Subnormal Results Research Articles

Cardiorespiratory fitness in adolescents and young adults with Klinefelter syndrome - a pilot study.

Klinefelter syndrome (KS) may be associated with a wide spectrum of phenotypic changes including endocrine, metabolic, cognitive, psychiatric and cardiorespiratory pathologies in adults. However, in adolescence the clinical phenotype of KS is not well described, especially regarding physical fitness. The present study reports on cardiorespiratory function in adolescents and young adults with KS. Adolescents and young adults with KS were recruited in a cross-sectional pilot study. Biochemical parameters of fitness including hormonal status, a body impedance analysis, the grip strength, the amount of physical activity at home for 5 days via trackbands and anamnestic parameters were assessed. In addition, participants underwent an incremental symptom-limited cardiopulmonary exercise test (CPET) on a bicycle ergometer. Nineteen participants with KS aged 15.90 ± 4.12 years (range: 9.00 - 25.00) participated in the study. Pubertal status was Tanner 1 (n = 2), Tanner 2 - 4 (n = 7) and Tanner 5 (n = 10). Seven participants received testosterone replacement therapy. Mean BMI z-score was 0.45 ± 1.36 and mean fat mass was 22.93% ± 9.09. Grip strength was age-appropriate or above normal. 18 participants underwent CPET with subnormal results for maximum heart rate (z-score -2.84 ± 2.04); maximum workload (Wattmax; z score -1.28 ± 1.15) and maximum oxygen uptake per minute (z- score -2.25 ± 2.46). Eight participants (42.1%) met the criteria for chronotropic insufficiency (CI). Data from track-bands showed sedentary behavior for 81.15% ± 6.72 of the wear time. A substantial impairment of cardiopulmonary function can be detected in this group of boys to young adults with KS, including chronotropic insufficiency in 40%. The track-band data suggest a predominantly sedentary lifestyle, despite normal muscular strength as assessed via grip strength. Future studies need to investigate the cardiorespiratory system and its adaption to physical stress in a larger cohort and in more detail. It is feasible that the observed impairments contribute to the avoidance of sports in individuals with KS and may contribute to the development of obesity and the unfavorable metabolic phenotype.

Refractive Errors and Binocular Anomalies in Primary Schools in Uyoun Aljawa: A Small Urban Town in Saudi Arabia

AIM: To assess the prevalence of uncorrected refractive error (RE) and binocular vision (BV) anomalies in school-aged children in Uyoun Aljawa, a small urban town in Saudi Arabia.
 
 METHODS: This was a cross-sectional study of 417 students (aged 6–13 years old) conducted in two primary schools in Uyoun Aljawa from November 2019 to January 2020. All students underwent comprehensive eye examination that include: distance visual acuity (VA), Non- cycloplegic refraction, ocular alignment assessment with the cover test; Near Point of Convergence (NPC) evaluation, Near stereo-acuity with Titmus-fly Stereotest, and finally, colour vision was screened with Ishihara plates. 
 
 RESULTS: A total of 417 male schoolchildren (mean age ± SD: 9.2 ± 1.9) were included. In this study, 78 (18.4%) students had reduced vision (VA of ≤6/9) of which only 21 (27%) students had spectacles at the time of the study and 19.2% had uncorrected RE (VA of <6/18 and no corrections). Emmetropia was reported in 80.3% of children where hyperopia was the most common refractive error (8.9%) followed by myopia (7.7%), and simple astigmatism was reported only in 3.1%. Heterophoria was reported in 12.5% of the sample, 5.2% had convergence insufficiency, and 16.3% showed subnormal results in stereo-acuity and 11 cases had a colour vision deficiency.
 
 CONCLUSION: The results of this study reveal a high prevalence of RE and other BVA among schoolchildren in Uyoun Aljawa. Vision Screening programs of children for RE and BVA should be conducted at the community level and integrated into school health programmes.

