Perioperative brain shift and deep brain stimulating electrode deformation analysis: implications for rigid and non-rigid devices.

UNLABELLED: Deep brain stimulation (DBS) efficacy is related to optimal electrode placement. Several authors have quantified brain shift related to surgical targeting; yet, few reports document and discuss the effects of brain shift after insertion. OBJECTIVE: To quantify brain shift and electrode displacement after device insertion. Twelve patients were retrospectively reviewed, and one post-operative MRI and one time-delayed CT were obtained for each patient and their implanted electrodes modeled in 3D. Two competing methods were employed to measure the electrode tip location and deviation from the prototypical linear implant after the resolution of acute surgical changes, such as brain shift and pneumocephalus. In the interim between surgery and a pneumocephalus free postoperative scan, electrode deviation was documented in all patients and all electrodes. Significant shift of the electrode tip was identified in rostral, anterior, and medial directions (p < 0.05). Shift was greatest in the rostral direction, measuring an average of 1.41 mm. Brain shift and subsequent electrode displacement occurs in patients after DBS surgery with the reversal of intraoperative brain shift. Rostral displacement is on the order of the height of one DBS contact. Further investigation into the time course of intraoperative brain shift and its potential effects on procedures performed with rigid and non-rigid devices in supine and semi-sitting surgical positions is needed.

Chlamydia trachomatis persistence in the female mouse genital tract: inducible nitric oxide synthase and infection outcome.

It was previously reported that female mice resolve a primary Chlamydia trachomatis urogenital infection independent of inducible nitric oxide synthase (iNOS). We now report that although iNOS-deficient (NOS2(-/-)) mice resolve culture-apparent infection in a fashion similar to that of normal control (NOS2(+/+)) mice, they sustain significantly increased rates of disease, as assessed by hydrosalpinx formation. PCR amplification of ompA followed by Southern blot detection of amplicands revealed the presence of chlamydial DNA in the lower genital tracts of both NOS2(-/-) and NOS2(+/+) mice at > or =120 days postinfection and in upper genital tract tissues at >120 days postinfection. However, only NOS2(-/-) mice shed low numbers of viable chlamydiae from the lower genital tract after immunosuppressive treatment at 120 days postinfection. When cultured primary murine lung fibroblasts were activated in the presence of gamma interferon (IFN-gamma), inhibition of chlamydial growth occurred in both NOS2(+/+) and NOS2(-/-) cells, but the inhibition was reversible after removal of the cytokine in the NOS2(-/-) primary cell culture only. The iNOS-independent inhibition was microbistatic but was independent of 2,3-indoleamine dioxygenase activity. We conclude that chlamydial DNA and antigens persist in mice subsequent to culture-apparent resolution. In addition, IFN-gamma induces in vivo inhibition of chlamydial growth through microbistatic mechanisms in the absence of iNOS activity, but in the presence of iNOS activity, IFN-gamma is microbicidal and effects eradication.

Characterization of low-density lipoprotein uptake by murine macrophages exposed to Chlamydia pneumoniae.

Exposure to Chlamydia pneumoniae is correlated with atherosclerosis in a variety of clinical and epidemiological studies, but how the organism may initiate and promote the disease is poorly understood. One pathogenic mechanism could involve modulation of macrophage function by C. pneumoniae. We recently demonstrated that C. pneumoniae induces macrophages to accumulate excess cholesterol and develop into foam cells, the hallmark of early atherosclerotic lesions. To determine if C. pneumoniae-induced foam cell formation involved increased uptake of low-density lipoprotein (LDL), the current study examined macrophage association of a fluorescent carbocyanine (DiI)-labeled LDL following infection. C. pneumoniae enhanced the association of DiI-LDL with macrophages in a dose-dependent manner with respect to both C. pneumoniae and DiI-LDL. Interestingly, increased association was inhibited by native LDL and occurred in the absence of oxidation byproducts and in the presence of antioxidants. However, enhanced DiI-LDL association occurred without the participation of the classical Apo B/E native LDL receptor, since C. pneumoniae increased DiI-LDL association and induced foam cell formation in macrophages isolated from LDL-receptor-deficient mice. Surprisingly, DiI-LDL association was inhibited not only by unlabeled native LDL but also by high-density lipoprotein, very low density lipoprotein, and oxidized LDL. These data indicate that exposure of macrophages to C. pneumoniae increases the uptake of LDL and foam cell formation by an LDL-receptor-independent mechanism.

