The role of PKC in X-ray-induced megakaryocyte apoptosis and thrombocytopenia.

Thrombocytopenia is a critical complication after radiation therapy and exposure. Dysfunction of megakaryocyte development and platelet production are key pathophysiological stages in ionizing radiation (IR)-induced thrombocytopenia. Protein kinase C (PKC) plays an important role in regulating megakaryocyte development and platelet production. However, it remains unclear how PKC regulates IR-induced megakaryocyte apoptosis. In this study, we found that pretreatment of PKC pan-inhibitor Go6983 delayed IR-induced megakaryocyte apoptosis, and inhibited IR-induced mitochondrial membrane potential and ROS production in CMK cells. Moreover, suppressing PKC activation inhibited cleaved caspase3 expression and reduced p38 phosphorylation levels, and IR-induced PKC activation might be regulated by p53. In vivo experiments confirmed that Go6983 promoted platelet count recovery after 21 days of 3 Gy total body irradiation. Furthermore, Go6983 reduced megakaryocyte apoptosis, increased the number of megakaryocyte and polyploid formation in bone marrow, and improved the survival rate of 6 Gy total body irradiation. In conclusion, our results provided a potential therapeutic target for IR-induced thrombocytopenia.

X-rays Stimulate Granular Secretions and Activate Protein Kinase C Signaling in Human Platelets.

X-rays can induce morphological as well as functional changes in cells. Platelets are anuclear cellular fragments originating from megakaryocytes and are the major regulators in hemostasis and thrombosis. Platelet products are irradiated to avoid medical complications associated with platelet transfusion. So far, gamma, UV, and laser radiation have been used for this purpose. However, scientists are divided about the effects of radiation on platelet quality. The present study was designed to explore the possible effects of X-rays in washed human platelets and understand the molecular mechanism behind them. In the present study, we exposed washed human platelets to 10 or 30 Gy X-rays at 0.25 Gy/min. Flow cytometry, aggregometry, and western blot were performed to investigate the effect of X-rays on platelet degranulation, integrin activation, platelet aggregation, and apoptosis. It was found that X-rays immediately induced granular secretions with no effect on GP IIb/IIIa activation. Not surprisingly, due to granule secretions in irradiated platelets, platelet aggregation was significantly reduced. In contrast to granular secretions and platelet aggregation, X-rays induced mitochondrial transmembrane potential depolarization in a time-dependent manner to induce apoptosis and activated protein kinase C (PKC) signaling. This study revealed and explained the molecular mechanism activated by X-rays in washed human platelets. Here we also introduced Gö 6983, a PKC inhibitor, as an agent that counteracts X-ray-induced changes and maintains the integrity of platelets.

Determination of lansoprazole in pharmaceuticals using flow injection with rhodamine 6G-diperiodatoargentate(III) chemiluminescence detection.

A chemiluminescence (CL) method based on rhodamine 6G (R6G)-diperiodatoargentate(III) (silver(III) complex) reaction in acid solution is reported for the determination of lansoprazole (LNP) combined with a flow injection (FI) technique. The most likely mechanism for CL reaction was elucidated considering reported data, spectrophotometric and spectrofluorimetric studies. The weak CL reaction between R6G and silver(III) complex could be magnanimously increased in the presence of LNP with a limit of detection (LOD) of 0.002 mg L-1 (S/N = 3), a linear range of 0.01 to 10 mg L-1 (R2 = 0.9997, n = 7), a relative standard deviation (RSD) of 1.2 to 3.2% (n = 4) and an injection throughput of 140 h-1 . No interference activity of commonly found excipients in LNP was detected. After LNP extraction from pharmaceutical samples, the recovery rate ranging from 93 to 110% (RSD, 1.4-3.3%, n = 4) was calculated. The results of the proposed flow CL method were assessed with a spectrophotometric approach applying paired Student's t-test and the calculated value (0.178) was lower than the distributed value (2.20) at a 95% confidence limit.

Anti-inflammatory potential of spectroscopically analyzed trans-13-octadecenoic acid of Yucca elephantipes Regel roots: in-vitro and in-vivo analysis.

