Unilateral Malignant Glaucoma Postbilateral Implantable Collamer Lens: Effect of Miotics.

An implantable collamer lens® (ICL) V4c model (STAAR Surgical, Monrovia, CA, USA) was placed in the eye of a 31-year-old male patient with high myopia followed by the development of malignant glaucoma. After failing medical treatment for 5 days, a noncomplicated pars plana vitrectomy and anterior hyaloidectomy succeeded in breaking the aqueous misdirection. Sixteen months later, intraoperative miotics were purposefully withheld from the ICL surgery in the fellow eye and malignant glaucoma did not develop. Even though the patient's visual acuity postoperatively was 20/20, OU, a single small atrophic iris patch in the affected eye resulted in slightly more halos and glare in mesopic conditions as compared to the fellow eye. Earlier surgical intervention may have prevented iris ischemia and iridocorneal touch with its subsequent iris atrophy and resulted in an even more favorable visual outcome. Withholding intraoperative miotics during ICL surgery appeared to be beneficial in this case.

Canine pancreatic lipase immunoreactivity concentrations associated with intervertebral disc disease in 84 dogs.

OBJECTIVE: To determine the differences in serum canine pancreatic lipase immunoreactivity between dogs with intervertebral disc herniation and healthy control dogs. MATERIALS AND METHODS: Eighty-four client-owned dogs with intervertebral disc herniation, diagnosed by neurologic examination and imaging, and 18 healthy control dogs. Samples of whole blood were collected within 90 minutes of admission. Serum canine pancreatic lipase immunoreactivity concentrations were measured by a commercial immunoassay and evaluated for association with intervertebral disc herniation, signalment, neurolocalisation and the preadmission administration of glucocorticosteriods or non-steroidal anti-inflammatory drugs. RESULTS: Serum canine pancreatic lipase immunoreactivity concentrations were statistically increased in dogs with intervertebral disc herniation (P<0·01, n=38). A subgroup of dogs (19/38) with elevated canine pancreatic lipase immunoreactivity concentrations was re-evaluated between 2 and 4 weeks later, and 15 had resolution of clinical signs and values less than 200 µg/L. Serum canine pancreatic lipase immunoreactivity concentrations were not significantly correlated with clinical gastrointestinal disease, neurolocalisation or the preadmission administration of corticosteroids or non-steroidal anti-inflammatory drugs. CLINICAL SIGNIFICANCE: These results suggest that serum canine pancreatic lipase immunoreactivity concentrations are significantly elevated in dogs with intervertebral disc herniation.

A randomized, placebo-controlled 12-month trial of divalproex and lithium in treatment of outpatients with bipolar I disorder. Divalproex Maintenance Study Group.

BACKGROUND: Long-term outcomes are often poor in patients with bipolar disorder despite treatment; more effective treatments are needed to reduce recurrences and morbidity. This study compared the efficacy of divalproex, lithium, and placebo as prophylactic therapy. METHODS: A randomized, double-blind, parallel-group multicenter study of treatment outcomes was conducted over a 52-week maintenance period. Patients who met the recovery criteria within 3 months of the onset of an index manic episode (n = 372) were randomized to maintenance treatment with divalproex, lithium, or placebo in a 2:1:1 ratio. Psychotropic medications were discontinued before randomization, except for open-label divalproex or lithium, which were gradually tapered over the first 2 weeks of maintenance treatment. The primary outcome measure was time to recurrence of any mood episode. Secondary measures were time to a manic episode, time to a depressive episode, average change from baseline in Schedule for Affective Disorders and Schizophrenia-Change Version subscale scores for depression and mania, and Global Assessment of Function scores. RESULTS: The divalproex group did not differ significantly from the placebo group in time to any mood episode. Divalproex was superior to placebo in terms of lower rates of discontinuation for either a recurrent mood episode or depressive episode. Divalproex was superior to lithium in longer duration of successful prophylaxis in the study and less deterioration in depressive symptoms and Global Assessment Scale scores. CONCLUSIONS: The treatments did not differ significantly on time to recurrence of any mood episode during maintenance therapy. Patients treated with divalproex had better outcomes than those treated with placebo or lithium on several secondary outcome measures.

