Effect of rifabutin on ethambutol pharmacokinetics in healthy volunteers.

The effect of repeated administration of rifabutin on the pharmacokinetics and metabolism of ethambutol was evaluated in ten healthy volunteers. The subjects received a single oral administration of 1200 mg ethambutol on days 1 and 10 and a single daily oral dose of 300 mg rifabutin from days 3 to 9. No statistically significant difference was found in plasma pharmacokinetics (C(max), t(max), AUC, half-life and MRT) and in the renal clearance, whereas a significant decrease in the amount of unchanged ethambutol excreted in urine was observed. The decrease observed in ethambutol urinary excretion may be accounted for by taking into consideration the variability of the urinary excretion of ethambutol reported in the literature. However, a slight, likely not clinically relevant, induction or activation of kidney alcohol and/or aldehyde dehydrogenase isoenzymes by rifabutin cannot be ruled out at present. Evidence exists in the present study for autoinduction of rifabutin metabolism; this is shown by the lower plasma concentrations obtained 24 h after the seventh dose as compared to the theoretical concentrations.

Pedicle screw fixation for arthrodesis of the lumbosacral spine in the elderly. An outcome study.

STUDY DESIGN: An analysis of the outcome and effectiveness of instrumented arthrodesis of the lumbosacral spine in elderly patients conducted using a review of records, assessment of fusion via plain radiographs, and a two-part questionnaire. OBJECTIVE: To ascertain the outcome and efficacy of instrumented arthrodesis of the lumbosacral spine in patients 60 years of age and older. BACKGROUND DATA: From 1987 to 1991, 38 patients of at least 60 years of age underwent instrumented arthrodesis of the lumbosacral spine using the Wiltse or Selby pedicle screw fixation system (Advanced Spine Fixation Systems, Inc., Irvine, CA). Patients were considered for surgery only after attempts at conservative management, including physical therapy, medication, injection blocks, and home exercises, had proven unsuccessful. METHODS: Follow-up examinations were performed 3 months, 6 months, 1 year, and 2 years after surgery. Fusion was assessed using plain radiographs, including flexion-extension films. Inpatient and outpatient records were reviewed, and a two-part questionnaire was used to establish the effect of surgery on function and lifestyle. Thirty patients responded to the questionnaire. Follow-up observation of the patients ranged from 25 to 56 months. The mean age was 73.8 years (range, 60-90 years). RESULTS: The mean co-morbidity was 1.7. Based on the authors' method of evaluation of fusion, the fusion rate was 92%. Fifty-seven percent of the patients reported excellent or good results, 26% reported fair results, and 17% reported poor results. Functional gains of 50% or more were reported by 71% of the respondents. Female patients had significantly more complications than male patients, but reported comparable outcomes. CONCLUSION: Despite the increase in age, co-morbidity, and associated risk of perioperative complications inherent in this population, an outcome comparable with that of younger patients is reported.

A study of the pharmacokinetics and tolerability of ritipenem acoxil in healthy volunteers following multiple oral dosing.

The pharmacokinetics of ritipenem acoxil, the oral prodrug of the antibiotic ritipenem, were studied in volunteers after single and repeated dosing (500 mg, three times daily for 10 days). Concentrations of ritipenem and open beta-lactam ring metabolites were measured using HPLC/UV. Ritipenem did not accumulate significantly in plasma, owing to its half-life of about 0.7 h; the area under the curve for 0-8 h was on average about 10 mg x h/L. Plasma pharmacokinetics of ritipenem and metabolites were time-independent. A decrease of ritipenem renal clearance (87 versus 132 mL/min) and a slight increase in the amount of metabolites excreted in urine were observed following repeated dosing.

Evaluation of continuous intraspinal narcotic analgesia for chronic pain from benign causes.

