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Biomedical subjects

M P Johnson

Publications and source records attributed to M P Johnson.

At least 19 recordsLinked to original sources
PubMed1992

Triply discordant triplets: probability, management options, and risks.

The spontaneous occurrence of triplets is rare. With increased utilization of "assisted reproductive technologies," multifetal gestations have become more common. The empiric fetal risk for major malformation is approximately 3%. In a triplet pregnancy each fetus independently carries this risk so that the probability of having at least one malformed fetus is approximately 9%. It is much less likely to have 2 or 3 simultaneously but discordantly malformed fetuses in a multizygotic triplet gestation (.09% and .0027% risk, respectively). We report on the first case, to our knowledge, of an ovulation-stimulated triplet pregnancy complicated by 3-way discordance for major malformations diagnosed in the late second trimester by ultrasound. Fetus A was affected by congenital diaphragmatic hernia and trisomy 21; fetus B had encephalocele, a midline facial defect, and a cleft palate; and fetus C had evidence of unilateral claw hand but an otherwise normal fetal survey. At 19 weeks of gestation, fetus A was found to have spontaneously died, and a selective termination of triplet B was performed. We conclude: (1) the finding of a single major malformation in one fetus should lead to extensive search for malformations in all members of the pregnancy, and (2) the simultaneous occurrence of major malformations in more than one member of a multifetal gestation is a circumstance under which multiple selective termination deserves consideration. In this article we discuss important issues and caveats in the performance of selective termination for abnormal members of multifetal gestations.

Abnormalities, Multiple↗
PubMed1992

Benzofuran bioisosteres of hallucinogenic tryptamines.

The benzofuran analogues of the hallucinogens 5-methoxy-N,N-dimethyltryptamine and 5-methoxy-alpha-methyltryptamine were synthesized and evaluated for affinity at the serotonin 5-HT2 and 5-HT1A receptors in rat brain homogenate, labeled with [125I]-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane ([125I]DOI) and [3H]-8-hydroxy-2-(N,N-di-n-propylamino)tetralin ([3H]-8-OH-DPAT), respectively. At the 5-HT2 receptor, the benzofurans had slightly decreased affinities, approximately one-third and one-sixth those of the indoles, for the primary amines and the tertiary amines, respectively. The benzofurans also had lower affinity at the 5-HT1A receptor, but decreased only about 20-30% from that of the indole isosteres. Thus, the 5-HT1A receptor is less discriminating with respect to preference for an indole versus a benzofuran, although all of the compounds did have higher affinities for the 5-HT2 receptor than for the 5-HT1A receptor. It is suggested that benzofurans may be useful in the design of serotonin receptor ligands.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

Stereoselective LSD-like activity in d-lysergic acid amides of (R)- and (S)-2-aminobutane.

The (R)- and (S)-2-butylamides of d-lysergic acid were prepared and evaluated in behavioral and biochemical assays of 5-HT2 agonist activity. In rats trained to discriminate 0.08 mg/kg LSD tartrate from saline, both isomers completely substituted for the training stimulus. Similarly, both isomers were found to possess very high affinity in displacing [125I]-(R)-DOI ([125I]-(R)-1-(2,5-dimethoxy-4-iodophenyl)-2- aminopropane) from rat cortical homogenate 5-HT2 receptors and in displacing [3H]-8-OH-DPAT ([3H]-8-hydroxy-2-(di-n-propylamino)tetralin) from rat hippocampal 5-HT1A receptors. The difference in activity between the two isomeric amides was significant in both the behavioral and binding assays, with the R isomer possessing greater potency. Molecular mechanics were used to predict the active geometries of the subject compounds. It was found that the (R)-2-butylamide has a conformation quite similar to LSD, while the (S)-2-butylamide does not. These results suggest that stereochemical properties of the amide substituent of hallucinogenic lysergamides may exert a critical influence on activity. It is concluded that the conformation of the amide function may directly affect binding through stereoselective interactions with a hydrophobic region on the receptor, indirectly by inducing conformational changes elsewhere in the molecule, or by a combination of these two mechanisms.

