Varroa chemosensory proteins: some are conserved across Arthropoda but others are arachnid specific.

The tight synchronization between the life cycle of the obligatory parasitic mite Varroa destructor (Varroa) and its host, the honeybee, is mediated by honeybee chemical stimuli. These stimuli are mainly perceived by a pit organ located on the distal part of the mite's foreleg. In the present study, we searched for Varroa chemosensory molecular components by comparing transcriptomic and proteomic profiles between forelegs from different physiological stages, and rear legs. In general, a comparative transcriptomic analysis showed a clear separation of the expression profiles between the rear legs and the three groups of forelegs (phoretic, reproductive and tray-collected mites). Most of the differentially expressed transcripts and proteins in the mite's foreleg were previously uncharacterized. Using a conserved domain approach, we identified 45 transcripts with known chemosensory domains belonging to seven chemosensory protein families, of which 14 were significantly upregulated in the mite's forelegs when compared to rear legs. These are soluble and membrane bound proteins, including the somewhat ignored receptors of degenerin/epithelial Na+ channels and transient receptor potentials. Phylogenetic clustering and expression profiles of the putative chemosensory proteins suggest their role in chemosensation and shed light on the evolution of these proteins in Chelicerata.

Low ALT Levels Independently Associated with 22-Year All-Cause Mortality Among Coronary Heart Disease Patients.

BACKGROUND: Low alanine aminotransferase (ALT) blood levels are known to be associated with frailty and increased risk of long-term mortality in certain populations. However, the contribution of this marker to long-term outcome has not been assessed in patients with chronic coronary heart disease. OBJECTIVE: The aim of the current study was to assess the association between low ALT values and long-term, 22.8-year, all-cause mortality in this population. PARTICIPANTS: We examined the association of low ALT (<17 IU/l) with long-term all-cause mortality in the Bezafibrate Infarction Prevention (BIP) Registry population. KEY RESULTS: Appropriate laboratory and survival data were available for 6,575 patients, without known liver pathology, included in the BIP registry, with a median follow-up period of 22.8 years. The cumulative probability of all-cause mortality was significantly higher in the low ALT group compared with patients with higher ALT levels (65.6 % vs. 58.4 %; log-rank p < 0.001). Consistently, multivariate analysis, adjusted for multiple established predictors of mortality in this population, demonstrated that low ALT is independently associated with 11 % greater long-term (22.8 years) mortality risk [HR 1.11 (95 % confidence interval: 1.03-1.19; adjusted p < 0.01)]. CONCLUSIONS: Low ALT levels are associated with increased long-term mortality among middle-aged patients with stable coronary heart disease. This association remained statistically significant after adjustment for other well-established risk factors for mortality in this population.

Cardiovascular syncope: diagnostic approach and risk assessment.

Cardiovascular syncope, defined as a transient loss of consciousness resulting from a global cerebral hypoperfusion characterized by rapid onset and spontaneous rapid recovery, comprises events due to bradyarrhythmias, tachyarrhythmias, and structural cardiovascular disease. The evaluation of cardiovascular syncope must be careful and thorough as this type of syncope is associated with increased subsequent morbidity and mortality. In this review we provide current data regarding specific causes of cardiovascular syncope, diagnostic approach, risk stratification, and management of patients who experience a syncope event when a cardiovascular disorder is suspected to be a precipitating factor for the syncope event. Multiple risk stratifications studies were carried out to identify patients at high risk for cardiovascular syncope; we provide several prominent examples of such risk stratifications, with special focus on the congenital long QT syndrome (LQTS) as an example of an arrhythmogenic disorder associated with syncope and sudden cardiac death in young individuals without structural heart disease.

Transient osteoporosis associated with hyperhomocystinemia: a possible role for hyperbaric oxygen therapy.