Plants are always better choice for treatment of disease in contrast to synthetic agents due to their less toxicity, and free availability with minor limitations of identifications, purity and potency which should be addressed. The objective of current study was to explore the anti-inflammatory effect of methanol extract of Yucca elephantipes roots by using oxidative burst assay and carrageen an induced rat paw edema. GC-MS analysis was carried for the determination of ani-inflammatory potential of fatty acids and other phytochemicals present in Yucca elephantipes roots. Among fifteen detected compounds trans-13-octadecenoic acid, n-hexadecanoic acid and 4-hydroxy benzoic acid were found as 84.21%, 5.21% and 2.17% respectively. Oxidative burst assay showed anti-inflammatory potential of Yucca elephantipes roots 74.58±0.32% with IC50 of 15.3±2.2µg/mL as compared to Ibuprofen with percentage of inhibition 73.20±0.17% and IC50 was 11.2±0.98µg/mL. Fortunately, less than 8g/kg dose of the Yucca elephantipes roots found safe in albino rats. Interestingly, in-vivo carrageen an induced paw edema method proved its anti-inflammatory potential at dose 100 and 200mg/kg in albino rats. Conclusively, 200mg/kg dose of Yucca elephantipes roots extract was optimized for 88.89±0.015% anti-inflammatory effect which can be considered most potent, safe and better alternative of synthetic drugs.

Diagnostic accuracy of SPECT and PET myocardial perfusion imaging in patients with left bundle branch block or ventricular-paced rhythm.

BACKGROUND: The difference in diagnostic accuracy of coronary artery disease (CAD) between vasodilator SPECT and PET myocardial perfusion imaging (MPI) in patients with left bundle branch block (LBBB) or ventricular-paced rhythm (VPR) is unknown. METHODS: We identified patients with LBBB or VPR who underwent either vasodilator SPECT or PET MPI and subsequent coronary angiography. LBBB/VPR-related septal and anteroseptal defects were defined as perfusion defects involving those regions in the absence of obstructive CAD in the left anterior descending artery or left main coronary artery. RESULTS: Of the 55 patients who underwent coronary angiography, 38 (69%) underwent SPECT and 17 patients (31%) underwent PET. PET compared to SPECT demonstrated higher sensitivity (88% vs 60%), specificity (56% vs 14%), positive predictive value (64% vs 20%), negative predictive value (83% vs 50%), and overall superior diagnostic accuracy (AUC .72 (95% CI .50-.93) vs .37 (95% CI .20-.54), P = .01) to detect obstructive CAD. LBBB/VPR-related septal and anteroseptal defects were more common with SPECT compared to PET (septal: 72% vs 17%, P = .001; anteroseptal: 47% vs 8%, P = .02). CONCLUSIONS: PET has higher diagnostic accuracy when compared to SPECT for the detection of obstructive CAD in patients with LBBB or VPR.

Left atrial appendage myxofibrosarcoma: A rare masquerader of myxoma and thrombus-"all that glitters is not gold".

Left atrial appendage mass can occasionally pose a serious challenge to physicians to identify the nature of the mass with the aid of imaging techniques. We present a case of 67-year-old man, who was evaluated for suspected left atria myxoma. Transesophageal echocardiography revealed a heterogeneous density originating from left atrial appendage, thought to be most consistent with a myxoma. Cardiac magnetic resonance imaging, uncharacteristically, gave an equivocal picture, suggesting the mass to be a myxoma on initial imaging and a thrombus with evidence of liquefaction necrosis following postcontrast enhancement. Surprisingly, histopathology of the mass following its surgical excision yielded a rare diagnosis of myxofibrosarcoma.

Efficacy And Safety Of Interlocked Intramedullary Nailing For Open Fracture Shaft Of Tibia.

