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PubMed2002

Autoimmune responses to proliferating cell nuclear antigen multiprotein complexes involved in cell proliferation are strongly associated with their structure and biologic function in patients with systemic lupus erythematosus.

OBJECTIVE: To analyze the reaction of lupus sera with proliferating cell nuclear antigen (PCNA) multiprotein complexes (PCNA complexes), which are part of the protein machinery involved in cell proliferation. METHODS: PCNA complexes were purified from rabbit thymus extract by affinity chromatography using anti-PCNA monoclonal antibodies (TOB7, TO17, and TO30); monomeric and trimeric PCNA forms (AK-PCNA) were purified using anti-PCNA serum AK. The reactions to these antigens of 10 anti-PCNA-positive and 40 anti-PCNA-negative sera selected from 560 lupus patients were tested by immunoblotting, immunoprecipitation, and enzyme-linked immunosorbent assays (ELISAs). RESULTS: With one exception (serum OK), anti-PCNA-positive sera reacted exclusively with only the 34-kd polypeptide. In contrast, 14 of 40 anti-PCNA-negative sera reacted with multiple proteins within PCNA complexes. Most anti-PCNA-positive sera probably recognize as epitopes the binding sites for other proteins on PCNA, which are likely hidden when PCNA is complexed with other proteins. As a consequence, only serum OK reacted with the PCNA complex in a series of ELISAs. Using AK-PCNA as a competitive inhibitor, it was determined that serum OK reacts with both the 58-kd polypeptide and the 34-kd PCNA within complexes. Together with the results of a longitudinal analysis, these results suggest that the immune system of patient OK likely recognized the complexed PCNA protein, after which the autoimmune response spread to other elements of the complexes. CONCLUSION: Intermolecular-intrastructural help, leading to the spread of autoimmune response from PCNA to other proteins associated with its biologic function, plays a crucial role in the induction of the autoimmune response seen in lupus patients.

Antibodies, Monoclonal↗
PubMed1989

High volume lesser sac lavage in acute necrotizing pancreatitis.

The effect of lesser sac drainage with or without lavage on some early predictors and on outcome in acute necrotizing pancreatitis was analysed. The evaluation was made prospectively for 24 patients, in a single centre study. According to Ranson's criteria and laparotomy findings, the lavage and drainage groups were comparable and the pancreatitis was severe and necrotizing in both groups. In a longitudinal analysis of the first 4 postoperative days, lavage did not show any advantage over drainage, as measured by seven prognostic signs (serum creatinine, blood glucose, base excess, haematocrit, white blood cells, C-reactive protein and immunoreactive phospholipase A2 concentration). Furthermore, the study did not find that lavage had any positive effect on the incidence of mortality (36 versus 17 per cent in the drainage group) or on septic complications in acute necrotizing pancreatitis. In the total series the extent of pancreatic necrosis was an essential predictor of the outcome.

Acute Disease↗
PubMedDate not supplied

NHS direct: managing demand for primary care?

This paper considers how NHS Direct is affecting demand for primary care in particular out-of-hours services from GPs. This is reviewed through a 3-year study of NHS Direct and HARMONI, the integrated telephone health helpline based in West London. It describes the policy background and development of the services on the site, and some of the outcomes of the HARMONI commissioned research to answer the question 'Has NHS Direct increased the workload for HARMONI doctors?'. The research adopted both a qualitative and quantitative approach using cross-sectional and longitudinal analysis of the data collected. The analysis of the data reveals the issues as both complex and dynamic in nature. The research shows that while there has been no significant change to the total volume of activity, changes within patient groups notably the elderly and children, and in individual GP practices may be significant. In addition, the changes in organizational arrangements may influence significant changes in referral patterns such as GP out-of-hours visits. This was confirmed in the interview data indicating a link between the change in nurses' role from gatekeeper to patient advocate, which happened when they ceased to be employees of the part-time co-op and began to work instead for the 24 hours, 7 days a week NHS Direct service. The conclusions drawn are that behavioural and organizational changes are at least as significant as the evidence-based computerized decision support software in changing the demand for primary care. Further evidence cited is that a different demand pattern of calls was experienced by those local GPs not integrated into out-of-hours provision at NHS Direct West London at the time of the study.

After-Hours Care↗
PubMed1997

Low-fat diets may prevent weight gain in sedentary women: prospective observations from the population study of women in Gothenburg, Sweden.

