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1.
World J Gastroenterol ; 30(9): 1018-1042, 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38577184

ABSTRACT

A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26, 2023, at the Pakistan Kidney and Liver Institute & Research Centre (PKLI & RC) after initial consultations with the experts. The Pakistan Society for the Study of Liver Diseases (PSSLD) and PKLI & RC jointly organised this meeting. This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma (hCCA). The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients. This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation. The diagnostic and staging workup includes high-quality computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography. Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis. However, histopathologic confirmation is not always required before resection. Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging. The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification. Selected patients with unresectable hCCA can be considered for liver transplantation. Adjuvant chemotherapy should be offered to patients with a high risk of recurrence. The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions. Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage. Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.


Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Klatskin Tumor , Humans , Klatskin Tumor/therapy , Klatskin Tumor/surgery , Treatment Outcome , Hepatectomy/methods , Bile Duct Neoplasms/diagnosis , Bile Duct Neoplasms/therapy , Bile Duct Neoplasms/pathology , Cholangiocarcinoma/diagnosis , Cholangiocarcinoma/therapy , Bile Ducts, Intrahepatic/pathology , Cholangiopancreatography, Endoscopic Retrograde , Drainage
2.
Int J Surg Case Rep ; 111: 108902, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37806031

ABSTRACT

INTRODUCTION AND IMPORTANCE: Epithelioid hepatic angiomyolipoma (HAML) is a rare benign tumor predominantly found in women. Its occurrence during pregnancy is extremely rare. Accurate diagnosis of HAML is challenging due to its radiological resemblance to other hepatic neoplasms. We present a case of epithelioid HAML in a pregnant patient, highlighting the diagnostic and management challenges encountered. CASE PRESENTATION: A 24-year-old pregnant female, in her fifth month of pregnancy, presented with right hypochondrium pain and nausea. Radiological imaging suggested the possibility of a hepatic adenoma. The patient opted to continue the pregnancy with regular monitoring of the mass as well as fetal health. After delivering a healthy baby, the patient underwent successful mass excision and cholecystectomy. Histopathology of the liver mass confirmed the diagnosis of epithelioid HAML. CLINICAL DISCUSSION: Epithelioid HAML is a rare tumor often misdiagnosed. It is more aggressive and frequently associated with tuberous sclerosis complex (TSC) compared to other subtypes. The diagnosis of HAML can be challenging due to its resemblance to Hepatocellular Carcinoma and other hepatic neoplasms on radiological imaging. Immunohistochemistry plays a crucial role in confirming the diagnosis. Surgical excision is the recommended treatment, with complete removal to minimize the risk of recurrence. CONCLUSION: This case report highlights the rarity of epithelioid HAML during pregnancy and emphasizes the importance of a multidisciplinary approach in managing hepatic neoplasms. Close monitoring is crucial, considering the potential risks to the mother and fetus. Accurate diagnosis through histopathological evaluation, immunohistochemistry and a multidisciplinary approach are essential for appropriate management.

3.
ACG Case Rep J ; 10(10): e01163, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37799486

ABSTRACT

Calcifying nested stromal-epithelial tumor is a rare hepatic malignancy with approximately 50 cases reported in the literature. Its clinical presentation is nonspecific, and the diagnosis is mainly based on histology which shows nests of spindle and epithelioid cells along with a desmoplastic myofibroblastic stroma containing variable calcification and ossification. In this report, we present a case of a 24-year-old woman with a history of abdominal pain, distension, and dyspepsia. She had a palpable liver with normal liver function test results. Serum alpha-fetoprotein levels were within normal range, and serologies for hepatitis B and C virus remained negative. Radiological investigations (magnetic resonance imaging and computed tomography) showed a large, right hepatic lobe mass with tumor invasion into the right posterior portal vein, but the 2 modalities could not characterize the lesion. Finally, an ultrasound-guided biopsy of the liver lesion provided the diagnosis of calcifying nested stromal-epithelial tumor. The tumor was resected successfully.

