Homozygous mutations in NTRK1 gene underlie congenital insensitivity to pain with anhidrosis in Pakistani families

Congenital insensitivity to pain with anhidrosis is a rare autosomal recessive disorder presenting with loss of pain sensation, thermal sensation defects, and self-mutilating behavior. In the present study, we recruited two consanguineous pedigree showing pain insensitivity symptoms from Pakistan for clinical and molecular investigations. In family A, one female patient displayed classical CIPA symptoms along with microcephaly and severe intellectual disability. During course of the disease, her right foot was amputated and had remarkable dental degeneration and teeth shedding. In family B, one boy presented with classical symptoms of congenital insensitivity to pain with anhidrosis. Blood was collected from both families for molecular studies. Sequencing with the Ilumina Trusight One Sequencing Panel covering 4813 OMIM genes revealed a known homozygous mutation c.2084C>T; p.P695L of NTRK1 in family A and a novel truncated mutation c.2025C>G; p.Y681X in family B. Protein modeling analysis of both mutations (p.P695L and p.Y681X) predicted loss of the rigidity in tyrosine kinase domain of NTRK1 that led to conformational changes as well as deleterious effect on protein function. The known mutation was reported more than a decade ago in a family from Northern Israel and other non-sense mutation is newly identified. It is interested that most of NTRK1 mutations are associated with this domain. This is first ever report of NTRK1 variants in congenital insensitivity to pain with anhidrosis patients from Pakistan.

Prevalence of resistance to 1[st] line anti tuberculosis drugs at Rahim Yar Khan

Background: tuberculosis is an important infectious health issue and its control strongly rely upon effective treatment. The drug resistance and its pattern are important determinant of the treatment regimen, its duration and outcome

Objective: to determine the frequency and pattern of drug resistance among 1[st] line anti tuberculosis treatment

Methodology: it was a cross sectional study carried on 100 cases of smear positive TB. This study was conducted from 1[st] January 2010 to 30 June 2011. Detailed demographic data and history of ATT was taken and their sputa were sent for drug susceptibility testing on LJ media. The cases with drug resistance and no previous history of ATT were labeled as primary while those with previous history of ATT were labeled as secondary resistant cases. The data was entered and analyzed by using SPSS version 15

Results: out of 100 patients enrolled, drug susceptibility report was available for 87 isolates as sputum failed to grow any organism in 13 patients. Out of these 87 cases, 48 [55.17%] were males and 39 [44.83%] females with age range of 9-91 years. Seventeen out of 87 patients [19.5%] had previous history of ATT. Out of 87 isolate, 62 [71.26%] were sensitive to all 1[st] line drugs [R, H, E, Z, S] while 25 [28.74%] were resistant to one or more drugs. Primary resistance was seen in 17 [24%] out of 70 cases in contrast to secondary in 8 [47%] out 17. The difference between primary and secondary resistance among various drugs was statistically significant for isoniazid [p value 0.003] and pyrazinamide [p value 0.036] while the difference to streptomycin, ethambutol and rifampicin was insignificant with p values of 0.20, 0.35 and 0.09 respectively. There was no case of primary MDR-TB and 5.9% of secondary MDR-TB. None of the sociodemographic parameter was significantly associated with drug resistance

Conclusion: resistance to 1[st] line anti-tuberculosis drugs at Rahim Yar Khan is still common. There are good number of patients in which this resistance pattern compromise the currently recommended regimens. However, larger surveillance studies are needed to strengthen this evidence

Susceptibility pattern of 2[nd] line anti tuberculosis drugs at Rahim Yar Khan

Background: Pakistan has a high burden of drug resistant TB. Effective management of these cases needs the inclusion of 2[nd] line anti-tuberculosis drugs. A comprehensive knowledge of susceptibility pattern to these drugs is mandatory to formulate the best possible regimen

Objective: to determine the susceptibility pattern of 2[nd] line anti tuberculosis drugs

