Hemiarthroplasty or osteosynthesis in cervical hip fractures: matched-pair analysis in 892 patients

Our aim was to compare hemiarthroplasty (HA) and osteosynthesis (OS) in the treatment of cervical hip fractures using matched-pair analysis, especially with regard to different age groups. Data concerning all hip fractures (excluding pathological fractures) at the University Hospitals of Lund in Sweden, where osteosynthesis with LIH hook-pins was used exclusively, and of Oulu in Finland, using mainly cementless Austin-Moore hemiarthroplasty, were registered during 1989-1996 using the same standardized hip fracture forms filled in preoperatively and at 4 months follow-up. Altogether 446 pairs matched for age, sex, place of residence and walking ability at the time of fracture were found. Patients aged 55-80 years seemed to benefit more, with regard to function, from OS than older patients. At 4 months follow-up, 38% of HA and 48% of OS patients lived in their own homes, 16% and 27% were able to walk alone outdoors, and 11% versus 16% were able to walk without any aids, respectively. At 1 year follow-up, mortality was significantly lower among the OS patients, but the reoperation rate was significantly higher. In conclusion, OS is associated with a better function and lower mortality than HA, especially in younger patients, and it is recommended as the primary treatment for cervical hip fractures in patients younger than 80 years and with good ambulatory capacity, whereas the oldest patients can also be safely treated by HA.     

Permeability Profiles of M-Alkoxysubstituted Pyrrolidinoethylesters of Phenylcarbamic Acid Across Caco-2 Monolayers and Human Skin

Purpose. The purpose of the present research was to study 10 m-alkoxysubstituted pyrrolidinoethylesters of phenylcarbamic acid—potential local anesthetics. The relationships between the structure of the molecule, its physicochemical parameters (log D_oct, log k, R_M, solubility) were correlated to the permeability data obtained from permeation experiments in Caco-2 monolayers and excised human skin in vitro. Methods. The extent and mechanism(s) of permeability of the series were studied through a Caco-2 monolayer in the apical-to-basolateral (a-b) and basolateral-to-apical (b-a) directions. The MTT test was performed to determine cellular damage. In vitro transdermal permeability data were obtained from permeation experiments on excised human skin by using side-by-side chambers. Passive diffusion and iontophoretically enhanced permeability were measured. Results. In Caco-2 monolayers, similar results in the shape of the permeability curves were obtained for the two directions. In the b-a direction, the values of P_app were 2-6 times greater than in the a-b direction. A plot of drug permeability vs. the number of carbons in the alkoxychain plateaued first, after which the permeability decreased by the increasing lipophilicity of the drug. If the log D_oct of the ester was 3.4 and the MW > 385 Da, no measurable Caco-2 permeability was found. Cell damage was also higher by the more lipophilic compounds. In excised human skin, the relationship between the passive diffusion of the drugs and the number of carbons in the alkoxychain was parabolic (r ² = 0.95). Introducing low-level electrical current (iontophoresis), transdermal permeability of the more hydrophilic phenylcarbamic acid esters increased clearly. Conclusions. Lipophilicity and solubility of a compound have crucial roles in the permeation process. A very high lipophilicity has, however, a negative influence on the permeability, both intestinally and transdermally. Iontophoresis significantly increases the diffusion of small and less lipophilic compounds.     

Epidermolytic hyperkeratosis and epidermolysis bullosa simplex caused by frameshift mutations altering the v2 tail domains of keratin 1 and keratin 5

The cytoskeleton of epithelial cells is formed by heteropolymeric keratin proteins characterized by a central alpha-helical rod flanked by nonhelical head and tail domains of variable sequence. Most mutations described in 18 distinct keratins disrupt highly conserved regions at the boundaries of the rod, which have been recognized as zones of overlap during keratin alignment and assembly into intermediate filaments. We recently reported the first mutation located in a keratin tail domain (V2) in ichthyosis hystrix Curth-Macklin. In this study, we report two novel frameshift mutations that are predicted to alter the tail of keratin 1 or keratin 5, leading to an atypical form of epidermolytic hyperkeratosis and a mild form of epidermolysis bullosa simplex, respectively. Mutation analysis of the patient with epidermolytic hyperkeratosis revealed a de novo heterozygous nucleotide insertion (1752insG) in exon 9 of KRT1, predicted to result in an aberrant 69 residue keratin 1 tail. In the patient with mild epidermolysis bullosa simplex, we identified a single nucleotide deletion (1635delG) in exon 9 of KRT5 leading to frameshift and translation of an abnormal V2 domain, 35 amino acids longer than the native keratin 5 tail. Our results, together with previous observations, establish the existence of a subgroup of keratin disorders due to frameshift mutations altering the keratin tail domains that are characterized by phenotypic heterogeneity.     

