Herpes simplex virus (HSV-1) infection in a donor cornea.
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Biomedical subjects
Publications and source records attributed to O Adams.
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The World Health Assembly approved resolution WHA45.5 in 1992. This paper reports the findings of an evaluation of the implementation of this resolution using a survey technique. A total of 150 WHO Member States responded, for a 79% response rate. Findings suggest that the greatest strides worldwide have been made in education. While the data show that progress has been made at the country level, far more action is needed to strengthen nursing and midwifery if these cost-effective resources are to play a decisive role in improving the extent and quality of services, especially as delivered to people in the greatest need.
OBJECTIVE: To examine tolerance and efficacy of a zidovudine plus lamivudine combination in HIV-infected children without previous exposure to antiretroviral drugs. METHODS: Thirteen vertically infected children (aged 4 months to 10 years) were treated with zidovudine (approximately 100 mg/m2 three times daily) and lamivudine (4 mg/kg twice daily). CD4 T-cell count, plasma HIV RNA concentration, complete blood count and blood chemistry profile were monitored before treatment and at months 1, 3 and 6. RESULTS: In general, treatment was well tolerated. One child developed slight neutropenia in the presence of antineutrophil antibodies. CD4 cell count increased from 851+/-621 x 10(6)/l at baseline to 1073+/-945 x 10(6)/l at month 3 (P < 0.05) and to 1133+/-728 x 10(6)/l at month 6 (P = 0.01). CD4+ cell count increased in 10 patients after 3 months and in 11 patients treated for 6 months. One child showed a continuous decrease of CD4 cells despite treatment. Before treatment the plasma HIV RNA concentration was elevated in nine children (> 4.0 log10 copies/ml) and decreased in all of them: by month 1, the mean reduction was -1.16 log10 copies/ml; by month 3, -1.38 log10 copies/ml; and by month 6, -1.53 log10 copies/ml compared with baseline. However, one child showed steadily increasing viral load from 2.7 log10 copies/ml to a maximum of 4.52 log10 copies/ml, surprisingly in association with increasing numbers of CD4 cells. This child was switched to a new combination regimen after 6 months of treatment. Plasma HIV RNA levels below limit of detection were reached in six patients: after 1 month of treatment in one patient, after 3 months in five patients, and after 6 months in six patients. There was a mean reduction of viral load from 4.56 log10+/-4.63 log10 copies/ml (n = 13) to 3.8 log10+/-3.9 log10 copies/ml (P < 0.05; n = 9) after 1 month, to 3.67 log10+/-3.88 log10 copies/ml (P < 0.01; n = 13) after 3 months, and to 3.64 log10+/-3.95 log10 copies/ml after 6 months of treatment (P < 0.001; n = 13). CONCLUSIONS: This pilot study demonstrates the feasibility of zidovudine-lamivudine combination in children not previously exposed to antiretroviral drugs. This promising combination should therefore be evaluated in larger trials.
Cord blood DNA was tested for the presence of human herpesvirus 6 (HHV-6) DNA by the polymerase chain reaction. Specific DNA could be detected in the specimens of 5 (1.6%) of 305 babies born to ostensibly healthy mothers, indicating that intrauterine infection had occurred. These transmissions would not have been detected by serologic methods, because no specific IgM antibody could be found in the fetal sera. These results indicate that, in addition to infections acquired in early childhood, congenital infections may account for the HHV-6 seropositivity in children.
HIV-seropositive patients (n = 67) who had tolerated zidovudine for at least 24 weeks and deteriorated clinically or immunologically within 12 weeks prior to study entry were allocated in an alternating manner to didanosine chewable tablets (400 mg/day) plus zidovudine (500 mg/day) or dideoxicytidine capsules (2.25 mg/day) plus zidovudine (500 mg/day). The combination of didanosine and zidovudine resulted in a more pronounced increase of CD4 cells over time compared to the combination of dideoxicytidine with zidovudine (p < 0.002). The increase of CD4 cells was almost exclusively due to patients with more than 100 CD4 cells/microliters. Clinical end points (death, AIDS-defining disease, CDC IV event) were less frequent under didanosine plus zidovudine but failed to reach statistical significance (p = 0.07). For didanosine plus zidovudine the median time on medication during study was shorter (63% vs. 100%, p < 0.05) and the number of patients discontinuing medication prematurely due to side effects was higher (59% vs. 30%, p < 0.02). The present study favors the combination of didanosine and zidovudine in patients deteriorating while receiving zidovudine for > 24 weeks in respect to the time course of the CD4 cells. In this small sized study, there seemed to be fewer clinical events in patients on the didanosine combination compared to the combination with dideoxicytidine; however, this trend failed to reach statistical significance and needs therefore to be substantiated by larger studies. However, the lower compliance of the patients may hamper the efficacy of didanosine.
