Older adults: the next suicide epidemic? Suicide rates historically and currently are highest by age among those over the age of 65. Predictions of markedly higher rates for future older adults have been advanced. Possible alternative factors that might produce lower risk among future elderly Americans are presented and it is argued that future trends are uncertain. Predictions of elderly suicide are made based on an assumption of stable rather than changing rates. Constant rates produce estimates of more than twice the current number of suicides and a proportionate increase in the number of suicides from one in five for the 1980s to one in three by the year 2030. The elderly are and likely will be a group with high suicide risk. Immediate efforts to lower elderly suicide risk and avert high future rates are recommended.


Self-directed and other-directed aggressive behavior in a forensic sample. Fifty habitually aggressive men were assessed for self-directed aggressive behavior (SDAB) and other-directed aggressive behavior (QDAB). Subjects displaying SDAB were compared with subjects exhibiting exclusively ODAB. The former were found to engage in more frequent acts of verbal aggression, physical aggression against objects, and physical aggression against others, as well as in more severe acts of verbal aggression and physical aggression against others. They were also more likely to receive diagnoses of mental retardation, organic personality disorder, intermittent explosive disorder, or autism. Findings are consistent with the presence of a neurologically based behavioral dyscontrol in the SDAB subjects.


Suicide and the military justice system. The United States military is sensitive to suicide. There are military policies that direct the formation of active suicide prevention programs. The U.S. military emphasizes a humanitarian approach. Modern military law, however, may view suicidal behavior as deviant. The prosecution of this behavior, although theoretically possible, has never occurred until recently. The U.S. military has now convicted soldiers for attempted suicide and assisted suicide. This article reviews these recent court decisions and suggests revisions in the military law.


A suicide epidemic in a psychiatric hospital. The authors report in detail on an epidemic of six inpatient suicides in a psychiatric hospital in Finland. Suggestion and identification had an effect on the timing as well as on the method of four of the suicides. The epidemic is viewed from individual, network, and organizational perspectives. The authors speculate on how such epidemics could be avoided. An increase in inpatient suicide rates has been reported from many countries, and the Werther effect may thus become a topic of considerable importance in psychiatric hospitals in the future.


Gender differences in the psychosocial correlates of suicidal ideation among adolescents. Gender differences in the psychosocial correlates of suicidal ideation were studied. A sample of 613 high school students (ages 14-19) completed measures of suicidal ideation, depression, hopelessness, life stress, loneliness, alcohol and drug use, and reasons for living. The results of a discriminant function analysis indicated that males reported higher loneliness and substance abuse scores than females whereas females reported greater suicidal ideation, depression, and reasons for living. The results of multiple regression analyses found that, although the same four variables, depression, hopelessness, substance abuse, and few reasons for living emerged as significant predictors of suicidal ideation in both samples, the predictive equation accounted for more of the variance in ideation scores in females (57%) than in males (46%). In a final analysis a discriminant function analysis of the subscales of the reasons for living inventory revealed that females have a greater fear of death and injury whereas males have a greater fear of social disapproval over having suicidal thoughts. This may account for the greater rate of suicide completing among males. Fear of social disapproval, more anger and impulsivity, and less help-seeking behavior among males are offered as potential variables to explain the observed gender differences.


Adolescent suicide and defensive style.

Adolescent suicide and defensive style. This empirical study investigated the relation between ego defense mechanisms, diagnoses, and suicidality among 200 adolescent psychiatric patients ages 12 to 16 years. Based on a structured diagnostic interview, adolescents were divided into three groups: suicide attempters, suicidal ideators, and nonsuicidal patients. Using the Defense Mechanisms Inventory (DMI), suicidal adolescents scored higher on the defense of turning-against-self and lower on reversal, as compared to nonsuicidal adolescents. Although suicide was significantly more common among adolescents with an affective disorder, turning-against-self remained significantly associated with suicide attempt even when diagnosis was controlled for. Results demonstrate the importance of defense mechanisms in understanding adolescent suicidal behavior.


A test of Durkheim's theory of suicide in primitive societies. Primitive societies were classified as high, moderate, or low on independent measures of social integration and social regulation to test Durkheim's theory of suicide. The estimated frequency of suicide did not differ between those societies predicted to have high, moderate, and low suicide rates. Thus, Durkheim's theory was not confirmed. Possible reasons for these results are discussed.


[Substitution effects in the care for the elderly in Southeast Groningen]. Results are presented of a 'demonstration project' in care for the elderly in the region South-East Groningen. Three issues were at stake in this project: extension of home-care, interventions in the referral processes to nursing homes and homes for the aged and coordinated allocation and planning of services for the elderly. Effects of the intervention were assessed with a quasi-experimental control-group design. In this paper, the issue of substitution is addressed from two different angles. First, changes in utilization of services in the experimental period (1988-1990) were evaluated. Second, changes in disability of elderly clients were evaluated. In both analyses, controls for national developments took place. The analyses show that substitution occurred, both in terms of utilization of care (more home-care, less institutional care) and in terms of the levels of need of clients (increases in mean level of disability in the populations of home-care and homes for the aged).


[Voting behavior of the elderly: motivation and background]. On the occasion of the Dutch election for the Second Chamber of Parliament held on September 6, 1989 the Central Bureau of Statistics conducted a National Voters Survey (NKO). Voting behaviour and information about the backgrounds of this behaviour were collected among 1506 voters. A formerly developed explanatory model of party choice of the electorate also appears to apply to the 382 elderly voters (55 years and older) in the sample. The results show that party choice of elderly is mainly determined by the characteristics income, social class, religion, social values (social criticism) and opinions about politicians. The elderly differ from the younger voters (18-54 years old) on several points. For the elderly, the characteristics sex, education and social class play a more important role, whereas certain values (family values and postmaterialism) are more relevant for the 18-54 year-old group. In addition it turned out that as far as the explanation of party choice is concerned, the elderly are not a homogeneous group. Voters aged 75-plus in particular can be distinguished from the 55-64 and 65-74 year-old groups.


[The elderly and memory complaints. A study of self-knowledge about memory, depression and memory abilities]. A group of 24 elderly persons who applied for a memory training because of memory complaints is compared with a control group of 24 healthy persons (matched for age, sex, and education). The comparison concerned several memory tests, complaints above everyday memory, depression and aspects of meta-memory. Before training, the memory training group had more complaints about everyday memory and depression compared to the control group. The training group reported more decline in memory capacity and functioning compared to their earlier days. They also reported feelings of stress and anxiety related to memory performance in daily life. Before training, the training group had more general knowledge about basic memory processes and used memory strategies more frequently. On most memory tests no differences were found. Memory complaints of elderly people may therefore not only be related to memory abilities according to tests but also to individual (negative) beliefs in memory capacity and abilities.


Chloroquine-resistant Plasmodium vivax in Papua New Guinea. An Australian expatriate on regular weekly antimalarial prophylaxis with chloroquine base and Maloprim developed symptomatic Plasmodium vivax infection which failed to respond adequately to 600 mg of chloroquine base. More ominously, a resident of the Highlands region of Papua New Guinea contracted vivax malaria which failed to be cleared by 2400 mg chloroquine base administered over 4 d. Both patients had achieved appropriate blood and plasma concentrations of chloroquine after treatment. Chloroquine-resistant P. vivax is now a clinical fact in Papua New Guinea.


Innate resistance to new antimalarial drugs in Plasmodium falciparum from Nigeria. The rapid dissemination of chloroquine-resistant Plasmodium falciparum in West Africa has been well documented and represents a significant health threat to autochthonous populations. The methodical development of alternative chemotherapeutic agents demands that dispensing new antimalarial drugs (mefloquine, halofantrine, and artemisinine [qinghaosu]) be closely monitored in order to protect their clinical utility. Indeed, mefloquine-resistant strains of P. falciparum have been reported. We present data from experiments in vitro on the innate resistance of P. falciparum isolates to mefloquine as well as a disturbing observation of transient resistance to artemisinine. The implications for the extended efficacy of these new antimalarial drugs are addressed.


Immune activation during cerebellar dysfunction following Plasmodium falciparum malaria. Evidence for immune activation was investigated in 12 patients with a rare syndrome of self-limiting, delayed onset cerebellar dysfunction following an attack of falciparum malaria which occurred 18-26 d previously. Concentrations of tumour necrosis factor, interleukin 6 and interleukin 2 were all significantly higher in serum samples of patients during cerebellar ataxia than in recovery sera and in the sera of 8 patients who did not develop delayed cerebellar dysfunction following an attack of falciparum malaria. Cytokine concentrations in the cerebrospinal fluid were also significantly higher in ataxic patients than in controls. These findings suggest that immunological mechanisms may play a role in delayed cerebellar dysfunction following falciparum malaria.


Urinary neopterin in volunteers experimentally infected with Plasmodium falciparum. To investigate the kinetics of monocyte/macrophage activation in falciparum malaria we determined urinary neopterin values serially in experimentally infected volunteers. Three subjects who had been immunized with irradiated sporozoites via mosquito bites served as controls. These individuals remained aparasitaemic, afebrile and without a rise in neopterin after challenge by infective mosquitoes. Four non-immune subjects developed Plasmodium falciparum parasitaemia, fever (3 of 4) and sharp rises in neopterin. Parasite densities reached 10-100 parasitized erythrocytes per microliter before elevations in temperature or neopterin levels were detected. Onset of fever preceded the rise in neopterin excretion by one day. Prompt chemotherapy was associated with the clearance of parasites from the blood and the return of temperature and neopterin levels to normal.


Cutaneous leishmaniasis in western Venezuela caused by infection with Leishmania venezuelensis and L. braziliensis variants. Between 1975 and 1987, epidemiological studies were carried out in several rural and urban communities in the central part of western Venezuela, especially in the state of Lara. 115 positive cultures were obtained from human cases and identified by their reactivity patterns to a cross-panel of specific monoclonal antibodies using a radioimmune binding assay; 53 were Leishmania venezuelensis and 62 were L. braziliensis. Most of these stocks were also characterized by isoenzyme electrophoresis, which confirmed the identification of the L. venezuelensis isolates. The enzyme electrophoretic profiles of the L. braziliensis isolates, however, revealed two populations with distinct electromorphs, one related to the World Health Organization L. braziliensis reference strain while the other population appeared to be a hybrid between L. braziliensis and L. guyanensis. L. braziliensis variants showed the widest geographical distribution, and were found in 7 states: Districto Federal (Caracas); Lara (Barquisimeto, Crespo, Iribarren, Jimenez, Morán, Palavecino, Torres, Urdaneta); Nueva Esparta (Margarita); Portuguesa (Las Cruces, Rio Amarillo); Trujillo (Cuicas); Yaracuy (Agua Fria, Cambural, Guaremal); and Zulia (Zipa-Yare). L. venezuelensis was found in the following endemic regions: Lara (Barquisimeto, Iribarren, Jimenez, Morán); Merida (Zéa); and Yaracuy (Campos Elias), showing that this parasite has a much wider geographical distribution than was initially recognized and that both these species can occur simultaneously within the same endemic region. Five isolates of L. braziliensis were made from infected donkeys (Equus asinus) in Urdaneta, Lara State, suggesting a possible domestic reservoir of L. braziliensis.


