Changes in the choroid plexus, responses by intrinsic epiplexus cells and recruitment from monocytes after experimental head acceleration injury in the non-human primate. We have examined, by scanning and transmission electron microscopy, morphological changes in the choroid plexus of the lateral ventricles of the non-human primate brain after lateral head acceleration. We demonstrate passage of plasma and blood cells either through tears in blood vessels and the choroidal epithelium, or through the cells of the choroidal epithelium, 20 min after injury, together with morphological changes in that epithelium. At 3 and 4 h small cells with a reniform nucleus accumulate in the connective tissue core of the choroid plexus. We suggest that these are monocytes. At 6 and 12 h cells can be seen in enlarged intercellular spaces within the choroidal epithelium. These cells possess surface ruffles and we suggest that they are monocytes differentiating into macrophages and epiplexus cells. Further evidence for transepithelial migration of monocytes/macrophages is obtained at 7 days. However, at 28 days all blood has been removed from the surface of the choroid plexus and epiplexus cells possess an appearance typical of that in uninjured animals. The possible sources of epiplexus cells are discussed with reference to studies of responses after brain insult and of development. We have obtained no evidence in support of emperipolesis by monocytes through the choroidal epithelium. We suggest that monocytes/macrophages migrate, via an intercellular route, to differentiate into epiplexus cells, thus providing additional numbers of epiplexus cells after head injury.


Anchorage densities associated with hemidesmosome-like structures in perivascular reactive astrocytes. Electron microscopical examination of devastated and reticular gliosis-replaced areas of two human brains revealed novel anchorage densities (ADs) associated with hemidesmosome-like structures (HDLSs) in perivascular astrocytes; the densities, 200-300 nm away from the cell membrane overlying the basal lamina, ran parallel to the membrane. The subplasmalemmal ADs usually received fibrils from the main stream of the deeply located glial fibrils, and sent isolated 13- to 16-nm fibrils roughly perpendicularly to the unusually prominent and frequently continuous HDLSs on the inner leaflet of the cell membrane, undercoated by a thickened basal lamina. The variable profiles of the ADs indicated that they were cell membrane-connected sheets or meshes that were virtually completely composed of bundles of glial fibrils intercrossing at variable angles or running roughly parallel to one another. All these findings suggest that the ADs may provide a significant support to the cell membrane facing the perivascular space.


The effect of nerve crush and botulinum toxin on lead uptake in motor axons. After lead (Pb) is injected into striated muscle it binds to the sarcolemma of the neuromuscular junction (NMJ) and crosses into the terminal axons of motor neurons. To find out whether this intra-axonal accumulation of Pb is due to active transport or to diffusion down a concentration gradient, Pb uptake into motor axons of mice was studied at active and inactive NMJs. Twenty-four hours after sciatic nerve crush, 0.1 ml of 5% lead nitrate was injected into the tibialis anterior muscle and 30 min later the location of Pb was sought with electron microscopy and X-ray elemental analysis. A greatly reduced amount of Pb entered the axons after nerve crush compared to non-nerve crush animals, indicating that an active NMJ is required for intra-axonal Pb accumulation. To test if Pb could be entering the axon via recycling vesicles, botulinum toxin (BoTx) was injected into the muscle 24 h before Pb injection. There was no difference in intra-axonal Pb uptake in control and BoTx-injected animals, indicating that Pb is unlikely to use recycled vesicles to enter the axon.


Radio-immunotargeting in experimental animal models of intraperitoneal cancer. The field of immunotargeting, and the challenges met when this technique is applied in experimental animals or in patients, are reviewed. Even with highly specific monoclonal antibodies, non-specific uptake in normal tissues and high background level of unbound radioactivity in blood and extravascular body fluids remain significant problems. Further experimental work in animal model systems is needed to bring this technique from the state of being an experimental method, with limited clinical application, to a routine diagnostic or therapeutic method. Different animal models are available, and their potential for elucidation of the various methodological problems in radio-immunotargeting are discussed in the present paper. In our laboratory, two intraperitoneal models were devised, having relevance for gynecologic and other forms of intraperitoneal malignancies. These models were elaborated with special emphasis on the possibility for exact measurement of important parameters in immunotargeting reactions. In the first model, hybridoma cells are inoculated intraperitoneally to mimic intraperitoneal carcinomatosis, and the monoclonal antibody produced by the hybridoma is used as serum tumor marker. In the second model the tumor cells are contained within intraperitoneally implanted micropore chambers, resembling a localized tumor. An artificial tumor like this allows control with the antigen load in the target, and measurement of the concentration of the injected antibody in the fluid within the target.


Oncogene and growth factor expression in ovarian cancer. The varying tumor-biological behavior of ovarian carcinomas probably influences both their operability and response to chemotherapy, which are the most relevant prognostic factors. The phenotype of different ovarian carcinomas is obviously associated with an activation of the EGF/TGF-alpha signal pathway, including c-myc and c-jun expression. Analysis of EGF-R, TGF-alpha, c-myc and c-jun expression in 33 stage III/IV, and 2 stage I/II ovarian carcinomas with biochemical, molecular-chemical and immunohistochemical methods showed a correlation between the mRNA and protein levels of EGF-R and TGF-alpha for tumors with low or high expressing rates. However, the concentration of measurable free EGF-Rs seems to depend on the amount of TGF-alpha expression by the tumors. The EGF-R binding ligand TGF-alpha is produced by epithelial tumor cells; stromal cells are usually TGF-alpha-negative, as shown by immunohistochemistry. High expression rates of EGF-R. TGF-alpha and c-myc were detected in 6, 7, and 10 out of 35 ovarian carcinomas, respectively. C-jun mRNA was detected in 18/19 cases studied. Non-malignant tissues originating from myometrium or ovary expressed no (or only small amounts of) EGF-R or TGF-alpha mRNA, whereas a high c-myc expression was found in 1/7 normal myometria, and in 2/5 normal ovaries. There was no strong correlation between EGF-R/TGF-alpha and c-myc/c-jun expression.(ABSTRACT TRUNCATED AT 250 WORDS)


Oncogenesis in ovarian cancer.

Oncogenesis in ovarian cancer. Tumorigenesis is a multistep process involving mutations of dominantly acting proto-oncogenes and mutations and loss-of-function mutations of tumor suppressor genes. Some of these mutations may be inherited, but most of them are acquired. Models for the sequential steps of the genetic changes involved in tumor development have been proposed for certain cancers, such as colon cancer. In the case of ovarian cancer, relatively little is known about the genetic events associated with the initiation or subsequent progression and metastases of the tumor. Cytogenetic analysis has revealed a high incidence of both structural and numerical chromosome changes, and the extent of these changes seems to increase with tumor progression. Oncogene activations of the proto-oncogenes K-ras, c-myc and c-erbB-2 have been found more frequently in aggressive ovarian tumors and may be associated with poor survival. Tumor-specific allele loss involving putative tumor suppressor genes has been observed for loci at chromosomes 11p, 17p, and 17q,--loci commonly deleted in other cancers too. A relatively high incidence of allelic loss on chromosome 6q appears to be specific to ovarian carcinoma. Familial breast/ovarian cancer has been suggested to map to chromosome 8q. Recently we have found a germ-line mutation in the tumor suppressor gene p53 in a family with breast- and ovarian cancers, indicating that this is the predisposing gene in this family. Genetic changes important for the etiology of ovarian cancers seem to involve both somatic mutations of oncogenes and somatic or germ-line inactivation of tumor suppressor genes.


Intracellular actions of steroid hormones and their therapeutic value, including the potential of radiohalosteroids against ovarian cancer. The biological activities of steroid hormones are effected via intracellular receptors. The receptors are part of a ligand-activated family of transcription regulator proteins that are critical for steroid-regulated cell differentiation. With recombinant cDNA technology, yeast and cultured animal cells can be made to express mammalian cDNA steroid receptors from cDNA clones that contain deletions and substitutions. Among the leading problems addressed in these models is the characterization of sequences that promote association or interaction with other transcription regulating molecules, including oncogene products. Recently it has been found that heat shock proteins may serve not only to stabilize the receptor proteins but also to precondition the activation imparted by ligand binding. Aberrant receptor proteins can be found in ovarian cancer. Whether aberrant receptor proteins are associated with transformation in general or with a variable clinical response to steroidal or anti-steroidal therapy is not known. Even after chemotherapy, steroid receptors are expressed in the metastases of ovarian cancers seen clinically, and they may have potential uses for localization and treatment of receptor-rich cancers. Radioligand pharmaceuticals appropriate for imaging or for site-directed radiocytotoxicity can be sequestered to the nuclei of receptor-rich cancers. Initial clinical imaging and therapy trials with such pharmaceuticals have been approved and begun. In the use of halogenated estrogen radiopharmaceuticals, liver metabolism and enterohepatic recirculation are important considerations. Ascites prolongs retention of a radiohalogenated estrogen in the abdominal cavity. Distant metastases have been localized with [123I]-estrogen in breast cancer patients in pre-operative procedures. Receptor-mediated cytotoxicity occurs when estrogen receptor radioligand pharmaceuticals that are Auger electron emitters are used in vitro.


Inhibin as a marker for granulosa cell tumor. In order to determine whether serum-immunoreactive inhibin could constitute a biochemical marker for the presence and progression of ovarian granulosa cell tumors and their metastases, we measured immunoreactive inhibin concentrations in series of serum samples obtained from 8 patients with granulosa cell tumor. Six series were tested in retrospect. From these, three came from patients who had been treated with an abdominal hysterectomy and bilateral salpingo-oophorectomy. In the 2 patients with residual or recurrent disease, inhibin was elevated, 4 and 20 months respectively before clinical manifestations of recurrence became evident; it reflected the effects of secondary therapy. Inhibin remained undetectable in one patient who was free of disease during 11 years of follow-up. Inhibin concentrations were also inappropriately increased in 2 of 3 women with amenorrhea and infertility resulting from small granulosa cell tumors. After removal, inhibin concentrations became normal and fertility resumed. Fertility also returned in the third patient. There was a significant negative correlation between the serum inhibin and FSH concentrations, consistent with autonomous production of inhibin by granulosa cell tumors. It is concluded that granulosa cell tumors have the capacity to produce inhibin. In retrospect, inhibin proved to be a marker for both primary and also recurrent and residual disease.


