Doctors' requirements for reproducibility of diagnostic information

Two radiologists independently assessed 100 leg vein phlebograms for the presence or absence of deep venous thrombosis. In a subsequent questionnaire, 66 physicians were asked to state the level of agreement they would require to use conventional phlebography in their diagnostic decisions, and whether they would reduce their requirements if the phlebographic technique were made less painful and less expensive. The responses indicated physicians' requirements for reproducibility of a well-known routine diagnostic method may be unrealistic, and that physicians do not consider the inconvenience of an examination to the patient or its cost in setting their requirements for diagnostic precision.     

No increased risk of hypoglycaemic episodes during 48 h of subcutaneous glucagon-like-peptide-1 administration in fasting healthy subjects

Objective  It is uncertain whether the ability to avoid hypoglycaemia during fasting is preserved, and the risk of reactive hypoglycaemia after an oral glucose stimulus following a prolonged fasting period is increased at augmented glucagon-like peptide-1 (GLP-1) levels.
Design  A randomized, double-blind placebo-controlled cross-over study in eight healthy men to assess the safety, in terms of hypoglycaemia, of a continuously infused pharmacological dose of native GLP-1 during long-term fasting. After an overnight fast the fasting period continued for 48 h and was followed by a 3-h oral glucose tolerance test (OGTT). GLP-1(7-36 amide) or placebo was continuously infused subcutaneously and titrated to a dose of 4·8 pmol/kg per min.
Results  Two subjects in the GLP-1 group and one subject in the placebo group were withdrawn due to protocol specified plasma glucose (PG) ≤ 2·8 m m and neuroglycopaenic symptoms.
The infusion of GLP-1 resulted in pharmacological levels of intact GLP-1. During the fasting period PG, insulin and C-peptide levels declined and glucagon, GH and free fatty acid (FFA) levels increased with no differences between GLP-1 and placebo. During OGTT circulating levels of insulin and C-peptide were higher with GLP-1 infusion. However, PG was similar during GLP-1 vs. placebo infusions. GLP-1 infusion increased norepinephrine and cortisol levels during OGTT.
Conclusion  The counter-regulatory response during 48 h of subcutaneous GLP-1 infusion was preserved despite long-term fasting with no apparent increased risk of hypoglycaemic episodes. No reactive hypoglycaemia was observed when the fast was followed by an OGTT. Thus use of long-acting GLP-1 analogues may not increase the risk of hypoglycaemia.     

Erythropoietin acts as a trophic factor in neonatal rat intestine

BACKGROUND: Erythropoietin (Epo) receptors are present on enterocytes of fetal and neonatal small bowel but the role of Epo in the bowel is not known. AIMS: We tested the following hypotheses: (1) enterally dosed Epo is absorbed from the intestines of neonatal rats, (2) Epo acts as a trophic factor in developing small bowel, and (3) the trophic effects of Epo are dependent on the route of administration. METHODS: The dose dependent effects of enterally dosed recombinant human erythropoietin (rEpo 0--1000 U/kg/day) were studied in artificially raised rat pups and compared with dam raised controls and dam raised pups given rEpo in rat milk. After one week, reticulocyte counts, haematocrits, and plasma Epo concentrations were measured, and calibrated morphometric measurements of villi were performed. The effects of route of rEpo administration (enteral v parenteral) on erythropoiesis, bowel growth, and disaccharidase activity were studied in nursing pups treated for one and two weeks. RESULTS: Serum Epo concentrations ranged from undetectable (<0.6 mU/ml) to 8.4 mU/ml in control and enterally dosed pups (median 1.8 mU/ml), and from 4.9 to 82.3 mU/ml (median 20.4 mU/ml) in parenterally dosed animals. No increase in haematocrit or reticulocyte count was noted in enterally treated pups compared with controls after up to two weeks of treatment. Small bowel length was greater in rEpo treated pups, and a dose dependent increase in villus surface area which was independent of the route of dosing and associated with increased BrdU uptake was found. CONCLUSIONS: rEpo is not enterally absorbed in an intact and functional form from the intestines of neonatal rat pups. Thus enterally dosed rEpo has no erythropoietic effects. However, rEpo acts as a trophic factor in developing rat small bowel whether given enterally or parenterally.     

Regional differences in waiting time to pregnancy: pregnancy-based surveys from Denmark, France, Germany, Italy and Sweden. The European Infertility and Subfecundity Study Group.

