Pulmonary function profile in patients with benign goiters without symptoms of respiratory compromise and the early effect of thyroidectomy

Background: A large number of patients in our country develop goiters which seem to be apparently asymptomatic. Conventional radiography does not address the abnormal air flow dynamics. Flow volume loop studies have shown characteristic dampening of both inspiratory and expiratory curves. Pulmonary function tests (PFT) can provide a simple noninvasive method of assessing airway compromise. Aim: To address the effect of longstanding asymptomatic, benign goiter by performing PFT on the preoperative airway dynamics and the early postoperative changes at six weeks. Setting and Design: Tertiary care center, Prospective study. Materials and Methods: Sixty-four patients with benign goiters were included after they satisfied the necessary exclusion and inclusion criteria. Pulmonary function tests were performed in the pre and postoperative period. Statistical Analysis Used: SPSS ver. 10 software, Pearson's Bivariate correlation and students T test. Results: The preoperative PFT showed significant reduction in the Vital capacity (VC), Forced Vital Capacity (FVC), Forced expiratory volume in one second (FEV1), mid expiratory flow (MEF 25) and MEF 50 in the females and VC, FVC and FEV1 in males. Postoperatively significant improvement was observed in the tidal volume (VT) and FEV1 in the females and airway resistance in males. Conclusions: Pulmonary function tests can demonstrate the unmanifested abnormal airflow dynamics in benign asymptomatic goiters, which would have otherwise taken years to manifest. This abnormality improved after thyroidectomy, especially the forced expiratory maneuvers. The duration and weight of the goiter correlated well with reduction in FEV1 and its subsequent improvement after surgery in females.     

CD8dim but not CD8bright cells positive to CD56 dominantly express KIR and are cytotoxic during visceral leishmaniasis

This study reports a structural and functional heterogeneity of CD8⁺CD56⁺NKT cells, which usually decrease quantitatively during visceral leishmaniasis. Based on fluorescence intensity of CD8 receptors on CD56⁺NKT cells, two populations of CD8⁺CD56⁺NKT cells have been identified. These cells were recognized as CD8^dimCD56⁺NKT and CD8^brightCD56⁺NKT cells. We further analyzed the functional nature of CD8^dim and CD8^bright positive CD56⁺NKT cells. In comparison to CD8^brightCD56⁺NKT cells, a significantly higher percentage of CD8^dimCD56⁺NKT cells expressed KIR during VL. The percentage of CD8^dimCD56⁺NKT cells expressing KIR was found 4 fold higher in VL as compared to healthy subjects. But, the difference was insignificant in case of CD8^brightCD56⁺NKT cells. CD8⁺CD56⁺NKT cells release granzyme B to kill the infected cells. A categorical difference was also observed in the function of CD8^dimCD56⁺NKT and CD8^brightCD56⁺NKT cells during visceral leishmaniasis. The percentage of granzyme B expressing CD8^dimCD56⁺NKT cells was 2.83 fold higher in VL compared to healthy subjects. But, there was no significant difference in granzyme B expressing CD8^brightCD56⁺NKT cells in samples from healthy and VL subjects. However, within VL subject, the percentage of granzyme B expressing CD8^dimCD56⁺NKT cells was 5.7 fold higher in comparison to CD8^brightCD56⁺NKT cells. This study concludes that CD8^dimCD56⁺NKT cells are more cytotoxic than CD8^brightCD56⁺NKT cells during VL.     

