Lipofuscin in human glaucomatous optic nerves.

Lipofuscin accumulation has been observed in a number of neurodegenerative diseases. We recently found that autofluorescent particles also occur in the aged human optic nerve. In this study we sought to determine the nature of these particles and their correlation with aging, age-related macular degeneration (AMD) and primary open angle glaucoma (POAG). Groups of eight optic nerves from patients diagnosed with primary open angle glaucoma, age-related macular degeneration, age-matched controls and four optic nerves derived from controls younger than 42 years were used for the study. All samples were fixed in paraformaldehyde and frozen frontal sections were prepared. Sections were analyzed with fluorescence microscopy, bright field microscopy, Sudan black staining and spectrofluorometry using a confocal laser scanning microscope. Sections were photographed and analyzed to establish the distribution, quantity, and size of the autofluorescent particles. Additionally, transmission electron microscopy was used to determine the ultrastructural location of the granules. On unstained sections under light microscopy granules are detectable as pale brown inclusions and are easily stained with oil-soluble dyes, such as Sudan black. Granules fluoresce when excited at all tested wavelengths but lose their fluorescence after staining with Sudan black. These particles are distributed throughout the axonal columns, but not in the septa, and appear to be located within the glia ensheathing optic nerve axons. The histologic properties of the granules seen in the optic nerve sections correspond to lipofuscin aggregates, a result of incomplete degradation of oxidized proteins. Our morphometric analyses indicate that overall the optic nerves from control, glaucoma, and AMD donors contain similar amounts of lipofuscin. However, optic nerves derived from donors with glaucoma contain lipofuscin particles that are larger than those observed in the age-matched control and AMD groups. Furthermore optic nerves from glaucoma donors display a smaller diameter than those from age-matched controls resulting in a higher concentration of lipofuscin in glaucomatous optic nerves.

Measles aerosol vaccination.

Measles ranks fifth among the five major childhood conditions which are responsible for 21% of all deaths in low and middle-income countries. Measles immunization is considered the most cost-effective public health intervention in the world. In recent years, there has been a critical need to identify alternative routes of measles immunization, which are rapid, reliable, cost-effective, needle-free, and suitable for use in mass campaigns. Aerosol administration of measles vaccines in mass campaigns was first proposed by Dr. Albert Sabin. We review the different clinical trials that have been conducted using the classic Mexican device as well as issues regarding vaccine strain, presentation, and manufacturer. Results of clinical trials indicate that the method is safe and immunogenic in infants and school age children. The viral inoculum will probably need to be increased when administered to infants. From the logistical point of view, the use of the aerosol method has not been evaluated in routine immunization although feasibility of its routine implementation was proved in mass campaigns in Mexico. Cost savings will probably be demonstrated. As to licensure, its compliance with the appropriate international regulatory requirements for medical aerosol delivery devices is in process.

[Measles vaccination by the aerosol method in Mexico]. / La vacunación antisarampionosa en México por el método de aerosol.

The present work describes the anti-measles vaccination program by the inhaled aerosol method undertaken in Mexico between 1988 and 1990. Detailed descriptions are given of the equipment, staff, training programs, promotion and campaigns. The vaccine is specified: Edmonston-Zagreb strain cultured in diploid cells at the Instituto Nacional de Virología of the Secretaría de Salud in Mexico with titres varying from 1045 plaque forming units (PFU/ml) to 1048 PFU/ml administered in a 30 sec inhalation with aerosol. During this exposure period, 2800 to 4000 PFU per child are estimated to enter the child, of which approximately 25% is the retained doses, i.e. 700 to 1000 PFU/child. A total of 3760684 children of school and pre-school age have been vaccinated in 13 of the 32 federal entities of the country. No undesirable effects of any importance were observed, and the limited serological and field studies support the effectiveness and security of this method. On the other hand, the method is much cheaper, faster and better accepted by the population than the subcutaneous injection.

[Equity and health]. / Equidad y salud.

This paper discusses the right to health in Mexico. The authors present some ideas regarding equity and data which shows the existence of a deep inequity in the field of health in the country. The efforts of the social security agencies and of the Ministry of Health aimed at diminishing inequity in health are also described. The authors conclude that it is time to avoid retorical positions and attitudes of administrative solidarity and start to implement actions to improve the health conditions of those living in extreme poverty. These actions should include providing comprehensive health services to all the population, reinforcing specific preventive programs, improving certain basic health indicators and prompting intersectoral collaboration.

[Vaccination against measles. The situation in Mexico and America. Advances in the method of aerosol immunization]. / La vacunación contra el sarampión. Situación en México y América. Avances en el método de inmunización por aerosol.