BACKGROUND: Due to increasing population and changing human habits the number of accidents and high energy trauma is rising. Management of open fracture tibia is a complex problem and is a challenge for both orthopaedic and plastic surgeons. The study was carried out to ascertain the efficacy and safety of interlocked intra-medullary nailing for open shaft tibial fractures in patients presenting at or after 24hr of injury. METHODS: In this descriptive case series, over a period of 6 moths, 163 consecutive cases of open fracture of tibial shaft were reviewed in terms of clinical profile, time of presentation, and gender distribution. RESULTS: In this study mean age was 30±0.02 years. Males comprised 85% of study population while 15% were females. Gustilo-I type fracture and Gustilo-II type fracture was diagnosed in 90% and 10% patients respectively. Thirty three percent patients had wound infection while fracture union was found in 15% cases. Moreover interlocked intramedullary nailing for open fracture shaft of tibia was safe in 80% patients while this procedure was effective in 85%. CONCLUSIONS: Un-reamed, interlocked intra-medullary nailing may be considered as a suitable option for treatment of open fractures of tibia.

Outcome of ilizarov fixator in complex non-union of long bones.

OBJECTIVE: To evaluate the efficacy of Ilizarov fixator in the management of complex non-union of long bones. METHODS: The retrospective study was conducted at Ayub Teaching Hospital, Abbottabad, and Khyber Teaching Hospital, Peshawar, Pakistan, and comprised data of patients aged 14- 60 years of either gender with complex non-union of long bones between January 2006 and December 2013. Data, including age, gender, mechanism of injury, type of long bone involved, complications of surgery and final outcome, was documented on a pre-designed proforma. Outcome was graded using Association for the Study and Application of Methods of Ilizarov scoring system. SPSS 20 was used for analysis. RESULTS: There were 45 patients of whom 30(66.7%) were males and 15(33.4%) were females. The overall mean age was 32.20±12.48 years (range: 14-60 years).Of the 45 non-unions, 39(86%) healed successfully, and the mean time to union was 30.69±8.6 weeks (range: 16-52weeks).In terms of outcome, 29(64.44%) patients had excellent bone results, 9(20%) had good results, 2(4.44%) had fair results and 5(11.1%) had poor bone results. There were 32(71.11%) patients with excellent functional result, 8(17.77%) good, 2(4.44%) fair and 3(6.66%) patients had poor results. CONCLUSIONS: Ilizarov fixator gave good and excellent results in complex non-union of long bones by eradicating the infection, filling the defect with bone transport, and correcting the deformity and limb length discrepancy.

National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma.

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.

Changing trends of hepatitis B seromarkers amongst Pakistani population: a laboratory-based review.

OBJECTIVE: To study the changing trends of hepatitis B markers tested at Aga Khan University Hospital clinical laboratory according to the internationally recognised classification of hepatitis B profile. METHODS: The retrospective study involved analysis of laboratory records of hepatitis B profiles of all patients collected from January 2001 to December 2008 at the Aga Khan University Hospital's clinical laboratory. Patients with complete profile tested were categorised according to the Centre for Diseases Control classification of hepatitis B profile. SPSS 16 was used for statistical analysis. RESULTS: A total of 185,825 patients had serological markers for hepatitis B tested. Mean-age of reactive hepatitis B surface antigen (HBsAg) patients was 30+/-12.5 years. HBsAg reactivity was significantly higher in males than females (34% vs 12%; p <0.0001). HBsAg showed a slight decline in the percentage reactivity during the 8-year study period, while a gradual increase in hepatitis B surface antibody (HBsAb) reactivity was observed. Of the total, 23% patients belonged to the 'susceptible to infection' category; 39% patients were classified as 'chronically-ill'; 12% patients were categorised as 'immune due to hepatitis B vaccination. 3% patients were classed as 'acutely infected'. Overall, samples received from Peshawar, Quetta and Larkana showed very high reactivity rates. CONCLUSION: The study substantiated the general perception that levels of HBsAg is showing a decreasing trend, while levels of HBsAb are increasing perhaps due to better vaccination of population.

Numerical solution of heat and mass transfer using buongionro nanofluid model through a porous stretching sheet impact of variable magnetic, heat source, and temperature conductivity.

