Association between liver fibrosis and cognition in a nationally representative sample of older adults.

BACKGROUND AND PURPOSE: Liver fibrosis, a common yet often subclinical manifestation of chronic liver disease, may have an unrecognized role in cognitive impairment. We evaluated the association between a validated liver fibrosis index and cognitive measures among older adults. METHODS: We examined the association between liver fibrosis and cognitive performance among participants aged 60 years and older in the US National Health and Nutrition Examination Survey. Liver fibrosis was measured with the validated Fibrosis-4 (FIB-4) liver fibrosis score. The outcomes were performance on four standardized cognitive tests of immediate and delayed verbal learning, verbal fluency, and attention/concentration. We used linear regression to evaluate the association between FIB-4 score and performance on cognitive tests while adjusting for potential confounders. In sensitivity analyses, we examined this association in participants without known liver disease. RESULTS: Among 3217 adult participants, the mean age was 69 years, and 54% were women. Standard liver chemistries were largely in the normal range. However, 5.0% [95% confidence interval (CI) 4.0-6.0] had liver fibrosis based on a validated cut-off. In adjusted linear regression models, higher liver fibrosis scores were associated with worse immediate recall (ß -0.39; 95% CI -0.58, -0.21), language fluency (ß -0.46; 95% CI -0.72, -0.21), and attention/concentration (ß -1.34; 95% CI -2.25, -0.43), but not delayed recall (ß -0.10; 95% CI -0.20, 0.01). Results were similar when limiting the study population to participants without known clinical liver disease. CONCLUSION: Liver fibrosis, including subclinical liver fibrosis, may be an independent risk factor for cognitive impairment among older adults.

Acquired Oral Microflora of Newborns During the First 48 Hours of Life.

OBJECTIVE: To compare the oral microflora of a newborn during first hours after birth and after two days, and determine whether the newborn acquires his mother's microflora during this period. STUDY DESIGN: Saliva samples were taken from 50 newborns, on their first day of life, two days after, and from their mothers. Those samples were checked for total aerobic cultivated bacteria and mutans streptococci. RESULTS: Soon after birth, most newborns lacked any of the tested microorganisms in their oral cavity. Two days later, oral microorganisms were detected. A significant correlation was found between the total aerobic cultivated bacteria counts of the mothers, and of their newborns. CONCLUSIONS: It can be assumed, that on the first 48 hours of life, the newborn gains a major part of his oral microflora from his mother. These results might shade light on a possible to control and change the acquired microflora, at the very beginning of a human's life, creating a new, but less cariogenic flora. An accurate protocol should be examine to avoid this initial transmission during these days, while the mother and her newborn are still in the hospital, and thus might be possible to reduce caries prevalence in the future.

Salt shield: intracellular salts provide cellular protection against ionizing radiation in the halophilic archaeon, Halobacterium salinarum NRC-1.

The halophilic archaeon Halobacterium salinarum NRC-1 was used as a model system to investigate cellular damage induced by exposure to high doses of ionizing radiation (IR). Oxidative damages are the main lesions from IR and result from free radicals production via radiolysis of water. This is the first study to quantify DNA base modification in a prokaryote, revealing a direct relationship between yield of DNA lesions and IR dose. Most importantly, our data demonstrate the significance of DNA radiation damage other than strand breaks on cell survival. We also report the first in vivo evidence of reactive oxygen species scavenging by intracellular halides in H. salinarum NRC-1, resulting in increased protection against nucleotide modification and carbonylation of protein residues. Bromide ions, which are highly reactive with hydroxyl radicals, provided the greatest protection to cellular macromolecules. Modified DNA bases were repaired in 2 h post irradiation, indicating effective DNA repair systems. In addition, measurements of H. salinarum NRC-1 cell interior revealed a high Mn/Fe ratio similar to that of Deinococcus radiodurans and other radiation-resistant microorganisms, which has been shown to provide a measure of protection for proteins against oxidative damage. The work presented here supports previous studies showing that radiation resistance is the product of mechanisms for cellular protection and detoxification, as well as for the repair of oxidative damage to cellular macromolecules. The finding that not only Mn/Fe but also the presence of halides can decrease the oxidative damage to DNA and proteins emphasizes the significance of the intracellular milieu in determining microbial radiation resistance.

Alarm reaction of the top smelt, Atherinops affinis: reexamination.

We did not observe the reported alarm reaction of the top smelt Atherinops affinis (Ayres) when presented with a methanol extract of whole top smelt; we interpret the reaction as an experimental artifact. Rather, a methanol extract of top smelt is an attractant, as is methanol extract of shrimp.

