Observed Side Effects Research Articles

Targeting colorectal cancer with anti-epidermal growth factor receptor antibodies: focus on panitumumab

Panitumumab is a fully humanized monoclonal antibody with a high degree of affinity for the extracellular domain of the epidermal growth factor receptor. Phase II clinical evaluation of this drug, when administered as a single agent, in patients with metastatic colorectal cancer refractory to chemotherapy, demonstrated a modest objective radiographic response rate with acceptable toxicity; the most frequently observed side effect is rash. A randomized phase III study in subjects with chemotherapy-refractory metastatic colorectal cancer documented a progression-free survival advantage in subjects treated with panitumumab plus best supportive care versus best supportive care alone; a difference in survival was not observed, likely due to the high cross over rate. Primary tumor KRAS mutation analysis performed in this study indicated that the benefit was confined to those patients whose tumors did not contain a KRAS mutation. Further studies with panitumumab will be required to develop biomarkers of response and to determine if panitumumab has a role in combination with cytotoxic chemotherapy. This article summarizes the current state-of-the-science knowledge on panitumumab therapy in the treatment of advanced colorectal cancer.

Preliminary Experience With Conversion From Calcineurin Inhibitors to Everolimus in Cardiac Transplantation Maintenance Therapy

Introduction Everolimus has been prescribed both for initial and maintenance therapy after cardiac transplantation. Herein, we present our initial experience with everolimus as maintenance therapy after cardiac transplantation. Methods We retrospectively included all of our patients in whom therapy was changed from calcineurin inhibitors to everolimus between September 2006 and October 2007. We analyzed their baseline clinical characteristics, indications for conversion to everolimus therapy, and beneficial vs adverse effects of the maneuver. Results In 16 heart transplant recipients, therapy was changed to everolimus because of allograft vasculopathy (n = 8), renal failure (n = 4), or sirolimus toxicity (n = 4). Treatment with everolimus was initiated at a mean (SD) of 79.8 (52.7) months (range, 10–163 mo) after transplantation. The initial dose was 1.4 (0.2) mg (range, 1.0–1.5 mg), and the maintenance dose was 1 (0.31) mg (range, 0.5–1.5 mg). Follow-up was 7.28 (3.22) months (range, 0.5–13 mo). Observed side effects included hypertriglyceridemia, hypertension, and edema. Only 1 of 4 patients included because of sirolimus intolerance did not tolerate everolimus; renal dysfunction did not worsen in any of these 4 patients. No allograft vasculopathy was observed. Conclusions Renal function seem to stabilize after conversion to everolimus therapy in patients with previous progressive dysfunction. The safety profile was proved in all patients, although conclusions cannot be established about the evolution of allograft vasculopathy.

Feasibility of small animal cranial irradiation with the microRT system

To develop and validate methods for small-animal CNS radiotherapy using the microRT system. A custom head immobilizer was designed and built to integrate with a pre-existing microRT animal couch. The Delrin couch-immobilizer assembly, compatible with multiple imaging modalities (CT, microCT, microMR, microPET, microSPECT, optical), was first imaged via CT in order to verify the safety and reproducibility of the immobilization method. Once verified, the subject animals were CT-scanned while positioned within the couch-immobilizer assembly for treatment planning purposes. The resultant images were then imported into CERR, an in-house-developed research treatment planning system, and registered to the microRTP treatment planning space using rigid registration. The targeted brain was then contoured and conformal radiotherapy plans were constructed for two separate studies: (1) a whole-brain irradiation comprised of two lateral beams at the 90 degree and 270 degree microRT treatment positions and (2) a hemispheric (left-brain) irradiation comprised of a single A-P vertex beam at the 0 degree microRT treatment position. During treatment, subject animals (n=48) were positioned to the CERR-generated treatment coordinates using the three-axis microRT motor positioning system and were irradiated using a clinical Ir-192 high-dose-rate remote after-loading system. The radiation treatment course consisted of 5 Gy fractions, 3 days per week. 90% of the subjects received a total dose of 30 Gy and 10% received a dose of 60 Gy. Image analysis verified the safety and reproducibility of the immobilizer. CT scans generated from repeated reloading and repositioning of the same subject animal in the couch-immobilizer assembly were fused to a baseline CT. The resultant analysis revealed a 0.09 mm average, center-of-mass translocation and negligible volumetric error in the contoured, murine brain. The experimental use of the head immobilizer added 0.1 mm to microRT spatial uncertainty along each axis. Overall, the total spatial uncertainty for the prescribed treatments was +/-0.3 mm in all three axes, a 0.2 mm functional improvement over the original version of microRT. Subject tolerance was good, with minimal observed side effects and a low procedure-induced mortality rate. Throughput was high, with average treatment times of 7.72 and 3.13 min/animal for the whole-brain and hemispheric plans, respectively (dependent on source strength). The method described exhibits conformality more in line with the size differential between human and animal patients than provided by previous prevalent approaches. Using pretreatment imaging and microRT-specific treatment planning, our method can deliver an accurate, conformal dose distribution to the targeted murine brain (or a subregion of the brain) while minimizing excess dose to the surrounding tissue. Thus, preclinical animal studies assessing the radiotherapeutic response of both normal and malignant CNS tissue to complex dose distributions, which closer resemble human-type radiotherapy, are better enabled. The procedural and mechanistic framework for this method logically provides for future adaptation into other murine target organs or regions.

