Baseline incidence of adverse birth outcomes and infant influenza and pertussis hospitalisations prior to the introduction of influenza and pertussis vaccination in pregnancy: a data linkage study of 78 382 mother-infant pairs, Northern Territory, Australia, 1994-2015.

We conducted probabilistic data linkage of three population datasets for the Northern Territory (NT), Australia, to describe the incidence of preterm births, stillbirths, low birthweight and small for gestational age (SGA) per 1000 NT births; and influenza and pertussis hospitalisations per 1 00 000 NT births in infants <7 months of age, in a pre-maternal vaccination era. The Perinatal Trends dataset (1994-2014) formed the cohort of 78 382 births. Aboriginal mother-infant pairs (37%) had disproportionately higher average annual rates (AR) for all adverse birth outcomes compared to their non-Aboriginal counterparts; rate ratios: preterm births 2.2 (AR 142.4 vs. 64.7); stillbirths 2.3 (AR 10.8 vs. 4.6); low birthweight 2.9 (AR 54 vs. 19); and SGA 1.7 (AR 187 vs. 111). Hospitalisation (2000-2015) and Immunisation Register datasets (1994-2015), showed that influenza hospitalisations (n = 53) and rates were 42.3 times higher in Aboriginal infants (AR 254 vs. 6); and that pertussis hospitalisations (n = 37) were 7.1 times higher in Aboriginal infants (AR 142.5 vs. 20.2) compared to non-Aboriginal infants. These baseline data are essential to assess the safety and effectiveness of influenza and pertussis vaccinations in pregnant women from the NT. Remote living Aboriginal women and infants stand to benefit the most from these vaccines.

Modification of the restoration protocol for resin-based composite (RBC) restoratives (conventional and bulk fill) on cuspal movement and microleakage score in molar teeth.

OBJECTIVE: To modify the resin-based composite (RBC) restoration protocol for standardised Class II cavities in third molar teeth restored using conventional RBCs or their bulk fill restorative counterparts. Employing cuspal deflection using a twin channel deflection measuring gauge (during) and microleakage to determine marginal integrity (following) RBC restoration, the modified restoration protocol results were compared with traditional (oblique) restoration of Class II cavities. METHODS: Thirty-two sound third molar teeth, standardised by size and morphology, were subjected to standardised Class II cavity preparations and randomly allocated to four groups. Restorations were placed in conjunction with a universal bonding system and resin restorative materials were irradiated with a light-emitting-diode light-curing-unit. The cumulative buccal and palatal cuspal movements from a twin channel deflection measuring gauge were summed, the restored teeth fatigued thermally prior to immersion in 0.2% basic fuchsin dye for 24h, before sectioning and examination for microleakage. RESULTS: Teeth restored using conventional RBC materials had significantly higher mean total cuspal movement values compared with bulk fill resin restorative restoration (all p<0.0001). Teeth restored with Admira Fusion and Admira Fusion x-tra had significantly the lowest microleakage scores (all p<0.001) compared with Tetric EvoCeram and Tetric EvoCeram Bulk Fill restored teeth. The microleakage scores for the range of RBC materials tested were significantly reduced (all p<0.001) when the modified RBC restoration protocol was employed compared with the traditional Class II restoration technique. SIGNIFICANCE: Modification of the RBC restoration protocol of some conventional RBCs and bulk fill resin restoratives significantly improve bond integrity and could be translated as a validation of the limited clinical studies available on bulk fill materials in the dental literature where Class II cavities perform less well than Class I cavities following extended follow-up. CLINICAL SIGNIFICANCE: The results of the current study add further weight to experimental protocols employing cuspal movement (during) and cervical microleakage (following) RBC restoration of standardised cavities in natural dentition to provide an indication of polymerization shrinkage stress at the tooth/RBC restoration interface in a 'clinically meaningful context'.

Pertussis epidemiology prior to the introduction of a maternal vaccination program, Queensland Australia.

