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Biomedical subjects

J Hannibal

Publications and source records attributed to J Hannibal.

70 records · Page 4Linked to original sources

Distribution and effects of pituitary adenylate cyclase activating peptide in cat and human lower oesophageal sphincter.

1. The localization, tissue concentrations, and effects of pituitary adenylate cyclase activating peptide (PACAP) 27 and 38 were investigated in cat and human lower oesophageal sphincter (LOS), and compared with those of vasoactive intestinal peptide (VIP) and helospectin. 2. PACAP-immunoreactive nerve structures were found in the cat and human LOS, with an abundance in the circular smooth muscle layer. PACAP 27-immunoreactivity was often co-localized with VIP-immunoreactivity. 3. In cat tissue, PACAP (PACAP 27 plus PACAP 38) concentrations were 50 fold lower than VIP concentrations; in human tissue they were 10 fold lower. 4. PACAP 27, PACAP 38, helospectin I, and VIP induced concentration-dependent relaxations in circular smooth muscle preparations from cat and human LOS. The order of potency was: VIP > helospectin I > or = PACAP 27 > PACAP 38. NG-nitro-L-arginine, scopolamine, or apamin, did not influence the relaxant effects of PACAP 27 or VIP. 5. In cat preparations, both cyclic AMP and cyclic GMP levels were increased after exposure to PACAP 27 and helospectin I, whereas exposure to VIP was followed by an increase in cyclic AMP levels only. In human preparations, there was an increase in cyclic AMP levels without any change in cyclic GMP levels. 6. These results suggest that in the cat and human LOS, PACAP 27 and VIP can occur within the same nerve structures. PACAP 27 has a potent relaxant action, but its functional importance has to be established.

Animals↗

Pituitary adenylate cyclase-activating polypeptide: occurrence and relaxant effect in female genital tract.

The distribution, localization, and smooth muscle effects of pituitary adenylate cyclase-activating polypeptide (PACAP) were studied in the human female genital tract. The concentrations of PACAP-38 and PACAP-27 were measured by radioimmunoassays, and both peptides were found throughout the genital tract. The highest concentrations of PACAP-38 were detected in the ovary, the upper part of vagina, and the perineum. The concentrations of PACAP-27 were generally low, in some regions below the detection limit and in other regions 1 to 5% of the PACAP-38 concentrations. Immunocytochemistry revealed that PACAP was located in delicate varicose nerve fibers that were most abundant in the internal cervical os, where they mainly seemed to innervate blood vessels and smooth muscle cells. PACAP-38 and PACAP-27 (10(-10)-10(-6) M) caused a concentration-dependent relaxation of the spontaneous activity of the nonvascular smooth muscle strips from fallopian tube and myometrium in vitro. Likewise, both peptides (10(-10)-10(-6) M) caused relaxation of nonrepinephrine (10(-6) M)-precontracted intramyometrial arteries. No effect of the PACAP sequences, PACAP-(6-27), PACAP-(16-38), and PACAP-(18-27), on fallopian tube was observed. The findings suggest a smooth muscle regulatory role of PACAP in the human female reproductive tract.

