A lack of vision: evidence for poor communication of visual problems and support needs in education statements/plans for children with SEN.

OBJECTIVE: Visual dysfunction is more common in children with neurological impairments and previous studies have recommended such children receive visual and refractive assessment. In the UK, children with neurological impairment often have educational statementing for Special Educational Needs (SEN) and the statement should detail all health care and support needs to ensure the child's needs are met during school life. STUDY DESIGN: This study examined the representation of visual information in statements of SEN and compared this to orthoptic visual information from school visual assessments for children in a special school in Northern Ireland, UK. METHODS: The parents of 115 school children in a special school were informed about the study via written information. Participation involved parents permitting the researchers to access their child's SEN educational statement and orthoptic clinical records. RESULTS: Statement information was accessed for 28 participants aged between four and 19 years; 25 contained visual information. Two participants were identified in their statements as having a certification of visual impairment. An additional 10 children had visual acuity ≥ 0.3 logMAR. This visual deficit was not reported in statements in eight out of these 12 cases (67%). 11 participants had significant refractive error and wore spectacles, but only five (45%) had this requirement recorded in their statement. Overall, 10 participants (55%) had either reduced visual acuity or significant refractive error which was not recorded in their statement. CONCLUSIONS: Despite additional visual needs being common, and described in clinical records, the majority of those with reduced vision and/or spectacle requirements did not have this information included in their statement. If visual limitations are not recognized by educational services, the child's needs may not be met during school life. More comprehensive eye care services, embedded with stakeholder communication and links to education are necessary to improve understanding of vision for children with neurological impairments.

In-school eyecare in special education settings has measurable benefits for children's vision and behaviour.

OBJECTIVES: To determine whether implementation of comprehensive in-school eyecare results in measurable benefits for children and young people in terms of visual status, classroom behaviours and how well their visual needs are met. DESIGN: School-based observational study. PARTICIPANTS & METHODS: 200 pupils [mean age 10 years 9 months, 70% male, majority moderate (40%) or severe (35%) learning difficulty] of a special education school in the UK. A sector-agreed in-school eyecare framework including full eye examination and cycloplegic refraction, dispensing of spectacles (as appropriate) and written reporting of outcomes to parents/teachers was applied. Classroom behaviours were observed and recorded prior to, and after, the in-school eyecare. Surveys were employed to obtain visual histories from parents/teachers. School records and statutory documents were reviewed for diagnostic and learning disability classifications. Visual function and ocular health were profiled at baseline and significant visual deficits identified. Where such deficits were previously unrecognised, untreated or not compensated for (e.g. correction of refractive error, enlargement of educational material) they were recorded as 'unmet visual need'. At follow-up, 2-5 months after initial (baseline) measures, eye examinations, parent/teacher surveys and behaviour observations were repeated. Follow-up measures were used to determine if measurable improvements were evident in visual function, ocular health, the level of unmet need and classroom behaviour following implementation of in-school eyecare. RESULTS: 199 participants completed baseline and follow-up measures. 122 (61%) participants presented with at least one significant visual or ocular health deficit and 90 (45%) participants had at least one unmet visual need. Younger pupils and those with no previous history of eyecare were more likely to demonstrate unmet visual needs at baseline (OR 1.12 95% CI 1.03 to 1.21) p = 0.012; (OR 4.44 95% CI 1.38 to 14.29 p = 0.007 respectively). On follow-up, the number of pupils with unmet visual needs dropped significantly to 36 (18%) (McNemar's test p<0.001). Visual and behavioural metrics of participants without significant visual deficits or whose visual needs were adequately addressed at baseline remained relatively unchanged between baseline and follow-up (Wilcoxon signed rank p>0.05). Where significant refractive deficits were corrected at follow-up, near visual acuity improved significantly (Wilcoxon signed rank p = 0.013), however, poor spectacle compliance was a persistent cause of unmet visual need. Off-task behaviour reduced significantly after actions to address unmet visual needs were communicated to parents and teachers (Wilcoxon signed rank p = 0.035). CONCLUSIONS: The present study demonstrates for the first time measurable visual and behaviour benefits to children in special education settings when they receive comprehensive in-school eye examinations, on-site spectacle dispensing and jargon-free reporting of outcomes to teachers and parents.

