Orbital rhabdomyosarcoma metastatic to the contralateral orbit: a case report

OBJECTIVE: To report a rare presentation of metastatic orbital rhabdomyosarcoma and the corresponding findings on magnetic resonance imaging (MRI). DESIGN: Interventional case report. RESULTS: A 29-year-old white man was diagnosed with rhabdomyosarcoma of the left sinus and orbit for which he was treated with chemotherapy and radiation. Eighteen months after diagnosis, he returned with subacute right eye pain and dysmotility of his extraocular muscles. MRI revealed solitary enlargement of the right medial rectus muscle, and thyroidopathy was suspected. Over the next 2 months, symptoms progressed, and proptosis developed. MRI showed infiltration of seven extraocular muscles. A biopsy of right orbital tissues and the right medial rectus muscle was performed. Special tissue typing confirmed metastatic alveolar rhabdomyosarcoma. The patient underwent palliative radiation therapy and chemotherapy, but he ultimately died of disseminated disease. CONCLUSIONS: Rhabdomyosarcoma can rarely metastasize to the extraocular muscles. Earlier recognition of orbital metastasis through radiographic and biopsy findings, along with prompt and aggressive treatment, may prevent fulminant spread of rhabdomyosarcoma.     

Canalicular stenosis secondary to weekly versus every-3-weeks docetaxel in patients with metastatic breast cancer

PURPOSE: To compare the frequency of canalicular stenosis as a side effect of weekly versus every-3-weeks docetaxel in patients with metastatic breast cancer. DESIGN: Retrospective nonrandomized comparative trial. PATIENTS AND METHODS: Eighteen patients enrolled in a phase II study of weekly docetaxel plus trastuzumab and 18 patients enrolled in a phase II study of every-3-weeks docetaxel plus doxorubicin were evaluated. Each patient underwent a comprehensive ophthalmologic examination, probing and irrigation of the nasolacrimal duct, and, in some instances, a nuclear lacrimal scan. MAIN OUTCOME MEASURES: If epiphora (excessive tearing) was reported by the patient, its time of onset was documented. In patients with epiphora, presence or absence of canalicular stenosis was evaluated on the basis of the findings on probing and irrigation. The duration of treatment with docetaxel, the dose frequency, and the cumulative dose of docetaxel were recorded in each case. RESULTS: Fourteen patients (77%) receiving weekly docetaxel plus trastuzumab had epiphora. Nine of these patients had significant anatomic narrowing of the canaliculi. Bicanalicular silicone intubation or dacryocystorhinostomy was recommended in all nine patients. Eight patients underwent surgery and experienced complete or near complete resolution of epiphora. Although two patients (11%) receiving every-3-weeks docetaxel plus doxorubicin reported transient symptoms of epiphora, neither patient was found to have narrowing of the canaliculi, and the epiphora was not severe enough to justify surgical intervention. The mean duration of docetaxel therapy for the patients in this study was 19 weeks. The mean cumulative dose of docetaxel was higher in patients with canalicular stenosis than in patients without this side effect. CONCLUSIONS: Canalicular stenosis was more common in patients receiving weekly docetaxel than in those receiving every-3-weeks docetaxel for metastatic breast cancer. Bicanalicular silicone intubation early in the course of weekly docetaxel therapy should be considered, because this intervention can prevent complete closure of the canaliculi. Once complete or near complete stenosis of the canaliculi occurs, placement of a permanent Pyrex glass tube may become necessary to overcome the blockage of tear outflow.     

Marginal keratitis associated with administration of filgrastim and sargramostim in a healthy peripheral blood progenitor cell donor

PURPOSE: To describe a 61-year-old healthy peripheral blood progenitor cell (PBPC) donor who developed marginal keratitis and mild uveitis on the third day after receiving daily recombinant human granulocyte colony-stimulating factor (rhG-CSF; filgrastim) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; sargramostim) to mobilize PBPCs for allogeneic transplantation. METHODS: Interventional case report. RESULTS: The keratitis was treated with topical administration of 1% prednisolone acetate solution and resolved within 24 hours. The topical steroid dose was tapered and ultimately discontinued without recurrence of keratitis. CONCLUSION: Healthy PBPC donors receiving rhG-CSF or rhGM-CSF should be monitored for ocular complications, particularly marginal keratitis and uveitis.     

