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Biomedical subjects

M Keller

Publications and source records attributed to M Keller.

At least 127 records · Page 7Linked to original sources

24,25 Dihydroxyvitamin D supplementation corrects hyperparathyroidism and improves skeletal abnormalities in X-linked hypophosphatemic rickets--a clinical research center study.

Therapy for X-linked hypophosphatemia (XLH) only partially corrects skeletal lesions and is often complicated by hyperparathyroidism. 24,25(OH)2 D3 improves skeletal lesions in a murine model of XLH and suppresses PTH secretion in animals. Therefore, we undertook a placebo-controlled trial of 24,25(OH)2 D3 supplementation to standard treatment in patients with XLH to improve bone disease and reduce hyperparathyroid complications. Fifteen subjects with XLH receiving standard treatment [1,25(OH)2 D3 or dihydrotachysterol plus phosphate] were evaluated, supplemented with placebo, and reevaluated one yr later. 24,25(OH)2 D3 supplementation was then begun and studies repeated after another year. Each patient underwent a detailed evaluation of calcium homeostasis over a 24-h period. Rachitic abnormalities were assessed radiographically in children. Adults underwent bone biopsies. 24,25(OH)2 D3 normalized PTH values in nine subjects (peak PTH was 46.5 +/- 6.6 pmol/L at entry, 42.3 +/- 5.9 pmol/L after placebo, and 23.3 +/- 5.4 pmol/L after 24,25(OH)2 D3). Nephrogenous cAMP decreased at night, coincident with the decrease in PTH, and serum phosphorus was slightly greater with 24,25(OH)2 D3. Radiographic features of rickets improved during 24,25(OH)2 D3 supplementation in children, and osteoid surface decreased in adults. 24,25(OH)2 D3 is a useful adjunct to standard therapy in XLH by effecting correction of hyperparathyroidism and improvement of rickets and osteomalacia.

24,25-Dihydroxyvitamin D 3↗

[Phacoemulsification and topical anesthesia. Apropos of 40 cases].

BACKGROUND: To evaluate topical anaesthesia for cataract surgery. METHODS: Thirty-nine patients (40 eyes) underwent cataract surgery by phacoemulsification with topical anaesthesia consisting in instillations of tetracaine eyedrops. Thirty-four eyes were implanted with a foldable lens and 6 eyes received a PMMA lens. Final visual acuity (1 month minimum follow-up), patients reactions (sensibility, pain), anaesthetic and surgery difficulties were specially studied. RESULTS: Mean initial corrected visual acuity was 0.21. Mean final corrected visual acuity was 0.72; 90 % of the subjects experienced no pain. Implantation was the most sensitive moment. Eye mobility was not a problem except during capsulhorexis which had to be done with forceps. CONCLUSION: Simplicity of topical anaesthesia eliminates the complications of the other anaesthetic methods. It is necessary to have a close patient-surgeon relationship. Carefully chosen topical anaesthesia is an interesting alternative.

Aged↗

[Needs and utilization of ambulatory psychosocial services by cancer patients--exemplified by the oncologic day clinic].

Needs and acceptance of specific psychosocial care was assessed in a longitudinal study of 224 patients. In an oncologic adult day hospital chemotherapy patients express the strongest need for information and social counselling. Assessment of the need for psychosocial care depends on the sex of the patients, their coping resources, the course of the disease and differs between patients and therapists. With the progression of the disease acceptance of "informal" short contacts demanding little initiative from the patients was higher than of psychotherapy. Conclusions for the ambulatory psychosocial care of cancer patients are discussed.

Adaptation, Psychological↗

A new examination system using photoplethysmography to evaluate skin blood flow during exposure to vibration.

