Impact of real-time, dose-escalated permanent seed implant brachytherapy in intermediate-risk prostate cancer.

PURPOSE: To retrospectively evaluate biochemical control and toxicity in patients who underwent 125I seed brachytherapy (BT) for intermediate-risk prostate cancer (PCa). MATERIALS AND METHODS: Between January 2004-December 2014, 395 patients with intermediate-risk PCa underwent 125I BT. Of these, 117 underwent preoperative planning (PP; 145 Gy) and 278 real-time intraoperative preplanning (IoP; 160 Gy). All patients were followed for ≥ 6 months (> 5 years in 48% of patients and > 7 years in 13%). Median follow-up was 59 months. RESULTS: Biochemical relapse-free survival (BRFS) rates at 5 and 8 years were, respectively, 91.7% and 82.1%. By treatment group, the corresponding BRFS rates were 93.5% and 90% for IoP and 89% and 76.8% for PP. The maximum dose to the urethra remained unchanged (217 Gy) despite the dose escalation (from 145 to 160 Gy), without any significant increase in treatment-related toxicity (p = 0.13). Overall toxicity outcomes in the series were excellent, with only 3 cases (0.76%) of grade 3 genitourinary toxicity. CONCLUSION: The real-time intraoperative planning technique at 160 Gy yields better biochemical controls than the preoperative planning technique at 145 Gy. Dose escalation did not increase urinary toxicity. The excellent results obtained with the IoP BT technique support its use as the first treatment option in this patient population.

MRI assessment and outcomes in patients receiving neoadjuvant chemotherapy only for primary rectal cancer: long-term results from the GEMCAD 0801 trial.

Background: Primary chemotherapy has been tested as a possible approach for patients with high risk features but predicted clear mesorectal margins on preoperative MRI assessment. This study investigates the prognostic relevance of baseline and post-treatment MRI and pathology staging in rectal cancer patients undergoing primary chemotherapy. Patients and methods: Forty-six patients with T3 tumour > =2 mm from the mesorectal fascia were prospectively treated with Neoadjuvant Capecitabine, Oxaliplatin and Bevacizumab prior to surgery between 2009 and 2011. The baseline and post-treatment MRI: T, Nodal and Extra-mural venous invasion (EMVI) status were recorded as well as post-treatment MRI Tumour regression grade (TRG) and modified-RECIST assessment of tumour length. The post-treatment pathology (yp) assessments of T3 substage, N, EMVI and TRG status were also recorded. Three-year disease-free survival (DFS) and cumulative incidence of recurrence were estimated by using the Kaplan-Meier product-limit method, and Cox proportional hazards models were used to determine associations between staging and response on MRI and pathology with survival outcomes. Results: About 46 patients underwent neoadjuvant chemotherapy alone for high risk margin safe primary rectal cancer. The median follow-up was 41 months, 5 patients died and 11 patients experienced relapse (2 local, 8 distant and 1 both). In total 23/46 patients were identified with MRI features of EMVI at baseline. mrEMVI positive status carried independent prognostic significance for DFS (P = 0.0097) with a hazard ratio of 31.33 (95% CI: 2.3-425.4). The histopathologic factor that was of independent prognostic importance was a final ypT downstage of ypT3a or less, hazard ratio: 14.0 (95% CI: 1.5-132.5). Conclusions: mrEMVI is an independent prognostic factor at baseline for poor outcomes in rectal cancer treated with neoadjuvant chemotherapy while ≤ypT3a is associated with an improvement in DFS. Future preoperative therapy evaluation in rectal cancer patients will need to stratify treatment according to baseline EMVI status as a crucial risk factor for recurrence in patients with predicted CRM clear rectal cancer.

Persistent natural acidification drives major distribution shifts in marine benthic ecosystems.