Prognostic indices in ovarian cancer. Their significance in treatment planning. Ovarian cancer exhibits a wide spectrum of behavior, the effectiveness of therapies varies and the circumstances of patients differ. Better outcomes will require more selective treatment strategies considerate of these variables. 1. The need for treatment As long as outcome is affected more by disease than by treatment, survival will be determined by the bulk and growth-rate of residual tumor-prognostic factors reflect these. They indicate the need for treatment, but not whether benefit is likely. FIGO stage is the international standard, but this alone is inadequately predictive. Grade reflects virulence, but subjectivity has limited its usefulness. Newer quantitative pathology techniques (such as DNA ploidy) more reproducibly reflect behavior. Prognostic factors can be used to define subsets of patients at differing degrees of disease risk. 2. Efficacy of treatment No response predictors are yet of practical use in selecting primary chemotherapy on an individual basis. Generally, response is more likely if the tumor is less extensive and if dose and treatment frequency are higher. Monitoring biomarkers can more quickly identify those with a suboptimal response who may require a change or discontinuation of treatment. Re-laparotomy has limited usefulness. Response predictors for second-line treatment (e.g. the failure-free interval) are available and also have implications for new drug testing. 3. Suitability of treatment Advanced age or serious additional illness may render intensive treatment inappropriate. The informed patient's wishes are of prime importance. An evolving strategy of selective management is described.


Role of carboplatin in ovarian cancer. Current results and thoughts for the future. Carboplatin is a cisplatin analog that causes less nephrotoxicity, neurotoxicity and nausea and vomiting than its parent compound. In prospective clinical trials, carboplatin has been shown to be as active, but less toxic, than cisplatin in previously untreated patients with advanced ovarian cancer. However, carboplatin has not led to improved survival, compared with cisplatin. Studies are in progress to reduce the dose-limiting myelo-suppression of carboplatin in order to increase the dose intensity. In addition, new carboplatin combinations are also to be evaluated in clinical trials. The molecular basis for resistance to platinum compounds is also undergoing study and future clinical trials will evaluate modulations of resistance.


The controversial 'second-look' laparotomy. To determine optimal indications for and clinical assessment of the significance of relaparotomy, the data of 304 women with malignant ovarian tumours (of epithelial origin, predominantly, 72%) who had undergone a 'second-look' operation were analysed. 'Second-look' relaparotomies were performed 10-22 months after the initial operation, on the following clinical indications: 1) clinical remission after initial combined treatment (surgery + chemotherapy) in cases where malignant cells are found at systematically performed cytological examinations of ??? or lavage from peritoneal surfaces of the Douglas cul-de-sac plus high levels of CA 125 in blood serum (8 patients with stages I and II, FIGO classification); 2) remission after adequate combined treatment and following 6-10 cycles of polychemotherapy, in order to decide whether to abandon or continue with treatment (13 patients with stages III and IV); 3) clinical remission following initial operation which was voluminously non-radical (117 patients); 4) suspicion of tumour recurrence after adequate combined treatment (114 patients); 5) no suspicion of cancer recurrence, though with ventral hernia or other pathology requiring relaparotomy (22 patients). Complications arising at the 'second-look' operation or during the postoperative period were observed in 29 of the 304 patients (9.5%), giving a postoperative mortality of 0.9%. According to experience, the positive significance of 'second-look' operations to optimize treatment of patients with malignant ovarian tumours is obvious.


What do CA 125 and other antigens tell us about ovarian cancer biology? CA 125 is an antigenic determinant on a high molecular weight glycoprotein. A monoclonal antibody has been produced which recognizes this, and allows us to measure the expression of CA 125 in serum. Tissue distribution of the CA 125 determinant is most commonly seen in serous tumors of the ovary, with highest levels in borderline and frankly malignant serous cystadenocarcinomas. Occasionally cancers of the breast, gastrointestinal tract, and kidney will show elevated levels of CA 125. Normal tissues which show varying levels of CA 125 include decidual tissue and structures derived from celomic epithelium. CA 125 is clearly tumor associated, but not tumor specific. Quantitative correlation of CA 125 levels with tumor volume has not been demonstrated. This observation limits the clinical usefulness of CA 125 as a screening tool, particularly in premenopausal patients who do not have a diagnosis of ovarian cancer. An undetectable level of CA 125 antigen does not rule out the presence of an early ovarian cancer. When CA 125 is used to monitor disease state in patients with known ovarian cancers (whose tumors do express CA 125), changes in levels of CA 125 do correlate with gross changes in tumor volume. Good prognostic significance is attributed to a rapid decline in CA 125 levels following induction chemotherapy in patients with advanced ovarian cancer. However, an undetectable serum level of CA 125 does not predict clinical cure for a patient with ovarian cancer. Further clinical studies continue in the use of CA 125 as a screening tool and as a means to monitor treatment responses of known ovarian cancer.


Aminoterminal propeptide of type III procollagen in ovarian cancer. A review. The concentration of the aminoterminal propeptide of type III procollagen (PIIINP) in serum is a measure of the activity of the metabolism of type III collagen, which is a major constituent of soft connective tissues and of the connective tissue stroma of solid tumours. In advanced ovarian carcinoma, serum PIIINP serves as a tumour-associated antigen, its changes reflecting and preceding changes in the clinical behaviour of the malignancy. Elevated values of serum PIIINP are also observed in endometrial and cervical malignancies, though less frequently than in ovarian tumours. Very high concentrations of PIIINP are found in ovarian carcinoma ascites, suggesting an ongoing fibro-proliferative reaction in the peritoneal cavity as a response to the tumour.


Mucosal defense mechanism in health and disease. Role of the mucosal immune system. The mucosal immune system is characterized predominantly by the secretory antibody response and gut-associated lymphoid tissue, cellular part of the mucosal immune system. The secretory antibody system depends on local production and selective epithelial transport of secretory IgA and IgM. Furthermore, secretory antibodies and interactions between the intestinal epithelium and T cells are involved in the mucosal down-regulation of the systemic immune system. Neuropeptides play a crucial role in the regulation of mucosal immune responses. It is possible that impairment of the mucosal immune response contributes to the pathogenesis of various intestinal diseases, such as inflammatory bowel disease. Until recently, however, mucosal immunity received relatively little attention from both basic and clinical scientists. Further research on mucosal immunity seems to have promise in helping to provide new understanding of the immune mechanisms and pathogenesis of several gastrointestinal and systemic diseases.


Biological aspects of pituitary tumors induced by synthetic salmon calcitonin (TZ-CT) in Sprague-Dawley rats. Immunohistochemical and ultrastructural studies. Rat pituitary tumors induced by synthetic salmon calcitonin (TZ-CT) were studied by the indirect peroxidase-labeled antibody method, together with ultrastructure and serum hormone measurement. Immunohistochemically, TZ-CT-induced pituitary tumors showed staining for only rLH alpha subunit, and were negative for other peptide hormones including GH, PRL, alpha MSH and ACTH, and the beta subunit of glycoprotein hormones. Electron microscopic examination showed that the majority of tumor cells possessed numerous small secretory granules, 100 to 200 nm in diameter. The serum PRL concentrations of rats with TZ-CT-induced pituitary tumors were markedly elevated, but not beyond 130 ng/ml. From our data, TZ-CT-induced pituitary tumors are considered to be endocrinologically inactive and to produce alpha subunit. Furthermore, these tumors are thought to be potentially useful models of alpha subunit-producing pituitary tumors in humans. This is the first report to document the tumorigenesis of alpha subunit-producing pituitary tumors in rats after long-term treatment with calcitonin.


Fundamental morphological changes in human olivary hypertrophy. Morphological features of neurons in human inferior olivary nuclei were studied in 6 autopsied patients with dentato-olivary pathway lesions, who had survived for between 6 days and 15 months. Central chromatolysis-like neuronal enlargements were already present in the acute cases. Electron microscopy revealed round, homogeneous and electron-dense granules, varying in diameter from 0.15 micron to 2.5 microns, occurring frequently within the rough endoplasmic reticulum (ER) in the chromatolytic neurons of all 6 patients. No similar granules were observed in 6 controls. The vacuoles were due to dilatation of the rough ER, and often contained floccular materials. Neurofilamentous hyperplasia in the neurons was more frequently seen in the chronic cases. These findings suggest that the fundamental changes in the neurons in olivary hypertrophy occur within the rough ER.


Histologic changes in Graves' thyroid gland after 131I therapy for hyperthyroidism. The effect of 131I therapy was examined in 13 thyroid glands affected by Graves' disease 3 to 29 years after irradiation for hyperthyroidism. All of the patients had clinically palpable thyroid nodules. Two patients were in a latent hypothyroid, 6 in a euthyroid and 5 in a hyperthyroid state. The microscopic changes in the thyroids showed a pattern of multiple adenomatous nodules with cystic changes, marked oxyphilic cell changes with nuclear atypism and various degrees of chronic thyroiditis. Immunohistochemical staining for TG and T4 was negative to mildly positive in these oxyphilic cells and entirely negative for EGF and CEA. The DNA ploidy pattern was diploid pattern in 6 cases. One papillary-type microcarcinoma occurred, but there was no evidence of a relationship between the tumor and the irradiation. The pathologic findings in Graves' thyroid gland after 131I therapy are not specific, but pathologists should differentiate this lesion from adenomatous goiter, which occurs with no apparent cause, or from thyroid carcinoma because of the marked nuclear atypism of this lesion.


Neonatal Legionnaires' disease. Histopathological findings in an autopsied neonate. A neonatal case of legionnaires' disease (LD) is reported. A male neonate was admitted to our hospital with high fever and dyspnea, which had started 5 days after birth, and died due to severe pneumonia at 10 days old. An autopsy revealed small areas of granular consolidation scattered diffusely in the bilateral lungs. Microscopic examination of the lungs showed mainly lobularly distributed pneumonia. Extensive exudation of macrophages and neutrophils was observed in the terminal respiratory tract and alveolar spaces. Warthin-Starry and Gimenez staining and electron microscopy detected many coccobacilli in the cytoplasm of exudated macrophages and neutrophils. Immunofluorescence staining using antiserum against Legionella pneumophila, serogroup 1, showed a positive reaction. Bacteriological examinations of aspirate from the respiratory tract and autopsied lung tissue confirmed the presence of Legionella pneumophila, serogroup 1. Extrapulmonary LD was not detected. LD usually affects aged or immunocompromised hosts, but there was no evidence of immune deficiency in this case. Pediatric cases of LD have rarely been reported, and a survey of the literature revealed few neonatal cases. The present case may alert neonatologists and other medical personnel to the possibility of neonatal LD infection.