Aerial vision: unique adaptation in an intertidal fish.

Mnierpes macrocephalus, a clinid fish of rocky shores of the eastern tropical Pacific, makes frequent terrestrial sojourns. The normal fish eye is myopic in air because of curvature of the cornea. This is overcome in Mnierpes by the presence of two flattened corneal surfaces.

Current status of prognostic immunohistochemical markers for urothelial bladder cancer.

The management and prognostication of patients with urothelial carcinomas (UCs), the most common histological type of bladder cancer, is mainly based on clinicopathological parameters. Several markers have been proposed to monitor this disease, including individual cell cycle-related proteins such as p53, pRb, p16, p21 and p27. Other putative markers are the oncogene products of FGFR3 and the ErbB family, proliferation markers including Ki-67, Aurora-A and survivin and different components within the immune system. In this review, a total of 12 parameters were evaluated and their discriminatory power compared. It is concluded that, in single-marker analyses, the proliferation markers Ki-67, survivin and Aurora-A offer the best potential to predict disease progression since they were all able to demonstrate independent prognostic power in repeated studies. Markers related to the immune system (e.g. CD8+ cells, regulatory T cells and cyclooxygenase-2 expression) or oncogene products of the ErbB family and FGFR3 are less powerful predictors of outcome or have not been equally well studied. The cell cycle-related proteins p53, pRb, p16, p21 and p27 have been extensively studied, but their usefulness as single prognostic markers remains unclear. However, in multimarker analyses, these markers appear to add prognostic information, indicating that they may contribute to more accurate treatment of UC.

Phylogeography of the spotted sand bass, Paralabrax maculatofasciatus: divergence of Gulf of California and Pacific Coast populations.

Have the warm tropical waters and currents of the southern Gulf of California, Mexico (also known as the Sea of Cortez), formed a barrier to gene flow, resulting in disjunct populations in the upper gulf that are isolated from the outer Pacific Coast? Phylogeographic and genetic divergences of the spotted sand bass, Paralabrax maculatofasciatus, from three Gulf of California and two outer Pacific coastal locations were tested using mitochondrial DNA (mtDNA) control region sequences. Sequence data from two congeners that are sympatrically distributed along the outer Pacific Coast, the barred sand bass, P. nebulifer, and the kelp bass, P. clathratus, were used to gauge the levels of genetic divergences. Differences among the three species and between the northern gulf and outer Pacific coastal populations of P. maculatofasciatus also were analyzed using 40 allozymic presumptive gene loci. Allozyme and mtDNA analyses each revealed many fixed differences among the species. Three significant allozymic frequency differences and two fixed mtDNA substitutions differentiated the gulf and outer Pacific coastal populations of P. maculatofasciatus. Three unique mtDNA haplotypes and three unique allozyme alleles were identified from the outer Pacific coastal population. The gulf sites contained four unique mtDNA haplotypes and six unique allozyme alleles. Partitioning of the mtDNA variation revealed that 72% of the variance occurred between the gulf and outer Pacific Coast, 20% between sampling sites in the two regions, and 8% within the sites. There appears to be little gene flow across the waters of the southern Baja Penninsula, producing divergence estimated as 120,000 to 600,000 years between the outer Pacific coastal and the Gulf of California populations. This separation level may date to a hypothesized seaway closure near La Paz, Mexico, during the mid-Pleistocene, and characterizes other fish populations. A second pattern of deeper allopatric species-level divergences in some other fishes may date to a Pliocene closure of a mid Baja Penninsular seaway. Significant differences also were discerned in P. maculatofasciatus between the San Diego and central Baja California coastal sites and between the upper/central and the lower gulf locations. Variation between locations in the two regions may be indicative of larval retention and low adult migration, which needs to be tested further.

Urinary estrogen metabolites and breast cancer: a case-control study.

