Documenting asthma severity: do we get it right?

BACKGROUND: The 1997 National Asthma Education and Prevention Program (NAEPP) recommends a severity classification scheme to optimize the use of anti-inflammatory therapy for persistent asthma. Physician documentation of asthma severity is often used as a quality assurance measure. OBJECTIVE: To test the hypothesis that physician documentation of asthma severity is associated with appropriate use of anti-inflammatory therapy. DESIGN/METHODS: Setting: inner-city academic health center. First, we reviewed a consecutive sample of charts of scheduled pediatric patients. Then, we administered a structured parent survey regarding the child's asthma symptoms and current asthma therapy. We used NAEPP guidelines to classify patients' severity of asthma. The main outcome measure was appropriate use of anti-inflammatory therapy. Appropriate therapy was defined as: (1) mild persistent asthmatics using anti-inflammatory therapy, and (2) moderate-severe persistent asthmatics using inhaled steroids. Chart classification of asthma severity was compared with the NAEPP-applied classification. RESULTS: Of 784 charts, 214 (27%) were asthmatic. Of these, 176 (82%) were surveyed. The mean age was 7.4 years; 61% were males. Severity classification was documented in 77% of charts. Chart documentation differed significantly from survey classification for the same patients: (mild intermittent 54% vs. 40%, mild persistent 21% vs. 14%, moderate persistent 24% vs. 36%, severe persistent 1% vs. 10%; all p < .001). Correctly classified patients were more likely to be on appropriate therapy. CONCLUSIONS: Physicians underestimated the severity classification of asthmatic patients. Incorrect classification was associated with inappropriate asthma therapy. These findings have implications for the institution of asthma quality improvement programs.     

Term delivery in a woman with severe congenital neutropenia, treated with growth colony stimulating factor

The patient was diagnosed in childhood as having severe congenital neutropenia and had recurrent admissions with severe infections. In 1987, prior to getting married, she was sterilized. She continued to require i.v. antibiotics when she contracted a severe infection. On one occasion, she was treated with growth colony stimulating factor (G- CSF). Her increased neutrophil count was sustained following this treatment. In June 1993, she wished to start a family and underwent in- vitro fertilization (IVF) treatment. G-CSF was given prior to oocyte retrieval. She conceived on her first cycle and an ultrasound scan revealed a singleton pregnancy. Throughout the course of the pregnancy, her white cell count was monitored closely and remained at <1.0x10(9)/l. The pregnancy progressed uneventfully and at 37 weeks gestation she was admitted for G-CSF injections. At 38 weeks she was delivered of a boy weighing 3350 g, by elective Caesarean section. His white cell count was normal. This is the first case of G-CSF being used before conception and during pregnancy in a patient with congenital neutropenia. It shows that advances in cytokine therapy and close interdisciplinary liaison can lead to a successful outcome and help patients, who would otherwise remain childless, to achieve a family.      

Concentrations of domestic mite and pet allergens and endotoxin in Palestine

BACKGROUND: A few studies have compared indoor allergens and endotoxin levels between urban and rural settings as important determinants for asthma and atopy in children. However, no study was done in the Middle East or investigated refugee camps. METHODS: As part of a nested case-control study in Ramallah in 2001, we measured house dust mite and pet allergens, as well as endotoxin in dust collected from 110 children's mattresses and living room floors. RESULTS: Geometric mean (GM) concentrations of Dermatophagoides pteronyssinus (Der p1) antigen were 4.48 microg/g in mattress dust and 1.23 microg/g floor dust. The highest Der p1 levels were seen in refugee camps. Concentrations of Dermatophagoides farinae antigen (Der f1) were much lower (<0.08 microg/g dust). Concentrations of cat allergen (Fel d1) were highest in villages, and those of dog allergen (Can f1) were highest in mattresses from cities and in floor dust from refugee camps. GM of endotoxin levels were 25.7 EU/mg in mattress dust and 49 EU/mg dust in floor dust. CONCLUSIONS: Concentrations of Der p1 were high compared to Western European countries, but were lower compared to UK and Australia. Levels of pet allergens were lower than in Western Europe. Endotoxin levels were higher compared to developed countries. Indoor environmental factors such as dampness seemed to be important determinants for allergen and endotoxin, but living habits such as lack of mattress cover appeared unimportant.     

