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Biomedical subjects

B G Stuckey

Publications and source records attributed to B G Stuckey.

At least 19 recordsLinked to original sources

What is the optimal treatment for hypothyroidism?

Standard treatment of primary hypothyroidism is with thyroxine, with the aim of relieving symptoms and bringing the serum TSH (thyroid-stimulating hormone) concentration to within the reference range. Recent research suggests that in some patients symptoms of hypothyroidism persist despite standard thyroxine replacement therapy. The optimal treatment of these patients is not known. Adjusting the thyroxine dose until the serum TSH concentration is in the lower part of the reference range (eg, 0.3-2.0 mU/L) may be beneficial. Animal studies and a single small clinical trial suggest that a combination of thyroxine and T3 (triiodothyronine), rather than thyroxine alone, may be required for optimal thyroid replacement therapy. Further research is needed to determine why some patients appear to have a suboptimal response to thyroxine, and whether combined thyroxine/T3 treatment is preferable to thyroxine alone in these patients.

Aged↗

The biochemical and clinical course of postpartum thyroid dysfunction: the treatment decision.

OBJECTIVE: To follow the clinical and biochemical course of a cohort of women who had postpartum thyroid dysfunction (PPTD) at 6 months postpartum and to examine the treatment practices of general practitioners and endocrinologists in the setting of PPTD. DESIGN: Prospective longitudinal study. SETTING: Metropolitan, Perth, Australia. PARTICIPANTS: Eighty-six Caucasian women who were identified to have PPTD at 6 months postpartum in a cross-sectional study of 748 women. MAIN OUTCOME MEASURES: Characteristics of the clinical and biochemical course of PPTD and documentation of the treatment practices and factors influencing treatment of PPTD by general practitioners and endocrinologists. RESULTS: Sixteen of 86 women (19%) were receiving treatment at 9 months postpartum and by 30 months postpartum 27% of women had received treatment for PPTD. Fifty-one percent of those not treated were biochemically euthyroid at 9 months, although, for those with hypothyroid biochemistry at 6 months, the median TSH at 18 months was at the upper limit of the reference range. Thyroid peroxidase antibody titre fell over the 2 years of follow-up. There was no significant change in clinical parameters over the study. Forty-nine percent of endocrinologists and 73% of general practitioners reported that they required clinical signs or symptoms before initiating treatment for hypothyroid PPTD. CONCLUSIONS: In a cohort of women with postpartum thyroid dysfunction, a quarter received treatment. Elevated TSH in untreated women does not completely return to the normal median. The role of clinical assessment in treatment decision-making differs between primary care physicians and endocrinologists. A case is made for the early Institution of permanent thyroxine replacement in women with postpartum thyroid dysfunction, elevated TSH and positive thyroid antibodies.

Chi-Square Distribution↗

Bisphosphonate therapy for Paget's disease in a patient with hypoparathyroidism: profound hypocalcemia, rapid response, and prolonged remission.

Bisphosphonate treatment for severe Paget's disease leads to hypocalcemia followed by a secondary hyperparathyroid response to restore normocalcemia. A case is presented of a 60-year-old woman with polyostotic Paget's disease and postsurgical hypoparathyroidism. In 1993 her Paget's disease--alkaline phosphatase (ALP), 1260 U/liter (35-135 U/liter), and fasting urinary hydroxyproline excretion, 13.7 micromol/liter GF (0.4-1.9 micromol/liter)--was treated with intravenous pamidronate. Symptomatic hypocalcemia followed the first 60-mg dose, requiring large doses of calcium supplementation and calcitriol. Pamidronate therapy to a total dose of 360 mg was followed by rapid and prolonged remission with indices of bone turnover in the normal range within 2 months and persisting for at least 19 months after treatment. In 1999 relapse of Paget's disease--ALP, 511 U/liter (35-135 U/liter), and fasting urinary deoxypyridinoline/creatinine 53.1 micromol/mol (5-27 micromol/mol)--was treated with alendronate, 10 mg daily. Symptomatic hypocalcemia occurred again, requiring increased calcium and calcitriol therapy. Indices of bone turnover were within the normal range 9 weeks after the start of therapy. These responses were significantly more rapid and sustained than those observed in euparathyroid subjects. This case suggests that the lack of parathyroid response may modify the response to bisphosphonates by: (a) increasing intrinsic uptake of bisphosphonate into the pagetic skeleton, allowing response to a smaller dose; (b) increasing duration and severity of hypocalcemia after bisphosphonate therapy; and (c) removing the hyperparathyroid drive to reactivation of pagetic osteoclasts, leading to a prolonged remission. These observations have implications for optimizing bisphosphonate therapy both in Paget's disease and in osteoporosis.