Pertussis morbidity is highest in infants too young to be fully protected by routine vaccination schedules. Alternate vaccine strategies are required to maximise protection in this age-group. To understand baseline pertussis epidemiology prior to the introduction of the maternal pertussis vaccination program in 2014, we conducted a retrospective case series analyses of 53 901 notifications and temporal trends from 1997 to 2014. Notifications were highest in infants younger than 4 months of age and highest annual notification rates in infants younger than 1 month of age (308/100 000 per year). Amongst Aboriginal and Torres Strait Islander infants aged younger than 1 month, this rate was 576/100 000 per year. Notification rates were 40% higher amongst women 15-44 years, 62·4/100 000 population compared with men (44·5/100 000) and 90% higher in Aboriginal and Torres Strait Islander women of the same age (38·2/100 000) compared with men (19·7/100 000). Six infant deaths were identified, all younger than 2 months of age. Monitoring epidemiology in at-risk groups - infants too young to be vaccinated, women of childbearing age and Aboriginal and Torres Strait Islander peoples - following implementation of the maternal pertussis vaccination program will be important to assess its impact and safety.

A Four-Biomarker Blood Signature Discriminates Systemic Inflammation Due to Viral Infection Versus Other Etiologies.

The innate immune system of humans and other mammals responds to pathogen-associated molecular patterns (PAMPs) that are conserved across broad classes of infectious agents such as bacteria and viruses. We hypothesized that a blood-based transcriptional signature could be discovered indicating a host systemic response to viral infection. Previous work identified host transcriptional signatures to individual viruses including influenza, respiratory syncytial virus and dengue, but the generality of these signatures across all viral infection types has not been established. Based on 44 publicly available datasets and two clinical studies of our own design, we discovered and validated a four-gene expression signature in whole blood, indicative of a general host systemic response to many types of viral infection. The signature's genes are: Interferon Stimulated Gene 15 (ISG15), Interleukin 16 (IL16), 2',5'-Oligoadenylate Synthetase Like (OASL), and Adhesion G Protein Coupled Receptor E5 (ADGRE5). In each of 13 validation datasets encompassing human, macaque, chimpanzee, pig, mouse, rat and all seven Baltimore virus classification groups, the signature provides statistically significant (p < 0.05) discrimination between viral and non-viral conditions. The signature may have clinical utility for differentiating host systemic inflammation (SI) due to viral versus bacterial or non-infectious causes.

Characterizing adult attention-deficit/hyperactivity-disorder and comorbid borderline personality disorder: ADHD symptoms, psychopathology, cognitive functioning and psychosocial factors.

OBJECTIVE: To characterize adults with comorbid attention-deficit/hyperactivity-disorder (ADHD) and borderline personality disorder (BPD) with regard to ADHD symptoms, psychopathology, cognitive functioning and psychosocial factors. METHOD: A between-group design compared a group of individuals diagnosed with ADHD (n=40) with a group diagnosed with BPD and who also met the criteria for ADHD (ADHD+BPD) (n=20). RESULTS: Significant differences were observed for both childhood and current impulsivity symptoms, whereby ADHD+BPD exhibited increased impulsivity; no differences on self-report and cognitive measures of impulsivity were reported. The ADHD+BPD group scored significantly higher on measures of depression, anxiety and numerous other axis I and II conditions. The ADHD+BPD group scored significantly lower on most measures of intellectual functioning and attention, however largely not on those relating to response inhibition. Furthermore, group differences were observed for psychosocial factors, including education, substance use and criminal record. CONCLUSION: Comorbid ADHD and BPD is characterized by more symptoms of impulsivity, additional psychopathology, comparatively lower intellectual and attentional functioning and increased psychosocial difficulties.

Genital herpes: an Internet-based risk survey.

Genital herpes is one of the most common sexually transmitted infections worldwide. We established a web-based survey to determine risk for genital herpes and encourage people to attend for herpes simplex virus testing. A survey was established on the Australian Herpes Management Forum (AHMF) website, consisting of 16 demographic and sexual health-related questions. Each question carried a numerical risk-weighting based on epidemiological data; the higher the overall score, the greater the risk of herpes. To determine how representative our sample was in relation to age and sex, we compared our survey with Australian Census data. Between October 2006 and August 2007 there were 5572 responses, 4358 (92%) were Australian. Compared with the Australian population, the survey population had a higher proportion of individuals aged less than 34 years, and a lower population over 55. Six hundred and eighty-six (13.8%) were classified as low risk, 2558 (51.6%) as medium risk and 1710 (34.5%) as high risk of having acquired genital herpes. In total, 39% reported four or fewer, and 38% reported 10 or more, sex partners in their lifetime. A large number of individuals participated in this survey, confirming that the Internet is a useful tool for health promotion for genital herpes.

Combination treatment with ionising radiation and gefitinib ('Iressa', ZD1839), an epidermal growth factor receptor (EGFR) inhibitor, significantly inhibits bladder cancer cell growth in vitro and in vivo.

