Self-Rated Frailty and Mortality in Old Men: The Manitoba Follow-up Study.

BACKGROUND: While a multitude of definitions and operationalizations of frailty have been developed, rarely have these considered the perspective of the older adult themselves. This knowledge gap was addressed by examining older adults' self-rating of frailty. OBJECTIVES: To assess the validity of self-rated frailty and to determine whether self-rated frailty relates to mortality. DESIGN: The Manitoba Follow-up Study was initiated in 1948 as a prospective cohort study of 3,983 men. SETTING: Community dwelling older adult men. PARTICIPANTS: Survivors of the original cohort (231 men) were sent a quality of life survey in 2015. A response was received from 186 men, including 146 surveys completed by the participant himself and thus were eligible to include (completion rate of 78.4%). MEASUREMENTS: The quality of life survey is sent out annually to the study participants to ascertain information about mental, physical, and social functioning. In 2015, the Clinical Frailty Scale was adapted and added to the survey as a simple self-rating of frailty. RESULTS: The mean age of the 146 respondents in 2015 was 93.7 years (SD 2.7) Self-ratings of "moderate-severe" frailty, received from 132 men, were associated with worse measures of physical health and functional impairment, thus supporting the significance of self-rated frailty. Adjusted for age, the Hazard Ratio for mortality over the next 3 years was 3.3 (95% CI: 1.5, 7.1) for those who rated themselves as "mildly to severely frail" vs. "very fit or well, with no disease". CONCLUSION: The present study has illustrated that self-rated frailty is associated with other measures of health and that self-rated frailty predicts mortality over a three-year period. These findings support the utilization of older adult's self-ratings of frailty for new avenues of operationalizing frailty.

Safety and immunogenicity of TETRActHIB (a vaccine combining DTP vaccine and Haemophilus influenzae type B conjugate vaccine) administered to infants at 6, 10 and 14 weeks of age.

The safety and immunogenicity of TETRActHIB (a vaccine combining diphtheria and tetanus toxoids-pertussis vaccine (DTP) with Haemophilus influenzae type b (Hib) conjugate vaccine (polyribosyl ribitol phosphate conjugated to tetanus protein) (PRP-T)) was assessed in 131 Cape Town infants immunized at 6, 10 and 14 weeks of age. Serological responses to all component antigens were measured before the first dose and at 18 weeks of age. In addition, anti-PRP antibodies were measured at 9 and 18 months of age to determine long-term immunogenicity. The vaccine was well tolerated by infants and no significant side-effects were reported. Responses to Hib at 18 weeks of age were good in that most infants achieved a level of anti-PRP antibodies > or = 0.15 microgram/ml, indicative of short-term protection, and 70% achieved a level > or = 1 microgram/ml, indicative of long-term protection. The proportions of children with protective levels > or = 0.15 microgram/ml and > or = 1 microgram/ml were similar at 9 and 18 months of age, i.e. approximately 75% and 45%, respectively. Responses to tetanus and diphtheria toxoids were excellent and all infants achieved protective serological levels. Responses to pertussis were moderate in that approximately 65% achieved 'protective' serum levels of pertussis agglutinins, i.e. titres > or = 320. In conclusion, this study has shown that the DTP/PRP-T vaccine is safe, immunogenic and well tolerated in infants immunised at 6, 10 and 14 weeks of age. TETRActHIB is therefore suitable for inclusion in the World Health Organisation Expanded Programme on Immunisation (WHO EPI) schedule.

Design and fabrication of cast orthopedic implants with freeform surface textures from 3-D printed ceramic shell.

Three-dimensional printing is a solid freeform fabrication process, which creates parts directly from a computer model. The parts are built by repetitively spreading a layer of powder and selectively joining the powder in the layer by ink-jet printing of a binder material. 3D printing was applied to the fabrication of sub-millimeter surface textures with overhang and undercut geometries for use in orthopedic prostheses as bony ingrowth structures. 3D printing is used to fabricate ceramic molds of alumina powder and silica binder, and these molds are used to cast the bony ingrowth surfaces of Co-Cr (ASTM F75) alloy. Minimum positive feature sizes of the ceramic mold and, therefore, minimum negative feature sizes of castings were determined to be approximately 200 x 200 x 175 microm and were limited by the strength of ceramic needed to withstand handling. Minimum negative feature sizes in the ceramic mold and, therefore, minimum positive features in the casting were found to be approximately 350 x 350 x 175 microm and were determined by limitations on removal of powder from the ceramic and the pressure required to fill these small features with molten metal during casting. Textures were designed with 5 layers of distinct geometric definition, allowing for the design of overhung geometry with overall porosity ranging from 30-70%. Features as small as 350 x 350 x 200 microm were included in these designs and successfully cast.

