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Biomedical subjects

M Powell

Publications and source records attributed to M Powell.

At least 73 records · Page 4Linked to original sources

The outcome of hypophysectomy for prolactinomas in the era of dopamine agonist therapy.

OBJECTIVE: Dopamine agonists are the primary therapeutic modality for the majority of patients with prolactinomas, with pituitary surgery reserved for those patients intolerant of or resistant to these agents. Most published surgical series, however, contain patients treated by surgery as the primary therapeutic modality. Previous exposure to dopamine agonists or the selection of patients with prolactinomas resistant to conventional therapy may potentially compromise the surgical success rate. The purpose of this study was to evaluate the efficacy and safety of pituitary surgery for prolactinomas in a tertiary referral centre where the majority of patients were operated on after treatment with dopamine agonists. DESIGN: A retrospective review of the outcome of pituitary surgery for prolactinomas performed at a tertiary neurosurgical centre by a single neurosurgeon. PATIENTS: Twenty-three patients underwent excision of a macro and 11 excision of a micro-prolactinoma. MEASUREMENTS: Pituitary tumour diameter was determined by CT or MRI imaging. Pre and post-operative measurements were made of serum PRL concentration (off dopamine agonist therapy), free T4, free T3, LH and testosterone (males). Post-operative restoration of a menstrual cycle was taken to indicate resolution of hypogonadism in female patients. RESULTS: The majority (73.9%) of the patients with macro and all with micro-prolactinomas had received dopamine agonists preoperatively. Of the 23 patients with macroprolactinomas, in whom the median preoperative PRL concentration was 13255 mU/l, 17 (73.9%) had radiological evidence of suprasellar extension and 5 (21.7%) cavernous sinus invasion. Only 4 (17.4%) of the patients with macroprolactinomas had a normal serum PRL post-operatively, although there was an improvement in visual fields in 66% of those with preoperative defects. The median preoperative PRL concentration was 4309 mU/l in the patients with microprolactinomas, significantly lower than in the macroprolactinoma group (P = 0.02). Despite a significant fall in serum PRL postoperatively (median PRL 860 mU/l, P = 0.0001), only 45.5% of patients had a normal serum PRL concentration after surgery. CONCLUSIONS: The cure rate following pituitary surgery for prolactinomas in a tertiary referral centre was low when compared with previous series in which surgery was used as the primary therapeutic modality. We suggest this may result both from dopamine agonist pretreatment and the referral of prolactinomas resistant to conventional therapy. The outcome is probably a more realistic reflection of the results of pituitary surgery for prolactinomas as currently practised in the majority of neuroendocrine centres.

Adolescent↗

Continuity of care between obstetrical and pediatric preventive care: indicators of nonattendance at the first well-child appointment.

This study evaluates appointment behavior for first well-child visits for first-born children and identifies factors that target infants at increased likelihood for missing their first pediatric appointment. Timely appointments were not scheduled for 10.3% of newborns; 20.1% of those scheduling did not keep the first appointment. Younger, less educated mothers who did not remember when they had learned about well-baby care, and mothers of infants born in the newborn intensive care unit were unlikely to schedule the appointment; young mothers learning about well care from friends or relatives and who chose a pediatrician without a previous prenatal visit were more likely to miss the child's first appointment. Prenatal pediatric visits as well as prenatal classes and written materials may improve compliance with the first well-child appointment.

Adolescent↗

Autoantibodies to steroidogenic enzymes in autoimmune polyglandular syndrome, Addison's disease, and premature ovarian failure.

