Search PubMed⌕ Search

Biomedical subjects

D Loesch

Publications and source records attributed to D Loesch.

At least 19 recordsLinked to original sources
PubMed2006

Molecular and imaging correlates of the fragile X-associated tremor/ataxia syndrome.

OBJECTIVES: To assess changes in regional brain volumes associated with the fragile X-associated tremor/ataxia syndrome (FXTAS) and the molecular correlates of these changes. METHODS: We administered molecular, MRI, and neurocognitive tests to 36 male premutation carriers (ages 51 to 79), 25 affected and 11 unaffected with FXTAS, and to 21 control subjects of similar age and education. RESULTS: We found differences among the three groups in whole brain, cerebrum, cerebellum, ventricular volume, and whole-brain white matter hyperintensity, with the affected group showing significantly more pathology than the control and unaffected groups. Brainstem volume was significantly smaller in the unaffected group vs controls but did not differ from the affected group. Within the premutation sample, CGG repeat length correlated with reductions in IQ and cerebellar volume and increased ventricular volume and whole-brain white matter hyperintensity. CONCLUSIONS: The current findings, coupled with recent evidence linking the degree of neuropathology (numbers of intranuclear inclusions) to the size of the premutation allele, provide evidence that the neurodegenerative phenotype in the fragile X-associated tremor/ataxia syndrome is a consequence of the CGG repeat expansion.

Aged↗
PubMed2000

A phase II trial of high dose epirubicin in patients with advanced breast carcinoma.

BACKGROUND: Anthracyclines are among the most active drugs in the treatment of breast carcinoma and exhibit a steep dose-response curve in vitro. This trial was performed to determine the efficacy and toxicity of epirubicin in the treatment of patients with advanced breast carcinoma when administered as a single agent in maximal doses. METHODS: Patients with chemotherapy-naïve American Joint Committee on Cancer/International Union Against Cancer Stage IIIB or IV breast carcinoma received epirubicin, 180 mg/m(2), intravenously every 3 weeks for a maximum of 8 cycles of therapy. Hematopoietic growth factors and cardioprotective agents were not used routinely. RESULTS: Twenty-seven patients were entered in the study. Although NCI/CTC criteria Grade 4 neutropenia occurred in 96% of patients, epirubicin was administered at 83.1% of the planned dose intensity. The median fall in left ventricular ejection fraction was 10%; clinical cardiac toxicity was observed in 3 patients. Objective responses were observed in 21 patients, including 6 complete responses. CONCLUSIONS: High dose epirubicin was found to result in substantial hematologic toxicity but was highly active in the treatment of patients with advanced breast carcinoma.

Adult↗
PubMed1996

A phase I trial of recombinant human interleukin-11 (neumega rhIL-11 growth factor) in women with breast cancer receiving chemotherapy.

We performed a phase I trial of recombinant human interleukin-11 (rhIL-11) in women with breast cancer. Cohorts of three to five women were accrued to five dosage levels of rhIL-11 (10, 25, 50, 75, and 100 micrograms/kg/d). rhIL-11 alone was administered by a daily subcutaneous injection for 14 days during a 28-day prechemotherapy "cycle 0." Patients (pts) subsequently received up to four 28-day cycles of cyclophosphamide (1,500 mg/m2) and doxorubicin (60 mg/m2) chemotherapy followed by rhIL-11 at their assigned dose (days 3 through 14). Sixteen pts (13 stage IV, 3 stage IIIB) were accrued to this study. Median age was 53 years and median Eastern Cooperative Oncology Group Performance Status was 0. A grade 3 neurologic event was seen in 1 pt at 100 micrograms/kg. Because of the degree of grade 2 constitutional symptoms (myalgias/arthralgias and fatigue) at 75 micrograms/kg, dose escalation was stopped and 75 micrograms/kg was the maximally tolerated dose. No other grade 3 or 4 adverse events related to rhIL-11 were seen. The administration of rhIL-11 was not associated with fever. Reversible grade 2 fatigue and myalgias/arthralgias were seen in all pts at 75 micrograms/kg. Weight gain of 3% to 5% associated with edema was seen at doses > 10 micrograms/kg but a capillary leak syndrome was not seen. rhIL-11 alone was associated with a mean 76%, 93%, 108%, and 185% increase in platelet counts at doses of 10, 25, 50, and 75 micrograms/kg, respectively. No significant changes in leukocytes were seen. A mean 19% decrease in hematocrit was observed. Acute-phase proteins increased with treatment at all doses. Compared with patients at the 10 micrograms/kg dose, patients receiving doses > or = 25 micrograms/kg experienced less thrombocytopenia in the first two cycles of chemotherapy. We conclude that rhIL-11 has thrombopoietic activity at all doses studied, is well tolerated at doses of 10, 25, and 50 micrograms/kg, and at doses > or = 25 micrograms/kg has the potential to reduce chemotherapy-induced thrombocytopenia in this model.