The Population Study of Women in Gothenburg, Sweden is an ongoing prospective study of female residents who were recruited from the local registry in 1968-1969 when they were 38-60 years old. The data presented here were collected from 361 healthy women who underwent a baseline physical examination including a supplementary dietary history interview and returned for a second general health examination 6 years later. This report identifies a subgroup of 57 women who were sedentary during their leisure time and appear to have been particularly susceptible to gaining weight as a function of the fat content of their diets. Specifically, longitudinal analysis of body weights in the whole sample revealed a statistical interaction between leisure-time physical activity and habitual dietary fat intake (energy%), as reported at the baseline examination, in the prediction of subsequent weight change. Further stratified analysis suggested that weight changes were significantly dependent on dietary fat intake among the sedentary women only. High energy intake also predicted weight gain in the sedentary group, although the predictive value for a high-fat diet was of marginal significance after adjusting for total energy consumption. These results suggest that sedentary recreational activity plus a low-fat diet may have a combined contribution to weight change that is not equivalent to the sum of the separate effects. Such a synergy between two modifiable lifestyle factors seems highly relevant for prevention of obesity.

Adult↗
PubMed2001

Longitudinal sero-reactivity to human herpesvirus 8 (KSHV) in the Swiss HIV Cohort 4.7 years before KS.

The relationship between viral infection with Kaposi sarcoma-associated herpesvirus (KSHV) and the onset of Kaposi sarcoma (KS) in AIDS patients is incompletely understood. This study investigates the use of three serological assays to predict the development of KS in HIV-positive patients. Serially collected serum samples from 36 patients with KS and matched controls in the Swiss HIV Cohort Study (SHCS) were analyzed in a case control study. Three serologic assays to detect antibodies against KSHV (nuclear and membrane antigen immunofluorescence assay, N-IFA, M-IFA and ORF 65.2 ELISA) were used to determine the predictive value of KSHV-seropositivity. Serial samples from the cases were also analyzed to determine longitudinal patterns of seroreactivity and identify cases of seroconversion. Assay sensitivity for detection of KSHV antibodies was highest for M-IFA (83%), followed by N-IFA (74%) and 65.2 ELISA (52%). At the time of initial serum sampling (median 4.7 years before KS), only the N-IFA distinguished case and control sera (61% vs. 32%) and no assay was clearly predictive of subsequent onset of clinical KS. Moreover, an unexpectedly high rate of reversions to seronegativity were observed by N-IFA (27/33) as well as by 65.2 ELISA (11/26) in the longitudinal analysis. Analysis of the ORF65.2 ELISA index indicated that these reversions before the clinical onset of KS were associated with antibody levels that frequently hovered around the level of detectability. A marked increase in ORF 65.2 antibody titer occurred in a third of the patients at the time of KS diagnosis. Only two seroconversions were documented. KSHV infection within the SHCS is likely to have preceded HIV infection. KSHV infection alone is not highly predictive of KS development in this cohort of HIV-infected homosexual men as compared with matched controls. Three KSHV serologic assays, though sensitive at the time of clinical KS are inconsistently positive before the development of AIDS-related KS.

AIDS-Related Opportunistic Infections↗
PubMed2004

Intrahepatic CD8 T-lymphocytes and HBV core expression in relation to response to antiviral therapy for chronic hepatitis B patients.

Recognition of HBV-infected hepatocytes by CD8 T-lymphocytes is important for viral clearance. Expression of hepatitis B core antigen (HBcAg) in HBV-infected hepatocytes can trigger this antiviral T-cell response. The intrahepatic CD8 T-lymphocytes and HBcAg expression were investigated in relation to response to antiviral therapy. Forty chronic HBeAg-positive patients treated with either lamivudine (n = 20) or interferon-alpha (n = 20) were investigated. Ten patients from each treatment group exhibited a response. Liver biopsies were carried out before and after therapy. CD8 T-lymphocytes and HBcAg expression were detected by immunohistochemistry. The number of pretreatment intrahepatic CD8 T-lymphocytes was significantly higher in responders (P = 0.008). In responders baseline nuclear HBcAg expression tended to be lower (P = 0.09). Cytoplasmic expression was not significantly different between responders and non-responders (P = 0.46). The number of CD8 T-lymphocytes correlated with cytoplasmic HBcAg (r(s) = 0.31; P = 0.04); CD8 T-lymphocytes were situated in clusters of hepatocytes with cytoplasmic HBcAg. Longitudinal analysis showed a significant reduction of CD8 T-lymphocytes after treatment in responders (P < 0.001). Multivariate analysis revealed pretreatment CD8 T-lymphocytes and age as independent prognostic factors for response (n = 40). The number of pretreatment CD8 T-lymphocytes was the only independent prognostic indicator for response to interferon-alpha (P = 0.03); it was of borderline significance for lamivudine therapy (P = 0.06). It is concluded that the number of pretreatment intrahepatic CD8 T-lymphocytes is an important predictor of response to HBV therapy with either interferon-alpha or lamivudine. Response to therapy led to a significant reduction of intrahepatic CD8 T-lymphocytes. Co-localisation of CD8 T-lymphocytes and HBcAg-positive hepatocytes suggests antiviral activity predominantly at the site of maximum HBV replication.