Animals↗
PubMed1992

Rapid prenatal diagnosis by fluorescent in situ hybridization of chorionic villi: an adjunct to long-term culture and karyotype.

OBJECTIVE: This series was designed to assess in a pilot study the feasibility of using fluorescence in situ hybridization on chorionic villi. STUDY DESIGN: We constructed probes derived from specific subregions of human chromosomes 21, 18, 13, X, and Y that give a single copylike signal when used in conjunction with suppression hybridization. RESULTS: In a blind series of 47 samples all, including one trisomy 21, were correctly identified. The samples were correctly classified as disomic for five chromosomes. CONCLUSIONS: The combination of chromosome-specific probe sets composed primarily of cosmid contigs and optimized hybridization and detection allowed accurate chromosome enumeration in uncultured human chorionic villi; these results are consistent with those obtained by traditional cytogenetic analysis and suggest a use for fluorescence in situ hybridization as an adjunct to karyotyping when rapid results are needed.

Chorionic Villi↗
PubMed1992

The smaller than expected first-trimester fetus is at increased risk for chromosome anomalies.

OBJECTIVE: Intrauterine growth retardation associated with fetal chromosome anomalies is usually documented on ultrasonography late in the second trimester. However, we believe and attempt to document here that the impact of aneuploidy on fetal growth is evident much earlier (i.e., the aneuploid fetus may appear smaller than dates on ultrasonography even in the first trimester). STUDY DESIGN: For the population referred to our center for chorionic villus sampling from January 1988 to July 1991, we compared gestational age as calculated from the last menstrual period to that derived from fetal size as measured by crown-rump length. A cutoff of 7 days was chosen to select the study group. The remainder of our chorionic villus sampling population in which fetal size was expected was used as controls. We also divided those chorionic villus sampling patients by when a fetal death was observed by size. RESULTS: In the study period 3194 chorionic villus sampling procedures were performed and in 277 (8.7%) fetal length was smaller than expected by at least 7 days. Sixty (1.9%) chromosome anomalies were diagnosed by first trimester chorionic villus sampling in the study period. The frequency of chromosome anomalies was 4.3% in the study group and 1.7% in controls (p < 0.004). The more aberrant the karyotype on "postmortem chorionic villus sampling," the greater the growth retardation tended to be. CONCLUSIONS: In our chorionic villus sampling population a fetal crown-rump length smaller than dates is associated with a significant increase in risk of chromosome anomalies. Moreover, the larger the size-dates discrepancy, the higher the possibility that the aneuploidy affecting that pregnancy is of the severe or lethal type.

Adult↗
PubMed1992

Tuberculin skin test reactivity among adults infected with human immunodeficiency virus.

Infection with the human immunodeficiency virus type 1 (HIV-1) results in decreased cell-mediated immunity, which includes decreased delayed hypersensitivity to skin test antigens. HIV-1 seropositivity and skin test reactivity to purified protein derivative (PPD) were determined among 2042 healthy Haitian adults with normal chest radiographs. Among HIV-1-seropositive individuals, 52.3% (146/279) had PPD reactions greater than or equal to 10 mm compared with 67.2% (1184/1763) of the seronegative adults (P less than .001). However, the percentage of HIV-1-seropositive individuals with PPD reactions greater than or equal to 5 mm was similar to the percentage of seronegative adults with PPD reactions greater than or equal to 10 mm (180/279 [64.5%] vs. 1184/1763 [67.2%]). Assuming that the rate of prior infection with Mycobacterium tuberculosis was similar for HIV-1-seronegative and -seropositive populations, these data provide support for the recent recommendations to use induration of greater than or equal to 5 mm as evidence of past infection with M. tuberculosis in HIV-1 seropositive adults.