We present general comments on the epidemiology of measles considering the pre-vaccine era as well as the post-vaccine period in which some changes can be observed: the decrease in morbidity and mortality, the extension of the inter-epidemic interval, the increase in the mean age of infection, etc. We make some estimations about the vaccine coverage and the ideal age of immunization for the goal of eradication (assuming a lifelong immunity for the vaccinees). The technical problems in measles immunization are also revised explaining why no continental country has been able to eliminate the disease. We describe the epidemiological situation in North America, Mexico and Latin American countries. Lastly we present the Mexican experience with the inhaled aerosolised vaccine: the studies in Monterrey (Sabin et al, 1982), other investigation in Mexico, D.F. and in the State of Jalisco, as well as the mass campaigns in Aguascalientes in 1988 and in Coahuila and Nuevo León in 1989. We propose it as an effective, harmless, simple, inexpensive and practical method.

[Respiratory function in asthmatics deficient and non-deficient in alpha 1-antitrypsin]. / Función respiratoria en asmáticos deficientes y no deficientes de alfa-1-antitripsina.

The high prevalence of alleles S and Z in relation to deficient states of alpha-1-antitrypsin (alpha-1-AT) in patients with allergic bronchial syndrome has been tested in a sample of the population in Havana City. Due to the high incidence of bronchial asthma in Cuba, it is important to study the factors that might be involved in its etiology, and that is why the probable relation of alpha-1-AT deficiency to bronchial asthma is analyzed in this work. The phenotype for alpha-1-antitrypsin (alpha-1-AT) and the maximum expiratory flow were determined in 174 male and female ambulatory asthmatics between 15 and 82 years of age, by means of a manual flow meter. The possible relationship between the age at which asthma crisis shows up and the phenotype for alpha-1-AT was taken into account. In 108 patients who showed neither dyspnea nor auscultatory signs at the time of expiratory flow measurement, the influence of the phenotype for alpha-1-AT and the age at which the crisis show up on the maximum flow values and eventual interaction of both factors were studied. The maximum flow values reached by patients bearing different phenotypes according to the time of asthma development were also compared. The results did not show significant differences in any comparison made among the subjects with normal phenotypes for alpha-1-AT and the deficient phenotypes beares. Nevertheless, there might be differences in the respiratory function between normal and deficient phenotypes of alpha-1-AT that might be hidden because of the simultaneous occurrence of other factors participating in the etiopathogenesis of bronchial asthma.(ABSTRACT TRUNCATED AT 250 WORDS)

[Measurement of the peak flow in ambulatory asthmatic patients]. / Valoración del flujo pico en pacientes asmáticos ambulatorios.

The evaluation of the state of respiratory function in asthmatic patients is useful for/the physician to decide on a certain therapeutic method, to determine how this function is modified by the action of a drug treatment schema, etc. The purpose of this work is to describe the behaviour of the results obtained by measurement of the values of peak flow reached for asthmatic patients attended in the allergology service. The measurement was applied to a hundred asthmatic patients of both sexes, selected at random from asthmatic patients seen in outpatient visits. The individuals were tested in a sitting position, using respiratory peak flow standard model equipment (M. 286, Airmed House). The measurements were done on each patient at minimum intervals of one minute. The results obtained in this way were averaged and the resulting value was compared with that foreseen for each individual, by age, sex and height. The patients were classified into four groups according to the presence or absence of positive symptomatology and the presence or absence of wheezing in the auscultation. Comparisons of these groups, both binary and for the four groups, were made as well as an analysis of whether or not the number of individuals with reduction of peak flow and without wheezing was significant in the sample. It was concluded that the use of subjective information obtained from the patient as well as the presence or not of wheezing constitute index of relative value for the evaluation of the functional status of the asthmatic patient, because there is a significant association between the presence of these signs and important obstruction of the airway.(ABSTRACT TRUNCATED AT 250 WORDS)

Successful immunization of infants with and without maternal antibody by aerosolized measles vaccine. II. Vaccine comparisons and evidence for multiple antibody response.