Ocean acidification is receiving increasing attention because of its potential to affect marine ecosystems. Rare CO2 vents offer a unique opportunity to investigate the response of benthic ecosystems to acidification. However, the benthic habitats investigated so far are mainly found at very shallow water (less than or equal to 5 m depth) and therefore are not representative of the broad range of continental shelf habitats. Here, we show that a decrease from pH 8.1 to 7.9 observed in a CO2 vent system at 40 m depth leads to a dramatic shift in highly diverse and structurally complex habitats. Forests of the kelp Laminaria rodriguezii usually found at larger depths (greater than 65 m) replace the otherwise dominant habitats (i.e. coralligenous outcrops and rhodolith beds), which are mainly characterized by calcifying organisms. Only the aragonite-calcifying algae are able to survive in acidified waters, while high-magnesium-calcite organisms are almost completely absent. Although a long-term survey of the venting area would be necessary to fully understand the effects of the variability of pH and other carbonate parameters over the structure and functioning of the investigated mesophotic habitats, our results suggest that in addition of significant changes at species level, moderate ocean acidification may entail major shifts in the distribution and dominance of key benthic ecosystems at regional scale, which could have broad ecological and socio-economic implications.

Application of a modified Neff classification to patients with uncomplicated diverticulitis.

AIM: Severity of acute diverticulitis (AD) has traditionally been assessed using the Hinchey classification; however, this classification is predominantly a surgical one. The Neff classification provides an alternative classification based on CT findings. The aim of this study was to evaluate a modification of the Neff classification to select patients presenting with early-stage AD to receive outpatient management. METHOD: All patients with AD, presenting to a single unit, were prospectively studied. All patients underwent emergency abdominal CT and were assigned a Neff stage, including a modification (mNeff) to Neff Stage I. The Neff stages used were: Stage 0, uncomplicated diverticulitis; Diverticula, thickening of the wall, increased density of the pericolic fat; Stage I, locally complicated (our modification included substages Ia (localized pneumoperitoneum in the form of air bubbles) and Ib (local abscess); Stage II, complicated with pelvic abscess; Stage III, complicated with distant abscess; and Stage IV, complicated with other distant complications. Patients who presented with Stage 0 or Stage Ia were selectively managed as outpatients. Patients with comorbidity or the presence of the systemic inflammatory response syndrome (SIRS) were excluded. RESULTS: Between February 2010 and January 2013, 205 patients (mean age 59 years; age range 25-90 years) presented with AD. One-hundred and forty-nine met the radiological criteria for potential outpatient treatment. After applying the exclusion criteria, 68 were eventually assigned to an outpatient programme. Sixty-four (94%) successfully completed the outpatient treatment protocol; four patients were readmitted. CONCLUSION: Our mNeff classification allowed selected patients with AD to be successfully managed in an outpatient programme.

Plitidepsin as a successful rescue treatment for prolonged viral SARS-CoV-2 replication in a patient with previous anti-CD20 monoclonal antibody-mediated B cell depletion and chronic lymphocytic leukemia.

BACKGROUND: There is an urgent need for highly efficacious antiviral therapies in immunosuppressed hosts who develop coronavirus disease (COVID-19), with special concern for those affected by hematological malignancies. CASE PRESENTATION: Here, we report the case of a 75-year-old male with chronic lymphocytic leukemia who was deficient in CD19+CD20+ B-lymphocyte populations due to previous treatment with anti-CD20 monoclonal antibodies. The patient presented with severe COVID-19 pneumonia due to prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and was treated with two courses of the antiviral plitidepsin on a compassionate use basis. The patient subsequently achieved an undetectable viral load, and his pneumonia resolved. CONCLUSIONS: Treatment with plitidepsin was well-tolerated without any further hematological or cardiovascular toxicities. This case further supports plitidepsin as a potential antiviral drug in SARS-CoV-2 patients affected by immune deficiencies and hematological malignancies.

PIQA: pipeline for Illumina G1 genome analyzer data quality assessment.

SUMMARY: PIQA is a quality analysis pipeline designed to examine genomic reads produced by Next Generation Sequencing technology (Illumina G1 Genome Analyzer). A short statistical summary, as well as tile-by-tile and cycle-by-cycle graphical representation of clusters density, quality scores and nucleotide frequencies allow easy identification of various technical problems including defective tiles, mistakes in sample/library preparations and abnormalities in the frequencies of appearance of sequenced genomic reads. PIQA is written in the R statistical programming language and is compatible with bustard, fastq and scarf Illumina G1 Genome Analyzer data formats. AVAILABILITY: The PIQA pipeline, installation instructions and examples are available at the supplementary web site (http://bioinfo.uh.edu/PIQA).

Endoscopic biliary large-balloon dilation after endoscopic sphincterotomy for the treatment of large common bile duct stones. Case report.

