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Biomedical subjects

A Peters

Publications and source records attributed to A Peters.

At least 127 records · Page 7Linked to original sources

[Scaphocapitate dislocation-fracture of the wrist joint in the setting of multiple injury].

Scaphocapitate fracture syndrome (SCFS) as part of perilunar distortion injuries (PL, PLF) in the human wrist is still remarkably rare. The diagnosis is determined by careful physical and radiological examinations, including conventional radiographs. Computed tomography can be helpful in detecting such lesions. In our opinion, the high risk of post-traumatic arthrosis because of carpal instability in a osteoligamental injury requires operative reconstruction in nearly all cases. We report the possibility of operative treatment in a case of scaphocapitate fracture syndrome (Fenton) by implantation of 2-mm mini-bone screws, while the use of K-wires or Herbert bone screws has been described in former articles.

Accidental Falls↗

[Metastatic melanoma of low Breslow thickness].

We treated 8123 patients with invasive malignant melanoma were treated up to 1995. 2200 had invasive melanomas with less than 0.75 mm Breslow thickness; of these, 45 developed metastases. Three had second primary tumors with greater thickness. One case showed metastasis from another tumor. In two cases the metastases were not ascertained histologically. The remaining 39 cases showed some peculiarities: a greater proportion of late and of internal (as contrasted to regional) metastases. Most of these primary tumors had a Breslow thickness of more than 0.5 mm and were Clark level III or even IV. Male patients and primary tumor sites in the area of head and neck were significantly over-represented.

Adult↗

[First melanoma metastases after 10 years and more of remission].

36 (3.5%) of 1015 patients who had ten or more years of follow-up after treatment of invasive malignant melanomas (stage I and II, UICC 1978) in Hornheide 1967-1984 developed late metastases. The mean disease-free interval was 12.5 years. These patients were younger (mean age of 45.8 years) compared to the age of all melanoma patients at the time of primary therapy. The rate of late relapses was 2.8% in women (20/705) and 5% in men (16/310). In melanomas located on the trunk or on the legs in male individuals, the relapse was twice as high as in females. The median tumor thickness in patients with late progression was 1.5 mm; in patients without relapse 1.2 mm. The well known association of tumor thickness with the risk of metastases disappeared after a 10 years disease-free interval. The frequency of metastases (3.5%) did not vary in different thickness classes from 0.76 mm to 3 mm or more. Melanomas with a Breslow thickness < 0.75 mm had a risk of only 1.4%. 23 patients (64%) developed distant, only 13 (36%) regional late metastases as first evidence of recurrent disease. The survival of these patients correlated neither to the duration of previous relapse-free follow up, nor to site of the primary lesion nor to sex. It correlated only to the site of metastases: 83% of all patients with distant late metastases had a remaining life time of 14 months or less, but patients with regional metastases survived more than 7 years in 69% of the cases. We have been unable to define risk factors for late metastases.

Adult↗

Lack of correlation between plaque burden and cognition in the aged monkey.

To assess whether amyloid plaque accumulation in the monkey brain can account for age-related cognitive impairment that begins at about 20 years of age, we measured plaque content in the brains of 14 rhesus monkeys aged 5-30 years. We used immunohistochemistry employing the monoclonal antibody 6E10, which is specific to amino acids 1-17 of the amyloid beta peptide to identify amyloid plaques in serial coronal sections of the forebrain. Amyloid plaques accumulate with age, starting at 25 years of age and escalating after 30 years. Until the age of 30, plaques are only found in a few monkeys and are relatively sparse. Results from our group and others show that plaque content and the proportion of individuals afflicted with amyloid plaques increase with age. Although both cognitive dysfunction and plaque content increase with age, amyloid plaque content does not correlate with the cognitive dysfunction observed in elderly monkeys since even in very old subjects some cognitively impaired animals have few amyloid plaques and others with abundant plaques show only minor cognitive impairments. In summary, amyloid plaques appear to accumulate significantly only in monkeys over 25 years of age but do not appear to be a causal factor in age-related cognitive decline of the normal aging rhesus monkey.

Aging↗

The organization of double bouquet cells in monkey striate cortex.

