The structure and hormone content of the endocrine pancreas of the one-humped camel (Camelus dromedarius)

Little is known of the blood sugar regulation in the camel and the morphology and function of its endocrine pancreas. The present paper describes the light microscopic structure and hormone content of the endocrine pancreas of the one-humped camel. Staining of pancreatic sections with haematoxylin-eosin or aldehyde-fuchsin showed numerous islets evenly distributed in all parts of the pancreas. Immunocytochemical staining for insulin or glucagon indicated that islets were predominantly composed of centrally located B-cells, surrounded by a peripheral rim of A-cells. Corresponding stainings for somatostatin or pancreatic polypeptide (PP) demonstrated that D-cells comprised only a small part of the islet volume while PP-cells were common both within and outside the islets. There were no obvious differences between the frequency of the various islet cells in different pancreatic regions. The pancreatic hormone concentrations roughly corresponded to the frequency of the different islet cell types. Insulin appeared most abundant followed by glucagon, PP and somatostatin in decreasing order. The concentrations of each of the hormones were similar in different regions of the gland. It is concluded that the endocrine pancreas of the one-humped camel is dispersed into islets of the same size and cellular composition as has been described in many other mammalian species.     

Phylogenetic analysis of multiple FISH markers in oral tongue squamous cell carcinoma suggests that a diverse distribution of copy number changes is associated with poor prognosis

Oral tongue squamous cell carcinoma (OTSCC) is associated with poor prognosis. To improve prognostication, we analyzed four gene probes (TERC, CCND1, EGFR and TP53) and the centromere probe CEP4 as a marker of chromosomal instability, using fluorescence in situ hybridization (FISH) in single cells from the tumors of sixty‐five OTSCC patients (Stage I, n = 15; Stage II, n = 30; Stage III, n = 7; Stage IV, n = 13). Unsupervised hierarchical clustering of the FISH data distinguished three clusters related to smoking status. Copy number increases of all five markers were found to be correlated to non‐smoking habits, while smokers in this cohort had low‐level copy number gains. Using the phylogenetic modeling software FISHtrees, we constructed models of tumor progression for each patient based on the four gene probes. Then, we derived test statistics on the models that are significant predictors of disease‐free and overall survival, independent of tumor stage and smoking status in multivariate analysis. The patients whose tumors were modeled as progressing by a more diverse distribution of copy number changes across the four genes have poorer prognosis. This is consistent with the view that multiple genetic pathways need to become deregulated in order for cancer to progress.     

Plasma chromogranin A in patients with multiple endocrine neoplasia type 1.

Plasma chromogranin A (CgA) has been claimed to be a sensitive marker for neuroendocrine tumors, but its role in the early diagnosis of multiple endocrine neoplasia type 1 (MEN 1) pancreatic endocrine tumors has not been evaluated. We measured CgA in 36 patients with MEN 1, of whom 9 lacked pancreatic involvement, 20 had biochemical evidence of pancreatic endocrine tumors, and 7 displayed radiologically detectable pancreatic tumors. CgA was also analyzed in 25 patients with sporadic pancreatic endocrine tumors, 39 subjects with inflammatory bowel disease, 7 patients harboring nonendocrine pancreatic disease, and 19 healthy controls. Four of 9 of the MEN 1 patients without pancreatic involvement had elevated CgA. Furthermore, 60% with biochemically unequivocal tumors and all with a radiologically visible tumor showed elevations. All 25 patients with sporadic pancreatic endocrine tumor had increased CgA, as had 28% of patients with inflammatory bowel disease and 57% with nonendocrine pancreatic disease. Mean day to day CgA variation was 29% (range, 0-113%) in the neuroendocrine tumor patients and 21.0% (range, 0.0-47%, within reference range) among healthy controls. In summary, nonendocrine diseases may cause elevation of CgA, and its spontaneous variation can be considerable. Plasma chromogranin A is the most sensitive of the basal markers for neuroendocrine tumors, but cannot replace other established measures when screening for early pancreatic involvement in MEN 1.     

