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Biomedical subjects

M Unnikrishnan

Publications and source records attributed to M Unnikrishnan.

At least 19 recordsLinked to original sources

Surgical management of a pial arteriovenous fistula with giant varix in an infant.

A seven-month-old infant presented with a generalized seizure. The radiological evaluation revealed a large arteriovenous fistula in the left sylvian region. The fistula connected the left middle cerebral artery and the vein of Trolard. A giant varix was present at the venous end. The child underwent craniotomy, complete disconnection of the fistula and excision of the varix. Except for recurrent seizures, which were eventually controlled on anticonvulsants, the child's neurological development has been good on long-term follow-up of three years. Pial arteriovenous fistulae are rare intracranial vascular malformations. Though significant operative risks exist, they can be successfully managed surgically with good long-term prognosis.

Arteriovenous Fistula↗

Hyperperfusion syndrome after supraaortic vessel interventions and bypass surgery.

Cerebral hyperperfusion and hemorrhage is a recognized complication of endarterectomy, aortocarotid bypass surgery or angioplasty and stenting of the carotid or vertebral artery. We performed 87 balloon angioplasty, stenting and bypass surgery of arteries supplying the brain over the last 15 years. We have found 6 cases of hyperperfusion syndrome in a total of 87 procedures. So the incidence of hyperperfusion was noted as 6.89%. Two cases occurred after two combined procedures in a single sitting. Hyperperfusion syndrome is a well-known complication of craniocervical revascularisation procedures. But with proper care, including strict post procedural control of blood pressure and staged procedure in case of multiples vessel stenosis, these complications can be largely avoided.

Adult↗

Free radical scavenging reactions of sulfasalazine, 5-aminosalicylic acid and sulfapyridine: mechanistic aspects and antioxidant activity.

Reactions of sulfasalazine (SAZ) and its metabolites, 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP), with various oxidizing and reducing free radicals (hydroxyl, haloperoxyl, one-electron oxidizing, lipid peroxyl, glutathiyl, superoxide, tryptophanyl, etc.) have been studied to understand the mechanistic aspects of its action against free radicals produced during inflammation. Nanosecond pulse radiolysis technique coupled with transient spectrophotometry has been used for in situ generation of free radicals and to follow their reaction pathways. The transients produced in these reactions have been assigned and radical scavenging rate constants have been measured. In addition to scavenging of various primary and secondary free radicals by SAZ, 5-ASA and SP, 5-ASA has also been observed to efficiently scavenge radicals of biomolecules. 5-ASA has been found to be the active moiety of SAZ involved in the scavenging of oxidizing free radicals whereas reduction of SAZ produced molecular radical anion. The study suggests that free radical scavenging activity of 5-ASA may be a major path of pharmacological action of SAZ against inflammatory bowel diseases (IBD).

Aminosalicylic Acids↗

Enhanced susceptibility to superantigen-associated streptococcal sepsis in human leukocyte antigen-DQ transgenic mice.

Bacterial superantigens are believed to cause septic shock, although, because of the lack of superantigen-sensitive infection models, proof that superantigenicity underlies shock pathogenesis is lacking. This work demonstrates a clear superantigen effect in septic shock resulting from bacterial infection. Transgenic expression of human leukocyte antigen (HLA)-DQ, but not HLA-DR, specifically augments lymphocyte responses to streptococcal pyrogenic exotoxin A (SPEA). HLA-DQ transgenic mice had increased mortality after administration of SPEA or infection with Streptococcus pyogenes. Immune activation during infection was HLA-DQ transgene-dependent and was manifested by Vbeta-specific T cell repertoire changes and widespread lymphoblastic tissue infiltration. Unlike earlier models, which used toxin-induced shock, these T cell superantigen responses and lymphoblastoid changes were observed during invasive streptococcal sepsis. Lymphoid activation was undetectable in HLA-DQ mice infected with an isogenic SPEA(-) strain, which proves that a single superantigen can play a role in sepsis pathogenesis.

Animals↗

Complementation of a speA negative Streptococcus pyogenes with speA: effects on virulence and production of streptococcal pyrogenic exotoxin A.