In previous publications we proposed a model of cortical organization in which the pyramidal cells of the cerebral cortex are organized into modules. The modules are centred around the clusters of apical dendrites that originate from the layer 5 pyramidal cells. In monkey striate cortex such modules have an average diameter of 23 microm and the outputs originating from the modules are contained in the vertical bundles of myelinated axons that traverse the deeper layers of the cortex. The present study is concerned with how the double bouquet cells in layer 2/3 of striate cortex relate to these pyramidal cell modules. The double bouquet cells are visualized with an antibody to calbindin, and it has been shown that their vertically oriented axons, or horse tails, are arranged in a regular array, such that there is one horse tail per pyramidal cell module. Within layer 2/3 the double bouquet cell axons run alongside the apical dendritic clusters, while in layer 4C they are closely associated with the myelinated axon bundles. However, the apical dendrites are not the principal targets of the double bouquet cell axons. Most of the neuronal elements post-synaptic to them are the shafts of small dendrites (60%) and dendritic spines, with which they form symmetric synapses. This regular arrangement of the axons of the double-bouquet cells and their relationship to the components of the pyramidal cells modules supports the concept that there are basic, repeating neuronal circuits in the cortex.

Animals↗

Respiratory effects are associated with the number of ultrafine particles.

The association between fine and ultrafine particles and respiratory health was studied in adults with a history of asthma in Erfurt, Eastern Germany. Twenty-seven nonsmoking asthmatics recorded their peak expiratory flow (PEF) and respiratory symptoms daily. The size distribution of ambient particles in the range of 0.01 to 2.5 microm was determined with an aerosol spectrometer during the winter season 1991-1992. Most of the particles (73%) were in the ultrafine fraction (smaller than 0.1 microm in diameter), whereas most of the mass (82%) was attributable to particles in the size range of 0.1 to 0.5 microm. Because these two fractions did not have similar time courses (correlation coefficient r = 0.51), a comparison of their health effects was possible. Both fractions were associated with a decrease of PEF and an increase in cough and feeling ill during the day. Health effects of the 5-d mean of the number of ultrafine particles were larger than those of the mass of the fine particles. In addition, the effects of the number of the ultrafine particles on PEF were stronger than those of particulate matter smaller than 10 microm (PM10). Therefore, the present study suggests that the size distribution of ambient particles helps to elucidate the properties of ambient aerosols responsible for health effects.

Air Pollutants↗

Thyrotropin-releasing hormone gene expression by anterior pituitary cells in long-term cultures is influenced by the culture conditions and cell-to-cell interactions.

It has been suggested that TRH, synthesized by anterior pituitary (AP) cells in long-term monolayer cultures, may act as a paracrine or autocrine regulator. Because local control through messenger molecules depends on the cellular microenvironment, we were interested in studying the synthesis of TRH by AP cells in different culture systems and under various conditions. When AP cells were cultured as monolayers in medium containing 10% FCS for long periods of time (up to 3 weeks), a considerable increase in TRH content and prepro-TRHmessengerRNA (preproTRHmRNA) levels could be demonstrated by RIA and Northern blot analysis, whereas the cellular content of the TRH-like peptide pyroGlu-Glu-Pro-NH2 decreased with time in culture to undetectable levels. The release of TRH could be stimulated by depolarizing concentrations of K+ (55 mM), by the Ca++ ionophore A23187, and by GnRH, but not by CRH or GRF, indicating that TRH is stored in gonadotropes. Moreover, a combined in situ hybridization and immunocytochemical analysis demonstrated colocalization of LH in preproTRHmRNA-positive AP cells. When AP cells were cultured as reaggregates in the same (FCS-containing) medium, only a marginal increase in TRH content and preproTRHmRNA levels was observed. Irrespective of the culture systems and the culture conditions used, TRH gene expression was not observed when FCS was omitted. These results indicate that TRH gene expression more likely reflects derepression, rather than induction, of the TRH gene.

Animals↗

Medication use modifies the health effects of particulate sulfate air pollution in children with asthma.

