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Insect sting allergy with negative venom skin test responses.

BACKGROUND: In our 1976 controlled venom immuno rapy trial, 33% of 182 patients with a history of systemic reactions to insect stings were excluded because of negative venom skin test responses. There have been reports of patients with negative skin test responses who have had severe reactions to subsequent stings. OBJECTIVE: Our aim is to increase awareness about the patient with a negative skin test response and insect sting allergy and to determine the frequency and significance of negative skin test responses in patients with a history of systemic reactions to insect stings. METHODS: We prospectively examined the prevalence of negative venom skin test responses in patients with a history of systemic reactions to stings. In patients who gave informed consent, we analyzed the outcome of retesting and sting challenge. RESULTS: Of 307 patients with positive histories screened for our sting challenge study, 208 (68%) had positive venom skin test responses (up to 1 microg/mL concentration), and 99 (32%) had negative venom skin test responses. In 36 (36%) of the 99 patients with negative skin test responses, the venom RAST result was a low positive (1-3 ng/mL), or repeat venom skin test responses were positive; another 7 (7%) patients had high venom-specific IgE antibody levels (4-243 ng/mL). Notably, 56 (57%) of 99 patients with positive histories and negative skin test responses had negative RAST results. In patients with positive skin test responses, sting challenges were performed in 141 of 196 patients, with 30 systemic reactions. Sting challenges were performed on 37 of 43 patients with negative skin test responses and positive venom-specific IgE and in 14 of 56 patients with negative skin test responses and negative RAST results. There were 11 patients with negative skin test responses who had systemic reactions to the challenge sting: 2 had negative RAST results, and 9 had positive RAST results at 1 ng/mL. The frequency of systemic reaction was 21% in patients with positive skin test responses and 22% in patients with negative skin test responses (24% in those with positive RAST results and 14% in those with negative RAST results). CONCLUSIONS: Venom skin test responses can be negative in patients who will subsequently experience another systemic sting reaction. Venom skin test responses are negative in many patients with a history of systemic allergic reactions to insect stings and may be associated with positive serologic test responses for venom-specific IgE antibodies (sometimes strongly positive results). Venom skin test responses should be repeated when negative, along with a serologic IgE antivenom test. Better diagnostic skin test reagents are urgently needed.

Academic Medical Centers↗

Negative concord in child African American English: implications for specific language impairment.

In this study, African American English (AAE)-speaking children's comprehension of 2 different types of double negative sentences was examined and contrasted with that of a comparison group of Standard American English (SAE)-speaking children. The first type of double negative, negative concord, involves 2 negative elements in a sentence that are interpreted together as single negation. The second type of double negative, called true double negation, involves 2 negatives that are interpreted as independent negatives. A cross-sectional cohort of 61 (35 AAE, 26 SAE) typically developing children ranging in age from 5;2 (years;months) to 7;11 participated. The children responded to story-based grammatical judgment tasks that required them to differentiate between negative concord and true double negation. Results revealed no statistically significant differences between AAE- and SAE-speaking children in the way they interpreted negative concord and true double negation. However, there were significantly more correct responses to negative concord sentences across combined groups. In particular, the older children (i.e., 7-year-olds) produced more correct responses to negative concord than did the younger group (i.e., 5-year-olds). Explanations for these findings are framed in terms of children's knowledge about sentences with 2 negatives, the constraints affecting the interpretation of 2 negatives that include negative concord, and the clinical importance of negative concord for assessing specific language impairment in child AAE speakers.

Black or African American↗

Persistent negative symptoms in schizophrenia: an overview.

Persistent negative symptoms represent an alternative approach for assessing negative symptoms in the context of clinical trials. Persistent negative symptoms are designed to capture those symptoms that lead to functional impairment but are currently understudied and for which there are no currently available effective treatments. Persistent negative symptoms differ from the 2 most commonly used approaches: primary, enduring negative symptoms or deficit symptoms and negative symptoms broadly defined to include negative symptoms, regardless of their etiology or duration. In contrast to deficit symptoms, persistent negative symptoms may include secondary negative symptoms. However, in contrast to negative symptoms broadly defined, the secondary negative symptoms included in the assessment of persistent negative symptoms only include those that have failed to respond to usual treatments for secondary negative symptoms. In consequence, the presence of persistent negative symptoms identifies a patient population with clinically relevant symptomatology, which is larger than the one with the deficit syndrome but less heterogeneous than that captured through the use of a nonrestrictive definition of negative symptoms. This may facilitate the selection of subjects for inclusion into research and efforts to develop new pharmacological treatments and enhance our understanding of a relevant clinical problem. Ultimately, the investigation of the different entities characterized by negative symptoms, such as persistent negative symptoms, and the enhanced understanding of their biological and clinical characteristics may help to unravel the psychopathological and biological heterogeneity of schizophrenia.

