Azithromycin and moxifloxacin resistance determinants in Mycoplasma genitalium in Lleida, Spain.

OBJECTIVE: Mycoplasma genitalium (MG) is a microorganism related to sexually transmitted infections. Antibiotic resistance of MG leads to an increase in treatment failure rates and the persistence of the infection. The aim of this study was to describe the most frequent mutations associated with azithromycin and moxifloxacin resistance in our geographical area. METHODS: A prospective study from May 2019 to May 2023 was performed. MG-positive samples were collected. Real-time PCRs (AllplexTM MG-AziR Assay and AllplexTM MG-MoxiR Assay, Seegene) were performed in MG positive samples to detect mutations in 23S rRNA V domain and parC gene. RESULTS: A 37.1% of samples presented resistance determinants to azithromycin and the most common mutation detected was A2059G (57.9%). Resistance to moxifloxacin was studied in 72 azithromycin-resistant samples and 36.1% showed mutations, being G248T the most prevalent (73.1%). CONCLUSIONS: The resistance to different lines of treat ment suggests the need for a targeted therapy and the performing of a test of cure afterwards.

Role of creatine phosphokinase as a diagnostic marker in tubal ectopic pregnancy.

Background and Aim: Ectopic pregnancy (EP) is still one of the leading preventable causes of maternal morbidity and mortality in the first trimester. Amidst the use of sensitive assays for ß-HCG and high-definition ultrasonography for the identification of EP, the search for a more reliable and sensitive marker remains a challenge till date. Our aim was to determine the validity of creatine phosphokinase (CPK) and its isoenzyme (CPK-MB) in the prediction of tubal EP. Materials and Methods: A prospective and comparative diagnostic accuracy study was conducted among 105 pregnant women in the first trimester who met the eligibility criteria in the Department of Obstetrics and Gynecology, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences (NEIGRIHMS). The study included 35 patients each with tubal EP (EP), abortive intrauterine pregnancy (AP), and normal intrauterine pregnancy (NP). CPK, CPK-MB, and ß-HCG were measured among all the participants, and the participants were followed up longitudinally. Results: A total of 105 pregnant women were included. The mean CPK and CPK-MB levels were significantly higher among the women with EP when compared to NP (P < 0.05) and AP (P < 0.05) women; however, there was no significant difference between the NP and AP groups (P > 0.05). Moreover, the receiver operating characteristic (ROC) curve showed that both CPK and CPK-MB were good predictors of EP, with CPK (area under the curve [AUC] = 0.764) being a better predictor than CPK-MB (AUC: 0.650) in the diagnosis of EP. Conclusion: Early diagnosis of EP allows appropriate and timely management, which would not only reduce mortality and morbidity associated with the condition but also enable preservation of fertility and improve future pregnancy outcome. Hence, the need of the hour is a reliable biochemical diagnostic marker for EP, such as CPK.

Comparison of the efficacy of intravenous labetalol versus oral nifedipine in patients with severe pregnancy-induced hypertension beyond 30 weeks of gestation.

Hypertensive disorders of pregnancy affect 5% to 10% of all pregnancies globally. The aim of treatment is to bring down blood pressure (BP) quickly and smoothly, which is safe for the mother and baby. The aim of our study was to study the efficacy and safety of intravenous labetalol and oral nifedipine in severe pregnancy-induced hypertension. Materials and Methods: It is a retrospective observational study, intravenous labetalol 20 mg was given initially in escalating doses of 40 mg, 80 mg, 80 mg, and 80 mg every 15 mins up to a maximum dose of 5 or until the goal BP ≤150/100 mmHg was reached. Some women with severe pregnancy-induced hypertension were given oral nifedipine to control their BP according to the choice of the attending consultant. Nifedipine 10 mg tablet was given initially in repeated doses of 10 mg every 15 mins up to a maximum of five doses or until the goal of BP ≤150/100 mmHg was reached. Results: In our study, we found that there was a strong statistical significance in stabilizing the BP with oral nifedipine than with intravenous labetalol drug used. The majority of the patients in the oral nifedipine group got to normal BP quicker when compared to intravenous labetalol group patients. Conclusion: From this study, both drugs were found to be safe and effective in the reduction in BP. The use of nifedipine may be recommended in low-resource settings since it has an oral regimen and dosage is simple when compared to incremental intravenous dosing of labetalol.