An audit of referral time frames for ultrasound screening of developmental hip dysplasia in neonates with a normal antenatal clinical examination

AbstractIntroductionUltrasound has an established role in the detection of developmental dysplasia of the hip (DDH). Lack of uniformity in the appropriate age to perform studies in at‐risk children with a normal clinical examination at birth exists. Opening a new tertiary paediatric hospital saw a variety of referral time frames for initial screening ultrasound for DDH.MethodsLiterature review and retrospective clinical audit were undertaken. DDH ultrasounds of babies with the following criteria were reviewed: normal clinical examination and one or more risk factors. Patients were followed up via their electronic medical record.ResultsThere were 187 eligible patients: 124 (66.3%) had normal initial scans while 63 (33.7%) were recommended to have a follow‐up scan. Most subnormal results (Graf 2A or lower, laxity and/or less than 50% femoral head coverage) (n = 59, 93.7%) were scanned before 6 weeks of age, only four (6.3%) presented at 5 weeks after birth or later.DiscussionThis study identified a potential for reduction in follow‐up studies through delayed initial ultrasound, improving from 4 to 6 weeks of age, without adverse outcomes. Early screening ultrasounds may result in overdiagnosis of DDH during the maturation process of the neonatal acetabulum, potentially causing anxiety and unnecessary follow‐up.

Cognitive function in patients with childhood‑onset combined pituitary hormone deficiency not treated with growth hormone

Introduction. Growth hormone deficiency is a known factor leading to impairment of psychological performance but there are very few studies on cognitive function in adult patients with childhood‑onset combined pituitary hormone deficiency (ChO‑CPHD). Therefore, the aim of our study was to assess cognitive skills in adult patients with this disorder. Material and Methods. The study was performed in a unique group of 28 adult ChO‑CPHD patients, never treated with growth hormone (mean age 42.5 +/- 16.3 years; 12 women and 16 men). The assessment of cognitive performance (WAIS‑R) comprised scores of verbal IQ, non‑verbal IQ and particular qualitative analysis of subtests. Results. The mean score of full scale (IQ = 81,4) was below the normal when compared to the population norm (IQ = 100, SD +/- 15), although their verbal score (IQ = 85,7) was a bit higher than their nonverbal score (IQ = 81,7). Conclusions. The obtained result of total intelligence quotient (IQ) had shown equable subnormal results and a cognitive level below average in the study group. Decreased subscales of WAIS‑R are related to fluid intelligence (this may reflect abnormal brain development or could be linked to the influence of hormonal disorders in early life) as well as, emotional traits of personality.

Fifteen-year follow-up of upper limb function in children with moderate to severe traumatic brain injury

To describe the impaired fine-motor skills in patients with traumatic brain injury acquired in childhood. A total of 165 patients with traumatic brain injury, aged 0-17 years, injured during the period 1987-1991, were identified. Fifteen years post-injury a questionnaire was sent to the patients. Twenty-six of the subjects had upper limb problems, 15 of whom agreed to participate and 12 attended an evaluation. The Sollerman test was administered. This test consists of 20 activities, of which 7 hand-grips were used (pulp-pinch, lateral pinch, tripod pinch, 5-finger pinch, diagonal, transverse and spherical volar grip). Each sub-test was scored from 0 to 4 points. Each task must be performed within 20 s. The maximum score was 80. Bimanual fine motor skills were classified by Bimanual Fine Motor Function (BFMF). BFMF consists of 5 levels of function of each hand. Level I is normal function, level II-V means subnormal function in an increasing grade. Co-ordination, spasticity, 2PD and stereognosis were also measured. All patients had subnormal results on the Sollerman test. Fifty-eight percent had abnormal scores on the BFMF test. The Sollerman test seemed to be reliable at picking up hand motor problems, as all subjects who reported such problems scored subnormally. This is in contrast to the BFMF test findings, where only 60% of our group scored subnormally.

