Factors influencing metacarpal bone mineral density in adults with cerebral palsy

Several studies have examined bone mineral density (BMD) and related factors in children with cerebral palsy, but there are no such studies of adults with cerebral palsy. We evaluated BMD in 123 institutionalized adults (51 men aged 21–41 years and 72 premenopausal women aged 24–46 years) with cerebral palsy, and examined the associations of BMD with mobility level, use of anticonvulsant drugs, and abnormal calcium metabolism status. Hand radiographs were used to measure BMD of the second metacarpal bone (mBMD). Body weight (kg), height (m), and body mass index (BMI) were recorded. Serum calcium, phosphate, and alkaline phosphatase were measured. Abnormal calcium metabolism, defined as calcium 8.5mg/dl, phosphate 2.6mg/dl, or alkaline phosphatase 260U/l, was identified in 28% of the men and 31% of the women. Multiple regression analysis showed that the use of anticonvulsant drugs was significantly associated with lower mBMD in both sexes. Higher alkaline phosphatase level was significantly associated with lower mBMD in men. Mobility level (ambulation) was significantly associated with higher mBMD in women. Neither age nor BMI correlated with mBMD. Our findings indicated poor bone health status in adults with cerebral palsy and the existence of several factors that could affect bone metabolism in these patients.     

Bone mineral density in women with sarcoidosis

Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Almost any organs of the body, but mostly the lungs, are involved. Bone mineral density (BMD) can be affected directly or indirectly in chronic granulomatous systemic diseases such as sarcoidosis. The aim of our study was to evaluate BMD in premenopausal and postmenopausal sarcoidosis patients with or without prednisone treatment and to compare their BMD values with those of a control group having the same menopausal status. Thirty-five premenopausal women (18 untreated, 8 treated, and 9 controls) and 21 postmenopausal women (5 untreated, 5 treated, and 11 controls) were included in the study. All of the patients had a histologically proven diagnosis and were being followed-up at the Sarcoidosis Outpatient Clinic of our unit. BMD of the lumbar (L) spine and femoral neck was measured by dual-energy absorptiometry (DEXA). The subgroups of premenopausals and postmenopausals were compared separately. Comparison among the groups was performed by using analysis of variance. Age, duration of the disease, and body mass index were comparable in treated, untreated, and control subgroups of the pre- and postmenopausal groups, and the subgroups of postmenopausals had comparable durations since menopause. For premenopausals, BMD values at L1–4 were not significantly different among the subgroups (0.920 ± 0.08g/cm², 0.801 ± 0.09g/cm², and 0.910 ± 0.05g/cm², for untreated, treated, and controls, respectively). However, the BMD value at the femoral neck in treated patients (0.921 ± 0.1g/cm²) was significantly lower than the values in untreated patients (1.080 ± 0.2g/cm²; P 0.01) and in controls (1.028 ± 0.17g/cm²; P 0.05). For postmenopausals, the BMD value at L1–4 in controls (1.019 ± 0.07g/cm²) was significantly higher than the values in untreated patients (0.783 ± 0.01g/cm²) and in treated patients (0.751 ± 0.08g/cm²; P 0.001 for both). The BMD value at the femoral neck in controls (0.890 ± 0.1g/cm²) was higher than the values in untreated patients (0.745 ± 0.08g/cm²) and treated patients (0.747 ± 0.1g/cm²), but the difference was not statistically significant (P = 0.06). We concluded that sarcoidosis patients, especially postmenopausal patients with corticosteroid treatment, may have an increased risk of bone mineral loss. Large-scale studies are warranted in order to delineate the exact roles of the disease itself, menopausal status, and corticosteroid treatment in this bone mineral loss.     

The effects of calcitonin on bone resorption in hyperthyroidism: a placebo-controlled clinical study

