Ocular neovascularization: an epidemiologic review

Neovascularization occurs in many eye diseases, and its epidemiologic impact is significant. However, data on the prevalence and incidence of ocular neovascularization have never been compiled to demonstrate its pervasiveness. This overview of ocular angiogenesis provides a review of the epidemiologic literature for neovascularization in various parts of the eye, including the cornea, iris, retina, and choroid. Relevant disease states are reviewed, as are their risk factors, so that their pathogenesis can be better understood. Data on the prevalence and incidence of the major diseases involving angiogenesis are synthesized to provide statistical evidence of the span and magnitude of ocular neovascularization. These prevalence and incidence data on ocular neovascularization are extrapolated to USA population data where possible, and "worst-case" estimates are calculated as well. Information was gathered with a search of the MEDLINE database, published monographs and volumes, and consultation with a number of primary authors. This study attempts to unify much of past and present epidemiologic research, and the information is presented in sections divided according to the anatomy of the eye.     

Insulin-dependent diabetes mellitus in Santiago, Chile: the role of immunogenetic and environmental factors

The role of HLA class II alleles in the genetic susceptibility to develop insulin-dependent diabetes mellitus (IDDM) was examined by means of PCR and oligospecific probes in 63 IDDM children and 74 controls subjects. In diabetic patients we found a significant increase in the alleles frequency DR3, DR4, DQB1*0302 and DQA1*0301 compared to the control group, where the most prevalent alleles were DR2, DR14 (DRB1*1402), DQA1*0101 and DQA1*0201. All the risk genotypes in the diabetic group were similar than in other caucasian groups: DR3/DR4-DQB1*0201/0302-DQA1*0301/0501 and DR4/DR4-DQB1*0302/0302-DQA1*0301/0301. The homozygote character no asp57 conferred an absolute risk (AR) of 3.87 and the marker Arg52 an AR of 5.78/100.000 bab year. The homozygosis for both markers (no Asp57 + Arg52) had an AR of 7.56/100.000 bab year. Regarding environmental factors associated with IDDM, our population under study showed a low prevalence of infectious agents (mainly mumps and rubella, specifically associated with IDDM) and a high prevalence of effective breast-feeding (over 3 months). These factors could be exercising a protector role in the development of IDDM. The factors that appear to be important in the low incidence of IDDM in Santiago de Chile are: the low prevalence of infectious agents related to IDDM, the high percentage of breast-feeding children in the population, the reduced frequency of susceptible molecules as DR3, DQB1*0201 (compared to other caucasian groups) and the presence of protective genotypes related to DR13 and DR14 observed in the non diabetic children.     

Health economics and clinical pathology

A 3-y-old child ingested SUCCIMER capsules to receive a dose of 185 mg dimercaptosuccinic acid/kg body weight. No adverse effects occurred.     

Atopic eczema: a clinical psychiatric study

The method of Deutsch and Weeks was modified to provide a reliable and reasonably quick method for assaying the L-ascorbic acid content of culture medium. The modified method was used to determine the decay of L-ascorbic acid under various conditions of culture and the concentration of the vitamin in commercially prepared media. The half-life of L-ascorbic acid in a modified New circulator gassed with 95% O2 + 5% CO2 was 1.5 hr.; and when gassed with 20% O2 + 5% CO2 + 75% N2, about 2 hr. In Petri dishes gassed with 20% O2 + 5% CO2 + 75% N2, the half-life of L-ascorbic acid was 0.9 hr. About 4% of the L-ascorbic acid was lost per day when medium was stored at 0 degrees C and about 9% per day when stored at 5 degrees C. When medium with an initial content of 300 microng per ml was stored at room temperature, the half-life was found to be 15.5 hr. The L-ascorbic acid in five commercially available media, which contain the vitamin in their formulations, was assayed immediately after their delivery to the laboratory. The values of L-ascorbic acid measured in these media were in all cases far lower than prescribed. A continuous-flow organ culture system has been designed which allows the provision of a relatively constant level of L-ascorbic acid to explant by taking advantage of the slow oxidation of L-ascorbic acid at 0 degrees C.     

Pesticide exposures and fetal death: a review of the epidemiologic literature

Despite considerable concern regarding the effects on reproductive outcome of exposures to pesticides, convincing evidence for the developmental toxicity of occupational and environmental pesticide exposure in humans is lacking. In this comprehensive review of the English language epidemiologic literature, we summarize studies that have examined potential associations between fetal deaths (both spontaneous abortions and stillbirths) and specific pesticides, as well as maternal and paternal employment in occupations with potential for exposure. While many of the epidemiologic studies to date suffer from methodologic problems, the data are suggestive of increased risks of fetal deaths associated with pesticides in general and maternal employment in the agricultural industry. There is a clear need for epidemiologic research that focuses on specific pesticide products or chemical families, with improved exposure assessment. The potential role of solvents in developmental toxicity associated with pesticide use by both males and females should also be considered.     