Prior genital tract infection with a murine or human biovar of Chlamydia trachomatis protects mice against heterotypic challenge infection.

We sought to assess the degree of cross-protective immunity in a mouse model of chlamydial genital tract infection. Following resolution of genital infection with the mouse pneumonitis (MoPn) biovar of Chlamydia trachomatis, mice were challenged intravaginally with either MoPn or human serovar E or L2. The majority of animals previously infected with MoPn were solidly immune to challenge with either of the two human biovars. Surprisingly, approximately 50% of animals became reinfected when homologously challenged with MoPn, although the secondary infection yielded significantly lower numbers of the organism isolated over a shorter duration than in the primary infection. Primary infection with serovar E also protected against challenge with MoPn or serovar L2, although the degree of immune protection was lower than that resulting from primary infection with MoPn. Blast transformation and assessment of delayed-type hypersensitivity indicated that mice previously infected with either human or murine biovars produced broadly cross-reactive T cells that recognized epitopes of either murine or human biovars of C. trachomatis. Immunoblotting demonstrated that primary MoPn infection produced immunoglobulin G (IgG) antibody to antigens of MoPn as well as at least three distinct antigenic components of human serovar E, one of which was identical in molecular weight to the major outer membrane protein (MOMP). Primary infection with serovar E produced IgG antibody reactive against serovar E but not MoPn MOMP and against at least one ca. 60-kDa protein of both chlamydial strains. Our results indicate that primary genital infection of mice with murine C. trachomatis induces immunity against challenge with either of two human biovars.

Inducible nitric oxide synthase does not affect resolution of murine chlamydial genital tract infections or eradication of chlamydiae in primary murine cell culture.

Mice lacking inducible nitric oxide synthase (iNOS) or treated with iNOS inhibitors resolved chlamydial genital tract infections. Additionally, treatment of primary murine cell cultures with gamma interferon restricted chlamydial growth in the absence of nitric oxide. From these results, iNOS activity is unnecessary for the resolution of chlamydial genital tract infections in mice and inhibition of chlamydial growth in culture.

Reactivation of chlamydial genital tract infection in mice.

A model was developed to study chlamydial quiescence in C3H/HeN (C3H) and C57BL/6N (C57) mice following genital tract infection by Chlamydia trachomatis MoPn. Reactivation of chlamydial shedding following immunosuppression indicated that viable MoPn remained in the genital tract for up to 4 or 5 weeks after the apparent clearance of a primary infection. Either cyclophosphamide or cortisone acetate treatment could cause reactivation, but cyclophosphamide was more effective. However, the frequency of reactivation by either drug diminished with time in both mouse strains. Progesterone treatment prior to infection of C57 mice greatly reduced the frequency of reactivation by cyclophosphamide and also correlated with the development of marked fluid accumulation and distension of the uterine horns in the vast majority of those animals. This pathology was apparent by 5 to 7 weeks postinfection and was consistently seen through 110 days postinfection. Neither of these phenomena was observed in C57 mice that had not been treated with progesterone or in C3H mice under any conditions tested. The infecting dose of MoPn did not clearly influence the frequency of reactivation in either inbred strain as defined by this model.

Dissemination of Chlamydia trachomatis chronic genital tract infection in gamma interferon gene knockout mice.

