Pelvic stress injuries: the relationship between osteitis pubis (symphysis pubis stress injury) and sacroiliac abnormalities in athletes

OBJECTIVE: To demonstrate with radiographic imaging the association between pubic stress injury and sacroiliac abnormalities in athletes. DESIGN AND PATIENTS: Eleven athletes (9 men and 2 women), comprising seven male long-distance runners, one male soccer player, one male and two female basketball players, were imaged with plain films for complaints of pubic symphysis pain, sciatica, groin pain, or a combination of these complaints. In addition to the plain films, four patients were imaged with CT, two patients had MR imaging, and a bone scan was performed in three patients. Anteroposterior plain films of the pelvis of 20 patients without back pain or pubic pain were evaluated for comparison as a control group (ages 18-72 years, average 49 years; 11 women and 9 men). RESULTS: All athletes showed plain film evidence of either sclerosis, erosions or offset at the pubic symphysis. Four had avulsion of cortical bone at the site of insertion of the gracilis tendon. Four patients demonstrated sacroiliac joint abnormalities on plain films consisting of sclerosis, erosions and osteophytes, and in one of these athletes, bilateral sacroiliac changes are present. Two patients with normal sacroiliac joints on plain films had a bone scan showing increased radionuclide uptake bilaterally at the sacroiliac joints. One patient with both plain film and CT evidence of sacroiliac abnormalities had an MR examination showing abnormal signal at both sacroiliac joints and at the pubic symphysis. A sacral stress fracture was found on CT in one patient with complaints of sciatica. In the control group, six patients, all over the age of 55 years, had mild sclerosis of the symphysis, but no plain film evidence of sacroiliac abnormalities. CONCLUSION: We have found a group of athletes in whom stress injuries to the pubic symphysis are associated with changes in the sacroiliac joint as demonstrated by degenerative changes or in the sacrum as manifested as a sacral stress fracture. These findings are probably due to abnormal stresses across the pelvic ring structure that lead to a second abnormality in the pelvic ring. The abnormality in the sacrum is not always well seen with conventional imaging. Recognition of the association of stress injury of the symphysis with back pain is important in that it can help avoid inappropriate studies and diagnostic confusion.     

Peripartum pubic symphysis separation: a case series and review of the literature

Peripartum pubic symphysis separation is a recognized complication of pregnancy with incidence estimates ranging from 1:300 to 1:30,000. Characteristic symptoms of symphyseal separation include suprapubic pain and tenderness with radiation to the back of legs, difficulty ambulating, and occasionally, bladder dysfunction. Clinical history, presenting symptoms, and response to therapy are sufficient to make the diagnosis, although radiographic documentation of symphyseal separation by x-ray or ultrasound are frequently used to confirm the diagnosis. The underlying etiology of symptomatic symphyseal separation has not been fully elucidated. Associations with multiparity, macrosomia, pathological joint loosening, and increased force placed on the pelvic ring have been suggested as possible etiologies. Conservative therapy, including bedrest, pelvic binders, ambulation devices, and mild analgesics usually result in a complete recovery with 4 to 6 weeks. The occurrence of a symphyseal separation should not significantly alter the management of subsequent pregnancies, and conservative therapy is recommended for any recurrence of symptoms. A retrospective review of our experience with 5121 deliveries from 1994 to 1995 found 9 cases of peripartum symphyseal separation, resulting in an incidence of 1 of 569 deliveries. Details regarding this case series and a review of the literature are presented.     

