Dysphonia as an unusual toxic event of oxaliplatin-based chemotherapy.

Oxaliplatin is a new, third-generation platinum complex. It has a good safety profile characterized by low hematological-gastrointestinal toxicity. No significant nephro-ototoxicity has been observed. Acute peripheral neuropathy is a common event affecting, as grade 1 or 2, 85-95% of patients. Recently, data on dysphonia toxicity, after the administration of oxaliplatin, has been reported in literature. This toxicity with acute onset can be misunderstood if not carefully looked for. However, it is self-limiting and a non-permanent (grade 1-2) neurotoxic phenomenon, which impairs transiently the quality of life of a percentage of oxaliplatin-treated patients. We report our experience in consecutive patients affected by advanced colorectal cancer treated with oxaliplatin-based chemotherapy. Overall, we observed 13 (16%) cases of dysphonia out of 81 consecutive patients treated with oxaliplatin-based chemotherapy. This toxic effect was self-limiting and all patients recovered rapidly. Nonetheless, a deeper understanding of this phenomenon is essential to give correct information to the patients.

Ifosfamide in advanced/disseminated breast cancer.

Ifosfamide is an alkylating agent active in various tumor types including breast cancer. The availability of mesna (sodium 2-mercaptoethanesulfonate) has increased its safety, avoiding the main dose-limiting side effect, urotoxicity. Interesting activity as a single agent, with response rates ranging from 7 to 30%, is reported in pretreated patients; more attractive data derived from phase II studies on ifosfamide combined with drugs known to be active in advanced breast cancer show response rates always over 35%. This review has taken in consideration papers published after 1995 and available on PubMed medline: the data indicate a potential usefulness of ifosfamide in the clinical management of advanced breast cancer, even if the exact therapeutic role of the drug in this setting should be derived from randomized studies not yet available.

Ifosfamide in the adjuvant therapy of soft tissue sarcomas.

Ifosfamide and anthracyclines are the only active agents in advanced soft tissue sarcomas. Doxorubicin was always used in sarcomas, whereas ifosfamide was reintroduced in the clinic after the discovery of mesna which prevents its typical dose-limiting toxicity: hemorrhagic cystitis. In the adjuvant setting, doxorubicin was used alone or in combination in the first-generation trials, whereas its parent compounds epirubicin and ifosfamide were employed in the second-generation adjuvant trials, which started in the early 90s. Other relevant aspects of the second-generation trials are the use of the hematopoietic growth factors and the increase of the dose intensity, the introduction of more restrictive selection criteria and the use of the two most active agents, ifosfamide and anthracyclines. Only the Italian cooperative trial has been concluded, and the results reported and updated. After a median follow-up of 89.6 months (range 56-119), the intention-to-treat analysis still reveals a difference in overall survival which, however, is not statistically significant. However, the 5-year overall survival estimate, which is a reasonable end point for the survival analysis of adjuvant treatment in soft tissue sarcomas, was 66.0 and 46.1% for the treatment and the control groups, respectively (p = 0.04).

Gliding properties of the long head of the biceps brachii.

To elucidate the role of mechanical forces that resist motion of the long head of the biceps brachii, the gliding resistance of the tendon during abduction and adduction was measured. Nine human cadaveric glenohumeral joints were obtained (mean age 68 years, range 47-84). A testing device was developed to simulate glenohumeral abduction and adduction motion. Gliding resistance was calculated as the force differential on the proximal and distal ends of the biceps brachii at five glenohumeral angles (15 degrees, 30 degrees, 45 degrees, 60 degrees and 75 degrees ). The average gliding resistance in abduction at 15 degrees, 30 degrees, 45 degrees, 60 degrees and 75 degrees for a 4.9 N load was 0.41, 0.40, 0.36, 0.32 and 0.28 N, respectively. At these same angles, but during adduction motion, the force on the proximal tendon end was either identical or less than the distal tendon end (p>0.46) indicating a lack of resistance and even a phenomena of "negative" resistance in which some other force overcame the friction. The difference in gliding resistance between abduction and adduction was significant (p<0.05). The results indicate that forces opposing biceps tendon gliding are more complicated than simply due to friction. Tendon deformation inside the bicipital groove produces a direction-dependent effect due to a mechanism of elastic recoil. Understanding forces that are absorbed by the tendon during active motion may provide insight into pathological changes that develop inside and around the tendon.

