Is esophoria a factor in slowing of myopia by progressive lenses?

PURPOSE: Our previous findings suggest that myopia can be slowed by wearing progressive lenses, and one possible mechanism for this is through the oculomotor system. We reanalyzed our findings to investigate the relationship between baseline oculomotor parameters and change in refraction, and between the change in these values and change in refraction. METHODS: Children who wore progressive lenses (N = 38; 26 with +1.50 D addition, and 16 with +2.00 D addition) or single-vision lenses (N = 32) had refraction, distance heterophoria, near heterophoria, and stimulus AC/A ratio measured prospectively over a 2-year period. RESULTS: There were no statistically significant correlations between baseline heterophoria or AC/A values and change in refractive error. Distance and near heterophoria did not change significantly over the 2 years of the experiment; AC/A ratio decreased significantly, but in an equivalent manner for both groups. In the combined progressive lens group, change toward more exophoria at near was associated with less myopia progression. However three-way analysis of variance (visit x lens type x esophoria/nonesophoria) showed significant main effects in refraction over all five visits. There was a significant interaction between lens type and visits; there was no significant interaction between lens type and esophoria/ nonesophoria grouping. Three-way analysis of variance showed a statistically significant decrease of AC/A ratio over all five visits; there was no interaction of visit by lens or visit by phoria grouping. CONCLUSIONS: Although there were no statistically significant differences between esophoric and nonesophoric subjects, there was only 46% as much myopia progression in the progressive lenses-esophoric group as in the progressive lenses-nonesophoric group. In addition, there were no differences in AC/A ratio between esophoric and nonesophoric subjects. However these findings are not definitive. This experiment was not designed to discriminate between refraction and oculomotor changes in esophoric and nonesophoric subjects and lacked the necessary statistical power to do so.

Protection against hypoxia-reoxygenation in the absence of poly (ADP-ribose) synthetase in isolated working hearts.

Peroxynitrite and hydroxyl radical are reactive oxidants produced during myocardial reperfusion injury. They have been shown to induce dysfunction in cardiac myocytes, in part, via the activation of the nuclear enzyme poly (ADP-ribose) synthetase (PARS). These oxidants can trigger DNA single strand breakage, which triggers PARS activation, resulting in cellular NAD+ and ATP depletion and cytotoxicity. Recent work has demonstrated that hypoxia-reoxygenation of cardiac myocytes in vitro also causes peroxynitrite formation, PARS activation and cytotoxicity. In the present study, using hearts from genetically engineered mice lacking PARS, we have investigated whether the absence of PARS alters the functional response to hypoxia reoxygenation. Isolated work-performing mouse hearts were stabilized under the same loading condition (cardiac minute work of 250 mmHg x ml/min, an afterload of 50 mmHg aortic pressure and similar venous return of 5 ml/min, resulting in the same preload). After 30 min equilibration the hearts were subjected to 30 min hypoxia followed by 30 min of reoxygenation. At the end of the reoxygenation, in hearts from wild-type animals, there was a significant suppression in the rate of intraventricular pressure development (+dP/dt) from 3523 to 2907 mmHg. There was also a significant suppression in the rate of relaxation (-dP/dt) in the wild-type hearts from 3123 to 2168 mmHg. The time to peak pressure (TPP) increased from 0.48 to 0.59 ms/mmHg and the half-time of relaxation (RT1/2) increased from 0.59 to 0.74 ms/mmHg. In contrast, in the hearts from the PARS knockout animals, no significant suppression of +dP/dt (from 3654 to 3419 mmHg), and no significant increase in the TPP (from 0.462 to 0.448 ms/mmHg) were found, and the decrease in -dP/dt was partially ameliorated (from 3399 to 2687 mmHg) as well as the half-time of relaxation (from 0.507 to 0.55 ms/mmHg) when compared to the response to the wild-type hearts. The current data demonstrate that the reoxygenation induced suppression of the myocardial contractility is dependent on the functional integrity of PARS.

Large supplements of nicotinic acid and nicotinamide increase tissue NAD+ and poly(ADP-ribose) levels but do not affect diethylnitrosamine-induced altered hepatic foci in Fischer-344 rats.