High yield direct Br-bromination of monoclonal antibodies using chloramine-T

Monoclonal antibody (MAb) A33 was labeled with the positron emitter ⁷⁶Br ( T_1/2=16.2 h). Direct labeling was done using the conventional chloramine-T method. After optimization of the labeling conditions, a maximum yield (mean ± max error) of 77 ± 2% was obtained at pH 6.8. In vitro binding of ⁷⁶Br-A33 to SW1222 colonic cancer cells showed that the immunoreactivity was retained. Also, the MAbs 38S1 and 3S193 and the peptide hEGF were ⁷⁶Br-labeled, resulting in labeling yields (mean ± max error) of 75 ± 3%, 63 ± 4%, and 73 ± 0.1%, respectively. We conclude that antibodies and peptides can be labeled conveniently with ⁷⁶Br for the purpose of whole-body tumour imaging by positron emission tomography.     

Optimized indirect br-bromination of antibodies using n-succinimidyl para-[br]bromobenzoate for radioimmuno PET

Monoclonal antibody 38S1 was radiobrominated with the positron emitter ⁷⁶Br (T_1/2 = 16.2 h). Indirect labeling was performed using N-succinimidyl para-(tri-methylstannyl)benzoate (SPMB) as the precursor molecule. SPMB was labeled using Chloramine-T yielding N-succinimidyl para-[⁷⁶Br]bromobenzoate, which was then conjugated to the antibody. Optimization of the labeling conditions and further conjugation gave a total yield ( mean±max error) of 49±2%. The immunoreactivity of the antibodies was retained after labeling. Thus, antibodies intended for positron emission tomography can be labeled with ⁷⁶Br, which gives high yields and preserved immunoreactivity when using the SPMB technique described.     

The management and clinical knowledge of headache disorders among general practitioners in Norway: a questionnaire survey

BackgroundGeneral practitioners (GPs) diagnose and manage a majority of headache patients seeking health care. With the aim to understand the potential for clinical improvement and educational needs, we performed a study to investigate Norwegian GPs knowledge about headache and its clinical management.MethodsWe invited GPs from a random sample of 130 Norwegian continuous medical education (CME) groups to respond to an anonymous questionnaire survey.Results367 GPs responded to the survey (73% of invited CME groups, 7.6% of all GPs in Norway). Mean age was 46 (SD 11) years, with an average of 18 (SD 10) years of clinical experience. In general the national treatment recommendations were followed, while the International Classification of Headache Disorders and other international guidelines were rarely used. Overall, 80% (n = 292) of the GPs suggested adequate prophylactic medication for frequent episodic migraine, while 28% (n = 101) suggested adequate prophylactic medication for chronic tension-type headache (CTTH). Half (52%, n = 191)) of the respondents were aware that different types of acute headache medication can lead to medication-overuse headache (MOH), and 59% (n = 217) knew that prophylactic headache medication does not lead to MOH. GPs often used MRI in the diagnostic work-up. GPs reported that lack of good treatment options was a main barrier to more optimized treatment of headache patients.ConclusionThe knowledge of management of CTTH and MOH was moderate compared to migraine among Norwegian GPs.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-021-01350-3.     

Caregiver-reported antiretroviral therapy non-adherence during the first week and after a month of treatment initiation among children diagnosed with HIV in Ethiopia

To achieve optimal virologic suppression for children undergoing antiretroviral therapy (ART), adherence must be excellent. This is defined as taking more than 95% of their prescribed doses. To our knowledge, no study in Ethiopia has evaluated the level of treatment adherence at the beginning of the child’s treatment. Our aim was therefore to evaluate caregiver-reported ART non-adherence among children and any predictors for this during the early course of treatment. We conducted a prospective cohort study of 306 children with HIV in eight health facilities in Ethiopia who were registered at ART clinics between 20 December 2014 and 20 April 2015. The adherence rate reported by caregivers during the first week and after a month of treatment initiation was 92.8% and 93.8%, respectively. Our findings highlight important predictors of non-adherence. Children whose caregivers were not undergoing HIV treatment and care themselves were less likely to be non-adherent during the first week of treatment (aOR?=?0.17, 95% CI: 0.04, 0.71) and the children whose caregivers did not use a medication reminder after one month of treatment initiation (aOR?=?5.21, 95% CI: 2.23, 12.16) were more likely to miss the prescribed dose. Moreover, after one month of the treatment initiation, those receiving protease inhibitor (LPV/r) or ABC-based treatment regimens were more likely to be non-adherent (aOR?=?12.32, 95% CI: 3.25, 46.67). To promote treatment adherence during ART initiation in children, particular emphasis needs to be placed on a baseline treatment regimen and ways to issue reminders about the child’s medication to both the health care system and caregivers. Further, large scale studies using a combination of adherence measuring methods upon treatment initiation are needed to better define the magnitude and predictors of ART non-adherence in resource-limited settings.