Comparison of parasitological and immunological methods in the diagnosis of leishmaniasis in Ethiopia. The sensitivity and specificity of parasite demonstration methods (smear, culture and histology) and serological assays (enzyme-linked immunosorbent assay [ELISA], direct agglutination test and immunoblot) were compared in the diagnosis of leishmaniasis in Ethiopia. Culture was found to be the most sensitive diagnostic method, followed by ELISA, for the diagnosis of cutaneous leishmaniasis (CL). When the clinical type of CL was taken into consideration, serological and parasitological methods were equally good for the diagnosis of diffuse cutaneous leishmaniasis. Overall, the serological assays were not sensitive enough to diagnose all the parasitologically confirmed cases of localized cutaneous leishmaniasis. Both groups of diagnostic methods performed equally well in the diagnosis of visceral leishmaniasis patients. In cases of CL where clinical diagnosis was a problem and histology could not give a definitive diagnosis due to the absence of demonstrable parasites, one of the serological assays, preferably ELISA, was very useful in establishing the final diagnosis.


Cutaneous leishmaniasis in south-western Ethiopia: Ocholo revisited. The borough of Ocholo, on the western side of the Ethiopian Rift Valley, is an endemic focus for Leishmania aethiopica infection and has been surveyed thrice between 1987 and 1990. In 1989, 3022 inhabitants (> 95% of the population) were interviewed and examined. The overall prevalence of localized cutaneous leishmaniasis (LCL) was 3.6-4.0%, with a peak value of 8.5% in the 0-10 years old age group. In half of the patients the active disease was estimated to last for 9.6 +/- 6 months; in 10%, it exceeded 3 years. Scars of LCL were present in 34.3% of the residents. Leishmanin skin tests were positive in 54% of 120 school-children without signs of the disease. Therefore, in Ocholo a minimum of 71.6% of the population has been exposed to L. aethiopica infection. Two cases of the diffuse form of cutaneous leishmaniasis were observed. In this highland biotope, Phlebotomus pedifer was found to be the major, and possibly the only, vector for L. aethiopica.


Detecting malaria sporozoites in live, field-collected mosquitoes. A method is described for identifying malaria-infected mosquitoes, without killing them or hampering their fitness. Individual mosquitoes were induced to salivate on coverslips, and sporozoites, deposited on the glass surface, were visualized by Giemsa staining. Of 21 mosquitoes found to contain sporozoites by salivary gland dissection, 13 had delivered sporozoites on coverslips. A positive correlation was found between the amount of saliva expelled and ejection of sporozoites, indicating that the sensitivity of the method may be increased by improving the probing behaviour of the mosquitoes. The procedure described may be suitable for selecting infected mosquitoes which are able to eject sporozoites during probing. Being applicable to wild Anopheles and to large numbers of mosquitoes, the method lends itself for use in field studies on malaria.


Identification of Leishmania from mucosal leishmaniasis by recombinant DNA probes. Three cases of mucosal leishmaniasis are described. Parasites isolated from mucosal lesions were identified by Southern blot analysis of their genomic deoxyribonucleic acids (DNAs) using recombinant DNA probe pDK20. Parasites from 2 patients were identified as Leishmania donovani s.l. One of the patients had pure mucosal lesions, while in the second patient there was dissemination of the parasite to other organs. The spectrum of the disease caused by L. donovani is discussed. The parasite from the third patient was identified as L. major.


HIV-Leishmania co-infections in Italy. Isoenzyme characterization of Leishmania causing visceral leishmaniasis in HIV patients. Visceral leishmaniasis (VL) infections in patients with human immunodeficiency virus (HIV) infection are dramatically increasing in Mediterranean countries such as Spain, France and Italy. A study has been carried out to characterize biochemically the agents of typical or unusual VL in subjects with HIV infection and to compare results with those obtained so far from VL and cutaneous leishmaniasis (CL) infections in HIV negative subjects. Twelve Leishmania stocks were isolated from 8 HIV patients and typed through the electrophoretic analysis of 14 isoenzymes. All the stocks were identified as L. infantum s.l. According to zymodeme classification, the results can be summarized as follows: (i) only half of the subjects were infected with the expected commonest viscerotropic zymodeme in the Mediterranean area, MON 1; (ii) 2 patients were infected with the most widespread agent of CL in Italy, L. infantum MON 24; (iii) one subject was found infected with a zymodeme (MON 78) which, so far, has been found only in Malta as an agent of CL; (iv) one subject was infected with a new zymodeme, MON 136, which shares biochemical characteristics with 2 dermotropic L. infantum zymodemes, MON 78 and MON 111. Thus, half of the HIV patients surveyed displayed severe visceralization of parasites usually showing low virulence in HIV negative subjects.


Enzyme-linked immunosorbent assay based on monoclonal and polyclonal antibodies for the detection of Entamoeba histolytica antigens in faecal specimens. A murine monoclonal antibody (MAb) (Eh208C2-2) raised against crude lysate of the pathogenic HM-1:IMSS strain of Entamoeba histolytica was used in an enzyme-linked immunosorbent assay for the detection of E. histolytica antigens in faecal specimens. The detection limit of the assay was 110 and 280 amoebae/ml of the HM-1:IMSS and HK-9 strains in phosphate-buffered saline, respectively. The assay was applied to single stool samples from 3 groups of individuals comprising 40 patients whose stools were positive for E. histolytica trophozoites and/or cysts (group I), 48 patients whose stools were negative for E. histolytica but positive for other parasites (group II), and 36 parasitologically-negative healthy controls (group III). Positivity rates of 77.5%, 2.1% and 2.7% were found in samples from groups I, II and III respectively. Specificity, positive and negative predictive values, and efficiency of the assay were 97.6%, 93.9%, 90.1% and 91.1% respectively. When group I samples were further divided into a trophozoite-positive subgroup IA (13 samples) and a cyst-positive subgroup IB (27 samples), the positive rates were 100% and 66.7%, respectively (P < 0.025).


Entamoeba histolytica: erythrophagocytosis, collagenolysis, and liver abscess production as virulence markers. High rates of erythrophagocytosis and collagenolysis in vitro have been regarded as indicative of virulence in vivo of Entamoeba histolytica trophozoites. In the present study, the erythrophagocytic index and the collagenolytic activity of 3 axenic lines of E. histolytica, strain HM1:IMSS, were measured. The 3 lines shared the same pathogenic zymodeme but showed clear-cut differences in the extent of liver damage induced in hamsters. A direct correlation between collagenolysis in vitro and the size of liver abscesses produced by each line of E. histolytica trophozoites was found. In contrast, the line with the highest erythrophagocytic index produced small amoebic abscesses in hamsters, whereas the line with a relatively low erythrophagocytic index produced the largest liver lesions. It is concluded that the extent of collagenolytic activity is a better marker of virulence of E. histolytica cultured under axenic conditions than is erythrophagocytosis.


Quantitative detection of schistosomal circulating anodic antigen by a magnetic bead antigen capture enzyme-linked immunosorbent assay (MBAC-EIA) before and after mass chemotherapy. The magnetic bead antigen capture enzyme-linked immunosorbent assay (MBAC-EIA) has been applied to detect schistosomal circulating anodic antigen (CAA) in pre- and post-treatment sera from 55 individuals in a Schistosoma mansoni control project in the Blue Nile valley of western Ethiopia. The amounts of CAA detected by this assay were positively correlated with the numbers of eggs per gram of faeces (epg). A significant reduction in CAA levels as measured by the MBAC-EIA was observed after mass chemotherapy. The sensitivity was 88-89% in clinically significant cases excreting more than 100 epg. In light infections, however, the sensitivity was lower. None of 32 uninfected Norwegian blood donors or 12 Ethiopian immigrants to Norway were positive. The specificity was thus estimated to be 100%. The test is rapid (1-2 h) and simple to perform without sophisticated equipment and could therefore, with slight modification, be used as a reliable method of diagnosis at field level in endemic areas undergoing mass chemotherapy campaigns or population surveys.


Serum laminin in hepatic schistosomiasis. Serum laminin levels were measured in patients with chronic hepatic schistosomiasis. A significant increase in the mean serum laminin level was observed in 14 patients with hepatosplenic schistosomiasis (2.57 +/- 0.83 units/ml [standard deviation]) compared to the level in 10 patients with the hepatointestinal form of the disease (1.38 +/- 0.45 units/ml) and in the control group of 10 (1.15 +/- 0.31 units/ml). In the hepatosplenic patients there was a significant direct relation between serum laminin and percutaneous splenic pulp pressure (r = 0.68). However, this relation was not observed with either liver function tests or levels of N-terminal propeptides of type III procollagen. These findings are compatible with an increased production of laminin in hepatosplenic schistosomiasis, which may be related to the observed enlarged liver and spleen basement membranes in such disease.


Prevalence of hookworm infection and its association with low haematocrit among resettlers in Gambela, Ethiopia. A cross-sectional survey of hookworm infection and haematocrit (HCT) levels was conducted in 7 resettled villages and 3 indigenous villages on sample populations selected by two-stage random sampling. Of 614 resettled persons and 187 indigenous persons, 65.5% and 60.4% respectively were infected with hookworm. Mean haematocrits for 664 resettled and 222 indigenous persons were 33.1% and 35.2%, respectively. A significant association (odds ratio = 2.65) was found between low haematocrit level (below the median for the sample population) and hookworm infection in the resettled population. Suggestions are made on the need for further studies and intervention programmes.


Natural infections of Dirofilaria immitis in Aedes (Stegomyia) polynesiensis and Aedes (Finlaya) samoanus and their implication in human health in Samoa. Dirofilaria immitis infections were observed in Aedes polynesiensis and Ae. samoanus in Samoa, together with Wuchereria bancrofti infections, in a study on sub-periodic bancroftian filariasis during 1978-1980. In the 4 indicator villages, the infection rate in Ae. polynesiensis was 0.46% and the infective rate 0.09% (15,223 mosquitoes were dissected). The infection rate in Ae. samoanus was 0.20% and the infective rate 0.08% (10,089 dissected). In 45 selected villages throughout the country, Ae. polynesiensis infection and infective rates were 0.92% and 0.29% (7575 dissected) and the rates for Ae. samoanus were 0.21% and 0.07% (9093 dissected). Infection with D. immitis was comparable in degree and distribution to that with W. bancrofti. There was a steady and consistent exchange of parasites between the human and canine populations, creating conditions favourable for human dirofilariasis in Samoa. Clinicians are warned against this probable human infection.


