Normal Subjects Mean Research Articles

On- and off-responses of the photopic electroretinograms in x-linked juvenile retinoschisis

PURPOSE: To examine the physiologic condition of the middle retinal layer of patients with X-linked juvenile retinoschisis (xlRS) by studying the on- and off-responses of the photopic electroretinograms (ERGs). METHODS: Eleven unrelated Japanese men (mean age; 24.9 ± 7.6 years) who were clinically diagnosed with xlRS and molecularly confirmed as having XLRS1 mutations were investigated. For the photopic ERGs, the a-, b- and d-wave amplitudes elicited by long duration stimuli were recorded, and the responses from the xlRS patients were compared to those recorded from normal subjects ( n = 14, mean age, 27.5 ± 4.5 years). We also examined the relationship between the photopic ERG responses and the genotype. RESULTS: No significant difference was found between the a- and d-wave amplitudes in the xlRS patients (34.2 ± 8.7 μV, 52.5 ± 10.4 μV, respectively), and those in normal subjects (40.4 ± 10.3 μV, 44.7 ± 6.3 μV, respectively). The mean b-wave amplitude in the xlRS patients was significantly smaller (10.5 ± 7.7 μV) than the mean of normal subjects (46.4 ± 10.2 μV) ( P < 0.0001). No significant correlation was found between the ERG responses and the locus of the mutation. CONCLUSION: The photopic ERG demonstrated considerable impairment of the on-pathway arising from an abnormality of the on-bipolar cells or possibly secondary to Müller cell abnormality in xlRS.

Quantitative Computed Tomography Detects Air Trapping due to Asthma

The purpose of this study was to prospectively see if quantitative computed tomography (QCT) could separate asthmatic patients from normal control subjects. The QCT results were also correlated with the pulmonary function tests (PFT) that were done on both the asthmatic patients and control subjects. Eighteen adult nonsmoking asthmatics and 22 adult control subjects were entered into the study. Quantitative CT was performed at the level of the transverse aorta and just above the diaphragm at both end inspiration and end expiration in all patients and control subjects: 10-mm and 1.5-mm collimation using a high spatial frequency algorithm was used to obtain the QCT examinations. The percent of pixels below -900 Hounsfeld units, pixel index, in each of the QCT axial images of the lungs was calculated for each asthmatic and control subject in the study. Pulmonary function testing was performed on both the asthmatics and control subjects and included determination of FEV1, FVC, FRC, RV, and TLC. Unpaired Student's t test analysis of the QCT data was done to statistically compare the asthmatics with the control subjects. Linear regression analysis was done to compare the QCT results with PFT data on the asthmatics and control subjects. When scans were performed at end expiration, at a level immediately superior to the diaphragm, the mean pixel index was significantly higher in asthmatic subjects compared with normal individuals on both CT (mean for normal subjects 0.16 vs 4.45 for asthmatics, p < 0.004) and high-resolution CT (HRCT) images (mean for normal subjects 1.04 vs 10.03 in asthmatics, p < 0.0001) indicating more areas of low attenuation in asthmatics. The CT and HRCT images from the lower lung zones that were performed at end expiration provided the best separation between the groups. The pixel index on expiration correlated with the degree of air trapping and airflow limitation in the asthmatic group based on FEV1, FRC, RV, and to a lesser extent, FVC. Expiratory QCT is a useful method to assess air trapping in asthmatic patients. The percent of abnormal lung in asthmatics as determined by QCT has a significant correlation with the PFTs that reflect air trapping in asthmatic patients. Quantitative CT may be helpful in assessing degrees of air trapping present in other diseases affecting the airways.

