Retrospective analysis of an outbreak of B virus infection in a colony of DeBrazza's monkeys (Cercopithecus neglectus).

In 1981, an outbreak of herpetic disease developed in a colony of DeBrazza's monkeys (Cercopithecus neglectus). In seven of eight infected animals, clinical signs of infection included vesicular and ulcerative lesions on the lips, tongue, and/or palate. Histologic examination of lesions revealed intranuclear inclusion bodies, and electron microscopy revealed nucleocapsids and virions with typical herpesvirus morphology. Although a virus was isolated that appeared similar to monkey B virus, techniques available at the time did not allow precise identification of the virus. Analysis of serum from one surviving monkey collected 12 years after the outbreak revealed a pattern of reactivity characteristic of B virus-positive serum on the basis of results of ELISA and western immunoblot analysis. Polymerase chain reaction analysis of archived paraffin-embedded tissue specimens and molecular analysis of the one viral isolate obtained from a DeBrazza's monkey indicated that the virus responsible for the outbreak was a new genotype of B virus. Testing of sera from lion-tailed macaques (Macaca silenus) housed in an adjacent cage at the same zoo indicated that these animals harbored this virus and, thus, were the likely source of the virus that infected the DeBrazza's monkeys. This study documents usefulness of archiving samples from disease outbreaks for later analysis. In addition, this incident underscores the importance of considering herpes B virus infection when outbreaks of disease having characteristics of herpetic infections develop in nonhuman primates kept at institutions that also house macaques.

Differential trace amine alterations in individuals receiving acetylenic inhibitors of MAO-A (clorgyline) or MAO-B (selegiline and pargyline).

Marked, dose-dependent elevations in the urinary excretion of phenylethylamine, para-tyramine, and meta-tyramine were observed in depressed patients treated for three or more weeks with 10, 30, or 60 mg/day of the partially-selective inhibitor of MAO-B, selegiline (l-deprenyl). In comparative studies with other, structurally similar acetylenic inhibitors of MAO, pargyline, an MAO-B > MAO-A inhibitor used in doses of 90 mg/day for three or more weeks, produced elevations in these trace amines which were similar to those found with the highest dose of selegiline studied. Clorgyline, a selective inhibitor of MAO-A used in doses of 30 mg/day for three or more weeks (a dose/time regimen previously reported to reduce urinary, plasma, and cerebrospinal fluid 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) > 80%, indicating a marked inhibitory effect on MAO-A in humans in vivo) produced negligible changes in trace amine excretion. In comparison to recent studies of individuals lacking the genes for MAO-A, MAO-B, or both MAO-A and MAO-B, the lack of change in trace amine excretion in individuals with a mutation affecting only MAO-A is in agreement with the observed lack of effect of clorgyline in the present study. Selegiline produced larger changes in trace amines--at least at the higher doses studied--than found in individuals lacking the gene for MAO-B, in agreement with other data suggesting a lesser selectivity for MAO-B inhibition when selegiline was given in doses higher than 10 mg/day. Overall, trace amine elevations in individuals receiving the highest dose of deprenyl or receiving pargyline were approximately three to five-fold lower than the elevations observed in individuals lacking the genes for both MAO-A and MAO-B, suggesting that these drug doses yield incomplete inhibition of MAO-A and MAO-B.

Phospholipase A2-mediated inflammation induces regression of malignant gliomas.

An ideal form of cancer therapy is the harnessing of innate immunity to eradicate spontaneously arising clones of malignant cells. To date, attempts to develop effective immunotherapies have met with limited success. Prostaglandins and leukotrienes, collectively known as eicosanoids, are important mediators of immune and inflammatory responses. Harnessing these compounds could be a method to treat cancers. Eicosanoids are formed after cleavage of fatty acids from phospholipids by phospholipase enzymes. We have previously described, characterized and cloned a naturally occurring mammalian activator of phospholipase A2. Injection of a 24 amino acid peptide from this phospholipase A2 activating protein (PLAP), resulted in induction of an acute inflammatory response, and a concomitant regression of gliomas in rats. Administration of 500 micrograms of this protein resulted in a 50% decrease of the tumor mass within 72 h. Tumor regression coincided with a greater than twenty-fold increase in levels of prostaglandin E2(PGE2) and leukotriene B4(LTB4), and a marked infiltration of natural killer(NK) cells. These data suggest that activation of phospholipase A2 and modulation of the eicosanoid biosynthetic pathway may provide a novel therapeutic strategy for the successful treatment of malignant tumors of the nervous system.

The advantages of using triple-marker screening for chromosomal abnormalities.