Serological evaluation of the 12 kDa subunit of antigen B in Echinococcus granulosus cyst fluid by immunoblot analysis. This study evaluated the 12 kDa (smallest) subunit of Echinococcus granulosus antigen B as a diagnostic molecule. Using immunoblotting, 90.9% of cystic hydatid patients, 40% of alveolar hydatid patients and 5.5% of cysticercosis patients showed sero-reactivity to this subunit. Human antibody response to the 12 kDa molecule appeared independent of factors such as parasite strain or host population responsiveness. The majority of infection sera, and some normal human controls, also recognized the 38 kDa subunit of antigen 5.


Dengue 1 epidemic in French Polynesia, 1988-1989: surveillance and clinical, epidemiological, virological and serological findings in 1752 documented clinical cases. An epidemic of dengue 1 occurred in French Polynesia in December 1988 and June 1989. This paper records (i) the trend of the outbreak and its surveillance and (ii) the clinical, epidemiological and virological data obtained from 1752 documented cases. The epidemic reached its peak in February in Tahiti Island, 7 weeks after its recognition. Among 6034 suspect cases reported by sentinel physicians, 60.3% were < 20 years old. The illness was classical dengue. No fatality or case of dengue haemorrhagic fever/dengue with shock syndrome was reported. Of 4792 patients subjected to laboratory testing, 41% were confirmed as positive. The serological attack rate was c. 40%. The estimated number of dengue infections in the Windward Islands was about 20,000. Transmission was associated with Aedes aegypti. Study of documented cases showed a higher confirmation rate in both the civilian population < 15 years old (46.5%) and the susceptible French military population (47.6%) than in older civilians (31.1%, P < 0.05). Furthermore, primary dengue infections were predominant in both of the first 2 groups. The diagnosis was mostly confirmed (i) by virus isolation on day < 5 of illness and (ii) by detection of immunoglobulin (Ig) M on day > or = 5 of illness. The study showed that adequate surveillance of an epidemic requires both clinically and laboratory-based systems.


An outbreak of typhoid due to multidrug resistant Salmonella typhi in Pondicherry. An outbreak of typhoid due to multi-drug resistant Salmonella typhi is reported from Pondicherry, India. While the average prevalence of drug resistant strains in 1980-1988 had been 11.7%, it increased to 52% in 1989-1990. The majority of strains (80.8%) were resistant to chloramphenicol, streptomycin, tetracycline and ampicillin; 40% were resistant to co-trimoxazole. Minimum inhibitory concentrations to 8 antibiotics for 17 representative strains were more than 10-fold greater than those of 13 sensitive strains. The multi-resistance was shown to be plasmid mediated in direct conjugation experiments and the strains belonged to Viphage type O, biotype II.


Oligonucleotide probes to identify three sibling species of the Anopheles farauti Laveran complex (Diptera: Culicidae). We have sequenced recombinant plasmid probes for each of 3 Anopheles farauti complex species and identified internal oligonucleotides of 25-26 base pairs, specific for each member of the complex. Synthetic oligonucleotides oAf1, oAf2 and oAf3, when radiolabelled and hybridized with deoxyribonucleic acid from An. farauti, reacted as highly specific probes for An. farauti numbers 1, 2 and 3 respectively. These probes are effective on air-dried or alcohol-preserved larval, pupal or adult specimens.


Risk factors in transmission of brucellosis from animals to humans in Saudi Arabia. A case-control study was undertaken to determine for the first time the specific aetiology of animal to human transmission of brucellosis in Saudi Arabia. Cases consisted of all patients with brucellosis attending the primary care clinic of the Riyadh Al-Kharj Hospital programme in central Saudi Arabia. A sample of individually matched controls was selected concurrently from patients attending the same clinic for unrelated problems. Cases and controls responded to a 48 item questionnaire on exposure to established risk factors for brucellosis. Greatest risk was found to be associated with indirect contact with animals (the consumption of unpasteurized dairy products), as opposed to direct contact with animals. When specific animal products were considered, greatest risk was associated with the consumption of milk and laban (buttermilk), as opposed to cheese or uncooked liver. When specific animal species were considered, greatest risk was associated with products derived from sheep and goats as opposed to camels and cattle. When direct contact with animals was considered, the study found a very high risk associated with assisting in animal parturition, but no significant risk associated with other direct (unspecified) animal contact.


Persistent and acute diarrhoea as the leading causes of child mortality in urban Guinea Bissau. An investigation of child mortality in a semi-urban community, Bandim II, in the capital of Guinea Bissau was carried out from April 1987 to March 1990. 153 deaths were recorded among 1426 live-born children who were followed for 2753 child-years. The under-five mortality risk was 215 per 1000 children (95% confidence interval [CI] 176-264), infant mortality 94 per 1000 (95% CI 73-115), and perinatal mortality 52 per 1000 (95% CI 41-63). By prospective registration of morbidity, post-mortem interviews, and examination of available hospital records, a presumptive cause of death was established in 86% of the deaths. Persistent and acute diarrhoea were the most frequent causes of death, accounting for 43 and 31 deaths per 1000 children, respectively. Fever deaths (possibly malaria), neonatal deaths, acute respiratory infections, and measles were other frequent causes. The access to health services was relatively easy: 75% of the children who died had attended for treatment at a hospital or a health centre. It is important to find ways of preventing and managing persistent diarrhoea, the major cause of death, and to improve the control of acute diarrhoea by a targeted approach.


Prognostic significance of rises in parasitaemia during treatment of falciparum malaria. Transient rises in parasitaemia occur commonly during the treatment of falciparum malaria but their prognostic significance has not been well defined. Twelve-hourly parasite counts from 133 malaria patients who were ultimately cured were therefore compared with counts from 97 therapeutic failures to determine if increase in parasitaemia was a useful early indicator of poor treatment response. Parasitaemia in both groups frequently rose during the initial 12 h of therapy (41% of all patients), but rising counts thereafter were rarer in treatment successes (P < 0.01). The relative risk of treatment failure was 3.8 if the count was higher at 24 h than 12 h, rose to 7.8 for increases at 48-60 h, and was 13.7 and 19.4 for counts above admission levels at 48 h and 60 h. These data suggest a way to identify patients at high risk of treatment failure.


Insecticide impregnation can restore the efficiency of torn bed nets and reduce man-vector contact in malaria endemic areas. Three trials with torn bed nets impregnated with permethrin and deltamethrin were made under field conditions at the Soumousso Field Station and the Vallée du Kou rice-field area, both in Burkina Faso, and the Djoumouna fish pond area in the Congo Republic. Even a considerably torn correctly impregnated bed net could be an useful method for limiting human-anopheline contacts. But bed nets in poor condition, i.e. too little impregnated and too much torn, cannot protect the users against anopheline bites. Protection increases with insecticide concentration, but at a high dosage insecticide could have more a repellent than a killing effect. Therefore a balance has to be found for the optimum rate of insecticide treatment of bed nets to obtain a real reduction in malaria transmission and morbidity, in every epidemiological situation.


The effect of artemisinine, its derivatives and mefloquine against chloroquine-resistant strains of Plasmodium falciparum in vitro. A 48 h in vitro test of the efficacy of artemisinine, dihydroartemisinine, artemether, mefloquine and chloroquine was carried out against 3 chloroquine-resistant strains of Plasmodium falciparum, strains K1 and T996 from Thailand and LS21 from India. A sigmoid Emax model was fitted to all in vitro inhibition data for each combination of drug and strain. Strains K1 and LS21 were strongly resistant to chloroquine, whereas T996 was partially resistant. Artemisinine, dihydroartemisinine and artemether were active against all strains, with complete growth inhibition at 10(-7) M. Artemether and dihydroartemisinine were both more potent than artemisinine, with 50% effective (EC50) values of 0.57-1.6 nM and 0.36-3.1 nM respectively; the EC50 of artemisinine was 1.5-6.1 nM for the 3 strains. The EC50 values for mefloquine were 46-185 nM. At higher concentrations, strains K1 and LS21 were fully inhibited, while with strain T996 mefloquine did not fully inhibit even at the highest concentration, 1.28 x 10(-6) M. It is concluded that artemisinine and its derivatives were highly effective against the 3 chloroquine-resistant strains, one of which showed borderline resistance to mefloquine.


The relationship between the response of Plasmodium falciparum malaria to mefloquine in African children and its sensitivity in vitro. The clinical efficacy of two doses of mefloquine (15 and 25 mg/kg body weight) was evaluated in 85 children suffering from acute symptomatic falciparum malaria. The cure rate on day 28 was 100% in both groups. There was no significant difference (P > 0.05) in the mean parasite and fever clearance times in both groups (48.5 +/- 14.6 and 32.0 +/- 12.7 h respectively for the 25 mg/kg group and 49.0 +/- 15.1 and 30.0 +/- 13.3 h respectively for the 15 mg/kg group). There was also no significant difference (P > 0.05) in these values between children with hyperparasitaemia (53.6 +/- 11.1 and 36.0 +/- 17.0 h respectively) and those without hyperparasitaemia (49.1 +/- 13.6 and 31.8 +/- 14.6 h respectively). Recurrence of parasitaemia was observed after day 30 in 2 patients in the 15 mg/kg group and in 1 patient in the 25 mg/kg group. In vitro, 3 of 21 isolates showed reduced susceptibility to mefloquine, with minimum inhibitory concentrations (MIC) > 67 nM/litre. The MIC and 50%, 90% and 99% inhibitory concentrations were 200.8, 6.27, 31.7 and 119.6 nM/litre respectively. Four of 22 isolates were resistant to chloroquine (MIC > 108 nM/litre). Isolates that showed low sensitivity to mefloquine in vitro were sensitive to chloroquine in vitro, and the 4 that were resistant to chloroquine were sensitive to mefloquine. Irrespective of MIC and dose of mefloquine, parasitaemia cleared in all subjects in 96 h or less.(ABSTRACT TRUNCATED AT 250 WORDS)


Ciprofloxacin does not achieve radical cure of Plasmodium falciparum infection in Sierra Leone. Recently, activity in vivo of norfloxacin has been reported against Plasmodium falciparum and, in vitro, ciprofloxacin has been found to be even more potent than norfloxacin. We therefore treated one patient infected with chloroquine-resistant P. falciparum at relatively low parasite density with ciprofloxacin, 200 mg intravenously twice daily for 3 d. This treatment failed to produce radical cure, although some suppressive effect was probably obtained. The growth of the P. falciparum isolate in vitro was inhibited at 12.5 micrograms/ml, whereas the plasma concentration recorded 1 h after infusion was only 1.2 microgram/ml. It is concluded that, if ciprofloxacin is to be used for treatment of malaria, a higher dose than that normally used for bacterial infections is necessary.


