scholarly journals Evolution of Chronic Pain in Sickle Cell Disease

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1297-1297 ◽  
Author(s):  
Michael Pope ◽  
Camila Albo ◽  
Kyle Michael Kidwell ◽  
Hongyan Xu ◽  
Latanya Bowman ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Substance P ◽  
Sickle Cell ◽  
Cell Activation ◽  
Statistical Significance ◽  
Age Groups ◽  
Mast Cell Activation ◽  
Age Group ◽  
Opioid Use ◽  
Age Dependent

Abstract Vaso-occlusive episodes (VOE), are the most common cause of health care encounters and are considered to be a hallmark of sickle cell disease (SCD). It has been increasingly recognized that many SCD patients, especially adults experience daily chronic pain (PiSCES study). While adolescents and young adults experience mostly acute episodic nociceptive pain, a significant number of adults develop chronic neuropathic and centralized pain. Although the precise mechanisms underlying this age-related transition in pain phenotype are not clearly understood, some factors that contribute to this phenomenon include chronic inflammation, organ damage and opioid induced hyperalgesia. Vincent et al (Blood, 2013) showed that mast cell activation is an important contributor to neurogenic inflammation and chronic pain in a mouse model of SCD. In an observational translational study, we recently reported that SCD patients with chronic pain (those who report pain >50% of time) were older and had higher levels of mast cell activation markers, plasma tryptase and substance P, compared to SCD patients who did not have chronic pain (Kuei et al, Blood, 2015). We report here the results of a prospective study of SCD patients (SS and Sβ0 thal) in different age groups. We tested the hypotheses that i) evolution to chronic pain is an age-dependent phenomenon, with higher frequency in older subjects, and ii) serum tryptase and substance P levels can be used as markers of chronic pain. A total of 36 subjects with SCD from the patient population of Pediatric and Adult sickle cell clinics of the MCG Sickle Cell Center were enrolled; these included 6 subjects aged 15-19, and 10 adults each in the age groups of 20-29, 30-39, and ≥40, respectively. Informed consent was obtained. Information on the frequency of VOEs (hospitalizations and ED visits) in the last 2 years, presence of chronic pain, hydroxyurea (HU) exposure, opioid usage as morphine equivalents within the past year, CBC, retics, CMP and % Hb F were collected. Quantitative sensory testing (QST) was performed using three different modalities: pressure pain sensitivity using a hand held computerized algometer AlgoMed, Medoc, Israel); heat and cold sensitivity (Q-Sense, Medoc, Israel); and Von Frey monofilament for neuropathic pain. Plasma tryptase and substance P levels were assayed by ELISA using kits from Biomatik inc, and Enzo Life Sciences, respectively. The results (lab tests, QST, VOEs, HU usage, plasma tryptase and substance P levels) are summarized in Table 1. Overall, there was an age dependent increase in the frequency of subjects with chronic pain; while 16.7% of patients in the 15-19 age group experienced chronic pain, this increased to 60.0% in the 20-29 year olds, and to 63.6% in those 30-39 years of age as shown in Figure 1. Among patients ≥40 years, 40.0% reported experiencing chronic pain. VOE frequency (average of last 2 years) was highest in the 20-29 age group (11.0/year) followed by 5.6 in the 30-39 age group. It was 2.57/year among 15-19 year olds, and 2.70/year in patients ≥40 years (p=0.004). Although Hb F and MCV was highest among ≥40 group (20.4%, and 112.1 fl, respectively), this did not reach statistical significance. As seen in the Table, BUN and creatinine showed a significant age dependent increase indicative of progressive organ damage. There was no significant difference between different age groups in other laboratory parameters, QST results, and plasma tryptase and substance P levels. The significant finding of this study is the higher frequency of VOEs in the 20-39 age group, compared to adolescents and patients 40 years and above. Although this finding is paralleled by a trend in opioid use, and frequency of chronic pain, these did not reach statistical significance in this relatively small group. The other interesting observation is the relatively mild course of disease in those ≥40 years of age (lower frequency of chronic pain, lower opioid use, lower VOE frequency). This seemingly paradoxical finding can be explained either by a survival advantage of the relatively mild patients, or a better adherence to HU, as suggested by higher MCV and Hb F in this group. The transition from adolescence to young adulthood is associated with a higher morbidity in SCD. Factors contributing to this phenomenon should be studied in a larger cohort. Disclosures Kutlar: Novartis Pharmaceuticals: Research Funding.