Diagnostische Zuverlässigkeit eines Elternfragebogens (SBE-3-KT) zur Erfassung von Kindern mit Sprachentwicklungsstörungen bei der U7a

Up to now, no German language test for children has been controlled for diagnostic accuracy. Therefore the application of language tests in clinical diagnostics is limited. The aim of the study was to determine the diagnostic validity of the SBE-3-KT, a parent questionnaire for identification of children with developmental language disorders at the age of 3 years. Language skills of 91 children (aged from 33 to 38 months) were assessed by clinical examination and language tests (SETK 3-5, SSV) blinded against SBE-3-KT results. To calculate validity scores SBE-3-KT results were referenced to expert rating and results on language tests. All children who were sorted in the language disorders group according to the expert rating were also classified as having language impairment on SBE-3-KT (high sensitivity) and all children with normal results on SBE-3-KT were sorted by experts in the unimpaired group (high negative predictive value). On the other hand, 8% of the unimpaired children according to experts were false positive classified by SBE-3-KT (specificity 92%, positive predictive value 50%). The correlations between subtest measures of SBE-3-KT and SETK 3-5 varied between rSp=0.42 and 0.63 (p<0.001). The parent questionnaire SBE-3-KT can be recommended for routine use in pediatric praxis. Three year old children with developmental language disorders are identified with high accuracy. In cases of subnormal results on parent report a further assessment is necessary to clarify the subtype and the etiology of the language abnormalities.

Tourette syndrome in the general child population: Cognitive functioning and self- perception

The aim of the study was to examine the cognitive function and self-perception in a school-population-based sample of children with Tourette syndrome (TS). Many studies have examined cognitive and emotional functioning in clinical samples but to our knowledge, there is no population-based study of TS in schoolchildren. In a population-based sample identified in a rigid diagnostic procedure (n = 25), cognitive functioning and self-perception were examined. There was a large variation in the cognitive functioning of children with TS, at least one third obtaining subnormal results. The profile of index scores on the Wechsler Intelligence Scale for Children (WISC) factors was somewhat uneven, with the freedom from distractibility and processing speed factors presenting the lowest median scores. The TS group had more negative self-perceptions than a comparison group. Tic severity or age at onset was not associated with cognitive performance or self-perception. Children who were taking medication had lower full IQ scores than children who were not. Low cognitive abilities and negative self-perception may be common in community-based samples of children with Tourette syndrome.

Visual and cognitive function in adolescents born with very low birth weight ‐ a 15‐ year follow‐up

Abstract Purpose To describe visual functions in adolescents with VLBW in comparison with a matched control group and to investigate associations with white matter damage of immaturity (WMDI), optic disc measurements and cognitive functions in the VLBW group. Methods A total of 86 VLBW children survived the neonatal period during a 15 months period in the southeast region of Sweden. Fifty‐nine of those, and 55 term control infants, participated in the 15‐year follow‐up study. Structural assessments included brain MRI, digital analysis of fundus photographs and cycloplegic refraction. Functional evaluations comprised best corrected visual acuity, stereo acuity, visual fields, ocular alignment, cognitive visual problems and intellectual level. Results VLBW was significantly associated with smaller mean neural retinal rim area (in normal sized optic discs), subnormal visual acuity, subnormal stereo acuity and subnormal visual fields and increased frequency of astigmatism and ocular misalignment. Cognitive visual problems were more common and intelligence quotients were significantly lower in the VLBW group. WMDI occurred in 28% of the VLBW subjects. WMDI was significantly associated with visual field subnormality, myopia, ocular misalignment and cognitive visual problems. Subnormal results of performance subtests were associated with decreased visual and stereo acuity, ocular misalignment and cognitive visual problems. Conclusion This study confirms previous observations that adolescents with VLBW are at a disadvantage regarding visual and cognitive outcome compared with adolescents with normal birth weight. Adolescents with WMDI had more pronounced visual and cognitive dysfunction.

