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Sutherlandia frutescens is a medicinal plant, traditionally used to treat various types of human diseases, including cancer. Previous studies of several botanicals link suppression of prostate cancer growth with inhibition of the Gli/hedgehog (Gli/Hh) signaling pathway. Here we hypothesized the anti-cancer effect of S. frutescens was linked to its inhibition of the Gli/Hh signaling in prostate cancer. We found a dose- and time-dependent growth inhibition in human prostate cancer cells, PC3 and LNCaP, and mouse prostate cancer cell, TRAMP-C2, treated with S. frutescens methanol extract (SLE). We also observed a dose-dependent inhibition of the Gli-reporter activity in Shh Light II and TRAMP-C2QGli cells treated with SLE. In addition, SLE can inhibit Gli/Hh signaling by blocking Gli1 and Ptched1 gene expression in the presence of a Gli/Hh signaling agonist (SAG). A diet supplemented with S. frutescens suppressed the formation of poorly differentiated carcinoma in prostates of TRAMP mice. Finally, we found Sutherlandioside D was the most potent compound in the crude extract that could suppress Gli-reporter in Shh Light II cells. Together, this suggests that the S. frutescens extract may exert anti-cancer effect by targeting Gli/Hh signaling, and Sutherlandioside D is one of the active compounds.

In this study we estimated occurrence of the booster effect in a population infected with the human immunodeficiency virus (HIV) and assessed the relation between the booster effect, T-lymphocyte CD4 cell counts, tuberculosis risk categories, and HIV exposure categories. Patients were recruited from 13 participating sites of the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA). A two-stage tuberculin skin test was applied to 709 HIV-infected patients using the Mantoux method. An induration reading5 mm on the first test andor = 5 on the second skin test defined the booster effect. Overall, 18 patients, or 2.7% (95% confidence interval, 1.6 to 4.2) experienced the booster effect. Boosted responses were seen in eight (2.1%) anergic patients, six (4.5%) nonanergic patients, and four (2.5%) with anergy status unknown. Boosting was noted in 1 of the 131 women enrolled. Age, race, CD4 cell count, injection drug use, anergy status, tuberculosis risk categories, and HIV exposure categories were not predictive of boosting. The booster effect occurs in a small percentage of HIV-infected patients tested, thus identifying small numbers of patients with latent tuberculosis infection. The two-stage procedure is probably of limited value in the diagnosis of latent tuberculosis in HIV-infected persons.

To determine the effects of varying inspired O2 on positive radial acceleration (+Gz; i.e., head-to-foot inertial load) duration tolerance, seven men were exposed to the +4.5- to +7.0-Gz simulated aerial combat maneuver (SACM) by use of the Armstrong Laboratory (Brooks Air Force Base) centrifuge. Exposures were repeated on different days while subjects breathed gas mixtures of fractional concentration of O2 in inspired air (FIO2) between 0.12 and 0.6. SACM duration tolerance was positively related to inspired O2 of FIO2 between 0.12 and 0.2 but was unchanged at FIO2 between 0.2 and 0.6. SACM exposure decreased arterial O2 saturation and increased heart rates; SACM-induced changes were additive to FIO2 effects. The positive relationship between blood lactate and SACM duration tolerance at all FIO2 indicated an anaerobic component. It is concluded that SACM duration tolerance is limited by reduced FIO2 but not enhanced by hyperoxia. Thus the aerobic component of +4.5- to +7.0-Gz SACM duration tolerance is much greater than previously believed.

1. 1. The relationship between seasonal changes in environmental temperature and hematological parameters was investigated in mature, single comb white leghorn (SCWL) male chickens. 2. 2. Samples of blood plasma, obtained monthly from two groups of birds over two separate 12 month periods, were analysed for corticosterone (CT), 3,5,3′-triiodothyronine (T3), thyroxine (T4), plasma protein (PP), and packed cell volume (PCV). 3. 3. Statistical analyses revealed that blood plasma concentrations of T3 were significantly correlated negatively with monthly dry-bulb temperatures. 4. 4. There were no consistent or significant relationships between monthly dry-bulb temperature and CT, T4, PP or PCV over the two 12 month periods. 5. 5. The results of this study indicate that blood plasma concentrations of T3 are influenced by season of year in mature, male domestic fowl.

