Serious respiratory consequences of detergent ingestions in children

After ingesting or inhaling laundry detergent powder, eight children required hospital admission. The predominant symptoms were stridor, drooling, and respiratory distress. All but one patient underwent endoscopy of the airways and the esophagus, five children were admitted to the intensive care unit, and four children required endotracheal intubation. Laundry detergent ingestions are generally considered to have minor consequences, and there exists a paucity of literature on the subject. Evidence of significant morbidity incurred because of ingestion or inhalation of sodium carbonate-containing laundry detergent powder is presented, together with a review of the existing literature.     

Enhanced chondrogenesis and Wnt signaling in PTH-treated fractures.

Studies have shown that systemic PTH treatment enhanced the rate of bone repair in rodent models. However, the mechanisms through which PTH affects bone repair have not been elucidated. In these studies we show that PTH primarily enhanced the earliest stages of endochondral bone repair by increasing chondrocyte recruitment and rate of differentiation. In coordination with these cellular events, we observed an increased level of canonical Wnt-signaling in PTH-treated bones at multiple time-points across the time-course of fracture repair, supporting the conclusion that PTH responses are at least in part mediated through Wnt signaling. INTRODUCTION: Since FDA approval of PTH [PTH(1-34); Forteo] as a treatment for osteoporosis, there has been interest in its use in other musculoskeletal conditions. Fracture repair is one area in which PTH may have a significant clinical impact. Multiple animal studies have shown that systemic PTH treatment of healing fractures increased both callus volume and return of mechanical competence in models of fracture healing. Whereas the potential for PTH has been established, the mechanism(s) by which PTH produces these effects remain elusive. MATERIALS AND METHODS: Closed femoral fractures were generated in 8-wk-old male C57Bl/6 mice followed by daily systemic injections of either saline (control) or 30 microg/kg PTH(1-34) for 14 days after fracture. Bones were harvested at days 2, 3, 5, 7, 10, 14, 21, and 28 after fracture and analyzed at the tissue level by radiography and histomorphometry and at the molecular and biochemical levels level by RNase protection assay (RPA), real-time PCR, and Western blot analysis. RESULTS: Quantitative muCT analysis showed that PTH treatment induced a larger callus cross-sectional area, length, and total volume compared with controls. Molecular analysis of the expression of extracellular matrix genes associated with chondrogenesis and osteogenesis showed that PTH treated fractures displayed a 3-fold greater increase in chondrogenesis relative to osteogenesis over the course of the repair process. In addition, chondrocyte hypertrophy occurred earlier in the PTH-treated callus tissues. Analysis of the expression of potential mediators of PTH actions showed that PTH treatment significantly induced the expression of Wnts 4, 5a, 5b, and 10b and increased levels of unphosphorylated, nuclear localized beta-catenin protein, a central feature of canonical Wnt signaling. CONCLUSIONS: These results showed that the PTH-mediated enhancement of fracture repair is primarily associated with an amplification of chondrocyte recruitment and maturation in the early fracture callus. Associated with these cellular effects, we observed an increase in canonical Wnt signaling supporting the conclusion that PTH effects on bone repair are mediated at least in part through the activation of Wnt-signaling pathways.     

Outpatient management of chronic suppurative otitis media without cholesteatoma in children.

Prolonged antipseudomonal parenteral antibiotic therapy combined with daily aural toilet has been effective in resolving long standing ear discharge in children with chronic suppurative otitis media. However, such treatment suffered from the disadvantages of prolonged hospitalization. We conducted a prospective study to investigate the feasibility and efficacy of exclusive outpatient treatment of children with chronic suppurative otitis media without cholesteatoma who had failed ototopical/oral antimicrobial therapy. The treatment consisted of daily aural toilet (suction and debridement) and twice daily parenteral ceftazidime (50 mg/kg/dose). Thirty-seven children were included. The duration of discharge from the ear before treatment was 6 to 121 months (median, 30 months). Aerobic cultures yielded Pseudomonas aeruginosa in 97%, often with other organisms. The management and follow-up were performed jointly by otolaryngology and infectious diseases physicians using the hospital ambulatory services. The route of ceftazidime administration (intravenous or intramuscular) was chosen according to the parents' and patients' convenience. Discharge stopped within 3 to 20 days (median, 8 days) in all children but one. Seventy-six percent of the 29 children available for follow-up 12 months after treatment were still free of discharge. Our results demonstrate that a regiment combining daily aural toilet and twice daily parenteral ceftazidime is highly efficacious in resolving ear discharge in children with chronic suppurative otitis media without cholesteatoma and that such a regimen does not require hospitalization.     

