Novel deleterious mutation in MYO7A, TH and EVC2 in two Pakistani brothers with familial deafness

Objective: In Pakistan, 74% of consanguineous marriages are among the first cousins. Continuity of consanguineous marriages over generations increases the risk of recessive diseases such as deafness. The objective of this study was to investigate genetic origin of Pakistani deaf brothers with parents of consanguineous marriage

Methods: DNA was extracted from the blood through Qiagen kit. Paired-end sequencing library was prepared according to protocol of Illumina's TruSight Rapid Capture kit and TruSight Inherited Disease Panel. Library was normalized and used for Next Generation Sequencing through MiSeq. NGS data were analyzed using various bioinformatics tools

Results: Both brothers were found to have novel deleterious mutation in MYO7A [c.2476G>A] while the younger brother had additional novel deleterious mutation in TH [c.43C>T] and EVC2 [c.2614C>T] genes

Conclusion: It is concluded that in addition to novel mutations in MYO7A, TH and EVC2, the CDH23 and GJB2 can also be responsible for deafness in the family with consanguineous marriages.

Synthesis of drug metal complexes and their influence on human platelet aggregation

During the past few decades the emergence of inorganic medicinal chemistry has been developed novel therapeutic agents. Researcher's perseverance in this branch of chemistry has led them to explore further valuable chemical spaces by synthesizing metal complexes already known pharmacological agents for their potential use. However, it is in its early stage, this methodology has demonstrated metal complexes with better bioactivities than the parent ligand molecules. In this study, transition metal complexes of pyrazinamide [PZ], isoniazid [INH], fluconazole [FCZ], metformin [dimethylbiguanide, DMBG] and losartan potassium [LS-K] were selected to evaluate for their possible anti-platelets aggregation in the light of reports on divalent and trivalent cations like calcium, copper, manganese, magnesium, and cadmium may influence the process of thrombocytic activity and aggregation. The required evaluation was carried out on human plasma through an APACT 4004 platelet aggregation analyzer. Arachidonic acid [ADP] was used to gauge any alteration in platelet shape and aggregation process. The parent drugs showed some antiplatelets aggregation, however, their metal complexes demonstrated better efficacy

Paraphenylenediamine poisoning: clinical presentations and outcomes

Background: Paraphenylenediamine [PPD], also known as Kaala pathar, has become an emerging and life threating source of poisoning in Pakistan as well as in many other Asian and African nations. The aim of this study is to recognize the etiological factors, poisoning

Methodology: This observational prospective analytic study included 32 patients who presented in ICU of Nishtar Hospital, Multan. Patients were first managed conservatively by IV fluids, diuretics, antihistamines and steroids; tracheal intubation or tracheostomy was performed only if needed. Univariate analysis was used to determine the independent variables of mortality after PPD poisoning and odds ratios were calculated

Results: Cervicofacial edema, oral erythema and sore throat were most common clinical presentation of patients at the time of admission in ICU, with incidence rates of 93.8%, 81.3% and 75.0%, respectively. Acute renal failure occurred in 34.4% patients and acute hepatitis in 18.75% patients. The independent predictors of mortality after PPD poisoning were: male gender [odds ratio 16.62], dysphagia [odds ratio 9.92], hyperkalemia [odds ratio 84.0], development of cardiogenic shock [odds ratio 36.75], acute renal failure [odds ratio 16.62] and acute hepatitis [odds ratio 27.50]. Tracheostomy was required in all 30 [93.7%], and 13 [40.6%] patients required mechanical ventilation support. In-hospital mortality was 9 [28.1%]. Mean stay of patients in ICU was 3.47+/- 2.04 days

Conclusion: Paraphenylenediamine [Kaala Pathar] poisoning has become one of the major means of suicide attempts with very high mortality rate. Male gender, dysphagia at the time of presentation, hyperkalemia, cardiogenic shock, acute renal failure and acute hepatitis are the independent predictors of mortality after PPD poisoning

