Showing papers by "St Bartholomew's Hospital published in 1983"

Problems in the conceptual framework of patient satisfaction research: an empirical exploration.

Abstract: Survey research into patient satisfaction has been responsible for developing a number of related concepts concerning the ways in which patients evaluate the health care that they receive. Recently doubts have been expressed as to the adequacy of this approach for understanding how patients anticipate and respond to medical encounters. This paper reports a study of patients attending neurological outpatient clinics. The results suggest that the conceptual framework deriving from patient satisfaction research provides only partial and sometimes misleading insights into the perspectives of the patients studied. The paper concludes that patients' varying concerns with regard to their illness need to be more directly considered in explaining different responses to medical consultations. This approach enables a more sensitive evaluation of health care from the patient's point of view.

The genetic susceptibility to type 1 (insulin-dependent) diabetes: analysis of the HLA-DR association.

Abstract: HLA-DR and MT1, MT2, MT3 genotypes have been investigated in 123 Type 1 (insulin-dependent) diabetic subjects and their families. Ninety-eight percent of probands possessed either DR3 (relative risk = 5.0), or DR4 (relative risk = 6.8) or both antigens (relative risk = 14.3), emphasizing the strong association of the disease with these two antigens. Almost 51% of the probands were DR3, DR4 heterozygotes. The DR antigen combinations of the parents leading to DR3, DR4 heterozygous and to DR3 and DR4 homozygous offspring were analysed. There was a marked increase in DR3, DR4 heterozygosity, but no increase in homozygosity for these antigens compared with the expected frequencies. These results are compatible with the existence of two susceptibility genes operating at a locus or at loci closely linked to that of HLA-DR. There was a striking reduction of DR7 (relative risk = 0.1) and only five probands possessed DR2 (relative risk = 0.1). In each case, the other inherited allele was DR3 or DR4. Linkage disequilibrium between B7 and DR2 was much lower in the haplotypes of the probands than in the 'non-diabetic' parental haplotype. In contrast, the association of BW62 with DR4 was more pronounced in the haplotypes of the probands. There was no increase in recombination frequency in these families and no strong effect of HLA-DR on age of onset could be demonstrated. There was a significant shift towards DR identity compared with identity for the whole HLA haplotype (A, B, C and DR) in both healthy and diabetic siblings (p less than 0.025).

The sensitivity of isolated osteoclasts to morphological transformation by calcitonin.

Abstract: We recently developed a technique for isolating osteoclasts from other bone cells which allows the direct effect of hormones on these cells to be assessed. We found that calcitonin (CT), which inhibits osteoclastic bone resorption, abolished cytoplasmic movement in these cells. In this paper we use the shape-change which accompanies immotility to define the sensitivity of osteoclasts to human and salmon CT. Concentrations of human CT above 62 pg/ml and salmon CT above 3 pg/ml regularly induced the shape-change in osteoclasts which corresponds to complete inhibition of cytoplasmic motility. Morphological transformation of osteoclasts by such low concentrations implies that CT may inhibit bone resorption by inhibiting the motility of the bone-resorptive cell. Even relatively high concentrations of other hormones had no effect on the sensitivity of osteoclasts to CT. This suggests that the response of isolated osteoclasts to CT is sufficiently specific and sensitive to be used as a bioassay, and we used the ...

Pro- γ -melanocyte-stimulating hormone cleavage in adrenal gland undergoing compensatory growth