The effects of intranasal calcitonin on bone metabolism were investigated in patients with hyperthyroidism. Urinary deoxypyridinoline (uDPD) levels were measured as a bone turnover marker and lumbar spine (L2) bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DEXA) in 7 patients who were given only antithyroid drug (group 1), in 10 patients who were given antithyroid drug plus intranasal calcitonin (group 2), and in 10 healthy subjects who were given placebo (group 3) at the beginning and at the end of the study. The study continued until the patients with hyperthyroidism became euthyroidic according to the laboratory values. This period was approximately 3 months in groups 1 and 2. At the beginning of the study, uDPD was 21.5 ± 2.6nM DPD/mM creatinine in group 1, 23.3 ± 3.6nM DPD/mM creatinine in group 2, and 4.3 ± 1.2nM DPD/mM creatinine in group 3. uDPD levels measured in groups 1 and 2 were significantly higher than those in group 3 (P 0.001). Area BMD Z scores of the patients in groups 1 and 2 were significantly lower than the healthy controls (P 0.01, for both). At the end of the study, uDPD was 11.5 ± 1.6nM DPD/mM creatinine in group 1, 5.3 ± 0.6nM DPD/mM creatinine in group 2, and 4.4 ± 1.3nM DPD/mM creatinine in group 3. The levels of uDPD obtained in group 1 were significantly higher than those obtained in groups 2 and 3 (P 0.05, for both). The difference between groups 2 and 3 was not significant. Area BMD Z scores measured at the end of the study were found to be increased in groups 1 and 2 compared to early values, but the values were slightly lower than the normal values. In comparison of early and late uDPD values, the decrease in late period was statistically significant in groups 1 (P 0.05) and 2 (P 0.001). We concluded that bone turnover is high in hyperthyroidism. The treatment of hyperthyroidism decreases the rate of bone turnover, but it is not sufficient to prevent the degradation of bone in hyperthyroidism. The addition of intranasal calcitonin to the treatment of hyperthyroidism prevents the degradation of bone.     

Reduction in late postoperative pain after iliac crest bonegraft harvesting for cervical fusion: a controlled double-blinded study of 100 patients

Summary Background. A randomized prospective double-blinded study was conducted in 100 patients suffering from mono- or bisegmental cervical retrospondylosis or disc herniation.Method. In group I, 50 patients were treated by injection of 10ml Ropivacaine 7,5% at the iliac crest bonegraft donorsite. Local anaesthetic (LA) was injected through the wound drainage after closure of the muscle fascia, the suction drainage was opened after closure of the skin. Group II was treated with 0,9% saline. Operator and patient were blinded to the injected substance. Daily controls of pain intensity were made with the 10cm visual analog scale from 0 (no pain) to 10 (severe pain) for 5 days. All patients were questioned regarding pain character and movement provoking pain. Additional pain medication was standarized.Findings. Statistical analysis of mean pain intensity over the whole hospital stay showed a significant difference in pain intensity between the two groups (p=0,017, Chi-Square test). The comparison between pain intensity with LA and without LA showed a gradual increase in statistical significance from day 1 to day 5 (day 1: p=0,54, not significant; day 2: p=0,026; day 3: p=0,008; day 4: p=0,004; day 5: p=0,002).Interpretation. This data shows that intra-operative blockage of peripheral nociceptive structures results in decreased pain at later time points. We conclude that wound infiltration with 7,5% Ropivacaine after bonegraft removal at the iliac crest is effective in reducing postoperative pain.     

Treatment outcomes and mortality of 94 patients with acromegaly

Summary Background. Due to new therapeutic modalities and modified therapeutic goals outcome of patients with acromegaly may change over time and differ by centre. We analysed treatment outcomes and mortality of our patients with acromegaly seen between 1971 and 2003.Method. The cohort consisted of 94 patients who had been followed for 0.3–31 years (mean 10.6 years). Remission criteria were a normalized IGF-I concentration, a nadir GH level during oral glucose load of <1.0µg/l and a random GH value of <2.5µg/l.Findings. Transsphenoidal surgery achieved remission in 80% of patients with micro-adenomas (<1cm), 65% with meso-adenomas (1cm to <2cm) and 27% with macro-adenomas (2cm). Patients with meso-adenomas operated on after 1995 tended to have a better outcome compared to those operated on before 1995 (Remission in 83% vs. 38%). Radiotherapy resulted in disease control in 22 of 47 patients (47%). Intramuscular depot formulation of octreotide (Sandostatin^® LAR^®) led to disease control in 17 of 26 patients (65%). After multimodal therapy persistent acromegalic activity remained in 18% of the patients; only one of them had an adenoma of <2cm. The standardized mortality ratio was 1.30 (95% CI 0.52–2.67) for patients in remission and 1.38 (95% CI 0.51–3.00) for patients with persistent acromegalic activity.Conclusions. Most patients with adenomas of <2cm can be expected to achieve remission by transsphenoidal surgery alone. Furthermore, virtually all patients with adenomas of <2cm and more than 80% of patients with adenomas of 2cm can be expected to achieve remission by adjuvant treatment. Aggressive multimodal therapy is critical in the management of acromegaly reducing mortality risk close to that of the general population.     

