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Biomedical subjects

G Mayer

Publications and source records attributed to G Mayer.

At least 127 records · Page 7Linked to original sources

Circadian temperature and activity rhythms in unmedicated narcoleptic patients.

Fifteen unmedicated narcoleptic patients with and without sleep-onset REM period (SOREMP) were compared with 16 unmedicated, age-and-sex-matched control subjects with respect to polygraphic, core body temperature and motor activity recordings. Whereas narcoleptic patients with SOREMPs had significantly more quiet wakefulness during sleep, those without SOREMPs had significantly more quiet wakefulness during daytime than the other groups. Compared with that of controls, temperature of both narcoleptic groups showed (a) less rise of temperature curve in the morning, (b) dampening of temperature amplitude, (c) phase advance of acrophase, and (d) advance of temperature minimum after sleep onset. Maximal temperature decline occurred earlier in patients with SOREMPs during naps and sleep than in the other groups. We could confirm parallels between temperature and motor activity with controls and found no change in the oscillator of narcoleptic patients. Advanced temperature minima and first REMPs relative to sleep onset and maximal temperature decline occurring nearer to sleep onset indicate a defect in the temperature-locked triggering of REM in narcoleptic patients with SOREMP and a circadian rhythm disorder.

Adult↗

Low dose angiotensin converting enzyme inhibition and glomerular permselectivity in renal transplant recipients.

In this study, we determined the fractional clearance of neutral polydisperse dextrans (theta D) and monodisperse dextran sulfate (theta DS) to describe glomerular size and charge selectivity in 25 renal transplant recipients with proteinuria. Thirteen were treated with low dose lisinopril for six months (group 1) and 12 patients without ACE inhibitor therapy formed group 2. Mean arterial blood pressure was stable (group 1, 112 +/- 4; group 2, 109 +/- 2 mm Hg at baseline and after 6 months) whereas creatinine clearance, glomerular filtration rate and renal plasma flow decreased nonsignificantly but were comparable at any time. Lisinopril treatment lowered filtration fraction (22 +/- 2 vs. 19 +/- 2%, P = 0.07) whereas no change was seen in group 2 (20 +/- 2%). The fractional protein excretion (mg urinary protein per day/ml creatinine clearance per day) was stable in group 1, but significantly increased in group 2. The same pattern was found for theta D larger than 56 A. theta DS was stable and consistently elevated in both groups at any time. We conclude that low dose ACE inhibitor treatment in proteinuric renal transplant recipients stabilizes glomerular size selectivity independently of its systemic hemodynamic effects.

Angiotensin-Converting Enzyme Inhibitors↗

[Psychological, psychotherapeutic and other non-pharmacologic forms of therapy in treatment of insomnia. Position of the "Insomnia" Study Group of the German Society of Sleep Research and Sleep Medicine].

Psychological and psychotherapeutic techniques are an essential part of the treatment of insomnia. Mainly two facts stress the importance of psychological/psychotherapeutical strategies for insomnia: (1) Concepts for non-drug treatment aim at improvement of the symptoms and the underlying cause of the disease and (2) disadvantages of hypnotic therapy such as substance abuse or addiction are avoided. Effective treatment techniques such as patients education and counseling, sleep hygiene, stimulus control and relaxation techniques should be known to every therapist, especially general practitioners who treat the majority of patients haring difficulties in initiating or maintaining sleep. Several other effective behavioural techniques, e.g. sleep restriction, or cognitive therapy, and psychotherapy should be used only by skilled and trained experts. Insomniacs with chronic and severe complaints should be treated by therapists with experience in sleep medicine. Multimodal treatment strategies are provided for by sleep disorder centres and combine effective treatment elements in structured therapeutic concepts. There is absolute consensus of opinion that every hypnotic treatment of an insomniac patient should be combined with basal elements of non-drug treatment strategies.

Behavior Therapy↗

The long-acting dopamine agonist bromocriptine mesylate as additive immunosuppressive drug after kidney transplantation.