Intraspinal narcotic analgesia (INA) has been used for chronic pain from nonmalignant causes with moderate success. To ascertain the efficacy of the morphine pump, we reviewed the 2-year results of continuous INA in 18 patients with failed back syndrome or arachnoiditis and intractable, debilitating pain that was unrelieved by conventional means. All patients underwent a trial screening of single-dose intrathecal narcotics with good pain relief. After 2 years, 8 pumps were still functioning, 8 patients had the pump removed or turned off, and 2 patients were lost to follow-up. Our patients averaged 1.4 additional procedures or hospitalizations after initial pump insertion. Overall, only 4 patients had objective evidence of benefit from INA, for a success rate of 25%. Results of this review suggest INA should not be used for the long-term management of chronic pain from nonmalignant causes.

Assessment of pseudarthrosis in pedicle screw fusion: a prospective study comparing plain radiographs, flexion/extension radiographs, CT scanning, and bone scintigraphy with operative findings.

Twenty-five consecutive patients who had previously undergone lumbar fusion using stainless steel pedicle screw instrumentation and complained of persistent, severe pain were identified for prospective study. All patients had been scheduled for hardware removal and fusion inspection. Studies to rule out pseudarthrosis included plain radiography, flexion and extension radiography, computed tomography, and bone scintigraphy. Each preoperative radiographic study was then evaluated in a blinded fashion by a single independent radiologist and was determined to show fusion or pseudarthrosis. Each patient then underwent surgery, at which time the pedicle screw instrumentation was removed and the fusion was inspected. Using surgical inspection as absolute evidence of fusion or pseudarthrosis, statistical analysis was undertaken to evaluate the predictive value of the radiographic studies singly and in combination. No statistically significant correlation was found.

The use of antibiotics for wound prophylaxis in spinal surgery.

The principle of spinal surgery prophylaxis is to prevent naturally occurring organisms from infecting a sterile site. Avoiding infection is the most important concern in decreasing morbidity in the immediate perioperative period. Prophylactic cephalosporin is mandatory. Suction drains should be used until output is minimal. This lessons the chance of hematoma formation. Hematomas are excellent culture media and may result in seromas. Aspiration of seromas that are painful can lead to another source of possible infection. The efficacy of topical irrigants in preventing infections during lumbar spine surgery remains to be answered.

Tissue polypeptide specific antigen (tps) and cytokeratin 19 fragment (CYFRA 21.1) immunoradiometric assay in non small cell lung cancer evaluation.

The aim of our work was the evaluation of the immunoradiometric assay (IRMA) of two cytokeratinic markers, TPS and CYFRA 21.1, in clinical setting on non small cell lung cancer (NSCLC). Serum samples were obtained from 148 untreated NSCLC patients, 60 patients with non malignant lung diseases and 100 healthy subjects: TPS and CYFRA 21.1 serum levels were assayed by IRMA methods. Diagnostic performance of the markers was evaluated and the TPS and CYFRA 21.1 distribution analysed according to some different clinical and biological variables as histological subtypes, stage and survival time by using the Mann-Whitney "U"-test. Sensitivity, specificity and accuracy were 0.54 (80/148), 0.47 (28/60), 0.52 (108/208) and 0.73 (108/148), 0.74 (44/60), and 0.73 (152/208) for TPS and CYFRA 21.1 respectively. CYFRA 21.1 demonstrate a higher sensitivity than TPS in all stages of the disease and in the spinocellular and adenocarcinoma histological subtypes while TPS sensibility is higher in large cell carcinoma. The CYFRA 21.1 specificity is better than TPS probably by reason of its preferential distribution in respiratory epithelium. Both markers serum levels differ significantly between Stage I-II and IV and between Stage I-II-IIIa and IIIb-IV but neither TPS nor CYFRA 21.1 can discriminate Stage IIIa from IIIb. No significant differences were found in the serum expression of the markers by the different histological subtypes. A value of both markers less than the selected cut-off is related to a longer survival of the patients apart from therapy (p < 0.05). Our conclusion supports similar behaviour of these markers in NSCLC and indicates CYFRA 21.1 as the more needed biochemical index to evaluate NSCLC patients.