Hospital Readmissions Following Abdominal Aortic Aneurysm Repair

In-hospital outcomes associated with abdominal aortic aneurysm (AAA) repair are well described. However, little is known about post-discharge readmission rates, lengths of stay, associated mortality, and costs. We examined 206 consecutive patients who underwent AAA repair at two American hospitals between 1998 and 2000. Index hospitalization and 6-month readmission data were extracted from a resource and cost accounting system used by both hospitals. Among the 206 patients, 183 survived until discharge (mortality rate 11.2%). Among the surviving patients, 38 (21.0%) were readmitted within 6 months. Half of the readmissions occurred within two weeks of discharge, with patients presenting with a diverse array of complications. Nonelective repair and diabetes mellitus were independent predictors of hospital readmission (OR=2.83, 95% CI=1.25-6.40, p=0.01; OR=6.60, 95% CI=1.02-42.4, p=0.047, respectively). For each readmission, the mean length of stay was 10.7±2.5 days and the mean cost was $13,397±3,381. The cumulative number of hospital days during the 6 months post-discharge was 17.7±3.5 days for each readmitted patient and the mean per-patient total cost was $23,262±5,478. The mortality rate among readmitted patients was 13.2%. Overall, readmissions following AAA repair accounted for a cost >50% over and above the cost of the readmitted patients index hospitalization. Hospital readmissions are common during the 6 months following AAA repair. Patients who are readmitted experience long lengths of stay and high mortality rates, and their care incurs high costs.Dr. Eisenberg is a Physician-Scientist of the Quebec Foundation for Health Research. Dr. Pilote is a Physician-Scientist of the Canadian Institutes for Health Research.     

Enhancement of recombinant human bone morphogenetic protein-2 (rhBMP-2)-induced new bone formation by concurrent treatment with parathyroid hormone and a phosphodiesterase inhibitor,pentoxifylline

We investigated the enhancement of new bone |formation elicited ectopically by recombinant human bone morphogenetic protein-2 (rhBMP-2), using parathyroid hormone (PTH) and a phosphodiesterase inhibitor (PDEi), pentoxifylline (PTX), in an animal model. Collagen sponge sheet discs containing rhBMP were implanted onto the back muscles of mice. PTX alone (200mg/kg body weight [BW]), PTH(1–34) (10µg/kg BW), PTX plus PTH (200mg/kg BW and 10µg/kg BW, respectively), or vehicle (control) were injected subcutaneously daily for 3 weeks after implantation. At the end of this period, rhBMP-2-induced ectopic ossicles were harvested from each group of animals. Ossicles from the PTX-treated group were significantly larger in size, with unchanged bone mineral density (BMD), as compared with the ossicles from the controls. In contrast, the ossicles from the PTH-treated group had significantly higher BMD, but showed no difference in size when compared with those from the control animals. The ossicles of the PTX + PTH treatment group were significantly larger than those of the control and PTH treatment groups. In addition, the BMD of the harvested tissues from the PTX + PTH treatment group was signifi-cantly higher than that of tissues from the control and PTX treatment groups. Although the calcium content of ossicles was significantly higher in the PTX-, PTH-, and PTX + PTH-treated groups than in the control group, the Ca content of ossicles from the PTH + PTX-treated group was highest (two times that of controls), followed by the PTH- and PTX-treated groups.     

Comparison of anesthetic effects of epidural and intravenous administration of buprenorphine during operation

Thirty six patients were received epidural anesthesia with or without buprenorphine (BPN) during upper abdominal surgery. They were divided into three groups of 12 patients as follows; G-I received 20ml of 1% lidocaine epidurally, G-II received 20ml of 1% lidocaine epidurally and 0.6mg BPN intravenously, G-III received 20ml of 1% lidocaine with 0.6mg BPN epidurally. Additional 5ml of 1% lidocaine was given to any patient if systolic blood pressure or heart rate increased 10% compared to control value. Trachea was intubated following anesthetic induction with thiopental. The lungs were ventilated with a mixture of N₂O/O₂ (33%) and pancuronium was used for muscle relaxation. The total required doses of lidocaine in G-II and G-III were decreased 60% compared to control group (G-I) (P 0.05). The mean period of time until the first administration of pentazocine for postoperative pain was 13 ± 10hr (mean ± SD) in G-II and 19 ± 24hr in G-III compared to 5 ± 4hr in G-I (P 0.001). The dose of the administration of pentazocine that was required for pain relief during the first 48 postoperative hr in G-III was 54 ± 10mg (mean ± SD) compared to 150 ± 21mg in G-I (P 0.02) and 106 ± 28mg in G-II (P 0.05). Recovery from anesthesia in G-III was more rapid than that in G-I (P 0.05). The Pa_{CO 2} values in G-II and G-III increased 15% compared to control group at about 4hr and 8hr after administration of BPN, but any clinical treatment was not needed for them. Nonrespiratory side effects, e.g., nausea, vomiting, fatigue and headache, were comparably common in all groups. Mild hematuria associated with acute hypotension occurred in two patients in G-II (17%) immediately after the intravenous injection of 0.6mg of BPN. The results showed that 0.6mg of BPN given epidurally demonstrated better anesthetic and more potent postoperative analgesic effects and lesser side effects than 0.6mg of BPN given intravenously in patients undergoing upper abdominal surgery.(Yonemura E, Fukushima K.: Comparison of anesthetic effects of epidural and intravenous administration of buprenorphine during operation. J Anesth 4: 242–248, 1990)     

