Intravenous and intraruminal administration of short chain fatty acids increase the potential difference across the sheep rumen epithelium.

The effect of intraruminal loads of a propionate/butyrate mixture and of intravenous administration of butyrate on the potential difference across the rumen epithelium (PD) was studied in conscious sheep. The PD was elevated during the measurement period 5 to 15 minutes after intraruminal loading with a propionate/butyrate mixture. Intravenously injected butyrate caused a prompt transitory increase in PD. The results show that both intraruminal and intravenous administration of certain short chain fatty acids stimulated the PD indicating altered ion transport properties across the rumen epithelium.


[The effect of fermented-milk bifidumbacterin on the intestinal microflora of test pilots].

Bacteriological study of intestinal microflora in test pilots, regularly exposed to excessive physical, as well as nervous and emotional strain, has revealed changes in the composition of their intestinal microflora. Correction of microflora by means of bifidumbacterin, a curative lactic fermentation alimentary product, was carried out. Rapid and effective restoration of intestinal microflora and improvement of the general state of patients were noted, which made it possible to recommend this product as a prophylactic remedy for subjects at risk of development of dysbiotic disturbances.


[Expert research on sera yielding false-positive results for HIV antibodies during screening].

The significance of different serological methods and assay systems for the verification of false positive cases of HIV infection has been analyzed on the basis of materials obtained in arbitration studies. As demonstrated by this analysis, the use of such highly specific and sensitive systems as Huma-Lab, Enzygnost, Serodia and Erythrorecombinant has made it possible to obtain a reliable result as early as at the first stage of expert diagnosis in the enzyme immunoassay and the agglutination test. The methods of radioimmunoprecipitation and indirect immunofluorescence have permitted a more precise differentiation of doubtful results than that achieved by immune blotting.


[The diagnostic value of different test systems for the screening determination of antibodies to the human immunodeficiency virus].

Evaluation of the quality of enzyme immunoassay (EIA) systems by their sensitivity and specificity is inadequate, mainly due to the impossibility of detecting early or latent HIV infection in humans as it manifests by seroconversion only to a few HIV proteins. The additional evaluation criterion (confirmation rate) has been introduced, and an original method for the integral evaluation of the quality of assay systems intended for the diagnosis of HIV infection by EIA techniques has been proposed.


[The formation of host-parasite relationships in an experimental mixed pathology of opisthorchiasis-tuberculosis as dependent on the phase of the Opisthorchis infestation].

Superinfection of animals having Opisthorchis invasion with Mycobacterium tuberculosis leads to destabilization of host-parasite relationships in opisthorchiasis and formation of new host-parasitocenotic interrelations whose manifestation depends on the phase of the invasive process. At the acute invasive phase of mixed pathology (2 weeks) the activity of the host's immune system increases, while the biological activity of helminths and the number of M. tuberculosis colonies decrease. And on the contrary, at the subacute phase of mixed pathology (2.5 months) the activity of the host's immune system decreases, while the reproductive activity of helminths and the isolation rate of M. tuberculosis from pulmonary tissue increases in comparison with the groups of animals with monoinvasion and monoinfection.


[Pasteurized milk as a factor in the transmission of the causative agents of yersiniosis].

From 43 (35.8%) out of 120 samples of pasteurized milk used by volunteers 182 cultures of five Yersinia species--Y. enterocolitica, biovar 1 (70.3%), Y. intermedia (18.1%), Y. frederiksenii (7.7%), Y. kristensenii (3.3%) and Y. aldovae (0.5%)--were isolated in the course of bacteriological studies carried out in 1987-1990. The isolated Yersinia cultures belonged to nonpathogenic pyraminidaze-positive serovars. Yersinia pathogenic bio/serovars (4/O3, 2/O9, 1B/O8) were not detected. No deviations from the normal state were registered in the volunteers drinking pasteurized milk, and Yersinia could be isolated from their feces only during the first 3 days following milk consumption. In 390 patients examined for the presence of Yersinia infections the isolation rate of Yersinia of biovar 1 (99.6% of the cultures) varied between 4.4% and 21.3% and correlated with the increase of the isolation rate from milk (13.6% to 53.9%). The results of the study suggest that unboiled pasteurized milk contributes to the spread of Yersinia carriership among the population.


[Staphylococci in the microbiocenosis of the skin of the hands].

The skin autoflora on the pad of a forefinger and the back and palm of a hand was studied in 40 healthy males aged 18-60 years by the modified washing and scraping method of P. Williamson and A. Kligman. 638 cultures of aerobic microorganisms, including coccal (55.3%) and bacilliform (44.7%) microbes, were isolated. In 6 persons (15%) coagulase-positive staphylococci were detected. Out of 10 coagulase negative species of this genus, S. epidermidis, S. saprophyticus and S. warneri occurred most frequently on the skin of hands. The highest density of bacterial populations (10.970 +/- +/- 1.845 cells/sq. cm) was registered on the back of hands, the surface of palms was found to have somewhat lower density (8.679 +/- 1.282 cells/sq. sm) and the skin of forefingers, the lowest density of bacterial populations (6.878 +/- +/- 1.137 cells/sq. sm). 17.5% of examined persons were found to be carriers with S. aureus isolated from their nasal mucosa. S. aureus isolated from the skin surface and the nasal cavity of different persons belonged to different phage variants, but S. aureus isolated from the nasal cavity and the skin of the same person belonged to one phage variant.


[The correction of the functional activity of alveolar macrophages in inducing a primary immune response in influenza].

The functional activity of alveolar macrophages obtained from mice, both healthy and infected with influenza virus A/Aichi 2/68 (H3N2), as manifested by their capacity to initiate the development of primary immune response to sheep red blood cells and Escherichia coli lipopolysaccharide after the transfer of these macrophages to intact syngeneic recipients was studied. The capacity of alveolar macrophages to perform antigen-presenting functions in the induction of humoral immune response was shown, and at the same time the development of experimental influenza infection was found to essentially decrease these properties. The injection of the immunomodulating agent diuciphon into experimental mice somewhat enhanced the immune response after the syngeneic transfer of alveolar macrophages from infected mice to intact recipients.


[The opsonizing activity of the sera of hamadryas baboons immunized with a preparation of the outer membranes of Francisella tularensis (based on data from the luminol-dependent luminescence method)].

The opsonizing properties of sera obtained from hamadryas baboons immunized with the preparation of F. tularensis outer membranes (OM) were studied with the use of luminol-dependent chemiluminescence (CL) of whole blood. The immunization of monkeys with the OM preparation was shown to lead to the formation of functionally active antibodies possessing opsonizing properties with respect to virulent F. tularensis. Immune sera obtained from the animals immunized with live vaccine and from those immunized with OM preparation had no essential differences in their opsonizing properties. The level of IgG antibodies in immune sera correlated with the CL parameters of whole blood in the presence of F. tularensis opsonized with these sera. Increased CL of phagocytes observed after addition of bacteria and immune sera under test to whole blood taken from a nonimmune donor made it possible to evaluate the functional activity of antibodies, thus permitting its use as a test for the evaluation of the effectiveness of new vaccine preparations.


[The antigenic and allergenic properties of an extract from the house dust mite Dermatophagoides farinae].

To evaluate the antigenic composition and allergenic activity of D. farinae extracts, the methods of rocket and cross immunoelectrophoresis, gel chromatography and the inhibition of the radioallergosorbent test have been used. The presence of 9-20 antigenic components has been established. The fractions of the extract with a molecular weight of 10-200 kD possessed the highest capacity of inhibiting the binding of specific IgE antibodies from the pool of sera from patients sensitized to D. farinae.


[Experience with the use of an immunoglobulin erythrocyte preparation for the early laboratory diagnosis of pseudotuberculosis].

An immunoglobulin erythrocytic preparation for the rapid detection of Yersinia pseudotuberculosis was developed. The preparation was shown to be specific and sufficiently sensitive (8 x 10(5) microbial cells/ml). The preparation was used for the examination of 102 patients; in 62 of these patients the diagnosis was confirmed by means of common laboratory and clinical methods. Y. pseudotuberculosis antigen was detected in the blood of 39 patients (63%), and in 12 patients (29.4%) the results of traditional laboratory tests were negative. In 19 out of 23 patients the coincidence of the results of bacteriological and seroindication study was registered. During the study of the remaining 40 patients the antigen was detected only in 6 patients, including 3 patients with enteric yersiniosis.


[The biological properties of Bifidobacterium].

The possibility of the formation of exoenzymes, such as DNAase, RNAase and hemolysin, by bifidobacteria was studied in comparison with their acid-forming and adhesive activity. Bifidobacterium reference strains, originally isolated from healthy adults and children, were studied. The study involved altogether 73 strains of bifidobacteria, including 24 B. bifidum strains, 13 B. adolescentis strains, 7 B. infantis strains, 10 B. breve strains and 19 B. longum strains. The bifidobacteria under study were shown to differ not only in the presence and activity of properties useful for macroorganisms, but also in the presence of enzymes having depolymerizing activity (DNAase, hemolysin). Thus, out of 73 strains under study 9 proved to be DNAase-positive and 6, hemolysin positive. At the same time a specific feature of bifidobacteria was their high acid-forming activity with the complete absence of RNAase activity and insignificant DNAase- and hemolysin-forming activity.


Use effectiveness of the Cytobrush in the primary care setting.

Numerous studies indicate that Papanicolaou smears contain better cellular material when the technique for collecting the sample employs the Zelsmyn Cytobrush. Few studies, however, have examined its ability to increase the percentage of abnormal Papanicolaou smear results in actual clinical practice. This study looked at 7999 Papanicolaou smears done by 46 primary care physicians to determine the percentage of abnormal results during two different periods. The Cytobrush technique was then implemented; and after 6029 Papanicolaou smears, the percentage of smears with abnormal findings was recalculated. The proportion of Papanicolaou smears demonstrating significantly abnormal cells remained constant during the three observation periods: 1.81 percent during the first period, 1.96 percent during the second period (before the Cytobrush technique was implemented), and 1.96 percent during the third period (after the Cytobrush technique was implemented). It seems logical that Papanicolaou smears containing better cellular material from the squamocolumnar junction would increase the yield of Papanicolaou smears with cancerous and precancerous cells. Our study, however, did not confirm this supposition. While evaluation of Papanicolaou smear technique based on quantity and quality of cellular material is important, we believe the effectiveness of any technique must be evaluated from another perspective--the actual practice setting.


