Durable response to docetaxel in a case of primary seminal vesicle adenocarcinoma with zinner syndrome.

ABSTRACT: Primary adenocarcinoma of the seminal vesicles is a rare tumor. Congenital seminal vesicle cysts are often associated with unilateral renal dysgenesis or agenesis (Zinner syndrome). Zinner syndrome is a rare congenital malformation represented by a group of characteristics: ipsilateral renal agenesis, ejaculatory duct obstruction, and seminal vesicle cyst. There have been 214 cases in the literature with abdominal pain and lower urinary tract symptoms as the most common presentation. Most cases are diagnosed incidentally. We report a case of a 39-year-old male presenting with recurrent hematuria for 12 years, diagnosed as metastatic primary clear cell adenocarcinoma of seminal vesicle with Zinner syndrome. He was managed symptomatically with radiation therapy, hormonal therapy, and palliative chemotherapy. He is living with a well-controlled disease at present.

Association Between Maternal Literacy and Child Immunization According to the Expanded Program on Immunization Schedule in a Primary Health Care Center of a Squatter Settlement in Karachi.

Background An increase in maternal education may influence vaccine administration to a significant extent, therefore reducing the childhood mortality rate. Hence, this survey aims to establish an association between maternal literacy and childhood immunization in children under five years of age. Methods A questionnaire-based cross-sectional study was conducted in a primary healthcare center of a squatter settlement in Karachi, Pakistan. Mothers of 250 children under the age of five years were interviewed. We used IBM SPSS Statistics for Windows, version 20 (released 2011; IBM Corp., Armonk, New York, United States) for data analysis to assess the relationship between maternal education and childhood immunization. Results The survey revealed that complete vaccination coverage among children under five years of age (n=250) was 71.7%, while 24.6% were partially vaccinated and 2% were unvaccinated. The most common reason for unvaccinated children was the parents' personal choice (80%), while incomplete vaccination was majorly due to a medical condition (30.2%).  Conclusion According to the survey, maternal educational qualification did not prove to be directly associated with vaccination coverage in children. However, a multi-centered study with larger sample size and multiple populations as targets would provide more accurate outcomes.

LINC01023 Promotes the Hepatoblastoma Tumorigenesis via miR-378a-5p/WNT3 Axis.

Hepatoblastoma is the most common type of hepatic tumors occurring in children between 0 and 5 years. And the exact pathophysiology of the disease is still mysterious. Accumulating studies on LncRNA have shown its pivotal role in the development and progression of distinct human cancers. However, the role of LINC01023 in hepatoblastoma is unknown. The relative expression of LINC01023, miR-378a-5p, and Wnt3 on hepatoblastoma tissue and cell lines was determined by quantitative polymerase chain reaction (qRT-PCR). The effect of LINC01023 downregulation and upregulation on cell proliferation, colony formation and apoptosis activities in HUH6 and HepG2 Cells was assessed by CKK8, clonogenic and flow cytometry analysis, respectively. Dual luciferase, RNA immunoprecipitation (RIP), and RNA pull-down were performed to confirm the interaction between LINC01023 and miR-378a-5p. Similarly, Dual luciferase assay was performed to confirmed the interaction between Wnt3 and miR-378a-5p. The xenograft tumorgenicity test was performed to elucidate the tumorgenicity potential of LINC01023. LINC01023 was significantly upregulated in hepatoblastoma tissue and cell lines rather than in adjacent normal hepatic tissue and QSG7701 cell lines. LINC01023 silencing attenuated cell proliferation, colony formation and increased cell apoptosis. Conversely, LINC01023 upregulation results in significant increase in cell proliferation, and colony formation activities however, a significant reduction in apoptosis activity was reported. Interaction between the LINC01023 and WNT3 was confirmed by dual luciferase assay. Xenograft animal tumorgenicity test confirmed the in-vivo tumorigenesis potential of LINC01203. To the best of our knowledge, this study is the first study demonstrating the role of LINC01023 in hepatoblastoma tumorigenesis through the LINC01023/miR-378a-5p/Wnt3 axis. It could be a potential therapeutic target and a prognostic biomarker in hepatoblastoma.

