PubMed Health⌕ Search

Biomedical subjects

A Adler

Publications and source records attributed to A Adler.

At least 109 records · Page 6Linked to original sources

Microsurgical fertilization procedures: the absence of stringent criteria for patient selection.

Subzonal sperm insertion and partial zona dissection were applied in 250 in vitro fertilization cycles in couples (n = 200) with abnormal semen analyses; 61 clinical pregnancies were established (24% per egg retrieval). Patients were selected without using minimal cutoff criteria. The study included patients with 0% normal sperm forms (strict criteria), no motile sperm (but some live cells), and sperm counts which could be assessed only after centrifugation. Patients were categorized into three subsets. Group A (n = 116 cycles) failed to fertilize in a previous cycle. Group B (n = 40) was excluded from IVF due to the severity of sperm profiles, such as a maximum of 2% normal forms. Group C (n = 94) constitutes those patients for whom a standard cycle could possibly result in failure. Monospermic fertilization rates were 18% (A), 19% (B), and 24% (C). The incidences of embryo replacement were 63% (A), 53% (B), and 69% (C). Rates of clinical pregnancy were 22% (A), 23% (B), and 28% (C). The presence of one, two, or three semen abnormalities did not correlate with the outcome of microsurgical fertilization. Twenty-two percent of patients with combined oligoasthenoteratozoospermia became pregnant. Moreover, ongoing pregnancies were established in instances with 0% normal sperm forms and no progressively motile spermatozoa. It is concluded that stringent cutoff criteria may not be necessary when both partial zona dissection and subzonal sperm insertion are performed efficiently.

Culture Techniques↗

Partial zona dissection or subzonal sperm insertion: microsurgical fertilization alternatives based on evaluation of sperm and embryo morphology.

OBJECTIVE: To establish guidelines for application of partial zona dissection, subzonal sperm insertion, and regular in vitro fertilization (IVF) in severe male factor patients. DESIGN: Two studies were performed: partial zona dissection and IVF was applied in 57 couples during the first period, and subzonal sperm insertion was also applied in a second group of 47 couples. SETTING: Procedures were performed in an academic research environment. PATIENTS, PARTICIPANTS: Couples who failed fertilization previously, others not acceptable for IVF, and a third group in whom IVF was expected to fail. INTERVENTIONS: Oocytes were micromanipulated with either partial zona dissection or subzonal sperm insertion, or the zona pellucida was left intact. Embryos were replaced in patients prophylactically treated with methylprednisolone and antibiotics. MAIN OUTCOME MEASURES: Because several microsurgical fertilization techniques are now available, this study was performed to compare sperm parameters, embryo morphology, fertilization, and implantation rates after application of two successful micromanipulation procedures. RESULTS: Twenty-one pregnancies were established in 104 patients, 5 definitely from subzonal sperm insertion and 4 from partial zona dissection. Patients who failed IVF before had a similar chance of pregnancy after the use of micromanipulation, as first time patients (9/53 versus 12/51). In a subgroup of 15 patients who failed IVF with insufficient numbers of motile sperm, fertilization was significantly higher after subzonal sperm insertion. Partially zona-dissected embryos from couples with severe teratozoospermia (less than or equal to 5% normal forms; strict criteria) had significantly more morphological abnormalities than those from patients with moderate teratozoospermia (6% to 10% normal forms). In severely teratozoospermic patients, significantly fewer partially zona-dissected than subzonally inserted embryos implanted. CONCLUSIONS: The decision of which micromanipulation method to perform can possibly be based on careful analysis of sperm morphology.

Embryo Implantation↗

[Effectiveness of Burch colposuspension in females with recurrent stress incontinence--a urodynamic and ultrasound study].

A collective of 31 women with recurrent stress urinary incontinence was subject to Burch colposuspension. The average time interval between the primary treatment (anterior colporrhaphy) and surgical colposuspension was 5.5 years. All patients underwent clinical, urodynamic and sonographic assessment of incontinence prior to and after surgery. The follow-up examination was performed at an average of 14.5 months after colposuspension according to the method reported by Burch. In 87% of patients, continence was achieved. 90% of patients were able to void without any formation of residual urine in the bladder. In the attempt to optimise the diagnostic and therapeutic procedures pertaining to female incontinence, introitus sonography and urodynamic assessment have proved to be valid adjuvant tools.