BACKGROUND: Acute rejection is an important risk factor for kidney graft loss. As evidence suggests that prolactin has important immunostimulatory properties, we conducted a randomized, prospective open trial in which bromocriptine, a drug suppressing prolactin secretion, was administered as an additive immunosuppressive drug after first cadaver kidney transplantation. METHODS: In the treatment group bromocriptine was given intramuscularly to 22 patients after their first kidney transplantation along with conventional immunosuppression (cyclosporin A, glucocorticoids). Twenty-three patients receiving only conventional immunosuppression served as control subjects. The incidence of acute graft rejections, graft losses, and infections was evaluated. RESULTS: Serum prolactin concentrations were slightly elevated above normal values before transplantation (32 +/- 5.3 ng/ml) and decreased to values between 13 and 16 ng/ml in the control group and were totally suppressed in the bromocriptine group. After 6 months of follow-up overall patient and allograft survival was 97.7% and 91% respectively. Acute rejection episodes occurred in 31 patients (77.5%): 15 in the bromocriptine group vs 20 in the control group (n.s.). In each group eight patients experienced a cytomegalovirus infection. The incidence of severe bacterial infections (i.e. pneumonia and sepsis) was five and six respectively. The necessity of haemodialysis after transplantation was 3.1% in the patients on bromocriptine and 23% in those without. CONCLUSIONS: Suppression of circulating prolactin concentration by bromocriptine did not improve the clinical outcome of patients after kidney transplantation receiving cyclosporin and prednisolone.

Acute Disease↗

Extensive HLA class II studies in 58 non-DRB1*15 (DR2) narcoleptic patients with cataplexy.

Narcolepsy is a sleep disorder that has been shown to be tightly associated with HLA DR15 (DR2). In this study, 58 non-DR15 patients with narcolepsy-cataplexy were typed at the HLA DRB1, DQA1 and DQB1 loci. Subjects included both sporadic cases and narcoleptic probands from multiplex families. Additional markers studied in the class II region were the promoters of the DQA1 and DQB1 genes, two CA repeat polymorphisms (DQCAR and DQCARII) located between the DQA1 and DQB1 genes, three CA repeat markers (G51152, T16CAR and G411624R) located between DQB1 and DQB3 and polymorphisms at the DQB2 locus. Twenty-one (36%) of these 58 non-DR15 narcoleptic patients were DQA1*0102 and DQB1*0602, a DQ1 subtype normally associated with DRB1*15 in DR2-positive narcoleptic subjects. Additional microsatellite and DQA1 promoter diversity was found in some of these non-DR15 but DQB1*0602-positive haplotypes but the known allele specific codons of DQA1*0102 and DQB1*0602 were maintained in all 21 cases. The 37 non-DQA1*0102/DQB1*0602 subjects did not share any particular HLA DR or DQ alleles. We conclude that HLA DQA1*0102 and DQB1*0602 are the most likely primary candidate susceptibility genes for narcolepsy in the HLA class II region.

Cataplexy↗

Biotinyl-tyramide: a novel approach for electron microscopic immunocytochemistry.

The biotinyl-tyramide protocol recently introduced for sensitive light microscopic immunocytochemistry was applied to electron microscopy and revealed various tissue antigens with high resolution. The protocol consists of an indirect method in which thin tissue sections are incubated successively within a specific primary antibody, followed by a biotinylated secondary antibody, streptavidin-HRP, and then finally with biotinyl-tyramide. The reaction product appears as a dense filamentous material that is deposited over particular cellular compartments. The labeling obtained for the antigens tested, amylase and heat-shock protein 70 in pancreatic acinar cells, insulin in pancreatic beta-cells, and carbamoyl phosphate synthetase and catalase in liver tissue, was found to be highly specific, with the labeling for each antigen confined to its particular cellular compartment. Background levels and nonspecific deposition of the staining were negligible. The use of biotinyl-tyramide therefore appears to be an alternative sensitive technique for immunoelectron microscopy.

Amylases↗

Parameters associated with chronic renal transplant failure.

BACKGROUND: Although chronic progressive renal transplant failure (CPTF) is one of the leading causes of end-stage renal disease its exact pathogenesis is still incompletely understood. Histopathological as well as clinical similarities between chronic native kidney diseases and CPTF open the possibility that the latter condition is not exclusively due to a prolonged immunological insult to the grafted organ but also is caused by a mismatch between the metabolic demands of the recipient and the excretory capacity of the transplanted kidney. In this retrospective study we defined clinical parameters which are associated with CPTF. METHODS: Creatinine clearance was followed in 469 patients 45 +/- 0.9 months after transplantation for 2 years. Various immunological and non-immunological parameters were included in an univariate and multivariate regression analysis to define those which are independently associated with CPTF, defined as a decrease of creatinine clearance during the study period. RESULTS: Of all the parameters proteinuria, systolic blood pressure, high Cyclosporin trough concentrations and the cumulative steroid dose were found to be significantly associated with CPTF. A persistent proteinuria of > 2 g/d during the observation period was found to have a positive predictive value of 83% for a deterioration of excretory kidney function of > or = 25% within 2 years. CONCLUSION: In CPTF immunological as well as non immunological factors are independently associated with the decline of excretory allograft function in the late postoperative period.

