Calcium decreases transparency of homogenate from lens cortex and has no effect on nucleus

We studied the effects of calcium on transparency in homogenates of cortical and nuclear cells from calf lenses. Calcium was mixed into samples of homogenate to final concentrations between 0 and 50 mM and the transparency of the calcium-treated homogenates was measured using laser transmittance. In the presence of 10 mM calcium, the transmittance of cortical homogenate decreased 50% while the nuclear homogenate lost less than 4% transmittance after 24 h at 37 degrees C. To better understand the contribution of cytoplasm and membranes to opacity, the nuclear and cortical homogenates were centrifuged to separate membranes from the cytoplasm. When 10 mM calcium was added to cortical homogenate which was then centrifuged, the transmittance of the membrane fraction decreased nearly 60%, while the fraction without membrane decreased only 10%. The strong effect of calcium on the membrane fraction was accompanied by an increase in specific gravity of membranes from 1.23 to 1.32. Ten- and 20 mM calcium had no effect on transparency of membranes or cytoplasm separated from nuclear homogenate, and 50 mM calcium produced only a slight opacity. The results indicate that an effect on membrane-protein interactions may be important in the loss of transparency produced by calcium in cells of lens cortex.     

The bioavailability and nonlinear pharmacokinetics of MK-679 in humans

MK-679 (R(?)-3-((3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)(3-(dimethylamino)-3-oxopropyl)thio)methyl)thio(propanoic acid) is a potent and specific LTD₄-receptor antagonist. The disposition of MK-679 was investigated in a three-way crossover study in 12 healthy males receiving single intravenous doses of 75, 250, and 500 mg of MK-679. A greater than proportional increase in the area under the plasma concentration—time curve of MK-679 was observed with increase in dose. The plasma concentration data for each subject fitted well to the differential equations for a two-compartment model with linear tissue distribution and Michaelis-Menten elimination from the central compartment, indicating that the elimination of MK-679 in humans is saturable. In a previous study, the disposition of MK-679 in humans was also dose-dependent when given together with its S(+)-isomer, L-668,018. Thus, the disposition of MK-679 in humans is dose-dependent regardless of the presence of its stereoisomer. Also, the bioavailability of MK-679 was determined in six healthy males receiving simultaneously an oral dose of 250 mg of MK-679 and intravenous infusion of 1 mg ¹⁴C-MK-679. Results of this study indicate that the oral bioavailability of MK-679 is nearly quantitative.     

Phase I and pharmacologie study of liposomal daunorubicin (DaunoXome)

Summary We have completed a phase I and pharmacology study of liposomally-encapsulated daunorubicin (DaunoXome). Of 32 patients entered, 30 were evaluable. No toxicity was encountered at the initial doseescalation steps from 10 to 60 mg/m². At 80 mg/m², two patients manifested grade 2 neutropenia. At least grade 3 neutropenia occurred in all patients receiving 120 mg/m². Alopecia and subjective intolerance were mild. Cardiotoxicity was not observed except for an episode of arrhythmia in a patient with lung cancer and prior radiation. Only one minor objective response was observed in this population of refractory solid tumors. Pharmacokinetics differed from those of the free drug with no detection of daunorubicinol. We recommend future phase II studies with a dose of 100 mg/m² in previously treated and 120 mg/m² of DaunoXome in previously untreated patients with solid tumors.EDW is supported in part by ACS award 92-14-1     

Techniques of splenic preservation using fibrin glue

Fibrin glue (FG) was used to achieve hemostasis of 16 splenic injuries in 14 patients. The etiologies of injury included five gunshot wounds, two stab wounds, four iatrogenic injuries, and five patients with blunt splenic trauma. The intraoperative blood loss averaged 1.8 +/- 2.4 (SD) liters and patients were transfused 3 +/- 2 units of blood perioperatively. The amount of FG required to achieve splenic hemostasis averaged 11 +/- 8 ml and varied directly with the grade of injury. One patient with a splenic hilar vascular injury (Grade V) underwent splenectomy following failure to achieve complete hemostasis despite the use of 25 ml of FG. All other splenic injuries were successfully managed using less than 25 ml of FG. Postoperative computerized tomographic (CT) scanning, performed in ten patients, was negative for rebleeding or abscess formation. The overall splenic salvage rate was 86%. FG was effective in achieving hemostasis of both superficial and deep splenic injuries. Its use as an adjunct in trauma surgery should result in increased splenic salvage rates compared with that obtained using conventional surgical techniques.     

Carbohydrate metabolism in children receiving growth hormone for 5 years

Carbohydrate metabolism was evaluated by fasting and postprandial glucose, insulin, and hemoglobin (Hb)A_1c levels in children with chronic renal insufficiency and various other growth disorders treated with growth hormone. Mean fasting and postprandial glucose remained unchanged throughout the 5-year study period in all four study groups. Median fasting insulin levels rose from lownormal levels into the normal range after 5 years of growth hormone. Average fasting insulin level after 5 years was 10 mU/l. Median postprandial insulin values also rose, yet remained within the normal range at the 5-year mark. Mean Hb A_1c levels remained within low to middle end of the normal range in the patients with growth hormone deficiency, Turner syndrome, and idiopathic short stature. Mean Hb A_1c levels at the 5 years were slightly elevated to 6.3% for the patients with chronic renal insufficiency.     

How Frequent Are Asthma Exacerbations in a Pediatric Primary Care Setting and Do Written Asthma Action Plans Help in Their Management?

Purpose. In the National Heart, Lung, and Blood Institute Guidelines for the Diagnosis and Management of Asthma, the expert panel recommends that a written asthma action plan be provided for all patients with asthma. Studies evaluating the usefulness of the asthma action plan in children are limited. We aim to determine exacerbation frequency and usefulness of the asthma action plan in managing exacerbations that occur in a pediatric primary care setting. Methods. Caretakers of asthmatic children attending the general pediatric clinic in an inner-city hospital completed a one-page questionnaire covering topics such as asthma severity, frequency of exacerbations, and possession/usefulness of an asthma action plan. Although controversy exists over the definition of yellow and red zone exacerbations, we defined the yellow zone as symptoms that require albuterol more than three times a day or more than two nights in succession. The red zone was defined as symptoms requiring systemic corticosteroids and/or an urgent physician visit. Results. Seventy of 75 subjects completed the survey. Almost 80% of respondents carried the diagnosis of persistent asthma, whereas the remainder had intermittent asthma. Exacerbation frequency over a 3-month period was determined. Approximately 80% of children experienced at least one yellow zone episode: 42% had one or two yellow zone episodes, and 39.6% had between three and five episodes. Sixty-three percent of patients did not experience a single red zone exacerbation. Almost 75% (44 of 59) of subjects possessed an asthma action plan. Ninety percent (37 of 41) of respondents with action plans found the plan to be useful in managing exacerbations. Conclusion. Approximately four of every five asthmatic children seen in this primary care setting experienced a yellow zone exacerbation at least once during a 3-month period. One third experienced at least one red zone episode. Nine of every 10 caretakers with an action plan reported the asthma action plan to be of value in managing exacerbations.     

Keratoacanthoma-Like Squamous Cell Carcinoma Within the Fibroepithelial Polyp

Acrochordons (skin tags) are often considered clinically insignificant cutaneous redundancies that should be removed and destroyed with no histopathologic analysis performed. One rarely finds another neoplasm within an acrochordon. We describe a patient with an acrochordon that contained a squamous cell carcinoma that had features resembling a keratoacanthoma. This is the first time to our knowledge that an invasive squamous cell carcinoma has been described within an acrochordon.