A general swimming response in exhausted obligate swimming fish.

Marine organisms normally swim at elevated speeds relative to cruising speeds only during strenuous activity, such as predation or escape. We measured swimming speeds of 29 ram ventilating sharks from 10 species and of three Atlantic bluefin tunas immediately after exhaustive exercise (fighting a capture by hook-and-line) and unexpectedly found all individuals exhibited a uniform mechanical response, with swimming speed initially two times higher than the cruising speeds reached approximately 6 h later. We hypothesized that elevated swimming behaviour is a means to increase energetic demand and drive the removal of lactate accumulated during capture via oxidation. To explore this hypothesis, we estimated the mechanical work that must have been spent by an animal to elevate its swim speed and then showed that the amount of lactate that could have been oxidized to fuel it comprises a significant portion of the amount of lactate normally observed in fishes after exhaustive exercise. An estimate for the full energetic cost of the catch-and-release event ensued.

Genes within the major histocompatibility complex predict NIDDM in African-American women in Alabama.

OBJECTIVE: To test the hypothesis that genes within the major histocompatibility complex (MHC) are associated with gestational diabetes mellitus (GDM) and, subsequently, non-insulin-dependent diabetes mellitus (NIDDM) in African-American women. RESEARCH DESIGN AND METHODS: African-American women who presented with GDM were compared with pregnant African-American control subjects. Following pregnancy, GDM patients were assessed at various intervals of time (median = 6 years) to determine whether they had developed diabetes. RESULTS: GDM patients who required insulin during pregnancy possessed a significantly higher frequency of A33, DR2, DR9, and BF-S phenotypes than control subjects. GDM patients who subsequently developed NIDDM had a significantly higher frequency of B41, DR2, and BF-S and a lower frequency of DR1 and DR6 phenotypes than control subjects. Even after controlling for age and body mass index, B41 and DR2 were independent predictors of developing insulin-requiring GDM and NIDDM in GDM subjects. CONCLUSIONS: These results suggest that either one or more genes within the MHC are involved in the etiology of NIDDM.

Reversal and convergence in marsupial chromosome evolution.

The karyotypes of marsupial species are characterized by their relatively low number of chromosomes, and their conservation. Most species have diploid numbers lying between the two modes, 2n = 14 and 2n = 22, but the karyotype of Aepyprymnus rufescens is exceptional in containing 2n = 32 chromosomes. Many differences in diploid number between marsupial species can be accounted for by particular fissions and fusions, which are easy to detect because of the low numbers of chromosomes in each karyotype. This should be a system in which it is possible to detect reversals and repeated chromosome rearrangements. We have used chromosome-specific paints derived from A. RUFESCENS to compare the karyotypes of eight marsupial species, representing closely and distantly related taxa, to trace chromosome change during evolution, and especially to detect reversals and convergence. From these and other painting comparisons, we conclude that there have been at least three reversals of fusions by fissions, and at least three fusions or fissions that have occurred independently in different lineages.

Free-radical metabolites of acetaminophen and a dimethylated derivative.

The oxidation of acetaminophen (4'-hydroxyacetanilide) to the corresponding N-acetyl-p-benzoquinone imines by plant and mammalian peroxidases is discussed. The acetaminophen free radical (N-acetyl-4-aminophenoxyl) has been reported as an intermediate. It is very reactive and forms melanin-like polymeric products. Application of a fast-flow system makes it possible to detect the transient species and clearly distinguish it from persistent paramagnetic melanin polymers. A model system, leading to more stable metabolites, can be obtained by introduction of methyl groups next to the oxygen, 3',5'-dimethylacetaminophen (3',5'-dimethyl-4'-hydroxyacetanilide). The ESR spectrum of the free radical formed could be completely analyzed and confirmed by deuterium substitution. The data are consistent with the assignment to a phenoxyl free radical (N-acetyl-2,6-dimethyl-4-amino-phenoxyl). Its formation is discussed in terms of substrate, hydrogen peroxide and enzyme concentration dependence. It is believed to be formed via a direct one-electron oxidation of 3',5'-dimethyl-4'-hydroxy-acetanilide. The radical does not form polymers or react with nucleophiles. Its redox behavior is discussed. The possible reaction of these phenoxyl free radicals with oxygen is thought to be negligible.

Prenatal diagnosis of autosomal recessive polycystic kidney disease (ARPKD): molecular genetics, clinical experience, and fetal morphology.