Correction: In-school eyecare in special education settings has measurable benefits for children's vision and behaviour.

[This corrects the article DOI: 10.1371/journal.pone.0220480.].

Apolipoprotein CIISt. Michael. Familial apolipoprotein CII deficiency associated with premature vascular disease.

A 60-yr-old woman and her brother, products of a consanquinous mating, were chylomicronemic. The chylomicronemia in both subjects was found to be due to the absence of functional apoCII. A mutant form, designated apoCIISt. Michael (apoCIIs), was identified by two-dimensional electrophoresis and Western blot using anti-apoCII antiserum. The isoelectric point of apoCIIs was similar to that of normal apoCII, but its apparent molecular weight was 3,000 greater. Tryptic peptides of apoCIIs were identified that had retention times in reverse-phase high pressure liquid chromatography and amino acid compositions indistinguishable from that of residues 1 to 48 and 51 to 55 of normal apoCII. The complete sequence of apoCIIs was deduced from a combination of the sequence analysis of tryptic peptides corresponding to residues 56 through 96 and the known sequence of the apoCII gene. ApoCIIs differed from apoCII at residue 70 where Gln70 was replaced by Pro70 and the sequence terminated with Pro96. This is consistent with a base insertion in the codon for Asp69 or Gln70 in the apoCII gene and a subsequent translation reading frame shift. Both patients were homozygous for apoE-4. This and the absence of normal apoCII is consistent with homozygozity at the apoE-CII gene locus on chromosome 19. Both siblings and several relatives had premature ischemic vascular disease, in contrast with its apparent absence in other apoCII-deficient families.

5'-flanking sequences mediate butyrate stimulation of embryonic globin gene expression in adult erythroid cells.

A stable transfection assay was used to test the mechanism by which embryonic globin gene transcription is stimulated in adult erythroid cells exposed to butyric acid and its analogs. To test the appropriate expression and inducibility of chicken globin genes in murine erythroleukemia (MEL) cells, an adult chicken beta-globin gene construct was stably transfected. The chicken beta-globin gene was found to be coregulated with the endogenous adult mouse alpha-globin gene following induction of erythroid differentiation of the transfected MEL cells by incubation with either 2% dimethyl sulfoxide (DMSO) or 1 mM sodium butyrate (NaB). In contrast, a stably transfected embryonic chicken beta-type globin gene, rho, was downregulated during DMSO-induced MEL cell differentiation. However, incubation with NaB, which induces MEL cell differentiation, or alpha-amino butyrate, which does not induce differentiation of MEL cells, resulted in markedly increased levels of transcription from the stably transfected rho gene. Analysis of histone modification showed that induction of rho gene expression was not correlated with increased bulk histone acetylation. A region of 5'-flanking sequence extending from -569 to -725 bp upstream of the rho gene cap site was found to be required for both downregulation of rho gene expression during DMSO-induced differentiation and upregulation by treatment with NaB or alpha-amino butyrate. These data are support for a novel mechanism by which butyrate compounds can alter cellular gene expression through specific DNA sequences. The results reported here are also evidence that 5'-flanking sequences are involved in the suppression of embryonic globin gene expression in terminally differentiated adult erythroid cells.

Dynamic deformability of sickle red blood cells in microphysiological flow.

