Immunology

A selection of interesting papers that were published in the two months before our press date in major journals most likely to report significant results in immunology.     

Metabolic myocardial viability assessment with iodine 123-16-iodo-3-methylhexadecanoic acid in recent myocardial infarction: Comparison with thallium-201 and fluorine-18 fluorodeoxyglucose

The best test presently available to ascertain residual viability within an infarct-related area involves the use of fluorine-18 fluorodeoxyglucose (FDG) to detect the persistence of some cellular metabolism. Rest reinjection of thallium-201 is a less accurate alternative but is easy to perform. Iodinated fatty acids, which are used with standard gamma cameras, are proposed as markers of cellular metabolism. This study was performed to assess the value of 16-iodo-3-methyl-hexadecanoic acid (MIHA) as a marker of the residual cellular metabolism by comparison with FDG in patients with a recent myocardial infarction, and to evaluate its contribution compared with the²⁰¹Tl stress-redistribution-reinjection technique. Stress-redistribution-reinjection²⁰¹T1 imaging, rest MIHA imaging and glucoseloaded FDG imaging were performed in 22 patients with recent myocardial infarction. Out of the 628 myocardial segments obtained from the left ventricular analysis, 400 were hypoperfused (relative uptake <0.75 of maximum uptake on stress²⁰¹T1 imaging), 177 of which were severely hypoperfused (relative uptake <0.50). Receiver operating characteristic (ROC) curves for predicting metabolic myocardial viability with FDG were derived from the results in respect of (a)²⁰¹T1 activity during exercise, redistribution and reinjection and (b) MIHA up-take, using the two FDG thresholds most commonly considered to define metabolic viability (0.50 and 0.60). Analysis of the 400 hypoperfused segments demonstrated that²⁰¹T1 reinjection was the most accurate test in predicting the presence of myocardial viability (area under the ROI curves=0.85 and 0.86 at the 0.50 and 0.60 FDG thresholds, respectively;P<0.05 vs other tests). The global predictive values of MIHA and²⁰¹T1 reinjection were, respectively, 0.87 and 0.89 at the 0.50 FDG threshold (NS), and 0.82 and 0.87 at the 0.60 FDG threshold (NS). When only the 177 severely hypoperfused segments were considered,²⁰¹T1 reinjection remained the most accurate test (accuracy 0.84 at the 0.50 FDG threshold and 0.82 at the 0.60 FDG threshold), while the accuracy of MIHA decreased significantly (0.78 at the 0.50 FDG threshold and 0.73 at the 0.60 FDG threshold,P<0.05 vs²⁰¹T1 reinjection). In all circumstances, MIHA was less specific than²⁰¹T1 reinjection for the detection of metabolic viability. In conclusion, in patients with recent myocardial infarction, MIHA accurately detects the persistence of metabolic viability, but is not superior to²⁰¹T1.     

Coronary atherosclerosis in cardiac transplant patients treated with total lymphoid irradiation.

BACKGROUND: Multiple episodes of rejection following cardiac transplantation have been associated with an increased incidence of coronary atherosclerosis. Total lymphoid irradiation (TLI) has been shown to be a successful treatment for persistent allograft rejection, but its effect on coronary arterial disease has yet to be evaluated. METHODS: From 1987 to 1999, 40 patients required TLI for persistent or recurrent allograft rejection following heart transplantation. Each patient's (Group 1, n = 31) post-transplant coronary angiograms were examined and compared with those of a control group (Group 2, (n = 32) matched for time of transplantation. Degree of coronary stenosis was assessed on a 6-point scale. All patients received induction therapy (rabbit anti-thymocyte globulin or OKT3) and standard triple immunosuppressive therapy. TLI (80 cGy x 10 fractions) was used for the treatment of recurrent or persistent rejection on the basis of clinical indications. Actuarial survival, number and treatment of rejection episodes, and severity of coronary artery disease were compared in each group. RESULTS: Recipient gender, age, race and cytomegalovirus (CMV) status at time of transplant, along with donor gender, CMV status and graft ischemia time, were similar in both groups. Group 1 donor age was younger than that of Group 2 (22.2 +/- 11.2 vs 31.5 +/- 13.6 years, p = 0.004), and the indication for surgery in Group 1 patients was more likely to be ischemic heart disease (15 of 31 vs 6 of 32, p = 0.02). Mean follow-up was 5.7 +/- 3.5 years in Group 1 vs 6.9 +/- 3.8 in Group 2 (p = NS). Group 1 had more rejection episodes (4.4 +/- 2.2 vs 2.3 +/- 2.0, p = 0.0002) and more steroid treatments (9.78 +/- 4.0 g vs 5.14 +/- 4.7 g, p < 0.0001), but less coronary artery disease compared with Group 2 (p = 0.035). CONCLUSIONS: Despite multiple episodes of rejection, patients treated with TLI after cardiac transplant appear to develop less coronary atherosclerosis than appropriately matched controls.     