Poly(ADP-ribose) is a homopolymer of ADP-ribose units synthesized from NAD+ on nuclear acceptor proteins and is known to be involved in DNA repair. It is not known whether large oral doses of the clinically utilized NAD precursors nicotinic acid or nicotinamide affect poly(ADP-ribose) metabolism or the cellular response to DNA damage. In our first study, using Fischer-344 rats, 2 wk of dietary nicotinic acid supplementation (500 and 1000 mg/kg diet) caused elevated levels of NAD+ in the blood, liver, heart and kidney, while nicotinamide caused elevated levels only in the blood and liver, compared with controls fed a diet containing 30 mg/kg nicotinic acid. Both nicotinic acid and nicotinamide, at 1000 mg/kg diet, caused elevations in liver NAD+, by 44 and 43%, respectively. Only nicotinamide, however, elevated liver poly(ADP-ribose) (63% higher than control group). Following treatment with the hepatocarcinogen diethylnitrosamine, higher levels of hepatic NAD+ were observed in rats fed both nicotinic acid and nicotinamide at 1000 mg/kg diet, but only nicotinic acid supplementation caused a greater accumulation of hepatic poly(ADP-ribose) (61% higher than control group). Neither of the dietary treatments significantly affected the proportion of the liver occupied by placental glutathione-S-transferase positive foci. These results show that poly(ADP-ribose) synthesis is not directly responsive to hepatic NAD+ levels during niacin supplementation, and that the mechanisms of action of nicotinic acid and nicotinamide are different. The observed changes in poly(ADP-ribose) metabolism do not appear to cause any change in susceptibility to chemically induced carcinogenesis in this organ.

Reducing blood donor exposures in low birth weight infants by the use of older, unwashed packed red blood cells.

We performed a prospective, randomized masked trial to determine whether the use of dedicated units of packed red blood cells equipped with seven satellite bags would reduce donor exposures in infants with birth weights < 1500 gm. We also examined the use of unwashed and older red blood cells. Red blood cells given to the study group were used without washing and until their expiration date (35 to 42 days). Changes in blood pH, potassium, ionized calcium, and hemoglobin were determined with each transfusion and compared with data collected from a control group that received washed, younger red blood cells. There was a 64% reduction in donor exposures in the study group. Changes in infants' blood pH and calcium levels with transfusion were the same in the two groups. There was a clinically unimportant difference in potassium levels. A greater rise in hemoglobin values occurred when washed cells were used. There was no correlation between changes in the blood levels measured and the age of unwashed cells infused. We conclude that the use of red blood cells from satellite bag-equipped dedicated units decreases donor exposures, and that the practices of using only younger red blood cells and of saline washing of red blood cells before infusion, are unwarranted.

The effect of niacin deficiency on diethylnitrosamine-induced hepatic poly(ADP-ribose) levels and altered hepatic foci in the Fischer-344 rat.

Poly(ADP-ribose) is synthesized on nuclear proteins in response to DNA damage and plays an important role in DNA repair. Niacin and tryptophan are dietary precursors to NAD+, which is the substrate for poly(ADP-ribose) synthesis. This study examined the influence of niacin status on poly(ADP-ribose) metabolism and carcinogenesis. Diets devoid of added niacin, with different levels of tryptophan, were used to produce moderate and severe niacin deficiencies in male Fischer-344 rats. Control rats were pair fed niacin-replete diets. After a 21-day feeding period, rats were injected with diethylnitrosamine (DEN) (Expt 1, 200 mg/kg ip; Expt 2, 100 mg/kg ip). In Experiment 1, blood and liver NAD+ and liver poly(ADP-ribose) were measured over the next 15 hours. Whereas blood and liver NAD+ were decreased by niacin deficiency, blood NAD+ was not affected by DEN. Liver NAD+ decreased significantly in response to DEN treatment in the pair-fed groups, but it did not change in the niacin-deficient groups. Unexpectedly, at 10 hours postinjection, liver poly(ADP-ribose) accumulation was greater (p < 0.05) in the niacin-deficient than in the pair-fed rats (n = 9), despite lower initial NAD+ levels and a lack of NAD+ disappearance in niacin-deficient livers. In Experiment 2, livers were examined for the presence of altered hepatic foci three months after DEN exposure. There were no significant differences in the percentage of liver occupied by foci between the niacin-deficient and pair-fed groups (n = 8). These results indicate that niacin-deficient rats were able to accumulate higher concentrations of hepatic poly(ADP-ribose) in response to DEN and did not show elevated susceptibility to initiation of altered hepatic foci.

Dietary niacin deficiency lowers tissue poly(ADP-ribose) and NAD+ concentrations in Fischer-344 rats.