Decreased mononuclear leukocyte TSH responsiveness in patients with major depression.

A subgroup of individuals with major depressive disorder have an impaired thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH). The molecular relationship between the mechanism of this "blunted" TSH response and depression is unknown. Numerous recent studies have characterized similarities and interactions between the immune and neuroendocrine systems. As the immune system both produces and responds to TSH, we utilized a peripheral blood leukocyte system to compare immunoreactive (ir)-TSH responsiveness in 10 adult patients (1 man, 9 women) with Research Diagnostic Criteria for major depressive disorder to that of 9 control subjects. All subjects had normal baseline serum TSH and T4 concentrations. Isolated mononuclear leukocytes were treated in vitro with either 0.5 micrograms/ml staphylococcal enterotoxin A (SEA), 50 micrograms/ml TRH, or no stimulant. After incubation, the cells were monitored for ir-TSH production by indirect immunofluorescence and reverse hemolytic plaque assay using antisera to TSH-beta. The culture supernates were analyzed by TSH radioimmunoassay. SEA- and TRH-treated cell cultures from depressed individuals had significantly fewer immunofluorescent positive cells, as well as significantly fewer and smaller plaques, than did similarly treated leukocytes from control subjects. The increase in supernatant ir-TSH was significantly less in TRH-treated cultures from depressed patients as compared to normals (p less than 0.05). These results suggest that examination of mononuclear leukocyte TSH production may reflect an altered state of neuroendocrine function and may thus be a useful marker for major depressive disorder.

Mononuclear leukocyte glucocorticoid receptor binding characteristics and down-regulation in major depression.

Some patients with major depressive disorder (MDD) have elevated plasma cortisol concentrations and show failure to suppress cortisol secretion upon administration of dexamethasone (DEX), yet they do not have Cushingoid features. To study whether this represents glucocorticoid (GC) resistance, [3H]-DEX-binding assays were used to measure, in vitro, the GC receptor affinity (1/Kd) and number (Bmax) in mononuclear leukocytes of 11 MDD patients and 15 control subjects. No receptor abnormalities were detected in the MDD group; thus any cellular defect leading to a lack of responsiveness to GC in the MDD patients, if present, probably lies beyond the initial receptor binding. DEX (1.0 mg orally) was administered to study in vivo GC receptor down-regulation. Compared to the control group, fewer depressed subjects down-regulated Bmax after DEX. By paired t-test, Bmax decreased significantly in the control group but not in the depressed group. Receptor number on the control day did not correlate significantly with the degree of receptor down-regulation, severity of depression or cortisol concentrations across all the subjects. These results do not lend support to previous reports suggesting that GC resistance in MDD results from a GC receptor-binding abnormality, and they emphasize the importance of considering receptor studies in the context of GC-mediated cell processes in order to identify the exact cellular defect(s) leading to GC resistance.

Toll-like receptor 4 in normal and inflamed lungs and other organs of pig, dog and cattle.

Bacterial diseases, especially those of the lung caused by Gram-negative bacteria, inflict significant economic loss associated with mortality and morbidity in domestic animals. Toll-like receptor 4 (TLR4) has recently been recognized as a major receptor for cellular interactions with lipopolysaccharides derived from Gram-negative bacteria. However, there are no data on the expression of TLR4 in various organs of domestic animals. We performed immunohistochemistry and immuno-gold electron microscopy to localize TLR4 in lung and seven other organs from normal pig, dog and calf (n=2 each) and in inflamed lungs from calves (n=4) challenged with Mannheimia hemolytica. The data show TLR4 in macrophages in lung, small intestine, liver and spleen in all the species and pulmonary intravascular macrophages in calves and pigs. Epithelium in lung, small intestine, cornea and convoluted and straight renal tubules was stained for TLR4. Vascular endothelium of large blood vessels only in lungs and skin was positive, and skeletal muscles were negative for TLR4. In inflamed lungs, airway epithelium showed reduced staining for TLR4 while staining in macrophages remained unaltered. These are the first immunocytochemical data on TLR4 expression in domestic animal species and show similarity in TLR4 staining in macrophages, epithelium and vascular endothelium among dog, pig and cattle.