A screening test for visual disorders based on Rarebit perimetry

Abstract Purpose To evaluate the clinical usefulness of a newly developed screening program, the VisuBit™ Quick test, based on the Rarebit perimetric technique (Frisén 2002). Methods Twenty‐one subjects (32 eyes), 6 males and 15 females, median age 47 years (27‐67), were examined using the VisuBit Quick and Full test, both including the Fovea test (4x3°visual field) and the Field test (30x20° visual field). Two subjects had amblyopia in one eye, one of these had normal visual acuity in the other eye and one had a history of central serous retinopathy in one eye, 2 subjects had a history of optic neuritis in both eyes and 2 had glaucoma in both eyes. All other eyes were healthy and had normal visual acuity. Results The correlation coefficients between number of unperceived stimuli in the Quick and the Full test were 0.95 in the Fovea and in the 0.86 Field test. In the Quick Field test more than 4 unperceived stimuli predicted a subnormal result (MHR &lt; 90%; Martin &amp; Wanger 2004) in the Full Test. In the Fovea Test more than 2 unperceived stimuli predicted a subnormal results (MHR &lt; 97%; Nilsson et al 2007). The positive and negative predictive values for the Quick Fovea test were 0.95 and 0.77, respectively. Corresponding values for the Quick Field test were 0.95 and 0.85. Conclusion The findings in this pilotstudy indicate that this implementation of the Rarebit perimetric technique may be useful for rapid screening for visual disorders.

Long-Term Neurodevelopmental Outcome of 167 Children After Intrauterine Laser Treatment for Severe Twin???Twin Transfusion Syndrome

Between 10% and 15% of monochorionic diamniotic twin pregnancies are complicated by severe twin–twin transfusion syndrome (TTTS), a cause of perinatal morbidity and death. The syndrome results from an unbalanced transfusion of blood across placental vascular anastomoses from one twin, the donor, to the other, the recipient. This prospective study was done to ascertain long-term neurodevelopmental outcomes in children born after intrauterine laser coagulation. The subjects were 167 infants from 127 pregnancies who survived severe TTTS in the years 1997 through 1999. At a mean age of 38 months, the children were assessed by a detailed physical and neurologic examination, Griffiths Developmental Test Scales and Snijders-Oomen NonVerbal-Intelligence Test (SON). Normal neurological findings were recorded in 87% of the children, and another 7% had minor abnormalities. Only 10 children, 6% of the total, had major neurologic abnormalities. Outcomes were comparable in former donors and recipients, and in infants born as twins and those born as singletons. The Griffiths test identified developmental delay in 25% of the 40 children tested. Seven of these 10 infants had severe neurologic abnormalities and the other 3 had minor abnormalities. Only 2 of 112 infants tested by the SON had subnormal results. All children who were neurologically normal had normal test results. Significantly more children with major or minor neurologic abnormalities were born before 32 weeks gestation compared with those who were neurologically normal. However, neither birth weight nor gestational age at the time of treatment was related to the outcome. These results, in children with severe TTTS who underwent fetoscopic laser coagulation, are more favorable than those reported from other studies. At present, this would appear to be the best available treatment for severe TTTS.

Failure of Assay to Identify Low Cobalamin Concentrations

We wish to report a serious problem in the ADVIA:Centaur® chemiluminescence assay for cobalamin (Bayer Diagnostics; formerly the ACS:Centaur® assay, Chiron Diagnostics). The problem is urgent for two reasons: (a) our findings suggest that many cobalamin-deficient patients are being missed; and (b) the assay is used by increasing numbers of laboratories, which some time ago abandoned radioisotopic methods and were recently faced with the withdrawal of widely used assays by Abbott Laboratories. Several months after our hospital’s clinical laboratory introduced the Centaur assay, we noted that the number of subnormal results being reported had declined from ∼15–20 to 4–5 per month. When we reassayed two serum specimens that had given subnormal cobalamin results with the Abbott IMx® method earlier and had been stored at −20 °C, the results obtained with the Centaur method were within reference values. As a result of these observations, we selected 33 sera from our research collection of specimens that had been assayed with our radioisotope dilution assay (RIDA) …

Hypothalamo-pituitary-adrenal axis suppression in asthmatics inhaling high dose corticosteroids

