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H Lederman

Publications and source records attributed to H Lederman.

At least 19 recordsLinked to original sources

How to improve IVF-ICSI outcome by sperm selection.

In previous studies, a new IVF method of intracytoplasmic morphologically selected sperm injection (IMSI) was introduced, based on motile sperm organellar morphology examination (MSOME). It was concluded that microinjection of morphologically selected sperm cells with strictly normal nucleus, defined by MSOME, improves IVF-ICSI outcome. The aim of the present study was to confirm this conclusion in new, enlarged study groups. Comparison between 80 couples, who underwent an IVF-IMSI trial, with matched couples, who underwent a standard IVF-ICSI procedure, confirmed that pregnancy rate following IVF-IMSI was significantly higher, and abortion rate significantly lower than in the routine IVF-ICSI (60.0 versus 25.0%, and 14 versus 40% respectively, P <or= 0.05). Another comparison was performed between matched IMSI groups, where embryos were obtained from microinjection by spermatozoa with a morphologically normal nucleus ('best' group, n = 70) and a 'second best' group was selected, where embryos were obtained from microinjection of spermatozoa with minimal morphological impairment, since no other sperm cells were available. It was confirmed that microinjection by 'second best ' spermatozoa result in significantly lower pregnancy and delivery rates and significantly higher abortion rates than microinjection with 'best' spermatozoa (25.7 versus 58.2%, P <or= 0.01; 17.1 versus 52.8%, P <or= 0.01, and 33.3 versus 9.7%, P <or= 0.02 respectively). The present study has strengthened previous conclusions.

Adult↗

Use of interferon alpha in intratumoral chemotherapy for cystic craniopharyngioma.

OBJECTIVES: This study analyzed the intratumoral activity of interferon alpha (IFN-alpha) in the treatment of cystic craniopharyngiomas. PATIENTS AND METHODS: From January 2000 to January 2004, nine patients presenting with cystic craniopharyngiomas were treated with intratumoral injection of IFN-alpha at the Pediatric Oncology Institute of the Federal University of São Paulo-Escola Paulista de Medicina. Age ranged from 1 year and 10 months to 18 years (mean 10 years). All intratumoral catheters were inserted by a subfrontal approach. Doses varied from 36 to 108 MU. RESULTS: There was complete disappearance of the lesion in seven cases. In two cases, partial reduction of tumor size was observed at follow-up. Follow-up varied from 1 year to 3 years and 6 months (mean 1 year 8 months). CONCLUSIONS: IFN-alpha proved to be an effective drug in the control of cystic craniopharyngiomas. Additional studies should be carried out to determine the optimal dose of IFN-alpha in the treatment of cystic craniopharyngioma. In addition, other drugs possessing high efficacy and low neurotoxicity should be analyzed.

Adolescent↗

Juvenile idiopathic inflammatory myopathies: the value of magnetic resonance imaging in the detection of muscle involvement.

CONTEXT: One of the major current challenges related to juvenile idiopathic inflammatory myopathy is the search for highly sensitive and specific non-invasive methods for diagnosis as well as for follow-up. OBJECTIVES: The aim of our study was to describe typical magnetic resonance imaging findings and to investigate the usefulness of this method in detecting active muscle disease in juvenile dermatomyositis and juvenile systemic lupus erythematosus patients. DESIGN: Transverse study, blinded assessment. SETTING: University referral unit (Pediatric Rheumatology section, Department of Pediatrics, Universidade Federal de São Paulo / Escola Paulista de Medicina). SAMPLE: Thirteen patients (9 girls) with dermatomyositis, as well as 13 patients (12 girls) with juvenile systemic lupus erythematosus and 10 normal children (5 girls), were enrolled in the study. MAIN MEASUREMENTS: Qualitative and quantitative analyses of gluteus maximus, quadriceps, adductors and flexors were performed and evaluated by two radiologists, blinded to all clinical information. Spin-echo in T1, DP, T2 and IR was used in all MRI images. RESULTS: The different muscle groups presented non-uniform involvement in the patients. The patients with dermatomyositis presented acute and chronic muscular alterations, while those with lupus presented only chronic myopathy, especially atrophy. In the dermatomyositis group, the major alterations were found in the gluteus and flexor regions (signal intensity and fat replacement). The signal intensity was increased in all acute myopathies. CONCLUSION: The qualitative and quantitative resonance analyses are useful in detecting clinically active disease in patients with dermatomyositis.

