Excellent agreement between genetic and hydrogen breath tests for lactase deficiency and the role of extended symptom assessment

Clinical manifestations of lactase (LCT) deficiency include intestinal and extra-intestinal symptoms. Lactose hydrogen breath test (H2-BT) is considered the gold standard to evaluate LCT deficiency (LD). Recently, the single-nucleotide polymorphism C/T− 13 910has been associated with LD. The objectives of the present study were to evaluate the agreement between genetic testing of LCT C/T− 13 910and lactose H2-BT, and the diagnostic value of extended symptom assessment. Of the 201 patients included in the study, 194 (139 females; mean age 38, range 17–79 years, and 55 males, mean age 38, range 18–68 years) patients with clinical suspicion of LD underwent a 3–4 h H2-BT and genetic testing for LCT C/T− 13 910. Patients rated five intestinal and four extra-intestinal symptoms during the H2-BT and then at home for the following 48 h. Declaring H2-BT as the gold standard, the CC− 13 910genotype had a sensitivity of 97 % and a specificity of 95 % with a κ of 0·9 in diagnosing LCT deficiency. Patients with LD had more intense intestinal symptoms 4 h following the lactose challenge included in the H2-BT. We found no difference in the intensity of extra-intestinal symptoms between patients with and without LD. Symptom assessment yielded differences for intestinal symptoms abdominal pain, bloating, borborygmi and diarrhoea between 120 min and 4 h after oral lactose challenge. Extra-intestinal symptoms (dizziness, headache and myalgia) and extension of symptom assessment up to 48 h did not consistently show different results. In conclusion, genetic testing has an excellent agreement with the standard lactose H2-BT, and it may replace breath testing for the diagnosis of LD. Extended symptom scores and assessment of extra-intestinal symptoms have limited diagnostic value in the evaluation of LD.

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Major Hereditary Gastrointestinal Cancer Syndromes: a Narrative Review

Journal of Gastrointestinal and Liver Diseases ◽

10.15403/jgld.2014.1121.262.maj ◽

2017 ◽

Vol 26 (2) ◽

pp. 157-163 ◽

Cited By ~ 1

Author(s):

Lakshmi Manogna Chintalacheruvu ◽

Trudy Shaw ◽

Avanija Buddam ◽

Osama Diab ◽

Thamer Kassim ◽

...

Keyword(s):

Gastric Cancer ◽

Genetic Testing ◽

Gastrointestinal Cancer ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Clinical Manifestations ◽

Micro Rna ◽

Diffuse Gastric Cancer ◽

Adenomatous Polyposis ◽

Cancer Syndromes

Gastrointestinal cancer is one of the major causes of death worldwide. Hereditary gastrointestinal cancer syndromes constitute about 5-10% of all cancers. About 20-25% of undiagnosed cases have a possible hereditary component, which is not yet established. In the last few decades, the advance in genomics has led to the discovery of multiple cancer predisposition genes in gastrointestinal cancer. Physicians should be aware of these syndromes to identify high-risk patients and offer genetic testing to prevent cancer death. In this review, we describe clinical manifestations, genetic testing and its challenges, diagnosis and management of the major hereditary gastrointestinal cancer syndromes.Key words: − − − − .Abbreviations: ACG: American College of Gastroenterology; AFAP: attenuated FAP; APC: adenomatous polyposis coli; CDH1: E-cadherin; CHRPE: congenital hypertrophy of the retinal pigment epithelium; CRC: colorectal cancer; FAMMM: Familial atypical multiple mole melanoma; FAP: Familial adenomatous polyposis; GC: gastric cancer; HDGC: Hereditary diffuse gastric cancer; IHC: immunohistochemical; IPAA: ileal pouch–anal anastomosis; IRA: ileorectal anastomosis; MSI: microsatellite instability; MMR: mismatch repair; miRNA: micro RNA.

