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Biomedical subjects

P Sharma

Publications and source records attributed to P Sharma.

At least 325 records · Page 18Linked to original sources

Cervical vascular injuries: a trauma center experience.

BACKGROUND: We analyzed 76 patients with cervical vascular injuries from penetrating neck trauma (n = 528) between 1977 and 1990 at a level I trauma center to evaluate the role of angiography in diagnosis and management and to assess the course and outcome of these patients. METHODS: Patients who were hemodynamically unstable underwent immediate surgical exploration. Stable patients were subjected to diagnostic investigation. Angiography was routinely performed to diagnose vascular injury in zones I and III and zone II if the trajectory was in the vicinity of major vessels. Therapeutic embolization was performed when possible at angiography; all other vascular injuries were treated surgically. RESULTS: Thirteen patients (2.5%) died of penetrating neck trauma, in 12 of whom hemorrhage was the contributing factor (12/76; 15.8% of patients with vascular injury). In nine patients who were hemodynamically stable vascular injury was diagnosed by angiography: 5 (6.8%) of 73 in zone I and 3 (5.4%) of 56 in zone III, four of whom underwent therapeutic embolic occlusion of the injured vessel. Injuries to vertebral and subclavian arteries and subclavian and innominate veins were often multiple, causing exsanguination and death (6.8% in zone I). In three patients with no preoperative neurologic deficit, the internal carotid artery was ligated without complication; in all other patients injury to the common carotid or internal carotid artery was repaired, in six of them with polytetrafluoroethylene grafts. CONCLUSIONS: Selective management of penetrating neck trauma should include routine angiography in zones I and III. Injuries to the common and internal carotid arteries should be repaired. The internal carotid artery may be ligated in the absence of preoperative neurologic deficit. Arterial injuries in the neck can be repaired with polytetrafluoroethylene grafts.

Angiography↗

"Universal" T helper cell determinants enhance immunogenicity of a Plasmodium falciparum merozoite surface antigen peptide.

Synthetic peptide constructs containing a limited number of epitopes are being currently investigated as subunit vaccines against a variety of pathogens. However, because of widespread nonresponsiveness to most such constructs, possibly attributable to MHC restriction, the choice of appropriate carrier molecules to enhance immunogenicity of peptides constitutes an important and essential aspect of designing synthetic immunogens for human use. Widely used vaccines such as tetanus toxoid (TT) have not been uniformly effective as carrier proteins because of the phenomenon of epitope-specific suppression in which induction of an immune response against a synthetic peptide conjugated to TT is prevented by preexisting immunity to TT. Recently, T cell determinants that can be recognized in the context of several class II MHC molecules have been identified in tetanus toxin as well as in the circumsporozoite protein of a human malarial parasite, Plasmodium falciparum. Such determinants can be potentially used to circumvent the problem of epitope-specific suppression. In the present study we evaluated two such T cell determinants, viz., tt830-844 from tetanus toxin and CST3 from the malarial parasite, for their ability to help induce a boostable antibody response and to overcome genetic nonresponsiveness to a synthetic 20-residue construct containing a B cell and an overlapping T cell epitope from a major merozoite surface protein of P. falciparum. Our data provide support for the view that widely recognized T cell determinants may be used as universal carrier molecules for general vaccination.

Adolescent↗

Influence of feeding regimen and postnatal developmental stages on antibacterial activity of pancreatic juice.

Antibacterial activity of pancreatic juice in the pig (n = 8) was investigated during early postnatal development and in cattle (n = 6) receiving a different feeding regimen. For pancreatic juice collection, a catheter was surgically implanted in the pancreatic duct. Reintroduction of pancreatic juice was achieved through a T-shaped cannula in the duodenum. Pancreatic juice was collected for 30 min in all cases. In piglets, collections were carried out at 2, 5-6, and 7-10 wk of age, and in cattle, after a standard meal, 48 h starvation, and following 24 h intraduodenal glucose infusion. Antibacterial activity was tested on Micrococcus Pyogenes strain ATTC 6538P by disc agar diffusion technique using nonactivated pancreatic juice, before and after heat treatment for 15 min at 65 and 100 degrees C, respectively. Piglets showed a significant rise in antibacterial activity of pancreatic juice after weaning. In cattle, 48 h of starvation resulted in a marked suppression of antibacterial activity. This activity was found to be normal after a standard meal and comparable to that after 24-h intraduodenal glucose infusion. Heating of pancreatic juice to 65 degrees C caused a 35% increase in the antibacterial potency, whereas heating to 100 degrees C completely abolished it. Additionally, dilution of pancreatic juice to 1:10 did not affect antibacterial potency.

Aging↗

Decreased mesenteric blood flow in experimental multiple organ failure.