Previous controlled studies have indicated that asthma medication modifies the adverse effects of sulfur dioxide (SO2) on lung function and asthma symptoms. The present report analyzed the role of medication use in a panel study of children with mild asthma. Children from Sokolov (n = 82) recorded daily peak expiratory flow (PEF) measurements, symptoms, and medication use in a diary. Linear and logistic regression analyses estimated the impact of concentrations of sulfate particles with diameters less than 2.5 microns, adjusting for linear trend, mean temperature, weekend (versus weekday), and prevalence of fever in the sample. Fifty-one children took no asthma medication, and only 31 were current medication users. Most children were treated with theophylline; only nine used sprays containing beta-agonist. For the nonmedicated children, weak associations between a 5-day mean of sulfates and respiratory symptoms were observed. Medicated children, in contrast, increased their beta-agonist use in direct association with an increase in 5-day mean of sulfates, but medication use did not prevent decreases in PEF and increases in the prevalence of cough attributable to particulate air pollution. Medication use was not a confounder but attenuated the associations between particulate air pollution and health outcomes.

Adolescent↗

Short-term effects of particulate air pollution on respiratory morbidity in asthmatic children.

Short-term effects of air pollution (consisting primarily of sulphur dioxide and particulate matter but with low acidity) on respiratory morbidity were studied in asthmatic children from Sokolov, Czech Republic. Eighty nine children with asthma, who recorded daily peak expiratory flow measurements, symptoms and medication use in a diary, were analysed for 7 months during the winter of 1991-1992. Air pollution measurements included: SO2, total suspended particulates (TSPs), inhalable particles, ie. particulate matter of aerodynamic diameter < or = 10 microm, particle strong acidity (PSA) and fine particle sulphate concentration (SO4). Linear and logistic regression analyses estimated the impact of air pollutants adjusted for trend, temperature and weekend and autocorrelated errors. Exposure to elevated levels of air pollution was associated with decreased peak expiratory flow rates, increased respiratory symptoms, increased prevalence of school absence and fever, and increased medication use. Prolonged exposure to particle SO4 showed the largest effect estimates. At the end of January, an air pollution episode occurred, during which respiratory symptoms, prevalence of fever, school absence and asthma medication increased. The association between respiratory symptoms and particulate SO4 was highly dependent on this episode, whilst the associations between lung function and SO4 as well as between fever and SO4 were still observed when this air pollution episode was excluded. Some evidence was found that exposure to air pollution might have enhanced the respiratory symptoms while children were experiencing respiratory infections. In this study, a panel of children with mild asthma experienced small decreases in peak expiratory flow and increased dyspnoea in association with fine particles formed during air pollution episodes.

Adolescent↗

Acute health effects of exposure to high levels of air pollution in eastern Europe.

Acute effects of winter-type air pollution characterized by high levels of SO2, moderate levels of particles, and low acidity were studied. A panel of 155 asthmatic children and 102 adults with a history of asthma from the former German Democratic Republic cities of Erfurt and Welmar and from the Czech Republic city of Sokolov participated from September 1990 through June 1992. The panelists recorded daily symptoms, medication intake, and peak expiratory flow (PEF). Statistical analysis was based on linear regression of population-averaged time series controlling for trend, meteorology, and autocorrelation. A temporospatial time series approach was also applied to the data to eliminate possible confounding by some known or unknown variables that occurred simultaneously in two of the study areas. Weak same-day effects and a stronger cumulative effect of air pollution on children was observed both for PEF and for symptoms. PEF decreased -0.90% (-1.35 to -0.46%), and a symptom score increased 14.7% (0.8-28.6%) in association with an average increase of 128 micrograms/m3 SO2 over the previous 5 days. Effects on adults were smaller and less consistent. Morbidity of children was best predicted by SO2 and sulfate concentrations. The authors conclude that prolonged, high exposure to winter-type pollution was associated with small adverse health effects in asthmatics.

Adolescent↗

Synthesis and growth inhibitory properties of glycosides of 1-O-hexadecyl-2-O-methyl-sn-glycerol, analogs of the antitumor ether lipid ET-18-OCH3 (edelfosine).

