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S Ahlawat

Publications and source records attributed to S Ahlawat.

17 recordsLinked to original sources

Enhanced immunogenicity of a contraceptive vaccine using diverse synthetic carriers with permissible adjuvant.

A vaccine directed against human chorionic gonadotropin (hCG) has previously undergone clinical testing demonstrating the feasibility of the approach in preventing pregnancy in women. Some individuals, however, did not respond adequately despite employing highly immunogenic bacterial toxoids as carriers. We investigated the potential of three promiscuous pathogen-derived Th peptides as carriers, employing alum as the adjuvant. While conjugation with each peptide improved the antibody response against hCG in mice of different haplotypes, immunisation with a combination of these peptide-conjugates generated anti-hCG responses higher than those achieved with the individual peptides or tetanus toxoid (TT). Antibodies were of high affinity and capable of neutralising the bioactivity of hCG but were devoid of anti-peptide reactivity. These results have implication for the design of hCG vaccine with improved immunogenicity for diverse population.

Adjuvants, Immunologic↗

High expression of human chorionic gonadotrophin beta-subunit using a synthetic vaccinia virus promoter.

We have constructed a recombinant vaccinia virus to express the beta-subunit of human chorionic gonadotrophin (betahCG), a secretory glycoprotein that is used as an antigen for a contraceptive vaccine. The cDNA encoding the subunit was cloned under the control of a synthetic promoter that could be recognised by a vaccinia virus RNA polymerase to direct transcription. The peak expression level of betahCG directed by a late synthetic promoter (Psyn) was 11.5 microg/ml, a level that was at least sixfold higher than that directed by the p7.5 early/late promoter. The expressed protein was correctly processed post-translationally such that it attained a conformation with correctly folded discontinuous epitope(s) similar to that seen in native betahCG.

Blotting, Southern↗

Humoral hyporesponsiveness to a conjugate contraceptive vaccine and its bypass by diverse carriers using permissible adjuvant.

A contraceptive vaccine directed against human chorionic gonadotropin (hCG) has previously undergone clinical testing that demonstrated the feasibility of the approach in preventing pregnancy in women. Some immunized volunteers however, did not respond with an adequate anti-hCG antibody response despite employing highly immunogenic bacterial toxoids as carriers. Since there is some evidence that T cell responses to a complex protein typically focus on a few immunodominant epitopes, we investigated the responsiveness to hCG in mice of different haplotypes using the protein carrier diphtheria toxoid (DT). Our data showed a differential carrier effect of DT. With the aim of making a more potent immunogen employing promiscuous pathogen-derived Th peptides as carriers, peptide:antigen stoichiometric ratios were optimized. When tested individually using alum as the adjuvant, three such peptide conjugates improved the anti-hCG response, though not consistently to levels higher than the DT conjugate. Immunization with a combination of these synthetic epitopes generated anti-hCG responses higher than those achieved with DT or with the individual peptides. Antibodies were of high affinity and capable of neutralizing the bioactivity of hCG, but were devoid of anti-peptide reactivity. These results support our view that differential hyporesponsiveness in a diverse population may arise from inadequate carrier effect and that it can be overcome by use of pathogen-derived broadly reactive non-B Th epitopes employing only alum, a permissible adjuvant.

Adjuvants, Immunologic↗

Meningococcal meningitis outbreak control strategies.

Meningococcal meningitis has been occurring worldwide in both endemic and epidemic forms. Serogroup A accounts for majority of cases of epidemic as well as endemic Meningococcal meningitis in developing nations, whereas group C and group B causes epidemic and endemic meningococcal meningitis in developed countries. Person to person spread of N. meningitides generally occurs through inhalation of droplets of infected nasopharyngeal secretions by direct or indirect oral contact. Incubation period varies from 2 to 10 days. N. meningitides typically causes acute infective illness characterized by sequential development of upper respiratory tract infection, meningococcemia, meningitis and focal neurological deficit. Over 90 per cent cases of adult meningococcal infections have cerebrospinal meningitis, whereas in children prevalence of meningitis is much lower (50 per cent). Acute meningitis manifests with fever, severe headache, vomiting and neck stiffness. Presentations may be non-specific in infants, elderly and in patients with fulminant meningococcemia. Diagnosis is confirmed with cerebrospinal fluid analysis. Overall mortality due to meningitis is usually around 10 per cent. In meningococcal septicemia, the case fatality rate may exceed 50 per cent. Preventive strategies include vaccination, chemoprophylaxis and early detection and treatment. Mass vaccination campaign, if appropriately carried out, has been documented to halt an epidemic of meningococcal disease due to serogroup A or C. In the present review we have discussed the available evidence with regards to prevention at primary, secondary and tertiary level. Public health approach to an outbreak of meningococcal meningitis in a community or an organization is also outlined.