Adolescent↗
PubMed1994

Sequential change of the hypervariable region of the hepatitis C virus genome in acute infection.

Hepatitis C virus (HCV) infection is characterized by persistence of liver inflammation that often leads to end-stage liver disease, although the mechanisms are not fully understood. A hypervariable region (HVR) has been reported in the E2/NS1 region of the HCV genome, in which striking diversity is found among different HCV isolates. To investigate the association of the HVR alterations with the clinical courses of HCV infection, a longitudinal analysis of the HVR in patients with acute HCV infection was carried out. Plasma samples were obtained at several times in three patients with acute hepatitis C. Plasma RNA was extracted and reverse transcribed, and DNA fragments that included the HVR were amplified by PCR. The sequences of the HVR were directly determined from the PCR products by the dideoxy chain termination method, from which amino acid sequences were deduced. In all cases, plasma HCV-RNA disappeared with the improvement of the initial alanine aminotransferase (ALT) elevation, but HCV-RNA reappeared about 1 year later with or without deterioration of the hepatitis. In a case of sporadic acute hepatitis, the HCV in the recurrent phase had seven amino acid substitutions in the HVR compared with that in the acute phase, although no amino acid changes were noted during the initial acute phase. In a case of posttransfusion hepatitis, a marked difference was observed between the acute and the recurrent phases, with an amino acid homology of 30% (8/27). The mutation rate of the HVR had a tendency to accelerate as the HCV infection progressed to the chronic stage.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed2007

Longitudinal growth and risk factors for growth deficiency in children treated for acute lymphoblastic leukemia.

BACKGROUND: Growth deficit has been reported as a frequent complication of the treatment of acute lymphoblastic leukemia (ALL). PROCEDURE: Longitudinal analysis of the growth of 129 children, from a total of 351 cases diagnosed between 1987 and 1994 in Brazil, was determined. Height data were converted into standard deviation Z scores. Only girls younger than 10 and boys younger than 12 years old at diagnosis were included. Patients were treated according to a German BFM-83 based protocol. Fifty-eight children received 18 Gy cranial irradiation, four 12 Gy, and two 24 Gy. Patients were aggregated into five non-excluding groups according to availability of height data at diagnosis, during the treatment, at the end of it, and several years after; 35 children reached their final height. RESULTS: Height deficit at the end of the therapeutic treatment was evident (P < 0.0001). Catch-up occurred 1 year after stopping treatment (P = 0.016). At the last follow-up, over 5 years after the end of treatment (n = 83) or at final height (n = 35), impressive height deficits were recorded (P < 0.0001 for both end points). Multivariate analysis demonstrated that growth impairment was more severe in children younger than 4 years at diagnosis and in those who received cranial irradiation. No significant effect of gender was observed. Children who were treated solely with chemotherapy also had significant height loss. CONCLUSIONS: Treatment of ALL in children is associated with growth deficit during the treatment and several years after it, affecting the final height negatively, particularly in patients younger than 4 and in those who received cranial irradiation.

Age Factors↗
PubMed1996

Filgrastim (RHG-CSF) related modulation of the inflammatory response in patients at risk of sepsis or with sepsis.