PURPOSE: External beam radiotherapy (EBRT) is the principal bladder-preserving monotherapy for muscle-invasive bladder cancer. Seventy percent of muscle-invasive bladder cancers express epidermal growth factor receptor (EGFR), which is associated with poor prognosis. Ionising radiation (IR) stimulates EGFR causing activation of cytoprotective signalling cascades and thus may be an underlying cause of radioresistance in bladder tumours. MATERIALS AND METHODS: We assessed the ability of IR to activate EGFR in bladder cancer cells and the effect of the anti-EGFR therapy, gefitinib on potential radiation-induced activation. Subsequently we assessed the effect of IR on signalling pathways downstream of EGFR. Finally we assessed the activity of gefitinib as a monotherapy, and in combination with IR, using clonogenic assay in vitro, and a murine model in vivo. RESULTS: IR activated EGFR and gefitinib partially inhibited this activation. Radiation-induced activation of EGFR activated the MAPK and Akt pathways. Gefitinib partially inhibited activation of the MAPK pathway but not the Akt pathway. Treatment with combined gefitinib and IR significantly inhibited bladder cancer cell colony formation more than treatment with gefitinib alone (p = 0.001-0.03). J82 xenograft tumours treated with combined gefitinib and IR showed significantly greater growth inhibition than tumours treated with IR alone (p = 0.04). CONCLUSIONS: Combining gefitinib and IR results in significantly greater inhibition of invasive bladder cancer cell colony formation in vitro and significantly greater tumour growth inhibition in vivo. Given the high frequency of EGFR expression by bladder tumours and the low toxicity of gefitinib there is justification to translate this work into a clinical trial.

Automated self-initiated blood pressure or 24-hour ambulatory blood pressure monitoring in pregnancy?

OBJECTIVE: To determine whether self-initiated and recorded automated blood pressure measurement can provide an accurate estimate of ambulatory blood pressure in pregnant women suspected of having 'white coat hypertension'. DESIGN: A prospective observational study. SETTING: Women's and Children's Health Unit, St George Hospital, a teaching hospital of the University of New South Wales. POPULATION: Pregnant women being assessed for possible 'white-coat hypertension'. METHODS: Sixty-six pregnant women who were undergoing 24 hour ambulatory blood pressure monitoring (ABPM) in their home or work environment also measured their blood pressure six times during this interval using a self-initiated automated blood pressure recorder (Omron HEM 705CP). Agreement between awake ABPM and Omron recorded blood pressures was tested by Bland-Altman analysis. MAIN OUTCOME MEASURE: Limits of agreement between blood pressures measured by each device. RESULTS: Average blood pressures obtained by the two devices were identical (125/77 mmHg) but limits of agreement were wide, -20 to +23 mmHg for systolic blood pressure and -9 to +15 mmHg for diastolic blood pressure. CONCLUSION: The Omron HEM 705CP is a useful device for measuring group average blood pressures in pregnant women suspected of having white coat hypertension but cannot reliably replace ABPM for clinical management of individual pregnant women.

Twenty-four-hour automated blood pressure monitoring as a predictor of preeclampsia.

OBJECTIVE: The purpose of this study was to determine the predictive ability of parameters of 24-hour ambulatory blood pressure monitoring for the development of preeclampsia or gestational hypertension in women who are already considered at risk for these disorders. STUDY DESIGN: One hundred twenty-two pregnant women who were considered high risk for the development of preeclampsia underwent 24-hour ambulatory blood pressure monitoring between 18 and 30 weeks gestation, while their condition was normotensive according to routine mercury sphygmomanometry. One hundred sixty-four healthy primigravid women who were considered at usual risk for preeclampsia underwent the same tests as a parallel study. Routine blood pressure, awake and sleep average blood pressure, and 24-hour mean average blood pressure were entered into multiple logistic regression as predictors of either preeclampsia or gestational hypertension; significant variables were then tested by a series of receiver operator curves. RESULTS: Eight percent of usual risk and 45% of high risk women experienced the development of preeclampsia or gestational hypertension. In both groups, the average routine mercury blood pressure and awake, sleeping, and 24-hour ambulatory blood pressure monitoring-derived blood pressure were significantly higher in women who later experienced the development of preeclampsia or gestational hypertension. In usual risk women, 24-hour systolic blood pressure of >or=115 mm Hg and sleeping systolic blood pressure of >or=106 mm Hg were predictive of later preeclampsia or gestational hypertension, but sensitivities were low (77% and 54%, respectively). In high risk women, sleeping diastolic blood pressure of >or=62 mm Hg and sleeping mean arterial pressure of >or=79 mm Hg were predictive of preeclampsia or gestational hypertension, but again sensitivities were low (70% and 65%, respectively). CONCLUSION: Awake and sleeping blood pressure are higher in midpregnancy in women who later experience the development of preeclampsia or gestational hypertension. Twenty-four-hour ambulatory blood pressure monitoring provides a noninvasive method of selecting some of these women, but this test has a sensitivity no better than that of other predictive tests, even in women at high risk for preeclampsia.