Wear of ultra-high-molecular-weight polyethylene cup articulating with 22.225 mm zirconia diameter head in cemented total hip arthroplasty

A number of studies have highlighted the increasing incidence of aseptic cup loosening with increasing depth of cup penetration by the metal head. We present our experience with a 22.225mm diameter zirconia head on a 9–10 taper articulating with an ultra-high-molecular-weight polyethylene (UHMWPE) cup in cemented total hip arthroplasties. We prospectively studied the wear of the UHMWPE cup articulating with a 22.225mm diameter zirconia head in cemented total hip arthroplasties. A total of 339 patients (153 men, 186 women, 373 hips) were included. The patients mean age at surgery was 52 years (17–76 years), with 41% age 50 years or younger. Their mean weight was 72.4kg (24–125kg). At a mean follow-up of 4.3 years (0–8 years) the mean penetration rate of the cup was 0.03mm/year (0–0.51mm/year). Altogether, 289 (77.5%) showed no measurable wear, 38 (10.2%) had a penetration rate of 0.11mm/year or less, 33 (8.9%) had a rate of 0.12–0.2mm/year, and in 13 (3.5%) the rate was more than 0.2mm/year. Ceramic–UHMWPE is the next stage in the evolution of total hip arthroplasty for addressing wear and any possible related issues.     

EnHurane supresses phrenic nerve-diaphragm Transmissionin vivo

We examined the effects of enflurane on the diaphragmatic function in 15 pentobarbital-anesthetized, mechanically ventilated dogs. They were divided into three groups of five animals each, according to the administered concentration of enflurane. The diaphragmatic function was assessed from transdiaphragmatic pressure (Pdi) and integrated diaphragmatic electromyography (Edi) developed at functional residual capacity against an occluded airway during bilateral supramaximal phrenic nerve stimulation at 0.5, 10, 20, 50 and 100Hz under quasiisometric condition. After a control measurement, enflurane was administered at a constant end-expired concentration (0, 0.5 and 1MAC) and the measurement was repeated after 1 hour of exposure. The Pdi amplitude generated by single twitch (0.5Hz) and during 10, 20 and 50Hz stimulation was unchanged between the groups. No change in Pdi during 100Hz stimulation was noted during 0 and 0.5MAC exposure, while it was reduced by 1MAC of enflurane. When the values of Pdi were expressed as % of maximum Pdi (%Pdi,max) that developed during control measurement and analyzed in terms of %Pdi,max—stimulus frequency relationship, a significant decrease in %Pdi,max was noted for 100Hz stimulation in 0.5 and 1MAC groups compared to the control. Similarly, Edi during 100Hz stimulation obtained in 0.5 and 1MAC groups was markedly depressed compared to the control. Edi during 50Hz stimulation was also decreased at 1MAC. Relative changes in Edi following enflurane administration were greater than the corresponding changes of Pdi. These results demonstrate that enflurane impairs diaphragmatic function through its inhibitory effects on neuromuscular transmission.(Kochi T, Ide T, Isono S, et al.: Enflurane supresses phrenic nerve-diaphragm transmission in vivo. J Anesth 5: 260–267, 1991)     

Analgesic dose-response relation in cervical epidural block

The relationship between the age and the spread of analgesia from different epidural anesthetic doses was examined by studying analgesic dose responses in cervical epidural analgesia. Two different anesthetic doses (5ml or 10ml) of 2% mepivacaine were injected into the cervical epidural space at a constant pressure (80mmHg) using an intravenous apparatus, and the spread of analgesia to pinprick was assessed. The significant correlation was found between the patients age and the number of spinal segments blocked (5ml:r = 0.8498, P < 0.01, 10ml:r = 0.5988, P < 0.01). The inverse linear relationship was found between the patients age and the segmental dose requirement (5ml:r = –0.6754, P < 0.01, 10ml:r = –0.5784, P < 0.01). Patients under 39 years of age showed a direct relationship between the dose injected and the number of spinal segments blocked, enabling prediction of the number of segments blocked with a given dose of local anesthetic. Doubling the epidural dose approximately doubled the number of spinal segments blocked. The analgesic dose-response relation in patients over 60 years of age differed from that in patients under 39 years of age and doubling the epidural dose did not double the number of spinal segments blocked. Progressively more extensive analgesia was obtained from a given dose of local anesthetic with advancing age. It was difficult to limit the extent of analgesia by injecting a smaller dose of local anaesthetic in the elderly.(Hirabayashi Y, Matsuda I, Inoue S et al.: Analgesic dose-response relation in cervical epidural block. J Anesth 2: 22–27, 1988)     

