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R K Gupta

Publications and source records attributed to R K Gupta.

At least 289 records · Page 16Linked to original sources
PubMed1995

Development of a guinea pig model to assess immunogenicity of Haemophilus influenzae type b capsular polysaccharide conjugate vaccines.

There is currently no animal model which reliably predicts the immunogenicity of Haemophilus influenzae type b (Hib) polysaccharide-protein conjugate vaccines in human infants. We evaluated various Hib vaccines in guinea pigs using techniques similar to the United States potency test for adsorbed diphtheria and tetanus toxoids with a view to developing a method for evaluating the potency of a combined adsorbed tetanus, diphtheria, pertussis and Hib conjugate vaccine. Groups of 6-8 guinea pigs received 1.5 single human doses of vaccine at 0 and at 6 or 8 weeks and were bled at 6 weeks and 2 weeks after the booster injection. Total antibodies to polyribosylribitolphosphate (PRP), the Hib capsular polysaccharide, were measured in individual animals and in serum pools by radioimmunoassay. The relative antibody responses of guinea pigs to Hib conjugate vaccines qualitatively resembled those of human infants. Unconjugated polysaccharide was not immunogenic; PRP-D produced a low antibody response, HbOC, PRP-T (Merieux) and Hib-T (MPMBL) produced a low response to the first dose and a strong anamnestic response to the booster (geometric mean anti PRP > 1 micrograms ml-1). PRP-OMP uniquely produced a strong response after the first dose which was further boosted by the second dose. Experimental Hib-T vaccine lots with low levels of conjugation were poorly immunogenic in guinea pigs. Combinations of DTP and Hib-T vaccines showed equivalent or greater immunogenicity than Hib-T alone. We propose that the guinea pig model may be useful to verify the immunogenicity of PRP conjugate vaccines and for pre-clinical evaluations of DTP-Hib combination vaccines containing PRP conjugates.

Animals↗
PubMed1995

Adjuvants for human vaccines--current status, problems and future prospects.

Adjuvants help antigen to elicit an early, high and long-lasting immune response with less antigen, thus saving on vaccine production costs. In recent years, adjuvants received much attention because of the development of purified, subunit and synthetic vaccines which are poor immunogens and require adjuvants to evoke the immune response. With the use of adjuvants immune response can be selectively modulated to major histocompatibility complex (MHC) class I or MHC class II and Th1 or Th2 type, which is very important for protection against diseases caused by intracellular pathogens such as viruses, parasites and bacteria (Mycobacterium). A number of problems are encountered in the development and use of adjuvants for human vaccines. The biggest issue with the use of adjuvants for human vaccines, particularly routine childhood vaccines, is the toxicity and adverse side-effects of most of the adjuvant formulations. At present the choice of adjuvants for human vaccination reflects a compromise between a requirement for adjuvanticity and an acceptable low level of side-effects. Other problems with the development of adjuvants include restricted adjuvanticity of certain formulations to a few antigens, use of aluminum adjuvants as reference adjuvant preparations under suboptimal conditions, non-availability of reliable animal models, use of non-standard assays and biological differences between animal models and humans leading to the failure of promising formulations to show adjuvanticity in clinical trials. The most common adjuvants for human use today are still aluminum hydroxide and aluminum phosphate, although calcium phosphate and oil emulsions also have some use in human vaccinations. During the last 15 years much progress has been made on development, isolation and chemical synthesis of alternative adjuvants such as derivatives of muramyl dipeptide, monophosphoryl lipid A, liposomes, QS21, MF-59 and immunostimulating complexes (ISCOMS). Other areas in adjuvant research which have received much attention are the controlled release of vaccine antigens using biodegradable polymer microspheres and reciprocal enhanced immunogenicity of protein-polysaccharide conjugates. Biodegradable polymer microspheres are being evaluated for targeting antigens on mucosal surfaces and for controlled release of vaccines with an aim to reduce the number of doses required for primary immunization. Reciprocal enhanced immunogenicity of protein-polysaccharide conjugates will be useful for the development of combination vaccines.

