[Leukopenia with unclear fever]. / Leukopenie mit unklarem Fieber.

We report on a 77-year-old male patient with neutropenic fever as a result of a newly diagnosed agranulocytosis. The patient was taking metamizole, which is a well known cause of agranulocytosis. The diagnosis of metamizole-induced agranulocytosis as an underestimated side-effect of metamizole could be confirmed by a bone marrow biopsy. The bone marrow and the blood count recovered completely after stopping the therapy with metamizole and administration of granulocyte colony-stimulating factor (G-CSF).

Evidence against solar influence on nuclear decay constants.

The hypothesis that proximity to the Sun causes variation of decay constants at permille level has been tested and disproved. Repeated activity measurements of mono-radionuclide sources were performed over periods from 200 days up to four decades at 14 laboratories across the globe. Residuals from the exponential nuclear decay curves were inspected for annual oscillations. Systematic deviations from a purely exponential decay curve differ from one data set to another and are attributable to instabilities in the instrumentation and measurement conditions. The most stable activity measurements of alpha, beta-minus, electron capture, and beta-plus decaying sources set an upper limit of 0.0006% to 0.008% to the amplitude of annual oscillations in the decay rate. Oscillations in phase with Earth's orbital distance to the Sun could not be observed within a 10-6 to 10-5 range of precision. There are also no apparent modulations over periods of weeks or months. Consequently, there is no indication of a natural impediment against sub-permille accuracy in half-life determinations, renormalisation of activity to a distant reference date, application of nuclear dating for archaeology, geo- and cosmochronology, nor in establishing the SI unit becquerel and seeking international equivalence of activity standards.

[Cardiopulmonary Exercise Testing (CPET) in severe COPD--a multicentre comparison of two test protocols]. / Spiroergometrie bei Patienten mit chronisch obstruktiver Lungenerkrankung--multizentrischer Vergleich von zwei Belastungsprotokollen.

Cardiopulmonary exercise testing (CPET) allows a valid evaluation of cardiopulmonary function capability and the recognition of existing limitations in COPD patients. Whereas the measurement of the different parameters of CPET and the evaluation of the results are standardised, this does not apply to the protocols chosen. The aim of this study was to evaluate whether the results of two different exercise protocols were comparable in an outpatient multicentre setting. Ninety COPD patients stages II-IV according to the Gold classification were examined by means of symptom-limited exercise testing on a bicycle with two different ramp protocols (10 Watts vs. 16 Watts/min) within seven days. The results show that a higher acceleration rate of the load was associated with shorter exercise duration and higher achieved exercise capacity. Gas exchange and ventilatory parameters did not show significant differences on comparing both protocols. In pulmonary practices COPD patients of the Gold stages II-IV can be examined safely and with validity by means of CPET. The application of a ramp protocol with a stepwise increase of 16 Watts/minute can be recommended, particularly as for this regimen standardised normal values are available.

Pancreatic diabetes manifests when beta cell area declines by approximately 65% in humans.

AIMS/HYPOTHESIS: Diabetes frequently develops in patients with pancreatic disorders. We aimed to determine the lower threshold of beta cell area for diabetes manifestation as well as the impact of insulin sensitivity on glucose homoeostasis in patients with pancreatic diabetes. METHODS: Eighty-two patients undergoing pancreatic surgery underwent pre-operative oral glucose challenge. Fractional pancreatic beta cell area was determined, and indices of insulin sensitivity and beta cell function were calculated. RESULTS: HbA1c and glucose levels were similar in patients with high and intermediate beta cell area, but were significantly higher in those with the lowest beta cell area (p < 0.0001). Insulin secretion was reduced only in patients with the lowest beta cell area (p < 0.001). The relative beta cell deficits at the onset of diabetes and impaired glucose tolerance were 64% and 21%, respectively, based on 2 h glucose levels. Deteriorating insulin sensitivity was associated with a small increase in the incidence of diabetes. CONCLUSIONS/INTERPRETATION: In conclusion, pancreatic diabetes probably develops after a reduction in beta cell area of ~65%. Post-challenge glucose excursions are much more closely related to pancreatic beta cell area than to fasting glycaemia, thereby underlining the usefulness of the OGTT in patients with pancreatic disorders.

[Doubtful nosological validity of the chronic whiplash syndrome]. / Fragliche nosologische Validität des chronischen Halswirbelschleudertraumasyndroms.

