Pharmacokinetic characterization of recombinant factor XIII (FXIII)‐A2 across age groups in patients with FXIII A‐subunit congenital deficiency

Three trials investigated the pharmacokinetics (PK) of recombinant factor XIII (rFXIII) A‐subunit. To compare the PK characteristics of rFXIII among trials and different age groups of patients. Dosing with rFXIII 35 IU kg^?1 every 4th week. Blood samples for PK assessments were collected regularly throughout the dosing interval from a total of 68 individual patients with FXIII congenital deficiency. The mean PK parameters were similar across the three age groups, and for the three trials, as well as constant over time based on results from patients participating in both mentor^?1 and mentor^?2 trials. The geometric mean half‐life ranged from 11.6 to 15.0 days, and the trough FXIII activity levels ranged from 0.15 to 0.21 IU mL^?1. The population PK model identified body weight as a statistically significant covariate influencing clearance (CL) and volume of distribution (V_d)_, with a similar increase in both parameters with increased body weight. The half‐life was not affected by body weight. Gender (females vs. males) and age category (paediatric vs. adult) did not affect CL. The PK profile of rFXIII, after dosing with 35 IU kg^?1 of rFXIII, was independent of age and comparable between trials and FXIII trough activity levels were constant. Despite rather large individual variation in the maximal FXIII activity levels, all individual mean trough activity levels were above 0.1 IU mL^?1 during the entire duration of the trials. The results support that monthly dosing with 35 IU kg^?1 of rFXIII to patients with FXIII A‐subunit deficiency, regardless of age, is adequate for prophylaxis.     

Joint Attention and Social Competence in Deaf Children with Cochlear Implants

The authors examined the influence of cochlear implants on joint attention and social competence in severe to profoundly congenitally deaf toddlers. Twenty-seven hearing mothers and hearing toddlers (HH dyads), and 26 hearing mothers and deaf toddlers, 9 with cochlear implantation (HD-cochlear dyads), and 17 with no cochlear implantation (HD-no cochlear dyads) were observed engaging in joint attention. Mothers provided ratings of children’s social competence. HH and HD-cochlear dyads displayed more joint attention than HD-no cochlear dyads. Children who were in dyads who engaged in more joint attention were rated by their mothers as higher on expressive and compliance behaviors and lower on disruptive behaviors compared to children who were in dyads who engaged in lower levels of joint attention. Findings suggest that cochlear implants may aid in the early socio-emotional development of some deaf children.     

Lewis blood group antigens in urine sediments from patients with urinary bladder carcinoma

Urine sediments from 20 patients with urinary bladder carcinoma, and from 11 healthy individuals were investigated for their content of Lea and Leb active glycolipids. The investigation was restricted to blood group phenotype Le (a-b+). All individuals exhibited both Lea- and Leb-active glycolipids. In healthy individuals the ratio Lea/Leb was less than 1 in 10 out of 11 cases, whereas in patients with bladder cancer the ratio Lea/Leb was greater than 1 in 11 out of 20 cases. No correlation between the Lea/Leb ratio on the one hand and tumour grade or stage on the other hand could be shown. The results indicate one possible explanation for the loss of ABH antigens in bladder cancer and also demonstrate the potential of detailed biochemical investigations on exfoliated material in urine.     

Comparative immunohistochemical demonstration of difucosylated carbohydrate antigens and CEA in adenomas and carcinomas of the rectum and rectosigmoid

The present immunohistochemical investigation reveals that difucosylated carbohydrate antigens (DFCA) are extensively expressed in rectal and rectosigmoid carcinomas while normal mucosa and hyperplastic polyps are mainly negative. The adenomas showed intermediate staining patterns where adenomas with villous structures and moderate-severe dysplasia resembled of carcinomas. CEA was more extensively expressed in both normal, premalignant, and malignant tissue. Thus, DFCA is better than CEA as a discriminator between normal and malignant tissue in the distal large bowel, and may be used in future studies with the intention of advancing our understanding of the neoplastic process and assessing clinical relevance.     

Changing patient characteristics in chronic hemodialysis

Patients accepted to chronic hemodialysis have changed. We analyzed these changes and survival, cause of death and other factors during 23 years at the Karolinska Hospital. Between 1965 and 1987, 274 patients were accepted: 60 are alive on dialysis, 75 died, 113 were transplanted, 25 sent to other units and one recovered renal function. The mean age increased from 44 to 55 years (p=0.001), the creatinine level at acceptance decreased from 1191 to 965 mumol/l (p = 0.001), the hemoglobin level rose from 70 to 85 g/l (p = 0.001) and the diastolic blood pressure decreased from 96 to 90 mmHg (p = 0.007). The number of co-morbid conditions increased from 1.2 to 1.4 (p less than 0.005). The diagnoses changed from over 90% primary renal disease to 20% systemic diseases such as nephrosclerosis and diabetes (p = 0.04). The chance of receiving a renal transplant decreased from 46 to 39% (p = 0.28). The transplanted patients were younger than the dialyzed patients 42 vs 47 years (p = 0.03) before 1980 and 49 vs. 56 years (p = 0.0001) after 1980. The cause of death changed. Withdrawal from dialysis increased from 5% of deaths before to 24% after 1980 (p = 0.047), cardiovascular deaths decreased from 85% to 55% (p = 0.01). Although the patients accepted for dialysis after 1980 had more serious renal disease and other degenerative diseases than those before, the mortality rate was reduced to only 1/4 to that before, in all age groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Malocclusion,psycho-social impacts and treatment need: A cross-sectional study of Tanzanian primary school-children