Frequency of Nucleophosmin 1 Expression by Immunohistochemistry in Acute Myeloid Leukemia.

Nucleophosmin (NPM1) mutation is one of the most common recurring genetic abnormalities seen in acute myeloid leukemia (AML). Immunohistochemistry serves as a cost effective and simple surrogate testing method for detection of NPM1 mutation. This study was conducted to evaluate the frequency of aberrant cytoplasmic nucleophosmin 1 expression in leukemic blast cells on formalin fixed bone marrow trephine biopsy (BMB) sections and also to correlate this data with the reference molecular method (reverse transcriptase-polymerase chain reaction; RT-PCR and gene sequencing), where available. Immunostains were performed using mouse anti-NPM1 monoclonal antibody on 71 paraffin embedded bone marrow biopsies (BMB) of patients with AML of any French-American-British (FAB) subtype. Results of immunohistochemistry (IHC) were then compared with the reference molecular method. The proportion of NPM1 expression by immunostaining in AML cases was found to be 17%. Twelve of the total 71 cases demonstrated cytoplasmic nucleophosmin (NPMc+) on immunostaining. Eleven of the positive cases that were correlated with the molecular standard demonstrated mutation in exon 12 of NPM1 gene. Cytoplasmic nucleophosmin expression by immunostaining was found to be in complete agreement with the standard molecular method. In a resource restricted setup, the information from this study might help in providing an inexpensive and accurate detection method to facilitate introduction of this marker in diagnostic and prognostic workup of AML especially in patients showing normal karyotype and no common recurrent translocations.

Plasmablastic Lymphoma: A Clinicopathological Study from a Tertiary Care Cancer Center in South India.

Background Plasmablastic lymphoma (PBL) is a rare aggressive B cell lymphoma that is commonly encountered in patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). In this case series, we describe the clinicopathological features of cases of PBL seen at a tertiary care center in South India. Materials and Methods Medical records of patients diagnosed with PBL between January 2009 and November 2017 were reviewed. PBL was defined as per the World Health Organization 2016 classification for hematopoietic and lymphoid neoplasms. The slides were reviewed with hematoxylin and eosin along with immunohistochemistry (IHC) including CD45, CD20, PAX5, CD79a, CD3, CD5, CD138, MUMI, EMA, ALK, and Ki67. Epstein-Barr virus (EBV) association was documented by rapid in situ hybridization (RISH) studies wherever possible. The demographic data, clinical presentation, treatment details, and outcomes are elaborated using descriptive statistics. Results During the study period, nine patients with PBL were identified. The median age at presentation was 47 years (range: 36-54 years). All patients had associated HIV/AIDS, eight (89%) had extranodal disease, and six (66%) had advanced clinical stage (stage III). All biopsies were positive for CD45, CD138, and MUM1, and negative for CD79a and T cell markers with a high Ki67 proliferation index (85-90%); CD20 was faint positive in one patient, and CD56 was positive in one (11%) patient. EBV-RISH was tested in two patients and was positive in one. Bone marrow was uninvolved in all the cases. At the time of last follow-up, three patients were alive. Treatment details were available in six patients. With frontline therapy, four patients achieved a complete remission (CR) and one patient developed progressive disease. Three of four patients in CR are alive till the last follow-up. Conclusion PBL is a rare form of lymphoma with predominant association with HIV, extranodal location, and characteristic IHC pattern.

Acute Myeloid Leukaemia with Gene Mutation: A Correlation with Haematological and Immunophenotypic Characteristics and Our Experience in a Tertiary Care Cancer Center in South India.