Poly(ADP-ribose) is synthesized in response to DNA strand breaks, using NAD+ as substrate, and has been implicated in the process of DNA repair. Because NAD+ can be synthesized from niacin or tryptophan, both of these components must be manipulated to alter niacin status. Six dietary treatments were used, including niacin-deficient (ND) diets and niacin-replete (NR) diets consumed ad libitum and the NR diets pair-fed (PF) to the ND intake. The ND, NR and PF diets contained either 80 g casein + 50 g gelatin/kg diet (8-5 diets) or 70 g casein + 60 g gelatin/kg diet (7-6 diets) to control tryptophan content. The 8-5ND and 7-6ND diets induced mild and severe symptoms of niacin deficiency, respectively, over a 3-wk period in male weanling Fischer-344 rats. Food intake and weight gain were suppressed in both of the ND groups compared with their respective NR controls. Weight gain was not different between ND animals and their PF counterparts. At 3 wk, blood, liver, kidney, heart and lung NAD+ concentrations for both 8-5ND and 7-6ND animals were all significantly lower than those for their respective PF groups. In the groups fed the 8-5 diets, liver poly(ADP-ribose) was lower in the ND group (64% of PF), with no difference between the NR and PF groups. In rats fed the 7-6 diets, poly(ADP-ribose) levels were further decreased in the ND group (43% of PF), but food restriction also exerted an independent effect (PF levels were 46% of NR levels).(ABSTRACT TRUNCATED AT 250 WORDS)

Genistein, a selective protein tyrosine kinase inhibitor, inhibits interleukin-2 and leukotriene B4 production from human mononuclear cells.

In this study, genistein, a selective protein tyrosine kinase (PTK) inhibitor, inhibited peripheral blood mononuclear cell (PBMC) proliferation and interleukin-2 production from cultures that were stimulated with phytohemagglutinin (PHA), phorbol 12-myristate 13-acetate (PMA) plus A23187, or PHA plus PMA, and genistein effectively blocked the PHA plus IL-2-induced PBMC proliferation. Further, we also found that genistein inhibited LTB4 production from A23187-stimulated cultures whereas H-7, a PKC inhibitor, had no effect on LTB4 production. Our results suggest that PTK may be necessary for the synthesis of LTB4.

Rapid solid-phase immunoassay for 6-keto prostaglandin F1 alpha on microplates.

We describe, for the measurement of 6-keto prostaglandin F1 alpha in biological media, a solid-phase immunoassay with immobilized antibodies that requires a total processing time of less than 2 h with hands-on time less than 30 min for 40 samples. The method combines the convenience of the microplate format with the sensitivity of radiolabeled prostaglandin derivatives as tracers in a competitive immunoassay. The intra- and interassay variations at 50% displacement of the radiolabeled prostaglandin derivative as tracer were 9.0% and 11.8%, respectively. At 50% displacement of the radiolabeled tracer, the sensitivity is about 20 pg per well. Optimal incubation time is between 60 and 90 min. Nonspecific binding was less than 1% if about 8 pg of tracer (approximately 25,000 counts/min per well) was used. Inhibition curves of samples in different dilutions were parallel to standard curves. The variation of bound radiolabeled prostaglandin derivative within the wells of one microplate (n = 96) was less than 3%. Human plasma samples and medium from tissue culture assayed for 6-keto prostaglandin F1 alpha correlated well with results obtained with a solid-phase assay based on use of magnetic particles (r = 0.99, n = 24 for culture-medium samples; r = 0.99; n = 26 for plasma samples.

Hemoccult screening for colorectal cancer.

A community hemoccult screening project for colorectal cancer resulted in the processing of 18,198 specimens. Positive test results were reported in 3 percent of the total, which ultimately resulted in the identification of 20 colorectal malignancies (0.1 percent) and 53 benign polyps (0.3 percent). The number of malignancies and polyps identified was disappointingly low. Our findings would challenge the concept of unsupervised mass screening from the viewpoint of cost-effectiveness; however, because of the numerous voluntary services and supplies, this particular project was useful in educating the public about early colon cancer detection.

Theoretical limitations on immunoassay sensitivity. Current practice and potential advantages of fluorescent Eu3+ chelates as non-radioisotopic tracers.

The sensitivity of any immunoassay is a complex function of the underlying physico-chemical basis of the technique and the size and source of 'experimental' errors. Analysis of this relationship emphasizes the distinction between competitive labelled analyte methods, e.g., RIA, and the non-competitive labelled antibody techniques, e.g., IRMA, implying that, in practice, non-competitive methods may display sensitivities which are orders of magnitude greater than similar competitive assays. The achievement of the potential sensitivity of the non-competitive methods depends to a great extent on the application of very highly detectable labels. The long fluorescent lifetime and large Stoke's shift of certain europium (Eu3+) chelates permits such sensitive detection in a commercially available time-resolved fluorimeter. We briefly outline the current application of Eu3+ labels in immunometric assay, compare the application of Eu3+ labels in the immunofluorometric assay of human TSH with conventional RIA and discuss the future potential of this technique.