Once-daily tobramycin therapy in lower respiratory tract infections.

In a multicenter Italian study of 104 adult patients with severe bacterial lower respiratory tract infections, the safety and efficacy of a regimen of high dose, once-daily tobramycin alone or in combination with antipseudomonas betalactams was assessed. The overall bacteriological response was an elimination of the original pathogen in 70% of the patients while the overall clinical response mirrored the bacteriological results with a successful clinical outcome in 78% of patients. Adverse experiences were, in general, few and mild without oto- or nephrotoxicity. The once-daily, high dose regimen of tobramycin proved to be a safe and efficacious therapy for severe lower respiratory tract infections in adult patients.

[Not Available]. / Valutazione dell'efficacia e tollerabilita di cefixima nel trattamento delle riacutizzazioni infettive delle BPCO.

An open, multicenter non-comparative study was carried out in 8 centres in Italy to evaluate the efficacy, safety and tolerability of cefixime (Suprax - Lederle), a third generation oral cephalosporin administered once daily to patients affected by exacerbation of chronic bronchitis. All patients, 124 males and 21 females, aged between 50 and 85, were treated with Suprax at the dose of 400 mg/day for a mean period of 7.4 days. Clinical and laboratory examinations were performed at: T0 (beginning of treatment), T1 (3-4 days after the beginning of treatment), T2 (end of treatment). The following signs/symptoms were recorded in order to evaluate the therapeutic efficacy: sputum quality and quantity, cough, dyspnoea, fever, bronchospasm, chest clinical findings. All these signs and symptoms significantly improved (p between < 0.001 and < 0.05; mean improvement for sign, weighted for time of improvement). Bio-humoral parameters were also recorded in order to evaluate potential therapeutic influences. A significant decrease was observed (p < 0.01 Student t test for paired data) in the white blood cell count and the leukocyte formula. The datum regarding the white blood cell count and leukocyte formula is to be considered a primary effect of the treatment, proving its success. A microbiological search for the pathogen responsible for the infectious process was also performed: in 70/145 subjects the responsible pathogen was identified. The micro-organism was eradicate in 66/70 at T2 (94.3%), the difference T0 = T2 is significant. The X-Ray evidence suggesting a chronic bronchitis, was also evaluated in 81 patients. At T2, in 75/81 subjects the X-Ray evidence turned out to be negative, while in 6/81 it remained positive. This difference was statistically significant (p < 0.01 sign test). An overall clinical evaluation showed a therapeutic success in 133/145 treated patients (91.7%). No side effects were observed.

The effect of surgical decompression on neurologic outcome after lumbar fractures.

From 1980 until 1989, 69 patients with lumbar fractures resulting in incomplete paraparesis were admitted to the authors' medical center for treatment. Thirty had anterior vertebrectomy, including 18 who had posterior instrumentation and four who had anterior instrumentation. Twenty-two patients were treated with a posterolateral decompression and fusion, including four who also required an anterior decompression. Nineteen of the remaining 21 patients required posterior spine instrumentation and fusion only. The American Spinal Injury Association (ASIA) motor index score was determined for each patient pre- and postoperatively and used to compare these three treatment groups. Average follow-up period for the patients was 19 months. The improvement in ASIA motor score for all patients treated with decompression averaged 10 and similar improvement was obtained in those who were treated with posterior decompression (10.2 points). The average improvement in those who had vertebrectomy was 9.9 points. For those who had fusion without decompression, average improvement was 4.2 points. Comparing those patients who were surgically decompressed, either anteriorly or posteriorly, with those patients who only underwent fusion, the difference in neurologic improvement was statistically significant. Neurologic outcome after lumbar fractures is improved by surgical decompression. The neurologic outcome results were similar after anterior and posterior decompression.