Transient osteoporosis of the hip is considered by some to be an early stage of avascular necrosis. Hyperbaric oxygen (HBO2) therapy, which may be of benefit in the treatment of avascular necrosis, might therefore be used in the treatment of transient osteoporosis of the hip. We present a case of transient osteoporosis associated with elevated levels of homocysteine in a 33-year-old white male, who was treated by HBO2. Treatment was administered at 2.5 ATA for 90 minutes once daily, five days per week. Regular follow-up examinations in the course of the HBO2 therapy revealed improvement in the patient's complaints and the findings of the physical examination. Repeated magnetic resonance imaging (MRI) performed after 40 and 90 sessions showed decreased edema and complete resolution of the edema, respectively. Evaluation 6 months after the completion of treatment revealed complete resolution of symptoms, with a normal physical examination.

Angiotensin II-induced apoptosis in rat cardiomyocyte culture: a possible role of AT1 and AT2 receptors.

OBJECTIVES: To investigate the mechanism of angiotensin II-induced apoptosis in cultured cardiomyocytes by determining which receptor subtype is involved, and what is the relationship between intracellular Ca2+ changes and apoptosis. DESIGN AND METHODS: Neonatal rat cardiomyocytes were pretreated with either the AT1 antagonist irbesartan or the AT2 antagonist PD123319 before exposure to angiotensin II. Apoptosis was evaluated using morphological technique, staining nuclei by Feulgen and Hoechst methods followed by image analysis and by in situ terminal deoxynucleotidyl transferase nick-end (TUNEL) labelling. TUNEL-positive cardiocytes were distinguished from other cells by double staining with alpha-sarcomeric actin. Intracellular Ca2+ changes were assessed by indo-1 fluorescence microscopy, and the effect of Ca2+ on angiotensin II-induced apoptosis was tested using the calcium channel blocker verapamil. RESULTS: Exposure to angiotensin II (10 nmol/l) resulted in cell replication and a three-fold increase in programmed cell death (P < 0.05). Pretreatment with either irbesartan (an AT1receptor antagonist, 100 nmol/l) or PD123319 (an AT2 receptor antagonist, 1 micromol/l) prevented the angiotensin II-induced apoptosis, indicating the presence of both AT1 and AT2receptors on cardiomyocytes. Exposure of myocytes to angiotensin II caused an immediate and dose-dependent increase in the concentration of intracellular free Ca2+ that lasted 40-60 s. The effect was sustained in a Ca2+ free medium. Pretreatment of cells with irbesartan (100 nmol/l) and PD123319 (10 micromol/l) blocked Ca2+ elevation. Pretreatment with verapamil (10 micromol/l) prevented angiotensin II-induced apoptosis. CONCLUSIONS: Angiotensin II-induced apoptosis in rat cardiomyocytes is mediated through activation of both AT1 and AT2 receptors. The apoptotic mechanism is not related to the immediate angiotensin II-induced Ca2+ rise from intracellular stores. However, it is accompanied by cardiomyocyte proliferation and requires Ca2+ influx through L-type channel activity.

Pharmacologic treatment of anxiety disorders in 1989 versus 1996: results from the Harvard/Brown anxiety disorders research program.

OBJECTIVE: This article reports on the pharmacologic treatment of patients diagnosed with generalized anxiety disorder (GAD) enrolled in a naturalistic long-term study of anxiety disorders, with enrollment in 1989 through 1991 and follow-up in 1996. METHOD: 711 patients were enrolled in the study during 1989-1991. At intake, 167 patients met DSM-III-R criteria for GAD; at 1996 follow-up, 103 patients met these criteria. The patients were divided into 3 groups by diagnosis: GAD alone (N = 18 at intake, N =11 at follow-up), GAD comorbid with another anxiety disorder (N = 84 at intake, N = 52 at follow-up), and GAD comorbid with Research Diagnostic Criteria-defined major depressive disorder, with or without another anxiety disorder (N = 65 at intake, N = 40 at follow-up). The groups were evaluated at intake and follow-up on whether they received medication and the types of medication they received. RESULTS: Nearly one third of patients in the 1989-1991 sample were not receiving any medication for treatment of their anxiety disorder; in 1996, 27% of patients still were receiving no medication. There was a decrease in benzodiazepine treatment and an increase in antidepressant treatment in 1996 for GAD patients who did not have comorbid depression or another anxiety disorder. CONCLUSION: The finding of one quarter to one third of patients with GAD receiving no medication is consistent with previous observations of undertreatment of depression. The findings on medication type suggest a shift in the type of medications being prescribed for treatment of GAD from exclusive benzodiazepine treatment to the combination of benzodiazepine and antidepressant treatment.

