Binding of osteopontin to the osteoclast integrin αvβ3

Occupancy of the chicken osteoclast _v3 integrin stimulates immediate cell signals. Peptides from osteopontin containing Arg-Gly-Asp and peptides from the osteopontin and bone sialoprotein sequences containing Arg-Gly-Asp stimulated immediate reductions in osteoclast cytosolic Ca²⁺. The changes in cytosolic Ca²⁺ required the Arg-Gly-Asp sequence, and were blocked by LM609, a monoclonal antibody to the _v3 integrin. Osteoclast stimulation by the proteins through the integrin did not require immobilization since soluble peptides produced changes in cytosolic Ca²⁺ and inhibited osteoclast binding to bone particles and bone resorption. The decrease in cytosolic Ca²⁺ stimulated by osteopontin and related peptides was due to activation of a plasma membrane Ca²⁺-ATPase. Thus, the data suggest that ligand binding to the osteoclast _v3 integrin results in a reduction in cytosolic Ca²⁺ which participates in regulation of osteoclast function.     

Relationship between plasma and bone concentrations of cefuroxime and flucloxacillin three different parenteral administrations compared in 30 arthroplasties

• (i) The objective was to determine the range of bone levels of cefuroxime and flucloxacillin achieved after one intravenous (IV) administration of different dosages of cefuroxime and flucloxacillin.
• (ii) Six groups of five patients participated in the study. The first three groups (A–C) received respectively 1500 mg, 1000 mg, and 500 mg cefuroxime intravenously and the second three groups (D–F) received 2000 mg, 1500 mg, and 1000 mg flucloxacillin intravenously.
• (iii) Parenteral administration of cefuroxime and flucloxacillin resulted in measurable bone concentrations in all patients.
• (iv) Large inter-individual variation in bone concentration was observed.
• (v) The bone concentrations of IV cefuroxime were higher (1500 mg, p = 0.0057; 1000 mg, p = 0.0260) than those of flucloxacillin. The bone concentrations of cefuroxime and flucloxacillin were dose dependent.

     

Renal tubular acidosis in the Silver-Russell syndrome

Several patients with the Silver-Russell syndrome (SRS) attending our Genetics Clinic were diagnosed as having persistent metabolic acidosis. Since this abnormality has not been reported previously in the SRS, we reexamined 33 SRS patients to evaluate the frequency and type of metabolic acidosis, the clinical and laboratory findings, and the growth pattern in SRS patients with and without metabolic acidosis. Among them, 14 had a consistent decrease in HCO levels. Renal studies in acidotic patients showed urine pH of 5.8 and 24 h urine calcium of <2.4 mg/kg/24 h; serum creatinine, excretion of glucose, and aminoacids were normal, as were renal ultrasound and excretory urography findings. These data supported the diagnosis of renal tubular acidosis, probably type II; the patients were treated with oral bicarbonate and acidosis was corrected successfully. Clinical manifestations were similar in acidotic and non-acidotic patients. The nutritional indices at diagnosis and at last evaluation (at least 8 months after diagnosis) were abnormally low in all patients; however, acidotic patients, treated with bicarbonate, showed an improvement of nutritional status particularly in the weight/height index, although the difference between groups after follow-up did not reach statistical significance. We suggest that metabolic acidosis due to renal tubular acidosis, probably type II, may occur in children with the SRS and should be looked for and treated in all patients. © 1995 Wiley-Liss, Inc.     

Anterior cervical discectomy for one- and two-level cervical disc disease: the controversy surrounding the question of whether to fuse,plate, or both