Autosomal-dominant nystagmus,foveal hypoplasia and presenile cataract associated with a novel PAX6 mutation

Autosomal-dominant idiopathic infantile nystagmus has been linked to 6p12 (OMIM 164100), 7p11.2 (OMIM 608345) and 13q31-q33 (OMIM 193003). PAX6 (11p13, OMIM 607108) mutations can also cause autosomal-dominant nystagmus, typically in association with aniridia or iris hypoplasia. We studied a large multigenerational white British family with autosomal-dominant nystagmus, normal irides and presenile cataracts. An SNP-based genome-wide analysis revealed a linkage to a 13.4-MB region on chromosome 11p13 with a maximum lod score of 2.93. A mutation analysis of the entire coding region and splice junctions of the PAX6 gene revealed a novel heterozygous missense mutation (c.227C>G) that segregated with the phenotype and is predicted to result in the amino-acid substitution of proline by arginine at codon 76 p.(P76R). The amino-acid variation p.(P76R) within the paired box domain is likely to destabilise the protein due to steric hindrance as a result of the introduction of a polar and larger amino acid. Eye movement recordings showed a significant intrafamilial variability of horizontal, vertical and torsional nystagmus. High-resolution in vivo imaging of the retina using optical coherence tomography (OCT) revealed features of foveal hypoplasia, including rudimentary foveal pit, incursion of inner retinal layers, short photoreceptor outer segments and optic nerve hypoplasia. Thus, this study presents a family that segregates a PAX6 mutation with nystagmus and foveal hypoplasia in the absence of iris abnormalities. Moreover, it is the first study showing detailed characteristics using eye movement recordings of autosomal-dominant nystagmus in a multigenerational family with a novel PAX6 mutation.     

Microcephaly with or without chorioretinopathy,lymphoedema, or mental retardation (MCLMR): review of phenotype associated with KIF11 mutations

Microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation (MCLMR) (MIM No.152950) is a rare autosomal dominant condition for which a causative gene has recently been identified. Mutations in the kinesin family member 11 (KIF11) gene have now been described in 16 families worldwide. This is a review of the condition based on the clinical features of 37 individuals from 22 families. This report includes nine previously unreported families and additional information for some of those reported previously. The condition arose de novo in 8/20 families (40%). The parental results were not available for two probands. The mutations were varied and include missense, nonsense, frameshift, and splice site and are distributed evenly throughout the KIF11 gene. In our cohort, 86% had microcephaly, 78% had an ocular abnormality consistent with the diagnosis, 46% had lymphoedema, 73% had mild-moderate learning difficulties, 8% had epilepsy, and 8% had a cardiac anomaly. We identified three individuals with KIF11 mutations but no clinical features of MCLMR demonstrating reduced penetrance. The variable expression of the phenotype and the presence of mildly affected individuals indicates that the prevalence may be higher than expected, and we would therefore recommend a low threshold for genetic testing.     

Ascending aortic aneurysms in unicommissural aortic valve disease

BackgroundAneurysms of the ascending aorta occur as result of intrinsic changes in the aortic wall and have been well documented in patients with bicuspid aortic valve (BAV). In few reported clinical studies, documenting aneurysmal dilatation in unicommissural aortic valves (UAV); there have been no comments on the aortic wall pathology. This study presents the pathological findings of the ascending aorta in patients with UAV.Materials and MethodsThe clinical data from 39 patients with concomitant excision of the UAV and aneurysmal aortic tissue were reviewed. In all cases, the gross features of the valve and aortic segments were noted and submitted for histology. The sections of the aorta were semi-quantitatively graded for the extent of medionecrosis, cystic medial change, fibrosis, and elastic tissue changes (fragmentation/ loss) in the media. The medial alterations were correlated with patient age, gender, and valvular dysfunction, and compared to aneurysmal disease in BAV and three-cuspid aortic valves (TAV) excised over a 3-year period.ResultsAmong 39 patients studied, a majority were males (92.3%), with a mean age at surgery of 39.92 years. Only three patients (7.69%) were above the age of 50 years. Eighteen patients (46.1%) had aortic stenosis with regurgitation. Ascending aorta diameters ranged from 4 to 5.5 cm. The overall pattern of medial changes was nearly the same in all cases of UAV, irrespective of age and nature of valvular dysfunction. Most cases showed mild histological changes, with medionecrosis and fibrosis being the more common and consistent features. However, varying grades of change affected different portions of the media and/or the aortic wall in the same patient. The changes in UAV aortae were comparable to the changes seen in the TAV and BAV, but these differed with the age of onset.ConclusionsThis study demonstrates the presence of medial changes in the ascending aortic tissue in all patients of UAV with aneurysms. These changes, while mild to moderate in degree, likely have a similar pathogenetic mechanism as those seen in BAV disease. The significant difference in age, at the time of surgery, suggests a more rapid progression of the aortic changes.     

