Altered top-down and bottom-up processing of fear conditioning in panic disorder with agoraphobia.

BACKGROUND: Although several neurophysiological models have been proposed for panic disorder with agoraphobia (PD/AG), there is limited evidence from functional magnetic resonance imaging (fMRI) studies on key neural networks in PD/AG. Fear conditioning has been proposed to represent a central pathway for the development and maintenance of this disorder; however, its neural substrates remain elusive. The present study aimed to investigate the neural correlates of fear conditioning in PD/AG patients. METHOD: The blood oxygen level-dependent (BOLD) response was measured using fMRI during a fear conditioning task. Indicators of differential conditioning, simple conditioning and safety signal processing were investigated in 60 PD/AG patients and 60 matched healthy controls. RESULTS: Differential conditioning was associated with enhanced activation of the bilateral dorsal inferior frontal gyrus (IFG) whereas simple conditioning and safety signal processing were related to increased midbrain activation in PD/AG patients versus controls. Anxiety sensitivity was associated positively with the magnitude of midbrain activation. CONCLUSIONS: The results suggest changes in top-down and bottom-up processes during fear conditioning in PD/AG that can be interpreted within a neural framework of defensive reactions mediating threat through distal (forebrain) versus proximal (midbrain) brain structures. Evidence is accumulating that this network plays a key role in the aetiopathogenesis of panic disorder.

Brain correlates of hypnotic paralysis-a resting-state fMRI study.

Hypnotic paralysis has been used since the times of Charcot to study altered states of consciousness; however, the underlying neurobiological correlates are poorly understood. We investigated human brain function during hypnotic paralysis using resting-state functional magnetic resonance imaging (fMRI), focussing on two core regions of the default mode network and the representation of the paralysed hand in the primary motor cortex. Hypnotic suggestion induced an observable left-hand paralysis in 19 participants. Resting-state fMRI at 3T was performed in pseudo-randomised order awake and in the hypnotic condition. Functional connectivity analyses revealed increased connectivity of the precuneus with the right dorsolateral prefrontal cortex, angular gyrus, and a dorsal part of the precuneus. Functional connectivity of the medial frontal cortex and the primary motor cortex remained unchanged. Our results reveal that the precuneus plays a pivotal role during maintenance of an altered state of consciousness. The increased coupling of selective cortical areas with the precuneus supports the concept that hypnotic paralysis may be mediated by a modified representation of the self which impacts motor abilities.

Effect of diethylcarbamazine citrate on fourth stage and adult Brugia malayi in cats.

Sixty-three experimental and 58 control cats were infected with Brugia malayi so that the developing and adult worms localized in the regional lymphatics of the hind legs. At 20 days after infection when Brugia were in the 4th larval stage, and at 8 weeks when worms were young adults, cats were divided into groups to test the efficacy of diethylcarbamazine citrate (DEC) at various dosage levels. At 100 mg total DEC/kg no 4th-stage larvae were seen in 5 cats compared with a mean of 20.4 living larvae in each of 5 controls. At this level of DEC, 2 of 5 cats had 1 and 2 adult worms while 4 of 4 controls had a mean of 23.2 living adult worms. At 50 and 25 mg/kg there was a substantial reduction of both 4th stage and adult worms when compared to controls. At 10 mg/kg, 4 of 6 cats had 4th-stage larvae but at a lower level (mean = 7.0) than in 6 controls (mean = 23.2). No reduction of either 4th-stage larvae or adult worms was seen at 1 mg/kg. This study establishes the efficacy of DEC against 4th-stage and adult Brugia malayi in cats, although considerably higher levels of the drug were required than the level previously determined to kill 3rd-stage larvae. It appears that the cat-B. malayi model will be an effective method to compare the efficacy of drugs against adult lymphatic-dwelling filariae.

Effect of diethylcarbamazine on third stage Brugia malayi larvae in cats.

Forty-one experimental and 37 control cats were each infected with 50 Brugia malayi larvae in such a way that a preponderance of the larvae remained localized in the popliteal lymph node or in the lymphatics of the leg draining into that node. During the 1st week after infection cats were treated with varying doses of diethylcarbamazine citrate (DEC). Two weeks after infection, necropsy for worm recovery was performed on treated and control cats. No living larva was recovered from 21 of 22 cats treated with a total of 10 mg DEC/kg body weight or greater. A single living larva was recovered in only 2 of 5 cats treated at 5 mg/kg. At 2 mg/kg, 8 of 10 cats had substantially fewer larvae than their controls; the remaining 2 were negative. In 4 cats treated with a total of 1 mg/kg, there was no reduction of larvae. All 37 untreated controls harbored living larvae, with a mean of 56% of the inoculum being recovered.

