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Platelets and sera from 12 patients with thrombotic thrombocytopenic purpura (TTP) and 12 healthy normal control subjects were examined. As determined by quantitative flow cytometry, prior to plasma exchange therapy platelet surface glycoprotein (GP) Ib levels were similar in TTP patients and normal controls (mean 20 188 and 20 226 molecules/platelet, respectively). Platelets from patients with TTP did, however, have significantly reduced levels of GPIIb/IIIa prior to plasmapheresis (mean 36 348 v 52 505 molecules/platelet in controls; P = 0.0004) and of GPIV (mean 13 321 v 26 212 molecules/platelet in controls; P = 0.0002). An increase in activated platelets, as determined by CD62 expression, was observed in 82% of patients. Increased platelet-associated immunoglobulins and/or complement was also seen in approximately 60% of the patients. In general, with return of platelet counts to normal levels following seven plasmaphereses, the above abnormalities were reversed, although often not to normal levels. Western blot analysis indicated the presence of antibodies reactive to platelet GPIV (88 kD) in 70% of pretreatment sera from patients with TTP; a similar band was observed in 80% of patient sera against microvascular endothelial cells. Immunofluorescence microscopic examination indicated the presence of antibody in pretreatment sera from patients with TTP to microvascular (73%) and large vessel (36%) endothelial cells. As measured by an indirect flow cytometric assay, pretreatment sera from 55% of patients with TTP were reactive with large vessel endothelial cells and 100% reacted with microvascular endothelial cells; reactivity was significantly greater against the microvascular endothelial cells (P = 0.0048) and was reduced following plasma exchange therapy. These results indicate abnormalities in platelet glycoprotein expression in TTP and suggest that anti-platelet and anti-endothelial cell antibodies play a role in the thrombocytopenia and vasculitis characteristic of this disorder.

Most supernumerary teeth are located in the anterior maxillary region. They are classified according to their form and location. Their presence may give rise to a variety of clinical problems. Detection of supernumerary teeth is best achieved by thorough clinical and radiographic examination. Their management should form part of a comprehensive treatment plan. This article presents an overview of the clinical problems associated with supernumerary teeth and includes a discussion of the classification, diagnosis and management of this difficult clinical entity.

Background: In children, exacerbations of tics and obsessive symptoms may occur after infection with group A beta-haemolytic streptococci. If post-streptococcal autoimmunity is the cause of the exacerbations, then children might respond to immunomodulatory treatments such as plasma exchange or intravenous immunoglobulin (IVIG). We studied whether plasma exchange or IVIG would be better than placebo (sham IVIG) in reducing severity of neuropsychiatric symptoms., Methods: Children with severe, infection-triggered exacerbations of obsessive-compulsive disorder (OCD) or tic disorders, including Tourette syndrome, were randomly assigned treatment with plasma exchange (five single-volume exchanges over 2 weeks), IVIG (1 g/kg daily on 2 consecutive days), or placebo (saline solution given in the same manner as IVIG). Symptom severity was rated at baseline, and at 1 month and 12 months after treatment by use of standard assessment scales for OCD, tics, anxiety, depression, and global function., Findings: 30 children entered the study and 29 completed the trial. Ten received plasma exchange, nine IVIG, and ten placebo. At 1 month, the IVIG and plasma exchange groups showed striking improvements in obsessive-compulsive symptoms (mean improvement on children's Yale-Brown obsessive compulsive scale score of 12 [45%] and 13 [58%], respectively), anxiety (2.1 [31%] and 3.0 [47%] improvement on National Institute of Mental Health anxiety scale), and overall functioning (2.9 [33%] and 2.8 [35%] improvement on National Institute of Mental Health global scale). Tic symptoms were also significantly improved by plasma exchange (mean change on Tourette syndrome unified rating scale of 49%). Treatment gains were maintained at 1 year, with 14 (82%) of 17 children "much" or "very much" improved over baseline (seven of eight for plasma exchange, seven of nine for IVIG)., Interpretation: Plasma exchange and IVIG were both effective in lessening of symptom severity for children with infection-triggered OCD and tic disorders. Further studies are needed to determine the active mechanism of these interventions, and to determine which children with OCD and tic disorders will benefit from immunomodulatory therapies.

The search for subtypes of OCD has led to increased appreciation of the importance of distinguishing early (prepubertal) versus later on-set, and of tic-related versus non-tic related subtypes, as well as postinfectious forms of the disorder. How these apparent typologies relate to each other remains to be elucidated. Careful longitudinal clinical descriptive studies, as well as the ongoing application of genetic, neuroimaging, and immunologic techniques, promise to advance our understanding of how genotype and environmental factors interact to produce the diverse clinical forms of OCD and to point the way to more effective treatment.

