Selection of patients with germline MLH1 mutated Lynch syndrome by determination of MLH1 methylation and BRAF mutation

Summary Aim: Retrospective analysis for determination of the effect of helical computed tomography (HCT) on utilization of V/Q lung scanning to diagnose pulmonary embolism (PE) in a large general hospital. Methods: A total number of 2676 V/Q scans of in- and out-patients referred to our department between March 1992 and December 1998 and between April 1997 and December 1998 were analyzed by an identical group of nuclear physicians. Results: Neither the total number of annually performed V/Q scans (446 ± 135) nor the mean age of patients (56 years ± 17) changed significantly since the introduction of HCT. However, the referral pattern was different. The percentage of patients with high and intermediate probability for PE decreased significantly from 15.2% to 9.4% (p < 0.01) and from 10.2% to 7.3% (p < 0.05), respectively. Low probability scans significantly increased from 37.8% to 42.7% (p < 0.05). The percentage of normal scans did not change significantly, however, there was a highly significant increase summarizing patients with normal and low probability scans (74.6% to 83.3%; p < 0.01). Conclusion: The introduction of HCT affected the selection of patients referred for V/Q lung scanning since V/Q scanning was primarily used to exclude rather to confirm PE.

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SERUM SOMATOMEDIN A IN GROWTH RETARDED CHILDREN

Acta Endocrinologica ◽

10.1530/acta.0.0880625 ◽

1978 ◽

Vol 88 (3) ◽

pp. 625-632 ◽

Cited By ~ 2

Author(s):

Naomi Hizuka ◽

Kazue Takano ◽

Kazuo Shizume ◽

Koichi Kawai

Keyword(s):

Growth Hormone ◽

Gh Deficiency ◽

Hormone Secretion ◽

Growth Hormone Secretion ◽

Human Growth ◽

Normal Growth ◽

Hormone Deficiency ◽

Selection Of Patients ◽

Selection Of

ABSTRACT The levels of serum somatomedin A were determined in 59 growth retarded Japanese children by a radioreceptor assay. Low levels were found in 10 children with growth hormone (GH) deficiency and 7 children with relative GH deficiency with means of 0.26 ± 0.03 and 0.48 ± 0.04 U/ml, respectively. Serum somatomedin A levels in 42 growth retarded children with normal growth hormone levels were within the range of normal adults, and did not correlate with degree of short stature. Significant increases of somatomedin A after hGH administration were found in children with growth hormone deficiency but not in children with normal growth hormone. These results show that determination of somatomedin A in serum correlates well with the state of growth hormone secretion, and is of great importance in the selection of patients for treatment with human growth hormone.

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Determination of basal enteroglucagon in plasma for selection of patients for small intestinal biopsy

Clinical Nutrition ◽

10.1016/0261-5614(87)90095-1 ◽

1987 ◽

Vol 6 ◽

pp. 20

Keyword(s):

Intestinal Biopsy ◽

Small Intestinal Biopsy ◽

Small Intestinal ◽

Selection Of Patients ◽

Selection Of

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A review of the determination of the early bactericidal activity of various antituberculosis agents

Suid-Afrikaanse Tydskrif vir Natuurwetenskap en Tegnologie ◽

10.4102/satnt.v22i2/3.215 ◽

2003 ◽

Vol 22 (2/3) ◽

pp. 79-88

Author(s):

P. R. Donald ◽

F. A. Sirgel ◽

A. Venter ◽

P. B. Fourie ◽

D. P. Parkin Parkin ◽

...

Keyword(s):

Bactericidal Activity ◽

Sputum Sample ◽

Sputum Specimen ◽

Successful Completion ◽

Sputum Production ◽

Colony Forming Units ◽

Sources Of Variation ◽

Selection Of Patients ◽

Selection Of

The early bactericidal activity (EBA) of an antituberculosis agent is the daily decline in log10 colony forming units of M tuberculosis per ml of sputum during the first two days of treatment with the agent. It reflects the capacity of an agent to kill the actively metabolising organisms in tuberculosis lung cavities. It offers a relatively cheap means to evaluate the antituberculosis activity of an agent in a small group of patients within a matter of months. This article summarizes the authors’ experience in seven published EBA studies and identifies sources of variation in the procedure. The patients who participated in these studies had a mean age of 33 years, a mean weight of 50 kg and there was extensive or massive involvement of the lungs in 55% of patients. The highest EBA values (0,50-0,66) were found in groups of patients receiving isoniazid and the lowest values (0,05 and 0,09 respectively), in patients receiving the aminoglycosides amikacin and paromomycin in a dose of 15 mg/kg body weight. The variation in EBA in 248 patients was 0,0312 and the variation ascribable to the process of sputum production and collection was 0,0233. This implies that the different aspects of sputum production and collection involved in obtaining a representative sputum sample are responsible for most of the variation in EBA results. The selection of patients for inclusion in EBA studies and their ability to co-operate in producing a representative sputum specimen are of critical importance in the successful completion of EBA studies.