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DIAGNOSTIC VALUE OF SPECIFIC ANTIBODY SYNTHESIS IN BRAIN OF PATIENTS WITH NEUROINFECTIONS

Wiadomości Lekarskie ◽

10.36740/wlek201908103 ◽

2019 ◽

Vol 72 (8) ◽

pp. 1437-1441

Author(s):

Pavel Dyachenko ◽

Igor Filchakov ◽

Anatoly Dyachenko ◽

Victoria Kurhanskaya

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Clinical Manifestations ◽

Diagnostic Value ◽

Diagnostic Challenge ◽

Specific Antibodies ◽

Intrathecal Synthesis ◽

Varicella Zoster ◽

Mrz Reaction ◽

Wide Range

Introduction: Viral encephalitis accounts for 40-70% of all cases worldwide, central nervous system infections pose a diagnostic challenge because clinical manifestations are not typically pathognomonic for specific pathogens, and a wide range of agents can be causative. The aim: To assess the diagnostic value of intrathecal synthesis of specific antibodies in patients with inflammatory lesions of the central nervous system. Materials and methods: Within the framework of the study, two groups of 90 people in each were formed from the patients with neuroinfections admitted to our Center. Intrathecal synthesis (ITS) of total (unspecific) IgG in members of one of group (group of compare) was determined. Brain synthesis of specific antibodies (Ab) to some neurotropic pathogens (herpes simplex virus 1/2, cytomegalovirus, Epstein-Barr virus, varicella zoster virus, rubella virus, Borrelies) was studied in the second group of patients (group of interest). There were no statistically significant differences between groups by gender and age. Encephalitis and encephalomyelitis prevailed among patients of both groups Results: ITS of total IgG was established in 30 (33.3 ± 6.1 %) patients of the first group with IgG index more than 0.6 indicating on inflammatory process in CNS and no marked changes of CSF. ITS of specific Ab was determined in 23 of 90 (25.6 ± 4.6 %) patients included into group of interest. In more than half of cases Ab to several infectious agents were detected simultaneously. ITS of various specificity, in particular, to measles and rubella viruses, and VZV, known as MRZ-reaction, is characteristic of some autoimmune lesions of CNS, multiple sclerosis first of all. In fact, further research of 5 patients with MRZ-reaction confirmed their autoimmune failure of CNS. Detection of ITS in the CSF samples didn’t depend on concentration of specific Ab in serum and CSF and wasn’t followed by HEB dysfunctions which were observed with the same frequency in patients with or without ITS (13.0 % and 13.6 % respectively). Conclusion: Specific Ab synthesis to several neurotropic pathogens in the CSF of significant part of examined patients was established. Thus, diagnostic value of ITS of specific immunoglobulins seems to be limited to cases in which autoimmune damage of the CNS is suspected.

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X-linked congenital adrenal hypoplasia: a case presentation

BMC Endocrine Disorders ◽

10.1186/s12902-021-00785-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Hong Ouyang ◽

Bo Chen ◽

Na Wu ◽

Ling Li ◽

Runyu Du ◽

...

Keyword(s):

Genetic Testing ◽

Hormone Replacement ◽

Slipped Capital Femoral Epiphysis ◽

Clinical Manifestations ◽

Addison’S Disease ◽

Addison's Disease ◽

Case Presentation ◽

Early Symptoms ◽

Congenital Adrenal Hypoplasia ◽

Adrenal Hypoplasia

Abstract Background Most patients with congenital adrenal hypoplasia (AHC) develop symptoms during infantile and juvenile periods, with varying clinical manifestations. AHC is a disease that is easily misdiagnosed as Addison’s disease or congenital adrenal hyperplasia (CAH). There was also a significant time difference between the age at which patients developed symptoms and the age at which they were diagnosed with AHC. Most patients showed early symptoms during infantile and juvenile periods, but were diagnosed with AHC many years later. Case presentation We are currently reporting a male patient who developed systemic pigmentation at age 2 and was initially diagnosed with Addison’s disease. At 22 years of age, he experienced a slipped capital femoral epiphysis (SCFE), a disease mostly seen in adolescents aged 8–15 years, an important cause of which is endocrine disorder. Testes evaluated using color Doppler Ultrasonography suggested microcalcifications. Further genetic testing and auxiliary examinations revealed that the patient had hypogonadotropic hypogonadism (HH) and DAX-1 gene disorders, at which time he was diagnosed with AHC complicated by HH. He was given hormone replacement therapy, followed by regular outpatient review to adjust the medication. Conclusions The typical early symptoms of AHC are hyperpigmentation and ion disturbance during infantile and juvenile periods, while few patients with AHC develop puberty disorders as early symptoms. AHC is prone to being misdiagnosed as Addison’s disease, and then gradually develops the symptoms of HH in adolescence. The definitive diagnosis of AHC ultimately is based on the patient’s clinical presentation, laboratory results and genetic testing results.