Repeat cycloplegic examinations at the Naval Operational Medicine Institute.

BACKGROUND: Cycloplegic examination is required for applicants who desire entry into Naval Aviation training. Before this study, all cycloplegic examinations performed at any site were repeated at the Naval Operational Medicine Institute (NOMI), Pensacola, FL, on all student naval aviator (SNA) candidates to assess for latent hyperopia which exceeded established limits for entry into training. HYPOTHESIS: Repeat cycloplegic examination does not vary sufficiently to change student status regarding physical qualification for training. METHODS: Data analysis of cycloplegic examinations repeated at the NOMI, for which the first and second examination were recorded in the Aviation Medical Data Retrieval System (AMDRS), over 10 yr. RESULTS: There were 3919 SNA applicants who had cycloplegic examinations repeated at NOMI. Of them, 3903 (99.59%) were within standards on the repeat examination. There were 16 candidates who were sent to NOMI with a previously disqualifying cycloplegic examination. On second cycloplegic examination, 15 were within standards for SNA. Only 15 of the SNAs with a first cycloplegic examination within standards were outside SNA standards on repeat examination. Of these 15, 12 were also outside SNA standards in distant visual acuity and/or in manifest refraction. The remaining 3 were found to have excessive myopia, not latent hyperopia, on the second cycloplegic examination. The standard deviation between the first and the second cycloplegic examination was computed to be less than 0.50 diopters in any meridian. CONCLUSION: The cycloplegic examination of SNA candidates need only be repeated if the first cycloplegic examination is outside the SNA limit or within two standard deviations of the SNA limit.

The prevalence and clinical significance of nocturnal hypertension in pregnancy.

OBJECTIVE: To determine (a) the prevalence of hypertension during sleep in pre-eclampsia and gestational hypertension, and (b) whether women with hypertension during sleep have worse pregnancy outcomes than hypertensive pregnant women with controlled (normal) blood pressure (BP) during sleep. DESIGN: Prospective double-blind cohort study. SETTING: Inpatients and outpatients managed in a day assessment unit (DAU) at St George Hospital, Sydney, Australia. PARTICIPANTS: A total of 186 hypertensive pregnant women, 158 of whom had successful 24 h BP monitoring; 40% had proteinuric pre-eclampsia (PE), 43% gestational hypertension (GH) and 17% essential hypertension (EH). INTERVENTIONS: Blood pressure, 24 h non-invasive, monitoring (Spacelabs 90207) was undertaken successfully in 158 women with PE, GH or EH, whether or not they were receiving antihypertensives. Women and clinicians were blinded to results of these BP monitors. Sleep hypertension was defined as BP > 117/68 mmHg at 26-30 weeks or > 123/72 mmHg after 30 weeks gestation. MAIN OUTCOME MEASURES: Maternal and fetal outcomes were compared between women with and without sleep hypertension and the prevalence of sleep hypertension was determined. RESULTS: Sleep hypertension was present in 59%, more commonly in PE (79%) than GH/EH (45%), P < 0.0001. Sleep hypertensives also had higher routine sphygmomanometer BPs [137(10)/91(7) mmHg; mean(SD)] than women with normal sleep BP [130(12)/ 87(8) mmHg] P = 0.007, and higher awake ambulatory blood pressure monitoring (ABPM) BPs [137(8)/88(7) versus 127(7)/79(6) mmHg], P < 0.0001. Awake, but not sleep, average heart rate was lower in sleep hypertensives [85(11) versus 91 (10) beats per minute, bpm], P = 0.002. Sleep hypertensives had a significantly greater frequency of renal insufficiency, liver dysfunction, thrombocytopenia and episodes of (awake) severe hypertension (P < 0.05), as well as lower birth weight babies [2715 (808) versus 3224(598) g, P < 0.0001]. CONCLUSIONS: Hypertension during sleep is a common finding in women with hypertensive disorders of pregnancy, particularly pre-eclampsia. These women also have higher awake BPs and a greater frequency of adverse maternal and fetal outcomes. These findings are largely explained by the greater likelihood of pre-eclamptics having sleep hypertension.