Disease Outbreaks↗

Plasma platelet aggregating factor and platelet aggregation studies in pre-eclampsia.

OBJECTIVE: A plasma platelet aggregation factor (PAF) has been implicated in the pathogenesis of platelet activation in thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). Similar mechanism may be operative in pre-eclampsia. METHODS: Coagulation profile and detailed in vitro platelet aggregation with various agonists were studied. PAF was demonstrated by spontaneous aggregation of normal platelets with test plasma. Non-parametric Wilcoxon's rank sum test and Krauskal Wally's one way analysis of variance were applied. RESULT: Twenty-two pre-eclamptic patients and 20 normal pregnant controls were studied. Anti-thrombin III levels were within normal range and fibrin degradation products were only border line raised ( > 10 < 40 micrograms/ml) in 14 (65.4%) patients. In vitro platelet aggregation was abnormal in 17 (77.2%) patients. PAF was demonstrable in 10 of 22 (45.5%) patients. CONCLUSION: Platelet aggregation studies indicated the presence of both activated (hyperaggregable) as well as exhausted (hypoaggregable) platelets in circulation. PAF demonstrable in 45.4% pre-eclampsia patients would suggest its role in the pathogenetic mechanism of platelet activation in this disease.

Adult↗

Vinblastine and danazol therapy in steroid resistant childhood chronic idiopathic thrombocytopenic purpura.

Various drugs such as vinca alkaloids, immunoglobulins and immunosuppressant drugs have been used with variable benefits in patients with chronic idiopathic thrombocytopenic purpura (CITP) refractory to steroid therapy. Vinblastine and danazol have been shown to decrease the expression of Fc (IgG) receptors on macrophages by different mechanisms. These two drugs were used in combination, with the presumption that they will have an additive effect in the treatment of CITP. Sixteen patients with CITP between 2 and 17 years of age, resistant to steroids, were treated with vinblastine given as an intravenous bolus dose at weekly intervals for 8 weeks (the induction phase), followed at monthly intervals for the next 6 months (the maintenance phase). Danazol was given daily in doses of 2-3 mg/kg body weight during both phases. Ten of the 16 (62.5%) patients had partial to complete response and 5 of these 10 patients had sustained remission after cessation of therapy. The initial outcome with the combination of these two drugs in CITP appears to be quite promising and requires further evaluation in a larger controlled study.

Adolescent↗

Hypofibrinogenaemia is the commonest congenital fibrinogen abnormality in north India.

Congenital abnormalities of fibrinogen are rare disorders and all the cases reported in the literature indicate that the incidence of afibrinogenaemia is much higher than hypofibrinogenaemia. Of the total of 20 cases reported from other parts of India only one was congenital hypofibrinogenaemia. In contrast, the present study showed eight patients with congenital hypofibrinogenaemia among a total of nine unrelated North Indian patients with a fibrinogen abnormality. This disproportionately high incidence of hypofibrinogenaemia suggests the existence of a distinct genetic defect in the North Indian population.

Adolescent↗

Lipid profile in the first-degree relatives of patients with precocious coronary heart disease in Rohtak area (Northern India).

Twenty-five patients with precocious coronary heart disease (CHD) (aged forty years or less) and 82 first-degree relatives were studied for lipid profile. Eighty-eight age- and sex-matched controls were also studied. The mean serum cholesterol, triglycerides, low density lipoprotein cholesterol, very low density lipoprotein cholesterol, and total cholesterol/high density lipoprotein cholesterol of patients and their first-degree relatives were significantly higher as compared with normal controls. High density lipoprotein cholesterol values were found to be almost identical in the patient group, their first-degree relatives, and normal controls. Hyperlipidemia was found in 68% of patients with CAD, of their first-degree relatives, and 24% of controls. Almost all lipid fractions in relatives of hyperlipidemic patients paralleled those of the patients suffering from CHD. Of 25 families studied, 16 had hyperlipidemia. In conclusion, it can be stated that there is a statistically significant hyperlipidemia in young patients with CHD that has a significant familial clustering, thus delineating a group of high-risk individuals (first-degree relatives of young coronary patients) for possible primary prevention of CHD. This familial clustering could be due to genetic or environmental factors; however, the relative contribution of these two factors requires further investigation.

Adolescent↗

Serum & tissue magnesium content in patients of aluminium phosphide poisoning and critical evaluation of high dose magnesium sulphate therapy in reducing mortality.