The effect of surgical intervention on rehabilitation time in patients with thoracolumbar and lumbar spinal cord injuries.

One hundred forty-seven patients with unstable low thoracic and lumbar fractures were examined. All patients had significant neurologic injuries. Ninety-one patients exhibited incomplete lesions whereas fifty-six had complete lesions. Age, sex, cause of injury, fracture location, fracture mechanism, and complications were recorded and analyzed. The average follow-up was 25 months (range 2-148). Incomplete neurologic lesions demonstrated a significant increase in ASIA motor points if both decompression and stabilization were performed at the same operative sitting. When decompression was performed before stabilization a decrease in improvement was noted. Patients with complete lesions demonstrated a significant reduction in rehabilitation time if stabilization was augmented with sublaminar wires rather than Drummond wires or Harrington rods alone.

Thigh compartment syndrome secondary to intertrochanteric hip fracture in a quadriplegic patient: case report.

Compartment syndromes in the thigh are rare and the diagnosis may be difficult in the light of subtle early physical findings in the patient with spinal cord injury. Clinical awareness of the impending compartment syndrome is important to provide timely proper treatment and avoid disabling deformities. A compartment syndrome should not be ignored in the paraplegic, because the potential for late fibrosis and contractures may limit the independence of such patients. Greater awareness and index of suspicion are needed to successfully recognize and promptly treat the compartment syndrome in this patient population.

Pharmacokinetics of rufloxacin once daily in patients with lower respiratory tract infections.

The pharmacokinetic properties of rufloxacin, a new quinolone antibacterial agent, were evaluated in ten patients with lower respiratory tract infections. Patients were given 400 mg of rufloxacin once a day for seven to nine days. Plasma concentrations of the drug were determined by high-performance liquid chromatography and bioassay at regular intervals during treatment. After the first administration, maximal plasma concentrations were 3.17 +/- 0.36 mg/l (mean +/- SEM) and were reached at 4.2 +/- 0.7 h. At the end of treatment peak plasma concentrations increased to 7.26 +/- 0.52 mg/l. Elimination half-life was 38.2 +/- 2.9 h, with a mean extent of accumulation of 2.96 +/- 0.30. Treatment was well tolerated, with no abnormalities noted during routine laboratory examinations. Two days after the last administration, measurable levels of rufloxacin were still observed in plasma, indicating that the long half-life of rufloxacin assures valuable antibacterial activity even after discontinuation of treatment.

Steady-state pharmacokinetics of rufloxacin in elderly patients with lower respiratory tract infections.

The pharmacokinetics of rufloxacin, after repeated doses, was evaluated in 12 elderly patients with lower respiratory tract infections. Patients were given a single loading dose of 400 mg on the first day of treatment and single daily maintenance doses of 200 mg for the next 6-9 days. Serum concentrations of the drug were determined by high-performance liquid chromatography (HPLC) at regular intervals during treatment and fitted to a one-compartment open model for repeated doses. The maximum serum concentration after the first dose was 6.46 +/- 1.06 (mean +/- SEM) micrograms/ml and was reached in 4.3 +/- 0.8 h after the first administration. The elimination half-life was 28.7 +/- 4.1 h. The area under the serum levels-time curve from 0 to 24 h was 103 +/- 14 micrograms/h/ml after the first dose. On the last day of observation it increased to 155 +/- 28 micrograms/h/ml, with a mean extent of accumulation of 2.3 +/- 0.3 times. The elimination half-life was comparable to those in other studies in healthy young subjects, while plasma levels were about 80% higher. These results suggest that in elderly patients elevated drug concentrations may be reached in the serum. Although no untoward reactions related either to the drug concentration in serum or the dose have been noted with rufloxacin, this patient population should nevertheless be monitored carefully for adverse effects.

A study of the effects of rifabutin on isoniazid pharmacokinetics and metabolism in healthy volunteers.