Adult↗
PubMed1995

Tandem autotransplantation for the treatment of metastatic breast cancer.

PURPOSE: To investigate the tolerability and impact on progression-free and overall survival of two consecutive cycles of high-dose chemotherapy (HDC) with autologous bone marrow transplantation (ABMT) in patients with previously untreated metastatic breast cancer. PATIENTS AND METHODS: Twenty-eight patients received conventional-dose induction therapy (ITx) followed by a planned two cycles of HDC with ABMT. Median age was 45 years (range, 34 to 60 years). Sites of disease were bone (seven patients), visceral (three), soft tissue (11), multiple (six), and CNS (one). The ITx regimens of cyclophosphamide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), methotrexate, fluorouracil, prednisone, and tamoxifen (CAMFTP) (three patients); fluorouracil, doxorubicin, and cyclophosphamide (FAC; 11 patients); cyclophosphamide, methotrexate, and fluorouracil (CMF; four patients); or doxorubicin or mitoxantrone/cyclophosphamide (10 patients) were given to maximum response (three to five cycles). HDC was cyclophosphamide 6 g/m2, carboplatin 2 g/m2, and etoposide 625 mg/m2 with ABMT. RESULTS: Of 28 patients, 24 received two (86%) cycles of HDC. Four received only one cycle due to persistent toxicity from course 1 (one patient), no response to course 1 (two), and death on course 1 (one). Grade 3 to 4 nonhematologic toxicities included mucositis (in one or both cycles in 21 of 28 patients; 75%), diarrhea, nausea, and vomiting. Reversible peripheral neuropathy was seen in 15 of 28 patients and was severe in one. Documented infections were seen in 19 of 52 cycles. There was one transplant-related death. Six patients were converted from partial remission (PR) to complete remission (CR) with HDC; two of 24 patients (8%) were converted from PR to CR with the second cycle of HDC. Progression-free survival rate is nine of 28 patients (32%) with median follow-up of 23 months (range, 13 to 36+ months). Eighteen of 28 patients (64%) have progressed at 1 to 17 months from ABMT. CONCLUSION: Two cycles of HDC with ABMT was well tolerated with a high response rate in patients with metastatic breast cancer. The importance of the second cycle of HDC in this population is unclear.

Adult↗
PubMed1992

Experience with direct molecular diagnosis of fragile X.

The utility of the pfxa3 probe for direct molecular diagnosis of the fragile X (FRAXA) has been established. This probe detects amplification of an unstable DNA element consisting of variable length CCG repeats. The size of the amplified fragment is correlated with phenotype and was determined using PstI digested DNA in family members. In 35 families with the fragile X, there was correspondence in 183 cases between the presence of an amplified unstable element and the presence of the fragile X chromosome independently determined by cytogenetics, position in the pedigree, or linked DNA markers flanking the fragile X. There was also correspondence in 124 cases between the presence of the normal 1.0 kb PstI fragment and absence of the fragile X chromosome independently determined by linked flanking markers. Six additional families considered to be isolated cases of 'fragile X' had been diagnosed before recognition of FRAXD. The pfxa3 probe confirmed the cytogenetic diagnosis in three families, the other three being rediagnosed as non-fragile X. A further two families had consistent expression of a different folate sensitive fragile site, FRAXE, close to FRAXA but not associated with fragile X syndrome and not detectable with the pfxa3 probe. Subsequent referrals were received from additional family members or from members of new families for whom carrier status had not been predetermined by linked markers. Direct pfxa3 diagnosis for the 135 females within these 222 additional cases was confirmed by dosage analysis with the control probe pS8.(ABSTRACT TRUNCATED AT 250 WORDS)

Artifacts↗
PubMed1992

Fragile-X syndrome: unique genetics of the heritable unstable element.