Microfilariae of Mansonella ozzardi in human skin biopsies.

Microfilariae of Mansonella ozzardi were seen in specimens of skin taken by biopsy from 4 of 6 subjects previously shown to be positive for microfilariae in the blood. While most of the microfilariae were confined to small blood vessels in the papillary and superficial reticular dermis, some were in perivascular spaces and a few were noted in the dermal interstitium. There was no microscopic evidence that the minimal cutaneous disease seen could be directly attributed to the microfilariae.

Effect of diethylcarbamazine citrate on Brugia malayi infections in cats following daily, weekly, or monthly administration.

Cats with patent infections of Brugia malayi were treated by intraperitoneal injection of diethylcarbamazine citrate (DEC) for 6 consecutive days, weekly for 6 consecutive weeks or monthly for 3 months. Each cat received a total of 100 mg DEC per kg. At necropsy 7 months after infection, no living worms were recovered from any of eight cats treated weekly and only one of nine cats treated daily had a single living Brugia. Five of nine cats treated monthly and six of eight untreated controls had one or more living worms. Cats treated weekly showed a larger decline in microfilariae than those of the other treated groups. The mean microfilariae level of untreated controls increased 2-fold. At necropsy, gross appearance of regional lymphatics in daily and weekly treated cats resembled those of uninfected controls more closely than those in cats treated monthly or untreated. Differences in degree of histological changes between groups of infected cats were not apparent. Weekly administration of DEC appeared to be the most effective regimen; monthly treatment was less effective.

A parasitologic survey for Mansonella ozzardi in the Comisaría del Vaupés, Colombia.

The prevalence of Mansonella ozzardi in the Comisaría del Vaupés of eastern Colombia was investigated as part of an extensive study of human filariasis in Colombia. Three hundred and forty-seven individuals from various parts of Vaupés were examined. The overall infection rate for M. ozzardi was 49%, but the distribution of the parasite was not uniform throughout the Comisaría. Microfilariae were found in both venous blood samples and ski biopsies of infected individuals. The rate of infection was 55% for males and 42% for females, and infection ratenerally low, with 88% of the positive films having less than 50 microfilariae.

Onchocerciasis focus in Colombia: follow-up study after 12 years.

This study is a follow-up of a 1965 investigation of the only known focus of Onchocerca volvulus in Colombia. In the first phase of the current study, 254 persons were examined. Of the 19 individuals found to be infected with O. volvulus, the youngest was a 16-year-old male. Among those included in the 1965 study, 22 were examined again for microfilariae. Two were positive in both studies, 4 were positive in 1965 but negative in 1977 and the remaining 16 were negative on both occasions. The prevalence of infection, based on identification of microfilariae in skin snips, was lower in the current study (7.5%) than the 15.1% recorded 12 years earlier. However, a 50% response to the Mazzotti test (administration of oral diethylcarbamazine) among a limited number of people upstream from the previously identified endemic area suggests that infection with O. volvulus may be quite widespread.

Survival of group A streptococci in dried human blood.

The resurgence of streptococcal infections in the USA and Europe and their high incidence in other parts of the world prompted an examination of the survival and maintenance of virulence of group A streptococci. Human blood containing group A streptococci was placed on small pieces of sterile paper towelling and allowed to dry at room temperature. At periods of 2, 8, 15 and 20 weeks later, the paper with the dried blood was placed in Todd-Hewitt broth and incubated at 37 degrees C overnight. All the samples tested at 2 weeks grew in broth, and with only one exception, grew in fresh human blood provided by five donors. At 8 weeks only two of the 10 strains failed to grow in broth; seven of the eight viable cultures also grew in blood. At 15 and 20 weeks after drying the eight cultures were still viable. Since seven were able to grow in fresh blood as well as in broth it is assumed that their virulence factor(s) had been retained.

Sarcoptes scabiei in histopathologic sections of skin in human scabies.

The usual methods of diagnosis remove Sarcoptes scabiei from its habitat. Thus, one has no appreciation of the host-endoparasitic interaction, especially the pathologic response of the surrounding tissue and the means by which the mite survives and lives its life cycle in the skin. The biopsy specimen described in this article demonstrates the tissue reaction that can be correlated with clinical symptoms. It also clearly depicts the actual position, morphological features, and developmental cycle of the mite in the skin.

Lymphatic patterns of cats infected with Brugia malayi and streptococcus.