To date, hematopoietic stem and progenitor cells from human umbilical cord blood (CB) have been employed in approximately 90 allogeneic (56 sibling and 34 unrelated) matched and mismatched transplantations worldwide with easy and successful restoration of hematopoiesis. Requests for stem cell preparations from CB will continue to increase. Thus, as a pilot study, the examination and standardization of unrelated cord blood-derived stem cell preparations and banking as well as their biologic characterization were initiated. Up to October 1995, a total of 574 samples [mean volume 79 +/- 26 ml, total nucleated cells (NC) 8.5 +/- 5 x 10(8), BFU-E 9.5 +/- 8.6 x 10(5), CFU-GM 5.7 +/- 6.3 x 10(5), CFU-GEMM 1.6 +/- 1.9 x 10(5)] from cord-derived or placental-derived residual blood have been defined by hematologic, immunologic, and microbiologic criteria. These CB samples were collected from the umbilical cord vein immediately after vaginal full-term delivery (n = 450) or cesarean section (n = 124) and stored frozen in liquid nitrogen. Seven percent of all samples collected could not be considered for potential transplants because of volumes < 40 ml. Only 5.0 ml of a CB sample is required for routine laboratory testing, consisting of HLA class I typing, HLA class II typing by sequence-specific oligonucleotide probes (PCR-SSOP), ABO typing, sterility control, assessment of progenitor and stem cells by colony-forming and LTC-IC assays, and CD34+ status. To assess the potential problem of contaminating maternal cells, a PCR was performed on 7 representative samples. During the initial 6 months of the unrelated CB collection program, a median bacterial contamination rate of 18% (20% skin flora species, 80% perineal flora species) was encountered, which has since been reduced to < 1% through practical experience. With regard to viral infections, maternal sera was tested for HBsAg (0.6% positive), anti-HCV (0%), anti-HAV (IgG 18%, IgM 0%), anti-HIV-1-2 (0%), anti-EBV (IgG 98%, IgM 0%), anti-HTLVI-II (0%), anti-CMV (IgG 43%, IgM 0.4%), toxoplasmosis (46%) and syphilis (0%). In addition, all cord blood samples were tested by PCR for CMV infection. With regard to its clinical relevance, it is important that only 0.3% of all the samples were positive for CMV by this sensitive method. This may represent a critical advantage of CB grafts over bone marrow (BM) since, in contrast, > 40% of the unrelated BM donors have been identified to be positive for CMV. An additional advantage of CB is that since 20% of CB samples were collected from ethnic minorities, it appears possible to balance common HLA types and uncommon HLA types represented in this group. In summary, with the extensive practical experience of the obstetric collection team as well as the stem cell-processing laboratory, it appears feasible to obtain a 90% yield of unrelated CB-derived stem cell preparations for banking, which clearly should meet the medical and regulatory qualification criteria required for clinical transplantation. To test the feasibility of hematopoietic transplant potential of unrelated CB for adult patients, ex vivo expansion of CD34+-enriched stem/progenitor cell populations isolated from fresh or frozen CB was attempted in the presence of rh-IL-3, rh-IL-6, rh-EPO, rh-GM-CSF, and rh-SCF with or without fit 3. At varying time points (days 0, 2, 4, 7, 14, 21), the contents of these cultures were analyzed for the numbers of cells, CFC (BFU-E, CFU-GM, CFU-GEMM), and LTC-IC. In this setting, the increase of cells was 200-fold, that of CFC 70-fold, and most importantly that of LTC-IC was 4.5-fold after 7 days in culture in the presence of flt3. In conclusion, LTC-IC derived from CB can be maintained and considerably expanded ex vivo from highly enriched CD34 + CB cell populations from fresh or frozen CB samples.