Hirschsprung's disease in cartilage-hair hypoplasia has poor prognosis

Purpose: Cartilage-hair hypoplasia (CHH) is a chondrodysplasia with growth failure, impaired immunity, and high incidence of Hirschsprung disease (HD). This study describes the outcome of CHH patients with HD. Methods: Among 147 patients with CHH, 13 were identified to have HD. Their medical records were analyzed for treatment, outcome, and complications of HD and compared with a control group of 169 patients with HD but not CHH. Results: Eight CHH patients had classic HD with rectosigmoid involvement, 2 had long segment colonic disease, and 3 patients had total colonic aganglionosis. Six of the 13 CHH patients (46%) had episodes of enterocolitis before the first surgery. Enterocolitis was complicated by colonic perforation in 2 cases. Eleven CHH patients (85%) had at least one episode of postoperative enterocolitis. Five patients (38%) with CHH and HD had died; 4 of enterocolitis-related septic infection and one of non-Hodgkin's lymphoma. In the control group, preoperative enterocolitis occurred in 14% and postoperative enterocolitis in 8%. Two controls (1.2%) had died. Conclusions: HD associated with CHH has poor prognosis in terms of postoperative morbidity and risk of death. These patients require particular attention during postoperative follow-up to detect potentially lethal complications.     

Aortopulmonary fistula after coarctation repair with Dacron patch aortoplasty

Fistulous communication between the aorta and the pulmonary parenchyma developed in a 38-year-old woman 19 years after repair of a congenital aortic coarctation with Dacron patch aortoplasty. The fistula, inducing intermittent hemoptysis, arose from the suture line between the prosthetic fabric and the aorta. There was no infectious background or aneurysm at the primary repair site. The aortic segment including the prosthetic patch was resected and replaced with a Dacron tubular vascular prosthesis.     

Hippocampal A beta 42 levels correlate with spatial memory deficit in APP and PS1 double transgenic mice

We investigated the role of hippocampal amyloid pathology in spatial learning impairment of a new mouse line carrying mutated human amyloid precursor protein (APP) and presenilin-1 (PS1) transgenes. The APP + PS1 mice were tested in spatial navigation in the water maze and in position discrimination in the T-maze at ages of 3-4 and 11-12 months, before and after the appearance of first amyloid plaques. The APP + PS1 mice were impaired in water maze acquisition and retention only at the age of 11-12 months, but performed equally to controls in the T-maze task at both ages. In the impaired older age group, the levels of total Abeta1-42 in the hippocampus of APP + PS1 mice correlated negatively with the retention score. Here we show for the first time that the age-dependent impairment in memory retention in the traditional water maze of APP + PS1 mice correlates with the amount of total Abeta in hippocampus even at a stage when the amyloid deposits cover less than 1% of the hippocampal volume.     

Effects of environmental tobacco smoke on the respiratory health of children

This review synthesizes current knowledge of the effects of prenatal and postnatal exposure to environmental tobacco smoke on the respiratory health of children. A Medline database search was conducted for 1966 through October 2000. Limited evidence was found that exposure in pregnancy influences fetal growth, increases the risk of preterm delivery, and predicts the development of asthma and reduced lung function later in life. Both occupational and home environments contribute to the exposure of pregnant women and thus indirectly to adverse effects on children. There is strong and consistent evidence that exposure in childhood causes chronic respiratory symptoms (eg, cough, phlegm, and wheezing) and induces asthma. Limited evidence supports the role of childhood exposure in the poor overall control of established disease. Postnatal exposure is likely to have a small adverse impact on lung function growth. Prenatal and postnatal exposures have an important impact on children's respiratory health. These effects are preventable if pregnant women and children are protected from exposure to environmental tobacco smoke.     

Evaluation of cocktail approach to standardise Caco-2 permeability experiments.