Pectolinarigenin Suppresses LPS-Induced Inflammatory Response in Macrophages and Attenuates DSS-Induced Colitis by Modulating the NF-κB/Nrf2 Signaling Pathway.

Pectolinarigenin (PEC), a natural flavonoid present in cirsium chanroenicum and citrus fruits, has possess the distinct pharmacological activities. However, its molecular mechanisms and pharmacological effects on intestinal illness have not been elucidated. In the present study, we investigated the potential beneficial effects of pectolinarigenin (PEC) on lipopolysaccharide (LPS)-induced macrophage cells and the dextran sulfate sodium (DSS)-induced colitis model. Our findings showed that PEC pretreatment inhibits the LPS-induced nuclear factor-kappa B (NF-κB) activation by interfering with the degradation of IκB-α. Further, increased Nrf2 protein expression was reported on PEC treated RAW 264.7 and THP1 cell lines. In addition, we revealed that PEC mediated the NF-κB/Nrf2 pathway regulation, which in turn inhibits the synthesis of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), interleukin-1beta (IL-1ß), and tumor necrosis factor-alpha (TNF-α) on RAW 264.7 and THP1 cells. Furthermore, PEC dose-dependently reduced the DSS-induced inflammation in the colon by regulating NF-κB/Nrf2 signaling pathway and enhancing the myeloperoxidase (MPO) activity and redox regulators such as superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and lipid peroxidation byproduct malondialdehyde (MDA) in DSS-induced inflamed colon. Similarly, we reported the minimal pathological damages in the PEC-treated mice colon, as well as increase goblet cell population and mucin-2 production. In conclusion, our findings demonstrate that PEC reduces the DSS-induced colitis in mice by regulating the NF-κB/Nrf2 pathway. Thus, PEC might be a promising therapeutic agent for the treatment of inflammatory bowel disease.

The clinical course, biochemical markers, and clinical outcomes of COVID-19 positive patients from the third wave in Pakistan: A retrospective cohort study.

Background: Third wave of COVID-19 has affected several countries. Case fatality rates from first and second waves are expected to be surpassed by the current wave due to various variant transmissions. This study was aimed to compare and contrast the significant clinical markers between survivors and non-survivors during the third wave of COVID-19 to assess severity and prognosis. Methods: It includes all the patients who were diagnosed with COVID-19 polymerase chain reaction (PCR) during the third wave, and were monitored for their disease course and outcomes. A total of 209 patients were included in the analysis via non-probability consecutive sampling method. Results: The median age was higher in non-surviving patients (p = 0.010). Majority of deaths occurred in intensive care patients (p < 0.001) and those with diabetes (p = 0.032) and hypertension (p = 0.003). Fever was the most predominant symptom in all patients (78.9%), dyspnea was common among expired individuals (p = 0.043) while recovered patients were more likely to be asymptomatic (p = 0.044). Gastrointestinal symptoms were not found marked during this wave. Being on ventilator has higher mortality (p < 0.001). Predominant radiological findings were interstitial patches or infiltrate (43.7%). Multivariable analysis showed hypertension (p = 0.042), BiPAP/CPAP (p < 0.001), being on ventilator (p = 0.004), and ARDS (p < 0.001) was associated with poor survival while patchy interstitial infiltrates on X-ray had good survival probability (p = 0.032). On Kaplan-Meier survival analysis, hypertension (p = 0.003), BiPAP/CPAP (p = 0.008), ventilator (p = 0.025), ICU stay (p = 0.001), high-grade fever (p = 0.001), and ARDS (p < 0.001) had reduced cumulative survival. Conclusion: Certain biochemical markers were more predictive of disease severity in the third-wave than the preceding waves.

