HAX-1 deficiency: Characteristics of five cases including an asymptomatic patient.

BACKGROUND: Mutations in the HAX-1 gene cause an autosomal recessive form of severe congenital neutropenia (SCN), which particularly manifests with recurrent skin, lung and deep tissue infections from the first few months of life. OBJECTIVE: We retrospectively evaluated the clinical and laboratory findings of the patients diagnosed with SCN carrying HAX1 gene mutations. METHODS: A total of five patients with SCN, carrying a HAX1 gene mutation, were evaluated in terms of clinical and laboratory findings. Mutation analysis of the candidate genes (HAX1, ELANE and CSF3R) was performed. RESULTS: All of the patients lived in Turkey; four of them were of Kurdish origin and one was Turkish. Of the five patients, three were girls and two were boys, and the mean age of the patients was 8.8 years old (range 4-15 years). The mean age of diagnosis was 25.8 months (range 2 months-5 years). The infections diagnosed included recurrent gingivitis, stomatitis, and skin and soft tissue abscesses. Developmental retardation and epilepsy were present in only one patient, whereas speech retardation was present in two. All of our patients had a HAX1 mutation, and are still alive and none of them has shown malignant transformation yet. CONCLUSION: Complete blood count should be performed and absolute neutrophil count should be evaluated in patients with recurrent severe infections. In the event that neutropenia is detected, they should be investigated in terms of SCN and mutation analysis should be performed.

Glycyrrhizin and long-term histopathologic changes in a murine model of asthma.

BACKGROUND: Licorice root has been widely used to treat bronchial asthma for many years. However, the effect of this herb on lung histopathologic features is not fully understood. OBJECTIVE: In this study, we aimed to determine the effects of oral administration of glycyrrhizin, an active constituent of licorice root, on lung histopathologic features in BALB/c mice, in which the model of chronic asthma was established. METHODS: Twenty-eight BALB/c mice were divided into 4 groups: control, placebo, dexamethasone, and glycyrrhizin. Mice in the treatment and placebo groups were sensitized with 2 intraperitoneal injections of ovalbumin and then were exposed to aerosolized ovalbumin for 30 minutes per day on 3 days each week for 8 weeks beginning on the 21st study day. In the last week of inhalational exposure, mice in the placebo group received saline and those in the treatment groups received either dexamethasone, 1 mg/kg, or glycyrrhizin, 10 mg/kg, via orogastric gavage for 7 consecutive days. Animals were humanely killed 24 hours after the last ovalbumin and drug exposure. Lung histopathologic findings were evaluated using light and electron microscopy. RESULTS: As evaluated in the control, placebo, dexamethasone, and glycyrrhizin groups, respectively, the mean (SD) basement membrane thickness was 306.34 (36.91), 657.52 (98.99), 405.13 (96.1), and 465.01 (121.48) nm; subepithelial smooth muscle thickness was 7.22 (1.37), 11.24 (1.85), 5.62 (1.15), and 7.76 (1.11) µm; epithelium thickness was 19.48 (1.22), 41.62 (5.49), 22.59 (3.18), and 25.54 (4.68) µm; number of mast cells was 1.34 (0.19), 3.62 (0.5), 2.06 (0.77), and 2.77 (0.23)/16,400 µm(2); and number of goblet cells was 0.32 (0.1), 4.92 (0.82), 0.66 (0.06), and 0.98 (0.15)/100 µm. Evaluation of lung histopathologic features demonstrated that the chronic asthma model of mice was successfully established, with significantly higher numbers of goblet and mast cells and increased thickness of epithelium, basement membrane, and subepithelial smooth muscle layers (P < 0.001 for all) in the asthma group compared with in the control group. The number of goblet (P < 0.001) and mast (P < 0.02) cells and the thickness of basement membrane (P < 0.001), subepithelial smooth muscle layers (P ≤ 0.001), and epithelium of the lung (P < 0.001) were found to be significantly lower in the glycyrrhizin group compared with in the placebo group. When the glycyrrhizin and dexamethasone groups were compared, there was no statistically significant difference between the 2 groups in the histopathologic parameters, including thickness of basement membrane (P = 0.514), subepithelial smooth muscle (P = 0.054), and epithelium (P = 1.0) and number of mast (P = 0.075) and goblet (P = 0.988) cells. CONCLUSIONS: The results of this study suggest that the group receiving glycyrrhizin had amelioration of all established chronic histopathologic changes of lung in the mouse model of asthma. Further studies are needed to evaluate the efficacy of glycyrrhizin in the management of asthma.

Characteristics of children with positive tuberculin skin test.

The aim of the study was to define the characteristics of children with latent tuberculosis diagnosed with positive tuberculin skin test (TST) and evaluate potential risk factors in children with positive TST. Children followed with the diagnosis of latent tuberculosis infection were included in the study retrospectively. Demographic characteristics of patients including history of atopy, respiratory infections, family history of tuberculosis and atopy, number of BCG vaccinations, findings of physical examination and laboratory data were extracted from patient's file. Eighty-one children (51 male, 30 female) who had positive TST were retrospectively evaluated in the study. Mean age of the patients was 8.00 ± 4.00 years. Only 13 (16%) of the children had contact with a case who had active tuberculosis. It was shown that the age of the patients, number of BCG scars and BCG vaccination significantly affected TST reaction size. TST size was not affected with time passed after last dose of BCG vaccination, family history of tuberculosis, presence of TST positive case in the family, exposure to cigarette smoke, number of household family members and presence of respiratory allergic disease. The patient's age, numbers of BCG vaccination and BCG scars significantly affect TST results in childhood. This may cause difficulty in diagnosing latent tuberculosis infection and in decision of initiating prophylactic treatment. The results of this study may show that recently developed, more accurate and convenient in vitro tests that they have higher costs and require sophisticated laboratory, can be used to diagnose latent tuberculosis.

Effect of Hedera helix on lung histopathology in chronic asthma.

Hedera helix is widely used to treat bronchial asthma for many years. However, effects of this herb on lung histopathology is still far from clear. We aimed to determine the effect of oral administration of Hedera helix on lung histopathology in a murine model of chronic asthma.BALB/c mice were divided into four groups; I (Placebo), II (Hedera helix), III (Dexamethasone) and IV (Control). All mice except controls were sensitized and challenged with ovalbumin. Then, mice in group I received saline, group II 100 mg/kg Hedera helix and group III 1 mg/kg dexamethasone via orogastic gavage once daily for one week. Airway histopathology was evaluated by using light and electron microscopy in all groups.Goblet cell numbers and thicknesses of basement membrane were found significantly lower in group II, but there was no statistically significant difference in terms of number of mast cells, thicknesses of epithelium and subepithelial smooth muscle layers between group I and II. When Hedera helix and dexamethasone groups were compared with each other, thickness of epithelium, subepithelial muscle layers, number of mast cells and goblet cells of group III were significantly ameliorated when compared with the group II. Although Hedera helix administration reduced only goblet cell counts and the thicknesses of basement membrane in the asthmatic airways, dexamethasone ameliorated all histopathologic parameters except thickness of basement membrane better than Hedera helix.