Medical costs of treating venous stasis ulcers: evidence from a retrospective cohort study.

Venous stasis ulcers (VSU) account for approximately 80-90% of lower extremity ulcerations. Given their prevalence and chronic nature, VSU are thought to impose a significant economic burden on Medicare (the USA's largest health insurance program) and other third party payers. However, comprehensive studies on the costs of VSU treatment are lacking. The objective of this study therefore was to examine comprehensively the direct medical costs of treating patients with a VSU in routine clinical practice. A cohort of 78 patients who presented with a VSU to the Cleveland Clinic Foundation (CCF), a large primary and tertiary referral center, was studied retrospectively. All inpatient and outpatient costs related to VSU treatment that were incurred during the year following VSU presentation or until the ulcer healed, whichever occurred first, were quantified. A total of 71 (91%) patients healed during the study. The average duration of follow-up was 119 days (median: 84 days). The average number of visits per patient was seven (range: 2 to 57). A total of 14 (18%) patients underwent 18 hospitalizations for VSU care. The average total medical cost per patient was $9685 (median: $3036). Home health care, hospitalizations and home dressing changes accounted for 48%, 25% and 21% of total costs, respectively. Total costs were related to duration of active therapy, ulcer size and the presence of at least one comorbidity (p<0.05). VSU are costly to manage, especially when time to healing is prolonged. The present findings reflect an underestimate of VSU costs since indirect costs were not examined. Time absent from work, forced early retirement, loss of functional independence and unquantifiable suffering may be additional factors that contribute to the overall burden of VSU.

Long-term quality of life after kidney and simultaneous pancreas-kidney transplantation.

We are using a validated questionnaire (SF-36) to annually assess health-related quality of life (QOL) in kidney and pancreas-kidney transplant recipients. The SF-36 consists of eight scales to assess physical functioning, general health, and mental functioning. Norms and 95% confidence intervals (C.I.) have been developed for the US population. At present, 1138 recipients with functioning grafts (520 Type I diabetic; 618 nondiabetic) 1-10 yr post-transplant have completed the questionnaire. Of the recipients, 446 completed the questionnaire once; 632 twice; and 53 three times (305 after 1 yr; 266 after 2 yr; 256 after 3 yr; 206 after 4 yr; 192 after 5 yr; 150 after 6 yr; 130 after 7 yr; 138 after 8 yr; 125 after 9 yr; 92 after 10 yr). For both diabetic and nondiabetic recipients, there was little change in average scores for each scale between years (p = NS). In relation to the US population, average scores for nondiabetics were below the 50th percentile on all 8 scales; for diabetics < 25th percentile on the physical functioning and vitality scales, < 50th percentile on all others. For both diabetic and nondiabetic recipients, average scores were higher than reported norms for patients with CHF, COPD, or depression but were similar to those with Htn or recent MI. Individual scores were then compared with age-matched means (+/- 2 SEMs) (95% C.I.) for the US population. At each year post-transplant, up to 40% of nondiabetic and up to 65% of diabetic recipients had scores below the 95% C.I. on individual scales (particularly the physical functioning and general health scales)--e.g. over 30% nondiabetic and up to 60% diabetic recipients had scores on the physical functioning scales below the 95% C.I. More diabetic recipients (vs. nondiabetics) reported poor QOL on the physical functioning, general health and social functioning scales. There was little difference in the mental health scales. For those with Type I diabetes, a similar percentage of kidney and K/P recipients reported QOL below the 95% C.I. for the age-matched population, except on the GH scale (better QOL for K/P recipients). We conclude that successful transplant recipients report health-related QOL below that of the age-matched general population but similar to those with other chronic diseases. Diabetic and nondiabetic recipients have similar scores on the mental health scales; nondiabetic recipients score better on the general health and physical functioning scales.

A recombinant single-chain human class II MHC molecule (HLA-DR1) as a covalently linked heterotrimer of alpha chain, beta chain, and antigenic peptide, with immunogenicity in vitro and reduced affinity for bacterial superantigens.

