Clinical and biochemical spectrum of hypokalemic paralysis in North: East India

Background:

Acute hypokalemic paralysis, characterized by acute flaccid paralysis is primarily a calcium channelopathy, but secondary causes like renal tubular acidosis (RTA), thyrotoxic periodic paralysis (TPP), primary hyperaldosteronism, Gitelman’s syndrome are also frequent.

Objective:

To study the etiology, varied presentations, and outcome after therapy of patients with hypokalemic paralysis.

Materials And Methods:

All patients who presented with acute flaccid paralysis with hypokalemia from October 2009 to September 2011 were included in the study. A detailed physical examination and laboratory tests including serum electrolytes, serum creatine phosphokinase (CPK), urine analysis, arterial blood gas analysis, thyroid hormones estimation, and electrocardiogram were carried out. Patients were further investigated for any secondary causes and treated with potassium supplementation.

Result:

The study included 56 patients aged 15-92 years (mean 36.76 ± 13.72), including 15 female patients. Twenty-four patients had hypokalemic paralysis due to secondary cause, which included 4 with distal RTA, 4 with Gitelman syndrome, 3 with TPP, 2 each with hypothyroidism, gastroenteritis, and Liddle’s syndrome, 1 primary hyperaldosteronism, 3 with alcoholism, and 1 with dengue fever. Two female patients were antinuclear antibody-positive. Eleven patient had atypical presentation (neck muscle weakness in 4, bladder involvement in 3, 1 each with finger drop and foot drop, tetany in 1, and calf hypertrophy in 1), and 2 patient had respiratory paralysis. Five patients had positive family history of similar illness. All patients improved dramatically with potassium supplementation.

Conclusion:

A high percentage (42.9%) of secondary cause for hypokalemic paralysis warrants that the underlying cause must be adequately addressed to prevent the persistence or recurrence of paralysis.     

Polymorphism in glutathione S-transferases: susceptibility and treatment outcome for head and neck cancer

The study investigates the association of polymorphism in glutathione S-transferases (GSTs) with susceptibility for head and neck squamous cell carcinoma (HNSCC) and its sites as well as treatment response in cases receiving chemotherapy (CT) and combination of CT-radiotherapy (CT-RT). The case-control study included 500 male cases and an equal number of healthy male controls. Odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated for the association between genotypes and cancer risk. An increase in the risk for HNSCC and cancers of oral cavity, larynx or pharynx was observed in cases with null genotypes of GSTM1 or GSTT1. The interaction of alcohol or tobacco with variant genotypes of GSTM1 or GSTT1 also resulted in a significant increase in the risk for HNSCC. Further, HNSCC cases carrying the null genotypes of GSTM1 and GSTT1 or variant genotypes of GSTP1 showed a significant and superior treatment response. The present data thus provides evidence for the association of polymorphisms in GSTs with risk for HNSCC and its treatment response.     

Altered expression of TGF-β1 and TGF-βR2 in tissue samples compared to blood is associated with food habits and survival in esophageal squamous cell carcinoma

In the transforming growth factor β (TGF-β) signaling pathway, TGF-β1 and TGF-β receptor 2 (TGF-βR2) are essential regulatory components which play an important role in different type of cancer. Expressions of TGF-β1 and TGF-βR2 were done by real-time qPCR in both biopsy and blood samples collected from esophageal squamous cell carcinoma (ESCC) patients (n = 76). The expression profiles were correlated with different lifestyle factors and clinicopathological parameters. Kaplan-Meier survival analysis and Cox regression analysis were performed to estimate survival and hazard outcomes of different parameters. TGF-β1 showed upregulation in 91% tissue samples (2.84 ± 1.34*) and 55% blood samples (2.43 ± 1.24*) whereas expression of TGF-βR2 showed downregulation in 89% tissue samples (0.27 ± 0.23*) and 75% blood samples (0.30 ± 0.26*). Among all the parameters, TGF-β1 expression is significant with histopathology grade, consumption of betel nut and smoked food whereas TGF-βR2 expression is significant only with dysphagia grade in both blood and tissue samples and while analyzing both male and female patients separately. Consuming alcohol and hot food, difference in tumor stage and metastasis were found to have statistically significant (P < 0.05) impact on survival and mortality of male patients while consuming hot food, tobacco, metastasis and TGF-βR2 expression in tissue level were found to associate with survival and mortality of female patients. Expression of both TGF-β1 and TGF-βR2 in tissue samples may be prospective biomarkers for screening of ESCC among the Northeast population. Survival outcomes and hazard analysis supports the importance of some clinicopathological and lifestyle factors on ESCC development, whereas expression study depicts association of change in expression of the studied genes in ESCC patients.*Mean fold change.     

