Tubulointerstitial nephritis caused by the antiviral agent foscarnet

The antiviral agent foscarnet has long been used in our unit to treat cytomegalovirus (CMV) infections in renal transplant patients. The clinical effect has been convincing and, apart from changes in serum calcium levels, very few side effects have been noted. We have, however, observed a nephrotoxic reaction in a series of patients with initially good renal function who therefore received high doses of foscarnet. Transplant biopsies performed in five of those patients revealed degenerative changes in the tubular epithelial cells as well as tubular calcium deposits and an infiltration of the interstitium by mixed mononuclear and polymorphonuclear leucocytes. Renal insufficiency was accompanied by high fever. After withdrawal of the drug, the temperature rapidly normalized, whereas serum creatinine continued to rise for about 3 days and then fell back towards previous levels. We conclude that transplant biopsies are of great value in distinguishing between a foscarnet nephrotoxic effect and CMV nephritis, various forms of rejection, and other causes of impaired renal function.     

Tears of the medial meniscus associated with increased radionuclide activity of the proximal tibia

Summary Three patients who presented with long-standing medial knee pain and normal radiographs had an isotope bone scan in an attempt to arrive at a diagnosis. In each case there was a well-defined area of increased uptake over the medial tibial condyle and arthroscopy subsequently revealed meniscal damage. After arthroscopic menisectomy each patient became asymptomatic and the bone scan returned to normal. We suggest that patients with incapacitating knee pain, normal radiographs and a positive bone scan undergo an arthroscopy even in the absence of clinical signs of meniscal damage.

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Résumé Trois malades qui présentaient depuis longtemps des douleurs de la partie interne du genou et dont les radiographies étaient normales ont bénéficié d'une scintigraphie afin d'essayer d'ðablir un diagnostic. Dans tous les cas il y avait une zone bien limitée d'hyperfixation au niveau de la partie interne de l'extrémité supérieure du tibia, et l'arthroscopie ultérieure découvrit une lésion méniscale. Après méniscectomie arthroscopique tous les malades furent soulagés et la scintigraphie redevint normale. Nous proposons que l'on pratique une arthroscopie, même en l'absence de signes cliniques d'atteinte méniscale, chez les sujets présentant des douleurs notables du genou, avec des radiographies normales et une scintigraphie positive.

     

Reversibility and reproducibility of histamine induced plasma leakage in nasal airways.

Plasma exudation is one cardinal factor in airways defence and inflammation. In inflammatory airway diseases such as rhinitis and asthma, however, plasma leakage may also have a pathogenetic role. Experimental data from animals indicate that highly sensitive, active, and reversible processes regulate the vascular and mucosal permeability to macromolecules. With the use of a nasal lavage model for the recovery of liquids on the mucosal surface the effect of histamine on the macromolecular permeability of the airway endothelial-epithelial barriers was studied in normal subjects. The concentrations of albumin, kinins, and N-alpha-beta-tosyl-L-arginine-methyl esterase (TAME) in nasal lavage fluid were measured and nasal symptoms assessed by a scoring technique. The reproducibility of three repeated challenges with 30 minute intervals on the same day was studied in 12 subjects and compared with the same procedure (three challenges) on a different day. Sneezing decreased significantly (p less than 0.05) after the first histamine challenge but was maintained thereafter. Otherwise, the mean values for symptoms and for markers of vascular leakage were very similar both for the three challenges in the same session and for the two challenge sessions on a different day. Sneezing, blockage, and secretions were associated with increased concentrations of TAME esterase (maximum 9000 cpm/ml), kinins (1.4 ng/ml), and albumin (0.3 g/l) in lavage fluid. Both the symptoms and the measures of plasma exudation were reversible and reproducible in the three repeat histamine challenges and at two challenge sessions on different days. These findings support the view that non-injurious, active processes regulate the inflammatory flow of macromolecules across airways endothelial-epithelial barriers. The present experimental approach would be suitable for studies of the modulatory effects of inflammatory stimulus induced plasma leakage and symptoms in human airways.     

