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Biomedical subjects

K Ramakrishnan

Publications and source records attributed to K Ramakrishnan.

At least 19 recordsLinked to original sources
PubMed1995

Patterns of colorectal liver metastases according to Couinaud's segments.

PURPOSE: It is commonly believed that the right lobe of the liver is the most frequent site of colorectal liver metastases. However, direct evidence for this is lacking in the literature. This study was designed to document and evaluate the pattern of liver metastases according to liver segments. METHODS: A retrospective medical records review of 270 patients with hepatic metastases from colorectal adenocarcinoma was performed to determine the pattern of metastases according to Couinaud's segments. There was operative confirmation of liver metastases in 202 patients (75 percent). A total of 1,166 segments were involved with liver metastases and were used in this analysis. Segment I was excluded from calculations because of its dual blood supply. When groups contained different numbers of Couinaud's segments an appropriate correction was made in the statistical comparison. RESULTS: There were 736 (63 percent) right lobe segments (V, VI, VII, VIII) and 430 (37 percent) left lobe segments (II, III, IV) involved with metastases (P < 0.001). Of 430 left lobe segments, 298 (69 percent) involved the left lateral segment (II, III) and 132 (31 percent) involved the medial segment (IV) of the left lobe (P = 0.25). When evaluating patients with 4 or less segments involved, there were 258 right lobe segments (75 percent) and 88 left lobe segments (25 percent) involved with metastases (P < 0.0001). Of 88 left lobe segments with 4 or less segments involved, there were 68 segments (77 percent) involving the left lateral segment and 20 segments (23 percent) involving the medial segment of the left lobe (P = 0.035). All of these relationships were statistically independent of the primary tumor site. CONCLUSIONS: We have documented an overall predominance of right hepatic lobe metastases independent of site of the primary colorectal carcinoma. However, when metastases occurred in the left lobe, the left lateral segment (II, III) was more commonly affected than the medial segment (IV), but this difference was statistically significant only when there were four or less segments involved with liver metastases.

Adenocarcinoma↗
PubMed1995

Associated atrial septal defects increase perioperative morbidity after ventricular septal defect repair in infancy.

Although closure of ventricular septal defects (VSDs) is currently associated with a relatively low risk, infants with associated atrial septal defects (ASDs) seem to have a higher perioperative morbidity. To clarify this impression, we reviewed our entire experience (since 1977) with closure of simple VSDs in 163 infants (age, < or = 12 months). Of these, 57 had significant ASDs (ASD-VSD subgroup). Hospital mortality was 3.7% (6/163) overall and 1.4% (2/145) since 1980. Actuarial survival at 10 years was 92% +/- 5%. Significant morbidity occurred in 15.5% (16/103) of the VSD subgroup versus 48.1% (26/54) of the ASD-VSD subgroup (p < or = 0.001). Multivariate analysis identified the presence of multiple VSDs and early date of operation as risk factors for hospital death, and younger age, an associated ASD, the size of the VSD, and use of hypothermic circulatory arrest as risk factors for significant perioperative morbidity. Compared with the VSD subgroup, the ASD-VSD subgroup had a higher hospital mortality (5.3% [3/57] versus 2.8% [3/106]), were younger (5.1 +/- 2.9 versus 7.2 +/- 2.9 months; p = 0.001), had a higher preoperative pulmonary artery pressure (70.2 +/- 19.0 versus 62.7 +/- 21.8 mm Hg; p = 0.08), needed more inotropic support (12.3% versus 3.7%; p = 0.07), needed more prolonged ventilation (3.3 versus 1.8 days; p = 0.02), and had longer postoperative hospital stays (11 versus 8 days; p = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1994

Long-term humoral and cellular immunity after vaccination with cell culture rabies vaccines in man.