Blood Pressure↗

[Differential diagnosis of seizures in sleep].

Epilepsies and the NREM and REM parasomnias represent the most important sleep-related attacks that can occur in conjunction with sleep apnoea. Most sleep-related attacks arise from certain sleep stages only, which facilitates their identification. Many attacks can only be classified by thorough observation and description, since they lack special electrophysiological correlates. EEG recordings with at least 16 channels and EMGs from several muscles are necessary for differential diagnosis. Video-documentation often reveals relevant additional information confirming the diagnosis.

Diagnosis, Differential↗

Angiotensin converting enzyme insertion/deletion polymorphism and short-term renal response to ACE inhibition: role of sodium status.

Angiotensin converting enzyme (ACEi) inhibition retards renal function loss, but the therapeutic benefit varies between individuals. Renoprotection is poor in patients with the ACE DD genotype. ACE genotype is reported to affect short-term antiproteinuric response to ACEi, a predictor of long-term renoprotection, in some studies but not in others. Short-term responses to ACEi are enhanced by stimulating the renin-angiotensin system, that is, sodium restriction. We hypothesized that the ACE genotype influences sodium dependency of the response to ACEi. Therefore, we performed a cross sectional analysis of short-term responses to ACEi (enalapril or lisinopril) in 88 patients with stable non-diabetic proteinuria (> 1.0 g/day) and variable sodium intake. ACE genotype distribution was: DD, N = 25; ID, N = 40; II, N = 23. Baseline proteinuria (5.9 +/- 0.7; 5.8 +/- 0.07; 4.8 +/- 0.8 g/day, respectively) and mean arterial pressure (108 +/- 3; 106 +/- 2; 107 +/- 2 mm Hg, respectively) were similar for the three genotypes. ACEi similarly reduced proteinuria (-49 +/- 5; -55 +/- 4, -48 +/- 6%, respectively) and blood pressure (-12 +/- 3; -14 +/- 1 and -12 +/- 2%, respectively) in the three groups. Interestingly, the responses to ACEi of proteinuria (r = 0.42, P < 0.05) and blood pressure (r = 0.41, P < 0.05) correlated with urinary sodium excretion in DD genotype but not in the ID (r = 0.05 and 0.17, resp) or II genotype (r = 0.09 and 0.08, respectively). Thus, in the DD group, individuals with a high sodium excretion had a less effective response to ACEi. We conclude that differences in sodium status could account for disparities between studies on the relationship between ACE genotype and response to ACEi, and that sodium restriction might be a strategy to circumvent treatment resistance in the DD genotype.

Adolescent↗

Glomerular proteinuria in renal transplant patients: mechanisms and treatment.

Proteinuria in chronic kidney transplant failure (CKTF) is due to an alteration of glomerular permselectivity and two major determinants can be characterized experimentally: (1) size selectivity, that is, the ability of the glomerular filter to progressively hinder the passage of macromolecules with increasing molecular radius and (2) charge selectivity, the ability to restrict filtration of negatively charged molecules more effectively than that of equally sized uncharged or cationic compounds. The fractional clearance values of neutral polydisperse dextran molecules create a sieving profile to describe size selectivity, and anionic dextransulfate is used to evaluate charge selectivity. We characterized permselectivity in renal transplants recipients with various degrees of proteinuria. Proteinuria < 1 g/day is caused by an isolated defect of glomerular charge selectivity, whereas nephrotic range proteinuria (characterized histologically by transplant glomerulopathy) is due to an additional impairment of glomerular size selectivity. This sequence is similar to the one observed in patients with chronic native kidney disease (such as diabetic nephropathy). It therefore can be speculated that therapeutic interventions which have been shown to reduce proteinuria in patients with chronic native kidney disease will also beneficially affect permselectivity in CKTF.

Humans↗

[Complications of nasal CPAP therapy. Consequences for general practice].

