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The first outbreak of avian influenza A (H5N1) occurred among humans in Hong Kong in 1997. To estimate the risk of person-to-person transmission, a retrospective cohort study was conducted to compare the prevalence of H5N1 antibody among health care workers (HCWs) exposed to H5N1 case-patients with the prevalence among nonexposed HCWs. Information on H5N1 case-patient and poultry exposures and blood samples for H5N1-specific antibody testing were collected. Eight (3.7%) of 217 exposed and 2 (0.7%) of 309 nonexposed HCWs were H5N1 seropositive (P=.01). The difference remained significant after controlling for poultry exposure (P=.01). This study presents the first epidemiologic evidence that H5N1 viruses were transmitted from patients to HCWs. Human-to-human transmission of avian influenza may increase the chances for the emergence of a novel influenza virus with pandemic potential.

The first documented outbreak of human respiratory disease caused by avian influenza A (H5N1) viruses occurred in Hong Kong in 1997. The kinetics of the antibody response to the avian virus in H5N1-infected persons was similar to that of a primary response to human influenza A viruses; serum neutralizing antibody was detected, in general, >/=14 days after symptom onset. Cohort studies were conducted to assess the risk of human-to-human transmission of the virus. By use of a combination of serologic assays, 6 of 51 household contacts, 1 of 26 tour group members, and none of 47 coworkers exposed to H5N1-infected persons were positive for H5 antibody. One H5 antibody-positive household contact, with no history of poultry exposure, provided evidence that human-to-human transmission of the avian virus may have occurred through close physical contact with H5N1-infected patients. In contrast, social exposure to case patients was not associated with H5N1 infection.

Transnational Criminal Organizations are a disease or plague on the world Using this construct, this paper examines the Russian Mafiya, one strain of this disease, and analyzes the resultant security implications for the United States. It begins with a review of the conditions that led to the recent emergence of the Russian Mafiya as a disease on the world community, followed by an examination of what this disease consists of, how it spreads, and its effects on the health of nation states and the world community. It then provides a review of United States actions to date to combat the disease of transnational criminal organizations in general, and the Russian Mafiya specifically, where examples exist. Finally, it ends with proposed actions to counter the influence of the Russian Mafiya and transnational criminal organizations in the future, both through U.S. unilateral and international means. Due to the scope of transnational criminal organizations, this paper does not attempt to analyze all transnational criminal organizations but concentrates on the Russian Mafiya as an archetype disease organism which threatens the world community.

Bone is the third most frequent site of disease in patients with blastomycosis, and the vertebrae are among the bones affected most often. We describe the clinical features and treatment of eight patients with vertebral blastomycosis and review the literature regarding this disease. All eight patients had destructive vertebral lesions evident on radiographs, and all had clinical or radiographic evidence of a contiguous abscess. The lower thoracic or lumbar regions were affected most often. Fever and skin lesions typical of blastomycosis were variably present. All but one patient had an abnormal chest radiograph. Treatment included long-term antifungal therapy and drainage of large fluid collections. Five of the eight patients were cured of their disease. Of the other 3 patients, 1 is still receiving therapy and is probably cured, 1 died of blastomycosis, and the status of 1 is unknown. In areas of endemicity, blastomycosis should be a diagnostic consideration for any patient with a destructive vertebral lesion.

Therapeutic outcome of patients being treated for systemic mycoses with amphotericin B is possibly related to the serum concentrations of this drug that are produced in these patients. Because current data are conflicting, the magnitude of these concentrations was restudied by using a bioassay which gave precise and accurate results. The highest of 155 serum concentrations was 2.01 μg/ml. Mean concentrations were 1.21, 0.62, and 0.32 μg/ml, at 1, 18, and 42 hr, respectively, after intravenous infusion of amphotericin B. This drug was detected in serum 7 weeks after completion of treatment, but it could not be detected 13 weeks after treatment. Drug levels did not appreciably decrease in serum stored for 8 to 9 months at − 10 C. Unequal serum content in assay tubes and measurement of assay turbidity by visual inspection may explain previously reported amphotericin B levels of 3.0 to 12.5 μg/ml.

1. 1. Recurrent paroxysmal tachycardia occurred in a patient with intermittent aberrant atrioventricular conduction. 2. 2. A pathway bypassing part, but not all, of the atrioventricular node is suggested as an explanation for the somewhat shortened P-R interval and the somewhat lengthened QRS. 3. 3. Both the presenting nodal tachycardia and the aberrant conduction mechanism were easily controlled by oral procaine amide.

Summary Infection with Brucella melitensis or Brucella abortus strain 19 increases the susceptibility of ABC mice to the lethality of brucella endotoxin. Mice infected with B. melitensis die within 8–48 hr after challenge with brucella endotoxin. This susceptibility is maximal between 2 and 4 weeks and persists for at least 8–12 weeks. The degree of susceptibility to brucella endotoxin has no correlation with quantitative spleen cultures in brucella-infected mice. Mice infected with B. melitensis are also more susceptible to the lethality of typhoid and coli endotoxins.