To determine the duration of anti-rabies immunity, peripheral blood of 18 vaccinees was obtained between 2 and 14 years after immunization. Peripheral blood mononuclear cells (PBMC) and serum were tested for the presence of either rabies virus-specific antibodies or rabies antigen-specific proliferation. Neutralizing immunoglobulin class G anti-rabies virus antibodies could be detected in sera of all vaccinees, but not in 18 age- and sex-matched controls. Rabies antigen-induced proliferation of PBMCs from vaccinees was significantly higher than that of controls. The anti-rabies T and B cell response showed no time-dependent pattern. These results suggest the induction of a long-term immunity after rabies immunization according to pre- and post-exposure schedules with inactivated cell culture vaccines against rabies.

Adult↗
PubMed1994

Typing of hepatitis C virus isolates by DNA enzyme immunoassay.

Recently, at least six types of hepatitis C viruses (HCV) have been identified. Different types of HCV appear to possess different pathogenic properties and a different sensitivity to interferon treatment. Typing of HCV isolates may therefore be an important diagnostic procedure. We report on a new method for identification of HCV types 1a, 1b, 2a, 2b and 3a which are most prevalent in Europe, North America and Japan. The assay is based on a combination of two well established techniques, the polymerase chain reaction (PCR) and DNA enzyme immunoassay (DEIA). In the first step of the method a cDNA of about 250 bp corresponding to the HCV core-region is amplified by nested PCR. The target cDNA is then hybridized to type-specific oligonucleotides fixed to a solid phase through an avidin-biotin bridge. The formed hybrids are detected by a standard ELISA using monoclonal antibodies reacting with double-stranded DNA. Typically, signal-to-noise (S/N) ratios between 18.2 and 48.6 could be observed when different HCV types/subtypes were analyzed by this method. The test was evaluated using cloned HCV cDNAs of known types and by sequence determination of some of the typed cDNAs. Typing of 115 isolates from Germany, Russia and Turkey revealed that subtype 1b (59-100%) and 1a (24-32%) are most prevalent in these countries.

Antibodies, Monoclonal↗
PubMed1990

The aetiology of bleeding peptic ulcer--as observed in a district general hospital.

A review was made of the hospital case notes of 124 patients admitted with symptoms of upper gastrointestinal haemorrhage due to bleeding peptic ulcer over a five-year period. A high proportion of the patients were found to be elderly and female, as observed by Walt et al 1986. This finding was more pronounced if the source of the bleed was a gastric ulcer. Many of these elderly patients had been on anti-inflammatory drugs at the time of presentation. Concomitant treatment with cimetidine or demulcents did not seem to prevent episodes of bleeding. Many patients on anti-inflammatory drugs bled repeatedly after apparently adequate medical or surgical treatment.

Adult↗
PubMed1989

Standardization of an enzyme immunoassay for the in vitro potency assay of inactivated tissue culture rabies vaccines: determination of the rabies virus glycoprotein with polyclonal antisera.

