Different interventions for preventing postoperative catheter-related bladder discomfort: a systematic review and meta-analysis.

OBJECTIVE: Catheter-related bladder discomfort (CRBD) is a common complication of intraoperative urinary catheterization. Various studies have evaluated the efficacy of different interventions in postoperative CRBD. The present review was performed to assess the efficacy of these interventions. METHODS: PubMed, Embase, and CENTRAL (Cochrane Central Register of Controlled Trials) databases were systematically searched to identify randomized controlled trials (RCTs) investigating the efficacy of different drugs for the prevention of postoperative CRBD. This review evaluated the incidence and severity of CRBD after different interventions at 0, 1, 2, and 6 h postoperatively. RESULTS: Forty-five studies including 31 different drugs were analyzed. Eleven drugs were investigated in more than two RCTs, of which dexmedetomidine, gabapentin, tolterodine, tramadol, ketamine, nefopam, oxybutynin, pregabalin, and pudendal nerve block (PNB) generally showed significantly higher efficacy than controls postoperatively. Solifenacin only showed significant efficacy compared with the control at 0 h, and intravenous lidocaine only showed significant efficacy compared with the control at 6 h. There were insufficient trials to draw conclusions regarding atropine, butylscopolamine, chlorpheniramine, clonidine, darifenacin, diphenhydramine, glycopyrrolate, intravesical bupivacaine, ketamine-haloperidol, pethidine-haloperidol, ketorolac, lidocaine-prilocaine cream, magnesium, hyoscine n-butyl bromide, oxycodone, paracetamol, parecoxib, trospium, resiniferatoxin, or amikacin. However, all but pethidine-haloperidol and chlorpheniramine showed some efficacy at various time points compared with controls. CONCLUSION: This review suggests that dexmedetomidine, gabapentin, tolterodine, tramadol, ketamine, nefopam, oxybutynin, pregabalin, and PNB are effective in preventing postoperative CRBD. Considering the efficacy and adverse effects of all drugs, dexmedetomidine and gabapentin were ranked best.

Successful oxaliplatin desensitization protocol in a patient with colorectal metastatic cancer.

INTRODUCTION: Platinum compounds are frequently used for the treatment of colorectal cancer as initial chemotherapy. Oxaliplatin is a third-generation platinum used for the treatment of stage III colorectal cancer and is associated with hypersensitivity reactions. The incidence of hypersensitivity reaction is approximately 12%, with 1-2% of patients developing moderate to severe reactions. CASE REPORT: A 54-year-old male patient with stage III B colon cancer was diagnosed and chemotherapy with oxaliplatin was indicated by the oncology service. Within 20 min of the first cycle of oxaliplatin, he developed dyspnea, laryngeal spam, foreign body sensation in the throat, nausea, and diarrhea; therefore, the infusion of oxaliplatin was suspended, and intramuscular epinephrine was administered and intravenous hydrocortisone along with chlorpheniramine with adequate resolution of symptoms.Management and outcome: Intradermal skin test performed at the concentration of 5 mg/ml (dilution 1:100) was positive. Due to the symptoms presented we decided to perform desensitization to oxaliplatin (total dose: 250 mg) with three bags-12 steps protocol with an initial concentration dose of 1/100 of the total dose in a course of 5.56 h with no hypersensitivity reactions. DISCUSSION: Approximately 50% of patients who are exposed to oxaliplatin may have hypersensitivity despite premedication. Desensitization protocol induces tolerance to a drug temporarily and is dependent on continuous exposure.

Desensitization in Iron Product Allergy.