Osteomyelitis often causes functional impairment due to tissue destruction. This report demonstrates a novel previously unappreciated role of osteoblasts. Samples of osteomyelitic bone and bacterially challenged osteoblasts produce increased amounts of antimicrobial peptides in order to combat bacterial bone infection. An osteomyelitis mouse model confirmed the osseous induction of the murine homologue of human beta-defensin-2, suggesting a central role in the prevention of bacterial bone infection. Antimicrobial peptides are effectors of the innate defence system and play a key role in host protection at cellular surfaces. Some of them are produced constitutively, whereas others are induced during infection. Human beta-defensins represent a major subclass of antimicrobial peptides and act as a first line of defence through their broad spectrum of potent antimicrobial activity. The aim of the present in-vitro and in-vivo investigations was to study the expression and regulation of human beta-defensin-2 in the case of bacterial bone infection and to analyse the effects of immunosuppressive drugs on bone-derived antimicrobial peptide expression. Samples of healthy human bone, osteomyelitic bone and cultured osteoblasts (hFOB cells) were assessed for the expression of human beta-defensin-2. Regulation of human beta-defensin-2 was studied in hFOB cells after exposure to bacterial supernatants, proinflammatory cytokines and immunosuppressive drugs (glucocorticoids and methotrexate) and was assayed by enzyme-linked immunosorbent assay. An osteomyelitis mouse model was performed to demonstrate the regulation of the murine homologue of human beta-defensin-2, named murine beta-defensin-3, by real-time reverse transcription-polymerase chain reaction and immunohistochemistry. Healthy human bone and cultured osteoblasts are able to produce human beta-defensin-2 under standard conditions. Samples of infected bone produce higher levels of endogenous antibiotics, such as human beta-defensin-2, when compared with samples of healthy bone. A clear induction of human beta-defensin-2 was observed after exposure of cultured osteoblasts to gram-positive bacteria or proinflammatory cytokines. Additional treatment with glucocorticoids or methotrexate prevented bacteria-mediated antimicrobial peptide induction in cultured osteoblasts. The osteomyelitis mouse model demonstrated transcriptional upregulation of the murine homologue of human beta-defensin-2, namely murine beta-defensin-3, in bone after intraosseous contamination of the tibia. Human and murine bone have the ability to produce broad-spectrum endogenous antibiotics when challenged by micro-organisms in vitro and in vivo. Immunosuppressive drugs, such as glucocorticoids or methotrexate, may increase the susceptibility to bone infection by decreasing antimicrobial peptide expression levels in case of microbial challenge. The induction of human beta-defensin-2 following bacterial contact suggests a central role of antimicrobial peptides in the prevention of bacterial bone infection.

The primary aim of surgery for pertrochanteric fractures of the femur is to regain preoperative mobility as quickly as possible. The aim of this study was to investigate whether clinical or radiological differences could be found between proximal femoral nails (PFN) and trochanteric gamma nails (TGN), with particular attention given to technical differences in implantation and early complications.This prospective study included 114 patients with PFN or TGN. Their average age was 78.9 years. Clinical and radiological examinations were evaluated over a 24-month period.The implantation time for PFN was 20 min less than for TGN in patients with 31A1 (AO) fractures, and 78.5% of all operations were complication-free. Problems occurred in 10 cases (seven PFN, three TGN) during nail insertion and were, in the case of TGN, all caused by fragment dislocation. Postoperative dislocation of the implant was observed in 12 cases [eight PFN (7%), four TGN (3.5%)]. Cut-out occurred in four cases with PFN implants, one of which was attributed to z-effect, and in two cases with TGN. Secondary varus deviation without cut-out occurred in one case with TGN and two cases with PFN. No significant differences in complication rates could be found between the two implants (p0.05).PFN are better suited to 31A1 fractures because of their higher rotational stability from the use of dual screws. A short femur and high antecurvation can cause insertion problems in PFN because of the nail design. It is advisable to choose the type of implant during preoperative planning after considering fracture type and patient anatomy.

Malalignment after osteosynthetic stabilization of lower leg fractures is still a common problem for trauma surgeons. The aim of the present study was to evaluate the incidence of torsional and varus- or valgus-malalignment of the lower leg subsequent to osteosynthetic stabilization techniques such as reamed nailing, unreamed nailing and tibial plating.70 patients with 73 fractures of the lower leg were included in the study. The fractures were treated consecutively in 37 cases with an unreamed nail (UTN), in 21 cases with a reamed nail and 15 cases were stabilized with a plate. During clinical follow-up after 5.7 years each patient was analyzed for malalignment of the lower leg with a CT-Scan and a dual-energy X-ray absorptiometry (DXA) analysis.Multi-level CT-scans revealed a significant rotational malalignment in 16.4 % of patients. Interestingly, all misaligned cases were treated with a nail (9.6 % UTN, 6.8 % reamed nail). Varus- or valgus-malalignment was detected in 5.4 % of cases all of whom had been treated with an intramedullary nail.Malalignment is still a common problem after osteosynthetic stabilization of lower leg fractures, whereby the majority of these cases can be expected after intramedullary nailing. Rotational malalignment can be detected by CT-Scans, whereas DXA analysis is a reliable procedure to diagnose varus- or valgus-malalignment after osteosynthetic stabilization of lower leg fractures.

Vitamin A toxicosis and vitamin E deficiency was diagnosed in a commercial rabbit-breeding colony and was associated with reproductive abnormalities, abortions, and poor survivability of kits in the breeding colony. Paresis and muscular dystrophy were noted in juvenile rabbits. Another group of New Zealand White rabbits from the same commercial colony was used to assess the effect of vitamin E-based therapy on clinical signs, reproduction, and vitamin A and E serum and liver levels. Blood samples were taken before and after dietary changes and vitamin E therapy. Serum vitamin E remained low after feeding a diet containing the recommended levels of vitamin E. Administration of vitamin E for 2 weeks lowered the serum vitamin A levels and increased the vitamin E serum and liver levels. In conclusion, vitamin E therapy appears to be an effective treatment for hypervitaminosis A.