Use of deep venous thrombosis prophylaxis by family physicians.

Accumulated data indicate that the administration of low-dose subcutaneous heparin reduces the incidence of deep venous thrombosis in high-risk surgical and medical patients. Because deep venous thrombosis predisposes to pulmonary embolism, it is generally accepted that reducing deep venous thrombosis will reduce pulmonary embolism, the most common preventable cause of death in hospitalized patients. There are few data, however, regarding physicians' use of heparin for deep venous thrombosis prophylaxis in medical patients. We reviewed charts of medical patients aged 50 years and older who were admitted to family practice services in a community teaching hospital and excluded patients who were not candidates for heparin prophylaxis. Eighty (65 percent) of 123 patients received heparin for deep venous thrombosis prophylaxis. Patients admitted to a residency teaching service were more likely to receive heparin for deep venous thrombosis prophylaxis than were patients admitted to nonteaching services (odds ratio 3.37, 95 percent confidence interval 1.26-9.21, P = 0.012). An association between the patient's number of risk factors for deep venous thrombosis and likelihood of receiving deep venous thrombosis prophylaxis approached statistical significance (P = 0.078). In our institution, heparin for deep venous thrombosis prophylaxis is frequently but not uniformly prescribed for appropriately selected family practice inpatients. No similar data for nonsurgical patients were found for comparison.


Evaluation of a latex agglutination test for the identification of Candida species in vaginal discharge.

The diagnosis of Candida vulvovaginitis using historical symptoms, pelvic examination findings, and results of traditional in-office laboratory tests is often inaccurate. Although Candida cultures can verify the diagnosis, they are not routinely used. We prospectively compared the accuracy of a commercially available, in-office, rapid, latex agglutination test (CandidaSure) for the identification of Candida species with results from Candida culture. The sensitivity of the latex agglutination test was 66 percent and the specificity was 63 percent when compared with Candida culture results in patients with vaginal symptoms. When compared with a microscopic evaluation using potassium hydroxide (KOH), the CandidaSure test had greater sensitivity but a lower specificity. In 74 percent of cases with a positive KOH preparation, yeast forms were present on culture, and little was gained by adding the CandidaSure test in this situation. The addition of the CandidaSure test in those cases with a negative KOH preparation resulted in increased sensitivity but also increased the number of false-positive diagnoses. The CandidaSure test has greater sensitivity than the KOH preparation, but it is less predictive of a positive culture. Because of this limitation, Candida should be documented by culture for any patient who has recurrent or persistent disease and a negative KOH slide.


Longitudinal study of a diabetes education and care intervention: predictors of improved glycemic control.

This study prospectively identifies those characteristics of office patients with diabetes that predict subsequent improvement in glycemic control in response to an educational intervention. Data on demographic factors, disease characteristics, and glycemic control were obtained on a consecutive series of patients referred by their primary physician to a 4-day outpatient diabetes education and care program. Follow-up measurement of glycosylated hemoglobin (HbA1C) was obtained from the same laboratory 2 months later. Analysis using logistic response models identified baseline characteristics associated with improved HbA1C. Among the 169 study subjects, 74 (44 percent) had at least a 20 percent improvement in HbA1C levels 2 months after the program. Among these subjects, mean HbA1C level was 10.6 percent before and 7.4 percent 2 months after the program. Factors associated with improvement in HbA1C values in bivariate and multivariate logistic models included duration of diabetes less than 2 years (risk ratio = 1.90, 95 percent confidence interval (CI) 1.30-2.76) and initial HbA1C level greater than 10 percent (risk ratio = 2.75, 95 percent CI 2.08-4.01). Baseline functional status, health locus of control, social support, knowledge of diabetes self-care, age, weight as percentage of ideal body weight, age at diagnosis, race, sex, family history of diabetes, type of diabetes, and mode of treatment were not significant predictors of improved HbA1C. Patients with shorter duration of diabetes and poor baseline glycemic control were most likely to have clinically significant glycemic responses to this program. Severity of disease and regression to the mean were unable to account for this association, leaving unanswered the question of the mechanism of this association. The data also identified a group of patients who do not respond well to this educational approach and for whom novel approaches to behavior change should be considered.


The complications of immobility in the elderly stroke patient.

Approximately 500,000 persons in the United States suffer a stroke each year; the majority of these individuals are 65 years of age or older. The neurological impairment occurring as the result of stroke can lead to both acute and chronic disability. Further medical complication and disability are often the result of immobility-related illness that occurs while the patient is still in the hospital. A MEDLINE search for articles published from 1980 to 1990 was made using the key words immobilization and stroke rehabilitation. The bibliographies of these articles, key rehabilitation and geriatric textbooks, the bibliographies of these textbooks, and the authors' personal files were also sources of information. Immobility-related medical complication and disability can be substantially reduced by identifying risk factors and applying preventive measures. As long-term providers of medical care, family physicians are in a position to devise a preventive care plan for immobility-related disability and to appreciate the beneficial effects of such a plan on patient outcome.


Venomous snakebite: past, present, and future treatment options.

Venomous snakebites continue to cause great morbidity, and treatment options are confusing the attending physician. In the United States approximately 45,000 snakebites occur each year, of which some 8000 are by 20 species of venomous snakes. Information on venomous snakes and snakebite treatment was gathered from the libraries of the Wilderness Medical Society and the Rocky Mountain Center for Wilderness Medicine in Boise, Idaho (co-supported by the Boise State University and the Family Practice Residency of Idaho), as well as from current literature files of physicians practicing wilderness medicine. Three genera of venomous snakes account for the majority of poisonous snake envenomations in this country. Most hospitalized victims are bitten either by rattlesnakes or copperheads or by unidentified snakes. Most of these bites occur during the summer months and are found on the extremities. Field treatment focuses on the application of a vacuum extractor and transportation to the nearest medical facility. Although constriction band use can be helpful, tourniquets, incision and suction, and ice therapy are contraindicated. Electric shock therapy is of no use and could cause serious injury. Hospital management focuses on rapid clinical evaluation and laboratory tests to establish the degree of envenomation, looking for clotting abnormalities. If envenomation has occurred and is reactive, polyvalent antivenin should be administered according to the degree of envenomation. Errors in diagnosis and treatment result in increased morbidity and put attending physicians at risk for litigation. Prevention remains the most successful approach to snakebite management.


Will family physicians really return to obstetrics if malpractice insurance premiums decline?

The loss of family physicians as obstetrics providers during the last decade has had a significant impact on access to obstetric services, especially for rural populations. The expense of malpractice premiums has been cited often as a reason for physicians' discontinuation of this service. Seventy-six family physicians in northern California who recently discontinued obstetrics were surveyed regarding their decisions related to obstetric practice. Those physicians who indicated that a decrease in malpractice premiums would allow them to consider resuming obstetrics were resurveyed by telephone the following year. This telephone survey occurred following a 25 percent decrease in malpractice premiums for obstetrics by the major malpractice insurance carrier for family physicians practicing obstetrics in the study area. Twenty-nine of the 76 physicians in the original survey who had recently discontinued obstetrics stated they would consider resuming if conditions changed. Twenty-six (90 percent) of these physicians indicated that malpractice premiums needed to change for them to consider resuming obstetrics. Following the reduction in premiums, none of these physicians reported plans to resume obstetrics or even a likelihood that they would be resuming obstetrics. This study found that family physicians who discontinued obstetrics and cited malpractice premiums as a barrier to resuming obstetrics are unlikely to resume when rates decline. This finding suggests that other issues might be equally or more important in this decision.


A five-step "microskills" model of clinical teaching.

Teaching family practice residents in a clinical setting is a complex and challenging endeavor, especially for community family physicians teaching part-time and junior faculty members beginning their academic careers. We present a five-step model of clinical teaching that utilizes simple, discrete teaching behaviors or "microskills." The five microskills that make up the model are (1) get a commitment, (2) probe for supporting evidence, (3) teach general rules, (4) reinforce what was done right, and (5) correct mistakes. The microskills are easy to learn and can be readily used as a framework for most clinical teaching encounters. The model has been well received by both community family physicians interested in teaching and newer residency faculty members.


Dermatologic manifestations of giardiasis.

We have presented a case of atopic dermatitis associated with Giardia lamblia infection, which has not been previously described. Review of the world literature shows an association between giardiasis and urticaria. Other allergic phenomena, such as angioedema and possibly arthropathy, also might be associated with this infection. When confronted with these clinical problems, giardiasis should be included in the differential diagnosis. As these complications respond to specific therapy, identification of this organism as its cause can be particularly rewarding.


Can physicians be induced to resume obstetric practice?

Decreased numbers of obstetric providers during the last decade have limited access to obstetrics care, especially for some groups of women. Increasing or stabilizing the number of providers could increase access. A questionnaire was mailed in 1989 to 1965 Washington State family physicians and obstetricians to determine their attitudes toward the practice of obstetrics. Sixty-six percent of physicians responded to the survey. Of those who had quit obstetrics in the previous 3 years, 42 percent of responding family physicians and 19 percent of responding obstetricians would consider resuming. Those family physicians willing to consider resuming their obstetric practices were more likely to have been in practice fewer years, employed by a health maintenance organization (HMO), or located in a rural area. A majority of all respondents cited excessive malpractice premiums and fear of malpractice suit as reasons for stopping obstetric practice. Family physicians willing to consider resuming obstetrics were more concerned about the overall number of obstetric providers in their area. Rural family physicians willing to consider resuming obstetrics listed poor backup or shared call more often as a reason they had quit. Attention targeted to the concerns of family physicians who have been in practice for a short time, who work for HMOs, or who are in rural practice might help induce some physicians to resume obstetrics.


Transport and in vivo elimination of cysteinyl leukotrienes.