Therapeutic window of an EpCAM/CD3-specific BiTE antibody in mice is determined by a subpopulation of EpCAM-expressing lymphocytes that is absent in humans.

MuS110 is a BiTE antibody bispecific for murine EpCAM (CD326) and murine CD3. A recent study has shown that microS110 has significant anti tumor activity at well-tolerated doses as low as 5 microg/kg in orthotopic breast and lung cancer models (Amann et al. in Cancer Res 68:143-151, 2008). Here, we have explored the safety profile of microS110 at higher doses. Escalation to 50 microg/kg microS110 caused in mice transient loss of body weight, and transient piloerection, hypomotility, hypothermia and diarrhoea. These clinical signs coincided with serum peaks of TNF-alpha, IL-6, IL-2, IFN-gamma and IL-4, and an increase of surface markers for T cell activation. Because activation of T cells in response to BiTE antibodies is typically dependent on target cells, we analyzed mouse blood for the presence of EpCAM(+) cells. Various mouse strains presented with a subpopulation of 2-3% EpCAM(+) blood cells, mostly B and T lymphocytes, which was not detected in human blood samples. In vitro experiments in which the number of EpCAM(+) cells in blood samples was either reduced or increased suggested that both T cell activation and cytokine release in response to microS110 was dependent on the number of target-expressing cells. In support for a role of EpCAM(+) lymphocytes in the observed side effects, reduction of EpCAM(+) blood cells in mice via a low-dose pre treatment with microS110 dramatically increased the tolerability of animals up to at least 500 microg/kg of the BiTE antibody. This high tolerability to microS110 occurred in the presence of non-compromised T cells. No damage to EpCAM(+) epithelial tissues was evident from histopathological examination of animals daily injected with 100 microg/kg microS110 for 28 days. In summary, these observations suggest that side effects of microS110 in mice were largely caused by an acute T cell activation that was triggered by a subpopulation of EpCAM(+) lymphocytes. Because humans have extremely low numbers of EpCAM(+) cells in blood, this toxicity of an EpCAM-specific BiTE may be specific for mice.

Boron neutron capture therapy (BNCT) for glioblastoma multiforme: A phase II study evaluating a prolonged high-dose of boronophenylalanine (BPA)