scholarly journals Characteristics and Potential Biomarkers of Adult Sickle Cell Patients with Chronic Pain

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 857-857 ◽  
Author(s):  
Camila Albo ◽  
Sanjiv Kumar ◽  
Michael Pope ◽  
Kyle Michael Kidwell ◽  
Niren Patel ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Mast Cell ◽  
Substance P ◽  
Cell Activation ◽  
Mast Cell Activation ◽  
Opioid Use ◽  
The Past ◽  
Chronic Pain Patients ◽  
Age Dependent ◽  
Pain Patients

Abstract A paradigm shift is occurring in our understanding of pain in patients with sickle cell disease (SCD). Vaso-occlusive episodes (VOEs) are crises of acute nociceptive pain, and have long been recognized as a hallmark of SCD (Brandow et al., 2017). While patients with SCD are traditionally considered to be at "steady state" and pain free between VOEs, recent studies have shown that a significant number of adults with SCD (~30%) experience daily chronic pain (>50% of the time in the past 6 months) (Smith et al., 2008). Although the precise mechanisms underlying this evolution from acute episodic to chronic pain are not well known, some contributing factors include age, chronic inflammation, organ damage, and opioid induced hyperalgesia (Stoicea et al., 2015; Rees et al., 2010). A recent study in a mouse model of SCD showed that mast cell activation was an important contributor to neurogenic inflammation and chronic pain (Vincent et al., 2013). We previously reported that SCD patients with chronic pain were older and had higher levels of mast cell activation markers, plasma tryptase and substance P, compared to those without chronic pain (Kuei et al., 2015). Recently, nerve growth factor (NGF) has been implicated in pathogenesis of some chronic pain syndromes (osteoarthritis), and clinical trials with anti-NGF monoclonal antibodies have been shown to result in superior pain control compared to placebo, opioids and NSAIDs. Here we report the results of our extended study of the evolution of chronic pain in SCD. A total of 72 subjects (age 15-66) were enrolled: 10 in the 15-19 age group, 19 in 20-29, 21 in 30-39, and 22 in ≥ 40. Patients transfused within the past 3 months and those who had an ED visit or hospitalization within the past 2 weeks were excluded. Information on the frequency of VOEs, presence or absence of chronic pain, HU therapy, opioid use (as mg morphine equivalents within the past 6 months), other medications and routine laboratory data (CBC, retics, chemistry panel, HbF) were collected. 4 mL of EDTA blood was collected at steady state and the plasma was separated by centrifugation and kept at -80 C. Plasma tryptase, substance P, and NGF levels were assayed by ELISA using kits from Biomatik inc (catalog# EKU07922), Enzo Life Sciences (catalog# ADI-900-018), and R&D Systems (catalog# DY256), respectively. Pressure pain threshold (PPTh) was measured using a hand-held digital algometer (AlgoMed, Medoc, Israel) four times at each of the following anatomic muscle groups on the left side of the body and then averaged for analysis: masseter, trapezius, and ulna in this consecutive order. Cutaneous mechanical pain was assessed using a Von Frey monofilament on the back of the subject's left hand. A baseline of one stimulus and then two separate series of 10 repeated stimuli each were conducted. The subject was asked to rate the pain on a scale of 0 to 10 (MFB, MF1 and MF2). Overall, 34 patients had chronic pain and 38 did not; there was an age dependent increase in the frequency of chronic pain, VOE frequency, opioid use and Von Frey MF values. Similarly, QST showed significantly lower pressure pain thresholds in subjects with chronic pain at ulna and trapezius (p=0.026 and 0.024 respectively). As expected, opioid use (daily morphine equivalents) was significantly higher in the chronic pain patients (52.8 mg vs 6.94 mg, p=0.009), suggesting a correlation between opioid use and hyperalgesia. Tryptase and substance P levels were higher in chronic pain patients, though the difference did not reach statistical significance. NGF levels were significantly higher in the chronic pain group (1126 pg/ml vs 473 pg/ml, p=0.051). Our results confirm previous observations that there is an age dependent increase in the proportion of patients with chronic pain (Table 1, Fig. 1-3). The trend towards higher levels of tryptase and substance P is in support of mast cell activation and neurogenic inflammation as a contributing factor to chronic pain (Vincent et al., 2013). To our knowledge, this is the first study of NGF as a possible contributing factor to chronic pain in SCD. If confirmed in larger multi-center studies, these observations could provide a rationale for novel interventions for chronic pain in SCD, via inhibition of mast cell activation/c-kit (tyrosine kinase inhibitors) or via repurposing of existing anti-NGF monoclonal antibodies as an alternative to opioids, whose inefficacy in chronic pain is well documented. Disclosures Kutlar: Novartis: Consultancy, Honoraria, Other: Personal fees, Research Funding; Bluebird Bio: Other: DSMB Member; Sancilio: Other: DSMB Chair.

