PubMed Health⌕ Search

Biomedical subjects

S Metz

Publications and source records attributed to S Metz.

At least 19 recordsLinked to original sources
PubMed1998

Substituted 2-iminopiperidines as inhibitors of human nitric oxide synthase isoforms.

A series of analogues of 2-iminopiperidine have been prepared and shown to be potent inhibitors of the human nitric oxide synthase (NOS) isoforms. Methyl substitutions on the 4-position (3) or 4- and 6-positions (8) afforded the most potent analogues. These compounds exhibited IC50 values of 0.1 and 0.08 microM, respectively, for hiNOS inhibition. Substitution with cyclohexylmethyl at the 6-position (13) afforded an inhibitor that showed the best selectivity for hiNOS versus heNOS (heNOS IC50/hiNOS IC50 = 64). Following oral administration, inhibitors were found to decrease serum nitrite/nitrate levels in an in vivo rat endotoxin assay. This series of 2-iminopiperidines were prepared via the described synthetic methodologies. The effect of ring substitutions on potency and selectivity for this class of cyclic amidines as NOS inhibitors is described.

Animals↗
PubMed1998

S-shaped in comparison to L-shaped partial sternotomy for less invasive aortic valve replacement.

OBJECTIVE: Evaluation of less invasive aortic valve replacement to minimize surgical trauma and achieve a better postoperative quality of life. METHODS: Thirty-three patients had aortic valve replacement using a 4-6 cm small incision and partial sternotomy only. Partial sternotomy was performed proximal (16), S-shaped (14) or horizontal (3). Access for cardiopulmonary bypass was via sternotomy (24) or the right femoral vessels (9). Patient age was 58+/-13 years, 21 had aortic stenosis and 12 aortic incompetence. RESULTS: Surgical exposure was sufficient and allowed for uncomplicated AVR in all patients. Mechanical valves (20), conventional bioprostheses (3), stentless bioprostheses (9) or a homograft (1) were implanted. Crossclamp time was not prolonged in comparison to the conventional technique. Intensive care stay and hospital stay were 1 and 10 days, respectively. One patient had to be reoperated for paravalvular leakage, two patients (horizontal sternotomy) had sternal dehiscence. Postoperative pain was low in most patients. CONCLUSION: Less invasive aortic valve replacement is feasible with good functional results. The S-shaped sternotomy approach is advantageous whereas the horizontal sternotomy is no longer performed due to a high rate of instability. This new technique will be further evaluated in comparison to the conventional approach.

Aortic Valve↗
PubMed1997

Antibody screening by enzyme-linked immunosorbent assay using pooled soluble HLA in renal transplant candidates.

The enzyme-linked immunosorbent assay (ELISA) using HLA class I molecules purified from pooled platelets has the potential to detect HLA antibodies with increased efficiency without sacrificing sensitivity or specificity. This test, which was originally developed in our institution, has been independently validated by recent studies and is now commercially available. We now present evidence of its usefulness as a routine HLA antibody screening test for renal transplant patients. A total of 515 patients were tested monthly by ELISA (13.9 tests/patient) and by antiglobulin-enhanced panel reactivity (6.3 tests/patient). In patients found to be unsensitized, the incidence of false-positive results was less for ELISA than for the panel studies. In patients who were highly sensitized, both tests performed equally well, whereas discordant results were registered mainly in cases of mild sensitization. Because 66% of our patients were not sensitized, the ELISA was effective in reducing the number of more involved tests aimed at characterizing the antibodies. These results provide a foundation to use the pooled platelet HLA ELISA on a routine basis for HLA antibody screening.

Antibodies↗
PubMed1997

Early lymphatic tumor cell dissemination in pancreatic cancer: frequency and prognostic significance.

