A 1-year-old sexually intact male Korat cat was referred for ophthalmological consultation due to anisocoria. Mydriasis with external ophthalmoplegia and absence of pupillary light responses in the right eye and nasofacial hypalgesia were seen. Cavernous sinus syndrome (CSS) was suspected. Bilateral deformities of the jaw and phalangeal bones, severe spinal pain and abnormal conformation of the lumbar spine were also present. Radiographic examination revealed several mineralised masses in the appendicular and axial skeleton, indicative of multiple cartilaginous exostoses. For further investigation of the CSS-related neurological deficits, the cat underwent computed tomography (CT) examination of the skull. CT images revealed a non-vascularised, calcified, amorphous mass originating from the right lateral skull base and superimposing on the sella turcica. Based on the severity of diffuse lesions and owing to the extreme pain clinical signs, the cat was euthanased. A diffuse skeletal and intracranial osteochondromatosis was diagnosed histologically.

ABSTRACT

BACKGROUND:

Treprostinil is a stable prostacyclin analogue approved for the treatment of pulmonary arterial hypertension (PAH) as parenteral or inhaled therapy. Treprostinil diolamine is a sustained-release oral formulation of treprostinil that was studied to determine if it could provide a more convenient prostacyclin treatment option for PAH patients with less severe disease.

OBJECTIVE:

To evaluate the efficacy and safety of oral treprostinil in PAH patients receiving stable background endothelin receptor antagonist (ERA) and/or phosphodiesterase type 5 inhibitor (PDE-5I) therapy.

METHODS:

A 16-week, multicenter, double-blind, placebo-controlled study in 310 PAH patients comparing the twice daily administration of oral treprostinil (n=157) to placebo (n=153). The primary endpoint was change in 6-minute walk distance (6MWD) at week 16. Secondary efficacy endpoints included: World Health Organization functional class, Borg dyspnea score, dyspnea-fatigue index, signs and symptoms of PAH, and clinical worsening.

RESULTS:

One hundred thirty-two (84%) oral treprostinil and 138 (90%) placebo patients completed the study. The mean dose (±standard deviation) of oral treprostinil for completers at week 16 was 3.1 ± 1.9 mg BID. The Hodges-Lehmann placebo-corrected median difference in 6MWD at week 16 was 10.0 m (95% confidence interval: -2 to 22; P=0.089). There were no significant changes in secondary endpoints. The most common adverse events associated with oral treprostinil included headache (71%), diarrhea (55%), nausea (46%), flushing (35%), and jaw pain (25%).

CONCLUSIONS:

The addition of oral treprostinil to background ERA and/or PDE-5I therapy did not result in a statistically significant improvement in exercise capacity. Side effects were common but were tolerated by most subjects. CLINICAL TRIAL INFORMATION: A 16-Week, International, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study of the Efficacy and Safety of Oral UT-15C Sustained Release Tablets in Subjects With Pulmonary Arterial Hypertension (FREEDOM-C2); NCT00887978.

The aim of this study was to evaluate the efficacy of diode superpulsed low-level laser therapy (SLLLT) in reducing experimentally induced orthodontic pain. Overall, 120 subjects (23.01 ± 1.39 years) were enrolled for a clinical trial. Subjects were randomly assigned to upper (U, N = 60) or lower (L, N = 60) jaw groups. All subjects received 4 elastomeric separators mesial and distal to the upper (U group) or lower (L group) right first molar and bicuspids. Each subject of the U and L groups was randomly assigned to laser (Ul, N = 20 and Ll, N = 20), placebo (Up, N = 20 and Lp, N = 20) or control (Uc, N = 20 and Lc, N = 20) sub-groups. Subjects in laser groups received a single GaAs diode SLLLT application (910 nm, 160 mW, beam diameter of 8 mm, applied for 340 s) immediately after placing orthodontic separators. Placebo groups received a simulated SLLLT and controls did not receive any therapy. All participants compiled a survey on pain duration and a 100-mm visual analogue scale immediately after the separators placement and after 12, 24, 36, 48, 72, and 96 h. Pain intensity of laser groups was significantly lower compared to placebo and control groups (p = 0.0001). In the laser group, 70 % of subjects felt pain, while in the placebo and control groups all subjects felt pain (p = 0.0001). The end of pain occurred earlier in laser compared to placebo and control groups (p = 0.021). A single-diode SLLLT application appeared to be effective in reducing the intensity and duration of experimentally induced orthodontic pain and could be used in daily orthodontic practice.

AIM:

Patients with metastatic osteosarcoma (OS) have a poor outcome with conventional therapies. Zoledronic acid (ZA) is a third-generation bisphosphonate that reduces skeletal-related events in many adult cancers, and pre-clinical data suggest a possible benefit in OS. This study assessed the maximum tolerated dose (MTD) and the feasibility of ZA when combined with chemotherapy in patients with metastatic OS.