Characteristics and Potential Biomarkers for Chronic Pain in Patients with Sickle Cell Disease

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 986-986 ◽  
Author(s):  
Nina Kuei ◽  
Niren Patel ◽  
Hongyan Xu ◽  
Leigh Wells ◽  
Latanya Bowman ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Mast Cell ◽  
Sickle Cell Disease ◽  
Substance P ◽  
Cell Activation ◽  
Neurogenic Inflammation ◽  
Mast Cell Activation ◽  
Cell Disease ◽  
Opioid Use ◽  
Pressure Pain

Abstract Vaso-occlusive episodes (VOE) or pain crises are a hallmark of sickle cell disease (SCD), with increasing recognition that a significant portion of SCD patients develop chronic pain. In the landmark PiSCES study (Smith et al), patients reported pain on 55% days, with ~30% reporting pain on >90% days. Thus, the episodic, nociceptive pain (VOE) in younger patients, evolves into a chronic pain syndrome, with neuropathic and centralized components in some adults. Kutlar et al (Blood, 2014), reported on the association of different pain related phenotypes (pain diaries, frequency of hospitalizations/ED visits, pressure pain threshold) with polymorphisms in candidate genes in 167 SCD patients, providing evidence that multiple signaling pathways and mechanisms are likely involved. In this study, 12 SCD subjects with "chronic pain", defined by reported pain >50% of days in pain diaries collected over 6 months, were enrolled (SCD-CP). 17 SCD patients who did not have chronic pain (SCD-NCP), and 9 non-SCD African-Americans (C) were enrolled as controls. Informed consent was obtained. Age, gender, Hb F levels, HU usage, and pressure pain algometer readings were recorded from SCD subjects. 8 ml of blood (EDTA) was collected from subjects at "steady state" and from normal controls. Plasma was separated and kept at -80 C until the assay. Plasma tryptase and Substance P levels were assayed by ELISA using kits from Biomatik, Inc. (catalog # EKU07922) and Enzo Life Sciences (Catalog #ADI-900-018), respectively. SCD-CP patients were significantly older than SCD-NCP: mean age 41 vs 32.2 (p=0.033). The pressure pain algometer readings did not differ significantly between SCD-CP and SCD-NCP at three sites (trapezius, ulna, masseter, p= 0.67-0.74). There were 12/17 patients on HU (70.6%) among SCD-NCP, and 6/12 (50%) among SCD-CP (p=0.435). Similarly, Hb F levels were not significantly different (14.7% in SCD-CP, vs 11.7% in SCD-NCP, p=0.446). Opioid use (average morphine equivalent as mg/day) was significantly higher in the chronic pain group (11.45 mg/day, vs 2.92 mg/day, p=0.015). Plasma tryptase and substance-P levels are shown in the table: Table 1. Tryptase (pg/ml) Substance-P (pg/ml) SCD-CP 1388.6 ±519.8 7221.1±7742.7 SCD-NCP 1023.64±221.04 5983.1±3473.0 Control 768.9±416.16 3939.7±1350.1 The difference in substance-P levels did not reach significance across groups by ANOVA (p=0.337) or in pairwise comparison between groups. However, tryptase levels were significantly different across groups by ANOVA (p=0.00615). Pairwise comparisons between two groups showed that tryptase levels were significantly different between SCD-CP and controls (p=0.0053). These results highlight characteristics of SCD patients with chronic pain: they are older, have a higher use of opioids, and have significantly higher tryptase levels. These observations support previous findings that age is a significant factor in transition to chronic pain in SCD. Higher dose of opioid use in SCD-CP could result from dose escalation to control pain; conversely, it could be argued that higher opioid use itself could be a factor in development of chronic pain through opioid-induced hyperalgesia. To our knowledge, this is the first study of plasma tryptase levels in SCD, in relation to different pain phenotypes. Tryptase is released into plasma with degranulation of mast cells and leads to inflammation, anaphylaxis, urticaria, and neuropathic pain. It binds PAR2 (protease activated receptor 2), releasing inflammatory mediators and substance P, inducing neurogenic inflammation. Elevated tryptase levels are found in systemic mastocytosis, and the newly recognized Mast Cell Activation Syndrome (MCAS). Vincent et al (Blood, 2013) showed that mast cell activation played an important role in neurogenic inflammation and chronic pain in a mouse model of SCD. They also demonstrated that inhibition of mast cell activation, via c-kit knockout or with imatinib or cromolyn sodium improved neurogenic inflammation and chronic pain. Two recent case reports (Murphy et al, Stankovic et al) document significant improvement in pain in SCD patients who developed CML, during treatment with imatinib. These observations, and the findings of our pilot study, not only suggest a novel mechanism and biomarker for chronic pain in SCD, but also a potential therapeutic target by inhibition of mast cell activation via c-kit pathway, or stabilization with cromolyn. Disclosures No relevant conflicts of interest to declare.