Transport processes control not only synthesis and release of LTC4 but also the elimination and excretion of LTC4 and its metabolites. (i) A primary-active ATP-dependent export carrier mediates the release of LTC4 from a leukotriene-generating cell, as exemplified by mastocytoma cells, and as measured in mastocytoma plasma membrane vesicles (2). (ii) Release of cysteinyl leukotrienes into the blood circulation is followed by a rapid elimination with an initial half-life of 38 sec in rats and 4.0 min in man, as measured with the labeled, representative LTC4 catabolite, N-acetyl-LTE4. (iii) 11C-labeled N-acetyl-LTE4 can serve for non-invasive studies on cysteinyl leukotriene elimination and excretion by the liver and kidney in the intact organism using positron emission tomography. An impairment of leukotriene transport from the liver across the canalicular membrane into bile, studied in mutant rats and in extrahepatic cholestasis, leads to a compensatory diversion of cysteinyl leukotriene elimination to the kidney. N-Acetyl-LTE4 labeled with a short-lived positron-emitting isotope provides quantitative insight into the pathways of cysteinyl leukotriene elimination in vivo. (iv) Cysteinyl leukotriene export from the liver into bile is mediated by an ATP-dependent primary-active export carrier. This decisive step in cysteinyl leukotriene elimination has been characterized in hepatocyte canalicular membrane vesicles (3). The leukotriene exporter is deficient in transport mutant rats. The leukotriene carrier is distinct from other ATP-dependent export carriers identified in this membrane domain, such as the ATP-dependent bile salt export carrier (25) and the multidrug export carrier (27).


[ICD-9 versus DSM-III in the psychoses: anamnestic and catamnestic implications].

We pretend with our study to compare the DSM-III diagnostic criteria with ICD-9 diagnostic criteria for psychotic episodes and to look for the diagnostic stability for both classifications. We studied 79 first psychotic episodes following ICD-9 and retrospectively we applied the DSM-III diagnostic criteria to the same patients. The mean follow up time was 46.6 +/- 6.7 months. In the ICD-9 the schizophrenic psychoses represented the main diagnostic group, not only the day they were discharged from the hospital 31.6% but also in the follow up 39.2%. On the other hand in the DSM-III, in the discharge day the schizophreniform disorder was the more frequent diagnostic 24%, while in the follow up the schizophrenic disorder came to the first position 32.9%. In the ICD-9 there was a 15.1% of diagnostic changes and in the DSM-III nearly the double 30.3%. In both classifications the unspecified and the atypical suffered a great diagnostic mobility; in both nosologies the schizophrenia was the most unchangeable diagnosis, no patient discharged with this diagnosis changed to another in the follow up. ICD-9 could be said that has a great sensitivity and an acceptable specificity for this entities, and DSM-III would have a moderate sensitivity but a very diagnostic specificity for these disorders.


Antimicrobial peptides of frog skin.

A mechanism of action for frog skin antimicrobial peptides has been proposed, based on the amphipathic nature of the peptides when they contact bacterial surfaces. This results in anion channel formation and penetration of the membrane which allows efflux of OH- and uncoupling of respiration in the bacteria. The question of occurrence of human antimicrobial peptides analogous to those in frogs has not been answered but early studies indicate that Erspamer's prediction is correct.


[Differential phenomenology of the paranoid psychoses in epilepsy].

First, the author makes reference to the psycho pathological and nosological questions associated with paranoid and schizophrenia-like psychoses in epilepsy and in particular to the non resolved problem of a distinction between these epileptic syndromes and the ones of schizophrenia. Starting from a phenomenological analysis of basic existential structures such as encounter or interpersonality, temporality and spatiality in a typical case of paranoid psychosis in epilepsy, the author tries to establish formal criteria which allow to distinguish these psychoses from schizophrenia. Thus it could be demonstrated that the structure of the encounter in the psychotic epileptic is quite conserved, both in what refers to the real and the delusional partner. His spatiality is characterized by the phenomenon of narrowness and his temporality by harassment, being necessary to underline the fact that, unlike what happens in schizophrenia, in the paranoid psychoses of epilepsy the space maintains its unity and the time its continuity. We could summarize the substantive difference between both types of paranoid psychoses with the following words: in paranoid syndromes in epilepsy what occurs is a change of state "within the world", while in schizophrenia it is a rather a modification of the "being-in-the world" itself or, with other words, it deals with a going out from the world constituted as community.


The regulatory protein of liver glucokinase.

Fructose, sorbitol and D-glyceraldehyde stimulate the rate of glucose phosphorylation in isolated hepatocytes. This effect is mediated by fructose 1-phosphate, which releases the inhibition exerted by a regulatory protein on liver glucokinase. In the presence of fructose 6-phosphate, the regulatory protein binds to, and inhibits, liver glucokinase. Fructose 1-phosphate antagonizes this inhibition by causing dissociation of the glucokinase-regulatory protein complex. Both phosphate esters act by binding to the regulatory protein, and by presumably causing changes in its conformation. The regulatory protein behaves as a fully competitive inhibitor. It inhibits liver glucokinase from various species, and rat islet glucokinase, but has no effect on hexokinases from mammalian tissues or from yeast, or on glucokinase from microorganisms. Kinetic studies indicate that the regulatory protein binds to glucokinase at a site distinct from the catalytic site. Several phosphate esters, mainly polyol-phosphates, were found to mimick the effect of fructose 6-phosphate. The most potent is sorbitol 6-phosphate, suggesting that fructose 6-phosphate is recognized by the regulatory protein in its open-chain configuration. Other phosphate esters and Pi have a fructose 1-phosphate-like effect. The stimulatory effect of fructose on glucose phosphorylation is observed not only in isolated hepatocytes but also in the livers of anesthetized rats. This suggests that fructose could be a nutritional signal causing an increase in the hepatic glucose uptake.


[Family response and alcohol consumption].

The present study has its main objective the analysis of family responses to excessive alcohol consumption. For this we used data derived from a cross-sectional epidemiological community survey directed to investigate, in a random sample of 1.800 persons of 18 to 65 years of age and representative of the population of Cantabria community responses to alcohol consumption. We applied, among other instruments, a questionnaire designed by the WHO for exploring alcohol consumption, and which has being extensively used in other settings. We found, among other things, that: i) The concern about parents excessive alcohol consumption has different repercussions depending of the sex of their children, thus producing more alcohol related problems in males; ii) The concern for the alcohol consumption of ones partner is more often seeing in females, thus females tend to be more sensitive to these problems, and also they tend to detect them earlier and be more tolerant to them; iii) Persons who worry for the alcohol consumption of their partners usually have also had parents with such sort of problems; iv) And lastly about 11% of males and 13% of females with adolescent children tend to worry about the children' excessive alcohol consumption.


Effect of Ha-ras on mitogen-induced Ca(2+)- and K(+)-fluxes.

Transforming Ha-ras enhances the mitogen-induced activation of both the Ca(2+)-influx and the furosemide-sensitive Na+/K+/2Cl-cotransporter. Both systems represent essential early steps of mitogenic signal transduction in NIH 3T3 fibroblasts.


[Depressive states in multiple sclerosis. Critical bibliographic review].

The aim of this paper is to review the question of depression in patients with multiple sclerosis (MS). Morbidity and methodological difficulties in the investigation of depressive states in MS are analyzed. Prevalence of depression in MS in previous series is critically compared. The role of chronic invalidity and topography of demyelinating lesions in the development of depression are considered. We also review the treatment of depressive states and future guidelines for investigation of this topic.


The utility of an anti-fos ribozyme in reversing cisplatin resistance in human carcinomas.

The results presented here demonstrate that expression of a fos ribozyme limits Fos protein synthesis and enhances sensitivity of A2780DDP cells to antineoplastic agents, including cisplatin. Moreover, the reversal of this resistance is associated with down-regulation of dTMP synthase, DNA polymerase beta, topoisomerase I and hMTII-A, genes previously linked to DNA synthesis and repair. Thus these studies further implicate the role of the c-fos gene in DNA synthesis through modulation of expression of dTMP syntase, DNA polymerase beta and topoisomerase I. Finally, the use of ribozymes to circumvent drug resistance suggests their potential utility as agents to inhibit tumor cell growth.


Factors affecting the mRNA levels for the non-heme iron and effector-binding subunits of ribonucleotide reductase.

Ribonucleotide reductase which catalyzes the rate-limiting step in the de novo synthesis of dNTPs is composed of two non-identical protein subunits which are not under coordinate control in terms of synthesis and degradation. The mRNAs for the effector-binding (EB) and non-heme iron (NHI) subunits are likewise not under coordinate control during cell cycle traverse. Inhibitors directed at the specific subunits of ribonucleotide reductase block DNA synthesis. These current studies show that drugs such as IMPY or hydroxyurea which specifically inhibit the NHI subunit cause a marked increase in the steady-state level of the mRNA for the NHI subunit while resulting in a decrease in the level of mRNA for the EB subunit. In cells treated with deoxyadenosine, the patterns of the mRNAs for the NHI and EB subunits were different from those seen in the IMPY- or hydroxyurea-treated cells. Control experiments utilizing inhibitors (aphidicolin or araC) directed at DNA polymerase showed that the pattern of changes in the mRNA levels for the NHI and EB subunits were specific for the reductase inhibitors. These changes in the mRNAs for the NHI and EB subunits may be due to drug-induced alterations in transcription rates and/or degradation rates for the specific mRNAs.


Growth hormone regulation of hepatic cytochrome P450 expression in the rat.

GH by means of its sexually differentiated secretory pattern is the predominant regulator of the expression of cytochrome P450 enzymes responsible for a sexual dimorphism of hepatic steroid metabolism. Other hormones, such as gonadal, thyroid and glucocorticoid hormones, as well as insulin appear to modulate the sexually differentiated expression of these enzymes. The major constitutively expressed sex specific forms of P450, belonging to the P4502C-subfamily, have been shown to be regulated by GH at the level of transcription. However, the GH postreceptor events leading to increased or decreased transcriptional activity are essentially unknown. Neither is the functional role of the soluble GH binding protein yet resolved. On-going protein synthesis is a prerequisite for GH transcriptional activation of the female specific P4502C12 but not for all GH effects in the hepatocyte. With regard to signalling mechanisms PKC activity appears to be permissive for the GH induction of P4502C12 but some as yet unidentified factor/kinase(s) may also be activated. The transcriptional control exerted on the rat P4502C-gene subfamily by the pattern of GH secretion offers a versatile tool to elucidate the molecular mechanisms of GH regulation of cytochrome P450 expression.


Purification, characterization, regulation and molecular cloning of mitochondrial protein kinases.