Major histocompatibility complex (MHC) class II molecules bind to numerous peptides and display these on the cell surface for T cell recognition. In a given immune response, receptors on T cells recognize antigenic peptides that are a minor population of MHC class II-bound peptides. To control which peptides are presented to T cells, it may be desirable to use recombinant MHC molecules with covalently bound antigenic peptides. To study T cell responses to such homogeneous peptide-MHC complexes, we engineered an HLA-DR1 cDNA coding for influenza hemagglutinin, influenza matrix, or HIV p24 gag peptides covalently attached via a peptide spacer to the N terminus of the DR1 beta chain. Co-transfection with DR alpha cDNA into mouse L cells resulted in surface expression of HLA-DR1 molecules that reacted with monoclonal antibodies (mAb) specific for correctly folded HLA-DR epitopes. This suggested that the spacer and peptide did not alter expression or folding of the molecule. We then engineered an additional peptide spacer between the C terminus of a truncated beta chain (without transmembrane or cytoplasmic domains) and the N terminus of full-length DR alpha chain. Transfection of this cDNA into mouse L cells resulted in surface expression of the entire covalently linked heterotrimer of peptide, beta chain, and alpha chain with the expected molecular mass of approximately 66 kDa. These single-chain HLA-DR1 molecules reacted with mAb specific for correctly folded HLA-DR epitopes, and identified one mAb with [MHC + peptide] specificity. Affinity-purified soluble secreted single-chain molecules with truncated alpha chain moved in electrophoresis as compact class II MHC dimers. Cell surface two-chain or single-chain HLA-DR1 molecules with a covalent HA peptide stimulated HLA-DR1-restricted HA-specific T cells. They were immunogenic in vitro for peripheral blood mononuclear cells. The two-chain and single-chain HLA-DR1 molecules with covalent HA peptide had reduced binding for the bacterial superantigens staphylococcal enterotoxin A and B and almost no binding for toxic shock syndrome toxin-1. The unique properties of these engineered HLA-DR1 molecules may facilitate our understanding of the complex nature of antigen recognition and aid in the development of novel vaccines with reduced superantigen binding.

Pregnancy after donor nephrectomy.

Potential female donors frequently ask whether unilateral nephrectomy will impair future childbearing capabilities. To address this question, we surveyed 220 women who underwent donor nephrectomy between 1985 and 1992. Of the 144 women who responded, 33 became pregnant after donation for a total of 45 pregnancies. Seventy-five percent of the pregnancies were carried to term without difficulty. Complications incurred during gestation included miscarriage (13.3%), preeclampsia (4.4%), gestational hypertension (4.4%), proteinuria (4.4%), and tubal pregnancy (2.2%). Four of the 45 pregnancies (excluding miscarriages) required preterm hospitalization, resulting in an overall morbidity of 8.8%. There were no pregnancy-related deaths, and no fetal abnormalities were reported. Problems with persistent hypertension, proteinuria, or changes in renal function were not noted. None of the above complications exceeded what has been noted for the general population. Infertility was a problem in 8.3% (3/36) of our respondents, compared with a worldwide incidence of 16.7%. Based on these results, we conclude that donor nephrectomy is not detrimental to the prenatal course or outcome of future pregnancies.

Employment patterns after successful kidney transplantation.

We studied 822 kidney transplant recipients followed 1-9 years to determine the dynamics of their entering and leaving the work force. Multivariate analysis revealed that not being diabetic and that being employed pretransplant were associated with a higher rate of posttransplant employment. Some recipients in all pretransplant employment categories, including those receiving disability benefits pretransplant, returned to full-time work posttransplant. The most rapid return to work was in those who had been working full-time or attending school pretransplant. After returning to work, a higher percentage of diabetic recipients stopped working; of those who stopped working, 50% received disability benefits. In contrast, nondiabetic recipients who stopped working full-time were more likely to be retired or working part-time; only 22% received disability benefits.

Functional cell surface expression by a recombinant single-chain class I major histocompatibility complex molecule with a cis-active beta 2-microglobulin domain.