In sickle cell disease (SCD), hemoglobin molecules polymerize intracellularly and lead to a cascade of events resulting in decreased deformability and increased adhesion of red blood cells (RBCs). Decreased deformability and increased adhesion of sickle RBCs lead to blood vessel occlusion (vaso-occlusion) in SCD patients. Here, we present a microfluidic approach integrated with a cell dimensioning algorithm to analyze dynamic deformability of adhered RBC at the single-cell level in controlled microphysiological flow. We measured and compared dynamic deformability and adhesion of healthy hemoglobin A (HbA) and homozygous sickle hemoglobin (HbS) containing RBCs in blood samples obtained from 24 subjects. We introduce a new parameter to assess deformability of RBCs: the dynamic deformability index (DDI), which is defined as the time-dependent change of the cell's aspect ratio in response to fluid flow shear stress. Our results show that DDI of HbS-containing RBCs were significantly lower compared to that of HbA-containing RBCs. Moreover, we observed subpopulations of HbS containing RBCs in terms of their dynamic deformability characteristics: deformable and non-deformable RBCs. Then, we tested blood samples from SCD patients and analyzed RBC adhesion and deformability at physiological and above physiological flow shear stresses. We observed significantly greater number of adhered non-deformable sickle RBCs than deformable sickle RBCs at flow shear stresses well above the physiological range, suggesting an interplay between dynamic deformability and increased adhesion of RBCs in vaso-occlusive events.

Traffic Light: prognosis-based eligibility for clinical trials of hematopoietic SCT in adults with sickle cell anemia.

Estimating prognosis in sickle cell anemia (SCA) assumes greater importance as intensive treatments, such as hematopoietic SCT (HSCT), are being tested. Here we estimate the mortality risk from the walk-PHaSST (Sildenafil Therapy for Pulmonary Hypertension and Sickle Cell Disease) trial of homozygous SCA patients with suspected pulmonary hypertension (19/468 deaths; 10 centers in the US and UK). Parallel investigations were also undertaken in the Cooperative Study of Sickle Cell Disease (CSCCD) and a contemporary urban sickle cell disease population (Case Western Reserve University-University Hospitals (CWRU-UH), Cleveland, OH, USA). One- and two-value positive predictive values for 2-year mortality (from study entry) are calculated using factors that include demographics, laboratory values and clinical evaluations. We define high-, intermediate-, and low-risk SCA as > 15%, 10-15% and < 10% 2-year mortality. In walk-PHaSST, no single factor qualifies as high-risk SCA, although several combinations of two factors (that is, both age > 35 years and history of chronic transfusion) do. Either elevated white blood cell count (> 13.5 × 10(3) cells/mcL, 7/70 deaths) or elevated Tricuspid Regurgitant Jet Velocity (⩾ 3.0 m/s, 8/67 deaths) was individually associated with intermediate-risk disease, as were many two-factor combinations. N-terminal pro-brain natriuretic peptide > 160 ng/L, lactate dehydrogenase > 600 IU/L, history of chronic transfusion, sepsis or age > 35 years are individually associated with low-risk SCA, as are many two-factor combinations. SCA risk was integrated with estimated donor type-associated risk from HSCT to form 'Traffic Light' eligibility criteria for clinical trials of HSCT. This method is adaptable to evolutions in clinical care.

A hepatic lipase gene mutation associated with heritable lipolytic deficiency.

Absent hepatic lipase (HL) activity results in dyslipidemia and premature atherosclerosis. DNA sequencing of the HL gene from subjects with heritable HL deficiency identified a new C to T substitution within exon 8 that in the mature enzyme caused a threonine to methionine change at position 383 (T383M). With a rapid DNA detection method we observed that all 6 individuals with complete HL deficiency from 2 families had the T383M mutation. None of 50 random unrelated unaffected subjects had this mutation. We propose that T383M is specific to families with heritable HL deficiency. Furthermore, structural variation at the HL gene, possibly in combination with other factors, appears to be etiologic in HL deficiency.

Methods for dealing with fats of unknown type in dietary surveys: the Lipid Research Clinic Population Study.

