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Biomedical subjects

A J Thomas

Publications and source records attributed to A J Thomas.

At least 37 records · Page 2Linked to original sources
PubMed2000

Effect of clinical and semen characteristics on efficacy of ovulatory stimulation in patients undergoing intrauterine insemination.

PURPOSE: We measured the effect of ovulatory stimulation (OS) upon intrauterine insemination (IUI) success rates, particularly among patients with risk factors for IUI failure. METHODS: Retrospective review of medical and laboratory results from 512 patients who underwent 1576 cycles of IUI with partner's sperm over a 3 year period. Data were collected on 3 risk factors for IUI failure (advanced female age > 37.7 years, prior corrective pelvic surgery, and poor post-wash sperm motility), and on method of OS (none, clomiphene citrate, or gonadotropin). RESULTS: Patients who underwent OS had significantly higher pregnancy rates (7.6%) than those who did not (4.7%, p = 0.02). However, when patients were stratified by their risk factors, OS made a significant difference only for patients without risk factors. These patients had a 15.5% per cycle pregnancy rate with OS, compared to 7.9% in unstimulated IUI cycles (p = 0.04). CONCLUSIONS: Ovulatory stimulation doubles IUI pregnancy rates among young patients without a prior pelvic surgery and with good post-wash semen quality. The benefit of OS for patients with risk factors for IUI failure is unclear. These patients should be counseled that their chances for success with IUI are limited, with or without OS.

Adult↗
PubMed2000

Improvement in motion characteristics and acrosome status in cryopreserved human spermatozoa by swim-up processing before freezing.

The purpose of this study was to examine if selecting a sperm population with improved motion characteristics before freezing reduces the deleterious effects of cryopreservation. Semen specimens from 15 normal donors were divided into two equal aliquots. The first aliquot received no treatment (control), and the second was processed by swim-up from a washed sperm preparation to select a sperm population with better motility and motion characteristics (swim-up). Both aliquots were cryopreserved by the liquid nitrogen vapour method. Percentage motility and motion characteristics were evaluated by computer-assisted semen analysis. Acrosome integrity as well as spontaneous and calcium ionophore-induced acrosome reactions before freezing and after thawing were assessed by fluorescein isothiocyanate conjugated peanut agglutinin combined with a supra vital dye (Hoechst-33258). Swim-up processing enabled selection of a sperm population with better motion characteristics, percentage motility and viability before freezing (P < 0.001), but with no difference in percentage of acrosome-intact spermatozoa (P = 0.63). After thawing, the swim-up specimens exhibited faster velocity and progression than untreated specimens (P < 0.001). They also had higher percentages of spermatozoa with intact acrosomes and spermatozoa able to undergo acrosome reaction in response to calcium ionophore (P < 0.05). Selecting a highly motile sperm population before freezing enhances overall post-thaw spermatozoa quality.

Acrosome Reaction↗
PubMed2000

Language hemispheric dominance in patients with congenital lesions of eloquent brain.

OBJECTIVE: In 90% of normal subjects, the left hemisphere is dominant for language function. We investigated whether congenital lesions of the left perisylvian regions altered cortical language representation in right-handed individuals. METHODS: Using functional magnetic resonance imaging, we studied language hemispheric dominance in five right-handed adult patients with congenitally acquired arteriovenous malformations (AVMs) originating from left hemispheric cortical language regions. The AVMs had not caused neurological symptoms during early development, but patients presented as adults with migraine, seizure, or minor hemorrhage. Results obtained from the AVM patients were contrasted to those from right-handed brain-injured stroke patients recovering from aphasia and to those from right-handed normal subjects. RESULTS: During silent picture naming and verb generation tasks, cortical language networks lateralized primarily to the right hemisphere in the AVM group, compared with the left hemisphere in the normal group. This right hemisphere-shifted language network in the AVM group exceeded the shifts toward right hemispheric dominance found in the stroke group. CONCLUSION: Patients with AVMs affecting the left perisylvian regions recruited the right hemisphere into language processing networks during early development, presumably in response to congenitally aberrant circulation. This early right hemisphere recruitment in the AVM patients exceeded the similar process in the brains of stroke patients whose left cortical language networks were damaged in adulthood. Our data provide evidence of effective plasticity in the developing human brain compared with the mature brain response to injury. Knowledge of cortical language representation should assist presurgical planning in patients with developmental anomalies affecting apparently language-dominant brain regions.

Adult↗
PubMed2000

Distribution of amyloid beta 42 in relation to the cerebral microvasculature in an elderly cohort with Alzheimer's disease.

