Association of HLA-DR11 with the anaphylactoid reaction caused by nonsteroidal anti-inflammatory drugs

BACKGROUND: Several HLA alleles have been associated with asthma induced by nonsteroidal anti-inflammatory drugs (NSAIDs). The existence of HLA markers linked to other NSAID-induced reactions, such as cutaneous and anaphylactoid reactions, has not been established. OBJECTIVE: The purpose of our work was to study the HLA-DRB1 and HLA-DQB1 alleles in patients with cutaneous and anaphylactoid reactions caused by NSAIDs. METHODS: We have analyzed 114 HLA DRB1 and 26 HLA-DQB1 alleles in 21 patients with anaphylactoid reactions caused by NSAIDs, 47 patients who had exclusively cutaneous reactions during single-blind, placebo-controlled oral challenges with NSAIDs, and 167 tolerant control subjects (29 of whom had also had an IgE-mediated anaphylaxis to different agents). HLA-DRB1 and HLA-DQB1 alleles were typed by the polymerase chain reaction sequence-specific primers method with genomic DNA. RESULTS: The frequency of HLA-DR11 alleles was 58.8% in the anaphylactoid reaction group, compared with 15.9% in the NSAID-tolerant healthy control subjects (OR, 7:3; 95% confidence interval, 2.8-19.0; P <.02) and 6.3% in the group of the patients with a tolerance for NSAIDs and with IgE-mediated anaphylaxis (OR, 18.75; 95% confidence interval, 4.3-81.1; P <.004). No differences were observed among HLA-DR11 alleles analyzed. There were no significant HLA-DQB1 associations with NSAID-induced anaphylactoid reactions. Patients with cutaneous reactions had HLA frequencies that did not differ significantly from the tolerant control subjects. CONCLUSION: The HLA-DRB1*11 alleles showed a positive association with NSAID-induced anaphylactoid reactions.     

Personality and clinical predictors of recurrence of depression

OBJECTIVE: To help clinicians more accurately predict outcomes of treatment for depression, variables associated with recurrence of depression in the year after treatment were examined in a group of patients who completed treatment for an index episode of depression. METHODS: Forty-two depressed patients who participated in a double-blind pharmacological treatment study were followed for one year after treatment was discontinued. Length of treatment for the index episode was determined by clinicians and ranged from eight to 76 consecutive weeks. Eighteen patients who had a recurrent episode (43 percent) and 24 patients who did not (57 percent) were compared on sociodemographic and clinical variables, including scores on the Eysenck Personality Questionnaire (EPQ). RESULTS: A combination of three variables predicted recurrence of depression in 90 percent of cases. They were an elevated EPQ score on the neuroticism subscale, a short duration of treatment of the index episode, and a slow onset of response to treatment of the index episode. CONCLUSIONS: The findings suggest that personality traits, treatment duration, and variations in response to treatment might have an impact on long-term treatment outcome. Clinicians should consider these factors when making treatment decisions for depressed patients.     

How often is extracorporeal membrane oxygenation needed in cases of congenital diaphragmatic hernia?

Some newborns with congenital diaphragmatic hernia (CDH) and severe pulmonary hypertension cannot be saved by conventional treatment and may obtain some benefit from extracorporeal membrane oxygenation (ECMO) as a bridging measure until adequate hematosis is possible. Early prediction of the insufficiency of optimal assistance is still unclear; we reviewed our recent experience with CDH patients in an attempt to evaluate the real need for ECMO in our institution. Between 1987 and 1994, 47 newborns with CDH manifested in the first 24 h were treated with maximal ventilatory assistance (including high-frequency ventilation in 12 cases) and vasoactive drugs prior to surgical repair. In order to summarize the ventilatory and blood-gas parameters, we determined oxygenation index (OI) and ventilatory index (VI) and compared the results in survivors and nonsurvivors. Overall survival was 60% (2 cases of Fryns' syndrome were excluded from analysis). OI was 10.3±5.7 (mean ± SD) for survivors and 46.2 ± 37.8 for nonsurvivors (P < 0.01). VI was 460.9±303 and 1,532±500.6, respectively (P <0.01). Bayesian analysis and receiver operating characteristic curves enabled us to select a threshold value of OI of 20 as the best means of predicting survival in our current conditions (sensitivity: 0.7, specificity: 0.83). The generally accepted figure of 40 had a sensitivity of 1 but a specificity of only 0.44. For VI, the best threshold value was 1,100 (sensitivity: 0.93, specificity: 0.94), whereas the generally used figure of 1,000 had 0.89 and 1, respectively. According to our results, with our current management conditions, approximately 50% of our CDH patients might have obtained some benefit from ECMO.     

Tissue-level biomarkers and biological effect of mercury on sentinel slugs, Arion ater