Autoantibodies to steroidogenic enzymes, steroid 17 alpha-hydroxylase (17 alpha-OH), cytochrome P450 side-chain cleavage enzyme (P450scc), and steroid 21-hydroxylase (21-OH), were measured using specific and sensitive immunoprecipitation assays (IPAs) in patients with various forms of autoimmune adrenal disease. Autoantibodies to 17 alpha-OH were detected in 6 of 11 (55%) patients with autoimmune polyglandular syndrome (APS) type I, 8 of 24 (33%) patients with APS type II, 11 of 56 (20%) patients with adrenal cortex antibody (ACA; measured by immunofluorescence)-positive patients without Addison's disease, and only 3 of 64 (5%) patients with Addison's disease. Autoantibodies to P450scc were found at a prevalence similar to those to 17 alpha-OH: in 5 of 11 (45%) APS type I patients, 10 of 24 (42%) APS type II patients, 11 of 56 (20%) ACA-positive patients without Addison's disease, and only 6 of 64 (9%) patients of the Addison disease group. Autoantibodies to 21-OH were found in a majority of patients with APS type I (7 of 11;64%), APS type II (23 of 24; 96%), Addison's disease (41 of 64; 64%), and ACA-positive patients without Addison's disease (48 of 56; 86%). All sera that were positive for 17 alpha-OH or P450scc were also positive for 21-OH autoantibodies, except in 1 case. There was good agreement between the presence of ACA measured by immunofluorescence and 21-OH antibodies measured by IPA in all patient groups studied, and this indicates that 21-OH is a major autoantigen in adrenal autoimmune disease regardless of whether the disease presents as isolated Addison's disease or APS type I or type II. Autoantibodies to 17 alpha-OH and P450scc appeared to be the major components of the steroid-producing cell antibodies measured by immunofluorescence. No autoantibodies to 21-OH, 17 alpha-OH, or P450scc were detected in 17 sera from patients with premature ovarian failure without evidence of adrenal autoimmunity (as judged by immunofluorescence studies), except for 1 serum in which low levels of 17 alpha-OH antibodies were found. Overall, our studies indicate that 35S-labeled 17 alpha-OH, P450scc, and 21-OH can be used successfully in IPAs for their respective autoantibodies. Assays such as these may well be valuable in the immunological assessment of patients at risk for or suspected of adrenal autoimmunity.

Addison Disease↗

The value of MRI in the assessment of traumatic intra-uterine adhesions (Asherman's syndrome).

Since the publication titled Amenorrhea Traumatica (atretica) by Asherman in 1948, this syndrome has been considered a well defined clinical entity. It is typically manifested by the formation of fibrous adhesions involving the uterine cavity, sometimes involving the internal cervical os. The major causes are surgical intervention of the post-partum uterus and elective termination of early pregnancy. The diagnosis is usually suggested by hysterography and confirmed by hysteroscopy. The MRI appearances are reported in four cases of Asherman's Syndrome in which the diagnosis was confirmed by hysteroscopy. The full range of MRI appearances in Asherman's Syndrome has not been established and to our knowledge there has been only one case reported in the literature.

Abortion, Induced↗

Recovery of vision following transsphenoidal surgery for pituitary adenomas.

The degree of recovery of vision is reported in 67 patients who underwent transsphenoidal surgery for pituitary adenomas compressing the visual pathways. There were no deaths, but 14 patients experienced postoperative complications. Overall, 88% showed visual improvement, 7% were unchanged and 4% were worse after surgery.

Adenoma↗

Lymphocytic adenohypophysitis: magnetic resonance imaging features of two new cases and a review of the literature.

Lymphocytic adenohypophysitis can cause pituitary expansion and hypopituitarism closely mimicking the features of a pituitary adenoma. Discrimination between these two conditions is of importance since, despite the similarity of their presentation, there are significant differences in pathophysiology. In contrast to pituitary adenoma, lymphocytic adenohypophysitis occurs almost exclusively in young women in relation to pregnancy, there is a preference for destruction of ACTH and TSH secreting cells and computed tomographic scanning shows uniform contrast enhancement in a proportion of cases. There is, as yet, no proven specific non-surgical treatment. There are anecdotal reports of a beneficial effect of steroids but there is also evidence that spontaneous resolution may occur. We have reviewed the literature and report two new cases of lymphocytic adenohypophysitis both of whom exhibited early striking diffuse homogeneous contrast enhancement on magnetic resonance imaging scanning which we suggest may be a diagnostic feature of this condition.

Adult↗

Comparison of proliferating cell nuclear antigen versus the more standard measures of rectal mucosal proliferation rates in subjects with a history of colorectal cancer and normal age-matched controls.