The effect of repeated administration of rifabutin on the pharmacokinetics and metabolism of isoniazid was evaluated in 6 healthy volunteers. The subjects received on day 1 and 9 a single oral dose of 300 mg isoniazid and from day 2 to 8 a single daily oral dose of 300 mg rifabutin. Two out of 6 subjects were shown to be rapid acetylators. No significant modification of the plasma pharmacokinetic profiles of isoniazid and acetylisoniazid was found. Evidence exists in the present study for autoinduction of rifabutin metabolism; this is shown by the lower plasma concentrations obtained 24 h after the seventh dose as compared to the theoretical concentrations.

Acute rupture of the tibialis anterior tendon: a case report.

Acute rupture of tendons on the dorsum of the foot is rare and the diagnosis can be difficult. We present the case of a 51-year-old man who sustained an acute rupture of the tibialis anterior tendon. Pain about the medial aspect of the midfoot and ambulation with a steppage gait were the keys to formulating a correct diagnosis. The tendon was repaired primarily 10 days after injury. At his final follow-up examination 6 months after surgery, the patient was asymptomatic and ambulated with a normal gait.

Pseudomonal osteomyelitis of the medial sesamoid bone.

Because osteomyelitis may complicate puncture wounds about the first metatarsophalangeal joint, we believe sesamoid roentgenograms are mandatory. These views may show subtle demineralization, which cannot be seen on standard films. Treatment must include excision of the sesamoid and culture-directed antibiotics.

Bacterial isolates and cigarette smoking in patients with chronic bronchitis: results from an Italian multicenter survey.

Patients who were cigarette smokers suffering exacerbations of chronic bronchitis were examined in eight outpatient clinics in five regions of Italy, three from the South (Campania, 82 patients; Sicily, 82 patients; and Puglia, 29 patients) and two from North (Lombardy, 33 patients; and Liguria, 50 patients). Haemophilus influenzae was the most frequently isolated bacterium in the patients' sputum (in 30% of the total group), followed by Streptococcus pneumoniae (in 20%), Staphylococcus aureus (in 25%), and Branhamella catarrhalis (in 7%). H. influenzae was the most common bacterium in the South (in 37%) and S aureus in the North (in 13%). Smoking index scores (number of cigarettes smoked daily x years of smoking) were 827 in patients in whom H influenzae was isolated; 691 in patients with S aureus; 599 in patients with S pneumoniae; 542 in patients with B catarrhalis; and 446 in patients in whom no isolates were found. Pulmonary function was most severely decreased in patients positive for H influenzae and S aureus. The results indicate an association between heavy cigarette smoking and lower respiratory tract infections that is influenced by regional differences.

Pseudoaneurysm of the radial artery as a cause of a late compartment syndrome. A case report.

Pseudoaneurysm has been reported in the literature as a cause of compartment syndrome. The onset of the subsequent compartment syndrome is usually early. Often, while the compartment syndrome is diagnosed and treated, the pseudoaneurysm is missed. A second operative procedure is then necessary. A 40-year-old woman illustrates an unusual case of a late compartment syndrome, following the development of a radial artery pseudoaneurysm three weeks after a penetrating injury. It is important to investigate the vascular tree in compartment syndromes after a penetrating injury, no matter how late the patient is seen.

Modified technique of intramedullary fixation for wrist arthrodesis.

Twenty-five normal subjects were studied to assess the possible relation of various wrist postures on grip strengths. Most subjects were found to have the strongest grip strengths in a position of neutral deviation and one half of their maximum extension. A small subpopulation normally postured their clenched fists in slight ulnar deviation rather than in neutral deviation. These patients were strongest in ulnar deviation and one half of their maximum extension. A modification of the wrist arthrodesis technique was developed using intramedullary pin fixation in a series of 10 patients. Fusion was successful in all 10 wrists. This technique retains the advantages of speed and simplicity of previous intramedullary fixation methods and also affords the additional advantage of permitting the wrist to be placed in varying degrees of extension and ulnar deviation.