The frequency of hypothalamo-pituitary-adrenal (HPA) axis suppression in asthmatics taking high dose (greater than 1000 micrograms daily) inhaled corticosteroids is unknown. HPA function was studied in 78 adult asthmatics taking long-term inhaled corticosteroids (median dose 1600 micrograms, range 1200-2650 micrograms daily). All patients except one were using metered dose aerosols; 15 were using large volume spacer devices. Median duration of high dose therapy was 13 months (range 1-54). Sixty-nine patients were taking beclomethasone dipropionate (1500 micrograms, n = 36; 2000 micrograms, n = 26, greater than 2000 micrograms, n = 7) and nine budesonide (1200 micrograms, n = 2; 1600 micrograms, n = 6; 1800 micrograms, n = 1). Four patients, all of whom were taking greater than 2000 micrograms beclomethasone dipropionate, were taking 200-400 micrograms of their total dose intranasally. Twenty-six patients had discontinued long term systemic corticosteroid treatment (at least 5 mg prednisolone daily, or equivalent, for a minimum of 6 months) between 7 months and 22 years prior to assessment. All patients had measurements of 9 am serum cortisol and 24-h urine free cortisol excretion and a short tetracosactrin test. Subnormal results were: 9 am cortisol less than 190 nmol l-1; rise in serum cortisol in response to tetracosactrin less than 200 nmol l-1 and/or achieved cortisol less than 500 nmol l-1; urine free cortisol less than 80 nmol 24 h-1. Hypothalamo-pituitary-adrenal suppression was defined as subnormal results in at least two of the three tests. Tests were performed at least 2 weeks after completion of any short course prednisolone treatments. Suppression was found in 16 (20.5%) patients (1500 micrograms, n = 6; 1600 micrograms, n = 1; 2000 micrograms, n = 7; 2400 micrograms, n = 2). Risk factors identified for this suppression were: (a) previous requirement for long-term systemic corticosteroids (10/26, chi 2 = 6.1, P less than 0.02); and (b) increasing duration of high dose inhaled therapy (median 28.5 months in suppressed vs. 12 months in normal, P less than 0.05). No clear relationship was identified between HPA function and dose, even when corrected for body surface area and there was no relationship between suppression and number of short courses of prednisolone in the preceding 12 months. Screening tests of HPA function should be performed in all asthmatics taking greater than or equal to 1500 micrograms inhaled corticosteroid daily. Unless function has been shown to be normal, all patients taking these doses should carry steroid cards.

Screening for hypothalamo-pituitary-adrenal axis suppression in asthmatics taking high dose inhaled corticosteroids

High dose inhaled corticosteroids may cause suppression of the hypothalamo-pituitary-adrenal (HPA) axis. Several tests are available to screen for this suppression but it is not clear which is the most useful. HPA function was assessed in 78 adult asthmatics inhaling long-term, high dose (median 1600 micrograms; range 1200-2650 micrograms) beclomethasone dipropionate (n = 69) or budesonide (n = 9). Screening tests performed in all patients were 9 am serum cortisol, short tetracosactrin test and 24-h urine free cortisol excretion. Eleven patients also underwent insulin stress tests. Subnormal results were: 9 am cortisol less than 190 nmol l-1; urine free cortisol less than 80 nmol 24 h-1; rise in cortisol in response to tetracosactrin or hypoglycaemia less than 200 nmol l-1 and/or achieved cortisol less than 500 nmol l-1. HPA suppression (defined as subnormal results of at least two of the three initial tests and/or subnormal response to hypoglycaemia), was found in 16 patients. In the 11 patients who underwent insulin stress tests, results of all initial tests were normal in three, one test was abnormal in three and two tests were abnormal in four patients. All three tests were abnormal in the remaining patient. The response to hypoglycaemia was normal in the three patients whose screening tests were all normal; HPA suppression was present in seven patients and one patient had a borderline result. Close correlation was observed between the maximum cortisol during hypoglycaemia and both urine free cortisol (rs = 0.84; P = 0.001) and post-tetracosactrin cortisol (r = 0.75; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Total acrosin activity correlates with fertility potential after fertilization in vitro