Between 1980 and 1996 we treated 23 patients for dislocated fractures of the talus. The injury was caused by a car accident in 61% and a high fall in 22%. Five patients had open wounds (22%), two developed compartment syndrome of the foot (9%) at an early stage, and 11 patients had multiple injuries. We used the classifications of Hawkins and Marti/Weber. All fractures were surgically treated by fixation with screw osteosynthesis, percutaneous wire transfixation, and/or external fixation. Fifteen patients with dislocated fractures of the talus underwent clinical and radiological follow-up examinations using the Kiel score.Four patients had excellent and three good results. In five patients with moderate, two with adequate, and one with poor results, we found additional injuries to the ipsilateral foot or leg in 50%. Of those patients, 73% developed peritalar arthrosis and 39% talar necrosis. Due to bony defects, anatomical reconstruction was unsatisfactory in 48%.Even immediate anatomical reduction and sufficient stabilization cannot always decrease the rate of talar necrosis and peritalar arthrosis.

Mice minute virus (MMV) and mouse parvovirus (MPV) type 1 are the two parvoviruses known to naturally infect laboratory mice and are among the most prevalent infectious agents found in contemporary laboratory mouse colonies. Serologic assays are commonly used to diagnose MMV and MPV infections in laboratory mice; however, highly accurate, high-throughput serologic assays for the detection of MMV- and MPV-infected mice are needed. To this end, the major capsid viral protein (VP2) genes of MMV and MPV were cloned and MMV recombinant VP2 (rVP2) and MPV rVP2 proteins were expressed by using a baculovirus system. MMV rVP2 and MPV rVP2 spontaneously formed virus-like particles that were morphologically similar to empty parvovirus capsids. These proteins were used as antigens in enzyme-linked immunosorbent assays (ELISAs) to detect anti-MMV or anti-MPV antibodies in the sera of infected mice. Sera from mice experimentally infected with MMV (n= 43) or MPV (n= 35) and sera from uninfected mice (n= 30) were used to evaluate the ELISAs. The MMV ELISA was 100% sensitive and 100% specific in detecting MMV-infected mice, and the MPV ELISA was 100% sensitive and 98.6% specific in detecting MPV-infected mice. Both assays outperformed a parvovirus ELISA that uses a recombinant nonstructural protein (NS1) of MMV as antigen. The MMV rVP2 and MPV rVP2 proteins provide a ready source of easily produced antigen, and the ELISAs developed provide highly accurate, high-throughput assays for the serodiagnosis of MMV and MPV infections in laboratory mice.

Several rodent helicobacters have been associated with chronic active hepatitis or inflammatory bowel disease. Severe combined immunodeficient (SCID) mice appear to be inherently susceptible to disease attributable to these emerging pathogens. With the advent of polymerase chain reaction (PCR) analysis, it has become clear that several as yet unidentified Helicobacter species may also colonize rodents, but their capacity to cause disease is unknown.A Helicobacter species isolated from feces of a BALB/c mouse and provisionally named "H. typhlonicus" was used to inoculate helicobacter-free 4-week-old SCID mice (n = 11 males and 11 females). At various weeks after inoculation, mice were sacrificed and liver and intestinal specimens were collected for histologic examination and PCR analyses.The C.B-17 scid/scid mice inoculated with "H. typhlonicus" developed moderate to severe proliferative typhlocolitis, similar to that seen in SCID mice infected with H. hepaticus or H. bilis. However, in contrast to mice infected with H. hepaticus or H. bilis, lesions of chronic active hepatitis were not detected in mice inoculated with "H. typhlonicus." A similar disease syndrome developed in SCID mice cohabitated with B6D2F1 mice naturally infected with a novel Helicobacter species that was genetically identical to "H. typhlonicus.""Helicobacter typhlonicus" joins a growing list of helicobacters that are capable of inducing enteric disease in immunodeficient mice.

Although children are injured everyday through accidents, road traffic, leisure or sports activities, internal lesions of the knee joint due to the trauma are rare. Diagnose and therapy follow rather empirical than analytical patterns. A retrospective, controlled study evaluates and recommends ways of treatment. Traumatic internal lesions of the knee where analysed in 76 children up to age 16. The pattern of injury changed with increasing age, the trauma remaining the same. Most common where injuries to the anterior cruciate ligament (ACL). Main cause where sports activities. Operative treatment seems to be the appropriate treatment. Osseous avulsions of the cruciates and collateral ligaments showed good results after transosseous refixation with a suture. Suturing of intraligamentous ACL-ruptures as well as patellar ligaments plasty showed unsatisfactory results. Secondary lesions due to instability of the knee where also observed in children. Children cannot self estimate the severity of the injury so subjective statements are insecure. Trauma, surgery, pain and immobilisation cause a marked malfunction of the sensor-motor system which is effectively treated by physiotherapy.

Helicobacter bilis is a recently identified species that colonizes the intestine and liver of mice. In immunocompetent mice, infections have been associated with mild hepatitis, and in immunocompromised mice, inflammatory bowel disease has been induced by intraperitoneal inoculation of the organism. We report inoculation of 6-week-old C.B-17 scid/scid mice by gastric gavage with approximately 10(7) H. bilis colony-forming units. Groups of mice were euthanized and necropsied 12, 24, and 36 weeks after inoculation. Mild to moderate proliferative typhlitis was evident in all mice at 12 and 36 weeks after inoculation and in most mice 24 weeks after inoculation. Mild to severe chronic active hepatitis was detected in 10 of 10 male mice and 3 of 10 female mice. These results indicate that H. bilis can cause moderate to severe enterohepatic disease in immunocompromised mice.