Methodology: this cross sectional study was carried out at Department of Pulmonology, Sheikh Zayed Medical College / Hospital, Rahim Yar Khan on smear positive cases of PTB. This study was conducted from 1[st] March 2010 to 30[th] April 2011. A total of 64 smear positive tuberculosis patients of any age and sex regardless of previous treatment with 1[st] line ATT and no history of prior exposure to 2[nd] line ATT were included. Sociodemographic data like age, sex, marital status and income were recorded. Early morning sputum samples were cultured on LJ medium at a reference lab. Drug susceptibility testing [DST] was done for ethionamide, amikacin, kanamycin, capreomycin and ofloxacin to determine the presence of resistance. The data was analyzed on SPSS version 15

Results: in this study, out of total 64 cases, 36 [56.25%] were males and 28 [43.75%] females with age range of 9 to 76 years. Thirteen cases [20.31%] had previous exposure to 1[st] line ATT. Twelve [18.8%] were resistant to one or more drugs. Resistance was highest for ofloxacin [14.1%] followed by ethionamide [6.3%], capreomycin [3.1%], amikacin [1.6%] and kanamycin [1.6%]. Sociodemographic characteristics also did not show any statistically significant association with drug resistance

Conclusion: there is high frequency of resistance to ofloxacin and ethionamide. To avoid addition of further resistance, DST should be available as early as possible by conventional methods or by rapid genotypic methods at the start of treatment

Factors affecting sputum smear conversion time in newly diagnosed pulmonary tuberculosis patients

Background: Patients having tuberculosis are registered in the TB DOTS program for their treatment. During the treatment sputum samples are sent periodically to the laboratory to check treatment efficacy. Usually after two months of treatment sputum smear becomes negative but presence of multiple cavities in the lung, bacillary load, diabetes mellitus and tobacco smoking, slows the sputum smear conversion time

Objectives: To determine the factors affecting sputum smear conversion time in newly diagnosed pulmonary tuberculosis patients

Study design, settings and duration: This cross sectional, analytical study was done by Pakistan Medical Research Council, TB Research Centre in collaboration with Institute of TB and Chest Medicine King Edward Medical University/Mayo Hospital, Lahore from April 2013 to March, 2014

Patients and Methods: All newly diagnosed pulmonary tuberculosis patients who were registered and given treatment by the DOTS program were included in the study. All patients underwent sputum smear microscopy along with Complete Blood Count and ESR at the time of enrollment. The patients were followed for next 6 months while on treatment. Sputum samples were tested at 2[nd] and 6[th] month to check the sputum conversion rate and indirectly to see the efficacy/compliance to treatment

Results: A total of 400 patients were enrolled with slightly more males [52%] as compared to females [48%]. Smear became negative within two months of starting treatment in 85.7% patients while in 14.2% it remained positive at 2[nd] and 6[th] months of therapy. There were more females [10.7%] whose sputum smear did not became negative as compared to males [3.5%]. Predominant factors affecting sputum smear conversion were low resistance, raised initial bacillary load, decreased hemoglobin level, and long duration of symptoms at the time of diagnosis

Conclusion: Factors like low resistance, high initial bacillary load and decreased hemoglobin levels affect the sputum smear conversion and should be addressed while assessing efficacy of anti-tuberculosis treatment

Post poliomyelitis syndrome: a rare sequel of acute poliomyelitis

Post poliomyelitis syndrome [PPS] is a rare sequel of acute poliomyelitis, usually seen 30-40 years after an acute episode. It is characterized by new muscle weakness seen in survivors of acute poliomyelitis. We describe a rare case of a 50 year old man; with a previous history of poliomyelitis in right lower limb who now presented with complaints of progressive left lower limb weakness for past two years. The diagnosis was made on the basis of clinical suspicion and EMG findings. PPS is not a well recognized disease in Pakistan and due to the lack of documentation; its true prevalence is not known. Though, over the years, cases of Poliomyelitis have decreased worldwide, however, PPS still remains a constant challenge for the physicians. This report highlights the impact of the disease on the quality of life of patients suffering from PPS and emphasis on the need for new therapeutic approach

