Phase I/IIa study of cetuximab with gemcitabine plus carboplatin in patients with chemotherapy-naive advanced non-small-cell lung cancer.

PURPOSE: This multicenter, open-label, phase I/IIa study was undertaken to establish the safety/toxicity profile of cetuximab in combination with gemcitabine and carboplatin in patients with chemotherapy-na?ve, epidermal growth factor receptor-positive, stage IV non-small-cell lung cancer. Secondary objectives were to gather preliminary evidence of efficacy including tumor response rate, time to progression, and overall survival. PATIENTS AND METHODS: Thirty-five patients received a total of 264 3-week cycles of treatment with cetuximab, carboplatin, and gemcitabine. An initial dose of cetuximab 400 mg/m2 intravenously was administered the first week, followed by weekly doses of 250 mg/m2. Carboplatin (area under the curve = 5, day 1) and gemcitabine 1,000 mg/m2 on days 1 and 8 were administered every 3 weeks. Patients were evaluated for tumor response after every two cycles of therapy. RESULTS: The most frequently reported adverse events related to cetuximab included an acne-like rash (88.6%), dry skin (34.3%), asthenia and skin disorders (31.4%), mucositis/stomatitis (25.7%), fever/chills (20%), and nausea/vomiting (17.1%). The majority of these toxicities were mild to moderate. One patient withdrew from the study because of a grade 3 allergic reaction. Myelosuppression was the most frequently observed toxicity related to chemotherapy. Responses among 35 assessable patients included 10 partial responses (28.6%). Twenty-one patients had stable disease. The median time to progression was 165 days, and the median overall survival was 310 days. CONCLUSION: The combination of cetuximab, carboplatin, and gemcitabine was well tolerated with an acceptable toxicity profile. Most grade 3 adverse events were attributable to chemotherapy. The response rate and median survival are encouraging and warrant additional investigation.     

Synergistic antinociceptive interaction between acetaminophen or metamizol and B vitamins in the formalin test

There is evidence that B vitamins produce antinociception in animals. However, potentiation of NSAID‐induced antinociception by B vitamins is unclear. The current study was designed to investigate the antinociceptive interaction between a mixture of B vitamins and either acetaminophen or metamizol. Acetaminophen (56–316 mg/kg), metamizol (32–178 mg/kg), and the mixture of B vitamins (32–178 mg/kg of thiamine, pyridoxine, and cyanocobalamin in a 100:100:1 proportion, respectively) or a combination of each drug with the B vitamins mixture was administered orally to female Wistar rats, and the antinociceptive effect determined in the formalin test. Isobolographic analyses were used to define the nature of the interaction between NSAIDs and B vitamins. Oral administration of either drug produced a dose‐related antinociceptive effect. Isobolographic analyses revealed that both acetaminophen or metamizol and the B vitamins mixture interacted synergistically in the formalin test, suggesting that these two combinations could be useful in treating inflammatory pain states. Drug Dev. Res. 66:286–294, 2006. © 2006 Wiley‐Liss, Inc.     

Current management of calculi in horseshoe kidneys

OBJECTIVES: To assess treatment options for calculi in horseshoe kidneys and the impact of extracorporeal shockwave lithotripsy (ESWL) on the management of renal stones. MATERIAL AND METHODS: From June 1971 to January 1998, 52 patients with horseshoe kidneys and calculi received treatment at our Urologic Stone Unit. There were 40 men (77%) and 12 women (23%). Average patient age was 41 years (range: 10-70 years). Clinical onset, treatment received and outcome were evaluated retrospectively. A successful outcome was defined as a patient without residual calculi or with fragments <0.4 cm in size. RESULTS: Clinical onset was mainly low back pain in 37 patients (71%). Eighty-nine stones were treated, i.e. an average of 1.7 treatments per patient. Before the ESWL era (May 1987), we performed two heminephrectomies, 16 pyelolithotomies, 12 pyelolithotomies combined with ureteropyeloplasty and one percutaneous nephrolithotomy. Since the advent of ESWL, seven pyelolithotomies and three pyelolithotomies combined with ureteropyloplasty have been done. ESWL was used to treat 48 calculi. In three cases the patient was placed in the prone position due to difficulties in stone focusing. In 37 cases (77%) patients were either rendered stone-free or had residual fragments <0.4 cm in size. Urinary diversion for obstruction was carried out in two cases (4%). CONCLUSIONS: At present ESWL is the first-choice treatment for calculi in horseshoe kidneys. It involves no significant focusing difficulties and is associated with a low incidence of obstructive complications. Open surgery is indicated in cases of stone-related pyeloureteral stenosis and in the presence of calculi >2-2.5 cm in size.     