Iron deficiency is the main cause of anemia in both sexes, with women being more commonly affected. Iron therapy is currently considered an effective and safe remedy to replenish the iron storages. Iron can be administrated both orally and intravenously. In particular, intravenous (IV) iron therapy is widely used when oral iron preparations are either not tolerated or ineffective. Indeed, IV iron improves iron stores more rapidly. Two main immunological responses have been described for iron hypersensitivity reactions (HSRs): IgE-mediated allergy and complement activation-related pseudo-allergy. Here, we report 3 cases of adult patients with iron allergy, who were successfully treated with two different desensitization procedures, respectively. Analysis of these cases demonstrates that, in the presence of HSRs to iron products, desensitization is an effective and safe procedure that prevents treatment discontinuation and hence allows therapeutic target achievement.

Aedes (Stegomyia) aegypti mosquito bite hypersensitivity in a dog: a case report.

BACKGROUND: Mosquitoes are vectors of several pathogens of considerable importance to humans and companion animals, including nematode helminths such as Dirofilaria immitis and Dirofilaria repens that cause heartworm disease and subcutaneous dirofilariosis, respectively. In addition to mosquito-borne pathogen transmission, mosquito bites can cause discomfort and irritation in pets, and even lead to severe hypersensitivity reactions. In the present study, we report an acute local hypersensitivity reaction in a dog following experimental exposure to Aedes (Stegomyia) aegypti. CASE PRESENTATION: A healthy six-year-old male beagle was included in an efficacy study in which dogs (n = 28) were exposed to Ae. aegypti mosquitoes. On Day - 6, the dog was allocated to one of the study groups, consisting of seven dogs to be treated on Day 0 with an imidacloprid/flumethrin collar. After sedation, animals were exposed to approximately 50 females of Ae. aegypti for 60 (± 5) minutes on Days - 6, 1, 7, 14, 21, 28, 55, and 83. On Day - 6, no allergic reaction to the mosquito bites was observed. However, on Day 1, corresponding to the second challenge, the dog demonstrated an acute allergic reaction characterized by swelling of the face (especially in the base of the muzzle and around the eyes), redness of the eyes, and conjunctival edema of the right eye was also observed. The dog was immediately treated with an intramuscular injection of a commercially available antihistamine treatment, Pen-Hista-Strep® containing a suspension of benzylpenicillin, chlorphenamine, dexamethasone, dihydrostreptomycin, and procaine at a dosage of 1 mL per 10 kg. A few hours after treatment, the dog showed noticeable improvement. CONCLUSIONS: This case provides the first evidence of canine acute local hypersensitivity reaction to mosquito bites under laboratory conditions. This observation suggests that invasive mosquito species such as Aedes spp. may affect the health and comfort of our companion animals, especially for pets with outdoor access without individual protective measures against insect bites.

The Effect of Aerosolized Chlorpheniramine Maleate on Exercise Induced Bronchospasm and Gas Exchange in Asthmatics.