Adolescent↗

Does acupuncture treatment affect sperm density in males with very low sperm count? A pilot study.

Classic therapies are usually ineffective in the treatment of patients with very poor sperm density. The aim of this study was to determine the effect of acupuncture on these males. Semen samples of 20 patients with a history of azoospermia were examined by light microscope (LM) and scanning electron microscope (SEM), with which a microsearch for spermatozoa was carried out. These examinations were performed before and 1 month after acupuncture treatment and revealed that the study group originally contained three severely oligoteratoasthenozoospermic (OTA), two pseudoazoospermic and 15 azoospermic patients. The control group was comprised of 20 untreated males who underwent two semen examinations within a period of 2-4 months and had initial andrological profiles similar to those of the experimental group. No changes in any of the parameters examined were observed in the control group. There was a marked but not significant improvement in the sperm counts of severely OTA males following acupuncture treatment (average = 0.7 +/- 1.1 x 10(6) spermatozoa per ejaculate before treatment vs. 4.3 +/- 3.2 x 10(6) spermatozoa per ejaculate after treatment). A definite increase in sperm count was detected in the ejaculates of 10 (67%) of the 15 azoospermic patients. Seven of these males exhibited post-treatment spermatozoa that were detected even by LM. The sperm production of these seven males increased significantly, from 0 to an average of 1.5 +/- 2.4 x 10(6) spermatozoa per ejaculate (Z = -2.8, P < or = 0.01). Males with genital tract inflammation exhibited the most remarkable improvement in sperm density (on average from 0.3 +/- 0.6 x 10(6) spermatozoa per ejaculate to 3.3 +/- 3.2 x 10(6) spermatozoa per ejaculate; Z = -2.4, P < or = 0.02). Two pregnancies were achieved by the IVF-ICSI procedure. It is concluded that acupuncture may be a useful, nontraumatic treatment for males with very poor sperm density, especially those with a history of genital tract inflammation.

Acupuncture Therapy↗

Short-term effects of large-dose vitamin A supplementation on viral load and immune response in HIV-infected women.

Vitamin A supplementation has been suggested for treatment and prevention of HIV infection. However, some in vitro data indicate that vitamin A may activate HIV. Randomly, 40 HIV-seropositive women of reproductive age were allocated to receive a single oral dose of 9900 micromol (300,000 IU) vitamin A or placebo. Plasma HIV-1 RNA concentration, total lymphocytes, selected lymphocyte subsets and activation markers, and in vitro lymphocyte proliferation to phytohemagglutinin (PHA) and Candida were measured before dosing and at various time points over an 8-week follow-up period. No differences were found between treatment groups in the frequency of signs or symptoms of acute vitamin A toxicity, nor were differences evident in any lymphocyte subset or activation marker at any time during follow-up. Mean and median viral load concentration at each time point and change in viral load from baseline to each follow-up point did not differ between treatment groups. No difference was measured between treatment groups in the proportion of women who responded to PHA or Candida. This study provides no evidence that high dose vitamin A supplementation of HIV-infected women is associated with significant clinical or immunologic adverse effects.

Adult↗

Activity of intraarterial carboplatin as a single agent in the treatment of newly diagnosed extremity osteosarcoma.

