The dietary supplementation of canthaxanthin in combination with 25OHD3 results in reproductive, performance, and progeny quality gains in broiler breeders.

The objective of this study was to evaluate the effects of the dietary supplementation of canthaxanthin and cholecalciferol (25OHD3) to broiler breeders and their progenies on their performance. Eighty 25-wk-old Cobb 500 broiler breeders were distributed according to a completely randomized design in 2 experimental treatments, with 10 replicates of 4 birds each. The treatments consisted of the supplementation or not of a corn-soybean meal diet with canthaxanthin + 25OHD3 to broiler breeders fed from 25 to 62 wk of age. Egg production, fertility, hatchability, hatchability of fertile eggs, embryonic mortality, and egg specific gravity were evaluated. Breeders were inseminated at 35, 45, and 62 wk of age, the eggs were incubated, and the performance of the progenies was evaluated. From the progeny of each breeder age, 300 male chicks were distributed according to a completely randomized design in a 2 × 2 factorial arrangement (chicks from breeders supplemented or not with canthaxanthin + 25OHD3 and chicks supplemented or not with canthaxanthin + 25OHD3), totaling 4 treatments with 5 replicates of 15 birds each. Canthaxanthin + 25OHD3 were supplied to the chicks until 21 D of age. The combination of canthaxanthin and 25OHD3, containing 69 mg of 25OHD3 and 6 g of canthaxanthin, was supplemented at 1 kg/t of feed. Breeders supplemented with canthaxanthin + 25OHD3 showed higher egg production, total hatchability, hatchability of fertile eggs, and lower early embryo mortality compared with those fed the control diet. Broilers from breeders fed canthaxanthin + 25OHD3 and supplemented with this additive up to 21 D of age presented a better feed conversion ratio and higher carcass and breast yields than those derived from nonsupplemented breeders.

Effect of dietary canthaxanthin and iodine on the production performance and egg quality of laying hens.

In this study, we aimed to evaluate the effect of canthaxanthin (CX) and iodine (I) on the production of laying hens, on counteracting debilitation of the vitelline membrane, and on inhibiting Salmonella growth in eggs stored at 30°C. Three hundred hens were reared in cages. Birds were divided into six feeding groups (10 hens × 5 repetitions) that were administered 0, 3 or 6 ppm of CX and 1 or 10 ppm of I with their diets. Laying rate, egg weights, and feed conversion ratios were controlled. The quality of fresh eggs was assessed in wks 25-26, 48-50 and 62-63 of hens lives. An additional batch of eggs was incubated at the temperature of 30°C, and egg quality changes were monitored on days 3, 6 and 9 of storage. Additionally, eggs collected from four experimental groups of hens whose diets had been iodated with 1 or 10 ppm of I and supplemented with 0 or 6 ppm of CX were infected under laboratory conditions with Salmonella, and incubated for 5 and 10 d. The laying rate, egg weights, and feed conversion ratio were significantly improved. Dietary inclusion of CX contributed to a higher resistance of the vitelline membrane of egg yolks, but only for fresh eggs. Vitelline membrane degradation during egg storage at 30°C was significantly counteracted by dietary inclusion of I at a dose of 10 ppm. The same I dose resulted in the complete inhibition of Salmonella growth until day 10 of incubation, but exclusively for eggs collected from 40-week-old hens. Dietary supplementation with 10 ppm of I was found to impart high level of resistance to the vitelline membrane against the growth of Salmonella in case of eggs stored at 30°C; therefore, I was found to be more beneficial by ensuring longer preservation than that of CX. However, dietary supplementation with CX was found to increase the resistance of vitelline membrane in fresh eggs.

Oral treatment with ACCUTANE does not increase measures of anhedonia or depression in rats.