OBJECTIVE: Molecular genetic analysis of FLT3, NPM1, and CEBPA is already the standard of care in patients with acute myeloid leukaemia (AML) and represents the most frequent genetic alterations and important diagnostic and prognostic indicators. This study was undertaken to determine the frequency of FLT3 and NPM1 gene mutations in our institution and to characterize the association between gene mutations and haematological parameters as well as immunophenotypic features. MATERIAL AND METHOD: Morphological, haematological and immunophenotypic characteristics of NPM1 and FLT3 mutations in 126 patients of de novo AML including adults and children were studied. Apart from the French American British (FAB) method for classification, blasts were assessed for cuplike morphology as per strict definition for cuplike nuclei, ≥10% blasts with nuclear invaginations ≥25% of the nuclear area. RESULTS: FLT3 mutation in 31/126 (25%) and NPM1 mutation was found in 17/126 (13.4%) of the AML patients. 6 (5%) samples were positive for both NPM1 and FLT3/ITD mutations. Associations between the FLT3 and NPM1 gene mutations with haematological and immunophenotypic characteristics are reported. CONCLUSION: The results suggest that presence of distinct morphology and haematological and immunophenotypic characteristics together may serve as important indicators and surrogate for NPM1 and FLT3/ITD mutations. Further, comprehensive studies on the biological effects of NPM1 and FLT3/ITD mutations and their interactions with other genetic alterations are needed to gain insight into the molecular mechanism of these mutations involved in the pathogenesis of AML.

Multiplex Approach in Classification, Diagnosis, and Prognostication in Acute Myeloid Leukemia: An Experience from Tertiary Cancer Center in South India.

INTRODUCTION: Acute myeloid leukemia (AML) is a heterogeneous group of disorders classified as per FAB subtypes and more recently by WHO by underlying genetic abnormalities. AIMS AND OBJECTIVES: This study aims to analyze the morphology, immunophenotype, cytogenetic and molecular abnormalities in around 200 patients of AML diagnosed over a period of 7 years at our institute and to determine relative frequency of various subtypes (based on FAB and WHO classification). An attempt to characterize the associations between hematological parameters, immunophenotype and these subtypes was also made. MATERIALS AND METHODS: All cases diagnosed as AML on morphology, cytochemistry and/or immunophenotyping and tested for recurrent genetic abnormalities during period of Jan 2008-July 2014 were included in the study. RESULTS: Age of presentation was younger in our AML patients as compared to western literature. Amongst FAB and WHO subtypes, M2 and t (15;17) PML-RARA were the most common groups respectively. As expected, CD33, CD13, were the most commonly expressed markers followed by HLA-DR, CD117, CD34 and CD14. Aberrant expression was seen in 62(41.6%) cases, most common was CD7 (15.4%), followed by CD56 (14.8%), CD19 (6.7%) and CD2 (4.7%). Significant associations between immunophenotypic markers and FAB subtypes as well as WHO subtypes were established. CONCLUSION: This is a hospital based study, giving a detailed account of frequencies of AML subtypes, hematological parameters and immunophenotypic markers in AML patients at our institute. Being a large and one of its kind study to establish significant associations between various haematological and immunophenotypic parameters with respective AML subtypes and genetic abnormalities, it might prove to be very useful in Indian setup where facilities for cytogenetic analysis are not available in many laboratories.

Clinical profile and outcomes of patients with Stage IV adenocarcinoma of lung: A tertiary cancer center experience.