Adolescent↗

Pituitary adenylate cyclase-activating peptide gene expression in corticotropin-releasing factor-containing parvicellular neurons of the rat hypothalamic paraventricular nucleus is induced by colchicine, but not by adrenalectomy, acute osmotic, ether, or restraint stress.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a newly discovered neuropeptide that is present in high amounts in hypothalamic neuroendocrine neurons and potently stimulates the accumulation of cAMP within cells of the anterior pituitary. We have employed several specific antisera recognizing different parts of the PACAP precursor to elucidate the distribution of PACAP-like immunoreactivities in the hypothalamic components of the hypothalamo-pituitary-adrenocortical axis in sections obtained from normal and colchicine-treated rats. Using immunohistochemistry with avidin-biotin-coupled peroxidase as a reporter system, high numbers of PACAP-immunoreactive perikarya were found in colchicine-pretreated rats in many of the parvicellular subdivisions of the hypothalamic paraventricular nucleus (PVN). A few cells were also found in the magnocellular subdivisions of the nucleus, and a similar small population of cells was observed in the dorsolateral aspect of the supraoptic nucleus. Using indirect immunofluorescence, the relation between CRF- and PACAP-containing neurons in the various parvicellular subnuclei of the PVN was studied, and a high degree of colocalization was demonstrated in the neurons of the medial parvicellular part of PVN. To further study the functional implications of PACAP in the hypothalamo-pituitary-adrenocortical axis, we examined the expression of PACAP messenger RNA (mRNA) in the PVN in response to five different stimulatory paradigms that previously have been shown to stimulate CRF mRNA expression in the medial parvicellular part of the PVN. The stimulatory challenges of adrenalectomy, restraint stress, ip injection of hypertonic saline, ether stress, and intracerebroventricular injection of colchicine induced significant elevations of CRF mRNA expression in the medial parvicellular part of the PVN. In contrast, the expression of PACAP mRNA, which is hardly detectable within the medial parvicellular part of the PVN, was induced only by colchicine treatment (from undetectable levels to 177 +/- 21 dpm/g; mean +/- SEM), whereas PACAP mRNA remained undetectable in this region of the PVN after exposure to any of the other stimulatory paradigms. The onset of colchicine-induced PACAP mRNA expression in the PVN was rapid (3 h), and PACAP mRNA levels remained elevated throughout the 48-h observation period. Considering the different topography and connections of the parvicellular subnuclei of the PVN, the current observations suggest that PACAP present in parvicellular neurons of the PVN may act not only as a neuroendocrine transmitter/modulator in the hypothalamo-pituitary-adrenocortical axis, but also as transmitter mediating neurotransmission conveyed from the PVN to preganglionic neurons of the autonomic system.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Cortex↗

Pituitary adenylate cyclase activating peptide (PACAP) mRNA in the rat neocortex.

In agreement with previous studies, Northern blots revealed expression of pituitary adenylate cyclase-activating peptide (PACAP) mRNA in the rat cerebral cortex. In order to identify the cells expressing PACAP mRNA, semiquantitative in situ hybridization histochemistry was applied. A moderate concentration of PACAP mRNA transcripts was determined in the cingulate and frontal cortices, whereas lower concentrations were found in other cortical areas. In emulsion dipped sections, grains were detected over cell bodies in cortical layers II, III and IV. Grains were diffusely distributed over cells in the outer granular layer of the anterior cingulate and the retrosplenial areas. In the outer pyramidal cell layer a few neurons contained a large number of grains. These data show that PACAP mRNA is present in cells outside the hypothalamus and implies that PACAP could play a broader transmitter role in the CNS than earlier anticipated.

Animals↗

Nitric oxide synthase-containing, peptide-containing, and acetylcholinesterase-positive nerves in the cat lower oesophagus.

The innervation of the cat lower oesophagus, including the lower oesophageal sphincter, was studied by enzyme histochemistry, immunohistochemistry, and confocal microscopy. In the lower oesophageal sphincter, and at a level 2 cm above it, no apparent differences were seen in the nerve distribution pattern. Among the nerve populations studied, acetylcholinesterase (AChE)-positive nerves were the most abundant in both these regions. The density of AChE-positive nerves was particularly marked in the circular muscle layer. A rich supply of nitric oxide synthase (NOS)-containing nerves was identified by using an antiserum against neuronal NOS, or by enzyme histochemical staining for NADPH diaphorase activity. Vasoactive intestinal peptide (VIP)-immunoreactive nerves had a similar distribution pattern as NOS-immunoreactive nerves, and nerves displaying immunoreactivity for NOS and VIP often showed profiles coinciding with AChE-positive nerves. As judged by confocal microscopy, immunoreactivities for helospectin, pituitary adenylate cyclase-activating peptide (PACAP) and VIP, to a large extent were found in the same nerves. At a level 7 cm above the lower oesophageal sphincter, the total nerve supply was less than in the sphincter itself and 2 cm above it. Immunoreactivity towards VIP, PACAP and helospectin was also found to co-exist with NOS and neuropeptide Y within the same nerve structures. It is concluded that there is an intricate innervation pattern in the feline lower oesophagus reflecting the complexity in the regulation of its motility.

Acetylcholinesterase↗

[Toxic epidermal necrolysis].

A case of severe toxic epidermal necrolysis is described, stressing the importance of multiorgan system involvement of the disease. A possible pathogenetic mechanism involving tumor necrosis factor is discussed.