We have shown previously that an isogenic SPEA-negative Streptococcus pyogenes strain did not attenuate virulence in a murine model of necrotizing fasciitis. The aim of this study was to confirm that streptococcal pyrogenic exotoxin A (SPEA) is not crucial for streptococcal invasiveness in murine invasive infection. The SPEA-negative S. pyogenes (H326) was complemented with speA extra-chromosomally to create strain H361 which produced 2.2-fold more SPEA compared with the parental speA(+)wild-type (H305). The growth phase-regulated expression of SPEA in vitro was unaffected in this strain. Complementation with speA resulted in reduced virulence and bacterial counts in invasive murine infection. SPEA production was quantitated from muscle tissue of infected mice. However, H361 did not produce more SPEA than H305 in vivo. We conclude that SPEA does not play a key role in invasive murine streptococcal infection.

Animals↗

Fate of hypertension after repair of coarctation of the aorta in adults.

BACKGROUND: Unrepaired aortic coarctation is known to have a detrimental effect on survival. The benefit of coarctation repair on systolic hypertension in adults has been questioned. This retrospective study was conducted to evaluate the impact of repair of aortic coarctation on systolic hypertension in adults. METHODS: Repair of aortic coarctation was performed in 84 patients aged 16-54 (mean 29) years. All patients were hypertensive before surgical intervention (mean systolic blood pressure 162 mmHg; mean diastolic blood pressure 93 mmHg). All patients underwent echocardiography and/or cardiac catheterization. The peak mean systolic gradient across the coarctation was 60 mmHg. The patients were followed after coarctation repair for between 1 and 12 (mean 5.2) years. RESULTS: There was significant regression of hypertension (P < 0.001) in all patients. Thirty-five patients (42 per cent) did not need any antihypertensive medication 3 months after surgery. The prevalence of hypertension at the last follow-up (after mean 5.2 years) was 31 per cent. CONCLUSION: Surgical repair of coarctation of the aorta in adults leads to regression of systolic hypertension and a decreased requirement for antihypertensive medication.

Adolescent↗

Teratoma masquerading as catamenial pleural effusion.

Pleural effusion is a common clinical entity in medical practice. We report a case wherein extensive investigations failed to yield a diagnosis and medical management including repeated thoracocentesis left the effusion refractory. The patient, a 26 years lady, gave a definite history of catamenial dry cough and wheeze. The mystery was unraveled following exploratory thoracotomy when a giant mediastinal teratomatous cyst with luteinized ovarian tissue was discovered and removed, leading to eventual cure for the patient.

Adult↗

The mouse tumor cell lines EL4 and RMA display mosaic expression of NK-related and certain other surface molecules and appear to have a common origin.

As a potential means for facilitating studies of NK cell-related molecules, we examined the expression of these molecules on a range of mouse tumor cell lines. Of the lines we initially examined, only EL4 and RMA expressed such molecules, both lines expressing several members of the Ly49 and NKRP1 families. Unexpectedly, several of the NK-related molecules, together with certain other molecules including CD2, CD3, CD4, CD32, and CD44, were often expressed in a mosaic manner, even on freshly derived clones, indicating frequent switching in expression. In each case examined, switching was controlled at the mRNA level, with expression of CD3zeta determining expression of the entire CD3-TCR complex. Each of the variable molecules was expressed independently, with the exception that CD3 was restricted to cells that also expressed CD2. Treatment with drugs that affect DNA methylation and histone acetylation could augment the expression of at least some of the variable molecules. The striking phenotypic similarity between EL4 and RMA led us to examine the state of their TCRbeta genes. Both lines had identical rearrangements on both chromosomes, indicating that RMA is in fact a subline of EL4. Overall, these findings suggest that EL4 is an NK-T cell tumor that may have retained a genetic mechanism that permits the variable expression of a restricted group of molecules involved in recognition and signaling.

Acetylation↗

Molecular analysis of the role of streptococcal pyrogenic Exotoxin A (SPEA) in invasive soft-tissue infection resulting from Streptococcus pyogenes.

Epidemiological studies strongly implicate the bacterial superantigen, streptococcal pyrogenic exotoxin A (SPEA), in the pathogenesis of necrotizing soft-tissue infection and toxic shock syndrome resulting from Streptococcus pyogenes. SPEA can act as a superantigen and cellular toxin ex vivo, but its role during invasive streptococcal infection is unclear. We have disrupted the wild-type spea gene in an M1 streptococcal isolate. Supernatants from toxin-negative mutant bacteria demonstrated a 50% reduction in pro-mitogenic activity in HLA DQ-positive murine splenocyte culture, and up to 20% reduction in activity in human PBMC culture. Mutant and wild-type bacteria were then compared in mouse models of bacteraemia and streptococcal muscle infection. Disruption of spea was not associated with attenuation of virulence in either model. Indeed, a paradoxical increase in mutant strain-induced mortality was seen after intravenous infection. Intramuscular infection with the SPEA-negative mutant led to increased bacteraemia at 24 h and a reduction in neutrophils at the site of primary muscle infection. Purified SPEA led to a dose-dependent increase in peritoneal neutrophils 6 h after administration. SPEA is not a critical virulence factor in invasive soft-tissue infection or bacteraemia caused by S. pyogenes, and it could have a protective role in murine immunity to pyogenic infection. The role of this toxin may be different in hosts with augmented superantigen responsiveness.