BACKGROUND: Since the 1980s, victims of traffic accidents in western countries increasingly report chronic symptoms which they attribute to a whiplash injury of the cervical spine. In an extensive review article published in 1996, it was, however, concluded that this so-called chronic whiplash syndrome has little nosological validity. It was now investigated whether this conclusion could be upheld by the results of later published studies. METHODS: Extensive evaluation was carried out of all the whiplash literature listed in Pubmed since 1996 with the question whether research over the last 15 years has achieved a better validation of this syndrome. RESULTS: Of the over 1,600 publications about whiplash since 1996, no study could be identified which confirmed the nosological validity of the chronic whiplash syndrome. CONCLUSION: As a positive consequence of the results of this study, accident victims suffering whiplash can be informed about the very good prognosis after whiplash in a more trustworthy way. Many iatrogenic injuries can thus be avoided. The expert opinion after whiplash without radiologically documented and/or neurologically confirmed significant acute traumatic injury which can cause chronic symptoms, should generally not be in favor of insurance benefits. The authors propose that all of a set of minimal criteria should be fulfilled if in exceptional cases a probable relationship between the trauma and chronic symptoms can be assumed.

[Unclear hepatopathy in a patient with atrial fibrillation]. / Unklare Hepatopathie bei einem Patienten mit Vorhofflimmern.

Although liver damage is a relatively rare adverse effect of oral anticoagulation with phenprocoumon, acute liver failure can be a serious treatment-associated complication. In this contribution, a patient with drug-induced liver failure during oral anticoagulation with phenprocoumon is presented. This case illustrates the need for close laboratory monitoring and suggests that phenrocoumon-induced liver damage should be considered along with other common complications of this treatment.

Diagnostic value of quantitative EUS elastography for malignant pancreatic tumors: relationship with pancreatic fibrosis.

PURPOSE: EUS elastography has been used to facilitate the diagnosis of pancreatic cancer, but as yet the interpretation of this procedure has been largely subjective. The present study has been designed to validate a quantitative approach for the analysis of EUS elastography, and to assess its relationship with pancreatic fibrosis. MATERIALS AND METHODS: 86 patients with malignant pancreatic masses and 28 control subjects without any evidence of pancreatic diseases were examined by EUS elastography. EUS video sequences were subjected to a quantitative analysis based on mean hue histogram analysis. Pancreatic fibrosis was determined by quantitative morphometry in tissue specimens from 36 patients. RESULTS: The mean RGB (red, green, blue) value was significantly higher in the cancer patients compared to the controls (14.0 ± 0.4 vs. 11.5 ± 0.9; p = 0.0085), albeit with significant overlap between the groups. In contrast, a much sharper separation between the groups was obtained based on the individual color values for blue, green and red (p < 0.0001, respectively). By these means, 100 % sensitivity and specificity for the distinction between tumor and normal tissue was obtained for the blue color value, while the red and green color values were less discriminative. The fractional fiber content of the tumors was unrelated to the respective hue histogram color values. CONCLUSION: Quantitative EUS elastography allows for clear differentiation between malignant pancreatic tumors and normal tissue. Using this approach, we demonstrated that the stiffness of pancreatic tumors is largely independent of their fiber content.

Determinants of glucose control in patients with chronic pancreatitis.

AIMS/HYPOTHESIS: Diabetes frequently develops in patients with chronic pancreatitis (CP). Partial pancreatectomy has emerged as a treatment option for such patients. We addressed whether the development of diabetes in CP patients is related to pancreatic beta cell area or clinical variables, and which factors predict the diabetes risk after partial pancreatectomy. METHODS: Fractional beta cell area was determined in pancreatic tissue samples obtained from 114 CP patients undergoing pancreatic surgery and related to measures of glucose control, as well as clinical and anthropometric data. Seventy-four patients without diabetes at the time of surgery were contacted again 2.5 +/- 1.0 years after partial pancreatectomy in order to obtain information about the post-operative development of diabetes. RESULTS: In the surgical samples in the whole cohort, pancreatic beta cell area was 0.40 +/- 0.06% in patients with and 0.64 +/- 0.06% in those without previously known diabetes (p = 0.039). There was an inverse non-linear relationship between pancreatic beta cell area and fasting glucose concentrations (r = 0.29) as well as HbA(1c) levels (r = 0.36). Nineteen out of 74 previously normoglycaemic patients (26%) developed diabetes over an average period of 2.5 years of follow-up. Pre-operative fasting glucose levels, HbA(1c) and BMI were identified as predictors of diabetes after partial pancreatectomy. However, pancreatic beta cell area did not differ in those who subsequently developed diabetes (0.66 +/- 0.15%) and those who did not (0.62 +/- 0.08%, p = 0.45). CONCLUSIONS/INTERPRETATION: Hyperglycaemia in CP patients is associated with reduced beta cell area. However, reduced beta cell area does not predict the development of diabetes, suggesting that other factors are more important determinants of alterations in glucose metabolism in patients with CP.

