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Biomedical subjects

P Warner

Publications and source records attributed to P Warner.

At least 37 records · Page 2Linked to original sources
PubMed1994

Preferences regarding treatments for period problems: relationship to menstrual and demographic factors.

Beliefs about periods and hysterectomy and preferences regarding treatment for period problems were assessed in 362 women--patients referred for menorrhagia, premenstrual syndrome, or dysmenorrhea (n = 99, 102 and 56 respectively), and a control sample (n = 105). Overall, women were predominantly in favor of a treatment which normalized periods (89%) and which coincidentally provided reversible contraceptive effect (74%), while they marginally preferred a one-off operation to tablets. Preferences with regard to contraceptive effect of treatment, effect on periods and hypothetical treatment option were most strongly related to reproductive status (p < 0.00002), in that nulliparous or unsterilized women were least likely to rate as acceptable a treatment that affected their periods or fertility. The women's feelings about their periods and their evaluation of the utilitarian consequences of hysterectomy were most strongly related to their report of menstrual problem(s), with the potential benefits of an end to periods being most often affirmed by women reporting 'severe' menorrhagia, dysmenorrhea or multiple period problems. In contrast, women's evaluation of the reproductive consequences of hysterectomy were most strongly related to reproductive status, with nulliparous women and unsterilized parous women finding them least acceptable. Feelings about periods did not predict intentions with respect to periods, or treatment preferences, and in this regard the usefulness of menstrual attitudes is questioned.

Adult↗
PubMed1994

Selecting financial indices to measure critical path outcomes.

The implications of using broad-based DRG data versus more specific clinical data must be presented when implementing a hospital-based case management program. Administrators and nurse managers must collaborate when defining and applying appropriate financial indicators and implementing critical paths. Knowledge of patient populations and case types addresses both quality and cost.

Diagnosis-Related Groups↗
PubMed1992

Quinoline antifolate thymidylate synthase inhibitors: variation of the C2- and C4-substituents.

Modifications to the bicyclic ring system of the potent thymidylate synthase (TS) inhibitor N-[4-[N-[(2-amino-3,4-dihydro-4-oxo-6- quinazolinyl)methyl]-N-prop-2-ynylamino]benzoyl]-L-glutamic acid (1, CB3717) have led to the synthesis of a series of quinoline antifolates bearing a variety of substituents at the C2 and C4 positions. In general the synthetic route involved the coupling of the appropriate diethyl N-[4-(prop-2-ynylamino)benzoyl]-L-glutamate with a disubstituted 6-(bromomethyl)quinoline followed by deprotection using mild alkali. The compounds were tested as inhibitors of partially purified L1210 TS. As a measure of cytotoxicity, the compounds were tested for their inhibition of the growth of L1210 cells in culture. Good enzyme inhibition and cytotoxicity were found for compounds containing chloro, amino, or methyl substituents at the C2 position with chloro or bromo substituents at C4. The effect on enzyme inhibition of varying the N10 substituent of 2h was similar to that observed in the quinazolinone-containing antifolates, indicating that the quinoline compounds may be interacting with the enzyme in a similar way to the quinazolinones. Also, the introduction of a 2'-fluoro substituent into the benzoyl ring of several of the quinoline antifolates led to an increase in both TS inhibition and the inhibition of L1210 cell growth. These data demonstrate that the N3-H of the pyrimidine ring of the quinazolinone antifolates is not required for binding to TS if appropriate substituents are placed at the C2 and C4 positions of the bicyclic ring system.

Animals↗
PubMed1991

The relationship between perimenstrual depressive mood and depressive illness.

In a study of 144 women, mainly self-designated PMS sufferers, the premenstrual depression experienced was, apart from its shorter duration, quantitatively and qualitatively similar to major depressive disorder for a substantial proportion of subjects. The associations with previous history of depression were complex: the severity of premenstrual depression was related to previous history of postnatal depression, whereas its duration (i.e., whether it persisted through longer) was related to a history of treatment with antidepressants. Two independent dimensions are proposed. (i) A menstrual cycle-related factor which in vulnerable women can results in severe and disabling premenstrual dysphoria, and which may be aetiologically related to a subgroup of postnatal depression. (ii) In a minority of women a more general propensity for depressive illness evidence as a tendency for any premenstrual depression to be prolonged.

Adult↗
PubMed1991

Quinazoline antifolates inhibiting thymidylate synthase: 4-thio-substituted analogues.

