Efficacy and safety of ibandronate in the treatment of opioid-resistant bone pain associated with metastatic bone disease: a pilot study.

PURPOSE: Bone metastases are associated with severe and sometimes intractable pain, compromising patient quality of life (QOL). This open-label pilot study investigated the effects of short-term intensive treatment with intravenous (i.v.) ibandronate on opioid-resistant bone pain in patients with skeletal metastases. PATIENTS AND METHODS: Eighteen patients with advanced tumors and metastatic bone disease received nonstandard treatment with 4 mg of ibandronate administered i.v. (2-hour infusion) for 4 consecutive days (16-mg total dose). Baseline opioid analgesic use was equivalent to 400 mg/d of morphine. Patients were assessed for 6 weeks or until death. Changes from baseline were determined for bone pain, opioid consumption, patient functioning, QOL, performance status, and biochemical markers of calcium metabolism and bone turnover. Renal function was assessed by serum urea and creatinine measurement. RESULTS: Short-term, intensive ibandronate treatment significantly reduced bone pain scores within 7 days (P <.001). Pain reductions were sustained over the study period. Ibandronate significantly improved QOL, patient functioning, and performance status (P <.05). Mean values of the urinary cross-links pyridinoline and deoxypyridinoline tended to increase after day 21, returning close to baseline values by day 42. There was no correlation between the change in crosslinks values and the change in pain scores after ibandronate treatment. Ibandronate was well tolerated, with no evidence of renal toxicity. CONCLUSION: Nonstandard, intensive treatment with i.v. ibandronate seems to have a marked analgesic effect in patients with opioid-resistant bone pain from metastatic bone disease. Further investigation is warranted.     

Duplex ultrasound evaluation of cavernosal peak systolic velocity and waveform acceleration in the penile flaccid state: clinical significance in the assessment of the arterial supply in patients with erectile dysfunction

The aim of this paper was to establish if duplex ultrasound parameters obtained for assessment of the patency of cavernosal arteries in the penile flaccid state can give sufficient clinical information without the use of intracavernosal injection of vasodilatory drugs. We assessed mean cavernosal peak systolic velocity (PSV) in the penile flaccid state (basal PSV), and after PGE1 injection (dynamic PSV) in 339 unselected patients with erectile dysfunction. In 55 of these patients the waveform acceleration in the flaccid state was also assessed. The results of the study can be summarized as follows: (1) a significant relationship was found between basal and dynamic PSV in the 339 patients (r=0.477; p < 0.0001); (2) a basal PSV >12.5 cm/sec was predictive of a dynamic PSV >/=30 cm/sec in 129/139 (92.8%) of the patients, whereas in patients with a basal PSV or <30 cm/sec could be found; and (3) an acceleration >1 m/sec2 in the flaccid state was coupled to a dynamic PSV >30 cm/sec in 43/46 (93.5%) of the patients independent of the basal PSV. In conclusion, these results suggest that the combined duplex ultrasound assessment of PSV and waveform acceleration in the penile flaccid state can predict arterial dynamic inflow in the majority (51/55; 92.7%) of patients with erectile dysfunction, with less time and expense and less discomfort for the patient.     

Uteroglobin and transglutaminase modulate human sperm functions

During the process of capacitation, spermatozoa undergo significant changes in membrane composition, including removal of decapacitating factors (DFs), which are present in seminal plasma, that lead to increased sensitivity to physiological stimuli of the acrosome reaction. In the present study we investigated the presence, localization, and effects on human spermatozoa of 2 proteins of seminal plasma origin, uteroglobin (UG) and transglutaminase (TG). These 2 proteins interact with one another because TG promotes covalent links of UG to sperm surface proteins. We found that UG is localized around the entire surface of ejaculated human sperm, whereas TG is predominantly localized in the neck. FACScan analysis confirmed the surface localization of both antigens and demonstrated that swim-up selection of spermatozoa was associated with a significant reduction in the contents of the 2 substances when compared with unselected samples. Western blot analysis of UG in total sperm lysates confirmed the lower content of the protein in swim-up-selected sperm. Swim-up-selected sperm were characterized by their ability to undergo a spontaneous, time-dependent increase of capacitation-characteristic chlortetracycline pattern of fluorescence and increase in responsiveness to progesterone. Such changes were not observed in unselected sperm. Exogenous addition of TG, together with recombinant rabbit UG, prevented the spontaneous increase in responsiveness to progesterone (acrosome reaction and intracellular calcium) at 24 hours in swim-up-selected sperm, suggesting the occurrence of a capacitation-inhibiting activity of the 2 substances. In addition, we found that endogenous UG and TG contents, as determined by FACScan analysis, were negatively correlated (P < .0001) with sperm motility and that exogenous addition of the 2 substances resulted in a substantial reduction of progressive motility (P < .01). Collectively, these data indicate that TG and UG represent 2 DFs, and contribute to understanding the biochemical mechanisms that characterize the process of capacitation.     

