Regulation of gene expression in PC12 cells via an activator of dual second messengers: pituitary adenylate cyclase activating polypeptide. In this study we demonstrate that the activator protein-1 (AP-1) DNA motif, initially considered to be unresponsive to cyclic AMP (cAMP), does function as a cAMP-response element in PC12 cells. A luciferase reporter gene driven by the collagenase promoter that contains the AP-1 motif is responsive to cAMP as well as phorbol esters when transfected in PC12 cells. We have recently shown that pituitary adenylate cyclase activating peptide (PACAP) has neurotrophic properties and activates both adenylylcyclase and the inositol lipid cascade in PC12 cells. Consistent with these actions, we demonstrate that PACAP is an effective activator of luciferase reporter genes whose promoters bear the AP-1 motif, as well as the related DNA element that binds the protein CREB. Both the cAMP and inositol lipid pathways appear to play a role in the activation of these motifs by PACAP. Mutation of the AP-1 motif and its juxtaposition to a heterologous promoter proves that the AP-1 motif is a locus for response to cAMP and PACAP. The luciferase reporter genes bearing the AP-1 motif are not cAMP responsive in HeLa tk- cells, indicating that the mode of second-messenger responsiveness is cell-type specific.


Percutaneous abdominal biopsy.

Percutaneous abdominal biopsy. The radiologically guided percutaneous needle biopsy is of proven value for evaluating intra-abdominal disease. Every region of the abdomen and pelvis is amenable to fine-needle biopsy. Accuracy rates are high with minimal risk to the patient. Current trends in biopsies tend to favour the use of larger core biopsy needles (18-gauge Biopty), and preliminary reports suggest that this is safe and may increase the diagnostic accuracy. Clinicians need not hesitate to call on their radiological colleagues to perform this most important procedure.


Transjugular and plugged liver biopsies. When a liver biopsy is indicated the transabdominal approach using either a Menghini or Tru-Cut needle has been shown to be an extremely safe procedure with very low morbidity and mortality rates in patients with normal or only mildly disturbed coagulation. When the coagulation status is severely deranged, however, several methods of obtaining a liver biopsy have been devised to circumvent the increased risk of bleeding. The transjugular approach has been shown to be both successful and relatively safe. The less cumbersome technique of plugging the needle track after percutaneous transabdominal biopsy has been reported relatively recently. Although it is likely that the latter method will produce good biopsy samples in the majority of cases (and in this regard it may prove to be better than the transjugular route), considerably more experience is required before its true complication rate is known. In a hospital where large numbers of transjugular biopsies are performed by experienced radiologists and in which skilled pathologists are used to interpreting the histological appearances of small, crushed liver samples, there is no compelling reason to change to the plugged biopsy technique. The more difficult question is whether hospitals in which the radiological and histological skills necessary for consistent success with the transjugular approach are not available should adopt the plugged biopsy method. The answer to this question is probably in the affirmative, but will depend on the confidence and interventional experience of the local operator and on more detailed factual information concerning the safety of the plugged method. With regard to the latter point, the publication of a large controlled study on the safety and efficacy of plugged liver biopsy would be a valuable contribution to the world literature on the subject.


Percutaneous management of pancreatic fluid collections. Percutaneous catheter drainage of both infected and non-infected pancreatic fluid collections is a safe, efficacious procedure. The results of this procedure depend upon proper selection of patients based upon their clinical status as well as the morphological findings depicted by computed tomography and endoscopic retrograde cholangiopancreatography, careful preprocedural planning and execution of the drainage procedure, good catheter care with follow-up imaging and contrast studies, and attention to the criteria of catheter removal. An average success rate of 80% should be expected with a complication rate of about 15%.


Percutaneous radiologic gastrostomy.

Percutaneous radiologic gastrostomy. Percutaneous radiologic gastrostomy is comparable to endoscopic gastrotomy in its simplicity, high success rate and lack of complications. Furthermore, it compares favourably with endoscopic gastrostomy in significant aspects such as a lower incidence of wound infection, reduced risk of aspiration and ease of conversion to jejunal placement. There are also fewer contraindications to radiologic placement and the cost is likely to be less than for endoscopic gastrostomy. Since the emergence of percutaneous endoscopic gastrostomy, clinicians have been re-evaluating the role of the gastrostomy in managing patients requiring nutritional support or gastrointestinal decompression. Percutaneous radiologic gastrostomy is an eminently suitable alternative to endoscopic or surgical gastrostomy.


The radiological management of gastrointestinal strictures and other obstructive lesions. Balloon dilation of gastrointestinal strictures using a radiologic, endoscopic or combined approach is a safe, effective means of managing an ever-increasing variety of stricturing processes. At present the ability to dilate strictures in the gastrointestinal tract is limited mainly by access. Balloon dilation is now well established in the management of oesophageal and anastomotic lesions. The place of balloon dilation in the management of Crohn's disease and in the management of malignant disease requires further evaluation.


The management of problematic biliary calculi. Recent advances in modern medical technology have significantly reduced the number of patients with 'problematic calculi'. When a patient does present with a difficult bile duct stone, various non-surgical treatment options are now available. In experienced hands, with healthy or high-risk patients, percutaneous treatment is as safe and as efficacious as endoscopy or surgery. Since it does not require general anaesthesia, and patients recover much more quickly than after surgery, the percutaneous approach is preferred when endoscopy fails to achieve ductal clearance. Surgery is indicated for patients with lesions requiring surgical removal or correction, but seldom for removal of biliary calculi alone.


Immune responses following competitive water tests in two species of macaques. A panel of immune parameters (lymphocyte activation by mitogens, natural cytotoxicity, and differential cell counts) was assessed in socially housed pigtail and bonnet macaques 1 and 2 weeks before, 48 h after, and 1 and 2 weeks after a competitive water test. Species differences were found in both baseline measures and the responses to the test: Immune measures observed during baseline periods were lower in pigtail macaques. Furthermore, only the pigtail macaques showed changes in mitogen activation and cytotoxicity at 48 h post-test. Dominance-related behaviors affected these responses both within and across social groups. The species differences may be accounted for by the differences in the behavioral responses of the two species to the test: Pigtail macaques consistently contested access to the water during the test, whereas bonnet macaques did not. These results suggest that the immune system can be modulated by psychosocial behavioral systems, particularly during times of stress.


Action of interleukin-2 and interleukin-4 on CRF mRNA in the hypothalamus and POMC mRNA in the anterior pituitary. We have used the technique of in situ hybridization histochemistry to determine corticotropin-releasing factor (CRF) mRNA in the hypothalamic paraventricular nucleus (PVN) and proopiomelanocortin (POMC) mRNA in the anterior pituitary of rats given a single ip injection of either interleukin (IL)-2 or IL-4. IL-2 increased POMC mRNA in the anterior pituitary in a dose-dependent manner. The effect was apparent both at 4 and 24 h after injection. No effect of IL-2 on CRF mRNA in the PVN was detected in these animals, suggesting that the increase in POMC mRNA was not driven by an increase in CRF. IL-4 was without effect at the hypothalamic level although this cytokine did result in a decrease in POMC mRNA in the anterior pituitary.


The neural and neuro-endocrine component of the human thymus. I. Nerve-like structures. The presence of nerve-like fibers in the human thymus was studied by immunohistochemistry on frozen tissue sections and sections of formalin-fixed paraffin-embedded tissue, for neurofilaments (Nf) of 68-, 160-, and 200-kDa (neuron-specific structural proteins), neuron-specific protein PGP9.5, tyrosin hydroxylase (noradrenergic innervation), chromogranin A (CHROM), synaptophysin (SYN), and the pituitary hormones follicle-stimulating hormone (FSH) and its beta-subunit, growth hormone, adrenocorticotropic hormone, luteinizing hormone, prolactin, beta-subunit of thyroid-stimulating hormone, and somatostatin. Noradrenergic profile-like immunoreactivity was observed in the medulla: immunolabeling was observed also for epithelial cells surrounding Hassall's corpuscles. For neurofilaments, only Nf 160-kDa immunoreactivity was observed in the thymic parenchyma, mainly in long-sized labeling patterns in the medulla. PGP9.5 immunolabeling occurred especially in the cortex, in dendritic labeling patterns compatible with the epithelial network at this location. The medulla showed PGP9.5 immunoreactivity in fiber-like patterns and in large-sized epithelial cells surrounding Hassall's corpuscles. Immunoreactive CHROM was seen in profile-like structures in the subcapsule, cortex, and medulla. SYN immunolabeling occurred focally around Hassall's corpuscles. Profile-like structures immunoreactive for pituitary hormones were observed in the medulla and in less density in the cortex. For FSH the highest density occurred in the cortex, where long-sized profile-like structures were present running over and in between cells, especially in the keratin-positive epithelial dendritic network (two-color immunohistochemistry).


The neural and neuro-endocrine component of the human thymus. II. Hormone immunoreactivity. We evaluated the presence of anterior pituitary hormones; follicle-stimulating hormone (FSH) and its beta-subunit (beta-FSH), luteinizing hormone (LH) and its beta-subunit (beta-LH), beta-subunit of thyroid-stimulating hormone (beta-TSH), adrenocorticotropic hormone (ACTH), growth hormone (GH), and prolactin (PRL); the placental hormone human chorionic gonadotropin (hCG); and somatostatin, in paraffin and frozen sections of the human thymus. Epithelial cells in the medulla were immunoreactive for most of these hormones, in varying density and intensity of labeling. The cells labeled varied from epithelial cells surrounding Hassall's corpuscles toward solitary cells or small epithelial aggregates in the medulla. FSH immunoreactivity did occur predominantly in epithelial cells of the cortex, in apparent contrast to the predominant medullary location of cells immunolabeled for beta-FSH. The epithelial nature of FSH-immunoreactive cells was confirmed by two-color immunohistochemistry with anti-keratin antibody. In addition to FSH, some epithelial cells in subcapsule and cortex were labeled by antibodies to beta-FSH, beta-LH, beta-TSH, ACTH, GH, and PRL. Some macrophage-like cells surrounded by a rosette of lymphocytes were immunoreactive for FSH and GH. Some interdigitating reticulum-like cells were labeled by anti-beta-LH. Immunolabeling of lymphocytes was found for hCG, especially lymphocytes in the medulla. Two-color immunohistochemistry with anti-CD3 revealed a strong CD3 expression on hCG-immunoreactive cells, whereas CD3-negative cells were hCG-negative. T cells immunolabeled for hCG were also found in peripheral lymphoid organs.


