Biomedical subjects
Publications and source records attributed to M Klein.
Patients who have undergone enucleation of the eye can be treated with glass eye prostheses, provided retention is adequate. Inadequate retention due to contraction of the conjunctival mucosa is a common problem which frequently affects the lower fornix first. This can be corrected using a free full-thickness buccal mucosa graft. Indications, operative procedures and postoperative results are presented.
AIM: This pilot study describes use of whole body PET (WB PET) for staging of melanoma. WB PET in conjunction with lymphoscintigraphy (LS) for evaluating status of the sentinel lymph node (SLN) in primary melanoma was investigated with comparison to histopathological results. WB PET was also used both for primary and metastatic melanoma for screening for distant metastases, restaging and follow-up. METHODS: Group I: 17 patients with primary cutaneous melanoma underwent LS, WB PET and SLN dissection. WB PET findings were compared with biopsy results at the SLN site and were used for screening for distant metastases. Group II: 17 patients with a history of melanoma underwent WB PET for follow-up and/or restaging. Results were confirmed or refuted by other radiological modalities or by biopsy or clinical follow-up. RESULTS: Group I: out of 20 SLNs identified by LS in the 17 patients, 18 were negative on WB PET and 2 were positive. 19/20 WB PET findings were confirmed either by histopathology or by clinical follow-up (20 mo). Accuracy was 94% for the assessment of the status of the SLN. Group II: WB PET findings altered staging and treatment in 12/17 patients and confirmed the validity of treatment in 3/17 patients. Overall, in 15/17 patients (88%), WB PET had an impact on treatment strategy. CONCLUSION: Further studies are required to demonstrate if WB PET can become a reliable non-invasive alternative to surgery in the characterization of the SLN. WB PET is important as a baseline in primary localized melanoma and decisively impacts patient management in metastatic melanoma.
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The effects of mental fatigue on planning and preparation for future actions were examined, using a task switching paradigm. Fatigue was induced by "time on task," with subjects performing a switch task continuously for 2 hr. Subjects had to alternate between tasks on every second trial, so that a new task set was required on every second trial. Manipulations of response-stimulus intervals (RSIs) were used to examine whether subjects prepared themselves for the task change. Behavioral measurements, event-related potentials (ERPs), and mood questionnaires were used to assess the effects of mental fatigue. Reaction times (RTs) were faster on trials in which no change in task set was required in comparison with switch trials, requiring a new task set. Long RSIs were used efficiently to prepare for the processing of subsequent stimuli. With increasing mental fatigue, preparation processes seemed to become less adequate and the number of errors increased. A clear poststimulus parietal negativity was observed on repetition trials, which reduced with time on task. This attention-related component was less pronounced in switch trials; instead, ERPs elicited in switch trials showed a clear frontal negativity. This negativity was also diminished by time on task. ERP differences between repetition and switch trials became smaller with increasing time on task.
Aortoenteric fistulas are a very unlikely cause of digestive bleeding. We present the case of a fifty six year old patient with a primary aortoduodenal fistula who consulted because of melena and a pulsating abdominal mass. He underwent three digestive endoscopies without arriving at any diagnosis. A computed axial tomography and an angiography showed an aneurysm of the abdominal aorta. With an exploring laparotomy a fistula was identified between the aneurysm and the fourth portion of the duodenum. An aortoaortic bypass was carried out followed by a surgical fix of the duodenum. The patient was released six days after the operation.
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Non-structural protein 2C is known to play a fundamental role in the replication of picornaviruses. Sequence analyses revealed that 2C belongs to a rapidly expanding group of proteins containing a consensus sequence for nucleotide binding (NTB). We report that echovirus 9 polypeptide 2C displays NTPase activity in vitro. In our experiments, several P2 genes were expressed in Escherichia coli as fusion proteins linked to glutathione S-transferase (GST) prior to purification close to homogeneity. In contrast to GST-2B, both GST-2C and GST-2BC showed ATPase as well as GTPase activity indicating that the site for NTB binding and splitting is located in 2C.