Kappa light chain nodular glomerulosclerosis with conspicuous crescent formation and tubulointerstitial injury. Report of a case. We describe a 39-year-old man who developed kappa light chain nodular glomerulosclerosis with superimposed conspicuous crescent formation and extensive tubulointerstitial injury. The clinical picture was characterized by nephrotic syndrome and rapidly progressive glomerulonephritis. Incessantly progressive loss of renal function culminated in irreversible renal failure 7 weeks after initial manifestations of renal insufficiency. The patient has since been maintained on thrice weekly hemodialysis with chemotherapy for five years. At the time of pathologic diagnosis by renal biopsy, there was no evidence of multiple myeloma, and no serum M-component or Bence-Jones proteinuria was detected. An initial bone marrow aspirate revealed the presence of 0.6% atypical lymphocytes as the sole abnormality, although these were later identified as atypical plasma cells. These cells had also infiltrated the renal interstitium. Crescentic kappa light chain nodular glomerulosclerosis lacking evidence of plasma cell dyscrasia should be included in the differential diagnosis of rapidly progressive glomerulonephritis.


Sacrococcygeal chordoma with a malignant spindle cell component. A report of two autopsy cases with a review of the literature. Two autopsy cases of sacrococcygeal chordoma which showed sarcomatous components in the primary and metastatic tumors are reported. Case 1 was a 48-year-old female who died 9 years after the development of the initial symptoms. Autopsy findings showed metastatic tumors consisted of malignant tumor cells similar to fibrosarcoma and osteosarcoma. Case 2 was a 63-year-old male who died 11 years after the development of the initial symptom. At autopsy only sarcomatous tumors resembling malignant fibrous histiocytoma (MFH) were observed in the metastatic lesions. Both cases were treated with irradiation. It is suggested that the appearance of sarcomatous tumor in current two cases of chordoma might be due to the phenomenon of tumor progression closely associated with irradiation therapy. These two cases can be categorized as "chordoma with a malignant spindle cell component" in a sense that highly malignant sarcomatous components existed in conjunction with chordoma in the primary tumors.


A case of pulmonary adenocarcinoma with sarcomatous elements initially manifested as a submucosal tumor of the stomach. A case of pulmonary adenocarcinoma, which was initially manifested as a gastric submucosal tumor, is presented. Endoscopy showed a submucosal tumor in the fundic region in a 79-year-old Japanese woman. Initial biopsy specimens of the stomach revealed atypical spindle cell proliferation, suggesting primary leiomyosarcoma of the stomach. However, biopsy specimens obtained one year later were diagnosed as malignant lymphoma or malignant histiocytosis of the stomach. Autopsy revealed a large necrotic lesion in the right S8 region with metastases in multiple organs. Microscopy demonstrated well to moderately differentiated adenocarcinoma containing spindle or pleomorphic sarcomatous elements. Metastatic nodules including the gastric tumors all showed sarcomatous elements with no epithelial component. Immunohistochemistry showed positive reactions for keratin, epithelial membrane antigen, and carcinoembryonic antigen in areas of carcinoma, whereas most of the sarcomatous elements revealed no positivity for any of the antibodies used, except for focal keratin and EMA positivity in the primary site. This is a rare case of pulmonary adenocarcinoma with sarcomatous elements discovered as a gastric tumor at initial diagnosis, resulting from metastasis of the sarcomatous element in the submucosa.


Cytogenetic characteristics of a malignant rhabdoid tumor arising from the paravertebral region. A case report. The pathological and cytogenetic features of an extrarenal malignant rhabdoid tumor (MRT) arising from the paravertebral region in an infant were investigated. The patient died 4 months after diagnosis, due to aggressive tumor progression. The tumor was composed of medium-sized round cells with cytoplasm containing eosinophilic inclusions, which ultrastructurally were composed of densely packed whorled intermediate filaments. Flow-cytometric analysis of the tumor cells revealed a diploid pattern. Amplification of the N-myc oncogene was not identified. Immunohistologically, the inclusion bodies showed a positive reaction with antiserum against vimentin. The tumor cells were not reactive with antiserum against epithelial membrane antigen, anti-keratin (polyclonal) or cytokeratin (monoclonal, CK1), but did react with 5H10, an antiserum established from human sarcomatous Wilms' tumor. This case is discussed with reference to the literature on extrarenal MRT, placing stress on the histogenesis of this tumor.


Partial upper airway obstruction during sleep. Studies with the static charge-sensitive bed (SCSB). Nocturnal respiration, the ballistocardiogram, and body movement activity were studied with the static charge-sensitive bed (SCSB) in snorers who represented a wide range of severity of sleep-related upper airway obstruction. The emphasis was to evaluate the performance of the SCSB as a noninvasive tool for assessing nocturnal breathing disturbances. The results show that periodic episodes of obstructive apnea or hypopnea can reliably be monitored with the method. Additional breathing abnormalities suggesting the presence of increased respiratory resistance and increased body motility were frequently observed not only in OSAS patients but also in snorers without apnea. Permanent morphological abnormalities of the upper airways were observed in pharyngeal CT in patients with OSAS but also in subjects with severe partial obstruction without apnea. The findings in the SCSB recordings clearly illustrate that there is a functional continuum from partial to complete upper airway obstruction during sleep. However, the structural differences of the upper airways observed between subjects with partial airway obstruction and with OSAS suggest that partial obstruction without apnea cannot always be considered as heralding the development of the OSAS, but rather as a separate entity, which may produce the same clinical signs and symptoms as in the OSAS. The SCSB turned out to be a simple but sensitive method to detect complete and partial upper airway obstruction during sleep. The SCSB may optimally yield information beyond reach of more complex recording systems. Nonapneic SCSB findings may have particular significance for the evaluation of preclinical stages of sleep-related upper airway obstruction.


Characterization of the antisecretory action of prostaglandin D2 in the rat colon. Previous studies have shown that prostaglandin D2 (PGD2) inhibits neuronally mediated secretion in the rat colon. This antisecretory action of PGD2 was further characterized by the use of a prostaglandin D receptor blocker. Prostaglandin D2 inhibited the neuronally mediated short-circuit current evoked by prostaglandin I2, which represents Cl- secretion. The concentration-response curve for the inhibition by PGD2 was shifted to the right in the presence of the prostaglandin D receptor blocker, AH 6809. AH 6809 had no effect on the short-circuit current response induced by prostaglandin E2 or iloprost, a stable prostaglandin I2 analogue, suggesting an interaction of the blocker with receptors specific for PGD2. A direct interaction of PGD2 with enteric neurones was studied by determining its effect on acetylcholine release from enteric neurones preloaded with [3H]choline. Prostaglandin D2 suppressed 3H release induced by electric field stimulation. It had, however, no effect on the release induced by depolarization with potassium. The results suggest that the inhibitory action of PGD2 on enteric cholinergic neurones is mediated by prostaglandin D receptors.


The importance of frequency and amount of electrical stimulation for contractile properties of denervated rat muscles. Soleus (SOL) and extensor digitorum longus (EDL) muscles were denervated and directly stimulated for 23-69 days through implanted electrodes employing three different patterns. The stimulation was delivered in impulse trains where the pulse frequency differed (20, 75, and 150 Hz), while the train duration (0.3 s) and train repetition rate (1 min-1) were identical. Consequently, the number of pulses varied such that higher frequency was combined with a higher amount of stimulation. In both SOL and EDL the high-frequency pattern resulted in shorter twitch time-to-peak, greater post-tetanic potentiation, and greater tetanic force than the low frequency. Isotonic shortening velocity was increased to the same extent by all the patterns in SOL whereas in EDL fast intrinsic shortening velocity was maintained by the low-frequency pattern while it was decreased by the high-frequency pattern. We attribute this unexpected effect on the EDL to the larger number of pulses in the high-frequency pattern. By combining the present findings with previous data on directly stimulated rat muscles we conclude: in SOL the twitch duration is influenced by both the frequency and the amount of impulse activity, higher frequencies and smaller amounts leading to faster twitches. The EDL twitch duration is similarly dependent on the amount of activity, but the role of frequency is more unclear. In both SOL and EDL the isotonic shortening velocity is reduced by increasing amounts of activity and there is no evidence that impulse frequency plays a role. In EDL force output is strongly influenced by the impulse frequency, low frequencies resulting in low force outputs irrespective of the amount of activity.


Cardiovascular and renal effects of intracerebroventricular angiotensin II in conscious sheep. Effects on systemic and pulmonary haemodynamics, renal electrolyte excretion, and plasma concentration of vasopressin, catecholamines, electrolytes and proteins in response to intracerebroventricular infusions of [Val5]-angiotensin II (ANG II) at 1, 2 and 4 pmol kg-1 min-1 in isotonic saline for 30 min were studied in conscious sheep (n = 6). Vehicle control infusions were performed in four of the animals. All three doses of ANG II were expected to increase CFS concentration of the peptide above physiological levels. All ANG II infusions were noticed to be dipsogenic, but the animals were not allowed to drink freely until at the end of the experiments (at 120 min post-infusion). The systemic arterial blood pressure increased significantly only in response to 2 and 4 pmol kg-1 min-1, concomitant with an increase of the systemic vascular resistance, whereas the cardiac output and heart rate remained unchanged. The central venous pressure increased only after administration of the highest ANG II dose, while pulmonary artery, and capillary wedge pressures were unaffected during all experiments. The plasma protein and K concentration fell in response to ANG II administration. Also here, the effects were significant only at 2 and 4 pmol kg-1 min-1. The plasma levels of vasopressin, noradrenaline, adrenaline and dopamine did not change significantly in response to any of the infusions. The renal Na excretion increased by 100-400%, but not in a strictly dose-dependent manner. Much smaller and more variable effects were seen on the renal K excretion.(ABSTRACT TRUNCATED AT 250 WORDS)


Pavlovian conditioning of corticotropin-releasing factor-induced increase of blood pressure and corticosterone secretion in the rat. Corticotropin-releasing factor (CRF) is clearly involved in the central regulation of the pituitary-adrenal axis and, moreover, of autonomic nervous system functions. Enhanced sympathetic activity with subsequent increases in blood pressure and heart rate and attenuation of the baroreceptor reflex results from the intracerebroventricular (i.c.v.) administration of CRF. Additionally, the peptide has a variety of potent effects on behavioural responses in animals similar to those observed after an experimentally evoked stress. It was therefore of obvious interest to examine whether CRF is a possible mediator of the learning processes associated with physiological stress reaction patterns. This report clearly demonstrates a classical conditioning of the endocrine (i.e. corticosterone secretion) and haemodynamic (i.e. blood pressure) sequelae following central CRF application and thus indicates that this mechanism is of physiological significance for learned stress responses.