Serum complement determinations in patients with quiescent systemic lupus erythematosus.

OBJECTIVE: To determine whether complement component analyses during a period of inactive disease can define clinically important subgroups and predict morbidity in patients with systemic lupus erythematosus (SLE). METHODS: We identified 277 patients with SLE whose disease became clinically inactive at some point after diagnosis. Serum samples were obtained at that time and tested for total complement activity (CH100) and antigenic levels of C1q, C1r, C1s, C3 and C4. Results of complement determinations were correlated with demographic characteristics and clinical findings in the followup period (mean observation period 4.25 years). RESULTS: We identified 25 (9%) patients with multiple complement determinations below the normal range. 24 other patients (8.5%) had a very low level of a single complement component. The group with multiple complement determinations below the normal range was much more likely than the normocomplementemic SLE controls to progress to renal insufficiency. In other respects, complement component determinations were neither reflective nor predictive of clinical course. CONCLUSION: In this group of patients with inactive SLE, complement component analyses did not generally correlate with longterm outcome; however, multiple low complement component determinations during disease quiescence was associated with increased risk of renal insufficiency.

Screening for diabetic retinopathy in South Africa with 60 degrees retinal colour photography.

OBJECTIVES: Comparison of 60 degrees mydriatic retinal photography, in screening for diabetic retinopathy, with diabetes clinic doctors, formal ophthalmological assessment, and with one or two 45 degrees fields. DESIGN: Consecutive subjects screened by clinicians and photography, and selected eyes evaluated by an ophthalmologist. Randomized photographs assessed through one or two 45 degrees fields (by masking the slides), and at 60 degrees. SETTING: The first 663 patients attending for routine clinic visits and screened for retinopathy. MAIN OUTCOME MEASURES: The relative diagnostic sensitivity of screening methods, the utility of screening one eye only, and the costs of photographic screening. RESULTS: Compared to an ophthalmologist's assessment, retinal photography had a sensitivity of 93% and a specificity of 89% for any retinopathy, and 100 and 75%, respectively, for severe retinopathy. Photography detected 28% more retinopathy (16% severe) than the clinicians. Compared to a 60 degrees field, one 45 degrees field missed 31%, and 2 x 45 degrees fields 11% of retinopathy. Of 57 patients with retinopathy meeting referral criteria, 31 pairs of eyes had substantially discordant scores. The cost of diagnosis in a patient requiring referral to ophthalmologist was about US $37.00. CONCLUSIONS: 60 degrees retinal photography compares well with an ophthalmologists screening, and is better than clinical and one to two 45 degrees field assessments. Both retinae should be screened. This method is cost-effective in our hands.

Mechanical properties of dense polylactic acid structures fabricated by three dimensional printing.

Polylactic acid (PLA) is a bioresorbable polymer that is used in a number of clinical situations. Complex shapes of PLA are commonly machined for bone fixation and reconstruction. Solid free from fabrication methods, such as 3D printing, can produce complex-shaped articles directly from a CAD model. This study reports on the mechanical properties of 3D-printed PLLA parts. 3D printing is a solid free-form fabrication process which produces components by ink-jet printing a binder into sequential powder layers. Test bars were fabricated from low and high molecular weight PLA powders with chloroform used as a binder. The binder printed per unit line length of the powder was varied to analyze the effects of printing conditions on mechanical and physical properties of the PLA bars. Furthermore, cold isostatic pressing was performed after printing to improve the mechanical properties of the printed bars. The maximum measured tensile strength for the low molecular weight PLLA (53 000) is 17.40 +/- 0.71 MPa and for high molecular weight PLLA (312 000) is 15.94 +/- 1.50 MPa.

[Investigational and methodological difficulties in the demonstration of cryoglobulins]. / Interpretations- und methodische Schwierigkeiten beim Nachweis von Kryoglobulinen.

Cryoglobulins and cryofibrinogens are special forms of cryopathies. With regard to the clinical findings, determination and analysis of cryoproteins can support the diagnostics. Because cryoproteins occur in patients and healthy persons, occasionally it may be difficult to estimate the clinical significance. We determined and analyzed cryproteins in 47 patients with the following diagnoses: urticaria (8), morbus Raynaud (10), acrocyanosis (7), vasculitis (3), collagenosis (6), lupus erythematosus (2), suspect of cryoproteinemia (9) and of cryofibrinogenemia (2). There were cryoproteins in 42 patients of the following characteristics: immunoglobulins A, G, M (14), fibrinogen (2), immunoglobulins A, G, M together with fibrinogen (26) with a considerable predominance of IgM. There was no correlation between the diagnoses and the cryoprotein types, and therefore it is reasonable to determine cryoproteins in close cooperation with the clinics. Contamination of the cryoprecipitates with hemoglobin from red blood cells can simulate alpha 2-macroglobulin and cause misinterpretations.