Axillary hibernoma: an unusual soft tissue tumor

Hibernomas are rare soft tissue tumors of brown fat differentiation. A case of a large axillary hibernoma, along with a review of its pathology, is presented. This tumor matches the largest hibernoma in the literature and is the largest in an axillary site.     

Immediate passive mobilization of the hip after internal fixation of acetabular fractures

The authors report the results obtained in 16 patients affected with displaced fracture of the acetabulum treated surgically and mobilized passively immediately after surgery by means of a continuous passive mobilization apparatus for the hip. The age of the patients at the time of trauma ranged from 21 to 54 years. The posterior wall was involved in 12 cases, while the anterior column was also involved in 4. Excellent or good reduction of the fracture was obtained in all of the cases. Immediately after surgery, a continuous passive motion apparatus for the hip was applied to be used for approximately 3 weeks. At final follow-up, which was obtained after a mean time of 5 years, all of the patients except 2 had obtained good results. Moderate joint deficit was present in 1 case, while sciatic nerve palsy that had already been observed prior to surgery persisted in another. Evident radiographic signs of coxarthrosis were not present in any of the cases. Based on the opinion of Salter et al. (1980), who in an experimental study had observed better healing of the cartilaginous lesions in the joints submitted to movement, immediately after surgery we applied a continuous passive motion apparatus for the hip in a group of patients affected with fracture of the acetabulum. As none of the patient followed-up by us presented evident signs of hip arthrosis, the authors hypothesize that continuous passive movement, immediately carried out after osteosynthesis, plays a significant role in preventing post-traumatic arthrosis of the hip. In truth, small irregularities of the acetabular cavity, possibly present after an apparently anatomical reduction, could be minimized by the plasmating effect of the head of the femur in movement.     

Recurrent remodeling after ventricular assistance: is long-term myocardial recovery attainable?

BACKGROUND: Long-term left ventricular assist devices (LVAD) have been used both as a bridge to heart transplantation and to recovery of native myocardial function. Despite much evidence for reversal of some of the structural and functional changes present in the failing heart during LVAD support, clinical evidence for sustained myocardial recovery is scant. We describe 2 patients in whom myocardial recovery during LVAD support led to device explanation only to have heart failure recur. This necessitated a second LVAD implantation, a process that we have termed recurrent remodeling. METHODS: The medical records of 2 patients with cardiomyopathy supported with HeartMate LVADs (Thermo Cardiosystems, Inc, Woburn, MA) were retrospectively reviewed. RESULTS: One patient was supported with an LVAD for 2 months, at which time the LVAD was explanted. Progressive deterioration of cardiac function followed, requiring a second LVAD 19 months after LVAD explanation. After 2 months of further LVAD support, a second episode of apparent myocardial recovery was observed during a period of device malfunction. The other patient was supported with an LVAD for 12 months, at which time the LVAD was explanted. The patient experienced progressive hemodynamic deterioration and required a second LVAD 6 months after LVAD explantation. Heart transplantations of both patients were successful. CONCLUSIONS: Our understanding of myocardial recovery in the setting of hemodynamic unloading with LVAD support has not yet progressed to the point where we are able to accurately predict successful long-term LVAD explantation. The evolution of reliable predictors of sustainable myocardial recovery will help to avoid further cases of recurrent remodeling requiring repeat LVAD implantation.     

