Treatment of age-related macular degeneration by laser photocoagulation. Visual results 2-8 weeks and 2-4 years after initial laser treatment

Laser treatment with blue-green argon, green argon and/or krypton red was performed on 578 eyes in 443 patients with neovascular age-related macular degeneration (AMD). The visual acuity was examined in all eyes 2 to 8 weeks after initial treatment and in 204 eyes in 167 patients 2 to 4 years after initial treatment. The short term results were as follow: 91/578 eyes (16%) had improved (greater than or equal to 2 lines on Snellen's charge or equivalent steps), 445/578 eyes (77%) remained unchanged and 42/578 eyes (7%) had deteriorated visual acuity (greater than or equal to 2 lines on Snellen's chart or equivalent steps). The reduction in visual acuity, may in about half of the 42 eyes be caused by too intensive laser application in the beginning of this study in 1983 and 1984 where treatment was applied with blue-green argon, which has now been abandoned. In the group with an observation time of 2 to 4 years, 42/204 eyes (21%) had improved, 119/204 eyes (58%) remained unchanged and 43/204 eyes (21%) had a deteriorated visual acuity. In the 204 eyes the subretinal neovascular lesion(s) were located extrafoveally in 52 eyes, juxtafoveally in 114 eyes and subfoveally in 38 eyes. It is to be pointed out, that even patients with a pre-laser visual acuity of 6/60 or worse obtained an improvement of visual acuity in 12/27 eyes. About 40% of the eyes needed re-treatment from 1 to 8 times. It is unknown whether the obtained results are to be considered marginal or more substantial.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fatal poisonings in Jutland (Denmark) during the 1980s

Summary During the period 1980 through 1989 a total of 1029 cases of fatal poisoning (638 men and 391 women) were examined at the Department of Forensic Medicine, Aarhus University, Denmark. In 68% of the cases death had been caused by drugs, whereas acute alcohol poisoning and carbon monoxide accounted for 15% and 14% of the cases, respectively. Alcohol was detected in more than half of the 1029 fatal poisoning cases, and in 42% of all cases the blood alcohol concentration was above 0.8 g/kg. In 57% of the cases death was categorized as accidental, only in 31% of the cases as suicide. Accidental deaths were especially predominant amongst drug and/or alcohol abusers. Propoxyphene was the drug found to have caused most fatal poisonings during the decade (30% of the drug-related deaths). Most of the propoxyphene-related deaths occurred during the early and mid-eighties. Barbiturate poisonings were quite frequent during the first half of the eighties. However, the number of deaths caused by barbiturates decreased significantly after 1986, when most barbiturates were withdrawn from the market. The number of deaths caused by narcotics and analgesics increased during the survey period, while no specific tendency was observed concerning antidepressants.     

Application of fluorescence in situ hybridization techniques in clinical genetics: use of two alphoid repeat probes detecting the centromeres of chromosomes 13 and 21 or chromosomes 14 and 22, respectively

Two cloned DNA fragments, one derived from an alpha satellite subfamily common to chromosomes 13 and 21, and the other derived from a similar subfamily common to chromosomes 14 and 22, have been used as biotinylated probes in in situ hybridization studies. Under high stringency conditions, chromosome specific centromeric labelling can be obtained. The applications of this technique in clinical situations are illustrated on metaphases from a fetus with trisomy 21, a fetus with trisomy 13, and a child with clinical features of cat-eye syndrome.     

HLA-A24 and survivin: possibilities in therapeutic vaccination against cancer

Recently, it was described that an HLA-A24 restricted peptide derived from the survivin splice variant survivin-2B can be recognized by CD8(+) cytotoxic T-cells. The identification of an HLA-A24 epitope is critical for survivin-based immunotherapy as HLA-24 is the most frequent HLA allele in Asia. Consequently, this survivin-2B epitope is already a target in a clinical study in patients with advanced or recurrent colorectal cancer expressing survivin. However, the splice variant survivin-2B has been described to be pro-apoptotic, and is only expressed at low levels in most malignant tissues. Furthermore, survivin-2B expression are significantly decreased in later tumor stages and inversely correlated with tumor differentiation and invasion. Consequently, survivin is a more general vaccination candidate than the splice variant survivin-2B. Here, we on the basis of spontaneous immune responses in HLA-A24+ cancer patients describes that a HLA-A24-restricted survivin epitopes does indeed exist. Consequently, this epitope is an attractive target for the ongoing survivin-based peptide immunotherapy against cancer.     

Costello syndrome with growth hormone deficiency and hypoglycemia: a new report and review of the endocrine associations

We describe an 18-month-old boy with Costello syndrome (CS) with proven partial growth hormone (GH) deficiency and hypoglycemic episodes. The hypoglycemia is deemed to be due to cortisol deficiency. This report represents the second published case of cortisol deficiency in the CS. A brief review of the endocrine disturbances in the syndrome is provided. We highlight the need for careful endocrinological evaluation of individuals with CS.     

