The purpose of this study was to define the relationship between cardiac depression and morphological and immunological alterations in cardiac tissue after multiple trauma. However, the mechanistic ...basis of depressed cardiac function after trauma is still elusive. In a porcine polytrauma model including blunt chest trauma, liver laceration, femur fracture and haemorrhage serial trans-thoracic echocardiography was performed and correlated with cellular cardiac injury as well as with the occurrence of extracellular histones in serum. Postmortem analysis of heart tissue was performed 72 h after trauma. Ejection fraction and shortening fraction of the left ventricle were significantly impaired between 4 and 27 h after trauma. H-FABP, troponin I and extracellular histones were elevated early after trauma and returned to baseline after 24 and 48 h, respectively. Furthermore, increased nitrotyrosine and Il-1β generation and apoptosis were identified in cardiac tissue after trauma. Main structural findings revealed alteration of connexin 43 (Cx43) and co-translocation of Cx43 and zonula occludens 1 to the cytosol, reduction of α-actinin and increase of desmin in cardiomyocytes after trauma. The cellular and subcellular events demonstrated in this report may for the first time explain molecular mechanisms associated with cardiac dysfunction after multiple trauma.
Locking plates have become a standard implant in the treatment of distal femoral fractures. Newer designs allow polyaxial screw placement as well as the ability to lock the lag screws.
The ...consecutive multi-centre study cohort consists of all distal femoral fractures treated with the NCB® Distal Femur plate (Zimmer, Warsaw, USA) and a minimum follow-up of twelve months. Fracture classification according the AO/ OTA system and the trauma mechanism radiological evaluation and complications were documented. Clinical evaluation consisted of the Short Form SF12 questionnaire (SF12), the Hospital for Special Surgery Score (HSS) and clinical assessment of range of motion.
Twenty-five patients with twenty-six fractures were available for follow-up with a minimum required follow-up of twelve months. 81% of the fractures were intra-articular. 48% of the patients were multi-traumatised, 38% having open fractures. All except two went to union (92%) with the primary procedure. The HSS Score was 79 (32-99) and the SF 12 (physical and mental) 40 (19-57) and 54 (21-66) at follow-up. There were five patients requiring surgical revision (19%).
These fractures are often combined with concomitant injuries. Using modern locked implants high union rates can be achieved with a good function and patient satisfaction when respecting biologic and biomechanical principles.
The free intracellular calcium concentration, Ca2+i, was studied in single myotubes using the fluorescent Ca2+ indicator fura-2. Myotubes cultured from satellite cells of small muscle specimens from ...Duchenne muscular dystrophy (DMD) patients were compared with human control myotubes and with myotubes cultured from MDX and control mouse muscle satellite cells. The resting Ca2+i levels in DMD and control myotubes were not significantly different, i.e. 104 +/- 26 nM (mean +/- SD, n = 190 cells from eight DMD patients) compared with 97 +/- 25 nM (175/seven controls) and were not significantly lower than the corresponding murine values (154 +/- 33 nM, n = 135 MDX myotubes; 159 +/- 34 nM, n = 135 controls). All myotubes reacted to 10 microM acetylcholine or 40 mM KCl with fast transient increases of Ca2+i. After application of a hyposmotic (130 mOsm) solution, Ca2+i was increased 1.5- to 3-fold within 2-3 min, the DMD myotubes tending to stronger reactions (significantly higher Ca2+i in 2 out of 6 cases). The response was usually transient, Ca2+i decreasing to the initial level within 10 min. Gadolinium (50 microM) reduced the response by 50%-70%, indicating that the osmotic shock increased Ca2+ influx. During exposure to high (15 mM) Ca2+e, Ca2+i of DMD and control cells was 1.5- to 2-fold higher. Adult muscle fibres from MDX mice and controls showed identical Ca2+ resting levels (n = 45 fibres from three mice in each case), but did not respond to decreased external osmolarity with a change in Ca2+i. The results indicate that lack of dystrophin in muscle fibres does not necessarily lead to increased Ca2+i.
