral cavity. METHODS: Time course and type of porphyrin accumulation were analyzed in neoplastic and surrounding normal tissue by measuring emission spectra of 5-ALA-induced protoporphyrin IX (PpIX) fluorescence at regular intervals for up to three hours following 15 min continuous rinsing of a 0.4% 5-ALA solution. After excitation with violet light of a high pressure xenon arc lamp (375-440 nm), fluorescence images in the red spectral range from the tumor tissue and the corresponding macroscopic visible tumor were recorded with a CCD camera. A quantitative analysis of the fluorescence contrast in neoplastic and surrounding tissue was performed using an optical multichannel analyzer. RESULTS: PpIX fluorescence was detected in the oral mucosa of all patients after local application of 5-ALA. PpIX in neoplastic tissue accumulated earlier in comparison to the surrounding normal tissue. The fluorescence contrast between tumor and host tissue was 10:1 and the maximum fluorescence was measured 1-2 hours following 5-ALA application. CONCLUSION: Labeling of mucosal lesions of the oral cavity with PpIX fluorescence induced by the local application of 5-ALA seems to be a promising diagnostic procedure for neoplastic lesions. Further investigations are required to assess the value of this new diagnostic procedure as a non-invasive and sensitive method for patients with head and neck cancer not only in pre- and postoperative diagnostic studies but also for a fluorescence-guided resection of tumors.

Administration, Topical↗
PubMed1995

Photodynamic therapy induces expression of interleukin 6 by activation of AP-1 but not NF-kappa B DNA binding.

Inducibility and regulation of the pleiotropic cytokine interleukin 6 (IL-6) upon photodynamic therapy (PDT) was studied in the epithelial cell line HeLa. Photofrin-mediated photosensitization resulted in a rapid and dose-dependent induction of IL-6 mRNA production. Maximal levels were reached after 4 h and had decreased to baseline levels after 24 h. This photochemical induction of IL-6 transcription was followed by a strong secretion of IL-6 protein. In comparison to stimulation by 12-O-tetradecanoylphorbol-13-acetate, the kinetics of IL-6 mRNA and protein synthesis after PDT were delayed, although the maximal amounts of secreted IL-6 protein were comparable. As compared to UV irradiation, on the other hand, PDT-induced IL-6 protein levels were 2- to 10-fold higher and were detectable 4 h earlier. Several potentially relevant regulatory DNA elements of the IL-6 promoter were analyzed by gel retardation assays for PDT-induced protein binding. Interestingly, increased AP-1 DNA binding was detected only at the distal AP-1-specific motif and not at the proximal site, differing in 1 bp. Binding of c-Fos-containing AP-1 heterodimers to the specific motif was up-regulated 30 min after PDT, reaching maximal activity at 4 h. This PDT-induced AP-1 activation was independent from protein kinase C activity. Photosensitization did not induce increased binding at the well-characterized NF-kappa B element, nor at the multiple cytokine- and second messenger-responsive element of the IL-6 promoter. By analyzing the molecular mechanisms of IL-6 up-regulation upon PDT, we provide evidence for regulatory differences compared to UV light, ionizing irradiation, or stimulation by phorbol ester. Furthermore, this study suggests that the "proinflammatory" cytokine IL-6 might be involved in the inflammatory reaction and subsequent immunological antitumor responses.

Base Sequence↗
PubMed1995

The alpha 1C-adrenoceptor in human prostate: cloning, functional expression, and localization to specific prostatic cell types.

1. Benign prostatic hyperplasia (BPH) causes urinary obstruction in aging men that frequently requires surgery to relieve the symptoms of urinary retention, nocturia, and micturition. Smooth muscle tone which contributes to the urethral constriction in the enlarged gland appears to be mediated by the alpha 1-adrenoceptors. In this paper, molecular and pharmacological approaches are used to establish the role played by the alpha 1C-adrenoceptor subtype in the prostate. 2. The alpha 1-adrenoceptor subtype(s) expressed in human prostate were investigated by use of polymerase chain reaction (PCR), Northern blot, and in situ hybridization. The alpha 1C subtype was found in both prostate stromal and glandular cells while alpha 1B and alpha 1D subtypes were expressed in glandular cells. High expression levels for alpha 1C were observed in prostate cancer tissues in both stroma and glandular cells. 3. Full length alpha 1C-adrenoceptor cDNA was cloned from human prostate. Stable mammalian cell lines expressing human alpha 1B-, alpha 1C-, and alpha 1D-adrenoceptors were made. Membranes prepared from these cell lines and human prostate were used to evaluate the pharmacological profiles of human alpha 1B-, alpha 1C- and alpha 1D-adrenoceptors in comparison to human prostate. Leverage plot analysis of compound affinities determined by competition for [125I]-I-HEAT binding demonstrated that the alpha 1C subtype is the predominant alpha 1-adrenoceptor in human prostate. 4. The alpha 1-adrenoceptors cause smooth muscle constriction by coupling to IP3 turnover and intracellular Ca2+ release. Using stable cell lines to measure IP3 production in response to noradrenaline, alpha 1C stimulated IP3 production most efficiently, with alpha 1B at an intermediate level, while little IP3 above background could be detected with alpha 1D. These results supported a functional role of the alpha 1C-adrenoceptor on prostate smooth muscle constriction by noradrenaline stimulation.

Amino Acid Sequence↗
PubMed1994

[Damage to tumor cells by photodynamic therapy].