Adult↗

The interrelationship of weight loss, dietary intake, and quality of life in ambulatory patients with cancer of the lung, breast, and ovary.

One hundred four consecutive patients with newly diagnosed small cell lung cancer, metastatic breast cancer, and ovarian cancer in good physical functional condition (performance rating 0-1 on Eastern Cooperative Oncology Group scale) were divided into a weight-losing group (> or = 5% unintentional weight loss within 3 mo; n = 48) and a weight-stable group (n = 56). Dietary intakes in relation to fat-free mass were not different in the two groups. According to the Quality of Life index and the General Health Questionnaire, weight-losing patients had significantly lower quality of life than weight-stable patients. In patients with weight loss, daily intakes of energy and protein correlated significantly with scores on the General Health Questionnaire. This study has shown that many ambulatory cancer patients do not eat enough to maintain weight and that even a moderate weight loss is associated with psychological distress and lower quality of life.

Adult↗

Effect of dietary counseling on food intake, body weight, response rate, survival, and quality of life in cancer patients undergoing chemotherapy: a prospective, randomized study.

PURPOSE: This study examined the effect of frequent nutritional counseling on oral intake, body weight, response rate, survival, and quality of life in patients with cancer of the lung (small-cell), ovary, or breast undergoing cyclic chemotherapy. PATIENTS AND METHODS: Of 105 assessable patients, 57 were randomized to receive nutritional counseling, and 48 to receive no nutritional counseling and consumption of an ad lib oral intake. The intervention group was counseled to achieve a daily energy and protein intake according to recommended dietary allowances. Counseling was standardized and performed by a trained dietitian, and took place twice monthly during a 5-month period from start of chemotherapy. RESULTS: Dietary counseling increased daily energy intake by approximately 1 MJ and protein intake by 10 g over the entire study period. There was no change in the control group. Counseling led to an insignificant increase in body weight, but triceps skinfold measurement increased significantly after 5 months. Response rate and overall survival did not differ between the groups. Quality of life measured by the Quality-of-Life index (QL-index) increased significantly in both groups, but did not differ between groups. CONCLUSION: No clinical benefit could be demonstrated despite long-term and continuous improved food intake in cancer patients with solid tumors undergoing aggressive chemotherapy.

Adult↗

Dietary intake in patients with small cell lung cancer: the effect of aggressive chemotherapy.

Energy and protein intake in 32 consecutive patients with small cell lung cancer was examined at initiation of cyclical chemotherapy and after 1 and 3 months. With each cycle intakes decreased in the first 2 days following chemotherapy, but were back to pretreatment levels on the third day. Eleven of the patients lost weight in the study period. Their energy and protein intakes were lower following chemotherapy compared to pretreatment intakes and to post-therapy intakes in weight-stable patients. Pretreatment intakes did not decrease over time, either in weight-losing or in weight-stable patients.

Aged↗

Tumour regression following chemotherapy does not increase food intake.

Forty-six patients with cancer of the breast, ovary or lung (small cell) were followed for 5 months after initiation of cyclical chemotherapy to examine if any changes in voluntary food intake or nutritional status were related to treatment response. The study showed a slight decrease in protein (P less than 0.05) and energy intake (not significant) at 3 months compared to pretreatment intakes in 31 patients with objective tumour regression. In 15 non-responding patients no changes were demonstrated. There were no changes in anthropometric status related to treatment response. Despite the lower protein intake in treatment responders p-albumin increased significantly compared to pretreatment value. Thus, initially successful chemotherapeutic treatment is not automatically followed by improved nutrition, and many of these patients are potential candidates for early dietary intervention.

Adipose Tissue↗

Electrical taste detection thresholds and chemical smell detection thresholds in patients with cancer.

Taste sensation in patients with cancer has previously been studied with the cumbersome method of chemical gustometry, which have produced inconsistent results. In this study taste thresholds were determined with the simple and reliable technique of electrogustometry in 51 patients with cancers of the lung (small cell), ovary or breast, and in 29 matched control patients with nonneoplastic disease. Chemical smell thresholds for phenyl-methyl-ethyl-carbinol were studied in the same group of patients. Electrical taste threshold was higher in patients with cancer compared with control patients (30 [12 to 80] microA versus 9.5 [6.1 to 24] microA; median [interquartile range], P less than 0.001). No differences were seen in smell thresholds. Patients who responded to chemotherapy obtained a decreased electrogustometric threshold at time of reevaluation (24 [8 to 64] microA versus 30 [15 to 90] microA; median [interquartile range], P less than 0.05). These results suggest an effect of the malignant disease itself on taste thresholds.

