Computed tomography of the osseous pelvis.

Computed tomography (CT) was used for study of the osseous pelvis in 43 patients with definitive pathological or clinical follow-up. CT accurately characterized and determined extent of bone and soft-tissue involvement; neoplasms and other disease processes, such as sacroiliac joint disease, were well localized. In cases of trauma, CT was able to identify, localize, and characterize fracture fragments and bone or joint displacement. CT was judged "useful" or "definitive" in 80% of all lesions and 96% of neoplasms studied.     

Local Anesthetic-Induced Methemoglobinemia During Transesophageal Echocardiography

We report a case of methemoglobinemia that occurred following topical benzocaine spray to the throat, leading to cancellation of the transesophageal echocardiography (TEE) procedure. Since the condition is potentially fatal, increased awareness of this disorder should result in its early recognition and treatment. (ECHOCARDIOGRAPHY, Volume 15, February 1998)     

Combined Interatrial and Intrapulmonary Shunting in Orthodeoxia Detected by Transesophageal Echocardiography

Contrast transesophageal echocardiography was found useful in diagnosing combined interatrial and intrapulmonary right-to-left shunts in a patient presenting with orthodeoxia. This was done by separately examining the pulmonary veins and the interatrial septum during intravenous normal saline injections.     

Effects of temperature on intracellular sodium, pH and cellular energy status in RIF-1 tumor cells

Most perfused tumor cell experiments are performed at 37 degrees C, the normal healthy body temperature. However, the temperature of subcutaneously implanted tumors in small animals is generally 29-33 degrees C when the rectal temperature of the animal is maintained at 37 degrees C. We have investigated the acute effects of increasing the temperature of perfused radiation-induced-fibrosarcoma (RIF-1) tumor cells from 33 to 37 degrees C (30 min) on intracellular sodium (Na(i)+) , intracellular pH (pH(i)), and bioenergetic status. Heating the cells by 4 degrees C produced a reversible increase in Na(i)+, slight acidification and no change in nucleotide triphosphate to inorganic phosphate ratio (NTP/P(i)) as measured by shift-reagent-aided (23)Na and (31)P NMR spectroscopy. In the presence of 3 microM 5-(N-ethyl-N-isopropyl) amiloride (EIPA), a potent and specific inhibitor of Na(+)/H(+) antiporter, the increase in Na(i)+ during the heating was completely abolished suggesting that the heat induced increase in Na(i)+ was caused by an increase in Na(+)/H(+) antiporter activity. However, the changes in pH(i) with the heating were identical with or without EIPA, indicating that pH(i) is controlled by other ion exchange mechanisms in addition to Na(+)/H(+) antiporter. NTP/P(i) was significantly higher in presence of EIPA for some time points during the heating suggesting that both NTP production and consumption rates may be altered during the heating. These results indicate that a slight increase in temperature from 33 to 37 degrees C induces significant changes in Na(+) physiology largely because of activation of Na(+)/H(+) antiporter but other ion exchange mechanisms are also involved in maintaining pH(i) in the RIF-1 tumor cells. Thus, care must be taken in choosing the temperature for perfused cell studies.     

Phase II study of autologous transplantation with interleukin-2-incubated peripheral blood stem cells and posttransplantation interleukin-2 in relapsed or refractory non-Hodgkin lymphoma.

