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Biomedical subjects

R H Martin

Publications and source records attributed to R H Martin.

At least 109 records · Page 6Linked to original sources

Indium-111 chloride scintigraphy in adult osteomyelitis.

Osteomyelitis is a common clinical problem that may be difficult to diagnose. We compared the performance of indium-111-labeled white cells ([111In]WBC) to 111In chloride ([111In]Cl) in two groups of adult patients suspected to have osteomyelitis or septic arthritis. Using [111In] WBC, 52 scans were performed on 51 patients. Nineteen patients had osteomyelitis. The sensitivity was 84% and specificity 82%. Using [111In]Cl, 48 scans were performed on 47 patients. Twelve had osteomyelitis. Sensitivity was 91%, and specificity was 89%. In each group, one false-negative study occurred in vertebral osteomyelitis. Three false-negative studies using [111In]WBC were due to failure to distinguish between combined bone and soft-tissue infection and soft-tissue infection alone. False-positive studies in both groups were due to overlying soft-tissue infection or inflammatory arthritis. Chi-squared test showed no significant difference in performance between the two agents. Indium-111 chloride is easier to prepare and use than [111In]WBC, which requires a time-consuming labeling process.

Adult↗

The effect of age on the frequency of sperm chromosomal abnormalities in normal men.

It has been suggested that advanced paternal age (independent of maternal age) is associated with an increased incidence of trisomy. However, studies of human liveborn offspring and of data from prenatal diagnosis have yielded conflicting results. To investigate this possible paternal age effect, we have studied sperm chromosome complements from 30 normal men of proven fertility stratified by age, with five males in each of six age categories (20-24, 25-29, 30-34, 35-39, 40-44, and 45+ years). Sperm chromosome complements were visualized after penetration of golden-hamster oocytes. A minimum of 30 complements were analyzed for each male. The analysis was performed blindly, without knowledge of the donor's age. The mean frequency of sperm chromosomal abnormalities in the individual men was 10.4% with means of 4.7% for numerical abnormalities and 6.2% for structural abnormalities. There was no relationship between age and the frequency of numerical abnormalities in sperm. Since there was a significant difference between the frequency of hyperhaploid and hypohaploid complements, these two types of numerical abnormalities were analyzed separately. There was no correlation between the frequency of hypohaploid complements and age. There was a significant negative correlation between age and the frequency of hyperhaploid complements. For structural abnormalities, there was a highly significant positive correlation with age. Thus, our results do not support the hypothesis of an increased risk of trisomy with paternal age.

Adult↗

The meiotic segregation of human sperm chromosomes in two men with accessory marker chromosomes.

Accessory marker chromosomes are occasionally discovered in normal individuals and they are presumed "clinically inert" since they do not appear to have any phenotypic effect. However, they do pose a theoretical risk at meiosis since they could disrupt the normal pairing and disjunction of homologous chromosomes. Sperm chromosome complements have been studied in two normal males, each of whom carry a small bisatellited accessory marker chromosome 47,XY, + mar (psps), to determine if these marker chromosomes are associated with an increased frequency of aneuploid gametes. Pronuclear chromosomes were visualized after in vitro fertilization of golden hamster eggs with human sperm. The frequency of sperm complements containing a marker chromosome was not significantly different from 50% as theoretically expected, in either male (17/43 and 13/31 with marker chromosomes). One male had 2/43 (4.7%) aneuploid sperm, which is very close to the average frequency of aneuploid sperm seen in control donors (5%). The other male had 6/31 complements with chromosomal abnormalities. One set of sperm chromosomes had structural abnormalities, and five (16.1%) had numerical abnormalities. This frequency of aneuploidy is significantly elevated over the frequency seen in control donors (P = .0002). It is particularly interesting that all the abnormalities involved small chromosomes, as would be expected if the marker chromosome participated in distributive pairing and thereby disrupted normal disjunction of chromosomes of similar size. These preliminary results suggest that accessory marker chromosomes may increase the risk of aneuploid gametes in some individuals.