An analysis of the CT morphology of fractured thoraco-lumbar vertebrae after treatment with internal fixation and transpedicular spongiosaplasty (SP).30 patients were examined following trauma and surgery after about 12 and 30 months by means of CT. The following were evaluated: width of the spinal canal; height of the vertebra and intervertebral space; degree of kyphosis; position, size and appearance of the SP and of the vertebral body.The width of the spinal canal was reconstituted in 91%; in 83% the anterior vertebral margin and in 35% the intervertebral space was reduced. A kyphosis of 8.9 degree was found on the followup examination. The SP showed a reduction in size (18/30) or could no longer be defined (6/30). Hypodense areas (28/30) with cavitation (12/30) were found in the vertebral body and the SP could be identified by a sclerotic margin (22/30).Treatment by this form of therapy was successful, reaction of the vertebral body against the spongiosaplasty could be identified.

Hyperplastic goiter was diagnosed during routine health monitoring of a closed Syrian hamster colony (SG). Adult and juvenile hamsters were affected at a prevalence of 45%. Histologic examination of the enlarged thyroid gland revealed marked follicular cell hyperplasia. Because prevalence of thyroid hyperplasia in this colony exceeded the 6 to 7% prevalence expected in aged hamsters, additional studies were performed to investigate the pathogenesis of this condition. Juvenile male SG hamsters and age- and sex-matched Syrian hamsters that did not have increased prevalence of goiter were obtained from an unrelated source (Fredrick Cancer Research and Development Center [FCRDC]). The thyroid glands of hamsters were evaluated by 123I radionuclide imaging. Eight of 18 SG hamsters and none of the FCRDC hamsters had a diagnosis of enlarged thyroid gland. Serum baseline and post-thyrotropin thyroxine concentrations in SG hamsters were not statistically different from those in FCRDC hamsters. To investigate whether diet played a role in development of hyperplastic goiter, for 6 months 15 FCRDC hamsters were fed the diet that had been fed to SG hamsters (mouse breeder diet), and five were fed a control diet. To determine whether dietary change would result in resolution of goiter, affected SG hamsters were fed a control diet for 3 months. At the end of each feeding trial, thyroid gland uptake of 123I was reevaluated. The amount of 123I taken up by the thyroid glands of FCRDC hamsters fed the mouse breeder diet was not significantly different from that of controls. In contrast, thyroid gland uptake of 123I remained high for all affected SG hamsters fed the control diet. On the basis of results of these investigations, diet was ruled out as the cause of goiter. Also, a diagnosis of euthyroid hyperplastic goiter was made for the SG hamsters. A genetic cause is suspected to play a role in the increased prevalence of goiter in SG hamsters.

To evaluate the clinical value of sagittal 2D- and 3D-reformations of the talus with and without electronic disarticulation compared to axial slices.23 patients with suspected traumatic lesions of the talus underwent 26 diagnostic CT examinations. Axial slices, sagittal reformations, and 3D-reformations without and with electronic disarticulation were performed. The sagittal 2D- and both types of 3D-reformations were compared to the axial slices with regard to their diagnostic information.Axial slices showed involvement of articular facets in 25 cases. Sagittal and 3D-reformations after electronic disarticulation depicted 23 fractures (23/25), 3D-reformations without electronic disarticulation showed none (0/23). Subluxation of the talocalcaneal joint was only visualised on axial slices three times. One complete luxation of this joint was shown on axial slices, sagittal and 3D-reformations without disarticulation. It was not visualised on 3D-reformations after disarticulation.The diagnosis must be made based on the axial slices, supported by sagittal reconstructions. 3D-reformations after electronic disarticulation provide a graphic, detailed and readily recognised image of the anatomy of transchondral fractures, and are very helpful in preoperative planning.

Infection with human immunodeficiency virus (HIV) has been associated with increased rates of single- and multidrug-resistant (MDR) tuberculosis in the New York City area. In order to examine the relationship of HIV infection to drug-resistant tuberculosis in other selected regions of the United States, we established a registry of cases of culture-proven tuberculosis. Data were collected from sites participating in an NIH-funded, community-based HIV clinical trials group. All cases of tuberculosis, regardless of HIV status, which occurred between January 1992 and June 1994 were recorded. Overall, 1,373 cases of tuberculosis were evaluated, including 425 from the New York City area, and 948 from seven other metropolitan areas. The overall prevalence of resistance to one or more drugs was 20.4%, and 5.6% of isolates were resistant to both isoniazid and rifampin (MDR). In the New York City area, HIV-infected patients were significantly more likely than persons not known to be HIV-infected, to have resistance to at least one drug (37% versus 19%) and MDR (19% versus 6%). In other geographic areas, overall drug resistance was 16%, and only 2.2% of isolates were MDR. In multiple logistic regression analyses, HIV infection was shown to be a risk factor for drug-resistant tuberculosis, independent of geographic location, history of prior therapy, age, and race. We concluded that HIV infection is associated with increased rates of resistance to antituberculosis drugs in both the New York City area and other geographic areas. MDR tuberculosis is occurring predominantly in the New York City area and is highly correlated with HIV infection.