Adult↗

Taste thresholds in patients with small-cell lung cancer.

Recognition thresholds for the four basic tastes (salt, sour, sweet and bitter) were tested by the forced-choice technique in 27 patients with small-cell lung cancer, and 22 weight-matched control patients with non-malignant diseases. No significant differences in threshold concentrations could be demonstrated. When patients who were losing weight were compared with weight-stable patients, significantly lower taste thresholds for bitter substances were found in weight losing groups in both cancer and control patients. Small-cell lung cancer patients who responded to therapy had obtained an increased threshold for bitter taste at the time of reevaluation than at the time of diagnosis, an effect that may be explained by the chemotherapeutic regimen. The results suggest that in patients with small-cell lung cancer it is not the cancer disease per se but the weight loss that often accompanies it that causes an increased taste sensitivity for bitter substances.

Aged↗

Food intake, eating-related complaints, and smell and taste sensations in patients with cancer of the lung, ovary and breast undergoing chemotherapy.

Nutritional status and energy and protein intake were studied in 52 patients with cancer of the breast, ovary or lung before, after 1, and after 3 cycles of aggressive chemotherapy. Pre-treatment intakes were somewhat lower than recommended and did not change after 3 cycles of chemotherapy, neither did nutritional status. Many patients had eating-related complaints, but these complaints did not increase significantly with chemotherapeutic treatment. In 31 patients electrical taste detection thresholds and chemical smell detection thresholds were measured before and after 3 cycles of chemotherapy. Changes in thresholds had no relation to changes in energy and protein intake. Perceived taste and smell changes were not reflected in chemosensory threshold values.

Journal Article↗

High-dose metoclopramide + lorazepam versus low-dose metoclopramide + lorazepam + dehydrobenzperidol in the treatment of cisplatin-induced nausea and vomiting.

In a randomized double-blind, cross-over trial of 34 patients receiving cisplatin-based chemotherapy (20-100 mg/m2), the antiemetic effect of high-dose metoclopramide (HDM) (10 mg/kg iv. loading dose + 7 hours continuous infusion) + lorazepam (L) (2.5 mg x 4 po) was compared with low-dose metoclopramide (LDM) (70 mg) + L (2.5 mg x 2 po) + dehydrobenzperidol (5 mg x 2 im). Among the 29 patients who completed the cross-over, HDM significantly reduced the number of vomiting episodes (p = 0.002) and the degree of nausea (p = 0.004). Seventeen patients preferred the HDM and 4 the LDM regimen (p = 0.01). Sedation was seen in all but 1 patient, and was graded as severe in 6 patients receiving the HDM and in 2 patients receiving the LDM regimen. No extrapyramidal adverse reactions were seen. We conclude that high-dose metoclopramide + lorazepam is a safe antiemetic regimen and significantly superior to low-dose metoclopramide + lorazepam + dehydrobenzperidol. Owing to the severe sedation which occurs in some patients, the dose of lorazepam should be individually adjusted.

Adult↗

[Prognosis in severe alcoholic intoxication].

Out of 489 patients admitted to the poisoning treatment centre in 1986, 122 had serum ethanol values of greater than or equal to 66 mmol/l (0.3 per cent). 55% of the patients were men and 45% women. 69.1% of this fraction was in the age range 30-49 years. Verbal contact could be achieved in 69.9%. 4.9% of the selected patients had systolic blood pressures of less than 90 mmHg. 0.8% had rectal temperatures of less than 36.5 degrees C. Aspiration of the gastric contents was performed in 63%. Tracheal tubes were inserted in 6.6% and three of the patients required ventilation. A woman of 36 years with a serum ethanol value of 0.32% died. 58.5% were alcohol addicts, among these 64% were males. 53% had psychiatric histories. The average stay was 1.0 days. Signs of serious poisoning were rare and therapeutic problems moderate. Contrary to what might be expected, no excess of non-abusers was found among the patients without verbal contact. The importance of close observation of persons with severe alcohol poisoning is emphasized.

Adult↗