Cure is possible by resecting colorectal isolated liver metastases. In non-resectable isolated colorectal liver metastases (CRLM), regional chemotherapy has been advocated to optimize the disease ...control in the liver in order to improve the results of the alternative, systemic chemotherapy. The drugs are delivered by means of hepatic artery infusion (HAI) via ports or pumps; pharmacological modifications of the hepatic arterial blood-flow-like HAI with starch microspheres or stop-flow and perfusion techniques were applied to improve HAI.
We reviewed the literature and report our progress, up to May 1999, in analyzing the validity of HAI for CRLM therapy.
In the majority of phase-II and -III trials, the response rates to HAI were significantly higher than those from systemic chemotherapy, and local disease control could be achieved even when HAI was used second line to systemic chemotherapy. The meta-analysis of randomized trials comparing HAI with either systemic chemotherapy (five trials) or, optionally, either 5-fluorouracil (FU) or symptomatic treatment (two trials) showed a significant advantage of HAI in response (41% vs 14%, P<10(-10)) and median survival time (15 months vs 11 months, P<0.0009). The active anabolite of 5-FU, 5-fluordeoxyuridine (5-FUDR), the drug of choice for HAI in those trials, may cause severe hepatotoxicity. To avoid this toxicity, we developed a HAI protocol using mitoxantrone, 5-FU plus folinic acid (FA) and mitomycin C (MFFM). The response rates of HAI with 5-FU plus FA or MFFM were 45% and 66%, the interim median survival times 19.8 months and 27.4 months. 5-Year survivors were observed in all our protocols. Since no severe hepatotoxicity occurred, 9 of 74 patients were resected after response to HAI with 5-FU plus FA or MFFM, without surgical mortality and with survival times from 2+ months to 58+ months.
The high response rates, the long survival times, the possibility of achieving 5-year-survival either by HAI alone or by resection after down staging with HAI all sum up to the evidence that HAI could be the primary choice of treatment for CRLM. Phase-III trials are conducted to compare the protocols with optimal regional versus systemic chemotherapy.
Locked plate devices offer advantages in the treatment of periprosthetic femur fractures associated with fixed total hip or total knee arthroplasty. The purpose of this study was to evaluate the ...early results and complications with a locked plate system (NCB-DF(R)).
A total of 31 patients (mean age 76 years, 7 males, 24 females) with a femur fracture above a fixed total knee arthroplasty (TKA, n=12) or a total hip arthroplasty (THA, n=19) were treated with a locked plate.
There were 11 complications necessitating revision: 6 implant failures, 2 in patients with a THA and 4 in patients with a TKA, 4 hematomas and 1 infection and 2 patients died. After 6 months all fractures had healed securely but a secondary correction was necessary in one patient.
Fixation of periprosthetic femur fractures with a locked plate system provided satisfactory results in patients with a THA, however, the relatively high implant failure rate in fractures above a stable TKA is a cause for concern.
Chronic low back pain (LBP) has been reported with a high incidence in elite rowers. It results in less effective training, long interruptions in training, and a drop in performance.
The authors ...hypothesized that exercise-induced LBP in rowers is caused by a chronic functional compartment syndrome (CFCS) of the multifidus muscle.
Controlled clinical trial.
The rowers were tested in their training camp. The control group was tested at a university hospital.
14 volunteer elite rowers complaining of LBP and 16 healthy volunteer amateur athletes.
Intramuscular pressure (IMP), tissue oxygenation pressure (pO2), and median frequency (MF) shift in the electromyographic power density spectrum during isometric fatiguing extension at 60% of maximum voluntary contraction.
At the beginning (controls 186.6 mm Hg vs rowers 60.2 mm Hg, P = .002) and the end (controls 224.1 mm HG vs rowers 77.1 mm Hg, P < .001) of the endurance exercise the median IMP was significantly higher in the healthy controls. Nearly identical resting pO2 was measured in both groups (controls 37.6 mm Hg vs rowers 37.3 mm Hg, P = .740). Rowers showed higher median MF shift (rowers -11.5 Hz vs controls -8.5 Hz, P = .079) during contraction.
These observations cannot sufficiently be explained by the CFCS model and suggest that factors other than IMP have an additional effect on pain generation during exercise in elite rowers.
Since the developments in systemic chemotherapy of metastasized colorectal cancer have not resulted in substantial gains in survival times, we wished to improve the course of isolated nonresectable ...colorectal liver metastases (CPLM) by hepatic arterial infusion treatment.