Reports of depression and/or suicide with ACCUTANE (13-cis-retinoic acid (13-cis-RA)) use prompted studies in a rodent model to ascertain its potential effects. Previously, there were no effects on measures of anhedonia (intake of a saccharin-flavored solution) and depression (forced swim test (FST) behaviors) in rats treated with 7.5 or 22.5 mg/kg 13-cis-RA [S.A. Ferguson, F.J. Cisneros, B. Gough, J.P. Hanig, K.J. Berry, Chronic oral treatment with 13-cis-retinoic acid (isotretinoin) or all-trans-retinoic acid does not alter depression-like behaviors in rats, Toxicol. Sci. 87 (2005) 451-459.]. Here, dose and temporal thresholds were investigated by increasing the maximum 13-cis-RA dose to 30 mg/kg, extending treatment duration, and measuring behaviors repeatedly. Beginning on post-natal day 59, male and female Sprague-Dawley rats were gavaged with soybean oil, 7.5 or 30 mg/kg/day of 13-cis-RA for approximately 19 weeks. FST behaviors were measured after 24, 82, and 131 treatment days and saccharin intake (0.03% solution) was measured at baseline and after 14, 35, 56, and 112 treatment days. Body weight and food intake were not altered by treatment. FST durations of swim, climb/struggle, and immobility were unaffected by 13-cis-RA at any time during treatment. More males than females required "rescue" in the FST but there was no treatment effect on number of rats requiring early removal. 13-cis-RA treatment had no effects on saccharin intake at any time. Given that the 7.5 mg/kg dose produces serum levels which parallel those of humans [S.A. Ferguson, P.H. Siitonen, F.J. Cisneros, B. Gough, J.F. Young, Steady state pharmacokinetics of oral treatment with 13-cis-retinoic acid or all-trans-retinoic acid in male and female adult rats, Basic Clin. Pharmacol. Toxicol 98 (2006) 582-587.], these results are quite relevant. Combined with previous results, these results provide further evidence that 13-cis-RA does not produce behavioral alterations indicative of depression in rats.

Steady state pharmacokinetics of oral treatment with 13-cis-retinoic acid or all-trans-retinoic acid in male and female adult rats.

Male and female Sprague-Dawley rats were orally gavaged with 13-cis-retinoic acid (7.5 or 15 mg/kg) or all-trans-retinoic acid (10 or 15 mg/kg) for 7 consecutive days. Blood was collected out to 8 hr after the last gavage on day 7. HPLC serum concentrations of 13-cis-retinoic acid, all-trans-retinoic acid, and 13-cis-4-oxo-retinoic acid were subjected to model independent pharmacokinetic analyses. Peak serum levels of 563 to 1640 ng/ml were observed for rats treated with 13-cis-retinoic acid at 1.5-2 hr after gavage. Peak serum levels of 183 to 267 ng/ml at 1.5 hr after gavage were observed for all-trans-retinoic acids. The elimination half-life of 13-cis-retinoic acid was about 1.5 hr while the elimination half-life of all-trans-retinoic acid was slightly longer. There were no sex differences for any parameter. Serum levels resulting from the 7.5 mg/kg 13-cis-retinoic acid were similar to those of human Accutane users.

Serum levels of albumin, triglycerides, total protein and glucose in rats are altered after oral treatment with low doses of 13-cis-retinoic acid or all-trans-retinoic acid.

Currently used to treat severe acne, 13-cis-retinoic acid (13-cis-RA) is under investigation for its anticancer effects as is the isomer, all-trans-retinoic acid (all-trans-RA). Here, the effects of oral 13-cis-RA or all-trans-RA treatment on serum chemistry, leptin and adiponectin levels were evaluated. Adult Sprague-Dawley rats were gavaged once daily for 7 consecutive days with 13-cis-RA (7.5 or 15 mg kg(-1)), all-trans-RA (10 or 15 mg kg(-1)) (n=24/sex/dose), or soy oil (n=16/sex) and blood was sampled 30-480 min after the last gavage. The body weight was unaffected; however, the liver/body weight ratios were increased by both doses of all-trans-RA. Sex differences were noted for levels of cholesterol, creatine, triglycerides, albumin, alanine aminotransferase and total protein. Both doses of all-trans-RA reduced albumin levels to approximately 90% of the control and total protein levels to approximately 93% of the control while substantially elevating triglyceride levels to approximately 66%-99% above the control. Additionally, triglyceride levels of the 15 mg kg(-1) 13-cis RA group were approximately 62% higher than the controls and total protein levels were approximately 5% less. Glucose levels were affected by sex and RA treatment in that males treated with 15 mg kg(-1) of 13-cis-RA or 10 mg kg(-1) all-trans-RA had lower (13%-19%) levels than the same-sex controls; however, females were not similarly affected. Neither 13-cis-RA nor all-trans-RA treatment had significant effects on the levels of blood urea nitrogen, aspartate amino transferase, leptin or adiponectin. On a mg kg(-1) basis, all-trans-RA was more potent than 13-cis-RA. These results replicate previous findings of RA-induced increased triglyceride levels. Additionally, several new findings indicate there may be sex-specific effects of RA treatment. Finally, neither treatment appeared to alter the typical diurnal cycles of these endpoints.