4.
Langenbecks Arch Surg ; 408(1): 308, 2023 Aug 14.
Article in English | MEDLINE | ID: mdl-37578661

ABSTRACT

PURPOSE: Thromboembolic complications remain a significant concern in postoperative patients, particularly those who have undergone liver transplantation. Warfarin has been the standard oral anticoagulant. Direct oral anticoagulants (DOACs) have several advantages over warfarin, including rapid onset of action and standardized dose guidelines. We aimed to assess the safety of rivaroxaban in living donor liver transplantation (LDLT) recipients. METHODS: This study was a single-center, retrospective descriptive analysis of LDLT recipients who received rivaroxaban between December 2020 and April 2022. A total of 27 recipients received rivaroxaban postoperatively. Liver function tests, immunosuppression levels, serum creatinine, and INR were recorded before the initiation of rivaroxaban and then on post-therapy days 1, 7, 14, 28, 90, and 180. RESULTS: Among the 27 recipients receiving rivaroxaban postoperatively, portal venous thrombosis was the most prevalent indication for anticoagulation (44.4%), followed by Budd-Chiari syndrome (29.6%). Nine patients had a twofold increase in either ALT or AST values, two of whom were treated for biliary strictures and the others for rejection. Eighteen patients were given tacrolimus, and eight were on cyclosporine, with one patient switched from tacrolimus to cyclosporine due to insufficient therapeutic levels. There were no incidents of bleeding or re-thrombosis during the 180-day follow-up period. CONCLUSION: Rivaroxaban may be a safe and effective alternative in LDLT recipients with no significant adverse incidents. Further studies with larger sample sizes are needed to confirm these findings and determine this population's optimal dose and duration of rivaroxaban therapy.


Subject(s)
Cyclosporins , Liver Transplantation , Humans , Rivaroxaban/adverse effects , Warfarin/adverse effects , Retrospective Studies , Liver Transplantation/adverse effects , Living Donors , Tacrolimus , Anticoagulants/adverse effects
5.
Front Mol Biosci ; 10: 1190669, 2023.
Article in English | MEDLINE | ID: mdl-37255540

ABSTRACT

The use of oncolytic viruses (OVs) in combination with cytokines, such as IL-12, is a promising approach for cancer treatment that addresses the limitations of current standard treatments and traditional cancer immunotherapies. IL-12, a proinflammatory cytokine, triggers intracellular signaling pathways that lead to increased apoptosis of tumor cells and enhanced antitumor activity of immune cells via IFN-γ induction, making this cytokine a promising candidate for cancer therapy. Targeted expression of IL-12 within tumors has been shown to play a crucial role in tumor eradication. The recent development of oncolytic viruses enables targeted delivery and expression of IL-12 at the tumor site, thereby addressing the systemic toxicities associated with traditional cancer therapy. In this study, we constructed an oncolytic virus, VSVΔ51M, based on the commercially available VSV wild-type backbone and further modified it to express human IL-12. Our preclinical data confirmed the safety and limited toxicity of the modified virus, VSV-Δ51M-hIL-12, supporting its potential use for clinical development.

6.
Sci Rep ; 13(1): 8341, 2023 05 23.
Article in English | MEDLINE | ID: mdl-37221310

ABSTRACT

Triple-negative breast cancer (TNBC) subtype is characterized by aggressive clinical behavior and poor prognosis patient outcomes. Here, we show that ADAR1 is more abundantly expressed in infiltrating breast cancer (BC) tumors than in benign tumors. Further, ADAR1 protein expression is higher in aggressive BC cells (MDA-MB-231). Moreover, we identify a novel interacting partners proteins list with ADAR1 in MDA-MB-231, using immunoprecipitation assay and mass spectrometry. Using iLoop, a protein-protein interaction prediction server based on structural features, five proteins with high iloop scores were discovered: Histone H2A.V, Kynureninase (KYNU), 40S ribosomal protein SA, Complement C4-A, and Nebulin (ranged between 0.6 and 0.8). In silico analysis showed that invasive ductal carcinomas had the highest level of KYNU gene expression than the other classifications (p < 0.0001). Moreover, KYNU mRNA expression was shown to be considerably higher in TNBC patients (p < 0.0001) and associated with poor patient outcomes with a high-risk value. Importantly, we found an interaction between ADAR1 and KYNU in the more aggressive BC cells. Altogether, these results propose a new ADAR-KYNU interaction as potential therapeutic targeted therapy in aggressive BC.