Early hyperbaric oxygen therapy for retinal artery occlusion.

PURPOSE: To assess whether early hyperbaric oxygenation (HBO) treatment has a beneficial effect on visual results after retinal artery occlusion (RAO). METHODS: A comparative retrospective study in which medical records of all HBO-treated RAO patients in our department were reviewed and compared with matched RAO patients not treated by HBO (from a different medical center). Mean visual acuity (VA) at completion of treatment, the presence or absence of improvement in VA between admission and discharge, and the mean change in VA between admission and discharge were noted. All patients treated by HBO had treatment no later than 8 hours after the beginning of visual symptoms. RESULTS: Mean VA at discharge was 0.2981 (6/20) in the treated group and 0.1308 (6/46) in the control group (p < 0.03). In the treated group, 82.9% had an improvement in VA between admission and discharge, compared with 29.7% of the control group (p < 0.00001). Mean improvement in VA was 0.1957 in the treated group and 0.0457 in the control group (p < 0.01). Differences in outcome measures between treatment and control groups were found to reflect the difference between treated and untreated hypertensive patients. No difference was found between treated and untreated non-hypertensive patients. CONCLUSIONS: Early HBO therapy appears to have a beneficial effect on visual outcome in patients with RAO. Further large-scale prospective controlled studies are needed to confirm this.

Comparing primary and secondary generalized anxiety disorder in a long-term naturalistic study of anxiety disorders.

This study explores the potential differences in comorbidity and course between primary generalized anxiety disorder (GAD), which develops before other anxiety disorders, and secondary GAD. As part of the Harvard/Brown Anxiety Research Project (HARP), a naturalistic, long-term, longitudinal study of 711 subjects from a variety of clinic settings with DSM III-R defined anxiety disorders, 210 subjects with GAD were identified. Of these, 78 (37%) had primary GAD, and 84 (40%) had secondary GAD; of the remainder, 28 (13%) had no other anxiety disorder and 20 (10%) developed GAD within a month of another anxiety disorder and were excluded from the analysis. All subjects were comorbid for at least one other anxiety disorder. Primary GAD subjects were more likely to be in episode at intake (90% vs. 77%, P = .04) and less likely than secondary GAD subjects to have current or past agoraphobia without panic disorder (3% vs. 11%, P = .04), social phobia (19% v. 52%, P = .001), simple phobia (14% v. 30%, P = .02), or post traumatic stress disorder (5% vs. 20%, P = .01). Subjects with primary GAD were also less likely to have current or past alcohol use disorders (17% vs. 37%, P = .004) or major depressive disorder (60% vs. 76%, P = .03). There were no significant differences in either treatment approaches or remission rates for primary compared to secondary GAD. Whether GAD first occurs before or after another anxiety disorder, it is similar in terms of prevalence, treatment, and course. The only significant differences between primary and secondary GAD lie in the rates of comorbidity of both other anxiety disorders and non-anxiety disorders, including major depression and substance abuse. These results support the concept of GAD as a valid, separate and distinct entity, whether it occurs primarily or secondarily.

Simple phobia as a comorbid anxiety disorder.