Tumor relapse occurs frequently in patients with ductal pancreatic head cancer despite the absence of residual tumor detectable at primary surgery. Therefore it has to be assumed that current tumor staging procedures fail to detect minimal amounts of disseminated tumor cells present in secondary organs, which might be the seed for subsequent metastatic relapse. We evaluated lymph nodes from 18 patients without overt metastases who had undergone radical tumor resection (R0 resection). Lymph nodes judged as "tumor-free" by routine histopathology were further examined for the presence of single tumor cells using immunohistochemistry with the antiepithelial monoclonal antibody Ber-EP4. Sixteen of 37 "tumor-free" lymph nodes (43.2%), obtained from 13 of 18 patients (72.2%), displayed Ber-EP4+ tumor cells. Twelve of these 18 patients presented at pT2 stage. Nine of 12 patients (75%) staged as pN0 had these cells. Two of six pN1 patients had no Ber-EP4+ in histopathologically tumor-free lymph nodes. Using multivariate Cox's regression analysis, the presence of Ber-EP4+ cells in "tumor-free" lymph nodes was an independent factor for a significantly reduced relapse-free survival (p = 0.006) and overall survival (p = 0.01). Remarkably, all patients who were restaged as lymph node negative by both histopathology and immunohistochemistry survived the observation period without recurrence. The frequent occurrence of disseminated tumor cells in patients with pancreatic cancer and their prognostic impact support the need for a refined staging system of excised lymph nodes, which should include immunohistochemical examination. Thus patients with a minimal residual tumor load who might benefit from an adjuvant therapy could be selected.

Adult↗
PubMed1996

Risk factors for non-Hodgkin's lymphomas in acquired immunodeficiency syndrome (AIDS)

The possibility that an agent in addition to the human immunodeficiency virus (HIV) may contribute to the etiology of non-Hodgkin's lymphoma in persons with acquired immunodeficiency syndrome (AIDS) was studied using participants from the Multicenter AIDS Cohort Study (MACS) of homosexual and bisexual men enrolled in 1984-1985 and also in 1987-1991. A nested case-control analysis was conducted. The primary source of information on potential exposures and characteristics of the participants was the baseline study entry interview that was conducted prior to the development of AIDS. A total of 84 cases of non-Hodgkin's lymphoma were identified and compared with 527 participants who developed AIDS but had no evidence of cancer. The groups were similar for most sociodemographic characteristics as well as sexual activity and past history of antecedent illnesses. Although the non-Hodgkin's lymphoma cases reported less frequent use of recreational drugs and cigarettes compared with other persons with AIDS, these differences were not significant. Non-Hodgkin's lymphoma cases reported more frequent intake of aspirin during the week before the interview. However, there were no differences between the comparison groups for long-term aspirin intake or intake of other analgesics. The absence of any specific and strong association between non-Hodgkin's lymphoma and the various behavior-related activities and exposures considered in this analysis suggests that these factors are not related to a second agent in the etiology of HIV-induced non-Hodgkin's lymphoma. The possibility that a very common agent in this study population or that differences in the nature of the immune dysfunction resulting from HIV infection could act as a cofactor for HIV-induced non-Hodgkin's lymphoma cannot be excluded.

Adult↗
PubMed1996

Failed emergency transtracheal ventilation through a 14-gauge intravenous catheter.

We encountered two patients who could be neither ventilated nor intubated after induction of anesthesia. In both cases, transtracheal ventilation failed after emergent cricothyroid membrane puncture with a 14-gauge intravenous (i.v.) catheter. In the first case, two catheters placed in rapid succession kinked, preventing gas exchange. In the second case, absence of a plunger on the needle-over-catheter assembly prevented confirmation of intratracheal placement. Both patients required emergent tracheal access by the surgeon. We suggest that transtracheal ventilation via standard i.v. catheters as a primary emergent rescue technique be reassessed.

Aged↗
PubMed1996

Methylene blue does not neutralize heparin after cardiopulmonary bypass.

OBJECTIVE: It was hypothesized that methylene blue could neutralize heparin in patients after cardiopulmonary bypass and become an alternative to protamine. DESIGN: This was a prospective unblinded study with patients serving as their own controls. SETTING PARTICIPANTS: A single, large university hospital. This study was conducted in patients scheduled for elective aortocoronary bypass grafting. INTERVENTIONS: When heparin was to be neutralized, patients received methylene blue, 2 to 12 mg/kg, diluted in 50 mL and infused over 20 minutes. If a clot was not observed or the activated coagulation time (ACT) remained elevated, protamine, 250 mg, was administered and the ACT was repeated. MEASUREMENTS AND MAIN RESULTS: No patient demonstrated clot after methylene blue infusion. ACT did not return to preheparin values in any patient. All patients required protamine to establish hemostasis. Protamine restored the ACT to preheparin values in every patient. The one patient who received 12 mg/kg experienced severe pulmonary hypertension. CONCLUSIONS: Methylene blue does not neutralize heparin after cardiopulmonary bypass.