Affect↗

False-negative results in screening programmes: systematic review of impact and implications.

BACKGROUND: When assessing whether a screening programme is appropriate, there is a particular obligation to ensure that the harms as well as the benefits are considered. Among these harms is the likelihood that false-negative results will occur. In some cases, the consequences of these can be difficult to assess, although false reassurance leading to diagnostic delay and subsequent treatment has been suggested. However, no test is totally accurate (with 100% sensitivity and specificity), and false-negative results are inherent in any screening programme that does not have 100% sensitivity. This review was carried out to assess the medical, psychological, economic and legal consequences of false-negative results that occur in national screening programmes. OBJECTIVES: (1) to determine the consequences of false-negative findings; (2) to investigate how their adverse effects can be minimised; to assess their implications for the NHS, including the impact of false-negatives on public confidence in screening programmes; to identify relevant theoretical perspectives that may be potentially useful when considering the implications of false-negative results. METHODS: A systematic literature review was carried out. This included a search of 18 electronic databases, various bibliographies and contact with experts to identify relevant literature and perspectives. Outcomes included in the review fell into four categories: medical outcomes (morbidity and mortality); psychological outcomes (distress, false reassurance, loss of confidence in services); economic outcomes (such as costs to the NHS); legal outcomes (such as litigation). Other outcomes, such as the impact of false-negatives on public confidence in screening programmes, were also included. The participants included individuals taking part in screening programmes, healthcare professionals and organisations responsible for screening programmes. Methodological details of the review are provided in the full report. RESULTS: A total of 6660 abstracts were screened, and 420 potentially relevant papers were identified. Most of the studies that were identified presented only anecdotal evidence. (1) Medical outcomes: In all, 13 papers presented quantitative information relevant to the medical consequences of false-negative results; seven of these were primary studies, and the remaining studies were literature reviews or models examining the likely impact of false-negative results. (2) Psychological outcomes: A total of eight published studies presented information on the psychological consequences of negative results in general; only one study, on antenatal screening, provided direct evidence of the psychological consequences of false-negative results, where they were associated with lower parental acceptance of the affected child and with blaming others for this outcome. (3) Economic outcomes: Only two studies presented information on the economic consequences. The strength of evidence from most of the primary studies was low. There is some evidence that false-negative results may have a large legal impact. For example, in cervical screening they have led to legal action and its associated costs, including payment of compensation; this is based on reports of events in both the UK and US health systems. There also seems to be a consensus in the literature that false-negatives may have a negative impact on public confidence in screening; evidence is again limited however. CONCLUSIONS: False-negatives are evident in all screening programmes, even when the quality of the service provided is high. They may have the potential to delay the detection of breast and cervical cancer, but there is little evidence to help assess their psychological consequences in these or other screening programmes. False-negatives are likely to lead to legal action being taken by those individuals affected, and potentially may reduce public confidence in screening. (ABSTRACT TRUNCATED)

False Negative Reactions↗

Prominent negative U wave in variant angina pectoris.

The extremely prominent negative U wave occasionally appears during a cardiac attack in variant angina pectoris. The clinical profile of the negative U wave was therefore studied in 80 patients with variant angina pectoris (VA) and 33 controls with resting angina pectoris (RA). The prominent negative U wave appeared in 55 of the patients with VA (68.8% of patients) and in 10 of the patients with RA (30.3%); thus, there was a significant difference in the appearance of the wave between the 2 groups of patients (p less than 0.001). The leads in which the negative U wave appeared were mostly consistent with those in which the ST segment was elevated. The negative U wave began to appear at about the time when ST-segment elevation began to improve; the wave then gradually became very prominent and then eventually disappeared. The patients with VA and also those with RA on whose ECGs the negative U wave appeared during exercise testing also had negative U waves during spontaneous episodes of angina. An investigation of the frequency of appearance of ST deviation and negative U waves during exercise testing, regardless of the type of angina pectoris, disclosed that the negative U wave appeared in 14 of 20 patients with ST-segment elevation (70% of patients), while the negative U wave appeared in only 52 of 519 patients with either no ST change or ST-segment depression (10.4%); thus, there was a significant difference in the appearance of the negative U wave between these 2 groups (p less than 0.001). Coronary cinearteriography failed to disclose any apparent difference between the appearance of the negative U wave and the presence of stenosis. The prognosis of VA and RA in patients with negative U waves was less favorable compared to those without negative U waves. In particular, we noted that of the 10 patients with RA associated with negative U waves, 4 died. Although the mechanism of the negative U wave is not yet known, we believe that the above findings contribute to its elucidation.