Autosomal recessive polycystic kidney disease (ARPKD) is one of the most common hereditary renal cystic diseases and has a high infant mortality. Prenatal diagnosis using fetal sonography can be unreliable, especially in early pregnancy. The ARPKD locus has been mapped to proximal chromosome 6p allowing haplotype-based prenatal diagnosis in "at-risk" families. From December 1994 to March 1997, we received 258 inquiries regarding prenatal evaluation and we have completed analyses in 212 families. To date, 65 prenatal analyses have been performed in 57 families. In the majority of the requesting families (45/57), the index children are deceased and their DNA was extracted from paraffin-embedded tissue. Eighteen fetuses were homozygous for the disease-associated haplotypes. In 12 of these fetuses, pathoanatomical examination demonstrated typical ARPKD changes consisting of dilated collecting ducts and the characteristic hepatic ductal plate malformation. These changes were detected in two fetuses as early as 13 weeks gestational age. These cases represent the earliest demonstration of ARPKD-associated histopathology reported to date. One high risk fetus was carried to term and turned out to be unaffected. However, the diagnosis of ARPKD remained doubtful in the index patient. Forty-three fetuses were either heterozygous or homozygous for a nondisease-associated haplotype and all infants born were phenotypically unaffected at birth. In four cases, a recombination event occurred between the flanking markers and no genotypic prediction was possible. Three of these pregnancies were terminated and necropsy of the fetuses confirmed ARPKD, while one fetus was carried to term and showed no abnormalities at birth. These results show that haplotype-based prenatal testing is feasible and reliable in pregnancies "at risk" for ARPKD. An absolute prerequisite for these studies is an accurate diagnosis of ARPKD in previously affected sib(s).

Comparison of different biomaterials for glaucoma drainage devices.

OBJECTIVES: To compare the inflammatory reaction associated with the insertion of silicone and polypropylene endplates and endplates made of a new biocompatible polymer, Vivathane, in the rabbit subconjunctival space. METHODS: Similar-sized endplates made of 3 different biomaterials were sutured to the sclera in the superotemporal quadrant of the rabbit eye. Thirty eyes of 15 albino New Zealand rabbits were randomly assigned to the 3 groups. Conjunctival vascular hyperemia was graded in a masked fashion among groups. At the end of 3 weeks, the enucleated eyes were examined histologically and using scanning electron microscopy. RESULTS: Polypropylene and Vivathane were associated with significantly more inflammation in clinical observations and based on histological grading. Silicone was associated with the least amount of inflammation. Three polypropylene and 1 Vivathane plate were extruded between the second and third week. CONCLUSIONS: Silicone is the most inert of the 3 materials tested. Inflammation associated with biomaterials may contribute to the failure of the glaucoma drainage devices. CLINICAL RELEVANCE: Bleb inflammation may be related to the biomaterial being used as the endplate. Endplates should be handled carefully during surgery to avoid creating rough spots.

Wegener's granulomatosis.

Clinical manifestations of Wegener's granulomatosis are nonspecific and indistinguishable from a variety of neoplastic, infectious, and inflammatory diseases. Ophthalmic disease is the presenting feature in nearly one sixth of patients with Wegener's granulomatosis and will ultimately develop in a majority. The discovery of antineutrophil cytoplasmic antibodies, particularly antiproteinase-3, has changed the clinical approach to evaluating patients suspected of having Wegener's granulomatosis. These antibodies are distinguished from other related autoantibodies because they produce a coarse granular pattern of cytoplasmic staining on indirect immunofluorescence with ethanol-fixed neutrophils. Treatment of Wegener's granulomatosis with oral cyclophosphamide and corticosteroids has decreased morbidity and improved survival, but side effects from long-term immunosuppressive therapy are common and sometimes serious. The effectiveness of trimethoprim-sulfamethoxazole in decreasing the number and severity of recurrences of Wegener's granulomatosis is being investigated. It remains to be determined if wide use of trimethoprim-sulfamethoxazole in limited Wegener's granulomatosis could further improve the quality of life for some patients.

Cystoid macular edema associated with latanoprost in aphakic and pseudophakic eyes.