Background: Some children with obsessive-compulsive disorder (OCD) and tic disorders appear to have symptom exacerbations triggered by group A beta-hemolytic streptococcal infections in a manner that is similar to rheumatic fever and its neurologic variant, Sydenham's chorea. Because penicillin prophylaxis has proven to be effective in preventing recurrences of rheumatic fever, it was postulated that it might also prevent streptococcal-triggered neuropsychiatric symptom exacerbations in children with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS). These children are identified by five clinical characteristics: presence of OCD or tic disorder, prepubertal onset, episodic symptom course, neurologic abnormalities (i.e., choreiform movements) and streptococcal-triggered symptom exacerbations., Methods: Thirty-seven children with PANDAS were enrolled in an 8 month, double-blind, balanced cross-over study. Patients were randomized to receive either 4 months of the active compound (twice daily oral 250 mg penicillin V) followed by 4 months of placebo, or placebo followed by penicillin V. Tic, OCD, and other psychiatric symptoms were monitored monthly. Throat cultures and streptococcal antibody titers were also obtained., Results: There were an equal number of infections in both the active and placebo phases of the study. There was no significant change seen in either the obsessive-compulsive or tic symptom severity between the two phases., Conclusions: Because of the failure to achieve an acceptable level of streptococcal prophylaxis, no conclusions can be drawn from this study regarding the efficacy of penicillin prophylaxis in preventing tic or OCD symptom exacerbations. Future studies should employ a more effective prophylactic agent, and include a larger sample size.

The successful defense of a medical malpractice case is a team effort between the defendant doctor and his or her attorney. However, the most common complaint voiced by physicians is the failure, real or perceived, of the selected attorney to keep them involved in the preparation of the case and its progress. To ameliorate this situation, the author explains how to participate in one's defense in a helpful and meaningful fashion.

Objective: To determine whether the recently published guidelines on neuroimaging in patients with new-onset seizures are applicable to children., Methods: We carried out a retrospective analysis of 107 neurologically normal children (excluding children with simple febrile seizures) who had undergone neuroimaging when they presented to the emergency department with a possible "first seizure.", Results: Eight of the 107 children had nonepileptic events (gastroesophageal reflux, syncopal event, rigor). Of the remaining 99 children, 49 had provoked seizures (complicated febrile seizure, meningo-encephalitis, toxic or metabolic abnormalities), and 50 had unprovoked seizures. A total of 19 children had brain abnormalities identified on computed tomography (CT) scan; 7 received further investigation or intervention as a result of CT scan findings (2 with tumors, 3 with vascular anomalies, 1 with cysticercosis, and 1 with obstructive hydrocephalus). CT scan abnormalities requiring treatment or monitoring were more frequently seen in children with their first unprovoked seizure (P < .01) and in those children whose seizure onset had been focal or who had focal abnormalities identified on postictal neurologic examination (P < .04)., Conclusion: In a child, a seizure in the setting of a fever rarely indicates the presence of an unexpected CT scan lesion requiring intervention.

Unlabelled: Maintaining the treatment result following orthodontic treatment is one of the most difficult aspects of the entire treatment process. Normal maturational changes, together with post-treatment tooth alterations, conspire against long-term stability. This article discusses the need for retention and provides an overview of retainers which enjoy widespread use., Clinical Significance: Permanent retention is increasingly being recommended as the only way to ensure long-term stability of an orthodontic treatment result. Dental practitioners should be familiar with the rationale for retention and the design of the appliances worn by the their patients.

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) is a relatively new diagnostic construct applied to children or adolescents who develop, and have repeated exacerbations of, tic disorders and/or obsessive-compulsive disorder following group A beta-hemolytic streptococcal infections. The proposed pathophysiology is that the group A beta-hemolytic streptococcal bacteria trigger antibodies that cross-react with the basal ganglia of genetically susceptible hosts leading to obsessive-compulsive disorder and/or tics. This is similar to the etiologic mechanisms proposed for Sydenham's chorea, in which group A beta-hemolytic streptococcal antibodies cross-react with the basal ganglia and result in abnormal behavior and involuntary movements. When first proposed, there was much controversy about the idea that streptococcal infections were etiologically related to rheumatic fever. In a like manner, discussion has arisen about the concept of infection-triggered obsessive-compulsive disorder and tic disorders. We review the historical background to these controversies, give an update on the findings provided by research on PANDAS, and address areas of future study.