Retinoic acid induced heparin-binding protein expression and localization during gastrulation,neurulation, and organogenesis

Retinoic acid induced heparin-binding protein (RIHB) is a highly basic, soluble polypeptide of the chick embryonic extracellular matrix. We have examined the expression and localization of RIHB during very early embryogenesis by in situ hybridization and immunohistochemistry. RIHB mRNA is very weakly detectable above background in the blastodiscs of unincubated eggs. The expression increases greatly over the first 24 hours of incubation, and is observed throughout the blastodisc in all three of the germ layers following gastrulation. As neurulation occurs, the expression becomes more restricted to certain areas, notably the ectoderm, the neural folds, and especially the notochord. After the neural tube has formed the expression in the tube itself decreases dramatically, whereas the expression in the head ectoderm and the notochord persists. After 72 hours of incubation expression remains relatively high throughout most of the embryo, with higher levels of expression in regions undergoing organogenesis and lower levels in organs which have already differentiated. RIHB protein is also weakly detectable in unincubated eggs as patches of immunoreactive material between the blastodisc and the vitelline. After 6 hours of incubation small regions of basement membrane are immunoreactive. RIHB is detected in this matrix, apparently before even fibronectin. The amount of RIHB protein increases dramatically over the first 24 hours of incubation. It is found in basement membrane separating the epiblast from the hypoblast, then later in that separating the ectoderm from the mesoderm. It is also detected surrounding individual cells, especially of the ectodermal layer. During neurulation RIHB is observed in the basement membrane surrounding the neural fold and the notochord, and in the lamina separating the ectodermal, mesodermal, and endodermal layers. Later in development, RIHB is detected in the basement membrane under the epidermis, throughout the developing limbs, and in the lamina of various developing organs, such as the eye, the pulmonary bud, the intestine, and the mesonephros. These results demonstrate that RIHB is highly expressed during the early embryonic period, by all three germ layers, and is an important and very early component of the embryonic extracellular matrix. Its very broad expression and localization argue for a more general role in development than its demonstrated weak neurotrophic activity. © 1994 Wiley-Liss, Inc.     

First evidence of fatal hantavirus nephropathy in India, mimicking leptospirosis.

Sir, In a recent Indian serosurvey [1], it was announced that ‘noreports of hantavirus infections in humans from India existed[before 2005]’. We wish to point out that serologicaland clinical evidence of hantavirus infection in India was alreadywell documented before 2005. From 1998 on, we screened leptospirosis-suspected cases in Indiafor the only known cosmopolitan hantavirus serotype, Seoul virus(SEOV). Wild rats are the reservoir     

Cortical Reorganization Allows for Motor Recovery after Crossed Cerebrocerebellar Atrophy

The authors report the case of a 33-year-old woman who exhibited, at the age of 17, a left-sided hemiplegia, which was followed by good motor recovery, though with a permanent deficit in fine finger movements. She had a widespread loss of neural tissue in the right hemisphere (crossed cerebrocerebellar atrophy), including (1) marked atrophy and thinning of the precentral and postcentral gyri; (2) widespread deep white matter destruction, including the corticospinal tract; and (3) crossed cerebellar atrophy. Except over the supplementary motor area (SMA), transcranial magnetic stimulation did not elicit motor evoked potentials in the affected hand. Nevertheless, during opening and closing of the affected hand, functional magnetic resonance imaging showed an activation of the lesioned primary sensorimotor cortex (SMC), as well as of the intact SMA and the parietal areas, but not of the ipsilateral motor areas. The authors speculate that recovery was achieved by a motor command generated in the SMC and the parietal cortex, passing through corticospinal axons originating in the SMA.     