Clinical spectrum and diagnosis of cobalamin deficiency [see comments

To better estimate how frequently patients with low serum cobalamin (Cbl) levels in current clinical practice are truly deficient in Cbl and to determine the incidence of atypical or nonclassic presentations of Cbl deficiency, we prospectively studied 300 unselected consecutive patients with serum Cbl concentrations less than 200 pg/mL seen at two medical centers over a 2-year period. Baseline hematologic, neuropsychiatric, and biochemical measurements were obtained, followed by a course of parenteral Cbl therapy and reassessment. A response to Cbl therapy was defined as one or more of the following: (1) an increase in hematocrit of 0.05 or more; (2) a decrease in mean cell volume of 5 fL or more; (3) a clearing of hypersegmented neutrophilis and macroovalocytes from the peripheral blood smear; and (4) an unequivocal and prompt improvement of neuropsychiatric abnormalities. Of the 300 patients with serum Cbl levels less than 200 pg/mL, 86 had one or more responses to Cbl therapy and 59 had no response. In 155, insufficient data was available. In the Cbl-responsive patients, normal values were found for the following tests: hematocrit, 44%; mean cell volume less than or equal to 100 fL, 36%; white blood cell count, 84%; platelet count, 79%; serum lactic dehydrogenase, 43%; and serum bilirubin, 83%. Peripheral blood smears were nondiagnostic in 6% when reviewed by the investigators, but 33% as reported by routine laboratories. Serum Cbl levels in the 100 to 199 pg/mL range were present in 38%. Neuropsychiatric abnormalities were noted in 28%, often in the absence of anemia, macrocytosis, or both. Serum levels of methylmalonic acid and/or total homocysteine were elevated greater than 3 SDs above the mean for normal subjects in 94% of the Cbl-responsive patients. We conclude that Cbl deficiency should be considered and investigated in patients with unexplained hematologic or neuropsychiatric abnormalities of the kind seen in Cbl deficiency, even if anemia, an elevated mean cell volume, a marked depression of the serum Cbl, or other classic hematologic or biochemical abnormalities are lacking. Levels of serum methylmalonic acid and total homocysteine are useful as ancillary diagnostic tests in the diagnostis of Cbl deficiency.

Clinical Spectrum and Diagnosis of Cobalamin Deficiency

Abstract To better estimate how frequently patients with low serum cobalamin (Cbl) levels in current clinical practice are truly deficient in Cbl and to determine the incidence of atypical or nonclassic presentations of Cbl deficiency, we prospectively studied 300 unselected consecutive patients with serum Cbl concentrations less than 200 pg/mL seen at two medical centers over a 2-year period. Baseline hematologic, neuropsychiatric, and biochemical measurements were obtained, followed by a course of parenteral Cbl therapy and reassessment. A response to Cbl therapy was defined as one or more of the following: (1) an increase in hematocrit of 0.05 or more; (2) a decrease in mean cell volume of 5 fL or more; (3) a clearing of hypersegmented neutrophilis and macroovalocytes from the peripheral blood smear; and (4) an unequivocal and prompt improvement of neuropsychiatric abnormalities. Of the 300 patients with serum Cbl levels less than 200 pg/mL, 86 had one or more responses to Cbl therapy and 59 had no response. In 155, insufficient data was available. In the Cbl-responsive patients, normal values were found for the following tests: hematocrit, 44%; mean cell volume less than or equal to 100 fL, 36%; white blood cell count, 84%; platelet count, 79%; serum lactic dehydrogenase, 43%; and serum bilirubin, 83%. Peripheral blood smears were nondiagnostic in 6% when reviewed by the investigators, but 33% as reported by routine laboratories. Serum Cbl levels in the 100 to 199 pg/mL range were present in 38%. Neuropsychiatric abnormalities were noted in 28%, often in the absence of anemia, macrocytosis, or both. Serum levels of methylmalonic acid and/or total homocysteine were elevated greater than 3 SDs above the mean for normal subjects in 94% of the Cbl-responsive patients. We conclude that Cbl deficiency should be considered and investigated in patients with unexplained hematologic or neuropsychiatric abnormalities of the kind seen in Cbl deficiency, even if anemia, an elevated mean cell volume, a marked depression of the serum Cbl, or other classic hematologic or biochemical abnormalities are lacking. Levels of serum methylmalonic acid and total homocysteine are useful as ancillary diagnostic tests in the diagnostis of Cbl deficiency.