PATIENTS AND METHODS:

Patients with a histological diagnosis of OS were eligible if they were <40years of age, had initially metastatic disease and met organ function requirements. Treatment combined surgery and a conventional chemotherapy regimen. ZA was given concurrent with chemotherapy for a total of eight doses over 36weeks. Three dose levels of ZA were tested: 1.2mg/m(2) [max 2mg], 2.3mg/m(2) [max 4mg] and 3.5mg/m(2) [max 6mg]. The MTD was determined during induction. Six patients were to be treated at each dose level, with an additional six patients treated with the MTD to help assess post-induction feasibility.

RESULTS:

Twenty-four patients (median age 13.5years [range, 7-22]; 16 females) were treated. Five patients experienced dose-limiting toxicities (DLTs) during induction, including three patients treated with 3.5mg/m(2). DLTs included hypophosphatemia, hypokalemia, hyponatremia, mucositis, limb pain and limb oedema. There were no reports of excessive renal toxicity or osteonecrosis of the jaw. The MTD was defined as 2.3mg/m(2) (max 4mg).

CONCLUSIONS:

ZA can be safely combined with conventional chemotherapy with an MTD of 2.3mg/m(2) (max 4mg) for patients with metastatic osteosarcoma.

An analysis was made of three different syndromes associated with p63 gene mutations, known as ectrodactyly-ectodermal dysplasia-clefting syndrome (EEC), ankyloblepharon-ectodermal dysplasia clefting syndrome (AEC or Hay-Wells) and Rapp-Hodgkin syndrome (RHS). The postoperative complications associated with their cleft reconstructions were also evaluated.Extensive demographic information, in particular of the clinical appearances, associated malformations, and the types and complications of the reconstructive surgical procedures, were recorded of these syndromic cases occurring in a database of 3621 facial cleft deformity patients. The data was analyzed using the Microsoft Excel program.A total of 10 (0.28%) cases of p63 associated syndromes were recorded: EEC (6), RHS (3), and AEC (1). The following clinical cleft appearances were noted - EEC = 6: CLA 1 -right side unilateral (female); CLAP 4 - right side (1) + left side (1) unilateral (male + female); bilateral (2) (males); hPsP 1 (female) (divided in 3 Black, 2 White, 1 Indian); RHS = 3: CLAP 2 (White males); hPsP 1 (White female); AEC = 1: CLAP bilateral (White male). Other features of the syndromes were: skin, hand, foot, tooth, hair and nail involvement, and light sensitivity. Postoperative complications included: (i) stenosis of nasal opening, especially after reconstruction of the bilateral cleft lip and the columella lengthening (2 cases), (ii) premaxilla-prolabium fusion (2 cases), (iii) repeated occurrence of oro-nasal fistula in the hard palate (4 cases), and (iv) dysgnathial development of midfacial structures (3 cases).Three different p63 associated syndromes (EEC, AEC, and RHS) were diagnosed (0.27% of the total facial cleft deformities database). The majority of the cases presented with a bilateral CLAP in males only. A number of females and males had unilateral CLA. The hPsP-cleft was recorded in females only. The associated ectodermal component most probably had a profoundly negative influence on postoperatively wound healing, which was observed in particular at the nasal openings, the premaxilla sulcus and in the hard palate mucosa. The reconstruction of p63 associated syndromes is a greater challenge than the usual cleft reconstruction to the surgeon.

Glossopharyngeal neuralgia is a relatively rare condition characterized by severe, paroxysmal episodes of pain localized to the external ear canal, the base of the tongue, the tonsil or the area beneath the angle of the jaw. This pain is many a times confused with Trigeminal Neuralgia and mistreated. There are various diagnostic and management dilemmas which are herein addressed in this review.

PURPOSE:

Apparent organic abnormalities are sometimes not identified among patients suffering from chronic pain in the craniocervical region. In some cases, parafunctional activities (PAs) are recognized. PAs are nonfunctional oromandibular activities that include jaw clenching and bruxism, but are considered as factors that contribute to craniomandibular disorders (CMDs). It is now recognized that PAs and CMDs influence musculoskeletal conditions of the upper quarter. Exercise therapy (ET) to improve jaw movement and psychological intervention (PI) to reduce PAs are useful for PAs and CMDs. We hypothesized that ET and PI would be effective for craniocervical pain without organic abnormalities.

METHODS:

Thirty-nine subjects suffering from craniocervical chronic pain were allocated into 3 groups: The control group received only pharmacological treatment; the ET group received jaw movement exercise (JME); and the ET-PI group received JME and PI. Pain and jaw movement were evaluated using a numerical rating scale (NRS).

