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Biomedical subjects

C J Richards

Publications and source records attributed to C J Richards.

At least 19 recordsLinked to original sources

Association between postpartum thyroid dysfunction and thyroid antibodies and depression.

OBJECTIVE: To define the relation between mood and autoimmune thyroid dysfunction during the eight months after delivery. DESIGN: Double blind comparison of the psychiatric status of women positive and negative for thyroid antibodies. Clinical examination and blood sampling for free triiodothyronine and thyroxine, thyroid stimulating hormone, and thyroid antibody concentrations at four weekly intervals. Psychiatric assessment at six, eight, 12, 20, and 28 weeks post partum. SETTING: Outpatient department of district hospital. PATIENTS: 145 antibody positive women and 229 antibody negative women delivering between August 1987 and December 1989. MAIN OUTCOME MEASURES: Thyroid status. Number of cases of mental ill health by the general health questionnaire, research diagnostic criteria, Hamilton 17 item depression scale, hospital anxiety and depression scale, and Edinburgh postnatal depression scale. RESULTS: Six weeks after delivery the general health questionnaire showed 62 (43%) antibody positive women and 65 (28%) antibody negative women had mental ill health (chi 2 = 8.18, p less than 0.005). Follow up of 110 antibody positive and 132 antibody negative women showed significantly greater depression by research diagnostic criteria in antibody positive women (47%) than antibody negative women (32%) regardless of thyroid dysfunction. Antibody positive women showed higher mean scores for depression on the Hamilton (6.01 v 3.89, p = 0.0002), Edinburgh (7.45 v 5.92, p = 0.031), and hospital depression scales (4.95 v 3.79, p = 0.003). CONCLUSION: Depressive symptoms are associated with positive thyroid antibody status in the postpartum period.

Autoantibodies

The sonographic appearances in postpartum thyroiditis.

During the postpartum period about 50% of women with circulating thyroid autoantibodies develop a transient autoimmune thyroiditis. To determine the sonographic appearances in postpartum thyroiditis (PPT), serial ultrasound (US) scans of the thyroid were performed in 135 postpartum women who were divided into three clinical groups: Group 1, 37 antibody positive subjects who developed PPT; Group 2, 28 antibody positive subjects in whom thyroid function remained normal; Group 3, 70 antibody negative controls. Thyroid hypoechogenicity was observed in 14/31 patients (45%) who were scanned between 4 and 8 weeks postpartum and who subsequently developed PPT (Group 1) compared with 4/24 patients (17%) in Group 2 (P less than 0.05) and 1/65 patients (1.5%) in Group 3 (P less than 0.001). In antibody positive patients, the positive predictive value of an abnormal scan during this period was 78%. Between 15 and 25 weeks postpartum thyroid hypoechogenicity was present in 32/37 patients (86%) in Group 1 compared with 11/28 patients (39%) in Group 2 (P less than 0.001) and 2/70 patients (3%) in Group 3 (P less than 0.001). Sonographic abnormality persisted beyond 32 weeks postpartum in 36/41 antibody positive patients (87%) who had exhibited thyroid hypoechogenicity earlier during the study and who had late scans. The characteristic US appearance in PPT is thyroid hypoechogenicity. The role of sonography in the prediction, diagnosis and follow up of patients with PPT is discussed.

Autoantibodies

The inhibitory effects of müllerian-inhibiting substance on epidermal growth factor induced proliferation and progesterone production of human granulosa-luteal cells.