Abstract: Regulation of the rapid compensatory growth seen in the remaining adrenal gland of rats following unilateral adrenalectomy is poorly understood. The role of adrenocorticotropic hormone (ACTH) is obscure as immunoneutralization of circulating ACTH does not affect the observed compensatory growth or hyperplasia. This finding, together with the fact that mechanical manipulation of one adrenal without extirpation is followed by growth only in the contralateral gland, has led to the concept of neural regulation of compensatory adrenal growth via a loop from one adrenal through the hypothalamus and back to the contralateral gland which is independent of ACTH secretion. We recently showed that peptides from the N terminal of ACTH precursor proopiocortin (POC), not containing the gamma-melanocyte-stimulating hormone (gamma-MSH) sequence, can stimulate adrenal mitogenesis and proposed that normal long-term adrenal growth and proliferation involves post-secretional proteolytic cleavage of pro-gamma-MSH [or N-POC(1-74)] to generate the mitogenic factor N-POC(1-48/49) and a C-terminal fragment N-POC(50-74), or rat gamma 3-MSH. We have now investigated this hypothesis further in rats by selectively quenching different regions of circulating POC peptides with specific antisera and observing the effect on the increases in weight, RNA and DNA normally seen in the remaining gland following unilateral adrenalectomy. Our results, reported here, suggest that neurally mediated proteolytic cleavage of the circulating inactive mitogenic precursor pro-gamma-MSH at the adrenal gland is the major mechanism of control of compensatory growth.

Diabetes and arterial hypertension.

Abstract: The epidemiology, pathogenesis, significance and management of hypertension in diabetic subjects are discussed. In Type 1 diabetes the presence of diastolic hypertension is closely related to the presence of diabetic nephropathy, from the stage of persistent proteinuria onwards. There may also be some elevation of systolic pressure. The apparent increased prevalence of hypertension in Type 2 diabetes is largely explicable, directly or indirectly, by obesity but there may be an excess of systolic hypertension among elderly patients. Hypertension in the diabetic population is associated with an increased incidence of both microvascular and macrovascular complications, but whether the high blood pressure is causal is not clear. The possible roles of sodium and insulin, the renin-angiotensin system, catecholamines and physical factors are explored. All current antihypertensive agents have additional limitations and disadvantages when used in diabetic patients: diuretics and beta-blockers are probably the initial drugs of choice. Only in the case of diabetic nephropathy is there yet reasonable evidence of antihypertensive treatment reducing the rate of progression of the disease.

Increased inflammatory reactivity in newly formed lining tissue

Abstract: The air pouch has been shown to provide a convenient model for studying the behaviour of synovial lining tissue. Air pouches of different ages were used to study the reactivity of newly developing lining tissue towards irritants known to cause inflammation. Pouches of 1 day in age were relatively inert in their reactivity as judged by the number of cells and volume of the exudate accumulating in the pouch. In contrast, 3-day-old pouches responded to a much greater extent, and 6-day-old pouches were highly responsive with a further increase in cell numbers and fluid volume. The different responses of 1-, 3- and 6-day-old pouches could be explained by (a) developing vascularity of the pouch, (b) formation of an organised lining of phagocytic cells, or (c) an increasingly organised mechanical barrier that retains the irritant and products of the inflammatory response. These studies of air pouch lining development permit a dissection of those components necessary for inflammatory reactivity of a lining tissue and may help explain the sensitivity of synovium to chronic inflammation.

Inhibition of osteoclastic motility by prostaglandins I2, E1, E2 and 6-oxo-E1.

Abstract: We have recently found that calcitonin (CT), a hormone which inhibits osteoclastic bone resorption, completely abolishes the normally intense cytoplasmic motility of isolated osteoclasts. Here we report that prostaglandin (PG)I2, PGE1, PGE2 and 6-oxo-PGE1 cause an identical change in behaviour to that induced by CT. The order of potency was PGI2 greater than PGE1 greater than 6-oxo-PGE1 greater than PGE2. We found that, unlike CT which causes prolonged immotility in osteoclasts, the effect of these PGs was transient. The transient nature of the inhibition was not caused by their decay or inactivation, nor was it due to production in the cultures of a stimulator of osteoclast motility. Osteoclasts refractory to one PG were also less sensitive to the others, but showed no loss of sensitivity to CT, suggesting that the PGs share a common receptor system, distinct from that for CT. The PGs, like CT, appear to operate by increasing the cyclic AMP level in osteoclasts. The identical nature of the response of osteoclasts to PGs and CT, and the shared use of cyclic AMP as second messenger, suggest that the PGs, like CT, act directly on osteoclasts to inhibit bone resorption by these cells. Osteoblasts are known to make PGs, and we suggest that osteoblasts make them as agents of the local control of osteoclastic bone resorption. Paradoxically, when PGs are added to bone in organ culture they stimulate bone resorption. Like PTH they increase osteoblastic cyclic AMP levels, and the effect of adding PGs to bone may be a transient direct inhibition of osteoclasts followed by a sustained PTH-like stimulation of osteoclasts through osteoblasts. This mechanism may account for the bone resorption seen in inflammatory and malignant disease.