The mitochondrial kinases responsible for the phosphorylation and inactivation of rat heart pyruvate dehydrogenase complex and the rat liver and heart branched-chain alpha-ketoacid dehydrogenase complexes have been purified to homogeneity. The branched-chain alpha-ketoacid dehydrogenase kinase is composed of one subunit with a molecular weight of 44 kDa; pyruvate dehydrogenase kinase has two subunits with molecular weights of 48 (alpha) and 45 kDa (beta). Proteolysis maps of branched-chain alpha-ketoacid dehydrogenase kinase and the two subunits of pyruvate dehydrogenase kinase are different, suggesting that all subunits are different entities. The alpha subunit of the rat heart pyruvate dehydrogenase kinase was selectively cleaved by chymotrypsin with concomitant loss of kinase activity, as previously shown for the bovine kidney enzyme, suggesting that the catalytic activity of pyruvate dehydrogenase kinase resides in this subunit. Polyclonal antibodies against branched-chain alpha-ketoacid dehydrogenase kinase, purified by an epitope selection method, bound only to the 44 kDa polypeptide of the branched-chain alpha-ketoacid dehydrogenase complex, substantiating that the 44 kDa protein corresponds to the kinase for this complex. Both kinases exhibited strong substrate specificity toward their respective complexes and would not inactivate heterologous complexes. The kinases possessed slightly different substrate specificities toward histones. Phosphorylation and inactivation of the branched-chain alpha-ketoacid dehydrogenase complex by its purified kinase was inhibited by alpha-chloroisocaproate and dichloroacetate, established inhibitors of the phosphorylation of the complex. cDNAs encoding the branched-chain alpha-ketoacid dehydrogenase kinase have been isolated from rat heart and rat liver lambda gt11 libraries. This represents the first successful cloning of a mitochondrial protein kinase. Preliminary data suggest that two different isoforms of the kinase may exist in different ratios in various tissues. No evidence was found for induction of the branched-chain alpha-ketoacid dehydrogenase complex nor its kinase by clofibric acid. Rather, clofibric acid is a potent inhibitor of the activity of the branched-chain alpha-ketoacid dehydrogenase kinase and this may be the molecular mechanism responsible for the myotonic effects of clofibric acid in man.


Regulation of mitochondrial carnitine palmitoyl transferases from liver and extrahepatic tissues.

Developments in our understanding of the complex CPT enzyme system over the past ten years have been reviewed. Liver CPT1, which is probably distinct from that in several extrahepatic tissues, is subject to up- or down-regulation of its activity and kinetic properties with changing physiological state. Evidence is now accumulating to support the notion that the catalytic and malonyl-CoA-binding entities of CPT1 are separate polypeptides.


Alanine glyoxylate aminotransferase deficiency: biochemical and molecular genetic lessons from the study of a human disease.

The decision to treat a patient with primary hyperoxaluria type 1 (PHI) by combined liver and kidney transplantation, the former to correct the metabolic lesion which was then thought to be deficiency of cytoplasmic 2-oxoglutarate:glyoxylate carboligase, and the latter to replace the organ which is destroyed, provided an opportunity to investigate the disease by modern biochemical methods. It was shown that 2-oxoglutarate:glyoxylate carboligase (the first decarboxylating component of 2-oxoglutarate dehydrogenase) is entirely mitochondrial so that deficiency of a cytoplasmic form of this enzyme could not be the cause of PHI. The deficient enzyme proved to be hepatic peroxisomal alanine:glyoxylate aminotransferase (AGT). The disease can be diagnosed enzymologically on percutaneous liver biopsies and this is possible for the fetus in utero. There are four types of genetically determined heterogeneity in PHI:(1) responsiveness and non-responsiveness to pharmacological doses of pyridoxine, in terms of an effect on the rate of oxalate production; (2) the presence or absence of residual catalytic AGT activity; (3) CRM+ and CRM-variants; (4) locational variation by virtue of which the enzyme (AGT) is mitochondrial and not peroxisomal. About one third of patients with PHI have residual AGT activity and at least a large proportion of these have mitochondrial and not peroxisomal AGT. The molecular features which guide peroxisomal and mitochondrial enzymes from their sites of synthesis into the appropriate organelle are reviewed and the possibilities for genetic variation in the relevant parts of the AGT molecule are discussed. The gene directing the synthesis of AGT has been cloned and sequenced, as has the AGT cDNA from a patient with mitochondrial AGT. Three point mutations causing amino acid substitution in the predicted AGT protein sequence have been identified: proline----leucine at residue 11, glycine----arginine at residue 170 and isoleucine----methionine at residue 340. The present evidence based on screening PHI patients and control subjects suggest that the substitution at residue 11, which cosegregates with that at residue 340, generates an amphiphilic alpha-helix which resembles mitochondrial targeting sequences but that misrouting of all the newly synthesized AGT into mitochondria requires the substitution at residue 170 which may act by impeding the entry of the enzyme into peroxisomes. The recognition of enzyme locational heterogeneity in PHI due to mutations affecting leader sequences should encourage a search for similar metabolic lesions in other inborn errors of metabolism affecting peroxisomal and/or mitochondrial enzymes.


Morphological evidence of function-related localization of phospholipids in the cell nucleus.

The evidence accumulated in recent years on the presence of phospholipids inside the interphase nucleus needs a precise localization of the nuclear sites of accumulation, transport and degradation of these molecules. A very useful approach for monitoring the fine localization of nuclear phospholipids is represented by a recently developed technique using gold-conjugated phospholipases. In fact, in addition to the phospholipids organized in bilayers in the membrane, this technique identifies amorphous lipoprotein complexes present in different cell areas as well as in the nucleus. In this way and using sample preparation systems which reduce lipid removal and translocation, such as cryofixation, cryosectioning, embedding in hydrophylic resins and cryofracturing, we have analyzed the subnuclear localization of phospholipids in different experimental conditions. The results indicate that: in interphase the nuclear phospholipids are localized mainly in the interchromatin spaces and in the nucleolar domain; the observed co-localization of phospholipids and ribonucleoproteins suggests that phospholipids are involved in the mechanism of transport and release of the transcripts; the demonstrated release of ribonucleoproteins after phospholipase digestion suggests that phospholipids mediate the binding between ribonucleoproteins and the nuclear matrix; significant changes of the phospholipid localization occur in the different phases of the cell cycle or in the course of induced cell differentiation.


A probability model for assessing exposure among respirator wearers: Part I--Description of the model.

The basic respirator equation states that the contaminant level inside a respirator (CI) is the product of the contaminant level outside the respirator (CO) and the decimal fraction penetration (P). On the basis of this relation, the authors present a probability model for the lognormal total distribution of CI levels among a respirator-wearing population; the model accounts for between-wearer and within-wearer variability in both CO levels and P values. The assumptions underlying the model are shown to be consistent with current knowledge about the variability in CO levels and P values. The model provides the basis for assessing the probability of overexposure to acute toxicants and to chronic toxicants among a respirator-wearing population.


A probability model for assessing exposure among respirator wearers: Part II-Overexposure to chronic versus acute toxicants.

A model describing the lognormal total distribution of contaminant levels inside a respirator (CI) is applied to assessing the probability of toxicant overexposure among a population of respirator wearers; the model accounts for between-wearer and within-wearer variability in ambient exposure levels (CO) and decimal fraction respirator penetration (P) values. The three exceedance probabilities are defined as PrI, the proportion of all CI levels over the permissible exposure limit (PEL); PrII, the proportion of wearers with an arithmetic mean CI level over the PEL; and PrIII, the proportion of wearers with a 95th percentile CI value over the PEL. PrII is considered that fraction of the population overexposed to a chronic toxicant; PrIII is considered that fraction overexposed to an acute toxicant. The behavior of PrII and PrIII over a range of exposure parameters is explored. An important observation is that a respirator-wearing population can have a substantial fraction of toxicant overexposure even though two conditions are met: (1) the P values for the population satisfy the criterion for the assigned protection factor (APF); and (2) the population arithmetic mean CO level is at or below the maximum use concentration (MUC), defined as APF x PEL. The authors recommend that the current MUCs for air-purifying respirators be reduced by one-half to reduce the potential respirator-wearing population fraction of overexposure and that appropriate exposure surveillance programs for all wearers be mandated.


An approach to evaluating and correcting aerodynamic particle sizer measurements for phantom particle count creation.

An aerodynamic particle sizer (APS) can be used to make real-time measurements of the aerodynamic particle size distribution over the range of 0.5 to 32 microns. This instrument is very useful in conducting health-related aerosol measurements involving aerosol generation, respirator efficiency, and particulate sampling efficiency. One of the two signal processors within the APS can create spurious or phantom particle counts that can significantly affect relative measurements and calculated mass distributions. In the APS, particle size measurement is based upon a particle's transit time between two laser beams that are perpendicular to an accelerating airflow. The signal processors measure each particle's transit from the time between the two pulses of scattered light that are generated as the particle passes through the two laser beams. When only a single pulse from a particle is detected, another pulse can cause the recording of a randomly sized phantom particle. The small particle processor (SPP), which measures particle transit from the times in digital increments of 4 nanoseconds, can create phantom particles; the large particle processor (LPP), which measures particle transit times in digital increments of 66.67 nanoseconds, is designed to prevent the creation of phantom particles. These two processors overlap in the range of 5.2 to 15.4 microns.(ABSTRACT TRUNCATED AT 250 WORDS)


Exact expressions for the bias and variance of estimators of the mean of a lognormal distribution.

Exact mathematical expressions are given for the bias and variance of the arithmetic and maximum likelihood estimators of the first moment (mean) of a lognormal distribution. On the basis of these exact expressions, and without the need for simulation, statistics on the bias and variance have been computed for a range of sample sizes and geometric standard deviations. The results reaffirm that an unbiased maximum likelihood estimator exists that has minimum variance. Contrary to some recent recommendations, this is the preferred estimator if the data truly come from a lognormal distribution.


Effect of the mosquito repellent DEET and long-wave ultraviolet radiation on permeation of the herbicide 2,4-D and the insecticide DDT in natural rubber gloves.