Approximately 50% of the hind legs of cats infected with Brugia malayi and insulted with a beta haemolytic streptococcus became elephantoid in appearance after four to six weeks. This condition was found to be reversible. Collateral lymphatic vessels were seen by lymphography in most of the Brugia-streptococcus-infected legs. The popliteal draining systems in two of three cats, which harboured no worms, appeared normal by lymphography at 18 weeks.

Experimental necrotic dermatosis induced by group G streptococci in mice.

Self healing necrotic lesions were produced on the backs of laboratory mice by injecting group G streptococci into the skin. The incidence and severity of necrotic dermatosis was dose related. When 1 x 10(1) colony forming units (cfu) were injected subcutaneously, lesions developed on three of 16 mice 4 days post inoculation. Injection of 1 x 10(3) cfu produced lesions on five of 16 mice and 1 x 10(5) cfu produced lesions on seven of 15 mice 3 days post inoculation. An inoculation of 1 x 10(7) cfu produced lesions on all of 16 mice 2 days post inoculation. Lesions produced by the 1 x 10(1) inoculum were smaller and had healed by the 15th day post inoculation, whereas lesions produced by the 1 x 10(7) inoculum persisted until the 24th day post inoculation. No mortality could be attributed to experimental design and all lesions healed without the use of medication or antibiotics.

Interspecific competition among Aedes aegypti, Ae. albopictus, and Ae. triseriatus (Diptera: Culicidae): larval development in mixed cultures.

Interactions among the larvae of Aedes aegypti (L.), Ae. albopictus (Skuse), and Ae. triseriatus (Say) were studied in trispecific and bispecific mixed populations under laboratory and field conditions. Competitive stress (as evidenced by the average time to first, 50, and 75% pupation and the total pupation periods for mixed populations of each species in comparison with their single species controls) was more pronounced in mixed cultures reared in glass jars in the laboratory than in tires under field conditions. In the laboratory, the larval development of Ae. aegypti reared together with Ae. albopictus or Ae. triseriatus, or both, larvae was accelerated significantly. Conversely, the time to pupation for Ae. albopictus and Ae. triseriatus was delayed when reared with Ae. aegypti. However, the average wing length of female Ae. albopictus and Ae. triseriatus was greater in the mixed cultures than in single species cultures. These data indicated that the effect of intraspecific competition was greater than interspecific competition. Adequate food and higher temperature appeared to promote rapid development and higher survival of the immature stages of the three Aedes species in tires placed in the field. In general, Ae. triseriatus larvae required a longer period for larval development and had greater larval mortality than either Ae. aegypti or Ae. albopictus. In mixed populations of Ae, albopictus and Ae. aegypti in the jars and food-rich tires, the periods needed to attain first, 50, and 75% cumulative pupation were not significantly different than in single species controls. We conclude that no clear-cut displacement occurred in mixed experimental populations of Ae. aegypti and Ae. albopictus.

Food ingestion and digestive enzymes in larval Aedes aegypti and Ae. albopictus (Diptera: Culicidae).

Frequency of the labral brush movements of first, second, and fourth instars of Aedes aegypti (L.) and Aedes albopictus (Skuse) was studied comparatively in the laboratory. A frequency of 197 strokes per min for the first and second instars was observed in the former species compared to 118 strokes per min in the latter species. A faster ingestion rate of algal cells also was observed in first and second instars of Ae. aegypti (mean 57.5 cells per s) compared with first and second instars of Ae. albopictus (mean 22.4 cells per s). The digestive enzymes chymotrypsin (EC 3.4.21.1) and trypsin (EC 3.4.21.4) were more active in the peritrophic membrane (including food contents) than in the midgut epithelium of both species. Chymotrypsin activity in 11-d-old third and fourth instars of Ae. albopictus was 28 times higher than in the corresponding stadia of Ae. aegypti, indicating that the former species may have a superior enzymatic process for digesting food proteins.

[MRI-assisted bile duct drainage: evaluation of passive catheter imaging in an animal model]. / MRT-gestützte Gallenwegsdrainage: Erprobung der passiven Katheterdarstellung an einem Tiermodell.

