Surgical treatment of glottic cancer: retrospective analysis of 192 cases in a multidisciplinary tertiary care centre in Pune, India.

OBJECTIVES: A multidisciplinary team approach is required for the preservation of voice and appropriate management of glottic cancer. This study aimed to investigate the outcomes of surgically treated glottic cancers of all stages. All aspects of surgical management, such as laser cordectomy, partial laryngectomy, total laryngectomy with voice prosthesis, and salvage laryngectomy, conducted at a single tertiary care institute in India, were reviewed. METHOD: A retrospective analysis of hospital records was performed for 192 glottic cancer patients who were surgically treated between 2003 and 2007. RESULTS: Patients with tumour stages 1 or 2 glottic cancer treated with laser cordectomy had a local control rate of 85 per cent and five-year survival rate of 98.6 per cent. The findings suggest that the number of partial laryngectomies performed for stage 3 tumours is declining. Patients with a tumour stage 3 lesion with a fixed hemilarynx or a tumour stage 4 lesion, treated with total laryngectomy, were found to have a five-year survival rate of 61.6 per cent. Nodal status was significantly associated with five-year survival rate. CONCLUSION: Surgery offers a viable five-year survival rate in glottic cancer patients.

Surgical response to the 2008 Mumbai terror attack.

BACKGROUND: Mumbai, the financial capital of India, was attacked by terrorists at various famous, densely populated places on 26 November 2008. The attack lasted for 60 h, resulting in multiple civilian casualties from bullet and blast injuries. The aim was to review the disaster management plan and analyse the injury patterns and surgical response. METHODS: The disaster management plan was activated in the Sir Jamshetjee Jejeebhoy Group of Hospitals as soon as the earliest casualties were reported. The casualty receiving area was converted into a triage zone; patients were accordingly sent to different stations for further management. There was rotation of the duties of the medical personnel every 8 h for increased efficiency. RESULTS: A total of 271 casualties were encountered, of which 108 were dead at admission. Some 163 patients were triaged, 23 of whom received primary care as outpatients. The remaining 140 patients needed admission to hospital; 194 operations were performed in 127 patients. There were six postoperative deaths. CONCLUSION: This was a unique terrorist attack targeted on civilians and continuing for more than 2 days. The casualties consisted of military injuries due to combined firearm and blast trauma. Primary triage, or onsite triage once the site is safe, optimizes management.

Endoscopic laser management of bilateral abductor palsy.

OBJECTIVE: To assess the results of endoscopic laser surgery in cases of bilateral abductor palsy on basis of respiration, preservation of voice (phonation) and swallowing. METHODS: This retrospective study includes 48 patients (34 males and 14 females) from 5 years to 68 years of age at the time of intervention. 41 cases were operated with subtotal arytenoidectomy and 7 with unilateral posterior cordectomy. 32 patients were operated with tracheostomy and 16 with combination of intuabtion and jet ventilation. RESULTS: 29 out of 32 tracheostomised patients were decannulated (91%). Respiration was adequate for daily routine activities in most of the operated patients. Phonation was normal to near normal in 32 cases out of the operated 34 adult patients (95%). Most of the patients had normal swallowing following surgery. CONCLUSION: Subtotal arytenoidectomy with endoscopic laser surgery in cases of bilateral abductor paralysis has established its place as a preferred surgical method to obtain good respiration, phonation and swallowing. It minimizes the surgical time, hospital stay and morbidity.

Structurally defined synthetic cancer vaccines: analysis of structure, glycosylation and recognition of cancer associated mucin, MUC-1 derived peptides.

