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Biomedical subjects

G Peter

Publications and source records attributed to G Peter.

At least 109 records · Page 6Linked to original sources

Meningococcal meningitis in familial deficiency of the fifth component of complement.

Absence of the fifth component of complement (C5) by immunochemical assay and marked deficiency by hemolytic assay (less than 0.1%) was found in a family in which the oldest male child had suffered severe and recurrent meningococcemia at age 15 years, two brothers developed meningococcal meningitis four years later (at ages 18 and 14 years), and a sister had the gonococcal arthritis-dermatitis syndrome. Although group-specific meningococcal antibody was present in the sera from all four siblings, serum bactericidal activity against Neisseria meningitidis could be demonstrated only in the presence of exogenous rabbit complement. Serum total hemolytic complement activity was undetectable in all four, but was restored to normal by the addition of purified C5. Subsequently, a second episode of group Y meningococcal meningitis was experienced by one brother and presumed gonococcal arthritis-dermatitis syndrome recurred in the sister. The family is the largest C5-deficient kindred to be reported and emphasizes the importance of C5 in host susceptibility to invasive Neisseria infections. In contrast to the peak incidence of N meningitidis disease in the general population in the first year of life, age of onset of meningococcal infection in these patients and in the 13 previously reported patients with terminal complement component deficiency has usually been in adolescence and early adulthood.

Adolescent↗

Does acrolein contribute to the cytotoxicity of cyclophosphamide?

To determine whether the release of acrolein from oxazaphosphorinane-cytostatics contributes to their cytotoxic action, the effect of 4-hydroperoxycyclophosphamide, 4-hydroperoxy-semi-cyclophosphamide, 4-hydroperoxy-dechloro-cyclophosphamide, and acrolein on murine L 1210 leukemia cells in vitro was compared by measuring the median survival time (MST) after transplantation of the tumor cells in DBA2/Han mice. We found that only 4-hydroperoxycyclophosphamide, which is able to release both acrolein and the alkylating metabolite phosphoramide-mustard, decreased the transplantability of L 1210 cells, while the structurally analogous 4-hydroperoxy-dechloro-cyclophosphamide and 4-hydroperoxy-semi-cyclophosphamide, which under physiological conditions only release acrolein but no alkylating split products showed no cytotoxicity. Acrolein itself showed only a marginal effect, when administered in concentrations equivalent to the release of acrolein from the oxazaphosphorinane-derivatives in test. In this case, however, significant lysis of the L 1210 cells was observed by estimating dye exclusion, while acrolein released intracellularly from 4-hydroperoxy-oxazaphosphorinane-compounds did not. This points to a different mechanism of the cytotoxic action of extracellular acrolein and acrolein released intracellularly from activated oxazaphosphorinane-compounds. The results suggest that the cytotoxic effect of activated cyclophosphamide is based on the alkylating moiety of the molecule. Neither the 4-hydroperoxy-group nor the activated oxazaphosphorinane-ring itself, nor acrolein released intracellularly during toxification of activated cyclophosphamide exert a direct cytotoxic effect. Thus, the release of acrolein from activated CP apparently does not contribute to the cytotoxicity of CP in vivo.

Acrolein↗

Synthesis and preliminary antitumor evaluation of 4-(SR)-sulfido-cyclophosphamides.

Crystalline 4-(SR)-sulfidocyclophosphamides, sulfido derivatives of activated cyclophosphamide (4-hydroxycyclophosphamide), were synthesized by ozonation of cyclophosphamide and reaction of the intermediate 4-hydroxycyclophosphamide with various thiols (HSR). The products were characterized by elemental analysis, 1H NMR and IR spectroscopy, and mass spectrometry. 1H NMR and polarimetric analysis demonstrated that they consist of racemic cis-isomers that are stable in the crystalline state at room temperature. In aqueous solution these derivatives are hydrolyzed to 4-hydroxycyclophosphamide and the corresponding thiol, with half-lives ranging between 4 and 17 min at 37 degrees C and pH 7. The cytotoxicity of 4-(S-ethyl)- and 4-(S-ethanol)-sulfidocyclophosphamide against Yoshida sarcoma ascites cells and the toxicity in rats were found to be practically identical with those of activated cyclophosphamide. A preliminary evaluation of the curative effect after a single IV injection of 4-(S-ethane)- and 4-(S-ethanol)-sulfidocyclophosphamide in rats bearing Yoshida ascites sarcoma or of 4-(S-ethanol)-sulfidocyclophosphamide in nu/nu mice bearing human breast carcinoma xenografts suggested that these sulfido derivatives possess the same oncostatic efficacy as activated cyclophosphamide itself.

Animals↗

Correlations between age-dependent protein and lipid concentrations in plasma and platelet functions in children.

The correlations between the levels of various plasma proteins and lipids and platelet function on glass and platelet factor 3 (PF 3)-availability in children of different age-groups were investigated. Several statistically significant positive and some significant negative correlations were found. Although conclusions based solely on such correlations should be considered with reservation, in our opinion the following factors should stimulate platelet function: prealbumin (adhesion and PF 3-availability in all age-groups, aggregation--specifically for children in puberty); alpha 1-antitrypsin (PF 3-availability); alpha 2-macroglobulin (platelet spreading capacity, PF 3-availability); plasminogen (platelet adhesion and aggregation--specifically for boys in puberty); caeruloplasmin (number of "free adhering platelets" spreading capacity); lysolecithin and lecithin (time-dependent increase of spontaneous platelet adhesion and aggregation, PF 3-availability); and free fatty acids (FFA) (PF 3-availability). Plasminogen and complement component C'3 show a negative relationship to the time-dependent increase of spontaneous platelet adhesiveness and aggregability in platelet-rich plasma.

Adolescent↗

Vancomycin treatment of cerebrospinal fluid shunt infections. Report of two cases.

The successful use of vancomycin is reported in two children with shunt infections due to Staphylococcus epidermidis which failed to respond to shunt removal. The previously reported experience with this drug is reviewed. The use of vancomycin should be considered in cases of shunt infections due to susceptible microorganisms and refractory to other therapeutic measures.

Cerebrospinal Fluid Shunts↗

Demographic factors in the epidemiology of hemophilus influenzae meningitis in young children.

To determine the effect of various demographic factors on the incidence of Hemophilus influenzae, type b meningitis, Rhode Island residents with H. influenzae in 1970-1974 were identified by review of data from the State Department of Health, a private health care research organization, death certificates, and hospital bacteriology laboratories. Of the 108 cases of H. influenzae, 99 (92%) occurred in children under five years of age. The disease incidence among black children under five (103.6/100,000/annum) was significantly (P less than 0.0005) higher than that among white children (23.9/100,000/annum). By eliminating the 29 of 185 census tracts in which the total population was greater than 5% black, disease incidence was studied in a virtually monoracial population. In these white census tracts, in which the population was 99.2% white, the occurrence of H. influenzae was not related to family income, education, number of household members, population density, or rate of hospitalization. These findings confirm the increased incidence of H. influenzae in blacks and indicate that socioeconomic factors do not affect the incidence of the disease in white children.

Black or African American↗