We report the synthesis of four new 4-thio-5,8-dideazafolic acid analogues and a 4-(methylthio) analogue structurally related to the thymidylate synthase (TS) inhibitor N10-propargyl-5,8-dideazafolic acid. Three N10-propargyl-4-thio-5,8-dideazafolic acid analogues had C2 amino, hydrogen, and methyl substituents. A 4-thio and a 4-(methylthio) compound each with hydrogen at C2 and ethyl at N10 were also synthesized. In general, the synthetic route involved thionation of the appropriate 4-oxoquinazoline; the sulfur thus introduced was then protected by methylation. Further protection with a pivaloyl group was required for the quinazoline bearing a 2-amino substituent. The protected quinazolines were treated with N-bromosuccinimide and the resulting 6-(bromomethyl) compounds were then coupled to the appropriate N-monoalkylated diethyl N-(4-aminobenzoyl)-L-glutamate in N,N-dimethylacetamide with calcium carbonate as base. The 4-thio-5,8-dideazafolic acids were obtained by removal of the methylthio group with sodium hydrosulfide, followed by deprotection of the carboxyl groups with cold dilute alkali. For the compound containing a pivaloyl protecting group, hot dilute alkali was used. To obtain the 5,8-dideazafolic acid containing a 4-(methylthio) substituent, the corresponding diester was treated with lithium hydroxide which selectively deprotected the carboxyl groups. The five compounds were tested as inhibitors of L1210 TS. It was found that replacement of the 4-oxygen of the quinazoline moiety by sulfur did not alter the TS inhibition. However, the introduction of a methylthio substituent at position 4 severely impaired TS inhibition. All 4-thio compounds were less cytotoxic to L1210 cells in culture than their 4-oxo counterparts.

Animals↗
PubMed1991

Paternally inherited effects of gamma radiation on mouse preimplantation development detected by the chimera assay.

It has previously been shown that type B spermatogonia in male mice treated with 0.05 Gy of X rays undergo an alteration expressed by progeny embryos as a cellular proliferation disadvantage in a chimera assay. We wished to obtain information on the assay's detection limit to ionizing radiation and on the radiosensitive target in male germ cells. Male mice were briefly irradiated with 137Cs gamma rays at nominal absorbed doses of 0.0, 0.0015, 0.005, 0.010, or 0.05 Gy and then mated for the next 8 weeks to untreated females. Four-cell embryos from treated males (experimental embryos) were paired with FITC-labeled embryos from untreated males (control embryos) to form aggregation chimeras. The chimeras were cultured for 30-40 h and examined under phase-contrast and UV illumination for the number of unlabeled cells (from the experimental embryo) and total chimera cell number, which were then expressed as "proliferation ratios" (No. unlabeled cells/total chimera cell No.). Significant decreases in proliferation ratios were observed at postirradiation weeks 4, 6, and 7 for the 0.01-Gy dose group and at weeks 5-6 for the 0.05-Gy dose group. In addition, significantly lower ratios were observed with early and mid four-cell embryos, but not with late four-cell embryos. These results suggest that mouse male germ cells express a radiosensitive target(s) whose detection limit by the assay lies at an absorbed dose between 0.005 and 0.010 Gy for brief gamma irradiation and whose effect on embryonic cell proliferation might decay by the second cleavage.

Animals↗
PubMed1990

Factors related to self-reporting of the pre-menstrual syndrome.

Menstrual health questionnaires were completed by a self-selected sample of the readership of a woman's magazine (n = 5457). Sixty-one per cent of subjects described themselves as suffering from pre-menstrual syndrome (PMS) and this was largely corroborated by ratings of symptoms pre-menstrually, menstrually and post-menstrually for the most recent cycle. Mood symptoms were more strongly implicated than physical ones. Self-report of PMS was found to be modestly associated with aspects of parity and oral contraceptive use, but strongly and positively related to the duration of 'natural' menstrual cycles (i.e. uninterrupted by pregnancy or steroidal contraception) and to psychosocial stress. There were interactions among psychosocial factors and between psychosocial load and duration of natural cycles.

Adaptation, Psychological↗
PubMed1989

A comparison of double beta-lactam combinations with netilmicin/ureidopenicillin regimens in the empirical therapy of febrile neutropenic patients.