Clostridium piliforme infection (Tyzzer's disease) was diagnosed in a colony of nude mice. Because spontaneous Tyzzer's disease had not been reported in nude mice, a study was undertaken to better define the clinicopathologic features of this disease outbreak. Sixty homozygous nude (nu/nu) females, 10 nu/nu males, and 10 heterozygous nude (nu/+) females were observed for signs of disease. Over a 3-month period, 43% of the nu/nu mice died or manifested clinical signs of disease and were euthanized, but nu/+ mice remained healthy. Clinical signs of disease were infrequently observed in nu/nu mice and, when evident, were followed by rapid deterioration and death. Gross and histologic lesions, including severe hepatic and intestinal necrosis associated with C. piliforme, were observed only in clinically affected animals. Clostridium piliforme isolated from diseased livers had marked cytotoxicity in in vitro assays. This outbreak is unique in that, contrary to a previous experimental report, nu/nu mice had increased susceptibility to Tyzzer's disease, suggesting that T cells may play an important role in host defenses against C. piliforme infection. In addition, this is the first report of a toxigenic isolate of C. piliforme recovered from mice. The cytotoxin produced by the isolate may have contributed to the severity of clinical disease and lesions.

The cilia-associated respiratory (CAR) bacillus is an unclassified, gram-negative bacterium that has been implicated as an etiologic agent of respiratory tract disease in laboratory rodents. A morphologically and antigenically similar organism has been identified in rabbits and is thought to be a related bacterium, although clinical signs of disease and histologic lesions are absent in infected rabbits. To compare the pathogenicity of rat- and rabbit-origin CAR bacillus isolates in rabbits, neonatal rabbits were experimentally infected with CAR bacillus isolates obtained from an infected rat and rabbit. Rabbits experimentally inoculated with rabbit-origin CAR bacillus had a nasal discharge, seroconverted and developed histologic lesions, whereas rabbits inoculated with rat-origin CAR bacillus seroconverted but did not have evidence of colonization of the respiratory tract. The CAR bacillus isolates were further examined at the genetic level by sequencing 1,261 base pairs of the 16S rRNA gene from six CAR bacillus isolates obtained from infected rabbits. A consensus sequence was obtained and compared with the analogous gene sequence data from rat-origin CAR bacillus isolates. Results indicated that these two organisms are distinctly different, with only 48.8% sequence homology. Comparison of the rabbit-origin 16S rRNA gene sequence with the database Genbank indicated that the organism is most closely related to members of the genus Helicobacter. Bacteria with the highest percentage of similarity with the rabbit-origin CAR bacillus were Helicobacter sp. strain Seymour and H. felis, with 91.1 and 90.8%, respectively. Findings of this study indicate that CAR bacillus isolates from rats and rabbits are host-specific and are different bacteria that belong to distinct genera.

In the New Zealand black (NZB) x New Zealand white (NZW) (B/W) mouse model of systemic lupus erythematosus (SLE), females die prematurely and males have late onset of disease. It has been proposed that testosterone protects B/W mice from rapidly progressive SLE. The mechanisms of androgenic suppression of the immune system, however, are not understood. We tested the hypothesis that testosterone exerts protective effects in males through classic receptor-mediated actions. Flutamide, a potent and specific androgen receptor blocker, was administered continuously to B/W mice from 6 weeks of age, and the animals were monitored in a longevity study. Our supposition that flutamide treatment would accelerate disease was upheld in female B/W mice. In females, flutamide clearly accelerated mortality and reduced longevity to (median) 30 weeks as compared with 37 weeks in controls (p = 0.003). In male B/W mice, mortality was identical in treated and control animals in the early phase of the study, and deleterious effects of treatment were apparent only after the first year of treatment. Flutamide-treated males had significant elevation of serum testosterone, but their atrophied seminal vesicles strongly suggested that peripheral androgen effects were blocked. Albuminuria, blood urea nitrogen, and anti-DNA antibodies were not altered by flutamide in females or males. The receptor-mediated effects of androgens on murine autoimmune disease were dependent on gender and were noted primarily in females and in males that survived past 1 year of age.

Pyrimethamine, 25 mg thrice weekly, was evaluated as primary prophylaxis for toxoplasmic encephalitis (TE) in a double-blind, randomized clinical trial in patients with human immunodeficiency virus (HIV) disease, absolute CD4 lymphocyte count of200/microL (or prior AIDS-defining opportunistic infection), and the presence of serum IgG to Toxoplasma gondii. Leucovorin was coadministered only for hematologic toxicity. There was a significantly higher death rate among patients receiving pyrimethamine (relative risk [RR], 2.5; 95% confidence interval [CI], 1.3-4.8; P = .006), even after adjusting for factors predictive of survival. The TE event rate was low in both treatment groups (not significant). Only 1 of 218 patients taking trimethoprim-sulfamethoxazole but 7 of 117 taking aerosolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia developed TE (adjusted RR for the trimethoprim-sulfamethoxazole group, 0.16; 95% CI, 0.01-1.79; P = .14). Thus, for HIV-infected patients receiving trimethoprim-sulfamethoxazole, additional prophylaxis for TE appears unnecessary.