Biomechanical comparison of effects of supraspinatus tendon detachments, tendon defects, and muscle retractions.

BACKGROUND: Rotator cuff ruptures are frequently associated with loss of strength of the shoulder. However, the characteristics of the rotator cuff tear that are responsible for the loss of force generation and transmission have not yet been identified. The purpose of this study was to compare the effects of supraspinatus tendon detachments, tendon defects, and muscle retractions on in vitro force transmission by the rotator cuff to the humerus. METHODS: The rotator cuff tendons from ten cadaver shoulders were loaded proportionally to the respective cross-sectional areas of their muscles. A fiberglass rod was cemented into the medullary canal of the humerus and connected to a three-component load cell for the measurement of the forces transmitted by the rotator cuff to the humerus. This study was performed with the humerus in a hanging arm position and with various sizes of supraspinatus tendon detachments, tendon defects, and muscle retractions. RESULTS: Detachment or creation of a defect involving one-third or two-thirds of the supraspinatus tendon resulted in a minor reduction in the force transmitted by the rotator cuff (< or =5%), while detachment or creation of a defect involving the whole tendon resulted in a moderate reduction (11% and 17%, respectively). Simulated muscle retraction involving one-third, two-thirds, and the whole tendon resulted in losses of torque measuring 19%, 36%, and 58%, respectively. Side-to-side repair of the one-third and two-thirds defects nearly restored the force transmission capability, whereas a deficit remained after side-to-side repair following complete resection. CONCLUSIONS: Our results support the rotator cable concept and correspond to the clinical observation that patients with a small rupture of the rotator cuff may present without a loss of shoulder strength. Muscle retraction is potentially an important factor responsible for loss of shoulder strength following large rotator cuff ruptures. CLINICAL RELEVANCE: Supraspinatus muscle retraction diminishes glenohumeral abduction torque significantly more than either a defect in the tendon or a simple detachment of the tendon from the tuberosity. In cases of irreparable defects, side-to-side repair may be worthwhile to restore muscle tension and the integrity of the rotator cable.

Transient left ventricular apical ballooning without coronary artery stenosis: a novel heart syndrome mimicking acute myocardial infarction. Angina Pectoris-Myocardial Infarction Investigations in Japan.

OBJECTIVES: To determine the clinical features of a novel heart syndrome with transient left ventricular (LV) apical ballooning, but without coronary artery stenosis, that mimics acute myocardial infarction, we performed a multicenter retrospective enrollment study. BACKGROUND: Only several case presentations have been reported with regard to this syndrome. METHODS: We analyzed 88 patients (12 men and 76 women), aged 67 +/- 13 years, who fulfilled the following criteria: 1) transient LV apical ballooning, 2) no significant angiographic stenosis, and 3) no known cardiomyopathies. RESULTS: Thirt-eight (43%) patients had preceding aggravation of underlying disorders (cerebrovascular accident [n = 3], epilepsy [n = 3], exacerbated bronchial asthma [n = 3], acute abdomen [n = 7]) and noncardiac surgery or medical procedure (n = 11) at the onset. Twenty-four (27%) patients had emotional and physical problems (sudden accident [n = 2], death/funeral of a family member [n = 7], inexperience with exercise [n = 6], quarreling or excessive alcohol consumption [n = 5] and vigorous excitation [n = 4]). Chest symptoms (67%), electrocardiographic changes (ST elevation [90%], Q-wave formation [27%] and T-wave inversion [97%]) and elevated creatine kinase (56%) were found. After treatment of pulmonary edema (22%), cardiogenic shock (15%) and ventricular tachycardia/fibrillation (9%), 85 patients had class I New York Heart Association function on discharge. The LV ejection fraction improved from 41 +/- 11% to 64 +/- 10%. Transient intraventricular pressure gradient and provocative vasospasm were documented in 13/72 (18%) and 10/48 (21%) of the patients, respectively. During follow-up for 13 +/- 14 months, two patients showed recurrence, and one died suddenly. CONCLUSIONS: A novel cardiomyopathy with transient apical ballooning was reported. Emotional or physical stress might play a key role in this cardiomyopathy, but the precise etiologic basis still remains unclear.