Three years audit of maxillofacial trauma at Abbasi Shaheed hospital, Karachi

The purpose of this retrospective study was to analyze the maxillofacial fractures treated during three years period with special attention to the age, causes, fractures pattern, clinical management and treatment modalities. Retrospective study. This study was carried out Oral and Maxillofacial Surgery Department of Abbasi Shaheed Hospital during the period of January 2008 to December 2010 236 Patients data compiled. The data were reviewed and analyzed in terms of age, gender, aetiology, anatomical site and treatment methods. A total of 236 patients were included in this study presenting with maxillofacial trauma out of these 93.6% were males and 6.4% female .Overall male to female ratio was 15:1.The most common age involved was second decade. The most common cause was RTA [82%] followed by fall [7.2%] and then assault [5.5%]. The fracture of the mandible was the most common constituting about [72.5%] of the maxillofacial fractures followed by Zygomaticomaxillary complex [ZMC] fracture [14.4%] and then Maxilla [5.9%]. Regarding treatment more than 50% patients received ORIF [Open reduction Internal fixation] via bone plates while remaining received MMF [Maxillo-mandibular fixation].In ZMC Fracture, Gillies Temporal approach alone is the most common approach accounting 67% of cases while in Le-forte fracture ORIF constitute the most common treatment method. The causes and pattern of maxillofacial fractures reflect trauma patterns within the community and, as such, can provide a guide for the design of programs geared towards prevention and treatment

Persistence of dengue symptoms among discharged dengue cases of Lahore, Pakistan

The signs and symptoms of acute dengue infection are well defined and characterized. However, little data is available about the persistence of these symptoms which depends upon the disease management and patient care. This study was conducted to determine the persistence of dengue symptoms in admitted cases who were discharged from hospital. Data of dengue cases who were admitted in 2 public sector hospitals was retrieved along with their complete addresses. Patients were approached and interviewed after getting the written informed consent. A pre-designed questionnaire was used to collect information about the persistence of dengue symptoms in the patients after they were discharged from hospital. Of 41 cases interviewed, 31 were males and overall mean age was 31 years. The case record showed that 15 cases had dengue shock syndrome, 14 dengue hemorrhagic fever and 12 dengue fever. The average period of illness after getting discharged was 19 days which was significantly higher in females [23 days] as compared to males [18 days]. Majority of the cases [except 04] reported persistence of dengue symptoms in which joint pain [29 cases], itching [17 cases] and exhaustion [14 cases] were more common. The persistence of joint pain after discharge was significantly associated with dengue shock syndrome. The current study showed significant association between joint pain and DSS which could be overcome through proper case management. Furthermore there is a need to follow admitted dengue cases after getting discharged from the hospital to avoid any complications

Lumbar Disc Degenerative Disease: Disc Degeneration Symptoms and Magnetic Resonance Image Findings

STUDY DESIGN: Cross sectional and observational. PURPOSE: To evaluate the different aspects of lumbar disc degenerative disc disease and relate them with magnetic resonance image (MRI) findings and symptoms. OVERVIEW OF LITERATURE: Lumbar disc degenerative disease has now been proven as the most common cause of low back pain throughout the world. It may present as disc herniation, lumbar spinal stenosis, facet joint arthropathy or any combination. Presenting symptoms of lumbar disc degeneration are lower back pain and sciatica which may be aggravated by standing, walking, bending, straining and coughing. METHODS: This study was conducted from January 2012 to June 2012. Study was conducted on the diagnosed patients of lumbar disc degeneration. Diagnostic criteria were based upon abnormal findings in MRI. Patients with prior back surgery, spine fractures, sacroiliac arthritis, metabolic bone disease, spinal infection, rheumatoid arthritis, active malignancy, and pregnancy were excluded. RESULTS: During the targeted months, 163 patients of lumbar disc degeneration with mean age of 43.92+/-11.76 years, came into Neurosurgery department. Disc degeneration was most commonly present at the level of L4/L5 105 (64.4%).Commonest types of disc degeneration were disc herniation 109 (66.9%) and lumbar spinal stenosis 37 (22.7%). Spondylolisthesis was commonly present at L5/S1 10 (6.1%) and associated mostly with lumbar spinal stenosis 7 (18.9%). CONCLUSIONS: Results reported the frequent occurrence of lumbar disc degenerative disease in advance age. Research efforts should endeavor to reduce risk factors and improve the quality of life.