In a retrospective analysis of 1,300 lower leg fractures, treated by operative stabilization in the years from 1980 to 1992, we examined disturbances of bone healing. In 55 patients (4.2%) faults in indication and completion of internal or external stabilization, infections with consecutive instability (43.6%), and bone defects (63.6%) led to prevention of bone healing. Conservation of blood supply and medial cortical support should be ensured.

This is the initial report of an unusually high incidence of exencephaly in inbred New Zealand White (NZW) mice and the congenic NZW-xid strain, in which animals are homozygous for the recessive X-linked immune deficiency (xid) gene. The predominant expression of exencephaly in female pups and a disproportionate decrease in numbers of female pups in litters suggested that exencephaly was part of a continuum of lethal defects expressed preferentially in females. Genetic influence in the expression of exencephaly in NZW mice was postulated because environmental cohort controls did not express this defect. NZW mice are an additional model for studying the pathogenesis of neural tube defects.

Heart rates were obtained simul- taneously from FM radio transmitters and heart rate monitors externally mounted on unanesthe- tized and unrestrained mixed-breed goats. Data from transmitters were highly correlated (r = .92, P < .0001) with data from monitors and the heart rates. percentage difference in heart rates between the two devices was less than that observed between animals. Analyses also revealed that radio trans- mitters provided a reliable, repeatable, and valid method for the noninvasive measurement of goat

A double-blind, placebo-controlled trial was set up to compare clindamycin and pyrimethamine as prophylaxis for toxoplasmic encephalitis (TE) in HIV-infected patients at risk of the disorder. Interim analysis showed that clindamycin-treated patients were 4.4 (95% confidence interval 1.3-15.2) times more likely to experience an adverse effect that necessitated withdrawal of the study drug than those who received placebo. Diarrhoea and rash were reported in 16 (31%) and 11 (21%), respectively, of 52 patients treated with clindamycin (300 mg twice daily) compared with 2 (6%; p = 0.06) and none (p = 0.01) of the 32 placebo-treated patients. The clindamycin arm of the trial was prematurely terminated, although recruitment to the pyrimethamine arm continues.

Eight adult New Zealand White rabbits were exposed individually, in series, to each of 23 effective temperatures (t(eff)) until body temperature (tb) increased 1.1 degrees C or for a period of 2 hours. Body temperature was measured to the nearest 0.1 degree C using FM radio transmitters in the pre-test (baseline) condition and at 2 minute intervals during the test conditions where t(eff) ranged between 21.7 and 34.7 degrees C. The frequency at which the rabbits displayed a 1.1 degree C rise in tb was related to the magnitude of the t(eff), with 100% of the rabbits manifesting this change at t(eff) greater than 30.2 degrees C. At t(eff) of 28.4 through 30.2 degrees C, some, but not all, of the rabbits showed a 1.1 degree C rise in tb whereas none displayed the 1.1 degree C rise in tb at t(eff) below 28.4 degrees C. The mean time necessary for the 1.1 degree C rise in tb was negatively correlated (P less than 0.01) to the magnitude of the t(eff). The significantly (P less than 0.01) elevated plasma corticosterone in rabbits exhibiting 0.6 degree C and 1.1 degree C rise in tb suggests that those animals were stressed physiologically by the experimental procedure. It is concluded that the conditions associated with increased tb induce physiological changes commonly associated with stressors and that the techniques reported herein should be useful in establishing upper environmental temperature limits for housing rabbits.

An inexpensive but reliable telemetry system for long-term, sequential monitoring of body temperature in up to 20 laboratory animals is described. The system consists of frequency-modulated (FM) temperature transmitters, remote-controlled power switches to extend battery life, a multi-channel telemetry receiver, and a frequency counter interfaced with a personal computer to record data. Analysis of body temperature data obtained from four New Zealand White rabbits confirms the reliability and value of this system.

The physiological changes in male rats during acclimation were studied following direct or stepwise exposure to heat (32.5 degrees C) in a controlled-environment room. The animals were exposed to each temperature for 10 days beginning at 24.5 degrees C and returning to 24.5 degrees C in the reverse order of initial exposure. Relative humidity of 50 +/- 2% and a 12-h light-dark photoperiod (light from 0900 to 2100 h) were maintained. Physiological changes in metabolic rate (MR), evaporative water loss (EWL), plasma corticosterone, body water turnover, and food and water intake were measured. The results indicate a significantly (P less than 0.001) elevated plasma corticosterone and MR in rats exposed directly to heat from control temperature (24.5 degrees C) but not in those animals exposed stepwise via 29.0 degrees C. All kinetic parameters of water pool changed (P less than 0.01) on direct exposure to heat, whereas rats exposed in a stepwise manner increased only pool turnover. In addition, exposure to experimental temperatures resulted in reduced (P less than 0.05) relative food intake and increased (P less than 0.05) water intake. Compared with the control condition of 24.5 degrees C, EWL was significantly (P less than 0.05) elevated when the animals were exposed either directly or in a stepwise fashion to 32.5 degrees C. These data suggest that the response to elevated temperatures is influenced by the temperature to which the rat is acclimated.