Subject(s)
Adenosine Deaminase , RNA-Binding Proteins , Triple Negative Breast Neoplasms , Humans , Aggression , Breast , Complement C4 , Histones , Triple Negative Breast Neoplasms/pathology , Adenosine Deaminase/metabolism , RNA-Binding Proteins/metabolism
7.
Molecules ; 28(8)2023 Apr 21.
Article in English | MEDLINE | ID: mdl-37110867

ABSTRACT

Overexpression of the thymidine phosphorylase (TP) enzyme induces angiogenesis, which eventually leads to metastasis and tumor growth. The crucial role of TP in cancer development makes it an important target for anticancer drug discovery. Currently, there is only one US-FDA-approved drug, i.e., Lonsurf, a combination of trifluridine and tipiracil, for the treatment of metastatic colorectal cancer. Unfortunately, numerous adverse effects are associated with its use, such as myelosuppression, anemia, and neutropenia. Since the last few decades, the discovery of new, safe, and effective TP inhibitory agents has been rigorously pursued. In the present study, we evaluated a series of previously synthesized dihydropyrimidone derivatives 1-40 for their TP inhibitory potential. Compounds 1, 12, and 33 showed a good activity with IC50 = 314.0 ± 0.90, 303.5 ± 0.40, and 322.6 ± 1.60 µM, respectively. The results of mechanistic studies revealed that compounds 1, 12, and 33 were the non-competitive inhibitors. These compounds were also evaluated for cytotoxicity against 3T3 (mouse fibroblast) cells and were found to be non-cytotoxic. Finally, the molecular docking suggested the plausible mechanism of non-competitive inhibition of TP. The current study thus identifies some dihydropyrimidone derivatives as potential inhibitors of TP, which can be further optimized as leads for cancer treatment.


Subject(s)
Enzyme Inhibitors , Thymidine Phosphorylase , Animals , Mice , Molecular Docking Simulation , Enzyme Inhibitors/pharmacology , Drug Discovery
8.
Transplant Proc ; 55(2): 402-407, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36878746

ABSTRACT

Living donor liver transplant in addition to its lifesaving therapy is a cost-effective alternate to long-term disease management in patients with chronic liver disease. Financial constraint is the biggest hurdle faced by patients in developing countries in availing the liver transplantation. So, we conducted this study to report a government-funded financial support system for liver transplant services. A total of 198 patients who underwent living donor liver transplant with at least 90 days follow-up were included in the study. According to proxy means test score, 52.2% patients were from low and middle socioeconomic groups and 64.6% of patients underwent liver transplantation through government support. Out of 198 patients who underwent liver transplantation 29.6% had monthly income below 25,000 Pakistani rupees ($114). In recipients, 90-day mortality was 7.1% and morbidity was 67.1%. Donor morbidity was 23.2% without any mortality. This financial model can serve as a valuable source for middle and low income group countries to overcome the financial challenge and make liver transplant an accessible, affordable, and economically viable option.


Subject(s)
Liver Diseases , Liver Transplantation , Humans , Living Donors , Financial Support , Income
9.
Diagnostics (Basel) ; 11(10)2021 Sep 22.
Article in English | MEDLINE | ID: mdl-34679437

