Renal graft rejection or urinary tract infection? The value of myeloperoxidase, C-reactive protein, and alpha2-macroglobulin in the urine.

Previous investigations have shown that the determination of two acute-phase proteins in the urine, C-reactive protein (CRPu) and alpha2-macroglobulin (alpha2-MGu), allows a noninvasive diagnosis of acute renal graft dysfunction. A reliable differentiation between rejection and urinary tract infection can be made only when considering the C-reactive protein in serum and urine at the same time (CRPs:CRPu ratio). Therefore, a diagnostic procedure independent of parameters other than urinary proteins is needed. As granulocytes play only a minor role in graft rejection but are a common feature in urinary tract infection, we determined a marker of granulocytes (myeloperoxidase) in urine (MPOu). Eighty-nine renal transplant recipients were included in the study. In normal courses, CRPu, alpha2-MGu, and MPOu were within the normal range. In 15 cases of acute interstitial rejection, an increased excretion of CRPu and alpha2-MGu could be confirmed, but MPOu could not be detected. On the occasion of acute vascular rejection (n=6), with the exception of one case, MPOu could not be observed. The pattern of the three urinary proteins differed in urinary tract infections (n=40): MPOu could be detected in all cases, CRPu in 50% of cases, and alpha2-MGu in 73% of cases. In patients with cytomegalovirus infection (n=7), no MPOu, CRPu, or alpha2-MGu was found. In conclusion, the simultaneous measurement of the three proteins allows a complete, noninvasive, differential diagnostic procedure of renal graft dysfunction.

Dementia in patients undergoing long-term dialysis: aetiology, differential diagnoses, epidemiology and management.

Dementia in patients undergoing long-term dialysis has not been clearly defined; however, four different entities have been described. Uraemic encephalopathy is a complication of uraemia and responds well to dialysis. Dialysis encephalopathy syndrome, the result of acute intoxication of aluminium caused by the use of an aluminium-containing dialysate, was a common occurrence prior to 1980. However, using modern techniques of water purification, such acute intoxication can now be avoided. Dialysis-associated encephalopathy/dementia (DAE) is always associated with elevated serum aluminium levels. Pathognomonic morphological changes in the brain have been described, but the mechanism for the entry of aluminium into the CNS is incompletely understood. The mechanisms involved in the pathogenesis of the neurotoxicity associated with aluminium are numerous. Although only a very small fraction of ingested aluminium is absorbed, the continuous oral aluminium intake from aluminium-based phosphate binders, and also of dietary or environmental origin, is responsible for aluminium overload in dialysis patients. Age-related dementia, especially vascular dementia, occurs in patients undergoing long-term dialysis as frequently as it does in the general population. The differential diagnoses of dialysis-associated dementias should include investigation for metabolic encephalopathies, heavy metal or trace element intoxications, and distinct structural neurological lesions such as subdural haematoma, normal pressure hydrocephalus, stroke and, particularly, hypertensive encephalopathy and multi-infarct dementia. To prevent DAE, dietary training programmes should aim to achieve the lowest phosphate intake and pharmacological tools should be used to keep serum phosphate levels below 2 mmol/L. To prevent vascular dementia, lifestyle modification should be undertaken, including optimal physical activity and fat intake, nicotine abstinence, and targeting optimal blood glucose, cholesterol and triglyceride levels, and blood pressure, to those outlined in current recommendations.

[Changes of cognitive brain functions in the elderly by Kneipp therapy]. / Veränderung kognitiver Hirnleistungen im Alter Durch Kneipp-Anwendungen.

