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Biomedical subjects

M Klein

Publications and source records attributed to M Klein.

At least 109 records · Page 6Linked to original sources
PubMed2001

Bolus high dose interleukin-2 for the treatment of malignant melanoma.

BACKGROUND: High dose interleukin-2 therapy, administered in bolus, is considered to be a reasonable treatment option in a selected group of patients with metastatic malignant melanoma. OBJECTIVES: To present our experience using this mode of therapy in 21 patients with metastatic melanoma. MATERIALS AND METHODS: The 21 patients in our study group comprised 13 men and 8 women with a mean age of 46 years (range 29-63). Their metastatic disease was present in all extracranial sites, dermal and sub-dermal metastases being the most common (15 patients had at least one site, in addition to other locations of metastases). Patients with intracranial disease were excluded due to the poor effectivity of IL-2 at this site. Treatment comprised a course of 2 weeks of therapy with a 1 week rest interval between. Radiological and physical evaluation was performed 6-8 weeks after the first course. If a response was achieved a second course of therapy was given. Patients received up to 14 planned doses of IL-2 in each week, 720,000 IU/kg of IL-2 per dose i.v. in 15 minutes. All treatments were given in the surgical ward, and only one patient was hospitalized in the intensive care unit. RESULTS: Of the 21 patients, one had a complete response that has lasted for 17 months and 5 patients had a partial response (range 3 months to 3 years). One patient died during treatment, and one patient who refused further treatment because of no response died a few days after completion of treatment. Prior to therapy three of the responders had received autologous vaccines with good immunological response (P = 0.115). Toxic side effects were significant, but they were treated successfully with no residual damage. CONCLUSIONS: High dose IL-2 can be administered safely in a surgical department. The response rates achieved in this series justify the use of high dose IL-2 in a selected group of patients. To improve response rates, a combination of autologous vaccines prior to high dose IL-2 may be recommended.

Adult↗
PubMed2001

Computer-guided surgery utilizing a computer-milled surgical template.

The primary objective of implant placement is to support prosthetic restorations that return patients to proper oral form, function, and aesthetics. Since correct implant placement can be a technique-sensitive process, it is performed in conjunction with various diagnostic and guidance procedures. For accurate diagnosis, radiographic templates, computed tomography scans, and surgical simulation software are unparalleled. This article demonstrates the manner by which computer-guided surgery and computer-milled surgical templates can enable precise implant placement for the entire implant team.

Alveolar Process↗
PubMed2001

Blood product use during routine open heart surgery: the impact of the centrifugal pump.

A prospective randomized study was done including 1,000 patients undergoing routine open heart surgery. Patients were randomly assigned to either a roller pump or a BioMedicus centrifugal pump with identical extracorporeal circuits. There were no significant differences between study groups. Actual blood products transfused and predicted transfusion requirements (using Cardiac RiskMaster) were examined as was chest tube drainage (CTD). The predicted transfusion requirement was 885 of 1,000 patients. Transfusions were required by 472 of 1,000. Risk factors as significant predictors of increased CTD and use of blood products were emergency surgery status, increased cross-clamp time, and higher predicted risk of mortality. The only significant predictor of decreased CTD was the use of a centrifugal pump. Predictors of increased length of stay were myocardial infarction, preoperative urea, age, and massive transfusion. Data provide evidence that use of the centrifugal pump improves patient outcomes by decreasing CTD and decreasing the requirements for transfusion, which results in a shorter hospital stay.

Blood Transfusion↗
PubMed2001

[Sentinel lymph node biopsy in breast cancer: a validation study and preliminary results].