ABSTRACT

MicroRNA is a small non-coding RNA (sncRNA) involved in gene silencing and regulating post-transcriptional gene expression. miRNAs play an essential role in the pathogenesis of numerous diseases, including diabetes, cardiovascular diseases, viral diseases and cancer. Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin's lymphoma (NHL), arising from different stages of B-cell differentiation whose pathogenesis involves miRNAs. Various viral and non-viral vectors are used as a delivery vehicle for introducing specific miRNA inside the cell. Adenoviruses are linear, double-stranded DNA viruses with 35 kb genome size and are extensively used in gene therapy. Meanwhile, Adeno-associated viruses accommodate up to 4.8 kb foreign genetic material and are favorable for transferring miRNA due to small size of miRNA. The genetic material is integrated into the DNA of the host cell by retroviruses so that only dividing cells are infected and stable expression of miRNA is achieved. Over the years, remarkable progress was made to understand DLBCL biology using advanced genomics and epigenomics technologies enabling oncologists to uncover multiple genetic mutations in DLBCL patients. These genetic mutations are involved in epigenetic modification, ability to escape immunosurveillance, impaired BCL6 and NF-κß signaling pathways and blocking terminal differentiation. These pathways have since been identified and used as therapeutic targets for the treatment of DLBCL. Recently miRNAs were also identified to act either as oncogenes or tumor suppressors in DLBCL pathology by altering the expression levels of some of the known DLBCL related oncogenes. i.e., miR-155, miR-17-92 and miR-21 act as oncogenes by altering the expression levels of MYC, SHIP and FOXO1, respectively, conversely; miR-34a, mir-144 and miR-181a act as tumor suppressors by altering the expression levels of SIRT1, BCL6 and CARD11, respectively. Hundreds of miRNAs have already been identified as biomarkers in the prognosis and diagnosis of DLBCL because of their significant roles in DLBCL pathogenesis. In conclusion, miRNAs in addition to their role as biomarkers of prognosis and diagnosis could also serve as potential therapeutic targets for treating DLBCL.

10.
Article in English | MEDLINE | ID: mdl-31258858

ABSTRACT

Background: Long-term oral anticoagulants (OAC) increases bleeding risk after the percutaneous coronary intervention (PCI) with dual antiplatelet therapy (DAPT) with Aspirin and P2Y12 inhibitors. We hypothesize that dual anti-thrombotic therapy (DATT) reduces bleeding without increased cardiovascular events. Objectives: DATT does not increase adverse cardiovascular events compared to triple anti-thrombotic therapy (TATT). Method: We searched MEDLINE, PUBMED, Google Scholar, Cochrane and EMBASE from inception to 6 April 2019 for randomized control trials (RCTs) comparing DATT to TATT after PCI. Results: We identified 641 citations (411 after excluding duplicates). Four RCTs with 5,317 patients (3,039 on DATT vs 2,278 on TATT) were included. DATT arm showed significantly reduced [total bleeding, 731 vs. 784, odds ratio [OR] = 0.51, Confidence Interval [CI] = 0.39-0.67, p < 0.00001, I2 = 71% (I2 = 0% without WOEST study)], [TIIMI major bleeding 60 vs. 80, OR = 0.56, CI = 0.4-0.79, p = 0.0009, I2 = 0%], and [TIIMI minor bleeding, 70 vs 126, OR = 0.43, CI = 0.32-0.59, p < 0.00001, I2 = 0%]. There was no difference in subsequent strokes, myocardial infarction, stent thrombosis, and mortality. A trend towards decreased non-cardiac deaths with DATT was observed, 14 vs 26, OR = 0.55, CI = 0.27-1.10, p = 0.09, I2 = 6%. Conclusions: DATT is associated with significantly reduced bleeding and a trend towards reduced non-cardiac death with no difference in adverse cardiovascular outcomes.

11.
Am J Case Rep ; 19: 1288-1291, 2018 Oct 30.
Article in English | MEDLINE | ID: mdl-30374015

ABSTRACT

BACKGROUND Thrombotic thrombocytopenic purpura is mostly characterized by symptoms and signs of hemolytic anemia, thrombocytopenia, renal impairment, fever and neurologic dysfunction. It is not always necessary to have all 5 characteristic symptoms, and presentations can vary. It can be congenital or acquired by any etiology that causes deficiency or dysfunction of ADAMST13 enzyme. CASE REPORT We present a case of a 71-year-old man who presented to our hospital initially with abdominal pain. He was diagnosed with pancreatitis, and conservative management was started with pain control and hydration. During the hospital course, the patient developed anemia that was hemolytic in nature, acute kidney injury and thrombocytopenia. He was then diagnosed as having TTP secondary to pancreatitis with additive effect of clopidogrel, as he had recently been started on clopidogrel due to percutaneous coronary intervention. He was started on prompt treatment with plasma exchange and intermittent dialysis, and he achieved full recovery after that. CONCLUSIONS TTP is a potentially fatal disease with high mortality risk. It is judicious to recognize and have high suspicion of TTP being caused by such rare causes (pancreatitis and clopidogrel), as immediate recognition and treatment can enhance survival.