As a preliminary step towards the use of cell surface single-chain class I major histocompatibility complex (MHC) molecules as T cell immunogens, we have engineered a recombinant gene encoding a full-length cell surface single-chain version of the H-2Dd class I MHC molecule (SC beta Ddm) which has beta 2-microglobulin (beta 2m) covalently linked to the amino terminus of a full-length H-2Dd heavy chain via a peptide spacer. The single-chain protein is correctly folded and stably expressed on the surface of transfected L cells. It can present an antigenic peptide to an H-2Dd-restricted antigen-specific T cell hybridoma. When expressed in peptide-transport-deficient cells, SC beta Ddm can be stabilized and pulsed for antigen presentation by incubation with extracellular peptide at 27 degrees or 37 degrees C, allowing the preparation of cells with single-chain molecules that are loaded with a single chosen antigenic peptide. SC beta Ddm can be stably expressed in beta 2m-negative cells, showing that the single-chain molecule uses its own beta 2m domain to achieve correct folding and surface expression. Furthermore, the beta 2m domain of SC beta Ddm, unlike transfected free beta 2m, does not rescue surface expression of endogenous class I MHC in the beta 2m-negative cells. This strict cis activity of the beta 2m domain of SC beta Ddm makes possible the investigation of class I MHC function in cells, and potentially in animals, that express but a single type of class I MHC molecule.

Renal transplantation for patients 60 years of older. A single-institution experience.

OBJECTIVE: The authors reviewed renal transplant outcomes in recipients 60 years of age or older. BACKGROUND: Before cyclosporine, patients older than 45 years of age were considered to be at high risk for transplantation. With cyclosporine, the age limits for transplantation have expanded. METHODS: The authors compared patient and graft survival, hospital stay, the incidence of rejection and rehospitalization, and the cause of graft loss for primary kidney recipients 60 years of age or older versus those 18 to 59 years of age. For those patients > or = 60 years transplanted since 1985, the authors analyzed pretransplant extrarenal disease and its impact on post-transplant outcome. In addition, all surviving recipients > or = 60 years completed a medical outcome survey (SF-36). RESULTS: Patient and graft survival for those > or = 60 years of age versus those 18 to 59 years of age were similar 3 years after transplant. Subsequently, mortality increased for the older recipients. Death-censored graft survival was identical in the two groups. There were no differences in the cause of graft loss. Those 60 years of age or older had a longer initial hospitalization, but had fewer rejection episodes and fewer rehospitalizations. Quality of life for recipients 60 years of age or older was similar to the age-matched U.S. population. CONCLUSION: Renal transplantation is successful for recipients 60 years of age or older. Most of them had extrarenal disease at the time of transplantation; however, extrarenal disease was not an important predictor of outcome and should not be used as an exclusion criterion. Post-transplant quality of life is excellent.

Recovery of function in survivors of the acute respiratory distress syndrome.

We performed a prospective cohort analysis to determine the rate and extent of improvement in pulmonary function abnormalities and self-perceived health for 1 yr after surviving an episode of the acute respiratory distress syndrome (ARDS). We also examined the effect of ARDS severity and etiology, age, and sex on functional recovery. Patients were recruited from the intensive care units of one hospital and followed at regular time intervals from extubation to 1 yr. Fifty-two of 82 eligible adult survivors (63%) consented to participate; 37 of 82 (45%) had at least two examinations, and 20 (24%) had complete follow-up. Risk factors for ARDS included sepsis (n = 12), trauma (n = 15), and other (n = 10). Pulmonary function and self-perceived health scores improved considerably in the first 3 mo after extubation, with only slight additional improvement at 6 mo. No further changes were evident at 1 yr. Patients with more severe ARDS had significantly lower pulmonary function tests than did other survivors throughout follow-up. These observations should be useful for clinical follow-up of ARDS survivors and provide specific information concerning the expected rate of functional recovery in these patients.

Could seborrhoeic dermatitis be implicated in the pathogenesis of parkinsonism?

The spouses of a group of aged sufferers have been demonstrated to have multifarious differences relevant to parkinsonism from matched controls, which were difficult to explain by selective mating, learned or reactive behaviour. Could parkinsonism be transmissible? The frequency of inflammation and scaling on head or neck was greater (P = 0.05) in these spouses (19 available) than in controls (36), the best discriminating site of inflammation being scalp (P = 0.02). Both seborrhoeic dermatitis and overt, or pre-clinical, parkinsonism occurred in sufferers and spouses: to presume they are not causally related is to accept multiple entities. In favour of seborrhoeic dermatitis being causal for parkinsonism, rather than vice versa, is the involvement of a known organism, Pityrosporum ovale, in the dermatitis, and that the evidence of parkinsonism in the spouses indicated that they were only part way down the path towards the clinical condition.