Anticoagulants↗
PubMed1995

The Multicenter AIDS Cohort Study: retention after 9 1/2 years.

In a longitudinal, multicenter study of 4,954 men at risk for human immunodeficiency virus infection and acquired immunodeficiency syndrome, data from the first 9.5 years of follow-up (April 1984 through September 1993) were used to determine differences between those who remained in the study and those who dropped out. Demographic variables (age, race, education, employment, and study center), health status (human immunodeficiency virus type 1 serostatus and depression), and behavioral characteristics (alcohol drinking, drug use, and anal-receptive intercourse) were analyzed. Strategies for promoting retention included having frequent contact with participants, generating trust, keeping participants well-informed, utilizing multiple resources for follow-up, and providing flexible methods of participation. After 9.5 years of follow-up, vital status was known for 4,385 (88.5%) of the participants. Results from multiple logistic regression showed that race, age, education, and smoking were each significantly associated with nonparticipation (p < 0.001). A high level of retention was maintained in this well-educated and highly motivated cohort of homosexual/bisexual men. Extensive follow-up methods may improve case-finding. Nonwhite race, younger age, less education, and smoking were important predictors of dropping out. These findings identify specific groups for targeting follow-up efforts to reduce potential bias due to dropout.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Cytosolic biosynthesis of GTP and ATP in normal rat pancreatic islets.

GTP and ATP are necessary for glucose-induced insulin secretion; however, the biosynthetic pathways of purine nucleotides have not been studied in pancreatic islets. The present work examines the cytosolic pathways of purine nucleotide synthesis using intact rat islets cultured overnight in RPMI 1640 medium containing either [14C]glycine (to label the de novo pathway) or [3H]hypoxanthine (to mark the salvage pathway), with or without mycophenolic acid or L-alanosine (selective inhibitors of cytosolic GTP and ATP synthesis, respectively). Addition of mycophenolic acid decreased total GTP content (mass) by 73-81%; although the incorporation of labeled hypoxanthine into GTP also fell by 87%, the incorporation of glycine did not change. Similarly, L-alanosine decreased ATP mass by 26-33% in the presence of either label; whereas the incorporation of hypoxanthine into ATP fell 59%, the incorporation of glycine was again not significantly decreased. Thus, both the de novo and salvage purine nucleotide biosynthetic pathways are present in rat islets; however, the salvage pathway appears to be quantitatively the more important source of nucleotides. This conclusion was supported by additional studies of the effects on nucleotide content and insulin secretion of various site-specific inhibitors of purine synthesis. These findings have potential relevance to the processes of mitogenesis, cell proliferation and differentiation of islet cells, as well as for the control of insulin secretion.

Adenosine Triphosphate↗
PubMed1995

Pro: glucose priming solutions should be used for cardiopulmonary bypass.

Current knowledge suggests that risks of glucose-containing solutions for patients undergoing CPB are hypothetical at best. Instead, patients may benefit from reduced perioperative fluid requirements bestowed by intraoperative glucose-containing solutions. This risk-benefit analysis does not apply to patients undergoing circulatory arrest. This population endures the certain risk of global CNS ischemia; furthermore, no studies address the effect of glucose on fluid requirements in this population. As the benefit of glucose during operations requiring circulatory arrest is unknown and the probable risk of exacerbating global CNS is high, deliberate hyperglycemia in this population is probably unwise. For patients undergoing CPB without circulatory arrest, the risk-benefit balance falls in favor of adding glucose. The contention that hyperglycemia worsens CNS deficits after cardiac operation is undocumented and may not be true. For their patients undergoing CPB, clinicians should seriously consider using glucose-containing priming solutions.

Cardiopulmonary Bypass↗
PubMed1993

Composite risk score for Kaposi's sarcoma based on a case-control and longitudinal study in the Multicenter AIDS Cohort Study (MACS) population.