Mutational Analysis of EGFR Mutations in Non-Small Cell Lung Carcinoma-An Indian Perspective of 212 Patients.

Lung cancer is the world's leading cause of cancer-related deaths. Epidermal growth factor receptor (EGFR) is one of the critical oncogenes and plays a significant role in tumor proliferation and metastasis. Patients with sensitizing mutations in the EGFR gene have better clinical outcomes when treated with tyrosine kinase inhibitors (TKI). This study expands our knowledge of the spectrum of EGFR mutations among lung cancer patients in the Indian scenario. This is a retrospective descriptive study of all newly diagnosed patients with lung cancer in tertiary care hospital in India. All the samples were subjected to real-time PCR (q-PCR) analysis and confirmation of rare novel mutations was done using Sanger sequencing. Clinicopathological characteristics, mutational EGFR status, and location on the exon and metastatic sites were evaluated. An analysis of total 212 samples showed mutations in 38.67% of cases. Among these, five (5.9%) samples had mutations in exon 18, 41 (48.8%) samples had mutations in exon 19, 12 (14.28%) samples had mutations in exon 20, and 26 (30.95%) samples had mutations in exon 21. Eleven (13.41%) were found to be uncommon EGFR mutations. Additionally, six (21.4%) samples that had EGFR mutations were also positive for brain metastasis. Future testing on bigger panels will help to characterize the incidence of genetic mutations and to determine the appropriate targeted treatment choices for NSCLC patients.

Paradigm shift from palliation to cure in metastatic microsatellite high colorectal carcinoma with immune checkpoint inhibitors.

Colorectal carcinoma (CRC) is one of the most frequently diagnosed malignancies worldwide with a high mortality rate. CRC is often plagued with significant treatment-related morbidity and mortality, and metastatic progression is common. With the advent of immunotherapy, inoperable and advanced cancers have shown favorable response. Immunotherapy has paved the way for survival of all those with advanced metastatic disease whose treatment was limited to palliative care. We explore the case of a 28-year-old female with advanced metastatic CRC refractory to chemotherapy and targeted therapy, managed with PD-1 inhibitor with complete clinical and pathological response in a relatively short period of time. The notion of upfront immunotherapy for advanced metastatic CRC with microsatellite instability is definitely reinforced by the favorable response seen in our case, and we hope that these findings would help reduce the dependence on chemotherapy as the mainstay therapeutic for advanced CRC.

Toxicity and Efficacy of a Novel GADD34-expressing Oncolytic HSV-1 for the Treatment of Experimental Glioblastoma.

Purpose: Glioblastoma (GBM) is the most common primary central nervous system cancer in adults. Oncolytic HSV-1 (oHSV) is the first FDA-approved gene therapy approach for the treatment of malignant melanoma. For GBM, oHSVs need to be engineered to replicate within and be toxic to the glial tumor but not to normal brain parenchymal cells. We have thus engineered a novel oHSV to achieve these objectives.Experimental Design: NG34 is an attenuated HSV-1 with deletions in the genes encoding viral ICP6 and ICP34.5. These mutations suppress virus replication in nondividing brain neurons. NG34 expresses the human GADD34 gene under transcriptional control of a cellular Nestin gene promoter/enhancer element, whose expression occurs selectively in GBM. In vitro cytotoxicity assay and survival studies with mouse models were performed to evaluate therapeutic potency of NG34 against glioblastoma. In vivo neurotoxicity evaluation of NG34 was tested by intracerebral inoculation.Results: NG34 replicates in GBM cells in vitro with similar kinetics as those exhibited by an oHSV that is currently in clinical trials (rQNestin34.5). Dose-response cytotoxicity of NG34 in human GBM panels was equivalent to or improved compared with rQNestin34.5. The in vivo efficacy of NG34 against two human orthotopic GBM models in athymic mice was similar to that of rQNestin34.5, whereas intracerebral injection of NG34 in the brains of immunocompetent and athymic mice showed significantly better tolerability. NG34 was also effective in a syngeneic mouse glioblastoma model.Conclusions: A novel oHSV encoding GADD34 is efficacious and relatively nontoxic in mouse models of GBM. Clin Cancer Res; 24(11); 2574-84. ©2018 AACR.

