Osteonecrosis of the jaw in a Crohn’s disease patient following a course of Bisphosphonate and Adalimumab therapy: a case report

Background

Cyclooxygenase-2 (COX-2, PTGS2) is an enzyme involved in the synthesis of prostaglandins and thromboxanes, which are regulators of biologic processes such as inflammation, cell proliferation and angiogenesis. COX-2 over-expression was reported in many (pre) malignant tissues, but data strongly vary and seem to depend on the methodology used.

Methods

Normal colorectal mucosa and paired cancerous tissue from 60 patients with colorectal cancer was investigated for the levels of COX-2 mRNA by real-time quantitative Polymerase Chain Reaction (qPCR). COX-2 levels were expressed relative to either: tissue weight or levels of the housekeeping genes beta-2 microglobulin (B2M) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH).

Results

COX-2 mRNA levels, normalized with respect to tissue weight or mRNA levels of the housekeeping genes B2M or GAPDH, were over-expressed in 80%, 70% and 40% of the colorectal tumor tissues, as compared to the paired adjacent normal colorectal mucosa samples, respectively. Highest mRNA COX-2 ratios tumor/normal were measured when expressed per mg tissue (mean ratio 21.6). When normalized with respect to the housekeeping genes B2M or GAPDH, mean tumor/normal ratios were 16.1 and 7.5, respectively.

Conclusion

Expression of COX-2 mRNA levels per mg tissue is most simple in comparison to normalization with respect to the housekeeping genes B2M or GAPDH. Levels of COX-2 mRNA are found over-expressed in almost 80% of the colorectal tumors, compared to paired adjacent normal colorectal mucosa, suggesting a role of COX-2 as a potential biomarker for cancer risk, whereas inhibitors of COX-2 could be of value in chemoprevention of colon cancer.     

Brucellosis among Hospitalized Febrile Patients in Northern Tanzania

Acute and convalescent serum samples were collected from febrile inpatients identified at two hospitals in Moshi, Tanzania. Confirmed brucellosis was defined as a positive blood culture or a ≥ 4-fold increase in microagglutination test titer, and probable brucellosis was defined as a single reciprocal titer ≥ 160. Among 870 participants enrolled in the study, 455 (52.3%) had paired sera available. Of these, 16 (3.5%) met criteria for confirmed brucellosis. Of 830 participants with ≥ 1 serum sample, 4 (0.5%) met criteria for probable brucellosis. Brucellosis was associated with increased median age (P = 0.024), leukopenia (odds ratio [OR] 7.8, P = 0.005), thrombocytopenia (OR 3.9, P = 0.018), and evidence of other zoonoses (OR 3.2, P = 0.026). Brucellosis was never diagnosed clinically, and although all participants with brucellosis received antibacterials or antimalarials in the hospital, no participant received standard brucellosis treatment. Brucellosis is an underdiagnosed and untreated cause of febrile disease among hospitalized adult and pediatric patients in northern Tanzania.     

Characterization of the acute pulse transit time response to obstructive apneas and hypopneas in preschool children with sleep-disordered breathing

Background

Surges in heart rate (HR) and blood pressure (BP) at apnea termination contribute to the hypertension seen in obstructive sleep apnea (OSA). Because childhood OSA prevalence peaks in the preschool years, we aimed to characterize the cardiovascular response to obstructive events in preschool-aged children.

Methods

Clinically referred children aged 3–5 years were grouped by obstructive apnea–hypopnea index (OAHI) into the following: primary snoring (PS) (OAHI ? 1 event/h [n = 21]), mild OSA (OAHI > 1– ? 5 [n = 32]), and moderate to severe (MS) OSA (OAHI > 5 [n = 28]). Beat-to-beat pulse transit time (PTT), an inverse continuous indicator of BP changes, and HR were averaged during the two halves (early and late) and during the peak after (post) each obstructive event and were expressed as percentage change from late- to post-event.

Results

We analyzed 422 events consisting of 55 apneas and 367 hypopneas. A significant post-event increase in HR and fall in PTT occurred in all severity groups (P < .05 for all). A greater response was associated with OSA, nonrapid eye movement sleep (NREM), cortical arousal, hypopneas, and oxygen desaturation (P < .05 for all).

Conclusions

Obstructive events elicit acute cardiovascular changes in preschool children. Such circulatory perturbations have been implicated in the development of hypertension, and our findings complement previous studies to suggest a cumulative impact of snoring on the cardiovascular system from childhood into adulthood.     