Spontaneous EDTA-independent cold platelet agglutination is a rare phenomenon that produces pseudothrombocytopenia when blood samples are analyzed in automated cell counters. We report a case of platelet cold agglutinins and an analysis by flow cytometry. A 49 year old woman presented with abnormal vaginal bleed secondary to uterine fibroids. Platelet clumping was observed in blood samples taken in EDTA-, heparin- and citrate-containing tubes. In flow cytometric tests, patient serum agglutinated 16% of normal platelets at 22 degrees C, and 7% of platelets after incubation at 37 degrees C; in contrast, 3% and < 1% of platelets were agglutinated at 22 and 37 degrees C, respectively, after incubation with normal serum. Minimal agglutination (< 10%) was observed with patient serum at a titre of 1:5 or at temperatures > 30 degrees C. After incubation at 4 degrees C, IgM antibody and C3 were increased on the patient's platelets; no significant amount of IgM or C3 was detected on normal platelets. The specificity of the platelet cold agglutinin was determined by competitive inhibition by monoclonal anti-CD41(GPIIbIIIa). Before the addition of monoclonal antibody, patient's serum agglutinated 16% of normal platelets at 22 degrees C; after addition of anti-CD41 only 2% of the platelets were agglutinated. This blocking effect was not observed with anti-CD42. The patient's platelets functioned normally as determined by CD62 and CD63 expression in response to thrombin, normal platelet aggregation in response to collagen, ADP, and ristocetin, and a normal template bleeding time. In summary, platelet agglutination by a platelet cold agglutinin was quantitated by flow cytometry, the responsible antibody was characterized as a low titre IgM with minimal activity > 30 degrees C, and competitive binding studies supported the GPIIbIIIa complex as the binding site for the antibody. Since the antibody did not affect platelet function, we believe that these patients will not suffer complications from their platelet cold agglutinin, but it could pose a problem under circumstances such as cardiac surgery with hypothermia.

All attendees participated in a round-table discussion regarding directions for research in autoimmune thrombocytopenic purpura (ITP). Suggested areas for study were grouped into five main areas: (i) improved classification of ITP identifying subsets of patients with differing clinical syndromes and response to treatment, and those more likely to have serious bleeding manifestations; identification of patients with reduced thrombopoiesis was emphasized; (ii) studies aimed at elucidating the aetiology and pathophysiology of ITP, with emphasis on distinctions between acute and chronic ITP and between patients responsive or refractory to therapy; these studies focused on measures of humoral and cellular immune dysregulation; (iii) studies of platelet function in ITP, with the intent of defining these abnormalities and correlating them with the clinical manifestations of the disease; (iv) new approaches to treatment, particularly of refractory patients; and (v) a miscellaneous group, which included development of an ITP registry, evaluation of the "burden" of disease, investigation of mood changes in ITP, etc. The discussion was not intended to be all-inclusive, but focused on the content of other talks in this symposium. It is hoped that some of these suggestions will be further developed for investigation in multicentre co-operative studies to improve the diagnosis, understanding and treatment of ITP.

Objective: We reported a possible risk factor which could identify patients with chronic hydrocephalus who are risk for sudden death., Methods: A retrospective review of medical records and computed tomographic (CT) scans was conducted on three patients with chronic hydrocephalus who suffered acute cardiorespiratory arrest without those signs which are normally associated with a progressive worsening of hydrocephalus., Results: All three of these patients were awake and communicative shortly before the life threatening or terminal event. All had experienced some recent worsening of neurologic signs or symptoms, but none had shown a progressive impairment of consciousness or major neurologic decline ordinarily associated with life threatening elevation of intracranial pressure. Absence of the perimesencephalic cisterns on head CT scans done prior to or just after the life threatening event was the only new radiologic finding common to all these patients., Conclusions: The absence of the perimesencephalic cisterns in an awake and alert patient with severe hydrocephalus indicates that the patient may be at risk for neurogenic cardiorespiratory failure. In such cases, (especially when there has been a recent, albeit mild, change in neurologic signs or symptoms), the neurologist should urge emergency ventriculostomy or shunting for the hydrocephalus.

This is a case report of a Caucasian female who presented with an unusual combination of dental anomalies: short roots on the maxillary central incisors and premolars, talon cusps, dentes invaginati, low alveolar bone heights, tubercles of Carabelli on the maxillary first and second permanent molars, with pyramidal root morphology in three of the second permanent molars. None of the anomalies alone are particularly uncommon but they have not previously been reported together. The occurrence of the anomalies is probably incidental as the conditions are aetiologically unrelated.

