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Biomedical subjects

L Harkness

Publications and source records attributed to L Harkness.

At least 19 recordsLinked to original sources
PubMed2002

Embryo development and establishment of pregnancy after embryo transfer in pigs: coping with limitations in the availability of viable embryos.

Embryo transfer and pregnancy maintenance strategies in pigs were evaluated with reference to situations in which limited numbers of viable embryos or micromanipulated embryos are available, such as pig cloning. Development of embryos with compromised zona pellucida was compared with development of embryos with intact zona pellucida. Micromanipulation had no effect on blastocyst production rates after development in vivo or in vitro, but development in vivo improved the number of embryos reaching the blastocyst stage. Transfer of embryos with compromised zona pellucida resulted in live piglets. Several hormone treatments to maintain pregnancy were tested in a model in which three embryos were transferred into unmated recipient gilts, compared with transfer of three embryos into mated recipients. None of the hormonal treatments resulted in pregnancy rates of more than 25% at term and no more than 9% of transferred embryos survived, in comparison with 50% of the mated recipients successfully carrying 25% of transferred embryos. Lastly, the developmental potential of parthenogenetic embryos was assessed and 62% of transferred embryos resulted in pregnancies, none of which continued beyond day 55 of gestation. After co-transfer of three fertilized embryos with 55-60 parthenogenetic embryos into each of six recipients, two live piglets were delivered. The results from the present study indicate that transfer of zona pellucida compromised embryos can yield litters of normal piglets. In addition, it was demonstrated in a model system involving the transfer of three fertilized embryos into mature gilts that hormonal pregnancy maintenance strategies support a low proportion of embryos to term. Lastly, the present study shows for the first time a comparably effective but novel alternative for pregnancy maintenance in the pig involving the co-transfer of parthenote embryos.

Animals↗
PubMed2001

Evaluation of gestational deficiencies in cloned sheep fetuses and placentae.

Sheep fetal development at 35 days of gestation was examined following natural mating, in vitro production (IVP) of fertilized embryos, or somatic cell nuclear transfer (NT). Five crossbred (Blackface x Black Welsh) and four purebred (Black Welsh) fetuses and their associated placentae produced by natural mating were morphologically normal and consistent with each other. From 10 ewes receiving 21 IVP embryos, 17 fetuses (81%) were recovered, and 15 of these (88%) were normal. The NT fetuses were derived from two Black Welsh fetal fibroblast cell lines (BLW1 and 6). Transfer of 21 BLW1 and 22 BLW6 NT embryos into 12 and 11 ewes, respectively, yielded 7 (33%) and 8 (36%) fetuses, respectively. Only three (43%) BLW1 and two (25%) BLW6 NT fetuses were normal, with the rest being developmentally retarded. The NT fetal and placental deficiencies included liver enlargement, dermal hemorrhaging, and lack of placental vascular development reflected by reduced or absent cotyledonary structures. Fibroblasts isolated from normal and abnormal cloned fetuses did not differ in their karyotype from sexually conceived fetuses or nuclear donor cell lines. Our results demonstrate that within the first quarter of gestation, cloned fetuses are characterized by a high incidence of developmental retardation and placental insufficiency. These deficiencies are not linked to gross defects in chromosome number.

Animals↗
PubMed1998

Randomised controlled trial of sucrose by mouth for the relief of infant crying after immunisation.

OBJECTIVES: To evaluate the effect of sucrose solution given by mouth on infant crying times and measures of distress in the immunisation clinic. DESIGN: Randomised, double blind, placebo controlled trial of sucrose solution 75% wt/vol v sterile water as a control. SETTING: The immunisation clinic of the Women's and Children's Hospital, Adelaide. PATIENTS: A total of 107 healthy infants attending for 2, 4, or 6 month immunisations with polio by mouth (Sabin), intramuscular diphtheria, tetanus, and pertussis (DTP), and intramuscular Haemophilus influenzae type b were randomised to receive 2 ml 75% sucrose solution or sterile water by mouth before the two injections. METHODS: The duration of infant crying was recorded during and immediately after two intramuscular immunisations and infant distress was assessed by a visual analogue scale (Oucher scores) independently by a nurse and a parent. RESULTS: The administration of 2 ml 75% sucrose solution by mouth reduced the infant crying time and Oucher distress scores after immunisation with DTP/H influenzae type b. CONCLUSIONS: Infant immunisation by intramuscular injection is a distressing procedure for infants and parents. Sucrose solution at a high concentration reduces infant distress and is safe and clinically useful in this setting.