Adult↗

Liver enzyme abnormalities in gram-negative bacteremia of premature infants.

BACKGROUND: Hyperbilirubinemia and liver enzyme abnormalities are commonly observed in sepsis. However, the frequency in premature neonates and the specific relation to gram-negative bacteria are not known. PATIENTS AND METHODS: Charts of all preterm infants who had positive blood cultures for either gram-negative bacteria or coagulase-negative staphylococci were reviewed. Neonates with gram-negative bacteremia (n = 54) were compared with neonates with coagulase-negative staphylococcal bacteremia (n = 31). In addition infants with gram-negative bacteremia and elevated liver enzymes (n = 25) were compared with infants with gram-negative bacteremia and normal liver enzymes (n = 29). RESULTS: Liver enzyme abnormalities accompanied 46.3% (25 of 54) of gram-negative bacteremia and 12.9% (4 of 31) of episodes of coagulase-negative staphylococcal bacteremia (P = 0.002). Serum concentrations of liver enzymes were significantly higher in infants with gram-negative bacteremia than in those with coagulase-negative staphylococcal bacteremia (P < 0.0001), but no difference in alkaline phosphatase serum values was observed. Infants with gram-negative bacteremia and elevated liver enzymes were not fed for a longer period than infants with gram-negative bacteremia and normal liver enzymes (7.3 +/- 6.3 days vs. 4.0 +/- 4.3 days, P = 0.03), and this was accompanied by significant conjugated hyperbilirubinemia (P < 0.0001). Ventilation, total parenteral nutrition and medications were not responsible for the observed differences. Klebsiella pneumoniae bacteremia was commonly associated with elevated liver enzymes (12 of 18), whereas none of the infants with Pseudomonas aeruginosa bacteremia had elevated liver enzymes. CONCLUSIONS: Gram-negative bacteremia is commonly associated with cholestasis in premature neonates. Liver enzyme abnormalities are more common than elevated conjugated bilirubin, not all gram-negative bacteria have the same effect and the lack of enteral feeding seems to play a more significant role than the administration of parenteral nutrition.

Bacteremia↗

The function of retinoid X receptors on negative thyroid hormone response elements.

