John P. Craig

Cholera--a possible endemic focus in the United States.

In September and October 1978, after a case of cholera had been discovered in southwestern Louisiana, 10 more Vibrio cholerae O-Group 1 infections were detected in four additional clusters. All 11 infected persons had recently eaten cooked crabs from five widely separated sites in the coastal marsh, and a matched-triplet case-control study showed a significant relation between cholera and eating such crabs (P = 0.007). V. cholerae O1 was isolated from estuarine water, from fresh shrimp, from a leftover cooked crab from a patients refrigerator, and from sewage in six towns, including three without identified cases. All isolates in Louisiana and an isolate from a single unexplained case in Texas in 1973 were biotype El Tor and serotype inaba; they were hemolytic and of a phage type unique to the United States--suggesting that the organism persisted undetected along the Gulf Coast for at least five years.

A permeability factor (toxin) found in cholera stools and culture filtrates and its neutralization by convalescent cholera sera.

A Permeability Factor (Toxin) Found in Cholera Stools and Culture Filtrates and its Neutralization by Convalescent Cholera Sera

Suppression of the immune response to diphtheria toxoid in murine schistosomiasis

Studies in humans and experimental animals indicate that infection with schistosomes results in impaired immune response to a variety of antigens. Since artificial immunization against a number of infections is frequently attempted in populations in which schistosomiasis is endemic, we have attempted to determine whether this impairment could be demonstrated in response to a commonly used immunogen. We have compared the serum antitoxin response to diphtheria toxoid (DTd) in normal, uninfected mice with that in mice bearing schistosome infections of different duration. Animals were infected with 100 Schistosoma mansoni cercariae 16, 12, 8, 4 and 2 weeks prior to, on the same day as, and 4 weeks after the first of three 1 microgram doses of DTd given at 3 week intervals. The antitoxin level of each mouse was taken as the mean of two sera obtained 1 and 2 weeks after the 3rd dose of DTd. The mean antitoxin level in uninfected-immunized control mice was 0.0457 Antitoxin Units (AU) ml-1. 71% of mice in this group developed antitoxin levels > or = 0.01 AU ml-1. Only 28% of the infected-immunized mice achieved antitoxin levels > or = 0.01 AU ml-1. In infected-immunized mice with infections of all durations, both the percentage of mice with > or = 0.01 AU ml-1 (0 to 50%) and mean antitoxin levels (0.003 to 0.016 AU ml-1) were lower than in uninfected-immunized mice. Antitoxin levels in animals infected 16, 12, 8 and 2 weeks prior to, simultaneously with, and 4 weeks after the first dose of DTd were significantly lower (P = < 0.05) than those of controls. Mice infected 4 weeks prior to the first dose of DTd had antitoxin levels 64% below controls but this difference was not significant. If similar immunosuppression occurs in human schistosomiasis, these findings may have implications for childhood immunization programs in areas where schistosomiasis is endemic.

Oxidation by trace Cu2+ ions underlies the ability of ascorbate to induce vascular dysfunction in the rat perfused mesentery.

Ascorbate has both antioxidant and pro-oxidant activities. We have previously shown that plasma levels of ascorbate induce constriction and blockade of dilatation mediated by endothelium-derived hyperpolarizing factor (EDHF). In this study we sought to determine if these detrimental actions were mediated by a pro-oxidant action of ascorbate. Since trace levels of transition metal ions including, Cu2+ and Fe3+, promote oxidation of ascorbate, we examined the effects of the chelating agents, cuprizone and deferoxamine, and of CuSO4 and FeCl3 on ascorbate-induced constriction and blockade of EDHF in the perfused rat mesentery. Cuprizone abolished and Cu2+ but not Fe3+ ions enhanced both ascorbate (50 μM)-induced constriction and blockade of EDHF. The blockade of EDHF produced by ascorbate in the presence of CuSO4 (0.5 μM) was abolished by the hydrogen peroxide scavenger, catalase, but unaffected by the scavengers of hydroxyl radical or superoxide anion, mannitol and superoxide dismutase (SOD), respectively. Consistent with these observations, the oxidation of ascorbate by CuSO4 led to the rapid production of hydrogen peroxide. Catalase, mannitol and SOD had no effect on ascorbate-induced constriction. Thus, in the rat perfused mesentery, both the constrictor and EDHF-blocking actions of ascorbate arise from its oxidation by trace Cu2+ ions. The blockade of EDHF results from the consequent generation of hydrogen peroxide, but the factor producing constriction remains unidentified. These detrimental actions of ascorbate may help explain the disappointing outcome of clinical trials investigating dietary supplementation with the vitamin on cardiovascular health.

Insulating and cooling effects of nasal endoscope sheaths and irrigation

Heat generated at the tips of nasal endoscopes have been shown to reach temperatures high enough to cause thermal tissue injury. Endoscope sheaths have the potential to minimize the risk of thermal tissue injury. The purpose of this study was to assess the abilities of plastic and metal endoscope sheaths and sheath irrigation to insulate against dangerous scope tip temperatures.

The Vibrio Diseases in 1982: An Overview

Members of the genus Vibrio are the causative agents of a major component of the diarrheal diseases of man, and of a small but intriguing number of systemic infections. In this brief overview I will outline my present perception of the nature and importance of diseases caused by vibrios, and then discuss a few of our own observations about toxin production by cholera vibrios. In other papers presented in this symposium, many of the participants will provide more detailed discussions of some of the topics which I can only introduce in this review.

Dimensions of the medial wall of the prelacrimal recess: Prelacrimal recess dimensions

Addressing anterior maxillary sinus pathology endoscopically that is inaccessible with an endoscopic modified medial maxillectomy requires either a prelacrimal approach (PLA) or an endoscopic Denkers approach (EDA). The PLA involves removing the medial wall of the prelacrimal recess (PLR), which is the bone between the pyriform aperture (PA) and nasolacrimal duct (NLD), from nasal floor to orbital floor. The PLA preserves the inferior turbinate and NLD, whereas both are sacrificed during an EDA. The purpose of this computed tomography (CT)‐based study was to determine the anteroposterior and superoinferior dimensions of the medial wall of the PLR.

The Current Status of Cholera Toxoid Research in the United States

One of the major efforts in cholera research in the United States has been the development of a cholera toxoid sufficiently free of somatic antigen that it would be suitable for the detection of any effectiveness that antitoxic immunity may have in preventing or ameliorating clinical cholera. In consideration of the degree of effectiveness of cholera vaccines [8-10] and the case rates of cholera that might be anticipated in various endemic areas [7], the Cholera Advisory Committee of the National Institutes of Health recognized that field trial populations would have to be very large if one wished to detect the effects of antitoxic immunity superimposed upon antibacterial immunity and therefore, from its earliest considerations, the committee established as one of the requirements for a toxoid that it be very low in somatic antigen content. It should be emphasized that the objective of the work to be reported here was the development of a toxoid that would be an experimental tool for the study of antitoxic immunity rather than at this time to develop an immunizing agent of optimal effectiveness.