Manual preoperative tracheal retraction exercise decreases the occurrence of postoperative oropharyngeal dysphagia after anterior cervical discectomy and fusion.

OBJECTIVE: Preoperative tracheal retraction exercise (TRE) to minimize the occurrence of postoperative oropharyngeal dysphagia after anterior cervical spine surgery. METHODS: A total of 220 patients admitted for elective anterior cervical spine surgery from January 2013 to December 2014 were retrospectively reviewed. The patients were allocated into two groups: TRE group and control group (without TRE). Modified dysphagia scoring system (MDSS) was used for evaluating the presence and severity of dysphagia symptoms at 1 week and 1, 3, and 6 months after surgery. Demographics such as age, gender, smoking, type of procedure, number of levels operated, duration of surgery, intraoperative blood loss, and instrumentation were analyzed. The clinical outcomes in both groups were compared with Neck Disability Index (NDI), Visual Analogue Scale (VAS) for arm and neck pain, and Odom's criteria for global outcome. RESULTS: In the first week postoperatively, 86 patients (39.1%) developed dysphagia, which decreased to 72 (32.7%), 5 (2.3%), and 4 (1.8%) after 1, 3, and 6 months, respectively. The patients who received the TRE prior to surgery had significantly better MDSS scores ( p = 0.032 for second-level, 0.022 for third-level, and 0.009 for fourth-level fusions) than control group patients who did not receive TRE at the first week of surgery. At the 1-month follow-up, the followed-up patients for second- to fourth-level fusions in the TRE group had improved MDSS scores than those in the control group ( p = 0.041 for second-level, 0.025 for third-level, and 0.0011 for fourth-level fusions). MDSS scores showed no significant difference between both the groups at 1 and 3 months postoperatively for single level anterior cervical fusion. NDI and VAS scores didn't yield any significant difference. Global outcome by Odom's criteria was 88.6%. CONCLUSION: Preoperative TRE can significantly reduce the occurrence of postoperative dysphagia after ACDF surgery. During follow-up, the incidence of postoperative dysphagia was significantly lower and had resolved at 3 months in all patients.

Simultaneous radical gastrectomy and coronary artery bypass grafting: a case report.

Coexistence of coronary artery disease and cancer with both requiring surgical treatment at the same time is rare. A 74-year-old male underwent elective coronary artery bypass grafting for unstable angina. In preoperative workup, the patient was incidentally discovered to have anaemia secondary to occult blood loss in his stool. This led to a preoperative upper GI endoscopy which showed a gastric carcinoma. Since both conditions required surgery, it was decided to perform simultaneous coronary artery bypass grafting (CABG) followed by distal radical gastrectomy. CABG was done using low-dose heparin, and after closing sternotomy, the radical gastrectomy was performed. Postoperative recovery was uneventful, and patient was discharged in stable condition on day 14. Follow-up after 6 months revealed no recurrence. Feasibility of simultaneous CABG and gastric cancer surgery, in particular, and various management strategies, in general, is discussed.

Component Separation Technique: an Effective Way of Treating Large Ventral Hernia.

Repair of large ventral hernia is a challenge for even experienced surgeons, as there are large defects with large contents, often with loss of domain. The large defects were bridged by various plastic surgical procedures like myofascial flaps or free flaps with high recurrences and complications. More often, the bridging was done with artificial prosthesis, leaving the defects open. This was accomplished by either open surgery (onlay, inlay, sublay or underlay) or laparoscopic intraperitoneal onlay meshes (IPOMs). However, non-closure of the midline had adverse effects on postural maintenance, respiration, micturition, defecation and biomechanical properties, which have a profound impact on the patients' overall physical capacity and quality of life. Component separation technique (CST) is a novel answer to the closure of midline with live, active tissues with or without the use of additional prosthesis. Though this technique was originally described in 1990, it has undergone lots of modifications like perforator preserving CST, endoscopic technique and posterior component separation. So, we present a series of 22 patients with large ventral hernia repaired using various options of component separation technique in the last 3 years.

