Lipid-drug conjugate nanoparticles of the hydrophilic drug diminazene-cytotoxicity testing and mouse serum adsorption.

Sleeping sickness is a widely distributed disease in great parts of Africa. It is caused by Trypanosoma brucei gambiense and rhodiense, transmitted by the Tse-Tse fly. After a hemolymphatic stage, the parasites enter the central nervous system where they cannot be reached by hydrophilic drugs. To potentially deliver the hydrophilic antitrypanosomal drug diminazene diaceturate to the brain of infected mice, the drug was formulated as lipid-drug conjugate (LDC) nanoparticles (NP) by combination with stearic- (SA) and oleic acid (OA). To estimate the in vivo compatibility, the particles were incubated with human granulocytes. Because as potential delivery mechanism the absorption of specific serum proteins (ApoE, Apo AI and Apo AIV) was found to be responsible for the delivery of nanoparticles to the brain, demonstrated using PBCA nanoparticles coated with polysorbate 80 (LDL uptake mechanism) the nanoparticles were incubated with mouse serum and the adsorption pattern was determined using the 2-D PAGE technique. As a result of this study, the cytotoxic potential was shown to decrease when diminazene is part of the particle matrix compared to pure fatty acid nanoparticles and the mouse serum protein adsorption pattern differs from the samples studied earlier in human serum. Especially, the fact concerning Apo-E that could be detected when the particles were incubated in human serum is absent after the mouse serum incubation, potentially, is a critical point for the delivery via the LDL-uptake mechanism but the data demonstrate that LDC nanoparticles, with 33% (wt/wt) drug loading capacity possess the potential to act as a delivery system for hydrophilic drugs like diminazene diaceturate and that further studies have to demonstrate the usability as a brain delivery system.     

Female patients complaining about hair loss: documentation of defective scalp hair dynamics with contrast-enhanced phototrichogram

BACKGROUND: The complaint of chronic hair loss frequently affects female subjects and there is little or no objective technology available in the general dermatology or even in the hair clinics to guide the observer in the management of the patient. The purpose of this report is to share the results of refined hair growth measurements that were collected in 92 female subjects complaining about hair loss. METHODS: Clinically they were classified as having a patterned hair loss according to Ludwig (L; n=50), diffuse hair loss (D; n=13) or no visible hair loss but complaining of hair shedding (N; n=29). Two scalp sites on the top of the head and one occipital site were investigated after clipping by close-up photography before and after a hair dye (contrast enhancement, CE). Forty-eight hours later a new photograph was taken after CE in view of phototrichogram analysis (CE-PTG). Finally a last hair clip was performed 30 days later and hair thickness and length determined for linear growth measurements (LHGR). RESULTS: Herein we confirm that the top of the head shows usually a higher hair density than occipital sites, a physiological observation that applies both to men and women. From the technological perspective, we also document that CE improves hair detection in all sites. Interestingly, in affected patients (L and D) the relative increase of hair counts after CE was much higher (range +22.4% to +28.3%) compared with apparently unaffected females (N; range +8.2% to +9.7%). This increase in hair counts was only due in part to the presence of less pigmented thinning hair (thickness less than 40 microm). Such thin hairs were found in statistically significantly higher proportions in younger patients with mildly severe (grade I) patterned alopecia (Ludwig: L). In other patients with hair loss and in more severe forms of patterned alopecia - especially in older patients - the thin hair is not detected in abnormal proportions. In all sites slower growth rates and decreased anagen percentages indicate a defective hair replacement programme distinguishing L patterns from diffuse hair loss and from apparently unaffected patients complaining of chronic hair loss. Globally, we also noted that increasing age is associated with significant regression of scalp hair (decreased hair counts, thinner hair and slower LHGR). CONCLUSION: On the basis of the present data together with female data from the literature and our own studies in male subjects, we suggest a three-step mechanism leading to hair loss 1.Shortening of growth phase the hair cycle with maintained thick hair, i.e. more frequent hair cycling that leads to more hair shedding. 2.Intermittent production of short thin hair, i.e. morphological evidence of miniaturisation. 3.Very occasional or almost no hair production, i.e. dormant follicles or irreversible follicular atrophy. Depending on the genetic background, hormonal microenvironment in the scalp and conditioning of individual hair follicle bio-responses, female and male patterned hair loss may end up into different phenotypes.     

Boerhaave’s syndrome: Primary repair vs. esophageal resection—Case reports and meta-analysis of the literature

Boerhaave’s syndrome is a life-threatening disease with a high mortality. With regard to the heterogeneity of treatment strategies, no comparative studies exist and recommendations remain controversial. Seventeen cases of Boerhaave’s syndrome operated on between 1989 and 2000 at our hospital were reviewed retrospectively to compare the time period between perforation and diagnosis, and the morbidity and mortality among the different treatment options. In addition, we conducted a meta-analysis of the literature including all series containing five or more patients and compared the findings with our own data. Our patients with a perforation history of less than 12 hours showed significantly fewer signs of sepsis compared to patients with a history of more than 12 hours. In a comparison of patients with primary repair vs. patients treated with esophageal resection or an exclusion operation, no differences were found. In the literature, patients with a long period of perforation (more than 24 hours) were treated more often with an esophageal resection than patients with primary repair. In cases of Boerhaave’s syndrome, primary suturing of the esophageal perforation should be reserved only for those patients presenting within 12 hours after perforation. In all other cases, depending on the extent of the tissue damage, a two-stage esophageal resection with cervical esophagostomy and gastrostomy is recommended as the safest treatment.     