PURPOSE: To investigate interactive MR-assisted bile duct drainage in pigs with the passive visualization technique using near real-time imaging. METHODS: 8 bile duct drainages were placed in an open low-field MR system (0.2 Tesla) in 4 pigs with surgically induced cholestasis. After planning the intervention with magnetic resonance cholangiography (MRC), both the puncture and catheter placement were interactively guided using a fast T2-weighted true FISP sequence. RESULTS: MRC enabled interventional planning in all puncture attempts. Punctures were unproblematic in all attempts, the bile ducts were punctured 6 times after the first and twice after the second attempt. Placement of the passively visible catheter was successful in all animals. The applied sequence enables interactive fluoroscopy-like positioning of the devices. CONCLUSION: The procedure introduced here enables reliable and fast placement of a bile duct drainage in an animal model using a low-field MR system.

Distribution and development of Brugia malayi in reinfected cats.

At various time periods after an initial exposure to 50 Brugia malayi larvae on one hind foot cats were reexposed to an additional 50 larvae in one of 3 ways: on the previously infected limb only, on the contralateral, uninfected limb only, or on both hind limbs simultaneously. At the time of reexposure uninfected controls were exposed to 50 larvae on one hind foot in a similar manner. From 2 to 4 weeks after reexposure to larvae, the cats were necropsied and the appropriate lymph nodes and vessels examined for adult or developing worms. An existing infection in one limb did not influence early migration or development of larvae introduced into the contralateral leg. Previous infection in the same limb did not consistently result in decreases in the number of developing larvae from the second exposure but did alter the distrubution of larvae. In repeat infections, larvae were consistently located in a moe distal area of the limb than were larvae from an initial infection at a comparable time.

Collagen metabolism in experimental filariasis.

Chronic lymphatic filariasis is accompanied by edema and fibrosis. In order to assess the latter response, the tissue content of collagen was measured in the skin and lymphatic vessels of normal and affected limbs of cats infected by Brugia malayi. Collagen content, expressed per gram wet weight of tissue, was increased in the infected limbs for both kinds of tissues. Moreover, the proportion of acetic acid soluble to total collagen was increased. The degree of crosslinking in soluble collagen was assessed by acrylamide gel electrophoresis and shown to be decreased in infected tissues. These data suggest an increased rate of collagen metabolism in Brugia malayi-infected tissues and provide data for future studies evaluating the efficacy of treatment in chronic experimental filariasis.

Degenerative changes in lymphatic endothelium of jirds infected with Brugia pahangi.

The quantitative changes of cytoplasmic vesicles and vacuoles in lymphatic endothelial cells of the mongolian jirds associated with Brugia pahangi infections were observed by transmission electron microscopy. The present study revealed a decrease in the proportion of cytoplasm occupied by vesicles and in the number of cytoplasmic vesicles in endothelial cells from lymphatic vessels harboring B. pahangi at 3, 4, and 10 mo after infection (3.55, 3.36, and 2.55 vesicles/micron 2, respectively) when compared with cells from uninfected control vessels (7.03 vesicles/micron 2). On the contrary, there was an increase in the area of vacuoles in endothelial cells of jirds at 3, 4, and 10 mo postinfection. The mean +/- SD diameter of vesicles in cells from lymphatic vessels at 10 mo after infection was significantly smaller (78.6 +/- 5.6 nm) compared to vesicles in uninfected vessels (87.5 +/- 9.7 nm).

Edema resulting from experimental filariasis.

Domestic cats and patas monkeys were infected with Brugia malayi so that the worms localized in the regional lymphatics of the hind legs. Reaction to the filarial parasites resulted in visible local edema in cats and disruption of normal lymph flow in the monkeys. Edematous tissue was examined grossly and by light and electron microscopy. Lymph flow patterns were examined by direct observation following injection of lymph staining dye and reflection of the skin, by X-ray following injection of radio-opaque contrast media, and by lymphscintigraphy after subcutaneous injection of radioisotopes. Clinical edema occurred in cats but not in monkeys. However, disruption of normal lymph flow in monkeys infected with Brugia could be demonstrated by lymphscintigraphy.

Evolution of lymph thrombi in experimental Brugia malayi infections: a scanning electron microscopic study.

Lymph thrombi in cats experimentally-infected with Brugia malayi were examined by scanning electron microscopy. A variety of morphological forms were noted and it appeared that thrombi undergo a maturation process characterized by at least three transitional phases. Initially, the thrombus consists of erythrocytes encased in fibrin (Phase I). Phase II thrombi are characterized by the appearance of phagocytic cells and fibroblasts on the surface of the thrombus. At the end of the maturation process, the thrombus surface consists solely of fibroblasts or endothelial cells, perhaps derived from the vessel wall (Phase III). Occlusion of the lymphatic lumen by thrombi and the accompanying inflammatory response triggered by B. malayi infection may be a major factor in the pathogenesis of lymph stasis in this disorder.