Tavaborole, a novel boron-containing small molecule for the topical treatment of onychomycosis, is noncarcinogenic in 2-year carcinogenicity studies.

Tavaborole, a cyclized boronic acid, has been approved by the Food and Drug Administration for the topical treatment of toenail onychomycosis. This novel, low-molecular-weight pharmaceutical compound has broad-spectrum antifungal activity against dermatophytes, yeasts, and molds responsible for the disease. Tavaborole was tested in 2-year carcinogenicity studies in mice (once daily dermal administration) and rats (once daily by oral gavage) as part of the extensive nonclinical safety program. There was no evidence of tavaborole-related neoplasms observed in either study. Based on the data gathered from these 2 carcinogenicity studies, tavaborole is considered noncarcinogenic.

Clinical presentations and biochemical profile in adult celiac disease patients in Hyderabad: Pakistan.

OBJECTIVE: To see the various clinical presentations and biochemical profile in adult celiac disease patients of Hyderabad Sindh. METHODS: A total 60 suspected cases of adult celiac disease, both males and females were screened out from Liaquat University of Medical and Health Sciences hospital and private clinics at Sadar Hyderabad Sind by non probability purposive sampling during a period from July 2011 to December 2012.Age ranged between 18 to 55 Years. A detailed history and clinical examination was done. Patients already on gluten free diet, age <12years, tuberculosis or cancer of intestine/colon and patients of diabetes and thyroid disorder were excluded, while patients having positive ant tTG (value >15 iu/ml detected by ELISA) were included. The biochemical profile including serum albumin, calcium ,ferritin, SGPT, Alkaline phosphatase and Haemoglobin were estimated in central Diagnostic laboratory LUMHS by taking 10 cc centrifuged blood sample. The data was plotted on SPSS 16, mean and percentages were calculated. RESULTS: All patients were divided in to three groups according to age. The most common group was 18-30 years; (mean, 23.5±5.6) comprised 56.6%. The commonest clinical presentation was diarrhoea in 50%, menstrual irregularity in 21%, walking problems 21%, undue fatigue in 15% and edema in 15%. P values calculated in quantitative variable of males and females. The p value was significant in between serum calcium (p 0.004), haemoglobin (p 0,004), serum ferritin (<0.005) and alkaline phosphatise (<0.005). CONCLUSION: This study showed that Adult celiac disease was present with entirely different clinical and biochemical profile in patients in this region.

Cardiovascular autonomic neuropathy (CAN) in patients of type 2 diabetes mellitus: a tertiary care hospital based study.