Chronic oral treatment with 13-cis-retinoic acid (isotretinoin) or all-trans-retinoic acid does not alter depression-like behaviors in rats.

Oral treatment with the anti-acne drug Accutane (isotretinoin, 13-cis-retinoic acid) has been associated with suicide ideation and depression. Here, depression-like behaviors (i.e., behavioral despair and anhedonia) were quantified in adult Sprague-Dawley rats gavaged daily beginning at postnatal day (PND) 82 with 13-cis-RA (7.5 or 22.5 mg/kg) or all-trans-retinoic acid (10 or 15 mg/kg ). Tested at PND 130-131 in the Forced Swim Test, 7.5 mg/kg 13-cis-RA marginally decreased immobility and slightly increased climb/struggle durations whereas neither all-trans-retinoic acid group differed from controls. Voluntary saccharin solution (0.03%) intake at PND 102-104 and PND 151-153 was not different from controls in any treated group, although all RA-treated groups had lower intakes. Swim speed in a water maze at PND 180 was similar across groups, indicating no RA-induced differences in physical ability. Open field activity was mildly decreased at PND 91 in 7.5 mg/kg-treated males only, but it was within the control range at PND 119, 147, and 175. Thus, at serum levels similar to those in humans receiving the drug, chronic 13-cis-RA treatment did not severely affect depression-like behaviors in rats. These data do not substantiate the hypothesis of 13-cis-RA-induced depression.

Four weeks of oral isotretinoin treatment causes few signs of general toxicity in male and female Sprague-Dawley rats.

Despite widespread use of isotretinoin for its anti-acne effects and its current evaluation in clinical trials as a cancer treatment, little is known about its general toxicity in adult nonpregnant animals, particularly after oral administration which mimics the human route. Here, adult male and female Sprague-Dawley rats were gavaged daily with 0 (soy oil), 7.5, or 15 mg/kg isotretinoin for 28 days during which time body weight, food/water intake, and estrous phase were measured. At sacrifice, organ weights were collected and concentrations of dopamine (DA), serotonin and metabolites were measured in frontal cortex, striatum, hippocampus, and diencephalon. Food intake was mildly decreased in both treated groups (approximately 15% in males and 7% in females); however, body weight and water consumption were unaffected. The estrous cycle appeared slightly affected (i.e., lengthened by 15 mg/kg, and both treated groups appeared to have less time in diestrus and more time in estrus). Kidney/body weight ratio was decreased by 7.5 and 15 mg/kg isotretinoin and spleen/body weight ratio was increased in the 7.5 mg/kg group. Males of the 7.5 mg/kg group exhibited significantly higher gonad/body weight ratios than did same-sex controls. Concentrations of monoamine and metabolites in the frontal cortex and diencephalon were unaffected. Nor were striatal DA and DOPAC concentrations affected; however, there were isolated effects on striatal HVA and 5-HIAA. Hippocampal DA concentrations were marginally increased. These data indicate mild effects resulting from oral isotretinoin treatment at doses which likely produce serum levels within the range of humans.

Human extraocular muscles in mitochondrial diseases: comparing chronic progressive external ophthalmoplegia with Leber's hereditary optic neuropathy.