Thoracic tissue thickness measured by transmission scintigraphy with 99Tcm

A flood source containing 25 mCi of technetium-99m (99Tcm) was used to measure thoracic tissue thickness (Tt) in 20 healthy subjects, 14 patients with cardiogenic pulmonary oedema, 8 patients with biopsy proven cryptogenic fibrosing alveolitis (CFA) and 10 subjects with radiographic evidence of severe, widespread emphysema. Unattenuated counts from the flood source were acquired first, and then with the subject seated between the flood source and the gamma camera, a second scan of transmitted counts was acquired. Assuming a constant linear attenuation coefficient of 0.135 cm-1, we calculated Tt per pixel of the gamma camera image, thus creating a profile of Tt throughout the length of the thorax. In normal subjects mean (S.D.) Tt at the base of the right lung was 10.8 (2.4) cm. In patients with pulmonary oedema, CFA and emphysema, mean (S.D.) values for Tt, in cm, were 12.9 (2.7) p less than 0.05, 14.4 (1.9) p less than 0.001 and 6.0 (1.1) p less than 0.0001 respectively. This simple, quick and inexpensive technique could be used to give regional measurements of Tt.

Functional Levels of α2-Macroglobulin in Plasma in Relation to Emphysema

In most studies, concentrations of alpha 2-macroglobulin are determined by immunological techniques. In this study, the amidolytic activity of porcine pancreatic elastase complexed with alpha 2-macroglobulin was measured using an elastase-specific substrate, succinyl-trialanyl-p-nitroanilide. The activities of plasmas from 47 emphysema cases were compared with 39 normal subjects. The age ranges of both groups were from 50 to 84 years. The mean activity of bound elastase in emphysema cases was 2.48 +/- 0.03 kU/l of plasma. The mean for normal subjects was 1.48 +/- 0.11 kU/l of plasma. The difference was very significant (2P less than 0.001). All except 2 of the emphysema cases had smoked. The same results were obtained when only people who had smoked for 25 years or more were included in the analysis. All the plasma samples of people included in the study were assayed by an immunological method for absolute level (in g/l) of alpha 1-proteinase inhibitor. The levels of alpha 1-proteinase inhibitor for all the persons studied fell within the normal range for MM-phenotypes (2 to 4 g/l).

Releasable vascular plasminogen activator and thrombotic strokes

Releasable vascular plasminogen activator was measured in 28 patients (14 males and 14 females) with a history of thrombotic strokes documented by computed tomographic scanning. Levels were compared with those in a control population of 126 healthy subjects with no history of thromboembolic disease. The patient population tended to have higher levels of activator than the control population, 0.53 Committee on Thrombolytic Agents (CTA) units/ml of plasma for patients versus 0.21 CTA units/ml for control subjects; however, there was a wide distribution of values, as reported in all previous populations. Since plasminogen activator levels distribute in a non-Gaussian manner, patient values and control values were stratified into deciles. By this approach, the distribution among the patient was not significantly different from that among the control subjects except in females, who demonstrated skewing to higher deciles (p = 0.019). It is concluded that thrombotic strokes are not associated with low levels of releasable vascular plasminogen activator, and in fact, these patients may present with levels considerably above the mean for normal subjects.