RESULTS:

After interventions, the NRS scores were significantly lower in the ET-PI group, compared with those in the other groups. Jaw movement improved 100% in the ET group, 92% in the ET-PI group, and 0% in the control group.

CONCLUSION:

A combination of jaw exercise and psychological intervention to reduce parafunctional activities is more effective than jaw exercise alone for the improvement of craniocervical pain without apparent organic abnormalities.

BACKGROUND:

Repeated injection of acidic saline into skeletal muscles of the leg in rodents induces a prolonged bilateral mechanical hyperalgesia that persists for up to 30 days and may be useful to model widespread muscle pain conditions. In this study, repeated injection of acidic (pH 3.3) saline solution into the masseter muscle of healthy human subjects was undertaken to determine if these injections are painful and whether they would induce a prolonged period of muscle sensitization to artificial and/or natural mechanical stimulation of the masseter and temporalis muscles.

METHODS:

Eighteen subjects (10 male, 8 female) participated in the study. Subjects received two injections of 0.5 mL acidic or regular isotonic saline 2 days apart, in a randomized, double blind, crossover design.

RESULTS:

There was no significant difference in pain intensity ratings when acidic saline injections were compared with regular saline injections. Pain area drawings were, however, significantly larger in response to the first injection of acidic saline than to the second injection of acidic saline or to either the first or second injection of regular saline. Repeated injection of acidic saline did not significantly alter pressure pain thresholds from the masseter or temporalis muscles on either the injected side or the opposite side over the 10-day post injection monitoring period. There was also no effect of injections on chewing.

CONCLUSION:

These findings indicate that, unlike in some rodent models, repeated injection of low pH solutions into jaw muscles of humans fails to induce a period of prolonged muscle hyperalgesia.

As women age and enter menopause, they are sometimes more susceptible than men to certain physical and mental disorders such as osteoporosis and late onset schizophrenia. Risedronate (Actonel©) is a bisphosphonate used for the treatment of osteopenia. Early initiation of pharmacotherapy for osteopenia is recommended to prevent greater bone loss. The most common side effects of risedronate include fever and flu-like symptoms, hypocalcemia, bone and joint pain, peripheral edema, fatigue, change in bowel movements, osteonecrosis of the jaw, and atrial fibrillation. Though reports in the professional literature of psychotic reactions to risedronate are scant, there have been FDA reports and of patient discussions of psychiatric side effects of this medication on popular websites. We report the case of M age 59, who was treated with risedronate for osteoporosis, and subsequently diagnosed with atypical psychosis after other organic causes were excluded. Though is conceivable that age-related psychosocial and physical factors triggered late-onset schizophrenia, the temporal relationship between the termination of treatment with risedronate and the improvement in her mental state, suggests that the risedronate might have triggered a psychotic reaction that resolved following cessation of treatment.

Jawbone cavitations (JC) are hollow dead spaces in jawbones with dying or dead bone marrow. These areas are defined as fatty degenerative osteonecrosis of the jawbone or neuralgia-inducing cavitational osteonecrosis and may produce facial pain. These afflictions have been linked to the immune system and chronic illnesses. Surgical debridement of JC is reported to lead to an improvement in immunological complaints, such as rheumatic, allergic, and other inflammatory diseases (ID). Little is known about the underlying cause/effect relationship.JC bone samples were analyzed to assess the expression and quantification of immune modulators that can play a role in the pathogenesis of IDs. The study supports a potential mechanism where JC is a mediating link in IDs.Samples of fatty softened bone taken from JCs were extracted from 31 patients. The specimens were analyzed by bead-based multiplex technology and tested for seven immune messengers.Regulated upon activation, normal T-cell expressed, and secreted (RANTES) and fibroblast growth factor (FGF)-2 were found at high levels in the JCs tested. Other cytokines could not be detected at excessive levels.The study confirms that JC is able to produce inflammatory messengers, primarily RANTES, and, secondarily, FGF-2. Both are implicated in many serious illnesses. The excessive levels of RANTES/FGF-2 in JC patients with amyotrophic lateral sclerosis, multiple sclerosis, rheumatoid arthritis, and breast cancer are compared to levels published in medical journals. Levels detected in JCs are higher than in the serum and cerebrospinal fluid of amyotrophic lateral sclerosis and multiple sclerosis patients and four-fold higher than in breast cancer tissue.This study suggests that JC might serve as a fundamental cause of IDs, through RANTES/FGF-2 production. Thus, JC and implicated immune messengers represent an integrative aspect of IDs and serve as a possible cause. Removing JCs may be a key to reversing IDs. There is a need to raise awareness about JC throughout medicine and dentistry.