INTRODUCTION: Exercise induced asthma (EIB) is an acute, reversible, usually selflimiting airways obstruction which sets in after exercise in patients with asthma. One popular mechanism of EIA is the increase in histamine and its metabolites in circulation after exercise, which leads to bronchoconstriction via histamine receptors in bronchi. Chlorpheniramine Maleate is potent, less sedative antihistaminic drug, which acts by inhibiting histamine release from mast cells. It is also said to have anticholinergic properties. The aerosol route of administration of a drug has the advantages of a faster onset of action, fewer side effects, and greater protection against EIB with respect to small airways function. This study was conducted to evaluate the effect of Chlorpheniramine Maleate aerosol inhalation on flow volumes and gas exchange. MATERIALS AND METHODS: 25 established patients of stabilized bronchial asthma (18 to 44 years) with history of EIA attending Allergy OPD, Medical OPD or Chest clinic were included in the present study. Patients were studied for 3 days in a week at the same time of day. Baseline spirometry was done to know test parameters, i.e. FEV1, PEFR and FEF50%. Gas exchange study during rest including minute ventilation (VE), oxygen consumption (VO2), Carbon dioxide produced per minute (VCO2), Respiratory quotient (R) was carried out. Patient was asked to perform exercise on bicycle ergometer. During exercise VE, VO2, VCO2 and R were recorded every 30 seconds. FEV1, PEFR and FEF50% were recorded immediately after and 5 min after completion of exercise. On day 2, same procedure was repeated with saline nebulisation before the exercise. On day 3, aerosolized Chlorpheniramine Maleate was used instead of saline for nebulisation. Values obtained were tabulated and analysed. OBSERVATIONS AND RESULTS: After exercise FEV1, PEFR, FEF50% decreased on all three days, but the fall in these parameters was less on Day III (prior nebulisation with Chlorpheniramine maleate) compared to previous days. There was significant increase in FEV1, PEFR and FEF50% (P<0.01, 0.05 and 0.05 respectively) which was seen 30 mins after inhalation of Chlorpheniramine maleate aerosol compared to placebo. Resting and exercise values of Minute Ventilation (VE), oxygen uptake (VO2) carbon dioxide expired, on all the three days were comparable and statistically not significant by the end of exercise. On day 2 and 3, 'R' as compared to that of day1 was slightly significant during rest and initial minutes of exercise but became insignificant after that till the end of exercise. CONCLUSION: This study shows that Chlorpheniramine causes bronchodilation during resting period by acting on the circulating or tissue histamine in asthmatics which contributes to an increase in resting bronchomotor tone. As there is incomplete inhibition of EIA by Chlorpheniramine, there may be some other associated mediator release for pathogenesis of EIA.

Immediate-type allergic and protease-mediated reactions are involved in scratching behaviour induced by topical application of Dermatophagoides farinae extract in NC/Nga mice.

Atopic dermatitis (AD)-like dermatitis can be induced by repeated topical application of an ointment containing Dermatophagoides farinae body (Dfb) extract in NC/Nga mice. This AD-like murine model also exhibits a biphasic increase in the number of scratching behaviour after topical application of Dfb ointment. In this study, we investigated the possible mechanisms underlying the scratching behaviour in each phase. An increase in the content of mast cell-derived mediators such as histamine and 5-hydroxytryptamine in the lesional skin and increased vascular permeability were observed in the early phase after the Dfb ointment application. Chlorpheniramine (H1 receptor antagonist) and cromoglycate (mast cell stabilizer) reduced the scratching behaviour in the early phase but not that in the later phase. Furthermore, the content of various endogenous pruritogens such as interleukin-31 and thymic stromal lymphopoietin in the lesional skin was increased 1 or 24 hours after the Dfb ointment application. Elevated expression of proteinase-activated receptor-2 (PAR-2) was also observed in the epidermis. Finally, gabexate (serine protease inhibitor) reduced the scratching behaviour in both phases, and anti-PAR2 antibody also showed a tendency to reduce both scratching behaviours. These findings suggest that immediate-type allergic reactions caused by mast cell degranulation and PAR-2 activation by proteases are involved in the scratching behaviour in this AD-like model.

Can H2 -receptor upregulation and raised histamine explain an anaphylactoid reaction on cessation of ranitidine in a 19-year-old female? A case report.

The anaphylactoid reaction described follows cessation of ranitidine in a 19-year-old female with the disease cluster: mast cell activation syndrome, hypermobile Ehlers-Danlos syndrome and postural tachycardia syndrome. Anaphylaxis can give wide-ranging symptoms from rhinorrhoea and urticaria to tachycardia and system-wide, life-threatening, anaphylactic shock. Individuals with a disorder of mast cell activation can experience many such symptoms. H2 receptor antagonists, such as ranitidine, are commonly prescribed in this population. A mechanism for the reaction is proposed in the context of ranitidine, as an inverse agonist, causing upregulation of H2 histamine receptors and raised histamine levels due to enzyme induction. This effect, following extended and/or high antihistamine dosing, may have implications for other individuals with a disorder of mast cell activation, such as mastocytosis or mast cell activation syndrome. There are potential policy and patient guidance implications for primary and secondary care with respect to cessation of H2 antagonists.