Fulminant variants of multiple sclerosis: local experience at Shifa International Hospital, Islamabad, Pakistan

To report a series of patients with fulminant variants of multiple sclerosis [MS] based on their clinical and radiological features This retrospective study consists of series of four patients with fulminant variants of MS seen between January 2008 and February 2011 at Shifa International Hospital, Islamabad. Pakistan. Out of Four patients, three were females, with mean age of 27 [range 13-40] years. Onset was acute with significant progression over 2 weeks in all cases. Presenting symptoms were hemiparesis and speech difficulty in all patients, 3 had visual impairment, and 2 had headache. CSF pleocytosis and raised CSF protein was seen in 3 patients. Visual evoked potentials were abnormal in one patient. Based on the characteristic MRI findings. 3 patients were diagnosed as Balo's concentric sclerosis and one patient with Marburg's variant of MS. All patients were initially treated with intravenous methylprednisolone followed by immunomodulatory therapy. Two patients received intravenous immunoglobulins [IVIG] and mitoxantrone, one received IVIG only and one received mitoxantrone only. On follow up, all 4 patients had shown marked improvement with independence in activities of daily living. Aggressive treatment with IVIG and mitoxantrone resulted in significant improvement in this small case series. Early and aggressive immunosuppression should be considered in patients with fulminant variants of MS

Acute disseminated encephalomyelitis [ADEM] presenting as a multiphasic encephalopathy: a case report

Acute disseminated encephalomyelitis [ADEM] is one of the demyelinating disorders of central nervous system [CNS] causing acute or relapsing-remitting encephalopathy. We report a male child, who presented with fever, fits and altered sensorium, with two identical events, 3 1/2 months apart. Neuroimaging showed high signal lesions on the T2 weighted images reflecting areas of demyelination and edema, consistent with ADEM. He responded with complete recovery after pulse steroids and intravenous immunoglobulin [IVIG] therapy

Eight episodes of Bell's palsy in an elderly male: a rare presentation

Bell's palsy is a common, idiopathic, lower motor neuron paralysis of the facial nerve. Multiple recurrent episodes, however, are rare. Most recurrent facial palsies are usually attributable to specific organic, environmental or familial causes. The highest number of idiopathic recurrences reported is eleven, while that in Asia is five. We present a unique case of eight relapses of Bell's palsy in an elderly Pakistani male. Extensive work-up failed to reveal a cause for the continued recurrence, which was associated with considerable loss of function over time

Incremental yield of submitting three sputum specimens for the diagnosis of pulmonary tuberculosis

To assess the efficacy and diagnostic yield of third sputum smear among pulmonary TB patients. This retrospective data analysis was done at PMRC TB Research Centre in collaboration with Institute of Chest Medicine, King Edward Medical University/Mayo Hospital Lahore, from January 2010 to December 2011. Patients presenting with respiratory symptoms, having abnormal chest X-rays and having a clinical suspicion of tuberculosis were asked to submit three sputum samples on two consecutive days [1[st]spot, 2[nd]early morning, 3[rd]spot] for acid-fast bacilli smear microscopy. Smears were prepared and stained by Ziehl-Neelsen method. A total of 7785 TB suspects submitted three sputum samples making a total of 23,355 slides for checking acid-fast bacilli using smear microcopy examinations. The smear positivity rate was 11.8%. About 12% suspects fulfilled the case definition of having one positive smear confirmed by a second smear, while, only 2.5% suspects fulfilled the case definition based on third smear in combination with first or second. A total 1164[15%] suspects had at least one positive smear; of these 896[77%] were positive in first smear, 190[16%] were negative in first smear but positive in second and 78[6.7%] were positive in third smear after two negative smears. Recently changed WHO criteria for examination of two sputum smears is based on evidences collected from the globe however, for Pakistan the value of third smear which picked almost 7% cases is quite significant and should still be practiced. Checking AFB using 3 sputum smears should still be practiced in Pakistan especially, for those who are initially negative on 2 smears