Adult↗

Sperm chromosome analysis in a man heterozygous for a paracentric inversion of chromosome 7 (q11q22).

Human sperm chromosomes were studied in a man heterozygous for a paracentric inversion of chromosome 7 (q11q22). The pronuclear chromosomes were analysed after in vitro penetration of golden hamster (Mesocricetus auratus) eggs. Ninety-four sperm chromosome spreads were examined, of which 34 contained the normal number 7 chromosome and 59 the inverted 7. This segregation was significantly different from the expected 1:1 ratio. The number of X- to Y-bearing sperm was 48 and 46 respectively. No sperm contained a recombinant chromosome caused by a crossover within the inversion. The frequency of chromosomal abnormalities in other chromosomes was 9.6%, which is not significantly different from the frequency observed in normal donors (8.9%) in our laboratory. These results suggest that the risk of chromosomally unbalanced sperm is not high for this paracentric inversion.

Animals↗

The renal washout parameter as an indicator of transplant rejection.

The accumulation of intravascular fibrin thrombosis in both acute and chronic renal rejection leads to a delay in the transit of perfusion. This study examines the renal washout parameter as an indicator of transit time. By mathematical simulation of renal time-activity curves various factors which can influence this parameter are investigated, a simple analysis is proposed and clinical results are correlated with biopsy findings. A washout parameter greater than 28 s is found to be consistent with histologically diagnosed rejection over a range of bolus qualities.

Graft Rejection↗

An increased frequency of human sperm chromosomal abnormalities after radiotherapy.

13 cancer patients were studied before radiotherapy (RT) and at regular intervals after RT to determine the effect of RT on chromosomal abnormalities in sperm. The men were 19-47 years old and received testicular radiation doses of 0.4-5.0 Gray. Human pronuclear sperm chromosomes were analysed after penetration of zona-pellucida-free hamster eggs. Unfortunately the hamster egg penetration rates were exceedingly low, both before and after RT and this limited the number of sperm chromosome complements which could be analysed. Before RT, the frequency of abnormal sperm chromosome complements was 0% (0/9). After RT, the majority of men were azoospermic for 24 months but complements could be analysed from 4 men. In the first 12 months the frequency of abnormalities was 13% (1/8) and at 24 months it was 13% (7/55). By 36 months after RT, most men had recovered sperm production and the frequency of abnormalities in 8 men was 21% (18/86), which is significantly higher than the rate in control donors (8.5%). For individual men the range was 6-67%, and there was a significant correlation between testicular radiation dose and the frequency of sperm chromosomal abnormalities. The frequencies of both numerical and structural abnormalities were significantly increased after RT. This is the first evidence that radiation may increase the frequency of chromosomal abnormalities in human gametes.

Adult↗

An investigation of human sperm pronuclear chromosome "gaps" using scanning electron microscopy.

A common cytogenetic finding in both Q-banded and solid Giemsa-stained preparations of pronuclear chromosomes obtained from cross-species fertilization of hamster oocytes by human sperm is the presence of a variable-length "gap" in the centromeric region. Scanning electron microscopy was used to investigate these altered chromosomal regions. The centromere in most eukaryotic organisms appears as a constricted region approximately 200-300 nm in diameter. In contrast, the gap portion of the centromeric region of pronuclear chromosomes was found to contain a chromatin fiber with a diameter of 80-150 nm. The detection of this fiber confirms that the chromosome arms are continuous, and the size of the fiber explains the gap appearance in the light photomicrographs. The morphology of the fiber is consistent with the concept that the normal chromatin packaging has been altered in varied regions within the centromere of these chromosomes.

Animals↗

Chromosomal analysis of unfertilized human oocytes.

Unfertilized human oocytes were obtained from women in an in-vitro fertilization programme. The women had a mean age of 29.4 years (range 24-35 years). Chromosomal complements could be analysed in 50 oocytes. Q-banding of the chromosomes facilitated identification of individual chromosomes: 34 oocytes (68%) had the normal haploid chromosomal complement, 14 complements were hypohaploid (28%), 1 complement was hyperhaploid (2%) and 2 had structural abnormalities (4%). (One oocyte had numerical and structural abnormalities). The 16 abnormal oocytes were obtained from 15 different women. A conservative estimate of aneuploidy in this sample is 4%; however, the frequency of aneuploidy may be higher if there is a predisposition to chromosome loss during oogenesis. This study provides information on the largest series of karyotyped unfertilized human oocytes published to date.