Alendronate↗

Erectile dysfunction, sildenafil and cardiovascular risk.

Cardiovascular risk factors are commonly associated with erectile dysfunction and should be identified and treated. Patients with cardiovascular diseases should be assessed and counselled regarding their fitness for sexual activity. The danger of concurrent use of sildenafil and nitrates under any circumstances, regardless of age and sex, must be highlighted at all levels of the community. Sildenafil is absolutely contraindicated in patients receiving treatment with long-acting nitrates for ischaemic heart disease. Patients who need sublingual short-acting nitrates infrequently should not be precluded from taking sildenafil, provided they are aware that sildenafil is not to be taken within 24 h of taking the nitrate.

3',5'-Cyclic-GMP Phosphodiesterases↗

Calcium absorption in postmenopausal osteoporosis: benefit of HRT plus calcitriol, but not HRT alone, in both malabsorbers and normal absorbers.

In a randomized trial involving 71 postmenopausal osteoporotic women with vertebral compression fractures, radiocalcium absorption studies using the (45)Ca single isotope method (alpha) were performed at baseline and after 8 months of treatment with either continuous combined hormone replacement therapy (HRT, as piperazine estrone sulfate 0.625-0.937 mg daily +/- medroxyprogesterone acetate 2.5 mg daily depending on uterine status) or HRT plus calcitriol 0. 25 microg twice daily. A calcium supplement of 600 mg nocte was given to only those women who had a daily calcium intake of less than 1 g per day at baseline, as assessed by recalled dietary intake. There was a significant decrease [0.74 (+/- 0.35 SD) to 0.58 (+/- 0. 22), Dalpha = -0.17 (+/- 0.26), p<0.0005] in alpha at 8 months compared with baseline in the HRT-treated group, but a significant increase [0.68 (+/- 0.31) to 0.84 (+/- 0.27), Dalpha = +0.16 (+/- 0. 30), p<0.003] in the HRT-plus-calcitriol treated patients, resulting in alpha being significantly higher after 8 months in the latter group than in the HRT-only group. Although 72% of the patients had been supplemented with calcium between the first and second studies, separate analyses revealed that the change in calcium intake had not affected the result. Further breakdown of the groups into baseline 'normal' absorbers (alpha >/=0.55) and 'malabsorbers' (alpha <0.55) revealed that alpha decreased with HRT treatment only in the normal absorbers, and remained stable in the malabsorbers. Conversely, following HRT plus calcitriol treatment, alpha increased only in the malabsorbers, the normal absorbers in this group remaining unchanged. In conclusion, our data show that HRT, of the type and dose used in this study, did not produce an increase in absorption efficiency; it was in fact associated with a fall. Increased absorption efficiency cannot be achieved unless calcitriol is used concurrently, and then only in patients with malabsorption. Calcitriol also had a significant effect in normal absorbers in that it prevented the decline in alpha seen with HRT alone, and thus should be considered in all patients with postmenopausal osteoporosis treated with HRT.

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Erectile dysfunction in general medicine practice: prevalence and clinical correlates.

Erectile dysfunction (ED) is a common problem in general medical practice affecting especially the elderly and those with cardiovascular disease and diabetes mellitus. A study was undertaken by questionnaire distributed to consecutive adult male attendees at 62 general medical practices. 1240 completed questionnaires were available for analysis. The mean age of participants was 56.4y (range 18-91 y). 488 men (39.4%) reported ED: 119 (9.6%) 'occasionally', 110 (8.9%) 'often', and 231 (18.6%) 'all the time' (complete ED). Among 707 men aged 40-69y 240 (33.9%) reported ED and 84 (11.9%) had complete ED. The prevalence of complete ED increased with age, rising from 2.0% in the 40-49 y age group to 44.9% in the 70-79 y age group. Only 11.6% of men with ED had received treatment. Hypertension, ischaemic heart disease, peripheral vascular disease and diabetes mellitus were frequently associated with ED. 40% of diabetic men aged 60 y or older had ED all the time.