Half-life measurements of long-lived radionuclides--new data analysis and systematic effects.

Half-lives of long-lived radionuclides, for example, (85)Kr, (90)Sr, (108m)Ag, (133)Ba, (137)Cs, (152)Eu and (154)Eu, were measured at the Physikalisch-Technische Bundesanstalt (PTB) by ionization chamber measuring systems, for some nuclides, during a period of about 30 years. In particular, the relative residuals of fitted raw data from current measurements by a modified Townsend balance (compensation method) showed small periodic yearly fluctuations. The interpretation of these fluctuations is discussed. To solve problems of instrument instabilities (fluctuations), a new method of data analysis is applied using least-squares fits of combinations of the current ratios of the various radionuclide sources with corresponding data points measured each at nearly the same time. The data are corrected for instabilities similarly to when using current ratios with a (226)Ra reference source. The new method of data analysis excludes possible systematic effects due to disequilibrium of the (226)Ra decay chain. The limits of the method are discussed including the elimination of outliers due to systematic errors. An uncertainty budget is presented with the corresponding uncertainty components. Relative residuals of the fits in the best cases of the order of +/-5x10(-4) have been achieved. The results comprise data until the end of 2008. They agree within the limits of their relative uncertainties, typically better than 1.5x10(-3), with those published earlier by PTB authors.

Expression of beta-defensin 4 is increased in human gastritis.

BACKGROUND: Infection with Helicobacter pylori (H. pylori) leads to the initiation of innate immune responses with increased antimicrobial peptide (AMP) expression in the gastric epithelium. This study aimed to determine the expression of the novel peptides beta-defensin 4 (hBD-4) and RNase 7 in infectious and non-infectious gastritis. Furthermore, pattern recognition receptors and mechanisms of regulation were characterized. MATERIALS AND METHODS: Expression of AMPs was quantified by real-time PCR in biopsies obtained from healthy individuals and patients with infectious and non-infectious gastritis as well as in AGS gastric epithelial cells infected with H. pylori. Distribution of hBD-4 in the gastric mucosa was characterized by in-situ hybridisation and immunohistochemistry. The role of Toll-like receptors (TLRs) 2 and 4 and associated signalling pathways was addressed. RESULTS: hBD-4 was expressed at low levels in gastric epithelial cells and was significantly upregulated in infectious and non-infectious gastritis. Standard eradication but not acid suppression therapy significantly decreased hBD-4 expression. Cytotoxin associated gene (cag)A positive H. pylori significantly increased the expression of hBD-4 whereas cagA negative organisms, non-viable bacteria or culture supernatants had no significant effect. Overexpression and downregulation of TLRs was not associated with an altered hBD-4 expression. However, blocking experiments revealed an essential role for the p38 mitogen-activated protein kinase. RNase7 was inconsistently expressed in biopsies and not significantly upregulated by H. pylori. CONCLUSIONS: hBD-4 may play a significant role in H. pylori associated gastritis. Inconsistent expression of RNase 7 does not support a pivotal role for this peptide in response to infection with H. pylori.

Metabolic consequences of a 50% partial pancreatectomy in humans.

AIMS/HYPOTHESIS: Partial pancreatectomy is frequently performed in patients with pancreatic tumours or chronic pancreatitis, but little is known about the metabolic impact of this intervention. We examined the effects of approximately 50% partial pancreatectomy on glucose homeostasis and insulin secretion. METHODS: Fourteen patients with chronic pancreatitis, ten patients with pancreatic carcinoma and 13 patients with benign pancreatic tumours or extra-pancreatic masses (control group) underwent 240 min oral glucose tolerance tests before and after pancreatic tail-resection (n = 12), duodenopancreatectomy (n = 19) or duodenum-preserving pancreatic-head resection (n = 6). RESULTS: Partial pancreatectomy led to a reduction in post-challenge insulin excursions by 49% in chronic pancreatitis patients, 52% in carcinoma patients and 55% in controls (p < 0.05). Nevertheless, post-challenge glucose concentrations were transiently ameliorated after surgery (p < 0.001). In the control participants, pancreatic-head resection caused a transient reduction of post-challenge glycaemia, whereas pancreatic-tail resection increased both fasting and post-challenge glycaemia (p < 0.05). Insulin sensitivity was highest in chronic pancreatitis patients before surgery (p < 0.01), but remained unchanged by the partial pancreatectomy. High pre-operative body weight and elevated fasting glucose levels were associated with poor glycaemic control after surgery. CONCLUSIONS/INTERPRETATION: Insulin secretion is diminished after pancreatic-head and -tail resection, but post-challenge glucose concentrations can be ameliorated after pancreatic-head resection. These data highlight the unequal impact of different surgical procedures on glucose control and suggest that obesity and high pre-operative glucose levels should be considered as risk factors for the development of hyperglycaemia after pancreatic surgery.