Background and purpose To evaluate the efficacy and safety of boron neutron capture therapy (BNCT) for glioblastoma multiforme (GBM) using a novel protocol for the boronophenylalanine–fructose (BPA-F) infusion. Patient and methods This phase II study included 30 patients, 26–69 years old, with a good performance status of which 27 have undergone debulking surgery. BPA-F (900 mg BPA/kg body weight) was given i.v. over 6 h. Neutron irradiation started 2 h after the completion of the infusion. Follow-up reports were monitored by an independent clinical research institute. Results The boron-blood concentration during irradiation was 15.2–33.7 μg/g. The average weighted absorbed dose to normal brain was 3.2–6.1 Gy (W). The minimum dose to the tumour volume ranged from 15.4 to 54.3 Gy (W). Seven patients suffered from seizures, 8 from skin/mucous problem, 5 patients were stricken by thromboembolism and 4 from abdominal disturbances in close relation to BNCT. Four patients displayed 9 episodes of grade 3–4 events (WHO). At the time for follow-up, minimum ten months, 23 out of the 29 evaluable patients were dead. The median time from BNCT treatment to tumour progression was 5.8 months and the median survival time after BNCT was 14.2 months. Following progression, 13 patients were given temozolomide, two patients were re-irradiated, and two were re-operated. Patients treated with temozolomide lived considerably longer (17.7 vs. 11.6 months). The quality of life analysis demonstrated a progressive deterioration after BNCT. Conclusion Although, the efficacy of BNCT in the present protocol seems to be comparable with conventional radiotherapy and the treatment time is shorter, the observed side effects and the requirement of complex infrastructure and higher resources emphasize the need of further phase I and II studies, especially directed to improve the accumulation of 10B in tumour cells.

Argatroban Associated Bleeding Complications.

Background: Heparin induced thrombocytopenia (HIT) is a frequently observed side effect observed with heparin administration. Treatment for this condition includes direct thrombin inhibitor (DTI) therapy. Major hemorrhagic complications are considered rare events in this setting.Methods: This is a case series of patients diagnosed with HIT in a tertiary medical referral center. The diagnosis of HIT was established on the base of clinical criteria. All included patients had positive HIT ELISA based antibody testing during the time interval from July 2006 to July 2007 and all patients were treated with argatroban. A systematic review for hemorrhagic and thrombotic complications of argatroban therapy was performed. Major hemorrhage was defined as clinically identified bleeding with the demand for transfusion therapy. Thrombotic complications were defined as thrombosis evidenced by imaging studies developing during argatorban therapy. We performed bivariate and multivariate logistic regression analysis to identify demographic and clinical factors that influence the development of complications of argatroban therapy as treatment for HIT. Examined covariates were gender, age, type of service the patient was admitted under (surgical versus medical), amount of comorbidities, preexisting history of gastrointestinal bleeding, documented thrombotic or thrombembolic event at the time point of HIT diagnosis and coexisting coexisting coagulopathy other than HIT.Results: We identified 102 patients with the diagnosis of HIT. The median optical density (OD) of the ELISA HIT immunoassay was 1.23 (95% CI 0.93–1.43). We identified 11 (10.7%) major hemorrhagic events in patients on argatroban. Four patients (3.9%) died as a consequence of major hemorrhagic complications. No thrombotic events were identified in our study cohort. As statistically significant; predictors for clinically relevant hemorrhagic complications in our model remained male gender, preexisting GI bleeding history and being patient on a surgical service.Conclusion: The incidence of major hemorrhagic episodes with agatroban therapy is significantly higher then generally reported and the mortality rate is very disturbing. These data suggest that alternatives to standard direct thrombin inhibitor therapy should be aggressively pursued.

Pyogenic granuloma in children: Treatment with topical imiquimod

We report the successful treatment of five children with facial pyogenic granuloma using topical imiquimod 5% cream. In all cases, resolution of the lesions was achieved within 2-4 weeks. Local erythema and scaling, consistent with a typical imiquimod response, was the most commonly observed side effect. No systemic complications were observed in any of the patients. There has been no recurrence of any of the lesions to date. Small mildly erythematous or hypopigmented macules remain at this stage of follow up.

Simulated consumer use of a battery‐powered, hand‐held, portable diode laser (810 nm) for hair removal: A safety, efficacy and ease‐of‐use study

Safety, efficacy and ease-of-use of a hair removal diode laser for consumer use were evaluated. The treatment group consisting of 77 appropriate users measured safety and efficacy from three self-administered treatments. The non-treatment group consisting of 44 inappropriate users measured safety from delivery of a single laser pulse. The mean hair reduction was 61% 3 weeks after the first treatment, 70% 3 weeks after the second treatment, 60% 1 month after the third treatment, 24% 2 months after the third treatment, 6% 3 months after the third treatment, 41% 6 months after the third treatment, 31% 9 months after the third treatment, and 33% 12 months after the third treatment. The only observed side effect for appropriate users was transient erythema. In simulated consumer use, the laser was highly effective at removing hair with minimal side effects for appropriate users.