Comparison of the inflammatory response between miniaturized and standard CPB circuits in aortic valve surgery.

OBJECTIVE: One of the complications of CPB is the systemic inflammatory response syndrome (SIRS). Recent developments tend to minimize the biological impact of CPB in using miniaturized closed circuit with reduced priming volume and less blood-air interface. The benefit of these miniaturized closed circuits in terms of inflammatory response has been proved in coronary surgery. However, in open heart surgery, the CPB circuit is no more closed and the benefit of the miniaturized set-up could disappear. The aim of the study is to compare the SIRS between standard and miniaturized circuits in aortic surgery. METHODS: Forty patients who underwent singular aortic valve replacement were randomly assigned either to a standard CPB (group A, n=20) or to a miniaturized CPB (group B, n=20). Pertinent clinical and surgical data were collected. Hematological parameters (leukocyte and neutrophil counts) and biochemical parameters (C-reactive protein, cytokine tests) were determined pre-, on and post-CPB. RESULTS: There were an increase in leukocyte and neutrophil counts and a decline in hematocrit in both groups. In both groups, there was a raise after CPB, in C-reactive protein, IL-6, TNF-alpha, neutrophil elastase, and IL-10. However, the raises of elastase and TNF-alpha were significantly lower after the weaning of miniaturized CPB (116+/-46 ng/ml and 10+/-4 pg/ml, respectively) compared to standard CPB (265+/-120 ng/ml, P=0.01 and 18+/-7 pg/ml, P=0.03). The raise of IL-10 is also lower with miniaturized circuit (15+/-6 pg/ml) compared to standard circuit (51+/-26, P=0.004). CONCLUSIONS: This study demonstrates in aortic surgery, the lesser inflammatory response of a miniaturized CPB compared to a standard CPB. However, there is always some inflammation after CPB and a small bio-reactive free perfusion circuit is still to be found in open heart surgery.     

Physician knowledge of herbal toxicities and adverse herb-drug interactions.

OBJECTIVE: To determine how knowledgeable physicians are regarding the toxic effects and drug interactions of herbal remedies. METHODS: An anonymous voluntary demographic survey and 16-question, multiple-choice quiz was distributed at educational meetings of emergency medicine and internal medicine physicians. The primary outcome measures were to determine whether significant associations existed between quiz scores and the amount of clinical experience, or between quiz scores and self-assessed familiarity with the topic of herbal toxicities and adverse herb-drug interactions. RESULTS: A total of 142 surveys and quizzes were completed by 59 attending physicians, 57 resident physicians, and 26 medical students. The mean subject score on the quiz was only slightly higher than would have occurred from random guessing. Neither the amount of the subjects' clinical experience, nor their self-assessed familiarity with herbal toxicities and drug interactions correlated significantly with the score on the quiz. CONCLUSION: The physicians and medical students surveyed had little training in herbal toxicities and drug interactions. They generally rated their familiarity with these topics as 'poor', and their scores on the quiz bore out this assessment as correct. Educational efforts might improve physician knowledge of the adverse effects of herbal remedies.     

Ipsilateral cluster headache and chronic paroxysmal hemicrania: two case reports

We report two patients with ipsilateral attacks of cluster headache and chronic paroxysmal hemicrania. The first patient, a 33-year-old man, started having attacks of chronic cluster headache at the age of 27. At 33, they were replaced by typical attacks of ipsilateral chronic paroxysmal hemicrania which showed a dramatic improvement with indomethacin 150 mg daily. After two days of complete remission, cluster headache attacks reappeared and persisted until verapamil, 360 mg a day, was added to indomethacin. The second patient, a 45-year-old man, first developed attacks of episodic cluster headache at the age of 35. At 44, he experienced ipsilateral typical attacks of chronic paroxysmal hemicrania, and two months later attacks of cluster headache. Under verapamil 240 mg daily, attacks of cluster headache disappeared, but those of chronic paroxysmal hemicrania increased in frequency until indomethacin 150 mg daily was added. These observations suggest a close relationship but not a similarity between cluster headache and chronic paraoxysmal hemicrania, and show the practical therapeutic interest of maintaining this distinction.