Activation of metabotropic glutamate 2/3 receptors reverses the effects of NMDA receptor hypofunction on prefrontal cortex unit activity in awake rats

Systemic exposure to N-methyl-d-aspartate (NMDA) receptor antagonists can lead to psychosis and prefrontal cortex (PFC)-dependent behavioral impairments. Agonists of metabotropic glutamate 2/3 (mGlu2/3) receptors ameliorate the adverse behavioral effects of NMDA antagonists in humans and laboratory animals, and are being considered as a novel treatment for some symptoms of schizophrenia. Despite the compelling behavioral data, the cellular mechanisms by which potentiation of mGlu2/3 receptor function attenuates the effects of NMDA receptor hypofunction remain unclear. In freely moving rats, we recorded the response of medial PFC (prelimbic) single units to treatment with the NMDA antagonist MK801 and assessed the dose-dependent effects of pre- or posttreatment with the mGlu2/3 receptor agonist LY354740 on this response. NMDA receptor antagonist-induced behavioral stereotypy was measured during recording because it may relate to the psychotomimetic properties of this treatment and is dependent on the functional integrity of the PFC. In most PFC neurons, systemic administration of MK801 increased the spontaneous firing rate, decreased the variability of spike trains, and disrupted patterns of spontaneous bursts. Given alone, LY354740 (1, 3, and 10 mg/kg) decreased spontaneous activity of PFC neurons at the highest dose. Pre- or posttreatment with LY354740 blocked MK801-induced changes on firing rate, burst activity, and variability of spike activity. These physiological changes coincided with a reduction in MK801-induced behavioral stereotypy by LY354740. These data indicate that activation of mGlu2/3 receptors reduces the disruptive effects of NMDA receptor hypofunction on the spontaneous spike activity and bursting of PFC neurons. This mechanism may provide a physiological basis for reversal of NMDA antagonist-induced behaviors by mGlu2/3 agonists.     

Screening for vesicoureteral reflux and renal scars in siblings of children with known reflux

The incidence of vesicoureteral reflux (VUR) in the general population is less than 1%, but it is high in families with reflux. The reported prevalence of VUR among siblings of index patients with reflux has ranged from 4.7% to 51%. Reflux carries an increased risk of pyelonephritis and long-term renal impairment. The purpose of this study was to identify the age-related incidence and severity of reflux, and the frequency of associated renal parenchymal damage in siblings of children with reflux in order to assess the use of screening at different ages. Between October 1994 and February 2003, 40 siblings of 34 index patients were screened with direct voiding cystography. 99( m ) technetium (Tc)-dimercaptosuccinic acid (DMSA) nuclear renal scans were performed in siblings with VUR to detect renal scarring. The cystograms were interpreted as showing the presence or absence of VUR and the DMSA scan as symmetrical or asymmetrical differential function, with or without renal scarring. Of 40 siblings, 17 had VUR, representing an incidence of 42.5%. The mean age at study entry of the 15 boys and 25 girls was 63 months (range 6 months to 12 years). The majority of siblings with abnormal DMSA scans were asymptomatic. Reflux was unilateral in 12 siblings and bilateral in 5. Of the 17 refluxing siblings (22 refluxing ureters), 7 (41.17%) had a history of symptomatic urinary tract infection (UTI). The frequency of VUR was nearly equal in siblings over 6 years and those younger than 6 years. Of the 17 siblings with VUR, 16 had DMSA scintigraphy. Of these, 5 were normal and 11 (68.75%) showed abnormalities (7 asymmetrical differential function and 4 parenchymal defect), which was bilateral in 7 and unilateral in 4. In conclusion, this study confirms a significant overall incidence of VUR and renal parenchymal damage in the siblings of patients with known reflux. The prevalence of reflux in older siblings is similar to that in younger siblings. Our review suggests that all siblings over 6 years should undergo a screening cystogram, even in the absence of urinary tract infection. DMSA scintigraphy of asymptomatic siblings appears to be beneficial in preventing renal injury.     