Recovery of cellular immune competence during treatment of protein-calorie malnutrition.

Fifty Bangladeshi children with severe protein-calorie malnutrition were randomly allocated at admission to four groups and sensitized to dinitrochlorobenzene either immediately or after 1, 2, or 3 wk of protein-calorie replacement therapy. Ability to initiate cutaneous hypersensitivity to dinitrochlorobenzene on admission was impaired when the total serum proteins was less than 5.5 g/dl, but uniformly recovered after 1 wk of feeding. Three severely malnourished children with total serum proteins less than 4.5 g/dl in whom sensitization was attempted before refeeding failed to respond despite repeated challenge, suggesting immunological tolerance to dinitrochlorobenzene. The data support the concept of a threshold serum protein level, at least as an indicator, below which cellular immunity may be temporarily, or even permanently, impaired.

The in vitro effect of the thymic factor thymopoietin on a subpopulation of lymphocytes from severely malnourished children.

Several investigators have shown that the proportion of T cell lymphocytes was greatly reduced while that of the B cell lymphocytes was virtually unaffected; thus the relative proportion of null cells was significantly increased in severely malnourished patients. Other studies have demonstrated that extracts of bovine thymus will induce an increase in the proportion of T cell rosettes from patients with various disorders. This study has demonstrated that peripheral blood lymphocytes from severely malnourished patients with secondary infections contain a subpopulation of lymphocytes which will respond in vitro in the presence of thymopoietin by increased numbers of E rosettes. These results also support the concept of a finite population of responder cells and indicate that other thymopoietin insensitive subpopulations of null cells are increased when the proportion of T cells are greatly suppressed. Further characterization of the lymphocyte subpopulation(s) affected by thymopoietin is needed.

Enhanced T-cell rosette formation in shigellosis by the in vitro use of thymopoietin.

The results from this study suggest that the large nul cell lymphocyte population seen in patients with Shigella dysentery, does contain a sub-population of cells that will respond in vitro to thymopoietin, a bovine thymic extract, by increased E-rosette formation. It is felt that this sub-population is in fact immature T-cells. A previous study has shown that an unusual leukaemoid reaction develops in a substantial number of patients with Shigella dysentery. The leukaemoid response was primarily granulocytic in nature but there was also a substantial increase in the mean number of lymphocytes. The proportion of the various populations of lymphocytes from leukaemoid and non-leukaemoid subjects were altered, B-cells remained constant, while the T-cells were depressed with a corresponding rise in the proportion of nul cells. The cumulative results of this and other studies demonstrate that the T-cell arm of immunity is compromised in shigellosis. Indeed the degree of compromise may ultimately be the decisive factor in determining the severity of this disease.

Sub-populations of peripheral lymphocytes from patients with shigella bacillary dysentery with associated leucocytosis.

In this study we ascertained the proportion and absolute number of T, B and nul cell peripheral lymphocytes from Shigella dysenteriae type I patients and compared these results with those from age matched controls. Single blood samples were collected from 13 Bangladeshi children who complained of symptoms for one or more weeks. Patients were divided into two categories, with and without a leukaemoid response. The leukaemoid response was primarily granulocytic in nature, but there was a substantial increase in the mean number of lymphocytes. Over one third of the lymphocytes were nul cells. These cells rose proportionally to the decrease of T-cells, as the proportion of B-cells remained within normal range. One leukaemoid patient died. The absolute number of lymphocytes was normal and the B-cells were normal in respect of both proportions and absolute numbers. T-cell percentage and numbers were well below normal values.

T and B rosetting lymphocytes in the blood of smallpox patients.

The proportion of T and B cells in the peripheral blood of smallpox patients was determined. The average initial percentage of T cells was depressed (41 +/- 8.4%) in comparison with uninfected controls (65 +/- 7.6%), while the initial B cell counts averaged 26 +/- 11.4% and 28 +/- 5.1%, respectively. However, initial B cell percentages in four infected patients (two of whom died) were between 9 and 14, which are considerably lower than any control value, the lowest of which was 19%. Review of the literature emphasizes the both cellular and serological immunity play a role in recovery from pox disease; the two patients who had the highest initial nul cell (lymphocytes not identified as either T or B cells) counts died, while none of five patients who had consistently low nul cell counts died.