Water intake and its thermal energy cost in reindeer fed lichen or various protein rations during winter. Captive reindeer were fed four different rations which supplied equal energy but varying amount of crude protein: lichens (3%), mixed hay plus lichens (10%) and two feed concentrates with medium (12%) or high (18%) protein content. Kinetics of total body water were measured with tritiated water from February to March 1985, and thermal energy cost of daily water intake was estimated. Biological half-time of water was shorter, and daily water intake significantly higher on the hay plus lichens diet and on the medium- or high-protein concentrates diet than on the lichens diet during March 1985. Similar differences were found between reindeer on medium-protein concentrate and on lichens at the end of the corresponding feeding period during April 1986. Daily water inflow was positively correlated with a dietary supply of digestible crude protein (r = 0.916). Thermal energy costs of daily water intake were highest 1.9 MJ (3.7 l-1) in reindeer on high-protein concentrate during March 1985, and 2.0 MJ (3.9 l-1) in reindeer on medium-protein concentrate during April 1986. The reindeer fed on lichens had minimal and nearly twice as small thermal energy cost of daily water intake (mean 1.1 MJ 2.1 l-1) as on either of the concentrates. Our results show that even a moderate feed protein ration can significantly increase free water intake and its thermal energy cost in reindeer as compared to dominant natural feed (lichens) during winter. Careful protein supplementation is recommended to support body condition with a concomitant addition of easily soluble carbohydrates to compensate for increased thermal costs of water intake.


Local infusion of IGF-I into the kidney of pituitary intact rats induces renal growth. To determine whether insulin-like growth factor I (IGF-I) exerts growth-promoting actions on the kidneys of pituitary-intact animals IGF-I was infused into the kidney via two different routes using osmotic pumps. In a first set of experiments IGF-I was infused directly into the tissue by the use of an implanted catheter traversing the kidney. It was found that a dosage of 50 micrograms IGF-I wk-1 but not 20 micrograms wk-1 caused a gain in weight of the kidney. The growth was accompanied with morphological alterations among the cortical distal tubules. As a marker for hyperplasia, a monoclonal antibody directed against the M1 subunit of ribonucleotide reductase (RR) was used. The altered cells stained with RR, as also did the tubule cells of the medullary thick ascending limb (mTAL). No RR staining was found in the bulk of renal mass, i.e. the proximal tubules, indicating that possible growth in these cells did not involve cell division. In a second set of experiments IGF-I at 50, 100 and 300 micrograms wk-1 was infused into the renal circulation via a side branch of the renal artery, the suprarenal artery. In these experiments, no growth response or morphological alterations of the tissue were found. These findings demonstrate that IGF-I, when administered directly into the parenchyma, causes growth of the kidney in normal animals. The data are compatible with a causative role for IGF-I in the course of renal growth.


Cepharanthin reduces thermotolerance by enhancing thermosensitivity in NIH3T3 cells. The effects of cepharanthin (Ce), glycyrrhizin (G), verapamil (V), and G plus V on induced thermotolerance in NIH3T3 cells were studied. Cells were heated with or without the drug at 45 degrees C for 20 min (the first heating), incubated at 37 degrees C for 12h (the incubation period), and heated again at 45 degrees C for 0-210 min (the second heating). G and V were added throughout the experiment, while Ce was added throughout the experiment or during only the first or second heating, or the incubation period. The cells were harvested after the second heating to evaluate cell survival. In control experiments without any drug, thermotolerance developed and reached the highest peak in the cells incubated for 12h at 37 degrees C. However, thermotolerance in the control cells was suppressed by incubating them at 0 degree C, but developed by subsequent incubation at 37 degrees C. This suggests that the acquisition of thermotolerance by the cells required metabolic processes during the incubation at 37 degrees C. When each drug was present throughout the experiment, only Ce or the combined use of G and V was effective in reducing thermotolerance. Thermotolerance was also suppressed in the presence of Ce during the second heating. These results indicate that Ce reduces thermotolerance by enhancing thermosensitivity rather than by inhibiting the development of thermotolerance.


A comparative study of dynamic CT and ultrasonic pulsed Doppler method for estimation of the portal blood flow. A new dynamic CT method for evaluating the portal blood flow is described. Thirty healthy volunteers were injected with non-ionic hypo-osmotic iodine contrast medium to estimate the portal blood flow. Time density curves (TD-curves) for the abdominal aorta and the main trunk of the portal vein were determined on the basis of data obtained by dynamic CT. From the TD-curves, portal blood flow coefficient and circulation time to flow into the portal vein (P-P time) were calculated. More detailed data of the TD-curves could be obtained by the new dynamic CT than by the previous methods. Subjects were simultaneously studied by an ultrasonic pulsed Doppler method which has been clinically accepted. There was a significant correlation between our dynamic CT method (portal blood flow coefficient) and the ultrasonic pulsed Doppler method concerning the measurement of portal blood flow. Therefore, it may be concluded that this CT method is reliable and clinically acceptable.


Significance of urinary albumin index in the urine collected arbitrarily in the morning. To evaluate urinary albumin index (UAI), the relationship between albumin excretion rate (AER) in the urine stored for 24 h and UAI in the urine collected arbitrarily on the morning of the same day was studied in 123 inpatients. The patients were admitted to our hospital from September 1, 1988 to August 31, 1989, consisting of 67 non-insulin dependent diabetics (Group 1), 40 patients with collagen disease (Group 2), and 16 patients with primary renal disease (Group 3). The relationship between log(e) AER and log(e)UAI was plotted on a graph. Pearson's rank correlation coefficients of Groups 1-3, Group 1, Group 2, and Group 3 were as follows: r = 0.725, r = 0.691, r = 0.855, and r = 0.611, respectively. The formula obtained by using Pearson's rank correlation coefficients to estimate log(e)AER from log(e)UAI in 123 cases of Groups 1-3, 67 cases of Group 1, 40 cases of Group 2, and 16 cases of Group 3 were: log(e)AER/log(e)UAI = 0.815, log(e)AER/log(e)UAI = 0.860, log(e)AER/log(e)UAI = 0.830, log(e)AER/log(e) = 0.722, respectively. In the present study, log(e)UAI was found to correlate well with log(e)AER. As AER is generally accepted to be the most reliable index to know the stage of albuminuria, UAI is considered to be clinically useful.


Concentration and uptake of taurine in umbilical blood platelets. The concentration and uptake of taurine in the umbilical and adult blood platelets were studied. Taurine was the most abundant free amino acid in both umbilical and adult blood platelets. The taurine concentration in umbilical blood platelets (2.30 pmoles/10(4) cells) was significantly lower than that of adult blood platelets (3.27 pmoles/10(4) cells) in contrast to the reverse relationship in taurine concentrations in umbilical and adult blood plasma. No other amino acid showed such significant difference in the concentrations between umbilical and adult blood platelets. Taurine uptake into umbilical blood platelets was temperature sensitive and sodium-dependent in a manner similar to that of adult blood platelets. The uptake conformed well to Hanes-plot. The Vmax of the uptake into adult blood platelets was about 3.6 times higher than that of umbilical blood platelets, but no significant difference was seen in the Km value between the two groups.


Spa therapy improves ventilatory function in the small airways of patients with steroid-dependent intractable asthma (SDIA). The improvement of ventilatory function by spa therapy was examined in 37 patients with steroid-dependent intractable asthma (SDIA) in relation to clinical asthma types. All subjects had been on long-term corticosteroid therapy before spa therapy. Spa therapy was found to improve the values of ventilatory parameters. The percent improvement in all subjects was +4.1% in %FVC, +8.9% in FEV1.0%, +9.8% in %PEFR, +22.0% in %MMF, +19.7% in %V50 and +28.2% in %V25, respectively. Relating to clinical asthma types, moderate improvement in %MMF and %V25 from 16.7% to 16.9% was observed in type Ia cases, and marked increase in %MMF, %V50 and %V25 was observed from 42.2% to 43.2% in type Ib cases. However, no significant increase was found in these parameters of types Ia or Ib after spa therapy. In patients with type II, a significant increase was shown in %V50 (p less than 0.05) and %V25 (p less than 0.01) after spa therapy. The results show that spa therapy improves the condition of small airways disorder in patients with SDIA.


Influences of ventricular pacing on hemodynamics, myocardial metabolism, and cardiac work efficiency: potential risks of rate-responsive ventricular pacing. The influences of ventricular pacing at a rate of 70 beats/min (bpm) on the systemic and coronary hemodynamics, myocardial metabolism, and cardiac work efficiency were evaluated in five patients with bradycardia. The results were compared to those obtained in six normal subjects at rest. In order to elucidate the effects of a relatively high rate of ventricular pacing, cardiovascular and metabolic variables were also obtained at 120 bpm in the normal subjects. It was observed that the patients eventually benefited from ventricular pacing at a rate of 70 bpm and improved in systemic hemodynamics. Although coronary hemodynamics and myocardial metabolism were accelerated, the cardiac work efficiency was not improved. A pacing rate of 120 bpm in the normal subjects did not appear to accelerate systemic hemodynamics, but adverse accelerations of coronary hemodynamics and myocardial metabolism were observed, and the cardiac work efficiency was remarkably reduced as a result. Our observations indicated that the coronary reserve capacity was very important for ventricular pacing, and suggested that an undue increment of the pacing rate not only might be meaningless but also might induce ischemic angina. Therefore, we should be cautious in using a rate-responsive pacing mode, particularly in determination of the upper limit of pacing rates, although many benefits with this pacing mode have recently been advocated.