Pegylated liposomal doxorubicin plus paclitaxel as an individualized chemosensitivity-directed treatment in advanced metastatic melanoma

8551 Background: Melanoma is a cutaneous neoplasm known for its high agressiveness and its poor prognosis once metastasized. Dacarbacine chemotherapy is actually considered standard first-line treatment of metastatic melanoma, with reported response rates of 6–7%. Due to this unsatisfactory situation, a number of non-standard anti-cancer drugs have been tested for improved efficacy. The present study was aimed to test doxorubicin plus paclitaxel in metastatic melanoma patients based on in-vitro chemosensitivity of this drug combination in fresh tumor samples. Methods: The primary study endpoint was objective response, secondary endpoints were safety and overall survival. Patients with histologically confirmed metastatic melanoma (AJCC stage IV), measurable tumor parameters, and an in-vitro chemosensitivity to doxorubicin plus paclitaxel which is superior to other test drugs determined by an ATP-based luminescence viability assay, were eligible. Patients received paclitaxel 175 mg/m2 i.v. followed by pegylated liposomal doxorubicin 30 mg/m2 i.v. at d1 every 28 days. Tumor assessment was performed every 8 weeks and evaluated according to RECIST. Treatment was continued at a tumor response of stable disease (SD) or better, and stopped in case of disease progression (PD) or intolerable side effects. Results: Out of 14 patients enrolled into this study, 12 received study treatment as first-line, and two as second-line therapy. Objective response was 14.3% (1 CR, 1 PR); progression arrest was 28.6% (1 CR, 1 PR, 2 SD). Median overall survival was 9.7 months. Common slight to moderate side effects were myelosuppression and neurotoxicity. Severe toxicities (CTC grade 3/4) were experienced by three patients (21.4%), with two of them presenting severe myelosuppression, and one experiencing myocardial infarction. Conclusions: Pegylated liposomal doxorubicin combined with paclitaxel shows significant efficacy in advanced metastatic melanoma if applied in an individualized, sensitivity- directed regimen. The observed side effects were comparable to other combination chemotherapies. This treatment regimen needs further evaluation in larger clinical trials containing standard therapy control groups. No significant financial relationships to disclose.

A randomized phase II trial of adjuvant chemotherapy with uracil / tegafur (UFT) and gemcitabine (GEM) vs. gemcitabine alone in patients with resected pancreatic cancer

4542 Background: GEM is now the standard therapy for patients with advanced pancreatic cancer (PC). However, there have been few randomized studies of adjuvant chemotherapy with GEM in patients with resected PC. Methods: Patients with invasive ductal pancreatic cancer who underwent radical surgery were enrolled. Within 8weeks after operation, pts were randomized to receive UFT and GEM (GU) or GEM alone (G). GEM was administrated at a dosage of 1g/m2 IV weekly X3 out of 4weeks and UFT at a dosage of 200mg/body/day orally continuously. Eligibility included histological residual tumor (R) 0 or 1, and no previous chemo- or/and radiation therapy. Primary endpoint was 1y disease free survival (DFS) rate and secondary endpoints included overall survival (OS) and side effects in both groups. Results: Between 05/02 and 12/05, 100 patients were randomized into the two arms of the trial (50 pts to GU and 50 to G). No pts were found to be ineligible. Pts characteristics were well balanced (GU/G) with regard to median age (62/63y), tumor status (T3+4 88/94%), nodal status (N positive 77/72%), histological residual tumor status (R0 76/68%). Until 03/06, 1y DFS rate was 50.3% in GU and 45.5% in G and there was no significant difference between two groups. The median OS was 20m in GU and 28m in G (Log rank test: N.S.). Grade 2 or more toxicities were observed in 67.3% of GU pts and 56.3% of G pts (N.S.). No grade 4 or more toxicity was observed in either groups. Leucocytopenia was the most frequently observed side effect in both groups (Grade 2 or more GU/G 49/46%). Conclusion: Preliminary results confirm the efficacy and safety of GEM based adjuvant chemotherapy for pts with resected PC, but addition of UFT with GEM dose not improve DFS as compared with GEM alone, so far. Final results will be presented at the meeting. No significant financial relationships to disclose.