BACKGROUND: The prevalence of the obstructive sleep apnea syndrome is about 5% in the entire population. The amount of treatment-indications grows for this particular sleep-related breathing disorder due to the increasing usage of diagnostic screening tests. In most cases, the positive-pressure ventilation, PPV (nCPAP, nBiPAP) is considered as a highly effective form of treatment, in comparison to other treating methods. The residential polysomnographic supervised adjustment of the treatment is optimally applied to most of the patients. Due to the increasing number of the treated patients, the reports about the appearance of short-termed side effects during the adjustment of the PPV become more frequent. PATIENTS AND RESULTS: We report on 9 patients who showed complications during the initial stage of treatment. The most common one, during the nCPAP-therapy, was the increase of central apneas. Because of this complication, a rapid optimization of the respiratory pressure or a change to a nBiPAP-therapy was necessary in 5 of the patients. 2 of the patients showed cardiac arrhythmias, some of which were severe. One patient produced a remarkable central hypoventilation during the initial phase of a nCPAP-therapy. The nBiPAP-titration combined with right-heart-catheter monitoring could demonstrate in another patient a possible cardiac decompensation through an increased ventilatory pressure. CONCLUSION: The risk of a positive-pressure ventilation is higher in patients with accompanying cardiac, pulmonary, neuropsychiatric and/or otorhinolaryngologic disorders. Considering the various predisposing factors of the patients we suggest an intensive apparative monitoring as well as stuff-supervision during the introduction to a respiratory treatment. If complications appear, a rapid improvement of the ventilatory pressure or a change to another respiratory treatment is indicated.

Aged↗

Serum tumor markers after renal transplantation.

The overall incidence of malignancy in renal transplant recipients is 100-fold higher compared with age matched controls. Routine clinical evaluation therefore often includes the determination of serum tumor markers AFP, CA19-9, CEA, CA125, CA15-3, PSA, and calcitonin. We evaluated the specificity and the sensitivity of these markers in 575 renal allograft recipients. Specificity varied between 0.69 (CA 125) and 0.96 (PSA) in 532 patients without cancer. Cyclosporine therapy and excretory allograft function did not affect marker concentration; impaired liver function was associated with significantly elevated AFP, CA19-9, CA125, and CA15-3 levels. In 43 patients with malignancies the sensitivity of the markers ranged between 0.2 (CEA) and 1 (CA 125, CA 15-3). We therefore conclude that routine screening of the transplant population with serum tumor markers is not useful because of the low sensitivity and specificity of these tests.

Adult↗

Renal function and glomerular permselectivity late after living related donor transplantation.

Living related kidney transplantation is the preferable procedure for renal replacement therapy. The aim of the current study was to determine systemic hemodynamic and intrarenal adaptions in donors and recipients late after living related kidney transplantation. Furthermore, glomerular permselectivity was assessed in these subjects. We studied mean blood pressure (MAP), glomerular filtration rate (GFR), renal plasma flow (RPF), microalbuminuria (MIA), 24-hr urinary protein excretion, and glomerular permselectivity (fractional clearance of neutral dextrans [thetaD] as a marker for size selectivity and fractional clearance of dextran sulfate [thetaDS] to assess charge selectivity) in 22 donors and 22 recipients. MAP was normal in the donor group (102 +/- 4 mmHg), but five patients had blood pressure above 140/90 mmHg. This 18%, however, is lower than the prevalence of hypertension in the age-adjusted general population in Austria. The recipients also had normal MAP at the time of study (99 +/- 3); however, 13 needed antihypertensive therapy. GFR and RPF were lower in recipients than in donors (53 +/- 8 vs. 72 +/- 11 and 314 +/- 74 vs. 412 +/- 86 ml/min respectively). In the donor group, GFR was 137 +/- 45% of the expected age-adjusted mean value/kidney due to hyperfiltration. Proteinuria and MIA were higher in the recipients than in the donors (0.39 +/- 0.22 vs. 0.07 +/- 0.04 g/day, 137 +/- 136 vs. 26 +/- 15 mg/day). Nonetheless, five donors had an elevated MIA. A higher need for antihypertensive medication could be observed in recipients with previous rejection episodes, as well as a significantly higher urinary protein excretion and MIA (0.7 +/- 0.42 vs. 0.24 +/- 0.14 g/day, 336 +/- 380 vs. 48 +/- 32 mg/day). ThetaDS was significantly higher in the recipients, whereas thetaDS of the donors was identical to the value obtained from 18 healthy controls (0.7 +/- 0.08 vs. 0.6 +/- 0.06). OD was similar in all groups studied. In conclusion, 76 months after uninephrectomy for renal donation, mild changes in glomerular permselectivity occurred in a subset of donors without affecting renal excretory function. In recipients, proteinuria was due to a defect in glomerular charge selectivity.

Adult↗

Atubular glomeruli in patients with chronic allograft rejection.