Role of high dose magnesium sulphate therapy was evaluated in 50 patients of Aluminium Phosphide (AIP) poisoning. Simultaneously serum and RBC magnesium levels were studied in these patients at six different points within first 24 hours. In non-survivors magnesium content of various tissues (brain, stomach, kidneys, liver, lungs and heart) was also estimated. Magnesium estimation (tissue as well as serum) was done using atomic absorption spectrophotometer. No significant difference was found in dose related mortality rates in patients treated with and without magnesium sulphate. The immediate causes of death in these patients included intractable shock, shock coupled with arrhythmias and adult respiratory distress syndrome (ARDS). Serum as well as RBC magnesium content was within normal range at all the six points (0, 1, 3, 6, 12 and 24 hours after arrival in hospital). Tissue magnesium content of various organs (in non-survivors) was more (p < 0.01) compared to that of corresponding organs in controls (accidental deaths). No significant alterations were seen in other serum electrolytes (Na, K, Ca, PO4). The data confirmed that neither there was any evidence of hypomagnesemia in these patients nor magnesium sulphate therapy improved survival. Survival can be improved (to some extent) with continuous cardiac monitoring and use of appropriate anti-arrhythmic agents. However, imposition of stringent restrictions on the free supply of AIP and caging of tablets in plastic packs with holes and spikes may yield better results in preventing AIP poisoning rather than treating these patients.

Adolescent↗

Role of serum ferritin in assessment of disease activity in acute & chronic leukemia.

Serum ferritin (SF) was estimated using double antibody sandwich ELISA in 83 patients of acute and chronic leukemia at various stages of the disease. In 35 patients of acute lymphoblastic leukemia (ALL) in remission, the SF levels fell significantly from 550.63 ng/ml at presentation to 319.56 ng/ml but remained significantly higher than the control values of 46.14 ng/ml. In 28 patients of acute myeloid leukemia (AML), the SF values at 775.0 ng/ml were much higher than those in ALL patients and showed no decline with remission. This pattern was also seen in patients of chronic myeloid leukemia in blast crisis (CML-BC) with SF levels of 804.03 ng/ml at presentation and 717.43 ng/ml at partial remission. The values of SF were lowest in patients of CML in chronic phase ranging from 271.5 ng/ml to 332.12 ng/ml and showed no relationship with variation in total leucocyte count. No correlation was found between SF values and various clinical and laboratory parameters such as age, sex, fever, organomegaly, haemoglobin and total leucocyte count. Thus, while there appeared to be a correlation between remission and SF values in ALL, no such correlation existed between the activity of the disease and SF in other types of leukemia.

Acute Disease↗

Indirect assessment of acute effects of ethyl alcohol on coronary circulation in patients with chronic stable angina.

Acute effects of ethyl alcohol on left ventricular performance, haemodynamic and electrocardiographic response to treadmill exercise test were studied in 20 patients with chronic stable angina. Following ingestion of 80 ml of whisky (43% ethyl alcohol by volume) the mean heart rate and rate-pressure product decreased significantly at the end of each stage of exercise compared to corresponding prealcohol values. There were also significant derangements in systolic time intervals parameters in the form of decrease in left ventricular ejection time I and increase in pre-ejection phase I and pre-ejection phase/left ventricular ejection time ratio after alcohol intake indicating a depression in left ventricular performance. However, following alcohol intake the mean exercise time (6.5 +/- 3.8 minutes) until onset of ischaemic ST segment depression decreased significantly (P less than 0.01) compared to the corresponding prealcohol exercise time (8.6 +/- 3.5 minutes). Interestingly, the mean rate-pressure product (an indicator of myocardial oxygen demand) at the onset of ischaemic ST segment depression was significantly less (P less than 0.01) when exercise test was done after alcohol intake compared to the corresponding pre-alcohol value. The data indicated that despite significant decrease in myocardial oxygen demand produced by alcohol intake, ST T changes developed early and at a lower rate-pressure product, indicating decreased blood flow to the ischaemic zones of the myocardium. This may be explained by the coronary steal effect produced by alcohol.

Adult↗

Dieulafoy's lesion: a rare cause of massive upper gastrointestinal haemorrhage.

Out of 900 cases of Upper Gastrointestinal haemorrhage seen during 1985-1989, 6 (0.67%) cases had Dieulafoy's lesion as the causative factor. All patients presented with massive upper gastrointestinal haemorrhage. The mean age of the patients was 46.3 year (32-60 yrs) and 4 were males and 2 females. No consistent associated medical factors could be identified. The diagnosis was established by emergency endoscopy which showed an active arterial spurter in 4 patients and located the bleeding site to be close to the fundus in other 2 patients. Injection sclerotherapy tried in 3 patients was not successful. Four patients had bleeding lesion along the greater curvature close to the fundus and two had on posterior wall but all within 6 cm. of gastroesophageal junction. All patients underwent curative emergency surgery with wedge resection of the lesion. We conclude that Dieulafoy lesion should be suspected in a patient with massive, recurrent and obscure upper gastrointestinal bleeding. Emergency endoscopy for diagnosis and prompt surgical intervention can cure the lesion which is potentially fatal if untreated.

Adult↗