Background  

studies on the relationship between children's malocclusion and its psycho-social impacts are so far largely unexplored in low-income countries. This study aimed to assess the prevalence of malocclusion, reported dental problems and dissatisfaction with dental appearance among primary school children in Tanzania. The relationship of dissatisfaction with socio-demographic characteristics, clinically defined malocclusion and psychosocial impacts of dental anomalies was investigated. Orthodontic treatment need was estimated using an integrated socio-dental approach.     

Increased cortical cell loss and prolonged hemodynamic depression after traumatic brain injury in mice lacking the IP receptor for prostacyclin.

Prostacyclin is the major arachidonic acid metabolite of the vascular endothelium and is produced mainly via the cyclooxygenase-2 pathway. By acting on the prostacyclin (IP) receptor on platelets and vascular smooth muscle cells, prostacyclin exerts vasodilatory and antiaggregative/antiadhesive effects. Previous studies have shown that prostacyclin production increases after brain trauma, but the importance of prostacyclin for posttraumatic hemodynamic alterations and neuron survival has not been investigated. This study evaluated if endogenous prostacyclin plays a role in the pathophysiologic process in the brain after brain trauma. This was performed by comparing prostacyclin (IP) receptor-deficient (IP(-/-)) mice and mice with functional IP receptor (IP(+/+)) after a controlled cortical injury regarding contusion volume, cerebral blood flow ([(14)C]iodoantipyrine autoradiography), number of perfused capillaries (fluorescein isothiocyanate-dextran fluorescence technique), the transfer constant (K(i)) for [(51)Cr]EDTA, and brain water content (wet vs dry weight) in the injured and contralateral cortex. Contusion volume was increased in IP(-/-) mice compared with IP(+/+) mice. Three hours after trauma, cortical blood flow was decreased in the injured cortex of both groups and the reduction in blood flow in the cortex of the IP(-/-) mice persisted from 3 to 24 h, whereas blood flow approached normal values in the IP(+/+) mice after 24 h. No differences could be detected between the two genotypes regarding other hemodynamic parameters. We conclude that the prostacyclin IP receptor is beneficial for neuron survival after brain trauma in mice, an effect that may be mediated by improved cortical perfusion.     

Revision of Unicompartmental to Total Knee Arthroplasty: Does the Unicompartmental Implant (Metal-Backed vs All-Polyethylene) Impact the Total Knee Arthroplasty?

Background

The aim of this study is to investigate differences in implant requirement, outcomes, and re-revision when total knee arthroplasty (TKA) was performed following unicompartmental knee arthroplasties (UKAs) with metal-backed (MB) compared to all-polyethylene (AP) tibial components.

Sumatriptan (5-HT1B/1D-agonist) causes a transient allodynia

Unpleasant sensory symptoms are commonly reported in association with the use of 5-HT1B/1D-agonists, i.e. triptans. In particular, pain/pressure symptoms from the chest and neck have restricted the use of triptans in the acute treatment of migraine. The cause of these triptan induced side-effects is still unidentified. We have now tested the hypothesis that sumatriptan influences the perception of tactile and thermal stimuli in humans in a randomized, double-blind, placebo-controlled cross-over study. Two groups were tested; one consisted of 12 (mean age 41.2 years, 10 women) subjects with migraine and a history of cutaneous allodynia in association with sumatriptan treatment. Twelve healthy subjects (mean age 38.7 years, 10 women) without migraine served as control group. During pain- and medication-free intervals tactile directional sensibility, perception of dynamic touch (brush) and thermal sensory and pain thresholds were studied on the dorsal side of the left hand. Measurements were performed before, 20, and 40 min after injection of 6 mg sumatriptan or saline. Twenty minutes after injection, sumatriptan caused a significant placebo-subtracted increase in brush-evoked feeling of unpleasantness in both groups (P < 0.01), an increase in brush-evoked pain in migraineurs only (P = 0.021), a reduction of heat pain threshold in all participants pooled (P = 0.031), and a reduction of cold pain threshold in controls only (P = 0.013). At 40 min after injection, no differences remained significant. There were no changes in ratings of brush intensity, tactile directional sensibility or cold or warm sensation thresholds. Thus, sumatriptan may cause a short-lasting allodynia in response to light dynamic touch and a reduction of heat and cold pain thresholds. This could explain at least some of the temporary sensory side-effects of triptans and warrants consideration in the interpretation of studies on migraine-induced allodynia.