Chronic fluoride exposure does not cause detrimental, extraskeletal effects in nutritionally deficient rats

On the basis of observations that endemic fluorosis occurs more often in malnourished populations, a series of studies tested the hypothesis that deficient dietary intake of calcium, protein or energy affects fluoride metabolism so that the margin of safe fluoride exposure may be reduced. The objective of the investigation was to determine whether changes in fluoride metabolism in nutritionally deficient rats resulted in manifestation of any extraskeletal toxic fluoride effects not observed in healthy animals. This investigation included two studies, one that monitored the effect of calcium deficiency on the effects of chronic fluoride exposure, and a second study that observed fluoride effects in rats that were deficient either in protein or in energy and total nutrient intake. Control and experimental rats received drinking water containing 0, 0.26 (5), 0.79 (15) or 2.63 (50) mmol fluoride/L (mg/L) for 16 or 48 wk. Control rats were fed optimal diets and experimental rats were fed diets deficient in calcium (Study 1) or protein (Study 2). An additional group of experimental rats (Study 2) was provided with a restricted amount of diet; thus these rats were deficient in energy and total nutrient intake. The intake, excretion and retention of fluoride were monitored; after the rats were killed, tissue fluoride levels and biochemical markers of tissue function were analyzed. Bone marrow cells were harvested from some of the rats, after 48 wk of treatment, for determining the frequency of sister chromatid exchange, a marker of genetic damage. Although there were significant differences among fluoride treatment groups in fluoride excretion and retention that resulted in significantly greater fluoride levels in tissues of the experimental rats, we were unable to detect any harmful, extraskeletal biochemical, physiologic or genetic effects of fluoride in the nutritionally deficient rats.     

Glutamate concentration in plasma, erythrocyte and muscle in relation to plasma levels of insulin-like growth factor (IGF)-I, IGF binding protein-1 and insulin in patients on haemodialysis

A simple, sensitive, and rapid method for simultaneous determination of residues of flumequine and its microbiologically active metabolite 7-hydroxyflumequine in 100 mg sheep edible tissues (muscle, liver, kidney, and fat) by liquid chromatography is reported. After liquid-liquid cleanup with ethyl acetate, tissue extracts were injected onto a Select B column. The 2 compounds were determined by ultraviolet and fluorimetric detection. The method was repeatable and reproducible for flumequine and 7-hydroxyflumequine in muscle, liver, kidney, and fat, with limits of detection below 2 and 3 micrograms/kg for flumequine and 7-hydroxyflumequine, respectively. Mean recoveries for flumequine were 90 +/- 7, 82 +/- 7, 89 +/- 5, and 82 +/- 6% in muscle, liver, kidney, and fat respectively. Mean recoveries for 7-hydroxyflumequine were 91 +/- 2, 90 +/- 4, 86 +/- 3, and 84 +/- 4% in muscle, liver, kidney, and fat, respectively.     

Intravascular ultrasound predictors of restenosis after balloon angioplasty of the femoropopliteal artery

The skepticism surrounding the potential benefits of resistance exercise training prevalent just decades ago has evolved over the years to an understanding of the integral nature muscular overload plays in the training programs for athletes. The science of training elite athletes is progressing rapidly, as insights into the physiological adaptations resulting from varying program configurations become available. Resistance training impacts several body systems, including muscular, endocrine, skeletal, metabolic, immune, neural, and respiratory. An understanding and appreciation of basic scientific principles related to resistance training is necessary in order to optimize training responses. Careful selection of the acute program variables in a workout to simulate sports-specific movements is required for optimal transfer of gains made in training to competition. Thus, whether athletes require predominantly eccentric, isometric, slow-velocity, or high-velocity strength or power in their athletic event will dictate the time commitment to each component and form the basis for designing individual workouts. Program variation over a training period is essential to maximize gains and prevent overtraining.     