Spinal cord stimulation for refractory angina pectoris: a retrospective analysis of efficacy and cost-benefit

BACKGROUND: Patients with refractory angina pectoris have severe symptoms despite optimal medication, but are not suitable for revascularisation. Spinal cord stimulation (SCS) has been used for treating refractory angina pectoris since 1985. The efficacy of SCS has been proven by randomised controlled trials and follow-up studies have shown that SCS is a safe treatment. The objective of the current study was to retrospectively analyse the clinical outcomes and cost-benefit of SCS in patients with refractory angina pectoris. METHODS: Eighteen months after SCS implantation, the effects on Canadian Cardiovascular Society (CCS) functional level and acute symptom relief of 24 patients with permanent SCS were analysed by review of medical records. Nineteen of these 24 patients were able to report their anginal frequency, nitroglycerin consumption and subjective perception on physical activity and quality of life. RESULTS: Angina frequency decreased from a median of 14.0 to 2.3 attacks/week (p < 0.01). Nitroglycerin intake decreased from a median of 27.5 to 1.5 doses/week (p < 0.01). Canadian Cardiovascular Society angina class improved from a median of three to two (p < 0.001). During a three-year period before SCS implantation, the hospitalisation rate and duration related to coronary artery disease increased progressively. The duration of hospitalisation increased from a median of three to 10 days/patient/year. In the year after SCS implantation the duration of hospitalisation decreased to a median of 0 day/patient/year (p < 0.001). The cost of hospital care due to coronary artery disease decreased significantly thereafter. The total cost of SCS procedure was recovered within 16 months after implantation, which is less than 40% of the device life span. CONCLUSIONS: This retrospective study indicates that SCS treatment alleviates angina symptoms and improves quality of life. The treatment is also effective in preventing hospitalisations and saving costs in hospital care. A prospective study is warranted to confirm the current observations.     

Ear measurement of temperature is only useful for screening for fever in an adult emergency department

Background

A new generation of ear thermometers with preheated tips and several measurements points should allow a more precise temperature measurement. The aim of the study was to evaluate if the ear temperature measured by this ear thermometer can be used to screen for fever and whether the thermometer is in agreement with the rectal temperature and if age, use of hearing devices or time after admission influences the temperature measurements.

Methods

Open cross-sectional clinical single site study patients, >?18?years old, who were acutely admitted to the short stay unit at the ED. A sample size of 99 patient per subgroup was recruited as random convenience series. As ear thermometer Braun Thermoscan Pro 4000® and as rectal thermometer Omron Flex Temp Smart ® was used. For different cut off of temperature the AUC was calculated and Bland-Altman analysis for calculation of 95% limits of agreement with rectal temperature, with subgroup analysis concerning age, time span from admission time and use of hearing aid.

Results

Among 599 patients the sensitivity to detect fever with an ear thermometer varied between 68 and 70% with AUC from 0.88–0.97. If the ear temperature was ≥37.5 oC, the sensitivity to detect patients with ≥38.0 oC rectally was 95% which raised to 100% for a rectal temperature of ≥38.3 oC. For the ear thermometer’s ability to determine the exact temperature the 95% limits of agreement were +/??0.8 oC. with no influence from age, duration of hospital stay or hearing aids.

Conclusion

The examined ear thermometer is able to detect fever, defined as ≥38 oC rectally in an adult ED population by using an ear cut-point of 37.5 oC, but not to measure the exact temperature. Used in this way around a fifth of the patients will still be in need of a rectal temperature measurement, but less than 5% with fever ≥38.0 oC will remain undetected and none with fever ≥38.3 oC. Age, admission time and use of hearing aid did not influence the temperature measurements.

Trial registration

Clinical Trials: ID NCT02977481, date 11/18/2016.