Studies were conducted to determine the effect of a commonly used insect repellent, DEET (N,N-diethyl-m-toluamide), on the permeability of rubber gloves used as chemical protective clothing (CPC) by pesticide applicators. Glove permeation analysis was conducted with an automated in vitro diffusion analysis (AIDA) method employing an in-house, flow-through permeation cell design. Permeation of 14C-ring-labeled 2,4-D (2,4-dichlorophenoxyacetic acid) in natural rubber glove material was 2.4 +/- 1.81% at 48 hr after treatment of the glove with 2,4-D applied with DEET; this was not significantly different (Student's t-test; p less than 0.05) from 3.2 +/- 3.46% permeation of 2,4-D observed without DEET. Similarly, there was no significant difference between the permeation of pp'-DDT (1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane) applied with DEET (11.7 +/- 5.02%) and without DEET (11.4 +/- 4.86%) to natural rubber glove material. Scanning electron microscopy of the natural rubber glove material, however, demonstrated disruption of the surface ultrastructure following a 24-hr treatment with DEET. The AIDA analysis also suggested that exposure of the glove material to long-wave ultraviolet (UVA) radiation enhanced the glove permeability to 2,4-D (6.2 +/- 0.73% [+UVA]; 0.3% +/- 0.14% [-UVA]) but had no effect on the permeation of DDT. Because the CPC of pesticide applicators is commonly exposed to solar UVA, this finding may raise concerns about the efficacy and safety of CPC in general.


Toxicological index and the presence in the workplace of chemical hazards for workers who breast-feed infants.

The increasing number of women in the workplace has made it more important than ever to ensure a safe work environment, particularly with respect to mothers who choose to breast-feed their babies. The Quebec Commission de la santé et de la sécurité du travail (CSST) Toxicological Index is fully involved in the provincial program for the protective reassignment of workers who breast-feed infants. The Infotox database provides peer-reviewed information concerning chemicals identified in the workplace that may appear in the mother's milk, possibly to be ingested by the breast-fed infant. Data extracted from the CSST computer system that holds information on 5,500 substances are presented. A total of 153 chemicals (2.7%) are recognized as being involved in some milk transfer. The strength of evidence is assessed with reference to strong or weak association (excretion or detection) in humans or in animals. Such an effect provides a useful basis for administrative decision involving protective reassignment as well as evaluation of work environment. Database users must be well informed about the identification of chemicals in breast milk because this is an essential step for the evaluation of the hazards of transferring chemicals encountered in the workplace from mother to baby. Actually, the main problem is that there are very few data in the scientific literature concerning milk transfer.


Prevention of perinatal transmission of the hepatitis B virus. Outcome of infants in a community prevention program.

To assess the outcome of infants born to hepatitis B surface antigen (HBsAg)-positive mothers who received prenatal and infant care in a large, public health care system. Follow-up of a cohort of infants born to HBsAg-positive mothers. Large, urban hospital providing prenatal care and obstetric services to county health departments. Forty-two infants born to HBsAg-positive women. Prenatal testing of women and immunoprophylaxis of infants with hepatitis B immune globulin at birth and hepatitis B vaccine at birth and ages 1 and 6 months. All 42 infants received hepatitis B immune globulin and the first dose of vaccine. Of forty-one infants (98%) who received the second dose of vaccine, 37 received it by age 4 months. Thirty-two infants (76%) completed the three-dose vaccine series by age 12 months, and 34 infants (81%) completed the series by age 18 months. The rate of completion of the hepatitis B vaccine series was comparable to that of infants receiving the third dose of diphtheria-pertussis-tetanus vaccine. Of 26 infants who completed the hepatitis B vaccine series and had follow-up serologic testing, 24 (92%) had adequate levels of antibody to HBsAg. Only one infant who did not complete the vaccine series had serologic evidence of hepatitis B virus infection. No infant was HBsAg-positive. Public programs serving urban populations can effectively deliver hepatitis B immunoprophylaxis to infants born to HBsAg-positive mothers.


Cefepime. Pharmacokinetics and clinical response in patients with cystic fibrosis.

To measure first-dose and steady-state plasma, urine, and sputum concentrations of cefepime and make preliminary assessments of the clinical efficacy of cefepime in patients with cystic fibrosis. Open noncomparative clinical trial. Memorial Miller Children's Hospital of Long Beach, Calif. Twelve patients, aged 4 to 41 years, with a confirmed diagnosis of cystic fibrosis and chronic bronchopulmonary infections. Patients received cefepime at 50 mg/kg per dose (maximum dose, 2 g per dose) given intravenously every 8 hours. Clinical evaluations, pulmonary function tests, quantitative sputum cultures, and sensitivity testing were performed before, at the end of, and 2 weeks after therapy. Mean (+/- SD) peak plasma concentrations after the first dose were 148.2 (36.6) mg/L; the following other values were included: half-life, 1.59 (0.46) hours; area under the curve, 292 (94) microgram/h per milliliter; total-body clearance, 3.01 (1.46) mL/min per kilogram; volume of distribution at steady state, 0.32 (0.10) L/kg; and percent of dose recovered in urine, 52% (27%). Steady-state and first-dose values were similar. Trough levels varied from 6.4 to 7.2 mg/L. Mean (+/- SD) sputum concentrations at steady state varied from 6.3 (5.4) to 4.8 (2.3) mg/L. At completion of therapy, nine of 10 patients' conditions were improved as indicated by clinical scores (greater than 10 points), forced vital capacity (greater than 10%), and a greater than or equal to 1 log decrease in sputum bacterial concentration. Cefepime was well tolerated in 10 patients, but rash and light-headedness developed in two patients. Pseudomonas aeruginosa minimum inhibitory concentration90 increased from the start (64 mg/L) to the end of therapy (256 mg/L) and was unchanged 2 weeks later. Based on these data and the potential advantage of a single agent for the treatment of mixed infections (Staphylococcus aureus and P aeruginosa), comparative clinical trials of cefepime and standard therapy for bronchopulmonary exacerbations in patients with cystic fibrosis appear to be warranted.


Iron state in female adolescents.

To document a subjective response to iron therapy in female adolescents. Double-blind, placebo-controlled prospective study. High school classes in an urban community in Israel. Twenty-nine girls, aged 16 and 17 years, who ingested syrup containing iron (daily for 2 months) and 30 girls who received a placebo. By the end of the study, a statistically significant improvement in three subjective parameters, ie, lassitude, the ability to concentrate in school, and mood was reported by the girls who ingested iron compared with the controls. Sixty-five percent, 100%, and 65% of the girls, respectively, who reported improvement in the above-mentioned parameters were hypoferremic initially and became normoferremic by the end of the study. Iron supplementation may be of benefit to female adolescents, as evidenced by their responses to subjective parameters.


Interrupted care. The effects of paging on pediatric resident activities.

To determine the content and urgency of pages and their effect on the activities of pediatric residents. Prospective survey. University-affiliated teaching hospital. Seventeen pediatric residents on regular pediatric services. None. On daily logs, interns recorded the activity interrupted by a page and rated the urgency and importance of the page. Almost half of all pages interrupted patient care activities, and 24% interrupted scheduled work rounds or teaching conferences. Interns reported that 34% of pages resulted in a change in patient treatment, but they rated 25% of all pages as unimportant. "Beepers" frequently interrupt pediatric residents involved in patient care activities and scheduled educational conferences. Studies of interventions aimed at decreasing unnecessary interruptions by pages are needed.


Sonography of multinodular thyroid gland in children and adolescents.

Multinodular disease of the thyroid gland is uncommon in children and adolescents, and has received little attention in the recent literature. This article reviews the clinical, sonographic, and pathologic findings in 16 children with multinodular disease of the thyroid gland, and draws attention to the high incidence of other associated clinical findings. This condition was associated with a triad including renal and digital anomalies in three patients, with McCune-Albright syndrome in two patients, with Hashimoto's thyroiditis in three patients, and with thyroid carcinoma in four patients. Three of five patients with a history of previous radiation therapy had thyroid carcinoma. Sonography is a proven valuable imaging modality for the study of thyroid disease in children and has contributed to our understanding of multinodular disease of the thyroid gland in this age group.


Growth hormone therapy in Turner's syndrome. Impact of injection frequency and initial bone age.

To determine the influence of the injection frequency and the initial bone age on the efficacy of treatment with biosynthetic growth hormone in Turner's syndrome. Randomized study. Referral-based pediatric endocrinology departments of seven university medical centers. Fifty-two patients with Turner's syndrome confirmed with chromosomal analysis. Somatotropin recombinant DNA (24 IU/m2 of body surface area) subcutaneously administered in three or six injections per week for 2 years. Patients who were older than 12 years at the beginning of the study received low doses of estrogen. The following statistically significant findings supported the use of six injections per week compared with three injections per week: the mean (+/- SD) increment in height during 2 years was 11.3 cm (3.8 cm) with six injections vs 8.6 cm (3.4 cm) with three injections; the increment in height standard deviation score was 0.9 cm (0.5 cm) vs 0.6 cm (0.3 cm); the growth velocity was 6.6 cm/y (2.0 cm/y) vs 5.2 cm/y (1.7 cm/y) in year 1 and 4.7 cm/y (2.0 cm/y) vs 3.4 cm/y (1.7 cm/y) in year 2; and the increment in height standard deviation score for bone age was 0.8 cm (0.5 cm) vs 0.4 cm (0.6 cm). For patients whose initial bone age was more than 13 years, growth velocity increased by 1 to 2 cm in year 1; in year 2 no increment was observed. We did not observe adverse effects. Biosynthetic growth hormone in a higher-frequency regimen in Turner's syndrome is more efficient in terms of increment in height, growth velocity, and height standard deviation score for bone age than treatment in a lower-frequency regimen. In patients with an initial bone age of more than 13 years, the response was poor. Longer follow-up is necessary to assess the effect on final height.


Adolescent body image and attitudes to anabolic steroid use.

Eleventh-grade students at seven high schools in central Arkansas were surveyed regarding anabolic steroid use, risk-taking behavior, satisfaction with body image, and attitudes and beliefs regarding anabolic steroids. A total of 1492 adolescents were surveyed. Fifty-one (7.6%) of 672 males and 12 (1.5%) of 806 females admitted anabolic steroid use. Fourteen students did not specify gender. Bivariate comparisons showed significant differences between users and nonusers in risk-taking behaviors and degree of satisfaction with body image and muscles. Users were more likely than nonusers to approve of anabolic steroid use in sports and to believe that anabolic steroid use could improve one's health. Multivariate analyses found gender, knowledge of beneficial side effects, knowing other anabolic steroid users, age, and race to be significantly related to anabolic steroid use. Information about steroids' effects seldom came from physicians, but often came from peers. Anabolic steroid use was strongly motivated by social influences, some knowledge of beneficial effects, and denial of adverse effects in white adolescent males in our study population.