Headache after concussion.

BACKGROUND AND PURPOSE: Chronic post-traumatic headache attributed to mild head injury is a somewhat disputed headache diagnosis. A main object of this study was to assess the validity of this diagnosis by studying the headache pattern of concussed patients that participated in one historic (n = 131) and one prospective cohort (n = 217) study. METHODS: Head injury patients were recruited from two hospitals in Kaunas, Lithuania. Controls were recruited amongst patients with minor orthopaedic traumas not involving the head and neck. RESULTS: When data from the two studies were pooled, no difference in any headache category (diagnosis, attack frequency, symptoms) was found one or more years after the trauma, except that photophobia was somewhat more prevalent amongst the concussed patients. In both injury groups, the existence of pre-traumatic headache was a predictor of post-traumatic headache, although pre-traumatic headache seems to have been underreported amongst the concussed patients. There was a significant negative correlation between the duration of unconsciousness and the headache. CONCLUSIONS: This negative correlation, and the lack of specificity indicates that headache occurring 3 months or more after concussion is not caused by the head or brain injury. Rather it may represent an episode of one of the primary headaches, possibly induced by the stress of the situation.

Calibration of a radionuclide calibrator system as a Bulgarian standard for activity.

A commercially available radionuclide calibrator of the type Curiementor 3 (PTW, Freiburg, Germany) was calibrated using activity standard solutions, from the Physikalisch-Technische Bundesanstalt (PTB), of a number of photon-emitting radionuclides, in particular those used in nuclear medicine: (18)F, (51)Cr, (67)Ga, (99m)Tc, (111)In, (123)I, (125)I, (131)I, (186)Re, (201)Tl, and for beta-emitting nuclides: (32)P, (89)Sr, (90)Y, (204)Tl. An energy-dependent efficiency curve was established to calculate efficiencies for photon-emitting radionuclides. The differences between experimental and calculated radionuclide efficiencies of the measuring system are of the order of a few percent. The performance of the system was checked for instrument stability, using a long-lived (137)Cs source, and for linearity using the decay of a (99m)Tc source. The calibration measurements were carried out with 2g of solution in standard PTB-type glass ampoules. The dependence of efficiency with varying solution mass and changing ampoule geometry is studied for some of the radionuclides. For example, geometry correction factors are determined for various solution volumes or ampoules with different wall thickness. The measuring system will enable the National Centre of Metrology (NCM) of Bulgaria to provide calibration services for activity measurements, which are traceable to PTB standards, and to organize national comparisons in order to improve the quality of measurements for nuclear medicine in Bulgarian hospitals. Furthermore, it should enable NCM to declare Calibration and Measurement Capabilities (CMCs) and to submit radioactive solutions to the International Reference System (SIR) at the BIPM in order to compare the results with Key Comparison Reference Values (KCRVs).

High-speed tensile test instrument.

A novel high-speed tensile test instrument is described, capable of measuring the mechanical response of elastomers at strain rates ranging from 10 to 1600 s(-1) for strains through failure. The device employs a drop weight that engages levers to stretch a sample on a horizontal track. To improve dynamic equilibrium, a common problem in high speed testing, equal and opposite loading was applied to each end of the sample. Demonstrative results are reported for two elastomers at strain rates to 588 s(-1) with maximum strains of 4.3. At the higher strain rates, there is a substantial inertial contribution to the measured force, an effect unaccounted for in prior works using the drop weight technique. The strain rates were essentially constant over most of the strain range and fill a three-decade gap in the data from existing methods.

Activity standardisation of (18)F and ionisation chamber calibration for nuclear medicine.

