Biomedical subjects

A Loehr

Publications and source records attributed to A Loehr.

9 recordsLinked to original sources

PubMed2006

A phase I and pharmacokinetic study of novel taxane BMS-188797 and cisplatin in patients with advanced solid tumours.

This phase I study investigated the maximum tolerated dose and pharmacokinetics of a 3-weekly administration of BMS-188797, a paclitaxel derivate, at three dose levels (DLs) (80, 110 and 150 mg m(-2) DL), combined with cisplatin (standard dose 75 mg m(-2)). In 16 patients with advanced malignancies treated, one patient experienced dose-limiting febrile neutropenia, sepsis and severe colitis at the 150 mg m(-2) DL; at the 110 mg m(-2) DL one episode of dose-limiting grade 3 diarrhoea/nausea occurred. Grade 3/4 haematological toxicities were leucopenia/neutropenia; grade 3 nonhaematological toxicities were neuropathy, nausea, diarrhoea and stomatits. Objective response was seen in four patients, with three complete remissions in ovarian and cervical cancer patients. Pharmacokinetics of BMS-188797 appeared linear through the 110 mg m(-2), but not through the 150 mg m(-2) DL. The mean+/-SD values for clearance, distribution volume at steady state and terminal half-life during cycle 1 were 317+/-60 ml min(-1) m(-2), 258+/-96 l m(-2) and 30.8+/-7.7 h, respectively. The maximum tolerated and recommended phase II dose for BMS-188797 was 110 mg m(-2) (1-h infusion, every 3 weeks) combined with cisplatin 75 mg m(-2).

Adult↗

PubMed2001

The generation and characterization of a cell line derived from a sporadic renal angiomyolipoma: use of telomerase to obtain stable populations of cells from benign neoplasms.

Angiomyolipomas are benign tumors of the kidney derived from putative perivascular epithelioid cells, that may undergo differentiation into cells with features of melanocytes, smooth muscle, and fat. To gain further insight into angiomyolipomas, we have generated the first human angiomyolipoma cell line by sequential introduction of SV40 large T antigen and human telomerase into human angiomyolipoma cells. These cells show phenotypic characteristics of angiomyolipomas, namely differentiation markers of smooth muscle (smooth muscle actin), adipose tissue (peroxisome proliferator-activator receptor gamma, PPARgamma), and melanocytes (microophthalmia, MITF), thus demonstrating that a single cell type can exhibit all of these phenotypes. These cells should serve as a valuable tool to elucidate signal transduction pathways underlying renal angiomyolipomas.

Actins↗

PubMed1999

Haploinsufficiency for the neurofibromatosis 1 (NF1) tumor suppressor results in increased astrocyte proliferation.

Individuals affected with neurofibromatosis 1 (NF1) harbor increased numbers of GFAP-immunoreactive cerebral astrocytes and develop astrocytomas that can lead to blindness and death. Mice heterozygous for a targeted Nf1 mutation (Nf1+/-) were employed as a model for the human disease to evaluate the hypothesis that reduced NF1 protein (neurofibromin) expression may confer a growth advantage for astrocytes, such that inactivation of only one NF1 allele is sufficient for abnormal astrocyte proliferation. Here, we report that Nf17+/- mice have increased numbers of cerebral astrocytes and increased astrocyte proliferation compared to wild-type littermates. Intriguingly, primary Nf1+/- astrocyte cultures failed to demonstrate a cell-autonomous growth advantage unless they were cocultured with C17 neuronal cells. This C17 neuronal cell-induced Nf1+/- increase in proliferation was blocked by MEK inhibition (PD98059), suggesting a p21-ras-dependent effect. Furthermore, mice heterozygous for a targeted mutation in another GAP molecule, p120-GAP, demonstrated no increases in cerebral astrocyte number. These findings suggest that reduced NF1 expression results in a cell context-dependent increase in astrocyte proliferation that may be sufficient for the development of astrocytic growth abnormalities in patients with NF1.

Animals↗

PubMed1992

Septicemia in 980 patients at a university hospital in Berlin: prospective studies during 4 selected years between 1979 and 1989.

A total of 980 episodes of clinically and bacteriologically proven septicemia were included in four prospective 1-year studies at a 1,300-bed university hospital in Berlin between 1979 and 1989. The incidence was 8.1 per 1,000 admissions. The percentage of patients with severe underlying diseases increased significantly from 67% to 95% over the decade. Septicemia due to gram-positive bacteria decreased from 47.3% in 1979 to 43.7% in 1986 and increased again to 51.2% in 1989. Septicemia due to gram-negative organisms decreased constantly from 45.0% in 1979 to 39.8% in 1989. The most frequently isolated species were Escherichia coli (26.4%), Staphylococcus aureus (18.9%), coagulase-negative staphylococci (10.2%), enterococci (7.7%), viridans streptococci (6.4%), Klebsiella species (5.5%), and pneumococci (5.0%). The overall mortality rate decreased significantly from 33.6% in 1979 to 20.8% in 1989. Mortality for episodes of septicemia due to gram-positive bacteria (25.5%) was higher than that for septicemia due to gram-negative bacteria (18.3%). Mortality rates associated with polymicrobic and fungal septicemia were higher than the overall mortality rate.

Bacteremia↗

PubMed1986

A direct interaction between Photosystem I and the chloroplast coupling factor.