Spectroscopic and cytotoxic studies of losartan complexes

Use of drug-metal complexes for the treatment of several human diseases has resulted in significant progress in the field of medicinal inorganic chemistry. The current study describes the synthesis and characterization of Cu [II] and Ni [II] complexes of Losartan, an antihypertensive drug. These complexes were evaluated for their cytotoxic activity against four human cancer cell lines; SNB-19, HCT-15, COLO-205 and KB-3-1. Spectroscopic characterization revealed that during complex formation, the metal was bound through the nitrogen atoms of the tetrazole moiety of the losartan molecule. The molecular formulas of copper [[Cu [LS][2] Cl[2]].6H[2]O] and nickel [[Ni [LS][2]Cl[2]]. H[2]O] complexes were found to be in agreement with the analytical data obtained through elemental analysis. For both the complexes, metal to ligand ratios of 1:2 were calculated. As revealed by FTIR, UV-Visible, and 1H-NMR studies, both the complexes displayed octahedral geometries. Scanning electron microscopy [SEM] revealed marked changes in the morphology of the complexes, compared to the pure drug. From XRD studies, characteristic crystalline peaks of pure losartan were observed whereas no prominent peaks were observed for its complexes. Complexes were found to be inactive in the cytotoxic activity test performed using SNB-19, HCT-15, COLO-205 and KB-3-1 cell lines

Fluconazole and its interaction with metal [II] complexes: SEM, Spectroscopic and antifungal studies

The human digestive tract contains some 100 trillion cells and thousands of species of micro-organisms may be present as normal flora of this tract as well as other mucocutaneous junctions of the body. Candida specie is the most common organism residing in these areas and can easily invade the internal tissues in cases of loss of host defenses. Modifications of previously existing antifungal agents may provide new options to fight against these species. Inorganic compounds of different antifungals are under investigations. Present study report six complexes of fluconazole with Cu [II]], Fe[II], Cd[II], Co[II], Ni[II] and Mn[II] have been synthesized and characterized by elemental analysis, IR, UV and H-NMR. The elemental analysis and spectroscopic data were found in agreement with the expected values as the metal to ligand value was 1:2 ratios with two chlorides in coordination sphere. The morphology of each complex was studied using scanning electron microscope and compared with fluconazole molecule the flaky-slab rock like particles of pure fluconazole was also observed as reported earlier. However, the complexes of fluconazole were showed different morphology in their micrograph. Fluconazole and its complex derivatives have also been screened in vitro for their antifungal activity against Candida albican and Aspergillus niger by MIC method. The complexes showed varied activity ranging from 2-20%

Dentigerous cyst associated with an ectopic maxillary third molar in maxillary sinus: a case report

Ectopic presence of teeth is a rare clinical event. Ectopic maxillary third molar in maxillary antrum may be confused with sino-nasal disease. Dentigerous cyst associated with an ectopic maxillary third molar is a very rare finding

Effect of intraperitoneal instillation of bupivacaine injection in terms of post-operative pain and duration of hospital stay in patients undergoing laparoscopic cholecystectomy

Objective: to assess the outcome of intraperitoneal instillation of bupivacaine injection in terms of post-operative pain [visual analogue score] and duration of hospital stay [in hours] in patients undergoing laparoscopic cholecystectomy

Material and Methods: in this study, a total of 150 patients were recruited after fulfilling the inclusion/exclusion criteria to assess the outcome of intraperitoneal instillation of bupivacaine injection in terms of post-operative pain [visual analogue score] and duration of hospital stay [in hours] in patients undergoing laparoscopic cholecystectomy

Results: most of the patients were between 41-50 years of age, mean age was 39.76+2.31, 44% [n=66] male and 56% [n=84] females. Stay at hospital [in hours] after laparoscopic cholecystectomy showed the 8.67% [n=1 3] stayed <9 hours, 89.33% [n=134] 9-18, 2% [n=3] 18- 24 hours and no patient with >24 hours, 8.67% [n=13] had excellent, 89.33% [n=134] had good and only 2%[n=3] had fair outcome [pain relief]

Conclusion: the assessment of outcome of intraperitoneal instillation of bupivacaine injection in terms of post-operative pain [visual analogue score] and duration of hospital stay [in hours] in patients undergoing laparoscopic cholecystectomy is found considerably good and may be promoted for use in routine clinical practices to make laparoscopic cholecystectomy more safe and effective

Frequency of depression, anxiety and stress in patients referred for endoscopy with symptoms of dyspepsia

OBJECTIVE: This study was aimed to see the frequency of anxiety, depression and stress in patients with dyspeptic symptoms referred for endoscopy

DESIGN: Cross sectional study

SETTING: Department of medicine and psychiatry Baqai Medical University, Fatima hospital, Gadap, Karachi

DURATION: The study was conducted from Jan 2011 to Jun 2011

METHOD: Patients referred from department of medicine with symptoms of dyspepsia were assessed at department of psychiatry Baqai University before endoscopy