Amyloid beta (A beta) deposits and neurofibrillary pathology are characteristic features of Alzheimer's disease (AD). The association of A beta with cerebral vessels is an intriguing feature of AD. While some degree of cerebral A beta angiopathy involving the leptomeninges and intraparenchymal vessels occurs in almost all cases of AD, the proportion of microvessels within a neocortical region containing deposits of A beta peptide is not known. In this study, we examined a cohort of clinically and pathologically evaluated AD cases to assess the percentage of cerebral microvessels in the temporal cortex and parahippocampal gyrus associated with the predominant, A beta 42 form of the peptide. We also assessed whether the distribution and burden of amyloid was related to apolipoprotein E (APOE) genotype. Using double immunostaining methods, we surprisingly found that at least 40% of the microvessels in the two brain regions contained A beta 42 deposits. There was no correlation of such localization with APOE genotype, however, epsilon 4 homozygotes revealed a greater burden of A beta 40. These observations suggest that high proportions of cortical microvessels are associated with A beta 42, which may affect microvascular function.

Aged↗
PubMed2000

Blunted respiratory responses to hypoxia in mutant mice deficient in nitric oxide synthase-3.

In the present study, the role of nitric oxide (NO) generated by endothelial nitric oxide synthase (NOS-3) in the control of respiration during hypoxia and hypercapnia was assessed using mutant mice deficient in NOS-3. Experiments were performed on awake and anesthetized mutant and wild-type (WT) control mice. Respiratory responses to 100, 21, and 12% O(2) and 3 and 5% CO(2)-balance O(2) were analyzed. In awake animals, respiration was monitored by body plethysmography along with O(2) consumption (VO(2)) and CO(2) production (VCO(2)). In anesthetized, spontaneously breathing mice, integrated efferent phrenic nerve activity was monitored as an index of neural respiration along with arterial blood pressure and blood gases. Under both experimental conditions, WT mice responded with greater increases in respiration during 12% O(2) than mutant mice. Respiratory responses to hyperoxic hypercapnia were comparable between both groups of mice. Arterial blood gases, changes in blood pressure, VO(2), and VCO(2) during hypoxia were comparable between both groups of mice. Respiratory responses to cyanide and brief hyperoxia were attenuated in mutant compared with WT mice, indicating reduced peripheral chemoreceptor sensitivity. cGMP levels in the brain stem during 12% O(2), taken as an index of NO production, were greater in mutant compared with WT mice. These observations demonstrate that NOS-3 mutant mice exhibit selective blunting of the respiratory responses to hypoxia but not to hypercapnia, which in part is due to reduced peripheral chemosensitivity. These results support the idea that NO generated by NOS-3 is an important physiological modulator of respiration during hypoxia.

Animals↗
PubMed2000

Elevation in late-life depression of intercellular adhesion molecule-1 expression in the dorsolateral prefrontal cortex.

OBJECTIVE: Late-life depression may be associated with vascular disease. The authors investigated this association by determining whether intercellular adhesion molecule-1 (ICAM-1), a marker of ischemia-induced inflammation, is elevated in the dorsolateral prefrontal cortex in depression. METHOD: The authors studied postmortem tissue from 20 depressed subjects and a matched comparison group of 20 nondepressed subjects. They used immunocytochemistry to stain ICAM-1 in blood vessels on sections of the dorsolateral prefrontal cortex and occipital cortex and quantitative true color image analysis to measure the proportion of vessels expressing ICAM-1. RESULTS: ICAM-1 was significantly higher in both the gray and white matter of the depressed subjects' dorsolateral prefrontal cortex than the comparison subjects' dorsolateral prefrontal cortex. The difference between these groups was much smaller in the gray and white matter of the occipital cortex. CONCLUSIONS: These findings support the vascular depression hypothesis, which has important implications for the understanding and management of late-life depression.

Age Factors↗
PubMed2000

Survival of patients with synchronous brain metastases: an epidemiological study in southeastern Michigan.

OBJECT: It has been suggested that synchronous brain metastases (that is, those occurring within 2 months of primary cancer diagnosis) are associated with a shorter survival time compared with metachronous lesions (those occurring more than 2 months after primary cancer diagnosis). In this study the authors used data obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results program to determine the incidence of synchronous brain metastases and length of survival of patients in a defined population of southeastern Michigan residents. METHODS: Data obtained in 2682 patients with synchronous brain metastases treated between 1973 and 1995 were reviewed. Study criteria included patients in whom at least one brain metastasis was diagnosed within 2 months of the diagnosis of primary cancer and those with an unknown primary source. The incidence per 100,000 population increased fivefold, from 0.69 in 1973 to 3.83 in 1995. The most frequent site for the primary cancer was the lung (75.4%). The second largest group (10.7%) consisted of patients in whom the primary site was unknown. The median length of survival was 3.2 months. There was no significant difference in the median survival of patients with primary lung/bronchus and those with an unknown primary site (3.3 months and 3.2 months, respectively). CONCLUSIONS: Patients who present with synchronous lesions have a poor prognosis, and the predominant cause of death, in more than 90% of cases, is related to systemic disease; however, despite poor median survival times, certain patients will experience prolonged survival.

