Experimental stress fractures of the tibia. Biological and mechanical aetiology in rabbits

We have shown that stress fractures can be induced in the tibial diaphysis of an animal model by the repeated application of non-traumatic impulsive loads. The right hind limbs of 31 rabbits were loaded for three to nine weeks and changes in the bone were monitored by radiography and bone scintigraphy. The presence of stress fractures was confirmed histologically in some cases. Most animals sustained a stress fracture within six weeks and there was a positive correspondence between scintigraphic change and radiological evidence. Microscopic damage was evident at the sites of positive bone scans. The progression, location, and time of onset of stress fractures in this animal model were similar to those in clinical reports, making the model a useful one for the study of the aetiology of stress fractures.     

FM sonography in diffuse liver disease: prospective assessment and blinded analysis

FM sonography - a signal-processing technique that uses frequency and phase information as well as amplitude data - shows promise in evaluation of patients with diffuse liver disease. In a prospective blinded review of 37 patients with biopsy-proved liver disease and 42 healthy volunteers, FM sonography was clearly superior to traditional amplitude-based (AM) sonography in distinguishing healthy from diseased subjects. Statistically significant differences were seen in accuracy (FM, 98.7%; AM, 84.8%), sensitivity (FM, 97.3%; AM, 70.3%), and negative predictive value (FM, 97.7%; AM, 78.8%). Our data also suggest that current FM sonographic techniques cannot differentiate among histologic findings associated with different hepatic parenchymal abnormalities. It is unclear, therefore, whether FM imaging can reduce the numbers of patients who require biopsy for diagnosis or the frequency of biopsy procedures in patients with known disease.     

Intraabdominal Mycobacterium tuberculosis vs Mycobacterium avium-intracellulare infections in patients with AIDS: distinction based on CT findings

Abdominal CT scans of 71 patients with AIDS who had proved disseminated infection due to Mycobacterium tuberculosis (27 patients) or Mycobacterium avium-intracellulare (44 patients) were reviewed retrospectively to identify radiologic features that can be used to distinguish the two infections. CT findings in patients with disseminated M. tuberculosis included focal lesions in the liver (11%), spleen (30%), kidneys (19%), pancreas (7%), and gastrointestinal tract (15%) and lymph nodes with central or diffuse low attenuation (93%). CT findings in patients with disseminated M. avium-intracellulare included marked hepatomegaly (20%); marked splenomegaly (14%); focal lesions in the liver (9%), spleen (7%), and kidneys (2%); diffuse jejunal wall thickening (18%); lymph nodes with central low attenuation (14%); and enlarged lymph nodes exclusively of homogeneous soft-tissue density (55%). The presence of focal visceral lesions and low-attenuation lymph nodes suggests disseminated M. tuberculosis, whereas marked hepatic and splenic enlargement, diffuse jejunal wall thickening, and enlarged soft-tissue-density lymph nodes suggest disseminated M. avium-intracellulare. Recognition of these CT features can lead to a tentative diagnosis so that appropriate therapy can be instituted before the results of mycobacterial cultures become available.     

Intracervical prostaglandin E2 gel. Safety for outpatient cervical ripening before induction of labor.

Cervical ripening prior to induction of labor is often necessary for medical complications of pregnancy. We proposed to prospectively determine the safety of administering prostaglandin E2 (PGE2) gel intracervically in an outpatient setting. Four hundred forty-six patients underwent 515 gel procedures as outpatients. Trained perinatal nurses placed 0.5 mg of PGE2, prepared in a standard methylcellulose base, in the intracervical canal. The PGE2 dose was administered every two hours for a total of three doses if labor did not start. The patient was sent home two hours after the last dose if she was not in active labor. Labor started in 90 patients (20%) during the gel procedure; they were admitted to the labor-and-delivery unit. The remaining patients were discharged. Eighty-eight patients (20%) were later admitted in active labor prior to scheduled induction. One patient (0.02%) was found to have occasional prolonged decelerations on admission and underwent a cesarean section two hours after admission; the Apgar scores were 8 and 9 and the arterial pH, 7.21. Hyperstimulation with excessive intrauterine activity caused significant deceleration of the fetal heart rate in four patients (0.8%), two of whom required transfer to the labor-and-delivery unit but none of whom needed a cesarean section for fetal distress. PGE2 gel can be administered safely intracervically as an outpatient procedure by trained perinatal nurses.     

Synovial membrane and cartilage changes in an arthrosis model. Instability and impact stress model

Surgical instability and repetitive impulsive loading was used to generate degenerative changes in knee joints of rabbits. Light- and electronmicroscopy was carried out at synovial membrane and cartilage samples. The instabilised joints had early synovial inflammation, preceding overall cartilage changes. Synoviocytes were activated and showed more and dilatated cytoplasmatic organells. Invaded round cells--potentially cartilage degenerative--were seen. In the loading model no initial synovial inflammation could be seen. Focal cartilage changes were located at the weight bearing zone. Two different inductive pathways may be involved in cartilage breakdown comparing the two arthrosis models. Mechanical factors seemed to trigger cartilage changes in the loading model, an inflammatory synovial pathway is likely to initiate cartilage breakdown in the instability model. Clinical relevance: The synovial membrane has the key-position for the cartilage degeneration in posttraumatic joint affections. The therapeutic use of antiphlogistic substances is indicated to supreme inflammatory mediators from the synovial membrane. This therapeutic concept seemed not to be useful in primary mechanical induced osteoarthrosis.     