Phase III double-blind comparison of intravenous ondansetron and metoclopramide as antiemetic therapy for patients receiving multiple-day cisplatin-based chemotherapy.

BACKGROUND. Ondansetron hydrochloride is a selective serotonin subtype 3 (5HT3) receptor antagonist that has been shown to be an effective antiemetic in patients receiving cisplatin chemotherapy. METHODS. This double-blind study compared the safety and efficacy of intravenous ondansetron with metoclopramide in patients receiving a 4- or 5-day regimen of cisplatin (20-40 mg/m2/day) combination chemotherapy. Forty-five patients were enrolled, and efficacy of the drug therapy could be studied for all 45. Patients were randomly assigned (1:1) to receive three daily intravenous doses of either 0.15 mg/kg ondansetron or 1 mg/kg metoclopramide. All patients were monitored daily for the number of emetic episodes (vomiting or retching), severity of nausea, adverse events, and laboratory safety parameters. RESULTS. Seven (30%) patients who received ondansetron had no emetic episodes throughout the entire study period compared with two (9%) who received metoclopramide (P = 0.077). The greatest difference in antiemetic efficacy was seen on day 1, when 18 (78%) patients who received ondansetron had no emetic episodes compared with 3 (14%) patients who received metoclopramide (P < 0.001). Significantly fewer antiemetic treatment failures (more than five emetic episodes or withdrawal from the study) occurred with patients given ondansetron (9%) than with those given metoclopramide (50%) during the entire study period (P = 0.002). The most commonly reported adverse event associated with ondansetron therapy was headache (controlled with acetaminophen), whereas diarrhea and restlessness were the most commonly reported adverse events associated with metoclopramide therapy. Extrapyramidal symptoms were judged to have occurred in 13 patients who received metoclopramide and 1 patient who received ondansetron. However, the patient who received ondansetron subsequently was judged to have had an anxiety attack. In patients with low or normal baseline transaminase values, a greater percentage who received ondansetron had transient increases as great as twice the upper limit of normal in aspartate transaminase (5% versus 0%) and alanine transaminase (17% versus 6%) than those who received metoclopramide. CONCLUSIONS. Ondansetron is superior to metoclopramide as antiemetic therapy for multiple-day cisplatin-based chemotherapy.     

High dose carboplatin/VP-16 plus ifosfamide with autologous bone marrow support in the treatment of refractory germ cell tumors.

We report seven patients with germ cell tumors which either recurred following a minimum of two regimens of platinum-based chemotherapy or were refractory to cisplatin. The patients were treated with one or two courses of high dose carboplatin (CBDCA) and etoposide (VP-16) plus ifosfamide (IFX) with mesna uroprotection and autologous bone marrow support. The doses given were CBDCA 500 mg/m2 every other day x 3 and VP-16 400 mg/m2 every other day x 3. IFX was given in a dose of 2 g/m2 daily x 5 days with mesna. The original intent of the protocol was to explore escalating doses of IFX, but excessive renal toxicity at the first dose level prevented escalation. Of the seven patients treated, four developed a marked decline in their renal function and three of the four required hemodialysis or hemofiltration. Six of seven patients treated had a decline in their serum markers indicating a response to therapy, but all have relapsed. Our conclusion is that while the combination of CBDCA/VP-16/IFX with ABMT is active in this group of patients, it is associated with excessive renal toxicity which is probably due to underlying renal dysfunction secondary to extensive prior cisplatin-based chemotherapy.     

