The microchromatographic measurement of fetal hemoglobin levels in hemoglobin C-associated conditions.

We report the microchromatographic estimation of fetal hemoglobin (Hb F) in 3 conditions associated with hemoglobin C: hemoglobin C-hereditary persistence of fetal hemoglobin (Hb C-HPFH), homozygous hemoglobin C disease, and hemoglobin SC disease. In the case of Hb C-HPFH (Case 1) the Hb F level by alkali denaturation was 32.5% while the Hb F level by microchromatography was 35.3%. In both cases of homozygous Hb C disease and Hb SC disease the Hb F level by alkali denaturation was less than 1% and the microchromatographic Hb F level was 0.7%. We conclude that microchromatographic methods for determination of Hb F levels can be employed in the Hb C-HPFH, homozygous Hb C, and Hb SC conditions. To our knowledge, the microchromatographic determination of Hb F levels has not been applied previously to the Hb C-HPFH condition or Hb C disease.

Hyperkalemia secondary to concurrent pharmacotherapy in a patient receiving home parenteral nutrition.

We report a case of probable combined octreotide- and heparin-induced hyperkalemia. The patient had been receiving home parenteral nutrition, enoxaparin, and octreotide for 10 months. She required very little potassium in her PN solution to maintain serum potassium concentrations in the normal range. The patient reportedly did not receive other medications or have clinical conditions that, to our knowledge, cause hyperkalemia. She maintained normal renal function throughout the hospitalization and did not appear to have any significant acid-base disorders. Practitioners should be aware of the potential for octreotide and heparin to cause hyperkalemia. Regular monitoring of serum potassium concentrations should be done for patients receiving octreotide and heparin to avoid hyperkalemia.

Annulate lamellae in human malignant tumors: report of three cases.

During the course of applying electron microscopy to diagnostic surgical pathological specimens, three malignant tumors (malignant melanoma, fibrous mesothelioma, lymphoblastic lymphoma) were found to contain annulate lamellae, distinctive intracytoplasmic organelles composed of membrane stacks interrupted by constrictions or pores. In one case both annuli and lamellae were present, a combination rarely described in human tissue and in animal models. In this material, the annuli of the annulate lamellae were structurally similar to nuclear pores. It is postulated that the abundant fibrils are probably related to the unusual configuration of the annulate lamellae. A morphologic relationship of the annulate lamellae to both the endoplasmic reticulum (cases 1 and 2) and the nuclear membrane (case 3) supports the theory that annulate lamellae may be related to both of these structures.

The in vitro and in vivo ocular pharmacology of olopatadine (AL-4943A), an effective anti-allergic/antihistaminic agent.

Olopatadine (AL-4943A; KW-4679) [(z)-11-[3-(dimethylamino)propylidene]-6, 11-dihydrodibenz[b,e]oxepine-2 acetic acid hydrochloride] is an anti-allergic agent which inhibits mast cell mediator release and possesses histamine H1 receptor antagonist activity. Studies were conducted to characterize the in vitro and in vivo pharmacological profile of this drug relevant to its topical ocular use. AL-4943A inhibits histamine release in a concentration-dependent fashion (IC50 = 559 microM) from human conjunctival mast cell preparations in vitro. Histamine release was not stimulated by AL-4943A at concentrations as high as 10 mM. In contrast, ketotifen stimulated histamine release at concentrations slightly higher than effective inhibitory concentrations. AL-4943A did not display any in vitro cyclooxygenase or 5-lipoxygenase inhibition. Topical ocular application of AL-4943A effectively inhibits antigen- and histamine-stimulated conjunctivitis in guinea pigs. Passive anaphylaxis in guinea pig conjunctiva was attenuated by AL-4943A applied 30 min prior to intravenous or topical ocular antigen challenge (ED50 values 0.0067% and 0.0170%, w/v, respectively). Antihistaminic activity in vivo was demonstrated using a model of histamine-induced vascular permeability in guinea pig conjunctiva. AL-4943A applied topically from 5 min to 24 hrs prior to histamine challenge effectively and concentration-dependently inhibited the vascular permeability response, indicating the compound has an acceptable onset and a long duration of action. Drug concentrations 5-fold greater than those effective against histamine-stimulated conjunctival responses failed to inhibit vascular permeability responses induced with either serotonin or Platelet-Activating-Factor. These data indicate that the anti-histaminic effect observed with AL-4943A is specific. These anti-allergic/antihistaminic activities of AL-4943A observed in preclinical model systems have been confirmed in clinical trials in allergic patients.