Comparison of amikacin dosing regimens in neutropenic guinea pigs with Escherichia coli infection

OBJECTIVE: To derive pharmacokinetic data for 3 amikacin dosing regimens in guinea pigs and to determine whether the antibacterial activity of 15 mg/kg of body weight given twice daily is equivalent to administering the drug more frequently. ANIMALS: 10 guinea pigs in pharmacokinetic trials, and 10 guinea pigs in pretreatment, control, and amikacin treatment groups. PROCEDURE: Amikacin pharmacokinetic data were determined in guinea pigs after single i.m. administration of 3.75, 7.5 and 15 mg/kg. Guinea pigs had been made neutropenic by treatment with cyclophosphamide. All guinea pigs were inoculated with 2.8 x 10(8) colony-forming units (CFU) of Escherichia coli in the thigh muscle, then were allotted to 5 groups: pretreatment (euthanized 4 hours after inoculation), control, and 3 amikacin treatment groups (3.75 mg/kg, q 3 h; 7.5 mg/kg, q 6 h; and 15 mg/kg, q 12 h). Amikacin administration was begun 4 hours after E coli inoculation and was continued for 72 hours. Numbers of E coli CFU in infected thigh muscle were determined for each guinea pig. RESULTS: Difference in survival between control and the amikacin-treated groups was significant. The E coli infection concentration (log10 CFU) increased significantly in the control, compared with the pretreatment, group. Infection concentration decreased significantly in all treatment groups, compared with the pretreatment group. There was no significant difference in bacterial killing among the 3 treatment groups. CONCLUSION: Amikacin had a significant effect on survival of neutropenic guinea pigs with E coli infection. Antibacterial activity did not differ among 3 doses of amikacin administered at different intervals. CLINICAL RELEVANCE: Aminoglycoside dosing regimen with high peak concentration and long drug-free interval is as efficacious as divided dose regimens.     

Ontogeny, function, and scaling of the mandibular symphysis in papionin primates

In vivo study of mastication in adult cercopithecine primates demonstrates a link between mandibular symphyseal form and resistance to "wishboning," or lateral transverse bending. Mechanical consideration of wishboning at the symphysis indicates exponentially higher stresses along the lingual surface with increasing symphyseal curvature. Lengthening the anteroposterior width of the symphysis acts to resist these higher loads. Interspecific adult cercopithecine allometries show that both symphyseal curvature and symphyseal width exhibit positive allometry relative to body mass. The experimental and allometric data support an hypothesis that the cercopithecine mandibular symphysis is designed to maintain functional equivalence--in this case dynamic strain similarity--in wishboning stress and strain magnitudes across adult cercopithecines. We test the hypothesis that functional equivalence during masticatory wishboning is maintained throughout ontogeny by calculating relative stress estimates from morphometric dimensions of the mandibular symphysis in two cercopithecine primates, Macaca fascicularis and M. nemestrina. Results indicate no significant differences in relative stress estimates among the two macaque ontogenies and an interspecific sample of adult papionin primates. Further, relative stress estimates do not change significantly throughout ontogeny in either species. These results offer the first evidence for the maintenance of functional equivalence in stress and strain levels during postnatal growth in a habitually loaded cranial structure. Scaling analyses demonstrate significant slope differences for both symphyseal curvature and width between the ontogenetic and interspecific samples. The distinct interspecific cercopithecine slopes are realized by a series of ontogenetic transpositions in both symphyseal curvature and width. Throughout papionin ontogeny, symphyseal curvature increases with less negative allometry, while symphysis width increases with less positive allometry versus the interspecific pattern. As symphyseal curvature and width are inversely proportional to one another in estimating relative stresses, functionally equivalent stress levels are maintained both ontogenetically and interspecifically, because the relatively slower rate of allometric increase in symphyseal curvature during growth is compensated for by a slower rate of allometric increase in symphyseal width. These results indicate the primacy of maintaining functional equivalence during growth and the need for ontogenetic data in understanding the evolutionary processes that affect form-function relations as well as the interspecific patterning of adult form across a clade.     