Adult↗
PubMed1992

First trimester interfetal size variation in well-dated multifetal pregnancies.

Sonographic measurements of multifetal pregnancy for dating and growth are considered identical to singleton pregnancies until the second trimester. Observations in 57 patients having triplets or more, who were referred for first trimester multifetal pregnancy reduction, suggest considerable size variability both within an individual pregnancy and among pregnancies of the same gestational ages (GAs). These data are unique because the GAs are precisely known, because the pregnancies were established by assisted reproductive technology. We observed a greater standard deviation at 12 and 13 weeks of GA. We also observed significant interfetal variation within an individual pregnancy. Because multifetal pregnancy reduction was performed, follow-up of any given fetus to term was not possible. We conclude that for high-order multiple gestations: (1) interfetal size variability begins much earlier than often stated; (2) differences in the degree of variability can be observed among different pregnancies of the same gestational age and within the same pregnancy, and (3) there is a trend for increasing variability with increasing gestational age.

Body Height↗
PubMed1992

Chorionic villus sampling: transabdominal versus transcervical approach in more than 4000 cases.

OBJECTIVE: To address the evolving trends in the choice of transabdominal or transcervical chorionic villus sampling (CVS) at a teaching hospital and to evaluate the influence of gestational age on the approach chosen. METHODS: We analyzed our CVS data base, which contained information from 1986-1991. The proportions of transabdominal and transcervical CVS were tabulated for each year. In addition, the distribution of the CVS approaches over the various gestational ages was examined. RESULTS: During the study period, 4290 CVS procedures were performed. The rate of the transabdominal technique was stable at about 15% per year except for the first 2 years, when essentially all procedures were transcervical. Use of transabdominal CVS increased with advancing gestational age, from 3.6% at less than 10 weeks' gestation to 97.6% at greater than 14 weeks (chi 2 = 120, P less than .001; r = 0.791). CONCLUSIONS: The choice between the transabdominal and transcervical approach to CVS largely reflects the route emphasized during the physician's training. When choice is based strictly on technical limitations due to placental position, the overall transabdominal CVS rate is approximately 15%. A shift from transcervical to transabdominal CVS occurs with increasing gestational age as the placenta gains bulk and moves away from the cervix. After 14 weeks' gestation, most procedures are performed transabdominally.

Chorionic Villi Sampling↗
PubMed1992

Determinants of parental decision to abort or continue after non-aneuploid ultrasound-detected fetal abnormalities.

OBJECTIVE: This study evaluated factors influencing the decision to abort after abnormalities in the karyotypically normal fetus were found through ultrasonography. METHODS: We reviewed all pregnancies complicated by ultrasound-detected abnormalities managed on our service from April 1990 through August 1991 (N = 262). Cases with associated karyotypic abnormalities were excluded (N = 35), as were cases diagnosed after the legal gestational age limit for abortion (N = 68). The remaining 159 cases were stratified into prognosis groups of "severe," "uncertain," and "mild." RESULTS: The prognostic severity of the ultrasound abnormality strongly correlated with the decision to abort (P less than .0001). Rates of termination were 0, 12, and 66% in the "mild," "uncertain," and "severe" groups, respectively. The patients' age, gravidity, and parity, and the fetal gestational age at diagnosis did not differ significantly between the groups. CONCLUSIONS: 1) In non-aneuploid pregnancies with an ultrasound diagnosis of fetal abnormality, the major predictor of the decision to abort was the severity of fetal prognosis. 2) The gestational age at diagnosis was not an important variable in the decision to abort for fetal structural abnormalities. 3) Parents who had fetuses with abnormalities associated with uncertain prognoses usually opted to continue the pregnancy. This appeared to be particularly true for defects that were potentially correctable in utero or by neonatal intervention (even if investigational).

Abortion, Induced↗
PubMed1992

Traditional and molecular cytogenetics.

