Urine high and low molecular weight proteins one-year post-kidney transplant: relationship to histology and graft survival.

Increased urinary protein excretion is common after renal transplantation and portends worse outcome. In this study we assessed the prognostic contribution of several urinary proteins. Urinary total protein, albumin, retinol binding protein (RBP), α-1-microglobulin, IgG and IgM were measured in banked urine samples from 221 individuals 1 year after renal transplantation (age 52 ± 13 years, 55% male, 93% Caucasian and 82% living donor). Levels of all proteins measured were higher than in normal nontransplant populations. Patients with glomerular lesions had higher urinary albumin than those with normal histology, while those with interstitial fibrosis and tubular atrophy plus inflammation (ci>0, cg = 0, i>0) had higher levels of IgG, IgM, α-1-microglobulin and RBP. Concomitant normal levels of urinary albumin, IgM and RBP identified normal histology (specificity 91%, sensitivity 15%,). Urinary levels of the specific proteins were highly correlated, could not differentiate among the histologic groups, and appeared to result from tubulointerstitial damage. Increased urinary excretion of the low molecular weight protein RBP was a sensitive marker of allografts at risk, predicting long-term graft loss independent of histology and urinary albumin. This study highlights the prognostic importance of tubulointerstitial disease for long-term graft loss.

Association of metabolic syndrome with kidney function and histology in living kidney donors.

The selection of living kidney donors is based on a formal evaluation of the state of health. However, this spectrum of health includes subtle metabolic derangements that can cluster as metabolic syndrome. We studied the association of metabolic syndrome with kidney function and histology in 410 donors from 2005 to 2012, of whom 178 donors were systematically followed after donation since 2009. Metabolic syndrome was defined as per the NCEP ATPIII criteria, but using a BMI > 25 kg/m(2) instead of waist circumference. Following donation, donors received counseling on lifestyle modification. Metabolic syndrome was present in 50 (12.2%) donors. Donors with metabolic syndrome were more likely to have chronic histological changes on implant biopsies than donors with no metabolic syndrome (29.0% vs. 9.3%, p < 0.001). This finding was associated with impaired kidney function recovery following donation. At last follow-up, reversal of metabolic syndrome was observed in 57.1% of donors with predonation metabolic syndrome, while only 10.8% of donors developed de novo metabolic syndrome (p < 0.001). In conclusion, metabolic syndrome in donors is associated with chronic histological changes, and nephrectomy in these donors was associated with subsequent protracted recovery of kidney function. Importantly, weight loss led to improvement of most abnormalities that define metabolic syndrome.

Air pollution accountability research: Moving from a chain to a web.

Air pollution accountability studies examine the relationship(s) between an intervention, regulation, or event and the resulting downstream impacts, if any, on emissions, exposure, and/or health. The sequence of events has been schematically described as an accountability chain. Here, we update the existing framework to capture real-life complexities and to highlight important factors that fall outside the linear chain. This new "accountability web" is intended to convey the intricacies associated with conducting an accountability study to various audiences, including researchers, policy makers, and stakeholders. We also identify data considerations for planning and completing a robust accountability study, including those relevant to novel and innovative air pollution and exposure data. Finally, we present a series of recommendations for the accountability research community that can serve as a guide for the next generation of accountability studies.

Improvements in the delivery of resuscitation and newborn care after Helping Babies Breathe training.

BACKGROUND: To evaluate changes in neonatal resuscitation and postnatal care following Helping Babies Breathe (HBB) training at a community hospital in rural Honduras. We hypothesized that HBB training would improve resuscitation and essential newborn care interventions. METHODS: Direct observation and video recording of delivery room care spanned before and after an initial HBB workshop held in August 2013. Rates of essential newborn care interventions were compared in resuscitations performed by individuals who had and had not received HBB training, and run charts recording performance of newborn care practices over time were developed. RESULTS: Ten percent of deliveries (N=250) were observed over the study period, with 156 newborn resuscitations performed by individuals without HBB training, compared to 94 resuscitations performed by HBB trainees. After HBB training, significant improvements were seen in skin-to-skin care, breastfeeding within 60 min of age, and delayed cord clamping after 1 min (all P<0.01). More babies cared for by HBB trainees received basic neonatal resuscitation such as drying and stimulation. Run charts tracking these practices over time showed significant improvements after HBB training that were sustained during the study period, but remained below ideal goals. With improvement in drying/stimulation practices, fewer babies required bag/mask ventilation. CONCLUSION: In a rural Honduran community hospital, improvements in basic neonatal resuscitation and postnatal essential newborn care practices can be seen after HBB training. Further improvements in newborn care practices may require focused quality improvement initiatives for hospitals to sustain high quality care.