Quantitative trauma mechanics in pelvic fracture

Quasistatic loading of the isolated pelvis and of the pelvis in situ is reported; dynamic loading with an impactor and on 90 degrees car/car side impact are then considered. The isolated pelvis was loaded laterally at the ala of the ilium and the pelvis in situ in the anterior-posterior direction in the area of the symphysis with universal dynamometer; the loading profile was a rigid disk 150 mm in diameter. Some dynamic tests were performed with an impactor with rigid disk 80 mm in diameter as impact surface; the impact was applied against the trochanter major area at a velocity of 30-35 km/h. Otherwise, the pelvic area was stressed by impact through the intrusion of the car side or by impaction of the pelvis against a rigid wall. In the tests conducted with isolated pelves, forces of 850-4850 N were measured; pelvic fractures were observed, specifically fractures of the acetabular margin, pubic bone, and ischium, and comminuted fractures of the symphysis and the iliosacral. In the impactor tests, forces of 6.5-11 kN were enough to cause, pelvic fracture except in one case, and fractures of the femoral neck were found in some cases in addition. With quasistatic anterior-posterior loading of the pelvis in situ, forces of 4,700-10,000 N were measured in cases in which fractures were found.     

Topical retinoic acid (tretinoin) for photoaging: conceptions and misperceptions

Sinusoidal rotation and rotational stimulation tests were used to examine vestibular function in guinea pigs. The results showed that there was no statistically significant difference in the mean number of nystagmus of semi-cycle sinusoidal rotation test and the duration of nystagmus of rotational stimulation test for both the control and test groups before treatment in albinos and pigmented guinea pigs. Meantime, daily subcutaneous injection of gentamicin 125 mg/kg body weight for 12 days in albinos and pigmented guinea pigs showed no significant change in vestibular function until the 7th day of treatment. Significant impairment of vestibular function was noticed on the 10th treatment day. At 5 days after treatment vestibular impairment reached its maximum and minimal recovery was seen at 14 days after treatment. No Further improvement of vestibular function was noticed three months after treatment. The methods are feasible and reliable.     

Assessment of symphysis morphology as a predictor of the direction of mandibular growth

The purpose of this study was to determine whether symphysis morphology could be used as a predictor of the direction of mandibular growth and to assess growth changes of the symphysis. Cross-sectional data included lateral cephalometric radiographs of 115 adults (58 women, 57 men) with the longitudinal sample a subset of 62 subjects (30 females, 32 males) at four age groups. The direction of mandibular growth was evaluated with seven cephalometric measurements that included Y-axis, SN to mandibular plane, palatal plane to mandibular plane, gonial angle, sum of saddle, articulare and gonial angles, percentage lower facial height, and posterior/anterior face height. The mandibular symphyseal dimensions studied were height, depth, ratio (height/depth), and angle. Symphysis morphology was found to be associated with the direction of mandibular growth, especially in male subjects with symphysis ratio having the strongest relationship. A mandible with an anterior growth direction was associated with a small height, large depth, small ratio, and large angle of the symphysis. Conversely, a posterior growth direction was associated with a large height, small depth, large ratio, and small angle of the symphysis. Symphysis dimensions continued to change until adulthood with male subjects having a greater and later occurring change compared with female subjects.     

Composition, constitution, and interaction of bone with hydroxyapatite coatings determined by FT Raman microscopy

Transfer of steroidal and nonsteroidal compounds across guinea pig amnion and chorion laeve was investigated as a function of stage of gestation, tissue orientation, steroid specificity, and molecular size. Each fetal membrane was examined at early and late stages of gestation, before and after pubic symphysis relaxation. Early amnion was impermeable to macromolecules and small charged molecules while [3H]estrone and [3H]pregnenolone were transferred, the latter depending on tissue orientation and involving conjugation at the basolateral interface. After symphysis dilation, amnion transferred all substrates tested with the exception of BSA; the molecular weight cutoff was approximately 5,000. Unlike amnion, early chorion transferred both free and conjugated steroids as well as inorganic sulfate. Transfer of estrone involved conjugation and depended on tissue orientation. Transfer of [3H]estrone-sulfate, [3H]estrone-glucuronide, and [3H]pregnenolone-sulfate was similar despite selective deconjugating activity toward estrone-sulfate. Near term, chorion was impermeable to inorganic sulfate and transfer of estrone-glucuronide depended on tissue orientation, involving deconjugation in the maternal to fetal direction. At no stage of gestation did chorion transfer macromolecules. These results suggest that the transfer of free and conjugated steroids across fetal membranes is differentially regulated by tissue, its stage of development, and direction of transfer.     