INTRODUCTION: Diabetes mellitus (DM) is a clinical syndrome characterized by hyperglycemia due to absolute or relative insulin deficiency. Cardiovascular autonomic neuropathy invokes potentially life threatening outcomes especially in poorly controlled diabetic patients. However, there is scarcity of epidemiological data for CAN in poorly controlled type 2 diabetic patients in Pakistan. OBJECTIVE: The objective of this study is to assess the frequency of cardiovascular autonomic neuropathy (CAN) in patients with poorly controlled type 2 diabetes mellitus in Pakistan. STUDY DESIGN: Descriptive cross-sectional. SETTING: Department of Medicine, Liquate University Hospital, Hyderabad/Jamshoro, Sindh, Pakistan. DURATION: February to November 2012. SAMPLING TECHNIQUE: Non-probability purposive. MATERIAL AND METHOD: This study included 207 patients, who all met the inclusion criteria and gave an informed consent for inclusion in the study. All the patients in the study were evaluated for CAN using four different clinical tests- Resting heart rate, test for orthostatic hypotension, hand gripping test and QTc interval on ECG. Resting Heart Rate of more than 100 beats per minute was taken as abnormal. Orthostatic hypotension was defined as a fall of systolic blood pressure >20 mmHg and/or diastolic blood pressure >10 mmHg on change of posture. The patients were asked to squeeze a small ball in hand gripping test and an increase in diastolic blood pressure <15 mmHg was considered abnormal. ECG recording with QTc interval >440 ms was considered abnormal or prolonged. Patients were labeled as CAN +ve if any two or more than two of the above listed tests were found positive/abnormal. RESULTS: In our study, 76 out of 207 (36.7%) of the patients with poorly controlled type 2 diabetes mellitus were found to have cardiovascular autonomic neuropathy (CAN). CONCLUSION: Cardiac autonomic dysfunctions are common in poorly controlled type 2 diabetes.

Thrombogenic catheter-associated superior vena cava syndrome.

Superior vena cava syndrome has historically been associated with malignancy. With the increasing use of indwelling central lines, catheters, and pacemakers in the past decade, there have been an increasing number of cases associated with thrombosis rather than by direct external compression. Patients presenting to the ED with an acute process of SVC syndrome need to be assessed in a timely fashion. Computed tomography angiography (CTA) or magnetic resonance angiogram (MRA) are superb modalities for diagnosis and can quickly be used in the ED. Treatment is oriented towards the underlying cause of the syndrome. In cases of thrombogenic catheter-associated SVC syndrome, anticoagulation is the mainstay of treatment. We present a case report and discussion of a 56-year-old male with a history of metastatic colorectal cancer and an indwelling central venous port with acute signs and symptoms of superior vena cava syndrome.

Mortui vivos docent--the dead teach the living: 18-flurodeoxyglocose positron emission tomography-computed tomography findings in a case of intravascular B cell lymphoma.

Intravascular large B-cell lymphoma is a rare and aggressive variant of diffuse large B-cell non-Hodgkin's lymphoma. Its atypical presentation often delays the diagnosis and due to its aggressive behavior, the diagnosis is made post-mortem in half of the cases. We present FDG PET/CT findings in a case of IVLCL. In our case, the report of the patient's bone marrow biopsy after death of the patient revealed the presence of IVLCL. After availability of final diagnosis, we reviewed the literature and a better explanation of the FDG PET/CT findings could be obtained. We describe this case, to call for heightened awareness in physicians for the rare but possible diagnosis of IVCLL, particularly in an elderly patient who presents with fever of unknown origin and demonstrates similar FDG PET/CT findings. Considering the characteristic scan findings described in our patient and other cases in literature, FDG PET/CT can be used in suspected cases of IVLCL for early diagnosis of this rapidly fatal malignancy.

Drug resistance patterns in pulmonary tuberculosis.

OBJECTIVE: To determine the resistance patterns of mycobacterium tuberculosis (MTB) isolates among category I and II patients of pulmonary tuberculosis. METHODS: This cross sectional study was conducted at the Department of Medicine, Liaquat University of Medical and Health Sciences Jamshoro, from November 2008 to September 2009. Patients were divided into category I and II. The sputa were collected, stained with Ziehl-Nielsen (Z-N) staining and ultimately inoculated on Lowenstein-Jensen (L-J) media for six weeks. Out of 890 pulmonary tuberculosis (PTB) patients, the growth was obtained in 285 cases. The Drug sensitivity testing (DST) for Isoniazid (INH), Rifampicin (RIF), Ethambutol (EMB) Pyrazinamide (PZA) and Streptomycin (SM) were performed. The data was analyzed on SPSS 10.0. A p-value of <0.05 was taken as significant. RESULT: Out of 285 cases, 176 (61.75%) were male and 109 (38.24%) female. The mean age was 37 +/- 19.90 years. The DST showed drug sensitive and drug resistant isolates in 80 (28.05%) and 205 (71.92%) cases respectively (p=0.001). The drug resistant tuberculosis (DR-TB) rates for individual drugs; INH, RIF, EMB, PZA and SM were 51,22%, 15.4%, 13.33%, 9%12, and 3.85% respectively (p=0.03). The MDR-TB isolates were detected in 120 (42.10%) cases, including 5 (5.88%) in category I and 115 (57.50%) in category II patients (p=0.0001). CONCLUSION: Drug resistant and multidrug resistant tuberculosis was observed mainly in category II patients. However, primary MDR was also observed in category I patients and reflects dissemination of MDR cases within the community.

