Novel biallelic loss-of-function mutations in / 亚洲男科学杂志(英文版)

Multiple morphological abnormalities of the sperm flagella (MMAF) is a specific type of asthenoteratozoospermia, presenting with multiple morphological anomalies in spermatozoa, such as absent, bent, coiled, short, or irregular caliber flagella. Previous genetic studies revealed pathogenic mutations in genes encoding cilia and flagella-associated proteins (CFAPs; e.g., CFAP43, CFAP44, CFAP65, CFAP69, CFAP70, and CFAP251) responsible for the MMAF phenotype in infertile men from different ethnic groups. However, none of them have been identified in infertile Pakistani males with MMAF. In the current study, two Pakistani families with MMAF patients were recruited. Whole-exome sequencing (WES) of patients and their parents was performed. WES analysis reflected novel biallelic loss-of-function mutations in CFAP43 in both families (Family 1: ENST00000357060.3, p.Arg300Lysfs*22 and p.Thr526Serfs*43 in a compound heterozygous state; Family 2: ENST00000357060.3, p.Thr526Serfs*43 in a homozygous state). Sanger sequencing further confirmed that these mutations were segregated recessively in the families with the MMAF phenotype. Semiquantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) was carried out to detect the effect of the mutation on mRNA of the affected gene. Previous research demonstrated that biallelic loss-of-function mutations in CFAP43 accounted for the majority of all CFAP43-mutant MMAF patients. To the best of our knowledge, this is the first study to report CFAP43 biallelic loss-of-function mutations in a Pakistani population with the MMAF phenotype. This study will help researchers and clinicians to understand the genetic etiology of MMAF better.

High burden of subclinical lead toxicity after phase out of lead from petroleum in Pakistan

Objective: To evaluate the frequency of subclinical lead toxicity

Study Design: Cross-sectional study

Place and Duration of Study: Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi, from January 2011 to December 2014

Methodology: Analysis of laboratory data for blood lead levels [BLL] was performed. Lead was tested by atomic absorption spectrometer. For all subjects, only initial test results were included while the results of repeated testing were excluded. Exemption was sought from institutional ethical review committee. BLL of 2-10 ug/dl and 10-70 ug/dl in children and adults, respectively were taken as subclinical lead toxicity

Results: Amongst the total number of subjects tested [n=524], 26.5% [n=139] were children [<16 years] while rest were adults. Overall median BLLs was 6.4 ug/dl [20.9-3.1]. The median BLL was 4 ug/dl [6.7-2.6] in children and 8.3 ug/dl [27.9-3.4] in adults, respectively. The BLL increased with age; higher levels were observed in age range 21-30 years of subjects [median lead level 16.9 ug/dl [36.1-4]] and lower level [4.2 ug/dl [6.8-2.6]] in children with <10 years of age. Only 16% [n=22] children had desirable lead levels while most had either subclinical [76%, n=106] or toxic lead levels [8%, n=11]. In adults, [55%, n=212] subjects had desired lead levels, and 40% [n=154] and 4.99% [n=19] had subclinical and toxic lead levels

Conclusion: Presence of subclinical lead poisoning even after phasing out of lead petroleum in Pakistanis is alarming, especially in children. A national population-based study to determine the lead status and targeted intervention to identify potential sources is need of the time

APACHE II scores as predictors of cardio pulmonary resuscitation outcome: evidence from a tertiary care institute in a low-income country

The aim of this study was to demonstrate that APACHE II scores can be used as a predictor of the cardio-pulmonary resuscitation [CPR] outcome in hospitalized patients. A retrospective chart review of patients admitted, from 2002 to 2007, at the Aga Khan University Hospital, Karachi, was done for this study. Information was collected on 738 patients, constituting all adults admitted in general ward, ICU, CICU and SCU during this time, and who had under-went cardiac arrest and received cardiopulmonary resuscitation during their stay at the hospital. Patient characteristics, intra-arrest variables such as event-witnessed, initial cardiac rhythm, pre arrest need for intubation and vasoactive drugs, duration of CPR and survival details were extracted from patient records. The APACHE II score was calculated for each patient and a descriptive analysis was done for demographic and clinical features. The primary outcome of successful CPR was categorized as survival >24 h after CPR versus survival <24 h after CPR. Multivariable logistic regression was used to assess the association between the explanatory variables and successful CPR. Patients with APACHE II scores less than 20 had 4.6 times higher odds of survival compared to patients with a score of >35 [AOR: 4.6, 95% CI: 2.4-9.0]. Also, shorter duration of CPR [AOR: 2.9, 95% CI: 1.9-4.4], evening shift [AOR: 2.1, 95% CI: 1.3-3.5] and Male patients [AOR: 0.6, 95% CI: [0.4-0.9] compared to females were other significant predictors of CPR outcome. APACHE II score, along with other patient characteristics, should be considered in clinical decisions related to CPR administration