Gene activation of molecules with carcinoembryonic antigen determinants in fetal development and in adenocarcinoma of the colon.

"Fingerprints" of 0.9% NaCl solution extracts obtained from fetal guts and individual adenocarcinoma of the colon show a randomized pattern of expression of carcinoembryonic antigen (CEA) determinants by CEA radioimmunoassay and isoelectric focusing. All CEA-containing antigens found in a pool of 20 primary adenomas were found at some stage in fetal development. No single CEA-reacting peak was typical of any one period of fetal development. When fetal gut profiles were grouped according to trimester in utero, however, an expanded gene pool was found in the second trimester which correlates well with maximum gastrointestinal growth and differentiation. Isoelectric focusing-CEA radioimmunoassay profiles of individual primary adenomas were similar to but never identical with individual fetal gut profiles. "Fingerprints" of metastatic adenomas of entodermal origin showed quantitative and qualitative increases in molecules with CEA determinants unlike these latter categories. Such data suggest that both integrator and controller gene activities may be lost in metastatic disease. Rather than "phase-specific gene sets" on different chromosomes being activated by various oncogenic modalities, it is more probable that individual chromosomes are involved in oncogenesis. While more data are needed to confirm this idea, it is safe to say that the expression of molecules with CEA determinants need not be caused by either derepressive or reexpressive gene activation. These data point to the individuality of gene expression of molecules with CEA determinants both in fetal development and in early neoplasia. Since CEA-reacting molecules were not found in tumors of ectodermal or mesodermal origin by these methods, such products should be termed carcino-developmental antigens of entodermal or colonic origin.

Ultrastructural localization of in vivo-bound complement in bullous pemphigoid.

Antihuman complement component C3 labeled with horseradish peroxidase was used to reveal the ultrastructural localization of complement in two cases of bullous pemphigoid. The complement deposits were shown to be exclusively located in the space between the plasma membrane of the basal cells and the basal lamina. This corresponds exactly to the ultrastructural localization of immunoglobulins in bullous pemphigoid.

Ultrastructural localization of in vivo bound immunoglobulins in bullous pemphigoid--a preliminary report.

The ultrastructural location of in vivo bound immunoglobulins in a case of bullous pemphigoid was determined by coupling peroxidase to antihuman gamma globulin. Immunoglobulin deposits were found exclusively in the space between the basal cells and the basal lamina. The location of the immunoglobulin in bullous pemphigoid thus differs from that in lupus erythematosus where immunoglobulins are found mainly below the basal lamina.

Partial purification of pemphigus-related epidermal antigens.

Epidermal antigens partially purified by either isoelectric focusing (the pH 5.2 peak) or concanavalin A (Con A) affinity chromatography react with Con A in tube precipitation reactions. Bands of identity between crude skin antigens, the Con A affinity antigens eluted with alpha-methyl glucoside and the pH 5.2 peak are formed in Ouchterlony gel with rabbit antisera (Rab) to the pH 5.2 antigen. Absorption of Rab or pemphigus antibodies (Pab) with A+ erythrocytes does not affect complement fixation reactions of Rab with the skin antigen nor abolish the ability of Pab to interact with the intercellular cement. The pH 5.2 epidermal antigens react weakly with Pab in tube precipitation reactions and only weakly, if at all, to inhibit Pab reactions in the region of the intercellular cement. High concentrations of Con A inhibit the Pab, peroxidase-anti-IgG tissue reaction whereas the converse inhibition does not occur. Simultaneous use of both Pab and Con A-perodixase reactions at Con A concentrations which do not inhibit Pab, causes enhanced tissue peroxidase reactions in the region of the intercellular cement. These preliminary data indicate that the Pab and Con A-reacting sites are localized on different molecules or antigenic determinants in the intercellular cement. They exclude the possibility that A-blood substances are involved in either site.