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How accurate are digital symptom assessment apps for suggesting conditions and urgency advice? A clinical vignettes comparison to GPs

BMJ Open ◽

10.1136/bmjopen-2020-040269 ◽

2020 ◽

Vol 10 (12) ◽

pp. e040269

Author(s):

Stephen Gilbert ◽

Alicia Mehl ◽

Adel Baluch ◽

Caoimhe Cawley ◽

Jean Challiner ◽

...

Keyword(s):

Gold Standard ◽

Symptom Assessment ◽

Primary Diagnosis ◽

Safety Performance ◽

Digital Tool ◽

Alphabetical Order ◽

Clinical Vignettes ◽

Gps Buoy ◽

Coverage Accuracy ◽

Young Old

ObjectivesTo compare breadth of condition coverage, accuracy of suggested conditions and appropriateness of urgency advice of eight popular symptom assessment apps.DesignVignettes study.Setting200 primary care vignettes.Intervention/comparatorFor eight apps and seven general practitioners (GPs): breadth of coverage and condition-suggestion and urgency advice accuracy measured against the vignettes’ gold-standard.Primary outcome measures(1) Proportion of conditions ‘covered’ by an app, that is, not excluded because the user was too young/old or pregnant, or not modelled; (2) proportion of vignettes with the correct primary diagnosis among the top 3 conditions suggested; (3) proportion of ‘safe’ urgency advice (ie, at gold standard level, more conservative, or no more than one level less conservative).ResultsCondition-suggestion coverage was highly variable, with some apps not offering a suggestion for many users: in alphabetical order, Ada: 99.0%; Babylon: 51.5%; Buoy: 88.5%; K Health: 74.5%; Mediktor: 80.5%; Symptomate: 61.5%; Your.MD: 64.5%; WebMD: 93.0%. Top-3 suggestion accuracy was GPs (average): 82.1%±5.2%; Ada: 70.5%; Babylon: 32.0%; Buoy: 43.0%; K Health: 36.0%; Mediktor: 36.0%; Symptomate: 27.5%; WebMD: 35.5%; Your.MD: 23.5%. Some apps excluded certain user demographics or conditions and their performance was generally greater with the exclusion of corresponding vignettes. For safe urgency advice, tested GPs had an average of 97.0%±2.5%. For the vignettes with advice provided, only three apps had safety performance within 1 SD of the GPs—Ada: 97.0%; Babylon: 95.1%; Symptomate: 97.8%. One app had a safety performance within 2 SDs of GPs—Your.MD: 92.6%. Three apps had a safety performance outside 2 SDs of GPs—Buoy: 80.0% (p<0.001); K Health: 81.3% (p<0.001); Mediktor: 87.3% (p=1.3×10-3).ConclusionsThe utility of digital symptom assessment apps relies on coverage, accuracy and safety. While no digital tool outperformed GPs, some came close, and the nature of iterative improvements to software offers scalable improvements to care.

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Abnormal interhemispheric functional connectivity in patients with strabismic amblyopia: a resting-state fMRI study using voxel-mirrored homotopic connectivity

BMC Ophthalmology ◽

10.1186/s12886-021-02015-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Shuang Zhang ◽

Gui-Ping Gao ◽

Wen-Qing Shi ◽

Biao Li ◽

Qi Lin ◽

...

