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Biomedical subjects

C Kraemer

Publications and source records attributed to C Kraemer.

13 recordsLinked to original sources

Treatment of childhood migraine attacks with oral zolmitriptan and ibuprofen.

The authors conducted a double-blind, placebo-controlled, crossover study to investigate the efficacy of oral zolmitriptan in the treatment of migraine in children and adolescents. Patients (n = 32) received placebo, zolmitriptan 2.5 mg, and ibuprofen 200 to 400 mg to treat three consecutive migraine attacks. Pain relief rates after 2 hours were 28% for placebo, 62% for zolmitriptan, and 69% for ibuprofen (p < 0.05). Both drugs are well tolerated with only mild side effects.

Administration, Oral↗

Mapping and structure of DMXL1, a human homologue of the DmX gene from Drosophila melanogaster coding for a WD repeat protein.

The DmX gene was recently isolated from the X chromosome of Drosophila melanogaster. TBLASTN searches of the dbEST databases revealed sequences with a high level of similarity to DmX in a variety of different species, including insects, nematodes, and mammals showing that DmX is an evolutionarily highly conserved gene. Here we describe the cloning of the cDNA and the chromosomal localization of one of the human homologues of DmX, Dmx-like 1 (DMXL1). The human DMXL1 gene codes for a large mRNA of 11 kb with an open reading frame of 3027 amino acids. The putative protein belongs to the superfamily of WD repeat proteins, which have mostly regulatory functions. The DMXL1 protein contains an exceptionally large number of WD repeat units. The DMXL1 gene is located on chromosome 5q22 as determined by radiation hybrid mapping and fluorescence in situ hybridization. Although the function of the DMXL1 gene and its homologues in other species remains to be discovered, the high level of evolutionary conservation together with the unusual structure suggests that it probably has an important function.

Amino Acid Sequence↗

A pilot study of melphalan, tumor necrosis factor-alpha and 41.8 degrees C whole-body hyperthermia.

PURPOSE: To evaluate the feasibilitv of sequencing (based on preclinical modeling) tumor necrosis factor-a (TNF) at two dose levels with melphalan (L-PAM) and 41.8 C whole-body hyperthermia (WBH) for 60 min. PATIENTS AND METHODS: Nine patients with refractory cancer were treated from October 1995 to June 1997. The study encompassed a total of 20 trimodality treatment courses. Three patients were treated at TNF dose level I (50 microg/m2) and six patients were treated at TNF dose level II (100 microg/m2). TNF was delivered as a 24-h intravenous infusion, 48 h prior to the combination of L-PAM and WBH; L-PAM was given over 10 min at target temperature at a dose of 17.5 mg/ m2 based on a previous phase I WBH/L-PAM trial. WBH was administered with an Aquatherm radiant heat device. RESULTS: Myelosuppression was the major toxicity associated with therapy, but there were no instances of bleeding or neutropenic fevers. Grade 3 thrombocytopenia was seen with 15% of treatments. Regarding absolute neutrophil count, 15% of treatments were associated with grade 3 toxicity, and 45% with grade 4 toxicity, and regarding white blood cell count, 50% of treatments were associated with grade 3 toxicity and 10% with grade 4 toxicity. The myelosuppression observed was equivalent to that seen in our earlier phase I study of WBH and L-PAM (without TNF). Only mild toxicities (grade 1 or 2) were associated with TNF; these were seen with <25% of treatments and included nausea, vomiting, diarrhea, fevers, and headache. There were no instances of hypotension. There was no relationship between toxicities observed and the two TNF dose levels. Mild WBH toxicities were seen with less than 15% of treatments; these included nausea, vomiting, and herpes simplex I. Responses included two complete remissions (malignant melanoma, TNF dose level I; breast cancer, TNF dose level II), and two disease stabilizations (both malignant melanoma, TNF dose level I). CONCLUSION: We conclude that the combination of TNF, L-PAM, and WBH is well tolerated at the dose levels studied. The clinical results justify further clinical investigation for this trimodality treatment approach.

Adult↗

The new gene DmX from Drosophila melanogaster encodes a novel WD-repeat protein.