INTRODUCTION: Sentinel lymph node biopsy (SLNB) has been recently proven to be an accurate staging method for breast cancer, replacing axillary lymph node dissection (ALND) in selected cases. We present our initial experience and the process of introduction and implementation of SLNB in a University Hospital setting. MATERIAL AND METHODS: 46 SLNB were performed in 42 consecutive female patients with invasive breast cancer. Treatment included 0.4mCi-2mCi of Tc-99m rhenium colloid injected either 2 hours before surgery (0.4 mCi) or the night before surgery (2 mCi). Four milliliters of Patent Blue V were injected peritumoral 10 minutes prior to skin incision in all patients. Following SLNB all women underwent subsequent ALND. Sentinel nodes were processed both with multiple (10-15) H&E sections and immunohistochemistry with cytokeratin antibodies stain. RESULTS: Blue dye, isotope or the combination of both identified 43/46 (93%) of the sentinel lymph nodes. ALND was performed only unilaterally in 4 patients with bilateral breast cancer bringing the total evaluable SLNB to 39. In the 39 patients in whom the sentinel node was successfully identified and underwent ALND, the SLNB was true positive (TP) in 17/39 (44%) true negative (TN) in 20/39 (51%) and false negative in 2/39 [(5%), both T2 lesions] with overall accuracy of 95%. In the last 10 cases all sentinel nodes were successfully identified with 70% TP and 30% TN. CONCLUSIONS: Experience with at least 30-40 consecutive cases for safe implementation of SLNB in clinical practice. Specific training and dedication is required for the entire team involved, including surgeons, nuclear medicine physicians and technicians and pathologists.

Adult↗
PubMed2001

Impact of a first-year primary care experience on residency choice.

We designed a retrospective cohort study of first-year medical students to assess the impact of a community-based primary care course, Introduction to Primary Care (IPC), on residency choice. In the group that took IPC (n=282), 48.2% entered generalist residencies (internal medicine, pediatrics, family medicine, or medicine/pediatrics), compared to 38.2% in the group that wanted IPC (n=398) and 39.6% in the group that did not want IPC (n=245). Controlling for gender, students who took IPC had a 40% higher odds of selecting a generalist residency than those who wanted to take IPC (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.04 to 1.95). There was no difference between those who wanted IPC and those who did not (OR, 1.08; CI, 0.78 to 1.52). The community-based primary care experience was positively associated with students' selection of generalist residencies.

Adult↗
PubMed2000

Immunization with recombinant canarypox vectors expressing membrane-anchored glycoprotein 120 followed by glycoprotein 160 boosting fails to generate antibodies that neutralize R5 primary isolates of human immunodeficiency virus type 1.

Antibodies generated by candidate HIV-1 vaccines in a phase I clinical trial were assessed for neutralizing activity with a panel of eight well-characterized, genetically diverse clade B primary isolates having an R5 phenotype. The vaccines consisted of one of three different recombinant canarypox vectors expressing membrane-anchored HIV-1(MN)gp120 (ALVAC vCP205, vCP1433, and vCP1452) followed by boosting with a soluble gp160 hybrid consisting of MNgp120 and the majority of gp41 from strain IIIB. Serum samples from a subset of volunteers in each arm of the trial, containing moderate to high titers of neutralizing antibodies to HIV-1 MN, were analyzed. Competition assays with peptides revealed that the majority of neutralizing activity was specific for the MN-V3 loop. Despite MN-specific neutralization titers that sometimes exceeded 1:500, no neutralization of primary isolates was detected and, in some cases, mild infection enhancement was observed. In addition, little or no neutralization of the HIV-1 IIIB heterologous T cell line-adapted strain of virus was detected. These results reinforce the notion that monovalent HIV-1 ENV is a poor immunogen for generating cross-reactive neutralizing antibodies.

AIDS Vaccines↗
PubMed2000

The relevance of adjuvant therapy in primary carcinoma of the fallopian tube, stages I and II: irradiation vs. chemotherapy.

INTRODUCTION: Primary carcinoma of the Fallopian tube (FTC) is a rare but extremely aggressive neoplasm. It must be expected to cause up to 40% of tumor-related deaths even in Stage I, and up to 57% in Stage II. Due to its rarity, there exist only a few and divergent reports on the value of adjuvant therapy. Therefore the present study aims at evaluating the influence of postoperative adjuvant therapy on FTC by studying the effects of irradiation and chemotherapy on the overall survival of patients in Stages I and II. PATIENTS AND METHODS: We investigated 95 cases of FTC in Stages I (n = 66) and II (n = 29) in a retrospective multicenter study. Group I (n = 32) are patients who underwent a complete irradiation with cobalt or photon energies of 23 MV (administering a daily dose of 2 Gy resulted in a total of 45-52 Gy in the pelvic areas). Group II (n = 31) consists of those cases who received postoperative chemotherapy with platinum. Thirty-two women were excluded from this study because they had other chemotherapies, incomplete irradiation, or no adjuvant therapy at all. RESULTS: Median survival time was 57 months in Group I patients (95% confidence interval 33-81 months), compared to 73 months (95% confidence interval, 68-78 months) in the chemotherapeutically treated Group II. This difference did not prove to be statistically significant (p = 0.476).If primary surgical therapy is included in the evaluation, and patients with total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO) are compared to those with additional radical lymphadenectomy (TAH+BSO+lymph nodes), the latter group's overall survival essentially improves but fails to reach statistical significance. Their 5-year survival rate is 83% against 58% in the TAH+BSO group (p = 0.12). CONCLUSION: Chemotherapy and irradiation are two adjuvant therapies that are similarly effective in FTC of Stages I and II, with chemotherapy being preferred at the present time. Primary surgical treatment, however, is of crucial impact on the prognosis of FTC.