scholarly journals Targeting pain at its source in sickle cell disease

2018 ◽  
Vol 315 (1) ◽  
pp. R104-R112 ◽  
Author(s):  
Kanika Gupta ◽  
Om Jahagirdar ◽  
Kalpna Gupta
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Genetic Disorder ◽  
Somatosensory System ◽  
Organ Damage ◽  
Mast Cell Activation ◽  
Cell Disease ◽  
Central Nervous Systems

Sickle cell disease (SCD) is a genetic disorder associated with hemolytic anemia, end-organ damage, reduced survival, and pain. One of the unique features of SCD is recurrent and unpredictable episodes of acute pain due to vasoocclusive crisis requiring hospitalization. Additionally, patients with SCD often develop chronic persistent pain. Currently, sickle cell pain is treated with opioids, an approach limited by adverse effects. Because pain can start at infancy and continue throughout life, preventing the genesis of pain may be relatively better than treating the pain once it has been evoked. Therefore, we provide insights into the cellular and molecular mechanisms of sickle cell pain that contribute to the activation of the somatosensory system in the peripheral and central nervous systems. These mechanisms include mast cell activation and neurogenic inflammation, peripheral nociceptor sensitization, maladaptation of spinal signals, central sensitization, and modulation of neural circuits in the brain. In this review, we describe potential preventive/therapeutic targets and their targeting with novel pharmacologic and/or integrative approaches to ameliorate sickle cell pain.

scholarly journals Family history of early onset acute lymphoblastic leukemia is suggesting genetic associations

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xinjun Li ◽  
Kristina Sundquist ◽  
Jan Sundquist ◽  
Asta Försti ◽  
Kari Hemminki
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Statistical Significance ◽  
Age Groups ◽  
Age Group ◽  
Genetic Associations ◽  
Sequencing Data ◽  
Cancer Data ◽  
Group 5 ◽  
Prostate Cancers