Per-operative findings of blocked ventriculoperitoneal shunt: a study of 72 cases

Most patients with hydrocephalus are treated with ventriculo-peritoneal [VP] shunt placement; however, malfunction is common and is usually caused by mechanical failure. The aim of this study was to evaluate the per-operative findings accompanying presumed VP shunt malfunction. This is a descriptive study of 72 patients operated for shunt malfunction in the Department of Neurosurgery, Postgraduate Medical Institute, Lady Reading Hospital, Peshawar from January to December 2008. Presenting symptoms and signs, clinical shunt function, operative findings and outcome were recorded. Common presenting features were vomiting, irritability and general toxic look of patients. Male to female ratio was 3:1. Upper end block was observed in 39 patients while lower end and reservoir block was noted in 13 and 2 patients respectively. Choroids plexus was found in 29.2% of cases with upper end block, shunt revision was performed in most of cases [80.6%]. The importance of clinical features cannot be overlooked in a patient with shunt malfunction. Upper end block due to choroids plexus is common operative finding

Response of oesophageal strictures to dilatation [Experience at Shaikh Zayed hospital, Lahore]

Out of three thousand patients evaluated for upper G.l. symptoms, forty five patients [1.5%] were found to have oesophageal strictures; 28 benign and 17 biopsy proven malignant strictures-7 adeocarcinoma, 9 squamous cell carcinoma and one lymphoma. Of 28 patients with benign strictures, 15 were due to acid peptic esophagitis, 6 due to intake of corrosive agents, 3 lower oesophageal rings, 3 due to repeated variceal sclerotherapy and one due to radiation. Response to dilatation by peroral bouginage was good in 15 cases [53.57%], satisfactory in 9 cases [32.14%] and poor in 4 patients [14.29%]. No complication, except haemorrhage in one case was noted

Three patients with common bile duct stones treated with endoscopic sphincterotomy [ERS]

Of the 4070 children admitted in the department of pediatrics at Sheikh Zayed Hospital, 830 [24%] presented with diarrhea. Eleven of these [1.3%] were diagnosed as cases of hemolytic uremic syndrome characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure. Only 3 had positive stool cultures [E. coli in 2 and shigella dysenteria in 1]. Two children expired [mortality 18%]. The rest recovered with conservative management and peritoneal dialysis [82%]. This syndrome has not been reported from other centers in Pakistan. It needs to be remembered as a complication of diarrhea and a cause of acute renal failure in children

Acute intermittent porphyria presenting as acute abdomen

The case of a 29 years old lady, who was admitted with frequent episodes of pain, vomiting abdominal distension and constipation has been presented. Having diagnosed as acute abdomen as acute abdomen, exploratory laparotomy was done. The diagnosis of Acute Intermittent Porphyria [AIP] was made, when on 7th post-operative day, she developed flaccid paralysis of all four limbs with normal conscious level. The etiology and pathogenesis of AIP has been discussed with a review of pertinent literature

Acute intermittent porphyria presenting as acute abdomen

The case of a 29 years old lady, who was admitted with frequent episodes of pain abdomen, vomitiny, abdominal distension and constipation has been presented. Having diagnosed as acute abdomen, exploratory laparotomy was done. The diagnosis of Acute Intermittent Porphyria [AIP] was made, when on 7th post-operative day, she developed flaccid paralysis of all four limbs with normal conscious level. The etiology and pathogenesis of AIP has been discussed with a review of pertinent literature