Mesenteric Cyst with GI Symptoms: A Fluid Approach to Treatment—Case Report and Literature Review

Digestive Diseases and Sciences - Mesenteric cysts are defined as a heterogeneous group of intra-abdominal cystic lesions of the mesentery or omentum that may be found in any portion of the...     

Retesting young adults with childhood-onset growth hormone (GH) deficiency with GH-releasing-hormone-plus-arginine test

Within an appropriate clinical context, severe GH deficiency (GHD) in adults has to be defined biochemically by provocative testing of GH secretion. Patients with childhood-onset GHD need retesting in late adolescence or young adulthood to verify whether they have to continue recombinant human GH treatment. GHRH + arginine (GHRH+ARG) is the most reliable alternative to the insulin-induced hypoglycemia test (ITT) as a provocative test for the diagnosis of GHD in adulthood, provided that appropriate cut-off limits are assumed (normal limits, 16.5 microg/L as 3rd and 9.0 microg/L as 1st centile). We studied the GH response to a single GHRH (1 microg/kg iv) + ARG (0.5 g/kg iv) test in 62 young patients who had undergone GH replacement in childhood, based on the following diagnosis: 1) organic hypopituitarism with GHD (oGHD) In = 18: 15 male (M), 3 female (F); age, 26.8+/-2.2 yr; GH peak < 10 microg/L after two classical tests]; 2) idiopathic isolated GHD (iGHD) [n = 23 (15 M, 8 F); age, 23.0+/-1.5 yr; GH peak < 10 microg/L after two classical tests]; and 3) GH neurosecretory dysfunction (GHNSD) [n = 21 (10 M, 11 F); age, 25.1+/-1.6 yr; GH peak > 10 microg/L after classical test but mGHc < 3 microg/L]. The GH responses to GHRH+ARG in these groups were also compared with that recorded in a group of age-matched normal subjects (NS) [n = 48 (20 M, 28 F); age, 27.7+/-0.8 yr]. Insulin-like growth factor I levels in oGHD subjects (61.5+/-13.7 microg/L) were lower (P < 0.001) than those in iGHD subjects (117.2+/-13.1 microg/L); the latter were lower than those in GHNSD subjects (210.2+/-12.9 microg/L), which, in turn, were similar to those in NS (220.9+/-7.1 microg/L). The mean GH peak after GHRH+ARG in oGHD (2.8+/-0.8 microg/L) was lower (P < 0.001) than that in iGHD (18.6+/-4.7 microg/L), which, in turn, was clearly lower (P < 0.001) than that in GHNSD (31.3+/-1.6 microg/L). The GH response in GHNSD was lower than that in NS (65.9+/-5.5 microg/L), but this difference did not attain statistical significance. With respect to the 3rd centile limit of GH response in young adults (i.e. 16.5 microg/L), retesting confirmed GHD in all oGHD, in 65.2% of iGHD, and in none of the GHNSD subjects. With respect to the 1st centile limit of GH response (i.e. 9.0 microg/L), retesting demonstrated severe GHD in 94% oGHD and in 52.1% of iGHD. All oGHD and iGHD with GH peak after GHRH+ARG lower than 9 microg/L had also GH peak lower than 3 microg/L after ITT. In the patients in whom GHD was confirmed by retesting, the mean GH peak after GHRH+ARG was higher than that after ITT (3.4+/-0.5 vs. 1.9+/-0.4). In conclusion, given appropriate cut-off limits, GHRH+ARG is as reliable as ITT for retesting patients who had undergone GH treatment in childhood. Among these patients, severe GHD in adulthood is generally confirmed in oGHD, is frequent in iGHD, but never occurs in GHNSD.     

Alprazolam,a benzodiazepine,does not modify the ACTH and cortisol response to hCRH and AVP,but blunts the cortisol response to ACTH in humans