PURPOSE: To describe four patients who developed cystoid macular edema shortly after onset of treatment with latanoprost. METHOD: Retrospective review of medical records of patients with open-angle glaucoma who developed cystoid macular edema shortly after starting latanoprost. RESULTS: The use of topical latanoprost was temporally related to the development of cystoid macular edema in four patients (six eyes; two aphakic eyes and four pseudophakic eyes). Cystoid macular edema resolved in all patients after latanoprost was discontinued. CONCLUSIONS: Cystoid macular edema is a potential complication of latanoprost therapy. Further observations are needed to determine if the risk of cystoid macular edema is limited to or greatest in patients who are pseudophakic or aphakic.

Direct electron spin resonance detection of free radical intermediates during the peroxidase catalyzed oxidation of phenacetin metabolites.

The oxidation of the phenacetin metabolites p-phenetidine and acetaminophen by peroxidases was investigated. Free radical intermediates from both metabolites were detected using fast-flow ESR spectroscopy. Oxidation of acetaminophen with either lactoperoxidase and hydrogen peroxide or horseradish peroxidase and hydrogen peroxide resulted in the formation of the N-acetyl-4-aminophenoxyl free radical. Totally resolved spectra were obtained and completely analyzed. The radical concentration was dependent on the square root of the enzyme concentration, indicating second-order decay of the radical, as is consistent with its dimerization or disproportionation. The horseradish peroxidase/hydrogen peroxide-catalyzed oxidation of p-phenetidine (4-ethoxyaniline) at pH 7.5-8.5 resulted in the one-electron oxidation products, the 4-ethoxyaniline cation free radical. The ESR spectra were well resolved and could be unambiguously assigned. Again, the enzyme dependence of the radical concentration indicated a second-order decay. The ESR spectrum of the conjugate base of the 4-ethoxyaniline cation radical, the neutral 4-ethoxyphenazyl free radical, was obtained at pH 11-12 by the oxidation of p-phenetidine with potassium permanganate.

Head and neck complications of epidermolysis bullosa.

Epidermolysis bullosa is a rare congenital skin disease which is characterized by easy formation of traumatic skin bullae. The disease is usually detected in early infancy due to the recurrent bullae. Prognosis is dependent on the histological variant which is present. A case of autosomal recessive epidermolysis bullosa is presented, which demonstrates many of the head and neck complications of the disease. Traditional skin care modalities as well as multiple surgical procedures such as skin grafts and the use of amniotic membrane were used without success. Limited natural healing, which was possibly promoted by oral phenytoin, has occurred.

Cutaneous manifestations of acute carbon monoxide poisoning.

A patient with acute carbon monoxide poisoning due to leakage of gas from the exhaust system in his automobile noted edema and blister formation over large areas of the skin of one half of his body. Rhabdomyolysis, acute but transient renal insufficiency, and hemolytic anemia developed subsequently.

Developing clinical decision-making skills in staff nurses; an educational program.

Clinical decision-making (CDM) is central to professional nursing practice. Use of this process enhances the nurse's ability to assess patients, to identify problems, and to plan individualized care. The Nursing Department at the Toronto General Hospital recognized that in order for nurses to effectively plan individualized care for their patients, they first needed help to develop their CDM skills. In response, a hospital-wide educational program was designed and implemented. This article describes the program and highlights the factors found to be crucial to its success. General recommendations are outlined for those who wish to design similar CDM skill-developing programs.

Increasing Medicaid clients' access to care. Church, state, and private providers collaborate.

Medicaid clients often have difficulty obtaining a physician referral and thus seek treatment for nonemergent conditions in hospital emergency rooms. A committee with representatives from Alexian Brothers Health System, Inc., Elk Grove Village, IL, and Catholic Charities of the Archdiocese of Chicago, Rolling Meadows, IL, has collaborated with six other organizations to put an end to this misuse of the healthcare system in Chicago's northwest suburbs. Catholic Charities Physician Referral Service came about as the result of research conducted by the committee which indicated that persons on public aid have limited resources available to secure primary healthcare. The committee also reviewed a United Way needs assessment and a survey of healthcare professionals and community leaders which substantiated that the community needed a referral service. In the past, Medicaid clients often had to make numerous futile telephone calls to locate physicians who would accept them. Through this service, however, Medicaid clients simply call Catholic Charities Physician Referral Service (which has information on participating physicians' specialty, location, and hospital affiliations) and then call the physician to whom they are referred. When physicians join the referral service, they specify the number of Medicaid patients they are willing to treat during the year. Catholic Charities will help the participating physicians secure payment from the Illinois Department of Public Aid for the health services they have provided.