Administration, Oral↗
PubMed1994

Midtrimester hemoperitoneum caused by placenta percreta in association with elevated maternal serum alpha-fetoprotein level.

We report a case of hemoperitoneum in the second trimester due to placenta percreta which was associated with an elevated maternal serum alpha-fetoprotein. A 29-year-old woman, gravida 4, para 1-0-2-1, was seen at 17 weeks' gestation with an acute abdomen. Maternal serum alpha-fetoprotein in a sample drawn 1 week previously revealed a value of 5.0 multiples of the median. At laparotomy, placenta percreta was discovered. This case of placenta percreta diagnosed in the second trimester was associated with an elevated maternal serum alpha-fetoprotein level. Physicians counseling patients with unexplained elevated maternal serum alpha-fetoprotein levels should include placenta accreta or percreta in the differential diagnosis and should maintain an awareness of its existence in patients with acute abdomen in pregnancy.

Adult↗
PubMed1991

Cytogenetic analysis of unfertilized human oocytes.

Cytogenetic studies were carried out on 180 oocytes that appeared unfertilized after in-vitro fertilization. The majority of the 135 that were informative had grossly haploid second meiotic metaphases, two were grossly diploid, and five had a variety of different abnormalities. Twenty-one oocytes were abnormally fertilized and included prematurely condensed sperm chromosomes. The frequency of this phenomenon varied according to the stimulation protocol, those oocytes maturing longer in vivo showing less propensity to abnormal fertilizations. Thirteen per cent of the analysable haploid metaphases were hyperhaploid but none contained extra whole chromosomes. The extra components were a single chromatid (one case), or two single chromatids replacing a whole chromosome (four cases). The data suggest that the chromatids arose as a result of premature centromere division at meiosis I, and that this may be a major mechanism for trisomy formation rather than non-disjunction of whole bivalents at meiosis I, as generally believed.

Cells, Cultured↗
PubMed1988

Elevation of urinary norepinephrine/cortisol ratio in posttraumatic stress disorder.

We have previously reported the unusual combination of low urinary free cortisol levels with high urinary norepinephrine excretion in posttraumatic stress disorder (PTSD) patients in comparison with four other patient groups: major depressive disorder, endogenous type; bipolar I, manic; paranoid schizophrenia; undifferentiated schizophrenia. Cortisol levels alone did not distinguish PTSD from paranoid schizophrenia patients and norepinephrine levels alone did not distinguish PTSD from bipolar I, manic, patients. In further consideration of these findings, we have found that combining the values for the two systems in a norepinephrine/cortisol (N/C) ratio provides a measure that significantly distinguishes PTSD from all the other patient groups throughout the hospitalization period. The N/C ratio was more than twice as high in the PTSD group than in all the other patient groups in the first sample following hospital admission, in the mean sample during hospitalization, and in the last sample before discharge. The mean N/C ratio for the PTSD group was 2.54, compared with a mean of .99 for the other four groups, which ranged from .81 to 1.18. The diagnostic sensitivity was 78% and the specificity was 94% for correct classification of PTSD in our sample. These preliminary findings yield further encouragement for exploring multivariate strategies, using hormonal ratios or profiles, in an effort to increase the diagnostic sensitivity of neuroendocrine criteria in the assessment of psychiatric patients.

Combat Disorders↗
PubMed1987

Sustained urinary norepinephrine and epinephrine elevation in post-traumatic stress disorder.

