Photofrin photodynamic therapy for treatment of AIDS-related cutaneous Kaposi's sarcoma.

OBJECTIVE: Kaposi's sarcoma, the most common malignancy in AIDS patients, often presents with painful cutaneous lesions that are difficult to treat effectively despite a wide variety of therapeutic approaches. We used photodynamic therapy in an attempt to provide effective palliative treatment for this disease. METHODS: Photodynamic therapy utilizes the activation by light of a photosensitizing drug that preferentially accumulates in tumor tissue such as Kaposi's sarcoma. We enrolled 25 patients who received 1.0 mg/kg of Photofrin 48 h before exposure to 100-400 J/cm2 of 630 nm light. RESULTS: Of the 348 lesions treated, 289 were evaluable: 32.5% had complete clinical response, 63.3% had partial clinical response and 4.2% were clinical failures. There was a strong correlation between response and light dose: 54% of lesions achieved a complete clinical response at optimum light dose (> 250 J/cm2). There was no correlation of response with CD4 cell count nor was there a change in CD4 cell count post-treatment. At 400 J/cm2 full field scabbing and necrosis occurred in 90% of the treated fields. Thus, the maximum tolerated dose was determined to be 300 J/cm2. At light doses of 250 J/cm2 and below the toxicities were limited to erythema and edema in the treatment field. Forty-three biopsies were taken 0.5 h to 4 months post-treatment. These showed little change in the B and T cell infiltrates identified. Kaposi's sarcoma cells disappeared post-treatment in certain lesions. CONCLUSION: Photofrin is effective palliative treatment for HIV-associated Kaposi's sarcoma.     

Awareness during anesthesia: a closed claims analysis.

BACKGROUND: Awareness during general anesthesia is a frightening experience, which may result in serious emotional injury and post-traumatic stress disorder. We performed an in-depth analysis of cases from the database of the American Society of Anesthesiologists Closed Claims Project to explore the contribution of intraoperative awareness to professional liability in anesthesia. METHODS: The database of the Closed Claims Project is composed of closed US malpractice claims that have been collected in a standardized manner. All claims for intraoperative awareness were reviewed by the reviewers to identify patterns of causation and standard of care. Logistic regression analysis was used to identify independent patient and anesthetic factors associated with claims for recall during general anesthesia compared to other general anesthesia malpractice claims. RESULTS: Awareness claims accounted for 79 (1.9%) of 4,183 claims in the database, including 18 claims for awake paralysis, i.e., the inadvertent paralysis of an awake patient, and 61 claims for recall during general anesthesia, ie., recall of events while receiving general anesthesia. The majority of awareness claims involved women (77%), younger than 60 yr of age (89%), American Society of Anesthesiologists physical class I-II (68%), who underwent elective surgery (87%). Most (94%) claims for awake paralysis represented substandard care involving errors in labeling and administration, whereas care was substandard in only 43% of the claims for recall during general anesthesia (P < 0.001). Claims for recall during general anesthesia were more likely to involve women (odds ratio [OR] = 3.08, 95% confidence interval [CI] = 1.58, 6.06) and anesthetic techniques using intraoperative opioids (OR = 2.12, 95% CI = 1.20, 3.74), intraoperative muscle relaxants (OR = 2.28, 95% CI = 1.22, 4.25), and no volatile anesthetic (OR = 3.20, 95% CI = 1.88, 5.46). CONCLUSIONS: Deficiencies in labeling and vigilance were common causes for awake paralysis. Claims for recall during general anesthesia were more likely in women and with nitrous-narcotic-relaxant techniques.     

DFP action on rat superior colliculus: localization and role of cholinergic receptors

DFP, an irreversible acetylcholinesterase inhibitor, markedly increases spontaneous unit activity and reduces light-evoked responses in the superficial layers of the rat superior colliculus (Cheney et al., 1987). The purpose of this study was to investigate: (1) the sites of DFP action within the retino-tectal pathway (retinal, central or both), and (2) the types of cholinergic receptors (muscarinic, nicotinic, or both) involved. DFP increased SGS unit activity when injected intraocularly, confining its action to the retina, or when given systemically in bilateral enucleate rats. Thus, DFP acts at both retinal and central sites to increase unit activity in the SGS. Pretreating with muscarinic receptor antagonists such as atropine or scopolamine blocked DFP's effects at both sites whereas the nicotinic receptor antagonist mecamylamine was ineffective. Moreover, DFP's actions were mimicked by injections of the muscarinic receptor agonist, oxotremorine. The oxotremorine effects were also blocked or reversed by treatment with atropine or scopolamine. We conclude that DFP acts at both retinal and central sites to influence SGS unit activity and, at both sites, muscarinic receptors mediate DFP's effects.     