Subject(s)
Clopidogrel/adverse effects , Pancreatitis, Acute Necrotizing/complications , Plasma Exchange/methods , Purpura, Thrombocytopenic/etiology , Purpura, Thrombocytopenic/therapy , Abdominal Pain/diagnosis , Abdominal Pain/etiology , Aged , Clopidogrel/therapeutic use , Follow-Up Studies , Humans , Male , Pancreatitis, Acute Necrotizing/diagnostic imaging , Pancreatitis, Acute Necrotizing/therapy , Purpura, Thrombocytopenic/physiopathology , Rare Diseases , Risk Assessment , Tomography, X-Ray Computed/methods , Treatment Outcome
12.
Gastroenterology Res ; 11(4): 295-304, 2018 Aug.
Article in English | MEDLINE | ID: mdl-30116429

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is a leading cause of death worldwide. Polyp detection rate (PDR) and adenoma detection rate (ADR) are key focus in endoscopic research for CRC screening and prevention. Use of anti-spasmodic agents during colonoscopy to help identify adenomas and polyps has remained a controversial topic. Hyoscine butyl bromide (HBB) is the most commonly used anti-spasmodic agent in patients undergoing colonoscopy. Some randomized controlled trials (RCTs) have questioned the clinical efficacy and safety of routine use of HBB for polyp and adenoma detection rates. METHODS: We conducted a systematic search in PubMed and MEDLINE from inception until February 10, 2018, for studies which compared HBB with placebo. We used RevMan version 5.3 for analysis. Procedural end-points were polyps, adenomas, and advanced adenoma detection rates, mean number of polyps detected and cecal intubation time. RESULTS: We included seven RCTs with 2,588 patients in our analysis. A total of 1,301 patients were randomized to HBB arm and 1,287 to the placebo arm. There was no significant difference in the primary outcome of polyp detection rate, 654 in HBB group vs. 616 in the placebo group, (odds ratio (OR) = 1.11, confidence interval (CI) = 0.93 - 1.34, P = 0.25). There was no difference in secondary outcomes of adenoma detection rate, 430 in HBB group vs. 396 in the placebo group, (OR = 1.06, CI = 0.89 - 1.26, P = 0.51), advanced adenoma detection rate, 92 in HBB vs. 95 in placebo group (OR = 0.95, CI = 0.70 - 1.30, P = 0.76), mean number of polyps detected (point estimate = 0.12, CI = 0.00 - 0.23, P = 0.05), adenomatous polyps (OR = 0.84, CI = 0.39 - 1.81, P = 0.65) and cecal intubation time (point estimate = 0.73, CI = -1.98 - 0.52, P = 0.25) between the two groups. CONCLUSIONS: The use of HBB in patients undergoing colonoscopy does not appear to improve polyp or adenoma detection rates. It showed a non-significant trend of increased mean number of polyps detected with HBB.

13.
Pak J Med Sci ; 34(1): 20-26, 2018.
Article in English | MEDLINE | ID: mdl-29643872

ABSTRACT

BACKGROUND AND OBJECTIVE: Ventricular septal rupture (VSR) is one of the fatal complications of myocardial infarction (MI). Surgery provides the maximum survival benefit. Our objective was to investigate the risk factors of surgical mortality and to do the survival analysis in the past six years at our hospital. METHODS: All the patients operated at CPE Institute of Cardiology Multan Pakistan, between 2009 and 2015 for repair of post MI VSR were analysed retrospectively for demographics, comorbidities, operative and post operative outcomes. The primary outcome was 30 days mortality. The follow up was done till April 2017 and the follow up data was obtained from hospital records and by telephoning the patients. SPSS was used for statistical analysis. P value < 0.05 was considered significant. RESULTS: A total of 31 patients were operated for VSR repair with a mean age of 57.19±7.73 years. Eighteen patients also had a concomitant coronary artery bypass grafting (CABG). The operative mortality in this series was 25.8% Univariate analysis showed that pre-operative ejection fraction (E.F) (p value 0.010) and cardiogenic shock (p value 0.031) were a significant risk factors for operative mortality while on logistic regression analysis only the cardiogenic shock was found to be an independent risk factor for operative mortality with the odds ratio of 2.17. Low ejection fraction only acted as a confounding variable. The mean survival at six years was 34 months with a survival rate of 28.6%. The additional CABG did not confer any survival benefit. CONCLUSION: The patients in cardiogenic shock pre-operatively have a high operative mortality. Low ejection fraction (E.F) acts as a confounding factor. Concomitant CABG does not confer any survival benefit.