AneuRx Device Migration: Incidence, Risk Factors, and Consequences

Success after endovascular abdominal aortic aneurysm repair (EVAR) is dependent on device positional stability. The quest for such stability has motivated different endograft designs, and the risk factors entailed remain the subject of debate. This study aims at defining the incidence, risk factors, and clinical implications of device migration after EVAR with the AneuRx® endograft. In this study we included all consecutive 109 patients submitted to primary AneuRx placement for infrarenal aortic or aortoiliac aneurysms. Preoperative computed tomography (CT) scans were reviewed for the following anatomic characteristics: neck length, diameter, angulation, calcification, and thrombus load; and sac diameter and thrombus load. Percentage of device oversizing relative to the proximal neck diameter was determined. All postoperative CT scans were reviewed, and the distance between the lowest renal artery and the craniad end of the device was measured. A 5-mm increase in such distance was considered indicative of device migration. Migration cumulative incidence was estimated by the Kaplan-Meier method, and its association with any of the preoperative anatomical characteristics was tested using Cox proportional hazards models. Median follow-up time was 9 (range, 1-31) months. Migration occurred in nine patients, corresponding to a 15.6% estimated probability of migration at 30 months (SE=5.1%). Migration was associated with the risk of proximal type I endoleak (hazard ratio=3.39, 95% confidence interval=1.46-7.87; p=0.007). This type of endoleak occurred in three of the migration-affected patients (33.3%); all of them were resolved by additional cuff placement at the proximal landing zone. No other migration-related reinterventions were performed. The only significant associations between anatomic factors and device migration probability were the protective effects of longer necks (odds ratio [OR]=0.71 for each additional 5 mm, p=0.045) and longer overlapped portions of neck and device (OR=0.56 for each additional 5 mm, p=0.003). There was a trend toward higher probability of migration among reverse-tapered necks (OR=1.75, p=0.109). Percentage of device oversizing correlated with early neck dilation (between preoperative and first postoperative diameters, correlation coefficient=0.4, p < 0.0001), but not with late neck dilatation (between first postoperative and 1.5-year scan diameters, correlation coefficient=0.29, p=0.112). There was a trend toward higher mean percentage of late dilation among migrators (11.4%, standard error of the mean [SEM] 2.6) than nonmigrators (5.7%, SEM=1) (p=0.08), but both groups had similar mean percentages of early dilation (3%, SEM=1.6%, vs. 5.5%, SEM=0.6%; p=0.365). This result indicates that device migration is not a rare event after AneuRx implantation. This phenomenon is associated with proximal type I endoleaks. Deployment of the endograft immediately below the renal arteries might help to prevent migration, since use of greater lengths of overlapped device relative to the proximal neck has a protective effect. Migration seems to be independent of the degree of device oversizing.Presented at the 29th Annual Meeting of the Peripheral Vascular Surgery Society, Anaheim, CA, June 4-5, Sergio M. Sampaio is a recipient of the Edward S. Rogers Clinical Research Fellowship in Vascular Surgery.     

Suppression of parathyroid hormone secretion in CAPD patients by intraperitoneal administration of Maxacalcitol