OBJECTIVE: The bad prognosis of primary carcinoma of the Fallopian tube is ascribed to early lymphogenous metastasis. Due to the rarity of cases, there exist only few and divergent results on the importance of lymph node metastasis in the relevant literature. Thus, our study aimed at detecting the incidence of lymph node metastases and their influence on overall survival, as well as at evaluating the therapeutic effect of radical lymphadenectomy. METHODS: We studied 158 cases of primary carcinoma of the Fallopian tube in a retrospective multicenter analysis. Group I (n = 38) consisted of patients who were subjected to radical pelvic and para-aortic lymphadenectomy in addition to total abdominal hysterectomy, bilateral adenectomy and omentectomy. The control group II (n = 71) underwent the same surgical procedures but without radical lymphadenectomy. Patients who received post-operative irradiation (n = 49) were excluded from the study. RESULTS: On average, 38 lymph nodes (range 12-68) were extirpated. In group I 42.1% of the cases showed lymph node metastases. Lymphatic dissemination was observed only after the carcinoma had spread beyond the organ (intraabdominal stage II); the incidence of lymph node metastases rose significantly (P = 0.02) with growing intraperitoneal tumour masses. Pelvic and para-aortic metastases occur simultaneously. Overall survival with tumour of equal size is markedly, but not significantly reduced (P = 0.18) if the lymph nodes are involved. If, however, radical lymphadenectomy is performed (group I) the median survival time increases to 43 months (95% confidence-interval 20-66), compared with 21 months (95% confidence-interval 10-32) in group II (P = 0.095). CONCLUSION: Correct staging is obtained only on the basis of pelvic and para-aortic lymphadenectomy. Radical lymphadenectomy in tumours of equal size may markedly prolong survival.
In spite of extensive prevention programs, the HIV epidemics is still spreading worldwide, in particularly in developing countries where clade C viruses predominate. WHO estimates that there are 16, 000 new cases of HIV infection daily and that 100 M individuals will be infected by the end of the next decade. In spite of its spectacular results in seropositive patients, high-activity antiretroviral therapy (HAART) cannot eradicate the virus and is faced with side-effects, problems of compliance and the emergence of drug-resistant viruses. Furthermore, its prohibitive cost severely limits its use in developing countries. Therefore, the development of a preventive vaccine remains the best strategy to control the HIV-1 epidemics and a public health priority. However, the development of such a vaccine remains a formidable challenge to both the industry and the scientific community (Burton DR, More JP. Why do we not have an HIV vaccine and how can we make one? Nat Med 1998;4:495-8).
BACKGROUND: Approximately 2.0%-2.5% of Ashkenazi Jewish women carry one of three founding mutations in the BRCA1 and BRCA2 genes, and each mutation is associated with a high lifetime risk of invasive breast cancer. We investigated the extent to which these three mutations contribute to breast cancer incidence in the Ashkenazi Jewish population. METHODS: We ascertained 457 Jewish women with prevalent cases of breast cancer who were unselected for age or family history of the disease; 412 of these women were tested for the three founder mutations (case patients). Control subjects consisted of 360 non-Jewish women with breast cancer (control patients) and 380 healthy Jewish women with no history of cancer (control subjects). RESULTS: Mutations were found in 48 (11.7%) of 412 Jewish case patients. Forty-six of 48 mutations occurred in women with early-onset breast cancer (<50 years) or a history of ovarian or early-onset breast cancer in a first-, second-, or third-degree relative. The estimated penetrance to age 70 years for breast cancer was 59.9% for the BRCA1 gene mutations and 28.3% for the BRCA2 gene mutation. Compared with Jewish control subjects, the relative risk (RR) of breast cancer for first-degree relatives of mutation carriers was 5.16 (95% confidence interval [CI] = 3.14-8. 48), but risk was also increased for relatives of noncarriers (RR = 1.66; 95% CI = 1.18-2.33). The RR of prostate cancer for first-degree relatives of Jewish case patients was 3.36 (95% CI = 1. 49-7.56). CONCLUSIONS: Approximately 12% of breast cancers in the Ashkenazi Jewish population are attributable to mutations in the BRCA1 or BRCA2 gene. Genetic testing may be useful when Jewish women with breast cancer are diagnosed before age 50 years or have a close relative with ovarian or early-onset breast cancer. An association between breast and prostate cancers was observed in our study population.
There is a need to improve the ability of subunit vaccines to induce CD8(+) CTL responses in humans, especially for vaccines used to prevent illness by organisms that undergo antigenic variation at their major neutralizing antibody sites, e.g., influenza A viruses and human immunodeficiency virus. Murine models have demonstrated the protective role of cross-reactive CTL against influenza A virus antigenic drift. We tested the ability of an adjuvanted carrier (Iscomatrix) to help human antigen-presenting cells present formalin-killed influenza vaccine to human CD8(+) CTL clones in vitro and in vaccinated humans. The results of a randomized, double-blind, controlled clinical study demonstrate that a single dose of a vaccine formulated into Iscom particles increased influenza A virus-specific CTL memory in 50-60% of recipients, compared to 5% of the recipients of the standard influenza vaccine.