Adult↗

Use of transurethral alprostadil (MUSE) (prostaglandin E1) for glans tumescence in a patient with penile prosthesis.

The presence of communication between the emissary veins from the corpora cavernosa and the circumflex veins draining the corpus spongiosum makes it possible for the transfer of alprostadil (prostaglandin E1) in MUSE from the spongiosal compartment to the cavernosal compartment of the penis after its absorption through the urethral mucosa. This leads to engorgement and tumescence of the corpus spongiosum as well as the corpora cavernosa. Lack of tumescence of the glans penis and poor penile girth can be a cause for disappointment and frustration in patients following penile prosthetic surgery. MUSE was used successfully in a patient with a Dynaflex penile prosthesis to enhance the tumescence of the glans penis. It will be a useful adjunct for patients in similar circumstances.

Alprostadil↗

Paget's disease: acquired resistance to one aminobisphosphonate with retained response to another.

Twenty-five years after the first paper on etidronate in Paget's disease, there are few published papers that address bisphosphonate resistance as a specific clinical phenomenon. We report our data from two studies. Study 1 is a retrospective study of 20 patients with moderate to severe disease who were treated with intravenous (iv) pamidronate (221 +/- 18 mg [SEM]; range 60-360 mg), and after biochemical remission and relapse were retreated with generally larger iv dosage (293 +/- 28 mg; range 180-600 mg). The nadir bone turnover values were similar: plasma alkaline phosphatase (pAP) in 20 patients was 243 +/- 40 IU/l (mean +/- SEM) after the first course, and 267 +/- 44 IU/l after the second (reference range [RR] 35-135 IU/l). Likewise, fasting urinary hydroxyproline excretion (HypE) in 14 of the 20 patients was 4.5 +/- 1.1 micromol/LGF and 4.1 +/- 0.9 micromol/LGF, respectively (RR 0.40-1.92 micromol/LGF). However the minimum duration of biochemical remission was significantly shorter after the second course-10.9 +/- 1.7 months (first) and 5.6 +/- 0.9 months (second) (p < 0.03; Friedman's ANOVA n = 17). A subgroup of 10 patients who were followed for three courses showed a significantly higher pAP nadir in the third course. Study 2 is a prospective study of 40 patients, 23 previously untreated (NILPREV) and 17 previously treated with iv pamidronate (PAMPREV) and in biochemical relapse, who were randomly allocated to either oral alendronate 40 mg daily in 3 month units, or iv pamidronate 60 mg every 3 months. Treatment was continued until pAP and fasting urinary deoxypyridinoline/creatinine (Dpy/Cr) ratios (RR 5-27 micromol/mol) were both in the reference range, or a clear plateau in each marker developed. At baseline, there were no significant differences in either marker between the two NILPREV groups and between the two PAMPREV groups. Using log-transformed data, in NILPREV the pAP reductions were significant and similar over the first 6 months. However, although each Dpy/Cr reduction was also significant, the difference in responses favored alendronate (p < 0.015). In PAMPREV both markers showed no significant response to pamidronate; comparison showed a significantly greater response to alendronate (pAP p < 0.02; Dpy/Cr p < 0.002). Using two-way ANOVA, the pAP responses to alendronate in NILPREV and PAMPREV were similar and those to pamidronate were different (p = 0.034). The percentage of patients with both markers in the RR at 6 months or earlier were identical in NILPREV patients: alendronate 87% and pamidronate 87%. However in PAMPREV they were different: alendronate 83% and pamidronate 0% (p = 0.003). These data indicate: 1) patients treated with the same aminobisphosphonates for two courses show similar nadir values of bone turnover markers but a shorter remission time after the second course. In a third course the nadirs are significantly higher; and 2) in the alendronate/pamidronate comparison, NILPREV and PAMPREV patients showed similar pAP responses to alendronate, but significantly different responses to pamidronate. Thus, patients showing acquired partial resistance to one aminobisphosphonate (usually after two or more previous courses) are still capable of remission after exposure to another compound of the same class.