Glycosylated antitumor ether lipids (GAELs), analogs of 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (1, ET-18-OCH3, edelfosine), were synthesized in good overall yields by glycosylation of 1-O-alkyl-2-O-methyl-sn-glycerol and tested for in vitro antineoplastic activity against a variety of murine and human tumor cell lines. Stereospecific glycosylation was achieved by the use of 2-O-acetyl-3,4,6-tri-O-benzylglucopyranosyl and -mannopyranosyl trichloroacetimidates as donors, with trimethylsilyl trifluoromethanesulfonate as catalyst in the presence of molecular sieves at -78 degrees C. The GAELs differ from 1 in having the sn-3-phosphocholine residue replaced by one of the following monosaccharide residues: beta- and alpha-2-deoxy-D-arabino-hexopyranosyl, alpha-D-mannopyranosyl, 2-O-methyl-beta-D-glucopyranosyl, and 2-O-methyl-alpha-D-mannopyranosyl. 1-O-Hexadecyl-2-O-methyl-3-O-(2'-deoxy-beta-D-arabino-hexopyranosyl)- sn-glycerol (2) was more effective than 1 in inhibiting the growth of MCF-7 (human breast cancer) and its adriamycin-resistant form MCF-7/adriamycin, and murine Lewis lung cancer cells. 2-Deoxy-beta-D-arabino-hexopyranoside 2 was also an effective growth inhibitor of two drug-resistant leukemic cell lines, P388/Adr and L1210/vmdr.

Animals↗

Age-related changes in oligodendrocytes in monkey cerebral cortex.

Compared with those in young monkeys (5-12 years of age), oligodendrocytes in area 46 of frontal cortex and primary visual cortex of monkeys over 25 years of age develop bulbous swellings along their processes. Such swellings are filled with characteristic inclusions that resemble age pigment, and other accumulations of these inclusions occur within the cell bodies of the oligodendrocytes in old monkeys. In addition, whereas the oligodendrocytes in young monkeys most commonly occur singly, in old monkeys it is common to find oligodendrocytes in groups or rows. These aggregates are often situated close to capillaries, and in some instances it is found that the cell bodies of the oligodendrocytes abut the basal lamina surrounding the capillary, so that the normally intervening astrocytic glial limiting membrane is absent. In these groups and rows, the perikarya of the oligodendrocytes are squashed close together, and it is common to find tight junctions formed between them. The cortices of the old monkeys also show extensive degeneration of myelin, and it is supposed that this is linked to the changes in the oligodendrocytes. It is hypothesized that the alterations in the oligodendrocyte-myelin system lead to changes in the rates of conduction along fibers whose myelin sheaths are affected, and this may be one of the causes of the behavioral changes associated with aging in primates.

Aging↗

[The therapy of a macroprolactinoma with the intramuscular application of a long-acting bromocriptine preparation].

HISTORY AND CLINICAL FINDINGS: Three years ago, a now 26-year-old woman with secondary amenorrhoea was found to have a prolactinoma which was treated with bromocriptine. However, because of side effects and psychosocial problems she took the drug only irregularly. There were no neurological symptoms and the visual fields were normal. Her weight was 97 kg and her height 168 cm. INVESTIGATIONS: Without treatment the serum prolactin concentration was 6978 microU/ml, while other endocrine parameters were unremarkable. Cranial computed tomography showed a suprasellar adenoma (craniocaudal diameter 1.0 cm). TREATMENT AND COURSE: Renewed treatment with bromocriptine (5 mg three times daily) brought prolactin concentration to within normal limits, but then rose again to at least 52,600 microU/ml when the patient took the drug irregularly, and the tumour grew to 2.8 cm. As the obesity (her weight now 120 kg) made neurosurgical intervention very risky a treatment trial with long-acting bromocriptine preparation (50 mg bromocriptine every 28 days intramuscularly), was undertaken. Serum prolactin concentration, measured at the end of the 28-day period, rapidly fell (6470 microU/ml after 3 months). Radiological examination indicated significant tumour shrinkage ( < 1.0 cm after 2 years). CONCLUSION: Repeated intramuscular administration of bromocriptine was an effective, well tolerated alternative (but not yet licensed in Germany) to oral dopamine agonists in the treatment of macroprolactinoma.