An expression vector was designed to test the structural requirements of the gp41 N terminus for human immunodeficiency virus type 1-induced membrane fusion. Mutations in the region coding for the N terminus of gp41 were found to disrupt glycoprotein expression because of deleterious effects on the Rev-responsive element (RRE). Insertion of an additional RRE in the 3'-noncoding sequence of env made possible efficient glycoprotein expression, irrespective of the mutations introduced into the RRE in the natural location. This permitted the insertion of the unique restriction site SpeI within the N-terminal sequences of gp41, allowing convenient and efficient mutation of the gp41 N terminus by using double-stranded synthetic oligonucleotides. Mutants with deletions of 1 to 7 amino acids of the N terminus were constructed. Expression and cleavage of all mutants were confirmed by Western immunoblot analysis with anti-gp41 antibodies. The capability of mutants to induce membrane fusion was monitored following transfection of HeLa-T4+ cell lines with wild-type and mutant expression vectors by electroporation and microinjection. The efficiency of cell-fusing activity decreased drastically with deletion of 3 and 4 amino acids and was completely lost with deletion of 5 amino acids. Cotransfection of the parent and mutant expression vectors resulted in reduced cell-fusing activity. The extent of this dominant interference by mutant glycoprotein paralleled the decrease in cell-fusing activity of the mutants alone. This suggests the existence of a specific N-terminal structure required for fusing activity. However, there does not appear to be a stringent requirement for the precise length of the N terminus. This finding is supported by the length variation of this region among natural human immunodeficiency virus type 1 isolates and is in contrast to the apparent stringency in the length of analogous N-terminal structures of influenza A virus and paramyxovirus fusion glycoproteins.
To study the efficacy of intravenous immunoglobulin in symptomatic infection with human immunodeficiency virus (HIV) we enrolled 35 patients with CD4 lymphocyte counts below 300/microliter in a randomized three-arm study. In addition to standard HIV treatment (e.g., zidovudine, aerosolized pentamidine), 13 patients were treated with 7.5 g and 11 with 40 g of a 7 S intravenous IgG preparation every 4 weeks over a period of 1 year. A control group of 11 patients remained on standard treatment. Clinical and laboratory parameters, including lymphocyte proliferation and in vitro immunoglobulin synthesis were evaluated prior to intravenous IgG administration. HIV-specific immunological abnormalities such as increased B-cell activation and B-cell immaturity were observed in all three study groups at the beginning of the study. Mitogen-induced lymphocyte proliferation was diminished. These disturbances were not influenced by intravenous IgG treatment. Further laboratory data and the course of the HIV infection (fever, antibiotic treatment, hospitalization, Candida and herpes simplex or cytomegalovirus infection) remained unchanged. Thus, our data with an observation period of 12 months do not support the use of intravenous IgG treatment in adult symptomatic HIV-infected patients with CD4 counts lower than 300/microliter.
Each of Canada's ten provinces has a publicly administered system of health insurance, funded by provincial and federal taxes, that is accessible to all citizens and covers all medically necessary services provided by physicians and hospitals. Canadians spend an estimated 9.2 percent of their gross national product on health care (about 2.8 percentage points below US spending), of which three quarters is public-sector spending. According to the Organization for Economic Cooperation and Development, Canada's health status is equal to or better than that of the United States, despite lower per capita health spending. About seven percent of the Canadian labour force works in health care, and attempts to introduce coordinated planning of human resources in health care have not as yet proceeded far. The predominant policy issue here is the supply and the role of physicians. It has been argued that entrenching within the system the fee-for-service method of paying physicians has created a disincentive to the delegation of responsibility to health personnel other than doctors. It is also argued that introduction of government-run health insurance provided the opportunity for human resource planning, but that the decision by governments to act only as the payer resulted in ad-hoc planning approaches. However, governments' concern over health care costs has led to a more direct role by them in the planning of the human resources in health. They are re-examining the autonomy and jurisdictional rights of the professions that deliver health care to Canadians.
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In Canada today, as in the past, men and women devote different amounts of time and effort to providing health care to their family and in the broader community. This paper examines "the social distinction between masculinity and femininity" in care-giving. Issues of gender inequality in care-giving have the potential to affect the formal health care system as the burden of caring will increase over the next few decades with the aging of society. This increase in need for care is occurring at a time when primary care providers--women--have additional demand on their time. Canadian society has been facing a series of social, demographic and economic shifts such as a higher divorce rate, two-income families, women's increasing professional commitments and first pregnancies at later ages, these factors may not affect women's willingness to care for others. However women may need support to provide the care. Assuming present trends, increasing need for families to care for elderly relatives may be inevitable. Perhaps society will recognize this need and provide support to those providing informal care. This could take the form of allowing individuals more time to provide care through child care leave, leave to care for parents and job-sharing. Support to those providing informal care might also be facilitated through community support services such as respite care, household maintenance, psychological support to care-givers, support groups, informal networks within a community and consideration of unconventional support methods.