Background Maxacalcitol (22-oxacalcitriol; OCT) is a novel vitamin D analogue. In previous clinical studies, OCT was administered three times a week to hemodialysis patients with refractory secondary hyperparathyroidism (2HPT), in whom it acted by inhibiting parathyroid hormone secretion, as well as causing mildly elevated serum calcium. However, intravenous injection of OCT, which requires frequent visits to the outpatient clinic, degrades the quality of life of patients with continuous ambulatory peritoneal dialysis (CAPD) who otherwise visit the clinic only once or twice per month. In the present study, we investigated whether transperitoneal absorption of OCT inhibited intact parathyroid hormone (i-PTH) in CAPD patients when the OCT was added to the peritoneal dialysis fluid.Methods Peritoneal dialysis fluid containing 20µg of OCT was injected into the peritoneal cavity of five CAPD patients. The serum and peritoneal fluid levels of OCT, i-PTH, calcium, and phosphate were measured before and after treatment.Results The mean concentration of OCT in peritoneal dialysis fluid rapidly decreased, from 25268.0pg/ml at 0h to 1694.0pg/ml at 2h and 44.9pg/ml at 4h. In contrast, the mean serum OCT level increased from the pretreatment level, which was below the detection limit of the assay, to 656.0pg/ml at 0.5h and a peak of 759.0pg/ml at 1h, and thereafter gradually decreased, to 713.8pg/ml at 2h and 555.8pg/ml at 4h. Mean i-PTH significantly decreased, to 83.9% of the baseline level, at 1h (P < 0.05) and thereafter stayed at around 90%. No consistent trends in calcium and phosphate levels were observed in the five patients.Conclusions By injecting OCT into the peritoneal cavity, i-PTH levels could be significantly decreased. These findings indicate the therapeutic efficacy of intraperitoneal administration of OCT for CAPD patients.     

Long-term results of rotational total hip arthroplasty: radiological analysis

We developed a rotational total hip prosthesis that has a 30mm diameter metal-covered head with a polyethylene liner with which it can rotate around the neck of the stem. Long-term results of the rotational total hip arthroplasty with cement were evaluated in 55 hips of 52 patients. The diagnosis was degenerative osteoarthritis in all patients. The mean follow-up was 11.2 years (range 5–19 years). Eight of thirty 7mm thick acetabular components were revised 7.6–14.3 years (mean 10.4 years) afterward. Two of twenty five 9.5mm thick acetabular components and two femoral components were revised at 12 and 15 years, respectively. The mean polyethylene wear in the 9.5mm thick acetabular components was significantly less than that in the 7mm thick components. The mean polyethylene wear inside the rotational head removed during the revision surgeries was 0.01mm in diameter and 0.03mm in depth per year, respectively. Fifty percent of the patients with 7mm thick acetabular components, 9.5mm thick components, and femoral components had surviving prostheses at 13.4, 15.2, and 16.3 years, respectively. It is possible that the rotational system reduces the stress against acetabular and femoral components, but the 30mm diameter head caused high friction torque and required at least 9.5mm thickness in the acetabular component.     

Osteosarcoma of the Hand and Forearm: Experience of the Cooperative Osteosarcoma Study Group

Background Osteosarcoma is extremely rare in the hand and forearm. Therefore, only limited data are available for planning treatment or predicting the outcome and prognosis of osteosarcoma in the peripheral upper extremity.Methods Epidemiological, clinical, and histopathologic data were analyzed in 39 patients with osteosarcoma of the forearm or hand who were enrolled in studies of the Cooperative German-Austrian-Swiss Osteosarcoma Study Group from 1977 to December 2000. In patients with high-grade osteosarcoma, the treatment entailed surgical resection in combination with chemotherapy, whereas patients with low-grade osteosarcoma underwent only surgery.Results The 5-year overall survival rate among the 33 patients with high-grade central osteosarcoma of the distal upper extremity was 86.2%±6.4%. The 5-year event-free survival rate was 65.4%±9.6%. Five of the eight patients with secondary metastases were in remission at the time of analysis. Four patients died of their disease, and two patients died of chemotherapy-related complications. The mean overall survival rate was 88.0%±6.5% in patients treated by wide or radical tumor resection and was 75.0%±21.7% in patients with nonwide margins of resection. Whether amputation or local resection was performed had no significant influence on the prognosis. All six patients whose osteosarcoma was not classified as high-grade central osteosarcoma were in remission at the time of analysis.Conclusions The results demonstrate a remarkably high survival rate for patients with high-grade osteosarcoma of the hand and forearm and confirm that multiagent chemotherapy in combination with wide excision is a highly effective treatment for this malignant tumor.Published by Springer Science+Business Media, Inc. © 2005 The Society of Surgical Oncology, Inc.     

Bench test assessment of the new Raumedic Neurovent-P ICP sensor: a technical report by the BrainIT group