We studied the effects of porcine factor VIII (P-FVIII; Hyate:C) and other coagulation products employed in the management of patients with hemophilia A, on platelet activation in vitro. Exposure of normal resting platelets to P-FVIII resulted in platelet activation, as manifested by increased expression of the platelet surface activation markers CD62, CD63, and activated-GPIIbIIIa, and by activation-induced modulation of expression of normal platelet membrane glycoproteins CD41, CD42, and CD36. In contrast, platelet activation was not observed after exposure of the platelets to human FVIII, FEIBA, recombinant FVIIa, or cryosupernatant plasma. As with thrombin, exposure of platelets to P-FVIII resulted in the generation of platelet microparticles, an effect not seen not with the other products. In contrast to the characteristic reduction in expression in the number of CD42 molecules detected on thrombin-activated platelets, P-FVIII-stimulated platelets showed a small increase in CD42 expression. In contrast to thrombin, P-FVIII did not cause platelet dense granule release. The results indicate that therapeutic P-FVIII activates platelets, likely in ways that are different from the platelet activation seen with thrombin. The observed platelet activation and microparticle generation may provide a "hypercoagulable" mechanism for hemostasis with P-FVIII therapy separate from, and additional to, that due to increased circulating FVIII levels.

Objective: The purpose of this study was to describe the clinical characteristics of a novel group of patients with obsessive-compulsive disorder (OCD) and tic disorders, designated as pediatric autoimmune neuropsychiatric disorders associated with streptococcal (group A beta-hemolytic streptococcal [GABHS]) infections (PANDAS)., Method: The authors conducted a systematic clinical evaluation of 50 children who met all of the following five working diagnostic criteria: presence of OCD and/or a tic disorder, prepubertal symptom onset, episodic course of symptom severity, association with GABHS infections, and association with neurological abnormalities., Results: The children's symptom onset was acute and dramatic, typically triggered by GABHS infections at a very early age (mean = 6.3 years, SD = 2.7, for tics; mean = 7.4 years, SD = 2.7, for OCD). The PANDAS clinical course was characterized by a relapsing-remitting symptom pattern with significant psychiatric comorbidity accompanying the exacerbations; emotional lability, separation anxiety, nighttime fears and bedtime rituals, cognitive deficits, oppositional behaviors, and motoric hyperactivity were particularly common. Symptom onset was triggered by GABHS infection for 22 (44%) of the children and by pharyngitis (no throat culture obtained) for 14 others (28%). Among the 50 children; there were 144 separate episodes of symptom exacerbation; 45 (31%) were associated with documented GABHS infection, 60 (42%) with symptoms of pharyngitis or upper respiratory infection (no throat culture obtained), and six (4%) with GABHS exposure., Conclusions: The working diagnostic criteria appear to accurately characterize a homogeneous patient group in which symptom exacerbations are triggered by GABHS infections. The identification of such a subgroup will allow for testing of models of pathogenesis, as well as the development of novel treatment and prevention strategies.

Children who present with extensive fractures of anterior teeth pose a difficult clinical problem. Pulpal and periodontal injuries must be carefully assessed and managed. Rapid restoration of the form and contour of the extensively fractured tooth is advisable, not only to improve esthetics but also to prevent unwanted tipping or tilting of adjacent teeth and overeruption of opposing teeth. A modified Essix retainer, simply constructed in the laboratory, can be used to provisionally restore the extensively fractured anterior tooth.

Many clinical trials concerning acupuncture are flawed by methodological problems. One of the major difficulties is the appropriate selection and use of a placebo control. This article evaluates the use of sham acupuncture as a placebo control and analyzes its credibility as a control treatment. Sixty-four subjects were assessed for their perception of whether they were receiving sham or real acupuncture while participating in a clinical trial of acupuncture. It was found that if used under specific experimental conditions, sham acupuncture can function as a credible control. Specific strategies are suggested to maintain the credibility of sham acupuncture as a placebo control.

We hypothesized that levels of N-acetyl-beta-glucosaminidase (NAG) would differ between patients making serious versus nonserious suicide attempts. The levels of NAG from 7 patients hospitalized for serious suicide attempts were compared to 3 patients whose suicide attempts were not rated serious. There was a significant difference in the mean NAG levels of the serious suicide attempters and the nonserious attempters, 25 versus 61; p = .036. Implications of this finding are discussed.

Bronchopleural fistulas associated with empyema can occur as a life-threatening sequelae after pulmonary resection, most frequently occurring after pneumonectomy. With the use of the flexible bronchoscope, the bronchopleural fistula of a 62-year-old critically ill woman was permanently sealed with a fibrin sealant and a small section of demineralized human spongiosa. Closure of bronchopleural fistulas with the application of fibrin sealant plus human spongiosa may offer a valuable addition to the armament of therapeutic alternatives.

Beckwith-Wiedemann syndrome (BWS) comprises multiple congenital anomalies with a risk of childhood tumours. Macroglossia is the most common manifestation. Two cases are presented to illustrate the importance of early referral and the role of preventive dentistry.