Possible relation between phenylthiocarbamide taste sensitivity and goitre

The ability or inability to taste the bitterness of phenylthiocarbamide [PTC] is a classic inherited trait that has been studied in relation to various diseases. This study was carried out to find out any possible association between PTC-taste sensitivity and goitre. A total number of 471 subjects were studied. Among them 224 subjects were normal, healthy adults, taken as control and 247 were patients of goitre coming to Nishtar Hospital Multan for treatment. A 0.5% solution of PTC was freshly prepared. A drop of PTC Wution was placed on the dorsum of the tongue and the person was asked to state the taste perceived. Person was asked to spit out the chemical and rinse the mouth with water afterwards. Patients of goitre were clinically diagnosed by inspection and palpation method out of 224 normal healthy adults, 18.3% were non-tasters to PTC. Among 247 patients of goitre 36.84% were non-tasters to PTC. Number of non-tasters was highly significantly [P0 < 001] increased in the goitre patients as compared with the normal subjects. Percentage of non-tasters was non-significantly increased among male patients of goitre as compared with the normal subjects. Among female population, 10.88% of normal healthy females were non-taster to PTC and 37.37% of females having goitres were found to be non-tasters to PTC. Difference was highly significant [P0 < .001]. Female non-tasters to PTC are more prone to develop goitre as compared with the normal healthy females. PTC non-taster status is a vulnerability marker for females

Prevalence of cardiac risk factors in acute ischemic stroke

To determine the prevalence of cardiac risk factors in patients presenting with acute ischemic stroke. We collected retrospective data of all stroke patients more than 16-years of age seen by the neurology section over a two year period [January 1, 2004-December 31, 2005]. Charts having complete history and relevant investigations were reviewed. There were a total of 250 stroke patients with a mean age of 63.3 years. 222 [88.8%] patients had ischemic stroke. 57/222 [25.6%] patients had at least one of the cardiac risk factors for ischemic stroke: 29 [50.8%] had a hypokinetic /akinetic left ventricular segment, 12 [21%] had atrial fibrillation, 7 [12.2%] had mitral annular calcification, 5 [8.7%] had a history of recent myocardial infarction, 3[5.2%] had cardiomyopathy and 1 [1.7%] patient had a mechanical valve. Hypokinetic/akinetic left ventricular segment with or without compromised systolic function was the most prevalent cardiac risk factor of ischemic stroke followed by atrial fibrillation

Genetics of cerebral venous thrombosis

Cerebral venous thrombosis [CVT] is rare compared to arterial causes of stroke. It is often encountered in young patients and may occur in children and neonates. Predisposition to CVT also has a genetic basis and inherited thrombophilias are known to cause 22.4% of the CVT cases. Inherited thrombophilias should be suspected if a patient has recurrent CVT, is less than 45 years age, has a family history of venous thrombosis or has no apparent acquired risk factor. Factor V Leiden [FVL] is the most common genetic risk factor, followed by the prothrombin gene mutation G20210A. Other less common inherited venous thrombophilias include deficiencies of Protein S, Protein C and antithrombin III. FVL, the G20210A prothrombin gene mutation and a deficiency of protein S and C, cause a reduction in the control of thrombin generation. Deficiency of antithrombin causes a decreased neutralization of thrombin. Both these mechanisms are responsible for venous thrombosis. Inherited thrombophilias with concomitant acquired risk factors like surgery, trauma, prolonged immobilization, pregnancy and puerperium, oral contraceptives, antiphospholipid antibodies and hyperhomocysteinemia may increase the risk of CVT manifold. Similarly the co-inheritance of two or more known mutations also increases the risk markedly. FVL, prothrombin G20210A mutation, increased factor VIIIc, protein C and S deficiency and antithrombin III deficiency have all been reported to cause neonatal stroke due to CVT. Maternal and foetal testing is suggested when CVT occurs in neonates

Acquired hepatocerebral degeneration in Hepatitis C infection

Patients with chronic liver disease [CLD] often have neurological sequelae, of which hepatic encephalopathy is the most frequent and reversible. Rare irreversible complications of CLD are acquired [non Wilsonian] hepatocerebral degeneration [AHCD] and hepatic myelopathy [HM]. To our knowledge, AHCD has rarely been reported in patients with hepatitis C virus [HCV] infection. We report a patient with HCV infection who developed AHCD and resulted in serious complications