This study sought to describe clinical and demographic characteristics differentiating patients with DSM-III-R simple phobias comorbid with one or more of five DSM-III-R index anxiety disorders as compared with those with the index diagnoses alone. From 711 subjects participating in a multicenter, longitudinal, naturalistic study of anxiety disorders, 115 subjects with comorbid simple phobias were compared with 596 subjects without simple phobias in terms of demographic data, comorbidity with other disorders, somatic and psychosocial treatment received, and quality of life. In addition, episode characteristics, types of simple phobias found, and course of illness were specified. Subjects with simple phobias had more additional comorbid anxiety disorders by history than did those without. Mean length of intake episode was 22.43 years and severity was typically moderate. Fears of heights and animals were the most commonly represented simple phobias. Subjects with uncomplicated panic disorder were less likely to have comorbid simple phobias than were subjects with other index diagnoses, and subjects with simple phobia were more likely to have comorbid posttraumatic stress disorder than were these without simple phobia. Subjects with and without simple phobias did not differ by somatic or psychosocial treatment received or in terms of quality of life. Simple phobia appeared in this study to be a chronic illness of moderate severity for which behavioral treatment methods of recognized efficacy were not being frequently utilized. Uncomplicated panic disorder may reflect some type of resistance to phobia development.

Peripartum cardiomyopathy occurring in a patient previously treated with doxorubicin.

We present a 28-year-old primigravida woman in whom congestive heart failure developed 3 months after delivery of a neonate. The patient underwent doxorubicin treatment 10 years previously. The combined cardiotoxicity of prior doxorubicin treatment and pregnancy is considered, and the importance of careful follow-up of cardiac function during pregnancy and postpartum in patients previously treated with doxorubicin is stressed.

Elevated levels of serum creatine kinase induced by hyponatraemia.

Elevated serum creatine kinase levels are one of the major criteria for the diagnosis of myocardial injury. Noncardiac causes such as muscular and brain damage may also be associated with elevated serum creatine kinase levels. Hyponatremia may induce increased serum creatine kinase in association with rhabdomyolysis or with hypothyroidism. A patient is described where three episodes of hyponatraemia not associated with rhabdomyolysis or hypothyroidism induced transient elevations of serum creatine kinase levels. The association between hyponatraemia and elevated creatine kinase levels should be emphasized to prevent erroneous diagnosis of myocardial injury.

Effects on pulmonary function of daily exposure to dry or humidified hyperbaric oxygen.

The purpose of this study was to examine the effects of breathing dry or humidified hyperbaric oxygen on pulmonary function. Pulmonary function tests were performed before and after each of 10 hyperbaric oxygen exposures at 2.5 atmospheres absolute (ATA) for 95 min in a group of 13 patients treated daily by hyperbaric oxygen for problem wounds. Patients breathed dry oxygen during five successive sessions and humidified oxygen during the remaining five. No differences were found between forced vital capacities (FVC) and maximal expiratory flows before and after hyperbaric oxygen exposure while breathing dry or humidified oxygen. Significant differences were found for the changes in the percentage of FVC expired in 1 s (FEV1%) and mean forced mid-expiratory flow rate during the middle half of the FVC (FEF25-75%) on day 1 alone: decrements of 1.42 and 2.96%, respectively, under dry oxygen, vs. increments of 3.93 and 34.4%, respectively, for humidified oxygen. Day-to-day decrements in the percent changes in FEV1% and FEF25-75% were observed while breathing humidified hyperbaric oxygen. These results demonstrate that repeated daily exposure to humidified hyperbaric oxygen abolishes the initial beneficial effect of humidification on peripheral airways flow characteristics.

Thermal status of wet-suited divers using closed circuit O2 apparatus in sea water of 17-18.5 degrees C.

A wet suit may not provide adequate thermal protection when diving in moderately cold water (17-18 degrees C), and any resultant mild hypothermia may impair performance during prolonged diving. We studied heat exchange during a dive to a depth of 5 m in sea water (17-18.5 degrees C) in divers wearing a full wet suit and using closed-circuit oxygen breathing apparatus. Eight fin swimmers dived for 3.1 h and six underwater scooter (UWS) divers propelled themselves through the water for 3.7 h. The measurements taken throughout the dive were the oxygen pressure in the cylinder and skin and rectal temperatures (Tre). Each subject also completed a cold score questionnaire. The Tre decreased continuously in all subjects. Oxygen consumption in the fin divers (1.40 l.min-1) was higher than that of the UWS divers (1.05 l.min-1). The mean total insulation was 0.087 degree C.m2.W-1 in both groups. Mean body insulation was 37% of the total insulation (suit insulation was 63%). The reduction in Tre over the 1st hour was related to subcutaneous fat thickness. There was a correlation between cold score and Tre at the end of 1 h, but not after that. A full wet suit does not appear to provide adequate thermal protection when diving in moderately cold water.