Retinoid X receptors (RXRs) form heterodimers with thyroid hormone receptors (TRs). RXRs increase DNA binding affinity of TRs and T3-mediated transactivation on positive T3 response elements (TREs). However, the role of RXRs on negative TREs, and the relation of RXRs to the dominant negative effect of mutant TRs, are not defined. To clarify the function of RXRs on negative TREs, we performed transient cotransfection studies using the rat glycoprotein hormone alpha promoter fused to luciferase gene (alphaLuc), and human TRH promoter fused to luciferase gene (TRH-Luc) as reporters. We found that the JEG-3 cell-alphaLuc system was very sensitive to TR regulation. Using TRbeta1 wild-type (WT) expression vector, 6.2 ng/well (170 ng/10 cm dish), and 0.2 ng/well (11 ng/10 cm dish) caused maximal, and half maximal, inhibition of Luc activities in the presence of 1 nM T3. A T3 dose dependent inhibition study was also performed. From these studies, we determined that the appropriate conditions in which to study alphaLuc transactivation, in a linear portion of the dose response curve, was using 0.8 ng/well TRbeta1 expression vector and 0.1 nM T3. Under these conditions, TRbeta1 mutant R316H (GH), but not G345R (Mf), showed a weak dominant negative effect at a 1:1 ratio in the presence of 0.1 nM T3 although neither mutant had detectable T3 binding affinity. Moreover this dominant negative effect of R316H on the alphaLuc reporter was enhanced in the presence of RXRgamma. Mutant G345R showed a stronger dominant negative effect than did R316H when using a double palindromic TRE fused to herpes simplex thymidine kinase-Luc reporter as a positive TRE. These results conform to the clinical features of R316H which is associated with apparent pituitary resistance of thyroid hormone (PRTH). Mutant R316H also showed a weak dominant negative effect with TRH-Luc at a 1:1 ratio in the absence or presence of RXRgamma. However RXRgamma did not enhance the dominant negative effect as it did using alphaLuc reporter gene. Electrophoretic gel mobility shift assay (EMSA) showed that RXR alpha augmented the DNA binding affinity of wild type and R316H TRs as heterodimers on the previously reported negative TREs of glycoprotein hormone alpha promoter, suggesting that RXR does not produce its response by removing TRs from these TREs. RXR alpha augmented DNA binding affinity of TRbeta1WT, and R316H showed a weaker heterodimer band than did the wild type in EMSA. Using the TRH-Luc reporter, basal activity was increased by wild type TRbeta1. However a TRbeta1 DNA binding domain mutant, (C127S) which can not bind to DNA, did not increase the basal activity. This indicates that DNA binding of the TR is required for increasing basal activity of TRH promoter. These results indicate that (1) RXR-TR heterodimers play a role in basal transactivation and T3 suppression of negatively regulated genes, and (2) RXRs increase the dominant negative effect of some mutant TRs on specific negative TREs. (3) This effect occurs without removing TRs from the TRE. (4) The differential dominant negative effect of mutant R316H (negative TRE > positive TRE) may explain, at least in part, the presentation of R316H as PRTH. (5) Augmentation of basal activity by wild type TRs on a negative TRE requires DNA binding.

Animals↗

A controlled trial of automated classification of negation from clinical notes.

BACKGROUND: Identification of negation in electronic health records is essential if we are to understand the computable meaning of the records: Our objective is to compare the accuracy of an automated mechanism for assignment of Negation to clinical concepts within a compositional expression with Human Assigned Negation. Also to perform a failure analysis to identify the causes of poorly identified negation (i.e. Missed Conceptual Representation, Inaccurate Conceptual Representation, Missed Negation, Inaccurate identification of Negation). METHODS: 41 Clinical Documents (Medical Evaluations; sometimes outside of Mayo these are referred to as History and Physical Examinations) were parsed using the Mayo Vocabulary Server Parsing Engine. SNOMED-C was used to provide concept coverage for the clinical concepts in the record. These records resulted in identification of Concepts and textual clues to Negation. These records were reviewed by an independent medical terminologist, and the results were tallied in a spreadsheet. Where questions on the review arose Internal Medicine Faculty were employed to make a final determination. RESULTS: SNOMED-CT was used to provide concept coverage of the 14,792 Concepts in 41 Health Records from John's Hopkins University. Of these, 1,823 Concepts were identified as negative by Human review. The sensitivity (Recall) of the assignment of negation was 97.2% (p < 0.001, Pearson Chi-Square test; when compared to a coin flip). The specificity of assignment of negation was 98.8%. The positive likelihood ratio of the negation was 81. The positive predictive value (Precision) was 91.2% CONCLUSION: Automated assignment of negation to concepts identified in health records based on review of the text is feasible and practical. Lexical assignment of negation is a good test of true Negativity as judged by the high sensitivity, specificity and positive likelihood ratio of the test. SNOMED-CT had overall coverage of 88.7% of the concepts being negated.

Abstracting and Indexing↗

Molecular biologic and scintigraphic analyses of somatostatin receptor-negative meningiomas.