The prophylactic value of clean intermittent catheterization and anticholinergic medication in newborns and infants with myelodysplasia at risk of developing urinary tract deterioration.

To determine if prophylactic use of clean intermittent catheterization and oxybutynin chloride is effective in preventing urinary tract deterioration in myelodysplastic children with high bladder pressure and detrusor-sphincter dyssynergia. Sequential, nonrandomized trial. Referral-based urodynamics facility and myelodysplasia program at a major city pediatric hospital. Twenty-six of 71 consecutive newborns with myelodysplasia who exhibited these urodynamic findings were treated prophylactically over 5 years, whereas 56 of 105 consecutive newborns with the same findings treated during the previous 7 years were treated expectantly. Clean intermittent catheterization and oxybutynin therapy were begun when these specific urodynamic findings were detected. Follow-up urodynamic studies and roentgenographic assessment of the urinary tract were performed periodically over 5 years. Oxybutynin eliminated uninhibited contractions in two of 14 newborns and lowered peak contractile pressure in the remaining 12. Oxybutynin also lowered bladder-filling pressure at capacity in all 12 additional neonates with only hypertonicity. Twenty-four (92%) of 26 children had normal kidney function and drainage during the observation period, two (8%) developed hydroureteronephrosis, and one of these two had vesicoureteral reflux. In a prior study of children similarly at risk who were treated expectantly, the roentgenographic appearance of the upper urinary tract had changed in 48%. Minimal side effects were noted with oxybutynin, and no adverse effects of clean intermittent catheterization were detected. Oxybutynin effectively reduces uninhibited contractions and lowers detrusor filling pressure, while clean intermittent catheterization allows bladder emptying at low pressures with no measurable side effects in these neonates. The overall effect maintains the integrity of the upper urinary tract in almost all myelodysplastic children at risk of urinary tract deterioration. Expectant therapy can no longer be advocated when these "at risk" children are identified because prophylactic treatment is so effective.


Tinea pedis in children.

To demonstrate that tinea pedis should be considered in the differential diagnosis of children with foot dermatitis. Patient series. Outpatient dermatology practice at the Children's Hospital of Pittsburgh (Pa). Children with culture-proven tinea pedis from 1987 until 1990. Fungal cultures were used to identify 13 girls and 13 boys ranging in age from 17 months to 18 years with tinea pedis. A parent was the probable source of infection in at least 25% of cases. Tinea pedis is not a rare occurrence in children and should be considered in any patient with a foot rash.


Establishing standards of orthostatic measurements in normovolemic adolescents.

To determine normal orthostatic heart rate and blood pressure changes in healthy adolescents. Survey. General adolescent clinic at a military teaching medical center in Honolulu, Hawaii. One hundred healthy normovolemic patients aged 12 to 19 years representing a cross section of individuals from a diverse military population during a 5-month study period. Convenience sample. None. The mean (+/- 2 SDs) orthostatic heart rate change in beats per minute was 21.5 +/- 21.2, with a range of 50 to -3 beats per minute. The mean (+/- 2 SDs) systolic blood pressure change was -0.9 +/- 15.7 mm Hg, with a range of 19 to -17 mm Hg. Orthostatic measurements in a normal adolescent population may result in a heart rate increase of 40 to 50 beats per minute and a systolic blood pressure decrease of 15 mm Hg. There were no significant differences between individuals with respect to age, race, sex, and body habitus. Healthy adolescents display wide variation in orthostatic measurements that exceed previously accepted standards. Further study is required to determine if sensitivity and specificity values exist for orthostatic measurements that can identify individuals with intravascular volume depletion.


Neonatal morphometry. Relation to obstetric, pediatric, and menstrual estimates of gestational age.

To determine gestational age-dependent neonatal morphometrics based on last menstrual periods (LMPs), Ballard examinations, and obstetric estimates of gestational age. Cross-sectional survey of 38,818 live-born neonates at a tertiary care center in Detroit, Mich. Consecutive sample of all viable, structurally normal, singleton neonates delivered at Hutzel Hospital from 1984 through 1991. Neonatal weights, lengths, and head circumferences were recorded at birth. Gestational age-dependent morphometrics were based solely on LMPs and compared with those based on obstetric estimates (using LMPs corrected by fetal ultrasound). Ballard examination had an 85.4% concurrence (within 14 days) with obstetric estimates of gestational age, but only a 69.9% (P less than .0001) agreement with LMP. Dating only by LMP significantly overestimated the prevalence of prematurity (odds ratio [OR], 1.3; 99% confidence interval [CI], 1.3 to 1.4) and postmaturity (OR, 5.0; 99% CI, 4.6 to 5.4), distorting apparent growth patterns, especially for preterm neonates. In contrast to previous studies based solely on LMPs, morphometric measurements increased beyond 40 weeks when dated by obstetric estimates. Gestational age-dependent neonatal morphometrics should not be based solely on LMPs.


The changing epidemiology of neural tube defects. United States, 1968-1989.

To describe the recent trends and epidemiologic characteristics of neural tube defects in the United States. Ongoing surveillance data. Two birth defect surveillance systems: the nationwide Birth Defects Monitoring Program and the Metropolitan Atlanta (Ga) Congenital Defects Program for 1970 through 1989 and 1968 through 1989, respectively. Between 1970 and 1989, using discharge diagnoses of approximately 1 million live-born and stillborn infants per year, the Birth Defects Monitoring Program identified 15,503 cases of spina bifida and anencephaly. Between 1968 and 1989, using discharge diagnoses and clinical records until age 1 year of 38,000 infants per year, the Metropolitan Atlanta Congenital Defects Program identified 800 cases of spina bifida and anencephaly. None. Nationwide, neural tube defect rates have declined from 1.3 per 1000 births in 1970 to 0.6 per 1000 births in 1989. In Atlanta, neural tube defect rates have declined from 2.0 per 1000 births in 1968 to 0.6 per 1000 births in 1989. Several changes in the epidemiologic characteristics of neural tube defects were observed: (1) the proportion of spina bifida cases has increased; (2) the proportion of neural tube defect cases compared with the proportion of other unrelated defects has increased; (3) the race ratio of whites to other races for isolated neural tube defect cases has declined in Atlanta; and (4) the rate of isolated neural tube defects in females has also decreased. The declining rates of neural tube defects can be partially explained by increased widespread prenatal diagnostic techniques, strongly suggesting the role of environmental factors in neural tube defects. In particular, the use of multivitamins and folic acid to prevent the occurrence of neural tube defects needs further evaluation. Nevertheless, the changing clinical and epidemiologic characteristics of cases over time points to the etiologic heterogeneity of these conditions.


Triplets and higher-order multiple births. Time trends and infant mortality.

To describe changes in rates of higher-order multiple births (triplets and higher) between 1972 and 1989, to compare infant mortality rates in infants of higher-order multiple births and singletons born from 1983 through 1985, and to compare infant mortality rates among higher-order multiples born from 1983 through 1985 with rates among those born in 1960. Population-based analysis of live births (1972 through 1989) and infant deaths (1960 and 1983 through 1985) in the United States. The rate of higher-order multiple births was calculated per 100,000 live births. Computerized national natality files for 1972 through 1989 and national linked birth/infant death data sets for 1960 and 1983 through 1985 from the National Center for Health Statistics, Centers for Disease Control. Live births to white and black women in the United States. None. Between 1972 through 1974 and 1985 through 1989 the rate of higher-order multiple births increased by 113% among infants of white mothers and by 22% among infants of black mothers. In whites the increase was mostly age specific and was not due to the upward shift in the maternal age distribution. The increase was particularly large in white women aged 30 through 34 years (152%) and 35 through 39 years (165%) and in more highly educated mothers. In blacks the modest increase in the rate of higher-order multiple births was mostly due to an upward shift in the maternal age distribution. From 1983 through 1985, mortality of infants of higher-order multiple births was about 15 times that of singletons. This was due almost entirely to the lower birth weight distribution of infants of higher-order multiple births. Their weight-specific mortality compared favorably with that of singletons. At 500 through 999 g, mortality was about the same. In weight categories between 1000 and 1999 g, mortality rates in higher-order multiple births were much lower: weight-specific relative risks ranged from 0.30 to 0.73. Between 1960 and 1983 through 1985 infant mortality in higher-order multiple births declined by about 50%. It is likely that much of the increase in the incidence of higher-order multiple births is due to the rise in the use of ovulation-inducing drugs for the treatment of infertility. This increase and the decline in mortality risk have created a much greater need for medical and social services for infants of higher-order multiple births and their families.


The pediatrician's role in encouraging parent-child communication about the acquired immunodeficiency syndrome.

We explored whether communication from pediatrician to parent to child might assist in education about and prevention of human immunodeficiency virus (HIV) infection by comparing parents of children aged 10 through 17 years who did discuss acquired immunodeficiency syndrome (AIDS) with their children with parents of children aged 10 through 17 years who did not discuss AIDS with their children. Secondary analyses of the National Health Interview Survey, a general population survey with items on AIDS. We compared the relative importance of various characteristics in distinguishing parents who did discuss AIDS from those who did not. Variables included whether the parents had received an informational brochure about AIDS from a health care provider. Twenty percent of respondents had at least one child between ages 10 and 17 years; 62% of these parents had discussed AIDS with their children. This percentage was greater for parents living in metropolitan statistical areas with fewer than 100,000 persons compared with parents living in larger cities (73.6% vs 62.7%). Seventy-four percent of women (n = 4745) had spoken to their children about AIDS; only 49% of men (n = 3271) had done so. This gender difference was present in both one- and two-parent households. Hispanics were significantly less likely than non-Hispanics to have discussed AIDS with their children (men, 38.9% vs 49.9%; women, 62.6% vs 74.2%). Gender by far was most strongly associated with talking to children about AIDS, followed by self-assessed knowledge, knowing someone infected with the HIV, and actual knowledge about HIV and AIDS. Parents who reported reading an AIDS-related brochure were significantly more likely to have spoken with their children than were parents who had not read such a brochure (76.2% vs 57.4%). Thirty-seven percent of parents receiving a brochure received one from a health care provider. Pediatricians can assist in efforts to prevent HIV infection and AIDS by educating parents, especially mothers, about AIDS; by providing them with well-designed brochures about AIDS; and by encouraging them to discuss HIV with their children in a developmentally appropriate manner.


