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BACKGROUND: This study compared perioperative outcomes as well as encounter and 90-day costs between patients undergoing traditional vs robotic total knee arthroplasty (rTKA). MATERIALS AND METHODS: A total of 430 TKAs (215 rTKAs, 215 traditional) were retrospectively reviewed. All rTKAs were performed with an imageless, second-generation robotic system. Cohorts were propensity score matched by age, sex, body mass index, and American Society of Anesthesiologists score. Perioperative data and 90-day complications were subsequently compared. Cox regression analyses evaluated survival to all-cause revisions. Univariable analyses compared total cost of care for the initial encounter and 90-day postoperative period. Multivariable regression analyses were then performed to evaluate associations with increased encounter and 90-day costs. RESULTS: Patients undergoing rTKA had a higher incidence of discharge home (86.5% vs 60.0%; P<.001). The rTKA cohort trended toward a lower incidence of 90-day emergency department visits, and there was a significantly lower percentage of 90-day readmissions (4.2% vs 13.5%; P=.001). Cox hazard ratio demonstrated no difference in survival to all-cause revisions (hazard ratio, 1.3; 95% CI, 0.5-3.7; P=.64). The cost of surgery was significantly higher in the rTKA cohort ($9292 vs $8392; P<.001); however, there was no difference in cost of encounter ($10,356.86 vs $10,396.44; P=.110) or at 90 days postoperatively ($11,103.89 vs $11,040.13; P=.739). rTKA did not have a significant association with increased cost at 90 days postoperatively (odds ratio, 0.96; 95% CI, 0.90-1.02; P=.180). CONCLUSION: rTKA had a higher intraoperative cost compared with traditional TKA. However, with increased home discharges and fewer 90-day readmissions, rTKA was not associated with increased cost at 90 days. [Orthopedics. 202x;4x(x):xx-xx.].
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BACKGROUND: The coronal plane alignment of the knee (CPAK) classification system divides coronal knee anatomy into 9 phenotypes, suggesting different soft tissue balancing is needed for optimal outcomes. We investigated the interplay between CPAK phenotypes and gap stress curves throughout the knee's range of motion, aiming to understand their impact on total knee arthroplasty balancing. METHODS: There were 1,112 total knee arthroplasty cases from 2 imageless robotic assisted navigation systems using posterior stabilized implants that were classified into CPAK phenotypes. Medial and lateral initial gap values were measured throughout the knee flexion-extension arc, gap curve morphologies were generated, and mediolateral (ML) gap balance was calculated for each phenotype. The most common phenotypes were included in this study, CPAK I to VI. RESULTS: Each phenotype exhibited a distinct gap curve morphology. Type I maintained the largest ML gap difference (-3.6 to -2.1), with the medial compartment tightest in extension. Type II showed relative laxity in the lateral compartment compared to the medial gap (-1.0 to -1.9), with the medial compartment tightening through flexion. Type III had a looser medial and tighter lateral compartment in extension that inverts to a tighter medial compartment in deep flexion (2.1 to -0.8), while Type IV showed a decreasing compartment difference with increased flexion (-3.7 to 0.6). Type V had fluctuating tightness (-0.6 to 1.8), and Type VI had the medial compartment tightening more with flexion (0.6 to 1.8). CONCLUSIONS: The distinct stress curves and ML gap behavior provide a "fingerprint" for each corresponding CPAK phenotype. Investigating these morphologies can help determine the best phenotype-specific treatments, including alignment strategy, implant selection, and gap balance, for optimal functional and patient outcomes.
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Background: Artificial intelligence (AI) in medicine has primarily focused on diagnosing and treating diseases and assisting in the development of academic scholarly work. This study aimed to evaluate a new use of AI in orthopaedics: content generation for professional medical education. Quality, accuracy, and time were compared between content created by ChatGPT and orthopaedic surgery clinical fellows. Methods: ChatGPT and 3 orthopaedic adult reconstruction fellows were tasked with creating educational summaries of 5 total joint arthroplasty-related topics. Responses were evaluated across 5 domains by 4 blinded reviewers from different institutions who are all current or former total joint arthroplasty fellowship directors or national arthroplasty board review course directors. Results: ChatGPT created better orthopaedic content than fellows when mean aggregate scores for all 5 topics and domains were compared (P ≤ .001). The only domain in which fellows outperformed ChatGPT was the integration of key points and references (P = .006). ChatGPT outperformed the fellows in response time, averaging 16.6 seconds vs the fellows' 94 minutes per prompt (P = .002). Conclusions: With its efficient and accurate content generation, the current findings underscore ChatGPT's potential as an adjunctive tool to enhance orthopaedic arthroplasty graduate medical education. Future studies are warranted to explore AI's role further and optimize its utility in augmenting the educational development of arthroplasty trainees.