A functional promoter polymorphism in the macrophage migration inhibitory factor (MIF) gene associated with disease severity in rheumatoid arthritis

The macrophage migration inhibitory factor (MIF) is a potent pro-inflammatory cytokine and regulates the anti-inflammator effects of glucocorticoids. An important role for MIF within the cytokine cascade is to act in concert with endogenous glucocorticoids to control the set-point and magnitude of the inflammatory response. Elevated expression of MIF in the circulation and in the synovial joint has been documented in rheumatoid arthritis. MIF also has been linked to the development of joint damage and disease pathology in experimental animal models. We describe herein a novel CATT-tetranucleotide repeat polymorphism at position -794 of the human Mif gene and show that it functionally affects the activity of the MIF promoter in gene reporter assays. We describe four genotypes which comprise 5, 6, 7, or 8-CATT repeat units and show that the 5-CATT allele has the lowest level of basal and stimulated MIF promoter activity in vitro. The presence of the low expressing, 5-CATT repeat allele correlated with low disease severity in a cohort of rheumatoid arthritis patients.     

Congenital malformation of the feet with low body height

Among 75 members of a Danish family, 12 were found with a syndrome not previously described. Clinically, the syndrome consists of low body height and rigid flat feet, with weight-bearing pain in the feet. Radiologically, the deformation of the feet is a medial synostosis between the talus and the calcaneus combined with ankle joint dysplasia. The cause of the syndrome is most probably an autosomal dominant gene with complete penetrance. No linkage was found of the gene to 18 marker genes.     

Identification of recurrent and novel mutations in the LDL receptor gene in Spanish patients with familial hypercholesterolemia. Mutations in brief no. 135. Online

We used the single strand conformation polymorphism (SSCP) method to investigate 13 apparently unrelated Spanish patients with familial hypercholesterolemia (FH) for mutations in the promoter region and the 18 exons and their flanking intron sequences of the low density lipoprotein (LDL) receptor gene. We found 16 aberrant SSCP patterns, and the underlying mutations were characterized by DNA sequencing. Five novel missense mutations, Q71E, C74G, C95R, C281Y and D679E, and one nonsense mutation, Q133X, were identified. We also found six missense mutations, S156L, D200Y, D200G, E256K, T413K and C646Y, and one stop codon mutation, W(-18)X, that were previously described in patients from other populations. A new frameshift mutation, 2085del19, was found in one patient. We also identified three splicing mutations; two of them are novel mutations, 1706-10G->A and 2390-1G->A, and the other one has been reported recently, 313+1G->C. Four patients were found to carry two different mutations in the same allele: Q71E and 313+1G->C; C95R and D679E; W(-18)X and E256K, and C281Y and 1706-10G->A. Our results demonstrate that there is a broad spectrum of mutations in the LDL receptor gene in the Spanish population.     

The effect of sodium lauryl sulphate and triclosan on hamster cheek pouch mucosa

It has recently been shown that triclosan protects the human skin from the inflammation that may be caused by exposure to sodium lauryl sulphate (SLS). The aim of the present study was to examine whether triclosan can protect the hamster cheek pouch mucosa from the irritation caused by exposure to SLS. After four daily applications of a paste containing SLS, the epithelium of the hamster cheek pouch showed consistently prominent structural changes, especially basal hyperplasia, acanthosis, hypergranulosis, and hyperkeratosis. Identical morphological changes were also observed after applications of a paste containing SLS together with triclosan. In contrast, after applications of a paste containing triclosan alone, the cheek pouch mucosa revealed a histological structure essentially similar to the non-treated control mucosa. From these results, we may conclude that SLS, but not triclosan, irritates the hamster cheek pouch epithelium. Moreover, triclosan does not protect the cheek pouch mucosa against structural changes induced by SLS. It must be taken into account that triclosan does not always offer protection against the side-effects of SLS.     

Antibody- and complement-mediated lysis of HIV-infected cells and inhibition of viral replication

HIV-1-positive antisera were tested for their ability to lyse HIV-1-infected cells in the presence of active complement. Cytolytic effects caused by sera derived from infected humans were slower than those observed with sera from immunised chimpanzees. Lytic but also negative sera were found among HIV-1-infected asymptomatic men as well as among clinical AIDS cases. Human antisera that lysed infected cells reacted similarly irrespective of whether the complement was heterologous or autologous. Analysis of complement-mediated lysis using defined antisera against recombinant HIV-1 env or core antigens suggested that gp160/gp120 and p24 can act as target antigens for an antibody- and complement-mediated cytolysis of infected cells. Complement alone reduced the spread of HIV-1 infection in CD4+ cells and the ability of HIV-1 and HIV-2 to form plaques in CD4-transfected HeLa cells. Co-operative effects of specific antibodies and complement were the most effective in inhibiting HIV infections.