14.
Pak J Med Sci ; 33(1): 106-110, 2017.
Article in English | MEDLINE | ID: mdl-28367182

ABSTRACT

BACKGROUND & OBJECTIVE: Antiplatelet drugs are frequently used after coronary artery bypass graft (CABG) surgery to prevent venous graft occlusion. The fear of bleeding complications prevents them to be given early post operatively, which is the time when antiplatelets use confers maximum benefit. Our objective was to determine the effect and influence of early aspirin therapy on fatal and nonfatal bleeding complications and blood requirements after coronary bypass surgery (CABG). METHODS: The patients who only underwent coronary artery bypass surgery for the first time in the past three years and did not have any bleeding diathesis were retrospectively analyzed from the cardiac surgery database of CPEIC Multan. The patients either received aspirin within six hours of CABG or had it given after 12 hours. The patients were analyzed for mean blood loss and number of blood units transfused. SPSS was used for statistical analysis. P value < 0.05 was considered significant. RESULTS: Total 281 patients received aspirin within six hours while 326 patients did not. Mean blood loss in early aspirin group was 727ml as compared to 767ml in the other group (p value 0.74). The median number of blood units transfused was 2 (p value 0.98). Our results did not show any statistical difference in both the groups. CONCLUSION: Aspirin can safely be given early after CABG without the fear of bleeding complications thus conferring the advantage of increased graft patency.

15.
Case Rep Gastrointest Med ; 2017: 6983434, 2017.
Article in English | MEDLINE | ID: mdl-28367340

ABSTRACT

Dieulafoy lesions are a rare etiology of gastrointestinal bleeding from a large caliber-persistent tortuous submucosal artery. They account for 1-2% of all causes of acute gastrointestinal hemorrhage with 80%-95% of these lesions located in the stomach along the lesser curvature. One-third of these lesions present at an extragastric location, with the proximal duodenum accounting for 15% of them. We present a 21-year-old male with no significant past medical history or risk factors, who presented with repeated syncopal episodes followed by hematemesis, found to have a Dieulafoy lesion located at the duodenal bulb. This lesion was diagnosed and successfully treated via upper endoscopy with epinephrine injection and the application of 2 endoscopic clips.

16.
Am J Case Rep ; 18: 181-185, 2017 Feb 20.
Article in English | MEDLINE | ID: mdl-28216610

ABSTRACT

BACKGROUND Kaposi sarcoma (KS) is known to involve the mucocutaneous tissues and the aero-digestive tracts. In acquired immune deficiency syndrome (AIDS) patients, KS has an aggressive course and carries poor prognosis. We present a case of pulmonary KS with osseous metastases as the first presentation of human immunodeficiency virus (HIV) infection in a young male. The lesions impressively decreased in size and numbers following initiation of highly active antiretroviral therapy (HAART). CASE REPORT A 34-year-old heterosexual male presented with a one month history of cough and 15-20 pound weight loss within six months. Examination revealed oral thrush, decreased breath sounds and crackles on the right lower lung base. Imaging showed a large right perihilar mass with multiple lytic lesions involving thoracic and lumber vertebrae, ribs, sternum, and clavicles. Blood and sputum cultures, smears for acid fast bacilli, and a QUANTIferon gold test were all negative. He tested positive for HIV and his CD4 count was 7 cells/uL. Bronchoscopy with biopsy was unrevealing. Pathology of the right hilar mass was diagnostic of KS. Following initiation of antiretroviral therapy his condition dramatically improved; repeat chest CT scan showed marked regression of the bony and pulmonary lesions. CONCLUSIONS The dual action of HAART on the recovery of the immune system and against human herpes virus 8 (HHV-8) may essentially cause regression of KS lesions.