Adult↗

Microsurgical fertilization and teratozoospermia.

Semen parameters were correlated with the outcome of partial zona dissection (PZD) in 42 couples with male factor infertility. Although fertilization rates were reduced, 12% of the embryos implanted following replacement. Spermatozoa from teratozoospermic sperm populations were able to fuse with oocytes following zona penetration through the artificial gaps. PZD followed by insemination with less than 5% normal spermatozoa led to 20 embryos which, upon replacement, did not implant. Motility and sperm count were not clearly correlated with the outcome of PZD and are therefore less useful indicators for patient selection. Teratozoospermic patients who previously failed to fertilize were compared to a group of similar patients who had not attempted IVF before. Although fertilization was significantly improved in first-time patients, 41% of the patients whose spermatozoa were initially unable to fertilize had at least one embryo when PZD was performed. Several pregnancies were established in this group. Subzonal sperm insertion (SZI) and PZD were compared in 19 patients using sibling oocytes. A significant fraction of spermatozoa from infertile men were able to fuse with the oolemma when directly inserted into the perivitelline area. Using a sucrose solution to shrink the ooplasm, only 1% of the oocytes were damaged during SZI. Monospermic fertilization rates following PZD and SZI were 15 and 16%, respectively. Both micromanipulation methods were successful in most patients. However, in two small groups of patients, only one technique resulted in fertilization.

Female↗

Sensitivity of exercise electrocardiography for acute cardiac events during moderate and strenuous physical activity. The Lipid Research Clinics Coronary Primary Prevention Trial.

We determined whether the exercise electrocardiogram predicted acute cardiac events during moderate or strenuous physical activity among 3617 asymptomatic, hypercholesterolemic men (age range, 35 to 59 years) who were followed up in the Coronary Primary Prevention Trial. Submaximal exercise test results were obtained at entry and at annual follow-up visits in years 2 through 7. ST-segment depression or elevation (greater than or equal to 1 mm or 10 microV-sec) was considered to be a positive test result. The circumstances that surrounded each nonfatal myocardial infarction and coronary heart disease death were determined through a record review. The cumulative incidence of activity-related acute cardiac events was 2% during a mean follow-up period of 7.4 years. The risk was increased 2.6-fold in the presence of clinically silent, exercise-induced, ST-segment changes at entry (95% confidence interval [Cl], 1.3 to 5.2) after adjustment for 11 other potential risk factors. Of 62 men who experienced an activity-related event, 11 had a positive test result at entry (sensitivity, 18%; 95% Cl, 8 to 27). The specificity of the entry exercise test was 92% (95% Cl, 91 to 93). The sensitivity and specificity were similar when the length of follow-up was restricted to 1 year after testing. For a newly positive test result on a follow-up visit, the sensitivity was 24% (95% Cl, 12 to 36), and the specificity was 85% (95% Cl, 84 to 86); for any positive test result during the study (mean number of tests per subject, 6.2), the sensitivity was 37% (95% Cl, 25 to 49), and the specificity was 79% (95% Cl, 77 to 80). Our findings suggested that the presence of clinically silent, exercise-induced, ischemic ST-segment changes on a submaximal test was associated with an increased risk of activity-related acute cardiac events. However, this test was not sensitive when used to predict the occurrence of activity-related events among asymptomatic, hypercholesterolemic men. For this reason, the utility of the submaximal exercise test to assess the safety of physical activity among asymptomatic men at risk of coronary heart disease is likely to be limited.

Adult↗

The interaction between oxygen and vascular wall.

