Abnormal intracellular calcium homeostasis in sympathetic neurons from young prehypertensive rats

Hypertension is associated with cardiac noradrenergic hyperactivity, although it is not clear whether this precedes or follows the development of hypertension itself. We hypothesized that Ca(2+) homeostasis in postganglionic sympathetic neurons is impaired in spontaneously hypertensive rats (SHRs) and may occur before the development of hypertension. The depolarization-induced rise in intracellular free calcium concentration ([Ca(2+)](i); measured using fura-2-acetoxymethyl ester) was significantly larger in cultured sympathetic neurons from prehypertensive SHRs than in age matched normotensive Wistar-Kyoto rats. The decay of the [Ca(2+)](i) transient was also faster in SHRs. The endoplasmic reticulum Ca(2+) content and caffeine-induced [Ca(2+)](i) amplitude were significantly greater in the young SHRs. Lower protein levels of phospholamban and more copies of ryanodine receptor mRNA were also observed in the young SHRs. Depleting the endoplasmic reticulum Ca(2+) store did not alter the difference of the evoked [Ca(2+)](i) transient and decay time between young SHRs and Wistar-Kyoto rats. However, removing mitochondrial Ca(2+) buffering abolished these differences. A lower mitochondrial membrane potential was also observed in young SHR sympathetic neurons. This resulted in impaired mitochondrial Ca(2+) uptake and release, which might partly be responsible for the increased [Ca(2+)](i) transient and faster decay in SHR sympathetic neurons. This Ca(2+) phenotype seen in early development in cardiac stellate and superior cervical ganglion neurons may contribute to the sympathetic hyperresponsiveness that precedes the onset of hypertension.     

Syndromic versus nonsyndromic atlantoaxial dislocation: do clinico-radiological differences have a bearing on management?

Background

This prospective study attempts to study the clinico-radiological differences between patients with syndromic AAD (SAAD), non-syndromic AAD (NSAAD), and AAD with Klippel–Feil anomaly (AADKFA) that may impact management.

Methods

In 46 patients with AAD [SAAD (including Morquio, Down, Larson and Marshall syndrome and achondroplasia; n?=?6); NSAAD(n?=?20); and, AADKFS (n?=?20)], myelopathy was graded as mild (n?=?17, 37 %), moderate (15, 32.5 %) or severe (14, 30.5 %) based on Japanese Orthopaedic Association Score modified for Indian patients (mJOAS). Basilar invagination (BI), basal angle, odontoid hypoplasia, facet-joint angle, effective canal diameter, Ishihara curvature index, and angle of retroversion of odontoid and vertebral artery (VA) variations were also studied.

Statistics

Clinico-radiological differences were assessed by Fisher’s exact test, and mean craniometric values by Kruskal–Wallis test (p value ≤?0.05 significant)

Results

Incidence of irreducible AAD in SAAD (n?=?0), NSA AD (11.55 %) and AADKFS (n?=?18.90 %) showed significant difference (p?=?0.01). High incidence of kyphoscoliosis (83 %) and odontoid hypoplasia (83 %) in SAAD, and assimilated atlas and BI in NSAAD and AADKFA groups were found. In AADKFA, effective canal diameter was significantly reduced(p?=?0.017) with increased Ishihara index and increased angle of odontoid retroversion; 61 % patients had VA variations. Thirty-five patients underwent single-stage transoral decompression with posterior fusion (for irreducible AAD) or direct posterior stabilization (for reducible AAD). Postoperative mJOAS evaluation often revealed persistent residual myelopathy despite clinical improvement.

Conclusions

Myelopathy is induced by recurrent cord trauma due to reducible AAD in SAAD, and compromised cervicomedullary canal diameter in NSAAD and AADKFA. SAAD in children may be missed due to incomplete odontoid ossification or coexisting angular deformities. In AADKFA, decisions regarding vertebral levels to be included in posterior stabilization should take into consideration intact intervening motion segments and compensatory cervical hyperlordosis. Following VA injury, endovascular primary vessel occlusion/stenting across pseudoaneurysm preempts delayed rehemorrhage.     

Association Between Ageing and Short-Term Survival Outcomes in Patients Undergoing Surgery for Primary Retroperitoneal Sarcoma

Annals of Surgical Oncology - As the population ages, more elderly patients are receiving surgery for retroperitoneal sarcoma (RPS). However, high-quality data investigating associations between...     

Management of Locally Recurrent Retroperitoneal Sarcoma in the Adult: An Updated Consensus Approach from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group

Annals of Surgical Oncology - Surgery is the mainstay of treatment for retroperitoneal sarcoma (RPS), but local recurrence is common. Biologic behavior and recurrence patterns differ significantly...     

Prevalence of celiac disease in nutritional anemia at a tertiary care center

Background

While anemia occurs in 80 % to 90 % of patients with celiac disease (CD), it may be the sole manifestation of CD. The prevalence of CD in Indian patients with nutritional anemia is not known.

Patients and Methods

Adolescent and adult patients presenting with nutritional anemia were prospectively screened for CD using IgA anti-tissue transglutaminase antibody (anti-tTG Ab) followed, if positive, by upper gastrointestinal endoscopy and duodenal biopsy.

Results

Ninety-six patients [mean?±?SD age 32.1?±?13.1 years and median duration of anemia 11 months (range 1 to 144 months)] were screened. Of these patients, 80 had iron deficiency anemia, 11 had megaloblastic anemia, and 5 had dimorphic anemia. Seventy-three patients were on hematinics and 36.4 % had received blood transfusions. Nineteen had a history of chronic diarrhea and the mean?±?SD duration of diarrhea in them was 9.7?±?35.8 months. IgA anti-tTG Ab was positive in 13 patients, of whom 12 agreed to undergo duodenal biopsy. Ten patients had villous atrophy (Marsh grade 3a in three, 3b in one, and 3c in six) and two did not. Thus, 10 patients with nutritional anemia (iron deficiency 9, vitamin B₁₂ deficiency 1) were diagnosed to have CD. On multivariate logistic regression, age, duration of symptoms, and presence of diarrhea were found to be the predictors of CD. All the patients with CD were put on gluten-free diet and with iron and vitamin supplementations and showed a significant improvement in hemoglobin concentration.

Conclusions

CD screening should be included in the work up of otherwise unexplained nutritional anemia.