INTRODUCTION: Pharmacological and nonpharmacological treatment of brain syndrome is multifarious. Until now, plain external applications of physical stimuli, as used daily in geriatric care, were not explored regarding their influence on cognitive brain function. The aim of this randomized cross-over study was to examine the influence of dermatoreceptive stimuli on cognitive brain function of healty geriatric volunteers. METHODS: 24 healthy volunteers (23 women, 1 man) were randomized into 2 groups (cross-over design). Group A (mean age +/- SD: 68.8 +/- 6.2 years) was treated according to the following regime: at first a 10-12 degrees C cold stimulus for 10 s (a so-called Kneipp face shower) and afterwards a cold wet pack of 10-12 degrees C at the neck for 1 min. Group B (age 69.8 +/- 5.3 years) was subjected to an identical procedure but with warm thermoindifferent temperatures of 34-36 degrees C. After 1 week the two groups were interchanged. The parameters of interest were the critical flicker frequency (CFF) and the latencies of the event-related P300 potentials of the visually evoked potentials (VEP), which can be considered the electroencephalographic substrate of the cognitive functional ability. The CFFs and the P300 latencies and amplitudes were measured directly before and 10 min after the application of the above-mentioned stimuli. Furthermore, the CFFs were recorded a second and third time 30 and 60 min later. RESULTS: Following application of cold-water stimuli, the CFF increased from (mean +/- SE) 32.55 +/- 0.44 s(-1) to 33.06 +/- 0.44 s(-1) (p = 0.003) 10 min after the stimulus. 30 min later the CFF was still elevated at 32.95 +/- 0.47 s(-1) (p = 0.043). The P300 latencies decreased by 4.8% (p < 0.001) after cold-water application from 266.5 +/- 5.28 to 253.7 +/- 4.22 ms. After warm stimuli they increased from 258.69 +/- 3.71 to 266.17 +/- 5.03 ms (p = 0.01). The P300 amplitudes were elevated by 5% only with the cold stimuli (p = 0.004). CONCLUSION: Cold water applied locally to face and neck region is able to provoke significant improvements of cognitive abilities.

[Guideline development for general medicine: the problem of dichotomized algorithm development]. / Allgemeinmedizinische Leitlinien-Entwicklung: Problematik der dichotomisierenden Algorithmenbildung.

Development of clinical guidelines in Germany is based on two divergent principles. One is the clinical position of individuality and clinical experience. The other is the strong adherence to the principles of evidence-based medicine and the scientific method, as demonstrated by the clear, algorithmic methodology of critical pathway development. We discuss the pros and cons of both concepts and try to find some sort of practical middle ground between the two extremes.

[The kidneys in aging]. / Die Nieren im Alter.

A progressive deterioration of renal anatomy and renal function with aging is inevitable. Glomeruli become sclerotic, renal mass declines, kidneys are shrinking and creatinine clearances decreases about 50% after the third decade of life. Renal aging in accelerated by risk factors of arteriosclerosis. The relationship of serum creatinine and creatinine clearance changes with age, since creatinine production is diminished. Old kidneys show a reduced ability to compensate stress, e.g., infection, medication, changes in blood pressure, and the risk of acute renal failure is increased. A glomerulonephritis in advanced age may be caused by a vasculitis; despite rapidly progressive course, early treatment can often improve renal function. The dosage of drugs eliminated by the kidneys has to be adapted in old patients. Despite only moderately elevated serum creatinine, renal function may be severely reduced in old persons and dialysis may be indicated. Dialysis and renal transplantation are possible therapeutic options despite advanced age.

[Severe metabolic alkalosis with a consciousness disorder]. / Schwere metabolische Alkalose mit Bewusstseinstrübung.

HISTORY AND CLINICAL FINDINGS: A 47-year-old man in a reduced general condition, presumed to be a chronic alcoholic, was hospitalised in a sleepy state and impaired level of consciousness (Glasgow Coma Scale 8). There were no focal neurological deficits, but all proprioceptor reflexes were weak. Body temperature was 36.8 degrees C, blood pressure 90/60 mm Hg, and heart rate 80/min. INVESTIGATIONS: Biochemical tests showed sodium concentration reduced to 121 mmol/l, potassium to 1.83 mmol/l, chloride to 55 mmol/l and, on the next day, phosphate to 0.11 mmol/l. Blood gas analysis demonstrated a noncompensated respiratory alkalosis (pH 7.69, bicarbonate 39.5 mmol/l and a base excess of 20 mmol/l. TREATMENT AND COURSE: The impaired consciousness was thought to be due to the marked alkalosis in combination with hypophosphataemia. The alkalosis was completely removed within 48 hours by administration of Ringer's solution and potassium chloride concentrate, without sodium chloride Phosphate deficit was neutralised with KH2PO4 infusion. Normal consciousness was restored. CONCLUSIONS: Even severe hypochloraemic alkalosis can be quickly reversed with infusion of chloride without sodium Successful treatment with chloride alone excludes alkalosis induced by mineralocorticoids.