AIMS: To compare the ultrastructural aspects of human extraocular muscles in two types of mitochondrial disease: chronic progressive external ophthalmoplegia (CPEO) and Leber's hereditary optic neuropathy (LHON). METHODS: Muscle samples of the medial rectus obtained from surgery in a sporadic case of CPEO associated with deleted mitochondrial DNA, and post mortem in a case of 3460/ND1 LHON were processed for electron microscopy (EM). The medial rectus from an autoptic time to fixation matched control was used to exclude postmortem artefacts. RESULTS: The CPEO specimen revealed focal areas of disruption and abnormalities of mitochondria in some muscle fibres, creating a "mosaic-like" pattern. In the LHON specimen a diffuse increase in both number and size of mitochondria (mean diameter 0.85 mum v 0.65 mum of control, p<0.0001) with swollen appearance and disorganised cristae filled all spaces of sarcoplasmic reticulum. In some areas the excessive number of mitochondria slightly distorted myofibrils. CONCLUSION: EM investigation of extraocular muscles in CPEO and LHON reveals marked differences. A "mosaic-like" pattern caused by a selective damage of muscle fibres was evident in CPEO, whereas a diffuse increase in mitochondria with preservation of myofibrils characterised the LHON case. These ultrastructural changes may relate to the different expression of the two diseases, resulting in ophthalmoplegia in CPEO and normal eye movements in LHON.

Correlation between retinal nerve fibre layer thickness and optic nerve head size: an optical coherence tomography study.

AIM: To investigate the correlation between retinal nerve fibre layer (RNFL) thickness and optic nerve head (ONH) size in normal white subjects by means of optical coherence tomography (OCT). METHODS: 54 eyes of 54 healthy subjects aged between 15 and 54 underwent peripapillary RNFL thickness measurement by a series of three circular scans with a 3.4 mm diameter (Stratus OCT, RNFL Thickness 3.4 acquisition protocol). ONH analysis was performed by means of six radial scans centred on the optic disc (Stratus OCT, Fast Optic Disc acquisition protocol). The mean RNFL values were correlated with the data obtained by ONH analysis. RESULTS: The superior, nasal, and inferior quadrant RNFL thickness showed a significant correlation with the optic disc area (R = 0.3822, p = 0.0043), (R = 0.3024, p = 0.026), (R = 0.4048, p = 0.0024) and the horizontal disc diameter (R = 0.2971, p = 0.0291), (R = 0.2752, p = 0.044), (R = 0.3970, p = 0.003). The superior and inferior quadrant RNFL thickness was also positively correlated with the vertical disc diameter (R = 0.3774, p = 0.0049), (R = 0.2793, p = 0.0408). A significant correlation was observed between the 360 degrees average RNFL thickness and the optic disc area and the vertical and horizontal disc diameters of the ONH (R = 0.4985, p = 0.0001), (R = 0.4454, p = 0.0007), (R = 0.4301, p = 0.0012). CONCLUSIONS: RNFL thickness measurements obtained by Stratus OCT increased significantly with an increase in optic disc size. It is not clear if eyes with large ONHs show a thicker RNFL as a result of an increased amount of nerve fibres or to the shorter distance between the circular scan and the optic disc edge.

5-AZA-2'-deoxycytidine (5-AZA-CdR): a demethylating agent affecting development and reproductive capacity.

The objective was to evaluate the effects of 5-AZA-2'-deoxycytidine (5-AZA-CdR) on postnatal development and reproductive capacity. Pregnant mice were administered 1 mg kg-1 5-AZA-CdR at gestation day 10. The body weights of F1 control and treated (in uterine-exposed) pups were recorded. To evaluate the reproductive capacity, 5-AZA-CdR F1 males and females were mated with control mice. The presence of plugs and the number of pregnancies were recorded. The 5-AZA-CdR F1 male mice were killed. Total body, testes and epididymis weights were recorded. Spermatid head counting, histological analyses and serum testosterone levels were performed. Body weights of 5-AZA-CdR F1 mice were statistically lower than controls (P < 0.01), with the females more strongly affected (P < 0.05). Male mating capacity appeared to be more adversely affected. Mating of 5-AZA-CdR F1 males with control females resulted in a lower pregnancy rate compared with control mating groups (P < 0.01). Gross testicular and epididymis weights were lower in 5-AZA-CdR F1 mice (P < 0.01). However, testicular and epididymis weights in these mice were higher than controls when correlated to body weight (P < 0.01). In 5-AZA-CdR F1 male mice, all measured reproductive parameters, including total number of spermatid heads per testis, are significantly lower (P < 0.01) than the controls except for the number of spermatid heads per milligram of testis.

