Peripheral blood cells from children with RASopathies show enhanced spontaneous colonies growth in vitro and hyperactive RAS signaling.

Germline mutations in genes coding for molecules involved in the RAS/RAF/MEK/ERK pathway are the hallmarks of a newly classified family of autosomal dominant syndromes termed RASopathies. Myeloproliferative disorders (MPDs), in particular, juvenile myelomonocytic leukemia, can lead to potentially severe complications in children with Noonan syndrome (NS). We studied 27 children with NS or other RASopathies and 35 age-matched children as control subjects. Peripheral blood (PB) cells from these patients were studied for in vitro colony-forming units (CFUs) activity, as well as for intracellular phosphosignaling. Higher spontaneous growth of both burst-forming units-erythroid (BFU-E) and CFU-granulocyte/macrophage (CFU-GM) colonies from RAS-mutated patients were observed as compared with control subjects. We also observed a significantly higher amount of GM-colony-stimulating factor-induced p-ERK in children with RASopathies. Our findings demonstrate for the first time that PB cells isolated from children suffering from NS or other RASopathies without MPD display enhanced BFU-E and CFU-GM colony formation in vitro. The biological significance of these findings clearly awaits further studies. Collectively, our data provide a basis for further investigating of only partially characterized hematological alterations present in children suffering from RASopathies, and may provide new markers for progression toward malignant MPD in these patients.

Adjuvant hyperbaric oxygen therapy (HBO2)for treatment of necrotizing fasciitis reduces mortality and amputation rate.

OBJECTIVE: A retrospective analysis of 42 patients with necrotizing soft tissue infections treated with adjunctive HBO2 to ascertain efficacy and safety. Overall mortality was 11.9% and morbidity 5%. SUMMARY BACKGROUND DATA: Necrotizing soft tissue infections have historically high rates of mortality and morbidity, including amputation. Common misconceptions that prevent widespread use of adjunctive HBO2 for this diagnosis include delays to surgery, increased morbidity, and significant complications. METHODS: Forty-two consecutive patients (average age 56.1) with necrotizing fasciitis presenting to a major referral center were treated with adjunctive HBO2 as part of an aggressive program of surgery, antibiotics, and critical care. Involved areas included the lower abdomen (15 patients), thigh and perineum (9 patients), flank (4 patients), lower leg (3 patients), and arm, shoulder, and axilla (2 patients). Co-morbidities included diabetes mellitus, chronic renal failure, intravenous drug abuse, peripheral vascular disease, and malignancy. RESULTS: Mortality was 11.9% (5 patients). Both amputations (a finger and a penis), occurred prior to transport to our facility. The average number of surgical debridements was 2.8 per patient; 1.25 performed prior to the start of HBO. The infectious process was controlled after an average of 7 HBO2 treatments were administered to ensure successful wound closure. Complications consisted of only mild ear barotrauma in 3 patients (7%), and confinement anxiety in 17 (41%) but did not prevent treatment. CONCLUSION: Compared to national reports of outcomes with "standard" regimens for necrotizing fasciitis, our experience with HBO2, adjunctive to comprehensive and aggressive management, demonstrates reduced mortality (34% v. 11.9%), and morbidity (amputations 50% v. 0%). The treatments were safe and no delays to surgery or interference with standard therapy could be attributed to HBO2.

Pulmonary edema associated with scuba diving : case reports and review.

Acute pulmonary edema has been associated with cold-water immersion in swimmers and divers. We report on eight divers using a self-contained underwater breathing apparatus (scuba) who developed acute pulmonary edema manifested by dyspnea, hypoxemia, and characteristic chest radiographic findings. All cases occurred in cold water. All scuba divers were treated with complete resolution, and three have returned to diving without further episodes. Mechanisms that would contribute to a raised capillary transmural pressure or to a reduced blood-gas barrier function or integrity are discussed. Pulmonary edema in scuba divers is multifactorial, and constitutional factors may play a role. Physicians should be aware of this potential, likely underreported, problem in scuba divers.

Hyperbaric oxygen therapy for radiation-induced brain injury in children.