Primary activity standardisations were performed on solutions of (18)F using 4pibeta-gamma coincidence counting and liquid scintillation counting (LSC) according to the CIEMAT/NIST method. A beta(+)-emission probability of 96.86% was used for both methods. The various standardised (18)F solutions were measured in ionisation chambers of the Physikalisch-Technische Bundesanstalt (PTB) and compared by determining radionuclide calibration factors. Already in 2001 an (18)F solution had been standardised at the PTB and compared with the results of nine national metrology institutes (NMIs), using the ISOCAL IV secondary radionuclide calibrators of the National Physical Laboratory (NPL) as transfer instruments and a (68)Ge check source solution. These results were linked to the International Reference System (SIR) at the Bureau International des Poids et Mesures (BIPM) by aliquots of solutions sent by the Laboratoire National Henri Becquerel (BNM-LNHB) and the NPL. Further on, in 2005, PTB sent an aliquot of an (18)F solution to the SIR for ionisation chamber measurements. A value of the equivalent activity was determined and included in the key comparison database (KCDB). The recent PTB value of the equivalent activity of the SIR is in good agreement with the key comparison reference value determined from five NMIs. These results confirm that the standardisation of (18)F solutions can be achieved with the accuracy required for use in nuclear medicine and, in particular, for applications in positron emission tomography (PET).

Examination of the diagnostic validity of 'headache attributed to whiplash injury': a controlled, prospective study.

Acute and chronic headache attributed to whiplash injury are new diagnostic entities in the International Classification of Headache Disorders, second edition. A main objective of the present study was to assess the validity of these nosologic entities by studying the headache pattern in an inception cohort of 210 rear-end car collision victims and in 210 matched controls. Consecutive drivers involved in rear-end collisions were identified from the daily records of the Traffic Police Department of Kaunas, Lithuania. A standard self-report questionnaire was sent to the drivers between 2 and 7 days after the collision, and their passengers were recruited as well. Headache and neck pain were evaluated within 7 days of the collision, at 2 months and 1 year after the collision. A control group of non-traumatized subjects received questionnaires at the time of the selection and 1 year later. Of the 75 collision victims who developed headache within the first 7 days of the collision, 37 had a clinical picture in accordance with the criteria for acute whiplash headache (i.e., concomitant neck pain) and 38 did not. For acute headache after collision, concomitant neck pain was of no relevance to the headache type or its course. In both these subgroups, migraine and tension-type headache could be diagnosed in similar proportions and the prognosis after 2 months and 1 year was also similar. Preexisting headache was a strong prognostic factor in both groups for both acute and chronic pain. Compared with the non-traumatized control group, the 1-year incidence of new or worsened headache, or of headache improvement, was the same. A likely interpretation of the data is that acute headaches after rear-end car collisions mainly represent episodes of a primary headache precipitated by the stress of the situation. We conclude that the nosologic validity of both acute and chronic whiplash headache is poor as the headaches, in accordance with the criteria lack distinguishing clinical features and have the same prognosis compared with headaches in a control group.

Activity standardization and nuclear decay data of 109Cd.

The activity of a (109)Cd solution has been accurately determined without using (109)Cd nuclear decay data such as emission probabilities. An ampoule containing this calibrated (109)Cd solution was sent to the Bureau International des Poids et Mesures to include the activity result in the database of the International Reference System (SIR). The emission rate of conversion electrons was measured by means of pressurized proportional counters as well as by a liquid scintillation spectrometer. The combination of the results with the photon emission rate measured with the aid of gamma-ray spectrometers yields the activity concentration. The measurement results were also used to deduce emission probabilities with high accuracy. For the 88 keV transition, a photon emission probability of p(gamma)=0.03663(33) and a total internal conversion coefficient of alpha(t)=26.30(25) were determined.

Photon-photon coincidences for activity determination: I-125 and other radionuclides.

Theory and experiment of photon-photon coincidence counting with distance variation for activity standardisation of radionuclide solutions are described. The activity of an I-125 solution from an international comparison organised by the BIPM in 2004 was determined. The value obtained agrees with other methods within a limit of 0.2%. The extension of this activity standardisation method to other radionuclides such as Cd-109 with I-125 as a tracer nuclide, In-111, Am-241 and I-124 with a radionuclidic impurity of I-125 is studied. Achieved uncertainties of the activities of Cd-109 and In-111 are of the order of 1.5%. The activity values of sources of Am-241 are determined relative to each other. Am-241 is used for checking the measuring system and as a long-lived reference source. After decay of the order of several I-124 half-lives, sources of I-124 with I-125 are measured to determine the I-125 activity portion.