Summary. Background. In clinical practice, fiberberoptic and piezo-electric ICP probes are often used for measuring intracranial pressure (ICP). A number of similar technologies, although performing well in bench test studies, have been shown to exhibit unacceptable zero drift, fragility or both during trials conducted under clinical conditions. Recently, a new technology has become available, the Neurovent-P (Raumedic AG+CO, Raumedic, Germany). As a pre-requisite for a clinical trial, we have conducted and report on bench test studies to confirm the manufacturers long term zero-drift performance for this technology.Method. In a test rig static tests (recording of 20mmHg pressure) and dynamic tests, ranging from 5 to 50mmHg have been performed.Findings. 10 ICP probes have been tested for a total of 60 days. All the catheters, after the connection with the ICU monitor displayed a static pressure of 0±1mmHg and did not required pre-insertion alteration. At five days, mean zero drift was 0.6±0.9mmHg. Overall, zero drift ranged from 0 to 2mmHg. At a fixed static pressure of 20mmHg, the mean recorded value was 20.6±0.8mmHg, ranging from 19 to 23mmHg. A regression analysis of the relationship between the applied pressure and the recorded pressure during the dynamic tests of the 10 catheters yielded a correlation coefficient R² of 0.997. Applying the Altman and Bland method to assess the bias and confidence limits for the Raumedic catheter responses during the dynamic tests against the applied gold-standard hydrostatic column pressures, the average bias of –0.66±0.85mmHg, with 95% CLs of –2mmHg and 1mmHg.Conclusions. Mean zero drift, after five days, was very small and long-term continuous recording of a stable pressure was very precise. The response at dynamic tests, i.e. the changes of pressure in a wide range, was excellent. The average bias of the Raumedic catheter compared with the hydrostatic column is very small. After this bench test, the next and most critical step will be to conduct a trial of this promising technology under more demanding clinical environment.     

Secondary growth of a cortical necrosis: effect of NOS inhibition by aminoguanidine post insult

Summary ¶Background. A cortical tissue necrosis from a focal freezing injury expands to 140% of its initial volume within 24hrs in rats. Previous studies of our laboratory have shown that administration of the NOS inhibitor aminoguanidine (AG) prior to trauma attenuates this process of secondary brain damage. Objective of the present study was to analyse whether this agent is also protective when treatment commences after the insult. Method. A highly standardized freezing lesion was induced in the brain cortex of 30 anaesthetized rats. The animals were divided into three experimental groups. Animals of group I (sham-5min, n=10) were sacrificed 5min after trauma for quantitative histomorphometric assessment of the primary cortical lesion. Animals of group II (sham-24h, n=10) received isotonic saline (16.7ml/kg b.w., i.p.) at 15min and 8hrs after trauma. In the treatment group (group III, AG-24h, n=10), AG was administered (100mg/kg b.w.) also at 15min and 8hrs after trauma. 24hrs later – the time point of maximal lesion spread – the animals of group II and III were sacrificed for quantification of the secondary lesion growth. Findings. The focal freezing injury produced a cortical necrosis volume of 6.07±1.04mm³ immediately after trauma (group I). After sham treatment, the necrosis expanded to 8.39±1.57mm³ within 24hrs (group II) corresponding to a lesion growth of 138% compared to the primary necrosis (p<0.01 vs. group I). In animals treated with AG after the trauma (group III), the volume of necrosis was significantly attenuated at 24hrs to 6.77±0.87mm³ representing an expansion of the lesion to only 112% (p<0.05 vs. group II). Thus, AG was inhibiting the secondary growth of necrosis by no less than 69%. Interpretation. The findings demonstrate that AG retains its neuroprotective potential against secondary brain damage from trauma even when administration begins after trauma.Published online October 20, 2003     

Combined effects of Inversed Ratio Ventilation (IRV) with positive end-expiratory pressure ventilation (PEEP) on cardiorespiratory function in acute respiratory failure

Combined effects of inversed ratio ventilation (IRV) with positive end-expiratory pressure (PEEP) on cardiorespiratory function were examined in 24 patients with acute respiratory failure. Patients were divided into two groups: the IRV group (n = 12) who showed no significant increase in Pa_{O 2} with a 6cmH₂O of PEEP and PEEP group (n = 12) who were ventilated mechanically with PEEP only at maximum level of 10cmH₂O. In IRV group step-wise prolongation of the I:E ratio from 1:1.9 to 2.6:1 or 4:1 was applied as a Pa_{O 2} was improved and in PEEP group also level of PEEP was increased from 0, 5 to 10cmH₂O after one hour period irrespective of Pa_{O 2}. Inversed ratio ventilation and PEEP increased significantly Pa_{O 2}/Fi _{O 2}, the increase being observed 6hrs (I:E = 2:1) and 2hrs (10cmH₂O) after starting IRV or PEEP. Further improvement of oxygenation was not observed in IRV even if I:E ratio was prolonged up to 2.6:1 or 4:1. These results suggested that combinations of IRV with PEEP were effective and an I:E ratio of 2:1 may be optimal, and IRV is advantageous compared to PEEP, but will take more long time to improve oxygenation than PEEP.(Sari A, Toriumi T, Yamashita S, et al.: Combined effects of inversed ratio ventilation (IRV) with positive end-expiratory pressure ventilation (PEEP) on cardiorespiratory function in acute respiratory failure. J Anesth 5: 105–113, 1991)     