We performed two studies to determine whether the lipid-lowering effect of viscous soluble fiber was modified by monounsaturated fatty acid (MUFA). First, psyllium (1.4 g/MJ) was compared with wheat bran (control) in 1-mo metabolic diets by using a randomized crossover design (n = 32 hyperlipidemic subjects). The background diet contained approximately 6% of energy as MUFA (20% of total fat). The second study (n = 27 hyperlipidemic subjects) was similar to the first but the background diet contained approximately 12% MUFA (29% of total fat) because of the addition of canola oil. At both fat intakes, psyllium resulted in significant reductions in total, low-density-lipoprotein (LDL), and high-density-lipoprotein (HDL) cholesterol compared with the wheat bran control. For the psyllium diet at 6% compared with 12% MUFA, the decreases in LDL cholesterol were 12.3 +/- 1.5% (P < 0.001) and 15.3 +/- 2.4% (P < 0.001), respectively. With the higher-MUFA diet triacylglycerol fell significantly over the control phase (16.6 +/- 5.5%, P = 0.006) and the ratio of LDL to HDL cholesterol fell significantly over the psyllium phase (7.3 +/- 2.8%, P = 0.015). Psyllium and MUFA intakes were negatively related to the percentage change in the ratio of LDL to HDL cholesterol (r = -0.34, P = 0.019 and r = -0.44, P = 0.002, respectively). Chenodeoxycholate synthesis rate increased (30 +/- 13%, P = 0.038) with the psyllium diet in the 12 subjects in whom this was assessed. We conclude that psyllium lowered LDL- and HDL-cholesterol concentrations similarly at both MUFA intakes. However, there may be some advantage in combining soluble fiber and MUFA to reduce the ratio of LDL to HDL cholesterol.

During a 7-month period, 29 units of feline whole blood in a hospital blood bank were confirmed, and 2 units were suspected, to be contaminated with Serratia marcescens. An investigation of the outbreak identified S marcescens in a jar of alcohol-soaked cotton balls and in a bag of saline solution used during venipuncture. Fifteen of the contaminated units were administered to 14 cats, and 6 of the 14 developed clinical signs of a transfusion reaction. The most common sign was vomiting; 4 cats died. The report underscores the importance of using aseptic techniques during collection of blood for transfusion and of thoroughly investigating any transfusion reaction.

This initial audit of 600 recently assessed Eastern Health Board orthodontic patients suggests that a large number of them (47 per cent) requires referral for routine restorative and preventive dental care. Closer links are needed with general dental practitioners and community dental surgeons to resolve these needs. The trend for a high referral of females and Class 11 Division 1 malocclusion type correlated well with studies in other countries.

The purpose of this study was to determine the duration of action of a single dose of hetastarch, a synthetic colloid, in hypoalbuminemic dogs. Thirty hypoalbuminemic dogs (albumin concentration, < or = 2.0 g/dL) received 1 dose of hetastarch each, with an average dose of 18.1 mL/kg. Doses ranged from 7.7 to 43.9 mL/kg, with the majority of doses (n = 26) in the range of 10 to 25 mL/kg. Dogs were allotted to one of several groups: all dogs, dogs with acute gastrointestinal protein loss, dogs with chronic gastrointestinal protein loss, all dogs with gastrointestinal protein loss, and dogs with nongastrointestinal protein loss. Colloid oncotic pressure was measured immediately before and immediately after hetastarch administration, and 12 hours after hetastarch administration. There was a significant (P < .001) increase in the mean colloid oncotic pressure after hetastarch treatment in all groups, except in the group with acute gastrointestinal protein loss. Twelve hours after hetastarch treatment, the mean colloid oncotic pressure had decreased significantly (P < .001) from the immediate post-treatment value in all groups, except in dogs in the groups with acute and chronic gastrointestinal protein loss. Twelve hours after hetastarch treatment the mean colloid oncotic pressure was not significantly (P < .001) different from the baseline mean colloid oncotic pressure in any of the groups. Twenty-three dogs (77%) survived their illness and were sent home, whereas, 7 (23%) died or were euthanized. The effect of a single dose of hetastarch on raising colloid oncotic pressure in dogs with hypoalbuminemia decreases significantly within 12 hours of administration, and is no longer significantly above baseline values. We conclude that multiple dosing is necessary to prolong the beneficial effects of hetastarch.

Background: Alprazolam has proven efficacy as a treatment for panic disorder, but the place of other benzodiazepines is less well established., Method: To compare the efficacy and tolerability of diazepam and alprazolam for the disorder, a placebo-controlled, double-blind trial was undertaken in two sites. Two hundred forty-one subjects with panic disorder or agoraphobia with panic attacks were randomly assigned to flexible doses of diazepam, alprazolam, or placebo for 8 weeks., Results: At the end of the trial, over 60% of subjects taking either diazepam or alprazolam were at least moderately improved compared with less than 30% of those taking placebo. On all measures of efficacy, subjects taking diazepam and alprazolam showed an equally favorable response. Despite some sedation early in the trial, both drugs were tolerated well. More severely ill subjects responded less well to either benzodiazepine., Conclusion: The results indicate that diazepam is an effective alternative to alprazolam for the treatment of panic disorder.