Subject(s)
AIDS-Related Opportunistic Infections/drug therapy , Antiretroviral Therapy, Highly Active/methods , Bone Neoplasms/drug therapy , HIV Infections/drug therapy , Immunocompromised Host , Lung Neoplasms/drug therapy , Sarcoma, Kaposi/drug therapy , AIDS-Related Opportunistic Infections/complications , Adult , Bone Neoplasms/secondary , HIV Infections/complications , Humans , Lung Neoplasms/pathology , Male , Neoplasm Staging , Sarcoma, Kaposi/secondary , Treatment Outcome
17.
Curr Top Med Chem ; 17(12): 1320-1330, 2017.
Article in English | MEDLINE | ID: mdl-28017149

ABSTRACT

Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus which is endemic to certain regions of the world and infects around 10-20 million people. HTLV-1 is the etiologic agent of Adult T cell leukemia/lymphoma and HTLV-1 associated neurological disorders including mainly HTLV-1 associated myelopathy/Tropical spastic paraparesis. The involvement of the central nervous diseases occurs among: HTLV-1 infected patients from endemic areas, HIV positive individuals and drug users. The ability of HTLV-1 to cause associated neuropathies starts with the virus crossing the blood brain barrier (BBB), then entering and infecting the cells of the central nervous system. As a consequence, to the viral attack, HTLV-1 infected lymphocytes produce pro-inflammatory cytokines like tumor necrosis factor alpha, Interleukin 1 beta and interleukin 6 which further disrupts the BBB. Different serological tests have been used in the diagnosis of HTLV-1. These include: ELISA, Western Blotting (WB), Immunofluorescence, Particle Agglutination and Polymerase Chain Reaction which is used as a confirmatory test. Danazol, pentoxifylline, azathioprine and vitamin C have been used in the treatment of the HTLV-1 associated neurological disorders. Other antiviral drugs (lamivudine, zidovudine), monoclonal antibodies (Daclizumab) and therapeutic agents (valporic acid, interferons) have also been evaluated. No known drug, so far, has been shown to be efficacious. The aim of this review is to present the complexities of HTLV-1 associated neurological disorders and their current ongoing treatment. In addition to discussing future possible therapeutic strategies, by targeting HTVL-1 viral components and gene/s products, for the treatment of those neurological conditions.


Subject(s)
Antiviral Agents/therapeutic use , Central Nervous System/drug effects , Human T-lymphotropic virus 1/drug effects , Nervous System Diseases/drug therapy , Central Nervous System/metabolism , Central Nervous System/virology , Human T-lymphotropic virus 1/metabolism , Humans , Nervous System Diseases/metabolism , Nervous System Diseases/virology
18.
Am J Case Rep ; 17: 837-840, 2016 Nov 09.
Article in English | MEDLINE | ID: mdl-27826136

ABSTRACT

BACKGROUND Non-valvular mural infective endocarditis (IE) is a rare bacterial growth on cardiac walls. Several risk factors have been reported. Echocardiography is an important diagnostic modality for diagnosing vegetation attached to the intracardiac walls. CASE REPORT We present the case of a 57-year-old man admitted with Staphylococcus aureus bacteremia due to an infected tunnelled hemodialyses catheter. Transthoracic echocardiogram did not show any abnormality, but transesophageal echocardiogram (TEE) revealed a 1.7×0.8 cm mobile echo-density attached to the surface of the interatrial septum in the left atrium, where the foramen ovale (FO) exists in utero. The patient was transferred to another facility for re-do sternotomy cardiac surgery, where these findings were confirmed intraoperatively. A biopsy of the mass was taken, which confirmed it to be a vegetation attached to the FO. CONCLUSIONS We report the first case in the literature of vegetation attached to the surface of the interatrial septum in the left atrium at the congenital location of the foramen ovale. There have been no previously reported cases in the literature with such novel imaging findings.