UNLABELLED: Somatostatin receptor scintigraphy (SRS) using 111In-octreotide has proven useful in the preoperative discrimination of expansive central nervous system lesions. Meningiomas, generally expressing human somatostatin receptor (hsst) on their surface, were detected with a sensitivity of about 100%. This finding was associated with the assumption that meningiomas lack an intact blood-brain barrier. However, this exclusion procedure became questionable when histologically proven meningiomas in which SRS was negative were reported. Therefore, the aim of this study was to discover why these meningiomas gave negative SRS results. METHODS: Before surgery, 46 patients with 47 meningiomas underwent standard MRI and SRS. Thirty-four of these patients with 35 tumors were also examined by 99mTc-diethylenetriaminepentaacetic acid (DTPA) brain scintigraphy. After surgical resection, hsst subtype 2 (hsst2) messenger RNA (mRNA) expression of 4 SRS-positive and 4 SRS-negative meningiomas was estimated semiquantitatively by reverse transcriptase polymerase chain reaction (RT-PCR). Translation of hsst2 mRNA into receptor proteins was proven immunocytochemically on the surface of 1 SRS-positive and 1 SRS-negative meningioma. Tumor specimens used for RNA extraction and RT-PCR and cultivated cells used for hsst2 immunostaining were tested for their meningioma nature by immunochemistry. RESULTS: SRS yielded positive results in 39 meningiomas with a tumor volume of 24.1 +/- 32.8 mL and negative results in 8 meningiomas with a volume of 3.9 +/- 6.5 mL. 99mTc-DTPA scintigraphy visualized 24 of 35 meningiomas. SRS was positive in all of them. In contrast, 11 meningiomas were (99mTc-DTPA negative. In these meningiomas, SRS was negative in 5 cases (5.4 +/- 8.1 mL), whereas the remaining 6 were positive (4.6 +/- 4.5 mL). None of the meningiomas was 99mTc-DTPA positive and SRS negative. RT-PCR revealed no significant difference of hsst2 mRNA expression between SRS-positive and SRS-negative meningiomas but showed varied expression among all meningiomas regardless of SRS results. Furthermore, hsst2 proteins were visualized immunocytochemically on the surface of cultivated cells of SRS-positive and SRS-negative meningiomas. CONCLUSION: SRS-negative meningiomas do express hsst2; thus, in these meningiomas SRS is false-negative. Because an insufficient sensitivity was excluded, 99mTc-DTPA scintigraphy identified a permeability barrier in SRS-negative meningiomas that explains their false-negative SRS results. SRS-negative meningiomas most likely meet the function of their tissue of origin (the meninges) to develop more-or-less intact permeability barriers.

Adult↗

Philadelphia chromosome-negative chronic myelogenous leukemia with rearrangement of the breakpoint cluster region. Long-term follow-up results.

BACKGROUND: Five to 10% of patients with chronic myelogenous leukemia (CML) do not have the Philadelphia chromosome (Ph), but one-third of them have rearrangements of the breakpoint cluster region (BCR-positive). METHODS: The authors analyzed the characteristics, treatment response, and prognosis of 23 patients with BCR-positive, Ph-negative CML, and compared them with patients with Ph-positive CML, Ph-negative BCR-negative CML and chronic myelomonocytic leukemia (CMML) treated during the same period. RESULTS: Seventeen patients had early chronic phase CML, 3 had late chronic phase, 2 had accelerated phase, and 1 had blastic phase. The median age was 44 years (range, 14-71 years), median platelet count was 402 x 10(9)/l, and median leukocyte count was 86 x 10(9)/l. Fourteen of the 17 patients with early chronic phase CML received alpha-interferon; 12 (86%) achieved complete hematologic remission. Median survival in chronic phase CML was 60 months (range, 3-90+ months). Patients with Ph-negative BCR-positive CML and those with Ph-positive CML had similar characteristics and outcome. Compared with patients with Ph-negative BCR-negative CML and CMML, patients with Ph-negative BCR-positive CML and Ph-positive CML were significantly younger, had a significantly higher incidence of leukocytosis, thrombocytosis, and peripheral and marrow basophilia, and a significantly lower incidence of anemia, thrombocytopenia, marrow blast percent, and peripheral and marrow monocytosis. The median survival was 60 months for Ph-negative BCR-positive CML, 73 months for Ph-positive CML, 25 months for Ph-negative BCR-negative CML, and 9 months for CMML (P < 0.001). When analyzed adjusting for their stage, patients classified with Ph-negative BCR-positive CML. Stage I disease had a significantly better survival than did patients with Ph-negative BCR-negative CML (P < 0.02). CONCLUSIONS: Patients with Ph-negative BCR-positive CML are similar to those with Ph-positive CML and should be treated with the same approaches.

Adolescent↗

Differing outcomes of gram-positive and gram-negative peritonitis.