This study was undertaken to determine if Müllerian-inhibiting substance (MIS) could block basal and/or epidermal growth factor (EGF)-induced proliferation and progesterone production by cultured human granulosa-luteal cells. Cells from follicles of individual patients were pooled, counted, and aliquoted into Ham's F-10 medium containing 10% MIS-free female fetal calf serum at 37 C in 95% air and 5% CO2. After assessing viability, cells were counted on days 4, 8, 12, and 16 of culture. EGF was added every other day at 0.2, 2, and 20 ng/mL beginning on culture day 4. The greatest stimulatory effect of EGF on cell proliferation was observed at 20 ng/mL on days 12 and 16. EGF increased progesterone production per cell after 4 days exposure, but this effect was lost after 8 days. Granulosa-luteal cells were cultured with 0.2, 2, and 20 ng/mL immunoaffinity purified recombinant human MIS (rhMIS) or conditioned medium from Chinese hamster ovary cells transfected with the human MIS gene, beginning on culture day 4. rhMIS demonstrated its greatest inhibitory effect on cell proliferation at 20 ng/mL on day 16. The rhMIS decreased progesterone production per cell after 4 days exposure, but only in the higher doses. Maintaining EGF at 20 ng/mL and varying rhMIS yielded significant reduction in EGF-mediated proliferation and progesterone production per cell at 2 and 20 ng/mL rhMIS. These experiments demonstrate rhMIS inhibits basal and EGF-stimulated human granulosa-luteal cell proliferation and progesterone production.

Adult

The independent effects of hyperandrogenaemia, hyperinsulinaemia, and obesity on lipid and lipoprotein profiles in women.

We performed this study to clarify the independent effects of hyperandrogenaemia, hyperinsulinaemia, and obesity on lipid and lipoprotein levels in women with hyperandrogenaemia (HA) and anovulation which we designated as the polycystic ovary syndrome (PCO). We examined fasting lipid, lipoprotein, sex hormone and insulin levels in 38 women (21 obese (ob), 17 non-obese (nob] with HA and anovulation (PCO) and 38 normal ovulatory women (21 obese, 17 non-obese), matched for age and weight. The women with PCO had significantly increased androgen levels compared to the normal women. However, total oestradiol levels were similar in the PCO and normal women. Mean fasting insulin levels and 2-h glucose levels (both P less than 0.001) were significantly higher in ob PCO women. There were significant decreases (P less than or equal to 0.01) in high-density lipoprotein (HDL) levels in both the obese groups (ob PCO and ob normal) compared to the non-obese (nob PCO and nob normal) groups. Otherwise, mean lipid and lipoprotein levels did not differ in the ob or the nob PCO women compared to the control groups. The correlations between sex hormone, lipid and lipoprotein levels differed in the four groups of women. After statistical adjustment for potential hormonal interactions, nob PCO women had significant positive correlations between testosterone and LDL levels (R = 0.51, P less than 0.05) and insulin and TTG levels (R = 0.61, P less than 0.01). Ob normal women had a significant positive correlation between oestrone and TTG levels (R = 0.44, P less than or equal to 0.05). We conclude that (1) PCO women are in a low to risk for CVD primarily because of the increased prevalence of obesity rather than the reproductive hormone abnormalities associated with this disorder. However, by their lipid profiles, the PCO women were still in a low to intermediate risk group for CVD.

Adolescent

A long-term follow-up of postpartum thyroiditis.

To investigate the long-term outcome of postpartum thyroiditis (PPT), 43 patients with PPT and 171 control women were evaluated 3.5 (range 2-4) years postpartum. Ten (23%) PPT patients were hypothyroid compared to none of the controls (P less than 0.001). Factors associated with the development of hypothyroidism were high antimicrosomal antibody titre measured at 16 weeks gestation (P less than 0.01), severity of hypothyroid phase of PPT, multiparity, and a previous history of spontaneous abortion. The presence of microsomal antibody but no PPT in one pregnancy did not prevent the occurrence of PPT in the next pregnancy in two patients and a further five patients had PPT in two successive pregnancies. There was no association between HLA haplotype, family history of thyroid disease, smoking or frequency of oral contraception, and the development of long-term hypothyroidism after PPT. It is concluded that permanent hypothyroidism is an important sequel to PPT and patients with PPT should be followed up appropriately.

Adult

Postpartum thyroid dysfunction and HLA status.

Nine-hundred-and-one women presenting in an antenatal clinic at the 60th week of pregnancy were tested for antithyroid antibodies. A group of 113 antibody-positive women and 108 antibody-negative age-matched controls were HLA typed and followed prospectively at 6-weekly intervals through pregnancy and for 12 months postpartum. Forty-five of the women developed biochemical evidence of postpartum thyroid dysfunction (PPTD) of whom 36 were antibody positive. Compared with a local control population (n = 600), and using multiplex analysis, there was a significant increase in the combinations HLA B8, DR3 and HLA A1, B8, DR3 from 22.5% to 40.0% (P less than 0.02) and from 18.6% to 35.6% (P less than 0.01) respectively in the women who developed PPTD. The well-recognized association of these haplotypes with other organ-specific autoimmune diseases provides further support for autoimmune events being implicated in the development of PPTD.

