The influence of protein solubilisation, conformation and size on the burst release from poly(lactide-co-glycolide) microspheres.

Encapsulation of proteins in poly(lactide-co-glycolide) microspheres via emulsion is known to cause insoluble protein aggregates. Following protein emulsification and encapsulation in PLGA microspheres, we used circular dichroism to show that the recoverable soluble protein fraction also suffers subtle conformational changes. For a panel of proteins selected on the basis of molecular size and structural class, conformational stability measured by chemical denaturation was not indicative of stability during emulsion-encapsulation. Partial loss of structure was observed for alpha-helical proteins released from freeze-dried microspheres in aqueous buffer, with dramatic loss of structure for a beta-sandwich protein. The addition of sucrose (a lyoprotectant) did not prevent the loss of protein conformation upon encapsulation. Therefore, the conformational changes seen for the released soluble protein fraction originates during emulsification rather than microsphere freeze-drying. Analysis of the burst release for all proteins in buffer containing denaturant or surfactant showed that the degree of protein solubilisation was the dominant factor in determining the initial rate and extent of release. Our data for protein release into increasing concentrations of denaturing buffer suggest that the emulsion-denatured protein fraction remains insoluble; this fraction may represent the protein loss encountered upon comparison of protein encapsulated versus protein released.     

Electron beam therapy for eyelid carcinomas

Forty-six (85%) basal cell and eight (15%) squamous cell carcinomas of the eyelids were treated with electron beams between 1963 and 1983. Lesion sizes ranged from microscopic to 4 cm, with 28 lesions larger than 1 cm. Thirty-eight lesions were treated with radiotherapy after incisional biopsy, and 16 were treated after excisional biopsy (specimens showed positive margins). Doses varied from 45 to 72 Gy, with daily fractions ranging from 2.12 to 4.0 Gy. There were six disease recurrences (10.9%): three in the treatment field and three at the treatment margin. Four of six recurrences were subsequently controlled by limited surgical excision and repair with preservation of the eye, whereas the other two required enucleation. Treatment sequelae such as skin atrophy, telangiectasis, and cosmetic results were evaluated in terms of radiotherapy parameters, pretreatment surgery, and size of the lesion. In 44 patients, the overall cosmetic result was judged as good to excellent, five patients had a mild to modest degree of deformity, and five had significant deformity. Such deformity was usually associated with tumor destruction or previous surgery. No major complications were noted.     

Serum protein electrophoresis patterns in chronic lymphocytic leukemia. Clinical and epidemiologic correlations

Serum protein electrophoresis (SPEP) data obtained at diagnosis were available for 98 of 342 patients with chronic lymphocytic leukemia (CLL) identified in a population-based case-control epidemiologic study. Patients tested with SPEP at diagnosis were significantly younger, more likely to have lymphadenopathy, and more likely to have had their conditions diagnosed at a university hospital than those not tested. Four categories of electrophoretic patterns were identified: normal (N = 56), hypogammaglobulinemia (N = 28), hypergammaglobulinemia (N = 11), and monoclonal gammopathy (N = 3). A higher proportion of those with hypergammaglobulinemia were black, and patients with hypergammaglobulinemia and monoclonal gammopathy were more likely to die within the first year following diagnosis than patients in the other SPEP groups. No association was found, however, between SPEP pattern and a clinical staging classification for CLL. These findings suggest that SPEP may be a useful adjunct in categorizing possible subtypes of CLL and developing future clinical staging classifications.     

Differences between mentally retarded and nonretarded persons' efficiency of auditory sentence processing

Mentally retarded adolescents and MA-matched nonretarded children participated in three experiments designed to examine differences in language-processing efficiency. A compressed speech technique was used in Experiments 1 and 2. Experiment 3 relied on a sentence-picture verification procedure. Our results suggest that retarded and nonretarded individuals differ in the speed with which they are able to execute the semantic-analytic processes but not necessarily the phonological encoding processes that are involved in auditory language comprehension. In addition, the data suggest a possible group difference in the quality of the semantic representation encoded during sentence processing.     

Characteristics and motives of women choosing elective induction of labour

Personal characteristics of healthy term pregnant women who chose elective induction or spontaneous onset of labour and the motives for their choice were assessed. Almost 50% of 237 women with uncomplicated pregnancies opted for elective induction when offered the opportunity. These women appeared to have had more complaints during their pregnancy and menstrual periods, more complications in their obstetrical history and to be more anxious about their labour than women who chose a spontaneous onset of labour. Predominant motives were a feeling of safety and the desire to shorten the duration of pregnancy. These characteristics and motives seem to reflect a lack of trust in physical reproductive functions. It is concluded that in evaluating effects of elective induction of labour, pre-existing differences between women who choose elective induction and women who opt for a spontaneous onset must be taken into account.     

Utility of operative ultrasound in the surgical management of liver tumors.

In this study the utility of operative ultrasound in the surgical management of 98 consecutive patients with liver and gastrointestinal tumors was assessed. All patients had preoperative work-up including ultrasound study of the liver as well as selective hepatic arteriography (50 patients) and computerized tomography of the liver (45 patients). At surgery, inspection and palpation of the liver as well as operative ultrasound examination were performed in all cases. Fifty-six patients were known to have liver tumors before operation, while 42 patients had their liver examined as part of the treatment of a primary gastrointestinal malignancy. A total of 126 liver tumors were found in 58 patients, all of whom were confirmed histologically. Eighteen nodules unsuspected before operation were found at surgery--nine by inspection and palpation of the liver, and nine others that were nonpalpable were found by operative ultrasound only. Eighteen lesions that were missed by all diagnostic modalities were found as secondary lesions on pathologic examination of the resected specimens. In addition to diagnostic applications, operative ultrasound was useful in localizing nodules and permitting guided biopsies deep in the hepatic parenchyma. In eight cases, segmental resections were performed with operative ultrasound to localize the plane of section and to catheterize the intrahepatic portal vein branch afferent to the tumor in order to perform balloon catheter occlusion of the vessel for control of bleeding. Operative ultrasound was found to be important in the surgical management of 19 of 98 patients (19%).