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Determination of enteroglucagon in plasma for detection of celiac disease in children.

Clinical Chemistry ◽

10.1093/clinchem/30.1.77 ◽

1984 ◽

Vol 30 (1) ◽

pp. 77-80 ◽

Cited By ~ 7

Author(s):

A F Kilander ◽

L Stenhammar ◽

G Lindstedt ◽

P A Lundberg

Keyword(s):

Celiac Disease ◽

Intestinal Biopsy ◽

Gastrointestinal Disorders ◽

Small Intestinal Biopsy ◽

The Mean ◽

Small Intestinal ◽

Untreated Celiac Disease ◽

Selection Of Patients ◽

Selection Of

Abstract To evaluate the plasma enteroglucagon assay as a test for the detection of celiac disease, we have determined basal and postprandial concentrations of enteroglucagon in plasma of children who underwent small-intestinal biopsy because of suspected celiac disease. In the 14 children with untreated celiac disease both basal [81 (SD 33) pmol/L] and postprandial [129 (SD 26) pmol/L] concentrations of enteroglucagon were significantly higher (p less than 0.001) than in the 45 children with other gastrointestinal disorders [24 (SD 9) pmol/L, and 50 (SD 22) pmol/L, respectively] and in the 15 children without gastrointestinal disorders [14 (SD 10) pmol/L, and 35 (SD 8) pmol/L, respectively]. All children with celiac disease had either basal or postprandial plasma enteroglucagon concentrations exceeding the mean + 2 SD of the results for the children with other gastrointestinal disorders. Eight of 10 children with celiac disease in whom both concentrations were measured had increased values for both. In our study the sensitivity for detection of celiac disease was 100% and the specificity 97%. Evidently determination of plasma enteroglucagon concentration is effective in diagnosing celiac disease, thereby improving the selection of patients for small-intestinal biopsy.

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Recent Advances in the Knowledge of Total Red Cell Volume, Production and Destruction

Blood ◽

10.1182/blood.v12.2.147.147 ◽

1957 ◽

Vol 12 (2) ◽

pp. 147-164 ◽

Cited By ~ 32

Author(s):

NATHANIEL I. BERLIN ◽

JOHN H. LAWRENCE ◽

PAUL J. ELMLINGER

Keyword(s):

Life Span ◽

Cell Volume ◽

Red Cells ◽

Red Cell ◽

Red Cell Volume ◽

Volume Production ◽

Adequate Evaluation ◽

Selection Of Patients ◽

Selection Of

Abstract Since anemia or polycythemia can result only from a change in rate of formation of red cells or a change in the life span of the red cells, a determination of the total red cell volume, Fe59 studies to estimate the rate and site of production of red cells, and C14-labeled glycine or Fe59 studies to determine the life span of red cells permit a description of the pathogenesis of any alterations in the erythropoietic state. This has been of great value in clinical hematology from the stand-point of understanding the basic nature of the various diseases and, in particular, the selection of patients with unusual anemias possibly related to hypersplenism who might benefit from splenectomy. Splenic erythropoiesis can be easily differentiated from splenic red cell destruction. Since two of these methods—the determination of the blood volume and the Fe59 studies—are now possible in general commumnity hospitals and since modifications of the Fe59 method permit the determination of the life span of the red cell, adequate evaluation of the erythropoietic state is now possible in general hospitals.

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Update on Biomarkers Associated to Cardioembolic Stroke: A Narrative Review

Life ◽

10.3390/life11050448 ◽

2021 ◽

Vol 11 (5) ◽

pp. 448

Author(s):

Ana Catarina Fonseca ◽

Pedro Coelho

Keyword(s):

External Validation ◽

Left Ventricular ◽

Narrative Review ◽

Cardioembolic Stroke ◽

Cardiac Monitoring ◽

Stroke Recurrence ◽

Wall Motion Abnormalities ◽

Selection Of Patients ◽

Selection Of

Background: In the last years, several studies were conducted that evaluated biomarkers that could be helpful for cardioembolic stroke diagnosis, prognosis, and the determination of risk of stroke recurrence. Methods: We performed a narrative review of the main studies that evaluated biomarkers related to specific cardioembolic causes: atrial fibrillation, patent foramen ovale, atrial cardiomyopathy, and left ventricular wall motion abnormalities. Results: BNP and NT-proBNP are, among all biomarkers of cardioembolic stroke, the ones that have the highest amount of evidence for their use. NT-proBNP is currently used for the selection of patients that will be included in clinical trials that aim to evaluate the use of anticoagulation in patients suspected of having a cardioembolic stroke and for the selection of patients to undergo cardiac monitoring. NT-proBNP has also been incorporated in tools used to predict the risk of stroke recurrence (ABC-stroke score). Conclusions: NT-proBNP and BNP continue to be the biomarkers most widely studied in the context of cardioembolic stroke. The possibility of using other biomarkers in clinical practice is still distant, mainly because of the low methodological quality of the studies in which they were evaluated. Both internal and external validation studies are rarely performed for most biomarkers.