Animals↗

Growth-phase-dependent expression of virulence factors in an M1T1 clinical isolate of Streptococcus pyogenes.

The effect of growth phase on expression of virulence-associated factors was studied by Northern hybridization in an M1T1 clinical isolate of Streptococcus pyogenes. Expression of M protein, C5a peptidase, and capsule was maximal in the exponential phase of growth, while streptococcal pyrogenic exotoxins A and B and mitogenic factor were maximally expressed in later phases of growth.

Bacterial Proteins↗

Abdominal aortic aneurysm repair in a patient with bilateral autotransplanted kidneys.

The case is presented of a 38-year-old male who presented with a large 10 cm x 8 cm pulsatile swelling in his abdomen. Thirteen years before, internal iliac arteries had been used to treat long segment occlusions and diseased state of both renal arteries. At the same time both kidneys had been transplanted to the iliac fossae. Digital subtraction angiography revealed a huge abdominal aortic aneurysm. Both kidneys were fully functional. As the renal transplants had been done extraperitoneally an easy transperitoneal approach was now possible. The maximum diameter of the aneurysm was 12 cm. An inclusion graft repair was carried out using a 16-mm woven Dacron graft. In the light of the favourable circumstances it was decided not to take any special protective measures against renal ischemia apart from keeping the aortic cross-clamp time short. The patient could be discharged with patent and normally functioning kidneys 10 days after surgery.

Adult↗

Malignant tumours in Omani children.

In an effort to understand better the epidemiology of childhood cancer in Oman, a retrospective review of hospital-based biopsy-proven malignant tumours was undertaken. A total of 313 cases of malignant diseases in children between the ages of 0 and 12 years were diagnosed in Oman during the 5-year period from January 1988 to December 1992, inclusive. Leukaemias were the most commonly occurring malignancies (32.3%), followed by lymphomas (29%) and brain tumours (11.2%). The male:female ratio was 1.3:1. The commonest presenting age group was 2 years, the majority of which were leukaemias and lymphomas. Differences and similarities between Omani data and those from other countries are discussed.

Age Distribution↗

Focal occlusive disease of the common femoral artery: a report of 20 cases.

Occlusive disease localized to the common femoral artery without contiguous involvement of the external iliac and superficial femoral arteries is distinctly uncommon in vascular surgical practice. Twenty patients with focal occlusive disease in 21 common femoral arteries are featured in this report. All except one had severe disabling symptoms: Fontaine classification was stage I in one patient, stage IIb in 13, and stage III in six patients. The probable aetiology, based on clinical features and angiographic observations, was identified as atherosclerosis (nine cases), thromboangiitis obliterans (three) and Takayasu's arteritis (two). Histological features of mucoid vasculopathy, a novel disorder, was seen in one patient while no specific aetiology was evident in five patients. Associated lesions were seen in fourteen patients: aortoiliac in one, femoropopliteal in seven (without any continuity to the common femoral lesion), internal iliac in three and tibial in three. Balloon angioplasty of the common femoral artery lesions was attempted in 14 patients with successful outcome in nine. Three patients (including two with failed balloon angioplasty), underwent thromboendarterectomy and two bypass procedures (iliofemoral, one; femoropopliteal, one). Late reocclusion occurred in one patient each in the angioplasty and surgical groups. There were no procedure-related complications in either group.

Adolescent↗

Posterior fossa abscesses. A review of 33 cases.

Thirty three cases of posterior fossa abscesses seen over a period of 20 years are reviewed. 84.8% of these were secondary to otogenic disease. Two abscesses were due to tuberculosis and one due to actinomycotic infection. The overall mortality was 12.1%. Total excision of the abscess with appropriate antibiotic therapy was associated with an operative mortality of 3.4%.

Brain Abscess↗