Measurement of proliferation rates by the more standard in vitro uptake techniques of [3H]thymidine and 5'-bromo-2'-deoxyuridine (BrdUrd) labeling indices (LIs) were compared to proliferating cell nuclear antigen (PCNA) in rectal mucosal biopsies from 16 subjects with resected colorectal cancer and 14 normal age-matched controls. Correlation coefficients for BrdUrd versus PCNA, [3H]thymidine versus PCNA, and BrdUrd versus [3H]thymidine were 0.691, 0.876, and 0.770, respectively. No significant differences (P > 0.05) were detected in total mean LIs between the LI methods for the normal group. In contrast, total PCNA LIs were found to be significantly different in the resected cancer patients when compared to either BrdUrd (P = 0.005) or [3H]thymidine (P < 0.001). A significant difference (P = 0.010) in total PCNA LI but not in total [3H]thymidine or BrdUrd LIs was also observed between normal controls and resected colorectal cancer subjects. Compartmental analysis of the cancer group versus the normals showed a significant difference in compartments 1 and 3 for PCNA LIs only. The reproducibility of two PCNA LI counts was excellent (r = 0.9). In addition, the reliability of mean LIs were > 0.8 with the exception of [3H]thymidine in the normal group (0.7). These study results demonstrate that PCNA LIs in human rectal mucosal biopsies are correlated highly with other more commonly used cellular proliferation measurements; however, PCNA LIs were found to be significantly higher than the other two methods in the resected colorectal cancer subjects.

Adult↗

Evolutionary relations among vertebrate muscle-type lactate dehydrogenases.

Gene duplication has produced two lactate dehydrogenase (LDH) isozymes, LDH-A and LDH-B, that are found in essentially all vertebrates. On the basis of the biochemical properties of the LDH-A and LDH-B isozymes, it has been suggested that each locus is orthologous among all vertebrates. However, phylogenetic studies have not supported a common evolutionary history among the LDH-A isozymes, particularly when those from lower vertebrates are examined. We present here the sequence of a muscle-type LDH from Fundulus heteroclitus, a teleost fish for which the LDH-B sequence has been determined and shown to be unrelated phylogenetically to tetrapod LDH-A isozymes. Although the sequence of the teleost muscle LDH shares certain features with the LDH-A of tetrapods, phylogenetic analyses do not support an orthologous relation among the LDH-A isozymes of teleost fish and tetrapod vertebrates.

Amino Acid Sequence↗

Specific T cell receptor gene rearrangements at the site of muscle degeneration in Duchenne muscular dystrophy.

Mononuclear cells infiltrate degenerating muscles of Duchenne muscular dystrophy (DMD) patients. Using a quantitative PCR, we first characterized the T cells infiltrating muscle biopsies from six DMD patients. High levels of TCR V beta 2 transcripts were observed in DMD muscle tissue. TCR V beta 2 transcripts from seven DMD patients and five controls were sequenced, and the VDJ junctional region analyzed in 166 clones. One specific amino acid motif, RVSG, was found in the third complementary determining region (CDR3) of TCR V beta 2 chains in samples from five DMD patients, but not in controls. A specific immune reaction at the site of tissue degeneration may play an important role in the pathogenesis of DMD.

Amino Acid Sequence↗

Sympathectomy for reflex sympathetic dystrophy: factors affecting outcome.

This study includes our 12-year experience with chemical sympathetic blocks and surgical sympathectomies for causalgic pain of reflex sympathetic dystrophy (RSD) with emphasis on factors affecting clinical outcome. Medical records of patients undergoing sympathectomies for causalgic pain were analyzed. The patients were classified according to Drucker et al. as stage I, II, or III. Results of chemical and surgical sympathectomies were analyzed using both univariate and multivariate methods. Twenty-one patients had lumbar and seven had cervicodorsal sympathectomies for RSD. The mean duration between initial injury and chemical sympathetic block was 10 months with a mean of 11.4 months to surgical sympathectomy. Ten patients (36%) had overt extremity trauma as the precipitating event. Ten patients (36%) had a lumbar laminectomy, three of whom developed the syndrome bilaterally. There was no operative mortality; however, 25% had transient postoperative sympathetic neuralgia. The early and late (> 6 months) satisfactory outcomes after surgical sympathectomy were 82% and 71%, respectively. Patients with stage II presentations were significantly more likely to have satisfactory early (92%) and late (79%) outcomes than stage III patients, 0% and 0% (p = 0.019). Patients with an excellent response to chemical sympathetic block were more likely to have satisfactory early and late surgical outcomes. The time between injury and chemical block and surgical sympathectomy was significantly shorter in patients who had satisfactory early and late surgical outcomes (p < 0.0001). Multivariate analyses demonstrated that the most important independent factor in determining early and late satisfactory outcomes of sympathectomy was the time between injury and sympathectomy (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The changing blueprints of the British NHS: the White Papers of 1944 and 1989.