Urinary norepinephrine and epinephrine levels (microgram/day) were measured at two-week intervals during the course of hospitalization in the following patient groups: post-traumatic stress disorder (PTSD); major depressive disorder (MDD); bipolar I, manic (BP); paranoid schizophrenia (PS); and undifferentiated schizophrenia (US). The mean norepinephrine level during hospitalization was significantly higher in PTSD (76 +/- 10.4 micrograms/day) than in BP (60.6 +/- 8.4 micrograms/day), MDD (41.2 +/- 4.7 micrograms/day), PS (33.4 +/- 4.9 micrograms/day) and US (34.3 +/- 5.9 micrograms/day) groups, according to Duncan's multiple range test, (F(4,39) = 6.94, p less than 0.0003). The norepinephrine elevations in the PTSD group were sustained throughout hospitalization. The only other group to show mean levels in this range was the BP group in the first sample after hospital admission. This finding supports prior psychophysiological studies indicating increased sympathetic nervous system activity in PTSD patients. The mean epinephrine level during hospitalization was also significantly higher in PTSD (22.7 +/- 2.4 micrograms/day) than in MDD (13.6 +/- 1.7 micrograms/day), PS (14.7 +/- 2.4 micrograms/day), and US (18.9 +/- 1.8 micrograms/day), but not higher than in BP (21.5 +/- 2.7 micrograms/day). The relationship of epinephrine levels among diagnostic groups was sustained throughout hospitalization. It appears likely that the main underlying mechanisms for elevations of both hormones are psychological, but further work will be required to establish the exact nature of these mechanisms.

Animals↗
PubMed1985

The norepinephrine-to-epinephrine ratio in patients with a history of suicide attempts.

Norepinephrine and epinephrine were measured serially in 24-hour urine collections from 99 male psychiatric inpatients with mixed diagnoses. The group was blindly divided into those with a previous history of at least one suicide attempt (N = 38) and those without such a history (N = 61). The ratio of norepinephrine-to-epinephrine levels was significantly lower in the group with a history of suicide attempts. The authors discuss the possibility that a low norepinephrine-to-epinephrine ratio is a risk factor for suicidal behavior.

Adult↗
PubMed1985

Long-term amitriptyline in chronic depression.

Medication was discontinued under a placebo-controlled, double-blind, six-month protocol with 17 chronically depressed patients who had been taking an average daily dose of 138 mg amitriptyline (AMI) for an average of 3.7 years. Only one of nine patients became depressed on active medication, while of the 15 patients receiving a placebo trial, 11 had a depressive recurrence at an average time of 9.3 weeks. These 11 were subsequently restarted on AMI, and responded similarly to the way in which acutely depressed patients respond, although the patients showed either a need for less AMI or decreased symptoms, compared to entry. Tolerance did not develop to anticholinergic side-effects during long-term medication. Twelve of the 15 patients on placebo showed a withdrawal reaction during the first few weeks of tapered AMI discontinuation which could be distinguished from recurrence of depression. This study suggests that the majority of patients on long-term antidepressant will suffer a recurrence of depressive symptoms when the medication is discontinued.

Amitriptyline↗
PubMed1984

Cross-national reliability study of a schedule for assessing personality disorders.

The inter-rater reliability of a schedule used to assess personality disorders was examined. The Personality Assessment Schedule (PAS) involves an interview with both the patient and a close informant and the ratings for the informant are given most weight in the final scoring. Videotaped interviews with 23 psychiatric patients, most of whom had a clinical diagnosis of personality disorder, and a close informant were scored by seven raters, four in the United Kingdom and three in the United States. Overall inter-rater reliabilities (using the intraclass correlation coefficient, RI) were generally good to excellent for each of the 24 personality variables tested, ranging between .66 and .94 for informants and between .51 and .91 for subjects. Corresponding reliability coefficients for overall mean PAS scores were .82 and .75, respectively. Consistent with these findings, there was little bias between the scores of American and British raters, although there was some tendency for American raters to score higher for the trait of eccentricity and lower for the trait of conscientiousness than was true for British raters. There was less bias for informants' ratings than for those of subjects. In a second set of analyses, it was shown that inter-rater reliability levels (using the Kappa statistic) were also good to excellent (.6 to .8) for the categorical diagnosis of personality disorder. These results, taken together, demonstrate that abnormal personality can be reliably assessed by both British and American raters.

Adolescent↗
PubMed1984

Assessing treatment response to the monoamine oxidase inhibitor isocarboxazid.