Common bile duct (CBD) stones extraction is usually performed by endoscopic sphincterotomy followed by removal by either a Dormia basket or extraction balloon catheter. However, some stones due to their size are not amenable to these procedures and extracorporeal or mechanical lithotripsy devices need to be used. Mechanical lithotripsy involves usage of a basket that will be inevitably destroyed which increases cost to the patient and endoscopy unit. The use of extracorporeal wave shock lithotripsy is an alternative; however it is not available widely. Reports about the use of hydrostatic large caliber balloon dilator (HLCBD) aiding in the extraction of large caliber CBD stones have concluded that is a safe and feasible therapeutic alternative. We present the case of a 25 mm x 30 mm CBD stone that could not be extracted using conventional methods. CBD dilation using HLCBD was performed after endoscopic sphincterotomy in an attempt to avoid mechanical lithotripsy.

[Endoscopic resection of ampullary adenoma.]. / Resección endoscópica de adenoma del ámpula de Vater.

Ampullary adenomas can occur sporadically or as part of familial adenomatous polyposis syndrome. Most of them are asymptomatic. Current standard of management is complete surgical or endoscopic resection, depending on depth of invasion and/or biliary tract involvement. The last can be established by endoscopic ultrasound or endoscopic retrograde colangiopancreatography. Surgical resection has high morbidity (25% to 65%) and mortality (10%) in unexperienced hands compared to endoscopic therapy (12% and 1%, respectively). Complications of endoscopic therapy ranges from 7% to 10%. Recurrence of adenomatous lesions treated endoscopically is 30%. Endoscopic surveillance after resection is mandatory. We present the case of a patient with an ampulla of Vater s adenoma successfully resected endoscopically previous assessment of the lesion by endoscopic ultrasound.

100% peer review in radiation oncology: is it feasible?

PURPOSE: Peer review has been proposed as a strategy to ensure patient safety and plan quality in radiation oncology. Despite its potential benefits, barriers commonly exist to its optimal implementation in daily clinical routine. Our purpose is to analyze peer-review process at our institution. METHODS AND MATERIALS: Based on our group peer-review process, we quantified the rate of plan changes, time and resources needed for this process. Prospectively, data on cases presented at our institutional peer-review conference attended by physicians, resident physicians and physicists were collected. Items such as time to present per case, type of patient (adult or pediatric), treatment intent, dose, aimed technique, disease location and receipt of previous radiation were gathered. Cases were then analyzed to determine the rate of major change, minor change and plan rejection after presentation as well as the median time per session. RESULTS: Over a period of 4 weeks, 148 cases were reviewed. Median of attendants was six physicians, three in-training-physicians and one physicist. Median time per session was 38 (4-72) minutes. 59.5% of cases presented in 1-4 min, 32.4% in 5-9 min and 8.1% in ≥ 10 min. 79.1% of cases were accepted without changes, 11.5% with minor changes, 6% with major changes and 3.4% were rejected with indication of new presentation. Most frequent reason of change was contouring corrections (53.8%) followed by dose or fractionation (26.9%). CONCLUSION: Everyday group consensus peer review is an efficient manner to recollect clinical and technical data of cases presented to ensure quality radiation care before initiation of treatment as well as ensuring department quality in a feedback team environment. This model is feasible within the normal operation of every radiation oncology Department.

Long-term outcomes in patients with schizophrenia treated with risperidone long-acting injection or oral antipsychotics in Spain: results from the electronic Schizophrenia Treatment Adherence Registry (e-STAR).

BACKGROUND: The electronic Schizophrenia Treatment Adherence Registry (e-STAR) is a prospective, observational study of patients with schizophrenia designed to evaluate long-term treatment outcomes in routine clinical practice. METHODS: Parameters were assessed at baseline and at 3 month intervals for 2 years in patients initiated on risperidone long-acting injection (RLAI) (n=1345) or a new oral antipsychotic (AP) (n=277; 35.7% and 36.5% on risperidone and olanzapine, respectively) in Spain. Hospitalization prior to therapy was assessed by a retrospective chart review. RESULTS: At 24 months, treatment retention (81.8% for RLAI versus 63.4% for oral APs, p<0.0001) and reduction in Clinical Global Impression Severity scores (-1.14 for RLAI versus -0.94 for APs, p=0.0165) were significantly higher with RLAI. Compared to the pre-switch period, RLAI patients had greater reductions in the number (reduction of 0.37 stays per patient versus 0.2, p<0.05) and days (18.74 versus 13.02, p<0.01) of hospitalizations at 24 months than oral AP patients. CONCLUSIONS: This 2 year, prospective, observational study showed that, compared to oral antipsychotics, RLAI was associated with better treatment retention, greater improvement in clinical symptoms and functioning, and greater reduction in hospital stays and days in hospital in patients with schizophrenia. Improved treatment adherence, increased efficacy and reduced hospitalization with RLAI offer the opportunity of substantial therapeutic improvement in schizophrenia.