The insulin receptor in insulin-dependent diabetes mellitus: An in vivo and in vitro study

Insulin binding to circulating monocytes was studied in eight nonobese patients with insulin-dependent diabetes mellitus (IDDM) in poor metabolic control, along with eleven normal subjects. Insulin secretory responses to glucose and tolbutamide were studied before treatment in the three newly diagnosed patients. Six of the patients underwent repeat insulin binding studies after improvement in metabolic control. Four metabolic abnormalities commonly seen in IDDM, hyperglycemia, ketonemia, acidemia, and hyperosmolarity, were simulated in vitro using cultured human lymphocytes (IM-9 line), and their effects on insulin binding examined. Insulin binding in poorly controlled insulin-dependent diabetics is heterogeneous. Mean tracer binding is slightly above the mean of normal subjects. The three newly diagnosed patients have minimal insulin reserve. They cannot be distinguished from previously treated diabetic subjects with poor metabolic control on the basis of insulin binding. There is no correlation of insulin binding, or R 0 (receptors/cell), or K e (affinity of the empty receptor) in the poorly controlled state with degree of ketonuria, fasting glucose concentrations, fasting growth hormone concentrations, or 8 a.m. cortisol concentrations. After treatment with insulin (5–78 days) mean tracer insulin binding fell significantly (9.05% ± 1.07% to 5.8% ± 1.08%, p < 0.05), associated with decreases of both R 0 and affinity. Insulin binding to cultured human lymphocytes was not altered by preincubation of cells for 18 hr at 37°C with varying concentrations of glucose (100–800 mg/dl), varying pH (6.6–7.6), or 40 mm β-OH butyric acid. There was a small but significant inverse correlation between tracer insulin binding and preincubation osmolality ( r = −0.42, p < 0.05). We conclude that (1) insulin binding in poorly controlled IDDM is normal or somewhat elevated similar to animal models of IDDM and distinctly different from non-IDDM, and (2) insulin binding decreases with insulin treatment and improvement in metabolic control, associated with both R 0 and affinity changes. These studies suggest that hyperglycemia, ketonemia, acidemia, and hyperosmolarity do not account for the changes in insulin binding observed in these patients. We have clearly demonstrated two types of regulation of the insulin receptor; type one requires the presence of the regulator in the binding assay, and is readily reversible so that the receptor has no “memory” for the effect, and type two which is readily demonstrable in the in vitro binding assay and for which the receptor has “memory.”

Graves' disease associated with elevated serum thyroxine-binding globulin concentrations.

Eleven cases of Graves’ disease associated with levated levels of T4-binding globulin (TBG) were examined. The patients consisted of 10 women and 1 man, none of whom was pregnant or receiving estrogenic drugs. Their liver functiontests were normal, except for elevated values of alkaline phosphatase. In the euthyroid state after herapy, total T1 values 10.6 ± 0.8 μg /dl (mean ± SD)] were in the upper normal range (5.073–11.0 μg/dl) and total Ta values (210± 49 ng/dl) were above he normal range (110–200 ng/dl). On the other hand, values of T3uptake (20.4 ±2.1%) were decreased (normal range, 23–34%),and TBG values (40.1 ± 4.8 μg/ml) were more than 3 SD above the mean of normal subjects (19.2 ±4.8 jug/ml in men and 22.7 ± 4.4 μg/ml in women). The mean (±SD) results of the thyroid function tests in the patients before therapy were as follows: total Ty3 20.6 ±2.9 jug/ dl; total T3 406 ±91 ng/dl; T3 uptake, 32.5 ± 5.5%; T, to T4 ratio, 19.5 ± 4.3 ng/g (>20 in untreated cases of Graves’ disease); and TBG, 29.6 ± 2.8 /g/ml. In untreated thyrotoxic patients with Graves’ disease, the TBG concentration was inversely correlated with the T3 to T1 ratio (r = −0.54; P < 0.001). Therefore, levated TBG levels could be predicted from the low values of the T3 to T4 ratio before therapy in 6 of the 11 patients. Examination of the 7 families of 8 cases revealed familial TBG excess in 5 families. Findings in 3 of these families were compatible with X-linked inheritance of TBGexcess. Elevated TBG in Graves’ disease is not a rare phenomenon. It is important to recognize such cases in the early thyrotoxic stage of the disease to avoid overmedication. The possible relation of Graves’ disease to an elevated TBG level is discussed.(J Clin Endocrinol Metab51: 325, 1980)