Preliminary studies suggest that the estrogen metabolite 16 alpha-hydroxyestrone is associated with breast cancer, whereas 2-hydroxyestrone is not. However, epidemiological studies evaluating this relationship and taking established risk factors for breast cancer into account are lacking. The purpose of this study was to examine the association of the ratio of the urinary estrogen metabolites (2-hydroxyestrone and 16 alpha-hydroxyestrone) and of the individual metabolites with breast cancer. A spot urine sample, a brief history, and clinical data were collected from breast cancer cases (n = 42) and from women coming to the hospital for a routine mammogram or attending a free breast cancer screening (n = 64). 2-Hydroxyestrone and 16 alpha-hydroxyestrone were measured by enzyme immunoassay, and the estrogen metabolite ratio (EMR; 2-hydroxyestrone:16 alpha-hydroxyestrone) was computed. Cases and controls were similar in terms of age (mean age of cases, 53.8 +/- 15.1 years, versus 54.2 +/- 10.4 years for controls; P = 0.9) and demographics. Mean EMR was not associated with breast cancer overall (1.67 +/- 0.80 versus 1.72 +/- 0.66; P = 0.7). However, in postmenopausal women, the mean EMR was significantly lower in cases compared to controls (1.41 +/- 0.73 versus 1.81 +/- 0.71; P = 0.05). The multivariate adjusted odds ratios for the intermediate and lowest tertiles of the EMR relative to the highest among postmenopausal women were 9.73 (95% confidence interval, 1.27-74.84) and 32.74 (95% confidence interval, 3.36-319.09), respectively. The test for trend was highly significant (P = 0.003). Analyses of the individual metabolites indicated that 16 alpha-hydroxyestrone was a strong risk factor. The EMR did not show any consistent associations with age, race/ethnicity, age at first birth, parity, body mass index, family history of breast cancer, smoking, or alcohol intake. These data suggest a strong, inverse association of the EMR and a strong positive association of 16 alpha-hydroxyestrone with breast cancer in postmenopausal women. Larger studies are needed to confirm these results and to assess the relationship of the EMR and of the individual metabolites with breast cancer, with attention to menopausal status and clinical factors and with adjustment for known breast cancer risk factors.

Prediction of response to treatment in chronic pain patients.

A seven-item rating scale reported by researchers from the Mayo Clinic to have high validity in identifying chronic pain patients who would benefit from inpatient treatment was administered to an outpatient sample. Initial results did not replicate the previous findings; inclusion of four additional variables (disruption of a close relationship, altered body image, history of childhood illness, and history of abuse in childhood) produced results comparable to the Mayo study. This expanded screening test appears to be a useful method for selecting patients in a pain-management program and warrants further investigation.

An individualized protocol is more accurate than a standard protocol for assessing exercise capacity after heart transplantation.

BACKGROUND: Subjective improvement and normalization of exercise tolerance are reported by most of patients after heart transplantation. However, objective measurements often do not confirm the subjective improvement. This disparate observation may be related to the methods used to test exercise tolerance. We postulated that an individualized, more gradual exercise protocol might allow a more accurate assessment of exercise tolerance than standard protocols for patients with transplanted, denervated hearts. METHODS: Eleven stable heart recipients exercised on a treadmill using two different protocols. Protocol A was a standard Naughton's protocol, and protocol B was an individualized Naughton's protocol, in which the slope of the treadmill was increased only after a steady state in heart rate and oxygen consumption had been achieved and maintained for 30 seconds. RESULTS: Patients exercised longer and reached a higher workload with protocol B than with protocol A. Time to anaerobic threshold was significantly prolonged by protocol B. Minute ventilation and oxygen consumption at anaerobic threshold were significantly higher with protocol B than with protocol A. At peak exercise, heart rate, oxygen consumption, oxygen pulse, and minute ventilation were similar with the two protocols and exceeded 75% of the predicted corresponding maximal values for a normal matched population. CONCLUSIONS: The use of an individualized, gradual exercise protocol for heart transplant recipients detected a significantly better submaximal exercise capacity than a standard protocol, which is more consistent with the subjective improvement in functional capacity in this population.

Triple-drug immunosuppression with steroid discontinuation by six months after heart transplantation.

BACKGROUND: Triple-drug immunosuppression with cyclosporine, azathioprine, and prednisone is associated with complications which might be reduced by steroid withdrawal. METHODS: In two groups of heart transplant recipients maintained on an identical regimen of cyclosporine and azathioprine, prednisone was withdrawn in group I patients (n = 35) by 6 months after transplantation, whereas in group II patients (n = 49) prednisone was never discontinued. RESULTS: Survival was similar in the two groups. The incidence of acute graft rejection was significantly higher in group I (54%) than in group II (12%), whereas infective complications were significantly lower in group I than in group II (0.63 versus 1.02 episode/patient). The degree of posttransplantation weight gain, lipid abnormalities, and incidence of hypertension were not modified by the fast tapering of prednisone, whereas the incidence of cataract and compression fracture and the degree of bone loss were significantly reduced in group I. Graft function and incidence of coronary artery disease were similar in the two groups. CONCLUSIONS: The present data suggest that prednisone can be safely withdrawn in heart transplant recipients without jeopardizing survival and graft function. Longer follow-up is needed to assess the full impact of early withdrawal of steroids from triple-drug immunosuppression, especially on long-term graft function and incidence of coronary artery disease. Benefits of early steroid withdrawal included a reduction in bone loss, which might ultimately have a major positive impact on the extent of long-term rehabilitation and exercise tolerance after heart transplantation.