Pubic tuberculous osteo-arthritis. Apropos of 2 cases

OBJECTIVE: The authors report an exceptional site of tuberculous osteo-articular infection which must be diagnosed before the destructive stage. OBSERVATIONS: Case 1 : a 21 years old woman presented an inflammatory pubic pain after a trauma with weight loss of 4 kgs in 3 weeks. She presented also 2 satellite inguinal nodes. Erythrocyte sedimentation rate (ESR) was elevated, X-rays showed an important osteolysis of the left ischio-pubic rami, tuberculous skin test (TST) was positive, mycobacterium tuberculosis (MT) could not be found neither in sputtum nor in urine but the node biopsy showed the specific features of tuberculosis. Evolution under a 6 months antibiotic treatment was good. Case 2 : a 19 years old woman, with history of tuberculous contagion, presented in April 1996 cervical nodes and a month later inflammatory pubic and knee pain with weight loss and vesperal sudation. ESR was elevated, TST was phlyctenular, MT searching and HIV serology were negative. X rays showed irregular osteolysis of the pubic symphysis. Scintigraphy showed an increased fixation of pubis and left knee. Cervical nodes biopsy diagnosed tuberculosis. Evolution was good under a 6 months antibiotic treatment. DISCUSSION: Many factors can favorize the development of a pubic tuberculosis and are similar for all forms of tuberculous osteo-articular infection (trauma and contagion in our cases). Radiological features, characterized by a slow evolution, are note specific. Diagnostic confirmation must be bacteriologic or pathologic, and if possible far from the pubic foci. Any traumatic medical procedure has to be avoided because of painful outcome and local risk. Evolution under specific treatment, even of short course (6 months), is sufficient for a good outcome. CONCLUSION: One must think to pubic tuberculous osteo-arthritis in any pubic pain even if it is post-traumatic especially, in endemic countries of tuberculosis.     

Genetic characterization of the murine Ym1 gene and identification of a cluster of highly homologous genes

The induction of Fos protein was examined within LHRH neurons of guinea pigs; the aim was to delineate relationships between subgroups of LHRH neurons during an LH surge in a laboratory rodent in which the distribution of LHRH neurons and the presence of a true luteal phase in the reproductive cycle resemble those in primates. Approximately one third of the forebrain population of LHRH neurons was examined in ovariectomized steroid-treated guinea pigs killed either before or during a steroid-induced LH surge. LHRH/Fos double-labeled neurons were more abundant in surging compared to presurge guinea pigs (p = 0.008) and were most abundant within the preoptic area and anterior hypothalamus. Nonetheless, double-labeled LHRH/Fos neurons were observed throughout the remainder of the population of LHRH neurons in surging guinea pigs. A relative loss of LHRH reaction product was detected by image analysis in the LHRH terminals in the median eminence of surging guinea pigs, consistent with augmented LHRH release. Thus, there appears to be a coordinated increase in Fos expression in subgroups of LHRH neurons, more pronounced in rostral, as compared to caudal, regions in guinea pigs killed after the peak of the steroid-induced LH surge.     

Autoregulation of central and peripheral growth hormone receptor mRNA in domestic fowl

LHRH neurons in guinea pigs, as in primates and other non-rodent species, are broadly distributed in the basal forebrain. In this study, knife cuts were made in the anterior hypothalamus, effectively separating more caudally positioned hypothalamic LHRH neurons from those in rostral preoptic areas. Guinea pigs with knife cuts displayed an LH surge in response to steroid administration. There was no significant difference in the number of LHRH neurons that expressed Fos in conjunction with an LH surge, although fewer total LHRH neurons were detected in the forebrain of knife-cut versus sham-cut animals. Knife-cut animals displayed a larger percentage of LHRH/Fos neurons in one region of the caudal hypothalamus than sham-cut animals. The area and perimeter of the LHRH reaction product within the cytoplasm of LHRH/Fos neurons were smaller than those of single-labeled LHRH neurons in sham-cut animals and in the caudal hypothalamus, but not the rostral preoptic area, of knife-cut animals. We conclude that caudal hypothalamic LHRH neurons separated from rostral preoptic regions are capable of sustaining an LH surge in guinea pigs. This finding is important, as LHRH neurons are present in the caudal hypothalamus, as well as in preoptic areas, of a large number of mammalian species, including humans.     