Interaction of glutathione-s-transferase genotypes with environmental risk factors in determining susceptibility to head and neck cancer and treatment response and survival outcome

The present case-control study aimed to investigate the role of interaction of glutathione-s-transferase (GST) genotypes with environmental risk factors in determining susceptibility to head and neck squamous cell carcinoma (HNSCC) involving 1,250 cases and equal number of healthy controls. An increase in the risk of HNSCC and its subsites (larynx, pharynx, and oral cavity) was observed among the cases with null genotypes of GSTM1 (odds ratio [OR] = 1.87) or GSTT1 (OR = 1.39) while reduced risk (OR = 0.81) was observed the cases with variant genotype of GSTP1. Tobacco use in the form of smoking or chewing interacted multiplicatively with GSTM1 or GSTT1 to increase the risk several folds (3–10 folds) in HNSCC and its subsites. Alcohol use also increased the risk (2–3 folds) to HNSCC and its subsites in cases with null or variant genotypes of GSTs, though this risk was of lesser magnitude when compared to the tobacco users. A synergistic effect of both, tobacco smoking and alcohol drinking, led to several folds (25-folds) increased risk to HNSCC among the cases with null genotype of GSTM1 and GSTT1 when compared to nonsmokers and nondrinkers with wild genotype of GSTM1 and GSTT1 in controls. Furthermore, cases with variant genotypes of GSTP1 (Val/Val) showed superior treatment response with improved survival rate and lower risk of death when compared to the patients with wild type genotype (Ile/Ile). The data suggest that though polymorphism in GSTs may be a modest risk factor for determining HNSCC risk, gene-environment interactions significantly modify the susceptibility to HNSCC by several folds.     

Myopathies of endocrine disorders: A prospective clinical and biochemical study

Introduction:

Major categories of endocrine myopathy include those associated with: Adrenal dysfunction (as in Cushing''s disease or steroid myopathy); thyroid dysfunction (as in myxedema coma or thyrotoxic myopathy); vitamin D deficiency; parathyroid dysfunction; and pituitary dysfunction. Steroid myopathy is the most common endocrine myopathy.

Objective:

To study the etiology, varied presentations, and outcome after therapy of patients with endocrine myopathies.

Materials and Methods:

Myopathy was evaluated by the standard clinical procedures: Detailed clinical history, manual muscle strength testing, and creatine phosphokinase (CPK). Endocrine disorders were diagnosed as per clinical features and biochemical parameters. The treatment was given to patients as per underlying endocrine disease. Myopathy was assessed before and after treatment.

Results:

Out of the 37 patients who were diagnosed with endocrine myopathies, thyroid dysfunction was the most common cause (17 cases), followed by vitamin D deficiency in nine, adrenal dysfunction in six, parathyroid dysfunction in three, and pituitary dysfunction in two. Some patients had atypical presentation (repeated falls in one, tongue fasciculations in one, neck weakness in five, one with ptosis and facial weakness, asymmetrical onset in one, and calf hypertrophy in one. The serum creatine kinase (CK) concentration did not correlate with muscle weakness. Following the treatment regimen which was specific for a given myopathy, 26 patients recovered fully.

Conclusion:

We found varied clinical presentations of endocrine myopathies. All the patients with neuromuscular complaints should be investigated for endocrine causes because significant number of them recovers fully with specific treatment.     