Mice (C57BL/6), treated with progesterone and infected intravaginally with the mouse pneumonitis strain of Chlamydia trachomatis (MoPn), acquired genital tract disease that ascended from the endocervix to the uterine horns, oviducts, and ovaries in a temporal fashion before the occurrence of spontaneous microbiological resolution by about 28 days after infection. Surprisingly, dissemination of MoPn in small numbers to draining lymph nodes, the peritoneal cavity, spleen, liver, kidneys, and lungs occurred in normal mice during the early stages of disease (7 to 14 days) in a portion of infected animals but resolved from these tissues, by microbiological criteria, prior to resolution of genital tract involvement. In contrast, gamma interferon knockout (IFN-gamma KO) mice exhibited dissemination of infection to a greater extent and for longer periods in a variety of tissues, and a portion of infected IFN-gamma KO mice failed to microbiologically resolve their genital tract disease. By comparison, C57BL/6 SCID mice uniformly failed to resolve their genital tract disease and exhibited high levels of dissemination to all tissues tested for extended (50-day) periods of times. Interestingly, although IFN-gamma KO mice failed to completely clear organisms from their genital tracts, they exhibited an attenuated infection indistinguishable from that of heterozygous littermates when challenged 112 days after primary infection. These data support a role for IFN-gamma in containing dissemination of MoPn from the genital tract to extragenital sites and in the microbiological resolution of infection. Data also indicate that IFN-gamma is not required for modulating reinfections, which normally follow a shorter and less dramatic course.

Larvicidal activity of blastospores and conidiospores of Beauveria bassiana (strain GK 2016) against age groups of Aedes aegypti.

Laboratory bioassays of two development stages, blastospores (BS) and conidiospores (CS) of Beauveria bassiana (strain GK 2016) against Aedes aegypti larvae were conducted at 27 degrees C. In Study 1, against 24 h post-hatched larvae, both BS and CS stages showed significant difference in their respective larvicidal efficacy over the control (P less than 0.0001). Larval mortality between 24 and 96 h post-exposure was significantly higher than any other time period investigated. Significantly higher larval mortality was observed with BS or CS at 10(8) ml-1 over lower concentrations (P less than 0.05). In Study 2, against different age groups, 12-24 h post-hatched larvae showed significantly higher mortality when treated with BS or CS than older age groups (P less than 0.05). A significant difference was found in the larvicidal potency of B. bassiana at different fungal stages.

Relationship between the resistance of crossbred cattle to ticks, Boophilus microplus (Canestrini, 1887) and Hyalomma anatolicum anatolicum (Koch, 1844).

Studies were undertaken to determine the effect of repeated pure infestations with Boophilus microplus on susceptibility to subsequent pure infestations with Hyalomma anatolicum anatolicum, and the effects of pure infestations with both species of tick on susceptibility to a series of mixed infestations. Crossbred (Bos indicus X Bos taurus) calves were infested with Boophilus microplus (17 times), H. a. anatolicum (four times), followed by five mixed infestations of B. microplus and H. a. anatolicum. The decline in B. microplus engorgement from a mean yield of 274.4 +/- 60.3 ticks per host after the first exposure, to a mean yield of 9 +/- 4.6 per animal after the seventeenth exposure, was observed in animals exposed to only B. microplus. This might be due to acquired resistance. However, these animals were found to be as susceptible to H. a. anatolicum as animals which had never been exposed to ticks of either species. A decline in the yield of H. a. anatolicum from a mean yield of 92.1 +/- 10.7 after the first exposure to 54.7 +/- 11.3 after the fourth exposure, indicated that the cattle could also acquire resistance to repeated pure infestations with this species. After repeated pure infestations with both tick species, cattle reacted to five mixed infestations showing a high degree of resistance to B. microplus and low resistance to H. a. anatolicum (mean yield for B. microplus was only 10 +/- 8.1 ticks per host after the first mixed exposure and declined to 1.3 +/- 1.7 after the fifth, whereas the mean yield for H. a. anatolicum was 71.4 +/- 11.3 ticks per host following the first exposure and declined to 37.3 +/- 7.8 after the fifth). Host responses elicited to one species do not provide cross-resistance to the second species used in this study.

Hemocyte population changes during the immune response of Aedes aegypti to inoculated microfilariae of Dirofilaria immitis.