Keyword(s):

Functional Connectivity ◽

Receiver Operating Characteristic ◽

Operating Characteristic ◽

Brain Activity ◽

Characteristic Curve ◽

Clinical Manifestations ◽

Resting State Fmri ◽

Diagnostic Value ◽

Functional Connections ◽

Receiver Operating

Abstract Background Previous studies have demonstrated that strabismus amblyopia can result in markedly brain function alterations. However, the differences in spontaneous brain activities of strabismus amblyopia (SA) patients still remain unclear. Therefore, the current study intended to employthe voxel-mirrored homotopic connectivity (VMHC) method to investigate the intrinsic brain activity changes in SA patients. Purpose To investigate the changes in cerebral hemispheric functional connections in patients with SA and their relationship with clinical manifestations using the VMHC method. Material and methods In the present study, a total of 17 patients with SA (eight males and nine females) and 17 age- and weight-matched healthy control (HC) groups were enrolled. Based on the VMHC method, all subjects were examined by functional magnetic resonance imaging. The functional interaction between cerebral hemispheres was directly evaluated. The Pearson’s correlation test was used to analyze the clinical features of patients with SA. In addition, their mean VMHC signal values and the receiver operating characteristic curve were used to distinguish patients with SA and HC groups. Results Compared with HC group, patients with SA had higher VMHC values in bilateral cingulum ant, caudate, hippocampus, and cerebellum crus 1. Moreover, the VMHC values of some regions were positively correlated with some clinical manifestations. In addition, receiver operating characteristic curves presented higher diagnostic value in these areas. Conclusion SA subjects showed abnormal brain interhemispheric functional connectivity in visual pathways, which might give some instructive information for understanding the neurological mechanisms of SA patients.

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Clinical and pathogenetic features of intestinal lesions in patients with type 2 diabetes mellitus

Modern Gastroenterology ◽

10.30978/mg-2021-5-30 ◽

2021 ◽

Author(s):

Y. Z. Dynia

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Growth Factor ◽

Proinflammatory Cytokines ◽

Transforming Growth Factor ◽

Clinical Manifestations ◽

Intestinal Damage ◽

Hydrogen Breath Test

Objective — to study the incidence and clinical and pathogenetic features of intestinal injury in patients with type 2 diabetes mellitus. Materials and methods. Examinations involved 138 patients with type 2 diabetes mellitus (DM 2), aged from 39 to 67 years (mean age 53 ± 5 years), including 82 women (59 %) and 56 men (41 %). In addition to general clinical methods, investigations included plasma levels of the transforming growth factor‑b1 (TGF‑b1) and vascular endothelial growth factor (VEGF), the hydrogen breath test with lactulose, endoscopic examination of the intestine with biopsy followed by staining with hematoxylin‑eosin, immunohistochemical determining of claudin‑1 and VEGF, and conduction of PAS‑reaction. Results. Diabetic enterocolopathy (DECP) was diagnosed in 72 (52.2 %) patients with DM 2. Clinical manifestations were nonspecific and similar to those of irritable bowel syndrome (IBS). It has been found that DECP correlates with the duration of the DM 2 course and was diagnosed more often in middle‑aged patients (52.1 ± 4.1 years). In patients with DECP, the increase in the proinflammatory cytokines TGF‑b1 and VEGF significantly exceeded those in IBS patients. Histologically the inflammatory cell infiltration in patients with DECP was more intense and diverse, there were signs of subatrophy of the glands with a relative decrease in the number of vacuoles in the goblet cells. The immunohistochemical study revealed that VEGF in the colon mucosa was visualized mainly in patients with DECP. Moreover, a tendency to a decrease in the claudin‑1 levels was established in these patients. Conclusions. Intestinal damage was revealed in 67.4 % of patients with type 2 diabetes mellitus, and DECP was diagnosed in more than half of patients. Diabetic enterocolopathy had nonspecific clinical symptoms, required differential diagnosis with IBS, and was not always accompanied with abdominal pain. The presence of DECP more often correlated with the bacterial overgrowth syndrome, and levels of proinflammatory cytokines in the blood plasma and intestinal mucosa of these patients was raised.