The purpose of this study was to investigate the suitability and reliability of n-in-one approach using FDA suggested compounds for standardising Caco-2 permeability experiments. Special attention was paid to the evaluation of rank order correlation and mechanistic insights of compound permeability. Transport studies with antipyrine, metoprolol, ketoprofen, verapamil, hydrochlorothiazide, ranitidine, mannitol and fluorescein were performed in 12- and 24-well formats, as single compounds and in cocktails under iso-pH 7.4 and pH-gradient (pH 5.5 vs. 7.4) conditions. Compounds were quantified using n-in-one LC/MS/MS analysis. The cocktail-dosing proved to be a feasible method to determine the permeability of the Caco-2 cell line and to introduce external standards for permeability tests. Even though sink conditions were lost in cocktail experiments for highly permeable compounds, the rank order of compound permeability and the classification to low and high permeability compounds remained unchanged between single and cocktail studies and permeability values of 12- and 24-well formats were directly comparable. Under pH-gradient conditions the margin between high and low permeability compounds was narrower due to the lower permeability (higher fraction of ionisation) of basic molecules. Of the compounds studied, antipyrine, metoprolol, hydrochlorothiazide and mannitol are suitable for evaluation and standardisation purposes of passive permeability, while fluorescein would function as paracellular marker under iso-pH 7.4. As efflux activity may vary between cell batches, verapamil is a useful marker for P-glycoprotein.     

Transient increase in procollagen propeptides in the CSF after subarachnoid hemorrhage

BACKGROUND: Meningeal fibrosis following subarachnoid hemorrhage (SAH) has been verified histologically in experimental animals and in human autopsy samples, but the clinical course of the intrathecal fibroproliferative reaction is unknown. The authors therefore studied time-related changes in the CSF concentrations of type I (PICP) and type III (PIIINP) procollagen propeptides in patients with recent SAH. Method: Fifty-two CSF samples were obtained from 39 patients with SAH treated surgically and eight samples from eight patients with SAH who were not surgically treated. The samples were analyzed for PICP and PIIINP by using radioimmunoassays. RESULTS: The authors found a time-dependent increase in PICP and PIIINP in the CSF of the patients with SAH. Two weeks after the hemorrhage, concentrations were four times higher in patients with SAH than the concentrations in the control subjects. Concentrations in patients with SAH then declined steadily, but remained slightly but significantly elevated even at 10 weeks. PICP and PIIINP did not correlate with the age or sex of the patient or the amount of blood in the initial CT scan. Four patients developed late posthemorrhagic hydrocephalus; their PICP and PIIINP levels were higher than in matched patients with SAH without hydrocephalus. CONCLUSIONS: Time-dependent changes in CSF concentrations of PICP and PIIINP suggest a transient fibroproliferative reaction in the meninges after SAH. The considerable magnitude and extended time course of the changes make the measurement of PICP and PIIINP practicable for the diagnosis of a fibroproliferative state in patients with recent meningeal disease. Furthermore, the results suggest a role for meningeal fibrosis in the development of late posthemorrhagic hydrocephalus.     

The effects of gender and age on the colonoscopic examination

The data concerning the influence of gender and age on a patient's toleration of and the technical difficulty of colonoscopy are conflicting. One hundred eighty patients (108 women and 72 men) undergoing colonoscopy were categorized into three age groups: the young (aged 2040 years), the middle-aged (aged 41-60 years), and the old (aged 61-75 years). The endoscopists assessed the examination immediately after the procedure. The patients completed a questionnaire before leaving the endoscopy unit and again 2 weeks later. The women rated colonoscopy after the procedure more painful (p < 0.01) and in the repeat questionnaire more painful (p < 0.05) and more difficult (p < 0.05) than men. Also, the endoscopists judged colonoscopy to be more difficult (p < 0.001) and the time taken to reach cecum longer (p < 0.01) for women. The young experienced more discomfort than the middle-aged or the old, as evaluated after the procedure (p < 0.05). In the repeat questionnaire, the young reported more discomfort and pain than the middle-aged (p < 0.05). The endoscopists also judged the examination to be more difficult and the time taken to intubate cecum longer for the old than for the middle-aged (p < 0.05) or the young (p < 0.01). Correspondingly, the examination time was shorter among the young when compared with the middle-aged (p < 0.05) or the old (p < 0.001). The young were least willing to repeat the examination (p < 0.05). Colonoscopy is less tolerable and more difficult for women. Although colonoscopy among the old patients was technically more difficult, they tolerated the procedure better than the young.