The treatment of visual pathway gliomas is controversial. The many retrospective studies reporting outcome data for patients with chiasmatic/hypothalamic gliomas are difficult to interpret for several reasons. First the natural history of these tumors is erratic with some reports suggesting that most visual pathway gliomas are hamartomas and follow an indolent course, and others reporting 10-year survival rates of close to 60%. Second, earlier studies did not clearly indicate which patients had neurofibromatosis type 1 (NF1) and recent evidence suggests that the natural history of optic gliomas is more favorable in patients with NF1. Third the methods and accuracy of diagnosis have changed dramatically and patients diagnosed before and after the advent of CT/MR imaging have often been included in the same series. While surgical resection is usually not a viable option for definitive treatment of these tumors, recent studies have shown favorable results after subtotal resection in selected patients. The efficacy of radiotherapy has not been unequivocally demonstrated and treatment-related morbidity has become a major concern, in particular, adverse effects on cognition and growth. Chemotherapy has been advanced as an viable alternative to avoid or delay the adverse affects of RT, but the long-term outcome benefits and adverse effects of treatment are just being defined. Despite the limitations of currently available information, sufficient data are now available to rational management quotelines for the majority of children with chiasmatic/hypothalamic gliomas.

There is some preliminary laboratory support for the proposed classification of depressed patients into depressive spectrum disease (DSD) and non-DSD. This study explores whether there is a difference in the levels of the norepinephrine metabolite, MHPG, in DSD and non-DSD patients. MHPG levels from 38 DSD patients were compared with 24 non-DSD patients. After controlling for the influence of age and gender on MHPG, the DSD patients had MHPG levels that were lower than non-DSD patients; 1655 +/- 90 mg/day vs. 1965 +/- 174 mg/day, respectively; P = 0.05. This study provides additional laboratory support for the DSD subtype. Possible implications of this finding are discussed.

Patients with depressive spectrum disorder (DSD) have low levels of the norepinephrine metabolite, MHPG. This study examines what happens to the low levels of MHPG following improvement of depressive symptoms. Sixteen depressed patients with a family history consistent with DSD showed no change in MHPG after 6 weeks of treatment. This was true for both treatment responders and nonresponders. The lack of change in low levels of MHPG suggests that reduced norepinephrine turnover is a biological trait of DSD patients. Implications of this finding are discussed.

Background: This study investigates the naturalistic course of panic disorder over four years and attempts to identify predictors for outcome., Method: 423 DSM-III-R panic disorder patients who had taken part in an international multicentre drug trial were selected for follow-up; we were able to re-interview 367 (87%). For panic attacks, phobic avoidance and disabilities the same rating scales were administered as had been used for the clinical trials., Results: While 61% of all patients experienced at least occasional panic attacks at follow-up, few suffered from serious phobic avoidance (16.7%) or serious disabilities (work 7.9%); family 8.7%; social 13.9%). Panic attack frequency at baseline, original trial medication and continuous use of psychotropic medication during follow-up are not related to outcome, whereas longer duration of illness and more severe phobic avoidance at baseline are unfavourable., Conclusion: The course of panic disorder is not uniform. Since long duration of illness and severe phobic avoidance at baseline are predictors for an unfavourable outcome, more rigorous efforts should be undertaken to detect and treat panic disorder at an early stage.

Objective: To report microsporidial keratoconjunctivitis in a patient infected with HIV who was treated with topical fumagillin., Case Summary: A 37-year-old white man who was experiencing redness, pain, irritation, decreased vision, and a foreign body sensation occurring in both eyes was referred to the ophthalmology clinic. The patient had a medical history significant for AIDS, Pneumocystis carinii pneumonia, and Cytomegalovirus retinitis. Conjunctival smears were taken and stained positive for the presence of Microsporidia. The patient was diagnosed with bilateral microsporidial keratoconjunctivitis and fumagillin therapy was initiated. After 5 days of therapy, the patient reported significant improvements characterized by a decrease in blurred vision with only slight blurring in the left eye, decrease in headache, and decreased foreign body sensation. The patient continued topical fumagillin therapy for more than 14 months, with only slight blurring in the left eye and no apparent ocular toxicity as a result of fumagillin therapy., Discussion: Although rare in occurrence, increasing numbers of documented microsporidial infections are being reported in the medical literature, particularly in individuals who are seropositive for HIV. Clinicians need to be cognizant of microsporidial keratoconjunctivitis as another opportunistic infection in this patient population., Conclusions: Although a curative agent has yet to be discovered, fumagillin represents a safe, effective, low-cost, topical agent for the treatment of microsporidial keratoconjunctivitis.