Adolescent↗
PubMed2000

Preventing upper extremity overuse injuries in child and adolescent athletes.

Physicians who treat young athletes must not only correctly diagnose specific musculoskeletal injuries but also pay attention to factors that predispose the patient to the injury. This article reviews the intrinsic and extrinsic factors that can lead to upper extremity overuse injury in child and adolescent athletes and describes the physician's role in preventing injury in this population.

Adolescent↗
PubMed1999

Progesterone is neuroprotective after acute experimental spinal cord trauma in rats.

STUDY DESIGN: A standardized rat contusion model was used to test the hypothesis that progesterone significantly improves neurologic recovery after a spinal cord injury that results in incomplete paraplegia. OBJECTIVES: To compare the effect of progesterone versus a variety of control agents to determine its effectiveness in promoting neurologic recovery after an incomplete rat spinal cord injury. SUMMARY OF BACKGROUND DATA: Progesterone is a neurosteroid, possessing a variety of functions in the central nervous system. Exogenous progesterone has been shown to improve neurologic function after focal cerebral ischemia and facilitates cognitive recovery after cortical contusion in rats. METHODS: A standardized rat contusion model of spinal cord injury using the New York University impactor that resulted in rats with incomplete paraplegia was used. Forty mature male Sprague-Dawley rats were randomly assigned to four groups: laminectomy with sham contusion, laminectomy with contusion without pharmacologic treatment, laminectomy with contusion treated with dimethylsulfoxide and dissolved progesterone, and laminectomy with contusion treated with dimethylsulfoxide. Functional status was assessed weekly using the Basso-Beattie-Bresnehan (BBB) locomotor rating scale for 6 weeks, after which the animals were killed for histologic studies. RESULTS: Rats treated with progesterone had better outcomes (P = 0.0017; P = 0.0172) with a BBB score of 15.5, compared with 10.0 in the dimethylsulfoxide control group and 12.0 in the spinal cord contusion without pharmacologic intervention group. This was corroborated in histologic analysis by relative sparing of white matter tissue at the epicenter of the injury in the progesterone-treated group (P < 0.05). CONCLUSIONS: Rats treated with progesterone had a better clinical and histologic outcome compared with the various control groups. These results indicate potential therapeutic properties of progesterone in the management of acute spinal cord injury.

Acute Disease↗
PubMed1999

Cryopreservation of sperm from patients with leukemia: is it worth the effort?

BACKGROUND: Intracytoplasmic sperm injection (ICSI) allows pregnancies to be established with a single sperm, improving the chances for men with severely impaired sperm quality to cause a pregnancy. Men with leukemia typically are of reproductive age and their fertility is threatened by initially impaired semen quality and cytotoxic chemotherapy. The authors examined the feasibility of sperm cryopreservation in men with leukemia before treatment and whether the type of leukemia is related to prefreeze or postthaw semen quality. METHODS: Records of 25 patients with acute (n=13) or chronic (n=12) leukemia who banked their sperm were reviewed. Semen characteristics were compared with those of normal donors (n=50) and between the 2 patient groups before and after cryopreservation. Motile sperm count (MSC), motility, curvilinear velocity (VCL), linearity, and amplitude of lateral head movement were compared between patients and healthy donors. No patient had undergone chemotherapy before sperm banking. The nitrogen vapor technique was used for sperm cryopreservation. RESULTS: Patients with leukemia had significantly lower prefreeze and postthaw MSC (P=0.0001), motility (P<0.05), and VCL (P<0.05) compared with healthy donors. The percentage change from prefreeze to postthaw in MSC and motility (P<0.05) was significantly greater in patients than in healthy donors. The effect of cryopreservation on semen quality was similar in patients with both acute and chronic leukemia. CONCLUSIONS: Patients with leukemia have poor prefreeze and postthaw semen quality compared with healthy donors. In this study the type of leukemia did not appear to affect prefreeze or postthaw semen quality and the postthaw MSC was sufficient for use with ICSI. Sperm cryopreservation should be offered to all men of reproductive age before the initiation of therapy for leukemia.