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A live recombinant canarypox vector expressing HIV-1 gpl20 MN tm/gag/protease LAI (ALVAC-HIV, vCP205) alone or boosted by a p24E-V3 MN synthetic peptide (CLTB-36) was tested in healthy volunteers at low risk for HIV infection for their safety and immunogenicity. Both antigens were well tolerated. ALVAC-HIV (vCP205) induced low levels of neutralizing antibodies against HIV-1 MN in 33% of the volunteers. None of them had detectable neutralizing antibodies against a nonsyncytium-inducing HIV-1 clade B primary isolate (Bx08). After the fourth injection of vCP205, CTL activity was detected in 33% of the volunteers and was directed against Env, Gag, and Pol. This activity was mediated by both CD4+ and CD8+ lymphocytes. On the other hand, the CLTB-36 peptide was poorly immunogenic and induced no neutralizing antibodies or CTLs. Although the ALVAC-HIV (vCP205) and CLTB-36 prime-boost regimen was not optimal, further studies with ALVAC-HIV (vCP205) are warranted because of its clear induction of a cellular immune response and utility as a priming agent for other subunit antigens such as envelope glycoproteins, pseudoparticles, or new peptides.
BACKGROUND: Prostaglandins have been shown to protect against a variety of liver insults, including ischemia-reperfusion injury. Decreased graft injury and improved survival have been demonstrated in animal studies of liver transplantation after donor pretreatment with prostaglandin before organ retrieval. This potential clinical application has not been examined in human subjects. PATIENTS AND METHODS: One hundred and six liver donors were randomly assigned to receive either prostaglandin I2 (epoprostenol, 500 microg intravenous bolus) immediately before cold perfusion or no drug as control. Donor and recipient characteristics were recorded, and liver function tests were monitored after transplant to assess the effect of epoprostenol on graft injury. RESULTS: Donor pretreatment with epoprostenol significantly improved the rapidity and homogeneity of graft reperfusion. Epoprostenol pretreatment also significantly reduced peak values of transaminases after transplantation: serum glutamic-pyruvic transaminase, control (851+/-121 international units [IU]/L) and epoprostenol (463+/-78 IU/L); serum glutamic-oxalaacetic transaminase, control (870+/-127 IU/L) and epoprostenol (463+/-78 IU/L); serum glutamate dehydrogenase, control (458+/-95 IU/L) and epoprostenol (170+/-30 IU/L); P<0.01 for all, by t test. Serum levels of bilirubin and alkaline phospatase were not significantly altered by donor pretreatment with epoprostenol. CONCLUSIONS: Reduction of ischemia-reperfusion injury by administration of epoprostenol before graft retrieval may have important applications in liver transplantation. Further studies are required to establish the mechanism of this effect and to define its precise role in clinical practice.
We have identified a splice variant of human neutrophil collagenase (MMP-8) transcript (MMP-8alt) that has a 91 bp insertion between codons for amino acid residues 34 and 35 of MMP-8 cDNA. This splice variant encodes an open reading frame for a 444 residue protein, lacking a secretory signal sequence. Our data suggested that, as opposed to the original MMP-8, the translation product of MMP-8alt is not a secreted protein; nevertheless, it is enzymatically active. Further studies aimed at identifying the physiological substrates of MMP-8alt protein may lead to uncover novel roles it plays in cellular physiology.
Early life responses to respiratory syncytial virus (RSV)-F DNA and RSV-F protein immunization were studied in murine models of neonatal immunization. RSV-F DNA induced similar antibody (Ab) responses, antigen-specific IFN-gamma production and cytotoxic T lymphocyte (CTL) responses in 1-week-old and adult BALB / c mice. In contrast, RSV-F protein induced much higher IL-5 responses in early life. Both vaccines elicited Ab and CTL responses in spite of maternal Ab, but with distinctive kinetics. Sequential RSV-F DNA priming / protein boosting primed 1-week-old mice for RSV-F-specific CTL responses, reduced IL-5 production and enhanced Ab responses. In contrast, IL-5 exceeded IFN-gamma responses when young mice were primed with protein and boosted with DNA. Last, when protein and DNA immunization were combined, a single vaccine dose induced early Ab responses, preferential IL-5 responses but strong CTL responses. Sequential or combined DNA / protein immunization thus represent interesting strategies for early life immunization.
Reconstructive plastic surgery is not always possible or advisable for nasal defects following tumor resections. Facial prostheses offer an alternative therapy. Since 1991, 37 patients with nasal defects after tumor surgery were treated in the Berlin Center of Facial Prostheses: 28 received "soft" silicone facial prostheses and 9 "solid" polymethylmetacrylate facial prostheses. In 35 patients protheses were bone-anchored: Brånemark implants were used in 12 patients and an Epitec frame construction in 23 patients. Glue-on prostheses were applied to only two patients. No intraoperative complications occurred at implant insertion. During following visits only minor inflammations were observed around implants and were treated locally. The implant success rate was 78% for the Brånemark implants (89.7% in non-radiated areas and 50% in radiated areas) and 100% in radiated and non-radiated areas for the Epitec system. Our investigation shows that given the right indication, the bone-anchored facial prosthesis is safe, cosmetically acceptable, uncomplicated and not stressful for the patient.