Autoantibodies

IgG subclass distribution and relative functional affinity of thyroid microsomal antibodies in postpartum thyroiditis.

An association between the development of postpartum hypothyroidism and high levels of IgG1 subclass microsomal (M) antibodies has been reported. Using an assay designed to detect reasonable levels of all the four IgG subclasses, we found no differences in the proportion of each IgG subclass in M antibodies of patients with postpartum hyperthyroidism or hypothyroidism compared with control postpartum patients with M antibodies but no thyroid dysfunction. However the total amount of M antibody of each IgG subclass was elevated above the controls in the patients with thyroid dysfunction. The relative functional affinity of M antibodies did not differ between controls and patients with hypothyroidism but declined 5 and 10-12 months after delivery compared to values at 2 months. These results do not support the suggestion that the amount of IgG1 subclass M antibodies particularly determines the course of postpartum thyroiditis. Rather, the total M antibody level, in all four subclasses, is associated with clinical outcome. Resolution of the disease, despite persisting M antibodies, may occur in part because the relative functional affinity of these antibodies declines after delivery.

Antibody Affinity

Basement membrane continuity in benign, premalignant and malignant epithelial conditions of the uterine cervix.

The pattern of basement membrane deposition in the uterine ectocervix was assessed in benign, premalignant and malignant conditions, using an indirect immunoperoxidase technique to detect laminin, an intrinsic basement membrane component. A semi-quantitative approach was used to assess the frequency of small breaks in the basement membrane. The cervical squamous epithelium in benign epithelial conditions has an almost completely continuous basement membrane, but the development of viral atypia or cervical intraepithelial neoplasia (CIN) is associated with the appearance of small basement membrane breaks. There is a correlation between increasingly severe CIN and increasing numbers of breaks, and there is a concurrent increase in the numbers of subepithelial inflammatory cells. The development of invasive neoplasm is associated with a sudden change to a fragmented pattern of basement membrane deposition, a finding which is of potential diagnostic use.

Basement Membrane

Post-partum thyroiditis can be painful.

A patient with post-partum thyroiditis is described. She was a 22 year old with a negative family history of autoimmune thyroid disease who was noted to have a high titre of antithyroid microsomal antibody during pregnancy. She developed mild hyperthyroidism 8 weeks post-partum but at 12 weeks she had a mildly painful enlarged thyroid gland. At 20 weeks post-partum she had severe thyroidal pain with dysphagia. The thyroid was exquisitely tender to palpation. She was treated with L-thyroxine and the pain resolved within 4 weeks. This is the first report documenting pain in the thyroid as a feature of post-partum thyroiditis.

Adult

Who are borderline patients?

"Borderline" is a term used with increasing frequency to describe certain difficult patients. It refers to a heterogeneous population of patients who tend to get involved in impaired doctor-patient relationships. Different areas of psychiatry have their own, often conflicting definitions of these disorders. Early trauma, neglect and genetic diatheses to axis I disorders commonly occur in the backgrounds of these patients. Most have a combination of factors. With the multiple different definitions and the potential for misuse of the term, it should be used with caution and with an understanding of what definition is being used. Treatment and prognostic implications need to be individualized.

Borderline Personality Disorder

Postpartum thyroid dysfunction in Mid Glamorgan.