Developmental variation in lumbosacropelvic anatomy of thoroughbred racehorses

OBJECTIVE: To describe the incidence and types of gross osseous developmental variations and ages of physeal closure in the caudal portion of the thoracic and lumbosacral spine and the pelvis in a sample of Thoroughbred racehorses. ANIMALS: Thoroughbred racehorses (n = 36) that died or were euthanatized at California racetracks between October 1993 and July 1994. PROCEDURE: Lumbosacropelvic specimens were collected, and all soft tissues were removed. The osseous specimens were visually examined. RESULTS: Only 22 (61%) specimens had the expected number of 6 lumbar and 5 sacral vertebrae. Eight (22%) specimens had thoracolumbar transitional vertebrae, and 13 (36%) had sacrocaudal transitional vertebrae. Articular process asymmetries were present at 1 or more vertebral segments in 30 (83%) specimens. Intertransverse joints (2 to 4 pairs/specimen) were bilaterally distributed in the caudal portion of the lumbar spine and the lumbosacral joint in 31 (86%) specimens. Five (14%) specimens had asymmetric distribution of the intertransverse joints. Intertransverse joint ankylosis was found in 10 (28%) specimens. Lumbosacral vertebral body physeal closure occurred between 4.9 and 6.7 years of age; pelvic physeal closure occurred between 5.2 and 5.8 years of age. Iliac crest and ischial arch epiphyseal formation was evaluated, using a grading system, and fusion to the underlying bone occurred at 7.2 years and 5.4 years of age, respectively. CONCLUSIONS: Numerous vertebral anatomic variations were commonly found in a sample of Thoroughbred racehorses. CLINICAL RELEVANCE: Normal anatomic variations and ages of skeletal maturity need to be considered in clinical evaluation of the equine spine and pelvis for differentiation from pathologic findings.     

Sonomorphology of endometriotic cysts

Syndesmotic sutures of the skull are formed by dense connective tissue and called "open"; they are "closed" by formation of a synostosis between adjacent bones. Open sutures are considered as areas of growth and as hinges. The importance of open sutures during the period of skull growth is reflected by pathological situations in which premature closure of the sutures occurs. As alterations of the FGF receptor have been reported in genetical disorders accompanied by premature suture closure (Bellus et al. 1996), the role of fibroblasts and connective tissue in the development of the sagittal suture of mice has been investigated by light and electron microscopy. Morphological changes of the sagittal suture at the following stages are reported: at embryonic day 18, days 1, 5, 9, 14, 20, 26, 28 after birth and in adult mice. Two skulls per stage were investigated. Early osteogenesis appeared in a thin plate, followed by a second plate underneath the first one. Both were separated by blood vessels. In general, vascularization preceded desmoid mineralization; the space around blood vessels was occupied by non-bone-forming cells leaving cavities for the presumptive bone marrow. Mineralization of the collagen-rich osteoid at the mineralizing rim of the bone plates was accompanied by apoptoses and cell disintegration. Newly formed bone was immediately covered by osteoblasts forming a sheet of bone-lining cells. At day 9, the double-layered bone plates of both sides reached the median area of the skull but were separated by non-mineralizing, collagen-rich connective tissue. From day 14 onwards, the bone plates thickened. Bone apposition, recognizable by the formation of collagen-rich osteoid and proceeding from day 14 pp onwards, occurred mainly at the outer and inner surfaces of the calvariae, but neither at bone marrow surfaces nor at the medial edges of the parietal bones. These opposite bone faces showed fewer osteoblasts and bone-lining cells, but an increased number of fibroblasts. Tendon-like collagen bundles connected both bone plates of the open suture of day 26 pp as well as in the adult mice, whereby synostotically closed areas alternated. Formation of an open, syndesmotic suture can, therefore, be described as a transition of bone-forming tissue into a bone-tendon junction. The results indicate the importance of the replacement of osteoblasts by fibroblasts at the sutural front of the bone plates in order to prevent a premature suture closure.     

