Clinical case report atypical myopathy in a young girl with 91 CTG repeats in DM1 locus and a positive DM1 family history

Myotonic dystrophy type 1 (DM1) is an autosomal dominant inheritable disease associated with an expansion of CTG repeats in the 3' UTR of the DMPK gene. The subject is an 11-year-old girl with atypical myopathy. Because the proband's family has a positive DM1 history, a molecular-genetic analysis for DM1 was performed. This study showed that proband had a small DMPK expansion (91 CTG repeats) although the observed myopathy would not normally be associated with DM1. These results show how the phenotypic manifestation of DM1 can have unusual symptoms with a completely unexpected relationship to genotype.     

Intradermal tests with vasomotor agents in chronic noninfectious rhinitis

The aim of this prospective study was to examine the skin reactivity to four vasomotor agents in chronic, non-infectious rhinitis patients, and to determine whether non-allergic rhinitis (NAR) patients differ from allergic rhinitis (AR) patients. Seventy four patients with NAR and 44 with AR were subjected to intradermal testing with papaverine (5 mg/ml), metacholine (0.02, 0.2 and 2.0 mg/ml), histamine (0.01, 0.1, 1.0 and 10.0 micrograms/ml), compound 48/80 (0.01, 0.1, 1.0 and 10.0 micrograms/ml) and saline. It was found that the frequency of pathological skin reactivity to papaverine in the patients with NAR (25/74) was significantly greater (p = 5.0 x 10(-3)) then in the patients with AR (4/44). No significant inter-group difference in skin reactivity to metacholine, histamine, compound 48/80 and saline was observed. The frequency of the total pathological skin reactivity to vasomotor agents, singly and in combinations, in patients with NAR (80%) was significantly greater (p = 0.03) than in patients with AR (61%). These findings suggested that the pathological skin reactivity to papaverine, metacholine, histamine and compound 48/80 was a feature of chronic, non-infectious rhinitis patients and it was more frequently associated with non-allergic than with the allergic etiology of rhinitis.     

Retinal cAMP levels during the progression of retinal degeneration in rhodopsin P23H and S334ter transgenic rats

PURPOSE: To test whether high levels of cAMP promote apoptosis and shorten the life of retinal rod photoreceptors, the changes in cAMP levels during retinal degeneration were analyzed in two transgenic rat models that express rhodopsin P23H and S334ter mutations. METHODS: Dark- and light-adapted heterozygous P23H (lines 1 and 3; P23H-1 and -3), S334ter line 4 (S334ter-4), and Sprague-Dawley (control) rats were studied at 4 to 8 weeks by cAMP enzyme competitive immunoassay and by cAMP immunocytochemistry. RESULTS: In control animals retinal cAMP content reached a steady state level at 30 days of age. Dark-adapted control retinas had up to 97% higher cAMP content than light-adapted retinas, and photoreceptor cells were the major source of this increase. Dark-adapted photoreceptors in all three lines of transgenic rats at advanced stages of retinal degeneration had cAMP content different from that of the control. In rats that express mutant rhodopsin, the number of photoreceptor cells was progressively reduced, because of retinal degeneration, but dark-adapted cAMP levels did not decline accordingly. P23H transgenic animals of both lines had higher levels of cAMP per photoreceptor cell count than control animals. This elevation was more pronounced as degeneration progressed. S334ter animals showed smaller cAMP elevation than P23H rats at a similar stage of retinal degeneration, but at a point when S334ter rats were undergoing rapid retinal degeneration, whereas in P23H rats retinal degeneration was slowing down. CONCLUSIONS: All three lines of transgenic rats carrying rhodopsin mutations show an increase in dark-adapted photoreceptor cAMP levels. A complex relationship exists between cAMP levels and the rate of cell death in the retina. Although initially higher levels of cAMP may promote cell survival and slow down retinal degeneration, ultimately, elevated cAMP levels may become toxic and may contribute to retinal cell death.     

Skin reactivity to vasomotor agents in non-eosinophilic and eosinophilic non-allergic rhinitis

The aim of this prospective study was to examine skin reactivity to four vasomotor agents and to determine whether non-eosinophilic rhinitis patients differ from patients with eosinophilic rhinitis. Nasal cytology enabled us to classify 74 rhinitis patients into a non-eosinophilic (n = 63) and an eosinophilic group (n = 11). Skin reactivity to intradermal tests with papaverine, metacholine, histamine and compound 48/80 was measured. No significant difference for papaverine, metacholine, histamine and compound 48/80, singly, was found between the non-eosinophilic and eosinophilic group.The frequency of the total pathological skin reactivity to vasomotor agents, singly and in combinations, was greater in the eosinophilic (91 per cent) then in the non-eosinophilic group (78 per cent) but intergroup difference was not significant. These findings suggest that pathologic skin reactivity to vasomotor agents is a feature of non-eosinophilic as well as eosinophilic non-allergic rhinitis patients and indicate that no difference is noticed in the skin reactivity between these groups.     

