Kanchan Kumar Mukherjee

A draft map of the human proteome

The availability of human genome sequence has transformed biomedical research over the past decade. However, an equivalent map for the human proteome with direct measurements of proteins and peptides does not exist yet. Here we present a draft map of the human proteome using high-resolution Fourier-transform mass spectrometry. In-depth proteomic profiling of 30 histologically normal human samples, including 17 adult tissues, 7 fetal tissues and 6 purified primary haematopoietic cells, resulted in identification of proteins encoded by 17,294 genes accounting for approximately 84% of the total annotated protein-coding genes in humans. A unique and comprehensive strategy for proteogenomic analysis enabled us to discover a number of novel protein-coding regions, which includes translated pseudogenes, non-coding RNAs and upstream open reading frames. This large human proteome catalogue (available as an interactive web-based resource at http://www.humanproteomemap.org) will complement available human genome and transcriptome data to accelerate biomedical research in health and disease.

Nonaneurysmal nonperimesencephalic subarachnoid hemorrhage: is it a benign entity?

BACKGROUND Although the clinical profile of patients with PMN SAH is well documented, there are scarce data available for patients with nonaneurysmal n-PMN SAH. In the present study, the clinical characteristics of patients with n-PMN SAH were analyzed and compared with those of PMN SAH and aneurysmal SAH. METHODS Patients with spontaneous SAH, in whom the initial DSA or 3-dimensional CTA result was normal, underwent another investigation (CTA/DSA). If the results of both of these were negative, a second DSA was done after 4 to 6 weeks. Patients in whom even the second DSA failed to reveal an aneurysm or any other vascular abnormality were labeled as nonaneurysmal SAH. Within this group, 2 different types were identified: PMN SAH and n-PMN SAH. RESULTS There were 61 patients in whom the results of the first DSA and CTA were both negative. In 2 of these patients, an aneurysm was demonstrated at a second DSA. Seven patients died before a second DSA could be done. After excluding these, there were 18 patients with PMN SAH and 34 with n-PMN SAH. There was no mortality in these patients; and at a mean follow-up of 1.8 years, all patients with PMN SAH and 94.1% of patients with n-PMN SAH had a good outcome. Associated comorbid illnesses were more frequent in patients with PMN SAH and n-PMN SAH as compared with the aneurysmal SAH patients. CONCLUSIONS Once an aneurysm is definitely excluded, patients with n-PMN SAH have a good outcome, and like PMN SAH, have a benign clinical course. However, a second DSA is mandatory to avoid missing an aneurysm or any other vascular lesion.

Decompressive surgery for acute subdural haematoma leading to contralateral extradural haematoma: a report of two cases and review of literature.

Development of a contralateral epidural haematoma during or immediately after cranial surgery is a well-described entity. However, in a case of acute subdural haematoma where the brain is usually tense, postoperative development of contralateral extradural haematoma is uncommon. We report two cases of contralateral extradural haematoma after decompressive surgery for acute subdural haematoma. We recommend routine postoperative CT immediately after cranial surgery for head trauma. This would help in timely detection and treatment of such a complication.

Congenital atlantoaxial dislocation: a dynamic process and role of facets in irreducibility

OBJECT Patient age at presentation with congenital atlantoaxial dislocation (CAAD) is variable. In addition, the factors determining irreducibility or reducibility in these patients remain unclear. The facets appear to contribute to the stability of the joint, albeit to an unknown extent. The objective of this paper was to study the characteristics of C1-2 facets in these patients and their bearing on the clinicoradiological presentation and management. METHODS Twenty-four patients with CAAD were studied. Fifteen patients had irreducible CAAD (IrAAD); 3 of these patients experienced incomplete reduction after traction, and 9 had reducible CAAD (RAAD). The images (CT scans of the craniovertebral junction in a neutral position) obtained in the parasagittal, axial, and coronal planes were studied with respect to the C1-2 facets and were compared with 32 control scans. The inferior sagittal and coronal C-1 facet angles were measured. The lordosis of the cervical spine (cervical spine angle calculated on radiographs of the cervical spine, neutral view) in these patients was compared with normal. The management of these patients is described. RESULTS The inferior sagittal C-1 facet angle and at least one coronal angle in patients with IrAAD were significantly acute compared with those in patients with RAAD and the control population. A significant correlation was found between age and the acuteness of the inferior sagittal C-1 facet angle (that is, the more acute the angle, the earlier the presentation). The lordosis of the cervical spine was exaggerated in patients with IrAAD. Three patients with IrAAD who had smaller acute angles experienced a partial reduction after traction and a complete reduction after intraoperative distraction of the facets, thereby avoiding a transoral procedure. An inferior sagittal C-1 facet angle of more than 150° in the sagittal plane predicted reducibility. Drilling a wedge off the facet in the sagittal plane to make the inferior sagittal C-1 facet angle 150° can reduce the C1-2 joint intraoperatively by posterior approach alone. CONCLUSIONS The acuteness of the inferior C-1 sagittal facet angles possibly determines the age at presentation and reducibility. The coronal angles determine the telescoping of C-2 within C-1. Patients with IrAAD can be treated using a posterior approach alone with the exception of those with extremely acute angles or a retroflexed dens. The exaggerated lordosis of the cervical spine in these patients is a compensatory phenomenon.