Adult↗

Myelinated axons and the pyramidal cell modules in monkey primary visual cortex.

In addition to the horizontal bands of myelinated axons that produce the line of Gennari and the inner band of Baillarger, the macaque primary visual cortex contains prominent vertical bundles of myelinated axons. In tangential sections through layer IVC, these axon bundles are regularly arranged. They have a mean center-to-center spacing of about 23 microns, and each one contains an average of 34 (S.D. +/- 13) myelinated axons. These bundles seem to be largely composed of efferent fibers, because in material in which pyramidal cells have been labelled in layer II/III and in layers IVA and IVB the axons of these neurons descend towards the white matter in bundles. However, it is doubtful whether all of the descending myelinated axons from the superficial layers emerge from the cortex, since counts show that the bundles contain maximum numbers of myelinated axons at the level of layer IVC, and that in layers V and VI their number is reduced by about 30%. Perhaps some of the axons enter the line of Baillarger, in layer V. When the bundles of myelinated axons and the clusters of apical dendrites of the layer V pyramidal cells are visualized simultaneously within layer IVC in electron microscopic preparations, it is apparent that their center-to-center spacing is similar, namely, about 23 microns and that a bundle of axons has a cluster of apical dendrites lying adjacent to it. Because of this association, and because axons from layer III pyramidal cells have been shown to enter the bundles, it is suggested that the myelinated axon bundles contain the efferent axons from the projection neurons in the individual pyramidal cell modules. However, in addition to the myelinated axons, the bundles contain unmyelinated axons, so that they also probably serve as the conduits for axons forming connections between layers. It is proposed that the pyramidal cell modules are the basic, functional neuronal units of the visual cortex, and since the neurons within a particular module can be expected to have slightly different inputs and response properties from those in neighboring modules, the individual axon bundles that emerge from each module would be expected to carry a unique set of efferent information.

Animals↗

The mechanism of somatic hypermutation studied with transgenic and transfected target genes.

Somatic hypermutation of Ig genes is beginning to be understood in molecular terms. Ig transgenes have served as model test genes and been shown to mutate, just as endogenous genes, with a peak of mutation over the VJ region and a sparing of the C region. The levels of somatic mutation appear to be related to the expression of the transgenes. DNA hypermethylation of modified Ig transgenes interferes with both expression and somatic hypermutation. Test substrates consisting of bacterial lacZ alpha or supFtRNA inserted within x transgenes were shown to be rescuable as expressible bacterial plasmids, but did not seem to be targeted. A synthetic sequence consisting of alternating restriction enzyme sites, that cannot be subject to methylation, was found to be a reliable transgenic substrate for easy assay of somatic mutation. The generation of a transgenic mouse with a x transgene in which the transcriptional promoter has been duplicated upstream of the C region has given new clues to the mutation mechanism. In this transgene, transcripts initiate from both the C region and the V region promoters, and both regions, but not the sequences between them, are hypermutated. These results suggest that somatic hypermutation is linked to the initiation of transcription. A model is proposed in which somatic mutation is dependent on transcription coupled DNA repair.

Animals↗

Somatic hypermutation of immunoglobulin genes is linked to transcription initiation.

To identify DNA sequences that target the somatic hypermutation process, the immunoglobulin gene promoter located upstream of the variable (V) region was duplicated upstream of the constant (C) region of a kappa transgene. Normally, kappa genes are somatically mutated only in the VJ region, but not in the C region. In B cell hybridomas from mice with this kappa transgene (P5'C), both the VJ region and the C region, but not the region between them, were mutated at similar frequencies, suggesting that the mutation mechanism is related to transcription. The downstream promoter was not occluded by transcripts from the upstream promoter. In fact, the levels of transcripts originating from the two promoters were similar, supporting a mutation model based on initiation of transcripts. Several "hot-spots" of somatic mutation were noted, further demonstrating that this transgene has the hallmarks of somatic mutation of endogenous immunoglobulin genes. A model linking somatic mutation to transcription-coupled DNA repair is proposed.

Animals↗