Over a period of 14 days a longitudinal analysis was performed on the effects of filgrastim (recombinant human granulocyte colony stimulating factor, rhG-CSF) administered to 20 postoperative/posttraumatic patients at risk of or with sepsis. The following parameters were determined: leukocyte counts, serum cytokine levels and the surface expression of functional antigens and adhesion molecules. Filgrastim (1 mu g/kg.day) was infused continuously on the first 3 days and tapered to 0.5 mu g/kg.day on the following 4 days or until discharge from the surgical intensive care unit. During infusion of filgrastim, G-CSF levels increased in 16 out of the 20 patients within 48 h. In these 16 patients, leukocyte counts increased in 15 out of 16 patients. Expression of CD64 was upregulated within 24 h. The expression of CD32 was upregulated in 8 out of 9 patients with an initial expression < 55%. LAM-1 expression was downregulated in all patients revealing an initial expression of LAM-1 > 40%. Soluble ICAM increased in 9 out of 11 patients. IL-8 decreased in all 6 patients presenting initial values of IL-8 > 90 pg/ml. IL-1RA increased in 10 patients. Filgrastim had no effect on the expression of CD14, CD16 and CD34 and on the levels of TNF-alpha and sTNF-R type I (p55). In conclusion, infusion of filgrastim in postoperative/post traumatic patients at risk of and with sepsis resulted in improved generation and function of neutrophils and appeared to counterregulate hyperactivation of proinflammatory processes.

Antigens, Surface↗
PubMed2001

Dissociation of LPS-induced monocytic ex vivo production of granulocyte colony-stimulating factor (G-CSF) and TNF-alpha in patients with septic shock.

Over a 6 month period, in 192 patients admitted to the intensive care unit (ICU), a longitudinal analysis of whole blood lipopolysaccharide (LPS)-induced ex vivo cytokine production was performed on a daily basis until discharge from the ICU or death. Twenty-one patients with proven infections were in septic shock for the first time and for at least 3 days' duration. Ex vivo LPS-inducible release of granulocyte colony-stimulating factor (G-CSF) was upregulated and that of TNF-alpha was downregulated in patients with septic shock, regardless whether they survived or died. In conclusion, LPS-induced ex vivo TNF-alpha and G-CSF cytokine release by monocytes is regulated differentially in patients with septic shock. Since upregulation of LPS-induced production of G-CSF occurred earlier in survivors than in non-survivors, rapidly elevated and sustained G-CSF responsiveness may contribute to survival in septic shock.

Adult↗
PubMed2001

Expression of TNF-alpha mRNA by peripheral blood mononuclear cells of multiple sclerosis patients treated with IFN-beta 1A.

The aim of the present study was to verify the expression of tumour necrosis factor (TNF)-alpha mRNA by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in unstimulated peripheral blood mononuclear cells (MNCs) of 15 relapsing-remitting multiple sclerosis (MS) patients who underwent treatment with IFN-beta 1a (6 millions of international units (MIU) i.m. once a week) and in 15 untreated MS patients matched for age and expanded disability status score (EDSS). At the same time the expression of TNF-alpha mRNA was assessed in 10 healthy age-matched control subjects. All MS patients were assessed at the basal time and after 6 months. At the basal time, the band of TNF-alpha mRNA was detectable in 12 out of the 15 untreated patients and in 13 out of the 15 patients who underwent IFN-beta 1a treatment. The higher TNF-alpha mRNA was evident in patients with gadolinium-enhancing lesions. At the 6-month follow-up, 13 out of the 15 untreated patients still had detectable values of TNF-alpha mRNA and no significant difference emerged when compared with basal time. On the contrary, the expression of TNF-alpha mRNA was absent at the same time in nine out of the 15 patients treated with IFN-beta 1a. A longitudinal analysis carried out monthly in eight MS patients (four untreated and four treated) revealed a transient increase in TNF-alpha mRNA expression in MNCs of all four treated patients in the first 3 months, supporting previous findings of an early immunoenhancing effect of IFN-beta 1a. This early activation is followed by an inhibitory effect of IFN-beta 1a on TNF-alpha mRNA expression in about 2/3 of treated MS patients when assessed at 6 months. Further long-term studies are needed to confirm this immunomodulatory effect of IFN-beta 1a not only on TNF-alpha but also on other cytokines of Th(1)and Th(2)types.

Adult↗
PubMed2002

Peaks of endogenous G-CSF serum concentrations are followed by an increase in respiratory burst activity of granulocytes in patients with septic shock.