Elevations of urinary N-acetyl-beta-glucosaminidase (NAG) were found in previous studies of epileptic patients using carbamazepine. Since NAG can be a sensitive indicator of urinary tract problems, it was postulated that carbamazepine could be causing urinary tract damage. To explore this issue further, 27 mood disorder patients who were taking carbamazepine were compared to 171 mood disorder patients who were not using carbamazepine. There were no significant differences in NAG levels between the two groups. A hypothesis is presented which states that the elevated NAG levels found in some seizure patients could be associated with abnormalities of serotonin metabolism.

There is evidence that serotonin and norepinephrine are in some way involved in the pathophysiology of anxiety disorders. Urinary levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and the norepinephrine metabolite vanillylmandelic acid (VMA) were measured in 46 patients with generalized anxiety disorder. There was a significant association between urinary levels of 5-HIAA and VMA: r = 0.79; p = 0.0001. Possible implications of this finding are discussed.

Twenty-one medication-free patients with generalized anxiety disorder (GAD) collected urine samples for 5-hydroxyindoleacetic acid (5-HIAA) and N-acetyl-beta-glucosaminidase (NAG). Nine patients with no comorbid psychiatric diagnosis showed a significant association between 5-HIAA and NAG, r = -0.683, p = 0.04. The possibility that NAG could be a marker for serotonin metabolism is discussed.

The levels of N-acetyl-beta-glucosaminidase (NAG) from 57 unipolar patients were compared to the scores of symptom severity for nine symptom clusters derived from the Symptom Check List (SCL-90). The depression and hostility clusters were significantly associated with NAG levels. In a separate study of 21 unipolar patients, six out of 31 mood symptoms were significantly associated with NAG levels, as were two out of seven tested RDC depression subtypes. Serotonin abnormalities may play a role in the production of many of these symptoms. A hypothesis that NAG could be a marker for serotonin activity is discussed.

Eight-four panic disorder (PD) and 29 generalized anxiety disorder (GAD) patients were compared with respect to abnormal personality traits assessed by a structured interview (Structured Interview for DSM-III Personality [SIDP]) and a self-report inventory (Personality Diagnostic Questionnaire [PDQ]). An earlier study using many of the same patients by Noyes et al. found PD patients to have more extensive axis I psychopathology than GAD patients. However, in this study it was the GAD patients who appeared to have greater axis II pathology. In particular, when using a subset of patients who had been matched for age and gender, the GAD patients reported more antisocial traits. This finding is particularly interesting, since the matched samples consisted primarily of women in their forties and fifties.

The purpose of this study was to evaluate the safety and efficacy of the synthetic colloid hetastarch in dogs with hypoalbuminemia. Individual doses of hetastarch ranged from 9 to 27 mL/kg, and multiple doses were used frequently. Total doses ranged from 9 to 59 mL/kg. Colloid oncotic pressure was measured in 13 dogs before and after treatment. Mean colloid oncotic pressure +/- SD was 9.32 +/- 2.35 mm Hg before treatment and 16.41 +/- 1.61 mm Hg in 8 healthy pet dogs used as controls. The difference in these values was significant (P < .001). There was a significant increase in mean colloid oncotic pressure after the first dose of hetastarch, but there was no relationship between the dose of hetastarch and the magnitude of increase in colloid oncotic pressure. Peripheral edema or body cavity transudates resolved or decreased in 83% of the dogs despite concurrent use of crystalloid fluid therapy. There was also no relationship between the dose of hetastarch and resolution of edema. Worsening of the results from coagulograms occurred in 5 of 18 dogs, and included increased prothrombin time (n = 1), increased partial thromboplastin time (n = 5), and decreased platelet count (n = 3). Bleeding that occurred in 3 dogs could not be directly attributed to the hetastarch. There was no relationship between the dose of hetastarch and worsening of the values in the coagulograms.

Alcoholics admitted to the hospital solely for detoxication have been studied by flow cytometry to evaluate changes in the surface markers of peripheral blood leukocytes. As we have shown previously, such patients have an elevated percentage of CD8hi lymphocytes that are HLA DR+; we now demonstrate that they also have striking alterations in the quantitative relationships of the fine T-cell subsets. Both CD4+ and CD8hi lymphocytes have a sharply reduced percentage of the L-selectin+ CD45RA+ subset, increased percentages of the CD45RA- subsets, and several other fine subset alterations. The fine subset profile suggests, according to current correlations of phenotype and function, that both CD4+ suppressor inducer and CD4-dependent CD8+ suppressor effector cells are reduced, whereas other subsets, including CD8+ CTL or their precursors, are increased in relative percentages. Some of the phenotypic changes are reversible over the several days following withdrawal. In other results, the percentage of CD8hi lymphocytes epxressing CD11b (beta-integrin) is shown to be reciprocal with the percentage expressing L-selectin both in normals and alcoholics. However, the regression function of CD11b vs. L-selectin on CD8hi cells is different for the alcoholics than for the normals, indicating an abnormality in the regulation of the expression of these two adhesion markers. Taken together, this abnormality of adhesion molecules and the fine subset alterations previously described indicate widespread changes in the peripheral lymphocytes of currently drinking alcoholics. These changes suggest functional deficiencies that may include alterations of lymphocyte traffic and other adhesion-dependent functions, and a shift in the balance of regulatory interactions.