Chronotherapy of malaria: improved efficacy of timed chloroquine treatment of patients with Plasmodium falciparum infections. The effect of routine treatment with chloroquine (10 mg/kg on days 1 and 2 and 5 mg/kg on day 3) on parasitaemia and parasitaemic profile of patients infected with Plasmodium falciparum was studied. As with P. vinckei petteri, the mid-term trophozoites of P. falciparum were the most susceptible stages to chloroquine treatment. It is suggested that, in order to diminish the frequency of drug administration and to lower the risks of chemoresistance developing, treatment should be diversified, using the drug which is most effective on the parasite stages present in the peripheral blood.


Epidemic visceral leishmaniasis in southern Sudan: identity and systematic position of the parasites from patients and vectors. Twenty-five strains of Leishmania donovani isolated from humans and Phlebotomus orientalis in an epidemic area of southern Sudan were shown to belong to 3 very similar zymodemes: MON 18 (11 strains), MON 30 (1 strain) and MON 82 (13 strains). The 3 zymodemes are very closely related and seem to behave as a single population.


Isoenzyme characterization of Leishmania braziliensis braziliensis isolates obtained from Bolivian and Peruvian patients. Thirty-four Leishmania isolates obtained from Bolivian and Peruvian patients infected with mucocutaneous leishmaniasis were characterized by isoenzyme electrophoresis using 10 enzymatic markers; all belonged to the subspecies L.b. braziliensis. Three isolates showed marked variation compared with the reference strain with respect to 5 or 6 enzymes. These variant isolates originated from patients with forms of the disease which were unresponsive to treatment.


High cell surface hydrophobicity of virulent Entamoeba histolytica isolates. Thirty isolates of Entamoeba histolytica were examined for their cell surface hydrophobicity. It was observed that increased hydrophobicity of the trophozoites was associated with lesion-forming ability in hamster liver, a higher rate of erythrophagocytosis and greater resistance to complement. The relationship of cell surface hydrophobicity to other virulence markers in E. histolytica is discussed.


An epidemiological study of a Schistosoma intercalatum focus in south-east Gabon. A Schistosoma intercalatum focus in south-east Gabon was studied between July 1989 and July 1990. Among the 356 permanent residents in the village, 354 provided stool specimens and 101 (28.5%) were excreting eggs (geometric mean of egg density = 101.4 eggs/g, with a range of 1-3200). The pattern of prevalence and intensity of infection with age showed the curve usually found in schistosomiasis, i.e. increasing during the first 2 decades of life and then gradually decreasing. The analysis by stepwise logistic regression of factors shown to be important in determining infection in other schistosomiasis clearly demonstrated the significant and independent effects of both age and water contact on infection by S. intercalatum. These similarities with other schistosomal infections could indicate that similar immune mechanisms were operating. Urine from 284 subjects, of whom 90 were egg excreters, was tested for circulating antigen by enzyme-linked immunosorbent assay using a Schistosoma genus-specific monoclonal antibody (Sm 10.27.12). The test was positive for 90 subjects but only 35 of these were egg excreters. Although S. intercalatum is usually considered of low pathogenicity in man, this study showed a relationship between egg excretion and both splenomegaly and lower haemoglobin levels, even after taking into account the confounding presence of Plasmodium falciparum.


Schistosoma haematobium infection in Egyptian schoolchildren: demonstration of both hepatic and urinary tract morbidity by ultrasonography. Parasitological, clinical and ultrasonographical studies were performed upon 422 schoolchildren aged 12-16 years living in a village in the Fayoum where Schistosoma haematobium, but not S. mansoni, was transmitted. Over half of the children gave a history of receiving praziquantel therapy during the preceding 2 years. Symptoms (e.g., haematuria, burning micturition), signs (e.g., hepatomegaly, splenomegaly) and urinary findings (e.g., haematuria, proteinuria) correlated better with the presence and intensity of S. haematobium infection after correcting for this variable. Renal obstructive lesions detected by ultrasound were 2 and 3 times as common in those with moderate and heavy infections as in those with no or light infections, and urinary bladder wall lesions were far more frequent in those with moderate and heavy infections. A mild grade of periportal fibrosis, hepatomegaly and splenomegaly were present in some children in all groups. However, the prevalence of splenomegaly correlated directly with the intensity of infection; liver lesions occurred much more frequently in children with infection or a history of treated infection than in non-infected children denying recent treatment; and no child had hepatomegaly or splenomegaly in the absence of periportal fibrosis.


Haemoculture of Leishmania (Viannia) braziliensis from two cases of mucosal leishmaniasis: re-examination of haematogenous dissemination. Leishmania parasites were isolated from peripheral blood leucocytes of 2 patients with mucosal disease among a total of 23 parasitologically confirmed cases of leishmaniasis. One had had mucosal leishmaniasis for 4 years and active pulmonary tuberculosis was also diagnosed. The other patient presented a cutaneous lesion on his right leg of 3 months duration and asymptomatic mucosal involvement. He had received intravenous antimonials before isolation of parasites. Both patients had positive indirect fluorescent antibody and Montenegro skin tests. L. (Viannia) braziliensis was isolated from both patients. This culture of parasites from leucocytes provided direct evidence for metastatic spread of Leishmania via the blood.


Schistosome circulating anodic antigen in serum of individuals infected with Schistosoma japonicum from the Philippines before and after chemotherapy with praziquantel. The presence of the schistosome circulating anodic antigen (CAA) in serum of patients infected with Schistosoma japonicum from The Philippines has been investigated using an enzyme-linked immunosorbent assay (ELISA). Serum samples were tested from 48 patients who excreted S. japonicum eggs, 9 individuals with a negative stool examination, and 20 controls with both a negative stool and a negative circumoval precipitin test. No false positive result was detected for the unequivocally negative controls. CAA could be demonstrated in 72.9% of the egg-excreting patients. A positive correlation between parasite burden (eggs per gram of faeces) and antigen level (CAA titre) was found (Spearman's rho = 0.48, P < 0.001, n = 48). Four of 18 sera from the egg-negative individuals were positive in the ELISA. In view of the fact that anti-worm antibodies were also detected in these 4 sera, those reactions suggest active infection not detected by stool examination. In serum from patients treated with praziquantel, a significant drop in CAA titre was seen within 5 d after treatment (Wilcoxon's chi T = -2.23, P = 0.0258, n = 21). In conclusion, the detection of CAA by ELISA in S. japonicum infection can give valuable information in both individual diagnosis and therapeutic drug monitoring, as well as in epidemiological studies or disease control programmes.


Wuchereria bancrofti infection in human and mosquito populations of a Polynesian village ten years after interruption of mass chemoprophylaxis with diethylcarbamazine. In 1991, a study on Wuchereria bancrofti microfilariae (mf) and infection rates was carried out in the human and mosquito populations of a Polynesian village where, 10 years before, the mf prevalence rate was 6.4% and twice-yearly mass treatment with 3 mg/kg of diethylcarbamazine (DEC) was interrupted. Venous blood samples were collected from 575 (97%) individuals aged 15 years or more, of whom 122 (21.4%) were mf positive. The mf carrier prevalence rate was 27.4% in males, significantly higher than that of 14% in females; it increased from 7-12% in the youngest age group (15-19 years) to 40-50% in the oldest (> or = 60 years) for both males and females. 387 mosquito collections were performed and 1748 female Aedes polynesiensis were dissected, of which 1176 were parous. Among the latter, 114 (9.7%) were infected with Wuchereria bancrofti larvae at L1, L2 or L3 stages. The mean number of larvae per mosquito was 2.46 (range 1-15). Of the 114 infected mosquitoes, 30 harboured L3 larvae, giving a 2.55% infective rate; the mean number of L3 larvae per mosquito was 1.15 (range 1-2). Such findings indicate that the interruption of systematic twice-yearly mass treatment with DEC (3 mg/kg) has resulted, after 10 years, in a substantial increase of microfilarial prevalence in humans, and in high infection rates in mosquitoes.


Albendazole for the treatment of human gnathostomiasis. The efficacy of albendazole was investigated in 112 patients with symptomatic gnathostomiasis; 49 received 400 mg twice daily, 51 received 400 mg once daily, and 12 patients received placebo, all for 21 d. Subsequent follow-up was for 6 months. Cure (no further swelling) was seen in 93.9% and 94.1% of the treatment groups but in none of the placebo group. Additionally, reductions in eosinophil counts and in immunoglobulin G antibody were observed after treatment. Side effects were minimal. Albendazole may be an effective compound for the treatment of gnathostomiasis.


Hepatitis delta virus infection in Bombay. From June 1985 to June 1989, sera from 425 cases of acute viral hepatitis were gathered from 2 hospitals in Bombay; 331 sera were positive for hepatitis B surface antigen and immunoglobulin M anti-hepatitis B core antigen, and the donors' disease was diagnosed as hepatitis B. Anti-hepatitis D virus was found in 124 of these sera, and hepatitis D antigen was present in 24 more, conclusively proving the presence of hepatitis delta infection in association with hepatitis B in Bombay. Among the 425 cases of hepatitis, 39 cases of fulminant hepatitis developed, of whom 31 died. Hepatitis B virus (HBV) was the apparent viral infection in 32 of the fulminant cases, and 20 (63%) of them also showed evidence of hepatitis D virus (HDV) infection, suggesting an aggravation of their clinical course due to concurrent HBV and HDV infections.


