The history and development of breast implants.

This review discusses the historical development of smooth and textured silicone gel filled implants, and examines the reasoning behind product development and aspects of surgical technique from a surgeon's perspective.

The growth of Japanese science and technology.

Several measures are used to delineate the remarkable growth in the Japanese technological position over the last decade. The share of U.S. patents issued to Japanese inventors has been rising at 1 percent per year. These patents are the most frequently cited patents in the U.S. system. By 1984, Japanese inventors obtained more U.S. patents than inventors in the United Kingdom, France, and West Germany combined, and the gap has been widening ever since. As measured by publications, the Japanese scientific position is more modest, with a 0.5 percent rise per year in papers and with barely average citation performance. These indicators characterize Japan as a technological powerhouse, with highly innovative technology, and an expanding but far less powerful scientific position.

In vitro characterization of an artificial dermal scaffold.

The treatment of extensive burn injuries has been enhanced by the development of artificial skin substitutes. Integra Artificial Skin, an acellular collagen-glycosaminoglycan (C-GAG) dermal equivalent requires a two-stage grafting procedure. However, preseeding the C-GAG dermal equivalent with cultured fibroblasts and keratinocytes, with the aim of performing a single-stage grafting procedure, may be beneficial in terms of replacing the requirement for traditional split-skin grafts. In this comparative in vitro study, the interactions of cultured human dermal fibroblasts and epidermal keratinocytes in Integra Artificial Skin in comparison to cadaver deepidermalized dermis (DED) was investigated. An increase in cell proliferation and migration in the C-GAG dermal equivalent was observed over time. Cocultures of fibroblasts and keratinocytes on both dermal equivalents showed positive expression of proliferation, differentiation, and extracellular matrix (ECM) protein markers. Organization of keratinocytes in the epidermal layers of DED composites were better compared to the C-GAG composites. Deposition of ECM proteins was enhanced in the presence of keratinocytes in both dermal equivalents. Results demonstrate that in vitro the C-GAG dermal equivalent is biocompatible for cell attachment, migration, proliferation, and differentiation. Preseeding Integra Artificial Skin with cultured autologous fibroblasts and keratinocytes for in vivo application, as a single-stage grafting procedure, warrants testing. A better clinical outcome may be achieved as shown by our in vitro results of the coculture composites.

High incidence of viral hepatitis among American missionaries in Africa.

Protestant missionaries (n = 360) serving in sub-Saharan Africa between 1967-1984 were studied to determine the risk of hepatitis A virus (HAV) and hepatitis B virus (HBV) infection. Personnel were serologically screened for antibody to both the hepatitis A virus (anti-HAV) and the surface antigen to the hepatitis B virus (anti-HBs) prior to departure, periodically during service abroad, and upon completion of their African tour. Rates of seroconversion were used as measures of the incidence of infection. Prior to service, 16% of the staff had anti-HAV and 3% had anti-HBs; post-service rates were 42% and 26%, respectively. Over 90% of the staff with greater than 20 years of service were seropositive for anti-HAV. For both viruses, the infection rate was highest during the first 1-2 years of service, when 28% of those susceptible to HAV and 11% of those susceptible to HBV became infected. Over the next decade, the median annual attack rate was 5.4% for HAV and 4.2% for HBV. Differences in the missionary HBV infection rate among the various African nations served tended to reflect differences in the magnitude of chronic HBV carriage among indigenous population groups. We conclude that missionaries to sub-Saharan Africa are at enhanced risk of both HAV and HBV infection, and that all should receive passive immunization with immune globulin and active immunization with hepatitis B vaccine.

Mortality trends of American missionaries in Africa, 1945-1985.