BACKGROUND: There is limited Indian data on clinical profile and treatment outcomes for patients with Stage IV adenocarcinoma of lung. AIM: We aimed to prospectively study the clinical profile and treatment outcomes for patients with Stage IV adenocarcinoma of lung at a tertiary cancer center. MATERIALS AND METHODS: One hundred and ninetyfour patients with Stage IV adenocarcinoma of lung were prospectively analyzed for demographic and molecular profile (epidermal growth factor receptor [EGFR] and echinodermal microtubuleassociated proteinlike 4anaplastic lymphoma kinase [EML4ALK] mutations). Patients with EGFR and EML4ALK mutations were treated with tyrosine kinase inhibitors. Patients without these mutations were treated with standard chemotherapy regimens. Maintenance chemotherapy was offered to patients as per standard guidelines. Clinical outcomes measured were response rate (RR), progressionfree survival (PFS), and overall survival (OS). RESULTS: Median age of patients was 56 years (range, 26-82) with a male:female ratio of 2.3:1. EGFR and ALK mutation testing was feasible in 169 (87.1%) and 164 (84.5%), respectively, and detected in 37.9% and 5.5% patients, respectively. Overall RR, PFS and OS of whole cohort were 44.3%, 6.9, and 15.5 months, respectively. PFS and OS of mutated group (EGFR, EML4ALK) were longer than nonmutated group (10.5 vs. 5.4 months, P < 0.0001 and 21.5 vs. 11 months, P = 0.0001, respectively). PFS and OS of patients who received pemetrexed maintenance were longer than those who did not receive maintenance (8.5 vs. 6.5 months, P = 0.1613 and 18.5 vs. 12.5 months, P = 0.0219, respectively). CONCLUSIONS: Mutation testing at diagnosis is feasible in the vast majority of patients with Stage IV adenocarcinoma of the lung. Patients with EGFR or EML4ALK mutation and those who received pemetrexed maintenance had better clinical outcomes.

Ewing's Sarcoma of the Calcaneum.

Ewing's sarcoma of the calcaneum is rare. Radiological features of this tumor can be misinterpreted as other benign bone tumors due to its rarity. The overall prognosis of Ewing's sarcoma of calcaneum is inferior compared to other sites of this tumor. Hence, these tumors should have extensive radiological evaluation and histological confirmation as misdiagnosis and treatment delays will have detrimental outcomes.

Guillain-Barré syndrome complicating pregnancy and correlation with maternal and fetal outcome in North Eastern India: A retrospective study.

BACKGROUND: Guillain-Barré syndrome (GBS) is rare in pregnancy with an estimated incidence between 1.2 and 1.9 cases per 100,000 people annually, and it is generally accepted that it carries a high maternal risk. Most reports of GBS with pregnancy are case reports only. AIM: Purpose of this retrospective study was to find the correlation between pregnancy and GBS. SETTINGS AND DESIGN: Records of patients admitted in neurology division were analyzed in a tertiary care teaching hospital in the northeastern Indian pregnant female population with GBS between 15-49 years during the period of 2009-2013. MATERIALS AND METHODS: We analyzed the records of 47 patients with pregnancy and GBS, evaluated and treated in our institute from August 2009 to December 2013. This is retrospective observational study done in North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences (NEIGRIHMS), India. RESULT: Predominant form of GBS was acute inflammatory demyelinating polyneuropathy (AIDP). The weakness started from the lower limbs in majority of patients. Ten percent of women had bifacial weakness. Most of patients had good maternal and fetal outcome. Two patients received intravenous immunoglobulin (IVIG). Only two patient required ventilator supports and one patient had intrauterine death (IUD) and died due to respiratory failure. CONCLUSION: Our results indicate that risk of GBS increases in third trimester and first 2 weeks after delivery. Demyelinating variety of GBS was common in our population. GBS natural course during pregnancy is mild and showed quick recovery. Maternal and perinatal outcome was good.

[The transpleurodiaphragmatic laparoscopic approach of rear dome liver cysts]. / Abordul laparoscopic transpleurodiafragmatic al chistelor hepatice de dom posterior.

The localizations of liver cysts in the posterior hepatic dome (segment VII) and the hydatid cysts in particular, difficult to approach in "conventional" open or laparoscopic surgery, with significant parietal sacrifices and "demolition", requires a secure atypical laparoscopic approaching way, with positive results for both patient and surgeon, with minimal impact, with social and professional reintegration and faster healing. Transpleurodiaphragmatic laparoscopic approach using "Device for aspiration of liver hydatid cyst or ovarian cyst (OSIM 120809/30.04.2008 Patent - Dan Sabau) asociated with the remarcable performances of the fragmentation device for hydatid cyst content (OSIM Patent no. 120810/30.04.2008 - Dan Sabau) is the best way to approach these problems, accessible for surgeons with minimum experience in laparoscopic and thoracic surgery. The relatively low number of cases allows only formulation of preliminary positive conclusions on the method, they will be validated by subsequent results.