An optoelectronic ear oximeter (Hewlett-Packard, model 47201A) was evaluated as a noninvasive method for determining arterial oxygen saturation (SaO2) in human subjects during exposure to various levels of accelerative forces. This physiological calibration involved exposing five subjects, while breathing air and wearing the ear oximeter for 60 s to each of three levels of accelerative forces (3, 5, and 7 G); arterial blood samples were withdrawn concurrently. SaO2 was calculated indirectly from the oxygen tensions (PaO2) measured from the sampled arterial blood with a blood gas analyzer and corrected for pH and base excess. These data were compared, as were similar data taken from the same subjects breathing three different hypoxic gas mixtures while resitng at earth's gravity (1 G). Regression analyses of these data for both experimental groups (a, G exposure, or b, hypoxic exposure), comparing the ear-oximeter SaO2 with the calculated SaO2, showed the ear oximeter to be accurate with correlation coefficients of 0.95 and 0.98, respectively.

A radioimmunoassay for corticosterone was developed and characterized using corticosterone antiserum (377, Niswende) and a simple ethanol extraction procedure. The antiserum appeared to be highly specific fo corticosterone. Intraassay variability was 3.67 +- 0.75% (mean +- SE) at 50 pg of corticosterone; interassay variability with a mean value of 51.15 pg was 6.98 +- 1.01%. Assay sensitivity was 9.48 +- 0.60 pg. Utilizing this assay, serum obtained from adrenalectomized and adrenalectomized-ovariectomized rats yielded lower corticosterone values than serum from intact or ovariectomized rats. Intact females had lower corticosterone values than intact males. Rats exposed to elevated temperature (32.5/sup 0/) displayed significantly (P < 0.001) elevated plasma corticosterone levels (48.48 +- 4.37 ..mu..g/100 ml) compared to control (24.5/sup 0/) animals (21.31 +- 2.02 ..mu..g/100 ml). The high specificity, sensitivity, precision, recovery level, and ease of this technique make it useful for the study of either serum or plasma corticosterone.

After acclimating individually housed male rats to temperatures of either 24.5 +/- 0.1 or 29.2 +/- 0.1 degrees C for 14 days, randomly paired animals from each group were acutely exposed (3 h) in series to experimental temperatures between 18.0 and 34.5 degrees C in a controlled environment room. Relative humidity of 50 +/- 0.3% and a 12-h light-dark photoperiod (light from 0900 to 2100 h) were maintained. Metabolic rate (MR) and evaporative water loss (EWL) were-measured using an open-flow system; thermistors were used to measure the rectal (Tre) and tail skin (Tts) temperatures. MR was relatively constant over a temperature range of 22.2 to 27.0 degrees C for rats acclimated to 24.5 degrees C and 20.0 to 29.2 degrees C for rats acclimated to 29.2 degrees C. Above and below these ranges, MR for both groups was significantly (P less than 0.05) elevated. At their respective acclimation temperatures, the absolute Tre and Tts of 29.2 degrees C rats were maintained at an elevated level compared with 24.5 degrees C rats. Although EWL for both groups was relatively constant between 18.0 and 27.0 degrees C, 24.5 degrees C rats displayed higher EWL changes at most environmental temperatures above 27.0 degrees C. At 34.5 degrees C, 29.2 degrees C rats dissipated 26% more metabolic heat by evaporation compared with 24.5 degrees C rats. These data suggest that acclimation temperatures of rats affected the thermoneutral zone and alter the set-point temperature around which thermal responses are regulated.

Four groups of 70-wk-old broiler breeder females were fed once daily at 0600, 1000, 1400, and 1800 h to determine the effect of feeding time and eating on body temperature. The photoperiod was from 0430 to 1930 h. Four floor pens of 30 hens each were assigned per feeding time. Following a 9-day adjustment period, body temperature was determined, in series, by rectal probe of 5 birds/pen at 7 and 3 h prefeeding and 1, 5, 9, and 13 h postfeeding. Body temperature was increased .5 C at 1 h postfeeding in all groups and at 5 h postfeeding in the 0600-h fed group. The rate of feed consumption was fastest with afternoon feeding. Four 1-yr-old broiler breeder males were implanted with an FM radio transmitter for monitoring body temperature and housed in an environmental control chamber. Body temperature was monitored when the birds were fed at 0600, 1000, 1400, and 1800 h. The chamber temperature cycled from 22.2 to 33.3 C (22.2 C: 2200 to 0800 h; 33.3 C: 1200 to 1600 h; 27.8 C: 0800 to 1200 h and 1600 to 2200 h). Lights were on from 0430 to 1930 h. Body temperature changes were also monitored under constant temperature (27.8 C) and light for birds fed ad libitum or at 1000 h. Body temperature increased as much as 1.5 C following feeding and reached a maximum at 5, 4, 3, and 2 h postfeeding at feeding times of 0600, 1000, 1400, and 1800 h, respectively. Males unable to feed displayed a significantly increased body temperature when they observed other birds eating. A specific body temperature response to feeding activity was observed only when males were fed once daily under constant environment.

Differential effects of chronic exposure to increased acceleration on antagonistic skeletal muscle pairs in chickens

SummaryOrgan and body mass changes in restrained adult, male domestic fowl were compared with tissue from control and fasted animals. Body mass loss rate in the restrained animals was 63.5% (p < .001) greater than in the fasted group, yet the two groups recovered at the same rate. Compared with controls and fasted animals, restrained fowl exhibited an increase in size of heart, lungs, kidneys, liver, and adrenals but a greater loss of spleen, superficial pectoral muscle, small intestine, and pancreas masses. Relative water content of organs generally increased in restrained and decreased in fasted animals. The data suggest that restraint—although accompanied by inanition—affects organ and body mass in the domestic fowl in a different way than does fasting.