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Aims: This study aims to assess the relationship between history of pseudotumour formation secondary to metal-on-metal (MoM) implants and periprosthetic joint infection (PJI) rate, as well as establish ESR and CRP thresholds that are suggestive of infection in these patients. We hypothesized that patients with a pseudotumour were at increased risk of infection. Methods: A total of 1,171 total hip arthroplasty (THA) patients with MoM articulations from August 2000 to March 2014 were retrospectively identified. Of those, 328 patients underwent metal artefact reduction sequence MRI and had minimum two years' clinical follow-up, and met our inclusion criteria. Data collected included demographic details, surgical indication, laterality, implants used, history of pseudotumour, and their corresponding preoperative ESR (mm/hr) and CRP (mg/dl) levels. Multivariate logistic regression modelling was used to evaluate PJI and history of pseudotumour, and receiver operating characteristic curves were created to assess the diagnostic capabilities of ESR and CRP to determine the presence of infection in patients undergoing revision surgery. Results: The rate of PJI for all identified MoM THAs was 3.5% (41/1,171), with a mean follow-up of 10.9 years (2.0 to 20.4). Of the patients included in the final cohort, 8.2% (27/328) had PJI, with a mean follow-up of 12.2 years (2.3 to 20.4). Among this cohort, 31.1% (102/328) had a history of pseudotumour. The rate of PJI in these patients was 14.7% (15/102), which was greater than those without pseudotumour, 5.3% (12/226) (p = 0.008). Additionally, logistic regression analysis showed an association between history of pseudotumour and PJI (odds ratio 4.36 (95% confidence interval 1.77 to 11.3); p = 0.002). Optimal diagnostic cutoffs for PJI in patients with history of pseudotumour versus those without were 33.1 mm/hr and 24.5 mm/hr for ESR and 7.37 mg/dl and 1.88 mg/dl for CRP, respectively. Conclusion: Patients with history of pseudotumour secondary to MoM THA had a higher likelihood of infection than those without. While suspicion of infection should be high for these patients, ESR and CRP cutoffs published by the European Bone and Joint Infection Society may not be appropriate for patients with a history of pseudotumour, as ESR and CRP levels suggestive of PJI are likely to be higher than for those without a pseudotumour. Additional investigation, such as aspiration, is highly recommended for these patients unless clinical suspicion and laboratory markers are low.
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Artroplastia de Reemplazo de Cadera , Granuloma de Células Plasmáticas , Prótesis de Cadera , Prótesis Articulares de Metal sobre Metal , Infecciones Relacionadas con Prótesis , Humanos , Artroplastia de Reemplazo de Cadera/efectos adversos , Masculino , Femenino , Granuloma de Células Plasmáticas/etiología , Persona de Mediana Edad , Infecciones Relacionadas con Prótesis/etiología , Estudios Retrospectivos , Anciano , Prótesis de Cadera/efectos adversos , Prótesis Articulares de Metal sobre Metal/efectos adversos , Adulto , Reoperación , Sedimentación Sanguínea , Anciano de 80 o más Años , Proteína C-Reactiva/análisis , Imagen por Resonancia Magnética , Estudios de Seguimiento , Factores de RiesgoRESUMEN
BACKGROUND: Opioid use after revision total hip arthroplasty (rTHA) has not been well characterized. The purpose of this study was to characterize preoperative, perioperative, and postoperative opioid use during rTHA. METHODS: Patients undergoing revision THA from 2010 to 2018 were screened for opioid use 3 months before revision surgery and tracked 24 months postoperatively. Patients were categorized as naïve or tolerant. Opioid prescriptions and average morphine milligram equivalents (MME) were compared between the two groups. RESULTS: One hundred twenty-four of 247 patients (50%) in the tolerant group averaged a preoperative MME of 23.7 mg/day. Postoperatively, tolerant patients received significantly higher daily MME at all time points, including at 3 months 31.4 versus 18.1 mg/day (P < 0.001), 6 months 19.9 versus 2.95 mg/day (P < 0.001), 12 months 14.3 versus 3.5 mg/day (P < 0.001), and 24 months 10.7 versus 2.17 mg/day (P < 0.001). Tolerant patients were more likely to have a prescription at 6 months (44% versus 22%), 12 months (41.4% versus 24%), and 24 months (38% versus 19.3%) (P < 0.001, P = 0.002, P < 0.001, respectively). DISCUSSION: Opioid-tolerant patients had higher postoperative MME requirements for longer recovery duration. Both groups reduced opioid use at 3 months and plateaued at 6 months. These findings can help the revision surgeon counsel patients and expectations.