Aflatoxin exposure, malaria and hepatitis B infection in rural Gambian children. Aflatoxin-albumin adduct levels were measured in serum samples obtained from a group of Gambian children. The relationships between exposure to aflatoxin and the prevalence of malaria, between exposure and humoral and cellular responses in vitro to defined malaria antigens and, amongst children with evidence of exposure to hepatitis B infection, between aflatoxin and carriage of the hepatitis B surface antigen (HBsAg), were assessed. Aflatoxin-albumin adduct was found in nearly all serum samples collected during a survey performed at the end of the dry season and levels of adduct were generally high (up to 720 pg aflatoxin-lysine equivalent/mg albumin). Higher levels of aflatoxin-albumin adduct were detected in Wollof children than in children of other ethnic groups and marked variation in mean adduct levels between villages was observed. Aflatoxin-albumin adduct levels were higher in children who were HbsAg positive and in children with Plasmodium falciparum parasitaemia than in controls. However, levels of adduct had no consistent effect on either malaria-specific antibody responses, lymphoproliferative responses in vitro, or morbidity from malaria during the subsequent rainy season. Much lower levels of aflatoxin-albumin adduct were detected in repeat samples obtained at the end of the rainy season. There was poor correlation between dry and rainy season levels of adduct in individual children. We have shown that Gambian children are exposed to high levels of aflatoxin. The seasonal variation of aflatoxin-albumin adduct and marked fluctuation of adduct with time in individual children need to be considered in the future planning of epidemiological studies using this marker of exposure.(ABSTRACT TRUNCATED AT 250 WORDS)


The role of sexual transmission in the epidemiology of hepatitis C virus in black South Africans. The role of sexual transmission of hepatitis C virus in Black South Africans was evaluated by a seroprevalence study of sentinel populations at varying risk for sexually transmitted diseases (STD). Prevalence of anti-hepatitis C virus antibodies was found to be 1.8% in an STD clinic sample of 272, 0.7% in a family planning sample of 148, 3.3% in a sample of 246 'blue collar' workers (81% of rural origin), and 0.9 in a sample of 117 new blood donors. All samples were from Black adults. The differences between them were not significant (P = 0.2348). In contrast, the prevalence of anti-human immunodeficiency virus antibodies in the STD sample (5.5%) was statistically significantly different (P = 0.00095) from the family planning clinic sample (1.4%) and the blue collar sample (0.8%) as well as from the reported prevalence for black blood donors in the Johannesburg area (0.7%). No evidence supporting a role for sexual transmission of hepatitis C virus was found, while the prevalence of infection appeared to be higher in rural populations and in males. These features are similar to hepatitis B in this population.


A short term projection of HIV infection and AIDS cases in Cameroon. By September 1991 Cameroon had reported 650 cases of the acquired immune deficiency syndrome (AIDS). The results from the sentinnel surveillance system showed a seroprevalence of human immunodeficiency virus (HIV)1 of 1.3% among pregnant women, 2.5% in people attending sexually transmitted disease clinics and 3.5% in tuberculosis patients in 1990. The estimated number of persons infected with HIV varies between 10,000 and 30,000. The World Health Organization projection model was used to make a short-term projection of HIV infection and AIDS cases; it indicated that the number of persons infected with HIV will double by the year 1995, with an estimated 8500 AIDS cases. Even in a low prevalence country such as Cameroon, the impact of the HIV epidemic is important and will result in a burden for the health care system.


Short-course treatment of typhoid fever with ciprofloxacin in south India. This study assessed the performance of short-course ciprofloxacin for the treatment of 34 adult patients with culture-positive typhoid fever. Patients received ciprofloxacin, 750 mg orally twice daily for 7 d. Measurement of response was based upon time from initial treatment to fever lysis, to afebrile state, and to symptom resolution. Ciprofloxacin-treated patients defervesced in a mean of 3.21 d (+/- 0.56), with stabilization of temperature in 4.0 +/- 0.73 d. After 90 d follow-up, no relapse or carrier was identified. Side effects during therapy were minimal.


Plague in Lushoto district, Tanzania, 1980-1988. Rodents were live-trapped in selected plague-inflicted villages from June 1980 to March 1988. Flea infestation rates were determined and the animals were serologically tested for plague. Clinically suspected and clinically healthy people in the affected areas were similarly tested for plague antibodies. Of 1596 rodent sera tested, 91 (5.7%) were positive for plague. These were mostly from Rattus rattus, Mastomys natalensis, Otomys spp. and Pelomys fallax. A total of 1772 fleas, of which Dinopsyllus lypusus, Xenopsylla brasiliensis and Ctenophthalmus calceatus comprised the largest proportion, was collected from the captured rodents. Total flea indices ranged from 0.67 to 1.12 fleas per rodent. A total of 2809 human cases and a mortality rate of 10.2% were recorded in 1980-1988. It was concluded that most rodent species in the area were suitable reservoirs of plague and that D. lypusus, X. brasiliensis and C. calceatus were probably responsible for transmitting the pathogen. Lack of effective quarantine measures during outbreaks was partly responsible for the spread of the disease to many villages, while inadequate rodent and flea control and poor sanitary measures could be responsible for continued outbreaks of plague in the area.


An evaluation of the hydrogen sulphide water screening test and coliform counts for water quality assessment in rural Malaysia. The H2S water screening test and the membrane filtration faecal coliform count were compared with Escherichia coli counts for water samples collected from household water sources and domestic drinking water in rural Malaysia. Water samples were taken from 151 wells, 44 taps supplying water from the treated municipal supply and 192 domestic stored water supplies. E. coli were detected in 20% of the samples (42% of wells, 7% of tap water and 6% of drinking water). Excellent correlation (Spearman's rank correlation rs = 0.93) was found between the faecal coliform and E. coli counts for all sample types. The H2S method was poorly correlated whether read at 18 or 30 h. False positive rates were highest for well water, and false negative rates were highest for both well and drinking water samples, with low E. coli counts. The faecal coliform test was an excellent predictor of the presence of E. coli in these water samples, while the H2S test was very inadequate.


Corneal ulceration in Tanzanian children: relationship between measles and vitamin A deficiency. Two 3-year prospective studies from 1982-1984 and 1986-1988 in Tanzania identified 189 children with corneal ulceration, of whom 31 (16.4%) were due to vitamin A deficiency. In 1982-1984, vitamin A deficiency was responsible for 23.4% of corneal ulcers (25 of 107) compared with 7.3% (6 of 82) from 1986-1988 (P = 0.006). It is postulated that the decrease in corneal ulceration due to vitamin A deficiency can be attributed to improved measles immunization coverage.


Corneal ulceration in Tanzanian children: relationship between malaria and herpes simplex keratitis. Two 3-year prospective studies from 1982-1984 and 1986-1988 in Tanzania identified 189 children with corneal ulceration, of whom 92 (48.7%) were due to herpes simplex keratitis. In 1982-1984 herpes simplex keratitis was responsible for 35.5% of corneal ulcers (38 of 107), compared with 65.8% (54 of 82) in 1986-1988 (P = 0.00006). It is postulated that the increase in corneal ulceration due to herpes simplex keratitis can be attributed to an increase in the incidence and severity of malaria infection.


Successful reversal of spontaneous diabetes in dogs by intraperitoneal microencapsulated islets. Long-term euglycemia by intraperitoneal transplantation of microencapsulated islets has not been described in the diabetic large animal model. In this study, we report the successful long-term reversal of diabetes by this method in spontaneous diabetic dogs. We have identified fundamental mechanism(s) associated with alginate-based microcapsule fibrosis, and have devised methods to ameliorate this problem. These include the use of purified alginate of low mannuronic acid content and cytokine suppression. Ten insulin-dependent, spontaneous diabetic dogs (insulin requirement 1-4 units/kg/day; absence of circulating C-peptide and diabetic K-values of 0.6 +/- 0.4) were entered into the study. Islets from mongrel donor pancreata were isolated and transplanted intraperitoneally either as free islet controls (n = 3) or as microencapsulated islet allografts (n = 7). In all seven encapsulated islet recipients, euglycemia was achieved within 24 hr (serum glucose failing from 304 +/- 117 to 116 +/- 72 mg/dl). IVGTT performed 14 days after islet transplant demonstrated normalization of K-values changing from a pretransplant level of 0.6 +/- 0.4 to 2.6 +/- 0.6. All animals receiving encapsulated islets remained euglycemic, free of the need for exogenous insulin, for a period of 63-172 days, with a median insulin-independence for 105 days. In contrast, recipients receiving free islets rejected their graft within seven days of implantation. In conclusion, this is the first report of long-term successful reversal of spontaneous diabetes in the large animal model by an intraperitoneal injection of encapsulated islets. The potential exists for this form of therapy to be explored in the treatment of type I diabetes in man.


Successful extended lung preservation with UW solution. Maximum preservation times of 4-6 hr continue to plague lung transplantation. The high-potassium colloid University of Wisconsin solution (UWS) has proved superior to the crystalloid modified Eurocollins' solution (ECS) for preservation of the liver, kidney, and pancreas. The purpose of this study was to compare UWS and ECS for extended lung preservation using a technique of combined pulmonary and bronchial artery perfusion. Simultaneous pulmonary artery and bronchial artery (via a closed aortic segment) perfusion was employed to harvest the lungs of ten mongrel dogs (wt 25-35 kg) using either UWS (n = 5) or ECS (n = 5) preservation solutions. Following 17 hr of cold (4 degrees C) pulmoplegic storage, the lungs were placed in an isolated perfused working lung (IPWL) apparatus. Seven freshly harvested lungs served as a control group (CON). Lung aerodynamics and gas exchange were evaluated at standard intervals until failure of the lung on the IPWL apparatus. Time until failure (mean +/- SEM) for each group was: CON = 209 +/- 14 min; UWS = 227 +/- 26 min; and ECS = 123 +/- 29 min. Only one of the ECS lungs lasted longer than 90 min. UWS-preserved lungs displayed a gas exchange efficiency equal to the CON group and better than that in the ECS-preserved lungs (lower A-aDO2, lower intrapulmonary shunt), suggesting better protection of the alveolar capillary membrane. Although the UWS lungs were initially less compliant than the ECS lungs, at no time was there a significant difference in the total work of respiration between the two groups. We conclude that UWS provides superior protection of the alveolar capillary membrane. The aerodynamic disadvantages of UWS preservation did not effect lung survival or total work of respiration.


Bile secretion and histology of liver autotransplanted into the pancreatic parenchyma. The pancreatic parenchyma was evaluated as a potential recipient site for hepatic fragment autotransplantation. Histologic and functional studies of hepatic autografts in the pancreas were performed in 15 mongrel dogs. Approximately 10 g of liver parenchyma was resected from each left lateral lobe. The remnant liver remained in situ. Bile secretion from the hepatic tissues implanted into the pancreas was estimated by measuring the indocyanine green (ICG)* concentration in pancreatic juice following intravenous ICG injection. One month following implantation, the hepatocytes in the pancreatic parenchyma were histologically colorless and did not have sinusoids. However, by the second month following implantation, hepatic nodules had grown extensively to become normal liver tissue, with sinusoids and a single liver cell-plate structure. At 4 months following intrapancreatic implantation the transplanted hepatic masses consisted of several hepatic lobules. Furthermore, ICG could be detected in the pancreatic juice of dogs surviving more than 2 months after implantation but no ICG could be detected in the pancreatic juice of normal controls. The present study provides direct evidence that hepatic grafts transplanted into the pancreas that has a ductal drainage system for bile secretion can reconstitute histologically normal liver tissue capable of secreting bile. This model can be used to understand the early steps of hepatic regeneration.