SUMMARY From 1944 through 1953 at the University of Arkansas Medical Center, therapy of 24 patients with primary lung abscess was inadequate: six died, ten required surgery, and only nine (38 per cent) had a good result. In contrast, of 63 patients treated from 1954 through 1963, only two died, 14 had surgery, and 55 (87 per cent) had a good result. In this group, age significantly influenced response; seven of eight with poor responses were over 60 years old. An analysis of the effect of antibiotics revealed that penicillin was very effective. In 51 patients given penicillin only, one died and three had inadequate healing, while surgery was necessary in only seven (14 per cent). In contrast, of 12 patients receiving combined antibiotics, one died, three had inadequate healing, and four required surgery. These results indicate that penicillin alone is adequate antibiotic therapy for primary pyogenic abscesses.

Post-traumatic renal insufficiency is important as a cause of illness and death in initially surviving combat casualties and may be seen in civilian medical practice after accidents or extensive surgery. Hypotension appears to be a primary etiologic factor although delay in therapy, inadequate blood replacement, increase in plasma hemoglobin and other pigments, and the severity of the wound may contribute to the extent of renal damage and to the hypotension itself. Impairment of renal function following trauma may be reflected in different patients by sensitive clearance tesfts only, by azotemia and decreased urinary concentrating ability, by transient oliguria or by marked oliguria of varying duration. This suggests a wide variability in the extent of functional and parenchymal renal injury. With few exceptions, only the oliguric patients develop sufficient electrolyte abnormality or clinical uremia to require special care. In the latter instances rapidly progressive potassium intoxication necessitates prompt evacuation to a treatment center and, in the patients reported here, was the major cause of death prior to the use of hemodialysis. In addition to potassium intoxication, evidence that accelerated tissue catabolism characterizes post-traumatic renal insufficiency is found in (1) rapidly developing clinical uremia with corresponding rates of NPN accumulation, (2) early signs and marked degree of weight loss and emaciation, and (3) edema formation on less than conventional fluid intake allowances. The contrast with acute renal failure of non-traumatic origin has been repeatedly emphasized. Frequently occurring extensive and progressive infection, impaired wound healing and a marked bleeding tendency in some patients complicate the clinical course and intensify the therapeutic challenge.

Summary The injection of Hemophilus pertussis vaccine increased the susceptibility to histamine in Swiss-Webster mice but not in ABC mice. Injections of intact brucella cells or of brucella endotoxin did not increase susceptibility to histamine in either Swiss-Webster or ABC mice. Both Swiss-Webster and ABC mice demonstrated an increased susceptibility to bacterial endotoxins after pertussis vaccine. Pertussis vaccination did not alter the susceptibility of Swiss-Webster mice to the histamine-releasing agent, 48/80. Pertussis vaccination abolished the protective action of chlorpromazine against endotoxin but did not alter the protection afforded by adrenocorticosteroids. The relationship between susceptibility to endotoxin and susceptibility to histamine following pertussis vaccine is discussed.

SummaryIntravenous injection of polyvinylpyrrolidone (P VPN-molecular weight 12,600) caused urinary excretion of trypan blue in rabbits, even when given 48 hours following injection of the dye. PVPN also protected mice against tetanus toxin but only when both toxin and PVPN were given intravenously at the same time. Since no protection was observed when therapy with PVPN was delayed or when the toxin was given in-traperitoneally, it was suggested that PVPN was ineffective against tetanus toxin fixed in the tissues.

Summary The single injection into mice of a sublethal amount of endotoxin from Brucella melitensis confers partial resistance to subsequent lethal doses for at least 4 mo. Three weekly injections confer a greater protection, which persists for at least 10 mo. Three weekly injections of endotoxins from Salmonella typhosa, Escherichia coli, or Shigella sonnei result in homologous resistance for 2 mo. Resistance to heterologous endotoxins in mice immunized with either brucella, typhoid, coli, or shigella endotoxins was inconstant and persisted less than 1 mo. A striking exception was that heterologous protection against brucella endotoxin was consistently present for at least 4 mo. Serum precipitins for heterologous endotoxins were formed in only 4 of 60 mice tested; in contrast, intradermal reactions to heterologous endotoxins occurred in 16 of 46 animals. Resistance to infection with Brucella melitensis was maximal in mice immunized with brucella endotoxin, but partial resistance occurred in mice immunized with heterologous endotoxins. The mechanism of resistance to endotoxin was discussed but no complete explanation was advanced.

SummarySalmonella typhosa endotoxin produced hypothermia, leukopenia, and death in both germ-free and conventional guinea pigs. The lethal dose was identical in both, but hypothermia and leukopenia were produced in conventional guinea pigs by only one-third of the amount required in germ-free animals.