Unobserved heterogeneity and censoring in the demand for health care

OBJECTIVE: To compare the accuracy of reduction, biomechanical characteristics, and mode of failure of two methods of acetabular osteotomy repair. STUDY DESIGN: Acetabular osteotomies were created in 16 paired hemipelves and stabilized with a screw/wire/polymethylmethacrylate composite fixation technique (SWP) or a 2-mm veterinary acetabular plate (VAP). Eight intact hemipelves were used as controls. SAMPLE POPULATION: Twelve canine cadavers. METHODS: Accuracy of osteotomy reduction was evaluated grossly and by measurement of articular incongruencies formed in polyvinylsiloxane impression casts. Acetabula were loaded in modified bending until failure using a universal testing machine. Data from load-deformation curves were used to determine the biomechanical characteristics of the repaired and intact acetabula. Mode of failure was evaluated grossly and radiographically. RESULTS: Osteotomy reduction was superior in acetabula stabilized with SWP. Mean values +/- standard deviation for load at failure and stiffness of the intact acetabula were 2,796 +/- 152.9 N and 267.5 +/- 61.9 N/mm. Corresponding values for SWP and VAP were 1,192 +/- 202.7 N and 136.3 +/- 76.5 N/mm, and 1.100.5 +/- 331.6 N and 110.0 +/- 51.3 N/mm, respectively. The mean load at failure and stiffness of intact acetabula was significantly greater than acetabula stabilized with SWP or VAP. There was no significant difference between SWP and VAP for load at failure or stiffness. Failure of acetabula stabilized with SWP occurred by fracture of the polymethylmethacrylate and ventrolateral bending of the wires. Acetabula stabilized with VAP failed by ventrolateral twisting of the plate and bending of the caudal screws. CONCLUSIONS: SWP and VAP provide comparable rigidity, however, the SWP facilitates more accurate osteotomy reduction. CLINICAL RELEVANCE: These findings support the use of the SWP technique as an alternative method of acetabular fracture repair.     

A novel mechanism for disposing of effete epithelial cells in the small intestine of guinea pigs

BACKGROUND: We previously showed that at the villus tips in the small intestine of guinea pigs effete enterocytes are not simply exfoliated into the lumen but phagocytosed by subepithelial macrophages, leaving only a thin apical cell portion in the epithelial lining. The aim of the present study is to investigate the fate of these apical pieces of enterocytes. METHODS: The ileum of guinea pigs was perfusion-fixed and processed for transmission and scanning electron microscopic observation. RESULTS: The apical cytoplasmic plates were found to be pushed by neighboring enterocytes and protruded from the epithelial surface, finally being pinched off into the lumen. In this process observed at the villus tips, the junctional complexes between the apical cytoplasmic plate and the adjacent enterocytes were preserved until the pinching-off of the plate. Luminal cell elements revealed a rich existence of cup-shaped or spherical cell fragments covered with microvilli; nuclei were never observed in the luminal fragments. CONCLUSIONS: The findings in the small intestine of the guinea pig are the first to account for the mechanism of the epithelial barriers being preserved while apoptotic enterocytes drop out at the tips of the villi.     