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Analgésicos Opioides , Artroplastia de Reemplazo de Cadera , Dolor Postoperatorio , Reoperación , Humanos , Analgésicos Opioides/uso terapéutico , Masculino , Femenino , Dolor Postoperatorio/tratamiento farmacológico , Persona de Mediana Edad , Anciano , Tolerancia a Medicamentos , Estudios RetrospectivosRESUMEN
BACKGROUND: The clinical impact of the surgical approach in total hip arthroplasty (THA) has been widely reviewed. This study evaluated the total encounter and 90-day costs of THA for 2 surgical approaches (posterior [P] and direct anterior [DA]) in 1 tertiary health system. METHODS: This is a retrospective review of 2,101 THAs (1,092 P and 1,009 DA) by 4 surgeons (2 with the highest volume of DA and P, respectively) from 2017 to 2022 at 1 academic center. Demographics, comorbidities, operative time, length of hospital stay, 90-day hospital returns, and complications were compared. The total encounter cost and 90-day postoperative cost were itemized. Multivariable regression analyses evaluated associations with increased cost at each time point. RESULTS: The DA cohort had a higher median encounter cost ($8,348.66 versus 7,332.42, P < .01), resulting from higher intraoperative (P < .01) and radiology (P < .01) expenses. Regression analyses demonstrated the DA was independently associated with increased encounter costs (odds ratio 1.1; 95% confidence interval 1.1 to 1.1; P < .01). There was a higher incidence of 90-day emergency department visits in the DA cohort (16 versus 12%, P = .02), with a trend toward increased readmissions. There was no difference in 90-day reoperations. Median 90-day cost was higher in the DA cohort ($126.99 versus 0.00, P < .01), and regression analyses demonstrated the DA had an association with increased 90-day cost (odds ratio 2.2; 95% confidence interval 1.5 to 3.0; P < .01). CONCLUSIONS: Despite a younger patient population, the DA was independently associated with increased encounter and 90-day costs in a single academic hospital system. This study may underestimate the cost difference, as capital costs such as specialized tables were not analyzed.
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Artroplastia de Reemplazo de Cadera , Tiempo de Internación , Humanos , Artroplastia de Reemplazo de Cadera/economía , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Tiempo de Internación/economía , Tiempo de Internación/estadística & datos numéricos , Tempo Operativo , Complicaciones Posoperatorias/economía , Complicaciones Posoperatorias/epidemiología , Readmisión del Paciente/economía , Readmisión del Paciente/estadística & datos numéricos , AdultoRESUMEN
BACKGROUND: Valgus knee deformity is observed in nearly 10% of patients undergoing total knee arthroplasty (TKA). The degree of polyethylene constraint required to balance a valgus knee remains controversial, and historically, posterior-stabilized (PS) designs have been favored. This study evaluated the survivorship of TKA done in valgus knees based on implant design and specifically compared posterior-stabilized (PS) and ultracongruent (UC) liners. METHODS: A total of 549 primary TKAs performed on valgus knees by fellowship-trained arthroplasty surgeons from 2013 to 2019 were reviewed. Demographics, comorbidities, degrees of preoperative deformity, implants used, and all-cause revisions until final follow-up were recorded. Cox regression analyses evaluated survival to all-cause revision in each cohort. The mean follow-up was 4.9 years (range, 2 to 9). RESULTS: There were 403 UC liners compared to 146 PS liners. There was no difference in patient age (68 versus 67 years; P = .30), body mass index (30.9 versus 30.4; P = .36), or degree of deformity (8.6 versus 8.8 degrees; P = .75) between the cohorts. At final follow-up, there were 5 revisions in the PS cohort (3.4%) versus 11 revisions in the UC cohort (2.7%) (P = .90). The most common reason for revision in both cohorts was periprosthetic joint infection (4 PS; 8 UC). Multivariable regression analyses controlling for age, body mass index, Elixhauser comorbidity score, sex, and degree of deformity demonstrated UC polyethylene liners were not associated with revision (hazard ratio 0.76; 95% confidence interval [CI] 0.26 to 2.21; P = .62). There was no difference in eight-year survivorship to all-cause revision, including aseptic and septic failure. CONCLUSIONS: Alternative polyethylene liners from the historically utilized PS liners for TKA for valgus deformity did not reduce survivorship. With modern polyethylene designs, UC inserts can be utilized for this deformity without increasing the risk of failure.