Adult↗

Chromosomal abnormalities in human sperm.

The ability to analyze human sperm chromosome complements after penetration of zona pellucida-free hamster eggs provides the first opportunity to study the frequency and type of chromosomal abnormalities in human gametes. Two large-scale studies have provided information on normal men. We have studied 1,426 sperm complements from 45 normal men and found an abnormality rate of 8.9%. Brandriff et al. (5) found 8.1% abnormal complements in 909 sperm from 4 men. The distribution of numerical and structural abnormalities was markedly dissimilar in the 2 studies. The frequency of aneuploidy was 5% in our sample and only 1.6% in Brandriff's, perhaps reflecting individual variability among donors. The frequency of 24,YY sperm was low: 0/1,426 and 1/909. This suggests that the estimates of nondisjunction based on fluorescent Y body data (1% to 5%) are not accurate. We have also studied men at increased risk of sperm chromosomal abnormalities. The frequency of chromosomally unbalanced sperm in 6 men heterozygous for structural abnormalities varied dramatically: 77% for t11;22, 32% for t6;14, 19% for t5;18, 13% for t14;21, and 0% for inv 3 and 7. We have also studied 13 cancer patients before and after radiotherapy and demonstrated a significant dose-dependent increase of sperm chromosome abnormalities (numerical and structural) 36 months after radiation treatment.

Aneuploidy↗

A prospective serial study of the effects of radiotherapy on semen parameters, and hamster egg penetration rates.

Cancer patients were studied before radiotherapy (RT) and at regular intervals after treatment (1, 3, 12, 24, 36, 48 months) to determine the effect of radiotherapy on semen parameters and sperm function as assessed by the hamster egg penetration assay. The cancer patients received testicular radiation doses of 0.4 to 5.0 grays (40 to 500 rads). The pre-radiotherapy semen profile varied considerably but in general the profile was poor: 7/11 men had a sperm concentration less than 20 X 10(6)/ml and a total count of less than 50 X 10(6), while the hamster egg penetration rates were also very low with a mean of 5% (range 0% to 15%). This is the first study demonstrating that sperm function as well as sperm concentration is impaired in cancer patients pre-radiotherapy. At 3 and 12 months post-radiotherapy, 8/11 men were azoospermic. By 24 months 8/11 were producing sperm although only 2 had hamster egg penetration rates greater than 15%. All men studied at 36 months (4) and 48 months (3) post-radiotherapy had recovered spermatogenesis but hamster egg penetration rates were still poor. There was a highly significant inverse correlation between testicular radiation dose and subsequent sperm concentration and hamster egg penetration rates.

Adult↗

Sensitivity and specificity of commonly used electrocardiographic criteria for left atrial enlargement determined by M-mode echocardiography.

To assess the sensitivity and specificity of 6 commonly used electrocardiographic criteria for left atrial (LA) enlargement, the rest ECGs of 99 patients in normal sinus rhythm were analyzed. Fifty-seven of the patients had LA enlargement and 42 had a normal LA dimension as determined by M-mode echocardiography. The 6 criteria studied and their respective sensitivities and specificities were as follows: (1) duration of the negative phase of the P wave in lead V1 greater than 40 ms: sensitivity, 83%; specificity, 80%; (2) notched P wave in any standard lead with an interpeak duration greater than 40 ms: sensitivity, 15%; specificity, 100%; (3) P terminal force (depth X duration of the terminal portion of the P wave) in lead V1 more negative than -0.04 mm X s: sensitivity, 69%; specificity 93%; (4) depth of the negative phase of the P wave in lead V1 greater than or equal to 1 mm: sensitivity, 60%; specificity, 93%; (5) total P-wave duration greater than 110 ms in any standard lead: sensitivity, 33%; specificity, 88%; (6) total P wave duration/P-R interval duration greater than 1.6: sensitivity, 31%; specificity, 64%. Combining 2 or more of these criteria did not substantially improve sensitivity and specificity.