Mortality trends of missionary staff serving in sub-Saharan Africa were tracked for the period 1945-1985. For 1945-1970, when more complete incidence data were available, the missionary death rate was approximately 40% lower, after adjustment, than would be expected in a comparable US population. This trend persisted through 1985. Between 1945 and 1970, the largest number of fatalities was attributable to malignancy, atherosclerosis, accidents, and infectious disease, and the greatest mortality risks, compared with the US experience, were from homicides, the complications of pregnancy, and infections, notably malaria, hepatitis, and polio. Beginning in the late 1950s, motor vehicle accidents became the leading cause of death. Since the 1960s, accidental causes of death have been approximately 50% higher than in the US, and homicides have been four times higher. During this same period, the infectious disease death rate decreased to approximately that within the US. Currently, the leading causes of mortality are motor vehicle accidents, malignancy, and atherosclerosis, followed by other accidental causes, notably aircraft mishaps and drownings. Viral hepatitis is presently the leading infectious disease cause of death. Other contemporary lethal infections include malaria, rabies, typhoid, Lassa fever, and retroviral infection. It was concluded that missionaries in sub-Saharan Africa had a death rate approximately half that expected in a comparable domestic control population. Preventive strategies, particularly relative to accident and infectious disease prevention, could effectively reduce mortality risk further.

No evidence for chloroquine-associated retinopathy among missionaries on long-term malaria chemoprophylaxis.

Chloroquine continues to have a limited role in the chemoprophylaxis against malaria. Although periodic ophthalmologic examinations are recommended with weekly suppressive dosing, the occurrence of retinopathy associated with this regimen is unproven. Surveillance of career missionaries was conducted to explore the association between total body burden of chloroquine and the development of retinopathy. Five hundred eighty-eight missionaries, reflecting 6,250 person-years of chloroquine exposure were surveyed; 53 persons reflecting 560 person-years exposure with a median cumulative chloroquine dose in excess of 300 g were examined. Only one case of chloroquine-induced retinopathy was detected. This occurred in a missionary who had inappropriately taken chloroquine daily for at least six years as an anti-inflammatory agent for a connective tissue disorder. We also observed that expatriates often overused chloroquine because of apprehension about malaria and used the drug for unrelated conditions. Our results failed to demonstrate an association between a weekly chloroquine dosing regimen and drug-induced retinopathy.

The risk of viral hepatitis A, B, C, and E among North American missionaries.

The seroprevalence and incidence of hepatitis A, B, C, and E virus infection were determined among North American missionaries (n = 328) serving in various geographic locations between 1967 and 1984. The mean age of subjects at entry into the study was 39.7 years (range 5-73 years); 65% were female; 89% had lived outside the United States before the study began. Seventy-eight percent of subjects served in sub-Saharan Africa during the study. At initial evaluation, 50.9% of the subjects had antibodies to hepatitis A virus (total anti-HAV), 8.5% to hepatitis B virus core antigen (total anti-HBc), 0.6% to hepatitis C virus (total anti-HCV by second-generation immunoblot assay), and 0% to hepatitis E virus (IgG anti-HEV). After an average period of service of 7.3 years (2,396 person-years total), 5.8% of the missionaries seroconverted to anti-HAV, 5.5% to anti-HBc, 0.6% to anti-HCV, and 0% to anti-HEV. This study indicates a relatively low risk of hepatitis C and E virus infection among missionaries while confirming the previously reported high risk of hepatitis A and B virus infection. Hepatitis A and B vaccination is recommended for long-term travelers to developing countries.

Pediatric Lassa fever: a review of 33 Liberian cases.

Thirty-three cases of pediatric Lassa fever were identified at Curran Lutheran Hospital and Phebe Hospital in Liberia between January 1980 and March 1984. All 18 fetal cases died and the case-fatality rate for 15 childhood cases was 27%. We identified four clinical presentations according to age, including a case of congenital Lassa fever, a condition not reported previously. Two cases of Lassa fever were found serologically during a one-month survey of all pediatric admissions at Curran Lutheran Hospital, 2.4% of those children who had serum pairs collected. We also identified a "swollen baby syndrome" consisting of widespread edema, abdominal distention, and bleeding. This distinctive clinical presentation of Lassa fever ended in death in three of four cases and was present in three of the four childhood deaths in this series. Its absence seems to be a good prognostic indicator in children.