Dipeptidyl peptidase 9 sets a threshold for CARD8 inflammasome formation by sequestering its active C-terminal fragment

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Female Genital Cutting and Deinfibulation: Applying the Theory of Planned Behavior to Research and Practice

At least 200 million girls and women across the world have experienced female genital cutting (FGC). International migration has grown substantially in recent decades, leading to a need for health care providers in regions of the world that do not practice FGC to become knowledgeable and skilled in their care of women who have undergone the procedure. There are four commonly recognized types of FGC (Types I, II, III, and IV). To adhere to recommendations advanced by the World Health Organization (WHO) and numerous professional organizations, providers should discuss and offer deinfibulation to female patients who have undergone infibulation (Type III FGC), particularly before intercourse and childbirth. Infibulation involves narrowing the vaginal orifice through cutting and appositioning the labia minora and/or labia majora, and creating a covering seal over the vagina with appositioned tissue. The WHO has published a handbook for health care providers that includes guidance in counseling patients about deinfibulation and performing the procedure. Providers may benefit from additional guidance in how to discuss FGC and deinfibulation in a manner that is sensitive to each patient’s culture, community, and values. Little research is available to describe decision-making about deinfibulation among women. This article introduces a theoretically informed conceptual model to guide future research and clinical conversations about FGC and deinfibulation with women who have undergone FGC, as well as their partners and families. This conceptual model, based on the Theory of Planned Behavior, may facilitate conversations that lead to shared decision-making between providers and patients.

     

Opposite links of positive and negative symptomatology with memory errors in schizophrenia

We wished to confirm and extend a previous correlational study of our group, suggesting that positive symptoms in schizophrenia were linked to an increase in certain types of memory errors, and negative symptoms to a decrease in other types of errors. A post-hoc analysis was conducted in 33 schizophrenic patients and 40 normal control subjects on memory errors collected in a free recall task and two types of recognition tasks. The memory errors were intrusions and list errors in free recall, and decision bias towards false alarms in recognition, all assumed to reflect a source-monitoring failure. In a first analysis, the patient sample was split along the median for positive symptoms as rated by the Scale for the Assessment of Positive Symptoms (SAPS). In a second analysis, it was split along the median for negative symptoms as rated by the Scale for the Assessment of Negative Symptoms (SANS). Patients with high ratings of positive symptoms made more memory errors (intrusions, list errors, false alarms) than those with low ratings, supporting the hypothesis of a link between positive symptomatology and source-monitoring failure. On the other hand, patients with high ratings of negative symptoms made fewer of these errors than the other patients. Fewer errors were specifically associated with more affective flattening, alogia and anhedonia, whereas avolition was entirely unrelated to them.     

A current appreciation of sites for pharmacological intervention in allergic conjunctivitis: effects of new topical ocular drugs.

Two important realizations about pathophysiological mechanisms involved in allergic conjunctivitis have led to novel drug discovery efforts and new topical ocular medications for prevention and treatment of this prevent allergic disease. The first of these, interspecies and intraspecies mast cell heterogeneity, was established in the mid-1980's by investigators working in the field of asthma. It is now appreciated that secretory responses as well as effects of pharmacological agents differ depending upon the mast cell population studied. Two types of human mast cells, the tryptase containing (T) and the tryptase/chymase containing (TC) mast cells, have been characterized in a variety of tissues. Significantly, Irani et al. (1) demonstrated by immunohistochemical staining that the mast cells present in conjunctival tissues from patients with allergic conjunctivitis were 100% TC. Functional responses of human conjunctival mast cells to a variety of secretagogues (2) were consistent with their classification as TC or connective tissue type mast cells. Importantly, the studies by Miller et al. mentioned above allowed the harvesting and preparation of human conjunctival mast cells for use in drug screening studies. Utilization of these cells has led to the identification of Patanol, the most effective human conjunctival mast cell stabilizer available for topical use in allergic conjunctivitis (3). These same studies demonstrated the lack of mast cell stabilizing activity for cromolyn and nedocromil in these connective tissue type, TC containing, human conjunctival mast cells. Similar lack of effect was noted with these drugs on human skin mast cell degranulation (4). The second important discovery in the area of allergic conjunctivitis has been the demonstration that conjunctival epithelial cells may contribute to the perpetuation of the allergic response. A report from Gamache et al. (5) identified cytokines produced by human conjunctival epithelial cells following treatment with a number of stimuli. Significantly, Sharif et al. (6) subsequently identified functional histamine H1 receptors on these same cell types. Recently, Weimer et al. (7) have shown that exposure of human conjunctival epithelial cells to histamine leads to the production of pro-inflammatory cytokines IL-6 and IL-8. Importantly, treatment of the epithelial cells with drugs that possess histamine H1 antagonist properties prevents cytokine production. It is noteworthy that first generation anti-histamines antazoline and pheniramine are not potent inhibitors of histamine-stimulated cytokine synthesis in intact epithelial cells, while newer anti-histamines Emadine and levocabastine are more potent. Surprisingly, Patanol was more potent as an inhibitor of histamine-stimulated cytokine production by the epithelial cells than would be predicted from its histamine H1 antagonist affinity. These inhibitory effects on conjunctival epithelial cell production of pro-inflammatory cytokines may contribute to enhanced clinical activity noted with these recently approved drugs.     