A high prevalence of postpartum thyroid dysfunction has been reported in several countries, but there have been no systematic studies of its prevalence in Britain. Among a group of 901 consecutive, unselected pregnant women thyroid autoantibodies were detected in 117 (13%) at booking. The clinical course of postpartum thyroid dysfunction, factors associated with its development, and its likely prevalence were defined in 100 of these women with thyroid antibodies and 120 women with no such antibodies who were matched for age. None of the women had a history of autoimmune thyroid disease. Normal reference ranges for thyroid function during pregnancy and post partum were established in the 120 women negative for thyroid antibodies. On the basis of these observations postpartum thyroid dysfunction was observed in 49 (22%) of the 220 women studied, and the prevalence in the total group of 901 women was estimated to be 16.7%. Thyroid dysfunction, mainly occurring in the first six months post partum, was usually transient and included both destruction induced hyperthyroidism and hypothyroidism. The development of the syndrome was significantly related to smoking more than 20 cigarettes a day and the presence of thyroid microsomal autoantibodies at booking. Of the 16 women with a family history of thyroid disease in whom thyroid microsomal autoantibody activity was detectable at booking, 11 developed thyroid dysfunction. Age, parity, presence of goitre at presentation, duration of breast feeding, and the sex and birth weight of the infant were not associated with the development of postpartum thyroid dysfunction. The mood changes experienced by women post partum may in part be associated with altered thyroid function during this time.

Adult

Comparison of magnetic resonance imaging and ultrasound in evaluating follicular and endometrial development throughout the normal cycle.

A prospective study was undertaken to evaluate and compare magnetic resonance imaging (MRI) and ultrasound (U/S) in monitoring follicular and endometrial development during the normal menstrual cycle. Results of MRI, U/S, estradiol (E2), and progesterone were obtained from five ovulatory volunteers on days 4, 8, 12, 16, 20, and 24 of the cycle. On U/S, all the women had only one dominant follicle, whereas MRI was able to detect a secondary cohort of follicles in three of five volunteers. Endometrial development on U/S and MRI showed similar patterns of growth with an increase on MRI from 5.8 +/- 1.1 mm on day 4 to a mean peak of 10.3 +/- 1.7 mm on day 24. A distinct feature of MRI was the demonstration of a junctional zone (JZ), which has a pattern of growth that resembles that of the endometrium, with accelerated growth from day 8 to day 16 (5.1 +/- .7 mm to 6.7 +/- .7 mm). The JZ corresponds anatomically to the distribution of the arcuate vessels and may therefore represent changes in blood supply to the endometrium. MRI, similar to U/S, is noninvasive and does not involve any radiation exposure but provides new information on uterine changes in the normal cycle. At present, its clinical applications are limited.

Adult

Fetal breathing movements and fetal distress.

Twenty-seven pregnancies were monitored by antenatal cardiotocographs, daily fetal movement counts and an assessment of fetal breathing activity by real time scanning, and the results of these tests were related to the development of fetal distress during the first stage of labour. The proportion of time during which fetal breathing movements were present, determined over only a short period of time, was found to be a useful predictor of fetal behaviour during a labour.

Female

Bicarbonate hemodialysis using a sorbent regenerative system.

In light of the concern about the use of acetate in dialyzate a simplified means of performing acetate-free hemodialysis has been developed using the sorbent regenerative system (RED). Fifteen sorbent bicarbonate hemodialyses free of acetate were performed on two patients for 4 or 6 hours. The initial dialyzate mixture contained 135 mEq/l NaHCO3 only. The infusate cations of K, Ca and Mg were in the form of chloride salts. A 30-minute titration of the sorbent cartridge with the bicarbonate dialyzate was necessary to release the excessive hydrogen ion from the cartridge which allowed the dialyzate bicarbonate to stabilize. The dialyzate Na fell during titration but rose during dialysis. The dialyzate Cl rose throughout titration and dialyses. The plasma bicarbonate rose significantly by the end of 4 and 6 hour dialyses. The blood pO2 and pCO2 did not change during dialysis and a significant rise in blood pH resulted. We conclude that bicarbonate dialysis is feasible and relatively easily accomplished in the sorbent system.

Bicarbonates

Inadequate removal of methanol and formate using the sorbent based regeneration hemodialysis delivery system.

The sorbent based hemodialysis delivery system was shown to be ineffective for the treatment of methanol intoxication. Clinical and in vitro studies showed rapid saturation of the sorbent cartridge for methanol and formate adsorption. Methanol and formate clearances were four fold less than achieved with the recirculating single pass delivery system. The sorbent delivery system should not be used for methanol intoxication.

Formates