The impact of arterialization on hepatic microcirculation and leukocyte accumulation after liver transplantation in the rat. This study investigated the influence of hepatic arterialization on early graft function, microcirculation, and leukocyte-endothelial interaction after syngeneic orthotopic liver transplantation in Lewis rats. Livers were preserved for 17 hr in UW solution and transplanted without rearterialization (group 1: n = 10) or with immediate arterial reconstruction (group 2: n = 10). Graft function was analyzed by bile flow; microcirculation was assessed by laser Doppler flowmetry (LDF) and intravital microscopy (IVM). In addition, flow behavior of leukocytes was quantified by IVM after i.v. injection of the WBC marker acridine orange. Improved graft function in group 2 was indicated by increased bile production during the observation period of 90 min after reperfusion (7.18 +/- 0.62 vs. 3.63 +/- 0.63 ml/100 g liver [mean +/- SEM] P < 0.001). In arterialized grafts LDF values increased by 22.9 +/- 3.8% upon reperfusion of the hepatic artery (P = 0.004). Arterialization increased WBC velocities in sinusoids (group 1: 0.29 +/- 0.02 mm/sec, group 2: 0.34 +/- 0.01 mm/sec, P < 0.001) and postsinusoidal venules (0.43 +/- 0.05 vs. 0.64 +/- 0.05 mm/sec, P = 0.029). In addition, the number of nonperfused midzonal sinusoids decreased significantly (8.5 +/- 2.2% of all sinusoids analyzed vs. 4.2 +/- 1.3%, P = 0.048). However, the marked sinusoidal and venular WBC adherence observed 1 hr after reperfusion was not altered by arterialization. It is concluded that arterial reconstruction in rat liver transplantation improves microvascular perfusion and graft function but this improvement does not relate to WBC accumulation within the graft. We propose that studies on hepatic preservation and postischemic reperfusion in the rat should be based on the physiological model of dual vascularization.


Ultrastructural changes and lipid peroxidation in rat adipomusculocutaneous flap isotransplants after normothermic storage and reperfusion. Parallel in vivo, histological, and ultrastructural studies were carried out and markers of lipid peroxidation (Schiff's bases [SB] and thiobarbituric-acid-reactive material [TBAR]) were measured in rat adipomusculocutaneous flap isotransplants that had been stored for 0, 2, 4, 6, and 8 hr under normothermic (37 degrees C) conditions and reperfused for specific periods. Flaps stored for 4 hr and treated with intravenous desferrioxamine (DFX) or hypertonic citrate flush (HCA) were also evaluated. In vivo assessment was made after 7 days of reperfusion. Flaps stored for 4 hr eventually exhibited partial necrosis in vivo, and neither DFX or HCA flush increased the area of surviving skin. Electron microscopy revealed extensive storage damage in epidermal, follicle, fat, and smooth muscle cells and in endothelium. HCA significantly preserved fat cells (P = 0.0035) and DFX diminished smooth muscle damage. Reperfusion injury was seen in endothelial cells in the form of swelling that was not prevented by HCA or DFX. Ultrastructural alterations correlated with changes in susceptibility to lipid peroxidation in fat but not in skin. The results of these parallel studies indicate that both free radical-dependent and independent mechanisms operate in ischemia and reperfusion injury in flap tissue and that fat has a greater predisposition to free radical damage than skin.


Late airway changes caused by chronic rejection in rat lung allografts. Airway disease after lung or heart-lung transplantation is one of late major complications, affecting the prognosis of the transplants. Little is known about the causes of airway changes. We performed rat lung transplantation and investigated the late airway changes of the long-term surviving lung grafts: allografts, BN to Lewis; isografts, BN to BN rat. All recipients were treated with CsA. We found airway changes, i.e., mucosal ulceration, granulation, submucosal fibrosis, which was located in the large airways, in four of five allografted lungs. The lung isografts showed no pathological abnormalities. Immunopathological studies disclosed the localized expression of MHC class II antigens on the bronchial epithelium of the large airways where recipient type dendritic cells accumulated in the submucosa and CD4 positive predominant lymphocytes infiltrated. These findings support the idea that the late airway changes in lung transplants are caused by immunologically mediated chronic rejection.


Pharmacologic, toxicologic, and marrow transplantation studies in dogs given succinyl acetone. A novel immunosuppressant, succinyl acetone (4,6-dioxoheptanoic acid), was studied in dogs. Results with bolus intravenous injections at doses ranging from 50 to 1600 mg/kg showed dose-dependent alpha and beta half-lives, ranging from 30 to 80 min and 7 to 27 hr, respectively. Results suggested that continuous i.v. infusion was necessary to maintain constant plasma levels. Four dogs were given 9.2 Gy total-body irradiation and autologous marrow transplants along with continuous i.v. infusion of succinyl acetone at 50, 100, 200, or 400 mg/kg/day for 21 days, and all four had rapid, sustained hematopoietic engraftment. However, two of the four dogs receiving 200 and 400 mg succinyl acetone/kg/day, respectively, developed bilateral hind-limb ataxia, with histologically confirmed cerebellar lesions in the dog given the higher dose, thus establishing a potential dose-limiting neurotoxicity. Prevention of graft-versus-host disease was studied in recipients of allogeneic marrow. Dogs were given 9.2 Gy TBI, followed by hematopoietic grafts from unrelated DLA-nonidentical or DLA-haploidentical littermate dogs. Succinyl acetone was given as continuous infusion for 21 days after transplant at doses of 100-300 mg/kg/day. Starting succinyl acetone on the day of marrow infusion in four dogs failed to prevent rapid onset of acute GVHD, and dogs survived no longer than controls. Starting succinyl acetone 3 days before transplant delayed the onset of acute GVHD and prolonged survival significantly compared with that of dogs not given postgrafting immunosuppression (P = 0.008); survival was comparable to that in previously reported dogs given either methotrexate or cyclosporine as postgrafting immunosuppression (P = 0.88 and 0.99, respectively). Seven of the sixteen allogeneic recipients developed evidence of neurotoxicity during succinyl-acetone infusion. Neurological dysfunctions were manifested by hind-limb ataxia and posterior paresis. In conclusion, succinyl acetone significantly delayed the onset of GVHD and prolonged survival of DLA-nonidentical marrow graft recipients but did not induce graft-host tolerance and was associated with dose-limiting neurotoxicity.


Hepatic artery pseudoaneurysm ligation after orthotopic liver transplantation--a report of 7 cases. Pseudoaneurysm (PA) is a rare but life-threatening complication of liver transplantation. The authors present their experience on 7 patients treated by ligation of a post-OLT PA. Hepatic artery ligation or embolization was performed from 10 to 70 days after liver transplantation. Of the seven patients, four survived, one developed a biliary stricture, treated by percutaneous balloon dilatation, two died of a complication not related to treatment, and one died of multiple organ failure.


The use of radiolabeled anti-CD33 antibody to augment marrow irradiation prior to marrow transplantation for acute myelogenous leukemia. Disease recurrence remains a major limitation to the use of marrow transplantation to treat leukemia. Previous transplant studies have demonstrated that higher doses of total-body irradiation result in less disease recurrence, but more toxicity. In this study, the possibility of delivering radiotherapy specifically to marrow using a radiolabeled anti-CD33 antibody (p67) was explored. Biodistribution studies were performed in nine patients using .05-.5 mg/kg p67 trace-labeled with 131I. In most patients initial specific uptake of 131I-p67 in the marrow was seen, but the half-life of the radiolabel in the marrow space was relatively brief, ranging from 9-41 hr, presumably due to modulation of the 131I-p67-CD33 complex with subsequent digestion and release of 131I from the marrow space. In four of nine patients these biodistribution studies demonstrated that with 131I-p67 marrow and spleen would receive more radiation than any normal nonhematopoietic organ, and therefore these four patients were treated with 110-330 mCi 131I conjugated to p67 followed by a standard transplant regimen of cyclophosphamide plus 12 Gy TBI. All four patients tolerated the procedure well and three of the four are alive in remission 195-477 days posttransplant. This study demonstrates the feasibility of using a radiolabeled antimyeloid antibody as part of a marrow transplant preparative regimen and also highlights a major limitation of using conventionally labeled anti-CD33--namely, the short residence time in marrow. Strategies to overcome this limitation include the use of alternative labeling techniques or the selection of cell surface stable antigens as targets.


Advantages of cyclosporine as sole immunosuppressive agent in children with transplanted kidneys. A prospective study of intentional stopping of steroids 6 months after transplantation was done with 29 pediatric renal transplant recipients with a mean age of 10.4 +/- 3.4 years. Immunosuppression consisted of cyclosporine and methylprednisolone. We stopped giving MP to 24 children: to twenty after six months, four after 11-20 months. "Crude graft survival" was 97% during a mean follow-up of 36.7 +/- 15 months. The rejection rate was 48% during the first 6 months and 29% in the period after stopping MP. At present, 20/24 children (83%) have remained on CsA alone (18 patients) or CsA and azathioprine (2 patients) during a mean follow-up of 30 +/- 17 months. CsA nephrotoxicity occurred in 20.6% of patients, gum hypertrophy in 45%, hypertrichosis in 24%, and neurological symptoms in two patients (6.8%). Linear growth significantly improved after stopping MP: mean catch-up growth for prepuberal children 1.38 height standard deviation score (HSDS) and for pubertal children 1.6 HSDS. Bone age did not increase more rapidly than chronologic age. Weight/height index (W/HI) also improved. There was also a significant reduction in the use of antihypertensive drugs. Calculated glomerular filtration rate was decreased, though not significantly, after stopping MP. Thus, when graft survival is good, stopping corticosteroids corrects the major handicap of children with irreversible uremia--the poor linear growth--and improves the W/HI and control of arterial pressure. Longer follow-up periods are necessary to exclude significant worsening of renal function and an increased incidence of chronic rejection after stopping the steroid.


The occurrence of cytotoxic and non-complement-fixing antibodies in the crossmatch serum of patients with early acute rejection episodes. In an earlier study we found a strong correlation between the presence of donor-reactive HLA-specific antibodies in the crossmatch serum and early acute rejection episodes. Our experience was also that some of these antibodies were not cytotoxic and could therefore not be detected using the microcytotoxicity assays. In the present study, 11 patients from the earlier study who had weakly positive B cell reactive cytotoxic antibodies of the IgG class were further characterized. In addition, 14 new patients were selected who experienced early acute rejections but had a completely negative donor-B cell cytotoxicity crossmatch. A group of 12 controls without immunological complications was added, as well as 5 patients with early graft losses due to nonimmunological causes. Using the flow cytometric crossmatch test we confirmed the presence of HLA-specific antibodies in all 11 patients from the earlier study. In addition, positive flow cytometric crossmatches shown to be caused by HLA antibodies were observed in 11 of the 14 patients with acute rejections and negative cytotoxic crossmatch. One of 17 control patients had antibodies that were not HLA-reactive. IgA antibodies as well as IgG subclass determinations were performed in all positive sera. A substantial proportion of patients had HLA-specific antibodies of non-complement-binding classes (IgG2, IgG4, IgA) often of higher titers than IgG1 and IgG3. The subclass distribution pattern was heterogeneous and often included several subclasses. We conclude that non-complement-fixing antibodies can also contribute to the risk for development of early acute rejections after necrokidney transplantation. Immunological mechanisms for these findings are discussed.