We introduce a new examination method developed at the University Dermatology Hospital in Tübingen in cooperation with the Institute for High Frequency Techniques of Aachen Technical College and the Metabo Factory in Nürtingen, Germany. The Tübingen workplace simulator for studying vibration white finger (VWF) syndrome standardized vibrations reproducing the vibration pattern of actual hand-held tools. This stimulator makes it possible to evaluate on-line the effects of defined vibrations on skin blood flow in the fingers and to investigate the etiopathogenesis of vibration white finger syndrome. The vibration simulator itself is modelled after an altered router with two side-mounted handles. The electronic speed control and exchangeable unbalance pins make it possible to adjust the frequency and amplitude of the vibrations to simulate actual conditions in the job. New developed photoplethysmographic sensors are fastened to the fingertips with double adhesive rings and measure blood flow in the skin. Measurements are recorded simultaneously with a multi-channel plotter. This method is not only useful as a diagnostic tool but has potential future applications in pre-employment screening in the affected industries and in the development of reduced-vibration tools.

Fingers↗

The likelihood of recurrence in bipolar affective disorder: the importance of episode recency.

These analyses used a high-intensity follow-up of of patients with bipolar affective disorder to describe the immediate and long-term risks for recurrence and the importance of sustained recovery to those risks. At the baseline evaluation, all patients were in episodes of Research Diagnostic Criteria major depressive disorder, mania or schizoaffective disorder (excluding the mainly schizophrenic subtype); those who were depressed at intake had a history of mania or schizoaffective mania. Raters re-evaluated these patients at 6-month intervals for 5 years and annually for the remainder of a 10-year follow-up. The following report describes relapse risks for the 186 patients observed to recover from their index episodes. Survival analyses quantified the likelihood of relapse over time, beginning after symptom-free periods of 4 months and 1, 2 and 3 years. Further survival analyses used treatment status as a censoring variable to estimate the eventual likelihood of recurrence among those who reported sustained compliance with lithium prophylaxis; the prophylaxis group remained under observation until they relapsed, were lost to follow-up or ceased taking lithium. Progressively longer symptom-free periods were clearly associated with lower relapse risks over the subsequent 4 years. Thereafter, however, this effect dissipitated. 7 years after recovery, the cumulative likelihood of recurrence was four in five for all bipolar patients and two in three for those whose index episode had been followed by at least 3 years without symptoms. Even with sustained lithium prophylaxis, the likelihood of at least one recurrence exceeded 70% within 5 years of recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Structure and expression of Euglena gracilis nuclear rbcS genes encoding the small subunits of the ribulose 1,5-bisphosphate carboxylase/oxygenase: a novel splicing process for unusual intervening sequences?

In the protist Euglena gracilis, the small subunit of the chloroplast enzyme ribulose 1,5-bisphosphate carboxylase/oxygenase is encoded by nuclear rbcS genes and synthesized as a polyprotein precursor containing eight mature small subunit molecules. This large precursor is encoded by at least eight different nuclear genes as ascertained by transcript analysis. The structure of three rbcS genes was established and the coding sequences were found to be interrupted by many intervening sequences (IVS). Apart from the first 5' intron involved in trans-splicing, none of these IVSs obeys the GT-AG rule characteristic of introns in higher eukaryote genes. Surprisingly, these IVSs are located at identical positions within the three genes studied. Moreover, extensive sequence homologies were found between IVSs located in the same gene as well as in different genes. The sequences of these homologous IVSs differ only by inserted and/or deleted sequences. The striking conservation of the 5' and 3' regions of these IVSs is correlated to their potential secondary structures. These structures, which bring the IVS extremities together with the exon boundaries, could be involved in a novel splicing process. The second 5' IVS is shown to be excised before the addition of the spliced leader sequence to the pre-mRNA. Similarly, two 3' IVSs are excised before the polyadenylation step. These results suggest that IVS splicing is faster than eukaryotic genomic cis-splicing and involves components other than those of the classical spliceosomes.

Amino Acid Sequence↗

Switching from 'unipolar' to bipolar II. An 11-year prospective study of clinical and temperamental predictors in 559 patients.