Treatment with gonadotrophin releasing hormone analogue in advanced prostatic cancer.

Abstract: Repeated administration of long acting analogues of gonadotrophin releasing hormone diminishes gonadal function and in men decreases testosterone concentrations; for this reason the effect of the analogue buserelin was studied in prostatic carcinoma. Twelve consecutive patients with newly diagnosed locally advanced or metastatic carcinoma of the prostate were treated. Each patient received intranasal buserelin in divided dosages of either 600 or 1000 micrograms daily. Suppression of the gonadotrophins and testosterone occurred in all patients. Objective and subjective signs of regression of disease were seen in nine patients. Buserelin offers an effective treatment of metastatic prostatic cancer without the side effects and cardiovascular risks associated with oestrogen treatment.

Pharmacological control of osteoclastic motility

Abstract: We separated osteoclasts from bone and observed the effect of several known and potential mediators of the control of bone resorption on their cytoplasmic motility. We already found that calcitonin (CT), a hormone that inhibits bone resorption, regularly causes complete inhibition of cytoplasmic motility, specific for osteoclasts, through a trypsin-sensitive membrane receptor [1]. We report here that prostaglandin I2 (PGI2) and dibutyryl cyclic AMP induce an identical change in osteoclastic behavior. We found that theophylline, which inhibits intracellular cyclic AMP degradation, and which itself had no effect on osteoclastic motility, potentiated the cytoplasmic inhibition caused by CT, PGI2, and cyclic AMP. This suggests that PGI2 and CT cause cytoplasmic quiescence by increasing the intracellular level of cyclic AMP, a view compatible with the known ability of CT to increase cyclic AMP in bone [2]. Parathyroid hormone (PTH), PGE2, and 1,25 dihydroxycholecalciferol (1,25 (OH)2D3), hormones known to stimulate osteoclasts, did not stimulate the activity of either active or quiescent isolated osteoclasts. The undoubted ability of these hormones to stimulate osteoclastic activity in vivo may therefore be mediated through a primary hormonal interaction with another cell type.

The association of lichen sclerosus et atrophicus and autoimmune-related disease in males.

Abstract: We have investigated the presence of autoimmune-related diseases and autoantibodies in twenty-five men with lichen sclerosus et atrophicus (LSA). These patients had a significantly higher incidence of autoimmune-related disorders than a control population and a higher incidence of autoantibodies than would be expected in the normal male population.

Cardiac electrophysiologic effects of flecainide acetate for paroxysmal reentrant junctional tachycardias

