Carboplatin desensitization.

BACKGROUND: IgE-mediated carboplatin hypersensitivity reactions occur in up to 30% of patients receiving this agent for chemotherapy of solid tumors, thus limiting therapeutic options. OBJECTIVE: To describe our experience with intravenous carboplatin desensitization regimens, which culminated in a standardized, successful protocol for safe administration. METHODS: Eight consecutive patients with ovarian cancer who had experienced severe anaphylactic reactions to carboplatin were referred to our hospital. Intradermal skin testing was performed by raising a 3-mm bleb by injection of undiluted carboplatin at 10 mg/mL, and the wheal size was read at 20 minutes. The outcomes of the various desensitization regimens were documented prospectively, and the experience gained was used to develop a standardized protocol for administration. RESULTS: All patients had positive intradermal skin test results. The first 3 patients were treated with short (90 minutes to 6 hours) desensitization protocols, and all protocols failed on the first or second infusions. These 3 and a subsequent 5 patients were given intravenous carboplatin according to a protocol of gradual dose escalation over a 4-log dose range given during a 4-day period, with subsequent 3-weekly infusions given more rapidly by omitting the most dilute log dose on each occasion. All patients tolerated the longer infusion protocol without event, and all but 1 patient experienced appropriate tumor marker response. CONCLUSIONS: Short carboplatin desensitization protocols (less than 6 hours) have an unacceptable failure rate in patients with carboplatin allergy, but longer infusion times (days) are well tolerated without recurrence of the allergic reaction and with good tumor response. In cases where carboplatin is the optimal therapeutic agent, clinicians should not be deterred by an anaphylactic reaction to it or by failure of shorter desensitization regimens.     

Innovative Wundtherapie und Hautersatz bei Verbrennungen

The success of modern burn therapy is based mainly on special burn intensive care, topical treatment, early eschar excision, and wound closure by immediate skin grafting or skin substitutes. This paper describes the current state of wound care and skin substitutes in burn therapy.     

Ultra-early evaluation of regional cerebral blood flow in severely head-injured patients using xenon-enhanced computerized tomography.

The role of cerebral ischemia in the pathophysiology of traumatic brain injury is unclear. Cerebral blood flow (CBF) measurements with 133Xe have thus far revealed ischemia in a substantial number of patients only when performed between 4 and 12 hours postinjury. But these studies cannot be performed sooner after injury, they cannot be done in patients with intracranial hematomas still in place, and they cannot detect focal ischemia. Therefore, the authors performed CBF measurements in 35 comatose head-injured patients using stable xenon-enhanced computerized tomography (CT), simultaneously with the initial CT scan (at a mean (+/- standard error of the mean) interval of 3.1 +/- 2.1 hours after injury). Seven patients with diffuse cerebral swelling had significantly lower flows in all brain regions measured as compared to patients without swelling or with focal contusions; in four of the seven, cerebral ischemia (CBF less than or equal to 18 ml/100 gm.min-1) was present. Acute intracranial hematomas were associated with decreased CBF and regional ischemia in the ipsilateral hemisphere, but did not disproportionately impair brain-stem blood flow. Overall, global or regional ischemia was found in 11 patients (31.4%). There was no correlation between the presence of hypoxia or hypertension before resuscitation and the occurrence of ischemia, neither could ischemia be attributed to low pCO2. Ischemia was significantly associated with early mortality (p less than 0.02), whereas normal or high CBF values were not predictive of favorable short-term outcome. These data support the hypothesis that ischemia is an important secondary injury mechanism after traumatic brain injury, and that trauma may share pathophysiological mechanisms with stroke in a large number of cases; this may have important implications for the use of hyperventilation and antihypertensive drugs in the acute management of severely head-injured patients, and may lead to testing of drugs that are effective or have shown promise in the treatment of ischemic stroke.     

The future of outcomes measurement: item banking,tailored short-forms,and computerized adaptive assessment

The use of item banks and computerized adaptive testing (CAT) begins with clear definitions of important outcomes, and references those definitions to specific questions gathered into large and well-studied pools, or “banks” of items. Items can be selected from the bank to form customized short scales, or can be administered in a sequence and length determined by a computer programmed for precision and clinical relevance. Although far from perfect, such item banks can form a common definition and understanding of human symptoms and functional problems such as fatigue, pain, depression, mobility, social function, sensory function, and many other health concepts that we can only measure by asking people directly. The support of the National Institutes of Health (NIH), as witnessed by its cooperative agreement with measurement experts through the NIH Roadmap Initiative known as PROMIS (www.nihpromis.org), is a big step in that direction. Our approach to item banking and CAT is practical; as focused on application as it is on science or theory. From a practical perspective, we frequently must decide whether to re-write and retest an item, add more items to fill gaps (often at the ceiling of the measure), re-test a bank after some modifications, or split up a bank into units that are more unidimensional, yet less clinically relevant or complete. These decisions are not easy, and yet they are rarely unforgiving. We encourage people to build practical tools that are capable of producing multiple short form measures and CAT administrations from common banks, and to further our understanding of these banks with various clinical populations and ages, so that with time the scores that emerge from these many activities begin to have not only a common metric and range, but a shared meaning and understanding across users. In this paper, we provide an overview of item banking and CAT, discuss our approach to item banking and its byproducts, describe testing options, discuss an example of CAT for fatigue, and discuss models for long term sustainability of an entity such as PROMIS. Some barriers to success include limitations in the methods themselves, controversies and disagreements across approaches, and end-user reluctance to move away from the familiar.     

Multiple internal resorptions in deciduous teeth: a case report

We report a case of rare multiple internal resorptions. Etiology of multiple internal resorptions is unknown. Interestingly, the patient had an atopic dermatitis, which is possibly related to multiple and rapid internal resorptions.     

Relationship of transforming growth factor beta 1 to angiogenesis in gastric carcinoma.

Transforming growth factor-beta (TGF-beta) comprises a group of multifunctional regulatory proteins, whose effects include angiogenesis. The expression of TGF-beta 1 in gastric carcinomas (70 cases) has been determined and related to pathological features and microvessel count by immunohistochemical staining for TGF-beta 1 and Factor VIII related antigen. Prominent reactivity for TGF-beta 1 was associated with the depth of invasion (r = 0.2; p < 0.05) and increased microvessel count (r = 0.5; p < 0.05). Also, the microvessel count had a significant correlation with invasiveness (r = 0.34; p < 0.05) and lymph node metastasis (r = 0.28; p < 0.05). These findings indicate that TGF-beta 1 may have a role in tumor invasion and angiogenesis.     

Flavonoids from the leaves ofRhododendron brachycarpum

The flavonoids isolated from the leaves ofRhododendron brachycarpum, were identified as quercetin, avicularin, quercitrin and hyperin.