Alprazolam (AL), a benzodiazepine which activates gamma-amino butyrric acid (GABA)-ergic receptors, exerts a clear inhibitory effect on the activity of the hypothalamo-pituitary-adrenal (HPA) axis and is able to markedly reduce the ACTH response to metyrapone-induced inhibition of glucocorticoid feedback. It has been suggested that its inhibitory action could be regulated by CRH or AVP mediated mechanisms. However, the effect of benzodiazepines on the HPA response to CRH or AVP is contradictory. It has been shown that benzodiazepines have specific receptors on the adrenal gland but it is unclear if they mediate biological effects in humans. In order to further clarify the mechanisms underlying the inhibitory effect of benzodiazepine on HPA axis in humans, we studied the effect of AL (0.02 mg/kg po at -90 min) or placebo in 7 healthy young volunteers (7 female, age: 26-34 yr; wt: 50-58 kg, BMI 20-22 kg/m2) on: 1) the ACTH and cortisol responses to hCRH (2.0 microg/kg iv at 0 min) or AVP (0.17 U/kg im at 0 min); 2) the cortisol, aldosterone and DHEA responses to ACTH 1-24 (0.06 and 250 microg iv at 0 and 60 min, respectively). After placebo, the ACTH and cortisol responses to hCRH (peaks, mean+/-SE: 29.8+/-4.4 pg/ml and 199.3+/-19.6 microg/l) were similar to those recorded after AVP (31.7+/-6.5 pg/ml and 164.8+/-18.0 microg/l); the cortisol response to 0.06 microg ACTH (190.4+/-11.8 microg/l) was similar to that recorded after hCRH and AVP but lower (p<0.01) than that after 250 microg ACTH (260.6+/-17.4 microg/l). AL did not modify the ACTH response to both hCRH (42.5+/-7.1 pg/ml) and AVP (33.3+/-2.7 pg/ml), which even showed a trend toward increase. AL also failed to significantly modify the cortisol response to both hCRH (156.3+/-12.7 microg/l) and AVP (119.4+/-14.5 microg/l), which, on the other hand, showed a trend toward decrease. The cortisol peaks after 0.06 microg ACTH were significantly reduced (p<0.02) by AL pre-treatment (115.0+/-7.7 microg/l) which, in turn, did not modify the cortisol response to the subsequent ACTH bolus (214.7+/-16.6 microg/l). The DHEA and aldosterone responses to all the ACTH doses were not significantly modified by AL. In conclusion, these data show that the HPA response to AVP as well as to hCRH is refractory to the inhibitory effect of AL which, in turn, blunts the cortisol response to low ACTH dose. These findings suggest that both CRH- and AVP-mediated mechanisms could underlie the CNS-mediated inhibitory effect of AL on HPA axis; in the meantime, these results suggest that benzodiazepines could also act on adrenal gland by blunting the sensitivity of the fasciculata zone to ACTH.     

An overview of the efficacy and safety of systemic treatments for psoriasis in the elderly

Introduction: Psoriasis in elderly patients is considered to be of emerging clinical relevance because of the increase in the aged segment of the population. Psoriasis in such a group raises significant management challenges. There is an age-related immunosuppression, a high frequency of comorbidities, and polypharmacy, which enhances the potential risk of drug interactions or side effects when an additional systemic treatment must be administered. Despite the aging of the general population, clinical studies focusing on treatment of geriatric psoriasis are limited. Patients > 65 years are often not included in randomized clinical trials. As a result, the geriatric population affected by moderate-to-severe psoriasis is usually under-treated.

Areas covered: This review focuses on the use of systemic treatments in elderly psoriatic patients and their efficacy and safety data, analyzing the available literature evidences.

Expert opinion: Conventional agents should be carefully evaluated in each patient considering the possible organ impairment, comorbidities, concomitant medications and contraindications. Apremilast is an appropriate treatment for elderly patients. Biologics represent a safe option for a long-term management of psoriasis. Etanercept, adalimumab, ustekinumab, secukinumab, ixekizumab, and brodalumab have not been associated to a higher risk of adverse events in the elderly.     

The readiness of the national health laboratory system in supporting care and treatment of HIV/AIDS in Tanzania

Background

Strong health laboratory systems and networks capable of providing high quality services are critical components of the health system and play a key role in routine diagnosis, care, treatment and disease surveillance. This study aimed to assess the readiness of the national health laboratory system (NHLS) and its capacity to support care and treatment of HIV/AIDS in Tanzania.

Methods

A documentary review was performed to assess the structure of the health system with reference to the status and capacity of the NHLS to support HIV diagnosis. Key informant interviews were also held with laboratory staff in all levels of the health care delivery system in four regions with different levels of HIV prevalence. Information sought included availability and utilization of laboratory guidelines, quality and the capacity of laboratories for diagnosis of HIV.

Results

The findings indicate that a well-established NHLS was in place. However, the coordination of HIV laboratory services was found to be weak. Forty six respondents were interviewed. In most laboratories, guidelines for HIV diagnosis were available but health care providers were not aware of their availability. Utilization of the guidelines for HIV diagnosis was higher at national level than at the lower levels. The low level of awareness and utilization of guidelines was associated with inadequate training and supervision. There was a shortage of human resource, mostly affecting the primary health care level of the system and this was associated with inequity in employment and training opportunities. Laboratories in public health facilities were better staffed and had more qualified personnel than private-owned laboratories.

Conclusion

Tanzania has a well established national health laboratory network sufficient to support HIV care and treatment services. However, laboratories at the primary health care level are constrained by inadequate resources and operate within a limited capacity. Improving the laboratory capacity in terms of number of qualified personnel, staff training on the national guidelines, laboratory diagnostic tools and coordination should be given a higher priority.