Prevalence of malingering in inpatient suicide ideators and attempters

OBJECTIVE AND DESIGN: In an attempt to study the pathogenesis of mucosal hypersensitivity in allergic rhinitis, we investigated the suppressive effects of cyclosporin A (CyA) and glucocorticosteroids on ovalbumin (OA)-induced hypersensitivity to topical histamine challenge. MATERIALS: Actively sensitized Dunkin-Hartley guinea pigs. TREATMENT: OA and alum were applied to guinea pigs intraperitoneally 3 times at two-week intervals. After general sensitization, OA inhalation was performed every day for 6 days as topical sensitization. Before inhalation, treatment with CyA (50 mg/kg, p.o.), glucocorticosteroids (beclomethasone propionate (1.0 mg/kg, i.p.), fluticasone propionate (FP, 0.5 mg/kg, i.p.)) or vehicle were performed, and the sensitivity to histamine was measured before and after the inhalation. Moreover, in actively (general and topical) sensitized guinea pigs, FP (0.5 mg/kg, i.p.) was applied every day for 5 days and histamine sensitivity was evaluated before and after the application. RESULTS: We found that histamine sensitivity was significantly increased by nasal antigen challenge in this guinea pig model, and that the occurrence of histamine hypersensitivity was inhibited by the pretreatment with CyA and glucocorticosteroids. Although multiple administration of FP gradually reduced the histamine hypersensitivity according to the period of administration, it did not significantly alter the histamine hypersensitivity after the occurrence of hypersensitivity. CONCLUSION: It is concluded that CyA and glucocorticosteroids suppress antigen-induced histamine hypersensitivity in a guinea pig model of allergic rhinitis.     

Inhibitory effect of low molecular weight heparin on the bronchoconstriction in ovalbumin-sensitized guinea pigs after antigen exposure

To elucidate the effect of low molecular weight heparin (LMWH) on the bronchoconstriction, we examined the serial changes of the resistance of respiratory system (Rrs) in ovalbumin (OA)-sensitized guinea pigs after antigen exposure. After sensitization of guinea pigs with repeated OA inhalation, Rrs was measured at immediate asthmatic response (IAR) and late asthmatic response (LAR) with or without LMWH inhalation. Alteration in the number of inflammatory cells of the lung by LMWH inhalation was examined in the broncholaveolar lavage fluid (BALF) and in the histological sections of airway walls. Peak Rrs at 1 min up to 9 min, except 8 min, after antigen exposure significantly decreased by the pretreatment with LMWH inhalation as compared with saline inhalation. Peak Rrs at LAR (after 4 hours up to 24 hours, except 6 hours) also showed a significant decrease in the pretreatment with LMWH inhalation. Pretreatment of LMWH exhibited a decrease of eosinophil percentage in BALF (5.5 +/- 1.2% from 8.2 +/- 0.4% in saline inhalation) and a decrease of infiltrated eosinophil count in airway walls (71.0 +/- 7.3 from 155 +/- 15.8 in saline inhalation). These data show LMWH might play an important role as an inhibitory factor to bronchial asthma.     

Aspects of cardiomyopathy in copper-deficient pigs. Electrocardiography, echocardiography, and ultrastructural findings

Pigs were made copper (Cu)-deficient to evaluate cardiac function and pathology, and electrocardiography. Fifteen-day-old pigs were fed a Cu-restricted diet over an 8 wk period and compared to Cu-adequate diet-fed pigs. Cardiac effects were examined concerning gross morphometry and ultrastructure, echocardiography, and electrocardiography, as well as serum cholesterol levels. The Cu-restricted diet-fed pigs exhibited a marked deceleration of growth and lower hematocrit, hemoglobin, and liver and serum Cu concentrations compared to the Cu-adequate diet-fed pigs. The Cu-restricted diet-fed pigs developed a significantly greater heart weight:body weight ratio, along with greater diastolic measures of ventricular wall and internal dimension relative to body weight. Electrocardiography in the Cu-restricted diet-fed pigs revealed one instance of electrical alternans and an intraventricular conduction disturbance and several instances of T-wave inversion. The Cu-restricted pigs also displayed a prolonged QT interval at the closure of study. Increased mitochondrial volume density and mitochondria:myofibril volume density ratio were observed in the Cu-restricted pig electron micrographs along with excessive lipid and glycogen inclusion and focal degradation of Z-lines, intercalated disk, and sarcomeres. Copper-restriction in young pigs results in cardiac pathology and electrical disturbances. These alterations are similar to those reported for young Cu-restricted rodents. Given then that many cardiac manifestations of developed Cu-deficiency appear conserved across specie lines, the potential for human disturbances in response to severe Cu-deficiency may be plausible.     