Hyperprolactinemia with normal serum prolactin: Its clinical significance.

Amenorrhea and infertility with an added feature of galactorrhea makes a provisional diagnosis of hyperprolactinemia. But again, normal serum prolactin with all clinical features of hyperprolactinemia might question the diagnosis and further management. The answer lies in the heterogeneity of the peptide hormone - the immunoactive and the bioactive forms. This has been further illustrated with the help of a case which had been treated with cabergoline.

Altered distribution of the debrisoquine oxidative phenotypes in children with type 1 diabetes mellitus.

OBJECTIVE: The recently observed increase in the incidence of type 1 diabetes mellitus (Type 1 DM) suggests a major role of environmental factors in the etiopathogenesis of the disease. The individual variation in cytochrome P(450)IID6 may influence the individual susceptibility to environmentally linked diseases. We aimed to evaluate the prevalence of cytochrome P(450)IID6 phenotypes in Hungarian children with Type 1 DM (n = 69) compared to healthy controls (n = 100). METHODS: Debrisoquine was administered orally and debrisoquine hydroxylation phenotype was determined as a metabolic ratio of urinary recovered debrisoquine and 4-hydroxydebrisoquine. RESULTS: Eight of the 100 healthy subjects (8%) and 15 of the 69 diabetic children (22%) (p < 0.05) had cytochrome P(450)IID6 poor metabolizer phenotype (metabolic ratio > or =12.6). CONCLUSION: Cytochrome P(450)IID6's activity may play a role in the development of Type 1 DM.

Formulation of diazepam containing rectal suppositories and experiences of their biopharmaceutical study.

Methodology and the results of the in vitro membrane diffusion and in vivo bioavailability studies are presented. The results confirm a correlation between in vitro and in vivo findings. Hydrophilic macrogol-mixture with great molecular mass can be recommended as the optimal vehicle for formulation of diazepam suppositories.

[Formulation of diazepam suppositories, results of rheological and biopharmaceutical studies. 2. In vitro membrane diffusion and in vivo absorption results]. / Diazepám-tartalmú végbélkúpok formulálása, reológiai és biofarmáciai vizsgálatának tapasztalatai. 2. In vitro membrándiffúziós és in vivo felszívódási eredmények.

In the first part of the publication the rheological properties of the vehicles used for the production of suppositories were studied in order to determine the ideal parameters for formulation. In this part a detailed methodology and the results of the in vitro membrane diffusion and in vivo bioavailability studies, are presented. The results confirm a general correlation between the in vitro and the in vivo findings. It seems that hydrophilic macrogol-mixture with great molecular mass can be recommended as the optimal vehicle for formulation of diazepam suppositories.

Distribution of calcitonin gene-related peptide immunoreactivity in the central nervous system of the frog, Rana esculenta.

The distribution of calcitonin gene-related peptide (CGRP), immunoreactive structures in the central nervous system of the frog, Rana esculenta, was studied using the peroxidase immunohistochemical method. Immunoreactive perikarya were found in all major parts of the brain. In the forebrain, neurons of the septohippocampal formation, the amygdala, the ventromedial and posterocentral thalamic nuclei, and the cerebrospinal fluid contacting neurons in the diencephalic periventricular organ showed immunoreactivity. The pear-shaped neurons of the optic tectum, and perikarya of the oculomotor nucleus in the midbrain were also immunoreactive. In the hindbrain, neurons of the cranial nerve motor nuclei, neurons of the superior vestibular nucleus, giant cells of the reticular formation, and preganglionic parasympathetic neurons of the superior salivatory nucleus were stained. Motoneurons presented immunostaining also in the spinal cord. Immunoreactive fibers were shown to occur in the olfactory tract, the striatum, the tegmentum and the basis mesencephali, the descending tract of the trigeminal nerve, the solitary tract, Lissauer's tract, and the dorsal horn of spinal cord. A comparison of the distribution of CGRP immunoreactivity in the mammalian and amphibian central nervous system revealed that, in relation to the size of the brain, CGRP is more extensively distributed in the amphibian than in the mammalian limbic system.