Glucocorticoid receptor binding in three different cell types in major depressive disorder: lack of evidence of receptor binding defect.

1. In order to further understand the apparent glucocorticoid resistance in major depressive disorder, circadian variation in cortisol concentration, dexamethasone suppression and glucocorticoid receptor binding in mononuclear leukocytes, polymorphonuclear leukocytes and cultured skin fibroblasts were measured in rigidly defined major depressive disorder patients and non-depressed psychiatric controls. 2. Mononuclear leukocytes binding to glucocorticoid correlated significantly with polymorphonuclear leukocytes binding to glucocorticoid, but both determinations failed to differentiate major depressive disorder and control subjects. 3. Initial and post-dexamethasone in vitro fibroblast binding to glucocorticoid was not different between major depressive disorder and non-depressed control subjects. 4. The phenomenon of glucocorticoid resistance in major depressive disorder remains unexplained.

Immediate versus delayed visual memory task performance among schizophrenic patients and normal control subjects.

In an exploratory study, 10 schizophrenic patients and 10 normal control subjects performed immediate and delayed memory tasks, which were variants of previously developed continuous performance tests. Both tasks required participants to identify five-digit numbers which were repeated. Numbers were presented in series for 500 ms each and separated by a 500-ms time-out period. In the immediate memory task, subjects were to respond if a number was identical to the one that had immediately preceded it. The delayed memory task differed from the first task in that a longer delay (3.5 s) between stimuli was introduced, and during this delay distracter stimuli appeared. While normal control subjects performed accurately on both tasks (exceeding 80% correct detections), schizophrenic patients performed poorly, performing worse on the delayed memory task than on the immediate memory task. Rates of commission errors (responses made to similar, but not identical numbers) were nearly equal between groups on the immediate memory task, but on the delayed memory task normal control subjects made relatively more commission errors while schizophrenic patients made fewer commission errors. No differences in response latencies were observed between subject groups or tasks. This paradigm may prove useful in discriminating subtle differences in immediate and delayed memory capability among psychiatric populations and normal control subjects.

Training health professionals in the recognition and treatment of depression.

A total of 423 health professionals, including physicians, psychologists, counselors, social workers, and nurses, attended a two-day program to increase awareness, recognition, and treatment of depression. In a preprogram opinion survey, nurses and social workers reported less perceived ability to recognize mood disorders compared with physicians and psychologists. In a group of 274 respondents who took a 20-item test of their knowledge about depression before and after attending the program, scores for all professions increased after the program and pretest differences in scores between professions decreased. The results suggest that training was successful in increasing knowledge about depression among a diverse group of health professionals.

New subscales for an anchored version of the Brief Psychiatric Rating Scale: construction, reliability, and validity in acute psychiatric admissions.

Attending psychiatrists completed an anchored version of the 18-item Brief Psychiatric Rating Scale (BPRS-A) based on admission and evaluation information on a total of 2,921 adult patients treated at 1 public sector acute psychiatric teaching hospital. Exploratory factor analysis was applied to a 6-month sample to construct 4 nonoverlapping subscales: Resistance, Positive Symptoms, Negative Symptoms, and Psychological Discomfort. Confirmatory factor analysis compared these new subscales to 3 other published subscale models using a second 6-month sample. Internal consistency, rater influence, and interrater agreement were estimated in separate studies. Discriminant validity was explored by comparison of diagnosis-based samples. Application of the BPRS-A as a debriefing instrument in the study of symptomatic change and the multiple challenges inherent in psychometric study of such a rating scale in realistic hospital practice are discussed.

In search of effective programs to address students' emotional distress and behavioral problems. Part II: Critique of school- and community-based programs.