Preclinical efficacy of emedastine, a potent, selective histamine H1 antagonist for topical ocular use.

Emedastine [1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)- benzimidazole difumarate] was evaluated for topical ocular anti-histaminic activity in histamine and antigen stimulated conjunctivitis models. Concentration-dependent inhibition of histamine induced vascular permeability changes occurring in the conjunctiva was observed when the time interval between topical ocular administration and histamine challenge ranged from 1 min to 8 hr. The calculated ED50 values obtained using intervals of 1 min, 30 min, 2, 4 and 8 hr were 0.0002%, 0.000035%, 0.0029%, 0.019% and 0.19%, w/v, respectively. Comparisons of relative potency 30 min post dosing between emedastine and other anti-histamines demonstrated that emedastine is equipotent to ketotifen, and 7, 7, 10, 10, 100, 357, 3333, and 5813 times more potent than brompheniramine, chlorpheniramine, clemastine, pyrilamine, levocabastine, pheniramine, diphenhydramine, and antazoline, respectively. Emedastine (0.1%) failed to significantly attenuate either serotonin or platelet-activating-factor induced vascular permeability changes indicating high selectivity for the histamine H1 receptor. In a passive conjunctival anaphylaxis model in guinea pigs, significant inhibition of the allergic response was observed following topical ocular administration of emedastine 5 min or 30 min prior to antigen challenge (ED50s 0.0046% and 0.00022%, respectively). These data clearly indicate that emedastine has potential as a topical ocular anti-histamine for treating allergic conjunctivitis.

All-terrain vehicle injury in children: strategies for prevention.

OBJECTIVE: A variety of educational efforts, policies, and regulations have been adopted to reduce all-terrain vehicle (ATV) injury in children. Despite this, ATV use by children continues and serious injuries are common. The purpose of this study was to investigate the knowledge, practices, and beliefs of ATV users to help develop effective educational strategies to promote safer ATV use. DESIGN: Focus groups were conducted to characterize participant ATV use and safety awareness as well as to explore avenues for prevention. Feedback on draft ATV safety public service announcements was elicited. Themes of transcribed focus group data were summarized. SETTING: Rural state with high ATV use and injury rates. SUBJECTS: Adult and adolescent ATV users. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Summaries of focus group discussions. RESULTS: ATV riders frankly discussed current use and safety behaviors and were aware of some ATV risks. Youths felt that age specific regulation was unlikely to be a helpful strategy. Participants endorsed messages demonstrating graphic consequences as likely to get the attention of young riders regarding risks. Educational settings were suggested, including hunter and driver safety classes. CONCLUSIONS: Efforts to improve ATV safety awareness should clearly show pediatric ATV injury risk and safety practices. Campaigns must also show realistic understanding of current use practices to be credible for users. Messages emphasizing the consequences of ATV use were endorsed as most likely to have impact. Approaches based on age based restrictions were considered unrealistic and alternative strategies were suggested.

Extended field radiation therapy in Hodgkin's disease: analysis of failures.

A retrospective analysis of 116 primary cases of stage I, II and III-A Hodgkin's disease demonstrated 27 failures, fourteen confirmed by biopsy. Twenty of the 27 (74%) were in lymph node areas only and seven had extranodal extensions. The most frequent site of failure was the hilar nodes and contiguous lung. The majority of failures (78%) occurred within 30 months of treatment and the cause of failure determined in 23 (85%), sixteen of which were due to technical errors of irradiation. Analysis of the dosimetry in the mediastinal, hilar nodes and contiguous lung failures revealed three factors which may have contributed to a low dose. These factors are: 1) the equivalent square, 2) off-axis beam diminution, and 3) the anteroposterior dose profile. Combined radiation therapy and chemotherapy was more effective than either modality alone in the treatment of these failures.