The possibility that an agent in addition to human immunodeficiency virus type 1 may be involved in the etiology of Kaposi's sarcoma in acquired immunodeficiency syndrome (AIDS) patients was investigated between 1984 and 1992 in this nested case-control analysis from the Multicenter AIDS Cohort Study (MACS) of homosexual and bisexual men. A total of 316 cases of Kaposi's sarcoma were identified and compared with 510 participants with AIDS and no evidence of cancer. More of the Kaposi's sarcoma cases were from Los Angeles and used a higher number of recreational drugs. The Kaposi's sarcoma cases were also more active sexually. There was a dose-response relation between Kaposi's sarcoma and the number of sexual partners, with an odds ratio of 2 between the most and least sexually active subgroups. The odds ratio for Kaposi's sarcoma increased to 4.18 (95% confidence interval 1.29-14.1) in the presence of a history of five infections. Hepatitis and gonorrhea contributed the most to this relation. The various observed odds ratios did not change after multivariate adjustment for the other risk factors. A model was developed combining all predictive associations into a composite risk score ranging from one to 12 and based on history of infections, sexual activity, use of poppers/nitrites, and having had sexual partners from the West Coast of the United States. The subgroup with the highest scores, compared to the subgroup with the lowest score, had an odds ratio of 8.93 (95% confidence interval 3.21-30.44) for Kaposi's sarcoma. A longitudinal proportional hazards analysis among all 2,190 human immunodeficiency virus type 1-seroprevalent men at study entry, based on this risk score and CD4 cells at baseline, confirmed these findings. Identifying these specific subgroups that are at high and low risk for Kaposi's sarcoma will help future investigations to be more focused in their search for an additional etiologic factor for Kaposi's sarcoma in AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1992

The progression of untreated HIV-1 infection prior to AIDS.

Using a case-control study of untreated men, we investigated the physical, mental, and economic effects of human immunodeficiency virus (HIV-1) infection prior to the diagnosis of acquired immunodeficiency syndrome (AIDS). Beginning 2 to 2.5 years prior to AIDS, case subjects reported more of 12 HIV-1 related symptoms and during the year prior to AIDS, at least 30.6 extra days of these symptoms than did control subjects. Within the 6 months preceding AIDS, case subjects' unemployment rose to 9% (P < or = .05) and depression to 34.2% (P < or = .001). At 6 to 12 months and within 6 months before AIDS, 17.1% and 31.5%, respectively, were anemic, while 37.7% and 64.7% had CD4+ counts less than 200 x 10(6)/L. Diagnosing AIDS at CD4+ counts less than 200 x 10(6)/L could significantly reduce pre-AIDS morbidity. Other implications of these findings are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Gene expression of type I phospholipase A2 in pancreatic beta cells. Regulation of mRNA levels by starvation or glucose excess.

Messenger RNA from intact rat pancreatic islets, or from transformed hamster beta (HIT) cells, hybridized with the cDNA probe for type I (but not type II) phospholipase A2. The levels of phospholipase A2 mRNA increased in islets from fasted rats; they decreased in islets cultured in a high glucose concentration (control values at 5.5 mM glucose = 150 +/- 6% of those at 22 mM) which impaired subsequent insulin secretion (reduction in second-phase release = 70 +/- 11%). These studies uniquely demonstrate that type I phospholipase A2 is expressed specifically in beta cells and that nutrient availability modulates transcript levels, an effect which could that nutrient availability modulates transcript levels, an effect which could contribute to the detrimental influence of prolonged hyperglycemia on islet function.

Animals↗
PubMed1991

Benefits of a glucose-containing priming solution for cardiopulmonary bypass.

Benefits from the use of glucose-containing intravenous and priming solutions during coronary artery bypass operation have not been documented, but an increased risk of postoperative neurologic deficit by hyperglycemia has been suggested. To determine benefits, 107 patients undergoing coronary artery bypass operation were managed identically except that one group (n = 54) received 5% dextrose in lactated Ringer's solution (D5LR) as the sole intravenous and priming solution during operation and a second group (n = 53) received the same solution without glucose (LR). During cardiopulmonary bypass, the D5LR group required significantly less additional crystalloid to maintain safe oxygenator levels and flow (1.8 +/- 3.3 vs 15.8 +/- 20.9 mL.kg-1.h-1) and produced more urine (3.5 +/- 3.2 vs 1.2 +/- 1.4 mL.kg-1.h-1). By 24 h after operation, fluid balance in the LR group was approximately 2 L more positive than in the D5LR group. Five days after operation, the D5LR group weighed less than preoperatively (-0.8 +/- 2.6 kg), whereas the LR group gained weight (+1.0 +/- 2.8 kg). We conclude that use of glucose-containing solutions during coronary artery bypass operation benefits patients by decreasing perioperative fluid requirements and postoperative fluid retention. Because embolism is the cause of most postoperative neurologic deficits, any increased risk by hyperglycemia is small.

Blood Glucose↗