To evaluate the possible relationship between total acrosin activity in spermatozoa and fertility potential after fertilization in vitro. Total acrosin activity of spermatozoa was measured in 101 in vitro fertilization (IVF) cases by an observer unaware of fertilization and cleavage results. University Hospital is a tertiary referral center offering a government supported In Vitro Fertilization Programme. Participants were couples undergoing IVF. A miniature assay measured total acrosin activity in the semen sample used for IVF. The proportion of mature oocytes fertilized, the proportion of mature oocytes transferred, and fertilization of at least one mature oocyte were considered outcomes with fertility potential. Total acrosin activity correlated with both the proportion of mature oocytes fertilized and the proportion of mature oocytes that were transferred as cleaving embryos. Total acrosin activity was higher in cycles when one or more mature oocyte fertilized compared with cycles with failed fertilization of all mature oocytes. The likelihood ratio for subnormal results indicates that measurement of total acrosin activity is a fair test of the fertilizing capacity of sperm.

Do large volume spacer devices reduce the systemic effects of high dose inhaled corticosteroids?

When used in high doses, inhaled corticosteroids may cause suppression of the hypothalamo-pituitary-adrenal axis. The influence of the mode of drug inhalation on the degree of this suppression is not clear. Hypothalamo-pituitary-adrenal function was assessed by measurement of 0900 h serum cortisol concentrations, a short tetracosactrin test, and 24 hour urine free cortisol excretion in 48 adults with asthma taking 1500-2500 micrograms beclomethasone dipropionate daily via a metered dose aerosol. Twelve patients had hypothalamo-pituitary-adrenal suppression, as judged by subnormal results from at least two of the three tests or (in one patient) by an abnormal insulin stress test response. These patients then changed to inhaling the same dose of beclomethasone dipropionate through a 750 ml spacer device (Volumatic). The endocrine tests were repeated from nine days to eight weeks later in 10 patients. Comparison with initial values showed that adding the spacing device caused an increase in the median 0900 h cortisol concentration from 126 nmol/l to 398 nmol/l, in the post-tetracosactrin cortisol concentration from 402 nmol/l to 613 nmol/l and in 24 hour urine free cortisol excretion from 54 nmol to 84 nmol. The rise in serum cortisol concentration in response to tetracosactrin did not change. Evidence of persisting hypothalamo-pituitary-adrenal axis suppression was present in only four of the 10 patients; the most pronounced improvements in function tended to occur in those who had never required long term oral corticosteroids. The results from this uncontrolled study suggest that asthmatic patients taking high dose beclomethasone dipropionate may minimise adverse effects by using a large volume spacer device.

Growth hormone testing in short children and their response to growth hormone therapy

Because current concepts of growth hormone (GH) testing and GH treatment have become controversial, we investigated the GH secretory patterns in children with normal and short stature. Twenty-four-hour serum GH levels were evaluated in three groups of children. Group 1 was composed of children with normal height (mean height = 0.02 SD, n = 33); group 2 was composed of short children (less than 5th percentile, n = 63) with normal results on provocative GH testing; and group 3 was composed of short children (less than 5th percentile, n = 7) with subnormal results on provocative GH testing. Mean +/- SD (range) GH levels during 24-hour studies of GH secretion were 1.6 +/- 1.1 (0.5 to 5.6), 1.8 +/- 1.2 (0.6 to 6.3), and 0.9 +/- 0.4 (0.5 to 1.7) ng/ml in groups 1, 2, and 3, respectively. No statistical difference existed in mean GH levels between groups 1 and 2 or between groups 1 and 3. The mean GH concentration from 24-hour studies in group 2 children did not correlate with chronologic age, height standard deviation, growth rates, or insulin-like growth factor 1 levels. The linear growth rate of 26 of 28 children in group 2 who received GH therapy for 6 months improved by 2 cm/yr or more; the mean +/- SD growth rate was 4.0 +/- 1.3 and 8.8 +/- 2.0 cm/yr during control and treatment periods, respectively, for these 28 children. Mean GH levels from testing did not predict response to GH during 6 months of therapy. Children with slower growth rates responded better to GH therapy (p less than 0.05). We conclude that (1) in 24-hour studies, GH levels in normal children overlapped with those of short children, including those with classic GH deficiency, (2) in 24-hour studies, GH levels did not predict responses of linear growth to short-term GH treatment, nor did they correlate with children's heights or growth velocities, and (3) the majority of short children in group 2 treated with GH for 6 months had an increase in linear growth velocity, the mean +/- SD change being 4.8 +/- 2.0 cm/yr.