The fragile site at Xq27.3 is an unstable microsatellite repeat, p(CCG)n. In fragile-X syndrome pedigrees, this sequence exhibits variable amplification, the length of which correlates with fragile-site expression. There is a direct relationship between increased p(CCG)n copy number and propensity for instability: individuals having large amplifications exhibit somatic variation due to increased instability. The instability of the p(CCG)n repeat, when transmitted through affected pedigrees, explains the unusual segregation patterns of fragile-X phenotype, referred to as the Sherman paradox. All individuals of fragile-X genotype were found (where testing was possible) to have a parent with amplified p(CCG)n repeat, indicating that few, if any, cases of fragile-X syndrome are not familial.

Blotting, Southern↗
PubMed1984

Evidence for polygenic epistatic interactions in man?

Studies of multifactorial inheritance in man have ignored nonadditive gene action or attributed it entirely to dominance. Reanalyses of dermatoglyphic data on monozygotic and dizygotic twins, siblings and parents and offspring suggest that a substantial proportion of variation in total finger pattern intensity is due to epistatic interactions between additive genetic deviations, not dominance. Bootstrapping and power simulations support this interpretation of the data. We believe this is the strongest evidence so far for polygenic epistasis in man.

Dermatoglyphics↗
PubMed1983

Dermatoglyphic sole patterns in 21 trisomics.

Frequencies of loop patterns on the proximal sole have been estimated in the sample of 21 trisomic subjects and compared with those previously obtained in a sample of normal individuals. Results indicate that, in Down's syndrome, a lowered pattern intensity, characteristic of the distal sole does not occur on the proximal sole. Studies of patterns on the proximal portion of the sole should be pursued using larger samples of 21 trisomics, providing that care is taken to obtain the best quality footprints; the main limitation in such studies is in the common occurrence of ridge dissociation. In addition, some previous estimates of the frequency of zygodactylous triradii on the distal sole have been reconsidered on the basis of the results obtained in the present sample of footprints with complete recording of areas under the toes.

Dermatoglyphics↗
PubMed1982

Directional and absolute asymmetry of digital ridge counts.

Distributions, correlations and weighted least squares estimates of the components of variation in right-left asymmetry for individual finger ridge counts have been obtained from 221 pairs of twins and 80 pairs of opposite sex siblings. Asymmetry has been measured by two indices: signed right-left difference representing unidirectional asymmetry and absolute difference, representing ambidirectional asymmetry. The results indicate that both types of asymmetry are largely under environmental control, but with significant genetic components, particularly in males. The proportion of genetic variation in these measures of asymmetry varies somewhat between individual fingers.

Dermatoglyphics↗
PubMed1981

Dermatoglyphic studies in the parents of trisomy 21 children I. Distribution of dermatoglyphic discriminants.

A sample of 312 parents of a child with complete trisomy 21 (168 mothers and 144 fathers) has been compared with 295 parents of non-mongol children (61 mothers and 134 fathers) with respect to distribution of individual dermatoglyphic discriminant scores. Selection of dermatoglyphic traits as well a weightings have been based on the discriminant function, constructed for normal controls against cytogenetically diagnosed trisomy 21 mosaics. The results indicate that the proportion of individuals with an increased chance of mosaicism is appreciably greater in a sample of both the mothers and the fathers of mongol children, as compared with the parents of non-mongol children. For D greater than + 3.00, including also the overlap range values, it is, on the average, twice as high as in the control parents, while for the D values greater than + 4.00, strongly indicative of mosaicism, it is about five times higher than in control parents. This is so in spite of the fact that all parents, who had previously been cytogenetically tested and diagnosed as mosaics, were not included in this sample. Although the meaning of these results cannot yet be completely understood, they justify the extension of the use of dermatoglyphic discriminants in studies on parental mosaicism in trisomy 21.

Age Factors↗
PubMed1979

An outbreak of infections caused by strains of Staphylococcus aureus resistant to methicillin and aminoglycosides. I. Clinical studies.