A behavioral profile of autoimmune lupus-prone MRL mice. Manifestations of the human autoimmune disease systemic lupus erythematosus (SLE) include a number of behavioral and cognitive deficits. The present study asks whether neurobehavioral dysfunction is present also in MRL mice that spontaneously develop most of the fundamental immunological aberrations of SLE. There are two congenic substrains of MRL mice that differ in the time of disease onset: MRL-lpr mice develop lupus early and MRL(-)+/+ develop the typical signs of disease relatively late in life. The behavior of these substrains was assessed at 7 to 11 weeks of age, a time that coincides with the onset of disease in MRL-lpr mice and the absence of known lupus symptoms in the MRL(-)+/+ group. When compared to the congenic MRL(-)+/+ control substrain, MRL-lpr mice were spontaneously less active, traversed a crossbeam slower, and ceased responding to the novelty of a new environment sooner. They were also more reluctant to leave their home base or travel far away from it and perseverated in their response bias during extinction and reversal learning. Immunological status was characterized by moderate proteinuria in both substrains and high titers of antinuclear antibodies in MRL-lpr but not MRL(-)+/+ mice. Histological analysis revealed minimal or no signs of joint pathology in MRL-lpr mice. Thus, this study shows the presence of behavioral dysfunction in mice with early stages of autoimmune disease and gives support for the idea that MRL mice may provide a useful model of neurobehavioral dysfunction in SLE. It is suggested that the behavioral profile of MRL-lpr mice may indicate increased "timidity," related to genetics, autoimmunity, or both.


Serum autoantibodies against glial fibrillary acidic protein in brain aging and senile dementias. Autoantibodies against glial fibrillary acidic protein (GFAP) were investigated by ELISA test in sera of patients suffering from senile dementias and in healthy aging people. One hundred eight subjects divided into control, vascular dementia (VD), presenile Alzheimer's disease (AD), and senile Alzheimer's disease (SDAT) groups were included in the study. VD patients showed the highest antibody titers when compared to controls, whereas AD had the lowest titers when compared to the other groups. These results do not support the utility of anti-GFAP antibodies as useful markers of Alzheimer's disease, suggesting that their presence is a secondary phenomenon to blood-brain barrier disruption.


Corticosterone-independent alteration of lymphocyte mitogenic function by amphetamine. Amphetamine, a neural stimulatory agent with acute effects mimicking those of stress, is shown here to elevate plasma corticosterone levels and suppress spleen and peripheral blood lymphocyte (PBL) mitogenic responses to concanavalin A (Con A) and phytohemagglutinin (PHA) when administered to rats. Pretreatment of the rats with propranolol, a nonselective beta-adrenergic receptor antagonist, totally prevented the amphetamine-induced suppression of lymphocyte mitogenic reactivity to Con A and PHA in the spleen and to PHA in the peripheral blood; however, the PBL mitogenic response to Con A was only partially restored. Although the amphetamine-induced alterations in immune function were prevented by propranolol pretreatment, the elevated plasma corticosterone response was not. This suggests that corticosterone is not modulating the mitogenic activity of splenic lymphocytes or PHA-reactive PBLs. On the other hand, Con A-reactive PBLs may be affected by corticosterone and/or other mechanisms, which may include the catecholamines.


A thymocytotoxic autoantibody reacts with the mouse brain cells in culture. Autoimmune-prone New Zealand Black mice produce a large amount of autoantibodies cytotoxic for thymocytes (natural thymocytotoxic autoantibodies, NTA). A monoclonal NTA (NTA260) has been found to react with brain tissues as well as the cell surface of thymocytes. We investigated the expression of NTA 260 antigen in the primary culture of fetal brain cells. NTA260 labeled strongly the cytoplasm of nerve cells after fixation, but failed to stain the living cells. Western blot analysis revealed that NTA260 recognized predominantly a band at approximately 53 kDa in brain and thymic extracts. These findings indicate that neuronal NTA260 antigen, which has a molecular mass similar to that of thymocytes, is likely an intracellular component.


Lack of [3H]quinuclidinyl benzylate binding to biologically relevant binding sites on mononuclear cells. We analyzed the binding characteristics of [3H]quinuclidinyl benzylate ([3H]QNB), a muscarinic cholinergic ligand, to rat and human mononuclear cells (MNC). Under various assay conditions, atropine-sensitive, saturable binding occurred with an apparent Kd of 10 nM. Conditions which disrupted the MNC membrane reduced total binding and eliminated specific binding. Muscarinic agonists were unable to inhibit [3H]QNB binding to MNC at concentrations up to 10(-2) M. Stereoisomers dexetimide and levetimide were equipotent inhibitors of binding (IC50 2 x 10(-5) M). We conclude that, although atropine-sensitive binding of [3H]QNB to MNC occurs, the binding is not consistent with the presence of a biologically relevant muscarinic cholinergic receptor.


Retinoids and contraception.

Retinoids and contraception. The main side effect of the retinoids is teratogenicity. Every dermatologist has a moral obligation to ensure that this effect is avoided, and the present publication is aimed at helping prescribe these drugs. After a review of the key properties of each of the retinoids on the market, the different forms of contraception available and their indication in young patients undergoing retinoid treatment are discussed. Unless otherwise contraindicated, oral contraception with an estrogen-progestogen formulation is the contraceptive method of choice for women undergoing retinoid treatment. The intrauterine device (IUD) is of little or almost no relevance for young women undergoing treatment with a retinoid. IUDs are indicated in older multiparae who have practised this form of contraception before starting retinoid treatment and who refuse to take the pill. Natural and local methods of contraception are totally unsuitable for women undergoing treatment with retinoids. However, they may be used as an additional precautionary measure by IUD users.


Serum SC5b-9 (terminal complement complex) level, a sensitive indicator of disease activity in patients with Henoch-Schönlein purpura. The concentration of the terminal complement complex (TCC), SC5b-9, was determined by enzyme immunoassay using 95 serum samples from 30 patients with Henoch-Schönlein purpura (HSP), 27 with other forms of inflammatory skin disease and 20 normal healthy donors. Twenty-five patients with HSP showed significantly increased TCC concentration in the active phase of the disease, during which newly formed urticarial or purpuric macules/papules could be seen. Skin biopsy specimens of skin lesions from patients with elevated TCC levels in nearly all cases contained the membrane attack complex of complement and consisted of C5b, C6, C7, C8, C9 without S protein on the vessel walls. Systemic and local activation of complement may thus possibly occur in HSP. Three patients with various manifestations of the disease were followed over a period of several years during which the active and inactive phases were scanned. TCC elevation in all cases was correlated with exacerbation of the disease. In contrast, C3, C4 and CH50 levels either remained normal or increased and thus were not reliable indicators of disease activity. Measurement of TCC should thus prove quite useful for monitoring the activity of HSP in patients in whom there is complement activation and also serve to facilitate clarification of the functions of complement in the pathogenesis of the disease.


Xeroderma pigmentosum variant associated with multiple skin cancers and a lung cancer. A 65-year-old Japanese man with a xeroderma pigmentosum (XP) variant, XP127TO, is described. The XP127TO skin fibroblasts exhibited the typical XP variant characteristics of a 1.5-fold higher sensitivity than normal cells to the lethal effect of 254 nm ultraviolet (UV) light and the normal level of unscheduled DNA synthesis induced by 254 nm UV. Caffeine dose-dependently increased the cytotoxic effect of 254 nm UV on XP127TO cells. Clinically, the patient developed not only 3 cutaneous squamous cell carcinomas on sun-exposed areas but also an adenocarcinoma of the upper lobe of the right lung. A review of the 14 documented Japanese XP patients with nonskin malignancies indicates that the incidence of nonskin malignancy in XP patients is much lower than that of skin cancer in XP but higher than that in the general population.


Soluble interleukin-2 receptor, CD4 and CD8 levels in melanoma: a longitudinal study. Serum levels of soluble(s) interleukin-2 receptor (IL-2R), sCD4 and SCD8 were analysed in 227 melanoma patients, using a sandwich enzyme immunoassay. Different stages of the disease were considered, and a longitudinal study with a 2-year follow-up was performed. Mean values of sIL-2R were significantly higher than in normal controls in all stages and correlated with the disease progression. sCD8 increases with stage progression were less striking, while sCD4 values were always in the normal range. We conclude that sIL-2R measurement is a useful clinical parameter in monitoring disease evolution in melanoma.


Practical considerations of melanoma/skin cancer screening clinics. In 1989 a voluntary melanoma/skin cancer screening clinic was held in Oss, the Netherlands. The campaign was carried out according to the free clinics conducted since 1985 in the USA. Our experiences with the first clinic urged us to improve on the organization of the screen. This produced a better yield of the second screen, conducted in 1990 in Arnhem. In this paper we present the practical and organizational implications of melanoma/skin cancer screening based on both screening exercises. It is emphasized that only dermatologists should screen. Concomitant public education will enhance self-selection of people at risk for melanoma/skin cancer. There should be ample provider time, sufficient auxiliary personnel and abundant examination rooms. Total-body skin examination is optional. Follow-up of positive screenees is mandatory. It is concluded that melanoma/skin cancer screening is feasible, particularly in countries with a high dermatologist-to-patient ratio.


Use of topical lithium succinate in the treatment of seborrhoeic dermatitis. Twenty-one patients with seborrhoeic dermatitis were included in an open trial of lithium succinate ointment (LSO) for a total duration of 8 weeks. The same clinician made assessments of the severity of redness, scaling, greasiness and overall clinical impression of the condition every 2 weeks. Because the results appeared to be satisfactory, we decided to perform a double-blind, placebo-controlled trial of LSO. Thirty patients with seborrhoeic dermatitis were included. The results also demonstrated the beneficial effect of LSO. A significantly higher number of patients treated with LSO showed remission or marked improvement compared with placebo. The main adverse events demonstrated consisted of minor transient skin irritation and/or stinging sensation. Studying the in vivo inhibitory effect of LSO on the growth of Pityrosporum revealed that Pityrosporum did not significantly have its growth inhibited by lithium. Topical lithium succinate appears to be a safe and an effective treatment for seborrhoeic dermatitis. The product presumably acts as an anti-inflammatory agent.