Adjuvants, Immunologic↗
PubMed1995

Cystic intracranial mass lesions: possible role of in vivo MR spectroscopy in its differential diagnosis.

Thirty-four patients showing cystic intracranial mass lesions on MR imaging were evaluated by in vivo proton MR spectroscopy (MRS) with the aim of detecting lesion-specific spectral patterns that may assist imaging in better tissue characterization. In vivo spectroscopy was performed using stimulated echo acquisition mode with echo times 20 and 270 m in all, and spin echo with echo time 135 m in 11 patients. All primary neoplasms (intra-as well as extra-axial) showed choline (3.22 ppm) resonance along with lipid and/or lactate (1.3 ppm). It was not possible to grade cystic gliomas based on N-acetyl asparate-to-choline ratio. High-grade gliomas (n = 8) showed lipid/lactate and low-grade gliomas (n = 6) showed only lactate. Seven patients with brain abscess showed resonances only from acetate (1.92 ppm), lactate (1.3 ppm) and alanine (1.5 ppm). Two cases of metastatic adenocarcinoma showed only lipid/lactate. In 7 patients with epidermoid cyst, lactate along with an unassigned resonance at 1.8 ppm was observed and could be easily differentiated from arachnoid cysts (n = 2), which showed only minimal lactate. A case of cystic meningioma could be differentiated from cystic schwannoma by the presence of alanine in the former. It is concluded that MR imaging, when combined with in vivo MRS, may help to better characterize intracranial cystic mass lesions.

Brain↗
PubMed1995

Brain metabolite changes on in vivo proton magnetic resonance spectroscopy in children with congenital hypothyroidism.

Localized in vivo proton magnetic resonance spectroscopy and imaging were performed in five children with untreated congenital hypothyroidism to look for biochemical markers of abnormal myelin and neuronal development. The patients had high levels of choline-containing compounds, which returned to normal with euthyroidism. These metabolic alterations may reflect blocks in myelin maturation that are reversible by thyroid hormone replacement throughout childhood.

Adolescent↗
PubMed1995

Retinoblastoma with micrometastasis to CSF.

A 28 mth old male presented with a squint and leukocoria. Clinical examination and computerized tomography (CT) suggested a unilateral retinoblastoma with distal optic nerve involvement. Investigations for distant metastasis including lumbar puncture cytology were negative. The eye was enucleated and 12 mm of optic nerve was excised via a combined neurosurgical/ophthalmological approach. Histopathological examination confirmed the optic nerve to the point of excision was free of tumor. However, cytology of cerebrospinal fluid (CSF) from the Sylvian fissure, taken at the time of surgery, revealed malignant retinoblastoma cells. The patient was treated with intrathecal and intravenous chemotherapy, and cranial radiotherapy. He is alive and well 4 yrs later. This case displays the importance of CSF cytology from the Sylvian fissure, as it dramatically changed the management and prognosis for the child. The role of lumbar puncture cytology in excluding CSF micrometastasis can be unreliable. A neurosurgical approach to the optic nerve has the potential to gain access to a long length of optic nerve, should it be involved with tumor, and also allows direct CSF sampling.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Renal aspergilloma due to Aspergillus flavus.

Renal aspergillomas have been reported only rarely. We report a case of Aspergillus flavus colonization of the renal pelvis and upper ureter of a patient with concomitant urinary schistosomiasis. The diagnosis was based on the demonstration of characteristic hyphal elements on direct microscopy and isolation of the fungus in culture. The patient was successfully treated with liposomal amphotericin B. This case emphasizes the importance of direct microscopic examination of urine specimens for prompt diagnosis of fungal infections of the urogenital system. Renal aspergilloma should be considered in the differential diagnosis of filling defects of the urinary tract, especially in patients who are immunocompromised.