Therapeutic effect of chlorpheniramine in treatingupper airway cough syndrome (UACS) and chronic rhinitis/sinusitis.

This paper aims to analyze the specific effect of chlorpheniramine on upper airway cough syndrome is related to its treatment of chronic rhinitis and sinusitis. A total of 218 patients admitted to hospital between March 2014 and June 2016 were treated with chlorpheniramine. The patients were divided into two groups based on treatment effect in follow-up visits (all were effective): effective group (114 cases, 52.29%) and ineffective group (104 cases, 47.71%). The proportion of complicated rhinitis or sinusitis of the two groups were compared, and improvement effect on clinical symptoms of chronic rhinitis and sinusitis after treatment was compared. The probability of rhinitis / sinusitis was 65.79% (75/114) in the effective group and 69.23% (72/104) in the ineffective group. There was no statistical difference between the two groups (P>0.05). In both effective and ineffective group, the symptoms such as chest tightness and shortness of breath and pharyngeal discomfort were improved to a certain extent, and the effective group had better improvement effect, but there was no statistical difference between the two groups (P>0.05). In addition, there was no correlation between improvement of cough and improvement of symptoms in the effective group, 21 cases of cough disappeared completely, while complete disappearance rate of other symptoms was only 57.15% (12/21). Chlorpheniramine is effective to some extent in treatment of upper airway cough syndrome, but chlorpheniramine in treatment of upper airway cough syndrome is not associated with rhinitis/sinusitis treatment.

Chlorpheniramine attenuates histamine-mediated aquaporin 5 downregulation in human nasal epithelial cells via suppression of NF-κB activation.

Background: Aquaporin 5 (AQP5) is most likely the primary water channel in the human nasal mucosa and acts as a key tight junction protein. The signaling cascades responsible for AQP5 regulation are still works in progress. Objective: This study sought to determine the effects of histamine and chlorpheniramine on AQP5 expression in human nasal epithelial cells (HNEpC) and to detect the signaling cascades responsible for these effects. Methods: HNEpC were cultured with four concentrations of histamine or chlorpheniramine in vitro. The sub-cellular distribution of AQP5 was explored using immunocytochemistry. The pharmacologic effects of histamine and chlorpheniramine on the expression of the phosphorylation of cyclic adenosine monophosphate-responsive element binding protein (p-CREB), the AQP5 and the NF-κB protein were examined using Western blotting. Results: AQP5 was found to be located in cell membrane and cytoplasm and present in every group without significant difference. Histamine inhibits the expression of AQP5 and p-CREB in HNEpC, while chlorpheniramine dose-dependently increases these protein levels with statistical significance. HNEpC treated with histamine and chlorpheniramine in turn showed the same trends as those intervened separately with these two drugs. Moreover, chlorpheniramine had the ability to reverse the inhibitory effect of histamine. Western blotting analysis revealed that after incubation with 10-4 M histamine, NF-κB protein was significantly heightened by 165% compared with the untreated control group. Again, such increase can be significantly reversed after chlorpheniramine treatment. Conclusions: The current study demonstrated that histamine inhibits CREB phosphorylation in HNEpC, which results in decreased AQP5 expression via activation of NF-κB pathway. Chlorpheniramine attenuates the inhibitory effect of histamine in p-CREB/AQP5 expression via suppression of NF-κB signal cascades. This observation could provide additional insight into the anti-inflammatory effects of H1-antihistamines that contribute to maintain airway surface liquid and mucosal defense.

Spinal SET7/9 may contribute to the maintenance of cancer-induced bone pain in mice.