Can We Eliminate Low-Density Lipoprotein Cholesterol-Related Cardiovascular Events Through More Aggressive Primary Prevention Therapy?

Intravascular levels of low-density lipoprotein cholesterol (LDL-C) at approximately ≤ 0.6 mmol/L are likely to minimize, and perhaps eliminate, LDL-C-related vascular toxicity while having no effect on essential, intracellular cholesterol homeostatic pathways, according to accumulated knowledge from basic science. Randomized clinical trials, observational reports, and Mendelian randomization trials are also forcing a reconsideration of what “normal” LDL-C means. Recent trials of secondary prevention have substantiated that such levels are safe and associated with a decreased risk of cardiovascular events (CVEs) compared with patients with higher levels of LDL-C. Similarly, treatment to this low range is associated with regression and stabilization of established atherosclerosis. Primary prevention trials also show that low levels of LDL-C are safe and associated with decreased risk of CVEs through cholesterol-lowering in adults with LDL-C ≥ 3.5 mmol/L or when levels are < 3.5 mmol/L in association with other cardiovascular risks. Although there are no randomized clinical outcome trials of familial hypercholesterolemia patients, such patients have very high, lifetime risk of CVE, and registry studies show that LDL-C reduction has nearly normalized their CVE rates. The possibility of familial hypercholesterolemia should be considered if LDL-C is > 4.5 and > 4.0 mmol/L at ages 18-39 years and younger than 18 years, respectively. On the basis of these convergent and internally consistent lines of evidence, in this article we speculate on a translational paradigm aimed at eliminating LDL-C-related CVEs through aggressive primary prevention strategies that are already proven and well accepted in principle.     

The Treatment of Medically Intractable Trigeminal Autonomic Cephalalgia With Supraorbital/Supratrochlear Stimulation: A Retrospective Case Series

Introduction: This is a retrospective case series of five patients with intractable trigeminal autonomic cephalalgia (TAC) who were implanted with a supraorbital/supratrochlear neuromodulation system. Objectives: The aim of this Institutional Review Board–approved study was to investigate the percentage of pain relief, treatment response, pain level, work status, medication intake, implantation technique, lead placement, programming information, and device use. Results: Trial stimulation led to implantation of all five patients. All patients reported improvement in their functional status in regard to activities of daily living. The device was revised in two patients due to skin erosion. It was later reimplanted in both patients due to worsening of symptoms, again with good pain relief. The device was explanted in two other patients because of the need to perform a magnetic resonance imaging or implant an automatic implantable cardioverter defibrillator. The follow‐up of the patients ranged between 18 months and 36 months, with a mean of 25.2 months. There was no change in work status. Following the implant, the Visual Analog Scale score was reduced to a mean of 1.6 from an initial mean score of 8.9. Three patients were completely weaned off opioid medications, while two patients continued to take opioid at a lower dosage. All patients experienced a decrease of the adjuvant neuropathic drugs. Conclusion: Supraorbital/supratrochlear nerve stimulation appears to be a promising modality for the treatment of patients with intractable TAC.     

Behavioural phenotype of a patient with a de novo 1.2 Mb chromosome 4q25 microdeletion

A female patient, 20 years of age, is reported with a history characterized by developmental and psychomotor delay, and during grammar-school period increasing learning problems, ritualistic behaviours and social withdrawal. Subsequently, challenging and autistic-like behaviours became prominent. The patient showed mild facial dysmorphisms, long thin fingers with bilateral mild short V metacarpals, and hyperlaxity of the joints. Neuropsychiatric examination disclosed obsessive, ritualistic behaviours and vague ideas of reference. Neuropsychological assessment demonstrated mild intellectual disability, mental inflexibility and incongruent affect. MRI-scanning of the brain showed no relevant abnormalities. Genome wide SNP array analysis revealed a 1.2 Mb de novo interstitial microdeletion in 4q25 comprising 11 genes, that was considered to be causative for the developmental delay, perseverative cognitive phenotype and dysmorphisms.To the authors knowledge, this is the first report of a de novo 4q25 microdeletion that presents with a specific behavioural phenotype.