[Endoscopic mucosal resection due to adenocarcinoma of the esophagus caused by Barrett's esophagus.]. / Resección endoscópica de la mucosa debido a adenocarcinoma de esófago originado en un esófago de Barrett.

The endoscopic therapy has been used in the treatment of early stage neoplastic esophageal lesions with great success. The endoscopic ultrasound is a useful tool for the correct staging of these lesions. The staging accuracy of esophageal cancer with endoscopic ultrasound reaches 80% for T stage and 77% for N stage. The endoscopic approach provides complete resection of lesions confined to the mucosal layer, is a safety procedure with complications reported to occur from 3% to 13%. The morbidity and mortality rates after an endoscopic mucosal resection have been reported to be less than those posterior to esophagectomy. We present a case of a patient with high surgical risk, who underwent an upper endoscopy because of long history of gastroesophageal reflux disease and uncontrollable hiccup with successful endoscopic mucosal resection with plastic cap and polipectomy loop of an early stage esophageal adenocarcinoma derived of Barrett s esophagus.

An organopalladium chromogenic chemodosimeter for the selective naked-eye detection of Hg(2+) and MeHg(+) in water-ethanol 1 : 1 mixture.

An organopalladium chemical dosimeter of Hg(2+) that methylates Hg(2+), undergoing a colour change in 1 : 1 ethanol-water with submicromolar sensitivity, gives rise to an aqua-palladium complex that is methylated by MeHg(+) in the presence of a dithiol compound, undergoing another colour change, thus making the system suitable for the naked-eye detection of Hg(2+) and MeHg(+), two environmentally important species of Hg(2+).

Simultaneous multidetermination of residues of pesticides and polycyclic aromatic hydrocarbons in olive and olive-pomace oils by gas chromatography/tandem mass spectrometry.

A multiresidue method for determining major pesticides and polycyclic aromatic hydrocarbons (PAHs) in olive oils in a single injection by use of gas chromatography/tandem mass spectrometry (GC-MS/MS) is proposed. Samples are previously extracted with an acetonitrile/n-hexane mixture and cleaned up by gel permeation chromatography. Electron ionization and chemical ionization allow pesticides and PAHs to be determined in a single analysis. The precision obtained was quite satisfactory (relative standard deviations ranged from 3 to 7.8%), and so were recoveries (84-110%). The linear relation was observed from 1 to 500 microg/kg for pesticides and 0.3 to 200 microg/kg for PAHs; also, the determination coefficient, R(2), was better than 0.995 in all instances. The proposed method was applied to the routine analysis of PAH and pesticide residues in virgin and refined olive oil and olive-pomace oil samples.

[Seropositivity for Chlamydia pneumoniae in patients with primary biliary cirrhosis]. / Seropositividad para Chlamydia pneumoniae en pacientes con cirrosis biliar primaria.