A total of 40 patients, fulfilling the inclusion criteria were enrolled for the study and their demographic variables were obtained using a Performa specially designed for this purpose. Urdu version of DASS [Depression Anxiety Stress Scale] was administered to the selected sample to establish the presence of three emotional states--anxiety, depression and stress. The DASS is a 42-item self report instrument designed to measure the three inter-related negative emotional states of depression, anxiety and tension/stress. The findings are mentioned in the results

RESULTS: A total of 40 patients comprising 29 females and 11 males ranging between 15-70 years of age with a mean age of 32.8 years completed the study. In the studied sample of 40 patients, 82.5% had anxiety, 60% had depression and 67.5 % had stress. Moreover 80% of sample group were found to have inflammatory changes on endoscopy and in this group anxiety was the most prominent emotional state. In the remaining 20% who had no inflammatory findings on endoscopy, depression, anxiety and stress were equally prevalent

CONCLUSION: Emotional disturbances in the form of anxiety, depression and stress were frequently seen in patients suffering from dyspepsia and anxiety was the most dominant among these three negative emotional states. Evaluation of anxiety in the management of dyspepsia is suggested

Gestational diabetes mellitus

Gestational diabetes mellitus is common disorder in pregnancy. It is associated with adverse pregnancy out come. There is no consensus regarding the optimal approach to screening of gestational diabetes mellitus. The present study has tried to observe the value of fasting blood glucose in screening of gestational diabetes. To determine the frequency of patients in whom fasting blood glucose and 100gm glucose tolerance show agreement for screening of gestational diabetes mellitus at 24-28 wks. Comparative cross sectional study. The study was conducted at Gynecology and Obstetrics department Shaikh Zayed Federal Post Graduate Institute Lahore. 6 months from 12 Nov 2010 to 11 May 2011. The study included 135 booked patients with positive family history of diabetes mellitus. All patients underwent fasting blood glucose at 24-28 weeks of gestation, regardless of results of fasting blood glucose on next visit they underwent 100g oral glucose tolerance test [OGTT]. The agreement between fasting blood glucose and 100g oral glucose tolerance test was calculated in frequency and percentages. The mean age of women in studied population was 27.15 +/- 3.70. Out of 135 patients 86.7% [117] showed agreement between results of fasting blood glucose and 100g OGTT while 13.31% [18] showed no agreement between both of the tests. Fasting blood glucose is a good screening option for gestational diabetes mellitus along with positive history. It provides a simple, cheap and more practical test for screening of gestational diabetes mellitus. However diagnostic confirmation with 100g OGTT should be done

Impact of cyclosporin immunosuppression on serum magnesium and its fractional excretion in renal transplant recipients

To evaluate the effect of cyclosporine [CSA] on serum magnesium and its fractional excretion in renal transplant recipients. A cross sectional comparative study on 50 live related renal transplant recipients on CSA therapy with serum creatinine <2.0 mg/dl and 30 healthy controls. Serum creatinine, magnesium and its fractional excretion and CSA levels were monitored. Patients were followed at 6 months. The mean serum creatinine in patients was 1.41 +/- 0.42 mg/dl, cyclosporine 210 +/- 66 ng/ml at a dose of 4.8 +/- 1.4 mg/kg/day. The serum magnesium was 1.77 +/- 0.32mg/dl vs 1.98 +/- 0.17mg/dl in healthy controls [p<0.05].Fractional excretion was 5.05 +/- 2.53% in patients vs 2.8 +/- 1.05% in controls [p<0.05]. No correlation was found between CSA levels [100-400 ng/ml] and serum magnesium [r = 0.053] or FEMg% [r = 0.215]. Of the 50 recipients 27 [54%] had FEMg% in the control range. At 6 months follow up no difference in CSA levels was found between recipients with FEMg% in the normal range vs those with FEMg >5%. However, serum creatinine increased from 1.42 +/- 0.30 mg/dl to 1.68 +/- 0.82mg/dl [p< 0.05]. CSA therapy lowers serum magnesium as compared to healthy controls and there is marked increase in FEMg% in 50% of the patients. Patients with FEMg >5% developed renal function deterioration. FEMg% can thus be a good follow up marker of CSA chronic toxicity in stable transplant recipients

Endorsement of Ellis' irrational beliefs as a function of diagnosis

Normal Ss [N=100] as well as patients [N=100] diagnosed as having depressive [N=50] and schizophrenic [N=50] disorders were asked to give their opinions with regard to Ellis' 11 irrational beliefs. The schizophrenic and depressive groups were noted to endorse at least 6 and 4 of the irrational beliefs, respectively, in striking contrast with the normal group who endorsed only one of the beliefs. Thus the data with regard to the two abnormal groups are consistent with rational-emotive theory