Peritonitis remains the leading cause of patient dropout from continuous peritoneal dialysis (CPD) therapy. Few studies have compared patient morbidity, mortality, and outcome for patients undergoing CPD who develop gram-positive and gram-negative peritonitis. We retrospectively reviewed the charts of patients who developed either gram-positive or gram-negative peritonitis between January 1, 1993, and December 31, 1995. Three hundred seventy-five patients who developed 415 episodes of gram-positive and gram-negative peritonitis were maintained on CPD therapy during this time period. There was no difference in age, race, and sex between patients who developed gram-positive or gram-negative peritonitis. More patients with diabetes developed gram-negative peritonitis than gram-positive peritonitis (53% v 40%, respectively; P < 0.05). Coagulase-negative staphylococcal species accounted for 47% of all gram-positive episodes, whereas Klebsiella organisms, Escherichia coli, and Enterobacter organisms accounted for 63% of all gram-negative episodes. Significantly more patients who developed gram-positive peritonitis continued CPD therapy 2 weeks and 6 months after the onset of peritonitis than patients who developed gram-negative peritonitis (97% v 73%; P < 0.05 at 2 weeks and 81% v 58% at 6 months; P < 0.05, respectively). Nine percent of the patients who developed gram-positive peritonitis died within 6 months after the onset of peritonitis, whereas 21% of the patients who developed gram-negative peritonitis died (P < 0.05). Patients who developed gram-negative peritonitis were significantly more likely to require hospitalization than patients who developed gram-positive peritonitis (74% v 24%; P < 0.001). More patients with gram-negative peritonitis required peritoneal catheter removal than patients with gram-positive peritonitis (18% v 4%; P < 0.001). Thirty-two percent of the patients who developed gram-positive peritonitis re-developed an episode of peritonitis with the same organism compared with only 9% of the patients who developed gram-negative peritonitis. Furthermore, peritonitis recurrence with the same organism within 6 months after the initial episode was noted in 60% of the patients with peritonitis caused by Staphylococcus aureus compared with 24% of patients with peritonitis caused by other gram-positive organisms (P < 0.05). We conclude that the outcomes of gram-positive and gram-negative peritonitis are different. When rates of peritonitis are used to predict outcome, it appears that gram-positive and gram-negative peritonitis rates need to be examined separately.

Adult↗

Helicobacter pylori-negative gastric and duodenal ulcers.

It is unclear whether Helicobacter pylori infection is essential to the development of peptic ulcers. In this study, we examined the rates of H. pylori-negativity among patients with peptic ulcers. We also attempted to clarify the characteristics of H. pylori-negative peptic ulcers to throw light on the pathogenesis of peptic ulcers. The study included 215 consecutive patients with gastric ulcers (GUs) and 120 consecutive patients with duodenal ulcers (DUs). After routine endoscopic examination and phenol red dye endoscopy, forceps biopsies were performed for culture, histology, and the rapid urease test. A patient was considered H. pylori-negative when the serum anti-H. pylori IgG and the three tests on biopsied specimens were all negative. H. pylori-negative rates were 3.2% in the patients with GUs and 1.7% in the patients with DUs. Lack of atrophy of the gastric mucosa was significantly more common in the H. pylori-negative patients with GUs. A history of ulcer disease was less common and antral ulcers were more common in H. pylori-negative GU patients, but not significantly so. As the urea breath test had not been performed, the possibility of a false-negative result cannot be completely ruled out, but we believe that the H. pylori-negative rate in our study is more reliable than these rates in previous reports, because we visualized H. pylori distribution by phenol red dye endoscopy to avoid false-negative results in biopsies, and we used both biopsy and serum anti-H. pylori IgG findings to establish an H. pylori-negative diagnosis. Since H. pylori-negative peptic ulcers certainly exist, H. pylori infection is thought not to be essential to the development of peptic ulcers. There were few differences between the characteristics of H. pylori-negative and H. pylori-positive peptic ulcers in our study. A large-scale study is required to clarify the characteristics of H. pylori-negative peptic ulcers.

Adult↗

Correlation between testosterone, gonadotropins and prolactin and severity of negative symptoms in male patients with chronic schizophrenia.