In 4- and 5-month-old infants in whom the undiluted chick embryo fibroblast (CEF) Schwarz strain measles vaccine had a poor immunogenic effect, there was an increase in immunogenicity when the high sugar concentration was diminished without reference to added albumin. The human diploid cell (HDC) measles vaccine was still superior in this age group even in a lower concentration of the Ikic, Edmonston-Zagreb strain of virus. More aerosolized, HDC Ikic strain virus was required for high seroconversion rates in 4- and 5-month-old infants who had higher titers of prevaccination plaque-neutralizing (PN) antibodies. Some of these infants had a delayed immune response that was absent at six weeks but present at three months after vaccination. The data provided evidence that the PN and enzyme-linked immunosorbent assay techniques measured different antibodies that develop and persist in different ways in 4- to 5-month-old infants. The HDC lyophilized measles vaccine yielded unexpectedly high seroconversion rates after subcutaneous injection of 5,000 plaque-forming units (PFUs) in 4-, 5-, and 6-month-old infants: 69%, 89%, and 100% respectively, at 14 weeks. In 12- to 23-month-old infants there was seroconversion of 92% and 100% at six weeks after inhalation of an estimated 175 PFUs of the CEF vaccine and 375 PFUs of the HDC vaccine, respectively. Within six weeks after vaccination, the PN antibody titers were significantly higher with the CEF vaccine (geometric mean titer of 2,275) than with the HDC vaccine (geometric mean titer of 343).

Mass vaccination against poliomyelitis in Mexico.

In 1959, oral poliovirus vaccine ( OPV ) was introduced as an antiepidemic measure in Mexico. As in many other developing countries, the vaccine was misused, coverages achieved were often poor, and an adequate cold chain was lacking. However, in 1972 a mass campaign reached 70% of children younger than five years of age, and consequently the reported cases declined sharply from 1.9 to 0.4 per 100,000 population. Due to economic restrictions, only single doses of monovalent type 1 OPV were administered to 80% of the target population in 1981, 1982, and 1983. The present incidence of poliomyelitis of 0.1 per 100,000 population represents a 96.7% reduction from the rate during the prevaccine era, when the annual average rate was 4.26 per 100,000. The present aim of poliomyelitis control is to maintain and decrease the present incidence of disease. Future plans are to continue mass vaccination in an attempt to reach small and isolated villages that have been without vaccination and limit possible rural foci of wild poliovirus.

Successful immunization of children with and without maternal antibody by aerosolized measles vaccine. I. Different results with undiluted human diploid cell and chick embryo fibroblast vaccines.

Inhalation of undiluted, aerosolized measles vaccine was immunogenic in 100% of 4- to 6-month-old and older children with and without residual maternal antibody when the human diploid cell (HDC) vaccine containing the Ikic (Edmonston-Zagreb) strain and 1% human albumin was used but in a smaller percentage of infants given a chick embryo fibroblast (CEF) vaccine, which contained the Edmonston-Schwarz strain, ten times more virus, and hypertonic sugar solution but no added protein. Prevaccination residual placentally transmitted plaque-neutralizing antibody titers of 25 to 512 that can prevent an immune response after subcutaneous injection of measles vaccine did not prevent an immune response after inhalation of aerosolized vaccine. There were no immediate clinical reactions in the 160 children who inhaled the aerosolized vaccines, and no significant subsequent reactions among the 96 children who were successfully immunized. There were no contact infections.

Measles in Mexico.

Comparison of the figures for measles morbidity in Mexico over the years is difficult because of the different rates of reporting of cases. In the 1960s, approximately 3% of the true number of cases of measles was reported, whereas in 1980 this percentage increased to approximately 20%. A more representative time curve can be drawn for mortality, which dropped sharply in 1973-1980 as a result of the extensive use of measles vaccine. The relationship between measles and immunization is close, and morbidity for the above period is a mathematical function of the number of doses of vaccine distributed. During 1981, about four million doses of vaccine were administered, and in 1982 another four million children will be immunized, with a coverage of 70% of the susceptible population. It is hoped that in 1982 the incidence of measles will decrease to the low levels obtained in 1974-1975, although eradication in the near future seems unlikely.

PIP: The relationship between measles and immunization is such that morbidity is almost a mathematical function of the number of doses of vaccine distributed. After Mexico's massive immunization campaign of 1973, a sharp decrease in measles morbidity and mortality was registered in 1974 and 1975. Unfortunately, the campaign was not able to eliminate measles completely because of 2 factors: the large number of small villages with scattered populations that were not reached by immunization brigades, and problems restricting vaccine distribution only to the targeted children 6-18 months of age. In 1976-79 the mass immunization strategy was abandoned in favor of routine immunization throughout the year for children who were brought to health centers as a result of vaccination promotional activities. Beginning in 1980, intensive phases of immunization were introduced into the routine year-long immunization program. It is hoped that the 1981-82 policy of routine year-long immunization in health centers as well as intensive house-by-house immunization activities will reach at least 70% of susceptible preschool children and reduce measles to the low incidence achieved in Mexico in 1974-75. Special attention will be paid to reinforcing levels of immunity in those states or zones where measles morbidity is greatest.