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Artroplastia de Reemplazo de Rodilla , Prótesis de la Rodilla , Polietileno , Diseño de Prótesis , Falla de Prótesis , Reoperación , Humanos , Artroplastia de Reemplazo de Rodilla/instrumentación , Anciano , Masculino , Femenino , Persona de Mediana Edad , Reoperación/estadística & datos numéricos , Articulación de la Rodilla/cirugía , Estudios Retrospectivos , Anciano de 80 o más AñosRESUMEN
A young stray entire female domestic shorthair cat was presented with symmetrical forelimb extensor rigidity, neck hyperextension and hindlimb paraplegia, characteristic of Schiff-Sherrington phenomenon (SSP), within 30 min of a motor vehicle accident. Radiographic and post-mortem studies disclosed complete transection of the spinal cord from traumatic dorsocranial luxation of the second lumbar vertebra, displacement of the sacrum from the ilium, seventh lumbar and first caudal vertebrae and multiple pelvic fractures. Other causes of forelimb extensor rigidity and neck hyperextension such as decerebrate and decerebellate rigidity were excluded by a lack of neurological signs consistent with these entities and unremarkable findings on post-mortem examination of the cranial cavity and brain and histological examination of the cerebrum, brainstem and cerebellum. To the best of the author's knowledge, this is the first report of SSP in the cat outside the experimental arena of decerebrate or non-decerebrate preparations following post-brachial spinal cord transection/cold block.
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Enfermedades de los Gatos , Traumatismos de la Médula Espinal , Femenino , Gatos , Animales , Rigidez Muscular/veterinaria , Traumatismos de la Médula Espinal/diagnóstico por imagen , Traumatismos de la Médula Espinal/etiología , Traumatismos de la Médula Espinal/cirugía , Traumatismos de la Médula Espinal/veterinaria , Columna Vertebral , Enfermedades de los Gatos/diagnóstico por imagen , Enfermedades de los Gatos/cirugíaRESUMEN
Purpose Enhanced recovery protocols for total hip arthroplasty (THA), using opioid-sparing techniques have become widely used. Reports of novel additions to multimodal pain control regimens have been published, however, a paucity of literature exists on the use of intravenous dexmedetomidine. In this study, we analyzed our experience with intravenous dexmedetomidine and hypothesized that it would reduce postoperative opioid use. Secondary outcomes were also examined, including post-operative hypotension, hemoglobin, length of stay, and discharge disposition. Methods All patients who underwent primary THA at a single tertiary-level center between January 1, 2016, and September 1, 2019, underwent investigation. Diagnosis, surgical approach, anesthetic type, body mass index (BMI), and American Society of Anesthesiologists (ASA) score were recorded. Postoperative clinical measures were analyzed, adjusting for patient and surgical characteristics. Results Of the 599 patients included in the study, 218 patients received intravenous (IV) dexmedetomidine, at a mean dose of 44.9 mg during their operative event. Using a multivariate model, patients in the IV dexmedetomidine group were estimated to have received 24% elevated morphine milligram equivalent at postoperative day zero compared to those in the control group (p = 0.05). In addition, patients in the IV dexmedetomidine group who underwent spinal anesthesia had increased odds of hypotension 3.47 times that of the control [odds ratio (OR) 1.43-8.43, p=0.006]. Conclusions Surprisingly, we found no opioid-sparing effects with the use of IV dexmedetomidine. IV dexmedetomidine may be used cautiously as an anesthesia adjunct with spinal anesthesia in the setting of primary THA, as the experience at our institution illustrated increased odds of postoperative hypotension. Level of evidence This retrospective case-control study has a level of evidence III.
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CASE: Failure of the modular junction in revision total knee arthroplasty is a rare complication. We report a patient with late, atraumatic failure of a modern, modular revision femoral component, with preoperative elevation of serum cobalt and chromium levels. Retrieval analysis showed extensive chemical corrosion. CONCLUSION: Failure of a modern, modular femoral component may cause metal synovitis and elevated serum metal levels. Subtle radiographic changes and preoperative serum metal levels may identify this complication.