The objective of this study was examine geographical variation in couple fecundity in Europe. The study was based upon all recently pregnant (or still pregnant) women within well-defined geographical areas in Europe (Denmark, Germany, Italy, Sweden and France) at a given time period in 1992. Altogether, 4035 women responded to a highly structured questionnaire. Highest fecundity was found in Southern Italy and Northern Sweden; lowest fecundity was seen in data from the East German centre. Approximately 16% of the study population had a waiting time of more than 12 months to become pregnant. Most of the pregnancies were planned (64%) and approximately 14% were the result of contraceptive failures. The study shows that smoking, body mass index, age and parity did not explain the differences in fecundity found between the centres. Regional differences in fecundity exist and the causes may be genetic or due to variations in behavioural and environmental exposures.     

Comparison of two dose calculation methods applied to extracranial stereotactic radiotherapy treatment planning.

BACKGROUND AND PURPOSE: Lung tissue is a special challenge for a dose calculation algorithm, especially in the case of extracranial stereotactic radiotherapy (ESRT) due to small field sizes in combination with large variations in tissue density. The present study investigates the choice of dose calculation algorithm for 18 patients with a single lung tumor and 8 patients with a single liver tumor. The dose calculation is performed with both the pencil beam convolution algorithm and the collapsed cone convolution algorithm with the same number of monitor units in both cases. In addition, the dose calculation with the collapsed cone convolution algorithm is also performed with modified field sizes in order to match the Planning Target Volume (PTV) peripheral dose of the pencil beam based treatment. RESULTS: For liver tumors, the mean Clinical Target Volume (CTV) dose calculated by the collapsed cone convolution algorithm and the pencil beam convolution algorithm is almost identical. For lung tumors, the mean CTV dose determined by the collapsed cone convolution algorithm differs up to 20%. Plans obtained by the two algorithms have field sizes which differ up to 8mm for the same number of monitor units and minimum dose to the lung PTV. CONCLUSIONS: The choice of dose calculation algorithm can have a large influence on a treatment plan for ESRT of the lungs.     

Electron microscopy of ultrasound-guided fine-needle biopsy specimens

A prospective 3-year study was undertaken in order to assess the value of electron microscopy (EM) as a supplement to routine light microscopy (LM) in ultrasound-guided fine-needle biopsy of suspected abdominal and retroperitoneal tumours. Eight-six of the 899 ultrasound-guided fine-needle biopsies performed during this period were supplemented with EM using the following indications: metastatic lesions with unknown primary tumour, primary retroperitoneal tumours, tumours with atypical clinical histories and where the primary LM evaluation was unable to determine tumour cell type. Two methods of obtaining material for EM were tested, namely, fine-needle aspiration and fine-needle histological biopsy (Surecut). Both methods yielded suitable material for EM evaluation in approximately 80% of the 76 cases where tumour cells were identified by LM. However, it was technically easier to process material for EM when obtained by fine-needle histological biopsy. The results of the 62 cases where suitable material for EM was obtained were grouped according to the histopathological and clinical value of the diagnosis. In 23 cases (37%) EM was without additional diagnostic value. In 12 cases (19%), EM supplied a more precise histopathological diagnosis, but the diagnostic gain was without clinical significance. In 27 cases (44%) EM was of significant clinical value, as the diagnosis by itself was enough to change the investigative procedure and/or the treatment of the patient.     

Guidelines for blood smear preparation and staining procedure for setting up an external quality assessment scheme for blood smear interpretation. Part I: Control material.

Blood smear analysis is a well known technique in medical laboratories. Clinical relevance of this analysis and its interpretation are very important. Consequently, monitoring of laboratory performance by an external quality assessment scheme is strongly recommended. Most starting external quality organizers set up a scheme for clinical chemistry. Due to a lack of guidance documents, many organizers are reluctant to offer a hematology scheme. This article aims to be a very practical guidance document for external quality assessment organizers for the set up of blood smear schemes.     

Digital densimeter for simple determination of urinary density.

Urinary density can be determined by measuring the change in the natural frequency of a hollow oscillator when filled with liquids of different density. The method requires only 0.6 ml of sample, and the precision is plus or minus 2. 5 - 10-4 g/cm-3. For clinical use a determination rate of approximately 60 samples an hour with a precision of 1 - 10-3 g/cm-3 may be reached.