Homozygous sequence variants in the WNT10B gene underlie split hand/foot malformation

Abstract Split-hand/split-foot malformation (SHFM), also known as ectrodactyly is a rare genetic disorder. It is a clinically and genetically heterogeneous group of limb malformations characterized by absence/hypoplasia and/or median cleft of hands and/or feet. To date, seven genes underlying SHFM have been identified. This study described four consanguineous families (A-D) segregating SHFM in an autosomal recessive manner. Linkage in the families was established to chromosome 12p11.1-q13.13 harboring WNT10B gene. Sequence analysis identified a novel homozygous nonsense variant (p.Gln154*) in exon 4 of the WNT10B gene in two families (A and B). In the other two families (C and D), a previously reported variant (c.300_306dupAGGGCGG; p.Leu103Argfs*53) was detected. This study further expands the spectrum of the sequence variants reported in the WNT10B gene, which result in the split hand/foot malformation.

Disease characteristics and treatment outcome of testicular germ cell tumors treated with platinum-based regimens

Objective: To determine the disease characteristics of testicular germ cell tumor, biochemical/radiological response to chemotherapy and common toxicity profile. Study Design: Case series. Place and Duration of Study: Institute of Nuclear Medicine and Oncology [INMOL], Lahore, from January 2010 to December 2013

Methodology: Fifty-one patients with histologically proven testicular germ cell tumor, who fulfilled the pre-defined eligibility criteria, were selected. Presenting symptoms and disease stage were studied. Patients were staged according to the AJCC 2010 staging criteria and prognosis was classified according to the IGCCCG Classification of Metastatic Germ Cell Cancer. Initial chemotherapy treatment was based upon the International Germ Cell Consensus Classification, 1997. Patients were also evaluated for chemotherapy-induced toxicity based on Common Toxicology Criteria version 4. SPSS version 16.0 was used for statistical analysis

Results: Main presenting symptoms included testicular pain [37.3%], testicular swelling [25.5%], and abdominopelvic pain [11.8%]. Most of the patients had mixed germ cell histology [p<0.001] and presented with advanced disease stage. Out of 51 patients, 41 [80.3%] achieved complete clinical remission after first line chemotherapy. All patients having complete response achieved 2-year survival and 37 [90.2%] had no evidence of recurrent disease. Four patients with recurrent disease achieved complete remission with second line chemotherapy. Five [9.8%] had partial response after first line chemotherapy while 2 [3.9%] progressed on treatment. All patients developed alopecia, 21 [41.1%] experienced other toxicities which were managed symptomatically and with minor dose modifications

Conclusion: Many patients with germ cell tumors presented with pain, and in an advanced stage, with mixed histology. Overall response rate was 90.2% with platinum-based chemotherapy

Erectile dysfunction in patients with nonalcoholic fatty liver disease

Background and study aims: There is a lack of studies on erectile dysfunction [ED] in patients diagnosed with nonalcoholic fatty liver disease [NAFLD]. The present study aimed to estimate the prevalence of ED in patients with NAFLD and to determine the independent predictors of ED in these patients

Patients and methods: We conducted a prospective, hospital-based study of 192 consecutive male patients with NAFLD. All patients underwent clinical evaluation; abdominal ultrasonography; test for viral hepatitis markers; and estimation of liver chemistry panel, complete blood count, prothrombin time, serum lipids panel, serum testosterone, and fasting serum levels of glucose, insulin, and C-peptide

Results: The mean age of the study population was 42.4 +/- 7.7 years [79.1% >/= 40 years]. Of the 192 patients with NAFLD, 88 [45.8%] had ED, 28 [14.6%] had metabolic syndrome, 25 [13%] had type-2 diabetes mellitus [DM], and 131 [68.2%] had insulin resistance [IR]. The mean level of serum testosterone was 3.17 +/- 2.94 ng/mL, while the mean insulin resistance index was 2.9 +/- 1.7. Mild ED [38.6%] was the most frequent grade of ED. Age >/= 40 years [odds ratio [OR] 6.4; 95% confidence interval [CI] 1.7-24.1; p- 0.006], IR [OR 5.9; 95% CI 1.7-20.6; p- 0.005], and low serum testosterone [OR 5.1; 95% CI 1.5-17.1; p- 0.009] were the predictors of ED

Conclusions: ED is a common disorder in male patients with NAFLD; both IR and low serum testosterone contribute to its development. Treatment of IR may carry a dual benefit of improving erectile function and decreasing the grade of hepatic steatosis