Topical immunotherapy for alopecia areata: re-evaluation of 139 cases after an additional follow-up period of 19 months. Within a group of 139 patients previously studied during treatment for alopecia areata with diphenylcyclopropenone (DCP), hair growth was re-evaluated after a period of 19 months following completion of our previous study. Fifty-four patients treated with DCP had total and 6 had partial but cosmetically acceptable regrowth. Twenty-five patients with total regrowth had stopped DCP treatment for a mean period of 15 months and had not relapsed. Nineteen of 28 patients who still applied DCP were in the process of stepwise discontinuation of treatment. Fifteen patients had subsequently been treated with squaric acid dibutylester (SADBE) after having acquired 'tolerance' to DCP; at the time of re-evaluation 3 of these patients had complete regrowth, and 4 patients had partial but cosmetically acceptable regrowth. Topical immunotherapy with DCP and SADBE had resulted in total regrowth in 57/139 patients (41.0%) and in partial but cosmetically satisfactory regrowth in 10/139 patients (7.2%). The type of involvement and duration of alopecia areata were factors of prognostic significance.


Cyclic neutropenia: a cause of recurrent aphthous stomatitis not to be missed. Cyclic neutropenia is a rare hematological disorder consisting of recurrent episodes of aphthous stomatitis and skin infections caused by a periodic decrease in blood neutrophil counts. We present the case of such a patient successfully treated with steroids. Recurrent aphthous stomatitis with a periodicity of around 3 weeks should alert the dermatologist to the possibility of cyclic neutropenia.


Three cases of allergic dermatitis due to intravesical mitomycin C. Irritant contact dermatitis has frequently been described in association with mitomycin instillation into the bladder. Three cases of allergic contact dermatitis in which patch tests demonstrated a type IV hypersensitivity reaction are reported. Patients showing skin reaction during mitomycin C vesical instillation should be patch tested to make a decision whether the drug might be continued (toxic reaction) or discontinued (allergic reaction).


Phthalic acid dermatitis caused by an organostannic compound, tributyl tin phthalate. We report a case of primary irritant contact dermatitis caused by an organostannic insecticide, tributyl tin phthalate, which has been thought to be stable and safe. A factory worker has been in contact with raw tributyl tin phthalate on one leg. Soon after taking a hot-water bath, he developed severely painful erythema on this leg. Patch tests and chemical analysis revealed that hot water hydrolyzed tributyl tin phthalate and produced concentrated phthalic acid. Since phthalic acid, a weak acid, was then concentrated, an acute irritant reaction appeared in this patient.


Squamous cell carcinoma--70 years after irradiation. The rare event of invasive squamous cell carcinoma 70 years after irradiation to the scalp for tinea capitis, occurred in a 75-year-old Caucasian male. The clinical, histological, roentgenologic and magnetic resonance imaging picture are described, and the literature is reviewed.


Doubled nail of the thumb. A rare form of polydactyly. Bifid thumb is a rare manifestation of polydactyly. The trait is autosomal dominant, but the expressivity is highly variable. It must be distinguished from apical dystrophy, a rare form of brachydactyly. Severe surgical procedures have been suggested for both functional and cosmetic reasons. Two families affected are described.


Eccrine angiomatous hamartoma: a multiple variant. A case of multiple eccrine angiomatous hamartoma present in a boy since birth is reported. Clinically, this condition must be differentiated from other neonatal angiomatoses. Sometimes the clinical findings are nonspecific, whereas histologic examination may exclude angiomatoses with visceral involvement. In our case the hamartomatous nature of this tumor is documented also by the presence of pilar structures intimately related to the eccrine-angiomatous complex in one of two lesions histologically examined. Therefore, the histologic classification of eccrine angiomatous hamartoma into subgroups seems to be excessive.


Dysplastic nevus syndrome: intrafamilial identification of carriers by cytogenetics. Seven members of a family with dysplastic nevus syndrome (DNS) were examined clinically; skin biopsies of unaffected skin from 6 were taken. Biopsy-derived cultivated fibroblasts were examined by cytogenetic methods, i.e. by measuring the spontaneous and the UVB- and UVC-driven increase in sister chromatid exchange (SCE). A male patient with malignant melanoma, his son and his nephew, both with multiple dysplastic nevi, showed a distinctive elevation of UV-induced SCE, whereas the other, unaffected members of the family showed normal values. These results give evidence that in siblings with DNS the affected members can be identified not only on clinicopathological grounds but also by UV-induced elevated SCE at the cytogenetic level.


[Effects of tiropramide on the activity of lower urinary tract in dogs and its interpretation]. The rhythmic contractions of urinary bladder under constant volume condition were evoked in decerebrate and de-anesthetized dogs, while various myogenic and nerve-mediated electrical and mechanical activities of smooth muscles were recorded from in vivo pelvic viscera. The vesical rhythmic contractions were transiently and partially blocked by intravenous application of tiropromide. This 'partial' block showed a good contrast to the 'complete' block of identical contractions, which was observed after application of oxybutynin, known as a potent anti-muscarinic drug. The bladder voiding cycles were observed in other decerebrate dogs, while the warmed Ringer solution was infused at a steady rate into the dome of the bladder until principal voiding contraction occurred in cystometric recordings. The initiation of voiding contraction was markedly delayed after intravenous injection of tiropramide. The delay of principal contraction was found to be due to successive appearance of falling waves in cystometric recordings. As a evident contrast, terodiline caused a significant reduction of voiding contraction height and shortening of clonic discharge phase of external urethral sphincters during voiding cycle. It is concluded that tiropramide does not reveal anti-muscarinic action which oxybutynin or terodiline does really show, instead tiropramide acts principally on bladder detrusor itself, especially on its relaxation phase of premature contraction to be prolonged. The evidences were also presented for electrophysiological identification of bladder detrusor and urethral smooth muscle.


[An experimental study of the diurnal changes in colonic motility centering on defecation]. The following findings have been obtained as a result of making an assessment regarding the diurnal changes in colonic motility by means of continuous measurement of contractile waves by using strain gauge force transducers and roentgenographic observation in conscious dogs. 1. Before defecation, the contractile force of the wave was weak, frequency of its emergence was also small, and transfer of intestinal content was slow, showing decrease of colonic motility. 2. After defecation, the gradually increasing and decreasing contractile wave groups became clear, and the contractile force was intensified concurrently with increase of its emerging frequency. Transfer of intestinal content to the anal side was rapid, and recovery of colonic motility was observed. 3. The recovery of the colonic motility after defecation was observed regardless of digestive or interdigestive state. 4. By intake of food, increase of the colonic motility corresponding to gastrocolic response was observed, but it was due to the increase of emerging frequency of contractile wave, for which no change was observed in contractile force or duration in each individual waves. 5. It was suggested that the contractile motion which undergoes gradual increase and decrease is the basic pattern in the colonic motility and that the colonic motility changes by the differences of amount, shape and hardness of intestinal content, and decreases gradually along with increase of intestinal content, but the basic pattern of contractile motion is restored by inflow of intestinal content into the colon which became empty after defecation. From the above it was considered to be inadequate to use the pattern classification of digestive and interdigestive state for the analysis of colonic motility and that assessments should be made centering on defecation.


Vaso-contractile responsiveness of perfused arterial segments to platelet-derived thromboxane A2. It remains not entirely accepted that changes in prostanoid metabolism in the blood vessel wall, as well as in whole blood, have a certain influence on vascular responsiveness to vasoactive agents. The aim of the present study is to elucidate whether platelet-derived thromboxane A2 (TxA2) participates in enhancement of vasoconstractile response to a pressor agent. Platelet aggregation was extraluminally induced by application of collagen to autologous platelet rich plasma (PRP), and then the PRP treated with collagen was infused into the perfusion system by means of a small infusion pump. All the prostanoids in the perfusate were assayed radioimmunologically. Infusion into the perfusion system of PRP treated with collagen, as well as that of untreated PRP, apparently caused pronounced enhancement of vasocontractile response to noradrenaline (NA), accompanied by elevations of both the level of TxB2, a stable metabolite of TxA2, and the TxB2/prostaglandin E (PGE) ratio. In addition, treatment with either OKY-046 (a Tx A2 synthetase inhibitor) or ketanserin (a selective S2-serotonergic antagonist) resulted in diminution of the raised vasoconstrictor response to NA induced by application of collagen to PRP. Thus, it is possible to draw the conclusion that platelet-derived TxA2, is as potent a vasoactive substance as 5-hydroxytryptamine (5-HT) and at least in part, contributes to the enhancement of vasocontractile response to NA (NA-R) during raised platelet aggregability.


[Effect of terazosin on lower urinary tract function in the male decerebrate dog]. The effect of terazosin on the lower urinary tract function was studied by combined recording of bladder and urethral pressures and external sphincter electromyogram in 8 male decerebrate dogs. Reflex micturitions were induced by bladder filling before and after terazosin. The statistical analysis was carried out on the urodynamic parameters. During the collecting phase, terazosin at doses of 10, 30 and 100 micrograms/kg produced a significant decrease in maximum urethral pressure in the dose dependent manner. Threshold pressure was significantly shown to decrease at doses of 30 and 100 micrograms/kg. In the urodynamic parameters of the emptying phase there was a significant decrease in maximum contraction pressure at 10 and 30 micrograms/kg, and in voided volume at 100 micrograms/kg. Terazosin seems to facilitate an initiation of the bladder contraction with a decrease in threshold pressure. In concludes that alpha 1 adrenergic activity seems to take an important role for the maintenance of the urethral pressure and to control the initiation of bladder contraction in modulation with threshold pressure.


[An experimental study of gastrointestinal motility during chronic large bowel obstruction]. Gastrointestinal motility and plasma PYY levels were investigated under chronic progressive large bowel obstruction in dogs. The obstruction device was applied around the descending colon at a laparotomy and gastrointestinal motility was recorded with strain gauge force transducers in the conscious state. Complete obstruction occurred at 26 days (21-33 days). The duration of postprandial interruption of motor complex (DIMC) in the antrum and duodenum were prolonged progressively, at partial obstruction (17.7 +/- 2.7 hr; p less than 0.05) and complete obstruction (23.0 +/- 4.0 hr; p less than 0.01) vs in control (13.7 +/- 1.9 hr), while DIMC in the small bowel showed no significant changes. Progressive obstruction caused hypermotility in the proximal colon to the obstruction and hypomotility in the distal colon. These dysmotility were improved after resection of the obstructed segment and anastomosis. Plasma PYY levels in the fasting state showed no significant increase at complete obstruction (42.6 +/- 14.5 pmol/l) vs in control (32.9 +/- 10.2 pmol/l).