BACKGROUND: Given the therapeutic and prognostic importance of the unipolar-bipolar dichotomy, predicting which patients will become bipolar subsequent to index diagnosis of major depressive disorder (MDD) is of paramount clinical significance. We sought to characterize the profile of patients with MDD who would convert to the more subtle bipolar subtype (known as BPII) on the basis of clinical and personality variables obtained during MDD episodes. METHODS: A total of 559 patients, comprehensively evaluated with the Schedule of Affective Disorders and Schizophrenia and "unipolar" MDD at entry, were administered 17 self-report personality measures. Hypomanic and manic episodes were systematically recorded over a prospective observation period of up to 11 years. We compared 48 converters to BPII (8.6%) with 22 converters to bipolar I (BPI) (3.9%) and the remaining larger group of unipolar patients. RESULTS: Except for greater acuteness, severity, and psychotic symptomatology, BPI converters were essentially similar to MDD nonconverters. By contrast, BPII converters were robustly distinguished from those with MDD who remained unipolar on the basis of self-report measures along the newly derived factors of Mood Lability, Energy-Activity, and Daydreaming. This profile was associated with early age at onset of MDD and pleomorphic psychopathology beyond the usual affective realm, high rates of substance abuse, as well as educational, marital, and occupational disruption and minor antisocial acts prior to discrete hypomanic episodes. Overall, BPII switchers had a more protracted and tempestuous course with shorter well intervals. "Habitual self" descriptions of temperamental instability during MDD episodes provided useful clinical information for predicting which depressed patients will switch to BPII, attaining a sensitivity of 91% for all three factors combined (23 items); Mood Lability alone (nine items) was the most specific predictor (86%), though of lower sensitivity (42%). CONCLUSIONS: The BPII subtype is best understood by such lability intruding into, and possibly its accentuation during, depressive episodes, thereby creating an intimate interweaving of trait and state. Clinicians must note that the foregoing temperamental profile appears more fundamental in defining the affective dysregulation of the BPII subtype than hypomanic episodes emphasized in DSM-IV.

Adult↗

A family study of manic-depressive (bipolar I) disease. Is it a distinct illness separable from primary unipolar depression?

OBJECTIVE: To determine whether bipolar I illness is autonomous or part of a multifactorial continuum with unipolar depression. In this study, we compare familial bipolar I illness and depression among three groups: probands with bipolar I disorder; probands with primary unipolar disorder; and controls. We also examine a continuum of severity between psychotic and nonpsychotic patients with bipolar I disorder. Considerable data suggest that bipolar I illness is distinct from unipolar illness as regards epidemiology, familial psychiatric illness, course, response to treatment, and biologic findings. METHOD: Probands were separated into bipolar I and primary unipolar depressive groups. Personally interviewed family members of these patients were compared on variables of bipolar illness or schizoaffective mania and unipolar or schizoaffective depression. A personally examined control group was compared with the relatives of the two proband groups. Similar analyses were performed using data obtained by a systematic family history method. For the same familial variables, psychotic and nonpsychotic manic probands were compared. RESULTS: Familial mania is more frequent in families of patients with bipolar disease than in controls or in families of patients with primary unipolar disorder. The latter two groups did not differ in amount of mania. Unipolar depressive illness or schizoaffective depression was higher in families of probands with bipolar and unipolar disorder than in controls. Probands with bipolar disease separated into those who had psychotic symptoms (including schizoaffective mania) and no psychotic symptoms did not differ from each other in risk for familial mania or depression. CONCLUSIONS: Bipolar I illness is a separate illness from primary unipolar illness because of an increase in familial mania. Patients with primary unipolar disease and controls show the same amount of familial mania. Lack of an increase in familial illness according to the severity of bipolar disease is against an affective continuum.

Adolescent↗

Familial depression versus depression identified in a control group: are they the same?