Cardiomegaly↗

Comparison of chromosomal abnormalities in hamster egg and human sperm pronuclei.

One thousand human sperm and hamster egg haploid karyotypes were analyzed at the pronuclear stage after in vitro penetration. The frequency of abnormalities in human sperm was 8.5%, with 5.2% aneuploidy and 3.3% structural abnormalities. The hamster egg complements had an abnormality rate of 3.8%, with 3.3% aneuploidy and 0.5% structural abnormalities. In both human and hamster complements, chromosome abnormalities were observed in all chromosome groups, demonstrating that all chromosomes are susceptible to nondisjunction, not just acrocentric or small chromosomes. There is an intriguing difference between the frequency of hyperhaploid and hypohaploid complements in human sperm and hamster eggs. In the human complements, 2.4% were hyperhaploid and 2.7% hypohaploid. This is very close to the theoretical 1 to 1 ratio expected from nondisjunction. The hamster egg complements had more hypohaploid (2.2%) than hyperhaploid (0.9%) complements, despite identical treatment. Higher rates of hypohaploidy are generally ascribed to artificial loss of chromosomes, but may in fact reflect a predisposition of oocytes to anaphase lag during meiosis. The frequency of abnormalities (both numerical and structural) is higher in human complements than in hamster. This may reflect an innate propensity for meiotic chromosome abnormalities in humans or may result from greater exposure of humans to mutagenic agents.

Adult↗

Analysis of human sperm chromosome complements from a male heterozygous for a reciprocal translocation t(11;22)(q23;q11).

A reciprocal translocation between chromosomes 11 and 22 (t(11;22)(q23;q11] is a site-specific translocation that is of particular interest because of the propensity for 3:1 segregation of the chromosomes during meiosis. There have been no published reports of chromosomally unbalanced offspring born as a result of adjacent 1 or 2 meiotic segregations in a heterozygote for this translocation. This could be explained by a meiotic mechanism which produces only 3:1 chromosomal segregations or by differential embryonic survival in which 2:2 adjacent segregations do not produce a viable pregnancy. To distinguish between these two possibilities, sperm chromosome complements from a man heterozygous for this 11;22 translocation were studied. The human sperm chromosomes were analysed after fertilization of zona pellucida-free golden hamster eggs. All possible 2:2 (alternate, adjacent 1, adjacent 2) and 3:1 segregations were observed and these segregations occurred in approximately equal frequencies. The frequency of other chromosome abnormalities, unrelated to the translocation, did not appear to be increased. These results indicate that the 11;22 translocation does not specifically cause 3:1 disjunction of chromosomes but that this segregation of chromosomes is more likely to result in a viable pregnancy.

Adult↗

Factors distinguishing couples at risk for nondisjunction.

Micronucleus frequencies were determined on 24 young parents of trisomic infants, 21 individuals with recurrent unexplained abortions, and 42 control individuals with proven reproductive success. In addition to measurements of spontaneous micronucleus frequencies, mitomycin C induced frequencies were determined at two doses (2.5 and 5.0 ng/mL). Using the 95% confidence limits established from control data as an arbitrary upper limit, 16 of 24 parents of trisomics and 5 of 21 recurrent aborters were detected by the micronucleus assay to above this cutoff. The effects of sex, age, pregnancy status, and a variety of environmental exposures were studied by comparing the micronucleus frequencies of the exposed and unexposed populations. The data suggested that vitamins were associated with a lower micronucleus frequency and tea drinking with an increased micronucleus frequency in parents of trisomics, an effect not seen in controls. These results suggest that a biologic basis for nondisjunction may be associated with elevation in spontaneous and induced micronuclei. In addition, tea and vitamins may modulate micronucleus frequencies in parents of trisomics who appear to be more sensitive to these influences than the controls.

Abortion, Habitual↗