The Gs-linked receptor GPR3 inhibits the proliferation of cerebellar granule cells during postnatal development.

BACKGROUND: During postnatal murine and rodent cerebellar development, cerebellar granule precursors (CGP) gradually stop proliferating as they differentiate after migration to the internal granule layer (IGL). Molecular events that govern this program remain to be fully elucidated. GPR3 belongs to a family of Gs-linked receptors that activate cyclic AMP and are abundantly expressed in the adult brain. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the role of this orphan receptor in CGP differentiation, we determined that exogenous GPR3 expression in rat cerebellar granule neurons partially antagonized the proliferative effect of Sonic hedgehog (Shh), while endogenous GPR3 inhibition by siRNA stimulated Shh-induced CGP proliferation. In addition, exogenous GPR3 expression in CGPs correlated with increased p27/kip expression, while GPR3 knock-down led to a decrease in p27/kip expression. In wild-type mice, GPR3 expression increased postnatally and its expression was concentrated in the internal granular layer (IGL). In GPR3 -/- mice, the IGL was widened with increased proliferation of CGPs, as measured by bromodeoxyuridine incorporation. Cell cycle kinetics of GPR3-transfected medulloblastoma cells revealed a G0/G1 block, consistent with cell cycle exit. CONCLUSIONS/SIGNIFICANCE: These results thus indicate that GPR3 is a novel antiproliferative mediator of CGPs in the postnatal development of murine cerebellum.

Cardiac autonomic neuropathy (CAN) in type-1 diabetes mellitus patients and its association with the duration of disease and glycemic control.

OBJECTIVE: To determine the frequency of Cardiac Autonomic Neuropathy (CAN) in type-1 Diabetes mellitus patients and its association with the duration of disease and glycemic control. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Medicine, Liaquat University Hospital, Hyderabad/Jamshoro, from December, 2004 to April, 2005. METHODOLOGY: Fifty patients of type-1 Diabetes Mellitus (DM) of >or=10 years duration were selected. CAN was evaluated in terms of presence of resting tachycardia, loss of sinus arrhythmia and heart rate response to Valsalva maneuver by electrocardiogram (ECG). An R-R variation with respiration of >15 beats per minute was taken normal, while 10-15 beats and <10 beats per minute were taken as borderline and definitive CAN respectively. QTc intervals were measured. Patients with HbA1c levels<7% were considered as well-controlled. The associations between CAN, the duration of diabetes and the diabetic control were determined. RESULTS: The mean age was 35.16+/-10.58 years with 32 males and 18 females. The mean values for the known duration of diabetes and HbA1c were 13+/-7.3 years and 9.36+/-2.5 mg/dl respectively. Definitive and borderline CAN were noted in 20% and 24% respectively. Variability of heart rate with respiration was significantly related to the duration but not to the control of the diabetes (p<0.05). QTc showed a significant correlation with the known duration of diabetes and heart rate variability with respiration (p<0.05). Most of the patients had uncontrolled glycemic status. CONCLUSION: Cardiac autonomic neuropathy is common in long standing type-1 diabetics. CAN resulted in prolonged QTc interval that may result in cardiac arrhythmias and even death. Intensive glycemic control improves the cardiac autonomic nerve functions.