BACKGROUND: Radiation-induced necrosis (RIN) of the brain is a complication associated with the use of aggressive focal treatments such as radioactive implants and stereotactic radiosurgery. In an attempt to treat patients with central nervous system (CNS) RIN, ten patients received hyperbaric oxygen treatment (HBOT). METHODS: Patients presented with new or increasing neurologic deficits associated with imaging changes after radiotherapy. Necrosis was proven by biopsy in eight cases. HBOT was comprised of 20-30 sessions at 2.0 to 2.4 atmospheres, for 90 minutes-2 hours. Sites of RIN included the brain stem (n = 2), posterior fossa (n = 1), and supratentorial fossa (n 7). Histologic types included brain stem glioma (n = 2), ependymoma (n = 2), germinoma (n = 2), low grade astrocytoma (n = 1), oligodendroglioma (n = 1), glioblastoma multiforme (n = 1), and arteriovenous malformation (n = 1). RESULTS: Initial improvement or stabilization of symptoms and/or imaging findings were documented in all ten patients studied and no severe HBOT toxicity was observed. Four patients died, with the cause of death attributed to tumor progression. Five of six surviving patients were improved by clinical and imaging criteria; one patient was alive with tumor present at last follow-up. CONCLUSIONS: HBOT may prove to be an important adjunct to surgery and steroid therapy for CNS RIN.

Chronic radiation proctitis treated with hyperbaric oxygen.

Chronic proctitis is a well-known complication of therapeutic irradiation. The results of hyperbaric oxygen therapy (HBO2) used in the treatment of chronic radiation proctitis are reported. From 1992 to 1995, 14 patients with chronic radiation-induced proctitis were treated with HBO2. Nine patients were treated in a monoplace chamber at 2.0 atm abs (203 kPa O2), and five patients were treated at 2.36 atm abs (239 kPa O2). Eight patients experienced complete resolution of symptoms and one patient had substantial improvement for a total response rate of 64%. Follow-up ranged from 5 to 35 mo. (mean 17 mo.). Five patients (36%) were classified as non-responders. Three experienced significant improvement during treatment but relapsed soon after therapy was discontinued, whereas two had no symptomatic improvement. Responders who had sigmoidoscopy after therapy showed documented improvement whereas no non-responders showed improvement. The authors conclude that HBO2 therapy should be considered in patients with chronic radiation proctitis.

The effect of hyperbaric oxygen therapy on a burn wound model in human volunteers.

A previous nonblinded study has suggested beneficial effects from hyperbaric oxygen treatment of superficial partial-thickness radiation burns in human volunteers. This protocol was designed to either confirm or challenge these previous findings in a randomized, blinded format. Twelve healthy, nonsmoking volunteers (7 males, 5 females) participated. All were screened for contraindications to hyperbaric oxygen therapy (acute sinusitis, otitis media, pneumonia, pregnancy, active cancer, pneumothorax) and given a single test hyperbaric exposure. A standardized wound model was employed for the painless creation of a volar forearm lesion on volunteers by applying a suction device to form a blister, excising its epidermal roof, and irradiating the exposed dermis with ultraviolet light. Subjects were randomized into either a hyperbaric oxygen group (100% oxygen at 2.4 ATA, n = 6) or the sea-level air-breathing equivalent control group (8.75% oxygen at 2.4 ATA, n = 6). Both groups then underwent standard hyperbaric therapy. The subjects, the hyperbaric oxygen chamber operators, and the monitoring clinicians were all blinded to the oxygen concentration administered. Each subject received two dives per day over a 3-day period. The wounds were studied noninvasively prior to treatment and once per day over 6 days for size, hyperemia, and exudation, with epithelialization as the endpoint. The averages for each measurement of the hyperbaric oxygen group versus the control group were computed by means of a one-tail t test; p was considered significant at less than 0.05. Daily wound size, hyperemia, and exudation measurements were significantly different on day 2. The hyperbaric oxygen group showed a 42 percent reduction in wound hyperemia, a 35 percent reduction in the size of the lesion, and a 22 percent reduction in wound exudation (p values of 0.05, 0.03, and 0.04, respectively). No significant difference was noted for epithelialization. Observed differences in wound size, hyperemia, and exudation were attributable to hyperbaric oxygen therapy. This study further supports earlier conclusions that hyperbaric oxygen therapy is beneficial in a superficial dermal wound.

Long-term results of aggressive management of diabetic foot ulcers suggest significant cost effectiveness.