Neoadjuvant therapy of stage III non-small cell lung cancer

During the past several years, there has been a resurgence of interest in preoperative or postoperative chemotherapy in patients with Stage III lung cancer. The staging system for lung cancer has recently been modified, and at the present time Stage III disease is now subdivided into Stage III-A (potentially surgically resectable for cure) and Stage III-B (unresectable). This article will review five recently completed studies utilizing neoadjuvant therapy in various types of Stage III lung cancer. The thoracic surgeon is faced with the dilemma of reviewing this literature and trying to make a conclusion as to what is appropriate therapy for Stage III disease. Unquestionably, neoadjuvant therapy appears to increase the resectability rate in Stage III-A disease and can make some Stage III-B patients anatomically resectable. It is hoped that future well-designed phase III studies can be accomplished in Stages III-A and III-B disease so that we can determine whether neoadjuvant chemotherapy is or is not beneficial for these patients.     

Glitazones and the management of insulin resistance: what they do and how might they be used.

Thiazolidinediones (glitazones) are the only compounds currently available that specifically target tissue insulin resistance. The two currently available drugs in this class, pioglitazone and rosiglitazone,are approved by the Food and Drug Administration for the treatment of type 2 diabetes mellitus only. The therapeutic potential of the glitazones for other consequences of insulin resistance has stirred considerable interest, especially with regard to their potential beneficial impact on atherosclerotic cardiovascular disease and diabetes prevention. They also have been considered in the management of polycystic ovarian syndrome, nonalcoholic fatty liver disease, and other consequences of insulin resistance. The nonglycemic potential of glitazones is a clinical area in rapid evolution, wherein most data are on the impact of the glitazones onsurrogate markers that are associated with diseases, not on disease outcomes. This article provides insight and guidance to clinicians on the diverse nonglycemic potential of glitazones until conclusive outcome data become available.     

Status of chemotherapy for testis cancer

Significant advances have been made in the treatment of advanced testicular cancer. These advances have been centered on better staging techniques with procedures such as computed tomography as well as the development of reliable serum markers. Based on these techniques, patients can be directed toward primary surgical therapy or systemic therapy. Cisplatin combination chemotherapy can be expected to cure approximately 80 per cent of all patients with advanced disease. Currently, cisplatin plus etoposide plus bleomycin is the standard treatment for patients with advanced disease. Newer trials are currently addressing the role of more aggressive therapy in patients with a poor prognosis while parallel trials examine the possibility of minimizing toxicity for those patients with good-risk disease.     

The HPV-16 E7 oncogene sensitizes malignant cells to IFN-alpha-induced apoptosis.

Interferons (IFNs) exert antitumor effects in several human malignancies, but their mechanism of action is unclear. There is a great variability in sensitivity to IFN treatment depending on both tumor type and the individual patient. The reason for this variable sensitivity is not known. The fact that several IFN-induced anticellular effects are exerted through modulation of proto-oncogenes and tumor suppressor genes may indicate that the malignant genotype may be decisive in the cell's sensitivity to IFN. To determine if a deregulated oncogene could alter the cellular response to IFN, a mouse lymphoma cell line (J3D) was stably transfected with the viral human papillomavirus-16 (HPV-16) E7 oncogene. The E7-transfected cells and their respective mock-transfected sister clones were treated with IFN-alpha and examined for possible IFN-induced anticellular effects. We found that the E7-transfected clones were greatly sensitized to IFN-alpha-induced apoptosis compared with their mock-transfected counterparts. Induction of apoptosis in the transfected cells correlated with the ability of IFN to activate parts of the proapoptotic machinery specifically in these cells, including activation of caspases and the proapoptotic protein Bak. In summary, our data suggest that transfection of malignant cells with the E7 oncogene can sensitize them to IFN-alpha-induced apoptosis. This demonstrates that an oncogenic event may alter the cellular sensitivity to IFN and might also have implications for treatment of HPV-related diseases with IFN.     

Osteoporosis: The Role of the Orthopaedist

Osteoporosis is one of the most prevalent musculoskeletal disorders encountered in orthopaedic practice today. This review provides an update on the pathophysiology of bone metabolism leading to osteoporosis, describes the latest methodology in the diagnostic workup of patients with low bone mass, and summarizes the current status of osteoporosis treatment regimens. The special needs of the osteoporotic fracture patient are also addressed. In general, load-sharing devices and sliding nail-plate constructs are preferred over rigid internal-fixation systems. Prolonged immobilization should be avoided.