Noncardiogenic pulmonary edema caused by decompression sickness: rapid resolution following hyperbaric therapy

Noncardiogenic pulmonary edema is a recognized but uncommon manifestation of type 2 decompression sickness. It typically occurs within 6 hours of a dive. Because the adult respiratory distress syndrome in this setting is believed to be due to microbubbles in the pulmonary vasculature, recompression in a hyperbaric chamber has been recommended as a form of therapy. A patient developed noncardiogenic pulmonary edema following a seawater dive to 75 feet. There was complete radiologic and clinical resolution within 5 hours of hyperbaric therapy.     

Isolation and characterization of murine cell surface components. I. Purification of milligram quantities of Thy-1.1

The Thy-l.1 molecule was isolated from the BW5147 murine lymphoblastoid cell line. The initial step in purification was the preparation of a crude plasma membrane fraction followed by acetone precipitation. The acetone pellet was solubilized using deoxycholate (DOC) and Thy-1.1 was purified by use of a Lens culinaris lectin affinity column and an AcA-34 gel filtration column. The purified glycoprotein with Thy-1.1 activity had a mol wt of approximately 25,000 daltons. The isolation of this molecule was effected by detecting Thy-I activity utilizing rabbit anti- mouse brain serum tested on rat thymocytes. Congenic anti-Thy-l.1 serum was ineffective in detecting Thy-l.1 after DOC solubilization. An antiserum prepared in rabbits to the purified Thy-1.1 was found to be cytotoxic to mouse and rat thymocytes. The cytotoxic activity of this antisera could be completely absorbed with AKR/Jax brain and thymus but was not absorbed by liver. In addition, AKR/Jax thymocytes totally absorbed all cytotoxic activity of the rabbit anti-purified Thy-1 serum for BW5147 cells suggesting that the cell line shares identical specificities with normal thymocytes. The purified Thy-1.1 molecule was able to totally absorb the cytotoxic activity of mouse congenic anti-Thy-1. These studies serve as a model for the isolation of other murine lymphoid cell surface components in quantities for detailed structural and functional analysis.     

Mild hemophilia A with factor VIII assay discrepancy: using thrombin generation assay to assess the bleeding phenotype

Summary.  Introduction:  In some patients with mild hemophilia A, there are discrepancies between 1-stage (1-st) and 2-stage (2-st) factor VIII (FVIII) clotting assays, and also chromogenic assays for FVIII activity (FVIII:C). We examined whether thrombography could provide a better evaluation of the hemostatic status of these patients. Methods:  Two families with such discrepancies and markedly contrasting clinical histories were studied. Family X had no serious bleedings, in contrast to family Y. Sixty-one moderate/mild hemophiliacs without discrepancy and 15 healthy subjects served as controls. Calibrated automated thrombography was performed with platelet-rich plasma after one freeze-thawing cycle and low tissue factor concentration. Results:  The chromogenic FVIII:C levels were higher (0.90 ± 0.15 and 0.47 ± 0.13 IU mL⁻¹) than the 1-st clotting ones (0.14 ± 0.05 and 0.10 ± 0.05 IU mL⁻¹) in family X and Y, respectively ( P  < 0.001). Mean endogenous thrombin potential (ETP) was 1579 ± 359 n m  min⁻¹ and 1060 ± 450 for healthy controls and hemophilic controls, respectively. For members of family X, the ETP values were 1188, 1317 and 2277 n m  min⁻¹, whereas for those of family Y they ranged from 447 to 1122 n m  min⁻¹. Two novel missense point mutations were evidenced: p.Ile369Thr in family X and p.Phe2127Ser in family Y. In family X, we postulate that the mutation is responsible for a delayed but non-deleterious FVIII activation. Conclusions:  Our results suggest that the hemostatic phenotype assessed by thrombography may be clinically relevant in moderate/mild hemophilic patients with discrepant FVIII:C results.