BACKGROUND: Chemotherapy has dramatically improved the rates of cure and survival of patients with localized and metastatic osteosarcoma. Nonetheless, the number of chemotherapeutic agents active against osteosarcoma is limited to doxorubicin, cisplatin, high-dose methotrexate, and ifosfamide. Carboplatin, a cisplatin analogue, has been tested as a single agent in patients with recurrent osteosarcoma or as part of multiagent chemotherapy in newly diagnosed patients. PROCEDURE: We tested the activity and toxicity of two cycles of intraarterial carboplatin as a "window therapy" (600 mg/m2 per cycle) in 33 consecutive patients with extremity osteosarcoma before the start of multiagent chemotherapy. Response was based on clinical (tumor diameter, local inflammatory signs, and range of motion) and radiological parameters (plain local films and arteriographic studies prior to drug administration). RESULTS: Patients' age ranged between 8 and 18 years (median age 13 years). Primary tumor originated from the femur (15 patients), tibia (10 patients), fibula (4 patients), humerus (3 patients), and calcaneus (1 patient). Only 7 patients (21%) had metastatic disease at diagnosis (5 in the lung and 2 in other bones). A favorable clinical and radiological response was documented in 81% and 73% of the patients, respectively. Clinical and radiological progression occurred in 12% and 9% of the patients, respectively. Seventeen of the patients remain alive and disease-free. Survival and event-free survival at 3 years for nonmetastatic patients are 71% (SE = 9%) and 65% (SE = 9%), respectively; for metastatic patients, the figures are 17% (SE = 15%) and 14% (SE = 13%), respectively. CONCLUSIONS: We conclude that carboplatin is an active agent in the treatment of newly diagnosed extremity osteosarcoma.

Adolescent↗

[Magnetic resonance study of the pineal region. Normal pineal gland and simple cysts].

A magnetic resonance imaging (MRI) study of the normal pineal gland and pineal simple cysts was performed in 762 cases. A fine section technique (maximum 3 millimeters) enabled most of the times the identifying of a normal pineal in addition to demonstrating that a pineal without any cyst shows an isointense signal in T1 and T2 which, in turn, is enhanced following gadolinium. The measure of the normal pineal was of about 6.1 millimeters in its diameter length. Pineal simple cysts were observed in a 2.6% frequency in relation to the whole series (762 cases); however reaches 6.1% when only the visualized pineals were considered (329 cases). Also, it was found out that simple cysts were not correlated to age or gender. Simple cysts characteristics are: dimension less or equal to 20 millimeters; absence of expansive effect; similar signal to that of the cerebrospinal fluid; absence of cyst growth.

Adolescent↗

Cell cycle checkpoints and DNA repair in Nijmegen breakage syndrome.

Nijmegen breakage syndrome is characterized by a variable T cell and B cell immunodeficiency, growth failure, and an increased risk of malignancy. It is inherited in an autosomal recessive manner and is biochemically related to ataxia-telangiectasia. Cells from a patient with Nijmegen breakage syndrome were unable to arrest cell cycle progression after exposure to ionizing radiation, and BrdU incorporation into newly synthesized DNA was uninhibited, demonstrating that these cells have an aberrant response to radiation exposure. Although gross chromosomal breakage was observed, dinucleotide repeat segments were stable over time, suggesting that other types of DNA stability were not affected. DNA-PK activity, which is mediated by a protein related to the ataxia-telangiectasia gene product and is intimately involved in DNA repair and VDJ recombination, was normal in cells from an NBS patient. Therefore, cells from patients with Nijmegen breakage syndrome have an abnormal response to radiation exposure similar to that seen in ataxia-telangiectasia.

Abnormalities, Multiple↗

Immunologic defects in patients with chronic recurrent sinusitis: diagnosis and management.

Twenty patients with chronic refractory sinusitis or rhinitis were identified to have immune defects on the basis of total immunoglobulin level, immunoglobulin G subclass, and vaccine response. Eight patients were immunoglobulin A deficient, five had low immunoglobulin levels with vaccine hyporesponse, and four had low immunoglobulin levels with normal vaccine responses. Three subjects showed isolated immunoglobulin G1 deficiency. Demographic variables such as age, sex, infection pattern, and any other related disorders were studied retrospectively, which may have contributed to the diagnosis. An immunologic screen was essential for the diagnosis of immunodeficiency in these patients. Treatment options included prophylactic antibiotics, management of associated allergies, functional endoscopic sinus surgery, and replacement therapy with immunoglobulin in selected patients.

Adolescent↗

Sperm quality of subfertile males before and after treatment with human follicle-stimulating hormone.