AbstractChildhood acute lymphoblastic leukemia (ALL) has an origin in the fetal period which may distinguish it from ALL diagnosed later in life. We wanted to test whether familial risks differ in ALL diagnosed in the very early childhood from ALL diagnosed later. The Swedish nation-wide family-cancer data were used until year 2016 to calculate standardized incidence ratios (SIRs) for familial risks in ALL in three diagnostic age-groups: 0–4, 5–34 and 35 + years. Among 1335 ALL patients diagnosed before age 5, familial risks were increased for esophageal (4.78), breast (1.42), prostate (1.40) and connective tissue (2.97) cancers and leukemia (2.51, ALL 7.81). In age-group 5–34 years, rectal (1.73) and endometrial (2.40) cancer, myeloma (2.25) and leukemia (2.00, ALL 4.60) reached statistical significance. In the oldest age-group, the only association was with Hodgkin lymphoma (3.42). Diagnostic ages of family members of ALL patients were significantly lower compared to these cancers in the population for breast, prostate and rectal cancers. The patterns of increased familial cancers suggest that BRCA2 mutations could contribute to associations of ALL with breast and prostate cancers, and mismatch gene PMS2 mutations with rectal and endometrial cancers. Future DNA sequencing data will be a test for these familial predictions.

scholarly journals The pediatric patient at a maxillofacial service: eye prosthesis

2006 ◽  
Vol 20 (3) ◽  
pp. 247-251 ◽  
Author(s):  
Beatriz Silva Câmara Mattos ◽  
Maria Cecília Montagna ◽  
Clemente da Silva Fernandes ◽  
Antonio Carlos Lorenz Sabóia
Keyword(s):  
Statistical Significance ◽  
Age Groups ◽  
Age Group ◽  
Significance Level ◽  
Gender And Age ◽  
Child Patient ◽  
Eye Prosthesis ◽  
School Of Dentistry ◽  
Prosthetic Eye ◽  
Orbital Region

Congenital absence or loss of the ocular globe during childhood causes psycho-social and cosmetic disorders and compromise the normal development of the orbital region. The literature relating to congenital or acquired etiology, due to trauma or disease, demonstrates the necessity of prevention and early detection in order to minimize the sequelae and disturbances in orbital growth. Installation of an eye prosthesis is essential to the rehabilitation process, so as to produce satisfactory development of the region. In order to characterize a profile of the child patient with this condition, a survey was carried out at the Prosthetic Eye sector, Out-patient Clinic, Discipline of Maxillofacial Prosthodontics, School of Dentistry, University of São Paulo (FOUSP), during the period from 1988 to 2003. The 124 (14.02%) patients within the age group of 0-13 years registered for ocular prosthesis were divided into a first group of 64 patients (51.62%) with 0-7 years, and a second group of 60 patients (48.38%) with 8-13 years. Fifty nine were girls and 65 were boys. No statistical significance was observed regarding the distribution of genders in the two analyzed age groups (p = 0.069). However, there was statistical significance at the level of 0.01 in relation to etiology, with higher prevalence of congenital and pathological disturbances in the younger group and traumatic occurrences in the older group. The etiology also presented variation according to the gender, at the significance level of 0.05, where girls presented three times less trauma than boys in the older age group. The necessity of prosthetic ocular repair was evenly distributed along the childhood period and the eye losses that required prosthetic treatment equally affected both genders. However, the etiology of eye loss varied according to the considered gender and age bracket.

Prevalence of non-pathogenic types of gastrointestinal protozoa in population in Slovakia and their potential importance in the aspect of public health

2018 ◽  
Vol 63 (4) ◽  
pp. 819-825 ◽  
Author(s):  
Adriána Dudlová ◽  
Pavol Jarčuška ◽  
Silvia Jurišová ◽  
Zuzana Vasilková ◽  
Vladimír Krčméry ◽  
...  
Keyword(s):  
Human Population ◽  
Statistical Significance ◽  
Age Groups ◽  
Gastrointestinal Symptoms ◽  
Developed Countries ◽  
Age Group ◽  
Potential Importance ◽  
Blastocystis Hominis ◽  
Factors Affecting ◽  
Total Prevalence