[Clinical and angiographic follow-up of young adults after PTCA plus intracoronary stents]. / Seguimiento clínico y angiográfico en adultos jóvenes post ACTP más stents intracoronarios.

We reviewed our work and evaluated clinical and angiographic results, as well as the follow up of young adult patients < 40 years that were subject to percutaneous trans-clinical coronary angioplasty (PTCA) with an endovascular prostheses (stent). From January 1995 to December 1999, 896 PCTA's performed using stents in 770 patients. Only one selected group of 30 patients (with 32 procedures, and an average of 1.06 stents per patients. Patients age ranged from 21 to 39 years old with an average of 32.8 + 52, 2, 29 (96%) were male and only one woman (3.3%). Nine patients (30%) had a severe angina, class III Braunwald and 21 (70%) had a previous history of myocardial infarcts. The average percent of arterial obstruction was 90.88 +/- 5.22 and the expulsion fraction. (EF) had a percent of 46.8 +/- 4.3 with ranges of 35 to 60%. Immediate angiographic success was 93.75% in only two patients (6.25%) with a 100% occlusion, and more than twelve weeks. There was no mortality, nor infarct, and no patient was sent to an urgent revascularization surgery. Clinical follow up lasted 50 weeks in all patients with the effort test using the electric Bruce type and for nuclear medicine. Only in 3 patients EF was reported, and tHalium with a slight septal ischemia. Angiographic control was included in 27 (90% patients between the 4th and 6th month. PTA with stent is a successful angiographic and clinical procedure in young adults < 40 years old; it constitutes a complete and efficient therapeutical revascularization procedure, and is an excellent option before undertaking an aortocoronary revascularization surgery.

Primary thrombophilia in Mexico. II. Factor V G1691A (Leiden), prothrombin G20210A, and methylenetetrahydrofolate reductase C677T polymorphism in thrombophilic Mexican mestizos.

We have shown that in Mexican mestizo patients with clinical features of primary thrombophilia, 39% have activated protein C resistance phenotype, 5% protein C deficiency, and 2% protein S deficiency. In the present study, in a group of 37 thrombophilic Mexicans and 50 normal controls, we assessed the factor V G1691A (Leiden), the prothrombin G20210A, and the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphisms. Four patients were found to be heterozygous for factor V Leiden, 5 heterozygous for the prothrombin 20210, 16 heterozygous, and 6 homozygous for the MTHFR 677. There were four individuals with co-segregation of alleles: two heterozygotes for the factor V Leiden/prothrombin 20210, one heterozygote for prothrombin 20210/MTHFR 677, and one heterozygote for prothrombin 20210/homozygote for MTHFR 677. For factor V Leiden, prothrombin 20210, and MTHFR 677 mutations, the allele frequencies were respectively 1% (+/-0.2%, alpha = 0.05), <1% and 51% (+/-5%, alpha = 0.05), with calculated relative risks for thrombosis of 5.94 (P = 0.08), >7.66 (P < 0.05), and 0.44 (P NS), respectively. In Mexican mestizo thrombophilic patients, the low prevalence of the factor V Leiden mutation (10.8%) and the high prevalence of the prothrombin 20210 mutation (13.5%) contrast with those identified in Caucasian thrombophilic patients (21% and 6%, respectively; P < 0.01). On the other hand, the high prevalence of the MTHFR 677 mutation gene both in normal controls (78%) and thrombophilic patients (61%) does not support a role of this mutation in the thrombogenesis of Mexican mestizo patients.

Diminished morbidity and mortality in portal hypertension surgery: relocation in the therapeutic armamentarium.