Fluid flow chronologically is widely recognized due to its various uses in turbines, the framework of spinning magnet stars, gyromagnetic generators, and chemical engineers observing the progression of petroleum through the aquifer, and blood vessels in the respiratory alveolar plate. Tropical cyclones, pools of water, and storms all exhibit rotational movement. The current investigation aims to analyse the micro polar fluid flow between two infinite vertical discs enclosing Hall impact, varying thermal conductivity, heat flux as well as anomalous heat generation. The implication of a chemical change combined with chemical potential improves mass propagation. Suitable similarity conversions are used to convert the defined problems into conventional differential equations (ODEs). Furthermore, by introducing new variables the ODEs are transformed into nonlinear coupled ODEs and then solved numerically by the RK 4th order along with the shooting technique. The velocity profiles decrease as suction parameter increases. The temperature field exhibits a rising behaviour for the increasing values of thermophoresis, Brownian and radiations parameters while the concentration field shows a decreasing behaviour. Shear stress at the upper wall increases when the rotation variable and suction variable are augmented. Heat transmission escalations at the bottom wall when Prandtl number and radiation factor are enhanced. The novelty of the present work is to examine the Buongionro model in the presence of a heat source and chemical reaction inside the Darcian porous rotating channel, which has not been investigated yet. In some limiting cases, a comparison of the on-going study with existing literature is also included to justify the contemplated problem.

Acute Hypoxia From Different Clinical Entities Can Potentially Break the Heart: Takotsubo Cardiomyopathy.

Takotsubo syndrome is characterized by transient regional left ventricular wall motion abnormalities and elevated troponin levels like those seen in classic myocardial infarction but without evidence of obstructive coronary artery disease. We present two uncommon cases of Takotsubo syndrome. In Case 1, a 64-year-old man presented with chronic obstructive pulmonary disease exacerbation who later developed chest pain and acute hypoxic respiratory failure. In Case 2, a 77-year-old woman with myasthenia gravis was admitted for acute hypoxic hypercapnic respiratory failure requiring mechanical ventilation following a myasthenic crisis. In both cases, serum high sensitivity troponin was elevated, electrocardiograph showed findings suggestive of infarction, and coronary angiogram did not show evidence of obstructive coronary artery disease. Echocardiogram in both patients revealed abnormal left ventricular wall motion, likely secondary to Takotsubo syndrome. Takotsubo syndrome is uncommon in the setting of chronic obstructive pulmonary disease exacerbation or myasthenic crisis, and proposed mechanisms for the disease include catecholamine surge, vasospasm of coronary arteries, and microvascular dysfunction. Takotsubo syndrome is reversible; thus, it is important to remove any trigger leading to catecholamine surge. Identification of such triggers and early diagnosis could help optimize pharmacotherapy.

Clinical characteristics and predictors of positive stool culture in adult patients with acute gastroenteritis.

OBJECTIVE: To identify the presenting features and spectrum of pathogens in adult patients with acute diarrhoea and to determine the predictors of stool culture positivity. METHODS: A descriptive study was conducted in a tertiary care hospital from April 1, 2005 to March 31, 2006. Medical records of all consecutive adult patients with history of acute diarrhoea were reviewed between June 2006 to December 2006 for clinical characteristics and laboratory investigations. RESULTS: A total of 454 patients were admitted from April 1, 2005 to March 31, 2006. Stool cultures were performed in 233 (50%) patients, 96 (42%) had positive results. Patients with positive stool culture compared to a negative Culture were found to have a younger mean age (43 vs. 53), greater number of unformed stools (16 vs. 11) and low serum bicarbonate level (16 vs. 20). Vibrio cholerae (86%) was found to be the most prevalent organism followed by Salmonella spp (6%), Campylobacter spp (5.2%), Shigella spp (2%). Ciprofloxacin was given to 97% patients along with fluid administration, and 78% were found to be resistant to quinolones. Most patients recovered before the finalized stool culture results. CONCLUSION: Careful selection of the patients based on their clinical presentation and initial laboratory work up can help to decide ordering of stool culture in adults with diarrhoea. Fluid resuscitation remains the main stay of treatment.

Successful emergency transcatheter aortic valve replacement in the setting of hemodynamically unstable prosthetic aortic valve stenosis.