Cancer-induced bone pain (CIBP) profoundly influences patients' quality of life. Exploring the mechanisms by which CIBP occurs is essential for developing efficacious therapies. Various studies have shown that proinflammatory factors were involved in CIBP. SET domain containing lysine methyltransferase 7/9 (SET7/9) may modulate the expression of NF-κB-dependent proinflammatory genes in vitro. However, whether SET7/9 may participate in the maintenance of CIBP remains unknown. In this study, NCTC 2472 cells were inoculated into the intramedullary space of the femur to establish a mouse model of CIBP. Upregulation of spinal SET7/9 expression was related to pain behaviours in tumour-inoculated mice. Intrathecal cyproheptadine (10 or 20 nmol) attenuated response to painful stimuli in a dose-dependent manner. Moreover, there was a concomitant decrease in spinal SET7/9 and RANTES expression. The antinociceptive effects of cyproheptadine were abolished by pre-intrathecal administration of SET 7/9 (0.2 µg) for 30 minutes before intrathecal cyproheptadine (20 nmol) administration. These results indicated that spinal SET7/9 may contribute to the maintenance of CIBP in mice. Hence, targeting of spinal SET7/9 might be a useful alternative therapy for the treatment of CIBP.

Characteristics of scratching behavior in ADJM mice (atopic dermatitis from Japanese mice).

In order to elucidate the characteristics of scratching behavior in atopic dermatitis from Japanese mice (ADJM) mice, the effects of some antagonists of pruritogens on this behavior were studied. Both male and female ADJM mice showed frequent scratching behavior around the face, abdomen and back. The number of scratching behavior around the face was greater than on the abdomen and back, and scratching behavior in female mice was significantly more frequent than in male mice. Histamine H1 antagonist, chlorpheniramine, p.o., inhibited this behavior potently and dose-dependently. Histamine H1 antagonist with serotonin 5-TH(5-hydroxytryptamine)2 antagonist, cyproheptadine, also inhibited this behavior. However, NK1 antagonist, aprepitant, p.o., had no significant inhibitory effect even at a dose of 100 mg/kg, p.o., Mu antagonist, naloxone, and kappa agonist, nalfurafine, significantly inhibited this behavior at doses of 0.3 mg/kg, s.c., and 0.01 mg/kg, p.o., respectively. Histamine contents in the skin of ADJM mice were significantly higher than in BALB/c mice. These results strongly indicate that scratching behavior in ADJM mice is related with histamine H1, opioid mu and opioid kappa receptors.

Successful readministration of trastuzumab after severe immune reactions in two breast cancer patients.

Trastuzumab is a standard treatment in breast cancer overexpressing Her2 oncogene. However, its administration carries the risk of severe immune adverse events which often lead to the discontinuation of trastuzumab. There is no clear guideline on how patients experiencing trastuzumab-related reaction should be rechallenged with the monoclonal antibody. Here, we present two case reports of patients who have presented severe anaphylactic reactions during trastuzumab infusion. Both of them have been successfully rechallenged in intensive care units with premedication, lower rate of infusion and vitals monitoring. Thereafter, trastuzumab could be continued without any serious adverse reaction. Given the positive impact of trastuzumab on patients' survival, treatment rechallenge should be carefully considered in patients who presented anaphylactic reactions.

Evaluation of the comparative efficacy and safety of artemether-lumefantrine, artesunate-amodiaquine and artesunate-amodiaquine-chlorpheniramine (Artemoclo™) for the treatment of acute uncomplicated malaria in Nigerian children.