Selective immunodeficiency affecting staphylococcal response.

Eight patients with recurrent staphylococcal infections, necessitating up to 213 hospital admissions in one patient, gave normal results with the usual immunological investigations, including measurement of serum IgG and IgG2. In the staphylococcal inhibition test all showed persistently subnormal results, corrected by the addition of compatible normal plasma or normal IgG therapy for 6 months to 21 years, and one died from staphylococcal septicaemia 6 months after withdrawal of treatment. The impairment in anti-staphylococcal response, with failure to produce adequate antibodies, was probably acquired in utero in four patients and inherited in two. In these six patients symptoms started soon after 4 months. In the remaining two the syndrome was acquired later in life.

Perisinusoidal fibrosis and basement membrane-like material in the livers of diabetic patients

A direct correlation exists between collagenization of Disse's space and the presence of diabetic microangiopathy in type I diabetes. To confirm and extend this finding, we studied four liver biopsy samples from two patients with type I diabetes (one with retinopathy) and two patients with type II diabetes (no retinopathy). All had normal or subnormal results on liver function tests and normal liver architecture. Levels of collagen types I, III, and IV, laminin, and fibronectin, as determined by immunocytochemical techniques, appeared increased in all patients. Liver biopsy samples were perfusion fixed for electron microscopy of sinusoids and sinusoidal cells. Numerous and thick collagen bundles could be seen in Disse's space, as could the increase of basement membrane-like material underlying the endothelial cells, perisinusoidal cells, and sinusoidal membrane of hepatocytes. Perisinusoidal cells were active and had abundant rough endoplasmic reticula and thick processes. This preliminary study indicates that collagenization of Disse's space is not specific to a certain type of diabetes. The increase of basement membrane-like material raises the question of whether liver sinusoids are truly different from other capillaries as far as diabetic microangiopathy is concerned.

Study of a mechanism responsible for anomalous results for free thyroxin by some analog assays for subjects with albumin deficiency.

I examined the effect of albumin deficiency, as might occur in pregnancy and nonthyroidal illness, on four analog-based assays for free thyroxin (Amersham's Amerlex, Diagnostic Products Corporation's Coat-A-Count "one-step," Clinical Assays' Gammacoat "one-step," and Corning's Immophase "single-step"). In subjects with albumin deficiency per se, Amerlex and Coat-A-Count results for free thyroxin were not significantly different from normal, whereas free thyroxin values by Gammacoat and Immophase assays were lower than that of the control. Furthermore, in the albumin-deficient group, the mean amount of thyroxin associated with antisera in each assay was significantly higher than that of the control and correlated well with the degree of decrease in free thyroxin. I conclude that subnormal results for thyroxin by analog assays, in euthyroid patients with albumin deficiency, is a function of the specific assays and is not a characteristic of analog assays per se. In addition, the study suggests that albumin deficiency alters the distribution between thyroxin and its binders in all four analog assays, but only in the Gammacoat and Immophase methods is this alteration sufficiently large as to distort assay results.

Phosphate metabolism in chronic liver disease

Phosphate metabolism was investigated in 26 patients with a spectrum of liver diseases and mean fasting plasma phosphate concentrations were in the low normal range. A standard oral load of phosphate was used to test absorption and was subnormal in the majority of patients with large bile-duct obstruction and alcoholic liver disease. Subnormal results were also seen in patients with primary biliary cirrhosis and cirrhosis secondary to chronic active hepatitis. These abnormalities appeared to be related to vitamin-D deficiency. Tubular reabsorption of phosohate was markedly reduced in 3 of 14 patients. The therapeutic implications of phosphate status in liver disease are important.