Antineoplastic Agents↗
PubMed2000

Spontaneous pattern formation in an effectively one-dimensional dielectric-barrier discharge system

In a dielectric-barrier discharge between diametrically opposite sides of a narrow tube, discharge filaments stabilize at regular intervals along the tube's length. Three types of periodic patterns are observed, as is a disordered state in which filaments fire at apparently random positions and times. Time-resolved current measurements indicate that for each spatial pattern, a particular number of discharge stages occur during the voltage half-cycle. A preliminary model of the pattern-formation dynamics is described, motivating further work on time-resolved imaging and investigations of surface charge distributions.

Journal Article↗
PubMed2000

The clinical value of serum concentrations of cancer antigen 125 in patients with primary fallopian tube carcinoma: a multicenter study.

BACKGROUND: Primary fallopian tube carcinoma (PFTC) is a rare disease, and data on the serum concentration of tumor marker cancer antigen 125 (CA 125) in patients with this disease are sparse. The authors assessed the clinical value of the serum concentration of CA 125 as a prognostic and monitoring marker in patients with surgically treated PFTC. METHODS: In a multicenter study, the concentration of CA 125 was measured in 406 serum samples from 53 patients with PFTC. The results were correlated with clinical data. RESULTS: The pretreatment median serum CA 125 level was 183 U/mL (range, 6.5-5440.0 U/mL) in patients with PFTC. In a univariate Cox regression model, tumor stage and serum CA 125 level were associated significantly with shortened disease free survival (P = 0.006 and P < 0.001, respectively) and with overall survival (P = 0.03 and P = 0. 001, respectively). Lymph node involvement, tumor grade, and patient age were not associated with the length of survival. A multivariate Cox regression model showed that pretreatment the serum CA 125 level was a prognostic factor of disease free and overall survival, independent of tumor stage (P = 0.005 and P = 0.01, respectively). The pretreatment serum CA 125 level was correlated with tumor stage (P < 0.001) but not with lymph node involvement (P = 0.8), histologic grade (P = 0.3), or patient age (P = 0.2). The serum CA 125 level during chemotherapy was correlated significantly with Gynecologic Oncology Group response criteria to chemotherapy (P = 0. 001). During the follow-up of patients, serum CA 125 levels reached sensitivity, specificity, positive predictive value, and negative predictive value of 92%, 90%, 67%, and 98%, respectively, for differentiating between no evidence of disease and the presence of recurrent disease. In 90% of the patients, an increase of serum CA 125 level preceded the clinical or radiologic diagnosis of recurrent disease with a median lead time of 3 months (range, 0.5-7.0 months). CONCLUSIONS: This is the largest study to date with respect to serum CA 125 levels in patients with PFTC. The current data indicate that the pretreatment serum CA 125 level is an additional independent prognostic factor of disease free and overall survival in patients with PFTC. The serum CA 125 level adequately defines the response to chemotherapy and displays good sensitivity and specificity characteristics during the follow-up of patients with PFTC.

Adult↗
PubMed2000

Recombinant viruses as a tool for therapeutic vaccination against human cancers.