Ultrastructural and lectin-binding studies have established that the melanotic encapsulation reaction of Aedes aegypti Liverpool strain against inoculated Dirofilaria immitis microfilariae (mff) is a hemocyte-mediated reaction. Total hemocyte counts from mff-inoculated (= immune-activated), saline-inoculated, and uninoculated female A. aegypti were determined using a hemocoel perfusion technique. Total hemocyte populations in uninoculated mosquitoes were significantly larger in younger mosquitoes, but no significant change was noted as mosquitoes aged beyond 14 days. Hemocyte populations in immune-activated mosquitoes increased from 1 to 3 days postinoculation (PI) and decreased on days 4 and 5 PI. Hemocyte populations at 1 to 4 days PI were significantly elevated in mff-inoculated A. aegypti as compared with saline-inoculated controls. Saline-inoculated mosquitoes displayed little change in total hemocyte numbers from 1 to 5 days PI, and their hemocyte populations were similar to those seen in uninoculated insects of the same age. Experiments involving the inoculation of [3H]thymidine along with mff or saline alone and studies involving the administration of colchicine suggest that increased hemocyte populations in immune-activated A. aegypti are a result of mitotic division of circulating blood cells.

Ticks parasitising the Indian buffalo (Bubalus bubalis) and their possible role in disease transmission.

A total of 13 ixodid tick species, Boophilus microplus, Haemaphysalis bispinosa, Haemaphysalis cornupunctata, Haemaphysalis himalaya, Heamaphysalis montgomeryi, Hyalomma anatolicum anatolicum, Hyalomma dromedarii, Hyalomma marginatum isaaci, Hyalomma (Hyalommina) brevipunctata, Hyalomma (Hyalommina) hussaini, Nosomma monstrosum, Rhipicephalus haemaphysaloides, and R. turanicus were collected off 424 buffaloes from the northwestern states of India. Ten tick species, Amblyomma testudinarium, B. microplus, Haemaphysalis anomala, Haemaphysalis arborensis, Haemaphysalis bispinosa, Haemaphysalis intermedia, Haemaphysalis nepalensis, Haemaphysalis neumanni, R. haemaphysaloides, and R. turanicus parasitising 194 buffaloes were collected from the northeastern states of India. In addition to tick-buffalo relationships, the incidence of haemoparasites in buffalo from these two regions was studied and the possible role of these ticks in disease transmission was discussed. Examination of blood films and lymph smears revealed Anaplasma marginale and Babesia bigemina in 6.2 and 2.6%, respectively, of buffaloes tested in the northeastern states, and 14.9 and 4.7%, respectively, in the northwestern states.

Evaluation of purified Theileria annulata sporozoite antigen from the tick Hyalomma anatolicum anatolicum.

Rabbits immunized with purified sporozoites from Hyalomma anatolicum anatolicum produced antibody to Theileria annulata specific antigens as measured by the indirect fluorescent antibody test. Nonspecific fluorescence which compounded the interpretation of the test was observed. Incorporation of Eriochrome black and Evans blue as a counterstain in the diluent buffer for the conjugate significantly reduced the background fluorescence.

Comparative studies on the melanization response of male and female mosquitoes against microfilariae.

The melanization response of adult male and female Aedes trivittatus and the black-eyed Liverpool strain of Aedes aegypti against intrathoracically inoculated Dirofilaria immitis microfilariae (mff) was assessed at 1, 3, and 5 days postinoculation (PI). The melanization reaction of males is significantly less effective than the response elicited by female mosquitoes. No mff in male A. aegypti and only 17% of mff recovered from A. trivittatus were fully melanized by day 5 PI compared with 80% and 100% complete melanization of recovered mff from A. aegypti and A. trivittatus females, respectively. A significantly greater percentage of mff retained their viability in males, and inoculation of heat-killed mff did not significantly increase the melanization response as compared with female mosquitoes. Males have significantly lower total hemocyte populations and hemolymph volumes than females, and the possible relationship of hemocyte numbers and reduced melanization capabilities in males is discussed.

Borrelia theileri: isolation from ticks (Boophilus microplus) and tick-borne transmission between splenectomized calves.

The bovine spirochete, Borrelia theileri, was detected in Giemsastained blood smears from a splenectomized calf 17 days after exposure to a laboratory colony of the tropical cattle tick, Boophilus microplus. Spirochetes were detected in the hemolymph and ovary of all engorged female ticks examined, indicating a high infection rate in this tick colony. Spirochetes were detected in a 2nd splenectomized calf 15 days after exposure to the larval offspring of ticks from the 1st calf. The only observable effect of infection in the 2 calves was a maximum rectal temperature increase to 40.2 C, which coincided with the first detectable parasitemia. The tick colony did not have any adverse effects, despite extensive multiplication of spirochetes in their tissues.