Since the introduction of anterior approaches to the cervical spine for the surgical treatment of degenerative disc disease, controversies have developed regarding the necessity of fusion following anterior cervical discectomy, the use of allografts instead of autologous bone for fusion, and, recently, the employment of anterior cervical plating systems in addition to fusion for uncomplicated disc disease. We reviewed seven clinical papers dealing with these issues; these articles surveyed a total of 1153 patients. Several observations can be made from these reviews. First, there is little or no difference in clinical outcome following single-level anterior discectomy, whether a fusion is performed or not, regardless of whether the operation was for soft discs or osteophytes. Second, most patients who underwent two-level discectomies had outcomes comparable to patients who underwent surgery at one level, regardless of whether they were fused or not. Data from four prospective randomized clinical studies in addition to multiple non-randomized or retrospective studies support these conclusions. Although the incidence of complications such as persistent postoperative posterior cervical and shoulder pain and kyphotic deformities is higher in unfused patients (and is quite significant in some series), the advantages conferred by interbody fusion such as biomechanical stability, decreased incidence of kyphotic deformity, and decreased pain are offset by graft and donor-site morbidity. Specific indications for fusion include multi-level discectomies, significant straightening of the cervical spine, failed prior fusions, and trauma. It has been demonstrated that comparable fusion rates can be achieved with allografts rather than harvested autologous bone. The advantages of autografts over allografts are relatively slight in most patients who undergo anterior fusion for one- or two-level disc disease, although patients with impaired healing, significant osteopenia, or concomitant microvascular disease, such as chronic smokers, may benefit from autologous bone. The use of allografts avoids donor-site morbidity in patients without these problems. Anterior cervical plates are useful for cases of instability requiring fusion (such as trauma); these implants may decrease reoperation rates and the incidence of delayed instability in select cases. However, the cost-effectiveness of their generalized use for uncomplicated cervical disc disease has not been demonstrated. In conclusion, a general statement regarding the optimal surgical treatment for cervical disc herniations using anterior approaches is difficult to make with this limited review. Surgeons' experience and familiarity with a particular approach are probably the most important factors in ensuring successful outcomes.     

c-Fos expression in the auditory pathways related to the significance of acoustic signals in rats performing a sensory-motor task

Neuronal activity was established in the auditory pathways in relation to behavioural response and cognitive information processing during a sensory-motor acoustic learning. Rats were trained in three consecutive phases. The first phase was an association between an auditory stimulus and a food reward; the second phase a simple discrimination between two sounds of different frequency components, and the third phase a more complex discrimination involving both spectral and spatial sound dimensions. Auditory stimuli were bursts of complex sounds lasting 500 ms. Neuronal activity related to the behaviourally relevant stimuli was established in 20 "learning" rats undergoing this protocol, which were progressively sacrificed at the beginning, middle and end of each phase. For comparison, activity was also established in four "control" rats exposed to the same stimuli delivered pseudo-randomly, thus carrying no behavioural meaning. Neuronal activity was assessed immunocytochemically using the functional marker Fos. To establish a baseline, two rats were unexposed to controlled acoustic stimulation ("unstimulated" rats). In the superior olivary complex (SOC), inferior colliculus (IC) and medial geniculate body (MGB), the number of Fos-like immunopositive cells was comparable in "learning" and "control" animals, but higher than in the "unstimulated" rats. In the auditory cortex (AC), most prominently in the secondary area Te2, the number of Fos-like positive cells differed between "learning" and "control" rats, suggesting that the auditory cortical areas may be involved in the encoding of the behavioural significance of the acoustic stimuli.     

High Bilirubin Levels Interfere with Serum Tartrate-Resistant Acid Phosphatase Determination: Relevance as a Marker of Bone Resorption in Jaundiced Patients

Serum tartrate-resistant acid phosphatase (TRAcP) activity is considered to be a biochemical marker of bone resorption. Recently, a lack of specificity of collagen-related markers for assessing bone turnover has been observed in patients with chronic liver disease. Thus, it could be of great interest to determine serum TRAcP activity in such patients. However, nonspecificity of the analytical reaction could occur when hemolyzed, lipemic, or icteric specimens are analyzed. Therefore, we have studied the interference caused by bilirubin in the measurement of serum TRAcP activity using the Hillmann method. The interference was assessed in two pools of serum containing different bilirubin concentrations but with similar total AcP levels. Mixing proportional parts of the two pools, 10 samples were also obtained. Serum activities of total AcP and TRAcP, and the concentration of bilirubin were measured in the 10 samples. Both the actual and the expected values obtained by theoretical calculations were compared. Serum bilirubin values of 2.4 mg/dl showed a negative interference of 15% in the determination of serum TRAcP activity, whereas values of bilirubin higher than 10 mg/dl interfered totally with the measurement of serum TRAcP. Bilirubin did not interfere with the total AcP determination. This study clearly shows the interference of bilirubin in the determination of serum TRAcP. This finding should be considered when bone metabolism disorders are evaluated in jaundiced patients. Received: 6 April 1998 / Accepted: 1 October 1998