Molecular genetics and clinical aspects of inherited disorders of nerve and muscle. Rapid progress has been made in elucidating the molecular genetic basis of several neuromuscular disorders in the past year. Candidate genes have been identified or analysed in hereditary motor and sensory neuropathy (HMSN) type I, X-linked bulbospinal neuronopathy and non-dystrophic myotonic disorders, and further mutations causing amyloidosis have been identified. A familial amyotrophic lateral sclerosis (ALS) locus maps to chromosome 21 in some families, and the chronic childhood spinal muscular atrophy (SMA), facioscapulohumeral muscular dystrophy (FSHD) and malignant hyperthermia loci have been localized more precisely.


Advances in myotonic dystrophy: a clinical and genetic perspective. The recent identification of the gene responsible for myotonic dystrophy and the recognition of an expanding unstable repeat sequence as the specific molecular defect, have resulted in rapid changes in clinical practice as well as in our understanding of the disorder. Against such a framework, this review traces the evolution of clinical and genetic knowledge of the disorder and emphasizes the continuing central role of thorough clinical investigation of those at risk for carrying the gene as an essential element of predictive testing for myotonic dystrophy.


X-linked dystrophies: from gene localization to gene therapy. Linkage studies have narrowed the interval to which the Emery-Dreifuss muscular dystrophy (EDMD) gene maps, raising prospects for isolating this locus. Diagnosis and carrier detection for Duchenne muscular dystrophy (DMD) have been improved, new isoforms of dystrophin have been identified, and gene transfer studies have raised the prospects for gene therapy.


Recent developments in the biology of dystrophin and related molecules. Important progress in the understanding of various aspects of dystrophin biology continued during the past year. This relates to basic biochemistry, isoforms, subcellular localization in skeletal muscle, regional distribution in brain, physiological role, abnormalities caused by gene mutations and nuclear domain characteristics. Major progress has also taken place in the characterization of the dystrophin-associated glycoprotein (DAG) complex and in the understanding of its role in anchoring dystrophin to the plasmalemma and providing a link to the extracellular matrix. Characterization of the human chromosome-6-related analogue of dystrophin led to the discovery that in Duchenne muscular dystrophy (DMD) this molecule is expressed diffusely at the muscle cell surface and could, in part, compensate for the dystrophin deficiency of DMD.


Mitochondrial diseases.

Mitochondrial diseases. With the discovery of mitochondrial DNA (mtDNA) mutations in different neuromuscular disorders, investigations now seek to clarify how the mutant mtDNA induces biochemical and morphologic defects. In one of the most important approaches human mutant mtDNA is transferred into cells that lack mtDNA to examine the relationship between the amount of mutant mtDNA and defects in cell growth, respiration and enzyme activities. The resulting cells are 'cybrids'; these clonal cells contain the heteroplasmic mutant and normal mtDNA from patients with mitochondrial diseases. The mitochondria become functionally defective when the amount of mutant mtDNA exceeds a certain threshold, which differs from mutation to mutation: 60 to 70% in chronic progressive external ophthalmoplegia (CPEO) and probably 95% in the syndromes of mitochondrial encephalopathy, myopathy, lactic acidosis, and stroke-like episodes (MELAS), and myoclonic epilepsy with ragged red fibers (MERRF). This threshold effect may explain the tissue-specific patterns of clinical expression.


Inflammatory neuropathy: pathogenesis and clinical features. The nature of the underlying mechanisms in inflammatory and immune-mediated neuropathies continues to represent an intensive area of research. Different auto-antibodies that are thought to cause specific neuropathic syndromes have been described. The involvement of T cells, cytokines, complement and class II molecules in the pathogenesis of these syndromes has also been studied. There is also intensive investigation into the area of immunotherapy, in particular in the use of intravenous immunoglobulin (Ig).


Spinal cord injury and its rehabilitation. The past year has witnessed a dramatic increase in the number of studies that have focused on psychosocial and behavioral components of spinal cord injury (SCI) rehabilitation. The current article reviews and synthesizes this research highlighting the most important contributions to the areas of psychological adjustment, employment, suicide and mortality, aging, substance abuse, cognitive impairment, and pain management.


Head injury and its rehabilitation.

Head injury and its rehabilitation. Investigation of outcome following head injury is changing from studies with a broad scope to more focussed issues concerning specific subgroups, the application of new technologies such as functional brain imaging, clinical trials of medication, and strategies of rehabilitation. This review primarily addresses outcome and intervention studies relevant to the sequelae and rehabilitation of head-injured patients.


Stroke rehabilitation.

Stroke rehabilitation. Stroke produces impairments, disabilities and handicap. At each level attention may be directed at methods of assessment, monitoring or predicting outcome, and evaluating effects of treatment. There has been a change in emphasis from impairment to disability and handicap. The most informative research has been directed at evaluating rehabilitation effectiveness.


Measurement in neurological rehabilitation. The measurement of impairment and disability can improve patient care and is now essential in clinical audit. Practical, useful measures are slowly being developed, both for use in specific diseases and for more general use. This review discusses both new measures and new work on more well-established measures.


Electroencephalography.

Electroencephalography. Recent advances in electroencephalography (EEG) research are presented. Particular emphasis is placed on sleep and epilepsy research in humans. In this context, among others, studies on the modifications of EEG epileptic activity during sleep are discussed in more detail. A large number of reports come from EEG monitoring during presurgical evaluation and surgical treatment of drug-resistant epilepsy; information provided by these studies is therefore considered with special attention.


Gaze and eye movement disorders.

Gaze and eye movement disorders. Cortical areas were explored with regard to saccade control: the lateral intraparietal (LIP) area is involved in the spatial aspects of sensorimotor processing; the supplementary motor area in goal-directed gaze control; and from lesion studies; the posterior parietal cortex in triggering visually guided saccades. Different studies have suggested that the spatial-to-temporal transformation takes place in the superior colliculus (SC) and the cerebellum. When the vestibulo-ocular reflex (VOR) produces inadequate eye movements, other supplementary mechanisms (e.g. non-visual, saccade) may play a role in correcting gaze. A classification of central vestibular disorders of the brainstem and VOR has been proposed, as manifested in any one of the three major planes of action (yaw, pitch and role).


Sensory evoked potentials: PERG, VEP, and SEP. The review summarizes current developments in pattern electroretinography practice and theory: generator sources and clinical applications. This is particularly relevant to neuronal disease of the central nervous system (CNS). Visual evoked potentials (VEPs) are discussed in reference to the evolution and follow up of multiple sclerosis (MS) and in conjunction with magnetic resonance imaging (MRI) demonstrated abnormalities. These reveal that the techniques are complementary. Sensory evoked potentials (SEPs) in conjunction with MRI studies are highlighted as quantitatively comparable in spinal cord disorders.


Event-related potentials.

Event-related potentials. Event-related potentials (ERPs) are scalp recorded electrophysiological responses that are related to an internal cognitive event. This review summarizes recent findings on the effects of neurologic disease and the origin of ERPs obtained in expectancy, attention, memory, and linguistic tasks. Cognitive ERPs allow the physiologic activity of the brain to be analyzed with exquisite temporal resolution. Our understanding of these potentials is incomplete at present. Advances in cognitive psychology and source localization of these surface potentials, however, may result in an increased understanding of both the organization of cognitive processing in the brain and cognitive deficits that result from neurologic disease.


Neuro-ophthalmology.

Neuro-ophthalmology. The anatomy, neurophysiology, semiology, and pathology of the pupillary reflexes are reviewed. Recent advances in the demonstration of midbrain pathways projecting to and from the Edinger-Westphal (EW) nucleus are discussed. Observations of the pupillary diameter and reflexes in premature infants can be helpful in the diagnosis of neurological disorders. A relative afferent pupillary defect (RAPD) without visual disturbances can be suggestive of midbrain lesions. Automated pupil perimetry is proposed as an objective method for the evaluation of the visual field. Tonic pupil, the pupil in diabetics, and blue-cone monochromatism are also discussed.


Neurophysiology in the science of speech. Electrophysiological recordings of the muscles involved in speaking (respiratory, glottal, oromandibular) have been added to the acousticograms (ACGs) for analyzing the latency times in verbal reactions, their coordination and their patterns. The electromyogram (EMG) has allowed to better identify the preparatory initiation and the modulation of the muscular stiffness. Meaningful changes have been obtained in aging processes, stuttering, and several neurological diseases. Event-related brain potentials have also been investigated during normal speaking and reading.


[Current data on GM-CSF (Granulocyte-Macrophage Colony Stimulating Factor) in acute myeloid leukemia]. GM-CSF (Granulocyte-Macrophage Colony Stimulating Factor) activates neutrophil, eosinophil, granular, and macrophage precursors through binding to specific receptors. GM-CSF receptor is a member of the "cytokine receptor superfamily", which displays a particular transmembrane structure. It is expressed in small amounts on normal mature blood or medullary cells, with a high affinity. On acute myeloid leukemia blasts (18 patients), our results agree with the review of the literature: GM-CSF receptors are in small amounts, of two types (high and low affinity), with no relation to the FAB classification of leukemias.


[Growth factors of cultured epithelial cells of breast diseases and breast carcinoma]. Primary cultures of non-malignant human breast tissues, benign mastopathies and breast carcinomas were raised in defined culture conditions and characterized for in vitro cell proliferation. Although some mastopathies had estradiol receptors they did not respond to hormone treatment. Epidermal growth factor (EGF) was capable of stimulating the 3 types of primary culture. In contrast, dexamethasone, insulin and transferrin stimulated only the proliferation of some benign mastopathies and carcinoma cells. Cholera toxin increased the cell growth of normal tissues and mastopathies but not of carcinoma in primary cultures. Taken together, these results show that epithelial cells from mastopathies differ from one another; some are similar to non-malignant cells, whereas others are comparable to tumor cells.


[Cancerology training in France].