ConclusionsThe results presented indicate that: (a) the method of obtaining a blood sample, including animal handling, can significantly affect the parameter being measured; and (b) duration of han...

The effect of beta-endorphin (beta-END) and the role of the adrenal and thyroid glands on body temperature were examined in male rats in a controlled environment room at 24.5 +/- 0.1 degrees C. Relative humidity of 50 +/- 0.3% and a 12L:12D photoperiod (L = 0900 to 2100 hr) were maintained. Rectal temperature (Tr) was measured using thermistors. Corticosterone and thyroid hormones were determined by radioimmunoassay. Intracerebroventricular (IVT) administration of varying doses (0.05 to 50.0 micrograms) of beta-END resulted in a hyperthermia that began 30 min post-IVT injection and continued for an additional hour. Intravenous injections of the same doses of beta-END resulted in little or no Tr response. The beta-END-induced hyperthermia was antagonized by intraperitoneal injection of naloxone. Pretreatment with propranolol, phenotolamine, or both drugs in combination did not block the hyperthermia caused by beta-END. Adrenalectomized or hypophysectomized rats receiving IVT injections of beta-END did not consistently display an increased Tr. beta-Endorphin administration had no detectable effect on serum corticosterone or thyroxine but serum triiodothyronine was decreased. These data suggest the acute hyperthermic action of beta-END is mediated centrally through opiate receptors and does not involve adrenergic receptors.

Adult, male Single Comb White Leghorn chickens (SCWL) were housed unrestrained in individual cages in a controlled environment room with a photoperiod of 12L:12D. By means of surgically implanted radio transmitter, body temperatures were recorded hourly for five consecutive days at each of six experimental temperatures: 23, 26, 29, 32, 35, and 38 C. The data were evaluated statistically by correlogram, periodogram, and harmonic analysis. Period length of each cycle was about 24 hr at all ambient temperatures. No significant differences in deep body temperature were observed until the ambient temperature reached 32 C; but highly significant increases were detected between 32, 35, and 38 C. Diurnal differences in body temperature ranged from .6 to 1.1 C. It has been suggested that the body temperature of male chicken may be under the control of a biological clock that synchronizes with the solar day.

Consider where the patient acquired the infection--in the community or the hospital. Gram-negative sepsis that develops after admission to a hospital or extended-care facility is likely to be caused by multiply-resistant organisms. Lack of fever does not reliably exclude sepsis in elderly patients. Among 27 afebrile patients found to have bacteremia-fungemia, diagnosis was made in one-third only after blood cultures were drawn, and almost one-half were already receiving antibiotics.

A technique using cerebral ventriculography for verification of intracerebroventricular cannula placement in the live rat is described. A radiopaque contrast medium, diatrizoate meglumine, was injected into the right lateral ventricle through a cannula stereotaxically implanted into the brain. Radiographic visualization of the radiopaque contrast material in the lateral ventricle and the subarachnoid space verified cannula placement. Transient muscular spasms were observed in about 38% of the injected rats but no lasting changes were observed in the behavior or appearance of these rats.

Thirty anesthetized, male White Leghorn chickens, approximately six months old (average body weight, 2.030 ± 0.048 kg.), individually inhaled radioactively labeled (I-128) monodispersed latex particles. Six birds each were exposed to one of five particle sizes (0.091, 0.176, 0.312, 1.1, and 3.7 to 7 microns). During exposure, the respiratory rate and tidal volume were monitored by a whole-body plethysmograph. Inhaled aerosol was detected externally for each of seven, equal-length sections along the axis of the body. Percentages of deposition for each section were calculated from the corrected time-decay activity. Significant differences (P

Body heat dissipation rates were determined in greyhound and beagle dogs, the rabbit, and the rat. Each group of animals was confined in standard cages in a controlled environment room maintained under conditions of 24 degrees C, 50% relative humidity, and fixed ventilation rats. Food and water were available ad libitum. Heat dissipation rates were determined for each group and normalized to an individual animal basis. The ratio of actual heat dissipation to standard metabolic rate, the metabolic heat ratio, was 2.01+/-0.18 for the greyhound, 1.98+/-0.03 for the beagle, 2.66+/-0.20 for the rabbit, and 1.95+/-0.13 for the rat. For each species, the ratio displayed a 24-hour cyclic pattern in which four contiguous maximum values differed significantly from four contiguous minimum values. The ratios of maximum values to minimum values were between 1.54 and 1.75.

New Zealand white rabbits and Wistar rats were exposed, in an acoustic chamber, to 1.5 hours of white noise per day at intensities of 107--112 decibels. Compared to the control condition of 60 decibels (background noise level), both rabbits and rats displayed increased adrenal weights (p less than 0.05). Rabbits also had decreased spleen and thymus weights (p less than 0.05). Rats had increased total leukocyte counts and a relative eosinopenia (p less than 0.05). Also, noise exposed rats exhibited a decrease (p less than 0.05) in food intake by the third day of noise exposure. There were no observed changes in hematocrit or plasma protein concentrations.