Translation of an immune response into therapy is probably the toughest task in designing vaccines for cancer due to the heterogeneity of the cell surface antigens which display tremendous variations in glycoforms. Consequently, a small segment (antigen) of cancer-associated mucin, in spite of generating antigen-specific immune responses, may be limited in therapeutic value. It is important that the synthetic segment resembles the native cancer-associated mucin in both structure and conformation. Synthetic cancer associated mucin derived 16 amino acid peptide GVTSAPDTRPAPGSTA and its partially glycosylated forms have demonstrated specific binding to two monoclonal antibodies, B27.29 and BCP8, raised against the native cancer associated mucin, MUC-1 and a MUC-1 derived synthetic peptide, respectively. In spite of the structural similarities at the core peptide level of both glycosylated and unglycosylated peptides, it appears that partial glycosylation does not inhibit and even slightly enhances binding to the MAb B27.29 indicating that the glycosylated synthetic peptide more closely resembles the native mucin epitope recognized by MAb B27.29. From molecular dynamic simulations using NMR derived distance constraints, both glycosylated and unglycosylated peptides have shown a type 1 beta turn involving the same amino acids in both glycosylated and unglycosylated peptides. The alpha GalNAc attached to the threonine (T3) and serine (S4) in the 16 amino acid sequence has not imposed any conformational changes to the peptide backbone nor has offered severe steric resistance to the binding of either antibody to the glycopeptides as indicated by hapten inhibition studies. Nevertheless, all peptides have displayed glycosylation dependent specificities in binding to these antibodies, i.e. the glycosylated peptides demonstrated relative higher affinities to the native mucin antibody B27.29 while the unglycosylated peptide is more specific to the MAb BCP8. Immune responses generated by these synthetic glycopeptides are highly specific in recognizing the native cancer associated mucin.

Immune sera and monoclonal antibodies define two configurations for the sialyl Tn tumor antigen.

Sialyl Tn (sTn) is a mucin-associated carbohydrate antigen expressed in most types of human adenocarcinoma. Defining the configuration of tumor cell surface sTn recognized by antibodies is important for understanding the basis for the cancer cell specificity of sTn-reactive mAbs, for the development of more effective mAbs, and for designing cancer vaccines against sTn. In this study, we compared the immunogenicity of synthetic single sTn disaccharide epitopes and clusters [sTn(C)] of 3 sTn epitopes covalently linked via serine to keyhole limpet hemocyanin [KLH; sTn-KLH and sTn(C)-KLH, respectively]. The cell surface sTn configurations were analyzed with the use of sera from mice immunized with these neoglycoproteins and a panel of sTn-reactive mAb. Sera from mice immunized with sTn-KLH reacted in direct and inhibition assays with sTn-human serum albumin (HSA) but only weakly with sTn(C)-HSA, whereas sera from mice immunized with sTn(C)-KLH reacted with sTn(C)-HSA but not with sTn-HSA. Both anti-sTn and anti-sTn(C) sera reacted with ovine submaxillary mucin (a natural source of sTn) and with sTn-positive human tumor cell line LS-C but not with sTn-negative LS-B cells. With regard to the sTn-reactive mAbs, B72.3 reacted exclusively with clustered sTn, whereas mAb B195.3R11 reacted preferentially with unclustered sTn. Results with mAbs TKH2, B239.1, and CC49 were less clear, although all reacted more strongly with clustered sTn than with unclustered sTn. These results suggest that sTn is recognized at the tumor cell surface in at least two quite distinct configurations, as clustered and nonclustered arrays.

Pharmacological effects of Withania somnifera root extract on GABAA receptor complex.

A methanolic extract of W. somnifera root inhibited the specific binding of [3H]GABA and [35S]TBPS, and enhanced the binding of [3H]flunitrazepam to their putative receptor sites. The extract (5 micrograms) inhibited [3H]GABA binding by 20 +/- 6 per cent whereas a concentration of 1 mg of the extract produced 100 per cent inhibition. The extract (5-100 micrograms) produced 20 +/- 4 to 91 +/- 16 per cent enhancement of [3H]flunitrazepam binding. In functional studies using 36Cl-influx assay in mammalian spinal cord neurons, W. somnifera root extract increased 36Cl-influx in the absence of GABA. This effect on 36Cl-influx was blocked by bicuculline and picrotoxin; and enhanced by diazepam. These results suggest that the W. somnifera extract contains an ingredient which has a GABA-mimetic activity.

Comparative evaluation of zinc sulfadiazine and silver sulfadiazine in burn wound infection.

One percent silver sulfadiazine has been commonly used as a topical antimicrobial agent after a burn injury. Incidence of burn wound colonization by Staphylococcus aureus in patients treated with silver sulfadiazine has spurred research for other agents. A topical preparation that contains zinc and sulfadiazine (Zad-G) was evaluated for in vitro antibacterial spectrum and in vivo efficacy. Muscle biopsy specimens of rats treated with Zad-G appear to have fewer colonies of S. aureus than groups treated with silver sulfadiazine. Topical therapy with Zad-G for patients with burns was comfortable, reduced wound infection, and was comparable to therapy with silver sulfadiazine. A topical Zad-G preparation that contains zinc sulfadiazine appears to be an effective alternative to silver sulfadiazine in the treatment of burn wounds.