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False diagnosis of and needless therapy for presumed gestational trophoblastic disease in women with an unusual site of residual pregnancy

Journal of International Medical Research ◽

10.1177/0300060518807600 ◽

2018 ◽

Vol 47 (2) ◽

pp. 673-681 ◽

Cited By ~ 1

Author(s):

Tong Gao ◽

Mingming Sun ◽

Liangqing Yao ◽

Wei Jiang

Keyword(s):

Clinical Manifestations ◽

Diagnostic Value ◽

Gestational Trophoblastic Disease ◽

High Serum ◽

Resonance Imaging ◽

Unusual Site ◽

Pelvic Mri ◽

Trophoblastic Disease ◽

False Diagnosis ◽

Magnetic Resonance Imaging Mri

Objective This study aimed to determine the diagnostic value of magnetic resonance imaging (MRI), hysteroscopy, and laparoscopy to avoid unnecessary treatment when patients present with clinical manifestations that are close to those of gestational trophoblastic neoplasia (GTN). Methods Three patients who were falsely diagnosed with presumed GTN and received needless chemotherapy in our hospital from July 2011 to March 2012 were studied. We also reviewed data of patients with similar clinical features who were diagnosed as having residual pregnancy in recent years. Clinical manifestations were evaluated. Results All three patients had persistently high serum β-human chorionic gonadotrophin levels and a mass with abundant blood supply in the uterus after termination of pregnancy. The patients were diagnosed with GTN and underwent chemotherapy. They responded poorly to chemotherapy and underwent surgery. The pathological diagnosis in all patients was residual pregnancy. In recent years, no patients were misdiagnosed because pelvic MRI, hysteroscopy, or laparoscopy was used when residual pregnancy could not be excluded. Conclusion Gynecologists should diagnose carefully when patients present with clinical manifestations that are close to those of GTN to avoid unnecessary treatment. MRI, hysteroscopy, and laparoscopy could be important examinations for excluding residual pregnancy.

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Association between Endoscopic Findings Vs. Serology Findings of Patients with Suspected Celiac Disease

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i56a33915 ◽

2021 ◽

pp. 301-307

Author(s):

Anwar Hussain Abbasi ◽

Khawaja Ishfaq Ahmed ◽

Nadeem Yousuf ◽

Mahjabeen Fatima Qureshi ◽

Muhammad Shahzeb Shaikh ◽

...

Keyword(s):

Celiac Disease ◽

Chronic Diarrhea ◽

Villous Atrophy ◽

Clinical Manifestations ◽

Final Analysis ◽

Normal Mucosa ◽

Diagnostic Value ◽

Endoscopic Evaluation ◽

Drug Induced ◽

Endoscopic Findings

Objective: To determine the association between endoscopic findings vs. serology findings of patients with suspected celiac disease Methods: All the suspected cases (based on their clinical manifestations) of celiac disease were initially recruited having age >14 years and <40 years of both gender. Patients who did not willing to participate, patients already taking gluten diet for more than 3 months, patients with other causes of chronic diarrhea and alternate diagnosis like thyrotoxicosis, whipple’s disease, giardiasis, patients with drug induced diarrhea, patients in whom we cannot perform endoscopy, pregnant women, and patients already diagnosed cases of celiac disease were excluded from this study. Celiac disease was confirmed based on positive anti-tTG antibodies. Endoscopic evaluation of duodenum was performed in all positive cases. Results: A total of 50 patients were recruited for final analysis. Diagnostic accuracy of endoscopy was 34.6%. Young population (31.14±6.07 years) with females predominance (72%, n=36) were more common than males. The most common symptoms were presence of chronic diarrhea (74%, n=37) followed by abdominal pain (52%, n=26), nausea & vomiting (34%, n=17), and least common was presence of constipation (2%, n=1). On endoscopic evaluation, out of 50 positive anti-tTG antibodies cases, 24 had normal mucosa while partial villous atrophy observed in 15 (30%) cases and total villous atrophy observed in 11 cases (22%). Conclusions: Celiac disease was more prevalent in young females and patients usually presents with history of chronic diarrhea. Anti-tTG antibodies have more diagnostic value than duodenal endoscopy. Villous atrophy was found in more than 50% of the patients who were diagnosed with celiac disease.