In vascular strips of canine carotid arteries stepwise lowering of oxygen tension from hyperoxic levels of 550 mmHg to 20 mmHg caused in preparations with endothelium a dose-dependent hyperpolarization and relaxation of smooth muscle cells when oxygen tensions between approximately 150 mmHg and 35 mmHg were attained. Pronounced hypoxia with oxygen tensions below 30 mmHg induced a depolarisation and an increase in force generation. During comparable investigations on vessel preparations without endothelium only a slight hyperpolarization and relaxation of the smooth muscle were observed when decreasing the oxygen tension from 550 mmHg to approx. 35 mmHg. In the presence of indomethacin (10(-5) M) a small but significant reduction in the hypoxia-induced hyperpolarization and decrease in smooth muscle tone was found in intact vascular strips with endothelium. Depolarisation and contraction occurred at oxygen tensions below approx. 50-60 mmHg.

Animals↗

Clinical algorithms teach pediatric decisionmaking more effectively than prose.

Despite the rapidly increasing volume of medical literature, little attention has been paid to the appropriate printed format for teaching clinical content. This study attempted to determine whether a clinical algorithm (CA) or prose is more effective for teaching clinical decisionmaking. Clerkship students, preclerkship students, and pediatric house officers in five medical centers in the USA and Israel were presented with clinical algorithms and prose describing management of fever in a child under 2 years of age, and management of meningitis in children. Knowledge of decisionmaking was measured before and after learning, using audio-taped clinical problems and learning time as measured. It was concluded that CAs are more effective and more efficient than prose for teaching clinical decisionmaking. When writing about clinical decisionmaking, the use of CAs should always be considered, especially if a series of interdependent decisions is being described.

Algorithms↗

Effect of the prostacyclin analogue iloprost on K+ permeability in the smooth muscle cells of the canine carotid artery.

The present contribution deals with the electro- and tracerphysiological correlations to vasodilatation observed under prostacyclin or O2 deficiency. Because of the extreme chemical instability of native PGI2, we used iloprost, a stable carbacyclin analogue. At concentrations between 10(-9) and 10(-6) mol/l, iloprost hyperpolarized the resting membrane of normal tone (V = -63.4 mV) and noradrenaline predepolarized vascular smooth muscle cells (V = -55.2 mV) of the canine carotid artery by 7.4 and 16.9 mV, respectively, in a concentration-dependent manner. Correspondingly, the isometric tension was decreased. In both experimental series, the half-maximal effect was attained at a concentration of 2 x 10(-8) mol/l. The coupling ratios developed tension versus membrane potential were 1.079 mV/mN in normal tone and noradrenaline treated preparations. Hyperpolarization and relaxation in the latter group, however, were much larger for the same iloprost concentrations. 42K+ efflux was stimulated by 250% with iloprost (10(-6) mol/l), whereas 24Na+ efflux was increased only by 50%. This resulted in an augmentation of K+ permeability by 340% and of Na+ permeability by 40%, respectively. The ratio PK/PNa rose from 16 to 49 with iloprost. These results lead to the conclusion that iloprost should be classified as a K+ channel opener.

Animals↗

A pilot study of intraperitoneal recombinant interleukin-2 and ex vivo activated intracavitary lymphocytes in patients with malignant peritoneal spread: I. Clinical aspects.

A novel approach to adoptive immunotherapy is described in this study. Of 13 patients with malignant effusions, nine were treated by intraperitoneal (IP) instillation of intracavitary lymphocytes (ICL), activated ex vivo by recombinant interleukin-2 (rIL-2, Cetus Co., Emeryville, CA) with escalating doses of IP rIL-2 and four by IP rIL-2 alone. ICL and rIL-2 were administered by repeated peritoneal punctures. Patients were divided into two groups: group I of six patients, who received activated ICL with low doses of IP rIL-2 (total dose not exceeding 6 X 10(5) units) and group II of seven patients, in whom escalating higher doses of rIL-2 were administered IP with or without activated ICL, in doses ranging from 10(6) up to 16 X 10(6) units, total dose. Total dose of ICL given ranged from 2 X 10(8) to 2 X 10(9) in both groups. The main objectives of this pilot study was to establish the feasibility of treatment by ex vivo activated ICL and IP rIL-2, to assess the toxicity associated with such a treatment, to escalate doses of rIL-2 to a maximal tolerable dose, and to look for clinical responses. The first two goals were achieved: such a treatment approach is feasible and is not associated with severe toxicity. The side effects observed during this study were usually mild in group I patients and more pronounced in group II patients. These included transient fever, chills, nausea, cellulitis at the puncture site, and one case of peritonitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Recombinant interleukin-2-activated intracavitary lymphocytes: phenotypic characteristics and effector function.