The magnitude of the concentrations of amphotericin B produced in serum of patients with systemic mycoses may significantly influence the outcome of therapy with this drug. Since amphotericin B is conventionally administered in intravenous infusions lasting 4 to 6 hr, we asked whether faster infusions of this drug might yield higher serum concentrations without an increase in dose. This question was studied in three patients who received 16 infusions of this drug: eight infusions administered slowly (5 hr) and eight administered rapidly (45 min). Serum concentrations after each rapid infusion were compared with those after a slow infusion administered to the same patient. The mean serum concentration of amphotericin B 1 hr after the rapid infusions (2.02 μg/ml) was significantly higher ( P < 0.001) than the mean serum concentration of amphotericin B 1 hr after the slow infusions of this drug (1.18 μg/ml). Mean serum concentrations 18 and 42 hr after rapid infusion remained slightly but not significantly higher than respective mean concentrations after slow infusions. By yielding higher initial serum concentration, rapid intravenous infusion may be therapeutically more effective than slow infusion of amphotericin B. Although rapid infusions caused no more toxicity than did slow infusions, the lack of greater toxicity with rapid infusion of amphotericin B should be further documented prior to extensive clinical application of this procedure.

INVOLVEMENT of the adrenal glands in patients with North American blastomycosis has usually been recognized only at autopsy in persons dying of disseminated disease. Apparently, such involvement rarely produces adrenal insufficiency since only 2 cases of North American blastomycosis associated with Addison's disease have been reported.1 , 2 In both patients symptoms of adrenal insufficiency developed some years after the onset of blastomycosis, one at eleven and a half years and the other at five years. The latter patient responded well to maintenance therapy with adrenocorticosteroids, but little details were given concerning the other patient. This report presents an additional case in . . .

Amphotericin B is effective in therapy for blastomycosis but causes a number of serious adverse reactions. Because ketoconazole has in-vitro activity against Blastomyces dermatitidis, we administered this agent in a dosage of 400 mg/d to 46 patients with blastomycosis, with 43 patients receiving at least 1 month of therapy. Thirty-five patients had cure without relapse over a mean follow-up of 17 months. Six had a relapse of infection but 4 of these had been noncompliant with therapy. Two patients improved initially but ultimately had progression of disease despite maintenance of adequate serum levels. Adverse effects were common but not severe. Three patients with extensive infection died--2 had received only one dose of ketoconazole and 1 had received therapy for only 2 weeks. The cure rate in these patients suggests that ketoconazole may replace amphotericin B as the initial treatment of blastomycosis that is not overwhelming.

SummaryMice protected against an initial lethal challenge with brucella endotoxin by treatment with cortisone acetate, 9-alpha-fluorohydrocortisone acetate, or chlorpromazine develop resistance to subsequent challenge to endotoxin.

The mechanisms by which patients ill with brucellosis develop their characteristic symptoms of fever, chills, myalgia, asthenia and malaise have not been precisely elucidated. In particular, the contributions of the brucella cell itself to the pathogenesis of these clinical features have not been extensively investigated. An unusual clinical observation (1) suggested that some component of the cell did play a significant role. When patients seriously ill with brucellosis due to Brucella melitensis were treated with chlortetracycline, an unexpected abrupt febrile response often occurred within 8 to 12 hours after the initial dose of the antibiotic. These adverse reactions could be abolished or ameliorated by administering smaller initial doses of the antibiotic. Such effects suggested to the observers that, as a result of the antibrucella activity of the chlortetracycline, brucella cells were killed, thus liberating some cellular component which then produced the febrile response. This component was presumably the endotoxin of the cell.

The nephropathy associated with methicillin sodium therapy is considered to be rare, but its prevalence is unknown. We reviewed the antibiotic therapy of 81 cases of Staphylococcus aureus bacteremia to establish the frequency and determinants of methicillin nephropathy in that disease. Fifty-two patients received methicillin; nine (17%) experienced the characteristic clinical signs previously associated with drug-induced acute interstitial nephritis. This nephropathy uniformly subsided after methicillin was withdrawn, and did not always include deterioration of renal function. Factors that correlated with methicillin nephropathy were endocarditis and prolonged treatment, but not intravenous drug abuse. There was only one adverse reaction among 29 patients treated with a cephalosporin. It was similar to the nephropathic reactions to methicillin. Thus, reversible renal abnormalities are prevalent during methicillin therapy, particularly among patients with staphylococcal infections such as endocarditis. When prolonged therapy with methicillin is required, the urinary sediment and renal excretory function should be monitored. ( Arch Intern Med 137:997-1000, 1977)

Excerpt In the 20 years that have elapsed since the classic review by Martin and Smith10focused attention on North American blastomycosis, numerous reports2, 4, 9, 11, 13, 14, 15have indicated that...

Excerpt It has been proposed that the altered neuromuscular activity in myasthemia gravis results from muscle antibodies formed by auto-immune mechanisms. Auto-antibodies to muscle were therefore s...