Helicobacter pylori gastric infection in gnotobiotic beagle dogs.

Establishment of infection with Helicobacter pylori and gastritis in nonhuman species is currently only successful in gnotobiotic piglets. This study was designed to determine whether H. pylori will colonize the gastrointestinal tract of gnotobiotic dogs. Gnotobiotic beagle pups were derived by standard methods. Group A (five dogs) was orally challenged with 3 x 10(8) H. pylori at 7 days of age. Group B (two dogs) received only peptone water but was contact-exposed beginning on day 23 postinfection (p.i.). Necropsy was performed on dogs on day 30 p.i. H. pylori colonized the stomach of all dogs (groups A and B). Urease map analysis correlated with the microbiologic findings and indicated that the density of colonization was less than that observed in human tissue. Organisms were also recovered from the pharynx, esophagus, duodenum, and rectum of 1, 2, 2, and 1 dog, respectively. All group A and one group B dog developed serum immunoglobulin G specific for H. pylori by day 30 p.i. Gross lesions were restricted to the stomach and consisted of small (less than 1 mm) lymphoid follicles. Microscopically, there were focal to diffuse lymphoplasmacytic infiltrates with follicle formation and mild to moderate infiltration of neutrophils and eosinophils in the gastric lamina propria. With the Warthin-Starry silver stain, organisms were seen on the surface of the gastric epithelial cells, beneath the mucus layer. We conclude that H. pylori colonizes the stomachs of gnotobiotic dogs for at least 1 month and the lesions resemble those seen in humans. H. pylori is transmissible by contact from infected to noninfected dogs.     

Role of subchondral bone in the initiation and progression of cartilage damage

Osteoarthrosis is a physiologic imbalance, a "joint failure" similar to "heart failure," in which mechanical factors play a role. The initiation and progression of cartilage damage are distinct phenomena. One of the mechanisms of initiation may be a steep stiffness gradient in the underlying subchondral bone. Progression of cartilage lesions probably requires stiffened subchondral bone. In such situations, transverse stresses at the base of the articular cartilage could cause deep horizontal splits in that tissue. The most likely cause of subchondral stiffening in an otherwise congruent joint is repeated failure of the musculoskeletal peak dynamic force attenuation mechanisms. The health and integrity of the overlying articular cartilage depends on the mechanical properties of its bony bed. In certain models of osteoarthrosis, alterations of the bony bed occur before the cartilage changes and suggest that this can occur in clinical conditions. Stiffening of the subchondral bone also can effect joint conformation, which involves deformation of articular cartilage and bone to create maximum contact areas under load.     

Chemotherapy by slowing glucosphingolipid synthesis

The hypothesis offered here is that many different illnesses could be treated by slowing the synthesis of glucosphingolipids (GSLs) with a suitable inhibitor. In people with inadequate hydrolases for the GSLs (e.g. Gaucher's disease), the lipids accumulate to a pathological degree. It should be possible to eliminate the accumulation by slowing the synthesis of the GSLs to match the ability of the patient to degrade them. In people with cancer, the tumors secrete excessive amounts of GSLs, which block the ability of the immune system to attack the tumor cells. By blocking the synthesis of tumor GSLs, it should be possible to enable the patient to generate antibodies and activated T cells that can destroy the tumor. Tumors exhibiting multidrug resistance may do so by synthesizing GSLs even faster than usual. It should be possible to restore the sensitivity of the tumor to anti-cancer drugs by inhibiting their synthesis of GSLs. Metastasis of tumors also appears to require the formation of GSLs, so an inhibitor should help block tumor dissemination. Diabetics tend to have high levels of blood glucose, which acts to stimulate kidney growth via more rapid synthesis of GSLs. This pathological growth can be blocked by inhibiting the formation of kidney GSLs. Viruses, bacteria, and bacterial toxins have been found to bind to specific GSLs of human and animal cells. Presumably, this binding leads to the damaging process of infection. It should be possible to treat such infections by depleting the host's body of its GSLs.     

Relationship between lower limb dynamics and knee joint pain

To test the hypothesis that appropriate and timely neuromuscular control of limb motions plays an important role in the preservation of joint health, we kinematically and kinetically examined the behavior of the legs of young adult subjects at heel strike during natural walking. We compared a group of 18 volunteers, who, we presumed, were preosteoarthrotic because of mild, intermittent, activity-related knee joint pain, with 14 age-matched asymptomatic normal subjects. The two groups of subjects exhibited similar gait patterns with equivalent cadences, walking speeds, terminal stance phase knee flexion, maximum (peak) swing angular velocity, and overall shape of the vertical ground reaction. However, our instrumentation detected statistically significant differences between the two groups within a few milliseconds of heel strike. In the knee pain group, the heel hit the floor with a stronger impact in this brief interval. Just before heel strike, there was a faster downward velocity of the ankle with a larger angular velocity of the shank. The follow-through of the leg immediately after heel strike was more violent with larger peak axial and angular accelerations of the leg echoed by a more rapid rise of the ground reaction force. This sequence of events represents repetitive impulsive loading, which consistently provoked osteoarthrosis in animal experiments. We refer to this micro-incoordination of neuromuscular control not visible to the naked eye as "microklutziness."