INTRODUCTION: Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by inflammatory injury and bile duct destruction. Recent studies suggest that Chlamydia pneumoniae could be associated with the development of PBC. The aim of this study was to determine the seroprevalence of C. pneumoniae in a cohort of patients with PBC. PATIENTS AND METHODS: The presence of IgG antibodies against C. pneumoniae was investigated in 46 patients with PBC and in 105 subjects without cirrhosis. RESULTS: Twenty-one patients (46%) with PBC had antibodies against C. pneumoniae compared with 74 subjects (71%) in the control group (OR = 0.6; 95% CI, 0.3-1.2; p = NS). Subanalysis of the PBC group showed that patients with C. pneumoniae antibodies had a higher frequency of advanced Child-Pugh stages (24% A, 52% B and 24% C vs 64% A, 32% B and 4% C; p = 0.01), a higher score on the Mayo Clinic Prognostic Index (7.8 +/- 2.1 vs 5.6 +/- 1.2; p = 0.004), a higher frequency of ascites (29% vs 4%; OR = 9.6; 95% CI, 1-87; p = 0.02), higher total bilirubin levels (4.5 +/- 2.5 mg/dl vs 2.4 +/- 4.3 mg/dl, p = 0.001) and lower serum albumin levels (2.6 +/- 0.9 g/dl vs 3.3 +/- 0.6 g/dl, p = 0.02). CONCLUSION: No association was found between C. pneumoniae infection and PBC in this study. An association was found between the severity of PBC and C. pneumoniae, which may suggest a deleterious effect of C. pneumoniae infection or a predisposition in advanced stages of PBC to acquire infection with this microorganism.

Evolución del síndrome de desgaste profesional, ansiedad y depresión en personal sanitario durante la pandemia de la COVID-19 / Evolution of burnout syndrome, anxiety and depression in healthcare personnel during the COVID-19 pandemic

Introducción. La pandemia de la COVID-19 ha producido un impacto en la esfera psicológica de los trabajadores sanitarios. El objetivo de este estudio es analizar la evolución del síndrome de desgaste profesional, la ansiedad y la depresión en el personal sanitario a lo largo de la pandemia de la COVID-19. Material y métodos. Estudio observacional de los profesionales sanitarios del Servicio de Neumología del Hospital Gregorio Marañón que ha prestado servicio entre diciembre de 2019 y enero de 2021. Se evaluó el síndrome de desgaste profesional mediante el cuestionario Maslach Burnout Inventory (MBI) y la ansiedad y depresión mediante los cuestionarios de Zung referido a diciembre de 2019 (situación basal), marzo de 2020 (primera ola) y enero de 2021 (tercera ola) en diferentes profesiones sanitarias. Resultados. Se incluyeron 62 participantes, de los cuales 15 (24,2%) eran varones. En cuanto a las profesiones sanitarias, 24 (38,7%) eran médicos, 22 eran diplomados universitarios de enfermería (DUE), 12 (19,4%) eran técnicos en cuidados auxiliares de enfermería (TCAE), y 4 (6,5%) eran otros profesionales. Se documentó un cambio significativo al alza del estrés emocional y de despersonalización y a la baja de realización personal tanto de forma global como estratificado por diferentes profesiones sanitarias excepto en otros profesionales. Se objetivó un aumento progresivo de la ansiedad, mientras que el aumento de la depresión no fue estadísticamente significativo. Conclusión. Durante la pandemia de la COVID-19, los profesionales sanitarios sufrieron un aumento progresivo del desgaste profesional y de la ansiedad. Es importante tener en cuenta la salud psicológica de los sanitarios (AU)

Introduction. The COVID-19 pandemic has impacted the psychological sphere of healthcare workers. The objective of this study is to analyze the evolution of burnout syndrome, anxiety and depression in healthcare personnel throughout the COVID-19 pandemic Material and methods. Observational study of the healthcare professionals of the Respiratory Department of Gregorio Marañón Hospital that worked between December 2019 and January 2021. Burnout syndrome was evaluated using the Maslach Burnout Inventory (MBI) questionnaire and anxiety and depression using the Zung questionnaires referred to December 2019 (baseline situation), March 2020 (first wave) and January 2021 (third wave) in different healthcare professions. Results. Sixty-two participants were included, of which 15 (24.2%) were male. Regarding the healthcare professions, 24 (38.7%) were doctors, 22 were nurses, 12 (19.4%) were technicians in auxiliary nursing care, and 4 (6, 5%) were other professionals. A significant upward change in emotional stress and depersonalization and a downward personal fulfillment were documented both globally and stratified by different healthcare professions except in other professionals. A progressive increase in anxiety was observed, meanwhile, the increase in depression was not statistically significant. Conclusion. During the COVID-19 pandemic, healthcare professionals suffered a progressive increase in burnout and anxiety. It is important to consider the psychological health of the healthcare personnel (AU)

Direct effect of phosphorus on PTH secretion from whole rat parathyroid glands in vitro.