OBJECTIVE: To assess the potential of short-term systemic administration of FSH for improving sperm quality, including ultrastructure, in teratozoospermic patients having normal endocrine profiles. DESIGN: Semen parameters were assessed prospectively using light microscopy (LM), biochemical analysis, and quantitative ultramorphological analyses within 2 months before FSH administration and within 5 days after the end of treatment. SETTING: Samples were collected from patients who were referred to the male fertility clinic at Bar-Ilan University. PATIENTS: Thirty-one patients with teratozoospermia who exhibited normal hormonal profiles and who failed to fertilize their wives in at least two previous IVF attempts (n = 17) or who had wives with apparent normal fertility unable to conceive for > or = 5 years (n = 14) were classified as subfertile. One hundred one males with no previous history of infertility, whose wives conceived after < or = 12 months of pregnancy expectation, served as the control group. INTERVENTION: Treatment was 75 IU FSH administered daily for 30 days. MAIN OUTCOME MEASURES: Pretreatment and post-treatment sperm evaluation of basic and quantitative ultramorphological analyses parameters. The hypothesis was FSH treatment may improve spermatid morphogenesis by its multiple actions on the Sertoli-gamete cell compartment without interfering with the testicular hormonogenic function. RESULTS: A significant improvement in agenesis of the acrosome and in the amorphous heads was observed, reaching normal values after treatment with FSH. The axonema deteriorated. No significant changes were observed in basic semen analysis parameters. CONCLUSIONS: Because malformations of the fine structure of the sperm head subcellular organelles seem to be prerequisites for the success of FSH treatment, ultramorphological examination of the sperm may serve as an indication for the probability of success of this treatment.

Adult↗

Defective antibody response to Hemophilus influenzae type b immunization in children receiving peritoneal dialysis.

Pediatric end-stage renal disease patients, maintained on chronic peritoneal dialysis (CPD), may have a variety of immunological abnormalities, including hypogammaglobulinemia and poor responses to vaccines. We measured antibody levels to Hemophilus influenzae type b (Hib) in 24 CPD patients. Eight children received primary Hib immunization while undergoing CPD. Of these, 1 of 8 (12%) lacked protective levels of antibody. In another child, who had an initial protective response, antibody levels were undetectable 12 months after immunization. Sixteen of the patients had not been immunized with Hib vaccine because they were more than 5 years old when the vaccine was licensed. In this group, 5 of 16 (31%) lacked protective levels of anti-Hib antibody. Of those available for follow-up, 3 responded normally to Hib vaccine. It is not sufficient to provide childhood immunizations to CPD patients with the assumption that those immunizations will lead to long-lived immunity. Antibody levels should be measured within a month of immunization and at regular intervals thereafter to document immunity.

Adolescent↗

Estimating fertility potential via semen analysis data.

The aim of this study was to evaluate diagnostic profiles for the assessment of semen analysis data with respect to male fertility potential. Semen samples taken from 208 patients of known fertility and suspected infertility were studied by conventional semen analysis methods. The data throw doubt upon the validity of an approach based on the number of deviations from the normal standard values defined by the World Health Organization. The alternative approach of a specific semen characteristic (particularly morphology) as the major predictor of fertility produced no beneficial results. However, the semen analysis index based on semen volume, sperm count, percentage motility and normal forms resulted in a high accuracy of classification but for only 44% of the cases, with 3% false negatives and 10% false positives using cut-off indices of > or = 0.6 and < or = -1.0 for defining 'fertile' and 'infertile' zones, respectively. In conclusion, it is emphasized that there are a number of specific semen analysis variables, each expressing a different aspect of male fertility potential which, when combined in correct proportion, do provide the optimal evaluation of the male fertility status. However, in order to increase the prognostic potential of the semen sample, new and meaningful parameters must be discovered.

Adult↗

Radiology of the suprapatellar region.

The gross and radiological anatomy of the suprapatellar region has been reviewed and its clinical application outlined. In most patients an accurate assessment of the presence of effusion and lipohaemarthrosis of the knee joint can be made and the possibility of excluding joint disease is discussed. In the individual patient the careful application of the radiological anatomy of this region may prevent mistakes in the localisation of various pathological processes.

Contrast Media↗

Quantitative ultramorphological analysis of human sperm: fifteen years of experience in the diagnosis and management of male factor infertility.