Acute Disease↗
PubMed1999

Identification and characterization of m1 selective muscarinic receptor antagonists1.

A series of esters of 1,4-disubstituted tetrahydropyridine carboxylic acids (I) has been synthesized and characterized as potential m1 selective muscarinic receptor antagonists. The affinity of these compounds for the five human muscarinic receptor subtypes (Hm1-Hm5) was determined by the displacement of [3H]-NMS binding using membranes from transfected Chinese hamster ovarian cells. One of the most potent and selective compounds of this series is an analogue of I [11, R1 = (CH2)5CH3], which has an IC50 value of 27.3 nM at the m1 receptor and possesses 100-fold (m2), 48-fold (m3), 74-fold (m4), and 19-fold (m5) selectivities at the other receptors. Thus, this analogue appears to be more selective on the basis of binding than the prototypical m1 antagonist, pirenzepine. Functional data, such as the inhibition of carbachol-stimulated phosphatidylinositol hydrolysis, on selected analogues confirmed the muscarinic antagonistic properties of this chemical series.

Animals↗
PubMed1999

Effect of seminal oxidative stress on fertility after vasectomy reversal.

OBJECTIVE: To evaluate seminal oxidative stress in men after vasectomy reversal and to determine whether seminal oxidative stress could predict fertility after vasectomy reversal. DESIGN: Measurement of seminal reactive oxygen species (ROS) and total antioxidant capacity (TAC) in normal donors, men who were fertile after vasectomy reversal, and men who were infertile after vasectomy reversal. SETTING: A male infertility clinic of a tertiary care center. PATIENT(S): Thirty men who underwent vasectomy reversal and 17 normal donors. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Semen characteristics, seminal ROS, and TAC were measured with chemiluminescence assays in samples from donors and reversal patients. RESULT(S): Mean adjusted seminal ROS (log [ROS+1]) was higher in infertile reversal patients (2.38+/-0.25) than in normal donors (1.30+/-0.14). Seminal ROS was also higher in all (fertile and infertile reversal combined) reversal patients than in donors. Total antioxidant capacity did not differ between groups. The ROS-TAC score, a composite index of seminal oxidative stress, was a significant predictor of fertility. A ROS-TAC score of 45 or greater had a positive predictive value of 73% in predicting fertility. CONCLUSION(S): Seminal oxidative stress is associated with vasectomy reversal. The ROS-TAC score is a possible predictor of infertility after vasectomy reversal.

Adult↗
PubMed1999

Peri operative ultrasound guided needle localisation of amputation stump neuroma.

Ten patients with clinically suspected neuromas following amputation were submitted for ultrasound examination. Neuromas in seven of the ten patients were identified as the cause of pain with ultrasound guided infiltration of local anaesthetic. Pre operative localisation, using breast localisation wires allowed the neuromas to be surgically excised with reduced dissection. This small study demonstrates that ultrasound is an effective method for identifying and localising neuromas in amputation stumps. This leads to reduced dissection and may lead to a better outcome in these patients.

Adult↗
PubMed1999

Sperm cryopreservation in patients with testicular cancer.

OBJECTIVES: To review a large experience with sperm cryopreservation in patients with testicular cancer and determine the effect of clinical stage and tumor histologic features on semen quality. METHODS: The prefreeze and post-thaw sperm quality of 157 patients with testicular cancer was compared with that of 50 normal donors. The impact of tumor stage and histologic features (pure seminoma, pure embryonal, or mixed germ cell) was also determined. A computer-assisted semen analysis was performed before and after cryopreservation. The motile sperm count (MSC), motility, and motion characteristics were measured before and after cryopreservation and compared between groups. RESULTS: Patients with testicular cancer had lower prefreeze and post-thaw MSC and motility compared with normal donors (P = 0.0001 for both). The curvilinear velocity and linearity were also significantly less in patients with testicular cancer (P <0.05 for both). The percentage of change in the semen characteristics did not differ between patients and donors, indicating that sperm from both patients and donors withstood the cryopreservation process equally well. Tumor stage (n = 143) and histologic features (n = 136) did not significantly influence semen quality. No individual histologic component significantly influenced MSC or motility. CONCLUSIONS: The effect of cryopreservation on sperm was similar in patients with testicular cancer and donors. Patients with poor prefreeze semen quality have poor post-thaw semen quality, and the effects of cryopreservation were not significantly affected by histologic features or stage. Our results indicate that routine sperm banking should be recommended for men with a diagnosis of testicular cancer to preserve future fertility potential.