[Cancerology training in France]. During the last years, training in cancerology in France has been developed extensively. The importance of training as a major element in the fight against cancer is now widely recognized. Cancerology teaching has been improved in the curse of clinical science for medical students as well as the training of general practitioners. Special courses qualifying for the Diploma of Specialised Complementary Studies in Oncology are available to Cancerologists. While appreciating the positive aspects of cancerology training at these different levels, we must stress a certain number of weak points that need to be corrected. Several propositions tending to further improve cancerology training are proposed. The implementation of these recommendations should allow France to maintain its rightful place in cancerology within the European Community.


[Ewing's sarcoma of bone in adults: an anatomic-clinical study of 30 cases]. The records of 30 adult patients with Ewing's sarcoma (ES) of bone treated between 1980 and 1990 at the Institut Curie were studied retrospectively; the diagnosis was reevaluated by histological and immunohistochemical analysis, using HNK and anti-neuron specific enolase (NSE) antibodies. The immunohistological analysis disclosed a significant staining of neoplastic cells in only few of our cases and is therefore of limited interest in the diagnosis of ES. Three groups of patients have been considered according to their clinical presentation: axial, peripheric and initial metastatic disease. The global prognosis is poor: the survival rate is 70% after a follow-up period of one year, and 23% after three years. The evolution was severe for patients with pelvic localization and/or initial metastatic disease. In contrast, five of six patients who are currently free of disease after a mean follow-up period of 42 months presented initial peripheric lesion. Four of these six patients were treated by a combination of surgical, chemical and radiation therapies.


[A study of VMMC protocol (vindesine, mitoxantrone, mitomycin C) as a salvage chemotherapy in advanced breast cancers]. One hundred and three patients previously treated with chemotherapy including an anthracycline were entered in a VMMC protocol study: vindesine (Eldisine), mitoxantrone (Novantrone) and mitomycin C (Ametycine). Group A consisted of 41 women who received the protocol published by Belpomme: vindesine (2.5 mg/m2 day 1 and 8) and mitoxantrone (12 mg/m2/day) every 4 weeks, and mitomycin C (8 mg/m2) every 8 weeks. Group B consisted of 62 patients who were treated with a modified protocol: vindesine (2.5 mg/m2) and mitoxantrone (12 mg/m2) every 3 weeks on day 1, and mitomycin C (8 mg/m2) every 6 weeks. Tolerance was acceptable with 79% of patients complaining of weakness. There was a 66% incidence of gastro-intestinal toxicity, a 10.7%-incidence of neurotoxicity (reversible dysethesias), and a 5.8% incidence of cardiotoxicity. There was considerable hematotoxicity of grade 2, 3 and 4: neutropenia 16.6%, thrombocytopenia 7.7%, anemia 21.4%. There was a 19.2% overall objective response rate (CR and PR) (95% confidence interval: 12-30) (CR: 3.2%). The median duration of the response was 39 weeks. There was no significant difference in response rates whether or not the patients (19 cases) were undergoing simultaneous hormonal therapy and no difference according to the protocol used. Similarly, neither menopause nor a previous response to anthracyclines had any effect on the response rate. The 19.2% response in this protocol is similar to other breast cancer salvage chemotherapy protocols for patients who have failed to respond to anthracyclines (< 20%).


[Role of radiotherapy in the treatment of bone metastases]. The most frequently encountered metastases during evolution of cancers are bone metastases, which involve painful syndrome. External radiotherapy is an effective and indisputable treatment to give relief to suffering patients. The modalities of the regimen of external radiotherapy are different according to the disease stage, the prognosis and eventually associated treatments such as chemotherapy, hormonotherapy or surgery. The dose can be delivered either according to normal regimen, hypofractionated radiotherapy, or half-body radiotherapy. Whatever the modalities, antalgic results noted in around 85% cases are very similar. On the other hand, the plastic action of external radiotherapy on lytic bone is also important.


[Laser therapy in the prevention and treatment of mucositis caused by anticancer chemotherapy]. The appearance of mucositis is a frequent and painful secondary effect of anticancer chemotherapy. Patients who develop oral toxicity during the first course of treatment will almost assuredly show identical side effects during each subsequent course unless the drugs are changed or the doses are lowered. In the absence of an efficacious antidote or preventive prophylaxis for such lesions to date, this report presents the results of a preliminary retrospective non-randomized study of the effect of soft-laser treatments on mucositis in cancer patients receiving combination chemotherapy, including 5-fluorouracil. Iatrogenic mucositis was observed during 43% of 53 chemotherapy cycles in the case control population. Curative laser therapy reduced the time to repair lesions and the rate of therapeutic modifications. For patients who received soft-laser therapy as a preventive measure, the incidence of oral complications was reduced to 6% during 101 cycles of chemotherapy. All of these patients, even those who have encountered mucositis before receiving preventive laser therapy, terminated their cancer therapy as originally scheduled. Well designed and carefully controlled trials will be necessary to define the place of helium-neon laser therapy in the repair and prevention of oral complications due to cancer chemotherapy.


[Measurement of quality of life. Application to the screening of psychological distress in cancer patients]. As cancer treatments are becoming more and more traumatic the quality of life of these patients must be taken into consideration. This study was set up in 1982 and aimed at screening patients suffering from major psychological distress using a quantitative assessment of the quality of life. A self-administered questionnaire (QLQ) and linear analogues (LA) were developed and validated. The patient's acceptance of these two measuring instruments was tested on a sample group of patients in the Oncology Department of Besançon University Hospital and gave a result of 94% which was higher than that of a psychological interview (64%). A comparison of the assessment of the quality of life by the patient, the psychologist and the physician is an important phase in this concept. Agreement by the doctor and the patient using the Karnofsky indices was moderate (62% of the cases using a simplified scale): patients tended to overstate the extremes. The overall scores and the different questionnaire items completed by the patient and the psychologist were correlated, but agreement varied according to each item. An attempt was made to establish a predictive value for the questionnaire and the linear analogues to identify patients suffering from major psychological distress and requiring psychosocial support by comparing the results of the tests with the assessment of the psychologist during an interview. A stepwise logistical regression selected a combination of three items which screened more than 80% of these patients. The linear analogues were not sufficiently discriminatory to be used. The overall results suggest that a quality of life measurement can be integrated into daily clinical practice.


[Multiple myeloma: current therapeutic approaches]. The therapeutic strategy in multiple myeloma depends on age and tumor mass. Stage I must not be treated. The Melphalan Prednisone regimen is the reference for induction therapy because polychemotherapies are generally not superior. At this phase, the addition of Interferon alpha seems to be interesting. This drug has an important role during the steady-state phase. VAD represents the most efficient chemotherapy. Body hemi-irradiation is also useful. The analgesic effect and the decrease in the tumoral mass are the striking effects of this treatment. In young patients, high dose chemotherapy with bone marrow transplantation is proposed. Verapamil and anti-IL6 antibodies are currently being evaluated. Symptomatic treatment is essential in this non curable disease.


[Statcan: a telematic system for checking mortality and incidence of cancer in France]. Statcan is an interactive system for consulting cancer mortality and incidence data in France. This system is accessible through the Minitel network and provides information concerning cancer mortality: number of deaths, basic rates, standardized rates for the French, European and world population, cumulative rates up to the age of 74 years as well as specific rates by age, sex and cancer site for France as a whole from 1968 to 1988 and by region for 1968, 1975 and for 1979-1988. National incidence data are available for 5 regions between 1978 and 1982. several complementary chapters provide information explaining the methodology used and help in formulating the questions.


[FGFB binding sites in cancers of the human breast]. We investigated binding characteristics of bFGF in membranes prepared from 4 human breast cancer cell lines (MCF-7, T-47D, BT-20 and MDA-MB-231) and 38 primary breast cancer biopsies. Results of competitive binding experiments were analysed using the "Ligand" program to determine binding site concentrations and affinities. bFGF mitogenic activity was also measured by [3H]-thymidine incorporation into DNA of breast cancer cell lines. The presence of high-affinity binding sites was demonstrated in each cell type (Kd: 0.5 nM). The presence of these high-affinity binding sites was confirmed by saturation experiments. A second class of low-affinity binding sites was detected in the 2 hormono-independent cells (BT-20: Kd = 2.9 nM; MDA-MB-231: Kd = 2.7 nM). bFGF stimulated the proliferation of MCF-7, 7-47D, BT-20 and not of MDA-MB-231 cell lines. In breast cancer biopsies, binding sites were detectable in 36/38 cases; high-affinity binding sites (Kd < 1 nM) were present in 19/39 cases and low-affinity binding sites (Kd > 2 nM) were present in 29/36 cases (the 2 classes of binding sites were present in 12 biopsies). No relation between FGF binding sites and node involvement nature or grade of tumor was evidenced. Negative correlations (Spearman test) were found between total bFGF binding site concentrations and estradiol receptor concentrations (P = 0.05) or progesterone receptor concentrations (P = 0.009). The demonstrations of 1), bFGF specific binding sites in breast cancer membranes; and 2) bFGF growth stimulation of some breast cancer cell lines, indicate that this factor could be involved in the growth of most breast cancers, and could act (among other factors) directly on the growth of cancer cells.


Immunolocalization of matrix metallo-proteinases and their tissue inhibitor in human mammary pathology. Matrix metallo-proteinases (MMPs) are a group of enzymes thought to be responsible for both normal connective tissue matrix remodelling and accelerated breakdown associated with tumor development. The distribution of 3 major matrix metallo-proteinases was studied in human mammary pathology: collagenase (MMP1) which degrades fibrillar interstitial collagens, a 72-kDa gelatinase (MMP2) which mainly degrades type IV collagen and denatured collagens, and stromelysin (MMP3) which has a wider range of action, degrading several matrix components including the core proteins of proteoglycans, laminin and non-helical regions of collagens. These MMPs and the MMP tissual inhibitor (TIMP1) were detected by immunohistochemistry in 30 benign and 79 malignant lesions of the breast. MMPs were detected in 1 fibroadenoma (collagenase) and 22 breast carcinomas: collagenase (9 cases), stromelysin (12 cases) and gelatinase (16 cases) with a limited distribution. Tumor cells were preferentially labelled and the localization of gelatinase and stromelysin at the periphery of some non-invasive and well-differentiated clusters supports the role of these enzymes in the breakdown of basement membranes. Only a few stromal cells (fibroblasts) were found to be immunopositive. In contrast, TIMP1 was more frequently detected, and was found in 7 benign lesions and 55 carcinomas out of 79. It was mainly localized at the periphery of the endothelial cells but was occasionally detected in cancer cells and fibroblasts.