Modification of naloxone-precipitated withdrawal symptoms in mice by drugs acting on alpha(2)-adrenoceptors

Modification of naloxone-precipitated withdrawal symptoms by drugs acting on alpha-adrenoceptors was investigated in morphine-dependent mice. Clonidine (0.05-1mg/kg) attenuated most withdrawal symptoms, but potentiated withdrawal hypothermia. Jumping was attenuated by doses of clonidine up to 0.3mg/kg, but markedly potentiated by 1mg/kg. Prazosin (0.05mg/kg) neither had effects of its own, nor influenced those of clonidine. Both yohimbine (0.05-5mg/kg) and idazoxan (1-10mg/kg) potentiated naloxone-precipitated withdrawal symptoms. When tested against a low dose of clonidine (0.2mg/kg), idazoxan dose-dependently reduced the suppressive effects of clonidine on jumping, "wet dog" shakes, burrowing and body-weight loss but potentiated the hypothermic response of clonidine. Yohimbine similarly reduced the suppressive effect of clonidine on body-weight loss and potentiated its hypothermic response, but unlike idazoxan, it did not influence the inhibition by clonidine of "wet dog" shakes, and markedly reversed the suppression of jumping and burrowing into potentiation. Yohimbine and idazoxan also differed with respect to their antagonistic profile against a high dose of clonidine (1mg/kg). Yohimbine further aggravated the potentiation of jumping by clonidine, reduced the effect on body-weight loss and reversed the suppression of burrowing by clonidine. On the other hand, idazoxan markedly reduced the potentiation of jumping by clonidine, and reversed its effect on "wet dog" shakes and burrowing. These findings indicate that clonidine has a biphasic effect on jumping, and disclose differences in the antagonistic profiles between yohimbine and idazoxan. The results suggest that in addition to alpha(2)-adrenoceptors, non-adrenergic imidazoline receptors sensitive to clonidine and idazoxan but not to yohimbine may modulate the expression of morphine withdrawal symptoms.     

Intractable hiccup induced by brainstem lesion

Four patients with brainstem lesions presented with intractable hiccup and mild to moderate neurological signs. Two of the patients had been initially diagnosed as having a psychogenic cause for their hiccup. Magnetic resonance imaging (MRI) demonstrated brainstem infarction in one case, tuberculoma at the junction of the medulla oblongata and the cervical spinal cord in two, and a vermian tuberculoma compressing the brainstem in one. The brainstem infarct and one of the medullary tuberculoma were not detected on high resolution enhanced computed tomography. The 3 patients with CNS tuberculoma were free of hiccup 1-5 months after antituberculous chemotherapy. It is proposed that hiccup is not an abnormal reflex, but a myoclonus generated by repetitive activity of the "inspiratory solitary nucleus" due to release of higher nervous system inhibitory/-regulatory control. The neuroanatomical network and the mechanisms underlying the formation of intractable hiccup are outlined. The value of MRI in the initial diagnosis and follow-up of patients with intractable hiccup due to brainstem lesions is emphasised.