Adult↗
PubMed1995

Nodular type of lymphocyte predominant Hodgkin's disease. A clinical study of 50 cases.

BACKGROUND: Lymphocyte predominant Hodgkin's disease (LP-HD), particularly that with a nodular pattern has been suggested to constitute a distinct disorder within the spectrum of Hodgkin's disease, this issue being based on clinical, morphological and immunological observations. Furthermore, the nodular LP-HD (N-LP-HD) has been considered to differ from the diffuse subtype (D-LP-HD), although the data are conflicting. The question addressed in this study was whether the clinical course of N-LP-HD differs from that of the D-LP-HD as well as the other subtypes of Hodgkin's disease. PATIENTS AND METHODS: 90 cases diagnosed as LP-HD at St. Bartholomew's Hospital (SBH) were reviewed. The histopathological classification was based on the original Lukes and Butler criteria for classical N-LP-HD. Clinical data were retrieved from case notes and a computer database. Stage was determined by the Ann Arbor criteria. Survival and remission duration analyses were performed for the group of patients with N-LP-HD and compared with an histological control group of patients with the other subtypes of Hodgkin's disease and the cases of LP-HD that have been reclassified. RESULTS: 1. 50/90 cases (56%) originally diagnosed as N-LP-HD qualified as N-LP-HD. No case with the diffuse subtype, could be identified. Twenty-three percent of the cases were reclassified as Mixed Cellularity and 11% as Nodular Sclerosis HD, whilst 10% as non-Hodgkin's lymphomas. 2. The majority of cases (78%) presented with early stage (I + II). Bone marrow and liver involvement were rare. 3. 92% of cases achieved complete remission. Recurrence developed in only 6/46 patients within 5-12 years. A second complete remission was achieved in 5/6 (83%) cases. Further recurrences have not yet occurred. 4. The overall survival of the 50 cases with N-LP-HD was 92% at 4 years and did not differ significantly from the 40 cases that have been reclassified. Remission duration however, was significantly better for the group of N-LP-HD being 81% at 12 years. 5. Second malignancies were common and developed in 6/50 cases (12%) with N-LP-HD within 10-15 years. These included: ALL (1 case), high grade B-NHL (2 cases), squamous cell carcinoma (1 case), glioma (1 case), lung carcinoma (1 case). 6. 12/50 patients died within a period of follow-up, up to 21 years. 1/3 of the deaths was attributed to the development of second malignancy. CONCLUSIONS: The diffuse variant of LP-HD is rare, having not been seen at St. Bartholomew's Hospital during this time period. The 50 cases with N-LP-HD showed a favourable course with presentation at an early stage, good response to treatment, late recurrences and remission duration other than the other subtypes of HD. The latter could be attributable to the early stage at presentation of N-LP-HD, since the remission duration on a matching on stage analysis was superficially better in favour of N-LP-HD (p = 0.06). The indolent course of the disease in combination with the risk of second malignancy cases raises the question whether histology should be taken into consideration in the development of new protocols for HD.

Adolescent↗
PubMed1995

Somatosensory evoked potential changes following electro-acupuncture therapy in chronic pain patients.

Somatosensory evoked potentials were recorded in 20 healthy volunteers and 20 patients with chronic pain undergoing electro-acupuncture therapy. The values of absolute peak latency and amplitudes of N19 and P22 in the control group were compared with the corresponding baseline values in the study group and after electro-acupuncture therapy at three stages during a 10-treatment cycle. On these occasions the intensity of pain was recorded using a 100 mm visual analogue scale score. Each patient in the study group had 10 treatments given on alternate days. The absolute peak latency of N19 was significantly delayed (p < 0.05) in chronic pain patients when compared to the control group. This increase in latency of N19 persisted after the first electro-acupuncture treatment (p < 0.05), tended to revert to normal after the fifth treatment (p > 0.05) and reverted completely to control values after the 10th treatment (p > 0.05). Visual analogue scores also decreased significantly (p < 0.05) after the fifth and 10th electro-acupuncture sessions. These observations suggest that there is an interaction of the neural mechanisms of electro-acupuncture with the thalamic generator of somatosensory evoked potentials i.e. N19.