Tuberculosis of the craniovertebral junction: is surgery necessary?

OBJECTIVE:Tuberculosis of the craniovertebral junction is an uncommon entity and its optimal management remains controversial. In this study, we present the evolution of management protocol of this disease in our institute in the past 3 decades. METHODS:A total of 51 patients with craniovertebral junction tuberculosis presenting as atlantoaxial dislocation from 1978 through 2004 were reviewed. The disease was rated from Stage I to Stage III, depending on the radiological findings. All patients received antitubercular treatment for 18 months. In the initial period of this study (1978–1986), all patients (n = 10) underwent surgery, usually a posterior fusion. In the second period (1987–1998), patients with less severe disease (Stages I and II, n = 14) were managed with external rigid immobilization, whereas patients with severe disease (Stage III, n = 11) underwent either a transoral decompression with or without posterior fusion or posterior fusion alone. More recently (1999–2004), all patients (n = 16) in all stages (Stages I–III) have been managed without surgery by a rigid external immobilization. RESULTS:Except for two patients who died (one because of miliary tuberculosis, the other because of acute hydrocephalus), clinical recovery occurred in all. Follow-up imaging demonstrated radiological healing as well, with regrowth of the destroyed bone. CONCLUSION:The mainstay of management of tuberculosis of the craniovertebral junction is prolonged antitubercular treatment with a rigid external immobilization. Surgery is not necessary, even in patients with advanced stages of disease. Complete clinical and radiological healing occurs in all patients with conservative treatment.

Posterior midline approach for large anterior/anterolateral foramen magnum tumours

The standard surgical approaches described for excision of anterior or anterolaterally placed foramen magnum (FM) tumours are the far lateral approach, the extreme lateral approach and the transoral approach. In general the posterior midline approach is considered not suitable for these lesions. We have operated on 27 patients with benign anterior/anterolaterally placed FM tumours in the last 8 years. Thirteen of these were operated via the posterior midline approach. All these 13 patients had large or giant tumours displacing the cervicomedullary region posteriorly and laterally. This allowed adequate access through this approach with minimal handling of neural tissue. For small lesions, the far lateral approach was used. Most of the patients improved significantly neurologically. We recommend the standard midline posterior approach for large/giant FM tumours as the tumour size itself provides enough working space for the surgeon. For small lesions, the far lateral approach is preferred.

Shunt surgery effects on cerebrospinal fluid flow across the aqueduct of Sylvius in patients with communicating hydrocephalus

We aimed to visualize and quantify the flow of cerebrospinal fluid (CSF) across the aqueduct of Sylvius in patients with communicating hydrocephalus using phase contrast MRI, and to evaluate the effect of ventriculoperitoneal (VP) shunt surgery on flow. We investigated aqueductal CSF flow using cine cardiac-gated phase contrast MRI in 10 normal volunteers and 10 patients with communicating hydrocephalus (who underwent VP shunt surgery). For qualitative evaluation, we used an in-plane phase contrast sequence in the midsagittal plane. Quantitative through-plane measurements were performed in the axial plane perpendicular to the aqueduct. The aqueduct area ranged from 0.02 cm(2) to 0.27 cm(2) in the shunt group; and from 0.01 cm(2) to 0.04 cm(2) in the control group (p<0.05). Aqueductal stroke volume (mean, standard deviation SD) ranged from 1.9 microL to 33.17 microL (17.41 microL, 10.1132) in the control group; and from 5.63 microL to 256 microL (87.20 microL, 79.0383) in the study group. Post-operatively the aqueductal stroke volume reduced significantly, ranging from 0.60 microL to 48.77 microL (13.19 microL, 18.08) (p<0.05). Peak systolic velocity (PSV) values in the patients before shunt surgery ranged from -1.05 cm/s to -8.10 cm/s (-4.39cm/s, 2.7619) and peak diastolic velocities (PDV) ranged from 0.62 cm/s to 5.16 cm/s (3.33 cm/s, 1.4451). Post- shunt; PSV values ranged from -0.37 cm/s to -3.90 cm/s (1.78 cm/s, 1.5143) and PDV range was 0.32 cm/s to 4.43 cm/s (1.78 cm/s, 1.6782). The post-operative reduction in velocity was significant (p<0.05). Thus, the aqueductal CSF flow after VP shunt was similar to flow in healthy volunteers.