Application of fluorescent in situ hybridization for 'de novo' anomalies in prenatal diagnosis.

Fluorescent in situ Hybridization (FISH) was carried out for three cases of abnormal karyotypes in prenatal studies. Two concerned de novo structural anomalies and the third a marker chromosome. The origin of the extra material could be defined in all three cases, which gives a better insight into the relationship between genotype and phenotype and makes more adequate genetic counselling possible.

Terminal transverse limb defects and early chorionic villus sampling: evaluation of 4,300 cases with completed follow-up.

Data from 4,300 consecutive cases following prenatal diagnosis by transcervical (TC) CVS (n = 1,570) and transabdominal (TA) CVS (n = 2,370) were evaluated. In the follow-up study only infants examined by a physician were included. Gestational age varied between 8.5 and 11.6 weeks (mean 10.3 weeks) for TC-CVS and between 9.3 and 20 weeks (mean 12.3 weeks) for TA-CVS 98% of TC-CVS was performed at 9-10 weeks, 80.7% of TA-CVS procedures were carried out at 12-15 weeks. Selective termination took place in 97 cases of TC-CVS (6.1%) and in 72 cases of TA-CVS (2.6%). Another 8 women had a termination for psychosocial reasons, resulting in 4,123 (1,469 TC, 2,654 TA) continuing pregnancies. The overall fetal loss rate < 28 weeks was 5.4% (n = 80) for TC-CVS and 2.6% (n = 70) for TA-CVS. The overall incidence of congenital abnormalities after birth was 0.9%. Two terminal transversal limb defects were detected in the TC-CVS group (0.14%) against one (0.04%) in the TA-CVS group.

Reproductive behaviour and prenatal diagnosis following genetic termination of pregnancy in women of advanced maternal age.

One hundred and fifty-one women of advanced maternal age who underwent genetic termination of pregnancy (TOP) were studied for their reproductive behaviour and the type of procedure for prenatal diagnosis in a subsequent pregnancy. A total of 59 women (39 per cent) had a further pregnancy. In all continuing pregnancies prenatal diagnosis was performed, of which 75 per cent consisted of chorionic villus sampling (CVS). Reproductive behaviour following a genetic termination was negatively correlated with maternal age and parity. Both reproductive behaviour and the choice to undergo a diagnostic procedure in the next pregnancy were independent of the type of diagnostic procedure in the previous affected pregnancy.

PIP: In the Netherlands, researchers studied the medical records of and followed-up on 151 women of advanced maternal age (at least 36 years old) who underwent amniocentesis or chorionic villus sampling (CVS) and elected to terminate the pregnancy due to an abnormal genetic finding (105 and 46 women, respectively) at Academic Hospital Rotterdam-Dijkzigt between January 1980 and December 1989. Researchers wanted to learn the women's subsequent reproductive behavior and determine whether the type of diagnostic procedure in the index pregnancy influenced the choice of diagnostic procedure in the next pregnancy. 61% did not experience a subsequent pregnancy. 59 women (39%) conceived again. Women who were at least 39 years old had a significantly lower subsequent pregnancy rate than 36-38 year old women (p .001). As parity increased, the subsequent pregnancy rate decreased (p = .005). 11 women experiencing a subsequent pregnancy suffered a spontaneous abortion. All of the remaining 48 women chose to undergo prenatal diagnosis again. 75% requested CVS, the prenatal diagnostic technique conducted during the first trimester of pregnancy, regardless of the technique used in the index pregnancy.

Prenatal diagnosis of spina bifida aperta after first-trimester valproate exposure.

In the context of a prospective study on the adverse effects of anti-epileptic drugs on fetal outcome, we evaluated our experience with prenatal diagnosis by ultrasonography and alpha-fetoprotein (AFP) determination in amniotic fluid. We compared these results with AFP values in maternal serum obtained prior to amniocentesis. From November 1985 to July 1990, amniocentesis at 16-18 weeks of gestation was performed in 267 pregnancies of 237 different women using anti-epileptic drugs. Among 92 pregnancies with maternal valproic acid use, five (including one concordantly affected monozygotic twin-pair) were terminated because of a spina bifida aperta, all prenatally diagnosed by AFP determination and acetylcholinesterase electrophoresis in amniotic fluid. The maternal serum AFP level was raised (> or = 2.5 multiples of the median (MOM) for singleton pregnancies and > or = 4.5 MOM for twin pregnancies) in only two of these five affected pregnancies. We emphasize that maternal serum AFP levels may be unreliable for prenatal screening for fetal neural tube defects in women taking valproate and recommend that amniocentesis and fetal ultrasound examination should be offered directly.