Complete disappearance of lung abnormalities on high-resolution computed tomography: A case of histiocytosis X

A case of pulmonary Langerhans cell histiocytosis, proved by both lung high-resolution computed tomography and lung biopsy, is described. Following smoking cessation, lung nodules and cysts gradually disappeared on serial computed tomography scans, with complete clearance of the lesions after 12 months. The role of tobacco smoking is discussed, in detail, against the background of the literature.     

Normative values of bone parameters of children and adolescents using digital computer-assisted radiogrammetry (DXR).

PURPOSE: To verify whether estimation of bone mineral density (BMD) using digital X-ray radiogrammetry (DXR) is possible on children and to determine normative values of both such a DXR-BMD estimate and a corresponding metacarpal index (DXR-MCI) on. PATIENTS AND METHODS: In retrospect, X-rays were selected of the hands of 200 healthy Caucasian children (120 boys and 80 girls, aged 4-18 yr). The involved children were selected among a larger group of children submitted to the surgical department of our institute for evaluation of a suspected fracture after an occurred trauma. All children with a verified fracture or a chronic bone-related disease, including bone age retardation or acceleration, were excluded from the study. Furthermore, only conventional X-rays with the same film and capture parameters were included. The images were scanned and analyzed using the Pronosco X-posure system V.2 (Sectra Pronosco, Denmark). DXR-BMD, DXR-MCI, and a porosity index (DXR-PI) were automatically calculated using the midshafts of the metacarpals II-IV. Mean values of DXR-BMD and DXR-MCI were calculated separately for girls and boys in 2-yr intervals. RESULTS: In the present study the system has been demonstrated to be capable of calculating DXR-BMD from conventional X-rays of the hand from children down to approx 6 yr of age. This ability depended somewhat on the diameter and the length of the involved metacarpals. The success rate was higher for large bones than for small bones. The system succeeded in analyzing the images of 110 boys and 68 girls. Values of DXR-BMD were observed to increase with age from 0.40 g/cm2 to 0.62 g/cm2 in the male group and from 0.39 g/cm2 to 0.54 g/cm2 in the female group. Girls aged 11-12 yr had a higher DXR-BMD than did boys, corresponding to the earlier entry to puberty of girls. Standard deviations (SDs) reached values of up to 0.05 g/cm2. DXR-MCI increased with age from 0.36 to 0.47 for boys and from 0.34 to 0.49 for girls with a maximum SD of 0.06. The correlation between DXR-BMD and age was r=0.83 and r=0.84 for boys and girls, respectively. The corresponding correlations for DXR-MCI was lower, with observed correlations of r=0.63 (boys) and r=0.68 (girls), respectively, with p<0.01 in all cases. The DXR-PI did not reveal a significant correlation to age (r=-0.31 and r=0.04. respectively) and showed SDs marginally higher than the calculated mean values. CONCLUSION: The newly available DXR-methodology seems to offer the ability to determine DXR-BMD and DXR-MCI in children starting with a bone age of 6. This possibility may be of special relevance for children suffering from chronic bone diseases that require repeated X-rays of the hand (e.g. to determine bone age). The acquired normative data suggest that the measurements are of clinical value owing to low age-dependent variability (SDs) relative to an observed high increase with age. The clinical value of the porosity index (DXR-PI) remains uncertain and is limited owing to a high inter-individual variability.     

Visual acuity estimates in noncommunicative elderly persons

The acuity card procedure has been shown to provide reliable grating acuity estimates in pediatric patients. The current study was conducted to determine the usefulness of this procedure in another group of persons in whom conventional acuity measurements are not possible, ie, nursing home residents who suffer from dementing disorders. Binocular visual acuity estimates were obtained in 13 cognitively impaired nursing home residents. Test sessions took 20-30 min each. Both test-retest agreement and inter-observer agreement of Teller Acuity Card (TAC) acuity estimates were good (within 0.5 octave for all residents), demonstrating that this procedure yields reasonable acuity estimates in noncommunicative nursing home residents. The authors stress the potential of this tool for nursing home administrators as well as for researchers.     

„Gesundheit“ im Studiengang „Pflege und Gesundheit“ an der FH Hamburg - Profil- und Bedarfsschätzung

At the Fachhochschule Hamburg, a new curriculum on ‘nursing and health’ will be started in summer 1996. This paper informs about ‘health’ in the new curriculum, and the intended emphasis on epidemiology and health promotion. Then the present state of health science instruction in Germany is characterized, and the historical development of interest in this subject. Finally, the short- and long-term need for public health professionals for the north-western part of Germany is estimated.     

Leakage associated with intermediate restorative material and glass-ionomer cement retrograde fillings: a human and sheep teeth comparison with 2 different aging procedures.

OBJECTIVES: Leakage around retrograde fillings is an important cause of endodontic surgery. This in vitro study sought to compare the following: (1) methylene blue dye leakage linked to retrofillings in human and sheep teeth with the degree of dye penetration when intermediate restorative materials and Chemfil were used as retrofillings, (2) the apical microleakage in filled with that in unfilled root canals, and (3) 2 storage techniques, incubator-based and subcutaneous implantation in rats. STUDY DESIGN: Tested were 198 human and 196 sheep teeth that were retrofilled with intermediate restorative material or Chemfil, then stored in an incubator or subcutaneously in rats for 10, 20, and 30 days before immersion in methylene blue dye for 24 hours. Linear dye penetration was evaluated, and the results were statistically analyzed by means of analysis of variance. RESULTS: Leakage between sheep and human teeth was significantly different (P <.05). Chemfil had significantly less leakage than intermediate restorative material after storage in rat (P <.05) for up to 20 days, but not after 30 days. No differences were found between leakage of unfilled and filled human root canal teeth. CONCLUSIONS: The sheep incisor is a poor experimental model of the human tooth, and both aging procedures demonstrate extensive leakage of retrofilling materials after long-term storage.