Clozapine-associated neutropenia following augmentation with sodium valproate.

Clozapine is gold standard for the management of treatment-resistant schizophrenia. It can offer life-changing symptom reduction where other antipsychotics have failed, and for these patients, treatment with clozapine should be maintained, if in any possible way. However, treatment with clozapine comes with a risk of developing potentially fatal adverse reactions, for example, severe neutropenia or agranulocytosis, in which case, treatment must be discontinued. Here, we present a case of clozapine-related neutropenia that commenced after the addition of sodium valproate. A subsequent re-challenge to clozapine resulted in severe neutropenia and led to the permanent cessation of clozapine treatment. The patient had been tolerating clozapine for more than a year before the addition of sodium valproate. The awareness of an interaction between clozapine and sodium valproate could help reduce the risk of clozapine-induced neutropenia and subsequent clozapine discontinuation.

Adherence to protocol in pregnant trauma patients? A 12-year retrospective study.

PURPOSE: We investigated whether the standard (ATLS) trauma protocol was adhered to in cases of suspected multi-traumatized pregnant patients and if serious injuries were overlooked. We hypothesized that radiographic studies would be less frequent in pregnant trauma patients. METHODS: Forty-eight pregnant trauma patients were received in the observational period from January 2000 until May 2012; median age 30 years (range 16-40) and median stage of pregnancy 22 weeks (range 4-40). A retrospective review of patient files was performed. RESULTS: Twenty-one percent of the pregnant trauma patients received a full trauma CT (T-CT) scan (head to pelvis), which was significantly lower than the percentage (62 %) of all primarily referred trauma patients in the same period. In the last four years of observation, the use of radiographic studies among pregnant trauma patients increased considerably. Along with this increase in the tendency to use T-CT over time during the observational period, there was also a rise in the median ISS. In addition, radiographic studies of the pelvis and abdominal area were performed only half as frequently as studies of the neck and chest. CONCLUSIONS: Adherence to the ATLS protocol in pregnant trauma patients was low in relation to radiographic studies but, in spite of this, no known significant injuries were missed. We found that a pelvic fracture seems to be predictive of a high risk of obstetric complications, such as intrauterine death or the need for cesarean section, but we were not able to relate trauma in general to a higher risk of cesarean section or premature birth.

Survival of autotransfused red cells. 51Cr studies in 10 knee arthroplasty patients.

We determined the long-term survival of red blood cells collected postoperatively from the surgical drains, filtered and autotransfused with the Constavac Blood Conservation System. 10 patients with knee arthrosis were treated with cementless total knee arthroplasty and postoperatively connected to the autotransfusion system. Shed blood was collected for 6 hours postoperatively and then reinfused. Before reinfusion, a fraction of the blood shed was radiolabeled with chromium-51 (51Cr). For a postoperative minimum period of 40 days the activity of 51Cr was measured in frequent venous blood samples. The time from 100% to 50% activity of the isotope (T50Cr) was 21 days, equal to that reported for banked autologous blood.

Early and late nasal symptom response to allergen challenge. The effect of pretreatment with a glucocorticosteroid spray.

We challenged 30 pollen-sensitive volunteers with allergen, recorded symptoms and signs over a 10-h period, and rechallenged them after 24 h, in order to characterize the early and late allergic symptom response in the nose. The challenge was performed after topical pretreatment with the glucocorticosteroid budesonide (200 micrograms twice daily) for 14 d and with placebo in a double-blind, cross-over trial. The early response, consisting of sneezing, discharge, and blockage, was followed by a weak late response, consisting of a few sneezes and nose-blowings, and of a sustained nasal blockage. These symptoms did not have a well-defined peak in time, and a biphasic symptom curve could not be identified. The rechallenge response showed increased nasal responsiveness. The degree of budesonide effect on the early response varied, depending on the symptom; there was a marked effect on sneezing (72% reduction; P < 0.01), a moderate effect on discharge (37% reduction; P < 0.01), and a slight effect on blockage (17% reduction of nasal inspiratory peak flow rate; P < 0.02). The degree of inhibition of the rechallenge response was similar to the effect on the initial early response. The effect on the late response was very pronounced for all symptoms and signs (97% reduction of sneezes, 76% reduction of nose-blowings, 96% reduction of blockage; P < 0.01). In conclusion, we found it difficult in the individual subject to identify a well-defined late symptom response by criteria similar to those employed to characterize the late response in the bronchi. The effect of budesonide was more marked on sneezing than on blockage, and the drug was considerably more effective on the late response than on the early response.

Allergen-induced increase of eosinophil cationic protein in nasal lavage fluid: effect of the glucocorticoid budesonide.