Treatment of acute graft-versus-host disease with a nonmitogenic anti-CD3 monoclonal antibody. Treatment with the monoclonal antibody OKT3 specific for the CD3 complex associated with the T cell antigen receptor can reverse acute rejection of human renal allografts. However, efficacy of anti-CD3 antibodies for treatment of patients with acute graft-versus-host disease after marrow transplantation has not been established. The dose-limiting side effects resulting from T cell activation induced by some anti-CD3 antibodies in vivo have discouraged their use for this application. We now report a phase I-II study of GVHD treatment with the anti-CD3 antibody BC3, a monoclonal murine IgG2b that, unlike OKT3, does not activate T cells. Fourteen patients were treated with BC3 after progression of acute GVHD despite treatment with cyclosporine and corticosteroids, and three patients received BC3 as primary treatment for GVHD. BC3 was administered at a dose of 0.1 or 0.2 mg/kg/day for seven or eight days. Five patients achieved complete resolution of GVHD, eight patients had partial improvement, two patients had no change, and two patients had progression of GVHD on therapy. Responses were sustained in 8 of 13 patients. Mild chills, fever, hypertension, and chest discomfort occurred in various combinations following 6 of 17 (35%) initial infusions of BC3 and following 4 of 99 (4%) subsequent infusions. In each instance it was possible to continue BC3 therapy without adjusting the dose or treatment schedule. In each patient treated, the absolute count of peripheral blood lymphocytes decreased transiently but returned to baseline within 22 hr after the first infusion. Circulating T cells had surface CD3 molecules saturated by the infused antibody in all but one patient. Four patients survived longer than one year after treatment with antibody BC3, and 13 patients died of infection or organ failure. Administration of the nonmitogenic anti-CD3 antibody BC3 was associated with improvement in the clinical manifestations of GVHD with minimal acute toxicity. Efficacy of antibody treatment did not depend on depletion of circulating T cells. Therefore, antibody BC3 may be achieving therapeutic immunosuppression by modulating T cell function. Controlled studies in patients treated earlier in the course of GVHD should determine whether antibody BC3 can improve survival.


Acute vascular rejection in renal transplantation--diagnosis and outcome. Thirty episodes of histologically verified acute vascular rejection in kidney transplant recipients were studied. In 11 grafts the rejection was mainly vascular, whereas in 19 grafts a concomitant cellular rejection was seen. Histological features prognostic for bad outcome were glomerular necrosis and thrombi in the arteries and arterioles. Characteristic findings in transplant cytology, i.e., high number of monocytes and low number of lymphocytes and blast cells were noted prior to the onset of clinical signs of rejection, and this finding was also persisting throughout the rejection episode. The numbers of lymphocytes and blast cells were significantly lower in grafts with a pure vascular rejection than in grafts with a concomitant cellular rejection. Vascular rejection was reversible in 15 cases. As rescue therapy plasmapheresis and added immunosuppression were often successful.


Noninvasive procedures for diagnosis of renovascular hypertension in renal transplant recipients--a prospective analysis. The purpose of this study was to clarify the selectivity and specificity of noninvasive procedures for diagnosis of clinically suspected posttransplant renovascular hypertension. We prospectively investigated 25 renal transplant recipients with arterial hypertension and clinically suspected stenosis of the graft artery (8 female and 17 male patients; ages 45 +/- 15 years). We performed a captopril test with 25 mg captopril (n = 25), renography with technetium-99m diethylene triamine penta-acetic acid (99mTc-DTPA) before and after angiotensin-converting enzyme (ACE) inhibition with determination of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) (n = 23) and color-coded duplex ultrasonography of the transplant kidney vessels (n = 24). Renal transplant artery stenosis (RTAS) was excluded by renal arteriography in 20 patients and by operative evaluation or clinical follow-up in 5 patients. We identified 4 patients with RTAS and renovascular hypertension. The noninvasive methods showed the following results (sensitivity/specificity): (1) captopril test: 75%/67%; (2) renography combined with ACE-inhibition: 75%/84%; and (3) color-coded duplex ultrasonography: 100%/75%. We conclude that in patients with clinical evidence of RTAS most noninvasive diagnostic procedures are not sufficiently accurate to exclude the diagnosis. Only color-coded duplex ultrasonography did not fail to detect all patients with RTAS and may act as a screening test. Intraarterial renal angiography remains the most reliable and as-yet indispensable diagnostic test for transplant recipients to rule out RTAS.


The effects of steroid withdrawal on the lipoprotein profiles of cyclosporine-treated kidney and kidney-pancreas transplant recipients. Lipoprotein profiles were measured before and two months after complete withdrawal of prednisone in 34 kidney and 9 kidney-pancreas transplant recipients subsequently maintained on cyclosporine and azathioprine. Withdrawal of steroid therapy was accompanied by a 17% reduction in total serum cholesterol levels. However, there was a parallel reduction in all other measured lipoprotein concentrations, including an 18% reduction in high-density lipoprotein cholesterol levels. In diabetic recipients of a kidney or kidney-pancreas transplant, the ratio of total to high-density lipoprotein cholesterol was unchanged after steroid withdrawal. In nondiabetic kidney transplant recipients, this ratio actually increased significantly following withdrawal of prednisone. These observations suggest that it is premature to presume that withdrawal of steroid therapy will reduce the cardiovascular risk related to hyperlipidemia in cyclosporine-treated kidney or kidney-pancreas transplant recipients.


Cyclosporine nephrotoxicity in lung transplant recipients. End-stage lung disease has been treated successfully by lung transplantation (LTXP) at our institution since 1983. We report on the renal function of 30 LTXP recipients who were followed for at least 6 months (mean, 39 months; range, 6-60 months). All patients received quadruple immunosuppressive therapy including cyclosporine A, with a trough serum level (RIA) between 150 and 250 ng/ml for the first 6 months between 125 and 150 mg/ml after 6 months. The mean serum creatinine (SeCr) increased from a baseline value of 75 +/- 3.5 to 182 +/- 13.9 microM at the end of the follow-up. The greatest change in SeCr occurred within the first 6 months post LTXP. Fifteen of 30 patients who were initially normotensive required at least one antihypertensive medication post LTXP. By the end of the follow-up, 9 patients had SeCr > 200 microM. Two patients in this institution have progressed to end-stage renal disease requiring dialytic therapy. CsA nephrotoxicity has emerged as a major source of morbidity in the lung transplant population. Nephrotoxicity occurs early, and there does not appear to be any trend toward reversibility despite a lowering of the dose. Renal parenchymal injury may be progressive, despite an apparent plateau of the SeCr in some patients.


Immunofluorescent localization and immunochemical determination of cyclophilin-A with specific rabbit antisera. We raised rabbit antisera against homogeneous bovine cyclophilin A (CypA) and we report their use for its immunofluorescent and immunochemical detection without resorting to cyclosporine binding. Indirect immunofluorescence demonstrated that in tissue culture cells CypA is present in the cytoplasm diffusely and also associated with vesicles and the Golgi apparatus. In mitotic cells CypA is increased in amount and redistributed away from cytoplasmic organelles. High levels of CypA were demonstrated in murine splenic erythroblasts and myeloblasts, but they became undetectable during differentiation to mature erythrocytes and granulocytes. Large, often granular, lymphocytes stained very intensely, but small lymphocytes demonstrated variable staining. Dot blot immunoassays demonstrated that murine tissues contain similar amounts of CypA. During CsA treatment murine liver can increase its CypA content much more than spleen. In summary, we demonstrated that cells known to be resistant to the effects of CsA have high levels of CypA. Also tissues that are resistant to CsA can increase their levels more than sensitive tissues upon CsA exposure. Taken together these results suggest that CypA plays a role in cell cycle progression and that sensitivity to CsA may not be simply a reflection of the baseline CypA levels, but may also be affected by the regulation of these levels. Further work is needed in order to delineate the role of CypA in the cell cycle and its relation to the action of CsA.


Patterns of T cell-accessory cell interaction in the generation of primary alloresponses in the pig. Partially inbred, MHC-homozygous miniature swine provide a unique model for the study of organ transplantation and the induction of tolerance in large animals. Models of both vascularized solid organ transplantation and bone marrow transplantation have previously been established. The availability of monoclonal antibodies reactive with porcine leukocyte subset antigens now makes possible studies of the cellular immunology in this species, affording the opportunity to examine mechanisms of transplant tolerance and graft rejection in increasing detail. Using such antibodies and peripheral blood leukocytes from pigs of recombinant MHC haplotypes, we have examined porcine T cell-accessory cell interactions in vitro with attention to T cell subsets and the class of MHC alloantigen stimulation. Primary allospecific MLR and CML cultures were studied after depletion of accessory cells from responder and/or stimulator populations. Although class II MHC antigens were expressed on the majority of porcine T cells before and after depletion, these cells were insufficient for antigen presentation, since there was an absolute requirement for ACs in the generation of primary alloresponses. Proliferative and CTL alloresponses could be generated provided that ACs of either stimulator or responder type were present. Selective depletion of CD4+ T cells from the responder population demonstrated: (a) that the interaction mediated by self ACs was CD4-dependent; (b) that two pathways exist for interaction involving allogeneic ACs; and (c) that the interaction involving allogeneic class II is CD4-dependent, while that with allogeneic class I is not.


Priming and cross-priming for H-Y in female mice. Although female mice (H-2b and H-2g) that are responders to H-Y are able to cross-prime for this antigen, their ability to do so varies from strain to strain and can be influenced by whether they are exposed to H-Y via a subcutaneous hind footpad inoculation of male cells or via a male skin graft. On the other hand, females (H-2k) that are low responders to H-Y only can be sensitized to male skin isografts following a hind footpad inoculation of syngeneic male cells.


Determination of tolerance to self E alpha peptides by clonal elimination of H-2E reactive T cells and antigen presentation by H-2A molecules. A series of three synthetic peptides spanning H-2E alpha k chain residues (90-110), (110-130), and (130-150) were synthesized and purified. Mice representative of H-2E- (B6, B10, B10.M, B10.Q, B10.S) and H-2E+ (B10.D2, B10.K, B10.RIII) were immunized with individual peptides and lymph node cells challenged in vitro. Both B6 and B10 mice respond to in vitro challenge to peptides (90-110) (cpm 20,000), (110-130) (cpm 40,000), and (130-150) (cpm 60,000). In contrast all H-2E+ haplotypes were unresponsive to all three peptides (cpms < 10,000). Furthermore, B10 mice could be rendered hyporesponsive to E alpha k peptide challenge following expression of an E alpha k transgene or mating to an H-2E+ strain. The H-2Ad,k,f,q,s alleles were associated with reduced peptide recognition. Furthermore, alteration of the H-2A beta chain in bm12 mutant mice resulted in impaired responses to all three peptides. Immunization with synthetic peptides comprising major histocompatibility molecules may yield insights into mechanisms of self-tolerance.