Acupuncture Analgesia↗
PubMed1995

Relationship of serum alanine aminotransferase (ALT) to body mass index (BMI) in blood donors: the need to correct ALT for BMI in blood donor screening.

A study was carried out on 1,028 voluntary blood donors to see how body mass index (BMI) correlated with the serum alanine amino transferase (ALT) activity. The mean ALT (U/l) values were 19.35, 27.63, 40.79 and 54.41 in the four BMI categories of < or = 20, 20.1-25, 25.1-30 and > 30, respectively. This study showed that the mean serum ALT level of obese subjects (BMI > 30 kg/m2), compared with the two categories of normal subjects (i.e. BMI < or = 20 and BMI = 20.1-25 kg/m2), was increased by 2.8 and 1.96 times, respectively. Compared with the BMI group < or = 20, there was a gradual per cent increase in the mean serum ALT in the three different BMI groups: 20.1-25 (+133%), 25.1-30 (+196%) and > 30 kg/m2 (+280%). This indicates the need to correct ALT values for BMI for blood donor screening, instead of using actual ALT values.

Adult↗
PubMed1995

Analysis of donor-deferral pattern in a voluntary blood donor population.

A retrospective analysis of records of the deferred donors from 1 October 1992 to 31 December 1993 was performed. Of 14,269 prospective blood donors (13,030 males and 1,239 females), 2,431 (16.4%) donors were disqualified for various reasons: 8.1% of the donors were deferred for non-pathological causes while 91.9% were deferred for medical reasons. The most common cause for non-pathological deferral was volunteers attending below the minimum acceptable age (5.2%). Abnormal findings on physical examination accounted for 57.2% of the deferrals in which low body weight was the most common finding (32.3%) followed by low Hb (18.6%). A past history of jaundice was the leading cause for deferral on medical interview. Numerous prospective donors are currently being deferred based on empirically derived criteria. By developing strategies to identify and rationalize donor selection criteria, the blood transfusion services should be able to decrease unnecessary deferrals.

Adolescent↗
PubMed1995

The V-region repertoire of Haemophilus influenzae type b polysaccharide antibodies induced by immunization of infants.

Haemophilus influenzae type b (Hib) is a significant pathogen for young children, and three Hib vaccines (named PRP-OMPC, HbOC, and PRP-T) are currently available for young children. Extensive studies of anti-Hib polysaccharide (PS) antibodies (Abs) have shown that the V regions of Abs against the Hib PS comprise a VH gene in the VH3 gene family and a VL gene from various K kappa and V lambda subgroups. To study immunogenic properties of the three vaccines in young children, we determined the VL subgroups and avidities of anti-Hib-PS Abs induced by the three clinically available conjugate vaccines. Ab avidity was measured by determining the concentration of a Hib-PS oligomer that abrogates half of the binding of immunoglobulin G anti-Hib-PS Abs to microwells. The PRP-OMPC vaccine induced lower-avidity Abs than the prelicensure HbOC vaccine (P = 0.05). When we compared anti-Hib-PS Abs expressing V kappa Ia, V kappa II, and V lambda subgroups, a greater Ab response was induced by the prelicensure HbOC vaccine than other vaccines (P < 0.05). When anti-Hib-PS Abs with the V kappa III subgroup were compared, however, both PRP-T and prelicensure HbOC vaccines induced a comparable response, which in turn was greater than those induced by the PRP-OMPC or the postlicensure HbOC vaccine (P < 0.001). The VL repertoire of Abs induced with the prelicensure HbOC or PRP-T vaccine in young children is dominated (about 80%) by anti-Hib-PS Abs using subgroup V kappa II. However, anti-Hib-PS using V kappa II VL accounts for only about 40% of the total anti-Hib-PS Abs induced with the PRP-OMPC vaccine or the postlicensure HbOC. Our data suggest that immunogenic properties of Hib vaccines in young children vary depending on the vaccine preparations as well as the vaccine types.