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Prevention of appendicular bone loss in Paget's disease following treatment with intravenous pamidronate disodium.

It has been shown previously that intravenous pamidronate treatment for severe Paget's disease is associated with appendicular bone loss. This 2 year study was designed to determine whether cotreatment with calcitriol and a calcium supplement would prevent this. Intravenous pamidronate was used to treat 49 patients with symptomatic Paget's disease. Patients were stratified into two groups of differing biochemical severity based on hydroxyproline excretion (HypE) expressed as micromoles per liter of glomerular filtrate (GF): (1) a severe group with HypE > 10 micromol/L GF; and (2) a moderate group with HypE 5-10 micromol/L GF. Within each group, patients were randomly allocated to receive supplements of calcium and calcitriol (supplemented) or no supplements (unsupplemented) after initiation of pamidronate therapy. The severe group received 360 mg of pamidronate as six doses of 60 mg once weekly and the moderate group received 240 mg as four weekly doses of 60 mg. Patients were followed for 24 months following treatment and had serial bone densitometry of the forearm measured as well as urine and plasma biochemistry. When the groups were combined, the unsupplemented patients showed a decrease in bone mineral density (BMD) at the ultradistal forearm site, which persisted to 24 months. Those supplemented with calcium and calcitriol showed an increase in BMD and the difference between the two groups was significant at all times posttreatment (p < 0.03). When the groups were analyzed separately, those with moderate disease again showed significant differences in BMD between supplemented and unsupplemented patients at all timepoints. In the severe group, the differences did not reach statistical significance due to smaller patient numbers. Similar changes in BMD were also observed at the forearm shaft site. When serial parathyroid hormone (PTH) levels (with the moderate and severe groups combined) were plotted against time since treatment the rise in PTH in the supplemented patients was less than the rise in the unsupplemented patients (p < 0.04). These results suggest that forearm bone loss after intravenous pamidronate treatment for moderate-to-severe Paget's disease can largely be prevented by administration of calcium and calcitriol. The mechanism may be a blunting of the secondary hyperparathyroidism that occurs after intravenous pamidronate. These findings may have wider application in moderate-to-severe Paget's disease treated with other bisphosphonates.

Administration, Oral↗

Postpartum thyroid dysfunction: clinical assessment and relationship to psychiatric affective morbidity.

OBJECTIVE: Postpartum thyroid dysfunction (PPTD), diagnosed using biochemical criteria, is usually transient with a wide range of reported prevalence rates. The specific clinical and psychiatric morbidity associated with PPTD is still uncertain. The aims of the study were to determine the point prevalence of PPTD in Australian women at 6 months postpartum and to assess the specific clinical and psychiatric morbidity in these women. DESIGN: Women who were Caucasian, aged 20-45 years and 4.5-5.5 months postpartum, were randomly selected and invited into the study. The respondents were assessed for biochemical and psychiatric morbidity. PPTD for this study was defined as TSH or free T4 outside the adult reference range. A double blind clinical assessment of PPTD women and their matched controls used standardized clinical hypo- and hyperthyroid clinical indices. PATIENTS: From the total randomly selected sample size of 1816 women, 748 participated. MEASUREMENTS: Biochemical measurements were serum TSH, free T4, microsomal antibody (MsAb) and thyroid peroxidase antibody (TPOAb), and thyroid receptor antibodies (only in women with low TSH). Psychiatric assessment involved screening all participants using the General Health Questionnaire 28, followed by classifying and quantifying severity of cases using DSM-III-R categories for depression and anxiety. Clinical signs and symptoms of hypo- and hyper-thyroidism were measured using weighted standardized indices. Thyroid size was assessed by palpation. Achilles tendon reflex time was measured by photomotograph. RESULTS: The prevalence of PPTD in the participants was 11.5% (95% CI 9.2-13. 8%), giving a minimum prevalence for the randomly selected sample of 4.7% (95% CI 3.7-5.7%). In the PPTD women, 54% had an elevated TSH, 30% had a suppressed TSH and the remainder had a low fT4 and normal TSH. Positive thyroid autoantibody titres in the PPTD group were 46. 5% for microsomal antibody (MsAb) and 63.9% for thyroid peroxidase antibody (TPOAb), and in the non-PPTD group were 1.7% and 4.9%, respectively. The 6 month point prevalence rates of depression, generalized anxiety disorder and panic disorder and/or agoraphobia were 9.4%, 1.4% and 3.1%, respectively. No relationship was found between PPTD status and the diagnosis of current depression or between thyroid antibody status and current depression. In women who were diagnosed as anxious at the time of assessment, the number of anxiety symptoms was higher in the PPTD group (P < 0.05). There was no difference in signs and symptom scores for the hypo- and hyper-thyroid clinical indices between PPTD women and their controls. CONCLUSION: This study has shown a high prevalence of postpartum thyroid dysfunction but there was no difference in the clinical and psychiatric signs and symptoms between cases and controls. In the social, psychological, physical and endocrine setting of the postpartum period, women with postpartum thyroid dysfunction are identifiable by the attending physician only by their abnormal thyroid function tests.