Comparison of duration of neuromuscular blockade with atracurium in obese patients

Objective: To compare the mean duration of atracurium induced neuromuscular blockade in minutes when dosed according to real body weight [RBW] or ideal body weight [IBW] to obese patients undergoing abdominal surgeries under general anesthesia

Study Design: Randomized controlled trial

Place and Duration of Study: Department of Anesthesiology, National hospital defense Lahore, From March 2015 to March 2016

Material and Methods: One hundred and fifty [150] patients were selected for this study and divided in to two equal groups [75 patients in each group], group-I [experimental group] and group-II [control group]. Sample size was calculated with 80% power of test, 95% confidence interval taking mean and standard deviation of duration of atracurium induced neuromuscular blockade in minutes in both groups i.e. 74.6 +/- 37.56 in real body weight group versus 40.02 +/- 22.5 in ideal body weight group. Non probability consecutive sampling technique was used. SPSS version 16 was used for data analysis. Frequency and percentages were used to present categorical data and mean +/- standard deviation for numerical data. Independent sample t-test was applied to compare the significance of outcome variables. A p-value of <0.05 was considered statistically significant

Results: There was a prolong duration of action in experimental group [real body weight group] 69.64 +/- 3.11 minute versus 46.33 +/- 2.77 minute in control group [ideal body weight group] which suggests that dose of atracurium should be calculated and given on basis of ideal body weight in obese

Conclusion: It was observed in our clinical trial that body weight calculation and dosage of atracurium accordingly has altered duration for recovery from blockade, the results of the study showed that atracurium when used according to ideal body weight as compared to total body weight has reduced duration of action. So atracurium dose should be calculated according to ideal body weight rather than total body weight in obese patients

Hookworm infection among patients with pulmonary tuberculosis: Impact of co-infection on the therapeutic failure of pulmonary tuberculosis

Objective/background: The aim of this study is to determine the rate of hookworm infection among patients with pulmonary tuberculosis [TB] and to find out if there is a relation between hookworm infection and the therapeutic failure of pulmonary TB

Methods: We carried out a prospective, hospital-based study. The study included 231 naive patients with pulmonary TB, consecutively. Patients were evaluated at the 4th month of therapy for persistence of Mycobacterium tuberculosis infection. All patients had clinical evaluation, laboratory investigations [including sputum culture and stool microscopic examination], and imaging studies [abdominal ultrasonography and chest radiography]

Results: The study population mean age was 42.7 +/- 13.9 years old with 26.8% of them 40 years old or more. Out of 231 patients, 133 [57.6%] were men. Therapeutic failure rate of pulmonary TB was 29.4%. Hookworm infection was diagnosed among 16.5% of patients and 27.7% had diabetes mellitus [DM]. Using multivariate analysis, it was found that age of 40 years or more [odds ratio [OR] 8.4; 95% confidence interval [CI] 1.7-41.3; p = .009], hookworm infection [OR 7.6; 95% CI 1.2-49.9; p = .034], and DM [OR 5.9; 1.2-28; p = .027] were independently associated with therapeutic failure of pulmonary TB among the study population with pulmonary TB

Conclusion: In conclusion, the rate of therapeutic failure of pulmonary TB is high. Besides older age and DM, hookworm infection can reduce the therapeutic response of pulmonary TB. Screening for and control of DM and hookworm infection among patients with pulmonary TB may improve their therapeutic response

Triple assessment efficacy in diagnosis of malignant breast lump

To determine the efficacy of triple assessment in diagnosis of malignant breast lumps in female patients taking core biopsy as a gold standard. Breast Clinic, Unit-III, Department of Surgery, Nishtar Hospital, Multan. October 2007 to March 2008. A total 0f 100 patients of breast lump, above the age of 14 years, having palpable lump of any size in breast were selected according to inclusion criteria. Out of 100 patients included in the study most of the patients were in the age group 45-54 years i.e. 46 [46%] followed by 32 [32%] in the age group 35-44 years. According to occupation 67 [67%] were house wives, 13 [13%] were teachers and 5 [5%] were nurses. In 48 [48%] patients the lump size was 2 cm, 35 [35%] patients had lump size from, 2-4 cm while in 17 [17%] patients lump size was > 4 cm. Presenting symptoms like lump was present in 50 [50%] patients, pain alone 25[25%] patients, discharge in 20 [20%] patients and discharge with pain in 5 [5%]. Lymph node status like grade-0 was seen in 60 [60%] patients, grade-1 in 21 [21%] patients, grade-2 in 15 [15%] patients and grade-3 in 4 [4%] patients. Triple assessment is a valuable tool for an accurate non surgical diagnosis of breast lump, allows assessment of breast cancer patient for conservative and neo-adjuvant primary treatment before surgical treatment