It was our aim to study the effect of nasal allergen provocation on the concentration of eosinophil cationic protein (ECP) in nasal lavage fluid, with and without glucocorticoid pretreatment. Twenty grass-pollen sensitive volunteers were provoked outside the pollen season on 2 consecutive days after pretreatment for 2 weeks with the glucocorticoid, budesonide, as a nasal spray (400 micrograms/day) and with placebo with a double-blind, crossover design. Nasal lavage fluid was repeatedly collected during a 10-hour period to study both early and late-phase responses. 99mTechnetium-albumin was added to the lavage fluid, making it possible to calculate the amount of secretion and the degree of dilution. The results were as follows: (1) There was no correlation between ECP concentration and dilution factor in the individual samples. (2) The mean concentration of ECP in lavage fluid from untreated, prechallenge noses was 400 micrograms/L. (3) The ECP level did not increase during the early phase response. (4) There was a late occurring increase in the ECP concentration (6 to 24 hours). (5) This increase was completely inhibited by budesonide pretreatment. (6) The glucocorticoid therapy also reduced the prechallenge ECP concentration. In conclusion, allergen provocation in the nose results in a late occurring increase of ECP in nasal lavage fluid, and one of the therapeutic effects of topical glucocorticoid therapy may be an inhibition of the allergen-induced increase of this cytotoxic molecule.

Seasonal allergic rhinitis and depot injection of a corticosteroid. Evaluation of the efficacy of medication early and late in the season based on detailed symptom recording.

It was the aim of this investigation to study the efficacy of a corticosteroid given as a depot injection in seasonal allergic rhinitis, the efficacy profile with regard to specific symptoms, and whether the injection is best given early in the season or later at the peak of the pollen count. An injection of 80 mg methylprednisolone showed a marked effect on nasal blockage lasting more than 4 weeks, and a moderate effect on eye symptoms, while the effect on nasal hypersecretion and sneezing could not be demonstrated. It is concluded that systemic corticosteroids may be indicated in severe hay fever, when symptoms, especially blockage, occur in spite of other types of therapy. If the physician prefers to give the corticosteroid as a depot injection, it is preferably given in the first half of the season when the pollen count is increasing.

Histamine and methacholine do not increase nasal reactivity.

Allergen provocation in the nose increases the non-specific nasal reactivity. The aim of this trial was to determine whether this 'priming effect' can be caused by histamine or methacholine, which is the most important biochemical mediator of allergic rhinitis, and an analogue to the important neurotransmittor, acetylcholine, respectively. Intranasal provocation tests with the two substances were carried out on thirteen normal subjects, and repeated 1 hr and 1 day later. The response, measured as the number of sneezes, the amount of blown secretion and the increase in nasal airway resistance, did not change with consecutive provocations. It was concluded that neither histamine nor methacholine were responsible for the allergen-induced 'priming' of the nasal mucous membrane.

Study of bacteria in the nasal cavity and nasopharynx during naturally acquired common colds.

It was the purpose of this study to examine whether the number of bacteria in the nose and nasopharynx changes during a common cold. Samples for bacteriological culture were taken from the nasal cavity of 29 and from the nasopharynx of 26 adult patients with naturally acquired colds. The bacteriological samples were taken on days 2, 4, 8 16, 32 and 64 after the first nasal symptoms. The results showed that there were few pathogenic bacteria in the nasal cavity and nasopharynx. There was no tendency to an increase in the number of positive cultures during the cold, although most patients had macroscopically purulent discharge on days 3-5. In conclusion, the study indicates that during an uncomplicated common cold, a bacterial infection is not responsible for the occurrence of purulent nasal discharge which may be a direct consequence of the viral infection.

Effects of oral norephedrine on common cold symptoms.

The aim of the trial was to examine the effectiveness of an oral decongestant in common cold. Thirty subjects with naturally acquired colds got a 100 mg sustained release tablet containing norephedrine on one day and a placebo tablet on another day in double blind design. Changes in nasal patency were assessed by rhinomanometry, measurement of nasal expiratory peak flow, and a self-assessment test, and the number of sneezes and of nose blowings were recorded in a 10 hours period after medication. Rhinomanometry, but not peak flow measurements showed a significant difference (p less than 0.02) two hours after medication, and the self-assessment of nasal blockage showed that the effect lasted for the entire 10 hours observation period (p less than 0.01). Nasal respiration was reestablished in half of the blocked noses. There was no effect on number of sneezes and nose blowings. In conclusion, oral norephedrine has a moderate decongestant effect, which may justify its use in adults with common colds. This symptom amelioration must be balanced against cost of therapy and risk of side effects. A prevention of otitis media and of sinusitis has not been documented in the literature.

Nasal reactivity in rhinitis.

The purpose of this review is to present data on nasal reactivity to methacholine, histamine and allergen in normal subjects, patients with common colds, perennial rhinitis and hay-fever. Nasal challenge is performed by spraying the agent into the nose and counting the sneezes, measuring the resulting secretion and the increase in nasal airway resistance during a 15 minute period. We found that there was a small increase in reactivity during a common cold, but a considerable increase during the hay-fever season and associated with perennial rhinitis. We conclude that a nasal challenge test may be a valuable tool as an objective parameter for the diagnosis and for the estimation of the severity of rhinitis. It may also be helpful in the evaluation of new drugs and give information regarding pathogenetic mechanisms as well as the mode of action of specific drugs.