Phosphorus retention is an important factor in the development of hyperparathyroidism secondary to renal failure. In vivo manipulation of phosphorus is associated with changes in serum calcium and calcitriol levels which in turn can modify parathyroid hormone synthesis and secretion. The present in vitro study evaluates whether high extracellular phosphorus has a direct effect on parathyroid hormone secretion. Fresh rat parathyroid glands were incubated in a media with phosphorus concentrations of 1, 2, 3, and 4 mM and subsequently exposed to calcium levels ranging from 0.4 to 1.35 mM. In 1.25 mM calcium, the parathyroid hormone secretion rate was similar in 1 and 2 mM phosphorus; however, a phosphorus concentration of 3 and 4 mM produced a 3- and 4-fold increase in the parathyroid hormone secretion, respectively, as compared with 1 mM phosphorus. While in 1 or 2 mM phosphorus an increase in calcium from 0.6 to 1.35 mM reduced parathyroid hormone secretion to 37%, in 4 mM phosphorus the same increase in calcium only inhibited parathyroid hormone secretion to 75%. Furthermore, the addition of arachidonic acid 20 microM, a substrate for inhibitory intracellular signal pathway, to the 4 mM phosphorus-1.35 mM calcium incubation media reduced the parathyroid hormone secretion to 34.5% (p < 0.05). In conclusion, our results indicate that in vitro, high phosphorus directly increases parathyroid hormone secretion.

CD5+ low-grade marginal zone B-cell lymphomas with localized presentation.

Marginal zone B-cell lymphomas (MZBCLs) are low-grade lymphomas that characteristically lack CD5 expression. However, rare cases of MZBCL have been described in which the lymphomatous B cells coexpress CD5 (CD5+ MZBCL). In 7 of 9 reported CD5+ MZBCLs, there was evidence of widespread disease. We report four additional cases of CD5+ MZBCL. Three cases were low-grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) involving the lungs, the conjunctiva (bilateral), and the uterus. The remaining case represented a monocytoid B-cell lymphoma involving a posterior cervical lymph node. Southern blot hybridization did not show rearrangements of bc11 or bc12 in the three cases analyzed. All four patients had localized disease and normal peripheral blood counts. Staging of bone marrow biopsies from three patients did not show evidence of bone marrow involvement. The remaining patient had bilateral conjunctival lesions that were present for 15 years without progression. These four additional cases of CD5+ MZBCL show that this group of low-grade B-cell lymphomas occasionally may exhibit an atypical phenotype. Furthermore, in this study, the CD5+ MZBCLs were clinically localized at presentation, in contrast to most other reported cases, which have had dissemination to bone marrow or peripheral blood.

Both duration and degree of hypercalcemia influence the reduced parathyroid hormone response to hypocalcemia after hypercalcemia.

The stimulation of parathyroid hormone (PTH) secretion by hypocalcemia is reduced when hypocalcemia is preceded by hypercalcemia. The present study investigates whether the duration and degree of hypercalcemia influence the reduced PTH response to hypocalcemia after hypercalcemia. In addition, the implication of the arachidonic acid (AA) signaling pathway in this effect is evaluated. The PTH response to hypocalcemia has been studied in a control group and in four groups of rabbits subjected to hypercalcemia for different periods of time (between 30 and 120 min) and at two levels of hypercalcemia (1 x 9 and 2 x 1 mM). AA levels have been measured in parathyroid glands from rabbits subjected to hyper- and hypocalcemia. When compared with controls, rabbits that had been hypercalcemic (2 x 1 mM) for 2 h showed a markedly attenuated PTH response to hypocalcemia (50% of normal PTHmax), rabbits that had been in hypercalcemia (2 x 1 mM) for 75 min had an intermediate PTH response to hypocalcemia (70% of normal PTHmax) and rabbits that had been subjected to either 30 min hypercalcemia of 2 x 1 mM or 120 min hypercalcemia of 1 x 9 mM had a normal PTH response to hypocalcemia. AA levels increased in hypercalcemia and decreased in hypocalcemia; however, no differences were observed at either calcium level in short-time (30 min) versus long-time (120 min) hypercalcemia. In conclusion, the attenuated PTH response to hypocalcemia after hypercalcemia is dependent on both the period of time that the parathyroid glands have been exposed to hypercalcemia and the degree of hypercalcemia. In addition, this reduced PTH response does not seem to be related to changes in the AA signaling pathway.