Effect of left atrial plication for the giant left atrium on left ventricular function. Left atrial plication (LAP) following Kawazoe's method was performed on eight patients with mitral valve stenosis associated with a giant left atrium. To investigate the effect of LAP particularly on left ventricular function, the preoperative and postoperative left ventricular function in these patients were compared. The data were also compared to that of the non-left atrial plication (non-LAP) group with left atrial dimension of 60 mm or over. In the LAP group, there were significant differences between preoperative and postoperative data in the following parameters; New York Heart Association (NYHA) class, cardiothoracic ratio, mean pulmonary arterial pressure (PAP), left ventricular end-diastolic pressure (LVEDP), left atrial dimension, stroke volume index, ejection fraction and cardiac index. On the contrary, in the non-LAP group, there were significant differences between preoperative and post-operative data in the following two factors; NYHA class and PAP. The size of the left atrium in the non-LAP group remained unchanged over the course of long-term follow-up. Despite severe clinical symptoms and severely reduced cardiac function of the patients in the LAP group, cardiac function in all patients improved satisfactorily. This suggests that left atrial plication has a considerably beneficial effect on left ventricular function, and therefore, may be recommended for patients with a giant left atrium.


Combination of epidermal growth factor and insulin is required for multicellular spheroid formation of rat hepatocytes in primary culture. We showed that the combination of epidermal growth factor (EGF) and insulin is an essential supplement to Williams' #E medium for the formation of floating multicellular spheroids in primary culture of rat hepatocytes. Isolated hepatocytes assembled to form floating multicellular spheroids within 96 h through transient assembly of monolayer islands within the initial 24 h in dishes coated with liver-derived proteoglycans. However, the assembly of multicellular spheroids was severely suppressed in the absence of either EGF or insulin. The reduction of spheroid assembly was correlated with decreased attachment and subsequent decreased formation of monolayer islands within 24 h. The minimum amounts of EGF and insulin required for the formation of floating spheroids were 1 ng/ml and 0.4 microgram/ml, respectively. These results suggest that the enhancement of hepatocyte attachment provided by the combination of EGF and insulin during the early phase of culture is required for the formation of floating spheroids.


Experimental study on veno-venous extracorporeal membrane oxygenation for respiratory failure after lung transplantation. Extracorporeal Membrane Oxygenation (ECMO) has been adopted as a means of strong respiratory support. In lung transplantation, reimplantation response is still a serious problem. It causes severe respiratory failure which is refractory to mechanical ventilation in some cases. The purpose of this study was to evaluate the effects of veno-venous ECMO after lung transplantation using a canine autotransplantation model. The autotransplantation model was created by keeping the left lung in a warm ischemic state for 2 h. After reperfusion, the right pulmonary artery was ligated. The following two groups were studied: Group 1, Control group, (no ECMO group) (n = 6). After reperfusion, both lungs were ventilated without ECMO. Group 2, ECMO group (n = 7). After reperfusion, veno-venous ECMO support was introduced with reduction of mechanical ventilation. In the no ECMO group, four of the animals died within 210 min after reperfusion. In the ECMO group, two of the animals died of severe pulmonary edema. Data of blood gas analyses (PaO2, PaCO2, and SvO2) after reperfusion were significantly better in the ECMO group, whereas there were no significant differences in both shunt fraction and pulmonary vascular resistance index. In this model with severe pulmonary edema induced by warm ischemia, veno-venous ECMO contributed to the improvement of hypoxemia and hypercapnia, but did not improve pulmonary hemodynamics.


The effect of follicle-maturing drugs on mid-cycle androgen levels in women with normal baseline levels. Theoretically, clomiphene citrate or human menopausal gonadotropins might have a higher chance of inducing pregnancy per cycle were it not for the concomitant rise in androgens induced by these follicle-maturing drugs. In the present study, mid-cycle androgen levels were evaluated in anovulatory women with normal baseline early follicular levels who were treated with either clomiphene citrate or human menopausal gonadotropins. The only mid-cycle androgen to rise above the normal range was androstenedione. However, no negative effects of elevated androstenedione levels on pregnancy rates were apparent. Thus, at least in women with normal baseline androgen levels, the use of follicle-maturing drugs does not appear to cause a rise in androgen levels except for androstenedione, and the rise in androstenedione at mid-cycle appears to have no adverse effect on conception.


Effects of cross-gender steroid hormone treatment on prolactin concentrations in humans. It is well known that peripheral prolactin levels are significantly higher in menarcheal women than in men. Higher levels of prolactin in menarcheal women are related to exposure to higher levels of estrogen in women than in men. Increased exposure to androgens in men has also been proposed as a possible reason to account for lower prolactin levels in men; however, this suggestion has not been conclusively proven. The current study sought to evaluate the cross-gender effects of male and female hormones on basal levels and the pituitary store of prolactin in humans. Four groups of individuals were involved: normal men and women, male and female transsexuals primed with female hormones and testosterone, respectively for at least 6 months. A metoclopramide challenge test was carried out on each subject of each group. Subjects were rested for 1 h, with an indwelling catheter in the antecubital vein, before a blood sample was collected for estimation of basal hormone levels. Following an oral ingestion of 10 mg of metoclopramide, blood samples were collected at 15, 30, 60, 90, 120, 150 and 180 min. Prolactin, estradiol and testosterone concentrations were measured by radioimmunoassay. Basal levels as well as metoclopramide-induced releases of prolactin (as measured by area under the curve) in normal women were significantly higher (p less than 0.05) than corresponding levels in normal men. Following long-term priming with female hormones, the pattern of response to metoclopramide in male transsexuals was dramatically changed.(ABSTRACT TRUNCATED AT 250 WORDS)


Vaginal bromocriptine--clinical and biochemical effects. Adverse effects occur in over 50% of women taking oral bromocriptine, causing at least 10% to discontinue treatment. Although the drug is absorbed from the vagina and reportedly caused no side-effects in one patient intolerant of oral bromocriptine, long-term clinical effects of daily vaginal administration have not been assessed. We have now given bromocriptine vaginally for up to 2 years to 31 hyperprolactinemic and five normoprolactinemic women, 17 of whom were intolerant of oral bromocriptine. The drug was well absorbed from the vagina and a daily dosage of 2.5 mg lowered serum prolactin levels in 28 of the hyperprolactinemic women (in 11 to within normal limits), restored menstrual cyclicity, and abolished galactorrhea; one of the four infertile women conceived. Minor side-effects occurred in only three women. Vaginal administration is clinically effective, avoids the adverse effects of oral therapy and could be the first-line treatment for patients requiring bromocriptine.


The frequency of salivary progesterone sampling and the diagnosis of luteal phase insufficiency. A profile of salivary progesterone concentrations, based on daily samples taken over a full menstrual cycle, provides a detailed picture of changes in luteal function, at the expense of analyzing a large number of samples. Strain can be placed on analytical services by assaying daily samples instead of one or a few serum (or saliva) samples. This study sought to determine the minimum number of salivary progesterone determinations which adequately describe luteal function. Daily salivary progesterone levels from 215 cycles, of which 29 cycles had progesterone profiles indicative of luteal phase insufficiency, were analyzed to ascertain the efficiencies of various sampling patterns of reduced frequency. A single mid-luteal salivary progesterone estimation or the mid-luteal Lenton progesterone index (n = 4) satisfactorily reflected the normal luteal phase, but a frequency of one sample every 3 days over the luteal phase (n = 5-6) was necessary to allow recognition of a short luteal phase or poor progesterone surge.


Comparison of ovarian response in the same women with the same or different lots of human menopausal gonadotropin. A variation in the bioactivity of different production lots of human menopausal gonadotropin (hMG) has been suggested. Therefore, we evaluated ovarian response to hMG in 14 women during three separate IVF cycles. The first two cycles were performed with the same lot (#03310027; Cycles A1 and A2); the third cycle utilized different lots of hMG (Cycle B). In all cycles, hMG was administered 3 ampules/day beginning cycle Day 3 and continued for at least 6 days. Estradiol and ultrasound evaluations were performed on Day 3, and then daily, beginning on cycle Day 8. Fourteen women completed all three cycles. There were no significant differences in baseline estradiol and ultrasound. Estradiol levels on Day 8 (A1, 754 +/- 130; A2, 700 +/- 107; B, 520 +/- 80 pg/ml, analysis of variance p greater than 0.5) and on Day 9 (A1, 1051 +/- 144; A2, 1140 +/- 155; B, 840 +/- 124 pg/ml, p greater than 0.05) were similar as well. The number of small (1.0-1.4 cm) follicles, large (greater than or equal to 1.5 cm) follicles, and total follicles (Day 8: total A1, 5.5 +/- 0.9; A2, 4.0 +/- 0.7; B, 4.5 +/- 0.9, p greater than 0.05; Day 9: total A1, 6.7 +/- 0.9; A2, 6.9 +/- 0.8; B, 6.9 +/- 0.9, p greater than 0.05) in all three cycles were also similar.(ABSTRACT TRUNCATED AT 250 WORDS)


Steroidogenesis in vitro of human granulosa-luteal cells pretreated in vivo with two gonadotropin releasing hormone analogs employing different protocols. We have previously observed impaired progesterone accumulation in vitro in response to human chorionic gonadotropin (hCG) by cells pretreated in vivo with a gonadotropin releasing hormone analog (GnRH-a). The present study was conducted in order to evaluate different protocols for GnRH-a in in vitro fertilization (IVF), employing two different available analogs. Granulosa-luteal cells were collected at ovum pick-up and stimulated with hCG. Buserelin (Bus) was employed as long (Bus-L) and short (Bus-S) protocol, and Leuprolide (Leu) was also used as long (Leu-L) and short (Leu-S) protocol. Progesterone accumulation in vitro was compared with cells treated with clomiphene citrate (CC) and gonadotropins. Maximal progesterone production was observed on culture day 6 using Bus-L in comparison to day 4 when clomiphene citrate was employed. While Leu-S showed a similar pattern of progesterone accumulation to clomiphene citrate, Leu-L and Bus-S had an intermediate pattern. The response to hCG was maximal on day 4 for the clomiphene citrate- and Leu-S-treated cells, while the rest of the protocols had a peak on day 6. In addition, hCG consistently stimulated progesterone production in all protocols except in Bus-L. These results confirm an altered progesterone accumulation in vitro when GnRH-a are used. The effect seems to be more evident in long protocols, especially when buserelin is used, suggesting a higher accumulation of the analog in follicular fluid.