Role of neuropoietic cytokines in development and progression of diabetic polyneuropathy: from glucose metabolism to neurodegeneration

Diabetic neuropathy develops as a result of hyperglycemia-induced local metabolic and microvascular changes in both type I and type II diabetes mellitus. Diabetic neuropathy shows slower impulse conduction, axonal degeneration, and impaired regeneration. Diabetic neuropathy affects peripheral, central, and visceral sensorimotor and motor nerves, causing improper locomotor and visceral organ dysfunctions. The pathogenesis of diabetic neuropathy is complex and involves multiple pathways. Lack of success in preventing neuropathy, even with successful treatment of hyperglycemia, suggests the presence of early mediators between hyperglycemia-induced metabolic and enzymatic changes and functional and structural properties of Schwann cells (SCs) and axons. It is feasible that once activated, such mediators can act independently of the initial metabolic stimulus to modulate SC-axonal communication. Neuropoietic cytokines, including interleukin-1 (IL-1), interleukin-6 (IL-6), leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), tumor necrosis factor alpha (TNF-alpha), and transforming growth factor beta (TGF-beta), exhibit pleiotrophic effects on homeostasis of glia and neurons in central, peripheral, and autonomic nervous system. These cytokines are produced locally by resident and infiltrating macrophages, lymphocytes, mast cells, SCs, fibroblasts, and sensory neurons. Metabolic changes induced by hyperglycemia lead to dysregulation of cytokine control. Moreover, their regulatory roles in nerve degeneration and regeneration may potentially be utilized for the prevention and/or therapy of diabetic neuropathy.     

Aryl Hydrocarbon Receptor is Involved in the Proinflammatory Cytokine Response to Cadmium

Objective To investigate involvement of the aryl hydrocarbon receptor(Ah R)in the immunomodulatory effects of cadmium(Cd).Methods The effect of Cd on Ah R activation(CYP1 A1 and CYP1 B1 m RNA expression)was examined in lung leukocytes of Cd-exposed rats(5 and 50 mg/L,30 d orally)and by in vitro leukocyte exposure.The involvement of Ah R signaling in the effects of Cd on the interleukin(IL)-1β,IL-6,and tumor necrosis factor(TNF)lung leukocyte response was investigated in vitro using the receptor antagonist CH-223191.Results Cd increased CYP1 B1(in vivo and in vitro)and CYP1 A1(in vitro)m RNA,indicating Ah R involvement in the action of Cd.In response to Cd,lung leukocytes increased IL-6 and decreased TNF at the gene expression and protein levels,but decreased IL-1βproduction due to reduced NLRP3.The Ah R antagonist CH-223191 abrogated the observed effects of Cd on the cytokine response.The absence of Ah R reactivity and cytokine response to Cd of leukocytes from the lungs of a rat strain that is less sensitive to Cd toxicity coincided with a high Ah R repressor m RNA level.Conclusion Ah R signaling is involved in the lung leukocyte proinflammatory cytokine response to Cd.The relevance of the Ah R to the cytokine response to Cd provides new insight into the mechanisms of Cd immunotoxicity.     

Epidemiology of myotonic dystrophy type 1 (Steinert disease) in Belgrade (Serbia)

The aim of this study was to estimate the incidence and prevalence of myotonic dystrophy type 1 (DM1) in Belgrade during the period 1983–2002.

The patients who had DM1 were ascertained through hospital records from all neurological departments in Belgrade during 1983–2002. The molecular genetic analysis was performed in all patents included in the study.

We identified 101 DM1 patients (52 males and 49 females). The average annual incidence rate of DM1 in Belgrade for the period observed was 2.0/1,000,000 (95% confidence interval (CI), 0.3–8.3), 2.1/1,000,000 (95% CI, 0.3–8.3) for males and 2.0/1,000,000 (95% CI, 0.3–8.3) for females. The highest age-specific DM1 incidence was registered in the age group 20–49: 3.4/1,000,000 (95% CI, 0.5–7.6), 4.0/1,000,000 (95% CI, 1.1–10.2) in males and 2.5/1,000,000 (95% CI, 0.5–7.6) in females. In the population of Belgrade, a cumulative probability of acquiring DM1 was 1 per 8621 for men and 1 per 9259 for women (1 per 8940 of the population for both sexes). The prevalence of DM1 in Belgrade on 31 December 2002 was 5.3/100,000 (95% CI, 4.2–6.6).     

A fatal case of Listeria monocytogenes sepsis and meningitis in a patient with Wegener's granulomatosis

The bacillus Listeria monocytogenes is widely distributed in the environment. Listeria monocytogenes most often causes infection in the neonates, pregnant women, elderly and immunosuppressed persons. We report on a case of fatal sepsis and meningitis in a 59-year-old woman receiving cyclophosphamide and glucocorticoid therapy for Wegener's granulomatosis over a 10-year period. Listeriosis should be suspected in case of sepsis and/or meningitis in patients who receive immunosuppressive agents. Since meningitis due to Listeria monocytogenes is not distinguishable clinically from other types of bacterial meningitis, antibiotics against Listeria monocytogenes should be included in the initial empirical therapy of bacterial meningitis in immunosuppressed patients, antibiotics against Listeria monocytogenes should be included.