Telediagnosis of oral lesions in primary care: The EstomatoNet Program.

OBJECTIVE: The diagnosis of oral lesions is often challenging for primary healthcare providers, which explains the high number of referrals to specialist care. This favors increases in waiting lines and delays in diagnosis, contributing to high mortality rates from oral cancer. This study aimed to summarize the experience of the EstomatoNet, a telediagnosis program catering to primary care dentists and physicians from southern Brazil. STUDY DESIGN: This exploratory study included all queries received by EstomatoNet from June 2015 to December 2016. Health providers (71 dentists and 18 physicians from primary care) submitted requests including clinical information and photographs of oral lesions by means of a cloud-based platform. Specialized oral medicine teleconsultants received the data, conveyed a diagnostic hypothesis, and conveyed management recommendations. RESULTS: Actinic cheilitis (n = 41, 15.8%), squamous cell carcinoma (n = 22, 8.5%), and inflammatory hyperplasia (21, 8.1%) were the most frequent diagnoses. Teleconsultants recommended referral to specialists in 42.9% of the cases, total biopsy in 23.6%, and follow-up in 16.2%. After the EstomatoNet use, the intention to refer the patients to face-to-face consultation reduced from 96.9% to 35.1%. CONCLUSION: Telediagnosis for oral lesions is feasible and has potential to improve the quality of primary health care by bridging the gap between primary and specialized health care.

Agouti-related protein (83-132) is a competitive antagonist at the human melanocortin-4 receptor: no evidence for differential interactions with pro-opiomelanocortin-derived ligands.

Interactions between pro-opiomelanocortin (POMC)-derived peptides, agouti-related protein (AGRP) and the melanocortin-4 receptor (MC4-R) are central to energy homeostasis. In this study we have undertaken comprehensive pharmacological analysis of these interactions using a CHOK1 cell line stably transfected with human MC4-R. Our main objectives were (1) to compare the relative affinities and potencies of POMC-derived peptides endogenously secreted within the hypothalamus, (2) to investigate the potency of AGRP(83-132) antagonism with respect to each POMC-derived peptide and (3) to determine whether AGRP(83-132) and POMC-derived peptides act allosterically or orthosterically. We have found that beta melanocyte-stimulating hormone (betaMSH), desacetyl alpha MSH (da-alphaMSH) and adrenocorticotrophic hormone all have very similar affinities and potencies at the MC4-R compared with the presumed natural ligand, alphaMSH. Moreover, even MSH precursors, such as beta lipotrophic hormone, showed significant binding and functional activity. Therefore, many POMC-derived peptides could have important roles in appetite regulation and it seems unlikely that alphaMSH is the sole physiological ligand. We have shown that AGRP(83-132) acts as a competitive antagonist. There was no significant difference in the potency of inhibition by AGRP(83-132) or agouti(87-132) at the MC4-R, regardless of which POMC peptide was used as an agonist. Furthermore, we have found that AGRP(83-132) has no effect on the dissociation kinetics of radiolabelled Nle4,D-Phe7 MSH from the MC4-R, indicating an absence of allosteric effects. This provides strong pharmacological evidence that AGRP(83-132) acts orthosterically at the MC4-R to inhibit Gs-coupled accumulation of intracellular cAMP.

[Adjuvant chemotherapy of human colorectal adenocarcinoma after growth on mice with congenital thymic dysplasia ("nude"). 1. Experiments to test the feasibility of combined chemotherapy with VCR and 5-FU (author's transl)]. / Adjuvante Chemotherapie humaner kolorektaler Adeno-Carcinome nach Wachstum auf kongenital thymusdysplastischen Mäusen "nude". 1. Untersuchungen zur Durchführbarkeit einer zytostatischen Kombinationstherapie mit Vincristin (VCR) und 5-Fluorouracil (5-FU).

Five-week-old syngeneic, female BALB/c nude mice were injected i.p. with vincristine (VCR) and 5-fluorouracil (5-FU) to determine the LD 20 of these drugs under spf-conditions. One hundred fifty animals were given dosages similar to those administered clinically, and a complete autopsy was performed on all nude mice. Whereas VCR caused splenic atrophy and regressive changes in the jejunal epithelium, the application of 5-FU was followed mainly by regressive changes in the transitional epithelium of the bladder, and 67% of the animals developed pneumonia. These pathohistological changes were also seen after a combined chemotherapy, and a temporary leucopenia was reversible. These experiments showed that chemotherapy of nude mice with VCR and 5-FU is possible provided they have been successfully xenotransplanted with human colorectal adenocarcinomas.

Adjuvant chemotherapy of human colorectal adenocarcinoma after growth on mice with congenital thymic dysplasia ("nude"). 2. Tumor remission following treatment with 5-FU and VCR of xenotransplanted primary human colorectal adenocarcinomas.

The poor 5-year survival rate of patients with malignant colorectal tumors calls for clarification of the question as to whether it is advisable to carry out postoperative adjuvant chemotherapy. In the present study a simple "in vivo" test is described with which the sensitivity of individual human adenocarcinomas of the colon, primary xenotransplanted onto syngeneic "nude"-mice suffering from congenital thymic dysplasia, to cytostatic therapy with 5-FU and VCR could be determined. Five of six primary xenotransplanted tumors showed a significant reduction in size following combined therapy with these drugs in doses comparable to those administered clinically, whereas one of the transplanted tumors remained unresponsive to therapy. On the basis of these results it is absolutely necessary that a comparison be carried out between the rate of tumor remission in groups of patients and animals undergoing the same chemotherapy.