[Coexistence of hepatic and pancreatic disease in the chronic alcoholic. Unusual or frequent situation?]. In all that has been written there is still some controversy about the importance of the simultaneous pathologycal involvement (functional and/or morphologic) of the pancreas and liver on the same alcoholic patient. Thus, and with the intention of reaching an agreement on the matter, we studied on one hand, on a functional basis, the exocrine pancreas in a group of alcoholic cirrhotics (n = 75) and, on the other, we analysed on a triple perspective--clinical, biological and anatomic-pathological--the pathological involvement of the liver in a series of cases (n = 20) with chronic calcifying pancreatitis. In such case, we verified that, essentially, the secretory capacity of the pancreas had diminished in 17.3% of the cirrhotic cases, while on the other hand, the clinical-laboratorial and anatomic-pathological analysis of liver on pancreatic patients showed clinical-biological suspicion of alcoholic hepatic disease, serious lesions considered pre-cirrhotic and established cirrhosis, respectively in 56.2%, 12.5% and 6.2% of the cases. We conclude that, although the idea of rarity in associating hepatic cirrhosis with chronic pancreatitis, came through on the clinical-symptomatological observation plan, certain investigations of functional and/or histopathological nature, run by us on alcoholic patients, proved to suffer from these affections, permitted us to indicate that the coexistence of pathological involvement of these two organs should not be underestimated.


[Risk or pre-term labor. A cross-sectional study of its determinant factors]. Substancial evidence links gestational duration to birth outcome, and a large number of determinants for premature delivery have been identified. However, most preterm births (gestational age of less than 37 weeks) remain unexplained, and there is a wide geographical variation in risk factors. The purpose of this epidemiologic survey was to study the relationship between gestational duration and the mother's demographic, obstetric and nutritional characteristics, clinical course of pregnancy and labour, alcohol, coffee and tobacco consumption, and prenatal care. Data were collected for 740 consecutive deliveries (3.6% preterm) corresponding to 750 live-births. Except for the number of prenatal visits, no relation was found between gestational age and the variables assessed (r approximately equal to 0). There was an increased risk for preterm delivery when a disease complicated the course of pregnancy (OR = 2.7), there were less than 6 prenatal visits (OR = 4.9), pelvic presentation (OR = 5.7) or twins (OR = 12.7). After adjustment for these variables only prenatal care and twinning remained significantly associated with an increased risk. In this population, the authors identified prenatal care as the most important modifiable factor associated with preterm delivery.


[Tetanus. A review of 54 cases].

[Tetanus. A review of 54 cases]. Tetanus continues to be a frequent illness with a high rate of mortality which mainly affects the elderly. In view of this, 54 cases treated in the ICU between 1983 and 1991 were studied. The clinical support with mechanical ventilation and the use of new drugs, which allowed for a more satisfactory sedation and muscular relaxation, and which permitted the control of the autonomic overactivity, were the most determinant factors in the reduction of mortality verified in the late years of our practice.


[Culture diseases. Brief review on the way characteristics of today's life affect the ways of mental disease]. Culture is expressed in the content of psychiatric symptoms. In this paper we try to establish a relationship between the pathoplasticity of some paradigmatic psychiatric disorders and characteristics of values and life styles in developed societies. We argue that some aspects of a marked hedonism hide a dangerous nihilism and they both articulate, in a discrepant way, with opposing responsible hiperrational and hypercompetitive register. Doctrinaire fanaticisms increase markedly in other places in the globe with endemic shortages while solid values lack in the societies of abundance. This affects mental health.


[Changes in cardiac output in the initial phases of hypertension]. In what concerns to the early phases of arterial hypertension, the difficulty of definition, the usually found hemodynamic changes, especially of cardiac output, and its changes during evolution to established hypertension, are referred. The role of genetic determinants of predisposition to hypertension and of strain situations as factors of precipitation, with acute rise of blood pressure and cardiac output, is emphasized. It is also referred the importance of the early detection of true hypertensives by studying their reaction to strain situations, being particularly promising the mental stress tests and the dynamic exercise tests.


[Central and peripheral vascular resistance]. Better knowledge of organ damage produced by arterial hypertension in multiple conditions led to the conclusion that blood pressure readings (the values) were not the only determinant but instead a whole range of factors dependent on the arterial wall characteristics. The concept of windkessel in relation to the stiffness and the compliance of the arterial system, the impedance at any given point evoking different volume/pressure/flow relationship (with pressure tracings) rekindled interest in this matter, leading to a more adjusted model. Invasive (micromanometers) and non-invasive methods (such as the echodoppler) are the investigation and clinical support of this new interest in an old idea developed before the epidemiological period of arterial hypertension study. The similitude between ageing and hypertension, the contraposition that is seen in youngsters, and other metabolic alterations test this model of winkessel.


[Renal dysplasia: clinico-pathologic review]. Histology records from 63 nephrectomies were reviewed; 22 patients had unilateral totally dysplastic kidneys and 5 had polar or segmental dysplasia. A clinicopathological study of these cases was undertaken. In the first group, there was a slight male preponderance and 75% of the patients presented were under two years of age. Urinary tract infection was the most common complaint. 4 patients were diagnosed in utero by ultrasound and 5 infants presented an abdominal mass. Hypertension was documented in a newborn baby. Ipsilateral lower urinary tract anomalies were found in 12 patients and those of the contralateral kidney in 2 children. There were 3 cases of extrarenal anomalies. Histological examination revealed 13 cases of multicystic dysplasia and 9 of solid dysplasia. Metaplastic cartilage was found in 1 case. In the group of segmental dysplasia, age ranging from 27 weeks' gestation to 8 years, at the time of the diagnosis. They all had duplex kidneys and 4 had ureterocele. Histological study in these cases was similar to the one found in the previous series, although superimposed inflammatory changes were more pronounced. Some of the theories regarding the pathogenesis of this disorder are reviewed and the importance of its diagnosis is emphasised.


[Psychosomatic research in ischemic cardiopathy]. The need felt in the last decades for research concerning the psychosocial aspects of Ischaemic Heart Disease is emphasized. Different methodologies of research in this area are described, as well as their usefulness in different kinds of studies. The main areas of research in Ischaemic Heart Disease and the more recent advances in some of them are mentioned. Finally, the most promising fields for future research in Ischaemic Heart Disease are emphasized.


[Benign pleural effusion caused by asbestos exposure]. The Authors present the first case described among us of benign pleural effusion of an asbestotic origin. They stress the importance of thoracoscopy (pleuroscopy) in the diagnosis of this situation. Attention is drawn to the fact that asbestotic lesions and asbestotic bodies have been found in the lung and, in particular, in the parietal pleura as well. They emphasize the fact that exposure to asbestos was not realized by the patient, which made the clarification of the situation more difficult. It was a CT scan that showed the signs suggestive of exposure to asbestos which raised the diagnostic suspicion. They conclude that every patient with a pleural effusion must be thoroughly questioned about exposure to asbestos. Even if the exposure is accepted, they consider that one should proceed to a pleuro-pulmonar biopsy by thoracoscopy. This biopsy allows demonstration of the characteristic histopathological lesions and rule out other etiologies, namely malignancy and tuberculosis. They suggest that these patients must be highly motivated to stop any smoking and kept under periodic surveillance.


Management of giant intracranial aneurysms. Based on an own material of 64 cases a survey is given on the management of giant intracranial aneurysms. Essential investigations are as well CT and Magnetic Resonance Scanning as detailed angiographic studies. With regard to the operative handling the following questions are discussed: approach; use of temporary vascular occlusion and related monitoring; preparation of the aneurysm neck for occlusion. In cases without recent subarachnoid haemorrhage morbidity and mortality were less than 10%. It was 15% in cases where recent haemorrhage had occurred.


Arteriovenous malformations of the posterior fossa. AVMs of the posterior fossa are reviewed on the basis of personal experience of 47 cases including 2 venous angiomas, 7 cavernous angiomas, 5 arteriovenous fistulas and 33 true arteriovenous malformations and of the few series reported in the literature. MRI is now an indispensable tool to define the exact localization of any malformation. Combined with angiography, it permits one to choose the most adequate therapeutic strategy and the best surgical approach. Radical cure is to be contemplated in most cases considering the often dramatic consequences of bleeding at the infratentorial level. Deep AVMs and moreover cavernous angiomas, even those located in highly functional structures such as the brain stem, can now be discussed for treatment. Encouraging results have already been obtained using, alone or in association, the recently advanced modalities of treatment: interventional neuroradiology, radiosurgery, and microsurgery.


Surgery of tumours of the lateral ventricle. Tumours of the lateral ventricle in most cases enlarge significantly before signs and symptoms are exhibited. In the years between 1980 and 1991 we encountered 55 patients of all age groups with tumours of the lateral ventricle. All were diagnosed either by CT or MRI, and in lesions with good enhancement on CT additional angiography was performed. All 55 tumours were operated upon using microsurgical techniques. The approach was chosen according to the location of the tumour, preferably transcortical. In selected cases large tumours were removed in a two-stage operation. Only in one frontal horn and Cella media tumour an interhemispheric transcallosal approach was used. Postoperative or surgically related mortality was experienced in 3 cases. Life expectancy and morbidity were dependent upon histology.


Treatment of tumours of the pineal region and posterior part of the third ventricle. The evaluation of tumours located in the posterior part of the third ventricle or pineal region is achieved best by magnet resonance imaging (MRI). It shows the exact localization and extent, the involvement of neighbouring structures like thalamus or quadrigeminal plate and the displacement of the large veins, the internal cerebral veins, the vein of Galen and the veins of Rosenthal. If only CT is available, angiography should be performed prior to operation to identify the course of the veins. In children with a pineal region tumour the "tumour markers" AFP and beta-HCG should be determined before operation. We approach the rare tumours entirely located within the posterior part of the third ventricle by the posterior interhemispheric transcallosal route with the patient in prone position with the head elevated. The same approach is used for pineal region tumours extending above the internal cerebral veins. Tumours arising from the posterior thalamus extending into the thalamus and ventricle as well, are better approached by the posterior transcortical transventricular route since the lateral view is rather limited by the midline approach. The most frequent tumours in the pineal region are approached if they are located below the internal veins by the infratentorial, supracerebellar route in the sitting position. A total of 60 cases are evaluated. If AFP and/or beta-HCG are positive a highly malignant nongerminomatous germ-cell tumour must be suspected. We recommend initial chemotherapy with a combination of Vinblastine, Ifosfamide and Cis-platin without biopsy to avoid tumour seeding. After the "markers" are normalized operative removal of the residual tumour and radiotherapy should be carried out. In a series of 13 children operated on for pineal region tumours a rigid neuropsychological and endocrine evaluation was performed with encouraging results. During the last 10 years we have performed 49 open operations and 11 stereotactic biopsies. 40% of the patients were children under the age of 18. 40% of the tumours in childhood and 60% in adults were benign. In childhood 24% were germinomas and 20% non-germinomatous germ cell tumours.