Part I of this article discussed the dimensions of students' emotional distress and behavioral problems and proposed school programs to address it. This section evaluates the school- and community-based programs advocated in educational, psychological, and psychiatric journals over the past five years. Twenty-nine articles were selected, and the programs classified by location, focus, and format. Their merits and limitations based on their results are discussed. This review found that (1) some programs poorly defined the study populations; (2) emotional distress was not included as a criterion; (3) a strictly behavioral approach or narrow focus on specific populations or issues prevailed. Only four programs used emotional expression and social support; (4) outcome measures focused on specific behaviors with only one study evaluating the emotional outcome; (5) none addressed the student's acceptance of the program; (6) only five measured the outcome beyond the immediate termination of the intervention, and only to a limited degree. While the programs reviewed support the likelihood that such interventions may be helpful, definitive conclusions which can be generalized to average high school students are still lacking. Recommendations for future school-based programs are proposed.

In search of effective programs to address students' emotional distress and behavioral problems. Part I: Defining the problem.

This article discusses the prevalence and seriousness of emotional difficulties and behavioral problems in students, with a special focus on high school students and the obstacles they encounter when addressing these problems. The educational, psychological, and medical literature which addressed the problem over the past five years was evaluated, and 22 references were selected. It was determined that the lack of consensus on the terms used to describe the problem prevented accurate assessment of its prevalence. However, one fifth to one third of the students were found to be affected, leading to serious educational, psychosocial, and economic difficulties--and more are likely to be affected in the 1990s. Since the school and mental health systems have not been entirely successful in addressing the problem, adolescents' patterns of seeking help indicate that peer support groups can be part of the solution. It was concluded that the enormity of the problem requires a low-cost gate-keeping mechanism to facilitate early identification and intervention. Thus, school peer-support programs, if proven effective, may complement traditional mental health services in addressing adolescents' emotional distress and behavioral problems.

Effectiveness of one-year participation in school-based volunteer-facilitated peer support groups.

This study evaluated the effectiveness of one-year participation in a program of volunteer-facilitated peer support groups conducted in a southeast Texas high school. One hundred eighteen students who experienced emotional distress or behavioral problems voluntarily participated in weekly groups facilitated by adult volunteers who were not mental health professionals. Seventy-six participants anonymously assessed the program using an instrument developed to evaluate the group experience. Results indicated that the program was highly accepted by the students even though two-thirds had initially felt uncomfortable in the groups. There was significant improvement in the interpersonal, internal, and school domains. Two-thirds of the alcohol and substance users reported reducing their intake or abstaining. The beneficial effects reported by a majority of the participants indicate that schools opting to implement this early intervention program can look forward to encouraging results within one year.

In search of effective programs to address students' emotional distress and behavioral problems part III: student assessment of school-based support groups.

Emotional distress and behavioral problems are common in high schools. This report describes the efficacy of an in-school program based on participation in volunteer-facilitated peer support groups in addressing these problems. Two hundred and fifty students who experienced such problems participated in weekly 50-minute peer support groups led by adult nonmental health professional volunteers. The students anonymously evaluated their progress and program acceptability using an instrument developed specifically to evaluate the group experience. Analysis of the evaluation of the 131 respondents documented the reliability of a proposed Self-Assessment Questionnaire which showed that participation led to improvement in school, interpersonal, and internal domains. The program was highly accepted and showed other signs of success: half of the alcohol and substance users reduced their intake, and 60% of those who considered dropping out of school continued their education. The results provide preliminary evidence that peer support groups show promise as an economical and well-accepted method for early recognition and management of emotional and behavioral problems in high schools. For some adolescents, these groups may be the only acceptable or available therapeutic modality.

Femoral taperosis: an accident waiting to happen?

A modular femoral head-neck junction has practical advantages in total hip replacement. Taper fretting and corrosion have so far been an infrequent cause of revision. The role of design and manufacturing variables continues to be debated. Over the past decade several changes in technology and clinical practice might result in an increase in clinically significant taper fretting and corrosion. Those factors include an increased usage of large diameter (36 mm) heads, reduced femoral neck and taper dimensions, greater variability in taper assembly with smaller incision surgery, and higher taper stresses due to increased patient weight and/or physical activity. Additional studies are needed to determine the role of taper assembly compared with design, manufacturing and other implant variables.

Neuroleptic-valproic acid combination in treatment of psychotic symptoms: a three-case report.