Association of microalbuminuria with slow acetylator phenotype in type 1 diabetes mellitus.

The genetically determined acetylator phenotype in diabetic children with and without increased urinary albumin excretion was investigated. Acetylator phenotype was determined according to Evans, and 24-hour albumin excretion rate (AER) was measured by immunoturbidometry in 86 children and adolescents with type 1 (insulin-dependent) diabetes mellitus and in 100 age-matched healthy controls. In diabetics, the fast acetylator phenotype was found in 36 (41.9%) patients and the slow one in 50 (58.1%); the control group had 52 (52%) fast and 48 (48%) slow acetylators. There were no significant differences in acetylator phenotypes between diabetic patients and control subjects (chi 2 = 1.0, NS). Among patients with normal albumin excretion (n = 70, mean age: 12.9 +/- 3.5 years, mean diabetes duration: 5.3 +/- 3.8 years, AER < 20 micrograms/min), 35 (50%) fast acetylators and 35 (50%) slow acetylators were found. In patients with elevated albumin excretion (n = 16, mean age: 14.0 +/- 3.2 years, mean diabetes duration: 4.9 +/- 3.0 years, AER > 20 micrograms/min), 1 (6.3%) patient was a fast acetylator and 15 (93.7%) were slow acetylators. A significant difference has been found between the two groups in the rate of fast/slow acetylators (chi 2 = 8.79, p < 0.01). The strong correlation between the slow acetylator phenotype and microalbuminuria in diabetics suggests that: (a) genetic factors may play a role in the development of diabetic nephropathy; (b) the acetylator status could be a useful tool to detect patients 'at risk' of nephropathy.

Pharmacogenetically hazardous drugs: a proposed new scoring method.

Similar doses of a drug given to different individuals can result in widely disparate plasma concentrations and hence effects. Beside intraindividual differences also inter-ethnic differences of drug response must be taken into consideration. Both inter-individual and inter-ethnic variations of drug response are mostly related to genetic factors (polymorphism) involved in drug metabolism and kinetics. The farmacogenetic disorders involved clinically result in pharmacogenetic side effects. In order to avoid pharmacogenetic side effects, beside phenotyping of the patients, selection of drugs subjected to different pharmacogenetic disorders may be of great clinical importance. Therefore, a scoring method was carried out for the selection of pharmacogenetically hazardous drugs. With regard to both genetic and environmental factors influencing the drug response, 140 suspicious drugs were studied and classified with the method. Eighteen was the maximum point value for genetic and 12 for contributing factors involved, so 30 was the maximum point number in each drug studied. Out of 140 substances 50 drugs (qualified with 20 points or more) proved to be hazardous in different pharmacogenetic disorders, among them several widely used agents, e.g. Diazepam, Isoniazid, Phenytoin, Warfarin, Quinidine, Tolbutamide, etc. The article sums up the findings in a Table and comments them. This scoring method may be useful in drug safety and preventive medicine.

Peroxide haemolysis of erythrocytes in children with diabetes mellitus.

Peroxide haemolysis of erythrocytes in children with diabetes mellitus was discussed. The peroxide haemolysis tests of erythrocytes of 32 healthy and 35 diabetic children were compared. The erythrocytes of diabetics were hemolyzed to a small extent when 2% H2O2 was used. If 5 and 10 mmol/l glucose were added, the peroxide haemolysis of the controls decreased but that of the diabetics did not change. The results of the examinations performed with pH 6.8 were compared to those of pH 7.4 and both in the diabetics and controls a slight haemolysis was observed.