Viral vectors can be used to express a variety of genes in vivo, that encode tumor associated antigens, cytokines, or accessory molecules. For vaccination purposes, the ideal viral vector should be safe and enable efficient presentation of expressed antigens to the immune system. It should also exhibit low intrinsic immunogenicity to allow for its re-administration in order to boost relevant specific immune responses. Furthermore, the vector system must meet criteria that enable its industrialization. The characteristics of the most promising viral vectors, including retroviruses, poxviruses, adenoviruses, adeno-associated viruses, herpes simplex viruses, and alphaviruses, will be reviewed in this communication. Such recombinant viruses have been successfully used in animal models as therapeutic cancer vaccines. Based on these encouraging results, a series of clinical studies, reviewed herein, have been undertaken. Human clinical trials, have as of today, allowed investigators to establish that recombinant viruses can be safely used in cancer patients, and that such recombinants can break immune tolerance against tumor-associated antigens. These promising results are now leading to improved immunization protocols associating recombinant viruses with alternate antigen-presentation platforms (prime-boost regimens), in order to elicit broad tumor-specific immune responses (humoral and cellular) against multiple target antigens.

Antigens, Neoplasm↗
PubMed2000

p53 expression in fallopian tube carcinomas.

Sixty-three women treated for primary carcinoma of the fallopian tube (PFTC) from 1980-1995 were retrospectively analyzed to study the impact of p53 expression on survival in primary carcinoma of the fallopian tube. The mean age of the patients was 61.2 years (range 37.3-80.2). Twenty-four (38%) patients were FIGO stage I, 11 (18%) stage II, 19 (30%) stage III and nine (14%) stage IV. Complete radical resection was achieved in 45 (71%) patients. In 56 (89%) women, surgery involved removal of the uterus, the adnexa, and/or the omentum or lymph nodes. Adjuvant therapy consisted of either chemotherapy (n: 31; 49%) or irradiation (n: 21; 33%). The 5-year survival rate for all cases was 43%. For stages I+II and III+IV the 5-year survival rate was 59 and 19%, respectively (P<0.00001). Twelve samples (19%) were p53-negative (tumours with <10% of nuclear staining) and 51 (81%) samples were p53 positive tumours with >10% of nuclear staining. The median survival for the p53-negative group was 40 and 21 months for the p53 positive group. No statistical significance between p53 expression and different FIGO stages was observed, however, a trend for a slightly better survival for the p53-negative group was observed.

Adult↗
PubMed2000

Air quality and pediatric emergency room visits for asthma in Atlanta, Georgia, USA.

Pediatric emergency room visits for asthma were studied in relation to air quality indices in a spatio-temporal investigation of approximately 130,000 visits (approximately 6,000 for asthma) to the major emergency care centers in Atlanta, Georgia, during the summers of 1993-1995. Generalized estimating equations, logistic regression, and Bayesian models were fitted to the data. In logistic regression models comparing estimated exposures of asthma cases with those of the nonasthma patients, controlling for temporal and demographic covariates and using residential zip code to link patients to spatially resolved ozone levels, the estimated relative risk per 20 parts per billion (ppb) increase in the maximum 8-hour ozone level was 1.04 (p < 0.05). The estimated relative risk for particulate matter less than or equal to 10 microm in aerodynamic diameter (PM10) was 1.04 per 15 microg/m3 (p < 0.05). Exposure-response trends (p < 0.01) were observed for ozone (>100 ppb vs. <50 ppb: odds ratio = 1.23, p = 0.003) and PM10 (>60 microg/m3 vs. <20 microg/m3: odds ratio = 1.26, p = 0.004). In models with ozone and PM10, both terms became nonsignificant because of collinearity of the variables (r= 0.75). The other analytical approaches yielded consistent findings. This study supports accumulating evidence regarding the relation of air pollution to childhood asthma exacerbation.

Adolescent↗
PubMed2000

From mutagenic to non-mutagenic nitroarenes: effect of bulky alkyl substituents on the mutagenic activity of 4-nitrobiphenyl in Salmonella typhimurium. Part I. Substituents ortho to the nitro group and in 2'-position.