Bone Mass and Strength in School‐Age Children Exhibit Sexual Dimorphism Related to Differences in Lean Mass: The Generation R Study

Bone strength, a key determinant of fracture risk, has been shown to display clear sexual dimorphism after puberty. We sought to determine whether sex differences in bone mass and hip bone geometry as an index of strength exist in school‐age prepubertal children and the degree to which the differences are independent of body size and lean mass. We studied 3514 children whose whole‐body and hip scans were measured using the same densitometer (GE‐Lunar iDXA) at a mean age of 6.2 years. Hip dual‐energy X‐ray absorptiometry (DXA) scans underwent hip structural analyses (HSA) with derivation of bone strength indices. Sex differences in these parameters were assessed by regression models adjusted for age, height, ethnicity, weight, and lean mass fraction (LMF). Whole‐body bone mineral density (BMD) and bone mineral content (BMC) levels were 1.3% and 4.3% higher in girls after adjustment by LMF. Independent of LMF, boys had 1.5% shorter femurs, 1.9% and 2.2% narrower shaft and femoral neck with 1.6% to 3.4% thicker cortices than girls. Consequent with this geometry configuration, girls observed 6.6% higher stresses in the medial femoral neck than boys. When considering LMF, the sexual differences on the derived bone strength indices were attenuated, suggesting that differences in muscle loads may reflect an innate disadvantage in bone strength in girls, as consequence of their lower muscular acquisition. In summary, we show that bone sexual dimorphism is already present at 6 years of age, with boys having stronger bones than girls, the relation of which is influenced by body composition and likely attributable to differential adaptation to mechanical loading. Our results support the view that early life interventions (ie, increased physical activity) targeted during the pre‐ and peripubertal stages may be of high importance, particularly in girls, because before puberty onset, muscle mass is strongly associated with bone density and geometry in children. © 2015 American Society for Bone and Mineral Research.     

Analgesic action of gabapentin on chronic pain in the masticatory muscles: a randomized controlled trial

Chronic masticatory myalgia (CMM) can be defined as constant pain in the masticatory muscles for more than 6 months and is influenced by the central nervous system. The antiepileptic agent gabapentin acts centrally and is used for managing different types of chronic pain conditions. The objective of this study was to evaluate the analgesic action of gabapentin on CMM. In this 12-week randomized controlled clinical trial 50 patients were randomly allocated into two study groups: 25 received gabapentin and 25 received placebo. The outcome measures utilized were pain reported on a VAS (VAS-pain), Palpation Index (PI) and impact of CMM on daily functioning reported on a VAS (VAS-function). Thirty-six patients completed the study. Gabapentin showed to be clinically and statistically superior to placebo in reducing pain reported by patients (gabapentin=51.04%; placebo=24.30%; P=0.037), masticatory muscle hyperalgesia (gabapentin=67.03%; placebo=14.37%; P=0.001) and impact of CMM on daily functioning (gabapentin=57.70%; placebo=16.92%; P=0.022). It can be concluded from this study that gabapentin is effective for the management of CMM.     

Detection of QTc interval prolongation using jacket telemetry in conscious non-human primates: comparison with implanted telemetry

Background and Purpose: During repeat-dose toxicity studies, ECGs are collected from chemically or physically-restrained animals over a short timeframe. This is problematic due to cardiovascular changes caused by manual restraint stress and anesthesia, and limited ECG sampling. These factors confound data interpretation, but may be overcome by using a non-invasive jacket-based ECG collection (JET). The current study investigated whether a jacketed external telemetry system could detect changes in cardiac intervals and heart rate in non-human primates (NHPs), previously implanted with a PCT transmitter.Experimental Approach: Twelve male cynomolgus monkeys were treated weekly with vehicle or sotalol (8, 16, 32 mg kg⁻¹) p.o. ECGs were collected continuously for 24 hours, following treatment, over 4 weeks. A satellite group of six NHPs was used for sotalol toxicokinetics.Key Results: Sotalol attained C_max values 1–3 hours after dosing, and exhibited dose-proportional exposure. In jacketed NHPs, sotalol dose-dependently increased QT/QTc intervals, prolonged PR interval, and reduced heart rate. Significant QTc prolongation of 27, 54 and 76 msec was detected by JET after 8, 16, and 32 mg kg⁻¹ sotalol, respectively, compared with time-matched vehicle-treated animals. Overall, JET-derived PR, QT, QTc intervals, QRS duration, and heart rate correlated well with those derived from PCT.Conclusions and Implications: The current findings clearly support the use of JET to quantify cardiac interval and rhythm changes, capable of detecting QTc prolongation caused by sotalol. JET may be a preferred method compared to restraint-based ECG because high-density ECG sampling can be collected in unstressed conscious monkeys, over several weeks.