Complement fixation for study of placental-type alkaline phosphatase.

Preparations of human placental alkaline phosphatase differing in specific enzyme activities were compared by microcomplement fixation assays using monospecific antisera. While both specific enzyme activity and complement fixation units increased 15,000-fold upon purification, the ratio between these units remained constant. Separation of an alkaline phosphatase preparation into 'A' and 'B' forms by ampholine isoelectric focusing indicated that these forms also possessed the same ratio of immunoreactive enzyme protein to enzyme activity. The correspondence of complement fixation units with specific enzyme activity indicates that complement fixation with monospecific antisera can be used to analyze structural differences among alkaline phosphatase isoenzymes.

Relation of glucose to alpha-fetoprotein in amniotic fluid.

A direct relationship between amniotic fluid glucose and alpha-fetoprotein (AFP) has been found between the 16th and 22nd weeks of pregnancy. This relationship is statistically significant (P less than .001) in each of the 6 gestational weeks tested, the coefficients of correlation vary from .74 to .91. The relationship between amniotic fluid AFP and another metabolite, urea nitrogen, was not significant (r = -.34), suggesting that the AFP-glucose relationship was not spurious. Absence of pregnancy-associated macroglobulins in the samples indicates that they were not contaminated by maternal serum. These data reflect an aspect of fetal metabolism or transport that should be investigated more thoroughly.

Partial vaginal agenesis with a urinary-vaginal fistula.

A patient with partial vaginal agenesis and a urinary-vaginal fistula is presented together with a review of the 12 cases reported previously. This unusual anomaly presents with cyclically recurrent hematuria; hypothetically, it results from failure of formation or canalization of the primitive vaginal plate together with partial persistence of the urogenital sinus. Surgical correction, ideally performed after puberty, requires resection of the fistula and mobilization of the apical vaginal segment for its anastomosis to the inferior vaginal pouch.

Complete duplication of the uterus and cervix with a unilaterally imperforate vagina.

Complete duplication of the uterus and cervix with a unilaterally imperforate vagina must be suspected when a unilateral pelvic mass terminates in a purpuric bulge of the lateral vaginal wall in a young woman with severely progressive dysmenorrhea. Intravenous pyelography will reveal renal agenesis ipsilateral to the imperforate vagina. The prompt and accurate diagnosis of this unusual anomaly should lead to transvaginal drainage of the retained menstrual fluids prior to irreversible damage of the pelvic viscera from chronic cryptomenorrhea.

Asymmetric hyperthecosis ovarii.

Testosterone and delta4-androstenedione concentrations, in venous blood obtained by percutaneous retrograde femoral catheterization of the ovarian and adrenal veins bilaterally, demonstrated the left ovary to be the predominant secretory source of androgens in an 18-year-old virilized female. Histologic examination of the excised ovarian tissue revealed asymmetric hyperthecosis ovarii and confirmed the biochemical data. This study demonstrates the accuracy of the venous catheterization method in locating preoperatively the hypersecretory source of androgens in virilized women. The favorable postoperative clinical result emphasizes the importance of an accurate preoperative diagnosis in virilized women even in the absence of ovarian neoplasia.

Use of beta-human chorionic gonadotropin in gestational aging.

Quantitative radioimmunoassay (RIA) of the beta chain of human chorionic gonadotropin (B-hCG) in serum has been used to evaluate the gestational status of 99 normal early pregnancies in contrast to 29 ectopic, threatened, aborted and/or terminated cases. Quantitative measurement of serum B-hCG-RIA standardized against the second international standard (2dIS) accurately established age of normal pregnancies in utero up to but not after three weeks postconception and with an accuracy of plus or minus four days between the third and eighth week of gestation. Quantitative urinary hCG-RIA standardized against the 2dIS were not useful for gestational aging. Useful serum hCG-RIA were identically linear and parallel with the 2dIS, had negligible crossreactivity with LH, FSH and/or TSH, and had low nonspecific binding. Of 13 hCG-RIA evaluated, only assays having these latter characteristics were able to detect ectopic pregnancies, spontaneous abortions, and/or threatened pregnancies with up to 90 percent accuracy. However, some assays not standardized to the 2dIS gave over 200 percent error in hCG serum values. Thus, correct choice of quantitative B-hCG reagents is necessary for early pregnancy assessment.