Morphometric studies were performed in 15 patients with chronic renal allograft rejection. Biopsy cores were serially sectioned so that atubular glomeruli could be identified and volumes of individual glomeruli could be measured. Control tissue was obtained from 9 cadaver donors and 8 living donors. Serial sectioning revealed that atubular glomeruli were as common as sclerotic glomeruli in chronic rejection. The prevalence of atubular glomeruli averaged 18 +/- 15% (mean +/- SD) in recipients with chronic rejection, 2 +/- 2% in cadaver donors, and 1 +/- 3% in living donors (P<0.05, recipients vs. donor groups). In comparison, the prevalence of sclerotic glomeruli averaged 19 +/- 13%, 4 +/- 7%, and 7 +/- 10% in the three groups (P<0.05 recipients vs. donor groups). Atubular glomeruli exhibited reduced mean volume (3.1 +/- 0.9 x 10(6)micron(3) vs. 4.5 +/- 1.5 x lO(6)micron(3), atubular vs. open glomeruli in recipients, P < 0.05) but could not be distinguished from open glomeruli by their appearance on single sections. Recipients with chronic rejection exhibited tubular atrophy and interstitial fibrosis with an increase in the interstitial volume fraction to 51 +/- 14% as compared with 29 +/- 6% in cadaver donors and 17 +/- 2% in living donors (P<0.05 recipients vs. donor groups). Similar interstitial expansion was observed in recipients with a high prevalence of atubular glomeruli, recipients with a high prevalence of sclerotic glomeruli, and also in four recipients in whom the predominant form of glomerular injury was transplant glomerulopathy. These results suggest that mechanisms responsible for development of atubular glomeruli are among the processes that contribute to loss of graft function in patients with chronic rejection.

Adult↗

[123I]IBZM SPET analysis of dopamine D2 receptor occupancy in narcoleptic patients in the course of treatment.

Elevated levels of central D2 dopamine receptors were found on postmortem examination in cases of human narcolepsy. In vivo investigations using positron emission tomography (PET) and single photon emission tomography (SPET) found no changes of D2 binding in the striatal structures. To investigate whether the elevated D2 receptors in postmortem investigations are due to long-term treatment effects, we applied 123I-labeled (S)-2-hydroxy-3-iodo-6-methoxy-([1-ethyl-2-pyrrolidinyl]methyl) benzamide (IBZM) ([123I]IBZM, a highly selective CNS D2 dopamine receptor ligand) and SPET in narcoleptic patients in the course of treatment with stimulants and/or antidepressants. Before treatment we found no changes in D2 binding in 10 patients (in comparison to 10 normal controls). After treatment (performed in five patients for 3 months) we found changes in D2 binding in four of them, indicating that the results of the postmortem studies could have been influenced by long-term medications. Human narcolepsy seems not to be related to a striatal D2 dopaminergic disturbance.

Adolescent↗

Multiple-dose pharmacokinetics of cefpirome in long-term hemodialysis with high-flux membranes.

Cefpirome is a cephalosporin eliminated primarily by kidneys that requires dosage reduction in patients with renal failure. The pharmacokinetic parameters were studied in 10 patients with end-stage renal disease who were receiving hemodialysis. Repeated intravenous administration of 2 gm cefpirome three times a week resulted in trough levels of 12.2 +/- 5.4 micrograms/ml and peak serum concentrations of 99.6 +/- 82.1 micrograms/ml. After 3 1/2 hours of hemodialysis with polysulfone high-flux membranes, 62.3% +/- 23.3% of cefpirome was removed. The interdialytic half-life was 9.35 +/- 0.99 hours, and the intradialytic half-life was 2.02 +/- 0.7 hours.

Adult↗

Effects of vitamin B12 on performance and circadian rhythm in normal subjects.

This preliminary study investigates effects of methyl- and cyanocobalamin on circadian rhythms, well-being, alertness, and concentration in healthy subjects. Six women (mean age 35 years) and 14 men (mean age 37 years) were randomly assigned to treatment for 14 days with 3 mg cyano-(CB12) or methylcobalamin (MB12) after 9 days of pre-treatment observation. Levels in the CB12 group increased rapidly in the first, then slowly in the second treatment week, whereas increase in the MB12 group was linear. Urinary aMT6s excretion was reduced by both forms of vitamin B12 over 24 hours with a significant decrease between 0700-1100 hours, whereas urinary excretion of potassium was significantly increased between 0700-1100 hours. Activity from 2300-0700 hours increased significantly under both forms of vitamin B12. Sleep time was significantly reduced under MB12 intake. In this group the change in the visual analogue scales items "sleep quality," "concentration," and "feeling refreshed" between pretreatment and the first week of treatment showed significant correlations with vitamin B12 plasma levels. Cortisol excretion and temperature were not affected by either medication. We conclude that vitamin B12 exerts a direct influence on melatonin. Only MB12 has a positive psychotropic alerting effect with a distribution of the sleep-wake cycle toward sleep reduction.

Adult↗