[Ambulatory geriatric screening--an overview. I: Concept and methodologic development]. / Ambulantes geriatrisches Screening--eine Ubersicht. Teil I: Konzept und methodische Entwicklung.

Scientific literature reveals different levels of efficiency in geriatric screening in the primary care setting. Part I of our review deals with the development of geriatric screening up to the implementation of regular health checks in Great Britain. Studies in primary care show that through screening 1-2 previously unknown conditions per patient can be detected, with a particularly high prevalence of unknown problems in the following areas: vision and hearing, continence, mobility, cognitive function, mood, isolation, and lack of help. Further research is still required to transfer the results of screening studies into primary care, particularly in validating instruments of geriatric assessments and selecting risk groups.

[Ambulatory geriatric screening--an overview. II: Evaluation of the effectiveness and current recommendations for screening implementation]. / Ambulantes geriatrisches Screening--eine Ubersicht. Teil II: Evaluation der Effektivität und aktuelle Empfehlungen zum Screeningeinsatz.

Geriatric screening detects many problems previously unknown to the primary health care physician. In spite of this, a valid judgement can only be made if the effectiveness of the induced intervention is proven. Prospective studies evaluating these screening-induced interventions show diverse results. Nevertheless, international task forces conclude from the evidence of existing studies that there are areas which are effective, efficacious, and enhance the quality of life. It remains a continuing task for research to develop geriatric assessment instruments as well as to set up objective guidelines of intervention in these areas.

Glomerular and tubular proteinuria as markers of nephropathy in rheumatoid arthritis.

OBJECTIVE: We examined the prevalence of nephropathy in unselected patients with rheumatoid arthritis (RA) by measurement of marker proteins for glomerular and tubular damage in urine. METHODS: A highly sensitive immunoluminometric assay was used to measure albumin, immunoglobulin G and alpha1-microglobulin in 24 h urines of 44 RA patients and a control group of 46 patients with generalized osteoarthritis (OA). RESULTS: Fifty-five per cent of RA patients were found to have proteinuria as a symptom of renal disease. Drug therapy or vasculitis were identified as possible reasons for proteinuria in only 25% of these patients; in most patients (75%), no reason for proteinuria was found. Tubular and mixed proteinuria were more frequent than glomerular proteinuria. Only 15% of the control group exhibited mild proteinuria, which was attributable to nephrotoxic factors. The renal function of RA patients and the control group did not differ significantly. CONCLUSIONS: Proteinuria is a frequent symptom of nephropathy in RA. Screening for renal disease in RA should not only include creatinine measurement and dipstick examination of urine, but also more sensitive methods to detect tubular and glomerular proteinuria as a marker of tubular and early stages of glomerular damage.

[Intestinal vasculitis and glomerulonephritis in hepatitis C- associated cryoglobulinemia]. / Intestinale Vaskulitis und Glomerulonephritis bei Hepatitis-C-assoziierter Kryoglobulinämie.

In a 53-year-old female patient with recurrent, sometimes bloody diarrhea, the long standing diagnosis of an ANA-negative lupus erythematosus with membranoproliferative glomerulonephritis, leucocytoclastic vasculitis and chronic hepatitis was ruled out and the diagnosis of a hepatitis C associated cryoglobulinaemia was established. The origin of the diarrhea was due to intestinal vasculitis as a result of cold food or beverages.

Cerebral autoregulation during whole-body hypothermia and hyperthermia stimulus.