Although several effective therapeutic options are available for bleeding from portal hypertension, surgery has a well-defined role in the management of patients with good liver function who are electively operated. The aim of this investigation was to evaluate the operative mortality and morbidity of portal blood flow-preserving procedures in a highly select patient population. The records of 148 patients operated on between 1996 and 2000 using one of two techniques (selective shunts or a Sugiura-Futagawa operation [complete portoazygos disconnection]) were analyzed with particular attention to operative mortality, postoperative rebleeding, and encephalopathy. Survival was calculated according to the Kaplan-Meier method. Sixty-one patients had distal splenorenal shunts placed, and 87 patients had a devascularization procedure. Operative mortality for the group as a whole was 1.2%. In the group with selective shunts, the rebleeding rate was 4.9%, the encephalopathy rate was 9.8%, and the shunt obstruction rate was 1.6%. Survival at 24 months was 94% and at 48 months was 92%. In those undergoing devascularization, the encephalopathy rate was 5% and the rebleeding rate was 14%. Survival at 24 months was 90% and at 48 months was 86%. Portal blood flow-preserving procedures have very low morbidity and mortality rates at specialized centers. In addition, a low rebleeding rate is associated with a good quality of life. Low-risk patients with bleeding portal hypertension should be considered for surgical treatment.

Analysis of HFE-codon 63/282 (H63D/C282Y) gene variants in mexican mestizos. Blood donors and patients with hereditary hemochromatosis.

BACKGROUND: The prevalence of hereditary hemochromatosis (HH) (H63D/C282Y) gene variants in Mexico is unknown. METHODS: Using amplification refractory mutation system polymerase chain reaction, an analysis of HFE-codon 63/282 (H63D/C282Y) gene variants was performed in a group of 153 Mexican mestizo blood donors and six individuals with familial iron overload. RESULTS: In normal blood donors, three heterozygotes for the C282Y mutation (2.0%) were found, whereas 18 heterozygotes and one homozygote for the H63D mutation (11.8% and 0.6%, respectively) were identified; there was one compound heterozygote for the C282Y/H63D mutation. These data resulted in allele frequencies of 0.013 (+/-0. 2%, alpha = 0.05) and 0.062 (+/-0.9%, alpha = 0.05), respectively, for these two mutations, results similar to those found in whites. In the six patients with the HH phenotype, two were found to be heterozygous for C282Y and one heterozygous for H63D; three individuals with HH had no gene mutations. Two heterozygous HH individuals were found to have iron overload associated with other conditions: one heterozygous for C282Y infected with HIV, and another heterozygous for H63D with heterozygous beta-thalassemia. CONCLUSIONS: The prevalence of C282Y and H63D HFE gene mutations in Mexican mestizos is similar to that found in other populations. In addition, other gene mutations responsible for HH in the Mexican mestizo population should be investigated, because, in three of six individuals with the HH phenotype, neither of the two mutations was recorded.

Assessment of residual disease in acute leukemia by means of polymerase chain reaction.

Along a 5-year period in a single institution, specific molecular markers were prospectively looked for in consecutive patients with acute leukemia, by means of polymerase chain reaction (PCR): In patients with acute lymphoblastic leukemia (ALL), the BCR/ABL and TEL-AML1 fusion transcripts as well as clonotypic immunoglobulin gene rearrangements were investigated, whereas in patients with acute myelogenous leukemia (AML) the PML-RAR alpha, AML1-ETO and CBF beta-MYH11 fusion proteins were assessed. Specific molecular markers were identified in 15/75 patients: Four with ALL (three with clonotypic IgG rearrangements and one with BCR/ABL) and 11 with AML (nine with the PML/RAR alpha fusion protein--M3 AML-, and two with the AML1/ETO fusion protein--M2 AML-). During follow-up periods ranging from 1 to 60 months, seven patients cleared the residual disease assessed by PCR (RD-PCR), whereas eight patients had either persistence of RD-PCR or a molecular relapse. For patients without or with RD-PCR, the 30-month survival (SV) was 86% and 14%, respectively, whereas median SV was > 60 and two months, also respectively (p < 0.01). Six of eight patients with detectable RD-PCR died, all of them within three months after the detection of the RD-PCR, whereas two of the patients that relapsed were rescued with treatment and entered a second molecular remission. Two of the three molecular relapses were detected without an overt morphological relapse. It is concluded that PCR is a valuable method for assessing residual disease and that early diagnosis of relapses may lead into effective salvage treatment in some instances.

Leber's hereditary optic neuropathy differentially affects smaller axons in the optic nerve.