Tumours of the limbic and paralimbic system. 240 patients with tumours of the limbic and paralimbic areas are presented. The following tumour growth patterns have been observed: they remain isolated to areas within the allocortex; they spread throughout allocortical regions; they spread from allocortical to mesocortical zones. With the exception of advanced malignant tumours there seems to be a tendency for tumours to spare the adjacent neocortical and medial structures. The tumours can be approached and extirpated using the trans-Sylvian approach and microneurosurgical technique. 56% have been histologically benign. 60% were below 40 years of age. Seizures were the leading manifestation (77%). In 95% the postoperative results were good. There was no peri-operative mortality.


Open stereotactic selective amygdalo-hippocampectomy for drug resistant epilepsy. Selective removal of the medio-basal temporal structures has been introduced as an alternative to standard temporal lobectomy in the treatment of intractable temporal lobe epilepsy not related to gross structural lesions. Various approaches have been described for the surgical excision of the amygdalo-hippocampal complex, each of them presenting advantages and limitations. The recently introduced computer-assisted technique of volumetric stereotactic excision of deep-seated intracerebral lesions combines precision of targeting with elimination of unnecessary cortical trauma and may potentially provide an alternative method in the treatment of temporal lobe epilepsy. We present our experience of stereotactic volumetric selective amygdalo-hippocampectomy in six patients with medically intractable temporal lobe epilepsy. The criteria for selection, the pre-operative evaluation and the operative technique are discussed. All patients had a cessation or considerable reduction in seizure frequency while the morbidity was minimal.


Surgery of hydrocephalus: past, present and future. The treatment of hydrocephalus, over the centuries, underwent three stages of evolution. During antiquity, middle ages and Renaissance, hydrocephalus was not understood. Medical treatment was useless; surgery was hopeless. The second stage extends from the XIXth century to the end of the first half of the XXth century. CSF circulation was now understood; surgery however, remained inefficient, but some patients survived with arrested hydrocephalus. The third stage begins in the nineteen fifties with the development of silicone shunts with a valve. Surgery transforms the prognosis of hydrocephalus, but the number of post-operative complications creates new problems. The different attempts that have been made during these past two decades to solve these problems are reviewed. They have resulted in a reduction of the mechanical and infectious complications. CSF overdrainage has been minimized. Percutaneous ventriculo-cisternostomies have in some cases replaced shunts. In the future, to improve outcome in these hydrocephalics, surgery, when indicated, should be performed as early as possible. Knowledge and prevention of the causes of hydrocephalus should be developed.


Early prediction of outcome in severe head injury. A survey is given of the development and actual state of the prediction of outcome in severe head injury. Thanks to the data collection in some large databanks it has become possible, in a relatively large number of cases, to estimate reliably the chances of survival and the chance of developing an intracranial haematoma base on clinical data and CT obtained during the first 24 hours. Later during the posttraumatic course prediction is possible of the degree of remaining disability in survivors, and the chances of developing epilepsy and neuro-behavioural sequelae. Due to changing management-regimens further data collection in international databanks is necessary.


Image directed stereotactic surgery for brain stem lesions. Advances in neurological imaging may have increased the diagnostic accuracy and the detection rate of intrinsic brain stem lesions, but a histological diagnosis is still an essential requirement for rational and appropriate management. Open exploration allows biopsy and resection in cases where an exophytic component is present. The surgical inaccessibility and the resultant morbidity of these approaches, however, associated with a low diagnostic yield in cases with no visible surface abnormality, are important limiting factors. A series of 45 brain stem lesions stereotactically approached with CT or MRI guidance is presented. A transcortical frontal pre-coronal trajectory was used in all of them. Haematoma was preoperatively diagnosed in 10 cases and the procedure was for therapeutic aspiration. Of 35 cases where the diagnosis was uncertain, although intrinsic tumour was suspected, positive results were obtained in 33, while unexpected findings of granuloma, lymphoma, angioma, leucoencephalopathy, vasculitis and radiation necrosis were found in over 10% of the cases. There were no operative deaths and the morbidity was low. In no case was there a permanent neurological deterioration directly related to the procedure, although there was a transient deterioration in two patients and one patient required early reaspiration of a haematoma. Image directed stereotactic approaches to brain stem lesions can combine a high degree of accuracy (offering positive histological diagnoses) with a low operative morbidity. MRI directed biopsies can complement CT guided ones thus increasing the number of suitable cases and improving the success rate. The frontal precoronal transcortical trajectory provides safe access to the majority of the brain stem targets.


Indications for neurosurgical treatment of chronic pain. Guidelines are presented for the neurosurgical treatment of chronic pain. In these guidelines a distinction is made between the pain of cancer and neurogenic pain. In cancer pain the survival time and the location of the lesion are the important guidelines. Possible procedures are: opioids via CSF route, lesions in nociceptive pathways and PV-PAG stimulation of the thalamus. In neurogenic pain, neurostimulation procedures, tailored to the location of the pain are procedures of first choice. There are however specific indications for other procedures depending on the aetiology of the pain. Causalgia and reflex sympathetic dystrophy: sympathetic blockade; Tic douloureux: radio-frequency lesion, glycerol, balloon inflation of the ganglion of Gasser, and microvascular decompression; Plexus avulsion: dorsal root entry zone lesion (D.R.E.Z.). There is a need for controlled prospective neurosurgical trials in which as a minimal rule an independent party should evaluate the results of the surgical procedure.


Surgery of intramedullary spinal cord tumours. MRI and Cusa have significantly modified the diagnosis and the treatment of intramedullary tumours. Our experience, based on 66 cases, is in favour of surgery performed when the patient's neurological status is still good. Radical surgery, whenever possible, is the best treatment and can be achieved for many histological diagnoses, even in gliomas where we succeeded in 36% of the cases. Surgery is the only way to be sure of the exact histological diagnosis of the lesion which can be suggested in 70% of the cases but not confirmed by MRI.


The future of neurosurgery.

The future of neurosurgery. Many factors influence the future of neurosurgery, among them the general growth of the world population with an increasing number of older persons and the political-economical development which differs markedly from region to region. Another important factor will be the biological and molecular revolution which has just begun and makes it likely, that some of the pathologies, which needed neurosurgical management, become accessible to conservative treatment in the future. Finally the neurosurgical sphere of activity is endangered by take-over tendencies of neighbouring medical specialties. Those of us who are in charge of neurosurgical organization and planning should take these and additional factors into consideration early enough, in order to give neurosurgery and neurosurgeons a chance to adapt to the future.


Neurosurgical publications in European journals. The number of papers published in European neurosurgical journals during the last decade (1980-90) was analysed using online databases. Thirteen journals devoted to neurosurgery were published in Europe at that time. In five of them neurosurgery appears together with other specialties. Almost 50% of all European neurosurgical journals are written in English. They published 68% of all papers by neurosurgeons appearing in the European neurosurgical journals during the last decade. Together with the American neurosurgical journals English was used in about 80% of all neurosurgical publications. Other languages used are German and French (9% each), Russian (5%), Czech or Slovak (4%), Polish (3%), Rumanian (2%). Most papers by European neurosurgeons originate from England, followed by Germany, France, Italy and Sweden. Of the East-European countries Polish neurosurgeons contributed with 782 publications, followed by Czechoslovakia (568), Hungary (501), USSR (470) and East Germany (452). The proportion of papers published in neurosurgical journals by European neurosurgeons to those in the journals devoted to other neurosciences varied from 99% in the USSR to 12% in Austria with an average of 38%. Citation analysis indicates that only a few of the journals have a large impact on neurosurgical publications, while the others have a rather limited influence.


Improvement in pulmonary function following smoking cessation. This study investigated improvement in pulmonary function following smoking cessation. It employed three indices of lung function that are sensitive to improvement following smoking cessation and that can be easily assessed within a clinical setting: maximum mid-expiratory flow (MMF), forced expiratory volume in 1 second (FEV1), and forced vital capacity (FVC). Smoking status was verified by saliva thiocyanate analysis. Significant improvement in MMF was evident after 3 months of cessation and was maintained at the 6-month follow-up. This study demonstrates that significant improvement in at least one parameter of lung function occurs within the time span typically used in smoking cessation programs.


Using knowledge maps and scripted cooperation to inform college students about patterns of behavior related to recurring abuse of alcohol. Objectives of this study were to determine the effectiveness of using a specific information format--graphic representations called knowledge maps--and an information processing strategy--scripted cooperation--in teaching college students about behavior patterns that underlie recurring abuse of alcohol. Participants in this three-session, 6-hour study were 111 Texas Christian University students recruited from undergraduate psychology classes. Participants were randomly assigned to one of two materials format conditions (map vs. text format) and to one of two processing strategy conditions (individual processing vs. scripted interaction with a partner). Results indicate that map format facilitated recall of the pattern information; processing with a partner appeared to enhance perception of the multidimensional nature of behavior that supports alcohol use.


[Carbamazepine: an efficient adjuvant treatment in schizophrenia]. Different studies published in the last years have focused on the psychotropic effects of carbamazepine (CBZ). This study tries to investigate the efficacity of CBZ as an adjunct treatment of schizophrenia. 20 patients with a diagnosis of paranoid schizophrenia, according to the RDC, have been investigated by double-blind method. Subjects are divided in two groups (n = 10). The first one is treated with CBZ (with dose in order to reach a plasma level between 8-12 mg /l) and Haloperidol (oral fixed dose: 30 mg /day). The second group only with Haloperidol (same dose). Clinic and psychopathological disturbances are evaluated with the BPRS, and secondary effects with the UKU scale. A clinical improvement (90%, measured by the BPRS) was observed for both groups, without significant differences. Patients treated with CBZ show an important reduction of neurological secondary effects related to neuroleptics (Haloperidol). Carbamazepine appears to be a useful treatment, combined with neuroleptics, for acute schizophrenic episodes.