     

Replication of interleukin 23 receptor and autophagy-related 16-like 1 association in adult- and pediatric-onset inflammatory bowel disease in Italy

AIM： To investigate gene variants in a large Italian inflammatory bowel disease （IBD） cohort, and to analyze the correlation of sub-phenotypes （including age at diagnosis） and epistatic interaction with other IBD genes. METHODS： Total of 763 patients with Crohn＇s disease （CD, 189 diagnosed at age 〈 19 years）, 843 with ulcerative colitis （UC, 179 diagnosed 〈19 years）, 749 healthy controls, and 546 healthy parents （273 trios） were included in the study. The rs2241880 [autophagy-related 16-like 1 （ATG16L1）], rs11209026 and rs7517847 [interleukin 23 receptor （IL23R）], rs2066844, rs2066845, rs2066847 （CARD15）, rs1050152 （OCTN1）, and rs2631367 （OCTN2） gene variants were genotyped. RESULTS： The frequency of G allele of ATG16L1 SNP （Ala197Thr） was increased in patients with CD compared with controls （59% vs 54% respectively） （OR = 1.25, CI = 1.08-1.45, P = 0.003）, but not in UC （55%）. The frequency of A and G （minor） alleles of Arg381Gln, rs11209026 and rs7517847 variants of IL23R were reduced significantly in CD （4%, OR = 0.62, CI = 0.45-0.87, P = 0.005; 28%, OR = 0.64, CI = 0.55-0.75, P 〈 0.01）, compared with controls （6% and 38%, respectively）. The A allele （but not G） was also reduced signifi cantly in UC （4%, OR = 0.69, CI = 0.5-0.94, P = 0.019）. No association was demonstrated with sub-phenotypes and interaction with CARD15 , and OCTN1/2 genes, although both gene variants were associated with pediatric-onset disease. CONCLUSION： The present study confirms the association of IL23R polymorphisms with IBD, and ATG16L1 with CD, in both adult- and pediatric-onset subsets in our study population.     

Oxidative stress mediates angiotensin II-dependent stimulation of sympathetic nerve activity

Evidence indicates that angiotensin II (Ang II) enhances sympathetic nervous system (SNS) activity centrally and peripherally, but the exact mechanisms of this activation are not well established. We have previously shown that infusion of Ang II in the lateral cerebral ventricle raises blood pressure (BP), renal sympathetic nervous system activity (RSNA), and norepinephrine (NE) secretion from the posterior hypothalamic nuclei (PH), and reduces the abundance of interleukin-1beta (IL-1beta) and neuronal NO synthase (nNOS) mRNA in the PH. Pretreatment with an Ang II type 1 (AT1) receptor antagonist abolished these effects of Ang II. The data support the hypothesis that Ang II stimulates SNS through activation of AT1 receptors and downregulation of nNOS. In the current studies, we tested the hypothesis that the effects of Ang II on central SNS are mediated by reactive oxygen species. To this end, we evaluated the effects of Ang II alone or in combination with 2 superoxide dismutase (SOD) mimetics, tempol (4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl) and polyethylene glycol-SOD (PEG-SOD) on BP, NE secretion from the PH, RSNA, and abundance of IL-1beta and nNOS mRNA in the PH Ang II raised BP, NE secretion from the PH, and RSNA and reduced the abundance of IL-1beta and nNOS mRNA in the PH. Tempol and PEG-SOD completely abolished these actions of Ang II. In conclusion, these studies support the hypothesis that the effects of centrally administered Ang II on the SNS are mediated by increased oxidative stress in brain regions involved in the noradrenergic control of BP.     

The anaerobic index: uses and limitations in the assessment of heart failure

Limitation of exercise tolerance is a hallmark of heart failure. Anaerobic threshold is a quantitative, reproducible, nonmotivational, submaximal index of exercise tolerance. The pathophysiological significance and methods of determination of anaerobic threshold are matters of debate. The principal aspects of such problems are discussed in this paper.     

Confocal Laser Scanning Microscopy of Liesegang Rings in Odontogenic Cysts: Analysis of Three-Dimensional Image Reconstruction

Liesegang rings are concentric noncellular lamellar structures, occasionally found in inflammatory tissues. They have been confused with various parasites, algas, calcification, and psammoma bodies. The authors examined Liesegang rings from oral inflammatory cysts by both optical and confocal laser scanning microscopy, and perfomed a three-dimensional reconstruction. These investigations indicate that Liesegang rings are composed of multiple birefringent concentric rings, resulting from a progressive deposition of organic substances, with an unclear pathogenesis.