Quantifying mammary duct carcinoma in situ: a wild-goose chase?

Duct carcinoma in situ (DCIS) is a malignant neoplasm of the breast that is limited to the glandular component. The introduction of mammographic screening allows for earlier detection of carcinoma, at the stage of DCIS, before it invades the surrounding stroma. Although DCIS has been studied extensively, its quantification remains a dilemma. Several methods for measuring DCIS exist, including clinical measurement, radiographic assessment, and gross pathologic assessment. Other methods have been employedfor this purpose, such as counting the number of tissue sections involved, direct measuring of DCIS from glass slides, and even counting the number of ducts involved. Furthermore, there is no consensus for assessing adequacy of margins. The myriad of techniques for quantifying DCIS has profound implications for treatment and for prognostic evaluation. The inherent difficulties in quantifying DCIS are multifactorial, and the need to establish a standardized approach for reporting the extent of DCIS by correlating radiographic, clinical, gross, and histologic findings is imperative.

An analysis of closed obstetric malpractice claims.

We reviewed all closed obstetric claims in the records of a major physician-sponsored malpractice insurer that has written policies from 1982 to the present. Of the 54 files closed during the 6.5-year period covered by this study, 21 (39%) involved physician reports of bad outcomes that did not lead to a formal claim. Of the 33 formal claims, 14 (42%) were dismissed, either by the plaintiff's attorney or by the courts. Eighteen of the remaining 19 claims were settled before trial, with an average payment to the plaintiff of $185,000. The one suit that went to trial resulted in a defense verdict. A review of the case histories demonstrated that in the majority of cases when a payment was made, probable medical negligence had taken place. Non-meritorious claims were not compensated. For those cases in which a payment was made, the size of the settlement was commensurate with the seriousness of the injury, which almost always involved damage to the infant. Poor physician judgment was the most common source of error.

Obstetric practice patterns in Washington state after tort reform: has the access problem been solved?

We surveyed all potential obstetric providers in Washington state in the spring of 1989 to determine whether the passage of tort reform in 1986 had improved access to care for rural and medically indigent women. We found that, although the exodus of family physicians from obstetric practice that had been observed between 1985-1986 appears to have slowed, there is still substantial net attrition among family physicians. As a result, rural patients are having increasing difficulty obtaining local access to obstetric care. By contrast, the supply of obstetricians and midwives seems to be stable. All three groups of providers are increasingly reluctant to provide care to the growing number of Medicaid patients. Although tort reform may have slowed the rate at which providers are quitting obstetrics, equilibrium has not yet been achieved. Shortages of rural physicians and inadequate Medicaid reimbursement rates must be addressed to improve obstetric access for underserved groups.

Do women choose their obstetric providers based on risks at entry into prenatal care? A study of women in Washington State.

OBJECTIVE: To study risk factors in a large population of women over a broad geographic area as they entered obstetric care, and to assess how they distributed themselves among the specialties. METHODS: Data from 1 year were gathered through a retrospective chart review of all women initiating care with randomly selected urban and rural obstetricians, urban and rural family physicians, and urban certified nurse midwives. RESULTS: The majority of women had at least one risk factor at entry into care. When a scoring system was applied to the data, 13.5% of the women were designated "high risk," which is consistent with findings of other studies. However, women did not distribute themselves to provider types according to risk. Higher-risk women were more likely to choose family physicians, especially in rural areas. Much of this difference can be attributed to young maternal age, late entry into care, and lack of health insurance or Medicaid sponsorship. CONCLUSION: These findings suggest that economics and geography are more likely to influence a woman's initial choice of provider than medical and obstetric risk.

Why do physicians stop practicing obstetrics? The impact of malpractice claims.

We studied all physicians who purchased obstetric malpractice insurance from the Washington State Physicians Insurance Exchange and Association between January 1, 1982 and July 1, 1988. Of the 690 physicians studied, 171 (32% of the family physicians and 10% of the obstetricians) discontinued obstetrics but remained in practice. Physicians who discontinued obstetric practice were older, more likely to practice in an urban area, and more likely to be in solo practice than those who did not. Obstetricians who discontinued obstetric practice had a higher rate of new obstetric malpractice claims than did those who did not quit practicing obstetrics--14.5 versus 6.2 claims per 100 physician-years of coverage. By contrast, those family physicians leaving obstetrics had a lower rate of new claims than their peers who did not quit. We conclude that older physicians--particularly those in urban and solo practice--are most likely to stop practicing obstetrics, regardless of specialty. In addition, being named as the target of an obstetric malpractice claim plays a significant role in the decision of some obstetricians to discontinue obstetric practice.