Agoraphobia without panic: clinical reappraisal of an epidemiologic finding

OBJECTIVE: In the United States, the consensus among clinicians and researchers, reflected in DSM-III-R, is that agoraphobia is a conditioned response to panic attacks and almost never occurs without panic attacks. The predominant view in the United Kingdom is that agoraphobia frequently occurs in the absence of panic. While clinicians report that they rarely see patients with agoraphobia who have no history of panic disorder, community studies report that agoraphobia without panic disorder is common. For example, the Epidemiologic Catchment Area (ECA) study found that 68% of 961 persons with agoraphobia had no history of panic attacks or disorder. METHOD: To understand this discrepancy, 22 subjects who had been diagnosed as having agoraphobia without panic disorder or panic attacks in the ECA study were blindly reinterviewed 7-8 years later with the Schedule for Affective Disorders and Schizophrenia--Lifetime Version Modified for the Study of Anxiety Disorders; data from these interviews were blindly reviewed by a research psychiatrist who was not involved in the original data collection or the reinterview process. RESULTS: On reappraisal, 19 of the 22 subjects had simple phobias or fears but not agoraphobia. One subject had probable agoraphobia without panic attacks, one had definite panic disorder with agoraphobia, and one had probable agoraphobia with limited symptom attacks. CONCLUSIONS: Epidemiologic studies that used the Diagnostic Interview Schedule and lay interviewers, such as the ECA study, may have over-estimated the prevalence of agoraphobia without panic. Agoraphobia without panic attacks occurs but is uncommon, and the diagnostic boundary between agoraphobia and simple phobia is unclear.     

HIV protease inhibitors: general review

Protease inhibitors are a new class of drugs which has demonstrated activity for the treatment of HIV infection. The function of the HIV protease is to split a polyprotein to create smaller proteins which will be incorporated in the structure of the virus. The eight cleavage sites of the polyprotein constitute a template for the synthesis of potential inhibitors. Today, only inhibitors of the Phe-Pro cleavage have shown an antiproteinase activity specific for HIV. Clinical trials in HIV infection with saquinavir, indinavir, and ritonavir have demonstrated a decrease in viral load measured by plasma HIV-RNA PCR and an increase in CD4 lymphocyte counts. The use of protease inhibitors leads to a more or less rapid selection of mutant resistant viruses. However, these new drugs, either used alone or in combination, constitute a new therapeutic approach for the treatment of HIV disease.     

St. Louis encephalitis: clinical and epidemiologic aspects, Mississippi, 1974

During July, August, and September 1974, 23 confirmed or presumptive cases of St. Louis encephalitis occurred in Mississippi. Attack rates were highest in the northwest corner of the state and among persons over 70 years of age. Rural and urban residents had similar attack rates. Nine persons have not resumed their pre-illness level of activity because of residual neurologic impairment six months after their illness. Additional cases of St. Louis encephalitis are expected in the next few years.     

Exfoliative toxin detection using reversed passive latex agglutination: clinical and epidemiologic applications

A rapid and simple method for detecting exfoliative toxin serotypes A and B from clinical isolates has been developed as a test kit (EXT-RPLA; Denka Seiken Co. Ltd., Niigata, Japan). This method is based on reversed passive latex agglutination. The detection limit of the EXT-RPLA observed for purified exfoliative toxin serotypes A and B was 1 ng/ml. We evaluated the clinical and epidemiologic uses of the EXT-RPLA. A total of 381 isolates of Staphylococcus aureus, 292 from various clinical specimens and 89 from the skin of dermatologic patients, were studied. The EXT-RPLA detected 19 exfoliative toxin producers, including 16 serotype A producers and 3 serotype B producers, but no double producers. The sensitivity and specificity of the EXT-RPLA were confirmed by the newborn mouse bioassay and a PCR assay for the structural genes for exfoliative toxin serotypes A and B (eta and etb, respectively). The overall positivity rate of exfoliative toxin producers was 5.0% (19 of 381), including 16 serotype A isolates and 3 serotype B isolates. Of the 89 isolates from the skin of dermatologic patients, 12 (13.5%) were positive for exfoliative toxin production. Only 2 (1.3%) of the 153 methicillin-resistant S. aureus isolates produced exfoliative toxin, while 17 (7.5%) of the 228 methicillin-sensitive isolates produced exfoliative toxin. The EXT-RPLA assay is a simple and reliable method for detecting exfoliative toxin, and we recommend its use for the rapid diagnosis of staphylococcal scalded skin syndrome. We also recommend its use for detection of this syndrome so that effective control measures can be taken against the spread of this syndrome.     