A non-competitive enzyme-linked immunoassay (ELISA) has been standardized to supplement the in vivo potency test used for the quality control of inactivated tissue culture vaccines against rabies. The essentials of the ELISA were: fixation of the virus in different dilutions of vaccine on the surface of microtitre plates; testing of the reference and up to six test vaccines on one plate; incubation with polyclonal antisera to rabies virus glycoprotein containing an excess of antibody; further incubation with a species-specific anti-IgG coupled to peroxidase; a final incubation with a substrate. The incubation periods were 1 h, 1 h and 30 min both at +37 degrees C. The relative potency determinations were made graphically or by a computer using a parallel line bioassay in which the potencies of the vaccines of unknown potency were tested against the reference preparation on a single microtitre plate. Under these conditions inactivated rabies vaccines of different types (virus strains, cell substrates, inactivation and concentration procedures) were tested for potency. Furthermore, it was possible with this in vitro method to assay adjuvanted vaccines, in process samples such as tissue culture supernatants with live or inactivated rabies virus, concentrates, and vaccines undergoing thermal stability tests. The rabies glycoprotein antigen-antibody reaction was highly specific according to the results and the glycoprotein content was measured quantitatively. The potency determined by the in vitro ELISA correlated with the in vivo NIH protection potency test. The lower limit of detection of the ELISA was 0.015 IU/ml. Quantitative antigen determination was possible with both homologous and heterologous antisera to rabies virus glycoprotein when vaccines of the same virus strain were tested. When the potencies of vaccines of different virus strain specificity were calculated, it was necessary to take into account the strain-specific antigenicity. Even so vaccines of high potency were found to give a stronger reaction with a heterologous serum than did weak vaccines with a homologous antiserum. Stability tests made on inactivated tissue culture vaccines such as vaccine from the human diploid cell strain (HDCS), from purified chicken embryo cell (PCEC) or from purified Vero cell rabies vaccine (PVRV), showed high stability of the glycoprotein antigen even after four months of storage at +37 degrees C or 24 h at +56 degrees C, provided that the vaccines were stored in a lyophilized state. The antigenicity of liquid vaccines was inactivated after a few hours at +56 degrees C. For tropical areas, therefore, only lyophilized vaccines should be considered.

Adsorption↗
PubMed1986

7-Deoxydaunomycinone quinone methide reactivity with thiol nucleophiles.

Under anaerobic conditions and with NADPH as a reducing agent, daunomycin is reduced in the presence of spinach ferredoxin: NADP+ oxidoreductase as the enzyme catalyst to its hydroquinone, from which intramolecular elimination of the C-7 glycoside proceeds to provide a quinone methide intermediate. This quinone methide is capable of bimolecular reaction with the thiolate nucleophiles N-acetyl-L-cysteine, N-(tert-butoxycarbonyl)-L-cysteine, and 1-thio-beta-D-glucose, providing a pair of C-7 diastereomers, when the reaction is carried out under the autocatalytic conditions offered by substoichiometric quantities of NADPH. With 0.4 equiv of NADPH, optimal yields of the adducts are obtained of approximately 65%. In each case, the 7S adduct is the major product, with the observed stereoselectivities (7S to 7R) ranging from 2.6 to 1 for N-acetyl-L-cysteine to 4 to 1 for both the N-(tert-butoxycarbonyl)-L-cysteine and 1-thio-beta-D-glucose as nucleophiles. By standard blocking and deblocking procedures, the complete set of complementary functionalized (7S)- and (7R)-N-acetyl and O-methyl 7-L-cysteinyl-7-deoxydaunomycinones is prepared. All efforts to extend this quinone methide trapping reaction to additional nucleophiles (such as I- or N3-), including the use of Fe(III) chelation, are unsuccessful. The Fe(III) chelate of daunomycin is however reduced by ferredoxin reductase and NADPH to the Fe(III) chelate of 7-deoxydaunomycinone, suggesting that quinone reduction of the chelate to the quinone methide has occurred. Of the new compounds prepared, only (7R)-7-S-(beta-D-glucopyranosyl)-7-thio-7-deoxydaunomycinone has biological activity. As an in vitro inhibitor of P388 cell growth, it has a 50% inhibitory concentration 25 times greater than that of daunomycin.

Animals↗
PubMed1983

Stereoselectivity of chloroperoxidase-dependent halogenation.