Accuracy of injury coding in Victorian hospital morbidity data

In Victoria injury surveillance data are drawn from hospital morbidity data. The accuracy and reliability of these data are often questioned. We aimed to ascertain the reliability of injury data in the Victorian inpatient minimum database. A random sample of 546 public hospital separations with principal diagnosis ICD-9-CM codes 800-999 was selected from four metropolitan hospitals. Medical records were reviewed, and the hospital coding was compared with the record content. The frequency of error in any coding field was 73 per cent (349/480); of diagnosis error, 61 per cent (292/480); of procedure error, 45 per cent (168/370); of error in the principal diagnosis, 19 per cent (93/480); and of error in external-cause codes (E-codes), 16 per cent (75/480). Ninety-four per cent of errors (87/93) in the principal diagnosis involved recoding within the same group of codes. Only 6 per cent (6/93) were recoded to principal diagnoses other than injury. Sixty-two per cent (181/292) were errors of omission of codes for comorbid conditions. Nearly half the errors in the principal diagnosis were minor, involving the last two digits. E-codes were more complete than diagnosis codes. The best predictors of error in the principal diagnosis were greater length of stay, type of injury code (poisonings and toxic effects were associated with lower error rates) and death as the outcome. While selection of data from secondary diagnosis fields may not provide complete data, the use of the principal-diagnosis code and E-codes for injury surveillance is feasible and reliable. The database is a valuable source of injury surveillance data, bearing in mind the limitations of coded hospital morbidity data.     

Infectious properties of human immunodeficiency virus type 1 mutants with distinct affinities for the CD4 receptor

Recent evidence suggests that primary patient isolates of T-cell-tropic human immunodeficiency virus type 1 (HIV-1 ) have lower affinities for CD4 than their laboratory-adapted derivatives, that this may partly result from tighter gp120-gp41 bonds that constrain the CD4 binding sites of the primary viruses, and that selection for increased CD4 affinity may be the principal factor in laboratory adaptation of HIV-1 (S. L. Kozak, E. J. Platt, N. Madani, F. E. Ferro, Jr., K. Peden, and D. Kabat, J. Virol. 71:873-882, 1997). These conclusions were based on studies with a panel of HeLa-CD4 cell clones that differ in CD4 levels over a broad range, with laboratory-adapted viruses infecting all clones with equal efficiencies and primary T-cell-tropic viruses infecting the clones in proportion to cellular CD4 levels. Additionally, all of the primary and laboratory-adapted T-cell-tropic viruses efficiently used CXCR-4 (fusin) as a coreceptor. To test these conclusions by an independent approach, we studied mutations in the laboratory-adapted virus LAV/IIIB that alter the CD)4 binding region of gp120 and specifically reduce CD4 affinities of free gp 120 by 85 to 98% (U. Olshevsky et al., J. Virol. 64:5701-5707, 1990). These mutations reduced virus titers to widely varying extents that ranged from severalfold to several orders of magnitude and converted infectivities on the HeLa-CD4 panel from CD4 independency to a high degree of CD4 dependency that resembled the behavior of primary patient viruses. The relative infectivities of the mutants correlated closely with their sensitivities to inactivation by soluble CD4 but did not correlate with the relative CD4 affinities of their free gp120s. Most of the mutations did not substantially alter envelope glycoprotein synthesis, processing, expression on cell surfaces, incorporation into virions, or rates of gp120 shedding from virions. However, one mutation (D457R) caused a decrease in gp160 processing by approximately 80%. The fact that several mutations increased rates of spontaneous viral inactivation (especially D368P) suggests that HIV-1 life spans may be determined by structural stabilities of viral envelope glycoproteins. All of the wild-type and mutant viruses were only slowly and inefficiently adsorbed onto cultured CD4-positive cells at 37 degrees C, and the gradual declines in viral titers in the media were caused almost exclusively by spontaneous inactivation rather than by adsorption. The extreme inefficiency with which infectious HIV-1 is able to infect cultured susceptible CD4-positive cells in standard assay conditions casts doubt on previous inferences that the vast majority of retrovirions produced in cultures are noninfectious. Apparent infectivity of T-cell-tropic HIV-1 in culture is limited by productive associations with CD4 and is influenced in an interdependent manner by CD4 affinities of viral gp120-gp41 complexes and quantities of cell surface CD4.     