Abstract The aim of the research was to determine the prevalence of non-pathogenic protozoa circulating in the human population of Slovakia. We particularly focused on the socially deprived areas with poor sanitation conditions, as they are one of the factors affecting the transmission of these infections. Within this study, 2760 people were coprologically screened for the presence of protozoan cysts. The analyzed group comprised 1173 men and 1587 women from different regions of Slovakia. The total prevalence (2.03%) of non-pathogenic protozoa species was determined. The prevalence of Entamoeba coli was 0.80%, the prevalence of Endolimax nana 0.58%, and the prevalence of Blastocystis hominis was 0.65%. The presence of non-pathogenic protozoa was more frequent in women than that in men, in all age groups. The highest incidence of Entamoeba coli was found in children aged one month – seven years (0.79%), the lowest in the age group of 19–88 years (0.66%). Endolimax nana was most frequent in 8–18 year-olds (0.95%), where the statistical significance was found (p<0.05). The prevalence of Blastocystis hominis by the age group ranged from 0.39 to 0.95%. We did not find any statistical significance (p>0.05) for Entamoeba coli, and similarly for Blastocystis hominis associated with the sex and age. Although the circulation of non-pathogenic protozoa in the human population is far from being limited to the developing countries, their occurrence is also frequent in the population of developed countries. Despite their controversial pathogenicity, they should not be neglected, particularly in the patients with gastrointestinal symptoms.

Age-related prescription medication utilization for the management of sickle cell disease among Texas Medicaid patients

2021 ◽  
Vol 17 (4) ◽  
pp. 301-310
Author(s):  
Nidhi Shukla, MS, MBA ◽  
Jamie C. Barner, PhD, FAACP, FAPhA ◽  
Kenneth A. Lawson, PhD, FAPhA ◽  
Karen L. Rascati, PhD
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Age Groups ◽  
Dual Therapy ◽  
Cell Disease ◽  
Opioid Use ◽  
Medication Utilization ◽  
Age Related ◽  
Nonopioid Analgesics ◽  
Chi Square Analysis

Introduction: Sickle cell disease (SCD) is associated with recurrent complications and healthcare burden. Although SCD management guidelines differ based on age groups, little is known regarding actual utilization of preventative (hydroxyurea) and palliative therapies (opioid and nonopioid analgesics) to manage complications. This study assessed whether there were age-related differences in SCD index therapy type and SCD-related medication utilization.Design and patients: Texas Medicaid prescription claims from September 1, 2011 to August 31, 2016 were retrospectively analyzed for SCD patients aged 2-63 years who received one or more SCD-related medications (hydroxyurea, opioid, or nonopioid analgesics).Outcome measures: The primary outcomes were SCD index drug type and medication utilization: hydroxyurea adherence, and days’ supply of opioid, and nonopioid analgesics. Chi-square, analysis of variance, and Kruskal–Wallis tests were used.Results: Index therapy percentages for included patients (N = 2,339) were the following: opioids (45.7 percent), nonopioids (36.6 percent), dual therapy-opioids and nonopioids (11.2 percent), and hydroxyurea (6.5 percent), and they differed by age-groups (χ2 = 243.0, p 0.0001). Hydroxyurea as index therapy was higher among children (2-12:9.1 percent) compared to adults (26-40:3.7 percent; 41-63:2.9 percent). Opioids as index therapy were higher among adults (18-25:48.0 percent; 26-40:54.9 percent; 41-63:65.2 percent) compared to children (2-12:36.6 percent). Mean hydroxyurea adherence was higher (p 0.0001) for younger ages, and opioid days’ supply was higher for older ages.Conclusions: Texas Medicaid SCD patients had low hydroxyurea utilization and adherence across all age groups. Interventions to increase the use of hydroxyurea and newer preventative therapies could result in better management of SCDrelated complications and reduce the frequency of pain crises, which may reduce the need for opioid use.

scholarly journals Impact of skull base development on endonasal endoscopic surgical corridors

2014 ◽  
Vol 13 (2) ◽  
pp. 155-169 ◽  
Author(s):  
Matei A. Banu ◽  
Amancio Guerrero-Maldonado ◽  
Heather J. McCrea ◽  
Victor Garcia-Navarro ◽  
Mark M. Souweidane ◽  
...  
Keyword(s):  
Skull Base ◽  
Developmental Process ◽  
Normal Population ◽  
Age Groups ◽  
Age Group ◽  
Restriction Sites ◽  
Age Dependent ◽  
Skull Base Lesions ◽  
The Impact ◽  
Anatomical Parameters