PURPOSE: Leber's hereditary optic neuropathy (LHON), though known to be due to 1 of 3 pathogenic mtDNA point mutations (nucleotide positions 11,778, 3460, and 14,484), usually manifests itself acutely in young adulthood with a stereotypical presentation of dyschromatopsia, loss of central vision, and loss of the papillomacular bundle nerve fiber layer. Histopathologic investigations have demonstrated devastating losses of axons with relative sparing of the most peripherally placed fibers in the optic nerves. This study was designed to morphometrically investigate the nerve fiber spectrum from ultrastructural studies of optic nerves obtained from 2 patients with LHON. METHODS: Two cases of LHON were molecularly characterized and the optic nerves from these cases studied by light microscopy and electron microscopy. Montages were made of electron micrographs cut orthogonal to fibers obtained from the periphery of each optic nerve, and these were then used for the measurement of each axon (short and long axis) and its myelin sheath. From this, a spectrum of nerve fiber layer was generated, yielding axon caliber profiles that could be compared between optic nerves. RESULTS: The total depletion of optic nerve fiber population in the 2 cases of LHON varied from 95% to 99%. Those fibers that were spared were limited to the peripheral optic nerve. The nerve fiber layer spectra of these remaining fibers showed a marked diminution of the first peak of axons of less than 1 micron in diameter, with relative emphasis of a second peak of axons of about 2 microns in diameter. In comparison to normal controls, this reflected a preferential loss of the smallest axons corresponding to the P-cell population. CONCLUSIONS: The clinical features of dyschromatopsia and central scotoma (with preservation of pupils) in LHON suggests the selective loss of the P-cell population known to subserve these (and not pupil) functions. This also correlates well with the fundus findings of early losses of the papillomacular bundle. The present study extends these findings to demonstrate a relative preservation of the M-cells in the optic nerve as reflected by the nerve fiber spectral profile. This selective loss of smaller fibers and their corresponding smaller retinal ganglion cells may, in addition to explaining the clinical features in LHON, provide valuable insights as to the exact pathophysiologic mechanisms by which mitochondrial impairment may induce apoptosis in vulnerable neurons.

Waldenström's macroglobulinemia is infrequent in Mexican Mestizos: experience of a hematological diseases referral center.

Along a 17-year period 7,373 patients were prospectively studied in a private practice Health facility; of these 11 were patients with Waldenström's macroglobulinemia; calculations from these data and previous publications show that this lymphoid malignancy represents in Mexico 0.18% of all hematologic malignancies, a figure 11 times lower than that described from caucasians. The median age was 65 years (range 31 to 84); there were 6 males and 5 females. Ten individuals were mexican mestizos, whereas one had a caucasian phenotype. The clinical features of the patients afflicted by the disease in Mexico were similar to those reported from caucasian populations. The median survival (SV) of the group of patients was 40 months, whereas the 42-month survival was 49%; the prognosis of the disease was relatively good despite the fact that complete remissions were unfrequent as a result of the treatment.

[Glycosilphosphatidylinositol-anchored cell surface protein deficiency in Mexican mestizo patients with aplastic anemia]. / Deficiencia de proteínas de superficie ancladas por glucosilfosfatidilinositol en células de pacientes mestizos mexicanos con hipoplasia medular.

The peripheral blood cells of ten patients with biopsy-proven aplastic anemia were studied by means of flow-cytometry in order to assess the expression of two phosphatidylinositol-anchored surface proteins: CD55/DAF (decay accelerating factor) and CD59/MIRL (membrane inhibitor of reactive lysis). An abnormal expression was found in five of these ten patients, whereas the "traditional" tests for paroxysmal nocturnal hemoglobinuria (PNH) were positive only on two of these five individuals. Five of the aplastic patients were treated with anti-thymocyte globulin and cyclosporin-A and three entered a complete remission; of the latter, one had CD55/CD59 deficiencies whereas two did not. Along the study period one patient with a hemolytic pattern of PNH was identified. It is concluded that CD55 and/or CD59 abnormalities are frequent in Mexican mestizo patients with aplastic anemia, that the aplastic presentation of PNH is more frequent in Mexico than the hemolytic presentation, that the flow-cytometric identification of CPI-anchored proteins is more sensitive than the "traditional" PNH tests, and that some patients with PNH-aplasia may respond to intensive immunosuppressive treatment. The flow-cytometric identification of GPI-anchored cell surface proteins should replace the "traditional" tests in the identification of patients with PNH.