A review of epidemiologic studies of triazine herbicides and cancer

We evaluated epidemiologic evidence pertaining to the human carcinogenic potential of triazine herbicides in general and of atrazine, the most common triazine. Cancers for which data are available included non-Hodgkin's lymphoma, Hodgkin's disease, leukemia, multiple myeloma, soft tissue sarcoma, colon cancer, and ovarian cancer. The investigations had methodologic limitations, including lack of in-depth exposure measurements and small numbers of subjects with heavy exposure and/or with many years since starting exposure, possibly required for the induction of cancer. The relation between triazines and non-Hodgkin's lymphoma has been assessed in four independent population-based case-control studies, reporting odds ratios ranging from 1.2 to 2.5. However, chance and/or confounding by other agricultural exposures may have produced these weak statistical associations. Furthermore, a pooled analysis of three of the case-control studies and the combined analysis of two retrospective follow-up studies did not demonstrate the types of dose-response or induction time patterns that would be expected if triazines were causal factors. The epidemiologic data pertaining to Hodgkin's disease, leukemia, multiple myeloma, soft tissue sarcoma, colon cancer, and ovarian cancer were inadequate for determining whether associations with atrazine or triazines exist in humans. For each of these cancers, only one or two studies evaluating the relationship were available, and the results of the studies typically were imprecise.     

Transforming growth factor-beta: a general review

Three isoforms of Transforming Growth Factor-beta (TGF-beta 1, beta 2 and beta 3) exist in mammals. They play critical roles in growth regulation and development. Each isoform is encoded by a unique gene on different chromosomes. All three of these growth factors are secreted by most cell types, generally in a latent form, requiring activation before they can exert biological activity. This activation of latent TGF-beta, which may involve plasmin, thrombospondin and possibly acidic microenvironments, appears to be a crucial regulatory step in controlling their effects. The TGF-betas possess three major activities: they inhibit proliferation of most cells, but can stimulate the growth of some mesenchymal cells; they exert immunosuppressive effects; and they enhance the formation of extracellular matrix. Two types of membrane receptors (type I and type II) possessing a serine/threonine kinase activity within their cytoplasmic domains are involved in signal transduction. Inhibition of growth by the TGF-betas stems from a blockage of the cell cycle in late G1 phase. Among the molecular participants concerned in G1-arrest are the Retinoblastoma (Rb) protein and members of the Cyclin/Cyclin-dependent kinase/Cyclin dependent kinase inhibitor families. In the intact organism the TGF-betas are involved in wound repair processes and in starting inflammatory reactions and then in their resolution. The latter effects of the TGF-betas derive in part from their chemotactic attraction of inflammatory cells and of fibroblasts. From gene knockout and from overexpression studies it has been shown that precise regulation of each isoform is essential for survival, at least in the long term. Several clinical applications for certain isoforms have already shown their efficacy and they have been implicated in numerous other pathological situations.     

Gender differences in psychiatric illness and treatments: a critical review

Controversy exists about the causation of gender differences long observed in the prevalence of mental disorders. Recent epidemiological, biochemical, and genetic research has shed further light upon both their etiologies and treatments. Both controversies and research are reviewed and critically examined.     

Schizophrenia and genetics: a review and critique for the psychiatric nurse

OBJECTIVES: To study the role of the LDL receptor in the clearance of chylomicron remnants in humans. DESIGN: Chylomicron remnant clearance was studied in five untreated subjects with heterozygous familial hypercholesterolaemia (FH) and nine normolipidaemic controls, by oral retinyl palmitate-fat loading tests. Fasting plasma triglycerides (TG), which are important determinators of chylomicron and remnant clearance, were not significantly different between FH (1.76+/-0.32 mmol L(-1), mean+/-SEM) and controls (1.26+/-0.18 mmol L(-1). Chylomicrons (Sf > 1000) and their remnants (Sf < 1000) were separated by flotation and their clearance was estimated by calculating the area under the 24 h-retinyl palmitate curve (AUC-RP). The factors determining chylomicron and remnant clearance were studied by univariate and multiple regression analysis. RESULTS: Triglyceride clearance in plasma, Sf > 1000 fractions and Sf < 1000 fractions was not significantly different between FH subjects and controls. In subjects with heterozygous FH, chylomicron remnant clearance was two-fold delayed (AUC-RP, 49.39+/-11.61 h.mg L(-1) compared to controls (27.45+/-3.95 h.mg L(-1); P = 0.048). Moreover, 28.4% higher fasting plasma TG in FH resulted in 44.4% higher areas under the remnant-curves compared to controls. The clearance of chylomicron RP was associated to plasma apo E (beta = 0.73, P = 0.011), plasma LDL cholesterol (beta = 0.62, P = 0.018) and plasma TG (beta = 0.58, P = 0.029). The clearance of remnant RP was associated to the diagnosis (FH vs. non-FH), but not to the well-known determinants of remnant clearance like plasma TG. CONCLUSIONS: The clearance of chylomicrons and large remnants isolated in the Sf > fraction depends primarily on the apo B, E (LDL) receptor and to a lesser extent on plasma triglycerides. The clearance of smaller chylomicron remnants isolated in the Sf < 1000 depends to a large extent on the apo B, E (LDL) receptor.