Risk of Helicobacter pylori infection among long-term residents in developing countries.

The seroprevalence and incidence of Helicobacter pylori infection were determined among 312 North American missionaries who were serving in developing countries between 1967 and 1984. The majority (81%) resided in sub-Saharan Africa. When initially evaluated, the missionaries had a mean age of 40 years, 65% were female, and all were of white race/ethnicity. An ELISA showed that the initial prevalence of IgG antibody to H. pylori was 17%. After a mean of 7.4 years of service (1917 person-years of exposure), 37 (14%) of 259 initially seronegative subjects seroconverted to anti-H. pylori, giving an annual incidence of 1.9%. These data indicate a relatively higher risk of H. pylori infection among missionaries compared with an annual incidence of seroconversion of 0.3-1.0% in industrialized nations. Long-term residents in developing countries should be evaluated for H. pylori infection when gastrointestinal symptoms develop.

Lassa virus antibodies in hospital personnel in western Liberia.

The sera of 844 Liberian hospital staff memebers were positive for Lassa Virus (LV) antibodies in a survey using the indirect fluorescent antibody technique (IFAT). In two hospitals in Lofa County near the Sierra Leone border, the prevalence, 15.4%, was significantly higher than the 8.4% in seven others. There were near differences between the prevalence among laboratory workers, 15.3%, and other workers, 7.7%, and between midwifery students, 21.2%, and midwives, 4.2%, suggesting their infection from patients or their blood products. However, the over-all prevalence among those with patient contacts was the same as that among those without direct patient contact; most LV infections were apparently acquired from sources other than patients in hospital. This finding, the lack of evidence of hospital outbreaks and the presence of comparable prevalences in all age groups suggest that LV infections occur on a continuing basis in this population. In one hospital the comparison of the results of IFAT and complement fixation tests revealed some who reacted by one technique and not by the other. In one person the titre by IFAT had dropped from 1:32 to undetectable levels in two years. This finding prompts caution in the interpretation of results.

Endemic Lassa fever in Liberia. V. Distribution of Lassa virus activity in Liberia: hospital staff surveys.

Serological testing of hospital personnel by the indirect fluorescent antibody (IFA) technique was used to indicate the distribution of Lassa virus (LV) activity in Liberia. Determination of the places of origin of the staff members as well as the sites of the hospitals indicated that LV is active in throughout Liberia. Prevalences of IFA varied from 3.8% at the J. J. Dossen Hospital on the coast in the south-east to 22.3, 23.5 and 40.4% in Lofa County hospitals inland in the north-west. Rises in LV antibody prevalences, high prevalences and relatively high IFA titres in hospital personnel suggest the LV activity is particularly high in Lofa, Grand Cape Mount and Nimba Counties.

Endemic Lassa fever in Liberia. VI. Village serological surveys for evidence of Lassa virus activity in Lofa County, Liberia.

Six villages in Lofa County, north-west Liberia, and one near the coast were surveyed for the presence of indirect fluorescent antibodies (IFA) to Lassa virus (LV). Prevalences were similar among males and females, and among various age groups. The prevalence of IFA positive sera, 6.4%, in two roadside villages was significantly higher than in two matched villages "in the bush", 1.9%. It was also higher in Gbanwei, a roadside village which did not maintain traditional sanitary measures, than in Zuwulo, similarly located but with maintenance of clean-swept areas without shrubbery or rubble between the houses. In another pair of villages, the one adjacent to a Mission Clinic with a very high prevalence of IFA positive staff members had significantly higher prevalence, 14.1%, than did the other, a roadside village with 5.1% seropositives. LV antibodies were also found in 4.3% of the inhabitants of a small coastal village near Robertsfield International Airport. Though LV infections are more common in villages in which traditional practices have been modified, they are present even in villages which are relatively unchanged. In the former they appear to be continuous while sporadic in the latter. The prevalences of IFA in the villages with the highest rates are about one third of what is found in personnel of hospitals near them, suggesting that hospital staff members acquire infections from patients as well as from the communities in which they live.