The aim of this study was to evaluate the relationship between plasma levels of testosterone, FSH, LH and prolactin and the severity of negative symptoms in patients with chronic schizophrenia. Fifty-four male inpatients with chronic schizophrenia participated in this cross-sectional study. Twenty-five age-matched men without a history of psychiatric disorders or endocrine illnesses were used as controls. All patients were on risperidone 4 mg/day or haloperidol 10 mg/day and anticholinegic medication, biperidine 3 mg/day. The patients were assigned to groups with predominant negative and nonpredominant negative symptoms on the basis of their scores on the Positive and Negative Syndrome Scale (PANSS). Plasma levels of testosterone and free testosterone in the patients with predominant and nonpredominant negative symptoms were significantly lower than those in normal controls. Furthermore, plasma levels of FSH and LH, in the patients with predominant negative symptoms but not in the nonpredominant negative symptoms, were significantly lower than those in the normal controls. In contrast, plasma level of prolactin in the predominant negative symptoms group but not in the nonpredominant negative symptoms group was significantly higher than the aged matched normal males. Significant inverse correlation between negative subscale scores of PANSS and plasma levels of testosterone and free testosterone in the patients with predominant negative symptoms were detected. There was also a positive correlation between prolactin plasma levels and negative subscale scores. The present study indicates that assessment of sex hormones and function of hypothalamic-pituitary-gonadotropin axis could be an important biological marker for the severity of negative symptoms in schizophrenia and these findings may change the present pharmacotherapy for negative symptoms based on neuroendocrinology profiles of patients with schizophrenia.

Adult↗

Negative signs and symptoms secondary to antipsychotics: a double-blind, randomized trial of a single dose of placebo, haloperidol, and risperidone in healthy volunteers.

OBJECTIVE: Despite the clinical observation that antipsychotics can produce negative symptoms, no previous controlled study, to our knowledge, has evaluated this action in healthy subjects. The present study assessed observer-rated and self-rated negative symptoms produced by conventional and second-generation antipsychotics in healthy volunteers. METHOD: The authors used a double-blind, placebo-controlled trial of single doses of haloperidol (5 mg) and risperidone (2.5 mg) in normal subjects. Thirty-two subjects were administered haloperidol, risperidone, and placebo in a random order. Motor variables and observer-rated negative symptoms were assessed after 3-4 hours and subjective negative symptoms and drowsiness after 24 hours. RESULTS: Neither of the active drugs caused significant motor extrapyramidal symptoms after administration. Haloperidol caused significantly more negative signs and symptoms than placebo on the Scale for the Assessment of Negative Symptoms (SANS) and two self-rated negative symptom scales: the Subjective Deficit Syndrome Scale total score and an analog scale that evaluates subjective negative symptoms. Risperidone caused significantly more negative signs and symptoms than placebo on the Brief Psychiatric Rating Scale (BPRS), the SANS, the Subjective Deficit Syndrome Scale total score, and the analog scale for subjective negative symptoms. After control for drowsiness, risperidone but not haloperidol produced more negative symptoms than placebo on the BPRS and the SANS. Significance was lost for the subjective negative symptoms with both drugs. CONCLUSIONS: Single doses of both haloperidol and risperidone produce negative symptoms in normal individuals. Drowsiness may be an important confounding factor in the assessment of negative symptoms in antipsychotic trials.

Adolescent↗

Positive and negative symptom behaviors and caregiver burden in the relatives of persons with schizophrenia.

OBJECTIVE: The relationships of perceived severity and responsibility attribution for positive and negative symptom behaviors to caregiver burden were investigated. Two types of burden were studied: objective burden (i.e., negative consequences such as physical problems, financial difficulties, and household tension), and subjective burden (i.e., emotional distress about disturbing behaviors). METHOD: Self-report measures were completed by 70 primary caregivers of persons with schizophrenia. RESULTS: Subjective burden was related to both the severity of positive and negative symptom behaviors, whereas objective burden was related only to the severity of negative symptom behaviors. Responsibility attribution for negative symptom behaviors was related only to objective burden. Caregivers who perceived patients as being less responsible for their negative symptom behaviors reported higher levels of objective burden. The relationship between responsibility attribution for negative symptom behaviors and objective burden remained significant, even after controlling for the severity of negative symptom behaviors. Caregivers' perceptions of patients' responsibility for positive symptom behaviors were not related to objective burden. CONCLUSIONS: As expected, perceived severity of negative symptom behaviors was related to objective caregiver burden, whereas severity of positive symptom behaviors was not. These findings suggest that negative symptoms may have a greater impact on role functioning that positive symptoms, leading to greater burden. However, contrary to expectations, less responsibility attribution for negative symptom behaviors was related to higher levels of objective caregiver burden. Caregivers who perceive patients as incapable of altering their negative symptom behaviors and meeting certain role obligations may assume extra responsibilities, leading to higher levels of objective burden. The results indicate that there may be disadvantages for caregivers associated with assuming that patients have no control over their negative symptom behaviors.