OBJECTIVE: Our purpose was to assess the utility of triple-marker serum screening for chromosomal abnormalities. STUDY DESIGN: Our laboratory received 10,605 samples that were between 15 and 22 weeks' gestation for maternal serum screening of chromosomal abnormalities. Triple-marker maternal serum screening consisted of alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol in conjunction with maternal age. Women > or = 35 years old were first offered amniocentesis. If they refused amniocentesis, they were offered the screening test. A second-trimester risk for trisomy 21 > or = 1:270 was considered screen positive. Patients were screen positive for trisomy 18 if all three markers were low: alpha-fetoprotein < or = 0.75 multiples of the median, unconjugated estriol < or = 0.60 multiples of the median, and human chorionic gonadotropin < or = 0.55 multiples of the median. RESULTS: The initial screen-positive rate was 8.3% (880 women); amniocentesis was offered to 766 (7.2%). Twelve of 16 ascertained cases of trisomy 21 (75%), two of three cases of trisomy 18 (67%), five cases of 45,X karyotype, and one case each of 45,X/46,XX, 47,XXY, 47,XYY, 46,XX,ins(2)(q21p13p15)mat, and 69,XXX karyotypes were identified in the screen-positive patients. All four known cases of trisomy 21 in the 886 women > or = 35 years old who were screened were detected, with a 21% false-positive rate. Omitting unconjugated estriol from our screening program would have resulted in detecting nine of 16 trisomy 21 and six of 12 other chromosomal abnormalities. The false-positive rate would have remained the same. CONCLUSION: In our sample cohort addition of unconjugated estriol to the screening program resulted in an increased detection rate of chromosomal abnormalities with no change in the false-positive rate. Considering the advancement in screening for chromosomal abnormalities, maternal age alone as an indication for amniocentesis should be reevaluated.

Herpesvirus papio 2, an SA8-like alpha-herpesvirus of baboons.

Several SA8 isolates obtained from baboons were compared to the prototype SA8 herpesvirus of African green monkeys. SDS-PAGE and restriction enzyme analyses revealed definite differences between green monkey and baboon isolates. DNA and amino acid sequences of the gB, gD and gJ glycoprotein genes exhibited substantial differences in variable regions. For the gB and gD, the amount of amino acid substitutions between SA8 and the baboon viruses was comparable to levels observed between analogous genes of SA8 & B virus or HSV1 & HSV2. Although a high degree of antigenic cross-reactivity was apparent, virus-specific antigenic determinants were also readily detected. Phylogenetic analyses supported separation of the baboon isolates and SA8 as distinct viruses. Taken together these results suggest that although closely related to SA8, the baboon viruses represent a distinct simian alpha-herpesvirus which we propose be designated Herpesvirus papio 2.

Inclusion body myositis as a cause of respiratory failure.

Inclusion body myositis (IBM) is a slowly progressive myopathy that has not been reported to affect respiratory muscles. It is often refractory to treatment and a muscle biopsy specimen is necessary for the diagnosis. This is a report of a patient with IBM who quickly progressed to respiratory muscle failure requiring intubation.

Predicting response to amitriptyline in posttraumatic stress disorder.

OBJECTIVE: This study evaluated the relation between baseline clinical phenomena and response to amitriptyline in patients with posttraumatic stress disorder (PTSD). METHOD: Data were obtained from an 8-week placebo-controlled, double-blind study of combat veterans. Bivariate and multivariate statistics were used to evaluate the relations between the following variables and outcome: age, depression, anxiety, severity of PTSD symptoms, personality, psychiatric comorbidity, level of exposure to trauma, and individual symptoms of depression, anxiety, and traumatic stress. Outcome measures were scores on the Clinical Global Impression scale, Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, and Impact of Event Scale. RESULTS: Drug response was related to lower baseline levels of depression, neuroticism, combat intensity, anxious mood, impaired concentration, somatic symptoms, feelings of guilt, and one intrusion and four avoidance symptoms of PTSD. CONCLUSIONS: The results demonstrate that response to amitriptyline is related to measures of depression, anxiety, PTSD, personality, and intensity of combat trauma. Similar relationships were not observed in the placebo group, suggesting a specific relationship to the drug.

MELAS point mutation with unusual clinical presentation.

Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) is a multisystemic mitochondrial disorder (Pavlakis et al. Advances in Contemporary Neurology. Philadelphia: Davis, 1988: 95-133) and most patients with the typical MELAS phenotype have a point mutation in mitochondrial DNA, an A to G transition at nucleotide 3243 (Goto et al. Nature 1990; 348; 651-653; Koboyashi et al. Biochem Biophys Res Commun 1990; 173: 816-822; Ciafaloni et al. Ann Neurol 1992; 31: 391-398). A 9-yr-old boy presenting with chronic asthma and depression was found to have abnormal mitochondria, partial defects of respiratory chain enzymes, and the MELAS point mutation.

Progressive nemaline rod myopathy in a woman coinfected with HIV-1 and HTLV-2.

Nemaline-rod myopathy was recently reported in eight young males infected with human immune deficiency virus type 1 (HIV-1). A 41-year-old woman had a 2-year history of progressive proximal-muscle weakness. Muscle biopsy demonstrated the presence of nemaline rods, predominantly in type 1 fibers. She was coinfected with HIV-1 and HTLV-2, as evidenced by positive polymerase chain reaction and serology. There was no lymphopenia or CD4 lymphopenia, despite an abnormal T-cell subset ratio, high CD8 count, skin anergy, and depressed in vitro response to mitogens. This case raises the possibility that dual infection may play a role in the pathogenesis of the rare nemaline-rod myopathies of HIV-infected patients.

A cognitive-behavioral therapy for sleep-maintenance insomnia in older adults.

Older adults (3 men, 4 women, aged 55 to 68 years) with chronic sleep-maintenance insomnia were treated sequentially with relaxation therapy (RT) and then with a cognitive-behavioral therapy (CBT) specifically designed for alleviating sleep maintenance problems. Sleep diaries and an objective measure of sleep, the sleep assessment device, showed only modest improvements in measures of wake time after sleep onset, sleep efficiency, and night-to-night sleep variability following RT. However, significant improvements in these measures were observed following CBT and at a 3-month follow-up. These findings, considered in conjunction with previous reports, suggest that CBT specifically addresses factors that sustain sleep maintenance complaints. Additional trials of CBT with larger samples are warranted.

Duchenne muscular dystrophy in a girl identified by dystrophin deficiency.

We report an isolated case of a girl aged three years six months with Duchenne muscular dystrophy. Analysis of the patient's DNA with a probe covering the DNA gene revealed no deletion. Dystrophin, studied in biopsied muscle from the patient, using antidystrophin antibody in combination with immunofluorescence, was nearly completely absent. In this sporadic case of female muscular dystrophy, the identification of dystrophin-deficient muscle fibers made it possible to establish an accurate diagnosis of DMD affected female.

Three cases of paraphilias responsive to fluoxetine treatment.

Three cases are presented in which fluoxetine was employed in the apparently successful treatment of paraphilia, a disorder which has been difficult to treat pharmacologically. Therapeutic benefit may have been related to the efficacy of fluoxetine in the treatment of obsessive compulsive disorders or to direct effects on sexual activity, or both.

Treatment of posttraumatic stress disorder with amitriptyline and placebo.

Amitriptyline hydrochloride was compared with placebo in 46 veterans with chronic posttraumatic stress disorder. Treatment continued up to 8 weeks, and efficacy was measured by five observer and two self-rated scales. Percent recovery rates were higher for amitriptyline than placebo on two measures. In patients who completed 4 weeks (n = 40), better outcome with amitriptyline was noted on the Hamilton depression scale only. In the group completing 8 weeks of treatment (n = 33), the drug was superior to placebo on Hamilton depression, Hamilton anxiety, Clinical Global Impression severity, and Impact of Event scales. There was no evidence for drug effects on the structured interview for posttraumatic stress disorder. Drug-placebo differences were greater in the presence of comorbidity in general, although recovery rates were uniformly low in the presence of major depression, panic disorder, and alcoholism. At the end of treatment, 64% of the amitriptyline and 72% of the placebo samples still met diagnostic criteria for posttraumatic stress disorder.

The corticotropin-releasing hormone test in patients with posttraumatic stress disorder.

To evaluate the hypothalamic-pituitary-adrenal (HPA) axis in patients with posttraumatic stress disorder (PTSD), we measured adrenocorticotropin hormone (ACTH) and cortisol responses following administration of corticotropin-releasing hormone (CRH) in 8 combat veterans with chronic PTSD. The PTSD patients had a significantly lower ACTH response to CRH compared to a control group of normal volunteers. Blunted ACTH responses occurred in patients with PTSD alone, as well as those PTSD patients who also had major depression. The cortisol response, although reduced, was not significantly different from normal. The blunted ACTH response to CRH in PTSD patients is similar to that seen in other psychiatric disorders, such as depression, panic disorder, and anorexia nervosa.