[Buprenorphine use, a bad prognostic indicator in drug dependence]. We studied 184 patients with DSM III-R diagnostic criteria for opiate dependence and classified them in order of their buprenorphine use: those who never used it (21%), others who used it from time to time (43.5%), and those who use it habitually (35.5%). The patients who use buprenorphine habitually have a poorer social functioning and are more disturbed clinically. They present too: more unemployment (p less than 0.05), longer time of opioid dependence (p less than 0.05), they offend usually (p less than 0.001), they traffic in drugs more than the other patients (p less than 0.001), mostly buprenorphine (p less than 0.001) and they are usually polydrug-addicts (p less than 0.001).


The abstinence violation effect and very low calorie diet success. This study evaluated the relationship between Marlatt and Gordon's (1985) Abstinence Violation Effect (AVE) and fasting outcomes of patients enrolled in a Very Low Calorie Diet (VLCD) and behavior education program. Within the first 11 weeks of the VLCD, 41 of 76 patients reported a fasting lapse and rated this lapse on an attribution scale. Patients reporting greater characterological attributions for their first lapse (i.e., a higher AVE) lost a smaller percentage of their excess weight during active fasting than patients reporting more situational attributions r(39) = -.36, p less than .025. First lapse AVE ratings did not distinguish between program dropout versus completer status, but high AVE dropouts did spend fewer weeks in the VLCD program than low AVE dropouts, r(12) = -.54, p less than .05. Although a faster's initial level of obesity accounted for the largest portion of weight loss outcome variance, the AVE accounted for a significant additional portion of outcome.


[Annual treated psychopathological morbidity. Demographic and diagnostic features]. We report in this study the demographic and diagnostic variables of all successive outpatients, age 16 years and older, treated during a one year time period, at a Psychiatric Unit of the Spanish Seguridad Social. Diagnosis were made following DSM-III Criteria. Epidemiologic parameters calculated were population based treated morbidity rates. The total number of patients seen was 1,119, annual rate of 13.16 per 1,000 population. Females outnumbered males significantly (rates of 18.25 and 8.41, respectively). Annual rates are compared with six months previously obtained rates. In general, a consistent sex/age epidemiologic profile was found for most DSM-III diagnostic categories. Implications for planning Mental Health Care Systems, as well as for evaluating Epidemiologic Field Surveys in Psychiatry, all of potential value, can be derived from the data.


[Psychiatric diseases in the elderly in an urban Aragonese population (Spain) and their relation to health determinants]. As a part of the SAMAR 89 Project on mental health, we present the results of a psychiatric epidemiological research (in two stages) in a representative sample of the elderly urban population of Zaragoza (Spain). We study the relation between psychological disorders and sociodemographic factors, and network and social support. In the first stage we use a adaptation of the Enquête Santé Quebec and the General Health Questionnaire of 28 items of Goldberg. The Clinical Interview Schedule and the monumental state of Folstein were used for the psychiatric diagnoses in the second stage (diagnoses criteria of the DSM-III). The psychological disorders were more frequent on the women, the more aged and the ones of low socioeconomic level. Also was detected a correspondence between bad mental health and problems in the network and social support.


A time series investigation of three nicotine regulation models. Time series data were collected twice daily for 62 days from 10 individuals on three variables related to smoking habit strength: number of cigarettes smoked, salivary cotinine, and carbon monoxide. The two purposes of this study were: (a) to evaluate which time series model(s) best fits each of the measures; and (b) to determine which model of nicotine regulation is consistent with the data. Three models of nicotine regulation were considered: (a) nicotine fixed effect; (b) nicotine regulation; and (c) multiple regulation. These models provide different predictions about the size and direction of the lag-one autocorrelation. Each measure was described in terms of one of a family of time series models represented mathematically as ARIMA (p, d, q). Models varied by individual, but a single model described the majority of subjects for all three variables. The clearest model identification was for the number of cigarettes smoked where an ARIMA (1, 0, 0) model with a moderate to strong negative dependency fit the majority of the subjects. This provided strong support for the multiple regulation model. An appendix provides a brief review of time series methodology.


Adequacy of recall of drinking patterns and event occurrences associated with natural recovery from alcohol problems. The adequacy of recall of drinking and events surrounding natural recovery from alcohol problems was investigated with 21 abstinent and 18 active untreated problem drinkers. During structured interviews, drinking was assessed for 6 years, and events were assessed for 1 year; both assessment periods ended about 6 years before data collection, which corresponded with the beginning of sobriety for abstinent subjects. The accuracy of subject reports of both variable classes was evaluated through comparisons with collateral reports, and the reliability of drinking reports was evaluated by reinterviewing a subset of subjects about 2 months after the first assessment. Reliability was generally high for subjects' drinking reports. Subject-collateral agreements were significant for drinking and event variables that collaterals could readily observe, but not for variables that were less observable. Current drinking status and the length of recall did not influence reporting accuracy. With some qualifications, these findings support the use of structured recall procedures to investigate drinking patterns and environmental circumstances related to natural recovery and highlight limitations in the use of collaterals as a verification method.


[Comparison of the attitudes of Brazilian and Spanish medical students towards mental disease]. The purpose of this study was to compare the attitudes towards mental illness held by Brazilian and Spanish medical students. These attitudes were measured by means of the Opinions about Mental Illness Scale (OMI), developed by Cohen and Struening in 1962 in the United States, and translated and adapted by Rodrigues in 1983. The scale was answered by 214 5th year students of the School of Medicine of Ribeirão Preto, Brazil (61), and of the School of Medicine of Salamanca, Spain (147), and the data were analysed through the transformation of the raw scores to seten scores. From the seven attitudinal dimensions yielded by the adapted OMI, the subjects showed significant differences in relation to the attitudes called Benevolence, Social Restrictiveness and Mental Effort Etiology. Other significant differences were also found when mean scores were grouped by respondents' sex and future medical specialization.


Relationship of diagnostic, demographic, and personality variables to self-reported stimuli for chemical use. While extensive research has been conducted to determine internal and external stimuli for drinking by alcoholics, the topic of how demographic, diagnostic, and personality variables may relate to these precipitants is largely unexplored. This study suggests that stimuli to use alcohol or drugs differ partly as a function of diagnosis (alcohol dependence vs. concurrent alcohol and drug dependence). Age, education, and gender do not appear related to the stimuli in either diagnostic group. Personality characteristics of cognitive reflectiveness, impulse control, sociability, and intrapunitiveness, however, seem to be associated with certain classes of high risk stimuli.


Predictors of smoking relapse among self-quitters: a report from the Normative Aging Study. We followed 235 adults for one year after a self-initiated attempt to stop smoking cigarettes. Relapse rates were much larger than expected in the early days and weeks after the quit attempt. Approximately 62% had relapsed by 2 weeks after their quit dates. Those who smoked any cigarettes at all in the post-cessation period (i.e., lapsed) had a 95% probability of resuming their regular pattern of smoking subsequently. Shorter periods of abstinence on prior quit attempts, greater pre-cessation consumption of alcoholic beverages, and lower pre-cessation levels of confidence in quitting were related to relapse. In addition, abstainers who reported decreased confidence after cessation concerning their ability to maintain abstinence were more likely to relapse thereafter. The presence of a greater proportion of smokers in the subjects' environment also increased the likelihood of relapse. Demographic variables such as age, gender, and education level did not predict relapse. Likewise, neither baseline psychosocial stress levels, nor post-cessation increases in stress were related prospectively to relapse. Clinical implications of finding are discussed.


Co-occurrence of substance abuse with conduct, anxiety, and depression disorders in juvenile delinquents. The purpose of the current study was to examine the co-occurrence of substance abuse and three other psychiatric disorders (conduct disorder, depression, anxiety) in an incarcerated juvenile delinquent sample. Diagnostic interviews were utilized to place participants in one of three groups: No substance abuse, alcohol/marijuana abuse, or polysubstance abuse. Frequency of diagnosis and number of symptoms of three psychiatric disorders were then examined. The results indicated that the diagnosis of conduct disorder increased significantly with the occurrence of substance abuse. Also, the number of symptoms for conduct disorder, anxiety, and depression increased with substance abuse. With polysubstance abuse the probability of having more than one of the other psychiatric diagnoses was above 50%. Potential explanations for the findings, focusing on the developmental trajectory for conduct problems and self-medication for internalizing disorders, are discussed.


The impact of prior substance abuse on treatment outcome for bulimia nervosa. The present investigation examined the significance of a past history of substance abuse on treatment outcome for bulimia nervosa. Seventy-five women with bulimia nervosa participated in a 6-week double-blind outpatient trial of desipramine; 19 patients had a history of substance abuse and 56 did not. Although patients with a history of substance abuse reported higher levels of anxiety and depression at presentation for treatment than patients without such histories, the two groups reported a similar age of onset of their bulimia nervosa and similar severity of eating pathology with regards to binge and vomit frequencies and measures of concern about body shape and weight. On all outcome measures, the improvement of the substance abuse group was equal to or greater than that in the group without a history of substance abuse. Results suggest that a past history of substance abuse has no implication regarding response to pharmacological treatment for bulimia nervosa.


Relationships among borderline features, body dissatisfaction and bulimic symptoms in nonclinical females. The present study evaluated the utility of combining measures of body dissatisfaction and borderline personality features in screening high-school girls who may be at risk for bulimia nervosa. Two samples (777 high-school girls and 22 bulimic women in-treatment) completed scales assessing borderline traits, body dissatisfaction, eating symptoms, and associated psychiatric disturbances. Students were divided into four groups, respectively showing: (a) high body dissatisfaction and borderline traits, (b) high body dissatisfaction alone, (c) high borderline traits alone, or (d) neither vulnerability component. Clinical and nonclinical groups were then compared for severity of eating and psychiatric symptoms. Girls displaying the combination of high body dissatisfaction and borderline traits (our presumed "high-risk" group) showed an elevated profile of eating and associated disturbances, highly comparable to the bulimic group. They were also more likely to receive threshold and subthreshold diagnoses of bulimia nervosa (according to simulated diagnoses based on self-report items) than subjects in other high-school groups. Implications of these findings were discussed with reference to the "two-component" model of eating disorders.