Object Scarce morphometric data exist on the developing skull base as a corridor for endonasal endoscopic approaches (EEAs). Furthermore, the impact of skull base lesions on its development has not been assessed. The authors describe a novel set of anatomical parameters characterizing the developmental process as well as the utility of these parameters in preoperative planning and a feasibility assessment of EEAs for neurosurgical treatment of skull base lesions in children. Methods Based on specific MRI sequences in 107 pediatric patients (2–16 years of age) without skull base lesions (referred to here as the normal population), 3 sets of anatomical parameters were analyzed according to age group and sex: drilling distance, restriction sites, and working distance parameters. A separate set of patients undergoing EEAs was analyzed in similar fashion to address the impact of skull base lesions on the developmental process. Results The volume of the sphenoid sinus significantly increases with age, reaching 6866.4 mm3 in the 14–16 years age group, and directly correlates with the pneumatization type (r = 0.533, p = 0.0001). The pneumatization process progresses slowly in a temporal-posterior direction, as demonstrated by the growth trend of the sellar width (r = 0.428, p = 0.0001). Nasal restriction sites do not change significantly with age, with little impact on EEAs. The intercarotid distance is significantly different only in the extreme age groups (3.9 mm, p = 0.038), and has an important impact on the transsphenoidal angle and the intracranial dissection limits (r = 0.443, p < 0.0001). The 14.9° transsphenoidal angle at 2–4 years has a 37.6% significant increase in the 11–13 years age group (p = 0.001) and is highly dependent on pneumatization type. Age-dependent differences between working parameters are mostly noted for the extreme age groups, such as the 8.6-mm increase in nare-vomer distance (p = 0.025). The nare-sellar distance is the only parameter with significant differences based on sex. Skull base lesions induce a high degree of variance in skull base measurements, delaying development and decreasing parameter values. Skull base parameters are interdependent. Nare-sellar distance can be used to assess global skull base development because it highly correlates with the intercarotid distance in both the normal population and in patients harboring skull base lesions. Conclusions Skull base development is a slow, gradual, age-dependent, sex-independent process significantly altering endonasal endoscopic corridors. Preoperative MRI measurements of the pediatric skull base are thus a useful adjunct in choosing the appropriate corridor and in assessing working angles and limits during dissection or reparative surgery. Skull base lesions can significantly impact normal skull base development and age-dependent growth patterns.

Tachykinin involvement in cutaneous anaphylaxis in the guinea pig

1988 ◽  
Vol 66 (11) ◽  
pp. 1361-1367 ◽  
Author(s):  
R. Hamel ◽  
A. W. Ford-Hutchinson ◽  
C. Blazejczak ◽  
A. Van Den Brekel
Keyword(s):  
Substance P ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Cell Activation ◽  
Significant Inhibition ◽  
Mast Cell Activation ◽  
Pig Skin ◽  
Permeability Changes ◽  
Tachykinin Antagonists ◽  
Flow Changes

Permeability changes in the guinea-pig skin following intradermal (i.d.) injection of tachykinin agonists or antigen were monitored through the extravasation of 99mTc-labelled human serum albumin and blood flow changes through the accumulation of 51Cr-labelled microspheres. A variety of synthetic and natural tachykinins, including substance P and neurokinins A and B, were shown to be potent inducers of permeability changes. Neurokinins A and B, but not substance P, were also shown to be apparent vasoconstrictor agents. Permeability responses in sensitized guinea pigs to i.d. injection of antigen and substance P, but not histamine, were abolished by pretreatment with the tachykinin antagonists [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P and [D-Pro2, D-Trp7,9]-substance P. Interpretation of such results was complicated by the fact that such antagonists may in themselves induce mast cell activation. Depletion of substance P containing neurons by pretreatment of guinea pigs with capsaicin also produced significant inhibition of antigen-induced permeability changes. These results indicate a possible role for tachykinins, such as substance P, in cutaneous anaphylaxis in the guinea pig.

Sign in / Sign up

Export Citation Format

Share Document