The relationship between peaks of G-CSF serum concentrations and respiratory burst activity of polymorphonuclear cells (PMN) was investigated in patients with postoperative or post-traumatic severe sepsis and septic shock. Over a 12 month period, a longitudinal analysis of G-CSF, TNF-alpha and IFN-gamma serum concentrations, burst activity of PMN, and expression of CD64 on the surface of PMN, were performed by ELISA technique and flow cytometric analysis, respectively, in 58 patients admitted to the intensive care unit (ICU) on a daily basis until discharge from the ICU or death. Out of these 58 patients, 27 with proven infections were in septic shock for at least 4 days' duration. Seventeen of these patients survived, whereas ten died. In 15 out of these 27 patients, 26 episodes of G-CSF peaks were observed, which were followed in most patients (13/15) by an increase in PMN burst activity, from 28% up to 540% (median 188%). Following the G-CSF peaks, CD64 expression on PMN remained at an increased level, followed by a marked decline 3 days later. TNF-alpha serum concentrations were elevated in most episodes (22/26), whereas IFN-gamma serum concentrations were below the detection level in 23/26 episodes. Taken together, peaks in G-CSF serum concentrations are followed by enhanced CD64 expression and increased burst activity of PMN in most patients with severe sepsis and septic shock. Thus, endogenous G-CSF increases neutrophil function in patients with severe sepsis and septic shock, necessary for resolution of bacterial infections in these patients.

Adult↗
PubMed1999

Factors predicting continued violence into young adulthood.

The delinquent behaviour of a sample of 150 Dutch adolescent to young adult juveniles was examined. These juveniles were arrested because of status offences and delinquency. Arrested adolescent juveniles reported more delinquent behaviour than adolescents in the normal youth population. At the onset of adulthood the number of previously arrested youth reporting serious delinquent behaviour had substantially dropped. This developmental pattern is comparable to the pattern found in the general population of normal adolescents. It suggests that the delinquency of many arrested juveniles is largely adolescence-limited, similar to the delinquency of normal youth. However, about one-third of the arrested juveniles continued to engage in delinquent behaviour into young adulthood. A longitudinal analysis of factors predicting continued violence into adulthood revealed that serious delinquency during adolescence, as well as increased parental control and decreased parental support, were associated with increased delinquency in early adulthood.

Adolescent↗
PubMed2002

Homeostatic proliferation but not the generation of virus specific memory CD8 T cells is impaired in the absence of IL-15 or IL-15Ralpha.

The generation and efficient maintenance of antigen specific memory T cells is essential for long-lasting immunological protection. Antigen specific memory CD8 T cells are known to be maintained via antigen-independent homeostatic proliferation. However, signals that drive memory T cell generation and/or influence the slow turnover of memory T cells are unknown. Recently, IL-15 has received attention for its potential effect on memory CD8 T cells. In this report we examine the role of IL-15 in the generation and maintenance of virus specific memory CD8 T cells using mice deficient in either IL-15 or the IL-15 receptor a chain. Both cytokine and receptor deficient mice mount a robust CD8 T cell response to infection with lymphocytic choriomeningitis virus (LCMV) that is initially only slightly lower than in control mice. Further, virus specific memory CD8 T cells are generated in both IL-15 -/- and IL-15Ralpha -/- mice. However, longitudinal analysis reveals a slow attrition of LCMV specific memory CD8 T cells in the absence of IL-15 signals. Indeed, direct examination of homeostatic proliferation reveals a severe defect in the turnover of antigen specific memory CD8 T cells in the absence of IL-15. Together these results suggest that IL-15 is not essential for the generation of memory CD8 T cells, but is required for homeostatic proliferation to maintain populations of memory cells over long periods of time.

Animals↗
PubMed1998

Antiviral cell-mediated immune responses during hepatitis B and hepatitis C virus infections.

Cell-mediated immune responses to hepatitis B (HBV) and hepatitis C virus (HCV) antigens are vigorous and multispecific in acute, self-limited infections. Moreover, the prevalent cytokine pattern of circulating virus-specific T cells from patients who recover spontaneously from acute hepatitis is Th1-like. Longitudinal analysis of the T cell response to HCV antigens from the early stages of HCV infection in patients who recover from hepatitis and those who do not indicates that weaker responses and a prevalent Th2 pattern of cytokine production is associated with viral persistence and chronic evolution of disease. Although similar sequential studies are missing in hepatitis B, the observation that HBV-specific T cell responses are very weak or totally undetectable in the peripheral blood of patients with long-lasting chronic hepatitis B suggests that strength and quality of virus-specific T cell responses at the early stages of infection may influence the final outcome of both hepatitis B and C. While T cell hyporesponsiveness seems to be an important determinant for HBV persistence once chronic hepatitis has developed, this mechanism appears to be less critical in chronic HCV infection, because the vigor and quality of HCV-specific T cell responses seem to improve as a function of the duration of infection. This is shown by the finding that HCV-specific CD4- and CD8-mediated responses are easily detectable in the peripheral blood of patients with long-lasting chronic hepatitis C and that production of Th1 cytokines predominates within their livers. HCV therefore seems to be able to persist even in the face of an active T cell response and to acquire the capacity to survive within a host environment apparently unfavorable to its persistence. The high variability of HCV may explain its efficiency in escaping immune surveillance.