Previous work suggested that interleukin (IL)-2 can be used for eradicating residual disease in autologous grafts and for preventing recurrence. We report a phase II study of autologous peripheral blood stem cell transplantation with in vitro IL-2 incubation of peripheral blood stem cells and posttransplantation IL-2 in patients with recurrent or refractory non-Hodgkin lymphoma. Salvage chemotherapy consisted of ifosfamide and etoposide. Responding patients underwent autologous peripheral blood stem cell transplantation. IL-2-incubated stem cells were infused on day 0. IL-2 1 mIU/m2 was given from day 1 until day 28. Four monthly maintenance cycles of IL-2 4 mIU/m2 subcutaneously twice daily days 1 to 5 and days 8 to 11 were administered thereafter. Eighty-four evaluable patients were enrolled, and 60 proceeded to transplantation, of which 56 received IL-2-incubated stem cells. The average received dose of posttransplantation IL-2 was 30% to 50% of planned. Only 42 patients received maintenance IL-2. The average received maintenance dose of IL-2 was also approximately 30% of planned. Most dose reductions were due to toxicity or patient refusal. Three-year survival and progression-free survival for all registered patients were 43% (95% confidence interval [CI], 33%-53%) and 31% (95% CI, 21%-41%), respectively. For the 60 patients undergoing transplantation, they were 59% (95% CI, 46%-72%) and 44% (95% CI, 31%-57%), respectively. There was no relation between the dose of IL-2 received and outcome. Survival and disease-free survival of the study group were similar to those of a previous study cohort that received unmanipulated stem cells and no systemic IL-2. Administration of IL-2-incubated peripheral blood stem cells and intensive posttransplantation IL-2 was associated with considerable but rapidly reversible toxicity. No effect on long-term outcome was observed.     

A novel use of photo messaging in the assessment of nasal fractures

We evaluated a new method of assessing patients referred to the otolaryngology department with nasal injury. Patients possessing a mobile phone with built-in camera took an image of their face and sent it to the department for assessment. A decision was then made as to whether the patient needed further consultation or treatment. This method of nasal fracture assessment might avoid unnecessary referrals to the department. A prospective single blinded study was carried out. Twenty-five patients with a nasal injury took photographs of their face using a mobile phone camera. These images were reviewed and assessment made about whether a nasal fracture was present. The patient was then clinically assessed, the clinical examination being the 'gold standard' method of assessment. There was little agreement between photographic and clinical assessment. Sixty-two percent of patients who were clinically assessed to have a nasal fracture requiring manipulation were not picked up on assessment of their image. The greatest agreement with clinical assessment was the patient's own opinion as to whether there was new deviation of their nasal bone.     

Application of the Stable Isotope Label Approach in Clinical Development—Supporting Dissolution Specifications for a Commercial Tablet Product with Tafenoquine,a Long Half-life Compound

Bioavailability/bioequivalence studies supporting clinical drug development or commercial supply of drug formulations are often time, cost, and resource intensive. The drug’s pharmacokinetic (PK) variability, systemic half-life, and safety issues may pose additional challenges. The stable isotope label (SIL) approach provides a useful tool to significantly reduce the study size in clinical PK studies. Tafenoquine (TQ) is an 8-aminoquinoline under development for preventing Plasmodium vivax malaria relapse. This SIL study assessed the impact of differences in the in vitro dissolution profiles on in vivo exposure of TQ tablets. Fourteen healthy volunteers received a single dose of 300 mg TQ Intermediate Aged or 300 mg TQ Control formulations in this single-center, two-arm, randomized, open-label, parallel-group study. Endpoints included the geometric means ratio of the area under the concentration-time curve (AUC_(0-t) and AUC_(0-∞); primary endpoint) and maximum plasma concentration (C_max) for Intermediate Aged versus Control TQ; correlation of PK parameters for venous versus peripheral (via microsample) blood samples; and safety and tolerability endpoints. Geometric mean ratios for PK parameters (AUC and C_max) and their 90% confidence intervals fell well within standard bioequivalence limits (0.80–1.25). Only one mild adverse event (skin abrasion) was reported. In summary, this SIL methodology-based study demonstrates that the observed differences in the in vitro dissolution profiles between the Control and Intermediate Aged TQ tablets have no clinically relevant effect on systemic TQ exposure. The SIL approach was successfully implemented to enable the setting of a clinically relevant dissolution specification.Clinical trial: This study (GSK study number 201780) is registered at clinicaltrials.gov with identifier NCT02751294.     

Amorphous calcific tumor of the mitral annulus echocardiographically mimicking a vegetation

We describe echocardiographic findings in an elderly patient with histologically proven amorphous tumor involving the posterior mitral annulus, mimicking a vegetation.