Eleven alkyl substituted derivatives of 4-nitrobiphenyl (4NBp) and two corresponding nitroso compounds were synthesised and tested for mutagenic potency in strains TA98 and TA100 of Salmonella typhimurium. The mutagenicity of compounds substituted ortho to the nitro group (3-methyl-, 3-ethyl-, 3-isopropyl-, 3-tertbutyl-, 3, 5-diethyl-, 3,5-diisopropyl-, and 3,5-ditertbutyl-4NBp) decreased with growing steric demand of the alkyl substituents in both tester strains. The most sterically hindered compounds were non-mutagenic even at highest concentrations. This reduction of mutagenicity is correlated with deviations from the coplanar orientation of the nitro group relative to the aromatic plane. Since a comparable decrease of mutagenicity for the nitroso compounds (4NOBp and 3-tertbutyl-4NOBp) was not observed, the first reduction step of non-planar nitro groups must be inhibited. Alkyl groups in the 2'-position of 4NBp (2'-methyl-, 2'-ethyl-, 2'-isopropyl-, and 2',4', 6'-trimethyl-4NBp) also reduced mutagenic activity with increasing size and removed it completely for the most sterically hindered species (2'-isopropyl-, 2',4',6'-trimethyl-4NBp). In this case, the co-planarity of the nitro group is not affected but the twisting of the two aromatic rings, which is associated with a less effective charge delocalisation of the nitrenium ion. The experimental mutagenicities of all nitro compounds were compared to predicted values, that are based on recently developed empirical equations. While there was reasonable correspondence for the parent compound (4NBp), its ortho methylated derivative (3-methyl-4NBp) and two highly hydrophobic dialkylated species (3,5-diisopropyl- and 3, 5-ditertbutyl-4NBp), predictions for all other alkyl substituted compounds were too high. Thus, steric parameters should be included to improve the general validity of predictions by means of quantitative structure-activity relationships (QSAR).

Biphenyl Compounds↗
PubMed2000

From mutagenic to non-mutagenic nitroarenes: effect of bulky alkyl substituents on the mutagenic activity of nitroaromatics in Salmonella typhimurium. Part II. Substituents far away from the nitro group.

Derivatives of 4-nitrobiphenyl, 4-nitrosobiphenyl, 2-phenyl-5-nitropyridine (2-aza-4-nitrobiphenyl) and 2-nitrofluorene, bearing various alkyl substituents far away from the nitro group (4'-position in nitrobiphenyls, 7-position in 2-nitrofluorenes) were synthesised and tested for mutagenic potency in strains TA98 and TA100 of Salmonella typhimurium. In the absence of S9 in both strains, mutagenicity of all4'-Ad (Ad=adamantyl). Changes of the molecular shape from 'planar' to non-planar caused by the bulk of the introduced substituents (without influencing the twisting of the nitro substituent or the phenyl rings in the biphenyl compounds) may be responsible for this effect by interfering with an efficient intercalation into DNA.A comparison between experimental and theoretical values as calculated from recently developed equations (QSAR) confirmed our previous results (see the preceding paper) that mutagenicity of alkyl-substituted nitroaromatics cannot be predicted by hydrophobicity and LUMO-energies alone without including steric parameters.

Biphenyl Compounds↗
PubMed2000

Neutron polarization induced by radio frequency radiation

We have measured that an unpolarized ultracold neutron beam gets polarized through its interaction with a resonant radio frequency field. Both spin components pass through the field and end up in one single spin state. We present a simple description for this surprising effect together with first experimental results.

Journal Article↗
PubMed2000

Plasmid DNA encoding the respiratory syncytial virus G protein is a promising vaccine candidate.

Respiratory syncytial virus (RSV) remains a major cause of severe respiratory diseases in infants, young children, and the elderly. However, development of a RSV vaccine has been hampered by the outcome of the infant trials in the 1960s with a formalin-inactivated RSV preparation. Enhanced lung disease was induced by the vaccination post-RSV exposure. Previous studies in mice primed with RSV G protein either formulated in adjuvants or delivered by recombinant vaccinia viruses have indicated that enhanced lung pathology resulted from a Th2-type host immune response against the viral G protein. However, in the present report, we have demonstrated that vaccination with plasmid vectors encoding either a full-length or a secreted G protein (DNA-G) clearly elicited balanced systemic and pulmonary Th1/Th2 cytokine responses in mice and did not induce an atypical pulmonary inflammatory reaction post-RSV challenge in cotton rats. DNA-G immunization also induced marked virus neutralizing antibody responses and protection against RSV infection of the lower respiratory tract of both mice and cotton rats. So far, only genetic immunization has been able to induce a balanced Th1/Th2 response with the RSV G protein, reminiscent of that induced by live RSV. Therefore, DNA-G is a promising immunogen for inclusion in a nucleic acid RSV vaccine.

Animals↗