Disorders of mucosal blood flow may contribute to gut barrier dysfunction in multiple organ failure (MOF). We evaluated alterations of mesenteric microcirculation in a rat model of MOF. Male Wistar rats received 1 mg/g body weight of zymosan A in 4 ml of mineral oil by intraperitoneal injection and were studied on Days 1, 3, and 5 following injection. A control group received no zymosan. The experimental group also received a fluid resuscitation regimen of 0.9 N saline subcutaneously equal to 0.1 ml/g body weight on the day of zymosan injection and 0.05 ml/g body weight daily thereafter. Day 1 animals tended toward a statistically significantly lower mean arterial pressure versus controls (86.6 +/- 8 mm Hg versus 106 +/- 5 mm Hg, F = 0.09 by ANOVA). Significant arteriolar vasoconstriction occurred on Days 1 and 3 versus control (70 +/- 4 microns and 57 +/- 8 microns versus 96 +/- 3 microns, F = 0.0002). Laser doppler velocity, indicating red blood cell velocity, expressed as a percentage of control paralleled this vasoconstriction (70 +/- 9 and 72 +/- 7%, respectively). We conclude that mesenteric arteriolar vasoconstriction occurs accompanied by decreased red blood velocity. We believe that this is indicative of decreased mesenteric perfusion in this zymosan model of MOF and that survival to Day 5 is associated with a reversal of these microcirculatory changes.

Animals↗

Antibody responses stimulated in rabbits, guinea-pigs and mice by recombinant and synthetic portions of a 75 kDa malarial merozoite protein.

The 75 kDa heat-shock-related protein (p75) of Plasmodium falciparum is an abundant, highly conserved, merozoite surface protein. A bacterial clone, C7, produces a polypeptide (C7Ag) of approximately 30 kDa representing the C-terminal 40% of p75. In several species of animals, the C7Ag stimulated high titre IgG antibodies which cross-react with p75. Two major portions of the C7Ag, theoretically predicted to have strong secondary structural preferences, were modelled with four synthetic peptides. An alpha-helical, hydrophilic region, modelled with a 28-mer, proved a poor immunogen in guinea-pigs and several strains of inbred mice, even though it had been a strong immunogen in rabbits. A disulphide-bonded region of the C7Ag was modelled with three peptides of increasing length, namely 49-, 64- and 76-amino acid residues. In general, the order of immunogenicity was 49 less than 64 less than 76-mer. Antibodies to the 76-mer and the 64-mer reacted strongly with the native parasite protein. The data also suggested that the 76-mer was a good model for the region of the molecule it was made to represent.

Animals↗

Neutron discrepancies in the DS86 Hiroshima dosimetry system.

More than a decade has passed since a complete revision was initiated of the radiation doses received by survivors of the Hiroshima and Nagasaki atomic bombings. The new dosimetry system (DS86) was completed in 1986 and adopted shortly thereafter. Overall, DS86 was noted to be a clear improvement over the old dosimetry system. However, based on limited validation measurements, troublesome inconsistencies were suggested for neutrons. Since 1986, a substantial number of additional neutron activation measurements have been made in mineral and metal samples from Hiroshima. Importantly, a large number of measurements have now been made at distances beyond 1 km. Here, inconsistencies between neutron activation measurements and DS86 calculations for Hiroshima are examined using all available measurement data, including new measurements for 36Cl which extend the measurement range to more than 1.7 km from the epicenter, and Monte Carlo modeling calculations for each sample measured. Results show that thermal neutron activation measured beyond approximately 1 km in Hiroshima (at distances most relevant for radiation-risk evaluation) is two to 10, or more, times higher than that calculated based on DS86. Similar trends observed when comparing results by several independent measurement laboratories, using different analytical methods, suggest that the DS86 calculations for low-energy neutrons are in error. Because of the importance of the Hiroshima data in radiation risk evaluation, this large discrepancy is in need of resolution.

Japan↗

Ethics, logistics and a trial of transurethral versus open prostatectomy.

An increased long-term morbidity rate after transurethral compared with open prostatectomy has recently been claimed on the basis of retrospective studies of operations done up to 20 years ago. These studies have led to a demand for a prospective trial. Most reports show that peri-operative mortality following prostatectomy is virtually confined to unfit men over 80 years old. Before agreeing to participate in a trial we examined our operative mortality in this group of patients. Between 1981 and 1987, 123 octogenarians underwent transurethral prostatectomy: 64 operations were elective and 59 were performed for retention. There were 2 operative deaths (1.6%), both from gram-negative septicaemia despite prophylactic antibiotics. There were no additional deaths in the first 12 months following surgery. Few of these patients would have been considered fit to undergo an open prostatectomy. Any proposed randomised trial would have to exclude such high risk patients until it can be shown that open prostatectomy is equally safe.

Aged↗

An aetiological profile of optic atrophy.