Tumor associated glycoprotein-72 (TAG-72) levels in patients with non-malignant and malignant disease. TAG-72 is a tumor-associated antigen identified by the monoclonal antibody B72.3. Serum levels of TAG-72 were measured in patients with non-malignant and malignant disease. TAG-72 is not a specific marker of cancer and slightly elevated levels of this antigen can also be detected in the serum of healthy subjects. However, our results show that specificity (92%) and positive predictive value (86%) of this marker are very high. TAG-72 levels above the cut-off limit of 6 U/mL were found in patients with tumors of various organs, including gastrointestinal, ovarian, lung and breast cancer. TAG-72 assay sensitivity is related to tumor stage with values being highest with advanced disease, especially in patients with gastric cancer and lung adenocarcinoma.


[Current role of chemotherapy in the treatment of invasive cancers of the bladder]. Treatment of bladder carcinoma with cystectomy and or radiotherapy provide 5-year survival rates of 28-50%. Phase II chemotherapy trials have proven its efficacy with a partial and complete response rate of 20% and 10% respectively for drugs such as cisplatin or methotrexate. Recent phase III studies have demonstrated the superiority of associations such as CMV, CISCA or M-VAC with complete response rates of 28-39%. Neoadjuvant chemotherapy may increase local control and offer the possibility of conservative treatment after complete tumor regression (one third of cases). The positive effect of neoadjuvant chemotherapy on survival has not yet been demonstrated and randomized trials are now in progress. The concomitant association of cisplatin or fluorouracil with radiation therapy provides high complete response rates (65-88%) in all published studies. A longer follow-up period is necessary to confirm these results in terms of local control gain and survival benefit, but this strategy seems to constitute a major advancement for patients unable to undergo radical cystectomy. Further studies are needed before extending this conservative approach to less advanced invasive bladder carcinoma. Adjuvant chemotherapy may decrease metastasis rate, but survival benefit has not yet been definitively established by randomized studies.


[Lymph node metastasis of melanoma of unknown primary tumor]. Sixteen patients with clinical stage II melanoma of unknown primary site (regional lymph node metastasis) were followed up between 1978 and 1988. The 5-year survival rate was 47%. These results seem to parallel those for stage II disease with known primary tumor sites, as has been observed in other data from the literature. The hypotheses put forward to explain such lesions are the spontaneous regression of the primary tumor, and the onset of primary malignant melanoma in the lymph nodes.


[Acute lymphoblastic leukemia and pregnancy. Apropos of a case]. The authors report on a case of a woman with acute lymphoblastic leukemia treated with cortisone therapy during pregnancy. No problems were encountered during the gestational period or at parturition; and no maternal or neonatal complications were observed.


Effects of metabolic control on ventricular function in type 2 diabetic patients. The effects of the metabolic changes of type 2 diabetic patients on ventricular function, especially diastolic ventricular function were investigated. An examination was performed before and after treatment of 18 diabetic patients divided into 3 groups: insulin therapy, oral hypoglycemic drugs and diet therapy (6 patients each). The results indicated that both systolic and diastolic ventricular dysfunctions observed were improved by the correction of hyperglycemia. Therefore it is necessary to treat diabetes mellitus as early as possible for the prevention of both cardiac dysfunction and microangiopathy.


Overall clinical effect of percutaneous coronary angioplasty: a critical analysis by follow-up and long-term angiography. In order to determine the clinical efficacy of coronary angioplasty, the outcome was analyzed in 557 patients who underwent initial angioplasty prior to the end of 1987. Primary success (reduction of stenosis greater than or equal to 20% and residual stenosis less than 50%) was achieved in 492 (88.3%) of the patients. Follow-up angiography showed patency (stenosis less than or equal to 50%) in 295 or 60.0% of the 471 patients and ultimate lesion patency was achieved by repeating angioplasty up to 4 times in 425 (91.4%) of 465 patients followed angiographically. At the 3-year angiography performed in 209 patients with patent lesions, only 2 patients exhibited progression of their disease at dilated sites, while 48 had new lesions. Taking into consideration the 55 patients with unsuccessful primary angioplasty, 10 patients with major complications and 9 patients with mild restenosis, 434 out of 530, or 81.9% of the patients appear to have benefited from angioplasty.


Urinary 11-dehydro-thromboxane B2: a quantitative index of platelet activation in cerebral infarction. Thromboxane A2 (TXA2) biosynthesis was studied in healthy subjects, patients with chronic cerebral infarction, patients under chronic aspirin treatment and patients with atrial fibrillation. Urinary 11-dehydro-TXB2, as a major metabolite of TXA2, was measured by radioimmunoassay. The extent of carotid atherosclerosis was determined by B-mode ultrasonography. The mean +/- SD urinary excretion in patients with cerebral infarction and distinct carotid-atherosclerotic lesions (1,725 +/- 239 ng/g creatinine, n = 6) was significantly higher (p less than 0.01) than in healthy subjects (911 +/- 239 ng/g creatinine, n = 44) and patients with cerebral infarction who had no distinct carotid lesion (1,050 +/- 191 ng/g creatinine, n = 6). The urinary excretion of healthy subjects was higher (p less than 0.01) in smokers (1,063 +/- 244 ng/g creatinine, n = 17) than in non-smokers (815 +/- 183 ng/g creatinine, n = 27). Aspirin largely suppressed 11-dehydro-TXB2 excretion (266 +/- 114 ng/g creatinine, n = 7). Three of 5 patients with atrial fibrillation showed very high values. Our results indicated that platelet activation occurs in the atherosclerotic lesions, and that urinary 11-dehydro-TXB2 is the appropriate analytic target for detecting platelet activation.


Hospital-onset tuberculosis in compromised host. A total of 21 patients developed active tuberculosis (TB) during hospitalization. Active TB was identified by bacteria-positive, biopsy or autopsy. Infection was confirmed to the lung, pleura, lymph node and miliary lesions and 7 patients had open tuberculosis. In half of the patients, chest X-ray films demonstrated unusual findings in adult tuberculosis: lower lung field pneumonia and miliary pattern. All the patients suffered from severe underlying diseases and an intensive therapy with steroid, immunosuppressive agents, antitumor drugs, radiation and operation was found as predisposing factors for TB occurrence. Nine patients recovered from current infection with anti-tuberculosis drugs; 14 patients died and TB directly caused death in 8 patients. These data strongly suggest that TB is one of the most important infections in compromised hosts. We emphasize that this infection presents a serious clinical problem in a general hospital today.


Abnormalities in platelets and vascular endothelial cells induced by glycated lipoproteins. We studied the effects of glycated lipoproteins of low- and high-density (LDL and HDL) on platelets and vascular endothelial cells. After pretreatment for 5 minutes at 37 degrees C, the thrombin-induced synthesis of thromboxane B2 in washed platelets was significantly increased by glycated LDL as compared with native LDL (198.9 +/- 16.2 vs 90.3 +/- 29.4 ng/10(9) platelets, n = 8, p less than 0.01). Platelet aggregation was also increased by glycated LDL as compared with native LDL. After treatment with platelet-rich plasma for 5 hours at 37 degrees C, these values were suppressed by native HDL vs the control (buffer), but not by glycated HDL. Abnormalities in the release of 6-keto prostaglandin F1 alpha and lactate dehydrogenase from vascular endothelial cells were also induced by glycated LDL and/or HDL. These observations suggest that abnormalities induced in platelets and vascular endothelial cells by glycated lipoproteins may play an important role in the development of atherosclerosis in patients with diabetes mellitus.


Simultaneous measurements of adenosine deaminase activity and tuberculostearic acid in pleural effusions for the diagnosis of tuberculous pleuritis. Adenosine deaminase (ADA) activity and tuberculostearic acid (TSA) levels in pleural effusions were measured in 18 patients with active tuberculous pleuritis, 16 patients suspected of having tuberculous pleuritis, 14 patients with carcinomatous pleuritis, and 19 patients suffering from pleuritis of non-malignant and non-tuberculous etiology. In the patients with active tuberculous pleuritis, ADA was elevated in 56% and TSA was positive in 78%. In 83% of these patients, either ADA was elevated or TSA was positive. ADA was elevated together with a positive TSA in 50%. In contrast, TSA was positive in only 6% and ADA was elevated in 24% of the patients with non-tuberculous pleuritis, and none of these patients showed the combination of an elevation of ADA and a positive TSA. These results suggest that simultaneous measurements of both ADA and TSA in pleural effusions are useful for the diagnosis of tuberculous pleuritis.


Seven patients with plasma cell granuloma (inflammatory pseudotumor) of the lung, including two with intrabronchial growth: an immunohistochemical and electron microscopic study. Seven patients (mean age, 50.7 +/- 20.4 years; range 21-77) with plasma cell granuloma (PCG) of the lung are reported. Cough and sputum were the most common presenting symptoms, followed by fever. Elevated erythrocyte sedimentation rate and serum C-reactive protein levels were found in all patients tested. Radiologically, five cases presented as solitary, well-circumscribed masses and two as ill-defined, pneumonia-like densities. One showed focal calcification. No predilection of occurrence was observed in either lobe of the lung. Histologically, the lesions consisted of a proliferation of mature plasma cells and reticulo-endothelial cells supported by a stroma of granulation tissue, with varying degrees of myxoid change or collagenization. Angioinvasion within the lesion was observed in 4 of the 7 cases. Immunohistochemical staining revealed the IgG-predominant polyclonal nature of the plasma cells, indicating a reactive inflammatory process rather than a neoplastic one. Electron microscopy confirmed the benign nature of the plasma cells with fibroblast and myofibroblast proliferation admixed with that of other inflammatory cells.


Humoral and cellular immunity to Candida albicans in patients with bronchial asthma. Delayed cutaneous reactivity to Candida albicans (C. albicans) and PPD (purified protein derivative) was examined in 52 patients with bronchial asthma in relation to the production of specific IgG4 antibodies against the antigen. 1. The frequency of a positive, immediate skin reaction to C. albicans was similar among the five age groups, ranging from 60.0% to 66.7%. 2. The incidence of a positive delayed skin reaction to C. albicans was lower in patients between the ages of 10 and 30 and tended to decrease with aging in the patients over the age of 51. 3. A delayed skin reaction to PPD was positive in patients between 31 and 50 with a higher incidence; this incidence decreased in patients over age 51. 4. The level of C. albicans-specific IgG4 antibodies was significantly higher (26.7 u/ml) in patients with a negative delayed skin reaction to the antigen than in those with a positive reaction (5.9 u/ml) (p less than 0.001). There was no correlation between delayed skin reaction to PPD and production of specific IgG4 antibodies.