Subjects who meet the criteria for an affective syndrome possibly are aetiologically heterogeneous. An approach to this possibility involves examining affectively ill subjects obtained by different methods of ascertainment. This study compares depressed and manic subjects who are related to affectively ill probands with affectively ill subjects who were obtained from a study of a control population, and, therefore, were less likely to be familial. The subjects were identified in a large collaborative study of depression where both family members as well as controls were personally interviewed and followed up for 6 years after admission to the study. Data were obtained on subtypes of affective disorder using the Research Diagnostic Criteria and information was gathered about psychiatric hospitalizations, suicide attempts, alcoholism and psychological functioning prior to admission. Similar assessments were made for the comparison groups for the 6 year period between intake and follow-up. Relatives of bipolar I/schizoaffective manic probands were more likely to show mania than affectively ill controls or relatives of unipolar/schizoaffective depressed probands. Affectively ill controls were less likely to be hospitalized and less likely to suffer from an incapacitating depression. They were also likely to have functioned in a more healthy fashion than the affectively ill relatives of the bipolars and unipolars, in the 5 years before admission to the study. In the 6 year follow-up, both the subjects themselves and raters assessed the depressed controls as functioning better than the affectively ill relatives of the probands. Further, assessment of global adjustment during the 6 year period was worse for the relatives of affectively ill probands than for the depressed controls. Length of major depression was longer in relatives of bipolar and unipolar probands than in controls. Though all of the subjects in this study met research criteria for an affective illness, there were marked differences in the qualitative aspects of these illnesses with the relatives of affectively ill probands, who functioned less well and had longer and more severe episodes and more hospitalizations.

Adaptation, Psychological↗

[Optic neuritis after wasp sting].

An allergic reaction after an insect sting is most common. However an inflammation of the optic nerve as a result is rare. The following case reports about a 20-year-old patient who suffered a temporary loss of sight after being stung by a wasp.

Adult↗

Correlation of clinical progression in human immunodeficiency virus-infected children with in vitro zidovudine resistance measured by a direct quantitative peripheral blood lymphocyte assay.

A rapid method for determination of zidovudine resistance was developed and results were correlated with clinical outcome in human immunodeficiency virus (HIV)-infected children. The zidovudine susceptibilities of HIV-1 isolates from 34 children were determined through a direct quantitative peripheral blood lymphocyte assay and compared with results of the AIDS Clinical Trials Group resistance assay. Patients' peripheral blood lymphocytes were 5-fold diluted and cocultured with donor lymphocytes and varying concentrations of zidovudine. Isolates were defined as sensitive if inhibited by < or = 1.0 microM zidovudine and resistant at > 1.0 microM. Children (n = 21) with zidovudine-resistant virus had greater evidence of disease progression than did those with zidovudine-sensitive virus (n = 11) as demonstrated by failure to thrive (57% vs. 9%, P = .01) and opportunistic infections (48% vs. 0, P = .006). This assay may be useful as a screening tool for development of clinically relevant zidovudine resistance.

Child↗

Effects of estrogen and progesterone on luteinizing hormone-releasing hormone messenger ribonucleic acid levels: consideration of temporal and neuroanatomical variables.

We examined temporal effects of estradiol (E2) and progesterone on cellular levels of LHRH messenger RNA (mRNA) in several brain regions. Female rats were ovariectomized and implanted with SILASTIC brand capsules of oil or E2 1 week later (day 0). Progesterone capsules were implanted on the morning of day 2. Using in situ hybridization histochemistry, we found that on day 2, E2 induced a complex temporal pattern of changes in LHRH mRNA levels. Levels in ovariectomized E2-treated animals were lower than control values in the morning, then increased before the LH surge and declined again as the surge waned. The magnitude of these changes was greatest in neurons of the rostral preoptic area/organum vasculosum of the lamina terminalis, but a similar pattern was detected in neurons of the medial preoptic area. No changes were seen in neurons of the diagonal band of Broca. Our finding that the effect of E2 on LHRH mRNA levels depends on the time of day and brain region examined largely reconciles discrepancies among previous studies. Progesterone triggered events that advanced the onset of and augmented the LH surge, but had no effect on LHRH mRNA levels. These findings support the hypothesis that the mechanism by which E2 induces region-specific changes in LHRH mRNA levels before the surge is separate from the progesterone-amplified mechanism that induces LHRH release.

Animals↗

Safety and effectiveness of an oral premedication regimen before cardiac surgery.