FDA approved transcatheter aortic valve replacement (TAVR) for the treatment of symptomatic aortic valve (AV) stenosis. Recent evidence reveals that TAVR is the treatment of choice in most patients with AV stenosis who are at high risk for surgical aortic valve replacement (SAVR). Per AHA guidelines, repeat valve replacement has been recommended for bio-prosthetic AV stenosis. Urgent TAVR for hemodynamically unstable patients with prosthetic AV stenosis is not supported by significant scientific data. However, there have been a few cases reported on emergency TAVR procedures in hemodynamically unstable patients with severe native AV stenosis. We are reporting a unique case of successful emergency TAVR in a hemodynamically unstable patient, who had severe symptomatic bio-prosthetic AV stenosis at the time of presentation.

When nerves fail: A cause of respiratory failure in a diabetic patient.

Background: Respiratory failure secondary to bilateral diabetic phrenic neuropathy is an uncommon clinical scenario. It is challenging to treat and often results in the need for long-term respiratory support. Case Presentation: We report a patient with long standing diabetes mellitus (DM) who presented with respiratory failure requiring mechanical ventilation. He was subsequently found to have reduced phrenic nerve and diaphragm compound action potential amplitude bilaterally on nerve conduction studies. Conclusion: Diabetic patients with unexplained shortness of breath should raise suspicion for diaphragmatic paresis from phrenic neuropathy.

The Novelty of Icosapent Ethyl in the Management of Hypertriglyceridemia and Alleviating Cardiovascular Risk.

Hypertriglyceridemia is believed to be independently associated with an elevated risk of cardiovascular disease (CVD) events. Lifestyle changes and dietary modifications are recommended for individuals with high serum triglyceride (TG) levels (150-499 mg/dl), and pharmacological therapy in addition to lifestyle modification is recommended when serum TG levels ≥ 500 mg/dl. A residual cardiovascular risk remains even in statin appropriate treated patients with CVD risk factors, and in this patient population, hypertriglyceridemia poses an independent and increased risk of ischemic events. In December 2019, the US FDA approved icosapent ethyl (IPE) as an adjunct to a maximally tolerated statin to reduce the risk of CVD events in adults with serum triglycerides > 150 mg/dl and have either established cardiovascular disease or diabetes and two or more additional CVD risk factors. Since IPE significantly decreases total ischemic events in the aforementioned patient population, it would be intriguing to know whether IPE alone added an advantage to lifestyle modification in the low-risk population, who has serum triglyceride between 150 mg/dl and 499 mg/dl.

Incremental prognostic value of visually estimated coronary artery calcium in patients undergoing positron emission tomography imaging.

OBJECTIVE: Visually estimated coronary artery calcium (VECAC) from chest CT or attenuation correction (AC)/CT obtained during positron emission tomography (PET)-myocardial perfusion imaging (MPI) is feasible. Our aim was to determine the prognostic value of VECAC beyond conventional risk factors and PET imaging parameters, including coronary flow reserve (CFR). METHODS: We analysed 608 patients without known coronary artery disease who underwent PET-MPI between 2012 and 2016 and had AC/CT and/or chest CT images. We used Cox regression to estimate the association of VECAC categories (≤10, 11-400, >400 Agatston units (AU)) with the primary outcome of all-cause death, acute coronary syndrome or stroke (mean follow-up 4.3±1.8 years). C-statistics assessed the relationship between PET parameters and VECAC with the primary outcome. RESULTS: Mean age was 58±11 years, 65% were women and 67% were black. VECAC ≤10, 11-400 and >400 AU was observed in 68%, 12% and 20% of subjects, respectively. Compared with VECAC ≤10, VECAC categories 11-400 (HR 2.25, 95% CI 1.24 to 4.08) and >400 AU (HR 3.05, 95% CI 1.87 to 4.98) were associated with the primary outcome after adjusting for traditional risk factors, MPI findings and CFR. Adding VECAC to a model that included PET-MPI, CFR and clinical risk factors improved the prognostic value for the primary outcomes (c-statistic 0.71 to 0.75 with VECAC, p=0.01). CONCLUSIONS: VECAC is a potent predictor of events beyond traditional risk factors and PET imaging markers, including CFR. These data further support the importance for routine VECAC implementation.

Single or Combined Applications of Zinc and Multi-strain Probiotic on Intestinal Histomorphology of Broilers Under Cyclic Heat Stress.