Intracerebral infarcts following clipping of intracranial aneurysms: incidence, clinical correlation and outcome

Subarachnoid hemorrhage (SAH) is a significant health care problem. One of the major determinants of outcome following surgery of intracranial aneurysms is development of intracranial infarcts. All patients underwent clipping for aneurysms in one year in the department of neurosurgery, PGIMER, Chandigarh were studied. Data regarding age, sex, date of ictus, date of admission, any co-morbidity, clinical grades at presentation, CT findings, infarcts, intraoperative rupture, and clinical status in the postoperative period were recorded. Outcome at discharge was assessed by Glasgow outcome scale (GOS). First, 174 patients were included in the study. Radiological cerebral infarctions occurred in 69 patients (39%). The most frequent location of infarct was deep perforator infarct followed by ACA territory infarct. 69.58% of patients developed infarct on the same side of aneurysm and 20.28% of patients developed infarct on opposite side, whereas 11% developed bilateral infarcts. Infarcts that occur early after surgery may be related to surgical factors whereas the late infarcts were probably as results of delayed ischemic deficits. Anatomical distribution of infarcts also showed two different patterns, infarcts limited to one vascular territory (more commonly seen in early onset infarcts) or multiple, cortical, bilateral infarcts (more commonly seen in late onset infarct). Patients with poor H&H grade, higher Fishers grade, intraoperative rupture and prolonged temporarory clipping had more chances of developing an intracranial infarct.

Effect of prophylactic ondansetron on postoperative nausea and vomiting in patients on preoperative steroids undergoing craniotomy for supratentorial tumors.

The exact incidence of postoperative nausea and vomiting (PONV) in patients on steroids undergoing neurosurgical procedures is not known. This prospective randomized double-blind study was planned to know the efficacy of prophylactic ondansetron in the prevention of PONV in patients on steroids as compared with placebo. Seventy adult patients of either sex who had received preoperative steroids (dexamethasone) for at least 24 hours and were scheduled to undergo craniotomy for supratentorial tumors were included. Patients were randomly allocated using a randomization chart to 1 of the 2 groups to receive either ondansetron 4 mg (group O) or 0.9% saline (group S) intravenously at the time of dural closure. Numeric Rating Scale score for nausea and pain intensity was recorded preoperatively and till 24 hours postoperatively. The 6-hour postoperative nausea score was significantly lower in group O [median, 0; interquartile range (IQR), 0 to 20] than in group S (median, 20; IQR, 0 to 20) (P<0.05). The incidence of vomiting was lower in group O (23%) than in group S (46%) (P<0.05). The total number of emetic episodes, the number of doses of rescue antiemetics given in the first 6 postoperative hours, and the total number of rescue antiemetics given were significantly lower in group O than in group S (P<0.05). Intravenous administration of 4 mg of ondansetron at the time of dural closure was effective in reducing the incidence of PONV and the rescue antiemetics requirement in patients on preoperative steroids undergoing craniotomy for supratentorial tumors.

Lead-induced peripheral neuropathy following Ayurvedic medication.

Lead poisoning following intake of Ayurvedic medication is one of the recent areas of concern. We report a case of a 58-year-old type II diabetic man who was stable with diet control and 30 mg pioglitazone per day. He took Ayurvedic medication for generalized weakness and developed peripheral neuropathy following its intake. He was found to have high blood and urinary lead levels and was diagnosed to have subacute lead poisoning. He was treated with d-Penicillamine for 8 weeks, following which his lead levels became normal. The use of d-Penicillamine was proved highly effective in treating a case of lead poisoning.