Hepatitis B↗
PubMed1996

Vascular dementia: perfusional and metabolic disturbances and effects of therapy.

Positron emission tomography (PET) has elucidated basic pathophysiological mechanism that produce the cognitive decline in vascular dementia (VD). The typical pattern of glucose metabolism seen in VD with scattered areas of focal cortical and subcortical hypometabolism differs from that in AD with marked hypometabolism affecting the association areas. The total volume of metabolically inactive tissue is significantly related to severity of dementia. Rather than the quantity of tissue destruction, the critical effect may be the quantity of cortical hypometabolism caused by subcortically induced disconnection. Studies with HMPAO SPECT have shown focal deficits in VD and AD patients that are comparable to those seen with FDG PET. In mildly demented patients performance for the classification AD versus VD is much better by PET because it might be more sensitive for imaging small functional pathological changes. A longitudinal analysis of rCMRGl in VD showed that the progression of dementia can be delayed by the adenosine uptake blocker propentofylline and that neuropsychological and metabolic changes are closely related.

Brain↗
PubMed1994

Low-dose hydrocortisone infusion attenuates the systemic inflammatory response syndrome. The Phospholipase A2 Study Group.

There is increasing evidence that the hypercortisolemia in inflammatory diseases suppresses the elaboration of proinflammatory cytokines, thus protecting the host from its own defence reactions. In severe sepsis and septic shock cortisol levels are usually elevated, but some patients may have relative adrenal insufficiency. This may contribute to the overwhelming systemic inflammatory response syndrome. We evaluated the impact of low-dose hydrocortisone infusion (10 mg/h) on the course of the systemic inflammatory response syndrome. This dose corresponds to a maximum secretory rate of cortisol achieved in corticotropin-stimulated healthy humans. In a prospective observational study 57 surgical patients with severe sepsis or septic shock were studied, of which in addition to the conventional treatment 12 patients were infused with low-dose hydrocortisone, and 45 were treated without any corticosteroid. In the longitudinal analysis the systemic inflammatory response--as judged by body temperature, cardiovascular response, and kinetics of inflammatory mediators such as phospholipase A2, C-reactive protein, and neutrophil elastase--started to differ in favor of the hydrocortisone-treated patients after 2 days of treatment (P < 0.05, Mann-Whitney U test). The difference disappeared after withdrawal of exogenous cortisol. Shock reversal was achieved in all patients treated with low-dose hydrocortisone. The data provide evidence that low-dose hydrocortisone infusion attenuates the systemic inflammatory response in human septic shock. From an immunological point of view a relative cortisol deficiency may contribute to the amplified immune response in systemic inflammatory diseases. A randomized clinical trial must clarify the impact of low-dose hydrocortisone infusion on the clinical course and outcome of septic shock patients.

Adrenal Insufficiency↗
PubMed1991

Serotonin-containing epithelial cells in rat duodenum. I. Quantitative morphometric study of the distribution density.

Serotonin (5HT)-containing epithelial cells in rat duodenum were studied quantitatively by three-dimensional morphometric analysis. Longitudinal sections covering the whole length of rat duodenum were stained by either 5HT immunohistochemistry or by glyoxylic acid fluorescent histochemistry. Three-dimensional values for positive cell density, namely the number of 5HT cells per unit volume of the epithelium, were obtained by stereological morphometry with the aid of a computer-assisted image analyzer. This analytical method provides an absolute value for the distribution density of 5HT-containing cells regardless of thickness of sections, or which of the two histochemical procedures is used. The mean number of such cells per unit volume was higher in the crypts than in the villi but varied little along the duodenum. The density of 5HT cells in a given duodenal region, however, varied greatly among individual animals. The villi of the 10 to 16-mm segment from the pylorus were identified as having the smallest individual variation and therefore as being the most suitable for statistical evaluation in future pharmacohistochemical investigations.

Animals↗