     

Kinins modulate the sodium-dependent autoregulation of renal medullary blood flow

OBJECTIVE: In the recent past it has become clear that the kallikrein-kinin system is closely intertwined with long-term blood pressure regulation. It was shown that a kinin B2 receptor blockade leads to a sodium-dependent rise in blood pressure. The underlying mechanisms of this phenomenon, however, remain unclear. The osmotic gradient of the renal medulla is a prerequisite for the preservation of volume and sodium by the kidney. We thus hypothesized, that a kinin dependent modulation of medullary blood flow accounts for the influence of sodium on blood pressure. METHODS: In 39 urethane anaesthetized rats pressure dependent regulation of whole kidney blood flow and cortical and medullary blood flow were estimated via laser-Doppler flux by a stepwise reduction of renal perfusion pressure to 30 mm Hg. RESULTS: In controls (n = 15), a reduction in renal perfusion pressure to 30 mm Hg lead to a concomitant reduction in whole kidney blood flow (25 +/- 3% of baseline) and cortical laser-Doppler flux (36 +/- 5% of baseline). In contrast, medullary laser-Doppler flux decreased only to 79 +/- 8% of the baseline level. Providing a 2% sodium chloride solution as drinking water over 5 days (n = 12), resulted in a significantly lower capability to autoregulate medullary flow (50 +/- 6% of baseline, P < 0.05). Acute subcutaneous administration of Hoe 140, a bradykinin B2 receptor antagonist (300 micrograms/kg bwt), restored autoregulation of medullary flow to almost normal levels (93 +/- 12% of baseline, P < 0.01 versus high sodium diet alone, n = 12). CONCLUSIONS: Our results indicate that B2 receptor blockade restores the attenuated autoregulation of medullary Doppler flux during sodium enriched diet. This, suggests that the kinin dependent impact of sodium on blood pressure regulation is mediated by modulations of medullary blood flow autoregulation.     

Asymptomatic bacteriuria during pregnancy with special reference to group B streptococci

The relationship between significant bacteriuria (SB), i.e. 2 subsequent voided urine specimens with greater than or equal to 10(5) colony forming units (CFU)/ml, and the occurrence of bacteria in the urinary bladder detected by bladder punction, was investigated in asymptomatic pregnant women. From 30 (70%) of the 43 women with SB studied, bacteria were isolated from the urinary bladder. The same bacteria were found in the bladders of all 21 women with Escherichia coli, the one with Klebsiella pneumoniae, and the one with Staphylococcus saprophyticus in midstream urine. Six of 10 patients with group B streptococci (GBS), 1 of 4 patients with Streptococcus faecalis, and none of 5 patients with Staphylococcus epidermidis in voided specimens had bacteria in the aspirated urine. Serotype III was isolated from 8/10 patients with SB caused by GBS. One child born to a woman with GBS SB but no bacteria in the urinary bladder, got early onset septicaemia. The poor predictive value of SB with GBS, S. faecalis and S. epidermidis necessitates the increased use of bladder puncture for diagnosis of true asymptomatic bacteriuria (AB), i.e. AB with bacteria in the urinary bladder. SB with GBS even without bacteria in the urinary bladder, may constitute a threat to the baby's health.     

The effect of arachidonic acid and its metabolites on acid production in isolated human parietal cells

The effect of arachidonic acid and its metabolites on the histamine-stimulated acid production in human isolated parietal cells provenient from endoscopic biopsies was examined. 14C-aminopyrine (14C-AP) accumulation in the parietal cells was used for evaluation of acid production. Histamine dose-dependently increased AP uptake. Histamine stimulation (taken as 100% at 10(-5) M) was significantly inhibited by prostaglandin (PG) E2 to 66 +/- 7% at 10(-8) M, 42 +/- 8% at 10(-6) M, and 13 +/- 10% at 10(-4) M (mean +/- SEM, n = 10). PGF2 alpha, PGD2, and PGI2 showed significant inhibitory effects only at very high concentrations (10(-5)-10(-4) M). Leukotriene (LT) B4 and LTC4 were without effect. The basal acid production (taken as 0%) was lowered significantly by 10(-6) M arachidonic acid to -20 +/- 7.4% (p less than 0.02, n = 10), and the histamine-stimulated (10(-6) M) acid production from 100% to 64 +/- 7.2% (p less than 0.001, n = 10). Aspirin (10(-3) M) increased basal (45 +/- 9.6%, p less than 0.001, n = 10) and histamine-stimulated (10(-6) M) acid production (164 +/- 16.3%, p less than 0.001). It is concluded that PGE2, the major product from arachidonic acid metabolism in the human gastric mucosa, is a significant inhibitor of the histamine-stimulated human parietal cell and may, in humans, play a role as a local physiologic inhibitor of acid secretion.