At 73 years for men and more than 80 years for women, Canada's life expectancy at birth compares favourably with other developed countries; Japan currently leads the world with 75.6 years for men and 81.4 years for women. In 1920-1922, fewer than six out of ten Canadians could expect to survive to their 65th birthday; by 1985-1987, this had risen to eight out of ten. At the oldest ages, the increases in survival are even more striking. In 1920-1922, just over one in ten Canadians could expect to reach their 85th birthday; by 1985-1987, this had increased to more than three out of ten. Since the 1920s, life expectancy has been higher in the Western provinces and lower in Atlantic Canada and Quebec. In 1950-1952, for example, a person born in Saskatchewan could expect to live four years longer than a person born in Quebec. By 1985-1987, this difference had been reduced to just over one year. Women have made much greater gains in life expectancy than men. In 1920-1922, women had an advantage in life expectancy over men of less than two years; by 1970-1972, this had more than tripled to seven years. Married men and women have a distinct advantage in longevity over other marital status categories. Married men may expect to live over eight years longer than never-married men, and more than ten years longer than widowed men. Married women can expect to live three years longer than never-married women, and four years longer than women who are either divorced or widowed. As of 1986, a boy born in highest-income quintile area in urban Canada can expect to live almost six years longer than a boy born in a lowest-income quintile area. For girls, the difference is almost two years. However, this socio-economic differential narrowed from 1971 to 1986.
In 1988, a total of 79,872 divorces were granted in Canada. This was a 12.2% decrease from the 1987 total of 90,985, the highest ever in Canada. Divorce levels have been generally high in the late 1980s, but data for several more years are required before the impact of the 1985 Divorce Act can be accurately assessed. The 1988 divorce rate in Canada for married women aged 15 and over was 1,256 per 100,000. The highest rates occurred in Alberta (1,498) and British Columbia (1,407), and the lowest in Newfoundland (669) and Prince Edward Island (844). The average duration of marriages ending in divorce was 12.5 years. The largest number of divorces occurred after five years, followed by six and four years. Among divorces granted in 1988 under the 1985 divorce law, separation for not less than one year was cited as the grounds in almost nine out of ten cases. Of all children affected by custody orders for divorces granted under the 1985 law, 76% were awarded to the wife, 12% to the husband, 11% to joint custody, and fewer than 1% to a person other than the husband or wife.
The importance of serological determination procedures for the diagnosis of pathogens was investigated in 207 episodes of pneumonia. The pathogenic organisms were detected in 138 cases; in 40 cases serological analysis helped to establish the diagnosis, while in 11 cases of pneumonia, the diagnosis was possible only with serology. The organisms most commonly found by serological investigations were Cytomegalovirus (n = 10), Aspergillus fumigatus (n = 7), and the influenza B virus (n = 7). Multiple infections, usually triggered by bacterial pathogens, were found in 48% of the cases of pneumonia with serological evidence of pathogens. In 71 episodes of pneumonia, the patients were immunosuppressed; in 11 cases, the causative organism was detected serologically.
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The reduction of socio-economic inequities in health is now an explicit objective of health policy in Canada. This study examines changes in mortality by income in urban Canada from 1971 to 1986 in terms of both relative and absolute differences between income groups. Street address information as shown on death certificates was used to code census tract of usual place of residence for deaths occurring to residents of Canada's Census Metropolitan Areas (CMAs) in 1971 and 1986. After exclusion of residents of health care institutions, 73,995 deaths were included in the study for 1971, and 88,129 for 1986. These deaths were analyzed by income quintile (based on census tract incidence of low income), age, sex, and cause of death. In 1971, the difference in life expectancy at birth between the highest and lowest income quintiles was 6.3 years for men and 2.8 years for women. By 1986, these differences had decreased to 5.6 years for men and 1.8 years for women. However, relative mortality (lowest compared to highest income quintile) at most ages changed only slightly over the 15 years. Relative infant mortality, for example, was 1.97 in 1971 and 1.82 in 1986. In 1986, 21% of total potential years of life lost (PYLL) prior to age 75 could be attributed to differences in quintile death rates compared to rates for the highest income quintile. Approximately 45% of this "excess" PYLL was for persons under 45 years of age. In 1971, the comparable figure was 67%. In 1986, the major causes of death contributing to income inequalities in mortality were: circulatory diseases, accounting for 25% of excess PYLL related to quintile differences; accidents, poisonings and violence, accounting for about 17%; and neoplasms, accounting for 15%. Respiratory diseases, ill-defined conditions, metabolic diseases and perinatal conditions each contributed 6-7% of excess PYLL. From 1971 to 1986, in terms of age-standardized morality rates (ASMRs) for all ages, certain causes of death showed increased mortality together with greater inequality by income, especially for males: these causes included lung cancer, suicide, metabolic diseases other than diabetes, and ill-defined conditions. Other causes of death showed either little change or less inequality by income but higher ASMRs: these included breast cancer, colon and rectal cancer, arterial diseases, alcoholism, mental disorders, and diseases of the nervous system.(ABSTRACT TRUNCATED AT 400 WORDS)
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