Characteristics of physicians with obstetric malpractice claims experience.

This study compared the demographic and practice characteristics of physicians with and without obstetric malpractice experience. The sample consisted of 387 family physicians and 204 obstetricians in Washington state who were insured for obstetrics by a major malpractice carrier between January 1982 and June 1988. Fifty-three physicians (9%) had an obstetric malpractice claim during the study period. The approximate overall rate of obstetric malpractice claims was low: 0.32 per 1000 deliveries. The higher the total delivery volume (exposure), the greater the chance of having malpractice experience. Although physicians with practices of over 200 deliveries per year were more likely to have had malpractice experience, their risk of malpractice experience per delivery was lower than that of providers doing fewer than 200 deliveries per year. Our work suggests that insurers might consider basing obstetric malpractice premiums on numbers of deliveries rather than specialty.

Do providers adhere to ACOG standards? The case of prenatal care.

OBJECTIVE: To examine the extent to which obstetric providers abide by prenatal practice guidelines published by ACOG. METHODS: The prenatal records were abstracted for low-risk patients initiating care with randomly selected urban obstetrician-gynecologists, rural obstetrician-gynecologists, urban family physicians, rural family physicians, and urban certified nurse-midwives in Washington state between September 1, 1988 and August 30, 1989. The prenatal care recorded in their medical charts was compared with the ACOG-recommended guidelines. RESULTS: Overall, providers of all five types adhered closely to the published standards. Certified nurse-midwives recorded a standard of practice that most closely matched that recommended by ACOG. Overall, there was less complete adherence in the recording of maternal height, fetal activity after 30 weeks' gestation, and fetal presentation at or after 36 weeks' gestation. Those laboratory tests that ACOG has recommended most recently (serum alpha-fetoprotein and diabetes screening) and those not recommended for routine use were ordered less often on average by providers. CONCLUSIONS: The cross-sectional nature of this study cannot demonstrate definitively that ACOG's guidelines have changed provider prenatal practices. However, these findings demonstrate that providers in varying specialties and geographic locations can adhere to a detailed set of clinical guidelines if they are appropriately disseminated and implemented.

Unrecognized thrombocytopenia and regional anesthesia in parturients: a retrospective review.

Charts from 2929 consecutive parturients were reviewed. Twenty-four had platelet counts less than 100,000/microL in the peripartum period. Seventeen of the 24 had predisposing causes for thrombocytopenia, including preeclampsia (nine), immune thrombocytopenia purpura (two), infection (three), placenta accreta (one), abruption (one), and excessive surgical bleeding (one). Seven had asymptomatic thrombocytopenia of unknown origin. Fourteen of the 24 thrombocytopenic patients received regional anesthesia, and none had permanent sequelae. Based upon this retrospective review, peripartal thrombocytopenia (15,000-99,000/microL) did not increase the risk of neurologic complications after a regional anesthetic. There have been no reports in the literature of spinal or epidural hematomas in parturients after regional anesthesia, except for one patient with a spinal ependymoma.

Verapamil increases the toxicity of local anesthetics.

The calcium channel blocker verapamil has, in addition to its other properties, been shown to be a local anesthetic. Its concurrent use in a patient undergoing regional anesthesia may, therefore, increase the potential risk for local anesthetic toxicity. To evaluate this possibility, the effect of verapamil on the median lethal dose (LD50) of lidocaine and bupivacaine in mice was determined. Immediate pretreatment with verapamil increased the mortality of mice given the LD50 dose of lidocaine to 74%, and in mice given the LD50 doses of bupivacaine, to 82%. In animals pretreated with verapamil and calcium chloride, the mortality associated with the administration of LD50 doses of lidocaine and bupivacaine decreased to 43% and 48%, respectively, thus returning the mortality rate back to the LD50 of the local anesthetics when administered alone. It seems that the combined administration of local anesthetic and verapamil results in a significant drug interaction: the resulting blockade of sodium and calcium channels apparently impairs membrane function to a greater degree than with either drug alone. Additional investigation is warranted, and caution should be exercised in giving verapamil to patients during regional anesthesia. Should an adverse drug interaction ensue, the administration of calcium may be beneficial.