Final results of a phase 2 study using continuous 5% Imiquimod cream application in the primary treatment of high-grade vulva intraepithelial neoplasia

Objectives. To investigate the activity of 5% Imiquimod cream in the primary treatment of vulva intraepithelial neoplasia (VIN) grade 2/3. Methods. Patients with histologically confirmed VIN 2/3 were recruited from regional colposcopy units. A Simon two-stage phase 2 study design was used. Imiquimod cream was applied over the abnormal VIN areas by the patients, using an escalating dose regimen for a total treatment duration of 16 weeks. Colposcopy assessments were performed every 2 weeks to evaluate for response. A historical cohort of VIN 2/3 patients treated with primary surgical ablation was used to compare recurrence patterns. Results. Thirty-nine patients enrolled in the study. Six patients dropped out due to side effects and non-compliance with study protocol. Thirty-six patients (92%) had VIN 3. Therapy was well tolerated with the most common observed side effects being only minor skin irritation at the application site. Histologic complete response was observed in 21 patients with partial response in another nine patients. The overall response rate was 77% using intention to treat principle. No VIN progression or cancer was diagnosed. At a median follow-up of 16 months in the whole study cohort, eight recurrences (20.5%) were observed. In comparison, the recurrence rate for primary surgically treated patients was 53.5% ( p = 0.013). Conclusion. Imiquimod cream was well tolerated and resulted in the regression in a majority of high-grade VIN lesions. The recurrence rate appeared to be comparable to primary surgical ablation.

Topical 2% cyclosporine A in preservative-free artificial tears for the treatment of vernal keratoconjunctivitis

Background: A double-masked, placebo-controlled trial to evaluate the short-term efficacy and safety of topical 2% cyclosporine A in preservative-free artificial tears for patients with vernal keratoconjunctivitis. Methods: Twenty patients with severe vernal keratoconjunctivitis were included in the study. All were treated with topical 2% cyclosporine A eye drops. One eye of each patient was administered 2% cyclosporine A in preservative-free artificial tears; the fellow eye received the placebo (vehicle) for the first 2 weeks, in a double-masked, placebo-controlled trial. Thereafter, the placebo eye received cyclosporine A (open trial). Symptoms and signs were scored on the day of enrolment and at the end of week 2,4, and 14. Results: At the end of week 2, no statistically significant decrease was noted from baseline in mean scores of either signs ( p = 0.18) or symptoms ( p = 0.50) in the eyes that received placebo. On the other hand, a statistically significant decrease was observed in both sign and symptom scores ( p < 0.001, for both) of eyes that received cyclosporine A. Significant differences were also noted at 2 weeks in mean scores of both signs and symptoms ( p < 0.001, for both) between the eyes that received cyclosporine A and those that received placebo. At week 4 and 14, statistically significant decreases in both sign scores and symptom scores were noted compared with baseline in the eyes that received cyclosporine A and in the eyes that had initially received placebo ( p < 0.001, for all). Interpretation: Topical 2% cyclosporine A in preservative-free artificial tears is effective in alleviating signs and symptoms of patients with severe vernal keratoconjunctivitis and had no observed side effects over the course of the study.

Non-Rash Skin Toxicities Associated with Novel Targeted Therapies

Many novel targeted agents have emerged against a variety of malignancies. Although papulopustular rash is the most commonly observed side effect associated with many of these agents, several non-rash skin toxicities have been identified that frequently result in the delay or discontinuation of anticancer therapy. These toxicities include skin hyperpigmentation, xerosis, pruritus, hair growth and color abnormalities, periungual and nail alterations, and hand-foot skin reaction. It is important to recognize these toxicities, so that they can be diagnosed early and treatment or dose modification can be initiated, if necessary. This review discusses several non-rash dermatologic toxicities observed with targeted therapeutic agents and guidelines for their diagnosis and treatment.