DmX is a novel gene from Drosophila melanogaster located on the X chromosome in region 5D5/6-E1. The molecular analysis of the genomic and cDNA sequences of DmX shows that the gene spans appr. 16kb and displays a mosaic structure with 15 exons. The 12kb long DmX transcript is present in Drosophila embryos, larvae and adults of both sexes. The open reading frame of DmX encodes a novel WD-repeat protein, containing at least 30 WD-repeat units. WD-repeat proteins contain a conserved motif of approximately 40 amino acids (aa), usually ending with the dipeptide Trp-Asp (WD). Homologues of the DmX gene exist in other dipteran species, in Caenorhabditis elegans and human, revealing that DmX is an evolutionarily well conserved gene. The inferred DMX amino acid sequence shows also limited, but significant similarity to a yeast ORF with unknown function. 1998 Elsevier Science B.V.

Amino Acid Sequence↗

[Posterior synechiae after Nd:YAG laser iridotomy. A clinical study].

METHODS: In 146 eyes/patients who underwent Nd:YAG laser iridotomy after glaucomatous attack or after prophylactic iridotomy, we evaluated whether the frequency of posterior synechiae depends on (1) glaucomatous attack, (2) preoperative miotic therapy, (3) postoperative antiglaucomatous therapy or (4) mode of intraoperative laser therapy. Out of 616 eyes with YAG iridotomy between 1983 and 1987, 146 eyes/patients fulfilled the inclusion criteria: observation time of minimum 3 months after iridotomy, preoperative examination without signs of preexisting synechiae, postoperative examination at discharge and a later control examination in mydriasis to exclude posterior synechiae. RESULTS: Eyes with and without glaucomatous attack and eyes with an without pre-operative long-term miotic therapy showed no significant difference in frequency of posterior synechiae. Eyes with postoperative long-term therapy with miotics or beta-blockers showed posterior synechiae significantly more often than eyes without post-operative miotic or beta-blocker therapy. Eyes that received DPE in the early post-operative period developed posterior synechiae significantly less often. The number of laser pulses and the mean total energy used were significantly higher in eyes which later developed posterior synechiae. In the group of patients with glaucomatous attack women outnumbered men by four to one, but there was no significant difference in refraction between women and men. CONCLUSIONS: Patients with glaucomatous attack are not at a higher risk of developing posterior synechiae than those without glaucomatous attack. Post-operative antiglaucomatous therapy, the number of laser pulses and the total energy alter the frequency of postoperatively developed posterior synechiae.

Adult↗

The nucleotide sequence of a 39 kb segment of yeast chromosome IV: 12 new open reading frames, nine known genes and one genes for Gly-tRNA.

The complete nucleotide sequence of a 39,090 bp segment from the left arm of yeast chromosome IV was determined. Twenty-one open reading frames (ORFs) longer than 100 amino acids and a Gly-tRNA gene were discovered. Nine of the 21 ORFs (D0892, D1022, D1037, D1045, D1057, D1204, D1209, D1214, D1219) correspond to the previously sequenced Saccharomyces cerevisiae genes for the NAD-dependent glutamate dehydrogenase (GDH), the secretory component (SHR3), the GABA transport protein (UGA4), the high mobility group-like protein (NHP2), the hydroxymethylbilane synthase (HEM3), the methylated DNA protein-cysteine S-methyltransferase (MGT1), a putative sugar transport protein, the Shm1 protein (SHM1) and the anti-silencing protein (ASF2). The inferred amino acid sequences of 11 ORFs show significant similarity with known proteins from various organisms, whereas the remaining ORF does not share any similarity with known proteins.

Chromosome Mapping↗

Phase I clinical trial of melphalan and 41.8 degrees C whole-body hyperthermia in cancer patients.

PURPOSE: To evaluate the biologic interactions and toxicities of melphalan (L-PAM) combined with 41.8 degrees C whole-body hyperthermia (WBH) for 60 minutes. PATIENTS AND METHODS: Sixteen patients with refractory cancer were treated (May 1992 to May 1995) with WBH alone during week 1) thereafter patients were randomized to receive either L-PAM alone on week 2 and L-PAM plus WBH on week 5, or the reverse sequence. Patients who demonstrated clinical improvement received WBH plus L-PAM monthly. Dose levels of L-PAM were 10 mg/m2 (n = 3), 15 mg/m2 (n = 3), 17.5 mg/m2 (n = 6), and 20 mg/m2 (n = 4). L-PAM was administered at target temperature; WBH was administered with an Aquatherm radiant-heat device (patent pending; Cancer Research Institute, New York, NY). RESULTS: Comparisons of mean WBC count and platelet nadirs for L-PAM alone and L-PAM plus WBH demonstrated that the addition of WBH resulted in nadir counts that were, on average, 25% lower. There were no instances of febrile neutropenia or bleeding. Toxicities allowed for escalation of L-PAM to 20 mg/m2; all four patients at this level experienced grade 4 myelosuppression. No significant myelosuppression was observed at 10 and 15 mg/m2. Grade 3 myelosuppression was observed in two of six patients at 17.5 mg/m2. Responses included complete remission (CR) of pancreatic cancer (10 mg/m2), partial remission (PR) of malignant melanoma in two patients (20 mg/m2), and transient clinical and/or serologic improvement in five patients. The pharmacokinetics of L-PAM were not altered by WBH. Observed cytokine induction by WBH is also discussed in detail. CONCLUSION: We conclude that L-PAM with 41.8 degrees C WBH is well tolerated. Clinical results are consistent with preclinical predictions and provide a foundation for second-generation trials now in progress.