Reproductive behaviour following spontaneous loss of pregnancy after prenatal diagnosis.

One hundred and fifty-eight women of advanced maternal age with complete follow up who experienced spontaneous fetal loss after prenatal diagnosis were studied for reproductive behaviour as well as prenatal diagnosis in a subsequent pregnancy. A higher rate of subsequent pregnancies amongst women who experienced an early spontaneous abortion after chorionic villus sampling (CVS) was expected compared with women who lost a pregnancy later during pregnancy after amniocentesis. Of the 92 women who underwent CVS in a previous pregnancy, 57 (62%) became pregnant again. Of the 66 women who underwent amniocentesis in the pregnancy that ended in fetal loss, 34 women (52%) had a subsequent pregnancy. The cumulative incidence of subsequent pregnancies was significantly influenced by maternal age but not by parity or the method of prenatal testing. Most women who decided on a new pregnancy opted for prenatal diagnosis. There was a preference for amniocentesis if the patient had previously undergone CVS. However, the reverse was not the case.

The risk of spina bifida aperta after first-trimester exposure to valproate in a prenatal cohort.

Use of antiepileptic drugs (AEDs) during pregnancy is associated with an increased risk of congenital malformations. Spina bifida aperta has been linked specifically to valproic acid (VPA) (estimated risk, 1 to 2%). The actual risk, the exclusive association of VPA with spina bifida and not anencephaly, and the precise causative relation remain matters of discussion. A prospective cohort study of pregnant women with epilepsy receiving AEDs and referred for prenatal diagnosis before week 22 of gestation was conducted, with follow-up to 3 months after birth. Pregnancies (291 singleton and 6 twin) in 261 women were evaluated. The prevalence of anomalies after exposure to any AED was 6.9%. For fetuses exposed to VPA, the prevalence was 9.4%, including six cases of spina bifida, two of which were in monozygotic twins (giving a prevalence rate of 6.3%, or 5.4%, if twins counted as one). Spina bifida was associated with a significantly higher average daily dose of VPA as compared with pregnancies with normal outcome (1.640 +/- 136 mg/d vs 941 +/- 48 mg/d, p = 0.0001). No relation was observed between the occurrence of spina bifida and type of maternal seizure or epilepsy, family history of epilepsy or neural-tube defects, or medical history. From these results we suggest that when the use of VPA during pregnancy cannot be avoided, the teratogenic risk might be diminished by reduction of the daily dose.

Perturbation of regulated secretion in the pancreatic acinar cell line, AR42J.

The regulated secretory pathway comprises accelerated discharge of proteins in response to hormonal stimuli, their presence in secretory granules (SG), and a long intracellular residence time. Dexamethasone induction of AR42J results in an increase in granule content and responsiveness to cholecystokinin (CCK). We studied the effects of conditions implicated in sorting of secretory proteins into the regulated pathway using [35S]methionine pulse-chase protocols that examine transport of secretory proteins from the rough endoplasmic reticulum (RER)----SG and specifically from the Golgi complex (GC)----SG. The latter uses a chase at 20 degrees C to allow accumulation of labeled proteins in the trans-Golgi, followed by a shift to 37 degrees C that initiates their transport to SG under test conditions. Quantitation of CCK-8-stimulated discharge of prestored amylase and of newly synthesized labeled proteins that have entered SG during the chase enables us to examine the effect of perturbants over selected parts of the pathway. The effects of acidic intracellular compartments, the cytoskeleton, protein synthesis, ATP, and temperature on pre- and post-Golgi entry of proteins into the regulated pathway were studied. NH4Cl, monensin, Na azide, incubation at 20 degrees C, and pertussis toxin retarded RER----SG transport without affecting amylase discharge. Only incubation with 20 mM NH4Cl or 1 microM monensin inhibited transfer of newly synthesized proteins from the late GC----SG. RER----Golgi or intra-Golgi transport thus appears to require ATP and possibly guanosine 5'-triphosphate (GTP)-binding proteins. Acidic compartments appear to be essential for sorting of secretory proteins from the GC----SG.

Origin of raised maternal serum alpha-fetoprotein levels in second-trimester oligohydramnios.

Concanavalin A (Con A) subtyping of alpha-fetoprotein (AFP) revealed higher concentrations of AFP non-reactive with Con A in sera of 12 pregnant women with second-trimester oligohydramnios and raised total serum AFP levels than in sera of 42 pregnant women with raised total serum AFP levels and a normal amniotic fluid volume. This suggests that in oligohydramnios the origin of excess AFP in the maternal compartment is amniotic fluid. It is proposed that oligohydramnios and the associated raised maternal serum AFP levels are caused by damage of the fetal membranes prior to 16 weeks of gestation resulting in leakage of amniotic fluid to the decidual tissue and resorption in the maternal circulation.