Serum prolactin levels in eighty patients with sarcoidosis

Serum prolactin levels were measured by radioimmunoassay in eighty patients (thirty-four males, forty-six females) with sarcoidosis before treatment. In twelve patients (15%) serum prolactin levels were more than two standard deviations above the mean of normal subjects. Hyperprolactinaemia was found most frequently (22%) in patients with radiological stage II; however, 14% of patients with stage I also had elevated serum prolactin levels. In most cases serum prolactin levels fell to within the normal range after treatment with corticosteroid in parallel with improvement of intrathoracic lesions. These findings suggest that hyperprolactinaemia may be due to hypothalamic involvement by sarcoid granulomata. We conclude that the measurement of basal serum prolactin levels using radioimmunoassay is a sensitive and practical method for screening patients with sarcoidosis for hypothalmic lesions.

SERUM LUTEINIZING HORMONE (LH) AND FOLLICLE STIMULATING HORMONE (FSH) CONCENTRATIONS IN SUBJECTS WITH SICKLE CELL ANEMIA (SCA)

LH and FSH concentrations were determined in sera obtained from 40 subjects (20 males and 20 females; ages 5-16 years) with SCA (homozygous hemoglobin S). Mean LH concentrations were significantly increased above those of comparable age normal subjects in 5-8 year old males (5.3 ± 0.6 mIU/ml vs. 3.4 ± 0.6 mIU/ml), 5-8 year old females (6.7 ± 1.4 vs. 2.6 ± 0.3) and 9-10 year old females (6.8 ± 1.9 vs. 4.0 ± 1.3). The mean FSH concentration was also significantly increased in 13-14 year old females (12.8 ± 1.5 mIU/ml vs. 8.0 ± 2.9 mIU/ml). The LH concentration in 10 subjects (4 males and 4 females ages 5-8 and 2 females ages 9-10) and the FSH concentration in 7 subjects (all females ages 11-16) were > 2 SD above the mean of normal subjects. The observed increase in LH concentration during the first decade of life is consistent with impaired gonadal function and correlates well with the period of greatest morbidity in SCA. while the observed increase in FSH concentration may represent racial variation in females (Clin. Res. 21:866, 1973), it is also consistent with impaired gonadal function. Transiently impaired gonadal function may, in part, account for the variations in sexual maturation seen in patients with SCA.

Patterns of immune response in chronic pulmonary histoplasmosis.

Humoral and cellular immunity were evaluated in patients with chronic pulmonary histoplasmosis. Results of histoplasmin skin tests and in-vitro histoplasmin-induced lymphocyte transformation agreed in the great majority of individuals. As a group, patients with chronic pulmonary histoplasmosis exhibited histoplasmin-induced lymphocyte transformation that was no different from normal subjects with positive skin tests. However, a wide spread of transformation values was observed, from reactivity greater than that in skin-test positive, normal subjects to absence of transformation. Six of 10 patients with active disease were found to have histoplasmin-induced transformation greater than the mean of normal subjects with positive skin tests. Two patients with active disease had negative skin tests and depressed in-vitro lymphocyte responsiveness not only to histoplasmin but also to candida extract and phytohemagglutinin. A consistent correlation between titers of CF or precipitin antibody in autologous serum and histoplasmin-induced transformation values could not be demonstrated. Impaired responsiveness of lymphocytes to histoplasmin was a temporary phenomenon in one patient whose transformation was retested over a period of a year.

Renin and acute renal failure: studies in man.

Plasma renin concentration was increased, usually appreciably, in 22 out of 25 patients with acute renal failure, the average value being 226 units/litre (mean for normal subjects 8.2 units/1.). The highest renin values were found in the first 10 days of the disease; lower and sometimes normal values were found subsequently. Unequivocal acute tubular necrosis was present in only two of the eight cases examined post mortem.These findings are compatible with Goormaghtigh's proposal that an excess of renin and angiotensin may act within the kidney to produce acute renal failure.