The stereoselectivity of chloroperoxidase halogenation of four substrates has been examined. Chloroperoxidase catalyzes the bromination, but not chlorination, of racemic 2-exo-methylbicyclo[2.2.1]hept-5-ene-2-endo-carboxylic acid (to the delta-lactone) and racemic bicyclo-[3.2.0]hept-2-en-6-one (to the 2-exo-bromo-3-endo-hydroxy-bromohydrin). These products are obtained in near quantitative yield and are racemic. The circumstances of the bromination strongly suggest that halogenation does not occur at the active site but rather by chloroperoxidase-catalyzed formation of Br2 and its release into solution. The inability of chloroperoxidase to halogenate these two alkenes at its active site most probably derives from a steric exclusion from the active site. The stereoselectivity of two additional substrates that undergo active site chlorination was determined. Methionine is quantitatively converted to a 50:50 ratio of the two methionine sulfoxide diastereomers. 2-Methyl-4-propylcyclopentane-1,3-dione is quantitatively chlorinated to 2-chloro-2-methyl-4-propylcyclopentane-1,3-dione. On the basis of optical rotation and proton nuclear magnetic resonance, this product is present as a 40:60 ratio of the racemic diastereomers. It is concluded that active site chlorination by chloroperoxidase proceeds without appreciable stereoselectivity.

Bromine↗
PubMed1983

Orchiopexy: trans-septal ipsilateral positioning.

Orchiopexy based on a method of testicular fixation by ipsilateral placement with a valvular passage through the septum is described. By passing the testis through the soft septum twice, a low scrotal position is assured without tension or risk of compression of the cord.

Adolescent↗
PubMed1982

Complexation of anthracycline antibiotics by the apo egg white riboflavin binding protein.

The apo chicken egg white riboflavin binding protein complexes several anthracycline antitumor antibiotics and their metabolites. The Kd value for three important anthracycline glycosides (adriamycin, daunomycin, aclacinomycin A) is approximately identical at 0.5 micro M. The anthracycline occupies the flavin binding site in this complex, having its D-B rings overlaying the region normally occupied by the riboflavin A-C rings, respectively. The glycoside of the anthracycline, attached to C-7 of the A ring, is exposed to the solvent; consequently, the binding protein discriminates poorly between anthracycline A ring geometric isomers. Anthracyclinones, metabolites lacking the C-7 glycoside, are bound about 10-fold more tightly. The basis for the occupancy by anthracyclines of this flavin binding site is a steric homology (both ligands contain planar, linear conjugated rings) permitting the energetically favorable displacement of water from the hydrophobic pocket. The binding protein-anthracycline complex has been used for anaerobic aqueous redox titrations. Dithionite reduction of the anthracycline glycoside provides, in a two-electron process, the 7-deoxyanthracyclinone, via reductive elimination. The bound 7-deoxyanthracyclinone is then further two-electron reduced to the bound hydroquinone. Semiquinone radical intermediates are observed transiently; these are neither stable in solution nor complexed to the binding protein. Oxidation of the hydroquinone is accomplished by several reagents (oxygen, hydrogen peroxide, ferricyanide, cytochrome c). In the case of 7-deoxydaunomycinone hydroquinone, a mixture of two products is produced upon oxidation; these are the chromo-7-deoxydaunomycinone (identical with the first 2-e- reduction intermediate) and its leuco isomer, 8-acetyl-7,8,9,10-tetrahydro-5,8,12-trihydroxy-1-methoxy-6,11-naphthacenedione (iso-7-deoxydaunomycinone). These studies provide useful information concerning the redox properties of the anthracyclines and suggest that these antitumor antibiotics may be capable of functioning as riboflavin antagonists in vivo.

Animals↗
PubMed1982

Synthesis and biological evaluation of a metazocine-containing enkephalinamide. Evidence for nonidentical roles of the tyramine moiety in opiates and opioid peptides.

In an effort to test the hypothesis that the tyramine moiety present in opiates and in opioid peptides plays an identical functional role at opioid receptors, a hybrid enkephalinamide (3) that contains (-)-metazocine (4a) in place of Tyr was synthesized. It was found that 3 and its congeners are inactive or feebly active in the electrically stimulated guinea pig ileum and mouse vas deferens preparations. The results of these studies suggest that the tyramine moiety in opiates and related structures does not play the same functional role as that in the opioid peptides. It is suggested that the different functional roles of the tyramine moiety in opiates and opioid peptides is a consequence of different modes of interaction with common receptors.

Animals↗