Polymorphism in cytochrome P450 1A2 and their interaction with risk factors in determining risk of squamous cell lung carcinoma in men

The present case-control study was carried out to investigate the association of functionally important polymorphisms of cytochrome P450 1A2 (CYP1A2) involved in the metabolic activation of tobacco derived procarcinogens with squamous cell carcinoma (SCC) of lung in North Indian men. The study consisted of 200 male cases with SCC of lung and an equal number of age and sex matched healthy controls. Our data showed that variant genotype of CYP1A2*1D and CYP1A2*1F were significantly associated with increased susceptibility to SCC of lung. Likewise, GSTM1 null genotype was found to be over represented in patients when compared to controls. Haplotype analysis revealed that haplotype, G-Tdel-T-C was significantly associated with risk to SCC of lung. Moreover, a significant increase in the risk to SCC of lung in the cases carrying combination of variant genotype of CYP1A2 with either CYP1A1 or GSTM1 have shown that gene-gene interactions may play an important role in squamous cell lung cancer risk. Our data also revealed that smokers or tobacco chewers carrying variant alleles of either CYP1A2*1D or CYP1A2*1F were at increased risk to SCC of lung, further demonstrating that CYP1A2 genotypes interact with environmental risk factors in enhancing the risk to squamous cell lung carcinoma.     

Strand‐specific mutational bias influences codon usage of weakly expressed genes in Escherichia coli

According to the selection‐mutation‐drift theory of molecular evolution, mutation predominates in determining codon usage bias (CUB) in weakly expressed genes (WEG) whereas selection predominates in determining CUB in highly expressed genes (HEG). Strand‐specific mutational bias causes compositional asymmetry of the nucleotides between leading and lagging strands (LaS) in bacterial chromosomes. Keeping in view the aforementioned points, CUB between the strands were compared in Escherichia coli chromosome. In comparison with HEG, codon usage of WEG was observed to be more biased toward strands: G ending codons were significantly more in leading strands than in LaS and the reverse was true for the C ending codons. In case of WEG, the GC₃ skews were found to be significantly different between the strands. This suggests that strand‐specific mutational bias influences codon usage of WEG to a greater extent than that of HEG. The differential effect of strand‐specific mutational bias in E. coli might be attributed to stronger purifying selection in the HEG than the WEG. The observation here in E. coli supports the SMD theory of molecular evolution.     

Varied presentations of moyamoya disease in a tertiary care hospital of north-east India

Introduction:

Moyamoya disease is a chronic progressive cerebrovascular disorder, characterized by stenosis or occlusion of bilateral internal carotid arteries (ICAs), anterior cerebral arteries (ACAs) and middle cerebral arteries (MCAs), accompanied by a collateral network of vessels formed at the base of the brain. Ischemia and intracranial hemorrhage are the common typical manifestations. However moyamoya disease has been associated with atypical presentations like headache, seizures and involuntary movements. Although frequently reported from Asian countries like Japan, China and Korea, only few studies reported on clinical manifestations of moyamoya disease from India.

Objectives:

To study the varied presentations of moyamoya disease in a tertiary care hospital of north-east India.

Material and Methods:

Relevant investigations were done to rule out other causes of moyamoya syndrome.

Results:

We report 6 cases of moyamoya disease with varied presentations from a tertiary care referral government hospital. Case 1, 2 and 6 presented with alternating hemiparesis. Case 3 had amaurosis fugax. Case 4 had history suggestive of ischemic stroke and presented with hemichorea. Case 4 had focal seizure as the only manifestation. Cases 4 and 5 notably had stenosis of posterior cerebral artery (PCA) in addition to stenosis of bilateral ICAs, ACAs and MCAs.

Conclusion:

Owing to its low incidence in India, moyamoya disease is easily overlooked as a possible diagnosis. However, because of its progressive nature, it is imperative to diagnose this disease early and offer surgical treatment to the patients.