Adolescent↗
PubMed1999

Relationship of total motile sperm count and percentage motile sperm to successful pregnancy rates following intrauterine insemination.

PURPOSE: This study sought (i) to investigate the relationship between postwash total motile sperm count and postwash percentage motile sperm in predicting successful intrauterine insemination and (ii) to determine the minimal postwash total motile sperm count required to achieve pregnancy with intrauterine insemination. METHODS: Five hundred four women, who underwent 1636 intrauterine insemination cycles with their partner's sperm for infertility treatment from 1993 through 1995, were included in this retrospective study. All patient charts were reviewed for age, infertility etiology, ovarian stimulation regimens, semen characteristics, and treatment outcome. To determine the relationship between total motile sperm count and intrauterine insemination outcome, patients were grouped as (1) less than 0.5 million, (2) 0.5 to 1 million, (3) 1 to 5 million, (4) greater than 5 million, and (5) greater than 20 million. RESULTS: Similar live birth rates (per cycle) were seen among the postwash total motile sperm count groups: group 1, 3.5%; group 2, 2.4%; group 3, 7.0%; group 4, 6.9%; and group 5, 7.0% (P = 0.37). However, regardless of the postwash total motile sperm count, the postwash motility predicted intrauterine insemination success at a cutoff value of 40%. CONCLUSIONS: The percentage of postwash sperm motility, and not the postwash total motile sperm count, can predict successful intrauterine insemination outcome. Such information can be useful in counseling patients regarding their chance of success with intrauterine insemination and in determining when alternate methods of assisted reproduction may be a better approach.

Female↗
PubMed1999

The reactive oxygen species-total antioxidant capacity score is a new measure of oxidative stress to predict male infertility.

The imbalance between reactive oxygen species (ROS) production and total antioxidant capacity (TAC) in seminal fluid indicates oxidative stress and is correlated with male infertility. A composite ROS-TAC score may be more strongly correlated with infertility than ROS or TAC alone. We measured ROS, TAC, and ROS-TAC scores in semen from 127 patients and 24 healthy controls. Of the patients, 56 had varicocele, eight had varicocele with prostatitis, 35 had vasectomy reversals, and 28 had idiopathic infertility. ROS levels were higher among infertile men, especially those with varicocele with prostatitis (mean +/- SE, 3.25 +/- 0.89) and vasectomy reversals (2.65 +/- 1.01). All infertile groups had significantly lower ROS-TAC scores than control. ROS-TAC score identified 80% of patients and was significantly better than ROS at identifying varicocele and idiopathic infertility. The 13 patients whose partners later achieved pregnancies had a mean ROS-TAC score of 47.7 +/- 13.2, similar to controls but significantly higher than the 39 patients who remained infertile (35.8 +/- 15.0; P < 0.01). ROS-TAC score is a novel measure of oxidative stress and is superior to ROS or TAC alone in discriminating between fertile and infertile men. Infertile men with male factor or idiopathic diagnoses had significantly lower ROS-TAC scores than controls, and men with male factor diagnoses that eventually were able to initiate a successful pregnancy had significantly higher ROS-TAC scores than those who failed.

Antioxidants↗
PubMed1999

Changes in respiratory timing induced by hypercapnia in maturing rats.

Premature infants respond to hypercapnia by an attenuated ventilatory response that is characterized by a decrease in respiratory frequency. We hypothesized that this impaired hypercapnic ventilatory response is of central origin and is mediated via gamma-aminobutyric acid-ergic (GABAergic) pathways. We therefore studied two groups of maturing Sprague-Dawley rats: unrestrained rats in a whole body plethysmograph at four postnatal ages (5, 16-17, 22-23, and 41-42 days); and ventilated, decerebrate, vagotomized, paralyzed rats in which phrenic nerve responses to hypercapnia were measured at 4-6 and 37-39 days of age. In the unrestrained group, the increase in minute ventilation induced by hypercapnia was significantly lower at 5 days vs. beyond 16 days. Although there was an increase in tidal volume at all ages, frequency decreased significantly from baseline at 5 days, whereas it increased significantly at 16-17, 22-23, and 41-42 days. The decrease in frequency at 5 days of age was mainly due to a significant prolongation in expiratory duration (TE). In the ventilated group, hypercapnia also caused prolongation in TE at 4-6 days but not at 37-39 days of age. Intravenous administration of bicuculline (GABA(A)-receptor blocker) abolished the prolongation of TE in response to hypercapnia in the newborn rats. We conclude that newborn rat pups exhibit a characteristic ventilatory response to CO(2) expressed as a centrally mediated prolongation of TE that appears to be mediated by GABAergic mechanisms.

Age Factors↗