OBJECTIVE: To evaluate the comparative efficacy and safety of artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ) and artesunate-amodiaquine-chlorpheniramine (AQC) for the treatment of acute uncomplicated malaria among Southwest Nigerian children. SUBJECTS AND METHODS: One hundred and sixty children aged 6 months to 14 years with acute uncomplicated malaria were randomized to AL (n = 53), ASAQ (n = 53), or AQC (n = 54). Enrollees were seen daily on days 0-3 and then on days 7, 14, 21, 28 and 42 for clinical and parasitological evaluations. Paired samples of genomic DNA at enrolment and at the time of recurrent parasitaemia were genotyped using nested PCR to distinguish between reinfection and recrudescence. Detailed haematological and biochemical evaluations were carried out in a subset of enrollees on days 0, 7 and 28 as part of a safety evaluation. RESULTS: Of the 160 children, 144 (90%) completed the study. The mean fever clearance times and parasite clearance times for AL, ASAQ and AQC were comparable (p = 0.94 and p = 0.122, respectively). On day 14, the adequate clinical and parasitological response (ACPR) for AL and AQC was 100% and for ASAQ it was 90% (p = 0.39). The PCR-uncorrected results on days 28 and 42 and the ACPR-corrected results on day 42 were similar for all drugs (p = 0.62 and p = 0.56, respectively). AQC resulted in the best parasite clearance and haematological recovery on day 2 (p = 0.022 and p = 0.018, respectively). Biochemical parameters were not adversely affected by the three artemisinin-based combination therapies (ACTs) and these were well tolerated. CONCLUSION: The three ACTs were efficacious and safe, but AQC resulted in a better haematological recovery on day 2 and higher cure rates throughout the study period.

[A case study of anaphylaxis in a pregnant woman]. / Choque anafiláctico en una gestante en el tercer trimestre de embarazo.

We report a case of anaphylaxis in a 35+5 week of pregnancy patient who came to the Emergency Room with shortness of breath, hypotension and loss on fetal wellbeing. Due to her medical history and given the clinical picture at that time, an anaphylactic shock was suggested as the most probable diagnose. The administration of dexchlorpheniramine and methylprednisolone resulted in an immediate and positive reaction. Simultaneously, an improvement in the fetus cardiotocographic record was objectified. The patient was hospitalized for 48 hours, after which she was discharged. In case of suspicion of anaphylaxis in a pregnant woman, four aspects should be handled: the severity of the anaphylaxis chart, individual complications regarding a pregnant woman, unfavorable effects of the regularly used treatment during that specific gestation, and the need of fetal extraction based of gestational age.

Current drugs for the treatment of dry cough.

Cough is one of the commonest symptoms of respiratory tract infections and is a frequent problem encountered in general practice as well as in hospital practice. A wide range of disease processes may present with cough and definitive treatment depends on identifying the cause and diagnosis. Specific treatment of the cause should control the cough, but this may not occur in all cases and in a sizeable proportion of patients, no associated cause can be found. An increased sensitivity of the cough reflex can be observed in patients with dry cough. Symptomatic relief must be considered when the cough interferes with the patient's daily activities and this is effectively treated with antitussive preparations which are available as combinations of codeine or dextromethorphan with antihistamines, decongestants and expectorants Antitussives are used for effective symptomatic relief of dry or non-productive cough. First generation antihistamines like chlorpheniramine and centrally acting opioid derivatives like codeine are often used alone or in combination in the management of nonspecific cough. Sedation caused by these is valuable, particularly if the cough is disturbing the sleep. Although there is extensive experimental data on single agent antitussives and antitussive combinations, there is a major paucity of published literature on these combinations in nonspecific cough. Treatment of dry cough remains a challenge in some patients and this article reviews the scope of the current drugs and combination of Codeine and Chlorpheniramine in the effective management of dry cough.

Focal rituximab-induced edematous reaction at primary cutaneous follicle center lymphoma lesions: case report and literature review.

Primary cutaneous follicle center lymphoma (PCFCL) is the most common cutaneous B cell lymphoma. It is most often indolent and responds well to rituximab. We present a case of transient rituximab-induced edematous lesions located exclusively on tumor papules in a patient treated for PCFCL. Based on this observation and on a review of the literature, we discuss the mechanism of this edematous reaction which does not seem to be allergic. Indeed, this focal reaction observed solely during the first infusion of rituximab is more likely linked with local cytokine release induced by B cell lysis in the skin. This reaction is neither unusual nor severe and should not lead to an interruption of rituximab.