Endemic Lassa fever in Liberia. I. Clinical and epidemiological aspects at Curran Lutheran Hospital, Zorzor, Liberia.

In a study to assess the epidemiological and clinical aspects of endemic Lassa fever (LF) in Liberia at Curran Lutheran Hospital (CLH), 44 cases were diagnosed by virological and serological techniques over a 22-month period. During one calendar month, testing of febrile patients admitted to the medical-surgical ward revealed six cases of LF, 13% of all febrile cases and 17% of those who were tested. As the study progressed the diagnostic skills of the hospital staff improved. The most common mistake was the diagnosis of a case of LF as pneumonia; the most potentially serious diagnostic problem was differentiating LF from typhoid fever, a readily treatable infection. LF may also mimic other diseases such as aseptic meningitis, pelvic inflammatory disease, gastroenteritis or arbovirus infection. We found a previously unreported symptom of LF, rib tenderness typical of costochondritis. The mortality rate in the medical-surgical ward was 5.4%; the over-all case-fatality rate was 13.6%. Women outnumbered men by nearly three to one, and had a higher mortality particularly noted in the pregnant. LF is common at CLH, and as many as 100 cases may occur annually at this hospital.

The use of Lassa fever convalescent plasma in Nigeria.

Lassa fever convalescent plasma (LFCP) has been administered to 27 patients in hospitals at Jos and Vom, Nigeria. Among serologically or virologically confirmed cases of Lassa fever (LF) given plasma on or before the 10th day, all eight survived, as did two of three possible LF cases. Of eight patients given LFCP after the 10th day, five died, as did all three possible LF cases. LFCP was also administered to five patients subsequently shown not to have LF, and to a suspected case contact; all survived without complications of therapy. There were 15 cases of LF during this time who did not receive plasma; 11 survived. Most cases of LF who received plasma and survived showed a rapid response to therapy, in contrast with the gradual recovery in those who did not receive LFCP.

Endemic Lassa fever in Liberia. III. Characterization of Lassa virus isolates.

Sixty-three virus isolates were obtained by inoculation of Vero cells with sera from 50 hospital in-patients in Liberia with acute febrile illnesses. 57 of the isolates were presumptively identified as Lassa virus (LV) by direct fluorescent antibody (DFA) staining of inoculated Vero cells. These, and six additional isolates obtained only by titration of supernatant fluids from inoculated Vero cells, were definitively identified as LV in a neutralization test. Two additional LV isolates were obtained from a patient's sera from Nigeria. By cross-neutralization tests, the Nigerian LV strains were serologically identical to the prototype Nigerian LV strain (PP) but were distinct from both a reference LV strain from Sierra Leone (SL), and from the Liberian (LIB) strains isolated in this study. The LIB and SL strains were closely related to each other, but not to the Nigerian LV strains. LIB LV strains were tested for virulence in strain 2 and 13 guinea-pigs, and a spectrum of virulence was observed which correlated only approximately with disease severity for human patients. Two human-lethal isolates killed all inoculated strain 2 and 13 guinea-pigs, whereas nine isolates from mildly ill patients were benign for guinea-pigs. Yet some LV isolates from severely ill or lethally infected patients, especially those from pregnant women and infants, were totally benign for guinea-pigs. These data suggest that antigenically distinct LV strains exist in nature, and that antigenically indistinguishable LV isolates may differ in virulence potential for various hosts.

Endemic Lassa fever in Liberia. IV. Selection of optimally effective plasma for treatment by passive immunization.