Osteoarticular sequlae of small pox: a case report

Small pox has been eradicated completely but its unique pathology and sequlae still come across in routine clinical practice. Osteoarticular changes following small pox infection has been elaborated in literature. We present a similar but rare patient with osteomyelitis variolosa and joint deformity involving elbow, wrist joints and humerus fracture. The condyles were typically elongated as central portion of distal humerus absorbed. Fracture united uneventfully following stabilization with dynamic compression plate and bone grafting. Patient showed satisfactory elbow function at the end of last follow-up.     

aVR – the forgotten lead

Electrocardiography continues to be a focal point of modern medicine, and the electrocardiogram (ECG) continues to be the most frequently ordered cardiac test. Most of the clinical importance of the ECG rests on the invaluable information it renders in diagnosing acute coronary syndromes and cardiac arrhythmias. However, the ECG is a valuable tool and diagnostic aid in the evaluation of many other conditions such as pericarditis and pulmonary embolism. Of the electrocardiographic leads, aVR has traditionally received less attention in clinical evaluation of the ECG. The present study discusses instances with pictorial examples in which lead aVR provides valuable clinical information and makes a case for close attention being paid to this ‘forgotten lead’.     

Role of Wake‐Promoting Basal Forebrain and Adenosinergic Mechanisms in Sleep‐Promoting Effects of Ethanol

Background: Ethanol intake has significant impact on sleep. However, the cellular substrates responsible for sleep promotion following ethanol intake are unknown. The purine nucleoside, adenosine, is responsible for mediating many neuronal and behavioral responses to ethanol. Studies performed in cell cultures suggest that ethanol inhibits equilibrative nucleoside transporter 1 to block the reuptake of adenosine resulting in increased extracellular adenosine. Adenosine also has a pivotal role in sleep regulation. Adenosine acts via A1 receptor to inhibit the wake‐promoting neurons of the basal forebrain (BF) resulting in the promotion of sleep. Is ethanol‐induced sleep associated with the inhibition of the BF wake‐promoting neurons? Do adenosinergic mechanisms in the BF have a role in sleep‐promoting effects of ethanol? Methods: To address these questions, we performed 3 experiments in Sprague–Dawley rats. First, we verified the effect of ethanol on sleep promotion. Second, we evaluated the effect of ethanol on c‐Fos expression (a marker of neuronal activation) in the BF wake‐promoting neurons and third we monitored the effects of A1 receptor blockade in the BF on ethanol‐induced sleep. Results: Significant increase in non‐rapid eye movement (NREM) sleep with a concomitant decrease in wakefulness was observed during the first 12 hours postethanol. REM sleep remained unaffected. Ethanol administration caused a significant decrease in the number of BF wake‐promoting neurons with c‐Fos immunoreactivity. Bilateral microinjections of a selective A1R receptor antagonist 8‐cyclopentyl‐1, 3‐dipropylxanthine into the BF significantly attenuated sleep‐promoting effects of ethanol. Conclusion: These results suggest that the inhibition of BF wake‐promoting neurons by adenosinergic mechanism may be responsible for the sleep promoting effects of ethanol. We believe our study is the first to investigate the cellular mechanisms responsible for the somnogenic effects of ethanol.     

Wounds due to a modified shot gun (home-made): A case report

In a case of firearm fatality, the autopsy surgeon is required to opine as to the range of fire in addition to the cause of death which will help in reconstruction of the events. Problems may arise in estimating the range of fire based on wound ballistics when there is an alteration or modification in the internal ballistics. We encountered such a case in the department of Forensic Medicine, Kasturba Medical College, Manipal, which is discussed.