Subject(s)
Endocarditis/complications , Foramen Ovale, Patent/complications , Heart Atria/diagnostic imaging , Streptococcal Infections/complications , Biopsy , Echocardiography, Transesophageal , Endocarditis/diagnosis , Foramen Ovale, Patent/diagnosis , Humans , Male , Middle Aged , Rare Diseases , Streptococcal Infections/diagnosis
19.
Am J Case Rep ; 17: 814-818, 2016 Nov 02.
Article in English | MEDLINE | ID: mdl-27803496

ABSTRACT

BACKGROUND Left atrial to esophageal fistula (LAEF) is a rare fatal complication of radiofrequency ablation (RFA) for atrial fibrillation and is associated with high mortality. Clinical features can be nonspecific and include fever, dysphagia, upper gastrointestinal (GI) bleeding, sepsis, and embolic stroke a after recent history of RFA for atrial fibrillation. CASE REPORT  A 57-year-old Caucasian male was brought to the emergency department (ED) by his family because of an altered mental status. He had undergone a radiofrequency ablation for paroxysmal atrial fibrillation three weeks earlier. Several hours after admission to the ED, the patient transiently became unresponsive and had a right sided hemiplegia. A brain MRI revealed multiple cerebral infarcts. On the following day, the patient had an episode of melena, and an esophagogastroduodenoscopy (EGD) was performed which did not reveal any source of bleeding. While the patient was being monitored in the intensive care unit (ICU), he had an episode of hematemesis and went into cardiac arrest from which he was successfully resuscitated and transferred to another facility. He had another EGD, which uncovered a flap of mucosa covering the lower third of his esophagus and a 1 cm fistulous opening was seen with fresh blood oozing out of it. The patient had another cardiac arrest during the endoscopy and died despite all measures. CONCLUSIONS We present this case to stress the importance of early diagnosis of LAEF. LAEF can be fatal if diagnosis is delayed or missed. Early surgical intervention can reduce LAEF morbidity and mortality. Newer diagnostic modalities such as endoscopic ultrasound (EUS) can be helpful in cases where conventional imaging is unclear.


Subject(s)
Atrial Fibrillation/surgery , Catheter Ablation/adverse effects , Esophageal Fistula/etiology , Heart Diseases/etiology , Postoperative Complications , Diagnosis, Differential , Endoscopy, Digestive System , Esophageal Fistula/diagnosis , Fatal Outcome , Heart Atria , Heart Diseases/diagnosis , Humans , Magnetic Resonance Imaging, Cine , Male , Middle Aged , Tomography, X-Ray Computed
20.
Saudi Pharm J ; 24(2): 220-5, 2016 Mar.
Article in English | MEDLINE | ID: mdl-27013915

ABSTRACT

Drug-drug interactions (DDIs) may result in the alteration of therapeutic response. Sometimes they may increase the untoward effects of many drugs. Hospitalized cardiac patients need more attention regarding drug-drug interactions due to complexity of their disease and therapeutic regimen. This research was performed to find out types, prevalence and association between various predictors of potential drug-drug interactions (pDDIs) in the Department of Cardiology and to report common interactions. This study was performed in the hospitalized cardiac patients at Ayub Teaching Hospital, Abbottabad, Pakistan. Patient charts of 2342 patients were assessed for pDDIs using Micromedex® Drug Information. Logistic regression was applied to find predictors of pDDIs. The main outcome measure in the study was the association of the potential drug-drug interactions with various factors such as age, gender, polypharmacy, and hospital stay of the patients. We identified 53 interacting-combinations that were present in total 5109 pDDIs with median number of 02 pDDIs per patient. Overall, 91.6% patients had at least one pDDI; 86.3% were having at least one major pDDI, and 84.5% patients had at least one moderate pDDI. Among 5109 identified pDDIs, most were of moderate (55%) or major severity (45%); established (24.2%), theoretical (18.8%) or probable (57%) type of scientific evidence. Top 10 common pDDIs included 3 major and 7 moderate interactions. Results obtained by multivariate logistic regression revealed a significant association of the occurrence of pDDIs in patient with age of 60 years or more (p < 0.001), hospital stay of 7 days or longer (p < 0.001) and taking 7 or more drugs (p < 0.001). We found a high prevalence for pDDIs in the Department of Cardiology, most of which were of moderate severity. Older patients, patients with longer hospital stay and with elevated number of prescribed drugs were at higher risk of pDDIs.

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