Adult↗

High prevalence of normal total calcium and intact PTH in 60 patients with proven primary hyperparathyroidism: a challenge to current diagnostic criteria.

BACKGROUND: Others have reported a clear distinction between patients with primary hyperparathyroidism (PHPT) and normal subjects using the intact PTH (iPTH) assay. AIM: We reviewed our last 60 surgically proven cases of PHPT, who had adequate preoperative biochemical assessment, to determine the usefulness of the iPTH assay, ionised calcium and other biochemical criteria in differentiating between normal subjects and patients with PHPT. METHODS: We conducted a retrospective cross-sectional study of all patients with surgically proven PHPT who had been referred to Sir Charles Gairdner Hospital, Perth, Western Australia for preoperative biochemical assessment. All cases had fasting preoperative blood and urine samples collected for ionised calcium, plasma total calcium, albumin, urine calcium excretion, renal phosphate threshold and iPTH. RESULTS: Fifty cases had a single or double adenoma and ten had hyperplasia. All except one had ionised hypercalcaemia but only 47 (78%) had an elevated corrected total calcium (cCa). Therefore 13 cases (22%) had a normal cCa and five of those patients (8%) had both an iPTH and cCa within the reference range. Forty-nine (82%) had an elevated ionised calcium (iCa) and iPTH; the remaining 11 (18%) had an iPTH within the reference range. Of this latter 18%, ten (91%) had a low renal phosphate threshold and five (45%) had significant renal calcium conservation: all 11 cases had at least one abnormality in the renal handling of calcium or phosphate and all normalised their plasma calcium postoperatively (ionised and corrected total calcium). CONCLUSIONS: One in five patients with proven PHPT have a non-elevated cCa and/or intact PTH. Ionised calcium should be measured in all suspected cases. Additional studies of renal calcium and phosphate handling are helpful to establish a diagnosis where any uncertainty exists.

Adult↗

Penile fibrosis in intracavernosal prostaglandin E1 injection therapy for erectile dysfunction.

Penile fibrosis (PF) may be a complication of intracavernosal injection therapy (ICI). It has been well documented as a side effect of papaverine, but there have been few reports associating penile fibrosis with prostaglandin E1 (PGE1, Alprostadil). Many authors did not find fibrotic changes in the penis while others reported penile fibrosis as a complication of intracavernosal PGE1 in only 0.76-2.1% of their patients. Recent studies, however, suggest that the incidence may be as high as 15%. Three hundred consecutive patients who returned to our Institute for repeat prescription of PGE1 were asked about penile curvature and deformity and the penis was examined for fibrotic change. Twenty-two were excluded because of concurrent or previous use of papaverine and/or phentolamine, 30 patients had pre-ICI evidence of fibrotic change and 3 had incomplete data. Of the remaining 245 patients, 57 (23.3%) were found to have penile fibrosis. These men, mean age 62 y (21-79), had been self injecting an average of 5.2 times per month (1-16) for an average period of 29.2 months (2-86). The mean dose of PGE1 used was 13 micrograms (2-60) and an average of 65.6 micrograms of PGE1 (3-360) was used per month. The mean total number of injections was 142.4 (8-810) and the mean total amount of PGE1 1703 micrograms (105-11,520). Penile fibrosis is hence a significant complication of intracavernosal PGE1 therapy. It is mandatory to examine patients methodically for fibrotic changes in the penis prior to commencement of treatment and at subsequent regular reviews. Patients should be specifically warned of the possibility of penile fibrosis and should be instructed on self examination so that they may report early changes if and when these occur.