Preliminary clinical experience using a newly developed minimal-invasive reference base in computer assisted foot surgery

In recent years, many new tools and techniques have been developed in computer assisted orthopaedic surgery primarily with an industry led effort in software innovation and development. Only a few research and clinical projects have focused on intraoperative difficulties. A common operative challenge in computer assisted orthopaedic surgery is the positioning of the reference base. Rigid fixation of a dynamic reference base is essential in navigated surgery of the extremities. The aim of this study was to develop a minimal-invasive screw which could be placed effectively and efficiently with rotational stability during computer assisted orthopaedic surgery. The minimal-invasive screw was initially evaluated in an artificial bone experiment. After successful results with the artificial bone experiment, it underwent testing in seven human cadaver thighs with ISO-C3D navigated drilling. Finally the screw was transferred into a clinical application during five foot surgeries. In 10 ISO-C3D navigated drillings, the lesions were targeted 100% of the drillings. A screw dislocation was not observed. In comparison to conventional one or two pin fixation systems, the newly designed small screw did not have any observed side effects such as artifacts. In addition, the screw generated less heterodyning than a conventional fixation system. The small screw design is an advantage in theatre. We believe the minimally-invasive screw allows the surgeon to use a tool that helps avoid common pitfalls from conventional fixation systems, and it may improve efficiency.

Mutational Pathways, Resistance Profile, and Side Effects of Cyanovirin Relative to Human Immunodeficiency Virus Type 1 Strains with N-Glycan Deletions in Their gp120 Envelopes

Limited data are available on the genotypic and phenotypic resistance profile of the alpha-(1-2)mannose oligomer-specific prokaryotic lectin cyanovirin (CV-N). Therefore, a more systematic investigation was carried out to obtain a better view of the interaction between CV-N and human immunodeficiency virus type 1 (HIV-1) gp120. When HIV-1-infected CEM cell cultures were exposed to CV-N in a dose-escalating manner, a total of eight different amino acid mutations exclusively located at N-glycosylation sites in the envelope surface gp120 were observed. Six of the eight mutations resulted in the deletion of high-mannose type N-glycans (i.e., at amino acid positions 230, 332, 339, 386, 392, and 448). Two mutations (i.e., at position 136 and 160) deleted a complex type N-glycan in the variable V1/V2 domain of gp120. The level of phenotypic resistance of the mutated virus strains against CV-N generally correlated with the number of glycan deletions in gp120, although deletion of the glycans at N-230, N-392, and N-448 generally afforded a more pronounced CV-N resistance than other N-glycan deletions. However, the extent of the decrease of antiviral activity of CV-N against the mutated virus strains was markedly less pronounced than observed for alpha(1-3)- and alpha(1-6)-mannose-specific plant lectins Hippeastrum hybrid agglutinin (HHA) and Galanthus nivalis agglutinin (GNA), which points to the existence of a higher genetic barrier for CV-N. This is in agreement with a more consistent suppression of a wider variety of HIV-1 clades by CV-N than by HHA and GNA. Whereas the antiviral and in vitro antiproliferative activity of CV-N can be efficiently reversed by mannan, the pronounced mitogenic activity of CV-N on peripheral blood mononuclear cells was unaffected by mannan, indicating that some of the observed side effects of CV-N are unrelated to its carbohydrate specificity/activity.

Stroma‐targeted palliative tumor therapy with biomodulators

In search of new strategies for the therapy of advanced tumors stroma-targeted approaches have been discussed recently, especially antiangiogenic therapies. It has turned out that some biomodulating drugs exhibit also effects against tumors beyond their original non-oncologic indication. Among these drugs are for example thalidomide,COX-2 inhibitors, PPARgamma agonists (thiazolidindiones) and mTOR antagonists (rapamycin). The antitumor efficacy of these therapeutics is fundamentally based on indirect effects on the stroma of the tumors. Combination therapies of these therapeutics seem to be superior to the use of single agents. These new biomodulating therapy approaches represent an interesting option for the palliative treatment of advanced tumors, especially as a supplement or extension of established chemo- and immunotherapeutic therapies, since they can be performed in an outpatient setting, the observed side effects are usually mild, and the therapies are therefore well accepted by the patients.