It has recently been pointed out that the 1989 White Paper Working for Patients, which provides the basis for the current reforms of the British National Health Service, has some common features with the 1944 White Paper A National Health Service, which was the unadopted model for the service produced by the Wartime Coalition Government. Moreover, it is likely that the Conservatives, if elected in the 1945 General Election, would have introduced a service based on a modified version of the 1944 document. We can compare these two blueprints to shed some light on Conservative thinking on health care over a period of nearly 50 years. There are some similarities in terms of the notions of purchaser and provider, contracts and pluralism. However, there are striking contrasts, notably in their attitude towards planning versus competition and local democracy versus patronage. It is claimed that the profound differences outweigh the apparent similarities and consequently the two blueprints show the discontinuity rather than the continuity of Conservative thinking on health care.

Delivery of Health Care↗

Cyst formation of the craniopharyngeal duct.

The craniopharyngeal duct is the route by which the adenohypophysis ascends from the pharynx to the pituitary fossa. Rathke's cleft cyst represents an expansion of primitive vesicles that lie between the pars intermedia and the pars anterior. These cysts are rare but have been detected more frequently with the more widespread use of CT and MRI. Three cases are described which illustrate the variety of positions that a cystic lesion of the craniopharyngeal duct can occupy. These cases provide a basis for the discussion of the embryological formation of the pituitary, cyst formation of the duct, and CT and MRI appearances of the cysts.

Adult↗

Labeled Schwann cell transplants versus sural nerve grafts in nerve repair.

This study evaluated the ability of Schwann cell transplants to enhance the recovery of function in injured nerves and compared the results to those produced by sural nerve grafts. Schwann cells were isolated from sciatic nerves, prelabeled with gold fluorescent dye admixed with collagen gel, and placed in resorbable collagen tubes. Twenty-four adult rats underwent severing of the bilateral sciatic nerves, with a 10-mm gap between the nerve stumps. The rats were then divided into two groups. A collagen tube with implanted Schwann cells was implanted in one leg of the Group I rats, and the contralateral leg served as a control and was repaired with a collagen tube filled with collagen gel only. The Group II animals received conduits packed with labeled Schwann cells in one leg to bridge the 10-mm gap; the contralateral leg was repaired with an autogenous sural nerve graft. Recovery of function was assessed physiologically and morphologically. Nerve conduction velocity and nerve action potential amplitude measurements showed that the Schwann cell implants induced return of function comparable to that of the sural nerve grafts. Morphological assessments of myelination suggested a tendency toward greater numbers of myelinated axons in Schwann cell implants than in sural nerve grafts. Anatomical analyses of gold fluorescent dye showed both high viability of prelabeled Schwann cells at 120 days after transplantation and migration as far as 30 mm away from the implant site.

Animals↗

Validation of proliferation indices as surrogate endpoint biomarkers.

During the 1990s, research interest in the use of chemopreventive agents to reverse human colon carcinogenesis increased exponentially. In parallel, there has been an increase in the need for putative surrogate endpoint biomarkers (SEBs) of cancer risk. Since the hallmark studies of Lipkin et al. and Terpstra et al., among others, the rate and patterns of rectal mucosal proliferation have been established as intermediate biomarker endpoints for colon cancer risk, modulated by potential chemopreventive agents including calcium, wheat bran fiber, and nutritional stress diets. Researchers rely heavily on these rectal mucosal proliferation indices as surrogate endpoints to evaluate the relative efficacy of various chemopreventive intervention strategies. Standardization through quality control/quality assurance (QC/QA) programs which continuously validate the accuracy, reproducibility, and variability of these indices is increasingly needed. Along with many others, we have attempted to validate 3H-thymidine and bromodeoxyuridine labeling indices in rectal mucosal biopsies as reliable SEBs. In this manuscript we outline a series of QC/QA steps that can be followed in the validation process for new as well as "old" biomarkers prior to their use as primary efficacy surrogate endpoints for chemopreventive agent intervention trials.

Adenoma↗

Atypical renal artery stenosis in a renal transplant: diagnosis by radionuclide techniques.

A case of a cadaveric kidney transplant recipient who developed progressively severe renal failure within 3 mo of transplantation secondary to renal artery stenosis is presented. The patient was primarily hypotensive and Doppler ultrasound showed normal flow. The problems in diagnosing this unusual case are reviewed. The findings on serial radionuclide studies eventually led to consideration of the correct diagnosis.

Adult↗

Respite care.

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Caregivers↗