Panic disorder versus panic disorder with major depression; defining and understanding differences in psychiatric morbidity.

The present study examined the impact of comorbid major depressive disorder (MDD) on psychiatric morbidity, panic symptomatology and frequency of other comorbid psychiatric conditions in subjects with panic disorder (PD). Four hundred thirty-seven patients with PD were evaluated at intake as part of a multicenter longitudinal study of anxiety disorders; 113 of these patients were also in an episode of MDD. Patients were diagnosed by DSM-III-R criteria utilizing structured clinical interviews. The 113 PD/MDD patients were compared with the 324 remaining PD subjects regarding panic symptoms at intake, sociodemographic, quality of life and psychiatric morbidity variables. Differences in frequency of other comorbid Axis I psychiatric disorders were assessed at intake; personality disorders were evaluated twelve months after intake. The results revealed the PD/MDD patients exhibit increased morbidity and decreased psychosocial functioning as compared to PD patients. Personality disorders were more prevalent in the PD/MDD group at six month follow-up assessment; the PD/MDD group also had an increased frequency of posttraumatic stress disorder (PTSD) and more comorbid Axis I anxiety disorders as compared to the PD group. The total number and frequency of panic symptoms was highly consistent between the two patient groups.

The infrequency of "pure culture" diagnoses among the anxiety disorders.

BACKGROUND: Anxiety disorders are known to commonly coexist in individuals, both with other anxiety disorders and with mental disorders from other groupings, such as affective disorders. We questioned how frequently anxiety disorders actually occur in isolation, as "pure cultures." METHOD: We examined diagnostic patterns among the 711 subjects entered into a large, multicenter study of anxiety disorders, the Harvard/ Brown Anxiety Disorders Research Program (HARP), which focused on panic, agoraphobia, generalized anxiety disorder, and social phobias as "index disorders" required for intake. RESULTS: We used various definitions for "pure culture." By all definitions, subjects with "pure culture" represented a minority, especially in cases of generalized anxiety disorder and social phobia, where comorbidity was virtually ubiquitous. "Pure culture" status was associated with later onset of illness and less chronicity. CONCLUSION: Future studies of anxiety disorder should aim to document the extensive comorbidity, rather than eliminate it by restrictive diagnostic exclusion criteria, lest they yield atypical or even misrepresented groups of patients. Clinicians should not stop at identifying only the "main" diagnosis but look for other, comorbid diagnoses that are often present.

Benzodiazepine use in anxiety disordered patients with and without a history of alcoholism.

BACKGROUND: People with a history of alcohol use disorders are thought to be at risk for misusing prescribed benzodiazepines. We examine the use of prescribed benzodiazepines in anxiety disordered subjects with and without a history of alcohol dependence or abuse. METHOD: A group of 343 subjects in the Harvard/Brown Anxiety Disorders Research Program (HARP) who were taking benzodiazepines at the time of entry into a prospective study of anxiety disorders serve as the study group. Subjects with (N=99) and without (N=244) a history of alcohol use or dependence (DSM- III-R) are examined for their reported total daily dose, p.r.n. use, or continued use of benzodiazepines. RESULTS: There is no significant difference in maximum daily dose or continued use of benzodiazepines over 12 months of follow- up. There is a clinically small but statistically significant difference in median daily dose during the second but not the first 6 months of follow-up for the alcohol history positive versus alcohol history negative groups. Additionally, there was significantly less reported use of p.r.n. benzodiazepines in the alcohol history positive versus alcohol history negative subjects during the second 6 months, but not the first 6 months, of follow-up. CONCLUSION: The presence or absence of a history of alcohol use disorders is not a strong predictor of the use of benzodiazepines in subjects with anxiety disorders over 12 months of prospective follow-up.

