Results of hepatitis B vaccination in sarcoidosis

BACKGROUND: Sarcoidosis is known to be associated with defects in cellular immunity, especially in reference to T helper lymphocytes. Anergy to a tuberculin skin test is most characteristic of this disease. OBJECTIVES: To further the data on impaired immunity, we studied the antibody response to hepatitis B vaccination in patients with sarcoidosis. METHODS: Serologic markers of hepatitis B virus (HBV) (HBsAg, anti-HBs, anti-HBc) were studied in 40 patients with sarcoidosis (32 female, 8 male; mean age: 45 +/- 11 years, range: 25-66 years) with a mean duration of disease of 6 years. While all the markers were negative in 22 patients (55%), 2 had isolated anti-HBc positivity and 16 had both anti-HBc and anti-HBs antibodies. Thirty-five age- and sex-matched healthy subjects were studied as controls. Recombinant HBV vaccines (Genhevac B Pasteur, 20 microg) were administered (at 0, 1, and 6 months) to 16 of the seronegative cases and the controls and antibody titres were measured 1 month after the last dose. The tuberculin skin test was negative in all cases. RESULTS: While none of the vaccinees in the diseased group responded, the control group yielded an antibody response rate of 85. 7% (30/35), with a mean titre of 257.9 mIU/ml. CONCLUSIONS: Patients with sarcoidosis were invariably unresponsive to standard vaccination, while some of the diseased subjects had already mounted a natural antibody response, either before or after the development of the original disease. Cellular immunodeficiency in sarcoidosis could be a suitable model for studying immunological interactions between HBV and the host.     

Decreased lifespan in female “Munchkin” actors from the cast of the 1939 film version of The Wizard of Oz does not support the hypothesis linking hypopituitary dwarfism to longevity

GeroScience - In laboratory mice, pituitary dwarfism caused by genetic reduction or elimination of the activity of growth hormone (GH) significantly extends lifespan. The effects of congenital...     

Is Family Screening Necessary in Brucellosis?

Brucellosis is an endemic disease in Turkey. Simultaneous infections among family members consuming infected dairy products have been reported. The most frequent signs and symptoms are nonspecific, and most human cases remain unrecognized. We aimed to screen family members of index cases with brucellosis. A questionnaire including demographical and epidemiological data was obtained. All cases were tested by slide agglutination tests (Rose Bengal test). Seropositive ones were further tested by tube agglutination tests (Wrigth test). In the index cases, Brucella antibody titers of ≥ 1:160 with and without clinical symptoms and 1: 80 with clinical symptoms were considered positive and the household members were enrolled into the study. Twenty-eigth index cases were identified among a total of 110 family members. Among family members, 90 (82%) were seronegative whereas 20 were seropositive. Among seropositive cases, 12 were asymptomatic and 8 were symptomatic. The most frequent symptoms of the index cases were fever, headache and arthralgia. Symptomatic cases were treated and asymptomatic ones followed up without therapy for a period of 6–12 months and none developed brucellosis. In conclusion, family members of the patients with brucellosis are under the increased risk of brucellosis because of a common source. Therefore, it can be considered that family screening may lead to early diagnosis of the disease and to the prevention of the complications.     

Large conductance Ca2+‐activated K+ (BK) channels promote secretagogue‐induced transition from spiking to bursting in murine anterior pituitary corticotrophs

Key points

• Corticotroph cells of the anterior pituitary are electrically excitable and are an integral component of the hypothalamic‐pituitary‐adrenal axis which governs the neuroendocrine response to stress.
• Corticotrophs display predominantly single spike activity under basal conditions that transition to complex bursting behaviours upon stimulation by the hypothalamic secretagogues corticotrophin‐releasing hormone (CRH) and arginine vasopressin (AVP); however, the underlying mechanisms controlling bursting are unknown.
• In this study, we show that CRH and AVP induce different patterns of corticotroph electrical activity, and we use an electrophysiological approach combined with mathematical modelling to show the ionic mechanisms for these differential effects.
• The data reveal that secretagogue‐induced bursting is dependent on large conductance Ca²⁺‐activated K⁺ (BK) channels and is driven primarily by CRH whereas AVP promotes an increase in single‐spike frequency through BK‐independent pathways involving activation of non‐selective cation conductances.
• As corticotroph excitability is differentially regulated by CRH and AVP this may allow corticotrophs to respond appropriately to different stressors.