Thirty-five adult cardiac surgical patients received 20 mg dipotassium clorazepate orally the evening before surgery and 2 mg flunitrazepam 60 min before induction of anaesthesia. If anaesthesia was to be induced after 08.30 hours patients received an additional 20 mg dipotassium clorazepate at 06.15 hours. The following measurements were made: peripheral arterial oxygen saturation (Spo2) breathing room air; anxiety by visual analogue scale; degree of sedation; and haemodynamic variables. Mean (Spo2) was 95.9% (SD 1.8%) on the day before surgery and 95.4% (SD 1.5%) on arrival at the operating room. When the operation started after 08.30 hours, mean (Spo2) at 09.00 hours was 96.0% (SD 1.4%). There were no detected episodes of hypoxaemia after premedication. Mean anxiety score decreased significantly from 3.9 (SD 2.6) on the day before surgery to 3.3 (SD 2.1) on arrival at the operating room (patients' score; P < 0.002) and from 4.6 (SD 2.4) to 3.3 (SD 2.0) (anaesthesiologists' score; P < 0.001). Nearly all patients were considered well sedated, which was reflected by normal haemodynamic variables on arrival at the operating room. The combination of clorazepate and flunitrazepam is effective oral premedication for adult cardiac surgery, causing no obvious desaturation even when supplemental oxygen is not given.

Administration, Oral↗

Thermococcus alcaliphilus sp. nov., a new hyperthermophilic archaeum growing on polysulfide at alkaline pH.

A novel coccoid-shaped, hyperthermophilic, heterotrophic member of the archaea was isolated from a shallow marine hydrothermal system at Vulcano Island, Italy. The isolate grew between 56 and 90 degrees C with an optimum around 85 degrees C. The pH range for growth was 6.5 to 10.5, with an optimum around 9.0. Polysulfide and elemental sulfur were reduced to H2S. Sulfur stimulated the growth rate. The isolate fermented yeast extract, peptone, meat extract, tryptone, and casein. Isovalerate, isobutyrate, propionate, acetate, CO2, NH3, and H2S (in the presence of S degrees ) were detected as end products. Growth was not inhibited by H2. Based on DNA-DNA hybridization and 16S rRNA partial sequences, the new isolate represents a new species of Thermococcus, which we named Thermococcus alcaliphilus. The type strain is isolate AEDII12 (DSM 10322).

Archaea↗

Formation of amide bonds without a condensation agent and implications for origin of life.

Amide bonds are of central importance for biochemistry; in the guise of peptide bonds, they form the backbone of proteins. The formation of amide bonds without the assistance of enzymes poses a major challenge for theories of the origin of life. Enzyme-free formation of amide bonds between amino acids has been demonstrated in the presence of condensing agents such as cyanamide. Here we report the formation of amide bonds in aqueous solution in the absence of any condensing agent. We find that the formation of pyrite (FeS2) from FeS and H2S can provide the driving force for reductive acetylation of amino acids with mercaptoacetic acid (HSCH2COOH). The redox energy of pyrite formation permits the activation of the carboxylic acid group, which is converted to a species that reacts readily with amines. This process provides support for the chemo-autotrophic theory for the origin of life, in which pyrite formation supplies the energy source for the first autocatalytic reproduction cycle.

Acetylation↗

Dependence of the utilization of a phenylalanine-free amino acid mixture on different amounts of single dose ingested. A case report.

For patients with phenylketonuria the daily ingested phenylalanine-free amino acid mixture is the most important source of nitrogen. It is recommended to ingest one third of the total amount combined with main meals. Some patients, especially the older ones, do not follow this recommendation; they ingest the entire daily amount of amino acid mixture in one portion. This intake mode leads to an increased oxidative utilization of the amino acids. To set up an example for this metabolic phenomenon, a 13C-leucine breath test was performed in one female phenylketonuric patient. She ingested a third of her daily amount of the amino acid mixture combined with an oral tracer of 3 mg 13C-leucine/kg body weight at breakfast. The breath test was carried out by a standardized time schedule over 5 h. Three days later the breath test was repeated when she ingested the total amount of amino acid mixture in only one portion at breakfast. Total daily caloric intake and food composition were not changed. On both days a 24 h urine was collected to determine total nitrogen loss. The 13C-content of expired air was analysed by gas isotope ratio mass spectrometry, the total nitrogen content was determined using a combustion unit. The 13C-elimination rate as a percentage of the applied 13C-tracer was 9.5% on the first test day as compared to 19.6% on the 2nd day. The corresponding total nitrogen excretion was increased (4.3-6.9 g/24 h).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