In a 22-month period, strains of Staphylococcus aureus resistant to methicillin and multiple aminoglycosides, (designated MARS) were recovered from 108 inpatients with nosocomial infections at a hospital in the midwestern United States. Sixty-six of these patients were staying in a burn unit, and 42 were on other hospital wards. Among the patients with burns, MARS were recovered from the burn wounds of 64%; 32% of the patients with burns had MARS bacteremia. The patients without burns were age-matched with patients with nosocomial infections caused by antibiotic-susceptible strains of S. aureus. Patients from whom MARS were isolated had a longer mean hospital stay (79.6 days vs. 36.9 days; P less than 0.01), developed infection later (26.5 days vs. 13.5 days after admission; P less than 0.01), and had received antibiotic therapy before infection more often (81% vs. 38% of patients; P less than 0.01) than patients in the comparative population. Types of infection and incidences of death and bacteremia were similar in the two groups. Antibiotic-resistant strains of S. aureus may cause serious infections and significant mortality.

Aminoglycosides↗
PubMed1979

Dermatoglyphic distances and position of 21 trisomy mosaics.

The position of 21 trisomy mosaics with an average proportion of trisomic cells approximating 0.5 in relation to normal subjects and those with complete 21 trisomy has been evaluated by means of dermatoglyphic distances, using samples of 142 mosaics, 302 normal controls and 225 complete 21 trisomics for males and females separately and combined. Distances were calculated by means of the simplified D2k method. Penrose's "size and shape" analysis of variance has been applied for comparison to obtain distance coefficients, C2H, based on pattern intensities. Results indicate that mosaics are not intermediate but much closer to 21 trisomics in spite of the fact that the average proportion of trisomic cells in blood approximates 0.5; secondly, that the degree of deviation from the intermediate position of the mosaic sample is roughly proportional to the degree of cytological mosaicism. The position of mosaics is appreciably more intermediate in respect of finger-tip patterns than in respect of palmar and sole loops and triradii. The results obtained here have thus given evidence for the usefulness of dermatoglyphic distances, which enable all the differences in frequencies or means of the respective characters to be conveniently represented by a single number, in studies of the abnormal development of phenotypic characteristics in cases of incomplete trisomy.

Dermatoglyphics↗
PubMed1979

Genetical studies of the palmar and sole patterns and some dermatoglyphic measurements in twins.

The within- and between-pair mean squares and means have been estimated for dermatoglyphic patterns on finger-tips, palms and soles and compared between samples of 110 MZ and 111 DZ twins of Polish origin. Dermatoglyphic patterns have been represented by topologically significant pattern elements (loops and triradii) on finger-tips, palms and soles, considered separately and in various combinations, ridge counts on finger-tips and on palms and several other palmar and sole measurements. Some genetic parameters such as: genetic variance (GCT) based on within and between mean squares of the two types of twins, the within-pair variance ratio and the covariance/variance ratio in MZ twins have also been obtained for all these traits and considered in relation to differences in respect of the total and between-pair variances and means for all specified characters. The highest values of genetic parameters have been obtained for pattern intensities and ridge counts on finger-tips, considered separately or combined, for the H hypothenar loop and the axial t triradii on palms, and for the majority of sole loops and triradii. The lowest values have been found for several palmar loops and measurements such as minutiae counts. These results are, in respect of some pattern elements, not in agreement with the estimated heritability based on correlations between other relatives. A comparison of genetic parameters for single loops or triradii and for their various combinations indicates that some pattern elements or their combinations may be each influenced by a specific genetic system which modifies their phenotypic expression. It is believed that the obtained results are, for some proportion of characters, clearly biased by inequality of the total variances in MZ and DZ twins.

Analysis of Variance↗
PubMed1978

Dermatoglyphic total patterns on palms, finger-tips and soles in twins.

110 palms of MZ twins and 111 like-sexed pairs of DZ twins have been compared in respect of a concordance rate of the palmar, sole and finger-tip total pattern types. Dermatoglyphic patterns have been classified according to the topological method, and the distributions of the numbers of discordant pattern elements from homolateral, heterolateral and bilateral comparisons in MZ and DZ twins, respectively, are presented. The highest concordance occurs in homolateral comparisons in MZ twins and the lowest in heterolateral comparisons. Bilateral concordance is highest for sole and finger-patterns, while palmar patterns present a considerable degree of dermatoglyphic asymmetry. Palmar, sole and finger-tip patterns are also not alike in homolateral concordance rates within MZ and DZ twin pairs. The differences between MZ and DZ twins are much more pronounced for sole patterns than for palmar or finger-tip patterns, which is also reflected in the estimated H values. For soles, this may be in some way related to the considerable symmetry of patterns. The fact that some pattern elements are intercorrelated may also introduce a bias in estimates of heritability, based on twin material.

Dermatoglyphics↗