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Artroplastia de Reemplazo de Rodilla , Articulación de la Rodilla , Humanos , Corrosión , Metales/efectos adversos , IonesRESUMEN
INTRODUCTION: Single-stage revision arthroplasty for periprosthetic joint infection (PJI) may yield comparable infection-free survivorship with two-stage revision arthroplasty. It is unclear if the most common mode of failure of single-stage revision arthroplasty is infection or aseptic loosening. In this meta-analysis, we sought to (1) determine survivorship and (2) compare rates of different etiologies of failure of single-stage revision total hip arthroplasty (THA) and total knee arthroplasty (TKA). METHODS: Preferred Reporting Items for Systematic Review and Meta-analyses guidelines search was done using search terms for "single stage revision," "exchange arthroplasty," "periprosthetic infection," "PJI," and "single stage." Patient demographics such as age, body mass index, and mean follow-up time were recorded. Overall survivorship and rates of revision surgery were aggregated using a random-effects model. Comparison of septic and aseptic loosening rates was done by risk difference and associated 95% confidence interval (CI) calculation. RESULTS: Twenty-four studies were identified with 2,062 and 147 single-stage revision THA and TKA procedures performed between 1984 and 2019, respectively. The weighted mean follow-up and age were 69.8 months and 66.3 years, respectively, with 55% men overall. The all-cause revision surgery rate was 11.1% and 11.8% for THA and TKA, respectively. The revision surgery rate secondary to infection and aseptic loosening and associated 95% CI for the risk difference for THA and TKA was 5.5% and 3.3% (-1.7% to 5.0%), and 3% and 8.8% (-11.4% to 2.3%), respectively. Revision surgeries due to instability and fracture combined and mortality rate were both less than 3%. DISCUSSION: Single-stage revision THA and TKA for PJI demonstrated overall high rates of survivorship, low mortality, and revision surgeries secondary to infection and aseptic loosening to be equivalent. Aseptic loosening after single-stage revision TKA might be higher than in primary TKA. As implant survivorship from infection improves in PJI, surgeons should be aware of aseptic loosening as an equally common mode of failure.
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Artritis Infecciosa , Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Infecciones Relacionadas con Prótesis , Masculino , Humanos , Femenino , Infecciones Relacionadas con Prótesis/etiología , Infecciones Relacionadas con Prótesis/cirugía , Supervivencia , Falla de Prótesis , Artroplastia de Reemplazo de Rodilla/efectos adversos , Artroplastia de Reemplazo de Cadera/efectos adversos , Artritis Infecciosa/etiología , Artritis Infecciosa/cirugíaRESUMEN
INTRODUCTION: Controversy exists on the ideal type of fixation in total knee arthroplasty (TKA). Noncemented fixation has been theorized to improve patient outcomes and longevity of implantation without increased risk of aseptic loosening or radiolucent lines. We sought to compare (1) patient-reported outcomes, (2) survivorship, and (3) revision rates for all-cause and aseptic loosening in a noncemented tantalum total knee with its cemented counterpart. METHODS: Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines were searched using a combination of keywords "trabecular metal," "tantalum knee," "total knee arthroplasty," and "cementless trabecular." Patient demographics such as age, sex, and body mass index were collected. Outcomes such as Knee Society Scores (KSSs), revisions, and radiolucent lines were recorded for analysis. RESULTS: Four randomized controlled trials involving 507 patients with an average 5-year follow-up were eligible for meta-analysis. No differences were observed in any demographics such as age, sex, body mass index, nor preoperative KSS. Patients in the cemented cohort improved from preoperative KSS 46.4 to postoperative KSS 90.4 while the tantalum cohort improved from 46.4 to 89.3. No statistical difference was observed in postoperative KSS mean difference between groups. Six patients from the tantalum group underwent revision with one patient for aseptic loosening. Twelve patients from the cemented group underwent revision with four patients for aseptic loosening. No statistical difference was observed between rates of revision, aseptic loosening, or radiolucent line development. DISCUSSION: Patient-reported outcomes improved postoperatively in both groups. No differences were detected between the cemented and noncemented TKAs in patient-reported outcomes, revision rates, or radiolucent line development. Noncemented tantalum fixation seems equivalent to cemented TKA survivorship. Longer term follow-up of these randomized controlled trials may provide a clearer understanding whether a difference exists.