Lung cancer accompanied by erythema.

Lung cancer accompanied by erythema. Skin manifestations associated with malignant diseases are designated syndroma dermatotumorale. A case of lung cancer combined with atypical erythema is reported. A 70-year-old man was admitted to hospital because of a 4-month history of atypical erythema of unknown origin. A nodule in the right lung was revealed on chest roentgenogram which was diagnosed as lung cancer. After right upper lobectomy, the erythema regressed gradually and disappeared completely in 7 days. It is suggested that the erythema was a manifestation associated with the lung cancer.


Kawasaki disease complicated by acute myocardial infarction due to thrombotic occlusion of coronary aneurysms 19 years after onset. A 25-year-old man with a history of Kawasaki disease from the age of 7 had acute inferior myocardial infarction. Emergency right coronary arteriogram showed successive coronary aneurysms at the proximal to middle portion of the right coronary artery, and total occlusion at the proximal segment. Intracoronary thrombolysis was performed and the right coronary artery was recanalized. On left coronary arteriography, coronary aneurysms and mild localized stenoses at the inlet and outlet of the aneurysms were found. It was suggested that the myocardial infarction was caused by thrombotic occlusion of coronary aneurysms complicated with Kawasaki disease.


Systemic lupus erythematosus with sensorineural hearing loss and improvement after plasmapheresis using the double filtration method. A 32-year-old female was diagnosed as having systemic lupus erythematosus based on her laboratory tests. In 1985 she began to complain of hearing difficulty. Her hearing ability deteriorated to the extent that her audiogram revealed a hearing loss of 90 db to 110 db in both ears in September 1989. She received two series of plasmapheresis treatments using the double filtration method. After two series of plasmapheresis treatments, her hearing improved dramatically. This improvement suggests that circulating immune complexes and anti-phospholipid antibodies might play a pathological role in the hearing impairment in SLE patient.


Heterotopic intestinal membrane in a retroperitoneal tumor. Plain abdominal X-rays of a 13-year-old girl with chief complaints of back pain revealed calcification in the upper left abdomen. A calcified tumor was confirmed at the dorsal side of the pancreatic tail upon admission. A completely formed colic membrane free of all other germ layers was discovered within the tumor, leading to a diagnosis of heterotopic colonic membrane. To our knowledge, there have been no other cases of heterotopic intestinal tissue of this type, so we consider this an extremely rare case worth reporting.


Recurrent intracranial hemorrhagic episodes in hepatopulmonary syndrome. A 57-year-old woman with hepatopulmonary syndrome was treated for eight years. Severe hypoxemia continued and her erythrocytosis was slowly progressive. Two episodes of intracranial hemorrhagic attack had occurred during the follow-up period and the patient died due to multiple organ failure after the second intracranial hemorrhage. Her autopsy findings confirmed not only established liver cirrhosis associated with intracranial hemorrhage but also the marked dilatation of pulmonary capillaries in both lungs. These findings suggest that secondary erythrocytosis in hepatopulmonary syndrome can be contributed to fatal intracranial vascular accidents. The containment of erythrocytosis should be considered in these patients.


Aseptic necrosis of unilateral scaphoid bone in systemic lupus erythematosus. An SLE patient developed aseptic necrosis of the right scaphoid bone 4 years after an episode of aseptic necrosis of bilateral femoral heads caused by corticosteroid treatment. Since the aseptic necrosis of the right scaphoid bone was preceded by the insidious exacerbation of SLE as evidenced by facial erythema, it was considered to be a result of vasculopathy due to active SLE. It took 14 months to make a correct diagnosis of the aseptic necrosis of the scaphoid bone by a chanced roentgenogram for the routine evaluation for osteoporosis. Therefore, the importance of an awareness of this possibility and repeated radiographic examinations is emphasized for the correct diagnosis of joint manifestations in SLE.


Renal handling of urate in two patients with hyperuricemia and primary hyperparathyroidism. Two patients with primary hyperparathyroidism had hyperuricemia due to the decrease in urate clearance. In analysis by 4-component model system, the tubular secretion of urate commonly decreased without changes in either filtered urate or presecretory reabsorption of urate. Both patients had a reduction of urea clearance, and both parathyroidectomy in the former case and intravenous infusion of saline in the latter case could reduce the serum urate level associated with the increase in the ratio of urate clearance to creatinine clearance. It is of interest that the former case with a higher serum urate level had a relatively higher postsecretory reabsorption, even with the decrease in tubular secretion of urate. However, the latter patient with a lower serum urate level had a decrease in postsecretory reabsorption of urate in proportion to the decrease in tubular secretion. These results suggest that in hyperuricemia patients with primary hyperparathyroidism, the reduction of tubular urate secretion via hypoperfusion of the capillary network is typically present, however, the severity of the hyperuricemia might be dependent on the dysfunction of the postsecretory reabsorption of urate.


Adult Still's disease with myocarditis and peritonitis. A 26-year-old woman had myocarditis and peritonitis during an acute multisystem attack of Still's disease. To our knowledge, these complications are rare manifestations of adult Still's disease. Treatment with high-dose adrenocorticosteroids was rapidly successful in controlling these manifestations.


Hypomagnesemia with increased metabolism of parathyroid hormone and reduced responsiveness to calcitropic hormones. A patient with severe hypomagnesemia due to chronic alcoholism is presented who repeatedly exhibited marked hypocalcemia with a dissociation between radioimmunoassay findings for mid region of parathyroid hormone (PTH-M) and immunoradiometric assay findings of serum intact PTH (PTH-intact). Serum PTH-M was moderately elevated whereas serum PTH-intact was in a low normal range every time when her serum magnesium (Mg) concentration was markedly reduced. There was also a marked reduction in serum osteocalcin concentration. Supplementation of Mg resulted in a sharp increase in serum PTH level with a rapid disappearance of the dissociation between the two immunoassays of PTH. Shortly after serum PTH and 1,25(OH)2D levels reached their peak, serum osteocalcin started to increase, and was elevated into a supranormal level with normalization of serum Ca concentration. Mg is thought to act as a mimic/antagonist of calcium (Ca), and high extracellular Ca is shown to cause an inhibition of secretion with a stimulation of degradation of PTH. Thus, these observations are consistent with the hypothesis that Mg deficiency causes an increase in the metabolism of PTH and a reduction in the secretion of bioactive intact PTH by increasing the sensitivity of parathyroid cells to Ca. In addition, the fact that hypocalcemia disappeared concomitant with a marked increase of serum osteocalcin from undetectable levels suggest that refractoriness of bone to calcitropic hormones is present which plays a significant role in the development of hypocalcemia under hypomagnesemia, and that serum osteocalcin can be a good marker for the assessment of the responsiveness of bone to calcitropic hormones in these patients.


Thymic carcinoma associated with pinealoma and terminating with peroxidase-negative acute myeloid leukemia. Thymoma is associated with a wide variety of syndromes. However, an association with peroxidase-negative acute myeloid leukemia and pinealoma, although feasible due to the marked influence of this tumor on the lymphoid system, has not been described previously. A patient with thymic carcinoma and pinealoma who developed peroxidase-negative acute myeloid leukemia as a late event is presented in this report.


Rounded atelectasis with pleuritis: diagnosis and surgical treatment. A 73-year-old male was admitted with a large rounded atelectasis with pleural effusion. The involved lung was refilled with air as soon as surgical decortication of the thickened visceral pleura covering it was performed. Surgical treatment is believed to be necessary when a large rounded atelectasis with pleural effusion persists for a long time, or when malignancy is not completely excluded.


Chlamydia trachomatis peritonitis: report of a patient presenting spontaneous regression of ascites. A 36-year-old Japanese woman complained of right hypochondralgia followed by ascites. Paracentesis showed a turbid, straw-colored sterile exudate. Computed tomography and magnetic resonance imaging of the abdomen revealed a left periuteric mass and ascites. The mass and ascites spontaneously regressed within a month with no specific treatment. Later, after the patient had been discharged from hospital, immunofluorescence antibody titers for Chlamydia trachomatis were successfully determined using stored ascitic fluid and serum. Though the number of cases of Chlamydia trachomatis peritonitis has increased, few cases with ascites have been reported, and spontaneous regression of the ascites is also rare.


Endometrial resection. A modern treatment of menorrhagia. In general menorrhagia is poorly understood and tends to be unsatisfactorily treated. The word menorrhagia is derived from the Greek men month and rhegynai, to burst forth. Patients complain of increased menstrual loss, requiring more sanitary protection, or of the passage of clots. Most patients with menorrhagia have no significant uterine abnormality and the woman's interpretation of her blood loss is insufficient and unreliable. Menorrhagia must be defined in terms of measured menstrual blood loss. Many medications effectively diminish blood loss, but the symptoms usually return after the therapy has been stopped. Long term treatment is also restricted due to the potential side effects associated with some drugs.


Pre-operative assessment for Mrs Bloggs. The pre-operative phase is the assessment phase for patients about to undergo surgery. This involves visiting the patient in the ward area, an opportunity for the patient to meet the nurse who will be responsible for their care when in theatre. It is also an opportunity for the nurse to assess the patient, plan care and give information to the patient about the operating and recovery rooms.


Care plans for the operating department. Very little, if any, of the care administered by the theatre staff within operating theatres has ever been fully documented. The person 'scrubbed' for the case and the circulating person accountable for the final swab, instrument and needle checks, sign their names in a ledger within theatre. A verbal exchange relating to the patient's operation, the dressings applied, any drains or implants in situ etc. may take place between the 'scub' person and the nurse into whose care the patient is to be entrusted. It is little wonder that we in theatres appear to have lost our identity as nurses and the role envisaged by our colleagues is one of a technician or that of being the surgeon's 'hand-maiden'! As stated in a previous Journal, 'The failure to define the nurse's role in the theatre can only mean one of two things--either nursing is not clearly demonstrated by theatre nurses or nursing does not exist within operating theatres'.


The health of the nation.