Screening for maternal depression in pediatric clinics.

The purpose of this study was to assess the frequency of and risk factors for depressive disorders among mothers of young children and to compare the eight-item RAND screening instrument for depressive disorders with an easily scored three-item version of the test. A cross-sectional survey. Five pediatric clinics in the Seattle-Tacoma, Washington area, two private practices, two university-affiliated teaching clinics, and the Madigan Army Medical Center pediatric clinic. Convenience sample of 667 English-speaking mothers who completed the depression items on an anonymous self-administered questionnaire on family health. None. The results of women surveyed showed that 19% were positive for depression on the RAND instrument. Women whose survey results were positive were younger (28.2 vs 30.3 years of age), had less education (12.9 vs 14.4 years), and had lower monthly incomes ($1803 vs $2923) than those who results were not positive. Positive scores were more common among women surveyed in teaching clinics (20%) and military clinics (24%) than among women surveyed in private practices (12%), among single vs married mothers (32% vs 15%), among nonwhites vs whites (29% vs 16%), and among those with positive screening test results for drugs compared with those with negative screening test results (45% vs 17%) (P less than .01 for all comparisons). Compared with the eight-item instrument, the three-item version had a sensitivity of 100%, a specificity of 88%, and a positive predictive value of 66%. Depression is common among mothers of young children. The three-item version compares favorably with the eight-item RAND screening instrument for depressive disorders.


Adequacy of hemodialysis.

Despite technical advances in the delivery of hemodialysis over the past decade, the mortality rate of hemodialysis-dependent, end-stage renal disease (ESRD) patients in the United States remains high. The increase in the number and severity of comorbid conditions of patients entering ESRD is a factor contributing to this high mortality. Nevertheless, there is increasing evidence that the dose of dialysis received by US patients is inadequate and that this plays a major role in the observed high mortality. In this review, we examine some of the parameters used to judge the adequacy of dialysis, as well as factors that can result in differences between prescribed and delivered dose of hemodialysis. Based on available evidence, we propose that for most patients the optimum dose of dialysis, above which further improvement of morbidity and mortality is doubtful, is represented by a delivered dose of dialysis equivalent to a Kt/V of 1.4 or greater, using biocompatible membranes. The prescription of this optimal dose of dialysis must be coupled with an ongoing effort to monitor delivery of the appropriate dose.


Blood pressure related separately to parenchymal fibrosis and vasculopathy of the kidney.

The term nephrosclerosis is customarily used to designate a pathological entity that tends to characterize subjects with high blood pressure; it refers to a condition of diffuse fibrous replacement of renal substance secondary to ischemia from hypertension-related vascular injury. The features of parenchymal fibrosis can be distinguished from those of vasculopathies in tissue sections, parenchymal fibrosis being measured by assessing the degree of interstitial fibrosis and by counting obsolete glomeruli, while vasculopathies are measured by determining arterial intimal fibroplasia and by counting hyalinized arterioles. A series of 166 autopsies in subjects aged 25 to 92 years, selected because ample documentation of blood pressure was available, was assessed. One form of vasculopathy, arterial fibroplasia, is a better correlate of high blood pressure than is parenchymal fibrosis in this body of data. Cases with much vasculopathy and little parenchymal fibrosis occurred frequently, and these subjects were usually hypertensive. Cases with little vasculopathy and much parenchymal fibrosis were also encountered, but these subjects were usually not hypertensive. The suggested conclusion is that blood pressure relates less to the renoprival state of nephron loss than it does to renal ischemia in patients with nephrosclerosis.


Effect of nifedipine and captopril on glomerular hyperfiltration in normotensive man.

Glomerular hyperfiltration and hypertension induced by extensive loss of renal parenchyma are suspected to accelerate progression of renal failure. Amino acid infusion or protein ingestion also modify renal hemodynamics and increase glomerular filtration rate (GFR). This phenomenon was used to study the influence of two commonly used antihypertensive agents, captopril and nifedipine, on renal hemodynamics at rest and during glomerular hyperfiltration. Thirteen healthy volunteers were studied on three separate days (days A, B, and C) in random sequence: inulin and p-amino hippurate (PAH) clearance were measured first under glucose infusion and afterwards under stimulation by amino acid infusion (0.35 mmol/kg/min; 4 mg/kg/min). Day A served as a control, where no medication was given. On day B, 10 mg nifedipine, and on day C, 25 mg captopril, were administered orally before study. Without premedication (= day A, control) GFR increased from 108.0 +/- 6.9 mL/min (SEM) to 131.7 +/- 7.0 mL/min (P less than 0.05). On day B (nifedipine), GFR before stimulation by amino acids was already elevated to 121.8 +/- 4.2 mL/min (P less than 0.05 compared with day A) and increased to 132.6 +/- 6.3 mL/min with infusion of amino acids, thus to the same range as on day A without medication. On day C, after captopril, GFR did not increase with infusion of amino acids (from 112.5 +/- 7.2 to 117.3 +/- 6.3 mL/min). Our results indicate the calcium channel antagonist nifedipine and the angiotensin-converting enzyme (ACE) inhibitor captopril differ in their effect on intrarenal hemodynamic parameters. Nifedipine induces hyperfiltration at rest and allows maximal hyperfiltration to develop under amino acid infusion.(ABSTRACT TRUNCATED AT 250 WORDS)


Clinical profiles of gross hematuria in autosomal dominant polycystic kidney disease.

There is little information on the characteristics, management, or sequelae of gross hematuria in autosomal dominant polycystic kidney disease (ADPKD). Therefore, we obtained detailed information regarding gross hematuria in 191 adult ADPKD subjects. Forty-two percent (N = 81) experienced at least one episode of gross hematuria. The mean age of the initial episode was 30 +/- 1 years; only 10% of subjects reported the first episode before age 16. Twenty-three percent of those with gross hematuria had experienced more than six occurrences. Sixty-two percent of patients with bleeding indicated a presumptive precipitating event, most commonly urinary tract infection (42% overall, 61% of females v 17% of males, P less than 0.01), or sports or strenuous activity (20% of males v 11% of females, NS). In 56% of subjects, the episode persisted for 2 to 7 days. Hypertensive ADPKD subjects were more likely to have gross hematuria than normotensive subjects (48% v 30%, P less than 0.02) and those with gross hematuria had larger renal size (820 +/- 87 v 588 +/- 52 cm3, P less than 0.03). Moreover, those subjects with more episodes of gross hematuria had a higher serum creatinine concentration than those with fewer episodes (serum creatinine: 0 episodes, 120 +/- 10 v greater than 5 episodes, 190 +/- 30 mumol/L, P less than 0.04 [1.4 +/- 0.1 v 2.1 +/- 0.3 mg/dL]). This association suggests that, although self-limited, cumulative episodes of gross hematuria may have an unfavorable impact on long-term renal function.


Renal prostacyclin biosynthesis is reduced in children with hemolytic-uremic syndrome in the context of systemic platelet activation.

Previous studies have reported various abnormalities in prostacyclin (PGI2) synthesis and metabolism in hemolytic-uremic syndrome (HUS). However, the conclusions of most of these studies are based on in vitro or ex vivo experiments that only give an indirect estimate of the actual biosynthesis in vivo. We studied the urinary excretion of PGI2 metabolites, taken as a marker of the actual biosynthesis, in six children with HUS during the acute phase of the disease and again when remission was achieved. Eight age- and sex-matched healthy children were studied as controls. Since HUS is also associated with platelet activation and consumption, we also studied the urinary excretion of thromboxane A2 (TxA2) metabolites. Urinary PGI2 and TxA2 metabolites were assessed by radioimmunoassay after high-performance liquid chromatography (HPLC) purification. Urinary excretion of the PGI2 hydrolysis product, 6-keto-PGF1 alpha, was significantly reduced in children with acute HUS as compared with controls, indicating a defective renal synthesis of PGI2. A significant inverse correlation was found between urinary 6-keto-PGF1 alpha and blood urea nitrogen (BUN), as well as plasma creatinine. At remission, urinary 6-keto-PGF1 alpha levels increased to values higher than those of controls. By contrast, the urinary excretion of the major PGI2 beta-oxidation product, 2,3-dinor-6-keto-PGF1 alpha, was comparable to controls, indicating normal systemic PGI2 biosynthesis. The urinary excretion of both TxA2 hydrolysis product, TxB2, and the major beta-oxidation metabolite, 2,3-dinor-TxB2, were lower than normal in the acute phase of HUS if expressed as absolute values.(ABSTRACT TRUNCATED AT 250 WORDS)


Renal thrombotic microangiopathy in patients with systemic lupus erythematosus and the antiphospholipid syndrome.

Current studies indicate that a thrombotic microangiopathy (TMA) identifies patients with systemic lupus erythematosus (SLE) who are at high risk of progressing to end-stage renal disease. We have observed two patients with SLE and one patient with a primary antiphospholipid syndrome (APS) who developed acute renal insufficiency with thrombocytopenia. Renal biopsies showed a TMA characterized by thrombi or by cellular and mucoid intimal hyperplasia of small arteries and arterioles. No arterial or arteriolar immune-complex deposits were detected by immunofluorescent or electron microscopy. Biopsies from one SLE patient and the APS patient showed no immune-complex glomerular disease. Both had serum antiphospholipid antibodies (aPL). aPL were not detected in the serum of the other SLE patient who had an active lupus nephritis. Acute renal failure and thrombocytopenia resolved in each case following treatment by plasmapheresis or prednisone and heparin. None of the patients were initially treated with cytotoxic drugs. As more knowledge is gained, the accurate identification of renal vascular lesions in SLE or related diseases could influence renal prognosis and choice of therapy. The cases reported here provide further evidence that a TMA can cause acute renal failure independent of lupus nephritis. TMA should be distinguished from other forms of renal vascular disease, particularly a noninflammatory lupus microangiopathy, which is probably mediated by subendothelial immune-complex deposits. The absence of immunoglobulin deposits in vessels involved by a TMA indicates that microvascular thrombosis is promoted by mechanisms other than those usually attributed to immune-complex disease. Phospholipid reactive antibodies may be pathogenetic in some cases.