Abstract: Intravenous flecainide acetate was administered to 33 patients undergoing routine electrophysiologic study: 18 patients had a direct accessory atrioventricular (AV) pathway and 15 patients had functional longitudinal A-H dissociation (dual A-H pathways). Flecainide was given to 14 patients during sustained AV reentrant tachycardia and to 9 patients during sustained intra-AV nodal reentrant tachycardia. AV reentrant tachycardia was successfully terminated in 12 of 14 patients. Tachycardia termination was due to retrograde accessory pathway block in 11 patients and AV nodal block in 1. During flecainide administration, tachycardia cycle lengths increased (327 +/- 55 to 426 +/- 84 ms) principally because of retrograde conduction delay in the accessory pathway (127 +/- 34 to 197 +/- 67 ms). After flecainide administration, tachycardia reinitiation was not possible in 6 patients. In all 18 patients with accessory AV pathway conduction, flecainide significantly increased both anterograde and retrograde accessory pathway effective refractory periods, with anterograde accessory pathway block in 3 patients and retrograde accessory pathway block in 8. Intra-AV nodal reentrant tachycardia was successfully terminated in 8 of 9 patients. Tachycardia termination was due to retrograde "fast" A-H pathway block in 7 patients and anterograde "slow" A-H pathway block in 1 patient. During flecainide administration, tachycardia cycle lengths increased (326 +/- 50 to 433 +/- 64 ms) due to both anterograde, A-H and H-V (AV 242 +/- 97 to 343 +/- 75 ms), and retrograde, earliest ventricular to earliest atrial (51 +/- 14 to 70 +/- 23 ms) conduction delay. After flecainide administration, reinitiation of intra-AV nodal reentrant tachycardia was not possible in 4 patients. In all 15 patients with dual A-H pathways, flecainide selectively prolonged the retrograde effective refractory period of the fast A-H pathway, having little effect on anterograde fast A-H pathway refractoriness or on anterograde and retrograde slow A-H pathway refractoriness. Anterograde fast A-H pathway block occurred in 1 patient and retrograde fast A-H pathway block occurred in 6 patients. No serious adverse effects were encountered during the study. Flecainide acetate is an effective agent for the acute termination of both orthodromic AV and intra-AV nodal reentrant tachycardias. This antiarrhythmic action appears to be mediated through a predominant effect on either accessory AV pathway or retrograde fast A-H pathway refractoriness.

Demonstration of an immune‐mediated mechanism of penicillin‐induced neutropenia and thrombocytopenia

Abstract: Severe neutropenia may be a more common complication of high-dose penicillin therapy than previously recognized. This report describes five such patients, one of whom also had thrombocytopenia. The neutrophil and platelet counts rapidly increased on stopping penicillin, and the bone-marrow, which was hypocellular in some cases, became normal. Further studies on one of these patients, using a fluorescent antiglobulin technique with paraformaldehyde-fixed cells, demonstrated a complement-fixing IgG penicillin antibody reacting with the patient's granulocytes and platelets in the presence of the drug. This suggested an immune mechanism similar to the well-recognized penicillin-induced immune haemolytic anaemia. The associated bone-marrow hypoplasia may also be due to antibody-mediated suppression of penicillin-coated precursor cells.

Impaired Semen Quality in Crohn's Disease—Drugs, Ill Health, or Undernutrition?

Abstract: Even though abnormalities of semen quality in inflammatory bowel disease have been attributed to sulphasalazine therapy, oligospermia was found in 46% of men with Crohn's disease, none of whom were receiving this drug. Oligospermia occurred more commonly than in men with coeliac disease (6%, P < 0.02), although disordered sperm motility and morphology were found commonly in both conditions. Our findings suggest that factors such as disease activity, nutritional status, and, possibly, other drugs must also be considered when investigating infertility in Crohn's disease.

Pregnancy-associated plasma protein A: a possible marker in the classification and prenatal diagnosis of Cornelia de Lange syndrome

Abstract: The concentration of human placental lactogen (hPL), pregnancy specific beta-1 glycoprotein (SP-1) and pregnancy-associated plasma protein A (PAPP-A) were analysed in consecutive serum samples from a patient who gave birth to a child with Cornelia de Lange syndrome. HPL and SP-1 were present in normal concentrations from week 20 to week 35 of gestation whereas PAPP-A could not be detected in any of the samples examined. Immunohisto-chemical examination of two placentae from Cornelia de Lange syndrome revealed normal localization of hPL and SP-1 but the absence of PAPP-A from the syncytiotrophoblast. The significance of association between Cornelia de Lange syndrome and compromised synthesis of PAPP-A is discussed.

Chemotherapy and the adult gonad: a review

Abstract: With survival in some cancers now a possibility, significance is attached to the details of survival. A holistic approach to the patient takes account of the sequelae of treatment consequent to cure. A high frequency of sterility is an important consideration when embarking upon the treatment of curable malignancies that affect younger populations, such as Hodgkin's disease, childhood leukaemia, non-Hodgkin's lymphoma, choriocarcinoma and testicular teratoma.

Exploratory scrototomy in 168 azoospermic males.