The design of the nutrition analysis tables adopted by the Lipid Research Clinics program of the National Heart Lung Blood Institute provides a specialized opportunity for assessing the fat component of 1-day dietary recalls. When the fat added during preparation of foods was unknown, rules were adopted for imputing composition. In order to investigate the effect that unknown fats produce on the apparent fatty acid composition of the diet, a detailed examination was made of 923 one-day dietary recalls from three clinics within the program. Total fat per recall from this sample averaged 107.6 g as calculated from visit 2 information. The average amount of unknown fat per recall at these three clinics was about 15.5%. About half the unknown fat at one clinic (Toronto-McMaster) could be identified and characterized through a procedure elected under Lipid Research Clinics protocol, "postinterview enquiry." Using this information, hypothetical "composite values," based on weighted means derived from the relative frequency of known use of fats and oils, were substituted for the unknown fat designations. Comparison of these composite values with values for known fats supports this approach and suggests the recommendation that postinterview information be collected for each region at the time of the inception of a new nutrition trial.

Source of variance in 24-hour dietary recall data: implications for nutrition study design and interpretation. Carbohydrate sources, vitamins, and minerals.

Beaton et al (Am J Clin Nutr 1979;32:2546-59) reported on the partitioning of variance in 1-day dietary data for the intake of energy, protein, total carbohydrate, total fat, classes of fatty acids, cholesterol, and alcohol. Using the same food intake data and the expanded National Heart, Lung and Blood Institute food composition data base, these analyses of sources of variance have been expanded to include classes of carbohydrate, vitamin A, vitamin C, thiamin, riboflavin, niacin, calcium, iron, total ash, caffeine, and crude fiber. The analyses relate to observed intakes (replicated six times) of 30 adult males and 30 adult females obtained under a paired Graeco-Latin square design with sequence of interview, interviewer, and day of the week as determinants. Neither sequence nor interviewer made consistent contribution to variance. In females, day of the week had a significant effect for several nutrients. The major partitioning of variance was between interindividual variation (between subjects) and intraindividual variation (within subjects) which included both true day-to-day variation in intake and methodological variation. For all except caffeine, the intraindividual variability of 1-day data was larger than the interindividual variability. For vitamin A, almost all of the variance was associated with day-to-day variability. One day data provide a very inadequate estimate of usual intake of individuals. In the design of nutrition studies it is critical that the intended use of dietary data be a major consideration in deciding on methodology. There is no "ideal" dietary method. There may be preferred methods for particular purposes.

Leguminous seeds in the dietary management of hyperlipidemia.

Seven male hyperlipidemic patients substituted approximately 140g dried beans daily for other sources of starch in their diet over a 4-month period. After this, mean fasting serum triglyceride levels were reduced by 25 +/- 5% (p less than 0.01) while total serum cholesterol levels were 7 +/- 2% (p less than 0.5) lower than the values measured during the previous five clinic attendances (12 +/- 2.5 months). However, low- and high-density lipoprotein cholesterol levels remained unaltered. While taking beans a nonsignificant fall (0.7 kg) was seen in body weight. Nevertheless no change was seen in macronutrient intake determined by 1-wk diet histories recorded both before and four times during the study, although cholesterol intake decreased by 80 mg (p less than 0.02). Reintroduction of dried leguminous seeds into a Western diet may be a useful adjunct to the management of hyperlipidemia.

Apolipoprotein and lipoprotein concentrations in familial apolipoprotein C-II deficiency.