A preclinical study of intracavitary lymphocytes (ICL) from malignant effusions of cancer patients is described. The object of this study was to evaluate the antitumor potential of ICL as a baseline for developing adoptive immunotherapy trial for ovarian carcinoma patients. The main parameters studied were functional cytolytic activity of fresh and recombinant interleukin-2 (rIL-2)-activated ICL and their phenotypic characteristics. Spontaneous cytolytic activity of ICL was detected in all samples tested against natural killer (NK)-sensitive targets (K562), while very low activity was shown against NK-resistant targets (Daudi) and fresh tumor cells. Activation in culture with rIL-2 generated cytolytic activity against NK-resistant targets and significantly augmented NK activity. The pattern of antitumor lytic activity of ICL resembles lymphokine-activated killer cell activity and is non-major histocompatibility complex restricted against a variety of tumor targets. Phenotypic characterization of fresh ICL showed the predominance of CD3+ cells with the CD4/CD8 ratio resembling that of peripheral blood lymphocytes. During culture with rIL-2, changes in phenotypic expression of activated ICL were detected: enrichment in NKH1+ cells (up to 65%), of CD8+ (up to 70%), and very late antigen (VLA)-1+ cells (up to 54%), concomitantly with a decrease in CD4+ population. The NKH1, CD8, and VLA-1 expression peaked at 2 weeks in culture and coincided with peak cytolytic activity of cultured ICL. Depletion of CD8+ cells from activated ICL resulted in a decreased proportion of cells expressing the NKH1 and VLA-1 phenotype, whereas depletion CD4+ cells led to enrichment in CD8, NKH1, and VLA-1 antigens. Cytolytic activity was significantly increased in CD4 depleted population against NK-resistant and NK-sensitive targets. In this study we found that rIL-2 activation and culture of ICL generates killer activity against NK-resistant and fresh tumor targets and that enrichment in expression of NKH1, CD8, and VLA-1 antigens is associated with effector function.

Antigens, Surface↗

Interleukin-2 induction of lymphokine-activated killer (LAK) activity in the peripheral blood and bone marrow of acute leukemia patients: II. Feasibility of LAK generation in children with active disease and in remission.

Activation and expansion in culture with rIL-2 of peripheral blood (PB) and/or bone marrow (BM) specimens derived from children with ALL and ANLL, with active disease (AP) and in remission were studied (RP). Baseline NK cytolytic activity from AP was found to be depressed, whereas RP-derived cells had normal NK activity, as assayed against K562 targets. Culture in rIL-2 significantly enhanced the NK activity of both AP- and RP-derived cells and generated LAK activity, as assayed by 4-hour 51Cr release, against NK-resistant Raji cell line and against fresh, allogeneic, and autologous tumor cells. Lytic activity against fresh, cryopreserved leukemia blasts was of lower than that found against cell lines. In three patients higher lytic activity against autologous than against allogeneic blasts was demonstrated. Expansion in culture with rIL-2 varied from twofold to 120-fold. rIL-2 activation and expansion was better in RP than in AP. The predominant phenotype of activated cells, as determined by flow cytometry, was [mean % (SD)]: CD3- = 54 (12), CD8+ = 55 (17), and NKH1+ = 26 (7). The consistently high level of CD8+ cells was accompanied by very low levels of CD4+ cells: mean = 11% (14). Double-marker analysis showed mean of 33% (10) for CD3+/NKH1+ cells and mean = 32 (11) for CD8+/NKH1+ cells, implying that these populations were overlapping. Kinetics of expression of cell surface markers during 2 to 3 weeks in culture showed that CD8+ and NKH1+ enrichment occurred during the first week and lasted for up to 4 weeks, whereas CD4+ expression decreased after the second week. A significant decrease in the expression of IL-2 receptors (CD25) was observed from the second week of culture. This study shows the feasibility of in vitro generation of killer cells from PB and BM of pediatric leukemia patients.

Antigens, CD↗