Traditional cytogenetic methods have relied on tissue culture techniques to generate adequate mitotic cells for the analysis of chromosome disorders for prenatal diagnosis. Chromosome banding techniques allow the evaluation of mitotic cells for structural and numerical aberrations and define the nature of any rearrangement. With the advent of fluorescent in situ hybridization methodology, which combines the molecular technologies of chromosome-specific probes and in situ molecular hybridization, it has become possible to analyze chromosomal numerical and structural aberrations from interphase cells. The use of molecular cytogenetic techniques should greatly increase the speed and diagnostic resolution of clinical specimens.

Chromosome Aberrations↗
PubMed1992

Fetal intracardiac potassium chloride injection to avoid the hopeless resuscitation of an abnormal abortus: I. Clinical issues.

OBJECTIVE: With the intention of preventing the attendant medical, ethical, and legal problems arising from the birth of live-born, anomalous fetuses, we initiated a program offering fetal intracardiac potassium chloride injection as an adjunctive measure in the setting of genetically indicated second-trimester abortion. METHODS: A lethal fetal injection was offered to patients carrying chromosomally or structurally abnormal fetuses at 19-24 weeks' gestation who desired abortion. When the patient elected this procedure, real-time ultrasound guidance was used to inject 3-5 mL of potassium chloride (2 mEq/mL) directly into the fetal cardiac chambers, followed by observation of fetal heart activity to ascertain cessation. Labor was subsequently induced with uterotonic prostaglandins. RESULTS: The procedure caused immediate cessation of fetal heart motion in 20 of 21 cases. There were no maternal complications. No fetuses were live-born. CONCLUSIONS: Direct fetal intracardiac potassium chloride injection effectively causes immediate fetal cardiac arrest. This approach may be adopted in cases of abortion by labor-induction methods at advanced gestations to ensure that the abortus is stillborn.

Abortion, Eugenic↗
PubMed1992

Fetal intracardiac potassium chloride injection to avoid the hopeless resuscitation of an abnormal abortus: II. Ethical issues.

Following the diagnosis of a genetic anomaly, some couples choose to have a legal abortion. However, following later abortions at greater than 20 weeks, the rare but catastrophic occurrence of live births can lead to fractious controversy over neonatal management. To avoid this situation, we have added fetal intracardiac potassium chloride injection to cause fetal cardiac arrest before induction of labor. The ethical issues surrounding such a practice are complex. We support this practice for three reasons: 1) The women's decision for abortion is protected because this practice assures her right for non-interference; 2) potential psychological harm to the patient and other family members is avoided; and 3) the potential for coercive intervention by other health care personnel is eliminated. At least three objections can be raised: 1) All abortions are unjust; 2) newborns and second-trimester fetuses at similar weights with identical defects should be managed in like fashion; and 3) the patient is not entitled to death of the fetus, only to evacuation of the uterine contents. On balance, we believe that our approach is justifiable ethically as it reduces the burden of conflict between the wishes of the patient and those of the neonatal care givers. It should be introduced only in situations in which the likelihood of civil or criminal liability or unwarranted medical intervention is high.

Abortion, Eugenic↗
PubMed1991

Enterobacter bacteremia: clinical features and emergence of antibiotic resistance during therapy.