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LYNCH SYNDROME IN RUSSIAN PATIENTS

Problems in oncology ◽

10.37469/0507-3758-2017-63-1-110-114 ◽

2017 ◽

Vol 63 (1) ◽

pp. 110-114

Author(s):

Aleksey Tsukanov ◽

Vitaliy Shubin ◽

Natalya Pospekhova ◽

Sergey Achkasov ◽

Dmitriy Semenov ◽

...

Keyword(s):

Lynch Syndrome ◽

Left Colon ◽

Repair System ◽

Cancer Syndrome ◽

Previous Surgery ◽

Genetic Characteristics ◽

Poorly Differentiated ◽

Selection Of Patients ◽

Metachronous Tumors ◽

Selection Of

Lynch syndrome is a hereditary colorectal cancer syndrome caused by mutations in the DNA repair system genes. We studied the clinical and genetic characteristics of 27 Russian patients with Lynch syndrome. Germinal mutations were found in genes MLH1 (14 patients), MSH2 (11 patients) and MSH6 (2 patients). Eight mutations have not been described previously. The clinical features of this group of patients consisted of early average age of the first cancer - 36.7 years, predominant (72.4%) damage of the left colon, occurs most (70.6%) metachronous tumors for 10 years after the previous surgery, high (53.6%) frequency of poorly differentiated adenocarcinomas. The described genetic and phenotypic pattern indicates a need for more targeted selection of patients with suspected Lynch syndrome as well as the feasibility of the development of clinical guidelines for monitoring and surgical treatment exactly Russian patients.

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Streamlining universal screening for lynch syndrome (LS): Towards improved yield of genetic counseling (GC).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.503 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 503-503

Author(s):

Stefania Sciallero ◽

Azzurra Damiani ◽

Simonetta Zupo ◽

Linda Battistuzzi ◽

Alberto Puccini ◽

...

Keyword(s):

Braf Mutation ◽

Universal Screening ◽

Protein Loss ◽

Adherence To Guidelines ◽

Repair Deficiency ◽

Pathology Reports ◽

Mlh1 Protein ◽

Consecutive Stage ◽

Selection Of Patients ◽

Selection Of

503 Background: LS is largely underdiagnosed although Universal Screening (US) in colorectal cancer (CRC) patients through MisMatch Repair deficiency (MMR-d) testing is widely endorsed. Low adherence to guidelines among oncologists may be partly due to a lack of consensus on whether all MMR-d patients should be referred to GC/Genetic Testing (GT). As BRAF mutation rules out LS, we estimated the increased yield of LS diagnosis from GC /GT which could be obtained by selecting candidates for GC through BRAF testing. Methods: From 2011 to 2016, 1447 consecutive stage I-IV CRC surgical patients at a single institution, underwent immunohistochemistry (IHC) for LS using anti MLH1, MSH2, MSH6 and PMS2 antibodies. Oncologists were invited to refer all MMR-d patients to GC/GT. BRAFV600E testing was carried out only in case of MLH1 protein loss at IHC. Results: MMR-d was found in 194 patients (13%), with 171 showing loss of MLH1 expression (88%). Oncologists referred 27 (16%) to GC. Among the 21 who underwent GC, BRAF testing and GT, 9 were BRAF wild type (wt) (43%) and none had LS. Among the 23 MMR-d patients with loss of expression of MSH2, MSH6 or PMS2 (≠MLH1), oncologists referred 9 to GC (39%): 7 underwent GC / GT and 3 carried LS (43%) at GT. Median age was 76 years (range 30-97) in the MMR-d group, 78 (range 41-97) in the MLH1 group and 63 (range 30-86) in the ≠MLH1 group. Overall, LS was diagnosed in 3 of the 28 MMR-d patients (11%) who underwent GC /GT, possibly an underestimate due to the advanced median age of our MLH1 loss patients. Had we only offered GC to the 9 BRAF wt patients among the 21 with MLH1 loss, we could have avoided 12 (57%) of the GC sessions conducted, increasing the yield of LS diagnosis from 3/28 (11%) to 3/16 (19%) (75% increase). Conclusions: When US for LS is adopted, a GC referral rate reduction of 57% among MLH1 loss patients, and an overall increase in the yield of GC of about 75% can be obtained by testing for BRAF mutation before oncologist referral to GC rather than after. As multistep selection of patients by oncologists may be unfeasible, CRC pathology reports with combined MMR-d and BRAF testing (for MLH1 loss at IHC) and an ‘LS suspicion alert’ could improve oncologists’ awareness of LS and compliance with guidelines.

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