Abstract

Anterior pituitary corticotroph cells are a central component of the hypothalamic‐pituitary‐adrenal (HPA) axis essential for the neuroendocrine response to stress. Corticotrophs are excitable cells that receive input from two hypothalamic secretagogues, corticotrophin‐releasing hormone (CRH) and arginine vasopressin (AVP) to control the release of adrenocorticotrophic hormone (ACTH). Although corticotrophs are spontaneously active and increase in excitability in response to CRH and AVP the patterns of electrical excitability and underlying ionic conductances are poorly understood. In this study, we have used electrophysiological, pharmacological and genetic approaches coupled with mathematical modelling to investigate whether CRH and AVP promote distinct patterns of electrical excitability and to interrogate the role of large conductance calcium‐ and voltage‐activated potassium (BK) channels in spontaneous and secretagogue‐induced activity. We reveal that BK channels do not play a significant role in the generation of spontaneous activity but are critical for the transition to bursting in response to CRH. In contrast, AVP promotes an increase in single spike frequency, a mechanism independent of BK channels but dependent on background non‐selective conductances. Co‐stimulation with CRH and AVP results in complex patterns of excitability including increases in both single spike frequency and bursting. The ability of corticotroph excitability to be differentially regulated by hypothalamic secretagogues provides a mechanism for differential control of corticotroph excitability in response to different stressors.

Abbreviations

ACTH

adrenocorticotrophic hormone

AVP

arginine vasopressin

BF

burstiness factor

BK channel

large conductance Ca²⁺‐ and voltage‐activated K⁺ channel

BK‐far

BK channels located distantly from voltage‐gated Ca²⁺ channels

BK‐near

BK channels in close proximity to voltage‐activated Ca²⁺ channels

CRH

corticotrophin‐releasing hormone

GFP

green fluorescent protein

HPA

hypothalamic‐pituitary‐adrenal

IK channel

intermediate conductance Ca²⁺‐activated K⁺ channel

IP₃

inositol trisphosphate

NMDG

N‐methyl‐d‐glucamine

PKA

protein kinase A

PKC

protein kinase C

POMC

proopiomelanocortin

STREX

stress regulated exon

ZERO

BK channels lacking STREX insert

     

Hereditary thrombophilic risk factors and venous thromboembolism in Istanbul, Turkey: the role in different clinical manifestations of venous thromboembolism.

The aim of this study was to investigate the hereditary thrombophilic risk factors in patients with venous thromboembolism (VTE) and whether these risk factors play a different role in patients with isolated pulmonary embolism (PE) as compared with patients with deep vein thrombosis (DVT) and patients with PE + DVT. The protein C (PC), protein S, antithrombin activities, homocysteine levels, and factor V Leiden (FVL) G1691A and prothrombin G20210A mutations were evaluated in 191 patients with VTE and 191 controls. The prevalence of FVL and PC deficiency were higher in patients (P = .003 and P = .02, respectively). There was no significant difference for the other risk factors. The combination of thrombophilic risk factors was significantly higher in patients with DVT + PE as compared with patients with isolated PE or DVT (P = .04). In conclusion, the most important hereditary risk factors for VTE in this study were the FVL mutation and PC deficiency.     

Sildenafil citrate and tamsulosin combination is not superior to monotherapy in treating lower urinary tract symptoms and erectile dysfunction

Purpose  

To evaluate the efficacy of sildenafil citrate only, 25 mg. Four times/week, tamsulosin only, 0.4 mg once daily, and the combination of both on lower urinary tract symptoms (LUTS) suggestive of benign prostate hyperplasia (BPH) and erectile dysfunction.     

Bilateral total knee arthroplasty in chronic, neglected congenital dislocation: a case report

This article describes a case of bilateral congenital knee dislocation treated with bilateral total knee arthroplasty. The patient had pain and disability while walking before the operation. Implants used in the surgery were constrained stems and they were applied with bone cement. After 6 years of follow-up, her joint range of motion at both knees was satisfactory and she was pain-free. The patient’s Knee Society Score and Functional Score improved from preoperative values of 12 and 0 for the right knee and 20 and 0 for the left knee to postoperative values of 55 and 15 for the right knee and 65 and 30 for the left knee. In the late presenting cases of the congenital knee dislocation, total knee arthroplasty has proved to be one of the treatment options with satisfactory outcomes.