Eukaryotic replication origins as promoters of bidirectional DNA synthesis. Recent work in yeast shows that eukaryotic origins of DNA replication are multipartite regulatory elements resembling promoters of transcription. As for the regulation of transcription, accessory transcription factors appear to function in concert with basic origin recognition factors to regulate initiation of DNA synthesis at specific subsets of origins. The participation of transcription factors in the regulation of DNA replication may facilitate temporal control of transcription and replication during the cell cycle, as well as providing a mechanism for integrating origin selection with the cellular transcriptional program.


The S locus of flowering plants: when self-rejection is self-interest. In certain families of flowering plants, a self-incompatibility (SI) locus prevents self-fertilization, by a specific interaction between the S-gene product produced in the pistil and the S-gene products borne on or expressed by the male gametophyte, the pollen grain. The female S-locus gene products for two families showing different types of SI have been putatively identified as major pistil glycoproteins (the S-locus-specific glycoproteins of the Brassicaceae and the S-RNases of the Solanaceae). However, they are distinct in sequence and mode of action. The nature of the S-locus gene product borne by the pollen is still uncertain in both systems.


Development of GPIIb/IIIa antagonists as antithrombotic drugs. Thrombosis represents a major target for development of drugs to prevent and treat a variety of cardiovascular and cerebrovascular diseases, which are the leading cause of morbidity and mortality in the Western world. This review by Andy Nichols and colleagues focuses on a central process in thrombosis, namely platelet aggregation, and how it can be inhibited by antagonists of the adhesion molecule GPIIb/IIIa. Successful and future therapeutic applications of GPIIb/IIIa antagonists, and their pharmacology, are considered in detail.


An approach to the management of tuberculosis in HIV endemic areas. The epidemic of HIV-associated tuberculosis is having a severe impact on tuberculosis control in sub-Saharan Africa, as well as the United States of America, and is expected to spread. Where facilities are limited, the association between HIV and sputum-smear negative tuberculosis hampers diagnosis; trials of anti-tuberculous therapy are indicated in some cases. Standard treatment regimens are effective, but thiacetazone should be avoided because of its association with severe, cutaneous adverse reactions. Treatment may have to be prolonged in HIV positive cases. Measures to maximize compliance with therapy are paramount. These include the use of the shortest possible regimens, of recognized potency, and emphasis on ensuring that the regimen is understood by and readily accessible to the patient.


How many bloods will a 'HIVCHEK' check? Multiple tests for HIV antibody for a single screening kit. Detection of HIV infection in blood donors or populations is usually by testing sera for antibodies to HIV-1 and HIV-2. Screening tests are now highly sensitive and specific, but still expensive and scarce in Africa. We tested the commercially available kits 'HIVCHEK 1 + 2' in two field laboratories, on specimens from blood donors and antenatal women in rural Zaire. We describe a method of using one test kit for up to five serum samples, saving money and time. In 491 antenatal mothers in Eastern Zaire, among whom the HIV seroprevalence was 3.3%, we compared 'HIVCHEK' results with results obtained by ELISA and Western blot. The 'HIVCHEK' multiple-sample method had a sensitivity of 82% and a specificity of 99.6%. In an area with an HIV seroprevalence of < 4%, using 'HIVCHEK' by the multiple sample method would lead to a saving of about 2,400 pounds for every 1000 individuals tested.


Aluminium phosphide poisoning.

Aluminium phosphide poisoning. Aluminium phosphide is a solid fumigant pesticide widely used in the Indian subcontinent as a grain preservative. Over the last 5 years there has been a dramatic increase in the number of cases of aluminium phosphide poisoning in India. Ninety-two patients with aluminium phosphide poisoning due to ingestion were studied over a period of 3 years. Abdominal pain, vomiting and restlessness were the common initial features followed by alteration in sensorium and shock unresponsive to conventional treatment. Electrocardiographic abnormalities were very common and highly variable. Routine serum biochemistry was usually unremarkable. Severe metabolic acidosis was common and mortality high (49%). The survivors recover completely without any residual organ damage. There is no known antidote.


Bacteriology of snakebite abscess.

Bacteriology of snakebite abscess. Thirty-eight cases of abscess secondary to pit viper envenomation are reviewed. The incidence of abscess formation was 9%. Results of aerobic cultures revealed growth of enteric, coliform organisms in 22 of 25 isolates obtained from previously unopened abscesses. Clinical evidence for co-existent anaerobic infection is presented. No cases of tetanus were encountered. Clinical and laboratory findings of patients in the study are correlated with a review of bacteriologic investigations of the oral flora of venomous snakes. Use of antibiotics effective against aerobic coliforms and histotoxic anaerobic organisms for prophylaxis and/or treatment of infectious complications of pit viper envenomation are recommended.


A simple scheme to improve compliance in patients taking tuberculosis medication. Compliance with prescribed treatment remains a major problem in the control of tuberculosis worldwide. We describe a simple method of improving patient compliance with hospital-based treatment. Eighty-two patients paid a deposit at the start of their treatment which entitled them to cheaper drugs and was refundable on completion of the prescribed course. Sixty-two per cent of patients completed the course compared with 23% of retrospective controls. A direct relationship was found between the amount of deposit paid and the rate of completion. Reasons why poor patients (who paid a lower deposit) may default are discussed, as are the merits of short-course drug regimens. It is recommended that similar schemes be assessed elsewhere.


Treatment of scabies in rural east Africa--a comparative study of two regimens. Scabies is endemic in Africa where living conditions make synchronous treatment of every member of the large extended family impossible. An open study was designed to investigate the optimum treatment of school children in rural Tanzania. In one school where 34 children (7%) were infested, treatment with benzyl benzoate was distributed to the affected child and those sleeping in close proximity. In another school where 29 pupils (6.4%) were affected, the above treatment was given along with soap and some scabicidal ointment (6% sulphur) to be used on residually affected areas. Again, the treatment was given to those sleeping in proximity. One month later 46% were clear at the first school and a significantly higher proportion (69%) at the second. I conclude that inefficient application of scabicidal treatment and lack of washing contribute to scabies treatment failures. Synchronous treatment of small groups within the extended family can be effective.


Sonographic changes following splenectomy for portal hypertension in Schistosoma mansoni. Eleven patients with portal hypertension due to infection with Schistosoma mansoni underwent splenectomy and devascularization operations. The patients were examined with ultrasound once preoperatively and twice postoperatively over a period of about 6 months. Following surgery there was significant and sequential reduction in the diameter of the portal vein at the hilum and the splenic vein at the pancreas. The liver lengths and index of liver size did not change significantly. No changes in the degree of periportal fibrosis could be detected.


[Cytogenetic effect in peripheral blood lymphocytes of children living in villages in the Ovruch District, Zhitomir Region of the Ukraine contaminated by radionuclides]. For the purpose of genetic indication of low level of chronic radiation exposure the cytogenetic monitoring of some critical children groups living in two contaminated Ukrainian villages was carried out. In all the groups the mean frequency of aberrant cells and chromosome type aberrations (including dicentrics, centric rings, chromosome translocations as well as polyploid cells) significantly exceeded control level. During the repeated examination of children from Vistupovichi (in 13 months after the first one) the striking increase of cytogenetic effect was revealed. Dicentrics and rings were registered in 79% of persons with the individual rate 0.5-1.5 and mean group frequency 0.57 per 100 cells. The authors tried to evaluate the average cumulative doses of radiation for examined groups using G. Littlefield equation for dicentric outcome under the low dose rate Cs-137 source and taking into account the assumption about the reducing of 50% dicentrics per year. According to this rough calculation, the revealed cytogenetic effect can correspond to the mean total dose of 33 cSv for Vistupovichi children.


[Genetic monitoring in connection with the Chernobyl accident]. The complex investigation has been provided to control the genetically influenced processes after Chernobyl accident in some Ukrainian regions. Some dangerous trends in genetic populational status were revealed in the Ukrainian regions surrounding Chernobyl power plant allowing for the increasing number of congenital anomalies among the newborns and the spontaneous abortions as well as higher proportion in aberrations of chromosome type in human somatic and embryos cells, higher incidence of structural defects in embryonal bone system and higher, compared with control, proportion of children with intensive catabolism (R-protein homeostasis).


[Cytogenetic study of the chorion and placenta in prenatal diagnosis of fetal pathology]. The experience of investigation of 230 chorion and placental biopsy in 209 women of high risk pregnancy group is presented. Two methods of "direct" chromosomal analysis have been compared. Prospects and high economic efficiency of chorion and placenta studies as against other methods of prenatal diagnosis, great role in a decrease of prenatal disease and mortality are confirmed.


[Results of the morphologic examination of abortuses and features of the pregnancy course when it is aborted in trimesters I and II]. Morphologic examination of abortuses has been carried out in the women, whose pregnancy proceeded under the threat of abortion. While analyzing the course of pregnancy and comparing with the results of the pathoanatomic examination, it is concluded that prenatal diagnosis is necessary in connection with the high risk of congenital developmental defects under the threat of abortion.


[Clinical and genetic analysis of the Townes-Brocks syndrome]. Due to the performed analysis of data from literature and the author's observations of the Taunse-Brock's syndrome a wide variability of phenotypic manifestations is shown, the diagnostic criteria of syndrome are determined, its autosomic-dominant inheritance with complete penetrance is confirmed.


[Electron microscopic and histochemical examination of hepatocytes in rat embryos exposed to the effect of a static electric field]. Static electric field with intensity of 150-80 V/cm has no teratogenic and embryolethal effect on the rat embryos. However, it provokes disturbance of the morphofunctional state of embryo liver, causes destructive-dystrophic changes in the parenchyma cells, decreases the content of nucleic acids, induces disturbances of the membrane systems of mitochondria and other cell structures.


[Quantitative characteristics of heterochromatin regions in human metaphase chromosomes at different stages of ontogenesis]. The comparative study of C-heterochromatic regions has been provided for 1, 9, 16 and Y chromosomes of 30 human embryonal in vivo lymphocytes of 6-8 gestational weeks (obtained with medical abortions), on the one hand, and in vitro lymphocytes of 100 phenotypically normal newborns, on the other hand. According to the results the heterochromatic regions of 1, 9 and Y are significantly shorter in embryonal chromosomes as compared with lymphocytes of newborns.