The purpose of the study contained herein was to investigate the effects of old traditional physiotherapeutic treatments on cerebral autoregulation. Treatment consisted of complete body immersion in cold or warm water baths. Fifteen volunteers were investigated by means of transcranial Doppler sonography and a servo-controlled noninvasive device for blood pressure measuring. One group of 8 volunteers (mean age, 27.2+/-3.5 yr; gender, 3 females/5 males) was subjected to cold baths of 22 degrees C for 20 min Another group of 7 volunteers (mean age, 52.1+/-8.5 yr; gender, 4 females/3 males) took hyperthermic baths at rising water temperatures from 36 degrees to 42 degrees C, increased by 1 degree C every 5 min. Each volunteer in both groups underwent autoregulation tests two to four times before, during, and after the thermic bath. Dynamic autoregulation was measured by the response of cerebral blood flow velocity to a transient decrease of the mean arterial blood pressure, induced by rapid deflation of thigh cuffs. The autoregulation index, i.e., a measure of the speed of change of cerebral autoregulation, was used to quantify the response. Further parameters were core temperature, blood pressure (mm Hg) and CO2et. During hypothermic baths, core temperature decreased by 0.3 degrees C (P = 0.001), measured between preliminary phase and the end of the bath; the autoregulation index decreased significantly (P < 0.05) from 5.3 before the bath to 4.25 during the bath. During hyperthermic baths, the autoregulation index increased from 6.0 to 7.5 and 8.9 (P < 0.001), with an increase of core temperature of 0.4 degrees C. The main cerebral autoregulation system is dependent on changes of core temperature, provoked by hypothermic or hyperthermic whole-body thermostimulus. Application of hyperthermic baths increased the autoregulation index, and hypothermic baths decreased the autoregulation index. Further studies are needed to prove the positive effects of thermo-stimulating water applications on cerebral hemodynamics in patients with cerebral diseases.

Changes of laboratory markers of cognitive brain function by thermostimuli in the elderly.

OBJECTIVE: Plain external applications of physical stimuli, which are used quite commonly in geriatric care in Germany, have not been studied for their influence on cognitive brain function. The aim of this randomized crossover study was to examine the influence of dermatoreceptive stimuli on cognitive brain function in healthy geriatric volunteers. METHODS: Twenty-four healthy volunteers (23 women, 1 man) were randomized into two groups (crossover design). Group A (mean age, 68.8+/-6.2 [SD] years) was treated with a 10 degrees C to 12 degrees C cold stimulus for 10 seconds (a so-called "Kneipp face shower"), followed by a cold 10 degrees C to 12 degrees C wetpack at the neck for 1 minute. Group B (mean age, 69.8+/-5.3 [SD] years) was subjected to an identical procedure but with warm to neutral temperatures of 34 degrees C to 36 degrees C. After I week the two groups were interchanged. The parameters of interest were the critical flicker frequency (CFF) and the latencies of the event-related P-300 potentials of the visual evoked potentials (VEP), which can be considered an electroencephalographic marker of the cognitive functional ability. The CFFs and the P-300 latencies and amplitudes were measured directly both before and 10 minutes after the application of the respective stimuli. In addition, the CFFs were recorded 30 and 60 minutes later. RESULTS: After cold water stimuli were applied, the CFF increased from 32.55+/-2.26/sec (mean+/-SD) to 33.06+/-2.25/sec (p = .003) 10 minutes after the stimulus. Thirty minutes later the CFF was still elevated at 32.95+/-2.3/sec (p = .043). The P-300 latencies, after cold water application, decreased by 4.8% (p < .001), from 266.5+/-21.1msec (mean+/-SD) to 253.7+/-16.9msec. After warm stimuli they increased from 258.69+/-14.8msec to 266.17+/-20.1msec (p = .01). The P-300 amplitudes were significantly elevated, by 5% (p = .004), only after cold stimuli. CONCLUSION: Cold water applied locally to the face and neck region can provoke significant changes in electroencephalographic markers as measured by an electroencephalographic marker (VEP and P-300 latency) and, by inference, may help to improve cognitive function in the elderly.

Primary hyperoxaluria type 1 causing end-stage renal disease in a 45-year-old patient.

Primary hyperoxaluria type 1 (PH1) is caused by deficiency of peroxisomal alanine-glyoxylate aminotransferase which is in humans exclusively expressed in liver cells. The disease is inherited as an autosomal recessive trait, and initial symptoms usually occur in early childhood. Up to the age of 25 years, 90% of the patients are symptomatic, and many patients develop end-stage renal failure. Pronounced medical care is necessary in PH1 patients to prevent generalized oxalosis with complications due to bone disease and peripheral gangrene. The rather short survival of patients on hemodialysis is caused by sudden arrhythmias and heart block. As no dialysis procedure is able to remove the daily produced oxalate, early transplantation is mandatory. Our 45-year-old patient is remarkable on the basis of the late manifestations of PH1. The diagnosis was delayed by unspecific symptoms of nephrolithiasis with recurrent pyelonephritis. Clinical course and diagnostic cornerstones of primary hyperoxaluria are outlined. The principles of conservative treatment and experiences with dialysis and transplantation are discussed.