The advantages of quantitative ultramorphological (QUM) sperm analysis in the diagnosis and treatment of male infertility are presented. The QUM methodology is based on three elements: complementary scanning electron microscopy and transmission electron microscopy observations of 7 sperm cell subcellular organelles (acrosome, postacrosomal lamina, nucleus, neck, axoneme, mitochondrial sheath, and outer dense fibers); systematic classification of the specific ultramorphological malformations into 4 pathological and the normal categories, indicating the morphological state of each subcellular organelle; and comparison between well-defined reference groups with opposite fertility status or treatment conditions. QUM has established 2 indices for the in vivo and in vitro male fertility potential: (1) Natural Fertility Index (NFI), with accurate prediction (97% sensitivity and 90% specificity) of 80% of the male patients; and (2) IVF score, with prediction of 76% of the nonfertilizing and 90% of fertilizing IVF groups. QUM has enabled assessment of ultramorphological indications for varicocele and radiation exposure. Varicocele causes defects in sperm head organelles related to early spermatid development, whereas ionizing radiation causes amorphous head shape. QUM established criteria for specific non-in-vitro therapeutic interventions, including varicocelectomy, follicle-stimulating hormone (FSH) administration, and acupuncture. The varicocele index enabled correct classification of 79 and 89% of patients with and without varicocele. Males with idiopathic impairment of sperm acrosome and nucleus are potential responders to FSH treatment, whereas patients exhibiting low sperm activity are candidates for acupuncture treatment. Patients with a low Natural Fertility Index are recommended for an assisted reproduction technique (ART). based on the ultramorphology of the tail axoneme. Patients who achieved pregnancy following intrauterine insemination or in vitro fertilization and those whose wives conceived only following intracytoplasmic sperm injection were classified with accuracy of 78 and 74%, respectively. QUM sperm analysis is clinically informative, nontraumatic, and cost-effective, and is recommended when the male infertility factor cannot be clearly diagnosed by routine tests prior to first ART trial.

Cell Nucleus↗

Quantitative ultramorphological (QUM) analysis of human sperm: diagnosis and management of male infertility.

The advantages of quantitative ultramorphological (QUM) sperm analysis in the diagnosis and treatment of male infertility are presented. QUM methodology is based on three elements: (1) complementary SEM and TEM observations of 7 sperm cell subcellular organelles: acrosome, postacrosomal lamina, nucleus, neck, axoneme, mitochondrial sheath, and outer dense fibers; (2) systematic classification of the specific ultramorphological malformations into 4 pathological and the normal categories, which indicate the morphological state of each subcellular organelle; and (3) comparison between well-defined reference groups with opposite fertility status or treatment conditions. QUM analysis has enabled the establishment of two indices that optimally express the in vivo and in vitro male fertility potential: The Natural Fertility Index (NFI), which allowed an accurate prediction (97% sensitivity and 90% specificity) of 80% of the naturally fertile and suspected infertile male patients, and the in vitro fertilization (IVF) score, which enabled prediction of 76% of the nonfertilizing and 90% of the fertilizing IVF groups. Validation tests confirmed these data. QUM also enabled assessment of ultramorphological indications for varicocele and radiation exposure: Both male factor etiologies indicated a persistent effect on the natural fertility potential, as expressed by structural changes in the nucleus. Varicocele was found to cause defects in the sperm head organelles related to early spermatid development, whereas ionizing radiation resulted in amorphous head shape. Criteria for specific non-in vitro therapeutic interventions such as varicocelectomy, follicle-stimulating hormone (FSH) administration, and acupuncture treatment were established. A varicocele index, which enabled the correct classification of 79 and 89% of the patients pre- and post-high ligation, respectively, was suggested to be a good indicator for varicocele which affects the fertility potential. Males exhibiting idiopathic impairment of sperm acrosome and nucleus were found to be potential responders to FSH treatment, whereas patients exhibiting low sperm activity proved to be good candidates for acupuncture treatment. Indications for selecting the optimal appropriate assisted reproduction technique (ART) procedure were found: Patients with a low Natural Fertility Index should be recommended for ART. A first choice ART selection should be performed according to an ART index based on the ultramorphological examination of the tail axoneme. The above index enabled correct prediction of 78% of the patients who achieved pregnancy following conventional ART (intrauterine insemination or IVF) and 74% of those whose wives conceived only following intracytoplasmic sperm injection. QUM sperm analysis is clinically informative, nontraumatic, and in the long run also cost-effective. This analysis should be performed when the male infertility factor cannot be clearly diagnosed by routine tests and prior to the first ART trial.

Acrosome↗