In a randomized trial ceftazidime plus piperacillin or azlocillin, and netilmicin plus piperacillin or azlocillin were used as initial empirical therapy in 202 febrile neutropenic episodes. Netilmicin plus azlocillin was the most effective combination with a clinical response rate of 81% in clinically and microbiologically documented infections compared with 63% for ceftazidime plus piperacillin. All of the episodes of Gram-negative bacteraemia treated with azlocillin responded compared with 43% of those treated with piperacillin. Gram-positive organisms accounted for 52% of all bacteriologically documented infections and 40% of the febrile episodes were treated with vancomycin for presumptive or documented Gram-positive infection. Patients treated with netilmicin had significantly more nephrotoxicity than those given the double beta-lactam combinations (14.8% vs 3.5%; P less than 0.05). However, this difference was not shown in those patients who did not receive concurrent vancomycin or amphotericin. The double beta-lactam combinations were associated with more hypokalaemia (58.2% vs. 37.7%; P less than 0.05) and more colonization with yeasts (24% vs. 10.4%; P less than 0.05) but there was no evidence that their use was associated with prolongation of neutropenia. These results indicate that ceftazidime plus a ureidopenicillin would be adequate empirical therapy in situations where the concomitant use of nephrotoxic agents precludes the use of aminoglycoside containing combinations.

Adult↗
PubMed1989

Reversal of desferrioxamine induced auditory neurotoxicity during treatment with Ca-DTPA.

Auditory neurotoxicity occurred in 13 (26%) of 50 evaluable patients receiving long term desferrioxamine chelation. In five of these patients, all of whom were receiving high doses of desferrioxamine, the toxicity caused deafness. These five patients were treated with subcutaneous calcium diethylene triamine pentacetic acid (Ca-DTPA) with zinc supplements instead of desferrioxamine, and their hearing improved during periods of seven to 19 months. Their serum ion concentrations remained unchanged. We suggest that all patients receiving long term desferrioxamine should have audiometric assessments at 6-12 monthly intervals. Ca-DTPA with oral zinc supplements should be considered as alternative to desferrioxamine as an iron chelating treatment in patients with auditory neurotoxicity.

Adolescent↗
PubMed1988

Mood, sexuality, oral contraceptives and the menstrual cycle.

4112 women completed a retrospective questionnaire indicating when during their last menstrual cycle they felt their well-being and sexual interest to be at their best and worst. The commonest pattern was for well-being to be lowest during the premenstrual and highest during the postmenstrual week. Sexual interest was strongly associated with well-being, suggesting that variations of well-being have a powerful effect on sexuality in the majority of women. Oral contraceptive users, though broadly similar in their reported pattern, were less likely to show peaks and troughs of well-being and highs and lows of sexual interest. This was most evident in the subgroup of monophasic pill users who showed the least tendency to variations in both well-being and sexual interest, and a greater tendency to show either peaks or troughs of well-being during menstruation. Triphasic pill users were intermediate between monophasic and non-pill users.

Adult↗
PubMed1987

Pulsatile LH secretion during the preovulatory surge in the ewe: experimental observations and theoretical considerations.

The secretion of LH during the preovulatory surge has been shown to be pulsatile in several species. We confirmed this phenomenon in intact ewes in two experiments in which we studied the LH surge in detail. In the first experiment, the levels of LH were measured in discrete blood samples taken every 5 min around the onset of oestrus in 5 intact Merino ewes. For 2-5 h immediately prior to the onset of the surge, the median pulse interval was 17.5 min (range 10-55) and the median pulse amplitude was 0.70 ng/ml (range 0.28-1.33 ng/ml). During the ascending phase of the surge, the pulse interval did not change significantly (median 18.3 min) but the median pulse amplitude increased 20 fold to 18.0 ng/ml. During the descending phase, the median pulse interval was 22.5 min and the median amplitude decreased to 8.1 ng/ml (P less than 0.005). During the surge, intervals of 10 min and amplitudes over 30 ng/ml were common. In the second experiment with 2 oestrous Romanov x Préalpes-du-Sud ewes, blood was withdrawn continuously and samples were pooled over 4 min periods for 19-27 h. In the resulting profiles, individual pulses were better defined but the pulse frequencies (median interval 15.2 min during ascending phase) and amplitudes (median 35.0 ng/ml) varied in similar fashion to the Merinos. Using a simple mathematical description of pulsatile secretion, and assuming that LH is only released in pulses, we also found that the high concentrations normally achieved during the surge can only be explained by pulse frequencies and amplitudes well above those normally observed in other physiological situations, including the follicular phase or following ovariectomy. These findings strongly support the experimental data and the combined results of the two studies suggest that the initiation and execution of the LH surge is probably accomplished by changes in the amplitude of pulses. A high frequency is also essential and our data suggest that it may be established some time before the onset of the surge proper, but this requires confirmation. Respectively, the changes in amplitude and frequency reflect the pituitary and hypothalamic components of the positive feedback mechanism. The theoretical study suggested that a change in clearance rate could also contribute to the surge and this awaits further investigation.

Animals↗
PubMed1987

The use of an LHRH agonist, buserelin, in the long-term management of premenstrual syndromes.