The efficacy of passive immunization for treatment of Lassa Fever (LF) is believed to depend on the titre of the neutralizing antibody infused. For the purpose of identifying optimal donors of LV-immune plasma, a population of LF-convalescent patients in Liberia was tested for prevalence of neutralizing antibody. Minimally protective titres, expressed as a log10 neutralization index, (LNI), were established in animal models as LNI greater than 2. LNI titres for 26 donors, tested eight or more months after illness, were modest: 16 titred 1 less than LNI less than 2, 4 titred 2 greater than LNI less than 3, and only 4 titred LNI greater than 3. Sequentially obtained plasma from six donors indicated that the LNI response was delayed relative to the indirect fluorescent antibody (IFA) response, that high titres (LNI greater than 3) occurred only after seven months and in only two of six patients. Most of the unselected LV-immune plasma will require concentration to therapeutically useful LNI titres. In a passive immunization experiment, guinea-pigs were protected by a late convalescent plasma (LNI = 4.8, IFA = 320) but not by an early plasma, (LNI = 0.6, IFA = 640), thus supporting the selection of immune plasma on the basis of the LNI. Cross serological testing with LV strains and convalescent plasma from patients in Sierra Leone, Liberia and Nigeria suggested that these LV strains were indistinguishable by cross-IFA, but were readily distinguishable by cross neutralization tests. Geographical matching of LV and plasma origins may thus be a factor in selection of optimal plasma for passive immunization of Lassa fever.

Endemic Lassa fever in Liberia. II. Serological and virological findings in hospital patients.

Patients admitted with fever to four Liberian hospitals were tested for Lassa fever (LF) by means of the indirect fluorescent antibody technique and by virus isolation. The incidence of LF and presumptive LF among consecutive febrile adult patients was 14% and 17% in two hospitals located in the interior; no cases of LF were found among 24 consecutive patients in a hospital near the coast. In the three inland hospitals the incidence of confirmed or presumptive LF among the patients in whom the diagnosis was seriously considered varied from 13% to 36%. Lassa virus was isolated from 17 patients out of the 59 cases found in this survey. LF is a common cause of fever in northern Liberia. The diagnosis depends upon the readiness of the staff to consider the diagnosis, the collection of blood specimens at appropriate times, and the preservation of sera at sub-freezing temperatures to permit survival of active virus and its subsequent recovery in an appropriate laboratory.

Can protracted relapsing fever resemble Lyme disease?

We report the case of a Protestant missionary who contracted tick-borne relapsing fever in 1979 while serving in the Sudan. Despite tetracycline treatment, his acute illness ran a protracted course, with migratory polyarthralgias lasting approximately 10 months. Symptoms recurred in 1984 and have persisted. At regular intervals, the patient has experienced recurrent episodes of fever, generalized fatigue, bilateral upper and lower extremity muscle weakness, and asymetric large joint polyarthralgia. Indirect fluorescent antibody testing of sera demonstrated titers of 1:16 for B. burgdorferi and 1:64 for B. hermsii, and immunoblotting confirmed past exposure to relapsing fever, but not Lyme disease. It is hypothesized that this individual's chronic symptoms have been related to relapsing fever, and that in certain situations or in select individuals, relapsing fever can be capable of producing a chronic clinical picture analogous to Lyme disease.

Koebner's phenomenon in burns: another complication following thermal injury.

The Koebner phenomenon is an uncommon postburn complication. The following report describes the emergence of viral warts on the hand of a child, 6 months after sustaining a superficial scald. The aetiology and immunological implications are discussed.

Pilot study into the IgG1 and IgG2 subclass response to polyvalent Pseudomonas vaccine in burned adults.

The IgG1 and IgG2 subclass response to thermal injury has been measured in a group of eight burned adults who received a single intramuscular injection of 0.5 ml of polyvalent pseudomonas vaccine (PPV), within hours of burn injury. The response in three of these patients is compared with the response in three matched patients who did not receive the vaccine. This single dose regimen of PPV did not appear to stimulate the early production of IgG1 or IgG2 and if subclass deficiency contributes to the risk of sepsis or toxin-mediated disease, as previous workers have established (Schur et al., 1970; Oxelius et al., 1981), then there is no apparent benefit in active immunization to reduce the risk in the early postburn period.