This study was undertaken to examine the hypothesis that the initial high limb salvage rate in patients with diabetes who are treated aggressively with a multidisciplinary approach to management of severe, chronic lower extremity wounds is durable and cost effective. In 1991 a cohort of 41 patients with diabetes with severe, chronic foot wounds was selected by a neutral, blinded observer who had no knowledge of the outcomes from a group of 101 consecutive such patients who had been treated at our wound center from 1983 to 1990. All had limb-threatening lesions, scoring 3 to 4 on the Wagner scale, were treated for at least 7 days with adjunctive hyperbaric oxygen, and had photographic and medical documentation. Durability of wound repair was examined in 1991 and 1993. Initial limb salvage was 85%. Mean hospital charges were $31,264, including average hyperbaric charges of $15,000. At the initial review, 28 of the patients with previously salvaged limbs (80%) were contacted. Of the 28 patients, 27 remained intact (96%). The mean durability of repair was 2.6 years. At the second review, the mean duration of repair in surviving patients was 4.6 years with no further expenditures relative to the salvaged limb. In patients who died, average durability was 3.4 years, also without additional expenditure referable to the salvaged extremity. Most complex lower extremity lesions were healed by a comprehensive wound care program which included vascular surgery and hyperbaric oxygen. The results were durable, and the treatment was cost effective and humane compared with early amputation.

Adjunctive hyperbaric oxygen therapy in the treatment of the diabetic foot.

The use of hyperbaric oxygen therapy for the treatment of conditions of local or focal hypoxia is not new. The author discusses the potential benefits of hyperbaric oxygen in the treatment of chronic wounds when used as a part of a multidisciplinary wound care program. Rationale and mechanism of action are discussed along with possible adverse effects. Costs of care and limb salvage rates are considered.

Adjunctive hyperbaric oxygen therapy in the treatment of thermal burns: a review.

Hyperbaric oxygen therapy provided in specially designed pressure chambers is currently the treatment of choice for decompression sickness, arterial gas embolism, and serious carbon monoxide poisoning. It is an important adjunct in the treatment of gas gangrene, chronic osteomyelitis, radiation injury, and indolent wounds. The potential benefit in the treatment of thermal burns is not well appreciated. Hyperbaric oxygen therapy may significantly reduce morbidity, mortality, and cost of care. The application of this technology based on the demonstrated beneficial effects on the pathophysiology of the burn wound merits consideration in selected patients.

Adjunctive hyperbaric oxygen in the treatment of thermal burns. An economic analysis.

Current reimbursement for burn care underscores the importance of cost containment in the treatment of burn injuries. We evaluate the economic impact of adjunctive hyperbaric oxygen in burns of 19% to 50% total body surface area in patients admitted to our burn center from January 1982 to July 1987. Length of hospitalization, number of surgical procedures, and total cost of care, exclusive of surgical fees, were examined. Eleven patients did not receive adjunctive hyperbaric oxygen therapy, whereas 10 did. The hyperbaric oxygen-treated group had an average decrease in length of stay of 14.8 days, a reduction of surgical procedures of 39%, and an average saving per case of $31,600.

Adjunctive hyperbaric oxygen therapy reduces length of hospitalization in thermal burns.

The use of adjunctive hyperbaric oxygen therapy as part of a comprehensive program of burn care at our institution has resulted in a statistically significant reduction in length of hospital stay (p = less than 0.012) with no increase in cost of hospital care in patients suffering burns over 18% to 39% of total body surface area.

Air embolism complicating percutaneous thin needle biopsy of lung.

Percutaneous thin needle biopsy, a widely used method for diagnosis of lung conditions, is generally safe and effective. A near-fatal air embolism is reported that occurred during percutaneous thin needle aspiration biopsy of the lung. Successful treatment was accomplished by hyperbaric oxygen therapy. Physicians should be aware of this possible complication and identify the location of the nearest chamber for possible transfer.

Treatment of radiation cystitis with hyperbaric oxygen.

A patient with severe radiation cystitis resistant to current therapy was treated with hyperbaric oxygen to facilitate closure of a vesicocutaneous fistula. In addition to the fistula healing, her symptoms of radiation cystitis have not recurred for over a year and a half.

Case report. Preoperative localization of a parathyroid adenoma using computed tomography and thyroid scanning.

We report a case of parathyroid adenoma correctly localized prior to operation by computed tomography (CT) and thyroid scanning. The use of CT and other noninvasive diagnostic modalities to aid the surgeon prior to initial operation for parathyroid adenoma is discussed.