Enhancement of hepatic microsomal esterase activity following soman pretreatment in guinea pigs

Soman (pinacolyl methylphosphonofluoridate), a highly toxic organophosphate compound, has been found to be a strong inhibitor of hepatic microsomal carboxylesterase in vitro, but an enhancer of carboxylesterase when administered in vivo. In response to this paradoxical observation, the objective of this study was to determine if soman could cause true enhancement of the metabolism of drugs in the guinea pig and, if so, to characterize the enhanced enzyme activity. Following the pretreatment of guinea pigs with 90% LD50 soman, enhancement of microsomal esterase activity was noted 12 and 24 hr after pretreatment. Using Michaelis-Menten enzyme kinetic studies, enhancement was found to occur with liver carboxylesterase and procaine esterase, but not with aniline hydroxylase. Since the soman-enzyme complex was known to undergo aging with the release of pinacolyl alcohol and the subsequent formation of pinacolone, the effects of these metabolites on the activity of liver microsomal enzymes in vitro were explored. Pinacolone and pinacolyl alcohol produced enzyme enhancement in vitro in a manner similar to that produced by soman pretreatment. These effects were compared with those made by acetone in the same incubations, since the enhancing influence of acetone has already been well documented. Similarity was found between the in vitro effects of acetone and the effects of pinacolone and pinacolyl alcohol. Lastly, the in vivo effects of pinacolone on the activities of the same liver microsomal enzymes were studied following pretreatment of the guinea pigs with 90% LDLo (lowest published lethal dose) pinacolone. Pretreating guinea pigs with pinacolone prior to killing them enhanced liver microsomal carboxylesterase and procaine esterase activities, but had no effect on microsomal aniline hydroxylase activity. This pattern of enzyme enhancement was similar to that observed after soman pretreatment. Therefore, soman was found to enhance hepatic microsomal esterase activity in the guinea pig in a manner similar to that seen with its metabolites, as well as acetone. This information may give insight into how the efficacy and toxicity of therapeutic drugs, other xenobiotics, and endogenous materials may be altered in individuals who survive an exposure to soman.     

Dietary vitamin D affects cell-mediated hypersensitivity but not resistance to experimental pulmonary tuberculosis in guinea pigs

Outbred, Hartley strain guinea pigs were fed purified diets varying only in their levels of vitamin D. The amounts of vitamin D in the diets were adjusted to represent 0, 25, 50, 100, or 200% of the recommended level (1,180 IU/kg of body weight) for guinea pigs. In some experiments, half of the animals in each diet group were vaccinated with Mycobacterium bovis BCG vaccine at the time the diets were introduced. Six weeks later, all guinea pigs were infected by the respiratory route with a low dose of virulent M. tuberculosis H37Rv. Vitamin D-deficient animals exhibited marked reductions in levels of the major vitamin D metabolite, 25-hydroxyvitamin D3, in plasma. Altered vitamin D intake was accompanied by changes in antigen (purified protein derivative)-induced, cell-mediated immune responses both in vivo (tuberculin hypersensitivity) and in vitro (lymphoproliferation). Dermal tuberculin reactivity developed more slowly in vitamin D-deficient guinea pigs but eventually achieved normal levels. The proliferation of splenocytes cultured with purified protein derivative was suppressed by both deficiency and excess of dietary vitamin D. Vitamin D status did not affect the abilities of naive guinea pigs to control primary, pulmonary tuberculosis, nor did it influence the protective efficacy of BCG vaccination. We conclude that changes in dietary vitamin D are associated with alterations in some cellular immune functions but may not be an important determinant of disease outcome in pulmonary tuberculosis, as has been suggested previously.