QUANTIFICATION OF FUNCTIONAL CHANGE AFTER TEMPORARY CHEMONEUROLYTIC INTERVENTION IN ANKLE SPASTICITY

subscapularis. Primary outcomes were pain measured by visual analog scale (VAS), physician global rating scale (PGRS), and measurement of range of motion (ROM) using goniometry. Secondary outcomes were arm function measured by the Fugl-Meyer score, and spasticity measured by modified Ashworth scale. Measurements were made at baseline and 2and 6-, and 12-wk after the injection by blinded evaluator. Result: At 12-wk post treatment the mean decrease in pain in the BoNT-A treated group was 5.4 vs. 2.3 in the triamcinolone group (P 0.05). Improvement in physician rating scale was 2.4 vs. 1.6 (P 0.05). The net change in the Fugl-Meyer score was significantly greater in the BoNT-A group than the triamcinolone group (14.7 vs. 2.1, P 0.05). However, there were no differences between treatment modalities with respect to changes in ROM and modified Ashworth scale at 12 wk. There were no observed side effects in either treatment group. Conclusion: Injection of BoNT-A into selected muscles of the shoulder girdle provided sustained and more significant relief of shoulder pain and improved function than intraarticular injection of triamcinolone acetonide.

Cidofovir bladder instillation for the treatment of BK hemorrhagic cystitis after allogeneic stem cell transplantation

We report a case of severe hemorrhagic cystitis after allogeneic transplantation in association with high BK viral load. After failure of aggressive hydration, platelet and blood transfusions, continuous bladder irrigation, and tapering of the immune suppression, we instilled cidofovir into the bladder, which resulted in decreased BK viral load and significant clinical improvement. Our case suggests that local cidofovir therapy for viral hemorrhagic cystitis is effective and well tolerated with no observed side effects.

Spontaneous neonatal chylothorax treated with octreotide

Chylothorax is the most common cause of pleural effusion causing respiratory distress in the neonate. Cases unresponsive to conservative management usually require surgery. We report a case of spontaneous neonatal chylothorax where surgery was avoided with the compassionate trail of octreotide. The chylothorax resolved promptly with no observed side effects. After reviewing the literature reporting the use of octreotide in the neonatal period, we found that neonates with isolated spontaneous chylothorax might be viewed as a group different from those with major cardiac malformations. They are at a lower risk for adverse effect of octreotide and lower threshold for commencement of octreotide may benefit them most.

Topical 2% cyclosporine A in preservative-free artificial tears for the treatment of vernal keratoconjunctivitis

<h2>Abstract</h2> <b>Background:</b> A double-masked, placebo-controlled trial to evaluate the short-term efficacy and safety of topical 2% cyclosporine A in preservative-free artificial tears for patients with vernal keratoconjunctivitis. <b>Methods:</b> Twenty patients with severe vernal keratoconjunctivitis were included in the study. All were treated with topical 2% cyclosporine A eye drops. One eye of each patient was administered 2% cyclosporine A in preservative-free artificial tears; the fellow eye received the placebo (vehicle) for the first 2 weeks, in a double-masked, placebo-controlled trial. Thereafter, the placebo eye received cyclosporine A (open trial). Symptoms and signs were scored on the day of enrolment and at the end of week 2,4, and 14. <b>Results:</b> At the end of week 2, no statistically significant decrease was noted from baseline in mean scores of either signs (<i>p</i> = 0.18) or symptoms (<i>p</i> = 0.50) in the eyes that received placebo. On the other hand, a statistically significant decrease was observed in both sign and symptom scores (<i>p</i> < 0.001, for both) of eyes that received cyclosporine A. Significant differences were also noted at 2 weeks in mean scores of both signs and symptoms (<i>p</i> < 0.001, for both) between the eyes that received cyclosporine A and those that received placebo. At week 4 and 14, statistically significant decreases in both sign scores and symptom scores were noted compared with baseline in the eyes that received cyclosporine A and in the eyes that had initially received placebo (<i>p</i> < 0.001, for all). <b>Interpretation: Topical 2% cyclosporine A in preservative-free artificial tears is effective in alleviating signs and symptoms of patients with severe vernal keratoconjunctivitis and had no observed side effects over the course of the study.</b>