Interim evidence of the renoprotective effect of the angiotensin II receptor antagonist losartan versus the calcium channel blocker amlodipine in patients with chronic kidney disease and hypertension: a report of the Japanese Losartan Therapy Intended for Global Renal Protection in Hypertensive Patients (JLIGHT) Study

Background. Insufficiency of renal function and high blood pressure influence each other and eventually result in life-threatening endstage renal disease. It has been proposed that proteinuria per se is a determinant of the progression of chronic kidney disease (CKD). The therapeutic strategy for patients with proteinuric CKD and hypertension should therefore be targeted with a view not merely toward blood pressure reduction but also toward renoprotection. Methods. We examined the effect of the angiotensin (AT)₁ receptor antagonist losartan and the calcium channel blocker amlodipine, throughout a period of 12 months, on reduction of blood pressure and renoprotection. This was done by assessing amounts of urinary protein excretion, serum creatinine (SCr), and creatinine clearance (CCr) in patients with hypertension (systolic blood pressure [SBP] 140mmHg or diastolic blood pressure [DBP] 90mmHg) and CKD (male, body weight [BW] 60kg: 1.5 SCr < 3.0mg/dl; female or male BW < 60kg: 1.3 SCr < 3.0mg/dl), manifesting proteinuria of 0.5g or more/day. Losartan was administered once daily at doses of 25 to 100mg/day, and amlodipine was given once daily at 2.5 to 5mg/day. No antihypertensive combination therapy was allowed during the first 3-month period. Results. A 3-month interim analysis revealed that, despite there being no difference in blood pressure between the two groups, there was a significant reduction in 24-h urinary protein excretion in the losartan group (n = 43), but there was no change in the amlodipine group (n = 43). Analysis of stratified subgroups with proteinuria of 2g or more/day and less than 2g/day showed that losartan lowered proteinuria by approximately 24% in both subgroups, while amlodipine lowered proteinuria by 10%, but only in the subgroup of less than 2g/day (NS). SCr and CCr did not change throughout the period of 3 months in either group. No severe or fatal adverse event was experienced in either group during the study period. Conclusions. Losartan appeared to be efficacious for renoprotection in patients with proteinuric CKD and hypertension, with the mechanism being independent of its antihypertensive action.     

Effects of Cilostazol on Human Venous Smooth Muscle

In this study, we evaluated the effect of therapeutic doses of cilostazol on human venous smooth muscle. Saphenous vein rings (two to four per patient sample) were suspended in tissue baths for isometric tension recordings. At the beginning of the experiment, optimal tension for isometric contraction was achieved for each ring in a stepwise fashion in the presence of norepinephrine (10^–2 M). Norepinepherine was then added cumulatively in half-molar increments and isometric tension developed by the rings was measured, thereby obtaining a dose-response curve. Following washout and reequilibration, the rings were precontracted with a 30-50% submaximal dose of norepinepherine determined from the dose-response curve and allowed to contract until a stable plateau was reached. Cilostazol was then added in a cumulative manner (680-2,720 g/L), and the tension generated was recorded. A total of 76 venous rings were tested, and all relaxed in the presence of cilostazol. The amount of relaxation increased as the concentration of cilostazol increased. Relaxation of 15±1.9% (mean±SEM) at low cilostazol doses (680 g/L) to 37±3% at high cilostazol doses (2,720 g/L) was demonstrated. A second finding of this study was demonstrated when the patient samples were divided according to the presence or absence of risk factors for arteriosclerosis. The specific risk factors examined included diabetes mellitus, smoking, hypercholesterolemia, and hypertension. The presence or absence of hypertension (n=52) or hypercholesterolemia (n=18) did not affect the amount of relaxation of the venous rings. Smokers (n=46) had less relaxation 16±2.4% (680 g/L) to 41±3.6% (2,720 g/L) compared to nonsmokers (n=53) who relaxed 22±3.5% (680 g/L) to 48±5.7% (2720 g/L). This did not reach statistical significance at any concentration cilostazol (p=0.11-0.18). Diabetics (n=53) did have statistically significantly less relaxation at every concentration of cilostazol compared to nondiabetics (n=11, p < 0.05). All venous rings relaxed in the presence of cilostazol. Veins of nondiabetics relaxed statistically significantly more than those of diabetics. Smokers had less relaxation than non-smokers, but this was not statistically significant. We are the first to demonstrate that human venous smooth muscle cells undergo relaxation when exposed to therapeutic concentrations of cilostazol.