The present investigation was to determine the extent to which mercury (Hg) provokes measurable effects on the structure of the digestive gland of slugs as well as to relate the extent of these effects to the cell and tissue distribution of Hg. For this purpose, slugs (Arion ater) received various dietary concentrations of Hg (from 0 to 1,000 g Hg/g food) as chloride for 30 days and were histologically examined every third day. Autometallography was used to demonstrate Hg as black silver deposits (BSD) in paraffin sections. The lysosomes and residual bodies of digestive cells resulted to be the major accumulation sites. In addition, Hg was also evidenced in lipofuscine granules of vacuoles in excretory cells but, however, it was rarely observed within calcium cells. Generally, the extent of BSD increased with dietary Hg concentration and exposure time but, however, it became significant lowered after exposure to 1,000 g Hg/g food for 30 when the digestive epithelium appeared almost devoid of digestive cells. On the other hand, significant changes were recorded in the quantitative structure of digestive tubules. Mean Epithelial Thickness (MET), Mean Luminal Radius (MLR) and Mean Diverticular Radius (MDR) were recorded as measures of the sublethal biological effect of Hg. MET, MLR/MET and MET/MDR were affected by Hg concentration (C), exposure time (T) and CxT interaction, changes in MET, MLR, MLR/MET and MET/MDR being explained by regression models after logarithmic transformation of the data. In order to explain the nature of the changes in the quantitative structure of the digestive tubules this investigation was complemented with qualitative histological observations. According to them, the excretory activity in digestive cells was initially enhanced. Afterwards, the relative numbers of digestive cells declined until the extreme cases of exposure to 1,000 g Hg/g for 27 to 30 days in which the digestive epithelium was mostly comprised of calcium and excretory cells. Concomitantly, some changes took place in blood vessels where Leydig cells became disrupted and the connective tissue layers thickened. Finally, it is suggested to use slugs in soil quality assessment as sentinel organisms (Slug Watch) in which biomarkers of exposure to metallic pollutants and of biological effect are recorded.     

Polyclonal 111In-IgG, 125I-LDL and 125I-endothelin-1 accumulation in experimental arterial wall injury

To test iodine-125 labelled low-density lipoprotein (¹²⁵I-LDL), polyclonal indium-111 labelled immunoglobulin G (¹¹¹In-IgG) and iodine-125 labelled endothelin-1 uptake in metabolically active atheromatous plaques after arterial wall injury, we performed balloon de-endothelialization of carotid arteries or abdominal aortas in 24 New Zealand male rabbits which were fed with a normal diet (n=14) or a hypercholesterolaemic diet (n=10) after surgery. Six weeks later the animals were injected with 200 Ci of (¹²⁵I-LDL), and/or with 100 Ci of ¹¹¹In-IgG or with 9 Ci of ¹²⁵I-endothelin-1. Forty-eight hours later the animals were sacrificed. Carotid arteries and aortas were removed, counted and fixed for autoradiography and light microscopy examination. Contralateral carotid arteries and thoracic aortas served as controls.Significant ¹¹¹In-IgG uptake was observed in the injured arteries at autoradiography, with localization mainly in the healing edges, and at well counting. The percentage of the injected dose per gram (%D.inj/g) was 0.0188±0.06 versus 0.0059±0.003 in controls (P< 0.05). There was no difference in ¹¹¹In-IgG uptake between arteries with injury alone and those with active atheroma formation at the site of the injury. Significant (¹²⁵I-LDL), uptake was observed only when lipid deposition was present at light microscopy (%D.inj/g of 0.0024±0.0005 vs 0.0010±0.0003 in controls, P < 0.05). ¹²⁵I-endothelin-1 accumulation was observed in four of five injured aortas both at autoradiography, with diffuse localization, and at well counting (%D.inj/g of 0.0012±0.0004 in the abdominal aortas vs 0.0008±0.0003 in the thoracic aortas).Polyclonal IgG may accumulate in injured arteries without active atheroma formation. Inflammatory reaction at the site of the injury may cause ¹¹¹In-IgG uptake independently of atheromatous plaque formation. LDL accumulation takes place only with active atheroma formation at the site of the injury. Use of labelled peptides such as endothelin-1 may provide further insight into the mechanisms of atheromatous plaque formation.     

Computerized axial tomography for the diagnosis of cerebral cysticercosis

Summary Computerized Axial Tomography (CAT) has proved extremely useful for the diagnosis of cerebral cysticercosis. The calcified small, multiple, and scattered cysts provide a typical image on CAT.The collection of non-calcified cysts in the subarachnoid spaces (racemose form) or in the ventricles may produce areas of low density similar to that of the cerebrospinal fluid. The dilatation of the ventricular system, extreme degrees of hydrocephalus, areas of cerebral atrophy, and other related changes induced by the cysts in the subarachnoid spaces are also clearly shown in the CAT. Four personal cases are reported.     

Physiological responses to high radiant heat exposure

The physiological responses to four levels of radiant heat (R) in combination with two work loads and three ambient humidity levels were studied on seven clothed young men. The globe temperature (t_g) ranged from 40 to 74°C; metabolic work load (M) was either 20 or 50% of maximal aerobic capacity (V?₀₂ max); ambient vapor pressure was either 13 or 23 mm Hg; and dry-bulb temperature (t_db) was 38 or 49°C. The criteria for heat strain were the changes in rectal temperature (T_re), mean skin temperature (T_sk), heart rate (HR), and sweating (Sw). Stress was defined by the calculated heat load requiring dissipation (M + R + C = E_req), the ambient evaporative capacity (E_max), and the skin wettedness (w), defined as the ratio of E_req/E_max. The progressive increase in R resulted in a concomitant rise of T_re and HR reflecting the physiological strain. Similarly the increase in either M or in the humidity resulted in higher T_re and HR. The changes in R or E_max were best defined by the w, thus w and the physiological responses were highly correlated. For practical application a multiple regression of the increments of HR(ΔHR) on t_db above neutral (25°C) and on t_g above t_db was derived as follows:

$\text{△HR}{}_{\mathrm{<mtext>bpm</mtext>}}\text{= 0.96(t}{}_{\mathrm{<mtext>db</mtext>}}\text{? 25°}\text{C}\text{) + 0.81(t}{}_{\mathrm{g}}\text{? t}{}_{\mathrm{db}}\text{) ? 1}$

It was concluded that the calculated skin wettedness is most suitable in the evaluation of heat stress.