Adult↗

Clinical, biochemical, hematologic, and radiographic responses in Paget's disease following intravenous pamidronate disodium: a 2-year study.

An intravenous dosage schedule using pamidronate disodium, based on biochemical severity, was used to treat 71 patients with Paget's disease who had no previous bisphosphonate treatment. Disease severity was stratified by fasting hydroxyproline excretion (HypE): Group (Gp) I (mild disease; HypE < 5.0 mumol/LGF) received a total dose of 120 mg; Gp II (moderate; HypE 5.00-9.99) received 180 mg; and Gp III (severe; HypE > or = 10) received 240 mg. Within each group patients were randomly allocated to receive daily 30 mg or 60 mg infusions. Observations for 2 years included pain scores, indices of bone turnover, and radiology of lytic lesions. There was no difference in biochemical responses, or in the percentage of patients with early fever, between the 30 mg and 60 mg daily subgroups; for convenience, 60 mg infusions are recommended. Neutrophils and total white cell counts were both significantly below baseline 4 days after the first infusion; lymphocytes were significantly reduced by day 2; and all three measures had returned to within the reference range by day 6. Remission was assessed at 6 months, when both plasma alkaline phosphatase (ALP) and HypE had reached stable nadirs. Increasing severity was associated with increasing resistance to suppression of HypE at 6 months to within the reference range: Gp I, 87%; Gp II, 44%; and Gp III, 0% (p < 0.0001 by chi-square test). Biochemical relapse at 2 years (defined as ALP 50% above the 6 month level) was also dependent on initial disease severity (Gp I, 6%; GpII, 39%; Gp III, 62%; p < 0.0005 by chi-square test). There was no association between time to relapse and either initial dose or log dose. Radiologic lytic lesions (in 22 patients) were all in remission at 3 months; however, relapse rates at 2 years appeared to be severity-dependent: Gp I, 13%; Gp II, 43%; and Gp III, 57% (n.s. by chi-square test). Remission rates based on a fall to < 50% of pretreatment of either HypE or ALP were more in accord with lytic lesion remission rates than were rates based on HypE falling to within the reference range. Pamidronate produced a significant reduction from baseline in Pagetic bone, Pagetic joint, and unrelated musculoskeletal pain in the first 6 months (p < 0.0001). From 0 months to 2 years the maintenance of improvement in bone pain (p < 0.005) and joint pain (p < 0.05) was significantly better than in unrelated pain. Pamidronate is a safe, welltolerated, and effective treatment for Paget's disease. In spite of larger dosage in severe disease, increasing severity was associated with resistance to normalization of biochemistry and a higher incidence of biochemical and radiological relapse at 2 years. Our current dosage recommendation would be for two 60 mg infusions for mild disease (Gp I); and four 60 mg infusions for moderate disease (Gp II). Severe disease (Gp III) remains a challenge; regardless of dosage, the majority of patients will be in relapse 2 years after a single course of treatment.

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The use of the vacuum erection device in the management of erectile impotence.

A retrospective survey was conducted to assess the use, efficacy and acceptance of the Vacuum Erection Device (VED) among 60 impotent men not satisfied with intracavernosal injection therapy. Forty three (72%) men filled out the questionnaires. Thirty nine (81%) of the men abandoned the device, the main reason being that 'it did not work'. One possible explanation for this was patient selection, testing the VED on men who had previously found injection therapy unsatisfactory. Patients' attitudes to the device were unfavourable overall. Sixty four percent of men had at least one minor side effect using the VED, the most common being discomfort. The role of the partner for men using this form of treatment is unresolved. In this study, the VED was no more effective than injections in overcoming erectile dysfunction, but the relative advantages of either treatment needs to be addressed in controlled clinical trials.

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