Two-hundred-eighty-day-old broiler chicks were divided into seven groups. The groups were designated as T1, thermoneutral zone; T2, heat stressed (HS); T3, HS + zinc (Zn) supplementation (30 mg/kg); T4, HS + Zn (60 mg/kg); T5, HS + probiotic (0.1 g/kg); T6, HS + probiotic (0.1 g/kg) + Zn (30 mg/kg); and T7, HS + Zn (60 mg/kg) + probiotic (0.1 g/kg). Significant decrease (p < 0.05) was observed in villus height (VH), VH to crypt depth ratio, and villus surface area of all intestinal segments in the T2 group when compared with the T1 group. The same parameters had significantly higher (p < 0.05) values in the jejunum and ileum of the Zn- and probiotic-supplemented groups (alone + combination) when compared with the T2 group. The birds exposed to HS showed fewer (p < 0.05) intraepithelial lymphocytes (IELs) in the jejunum and ileum than the T1 group, while their count increased in the jejunum and ileum with dietary treatments. In conclusion, Zn and probiotic positively modulated the intestinal microstructures of broilers kept under high environmental temperature.

Antimicrobial resistance profile of methicillin resistant staphylococcal aureus from skin and soft tissue isolates.

OBJECTIVES: To evaluate resistance rates in methicillin resistant Staphylococcus aureus (MRSA) against clindamycin, cotrimoxazole, tetracycline, fusidic acid, rifampicin and chloramphenicol isolated from skin and soft tissue infections (SSTI). METHODS: Descriptive analysis of SSTI samples yielding MRSA in clinical laboratory of a tertiary care center; receiving specimens across Pakistan from January 2005 to June 2007. MICROBIOLOGICAL METHODS: MRSA were identified using standard microbiological techniques. Susceptibility testing was performed by disc diffusion according to Clinical Laboratory Standards Institute (CLSI) against fusidic acid, tetracycline, cotrimoxazole, clindamycin, rifampicin and chloramphenicol. Minimum inhibitory concentrations (MIC) of rifampicin were determined using agar dilution method according to CLSI. RESULTS: During the study period 501 MRSA were isolated from SSTI. Overall variable susceptibility pattern with high resistance rates to tetracycline (82%), clindamycin (79%), cotrimoxazole (59%), and rifampicin (50%) were observed. Resistance to chloramphenicol (10%) and fusidic acid (9%) was low. CONCLUSION: There is a strong need in resource limited countries to review the utility of conventional antibiotics for the management of MRSA SSTI as new agents are expensive and not available. High resistance rates were observed against cotrimoxazole, tetracycline and clindamycin. Resistance to fusidic acid, rifampicin and Chloramphenicol was low.

Outbreak of dengue fever in Karachi 2006: a clinical perspective.

OBJECTIVE: This study reports clinical manifestations and spectrum of severity of dengue fever (DF), dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) in adult patients admitted during 2006 outbreak in Karachi. A rough estimation of cost of care was also calculated. METHODS: A cross-sectional study was done at a tertiary care hospital in Karachi from January to December 2006. Patients suspected of having DF with positive dengue IgM antibodies were included and records were reviewed. Patients were divided into DF, DHF and DSS as per WHO classification, and the severity of clinical manifestations was determined. RESULTS: A total of 278 (65.72%) of 423 patients admitted with suspected dengue illness had positive IgM titer. Mean age was 31 +/- 12.9 years, with 168 (60%) males and 110 (40%) females. Common presenting symptoms were fever (100%), vomiting (78%), epigastric pain (52%), bleeding tendencies (34%), and erythematous rash (33%). Thrombocytopenia (60%), Leucopenia (45%), elevated transaminases (ALT 71%; AST 88%), and deranged PT (22%) and aPTT (75%) were the predominant. Laboratory parameters: DF was diagnosed in 169 (61%) patients, 82 (29%) were classified as DHF, and 27 (10%) as DSS. Patients with DHF/DSS were younger <30 years (n=60, 55%) and had longer hospital stay (p=0.001). Case fatality rate for DHF/DSS group was 4.6%. CONCLUSION: It was estimated that endemicity of DF is on the rise in Karachi and a significant proportion of patients had DHF and DSS. Younger patients develop DHF and DSS and have high case fatality rate.