OBJECTIVES: To study the effect of previously administered antibiotics on the antibiotic susceptibility profile of Enterobacter, the factors affecting mortality, and the emergence of antibiotic resistance during therapy for Enterobacter bacteremia. DESIGN: Prospective, observational study of consecutive patients with Enterobacter bacteremia. SETTING: Three university tertiary care centers, one major university-affiliated hospital, and two university-affiliated Veterans Affairs medical centers. PATIENTS: A total of 129 adult patients were studied. MEASUREMENTS: The two main end points were emergence of resistance during antibiotic therapy and death. MAIN RESULTS: Previous administration of third-generation cephalosporins was more likely to be associated with multiresistant Enterobacter isolates in an initial, positive blood culture (22 of 32, 69%) than was administration of antibiotics that did not include a third-generation cephalosporin (14 of 71, 20%; P less than 0.001). Isolation of multiresistant Enterobacter sp. in the initial blood culture was associated with a higher mortality rate (12 of 37, 32%) than was isolation of a more sensitive Enterobacter sp. (14 of 92, 15%; P = 0.03). Emergence of resistance to third-generation cephalosporin therapy (6 of 31, 19%) occurred more often than did emergence of resistance to aminoglycoside (1 of 89, 0.01%; P = 0.001) or other beta-lactam (0 of 50; P = 0.002) therapy. CONCLUSIONS: More judicious use of third-generation cephalosporins may decrease the incidence of nosocomial multiresistant Enterobacter spp., which in turn may result in a lower mortality for Enterobacter bacteremia. When Enterobacter organisms are isolated from blood, it may be prudent to avoid third-generation cephalosporin therapy regardless of in-vitro susceptibility.

Adolescent↗
PubMed1991

[3H]monoamine releasing and uptake inhibition properties of 3,4-methylenedioxymethamphetamine and p-chloroamphetamine analogues.

The ability of several 3,4-methylenedioxymethamphetamine (MDMA) analogues to inhibit the uptake of [3H]serotonin (5-HT), dopamine (DA) and norepinephrine (NE) into synaptosomes was examined. In addition, the ability of the compounds to inhibit the uptake of [3H]5-HT and DA into synaptosomes from rats pretreated with reserpine (5 mg/kg i.p., 16 h pretreatment) was compared to control experiments. All of the test compounds were found to be potent releasers of non-vesicular 5-HT (the reserpine IC50 was significantly smaller than the control IC50). The range of 5-HT inhibitory activity corresponds well to the small range of ED50 values of the test compounds to substitute in drug discrimination experiments with animals trained to discriminate MDMA or S-(+)-N-methyl-1-(1,3-benzodioxol-5-yl)-2-aminobutane (S-MBDB) from saline. In contrast, there was a wide range of potency for the inhibition of NE and DA uptake. In addition, several of the analogues appeared to be pure uptake inhibitors of DA while others were found to be releasers of non-vesicular DA. Several of the compounds were very selective for 5-HT over DA or NE uptake inhibition, including 3-methoxy-4-methylamphetamine (MMA) and 5-methoxy-6-methyl-2-aminoindan (MMAI). A correlation was noted between the 5-HT neurotoxic potential of some of the test compounds and their relative ability to induce a release of non-vesicular DA. The potential catechol metabolites of the methylenedioxy-substituted compounds also showed potent monoamine releasing properties, suggesting that metabolism may play a role in the neurotoxic actions of some of these drugs. The present data support the hypothesis that drug-stimulated non-vesicular 5-HT release is primarily responsible for the discriminative cue of MDMA.

3,4-Methylenedioxyamphetamine↗
PubMed1991

Reduction in brain serotonin markers by alpha-ethyltryptamine (Monase).

alpha-Ethyltryptamine (Monase) is both an inhibitor of monoamine oxidase and a monoamine releasing agent. To determine whether alpha-ethyltryptamine induces serotonergic deficits similar to that of other monoamine releasing agents such as 3,4-methyl-enedioxymethamphetamine (MDMA) and para-chloroamphetamine (PCA), rats were given multiple doses (8 x 30 mg/kg s.c.) of alpha-ethyltryptamine acetate. Serotonin and 5-hydroxyindole acetic acid (5-HIAA) levels and the number of 5-HT uptake sites (determined from [3H]paroxetine binding) were significantly decreased in frontal cortex samples at one week killing. A significant decrease in 5-HT and 5-HIAA levels was also observed in rat hippocampal samples. The results provide evidence that alpha-ethyltryptamine may induce serotonin neurotoxicity similar to that of MDMA and PCA.

Animals↗