Oxy-helium treatment for refractory neurological decompression sickness: a case report.

A 49-yr-old male presented with paraparesis and urinary incontinence that appeared 10 min after surfacing from a dive. Treatment was started on an extended USN table 6, but the symptoms persisted. Twenty-four hours later, he was treated with oxy-helium table CX-30, resulting in marked improvement in gait and in sensory and motor function. Urodynamic examination indicated an upper motor neuron lesion; bilateral decreased amplitude of the somatosensory evoked potential was found on stimulation of the tibial nerves; no response below the upper limbs was elicited on central motor conduction time (CMCT) testing; MRI showed lesions in the lower dorsal cord. The patient's condition was further improved by an additional 10 hyperbaric oxygenation sessions, with complete restoration of urinary control and virtually complete sensory and motor recovery. Follow-up urodynamic studies were normal. CMCT recordings showed a bilateral lower limb small-amplitude response. The present case reinforces the limited clinical data regarding the value of oxy-helium in the treatment of neurological decompression sickness, even when primary treatment with oxygen tables is unsuccessful.

Profile of a large sample of patients with social phobia: comparison between generalized and specific social phobia.

This study examines a large cohort of subjects with social phobia, as part of a larger naturalistic and longitudinal study of 711 subjects with anxiety disorders. We focused on 176 subjects who were in an episode of social phobia at intake. We were particularly interested in evaluating the diagnostic distinction between generalized and specific social phobia. We compared these two groups along demographic characteristics, comorbidities, psychosocial functioning (health, role functioning, social functioning, and emotional functioning) and global assessment scores. We found that generalized social phobics tended to have an earlier age of onset as compared to the specific group; however, this is not a statistically significant difference at this level of analysis. The two groups did not differ for the current comorbidities examined. We observed no differences in the treatment received by the two types of social phobia subjects, and the two groups functioned equally well in terms of health and fulfilling social roles. In addition, we examined adverse childhood events (i.e., death of a parent, childhood abuse) and found no evidence for any differential impact these events might have on the type of social phobia. Although we did observe significantly greater fear of public speaking among the specific compared to the generalized group, which may indicate a qualitative difference between the subtypes, our results suggest that for most parameters, generalized and specific social phobia represent a continuum of similar and overlapping entities.

Necrotizing fasciitis: an indication for hyperbaric oxygenation therapy?

BACKGROUND: The accepted treatment protocol for necrotizing fasciitis (NF) consists of extensive surgery and wide spectrum antibiotics. Hyperbaric oxygenation (HBO) has been recommended as adjuvant therapy for NF, improving patient mortality and outcome. However, the beneficial effect of HBO for NF remains controversial. METHODS: A retrospective evaluation of treatment outcome in 37 patients treated for NF between 1984 and 1993 was carried out. The mortality rate, morbidity criteria, and risk factors for grave prognosis were compared between a group of 25 patients who received HBO as part of their treatment protocol and a group of the remaining 12 patients treated by surgical excision and antibiotics alone. RESULTS: The two groups were found to be similar with regard to age, gender, the incidence of individual risk factors for ominous prognosis, and the Acute Physiology and Chronic Health Evaluation (APACHE) II score for disease's severity on presentation. The mortality rate among the HBO-treated patients was 36%, as opposed to 25% in the non-HBO group. The mean number of surgical débridements required per patient was significantly higher in the HBO group: 3.3 compared with 1.5 in the non-HBO-treated patients. Although the average length of hospitalization for survivors was shorter for the HBO group, the difference between the groups did not reach statistical significance. CONCLUSIONS: The results of this study cast doubt on the suggested advantage of HBO in reducing patient mortality and morbidity when used as adjuvant therapy for NF.