Enteric ileal perforation primary repair versus loop ileostomy

Objectives: The aim of this study was to record the outcome of enteric ileal perforation, managed by primary repair versus ileostomy in terms of post-operative complications, mortality rate and hospital stay

Design and Duration: Quasi experimental study from January, 2009 to August, 2010

Setting: Surgical Unit-V, District Headquarters [Teaching] Hospital, Punjab Medical College, Faisalabad

Methodology: During the period of study 46 patients of enteric ileal perforation were divided in two groups on consecutive sampling basis. Detailed data of each patient including presentation, operative findings, procedures performed, post-operative outcome and histopathology was entered on a specially designed proforma. The main outcome measures found significant were post-operative complications, hospital stay and mortality rate. The data was compiled and analyzed by using SPSS-1B

Results: 46 Patients of enteric ileal perforation were studied during the period of 20 months, divided equally in 2 groups, Group A [loop ileostomy] and Group B [primary repair]. An increased rate of post-operative complications was seen in Group B [primary repair] when compared with Group A [loop ileostomy] with 21.74% patients landed up in peritonitis secondary to leakage from primary repair and 17.39% ended up with controlled feacal fistula formation. Mortality rate was twice higher in Group B [primary repair] when compared with Group A [loop ileostomy]. A ratio of 1:2.75 days was observed between hospital stay of Group A [loop ileostomy] to Group B [primary repair]

Conclusion: Enteric ileal perforation still represents a disastrous complication of enteric fever and constitutes a good number of patients presenting in surgical emergency with acute abdomen. Exteriorization of perforation in the form of loop ileostomy is more appropriate option for such patients as compared to primary repair of the perforation when compared in terms of postoperative complications, hospital stay and mortality rate

Incidence of abdominal tuberculosis in 186 cases of acute abdomen presenting in our surgical emergency department

Among 186 cases of Acute Abdomen, determining the frequency of abdominal tuberculosis patients with their outcome. A prospective case study from January, 2009 to June 2010. Surgical Unit-V District Headquarters [Teaching] Hospital, Faisalabad. Detailed data of each patient including presentation, operative findings, procedure performed, post operative outcome and histopathology was entered on a specially designed Performa, compiled and analyzed. During the period of study, 186 patients presented in the surgical emergency with complaints of acute abdomen out of which 54 [29.03%] were of abdominal tuberculosis. Mean age of presentation was 27.3 years. Operative findings showed predominance of ileocaecal hypertrophic tuberculosis [tuberculous mass] in 18 [33.33%] patients, followed by tuberculous adhesions, ileal strictures and plastic gut.The surgical procedures were performed according to their intra-abdominal findings out of which right hemicolectomy with ileocolic end to end anastomosis in 18 [33.33%] patients remained the commenest procedure performed followed by segmental ileal resection anastomosis, ileostomy and stricturoplasty. 20 [37.04%] patients reported to have post-operative complications in which wound infection in 7 [12.96%] remained the highest occurring postoperative complication followed by intra-abdominal collection, anastomotic leakage and septicemia. Mortality rate among the patients of abdominal tuberculosis in this study remained 5.56%. Complicated abdominal tuberculosis is the most common pathology of acute abdomen. By proper management of pre-complicated abdominal tuberculosis, this disastrous stage of disease resulting in so morbidity and mortality can be reduced

Diabetic nephropathy

Diabetic Nephropathy is the main cause of mortality in approximately 40-45% of all Insulin-dependent diabetics, appearing between 10th 30th years of onset of diabetes [1, 24, 28] with a suggested male preponderance [24]. Non Insulin-dependent diabetics are also affected by this sinister complication but the incidence is lower and other complications of diabetes dominate over it as cause or mortality. The intensity of problem can be well imagined by the fact that in United States 25% of total end-stage renal disease id due to diabetes costing about one dollars each year [I] while in U.K 11.1% of total intake of ESRF patients accepted for renal replacement therapy was due to diabetic nephropathy in 1984 and this proportion is rising [28] and in Europe 10% of annual intake have ESRF due to Diabetes