Buserelin, an LHRH agonist, was given by nasal spray to 20 women with premenstrual syndrome. In 10 women benefits were such that they continued treatment for periods varying from 5 to 15 months. There were significant improvements in mood and physical symptoms, and side-effects such as hot flushes were mild. The remaining 10 women were all made worse by the spray and stopped it within 2 months. Ovulation was blocked in all women though six showed evidence of ovulation during the first treatment month, and two women later in treatment. Of the long-term group, six eventually became amenorrhoeic, and four continued to menstruate. There was a significant improvement in symptoms during treatment in the long-term group. Physical symptoms continued to be worse before any menstrual bleeding. Mood change lost its relationship to menstruation. The adverse effects in the short-term group were sometimes severe and it is necessary to identify the characteristics of the woman who are likely to show such reactions before recommending this treatment for more general use.

Adult↗
PubMed1986

Sex therapy outcome research: a reappraisal of methodology. 1. A treatment study of male sexual dysfunction.

In the first section a controlled treatment study of male sexual dysfunction is described. 'Unlucky' randomization of subjects yielded treatment groups which differed with respect to variables of possible prognostic significance. Hence the results are largely uninterpretable. In the second section the predominantly negative or inconsistent findings in sex therapy outcome research are reviewed and methodological problems, such as those described in the first part, are considered as possible reasons for these negative findings. The interrelationships are explored between small treatment groups, prognostic variability, bias, power, and small expected treatment effects. A strategy for future research is proposed, with particular emphasis on the recognition and use of relevant prognostic indices.

Combined Modality Therapy↗
PubMed1985

Assessment of erectile function in diabetic and non-diabetic impotence by simultaneous recording of penile diameter and penile arterial pulse.

Simultaneous monitoring of penile diameter and penile arterial pulse during laboratory-based erotic stimulation with film and fantasy, has been used to compare diabetic and non-diabetic impotent men with non-impotent controls. The degree of erection to erotic film distinguished between organic and psychogenic aetiologies. The diabetic group showed smaller penile pulse amplitude changes than the other two groups. Amongst the diabetics, severe autonomic neuropathy was associated with impaired erectile and penile pulse amplitude responses. Severe retinopathy was associated with smaller baseline penile pulse amplitude as well as smaller amplitude response. Blood pressure response to erotic stimuli did not differ between the three groups. An analysis of the temporal relationship between penile diameter change and pulse amplitude change revealed differences between the groups that may prove to have diagnostic as well as theoretical implications.

Adult↗
PubMed1985

Relationship between the movement characteristics of human spermatozoa and their ability to penetrate cervical mucus and zona-free hamster oocytes.

In a group of normospermic donors exhibiting hamster oocyte penetration scores of 0-100%, multiple regression analysis indicated that only 20% of the variation in fertilizing potential could be explained by differences in the movement characteristics of the spermatozoa following incubation in vitro. When the movement characteristics of the spermatozoa in semen were considered this figure was reduced to 6.8% as a result of significant differences in the motility patterns exhibited by the seminal and post-incubation sperm populations. A much closer relationship was observed between the movement characteristics of human spermatozoa in semen and their ability to penetrate cervical mucus. When differences in motile sperm densities were taken into account, 76% of the variation in cervical mucus penetration could be accounted for by the existence of linear correlations with certain aspects of sperm movement (multiple R = 0.874). Of the various attributes of sperm motility measured (linear velocity of progression, frequency of rotation, amplitude of sperm head displacement, % rolling and % yawing), a failure to exhibit an adequate amplitude of lateral sperm head displacement was consistently found to be the most significant factor determining the success of sperm-cervical mucus interaction (R2 = 0.53).

Animals↗
PubMed1984

Pulsatile release of LH and oestradiol during the periovulatory period in women.

Blood was collected every 8 h in five women from Day 10 of the menstrual cycle for 5-7 d for the measurement of LH, oestradiol and progesterone. In all women the LH surge started between 2400 and 0800 h before there was any significant decline in the concentration of oestradiol. In order to investigate the pulsatile secretion of LH and estradiol during the mid-cycle surge, blood samples were collected every 5 min for up to 5 h. Immediately before and during the LH surge there were numerous episodic pulses of LH with an interpulse interval (44 +/- 7 min) very similar to that observed in two women with hypergonadotrophic hypogonadism (48 min). The concentration of oestradiol fluctuated in a similar manner although it was not always possible to relate each pulse of oestradiol to a corresponding pulse of LH. The mid-cycle surge of LH is characterized by frequent pulses of high amplitude. These results are compatible with the view that the positive feedback effect of oestradiol is due not only to enhanced sensitivity of the anterior pituitary to LHRH but also to the high frequency of LHRH pulses released from the hypothalamus.

Adult↗