Presence of antibodies to human immunodeficiency virus-1 in reference reagents of human origin in diagnostic kits.

We tested 54 reagents of human origin that were included in a number of diagnostic kits to be used as positive or negative control material, and for quality assurance, for the presence of antibodies to human immunodeficiency virus-1 (HIV-1). Of these, 12 (22%) reagents were found to give positive results for antibodies to HIV-1 by enzyme-linked immunosorbent assay and/or supplementary tests. These results suggest that some diagnostic reagents of human origin may be contaminated with HIV-1 and potentially may be infectious.

Donor to host transmission of disease via corneal transplantation.

A literature search was conducted to report all cases of documented transmission of infectious diseases from donors to recipients of corneal transplants. Fourteen such cases have been reported. There is no experimental or clinical evidence to suggest the transmissions of either hepatitis or syphilis via corneal grafting. Available evidence regarding a number of neurologic and other disorders in which a slow virus etiology has been implicated were reviewed. On the basis of this review, we are able to draw certain conclusions and guidelines for selection or rejection of donor material for transplant surgery.

The relative immunogenicity in mice of whole and split influenza virus.

The relative immunogenicity in mice of whole influenza virus, and virus split with different disrupting agents, was compared. Using the single radial immunodiffusion test to estimate the haemagglutinin antigen concentration in different virus preparations, it was found that, in general, split virus preparations induced substantially lower titres of HI antibody in mice than whole virus after one or two injections of the antigen.

Effect of aminophylline on coronary circulation and cardiac metabolism.

Doses of aminophylline commensurate with human doses, administered intravenously to dogs under chloralose anesthesia cause an increase in heart rate, a decrease in mean systemic arterial blood pressure, a rise in cardiac output, coronary blood flow and myocardial oxygen consumption and an increase in the oxygen content of the coronary sinus blood which resulted in a decrease in the coronary oxygen arteriovenous difference as the oxygen content of the arterial blood remained essentially unchanged. This increase in coronary blood flow in the presence of a decrease in arterial blood pressure is obviously due to a decrease in the resistance of the coronary bed, which is probably due, at least partially, to dilatation of the coronary bed. Furthermore, since aminophylline decreases the coronary oxygen arteriovenous difference although it raises the myocardial oxygen consumption, it is concluded that aminophylline increases the coronary blood flow more than the myocardial oxygen consumption.

Effect of dopamine infusion on the hemodynamics of normal and sympathectomized rhesus monkeys in endotoxin shock.

Infusion of endotoxin in chemically sympathectomized monkeys caused a fall in the mean aortic pressure, but the cardiac output, stroke volume, and central venous pressure were well maintained. Endotoxin-induced tachycardia in monkeys with functional sympathetics was not seen in the sympathectomized animals. Infusion of dopamine improved the hemodynamic and cardiovascular status, probably by causing vasoconstriction of the splenic and hepatic artery where the pooling of blood is believed to occur in endotoxin shock. However, these beneficial effects were not apparent when dopamine was administered in the chemically sympathectomized animal infused with endotoxin. Since chemical sympathectomy did not affect the endotoxin-induced decline in the systolic and mean aortic pressure or the severity of the endotoxin shock, it is suggested that catecholamines may not be the primary initiator or trigger substances in endotoxin shock.

Effect of Ca++ on the stability of influenza virus neuraminidase.

The neuraminidases of different strains of influenza virus varied in their stability at 37 degrees C. The enzymes of the strains with N1 neuraminidases were found to be unstable during incubation at 37 degrees C whereas the enzymes of the strains with the N2 neuraminidases were stable. Among the strains with N2 neuraminidases, the enzymes of some strains were inactivated during dialysis at 37 degrees C whereas the enzymes of others were stable. This observed loss of enzyme activity during dialysis at 37 degrees C was not restricted to a single substrate as the same loss of enzyme activity was observed irrespective of the size of the substrate used in the assay. The enzymically inactive neuraminidase was found to be non-antigenic and non-immunogenic. The inactivation of the enzyme could be prevented by the addition of Ca++ but not Mg++. Out results suggest that Ca++ is essential for the stability of the enzyme at 37 degrees C. The results would also suggest that the enzymic, antigenic and immunogenic sites are either the same or very closely situated on the surface of the neuraminidase molecule.