Lipoprotein and apolipoprotein concentrations were determined in 11 homozygous and 9 heterozygous subjects for familial apolipoprotein C-II (Apo C-II) deficiency. Apo C-II was not detectable in the homozygotes, with the exception of 1 subject who possessed immunochemically detectable quantities in one of two samples. Apolipoproteins C-III (Apo C-III) and E (Apo E) were elevated 2-3-fold in 9 of 11 homozygotes. Apo C-III, but not Apo E, correlated with triglyceride levels (1500-4100 mg/dl). However, both Apo C-III and Apo E correlated with the cholesterol levels and one another. Apolipoproteins A-I (Apo A-I), A-II (Apo A-II) and B (Apo B) were reduced to approximately 50-60% of normal values in association with very low levels of cholesterol in high density (HDL; 11 +/- 2 mg/dl) and low density (LDL; 19 +/- 6 mg/dl) lipoproteins in the homozygous subjects. These alterations were associated with a marked decrease in the proportion of plasma Apo C-III associated with HDL. The levels of apolipoprotein D (Apo D) were within the normal range. Nine obligate heterozygotes had Apo C-II concentrations (mean 1.8 +/- 0.5 mg/dl; range 1.2-2.7 mg/dl) which were approximately 40-50% of normal values (mean 2.9 +/- 0.9 mg/dl; range 1.7-5.6 mg/dl). The reduction in absolute amounts of Apo C-II was also reflected in a reduction of the ratio Apo C-II/Apo C-III in very low density lipoproteins (VLDL) and in a reduction in the ability of the sera to activate skim milk lipoprotein lipase. The concentrations of Apo A-II, Apo B, Apo C-III and Apo E were normal. Apo A-I concentrations were normal or slightly low in association with slightly reduced concentrations of HDL cholesterol and a low proportion of plasma Apo C-III in HDL in relation to LDL and VLDL in some heterozygotes. It is concluded that the marked alterations in the apolipoprotein levels in homozygous subjects are primarily a reflection of the deficiency of Apo C-II which results in severe hypertriglyceridemia. In heterozygotes, the partial deficiency of Apo C-II appears to result in a minor disturbance of the clearance of the triglycerides and Apo C-III rich particles but no marked changes in the concentrations of total lipids, lipoproteins and apolipoproteins in fasting plasma.

An apolipoprotein CII mutation, CIILys19----Thr' identified in patients with hyperlipidemia.

Five hyperlipidemic patients (one with Type III, three with Type IV, and one with Type V hyperlipoproteinemia) were found on isoelectric focusing to have both the normal isoform of apolipoprotein CII and a second isoform whose isoelectric point was consistent with a single charge change. The structure of the apolipoprotein CII variant was determined to be the same as normal apolipoprotein CII except for replacement of the normal Lys at amino acid residue 19 by Thr (C2K19T). The mutation was absent from 160 apoCII alleles screened from normolipemic subjects. The C2K19T substitution occurs in a domain of apolipoprotein CII postulated to contain a lipid-binding amphipathic alpha-helix. The presence of C2K19T in unrelated hyperlipidemic patients of various racial backgrounds suggests that, in combination with other factors such as mutations in apolipoprotein E, it plays a role in the development of hyperlipoproteinemias.

The effect of growth hormone secretagogues and neuropeptide Y on hypothalamic hormone release from acute rat hypothalamic explants.