Quality of corneal donor tissue in the greater-than-75-year age group

Impaired nasal breathing has been reported to cause changes in human head posture. The aim of this study was to assess whether there was any relationship between nasorespiratory function and variables of head posture in 58 young adults. The pressure flow technique was used to measure airflow rate and oral/nasal pressure and to calculate the smallest cross-sectional area of the nasal airway. A natural head position roentgenocephalogram was used to measure the craniovertical angulation (NSL/VER), craniocervical angulation (NSL/OPT), and cervical spine inclination (OPT/HOR). The results showed a trend toward enlarged craniocervical angulation and forward inclination of the cervical spine in subjects with a relatively large nasal cross-sectional area. Though the general opinion on the effects of reduced upper airway size on head posture is opposite, these results are an experimental confirmation of the theoretically expected mechanism that leads to increased head extension in obstructed subjects.     

Diphtheria toxin fused to granulocyte-macrophage colony-stimulating factor eliminates acute myeloid leukemia cells with the potential to initiate leukemia in immunodeficient mice, but spares normal hemopoietic stem cells

We studied the cell kill induced by granulocyte-macrophage colony-stimulating factor (GM-CSF ) fused to Diphtheria Toxin (DT-GM-CSF ) in acute myeloid leukemia (AML) samples and in populations of normal primitive hemopoietic progenitor cells. AML samples from three patients were incubated in vitro with 100 ng/mL DT-GM-CSF for 48 hours, and AML cell kill was determined in a proliferation assay, a clonogenic assay colony-forming unit-AML (CFU-AML) and a quantitative long-term bone marrow (BM) culture ie, the leukemic-cobblestone area forming cell assay (L-CAFC). To measure an effect on cells with in vivo leukemia initiating potential DT-GM-CSF exposed AML cells were transplanted into immunodeficient mice. In two out of three samples it was shown that all AML subsets, including those with long-term abilities in vivo (severe combined immunodeficient mice) and in vitro (L-CAFC assay) were reduced in number by DT-GM-CSF. Cell kill induced by DT-GM-CSF could be prevented by coincubation with an excess of GM-CSF, demonstrating that sensitivity to DT-GM-CSF is specifically mediated by the GM-CSF receptor. Therefore, binding and internalization of GM-CSF probably occur in immature AML precursors of these two cases of AML. The third AML sample was not responsive to either GM-CSF or DT-GM-CSF. The number of committed progenitors of normal bone marrow (burst-forming unit-erythroid, colony-forming unit granulocyte- macrophage, and cobble stone area forming cell [CAFC] week 2) and also the number of cells with long-term repopulating ability, assayed as week 6 CAFC, were unchanged after exposure to DT-GM-CSF (100 ng/mL, 48 hours). These studies show that DT-GM-CSF may be used to eliminate myeloid leukemic cells with long-term potential in vitro and in immunodeficient mice, whereas normal hemopoietic stem cells are spared.     

Stranger in Turkey

The author, a professor of nephrology, reports some impressions of his 7-year stay in Turkey. He worked at the Ege University in Izmir, traditionally one of the most 'western' cities. He and his wife, who gave unpaid assistance to dialysis patients, attempted to integrate into Turkish society as fully as possible. They traversed the country in weekends and holidays and introduced as many Dutch guests as they could to the unique archeological treasures, the magnificent nature and the extremely friendly population. Work at the university focused increasingly on cultivating a critical attitude with regard to the self, society and the trends and commercialization of medicine in Turkey and in the rest of the world. Self-reliance, also, had to be strengthened. Although this contravened the authority-based Turkish educational system, the efforts were clearly appreciated and even stirred enthusiasm in many of the younger people. There is no doubt that a foreign worker is regarded much more favourable in Turkey than in the Netherlands.     

Effect of mechanical treatment on healing after third molar extraction

The aim of this study was to determine the effect of subgingival scaling and root planing on healing of the distal surface of second molars following extraction of third molars. Twenty-eight patients with contralateral erupted third molars and pocket depths greater than or equal to 3 mm on the distal surface of the second molars participated in this study. Measurements of supragingival bacterial plaque, bleeding on probing, pocket depth, and relative attachment level were performed at baseline and 2 months after treatment. Extraction of contralateral third molars was carried out simultaneously. The experimental site received thorough scaling and root planing of the distal surface of the second molar, while the control site received extraction alone. Experimental sites showed significant improvement in all clinical parameters assessed compared to the control sites. In conclusion, periodontal lesions on the distal of second molars can be significantly improved following scaling and root planing after extraction of third molars.