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Early diagnosis of a newborn with tuberous sclerosis caused by a genetic mutation

Journal of International Medical Research ◽

10.1177/03000605211035895 ◽

2021 ◽

Vol 49 (8) ◽

pp. 030006052110358

Author(s):

Lin Qiao ◽

Yuting Yang ◽

Dongmei Yue

Keyword(s):

Genetic Testing ◽

Early Diagnosis ◽

Tuberous Sclerosis ◽

De Novo ◽

Clinical Manifestations ◽

De Novo Mutation ◽

Heterozygous Mutation ◽

Loss Of Function ◽

Autosomal Dominant Disorder ◽

Tsc1 Gene

Objective Tuberous sclerosis (TSC) is an autosomal dominant disorder, often detected during childhood. We present the results of genetic testing in a newborn with suspected TSC. Methods A newborn with no specific clinical manifestations of TSC showed evidence of TSC on magnetic resonance imaging and echocardiography. Next-generation sequencing (NGS) and multiple ligation-dependent probe amplification (MLPA) of the TSC1 and TSC2 gene exons were carried out to confirm the diagnosis. Results The results of MLPA were negative, but NGS showed a heterozygous mutation in the TSC1 gene comprising insertion of a T residue at c.2165 (exon 17) to c.2166 (exon 17), indicating a loss of function mutation. These results were verified by Sanger sequencing. This genetic change was present in the newborn but the parental genotypes were wild-type, indicating a de novo mutation. Conclusions In this case, a case of TSC caused by a heterozygous mutation in the TSC1 gene was confirmed by NGS sequencing. This indicates the suitability of genetic testing for the early diagnosis of clinically rare and difficult-to-diagnose diseases, to guide clinical treatment.

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PATHOGENETIC JUSTIFICATION OF NEW APPROACHES TO THE ASSESSMENT OF THE STATE OF ORAL CAVITY IN CHRONIC GENERALIZED PARODONTITIS

The actual problems in dentistry ◽

10.18481/2077-7566-2018-14-4-14-18 ◽

2018 ◽

Vol 14 (4) ◽

pp. 14-18 ◽

Cited By ~ 4

Author(s):

Владимир Базарный ◽

Vladimir Bazarnyy ◽

Лариса Полушина ◽

Larisa Polushina ◽

Арина Максимова ◽

...

Keyword(s):

Temporomandibular Joint ◽

Clinical Manifestations ◽

Diagnostic Value ◽

Diagnostic Methods ◽

Cochrane Library ◽

Russian State ◽

State Library ◽

The Cochrane Library ◽

Diagnostic Capabilities ◽

Diagnostic Technologies

Introduction. A variety of concepts and approaches to the analysis of the etiology and pathogenesis of temporomandibular joint dysfunctions, results in increased interest in the search for highly informative diagnostic methods, especially at the stage of pre-clinical manifestations. Objectives. The aim of the study was to analyze the possibilities of modern technologies in diagnostics of temporomandibular joint dysfunctions. Materials and methods. We studied original papers on the diagnostics of temporomandibular joint dysfunctions from several databases: Russian State Library, eLibrary, PubMed, The Cochrane Library, Google Scholar. Results. The review presents both generally accepted and alternative approaches to the diagnostics of different clinical manifestations in temporomandibular joint dysfunctions. We described the diagnostic value of occlusal disorders analysis in universal articulators, virtual articulators, T-scan system. Capabilities of teleroentgenography, axiography, electromyography, computed and magnetic resonance imaging were estimated as well. Conclusions. The literature review on the problem of diagnosing the temporomandibular joint dysfunctions showed a scientifically based spectrum of diagnostic capabilities of modern dentistry, a trend in the development of highly informative digital diagnostic technologies. Due to the diversity of the etiology and pathogenesis of the temporomandibular joint dysfunctions further in-depth studies of this issue are required.

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