Antibodies, Bacterial↗
PubMed1995

Comparative immunogenicity of conjugates composed of Escherichia coli O111 O-specific polysaccharide, prepared by treatment with acetic acid or hydrazine, bound to tetanus toxoid by two synthetic schemes.

Escherichia coli O111, of various H types and virulence factors, causes enteritis throughout the world, especially in young children. This O type is found rarely in healthy individuals. Serum antibodies to the O-specific polysaccharide of O111 lipopolysaccharide (LPS) protect mice and dogs against infection with this E. coli serotype. The O111 O-specific polysaccharide is composed of a pentasaccharide repeat unit with two colitoses bound to the C-3 and C-6 of glucose in a trisaccharide backbone; this structure is identical to that of Salmonella adelaide (O35), another enteric pathogen. Nonpyrogenic O111 O-specific polysaccharide was prepared by treatment of its LPS with acetic acid (O-SP) or the organic base hydrazine (DeA-LPS). The O-SP had a reduced concentration of colitose. These products were derivatized with adipic acid dihydrazide (ADH) or thiolated with N-succinimidyl-3(2-pyridyldithio) propionate (SPDP). The four derivatives were covalently bound to tetanus toxoid (TT) by carbodiimide-mediated condensation or with SPDP to form conjugates. Immunization of BALB/c and general-purpose mice by a clinically acceptable route showed that DeA-LPS-TTADH, of the four conjugates, elicited the highest level of LPS antibodies. Possible reasons to explain this differential immunogenicity between the four conjugates are discussed.

Acetates↗
PubMed1995

Liver abscess and disseminated intravascular coagulation in tuberculosis.

We report the case of a 55-year-old man with chronic renal failure, and a history of prolonged fever and jaundice. Radiological studies revealed a multiloculated irregular liver abscess. Mycobacterium tuberculosis was isolated from the abscess on smear and culture of aspirated pus. Haematological studies revealed the presence of disseminated intravascular coagulation. A detailed search failed to identify any reason for this other than the tuberculous infection. The treatment of tuberculous liver abscess and pathogenesis of disseminated intravascular coagulation in tuberculosis are discussed.

Disseminated Intravascular Coagulation↗
PubMed1995

Results of a randomized trial comparing MVPP chemotherapy with a hybrid regimen, ChlVPP/EVA, in the initial treatment of Hodgkin's disease.

PURPOSE AND METHODS: Between December 1984 and August 1992, 423 patients with newly diagnosed Hodgkin's disease (HD) were entered onto a randomized clinical trial that compared the regimen of mechlorethamine, vinblastine, procarbazine, and prednisone (MVPP) with a doxorubicin-containing hybrid regimen (chlorambucil, vinblastine, procarbazine, and prednisone/etoposide, vincristine, and doxorubicin [ChlVPP/EVA]). Median age for the group was 29.5 years (range, 15.2 to 68.8), and 52% had bulk disease. RESULTS: After chemotherapy, patients in the hybrid arm of the trial had a higher complete remission (CR) rate (68.1% v 55.3%) and a lower failure rate (2.4% v 12.5%) than those in the MVPP arm. There were also fewer deaths during treatment in the hybrid arm of the trial (five v 13). With a median follow-up period for survivors of 4.5 years (range, 0 to 9), actuarial 5-year progression-free survival (PFS) for all cases is 80% in the hybrid arm and 66% in the MVPP arm (P = .005). A nonsignificant trend toward a better overall survival in the hybrid arm of the trial has also been identified. CONCLUSION: These results suggest that ChlVPP/EVA hybrid is superior to MVPP in the treatment of HD. It has therefore been adopted as standard first-line therapy at the two centers.

Adolescent↗