Modeling the repair of DNA strand breaks caused by γ-radiation in a minichromosome.

The objective of the studies described here was the development of a mathematical model which would fit experimental data for the repair of single and double strand breaks induced in DNA in living cells by exposure to ionizing radiation, and which would allow to better understand the processes of DNA repair. DNA breaks are believed to play the major role in radiation-induced lethality and formation of chromosome deletions, and are therefore crucial to the response of cells to radiotherapy. In an initial model which we reported on the basis of data for the repair of Epstein-Barr minichromosomes in irradiated Raji cells, we assumed that DNA breaks are induced only at the moment of irradiation and are later removed by repair systems. This work gives a development of that mathematical model which fits the experimental results more precisely and suggests strongly that DNA breaks are generated not only by direct irradiation but also later, probably by systems engaged in repair of oxidative damage.

Rapid diagnosis of typhoid fever through identification of Salmonella typhi within 18 hours of specimen acquisition by culture of the mononuclear cell-platelet fraction of blood.

Detection of Salmonella typhi in blood by culture of the mononuclear cell-platelet layer was compared with other methods currently used for the diagnosis of typhoid fever. Colonies of S. typhi were present in all mononuclear cell-platelet layer-positive cultures within 18 h of plating and were identified within an additional 10 min by a coagglutination technique. In contrast, identification of all positive cultures by conventional blood culture required 3 days.

Use of a DNA probe to detect Salmonella typhi in the blood of patients with typhoid fever.

A DNA probe was used to detect Salmonella typhi from blood samples from 14 of 33 patients with culture-confirmed typhoid fever, using the equivalent of 2.5 ml of blood. In contrast, S. typhi was detected in 17 of the same 33 patients by culture of 8 ml of blood. The probe hybridized to blood samples of 4 of 47 patients from whom S. typhi was not isolated.

Rehydration and maintenance therapy of cholera patients in Jakarta: citrate-based versus bicarbonate-based oral rehydration salt solution.

We compared the therapeutic efficacy of a World Health Organization standard bicarbonate-based oral rehydration salt solution (BBORS) with a citrate-based oral rehydration solution (CBORS) in a randomized, double-blind, controlled trial in 130 dehydrated patients with cholera aged three to 82 years. On admission the 70 patients who received CBORS and the 60 who received BBORS were similar except that the serum CO2 content (mmol/liter) was significantly lower in the CBORS group (10.8 +/- 3.6 vs. 12.5 +/- 5.3). The incidence of vomiting postadmission (41% vs. 62%, respectively), the stool output during the first 24 hr (4,252 +/- 3,900 ml vs. 6,025 +/- 4,389 ml, respectively), and the time until the patients' conditions were considered normal (38.9 +/- 14.5 hr vs. 46.3 +/- 22.7 hr, respectively) were all significantly less in the CBORS group. The serum CO2 content increased more rapidly during the first 48 hr in the CBORS group (87% +/- 74% vs. 61% +/- 68% for the BBORS group); 23% of the patients receiving CBORS and 35% of the patients receiving BBORS were considered oral-therapy treatment failures. The results indicate that CBORS was superior to BBORS for rehydration and maintenance therapy of hospitalized cholera patients in Jakarta.

Reduction of mortality in chloramphenicol-treated severe typhoid fever by high-dose dexamethasone.

We compared high-dose dexamethasone (initial dose, 3 mg per kilogram of body weight) with placebo in a randomized, double-blind trial involving 38 patients with culture-positive, specifically defined severe typhoid fever. The patients in the two treatment groups ranged in age from 5 to 54 and were comparable at the outset. All patients received chloramphenicol. The case-fatality rate of 10 per cent (2 of 20 patients) in the dexamethasone group was significantly lower than the fatality rate of 55.6 per cent (10 of 18) in the placebo group (P = 0.003). There was no significant difference in the incidence of complications among the survivors in either group. Delirium, obtundation, and stupor were grave prognostic signs that were useful for predicting which patients were at high risk of dying before they became comatose or went into shock. Dexamethasone is unnecessary for most patients with typhoid but is recommended for all patients with suspected typhoid fever who are delirious, obtunded, stuporous, comatose, or in shock.