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Artroplastia de Reemplazo de Rodilla , Prótesis de la Rodilla , Humanos , Tantalio , Reoperación , Cementos para Huesos/uso terapéuticoRESUMEN
Hereditary myopathies are well documented in dogs, whereas hereditary dyserythropoietic anemias are rarely seen. The aim of this study was to further characterize the clinical and clinicopathological features of and to identify the causative genetic variant for a dyserythropoietic anemia and myopathy syndrome (DAMS) in English springer spaniel dogs (ESSPs). Twenty-six ESSPs, including five dogs with DAMS and two puppies that died perinatally, were studied. Progressive weakness, muscle atrophy-particularly of the temporal and pelvic muscles-trismus, dysphagia, and regurgitation due to megaesophagus were observed at all ages. Affected dogs had a non-regenerative, microcytic hypochromic anemia with metarubricytosis, target cells, and acanthocytes. Marked erythroid hyperplasia and dyserythropoiesis with non-orderly maturation of erythrocytes and inappropriate microcytic metarubricytosis were present. Muscle biopsies showed centralized nuclei, central pallor, lipocyte infiltrates, and fibrosis, which was consistent with centronuclear myopathy. The genome sequencing of two affected dogs was compared to 782 genomes of different canine breeds. A homozygous frameshift single-base deletion in EHBP1L1 was identified; this gene was not previously associated with DAMS. Pedigree analysis confirmed that the affected ESSPs were related. Variant genotyping showed appropriate complete segregation in the family, which was consistent with an autosomal recessive mode of inheritance. This study expands the known genotype-phenotype correlation of EHBP1L1 and the list of potential causative genes in dyserythropoietic anemias and myopathies in humans. EHBP1L1 deficiency was previously reported as perinatally lethal in humans and knockout mice. Our findings enable the genetic testing of ESSP dogs for early diagnosis and disease prevention through targeted breeding strategies.
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Anemia , Enfermedades de los Perros , Enfermedades Musculares , Animales , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/genética , Perros , Mutación del Sistema de Lectura/genética , Estudios de Asociación Genética , Humanos , Ratones , Enfermedades Musculares/genética , Enfermedades Musculares/patología , Enfermedades Musculares/veterinaria , SíndromeRESUMEN
Calcitriol has been shown to have multiple anti-prostate cancer effects both in vitro and in xenograft models, and associations between low levels of calcitriol and more aggressive forms of prostate cancer have been observed clinically. However, the concentrations of calcitriol required to have a substantive anti-cancer effect in vivo are toxic. In previous work, we had observed that the selective prolactin receptor modulator, S179D PRL, sensitized prostate cancer cells in vitro to physiological concentrations of calcitriol through an ability to increase expression of the vitamin D receptor. Here, we have investigated whether administration of S179D PRL would likewise sensitize androgen-insensitive human PC3 xenografts in vivo and do so without inducing tissue damage akin to hypervitaminosis D. Using low concentrations of both S179D PRL (250 ng/h) and calcitriol (up to 220 pg/h), we found no effect of each alone or in combination on the growth rate of tumors. However, there was increased central tumor death with their combination that was more than additive at 250 ng S179D PRL and 220 pg calcitriol per hour. Both S179D PRL and calcitriol alone were antiangiogenic, but their antiangiogenic effects were not additive. Also, both S179D PRL and calcitriol alone increased the number of apoptotic cells in tumor sections, but their combination reduced the number, suggesting more effective clearance of apoptotic cells. Histopathology of the livers and kidneys showed no changes consistent with hypervitaminosis D. We conclude that dual therapy holds promise as a means to harness the anti-tumor effects of well-tolerated doses of calcitriol.
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Congenital idiopathic megaoesophagus (CIM) is a rare, naturally occurring disorder of the dog that is characterised by deficient motility and dilatation of the oesophagus. Recent studies indicate that the vagal sensory system mediating reflexes induced by oesophageal distension is defective in, and may underlie the pathomechanism of this disorder. We sought to establish whether other distension sensitive vagal afferent systems were impaired in CIM, or whether the vagal afferent dysfunction was selective. Thus, we examined the Hering-Breuer lung inflation reflex (HBR), which is subserved by a contiguous and physiologically similar vagal afferent system, in five dogs with CIM in which oesophageal vagal afferent dysfunction had been demonstrated. At varying levels of lung inflation, we found the HBR to be normally graded and of normal strength in affected dogs and that this result was unlikely to be influenced by other factors known to alter the strength of the reflex. These observations provide evidence for an organ specific, selective vagal afferent dysfunction in dogs with CIM. It is possible that similar processes may be active in disorders of visceral organ systems subserved by vagal afferents in other species, including man.