Photodynamic therapy (PDT) is a new, promising method in the treatment of cancer. To gain insights into PDT-mediated tumour destruction we studied the influence of treatment with Photofrin and laser light on changes in cell volume and cell viability. A-Mel-3 tumour cells were subjected to Photofrin or illumination with laser light, or a combination of both (PDT). Cell volume was measured by flow cytometry and cell viability by the trypan blue exclusion test for up to 60 min after PDT and the respective controls. In addition, scanning and transmission electron microscopy were performed. Tumour cells incubated in concentrations of 0.75, 1.5 and 3.0 micrograms Photofrin/ml revealed a rapid increase in cell volume to 117%, 207% and 235% 30 min after PDT and to 147%, 210% and 199% 60 min after PDT. Cell viability with 1.5 and 3.0 micrograms Photofrin/ml and laser light was reduced to 83% and 44% at 30 min after PDT and to 38% and 17% 60 min after PDT. At Photofrin concentrations of 1.5 micrograms/ml and exposure to laser light scanning electron microscopy revealed extreme loss of microvilli and formation of blebs on the cellular surface. Transmission electron microscopy showed swollen mitochondria and ruptures of the cell membrane. This study demonstrates that PDT induces a significant time-dependent and dose-related increase in tumour cell volume. We suggest that the PDT-induced swelling of tumour cells contributes to the increase of interstitial fluid pressure and to impairment of microvascular perfusion of tumours.

Cell Division↗
PubMed1994

Measuring second-order selection bias in a work site health program.

Magnitude and direction of second-order self-selection bias were assessed in a sample of 93,807 IBM employees who participated in the company's Voluntary Health Assessment (VHA) Program, by comparing repeat participants with one-time participants and by simulating selection into the repeat sample. One-time and repeat VHA participants differed systematically but not uniformly in several health characteristics. Repeat participants improved significantly in risk-relevant behaviors and health risk measures. Simulation of selection bias by excluding healthier or less healthy participants from the repeat VHA sample showed findings of gain to be robust. In studies of gain, second-order selection bias cannot automatically be assumed to inflate gain nor to be of sufficient magnitude to affect conclusions about program effects. Simulation is a useful tool for gauging direction and magnitude of selection bias.

Adult↗
PubMed1993

Prosthetic valve endocarditis resulting from nosocomial bacteremia. A prospective, multicenter study.

OBJECTIVE: To determine the incidence of endocarditis in bacteremic patients with prosthetic heart valves and the risk factors for and the effect of duration of antibiotic therapy on development of endocarditis in such patients. DESIGN: Multicenter, prospective observational study. SETTING: Six university teaching hospitals with high-volume cardiothoracic surgery. PARTICIPANTS: One hundred seventy-one consecutive patients with prosthetic heart valves who developed bacteremia during hospitalization. MEASUREMENTS AND MAIN RESULTS: Patients were evaluated when they were identified as having bacteremia and 1, 2, 6, and 12 months after its occurrence. Of 171 patients, 74 (43%) developed endocarditis: Fifty-six (33%) had prosthetic valve endocarditis at the time bacteremia was discovered ("endocarditis at outset"), whereas 18 (11%) developed endocarditis a mean of 45 days after bacteremia was discovered ("new endocarditis"). Mitral valve location and staphylococcal bacteremia (Staphylococcus aureus or S. epidermidis) were significantly associated with the development of "new" endocarditis. All 18 cases of new endocarditis were nosocomial, and in 6 of these cases (33%) bacteremia was acquired via intravascular devices. Twenty-one patients without evidence of endocarditis at the time of bacteremia received short-term antibiotic therapy (< 14 days); 1 patient (5%) developed endocarditis. Eleven of 70 patients (16%) who received long-term antibiotic therapy (> 14 days) developed endocarditis (P > 0.2). CONCLUSIONS: Bacteremic patients with prosthetic heart valves were at notable risk for developing endocarditis, even when they received antibiotic therapy before endocarditis developed and regardless of the duration of such therapy. Intravascular devices were a common portal of entry.

Adult↗
PubMed1993

Effect of dietary n-3 versus n-6 polyunsaturated fatty acids on hepatic excretion of cholesterol in the hamster.

Dietary polyunsaturated fatty acids of the n-6 and the n-3 class show differing effects on serum lipids and hepatic lipoprotein metabolism, which could be induced by alterations in hepatocellular cholesterol balance. As both fatty acid classes exert parallel effects on lipoprotein uptake and synthesis of cholesterol in the liver, we studied whether they have differing effects on the excretory pathways for cholesterol. Male Syrian hamsters were fed for 3 weeks low-cholesterol diets supplemented (9% w/w) with either saturated (coconut fat), n-6 unsaturated (safflower oil) or n-3 unsaturated fatty acids (fish oil), which shifted the serum lipid levels. N-6 unsaturated fatty acids increased both the synthesis of cholic acid (+57%; P = 0.05) and, in fistula bile, the secretion of cholesterol (+37%; P < 0.05 vs. saturated fatty acids). By contrast, n-3 unsaturated fatty acids did not enhance synthesis of cholic acid or biliary secretion of cholesterol (-30%, NS). The fatty acid pattern of biliary phospholipids was modified according to the major unsaturated fatty acids in the diet. The alterations both in phospholipid fatty acid composition and in secretory ratio of cholesterol to phospholipids and bile acids persisted during controlled secretion of taurocholic acid at increasing rates. In conclusion, hepatic excretion of cholesterol is increased on dietary n-6 unsaturated fatty acids, and low on n-3 unsaturated fatty acids. These two dietary fatty acid classes change differently the fatty acid composition of biliary phospholipids and the secretory ratio of cholesterol to phospholipids and bile acids in bile.

Animals↗