Growth hormone (GH) secretagogues (GH-releasing peptides and their non-peptide analogues) stimulate growth hormone release via specific G-protein coupled receptors both directly from the pituitary gland and through stimulation of the hypothalamus. The exact mechanism of action in the hypothalamus is not known. The presence of endogenous GH releasing hormone (GHRH) seems to be necessary for the in-vivo actions of growth hormone secretagogues (GHSs), but data suggest that further factors must be involved as well. The effect of GHSs is not entirely specific for the GH axis; they release prolactin and stimulate the hypothalamo-pituitary-adrenal axis causing elevations in circulating ACTH and cortisol levels in both animal and human studies. Recently, it has also been suggested that GHSs stimulate hypothalamic neuropeptide Y (NPY) neurones. In the present study, we have therefore investigated the direct effect of several GHSs (GHRP-6, hexarelin and the non-peptide analogues L-692, 429 and L-692, 585) on GHRH, somatostatin (SS), corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) release in vitro in an acute rat hypothalamic incubation system. We also assessed the effect of NPY on GHRH, SS and AVP release. Freshly removed hypothalami were incubated in control media for 20 min and then in 1-4 consecutive 20-min periods in each of the test substances at different concentrations. There was no significant change in either the basal or potassium-stimulated release of GHRH or SS at low concentrations of any of the secretagogues; however, at millimolar doses a paradoxical inhibition of GHRH was observed with GHRP-6, hexarelin and L-692 585 (data are expressed as the ratio of treated to preceding basal release; at 20 min control group: 0.97+/-0.02, GHRP-6: 0.55+/-0.04, P<0.001 compared to control group; hexarelin: 0. 56+/-0.06, P<0.001, L-692,585: 0.70+/-0.03, P<0.001), while SS was stimulated after 60 or 80 min (at 80 min control: 0.80+/-0.03, hexarelin: 1.23+/-0.07, P<0.05 and L-692,585: 1.37+/-0.11, P<0.05). GHSs stimulated hypothalamic AVP release (at 20 min control: 0. 99+/-0.06 ratio to basal release, 10-4 M concentration of GHRP-6: 6. 31+/-1, P<0.001, hexarelin: 1.88+/-0.4, P<0.01, L-692,429: 1.90+/-0. 5, P<0.05 and L-692,585: 2.34+/-0.96, P<0.01), while no stimulatory effect was found on CRH release. NPY significantly stimulated SS and inhibited basal and potassium-stimulated GHRH release, while potentiating potassium-evoked AVP secretion. The Y1 receptor antagonist BIBP 3226 did not inhibit the effects of NPY on SS, GHRH or AVP release. We therefore conclude that, in this in-vitro rat hypothalamic incubation model, growth hormone secretagogues stimulate the release of AVP but have no effect on either GHRH, SS or CRH at low doses; at high doses paradoxically they inhibit the hypothalamic GH axis similar to in-vivo data in the rat. We speculate that these effects might be mediated by NPY.

Bleeding risk and platelet transfusion refractoriness in patients with acute myelogenous leukemia who undergo autologous stem cell transplantation.

Therapy for acute myelogenous leukemia can be complicated by alloimmunization to histocompatibility antigens (HLA), with resultant refractoriness to platelet transfusions. Autologous peripheral blood or bone marrow stem cell transplantation (referred here collectively as 'autoBMT') is emerging as a standard consolidative strategy in acute myelogenous leukemia (AML). We had noted life-threatening bleeding associated with platelet transfusion refractoriness following autoBMT; we therefore retrospectively analyzed 39 AML patients for this complication following BMT. All patients received high-dose chemoradiotherapy, followed by infusion of allogeneic sibling donor (n = 12, alloBMT) or autologous (n = 27, autoBMT) stem cells. HLA alloimmunization was assessed if patients were suspected of immune refractoriness to random donor platelet transfusions. Within 100 days of stem cell infusion, one of three alloBMT and six of 12 autoBMT recipients tested were HLA alloimmunized (not statistically significant, NS). Five of six HLA alloimmunized autoBMT patients experienced delayed bleeding, which contributed to their demise while still in remission (P < 0.001). Increased platelet requirements in HLA alloimmunized autoBMT recipients were observed between days 61 and 100 post-BMT, at a median of 211 platelet transfusions vs 0 in non-alloimmunized autoBMT patients (P < 0.01) and 17 in alloBMT patients. Our data suggest that platelet transfusion refractoriness, when associated with HLA alloimmunization, is a risk factor for increased platelet transfusion requirements, delayed bleeding, and poor outcome following autoBMT for AML.

Identification of coagulase-negative Staphylococci isolated from urinary tract infections.