Abstract: In 168 azoospermic males with normal or only slightly raised serum FSH levels, serum antisperm antibodies were measured, and the site of obstruction or the nature of the failure of spermatogenesis was defined by exploratory scrototomy with inspection of epididymes, vasography and testicular biopsy. When possible, surgical reconstruction was done by side-to-side epididymovasostomy, with vasovasostomy when necessary using 6/0 Prolene and no splints. Acquired blocks of cauda epididymis (34 cases) and vas (23 cases) were significantly more commonly associated with serum antisperm antibodies than congenital bilateral absence of vasa (29 cases) or blocks at the caput epididymis (48 cases), most of which were associated with sinusitis, bronchitis or bronchiectasis (Young's syndrome). Many of the former patients came from abroad, whereas most of the latter came from the British Isles. Sperm counts of 10 million per ml or more were produced by 23 (45%) of 51 adequately followed up patients with acquired blocks following surgical reconstruction, and 11 pregnancies (21.5%) were produced. Amongst those with spermatozoa in the ejaculate after surgery, serum antisperm antibodies were found significantly less often in those whose wives became pregnant compared with those who failed to produce pregnancies. It is concluded that failure of surgical treatment in some of these cases may have an immunological basis. No success was achieved with other groups.

Pro‐opiocortin related peptides in human pituitary and ectopic acth secreting tumours

Abstract: SUMMARY Basal and stimulated secretion of N-terminal pro-opiocortin (Pro-γ-MSH), ACTH and LPH from seven pituitary and three ectopic ACTH secreting tumours have been studied in vitro using a perfused isolated cell system. The peptides were shown to be released concomitantly and in equimolar amounts. The pituitary tumours responded to stimulation with rat stalk median eminence extracts (SME) and synthetic AVP. However, peptide release from the ectopic tumours, although pulsatile, remained autonomous. Prior to surgery, gel-chro-matographic profiles of plasma immunoreactive ACTH showed only one peak, which eluted in the position of 1–39 ACTH, in patients with the pituitary tumours, but there was a second peak of large molecular weight ACTH present in the plasma from those with the ectopic ACTH syndrome. This second form of ACTH could not be detected in any of the tumour cell column effluents. An eighth pituitary tumour was atypical, in its unusually large size, clinically aggressive nature and spectrum of peptide release. Although peptide release in response to stimulation with SME was similar to that observed with the other pituitary tumours, the chromatography of the plasma ACTH resembled the ectopic plasma pattern, showing two peaks of immunoreactivity.

A genetic polymorphism of a human urinary mucin

Abstract: We report here a novel genetically determined polymorphism of a human urinary mucin which is demonstrable by the separation technique of SDS polyacrylamide gel electrophoresis, followed by detection with radio-iodinated lectins. The mucins are demonstrable using various lectins but the polymorphism is most easily recognized using peanut agglutinin and we therefore propose to designate this new genetic locus PUM (peanut-reactive urinary mucin). Four common alleles have been identified and an autosomal codominant mode of inheritance has been found in the families studied so far.

The effects of sperm antibodies on fertility after vasectomy reversal.

Abstract: Antisperm antibodies have been measured in serum and in seminal plasma in 130 males before and after vasectomy reversal, and the occurrence of pregnancy has been analyzed in those partners who were trying to produce a pregnancy. All patients have been followed for at least one year. Sperm-agglutinating antibodies were found in the serum of 79% of patients; seminal plasma antibodies were present in only 9.5% before reversal, and this rose to 29.5% afterwards. Overall, pregnancies occurred in the partners of 44.6% of those men who were trying to produce children. Production of pregnancy was significantly less likely when the preoperative serum antisperm antibody titer was 512 or more, but no decrease in fertility was seen with titers below this. Similar numbers of pregnancies were produced by patients with or without seminal plasma antibodies in titers of up to 16; there are too few patients with titers above this level to permit further analysis. A randomized controlled trial of perioperative steroids showed that they produced no benefit. It appears that the antisperm antibodies associated with vasectomy reversal may differ fundamentally from those occurring in naturally subfertile males.