The response to the MAOI isocarboxazid was investigated in a two-phase protocol. Phase 1 was a double-blind, placebo-controlled study; Phase 2 was an open active medication trial for Phase 1 placebo patients who still met symptom criteria. In Phase 1, 60 male outpatients were randomly divided into placebo or active medication groups. Mean platelet MAO inhibition was 86% by Week 1, while significant symptomatic improvement was not seen until Week 3. In Phase 2, 16 of the symptomatic placebo patients were given an open trial on isocarboxazid; thus, 43 patients received a trial of active medication. Separation of responders (N = 26) from nonresponders (N = 17) by discriminant function analysis using 3 entry variables (platelet MAO activity, standing diastolic blood pressure, and psychomotor irregularity) accounted for 28% of the variance, with correct classification of 32 of the 43 patients.

Ambulatory Care↗
PubMed1982

Monoamine oxidase inhibitor-responsive depression.

Double-blind, placebo-controlled trials have documented the efficacy of some monoamine oxidase (MAO) inhibitors in treating certain depressed patients. This preliminary report of a 6-week, double-blind, placebo-controlled study of the MAO inhibitor isocarboxazid (Marplan) examines the time course of platelet MAO inhibition and treatment response, and describes symptoms that distinguish markedly improved from slightly improved responders. Thirty male outpatients, ages 28-64, randomly divided into placebo (n = 15) and active medication (n = 15) groups, were followed weekly. Medication was started at 20 mg daily and increased to achieve 90% platelet MAO inhibition. Data were analyzed for 24 patients who completed at least 3 weeks of the study. A clinician's global change rating at the study's conclusion showed that 12 of 13 patients (92%) in the active medication group improved, while 3 of 11 (27%) patients in the placebo group improved. Significant symptomatic improvement occurred in the active treatment group by week 3. Trends suggest that anxiety improved first (week 2), followed by depression (week 3), and finally cognitive outlook (week 6). Only minimal difficulties were observed with orthostatic hypotension, hypertensive crises, or other side effects. At baseline, the only significant difference between the markedly improved and slightly improved groups was greater psychomotor retardation in the markedly improved group. Trends suggest that the markedly improved group showed less depression, anxiety, sleep disturbance, and weight loss, fewer gastrointestinal complaints, and more helplessness and worthlessness.

Adult↗
PubMed1982

Neuroendocrine risk factors of suicidal behavior.

Three of 22 subjects in a study of neuroendocrine correlates of clinical change made serious suicide attempts, 2 of which were lethal. The suicidal subjects had significantly higher 24-hour urinary cortisol levels and significantly lower 24-hour urinary norepinephrine-to-epinephrine ratios than the nonsuicidal patients had. Although the cortisol finding confirms earlier reports, the norepinephrine-to-epinephrine ratio finding is new. The results support the concept that the clinical utility of neuroendocrine measures is enhanced by using a multihormonal profile.

Adult↗
PubMed1982

Recurrence of depression after discontinuation of long-term amitriptyline treatment.

In this study 10 of 17 patients receiving long-term amitriptyline treatment (average duration: 3.7 years, average dose: 138 mg) had their medication tapered and discontinued under double-blind conditions. Eight became depressed within 3 to 15 weeks. None of the 7 control subjects became depressed during the 6 months of the study. Those who became depressed also showed psychomotor retardation and sleep disturbance. Relief of longstanding anticholinergic side effects followed medication discontinuation. Some patients whose amitryptyline was discontinued experienced a mild withdrawal syndrome within the first 2 weeks, consisting of irritability, dream and sleep disturbance, and restlessness during the first few weeks.

Adult↗
PubMed1980

Platelet MAO and amitriptyline treatment.

Some tricyclic antidepressants have been reported to inhibit monoamine oxidase (MAO) activity in vitro in addition to blocking the reuptake of norepinephrine and/or serotonin. While the inhibition of MAO is reversible, platelet MAO activity in depressed patients responding to amitriptyline treatment has been reported to be reduced after drug treatment. In a reverse design, we measured platelet MAO activity and drug levels in patients chronically being treated with amitriptyline and again 2 and 4 weeks after stopping the medication. Although tricyclic drug concentrations were initially within the therapeutic range and undetectable on placebo treatment, platelet MAO activities were unchanged.

Amitriptyline↗