Valproic acid is infrequently used for treatment of psychosis. Three consecutive patients with severe neuroleptic-resistant psychotic symptoms responded dramatically to the combination of valproic acid and neuroleptics. All three had normal EEGs and CT scans. Outpatient follow-up showed that the combination was effective in maintaining remissions.

Divalproex sodium augmentation of haloperidol in hospitalized patients with schizophrenia: clinical and economic implications.

Divalproex sodium has been approved for use in treating bipolar disorder. Its usefulness in schizophrenia has yet to be adequately assessed. Three days after initiating haloperidol treatment, patients who were hospitalized for an acute exacerbation of schizophrenia received either valproate augmentation (early-augmentation group) or continued to receive haloperidol alone (no-augmentation group). Patients in the no-augmentation group who failed to respond 14 days after the dose of haloperidol reached 20 mg/day received valproate augmentation (delayed-augmentation group). By day 14, the early-augmentation group improved 32.4% more than the no-augmentation group. Fifty percent of the patients in the no-augmentation group failed to respond to haloperidol alone for 2 weeks. They improved by 29% upon the addition of valproate. Compared with those who received no or delayed augmentation, the early-augmentation group required 44.8% fewer inpatient days from the initiation of haloperidol treatment. Patient response to treatment was particularly noted in suspiciousness, hallucinations, unusual thought content, and emotional withdrawal. Early augmentation with valproate may reduce the length of inpatient stays and provide substantially better therapeutic outcomes. It is, however, premature to recommend changes in the standard clinical management of schizophrenia on the basis of the data provided herein, in view of the small sample and open-label nature of the report.

Randomized, placebo-controlled pilot study of divalproex sodium in the treatment of acute exacerbations of chronic schizophrenia.

Experimental and clinical data suggest that GABA-ergic drugs such as valproate may have a potential role in the treatment of schizophrenia. The authors designed a 21-day prospective, double-blind, randomized, placebo-controlled pilot study of divalproex sodium as add-on treatment to haloperidol in 12 hospitalized patients with acute exacerbations of chronic schizophrenia. All patients received haloperidol 10 mg/day for 3 days and 15 mg/day for the remaining 18 days. In addition, five patients were randomly assigned to receive divalproex augmentation and seven to receive placebo. The divalproex dose was adjusted to a target serum concentration of 75 microg/mL for 2 weeks; placebo replaced divalproex during the third and last weeks to determine any carryover effect. Psychiatric rating scales were administered at baseline and on days 7, 14, and 21. Although the placebo group improved with haloperidol treatment, the divalproex group demonstrated greater improvement. On day 21, the divalproex group had greater improvement from baseline on the Clinical Global Impression Scale (p < or = 0.04), Brief Psychiatric Rating Scale (p < or = 0.13), and Schedule for Assessment of Negative Symptoms scores (p < or = 0.007). After divalproex withdrawal on day 15, a carryover effect was observed during week 3. The authors concluded that the addition of divalproex sodium to standard antipsychotic drugs may prove effective in relieving the symptoms of acute schizophrenia. Future studies may benefit from the design of this pilot study. However, it is premature to apply this augmentation strategy in the clinical setting just yet because of the small sample size and the likely heterogeneity of the disorder.

Critical review of GABA-ergic drugs in the treatment of schizophrenia.

GABA-ergic medications may have a potential role in the treatment of schizophrenia. Laboratory evidence has generally supported the ability of gamma-aminobutyric acid (GABA) to reduce dopaminergic activity and has suggested that GABA may be effective in combating hypofrontality by acting on mesoprefrontocortical tracts in patients resistant to treatment with antipsychotic drugs. Although the results of clinical trials of several GABA-ergic compounds have been inconclusive because of methodologic limitations and drug toxicity, benzodiazepines and valproate seem to be associated with favorable treatment outcomes, especially when combined with typical antipsychotic agents. This study concludes that further investigation of the use of GABA in schizophrenia is likely to improve the understanding of the psychopathology of this illness and to expand our treatment alternatives. Also provided are suggestions to enhance the design of future studies, improve the potential for favorable treatment outcomes, and assist in predicting patients' responses to GABA-ergic medications.