Targeting metabotropic glutamate receptors for treatment of the cognitive symptoms of schizophrenia

Several lines of evidence implicate NMDA receptor dysfunction in the cognitive deficits of schizophrenia, suggesting that pharmacological manipulation of the NMDA receptor may be a feasible therapeutic strategy for treatment of these symptoms. Although direct manipulation of regulatory sites on the NMDA receptor is the most obvious approach for pharmacological intervention, targeting the G-protein coupled metabotropic glutamate (mGlu) receptors may be a more practical strategy for long-term regulation of abnormal glutamate neurotransmission. Heterogeneous distribution, both at structural and synaptic levels, of at least eight subtypes of mGlu receptors suggests that selective pharmacological manipulation of these receptors may modulate glutamatergic neurotransmission in a regionally and functionally distinct manner. Two promising targets for improving cognitive functions are mGlu5 or mGluR2/3 receptors, which can modulate the NMDA receptor-mediated signal transduction by pre- or postsynaptic mechanisms. Preclinical studies indicate that activation of these subtypes of mGlu receptors may be an effective strategy for reversing cognitive deficits resulting form reduced NMDA receptor mediated neurotransmission.     

Fetal hydrocephalus, intrauterine diagnosis and therapy considerations: an experimental rat model

Materials and methods Fetal hydrocephalus is induced by a single intraperitoneal injection of 8 mg/kg 6-aminonikotinamide (6-AN), a niacinamide antagonist, in Sprague–Dawley rats on day 13 of gestation. Laparotomy was carried out in some rats 3, 6, 7 and 8 days after the intraperitoneal injection. The fetuses were collected by uterotomy and fixed in a formalin solution after measuring head circumference and body length for further histological investigations. The ventricular areas and volumes of the lateral ventricles were measured using a computer morphometric technique after all fetuses were serially sectioned sagittally or coronally. Furthermore, 8 maternal rats (4 treated with 6-AN and 4 controls) were used for ultrasound investigation. The fetal ventricular system and the central canal were demonstrated and compared by transabdominal ultrasound in the 6-AN and control groups. On day 19 of gestation the cerebrospinal fluid (CSF) was drained in some fetuses for 18 h through a thin micro-catheter, which was inserted into the lateral ventricle. In some other fetuses the intracranial pressure (ICP) and the intra-amniotic pressure (IAP) were measured after Doppler sonography of the cerebral blood flow (CBF). These measurements were carried out using a transuterine approach following the laparotomy.Results Hydrocephalus was produced due to the closure of all outlets of the fourth ventricle. Macrocephalus was clear on day 17 (4 days after 6-AN injection). The entire ventricular system was dilated, including the aqueduct and foramen of Monro, and cerebellar hypoplasia was revealed.Conclusion Increased ICP in 6-AN fetuses was associated with decreasing CBF. The cerebral mantel was better developed after CSF drainage. The intra-amniotic pressure was increased in all pregnant rats and was either similar to or higher than ICP.     

Medium‐dose‐rate brachytherapy for cancer of the cervix: Preliminary results of a designed schedule

Aim: This retrospective analysis aims to report results from patients with cervical cancer treated by external beam radiation (EBR) with telecobalt and medium‐dose‐rate (MDR) brachytherapy and to establish the magnitude of brachytherapy dose reduction. Methods: Between June 2003 and September 2005, 77 patients with histological diagnosis of cervical carcinoma were treated with cobalt for external beam radiation, followed by one or two insertions of MDR with a dose rate from 220 ± 10 cGy/h. Median dose of EBR at whole pelvis was 50 Gy and the planned MDR schedule consisted of 1 or 2 insertions with 10–12 Gy to point A. Results: 77 patients were followed for median of 15 months (range: 1–33 months). Local control was achieved in 63 patients 81.8%. Local failure and overall failure rates were 11.7% and 19.5%, respectively. Overall incidence of rectal and bladder complication was 9.0% (7/77) and 7.8% (6/77), respectively. Conclusion: Results of this series suggest that use of telecobalt for EBR together with MDR brachytherapy with a dose reduction around 20% in comparison with low‐dose‐rate (LDR) brachytherapy can be an acceptable technique, especially in developing countries.