The health of the nation. This document, launched by the Government in July, 1992, represents the first national policy aimed at improving the overall health of the British population. It emphasises the purpose of the National Health Service--to improve health, not just treat sickness. This White Paper represents a beginning, with five target areas as priorities: Coronary heart disease and stroke; Cancers; Accidents; Mental illness; HIV/AIDS and sexual health


Change and the operating theatre nurse (1). The role of the nurse. Martin Hind proposes that the role of the operating theatre nurse is in need of a change to a more perioperative nature that emphasizes patient-centred nursing. He explores the reasons underpinning the need for this change in role will be.


Managing resources in the operating department. A number of articles on the problems of resource management have been published in these pages over the past few years. Although these articles highlighted some of the difficulties and problems faced by theatre nurses, none actually gave a means of resolving them.


Postoperative nausea and vomiting.

Postoperative nausea and vomiting. One of the most common and distressing side effects after surgery performed under general anaesthetic is postoperative nausea and vomiting (PONV). Indeed, for many patients, PONV is the most distressing feature of their operation and some may become anxious about having another operation because of this. The medical and economic consequences of PONV can also be serious. This article looks at the incidence, causes, and current management of PONV, and the development of a new drug for the prevention and treatment of this.


Post-registration education and practice. The Scottish scene. Post Registration Education has for many years been either Professional or Academic, however with the publication of the guidelines for P2000, many registered nurses have seen the two paths as one. The new education programmes for the Diploma of Higher Education in Nursing will commence throughout Scotland in August or September of this year.


'Something for your pain, dear'?

'Something for your pain, dear'? As a student nurse in the middle '70s, I recall being struck by the unsophisticated and somewhat haphazard way pain relief following surgery was managed. I had been expecting to receive tuition in the clinical environment, as my classroom studies had not included any reference to pain or pain management. I was, like other staff on the ward, largely ignorant of pain physiology and pain psychology, and accustomed to making subjective judgement of other people's pain, based largely on my own misconceptions and inappropriate inherited attitudes. This, in turn, led to analgesia being offered in much the same way as a 'nice cup of tea', 'Something for your pain, dear?' Standard doses of analgesia were prescribed for the majority of patients via intramuscular or oral routes, and the actual dose administered was randomly selected by nursing staff and delivered at varying intervals. Thankfully, over the last few years, things have started to change.


Burnout and risk factors for cardiovascular diseases. The burnout syndrome denotes a constellation of physical fatigue, emotional exhaustion, and cognitive weariness resulting from chronic stress. Although it overlaps considerably with chronic fatigue as defined in internal medicine, its links with physical illness have not been systematically investigated. This exploratory study, conducted among 104 male workers free from cardiovascular disease (CVD), tested the association between burnout and two of its common concomitants--tension and listlessness--and cardiovascular risk factors. After ruling out five possible confounders (age, relative weight, smoking, alcohol use, and sports activity), the authors found that scores on burnout plus tension (tense-burnout) were associated with somatic complaints, cholesterol, glucose, triglycerides, uric acid, and, marginally, with ECG abnormalities. Workers scoring high on tense-burnout also had a significantly higher low density lipoprotein (LDL) level. Conversely, scores on burnout plus listlessness were significantly associated with glucose and negatively with diastolic blood pressure. The findings warrant further study of burnout as a predictor of cardiovascular morbidity and mortality.


Coronary heart disease risk scales and reactivity in a prevention program assessment: failure to show positive relationships. This study was designed to evaluate relationships among the Jenkins Activity Survey, the Cook-Medley Hostility Scale, and cardiovascular reactivity measured during a semistructured interview in a hospital setting. Subjects were 201 business persons participating in a cardiovascular risk assessment interview component of a fitness program. Correlation analysis showed little evidence of significant positive relationships between self-report scores and reactivity in the total sample and among subjects with high resting blood pressures. Graphic analysis of total sample bivariate distributions, however, demonstrated patterns suggestive of nonlinear relationships. Evaluation of scatterplots and residual plots in conjunction with nonlinear and weighted least squares regression analyses nonetheless failed to reveal significant nonlinear relationships. The authors discuss implications of these findings.


Anger expression, hostility, anxiety, and patterns of cardiac reactivity to stress. The majority of studies investigating the relationships between psychological characteristics and cardiovascular reactivity to stress use a research strategy in which discrete traits are evaluated in isolation. The present study examined the effects of additive and/or interactive relationships among traits on cardiac reactivity to a mental arithmetic task. In addition, impedance cardiographic techniques were employed to examine potential relationships between such psychological traits and a specific measure--pre-ejection period (PEP)--of sympathic influence on the heart. Forty-nine undergraduate men performed a mental arithmetic task while continuous measures of PEP and interbeat interval (IBI) were collected. The subjects then completed questionnaires measuring anger expression, hostility, and trait anxiety. Analyses of variance (ANOVAs) showed a significant main effect for anger-out on PEP change from baseline, but not for IBI. Results also showed that anger-in interacted with anger-out and hostility to affect both PEP and IBI changes significantly. Other results indicated that subjects in the high anger-in/low anger-out and high anger-in/low hostility groups did not show significant PEP change, although they nevertheless showed significant IBI change. These results highlight the importance of the consideration of interactions among traits in predicting cardiac reactivity and of the importance of measuring specific indexes of sympathetic arousal.


Stress, anxiety, and cognitive buffering. Cognitive theories of psychopathology and therapy maintain that attitudes and beliefs mediate one's affective responses to life events. Anxiety and depression are thus consequences, not of an individual's circumstances, but of the distorted, irrational perspective from which these are viewed. Similarly, although less often considered, adaptive cognitions should serve as buffers against stressful life events. This proposition has received little attention, and the single study that attempted to address it directly failed to do so. The present investigation sought to reassess the buffering hypothesis. Ninety-seven subjects were evaluated as to (1) the levels of stress they had experienced in the recent past; (2) their current feelings of anxiety and depression; and (3) the extent to which they endorsed illogical, unrealistic attitudes. Dysfunctional attitudes demonstrated strong direct relations with psychological distress. Two of the several indices of life stress, total and negative scores on the Life Experiences Survey, also correlated with distress. There was no significant interaction between the attitude and stress measures. Cognitions, at least on the functional-dysfunctional dimension, did not moderate the impact of life events. Rather, both attitudes and life stresses were strong independent variables that, in additive fashion, provided considerable power for predicting distress.


Stress effects of personal control over hospital noise. Hospital critical care unit (CCU) sounds, instruction in personal control over noise, and stress were studied in 105 female volunteers attempting to sleep overnight in a simulated hospital environment. Subjects were randomly assigned to three groups--instruction in personal control over noise, no instruction in personal control over noise, or a quiet condition. The two noise conditions heard audiotaped recorded playback of CCU nighttime sounds. The subjects with instruction in personal control received directions for using a sound conditioner to block out unwanted sounds. This intervention failed to result in less stress. The results of group comparisons provided strong support for a causal relationship between CCU sounds and greater subjective stress (p less than .000) but not for physiological stress measured by urinary epinephrine. As predicted, scores for sensitivity of the person to noise were positively correlated with scores for noise-induced subjective stress (r = .226, p less than .05). Hierarchical multiple regression revealed that CCU sound levels independently accounted for 54% (p less than .001) and sensitivity to noise for 5% (p less than .01) of the variance in subjective stress.


Characteristics of elderly people taking psychotropic medication. A sample of 253 elderly people who had been taking psychotropic medication for at least 3 months were interviewed to establish their levels of morbidity and their subjective health status. The findings were compared with those of a control sample of 484 elderly people in the same area. Those taking psychotropic medication were older and more were female and widowed than were the control sample. Their subjective assessments of health status were worse as were the more objective measures of mental and physical morbidity; in addition they were taking more medication of other types. There were more falls among those taking psychotropic medication than those who were not; most excess falls took place indoors. It is possible that a proportion of this morbidity is a result of or exacerbated by medication, but care needs to be taken in interpreting a cross-sectional study. Older people, we suggest, may benefit from regular review of the need for psychotropic medication. Larger studies need to be initiated to investigate the association between morbidity and psychotropic medication.


Technical improvements in the repair of acute postinfarction ventricular septal rupture. Postinfarction ventricular septal rupture (VSR) is a high-risk complication following myocardial infarction (MI). Surgical treatment has evolved to improve an otherwise poor prognosis. Certain subsets of patients remain a formidable challenge. The presence of cardiogenic shock has consistently been found to have the highest risk. Over a 10-year period, our technique of repair has evolved from established procedures to one we believe confers superior results. Endocardial patching to viable myocardium reinforced with an epicardial patch not only corrects the shunt but maintains ventricular geometry and avoids tension on friable muscle. We report on a series of nine consecutive patients in cardiogenic shock. The operative mortality was 22%, none due to low cardiac output syndrome, shunt recurrence, or bleeding. All patients have been followed with transesophageal echocardiography at a mean period of 14 months (range 3-31 months). One patient is in New York Heart Association (NYHA) Class I, four are in NYHA Class II, and two in NYHA Class III.


Implantation technique for the HeartMate left ventricular assist device. The technique for implanting the HeartMate, an intraabdominally placed, pulsatile left ventricular assist device, is described. This device, which has been developed for potential use in patients requiring permanent left ventricular assistance, is currently undergoing clinical investigation in patients requiring temporary support as they await cardiac transplantation. This clinical experience has demonstrated device safety and efficacy, even for patients requiring extended periods of support.


Automatic implantable cardioverter defibrillator: surgical approaches for implantation. Surgical approaches for implantation of the automatic cardioverter defibrillator are sternotomy, left thoracotomy, subxiphoid, and subcostal. Although any one of these may be combined with insertion of one or more of the electrodes transvenously, surgical entry into the chest is required for every noninvestigational defibrillator implantation operation. The approaches differ in exposure provided for selecting electrode sites and for handling untoward events, in amount and location of tissue that must be divided or dissected, and in average time required. The operation is an electrical one. Its purpose is to obtain reliable rhythm sensing so that defibrillation or cardioversion shocks will occur only when necessary, and to obtain low enough defibrillation thresholds for shocks of 30 joules or less to have a 10-joule defibrillation safety margin. Many of the patients have had previous cardiac operations. They usually have low or very low ejection fractions. Intraoperative electrophysiological testing with often multiple defibrillation episodes is required. The choice of approach varies with the state of the patient, the institutional experience, and the surgeon. This article describes technique, and the advantages and disadvantages of the four approaches as used by four surgeons in four different institutions.