In the classical corneomandibular reflex (CMR), corneal stimulation elicits a bilateral eyelid blink and a brisk anterolateral jaw movement. We here describe 14 patients with a spontaneous palpebromandibular (eyelid-jaw) synkinesia (SPMS) in whom jaw movements, similar to those in CMR, regularly accompanied spontaneous eye blinks without an external corneal stimulus. Eleven of the patients with SPMS also had CMRs on corneal stimulation. Four patients had clinical and imaging evidence of brainstem lesions above the mid-pons, 5 patients had autopsy or imaging evidence of both bilateral cerebral and upper brainstem lesions, and 5 patients had clinical or imaging evidence of bilateral cerebral dysfunction. Topical corneal anesthesia administered to patients who had both CMR and SPMS blocked the CMR but had no effect on the SPMS. In patients with both SPMS and CMR, measurements of latency from onset of orbicularis oculi electromyographic activity to onset of lateral pterygoid EMG activity, and mandibular kinesiography of jaw velocity and direction showed that the eyelid-jaw synkinesias of CMR and SPMS had similar characteristics. We conclude that SPMS is pathophysiologically the same as the eyelid-jaw synkinesia of CMR and both synkinesias originate centrally, probably in the pons. In CMR, the jaw movement is primarily related to the blink rather than the corneal stimulus, but corneal stimulation may be necessary to overcome a higher threshold for expression of the synkinesia than in patients with SPMS. Like CMR, SPMS emerges in patients with upper brainstem or bilateral cerebral lesions and SPMS may therefore be a useful localizing clinical sign.

Urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) levels in 53 depressed women were compared to current suicidal thoughts or activity. Comparisons were also made between MHPG and past suicide attempts, number of past attempts, and seriousness of the worst attempt. There was a weak trend for current but not past suicidality to be associated with decreased MHPG levels.

Examination of the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in the urine of psychiatry patients has generally not been used because the reliability of urinary 5-HIAA levels has been questioned. Thirty-seven generalized anxiety disordered patients collected two consecutive urines for measurement of 5-HIAA. The correlation of the 5-HIAA collections was r = 0.82, p = 0.0001.

Background: Herpes gestationis (HG) is a rare, pregnancy-related skin disease characterized by the production of an autoantibody to a component of the hemidesmosome. It is associated with the class II antigens HLA-DR3 and HLA-DR4, but its potential association with the "class III antigens" C2, C4, and factor B has not previously been studied., Objective: Our purpose was to study complement polymorphism in HG., Methods: Using electrophoresis and immunofixation techniques, we determined the allele frequencies of C4A, C4B, C3, and factor B in 42 patients with a history of HG., Results: Ninety percent of patients carried a C4 null allele (C4*QO). No statistically significant association with C3 or factor B alleles was seen., Conclusion: HG is associated with the presence of a C4*QO. Whether the C4*QO is the primary genetic association, or whether the C4*QO is related to its linkage disequilibrium with DR3 and DR4 has yet to be determined.

Panic disorder is relatively common in older patients and may have serious consequences. The diagnosis is based on an accurate history of symptom onset and intensity. Symptoms include shortness of breath, dizziness, increased heart rate, trembling, and sweating. Effective treatment can be achieved with several kinds of medication, including benzodiazepines. Although physician and patient fears about benzodiazepines persist, panic-disordered patients with no history of drug abuse rarely develop substance dependence problems. Physical dependence occurs in a minority of patients and can be minimized by a slow tapering schedule. As with most medications, benzodiazepines need to be used with caution in older patients, who are more susceptible to adverse effects.

Thirteen depressed patients with documented histories of failure to respond to tricyclic antidepressant medications who reported multiple partial seizure like symptoms were given open trials of carbamazepine. Eleven of the 13 showed moderate to substantial improvement in affective status that was accompanied by significant mean changes on the Beck or Hamilton depression scales. In addition, the mean number of reported partial seizure-like symptoms decreased significantly with treatment. Dichotic word listening performance was the only neuropsychological variable that was impaired at baseline and was also the only cognitive performance that improved following treatment. These preliminary observations suggest that there is likely to be a subgroup of treatment-resistant, carbamazepine-responsive depressives who can be identified by evaluating for the presence of multiple partial seizure-like symptoms.