Adult↗

Phasic and enduring negative symptoms in schizophrenia: biological markers and relationship to outcome.

Negative symptoms have been associated with poor response to neuroleptics, enlarged ventricles, cognitive impairment, and poor outcome in schizophrenia. These associations appear, however, to be dependent on the phase of study, suggesting that acute-phase (phasic) negative symptoms may be pathophysiologically distinct from enduring negative symptoms that persist through the residual phase. To compare correlates of enduring and phasic negative symptoms, we studied 60 drug-free schizophrenic patients (DSM-III-R and SADS/RDC) at baseline, 4 weeks after neuroleptic treatment, and assessed the 1 year outcome. We rated positive and negative symptoms at baseline and 4 weeks after treatment. At baseline, premorbid function, neuropsychological function, ventricle-brain ratio (VBR) and symptom response to an anticholinergic agent were assessed, and a two-night sleep EEG and 1mg dexamethasone suppression test (DST) were conducted. Phasic negative symptoms were defined as the change in negative symptoms (baseline to 4 weeks) and enduring negative symptoms as severity of negative symptoms at 4 weeks. Patients had varying proportions of phasic and enduring symptoms; the two did not define distinct subgroups. Phasic negative symptoms were significantly correlated with global treatment response, positive symptom treatment response, response to anticholinergic agent, baseline post-dexamethasone cortisol, and shortened REM latency. Enduring negative symptoms were significantly correlated with residual positive symptoms and global psychopathology, VBR, poor performance on neuropsychological testing, decreased slow-wave sleep, poor premorbid function, and poor 1 year outcome. These data suggest that phasic negative symptoms and enduring negative symptoms may be caused by different pathophysiological mechanisms.

Adult↗

Bactericidal activity against coagulase-negative staphylococci is impaired in infants receiving long-term parenteral nutrition.

OBJECTIVE: To examine the role of total parenteral nutrition (TPN) in predisposing infants to infection caused by coagulase-negative staphylococci. SUMMARY BACKGROUND DATA: Total parenteral nutrition is an important means of providing essential nutrients to newborn infants. However, its use has been associated with complications, particularly infection caused by coagulase-negative staphylococci. Recent data suggest that TPN may modulate immune function; however, reports directly indicating impaired immunity against coagulase-negative staphylococci during TPN are limited. METHODS: Study 1 involved 31 infants younger than 4 months who had undergone surgery and were not receiving antibiotics; 20 were receiving TPN and 11 were receiving a normal enteral diet. An in vitro whole blood model was used to measure the host bactericidal activity against coagulase-negative staphylococci. Bacterial killing and phagocytosis were measured after a 45-minute challenge with viable coagulase-negative staphylococci. In study 2, whole blood killing and intracellular killing of coagulase-negative staphylococci were measured in five newborn infants (younger than 2 months) who were receiving long-term TPN (>10 days), five control infants receiving a normal enteral diet, and five healthy adults. RESULTS: In study 1, infants receiving a normal enteral diet showed a high capacity to ingest and kill coagulase-negative staphylococci. In contrast, the blood of infants receiving long-term TPN showed a reduction in coagulase-negative staphylococci phagocytosis and killing. There were significant negative linear correlations between the duration of TPN and killing of coagulase-negative staphylococci and phagocytosis of coagulase-negative staphylococci. In study 2, infants receiving long-term TPN had lower whole blood killing and intracellular killing than infants receiving a normal enteral diet and healthy adult volunteers. These data seem to indicate a neutrophil dysfunction mediated by TPN in infancy. CONCLUSIONS: Host defense mechanisms, including phagocytosis and killing of coagulase-negative staphylococci, are impaired during long-term TPN. The impaired bactericidal activity seems to be related to defective intracellular killing in neutrophils. These findings may explain the high rate of septicemia caused by coagulase-negative staphylococci in infants receiving TPN.

Adult↗