484 cases of optic atrophy were studied for the distribution pattern and significance of various etiological factors in different age groups of both sexes. Bilateral optic atrophy was found to be two and a half times as common as unilateral optic atrophy. Intracranial neoplasm (29.5%) was the most frequent known cause of bilateral optic atrophy in either sex and the most common tumor was chromophobe adenoma (48% of intracranial tumors) with highest incidence over 20 years of age. Craniopharyngioma was the most frequent tumor responsible for bilateral optic atrophy before 20 years of age. Intracranial glioma also emerged as an important cause of bilateral optic atrophy. Head injury due to road accidents and periocular trauma were the most common causes of unilateral optic atrophy in males, whereas no definite factor could be elucidated in unilateral optic atrophy in females. Vascular factors were the usual cause of optic atrophy after 40 years of age, highlighting the significance of thorough systemic evaluation.

Adolescent↗

Immunogenicity and efficacy trials in Aotus nancymai monkeys with model compounds representing parts of a 75-kD merozoite surface antigen of Plasmodium falciparum.

We tested the ability of a recombinant DNA-encoded fragment (C7Ag) of a Plasmodium falciparum merozoite protein (p75) and of two carrier-free peptide models (28-mer and 76-mer) to stimulate boostable antibody responses in Aotus nancymai monkeys. In addition, we evaluated protection against challenge with the Uganda Palo Alto (FUP) strain of this parasite. The data indicate that C7Ag elicited a strong and boostable IgG antibody response in all the monkeys immunized. However, studies with the peptide models demonstrated that various animals produce antibodies to different portions of this structure. When the post-boost sera from monkeys immunized with C7Ag were analyzed for reactivity against two major portions of C7Ag, most of the antibody response was observed against the disulfide-bonded 76-residue region that forms a conformational immunogenic epitope. In the same sera, antibody levels against the charged helical region modeled with a 28-mer were generally low. Immunization with synthetic peptides revealed that the 76-mer stimulated an antibody response almost as strong as C7Ag, with substantial cross-reactivity against the parasite antigen. The 28-mer evoked a response that was not efficient or uniform, and showed little reactivity with the authentic parasite antigen. Aotus nancymai was shown to be susceptible to infection with the Uganda Palo Alto strain of P. falciparum; however, maximum parasitemia varied markedly in both immunized and control monkeys. Statistical analysis failed to recognize differences in maximum parasitemia between the vaccine and control groups. The variation in maximum parasitemia suggests that the FUP strain in this species of Aotus is a poor model for the detection of differences in efficacy based on maximum parasitemia. This initial study with structures based on parts of the 75-kD merozoite surface antigen of P. falciparum indicated that both the recombinant-produced protein C7 and the 76-mer synthetic peptide, when combined with a Syntex adjuvant formulation, were safe and immunogenic in A. nancymai monkeys. However, the data emphasize the problems of using animal models to evaluate the potential effects of immunogens in humans.

Adjuvants, Immunologic↗

Rhythmic palatal myoclonus.

We report two cases of rhythmic palatal myoclonus (RPM) first presenting with symptoms unrelated to myoclonus and a possible etiology of encephalitis and the second presenting with ear click and palatal myoclonus. The response to treatment was unsatisfactory in both.

Adult↗

Kerosene oil poisoning--a childhood menace.

This study documents 3-year retrospective analysis of accidental kerosene oil poisoning in 70 children with regard to clinical profile, radiological changes and outcome. About 77% of cases were between 1 and 3 years old. Fifty children (71.4%) developed significant symptoms, with onset soon after to within 10 hours of ingestion. These included breathlessness (55.7%), fever (47.1%), cough (31.4%), restlessness (25.7%) and abdominal distension (15.7%). Chest X-rays were obtained in 65 children. Abnormal radiographs were seen in 45 (69.2%) children with right basal infiltrates being the commonest picture (21.4%). Ingestion of more than one ounce of kerosene oil adversely affected the clinical and radiological profile. Severely malnourished children had extensive radiological changes and poorer clinical outcome. One case developed myocarditis, a complication which has not been reported to the best of our knowledge. Mortality rate was 4.3%. All deaths occurred within 48 hours of admission.

Accidents, Home↗

Role of bacterial flora in the pathogenesis & management of atopic dermatitis.

The carriage state of Staphylococcus aureus and its role in the pathogenesis and management of atopic dermatitis were evaluated in 50 patients, aged 3 months to 12 yr. An equal number of age and sex matched controls were also studied. The positivity of Staph.aureus in patients with atopic dermatitis was 50 per cent from eczematous skin, 34 per cent from anterior nares and 26 per cent from normal skin. In controls, the comparative figures were 14 per cent from anterior nares and 10 per cent from normal skin. After institution of oral erythromycin or cloxacillin therapy (according to sensitivity), the colony counts dropped to 18 per cent from eczematous skin, 14 per cent from anterior nares and 8 per cent from normal skin after one week and to zero after 3 wk. This was associated with significant clinical improvement. The results of this study suggest that Staph. aureus aggravates the eczematous process in patients with atopic dermatitis and antibiotics decrease the severity and are useful in long term prognosis of the disease.

Anti-Bacterial Agents↗