Coagulase-negative Staphylococci isolated from urinary tract infections were identified using the API Staph-Ident System. Organisms were excluded if there was no sign of pyuria or if normal urethral flora was present in significant amounts. While Staphylococcus saprophyticus and Staphylococcus epidermidis accounted for 81% of the isolates from females, 87% of isolates from males were S. epidermidis, Staphylococcus warneri, or Staphylococcus haemolyticus. The females fell into two main age groups, those with infections due to S. saprophyticus (mean age 25 years) and those due to other Staphylococci (mean age 40-49 years). All males were in a single age group (mean age 70-74 years) irrespective of the infecting agent. In males, S. warneri was associated with cellular changes in the bladder. No similar association was apparent with the other organisms. The results suggest that, apart from S. saprophyticus, three species of Staphylococcus (S. epidermidis, S. haemolyticus, S. warneri) account for most urinary tract infections, irrespective of the sex of the patient.

Clinical comparison of the enterotube II and API 20E systems for bacterial identification.

The Enterotube II and API 20E were compared for their ability to identify clinical isolates of bacteria. They were found to have similar overall rates of correct identification. The Enterotube II possessed a lower requirement for extra tests in order to complete the identification, while the API system had fewer major errors. Both systems were found to be reliable and suitable for use in a clinical laboratory.

Leucocyte esterase determination as a secondary procedure for urine screening.

The use of a dipstick to detect leucocyte esteraseuria (Chemstrip L) was compared with the visualisation of leucocytes in a Gram stained smear for the detection of pyuria. The sensitivity and specificity of the two systems using the predictive value theory were similar. The use of a dual screening procedure (automation plus dipstick) allowed reliable 4 h screening of urine specimens for the detection of urinary tract infections.

Silencing and activation of embryonic globin gene expression.

An understanding of the mechanisms that control developmental stage-specific transcription of globin genes offers the promise of successful therapeutic activation of fetal or embryonic beta-type genes in beta-thalassemia syndromes. A large body of evidence supports the notion of conservation of such mechanisms across vertebrate species and validates the use of pre-clinical studies of silencing and activation of fetal or embryonic globin genes in animals. Using globin gene transfections into primary avian erythroid cells and cultured murine erythroleukemia cells, we have studied mechanisms involved in stage-specific embryonic beta-type globin gene silencing and activation. These studies show that 1) methylation of the exact CpG nucleotides that are methylated in normal adult erythroid cells in vivo is capable of blocking transcription of a transfected embryonic globin gene promoter via binding of a methyl DNA binding protein in primary erythroid cells. 2) Activation of embryonic beta-type globin gene transcription in adult erythroid cells by short chain fatty acids is mediated through specific DNA sequences both in the promoter and downstream of the promoter.

Pathogenesis of acidosis in hereditary fructose intolerance.

An 18-yr-old man with a classical history of hereditary fructose intolerance (HFI) developed typical biochemical changes following an oral fructose load: fructosemia, hypoglycemia, hypophosphatemia, hyperuricemia, and metabolic acidosis. Hypokalemia (3.1 meq/liter) was also noted. Three aspects of this case expand the published literature on this syndrome: (1) Metabolic acidosis was found to be due to both lactic acidosis and proximal renal tubular acidosis (RTA). We could quantitate the relative contribution of each, and found that urinary bicarbonate loss due to proximal RTA accounted for less than 10% of the fall in serum bicarbonate. The major cause of the metabolic acidosis was lactic acidosis. (2) Hypokalemia was found to be due to movement of potassium out of the extracellular space rather than to urinary loss. Potassium may have entered cells with phosphate or may have been sequestered in the gastrointestinal tract. (3) The coexistence of proximal RTA and acidemia made it possible to study the effect of acidemia on the urine-blood partial pressure of carbon dioxide (PCO2) gradient in alkaline urine (U-B PCO2). The U-B PCO2 measured during acidemia was much higher at the same urine bicarbonate concentration than in normal controls during alkalemia, providing evidence in humans that acidemia stimulates distal nephron hydrogen-ion secretion.