A regulation of the ATP-synthesizing complex by electron-transport rate has been found. The site of regulation could be localized within the Photosystem I region. The regulatory effect probably is produced by direct interactions between neighbouring charged protein complexes. The primary result is an increase in the percentage of those binding sites adopting a low-affinity state. This seems to lead to an enhanced leakage of protons out of the thylakoids, especially under those experimental conditions employing low nucleotide concentrations. Changes in the P/2e ratio can be observed, especially if the total ADP + ATP concentration used in the experiment is below 200 microM.

Adenosine Diphosphate↗

PubMed1985

A regulatory effect of the electron transport chain on the ATP synthase.

By the application of different experimental conditions, a variation of the apparent affinity of the chloroplast coupling factors 0-1 (CF0CF1) complex toward nucleotides was observed. This effect was paralleled by varying P/e2 ratios even in presence of millimolar ADP concentrations. This observations indicates that the electron transport system has a regulatory effect on the ATP synthase system. Different effects of mobile ionophores (uncouplers) and channel forming ionophores (gramicidin), respectively, indicated that either membrane-oriented charges--probably protons--or an electric potential difference was involved in the regulatory mechanism. When measuring photosystem II-dependent effects only, no regulation of the CF0CF1 complex could be detected in physiologically intact thylakoid preparations. This means that the regulatory active site must be localized between the 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone, (DBMIB) inhibition site and the methylviologen acception site.

Adenosine Diphosphate↗

PubMed1983

[Septicemia. Etiology, epidemiology, clinical aspects and prognosis in 446 patients].

Between 1979 and 1982 446 patients with clinically and bacteriologically established septicaemia were ascertained in a prospective study in a university hospital complex with 1200 beds. This corresponded to an incidence of 8,4 cases of septicaemia in 1000 admissions. In 47.1% of patients the infection had been acquired as out-patient, 52.9% were hospital-acquired. 53.1% of patients were more than 60 years of age, 71.3% had predisposing underlying diseases or risk factors. Main signs of infection were increased temperatures of more than 38.5 degrees C (77.8%), anaemia and leukocytosis. The fairly equal distribution of gram-positive (207) and gram-negative (200) organisms was remarkable. The most frequently isolated bacterial species were E. coli (25.3%), Staph. aureus (21.8%), streptococci (11.1%), Staph. epidermidis (8.4%), enterococci (8.2%), and Klebsiellae (6.5%). 29.1% of patients succumbed. Nosocomial disease, liver cirrhosis, underlying malignant diseases, infections with Staph. aureus, enterococci, pneumococci, Pseudomonas aeruginosa and polymicrobial aetiology had an unfavourable prognostic influence. Thus, frequency and mortality of septicaemic diseases remain of unchanged considerable relevance in medical and surgical units. At present, aetiology and treatment will again have to consider gram-negative organisms to an increased extent.

Adult↗

PubMedDate not supplied

Cisplatinum rechallenge in relapsed ovarian cancer patients with platinum reinduction therapy and carboplatin hypersensitivity.

Hypersensitivity reactions have been reported as limiting side effect in patients re-exposed to carboplatin for relapsed gynecologic malignancy. This study analyzed the incidence, clinical features, management, and outcome of carboplatin-associated hypersensitivity reactions. We performed a retrospective study and analyzed medical records of all gynecological cancer patients treated with carboplatin in our institution from 2000 to 2003. No hypersensitivity reactions were observed in 171 patients during the first carboplatin-containing chemotherapy. All six carboplatin-associated hypersensitivity reactions occurred in 69 patients who were re-exposed to carboplatin (9%). The median number of carboplatin cycles prior to hypersensitivity reaction was nine (range, 8-13). Cisplatin rechallenge was performed in five patients, and no hypersensitivity occurred. An increase in neurotoxicity (National Cancer Institute Common Toxicity Criteria grade 2) was documented in two patients who had residual neurotoxicity grade 1 due to prior taxane treatment. Cisplatinum rechallenge is a feasible strategy to overcome carboplatin hypersensitivity. However, close monitoring of neurotoxicity is necessary, particularly in patients with residual neurotoxicity due to prior platinum- and taxane-containing chemotherapy.

Carboplatin↗

PubMedDate not supplied

Sudden deafness: histopathologic correlation in temporal bone.

The histopathological study of two cases of sudden deafness is presented. The temporal bones showed cochleosaccular abnormality. The most striking pathological changes were collapse of the organ of Corti, atrophy of the tectorial membrane, atrophy of the stria vascularis, decrease in the number of the cochlear nerves, collapse of the saccular membrane and partial absence of the sensory epithelial layer in the saccular macula. These changes are quite similar in type to those occurring in labyrinthitis of known viral etiology and to those in previously reported cases of sudden deafness which were assumed to be of viral origin. This evidence suggests that a viral infection was the most probable etiology of sudden deafness in these ears. In addition, unusual findings of endolymphatic hydrops limited to the extreme basal end of the cochlear duct were found in Case 1. A patent cochlear aqueduct and circumscribed perilymphatic labyrinthine ossification in the superior seimicircular canal were also observed. With these histopathological findings, the possibility of viral infection via the meninges as well as via the hematogenous route into the inner ear is proposed.

Cochlea↗