Intestinal necrosis associated with postoperative orally administered sodium polystyrene sulfonate in sorbitol.

We estimated the incidence of intestinal necrosis in 752 hospitalized patients who had received sodium polystyrene sulfonate (SPS). Of these 752 patients, 117 were exposed within 1 week of surgery. Two cases of intestinal necrosis were discovered, both in patients who had received orally administered SPS in sorbitol within 1 week of surgery. Based on these two cases, the postoperative incidence of intestinal necrosis associated with SPS was 1.8%. For comparative purposes, we identified 862 patients who had undergone hemodialysis, renal transplantation, or cardiac transplantation, but did not receive SPS. No cases of idiopathic intestinal necrosis were found in this second group (P = 0.014). These data suggest that SPS in sorbitol-associated intestinal complications may be a relatively common occurrence in postoperatively exposed patients.


Cyclosporine nephropathy: morphometric analysis of the medullary thick ascending limb.

The effects of cyclosporine A (CsA) (12.5 mg/kg/d) on the medullary thick ascending limb (mTAL) were studied in five experimental groups: vehicle-treated control (C), salt depletion (SD), cyclosporine (CsA), and the combination of both salt depletion and cyclosporine for 3 (CsA-SD:S) and 8 (CsA-SD:L) weeks. Evaluation was performed on 1-micron plastic horizontal sections. mTALs were classified as either atrophic or nonatrophic by assessing mitochondrial density. The mean cross-sectional area of atrophic mTALs was found to be significantly smaller than the mean of nonatrophic mTALs in all treatment groups. The percentage of atrophic tubules was found to be significantly increased in both CsA-SD groups as compared with the other three treatment groups (P less than 0.01). Regression analysis indicated a rectangular hyperbolic relationship between the percentage of atrophic tubules and mean nonatrophic tubule cross-sectional area (P less than 0.0001). Thus, low levels of injury are associated with a rapid increase in cross-sectional tubular area (hypertrophy), and this response plateaued with increasing degrees of injury. Terminal plasma creatinine correlated with nonatrophic tubular cross-section area (r = 0.52, P less than 0.003). These studies indicate that CsA induces mTAL atrophy, which is more extensive with salt depletion. With limited injury, hypertrophy develops. However, the hypertrophic response cannot be sustained with increasing degrees of injury. The phenomenon of mTAL atrophy and hypertrophy is particularly important, since hypertrophy itself is a known risk factor for mTAL injury.


Dietary supplementation with L-arginine ameliorates the progression of renal disease in rats with subtotal nephrectomy.

We studied the effect of dietary supplementation with L-arginine for 6 weeks on the progression of renal disease in female Sprague-Dawley rats subjected to sham-operation (groups 1 and 2) or surgical ablation of 85% to 90% of the total renal mass (groups 3 and 4). All rats were fed a standard rat chow containing 22.8% protein. Rats in groups 1 (n = 5) and 3 (n = 9) served as controls and drank tap water ad libitum. Rats in groups 2 (n = 6) and 4 (n = 6) drank tap water supplemented with 1% L-arginine. Rats in groups 1 and 2 had similar values for glomerular and tubular function and serum chemistries 6 weeks after sham-operation. Sham-operated rats given L-arginine had significantly greater urine urea excretion than similar rats drinking tap water. Rats with subtotal nephrectomy (groups 3 and 4) had a significantly higher blood pressure, greater proteinuria, and a significantly lower plasma albumin than sham-operated rats (groups 1 and 2). Rats with remnant kidneys given 1% L-arginine (group 4) had significantly greater values for glomerular filtration rate (GFR) and P-amino hippurate (PAH) clearance than similar rats given tap water (group 3), despite comparable levels of systemic blood pressure, hematocrit, body weight, plasma chemistries, including L-arginine, and urine chemistries, except urea excretion. The remnant kidney of rats given L-arginine (group 4) had a greater number of normal or minimally abnormal glomeruli and fewer interstitial changes than that of rats given tap water (group 3).(ABSTRACT TRUNCATED AT 250 WORDS)


Decline in creatinine clearance in a patient with glomerulomegaly associated with a congenital cyanotic heart disease.

Glomerulomegaly is associated with congenital cyanotic heart disease and has heretofore been considered a benign condition. We describe a patient with congenital cyanotic heart disease and glomerulomegaly. Deterioration of renal function was demonstrated by comparison of creatinine clearances measured at the time of kidney biopsy and 4 years later. No alteration in kidney histology other than glomerulomegaly and focal glomerulosclerosis at autopsy could account for this deterioration. This is the first description of deterioration of renal function in a patient with glomerulomegaly and congenital cyanotic heart disease. This observation may influence the management of patients with glomerulomegaly and congenital cyanotic heart disease who are potential recipients of heart or heart-lung allografts.


Renal autotransplantation in the loin pain-hematuria syndrome: a cautionary note.

The current literature suggests that renal autotransplantation is nearly uniformly effective in controlling the severe and debilitating pain of the loin pain-hematuria syndrome (LPHS). However, we report two patients thought to have this syndrome in whom renal autotransplantation did not result in long-term control of pain. In case 1, autotransplantation resulted in immediate cessation of pain; however, the flank pain recurred 7 1/2 months later. The recurrent pain was also severe and debilitating, requiring narcotic medications for control. In case 2, autotransplantation of the left kidney resulted in chronic pain in the left pelvic area, the site of the autotransplanted kidney. In addition, the patient continued to experience chronic discomfort in the left flank and along the flank incision. One year after autotransplantation, the patient still requires multiple daily doses of narcotic medications for pain control. Our two patients represent the 13th and 14th reported patients subjected to renal autotransplantation for management of LPHS. They represent only the third and fourth reported patients with recurrence of pain after renal autotransplantation. Because studies with negative results are less likely to be reported in the literature than studies with positive results, it is possible that the literature overestimates the effectiveness of renal autotransplantation in the LPHS. To assess the true effectiveness of renal autotransplantation in LPHS, a survey of patients with LPHS who have undergone renal autotransplantation needs to be performed.


Reversible renal failure due to IgA nephropathy associated with osteomyelitis.

Clinical features of acute glomerulonephritis, with microscopic hematuria, red blood cell (RBC) casts, proteinuria, and acute renal insufficiency developed in a patient with chronic osteomyelitis. Before the development of osteomyelitis, renal function and findings on urinalysis were normal. Complete eradication of osteomyelitis by surgical amputation led to resolution of the abnormal urinary findings, and renal function returned to near pre-osteomyelitis levels. Although acute glomerular disease has been reported to occur as a rare complication of osteomyelitis, the unique feature of the present case was the histological finding of IgA nephropathy. There was no arthritis, purpura, skin rash, or gastrointestinal involvement to suggest a diagnosis of Henoch-Schönlein purpura and there was no evidence of chronic liver disease. The temporal relationship between the onset of the renal disease, which followed the development of chronic osteomyelitis, and its resolution following removal of the focus of infection, suggests that the IgA nephropathy may have been related directly to the osteomyelitis (secondary IgA nephropathy). Glomerular diseases associated with chronic bacterial infections, including osteomyelitis, are discussed, with emphasis on infections that have been associated with the development or exacerbation of IgA nephropathy.


Analysis of chromosome 22 deletions in neurofibromatosis type 2-related tumors.

The neurofibromatosis type 2 (NF2) gene has been hypothesized to be a recessive tumor suppressor, with mutations at the same locus on chromosome 22 that lead to NF2 also leading to sporadic tumors of the types seen in NF2. Flanking markers for this gene have previously been defined as D22S1 centromeric and D22S28 telomeric. Identification of subregions of this interval that are consistently rearranged in the NF2-related tumors would aid in better defining the disease locus. To this end, we have compared tumor and constitutional DNAs, isolated from 39 unrelated patients with sporadic and NF2-associated acoustic neuromas, meningiomas, schwannomas, and ependymomas, at eight polymorphic loci on chromosome 22. Two of the tumors studied revealed loss-of-heterozygosity patterns, which is consistent with the presence of chromosome 22 terminal deletions. By using additional polymorphic markers, the terminal deletion breakpoint found in one of the tumors, an acoustic neuroma from an NF2 patient, was mapped within the previously defined NF2 region. The breakpoint occurred between the haplotyped markers D22S41/D22S46 and D22S56. This finding redefines the proximal flanking marker and localizes the NF2 gene between markers D22S41/D22S46 and D22S28. In addition, we identified a sporadic acoustic neuroma that reveals a loss-of-heterozygosity pattern consistent with mitotic recombination or deletion and reduplication, which are mechanisms not previously seen in studies of these tumors. This finding, while inconsistent with models of tumorigenesis that invoke single deletions and their gene-dosage effects, lends further support to the recessive tumor-suppressor model.


Neurofibromatosis type 2 appears to be a genetically homogeneous disease.

Neurofibromatosis type 2 (NF2) is an autosomal dominant syndrome characterized by the development of vestibular schwannomas and other tumors of the nervous system, including cranial and spinal meningiomas, schwannomas, and ependymomas. The presence of bilateral vestibular schwannomas is sufficient for the diagnosis. Skin manifestations are less common than in neurofibromatosis type 1 (NF1; von Recklinghausen disease). The apparent clinical distinction between NF1 and NF2 has been confirmed at the level of the gene locus by linkage studies; the gene for NF1 maps to chromosome 17, whereas the gene for NF2 has been assigned (in a single family) to chromosome 22. To increase the precision of the genetic mapping of NF2 and to determine whether additional susceptibility loci exist, we have performed linkage analysis on 12 families with NF2 by using four polymorphic markers from chromosome 22 and a marker at the NF1 locus on chromosome 17. Our results confirm the assignment of the gene for NF2 to chromosome 22 and do not support the hypothesis of genetic heterogeneity. We believe that chromosome 22 markers can now be used for presymptomatic diagnosis in selected families. The NF2 gene is tightly linked to the D22S32 locus (maximum lod score 4.12; recombination fraction 0). A CA-repeat polymorphism at the CRYB2 locus was the most informative marker in our families (lod score 5.99), but because the observed recombination fraction between NF2 and CRYB2 was 10 cM, predictions using this marker will need to be interpreted with caution.