Adult↗

The sex determining region of Chironomus thummi is associated with highly repetitive DNA and transposable elements.

The dominant male sex determiner in chromosome III of the midge Chironomus thummi thummi is closely linked to a large cluster of tandem-repetitive DNA elements, the Cla elements, which are otherwise highly repetitive and distributed over more than 200 sites on all chromosomes. Chromosome III displays a hemizygous cluster of Cla elements in males but not in females. The chromosomal location of this hemizygous Cla element cluster is in the region of the male determiner M as localized by cytogenetic analysis. With Cla elements as hybridization probe, it was possible to clone a large part of the sex determining region. Molecular analysis of the DNA of males and females in this region displayed a number of differences between the two sexes. One striking difference is an unusual transposable element associated with the male sex determining region. The sex determining region also contains several other tandem-repetitive DNA elements in addition to the Cla elements. They are interspersed with single copy DNA. The accumulation of repetitive elements in the sex determining region interpreted as the result of a lack of recombination between the male/female heteromorphic region, although recombination in the other sections of chromosome III occurs.

Animals↗

Inhalation bronchography using powdered calcium ioglycamic acid.

In 16 baboons, reproducible bronchograms could be achieved by inhalation of 400--800 mg of powdered calcium ioglycamic acid. Anesthesia, tracheal intubation, or premedication were not necessary. In patients and volunteers, the inhalation of the contrast medium dust caused strong cough. Local anesthesia allowed inhalation for about 10 minutes, which resulted in successful demonstration of the pharynx, larynx, and trachea with bifurcation. Lobular and segmental bronchi were demonstrated only after a longer inhalation time. The contrast medium was completely eliminated and did not cause any recognizable adverse reaction. Nonspecific inflammatory reaction of the bronchial mucosa was seen microscopically in baboons.

Adult↗

Time of diagnosis, reoperations and long-term results of goniotomy in the treatment of primary congenital glaucoma: a clinical study.

PURPOSE: The aim of our study was to get information about the development of visual acuity, visual field and cup-disc ratio of patients with primary congenital glaucoma after IOP-regulating goniotomy by means of a katamnestic inquiry. The preoperative conditions of IOP, corneal diameter and corneal opacity were related to postoperative findings of visual acuity, visual field and cup-disc ratio reported by the treating ophthalmologists. METHODS: 196 patients were contacted, who had a goniotomy in the period from 1965 to 1983 at the University Eye Hospital Würzburg. Out of the 92 returned replies, the address of the treating ophthalmologists could be ascertained from 77 patients. Sixty of the 77 patients fulfilled the inclusion criteria: (1) primary congenital glaucoma and (2) IOP-regulating goniotomy as last surgery. RESULTS: I. In 76% of 106 eyes childhood glaucoma was diagnosed during the first year of life. II. In 72% of 60 eyes/patients with primary congenital glaucoma one goniotomy was sufficient to reach a normal IOP. In 18% a second and in 10% a third goniotomy was necessary, but without influence on the visual outcome. III. Even in the groups of eyes with a preoperative IOP of more than 40 mmHg, preoperative corneal diameter of more than 13 mm and preoperative severe corneal opacity more than 50% reached a visual acuity of 0.4-1.2 and more than 80% had a normal visual field. Only 9% of the eyes showed a cup-disc ratio of 0.6 or more. CONCLUSIONS: In primary congenital glaucoma even eyes with high preoperative IOP, large corneal diameters and severe corneal edemas had a good prognosis of visual outcome after goniotomy.

Adolescent↗