Patients (pts) with CRLM have a worse fate than those pts whose liver metastases could be resected. Systemic (i.v.) chemotherapy for CRLM/colorectal metastases does not improve survival to a relevant level (median survival time (med. surv.) after 5-Fluorouracil + Folinic Acid (5-FU + FA) i.v.: 6.4-14.3 months (m)). Hepatic artery infusion (HAI) with 5-Fluorode-oxyuridine (5-FUDR) has been demonstrated in a metaanalysis of randomized trials to be superior to i.v. treatment/palliative care (med. surv.: 15 vs. 10 m). The benefit of HAI with 5-FUDR, although recommended as treatment for CRLM, is severely compromised by the 5-FUDR induced hepatotoxicity, leading eventually to sclerosing cholangitis (SC)/liver scirrhosis. We have stepwise developed a protocol for HAI of CRLM, which is superior to HAI with 5-FUDR, and, most evidently, to systemic chemotherapy.
Between 1982-1997, 222 CR (L) M patients were treated within subsequent protocols (Table). In protocol A, 68 CRLM pts received HAI with 5-FUDR (A1: nonrandomized pts; A2: randomized pts). In protocol B (randomized pts.), 46 pts received 5-FUDR i.a. (via HAI) + i.v. In protocol C, systemic chemotherapy with 5-FU + FA was conducted in 34 pts with metastasized colorectal cancers, including CRLM. In protocol D 5-FU + FA was delivered via HAI in 25 pts with CRLM. In protocol E, based on in vitro phase II studies and the results of protocol D, Mitoxantrone and Mitomycin C were added to 5-FU + FA (MFFM). Fifty (50) CRLM pts received HAI with MFFM.
The response rates, med. surv. times, systemic toxicity and SC rates are shown in the table. HAI with MFFM produced objective responses in 66%, the med. surv. was 27.4 m, and no SC occurred. The ports surgically placed for HAI, e.g., in protocols D and E, functioned in 90%, 82%, and 76% 6, 9, and 11 m after start of the HAI. Quality of life in protocol E was high. Nine pts from protocols D + E with either partial (PR, 7 pts) or complete (CR, 2 pts) remissions received a secondary liver resection without hospital mortality, and 7/9 pts are living 2-58 m after liver resection, 2/9 pts died 11 and 22 m after resection. table: see text
Our learning curve to achieve optimal treatment of CRLM resulted in a protocol using HAI with MFFM. The results of this protocol (E) including the high remission rate, long median survival time, good port function, high quality of life, and, most interestingly, the possibility to downstage and resect primarily nonresectable metastases, seem to be superior to HAI with 5-FUDR of 5-FU + FA and to systemic chemotherapy with 5-FU + FA. This hypothesis is currently examined in a phase III study (HAI with MFFM vs. 5-FU + FA i.v.).
NSC-631570 (Ukrain) is a semisynthetic compound of thiophosphoric acid and the alkaloid chelidonine from the plant Chelidonium majus. It has been used in complementary herbal medicine for more than ...20 years for the treatment of benign and malignant tumors.
Between August 1999 and June 2001, 90 patients with histologically proven unresectable pancreatic cancer were randomized in a monocentric, controlled, randomized study. Patients in arm A received 1000 mg gemcitabine/m2, those in arm B received 20 mg NSC-631570, and those in arm C received 1000 mg gemcitabine/m2 followed by 20 mg NSC-631570 weekly. End point of the study was overall survival.
In all three arms therapy was well tolerated and toxicity was moderate. At the first re-evaluation in arm A 32%, in arm B 75%, and in arm C 82% showed no change or partial remission according to WHO criteria (arm A versus arm B: P<0.01, arm A versus arm C: P<0.001). Median survival according to Kaplan-Meier analysis was in arm A 5.2 months, in arm B 7.9 months, and in arm C 10.4 months (arm A versus arm B: P<0.01, arm A versus arm C: P<0.01). Actuarial survival rates after 6 months were 26%, 65% and 74% in arms A B and C, respectively (arm A versus arm B: P<0.05, arm A versus arm C P<0.01).
We could show that in unresectable advanced pancreatic cancer, NSC-631570 alone and in combination with gemcitabine nearly doubled the median survival times in patients suffering from advanced pancreatic cancer.
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