Constraints on the use of a nerve stimulator in peripheral conduction blocks when there is disturbance in the neuromuscular junction

An 81-year-old woman with right lower limb ischemia was scheduled for revascularization of a femoropopliteal bypass grafted 10 years earlier. A popliteal blockade, attempted as part of regional anesthesia with the aid of a nerve stimulator, was not achieved because the posterior tibial nerve could not be located. After surgery, the patient mentioned symptoms in the region of the right knee consistent with complex regional pain syndrome (Ducke's stage 3); the symptoms appeared after the first operation and would explain the absence of response to the nerve stimulator. Using a nerve stimulator to facilitate location of the various nerve trunks for anesthesia involves obtaining a motor response to electrical stimulation. The procedure is becoming more and more frequent because of its many advantages over other more traditional methods. However, it may be impossible to locate a nerve for a variety of reasons.     

Heart arrest in cemented hip arthroplasty

Hip arthroplasty is a common surgical intervention in our hospital practice, involving high perioperative risk related to patients age and multiple concomitant diseases. Hemodynamic complications described vary from slight hypotension during surgery to heart failure and sudden death, particularly if the operation involves a cemented femoral component. Because of the type of patients undergoing such operations (elderly patients, with osteoporosis and scarce cardiopulmonary reserve), the unclear origin of complications and the lack of consensus on what constitutes adequate monitoring during surgery, hip arthroplasty is problematic for the specialists involved. We report on five deaths during cemented hip arthroplasty; after reviewing the case history and autopsy report of one, we believe the events leading to death were triggered by massive pulmonary embolism.     

Acute ischemia of the hand as a complication of radial artery catheterization. Apropos of 2 cases following abdominal sarcoma surgery

Arterial catheterization is a simple technique that yields great benefits, such as continuous monitoring of arterial pressure and the possibility of taking repeated samples for analysis. However, it is not free of complications, the main ones being limb ischemia and gas embolism. To reduce the risk of complications, guidelines for insertion and maintenance of arterial catheters have been established. We report two cases of acute hand ischemia secondary to arterial catheterization. Both patients were undergoing surgery for sarcoma-type abdominal cancer and developed acute ischemia of the hand lasting several hours. The predisposing factor in both cases was the existence of a highly advanced sarcoma-type abdominal tumor, probably related to a state of hypercoagulability.     

Tetraplegia in the immediate postoperative period of stapedectomy

Management of the cervical spine in orotracheal intubation for general anesthesia is an important aspect of daily practice in anesthesiology. Also important are the requirements, techniques and consequences of patient position during surgery. We report a case of tetraplegia during the early postoperative period after stapedectomy for otosclerosis. After surgery, the spontaneously breathing patient was transferred to the recovery room, where a clinical picture of anesthesia and paralysis of all four limbs was evident. We ordered an emergency magnetic resonance image of the cervical spine, which revealed a massive acutely herniated disk at C6-C7 with signs of ischemia or necrosis of the medulla at the same level. After eight months, the patient was still paraplegic and lacked sensation in the lower limbs. Sensation and motor function in the upper limbs was nearly normal. We review the etiopathogenetic mechanisms that might be responsible for this clinical profile.