bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Endothelin 1 on Proximal Reabsorption and Tubuloglomerular Feedback
Authors: Romano G. , Giagu P. , Favret G. , Bartoli E.
Published: April 2003

Endothelin 1 (ET–1) is a powerful constrictor of the afferent glomerular artery, implicated in the occurrence of both functional and acute renal failure. Besides being produced by the endothelium, ET–1 is also secreted by proximal tubular cells, suggesting that it may act as an endoluminal messenger. The present study is intended to verify whether ET–1 may play a role in the tubuloglomerular feedback system. The experiments were performed in rat superficial glomeruli. In 25 nephrons we measured by the total collection technique the single–nephron glomerular filtration rate (SNGFR; nl/min) and reabsorption rates before (control) and during microinjection (MIJ) of ET–1 10–7 M into the first proximal convolution or Bowman’s space. The SNGFR rose from 27±3 to 61±11 nl/min (p<0.01), the percent proximal reabsorption rose from 43 to 74%, and the absolute reabsorption rose from 13±2 to 46±11 nl/min (p<0.01). In additional 23 nephrons the collections were performed at the earliest distal convolution accessible on the renal surface, while MIJ was performed in the last proximal convolution of the same nephrons. The SNGFR rose during MIJ from 22±3 to 40±6 nl/min (p<0.01), the percent reabsorption rose from 61 to 66% (p>0.77), and the absolute reabsorption rose from 12±2 to 26±4 nl/min, (p<0.003). Exposure of the macula densa to intraluminally injected ET–1 causes an abrupt increase in SNGFR of the experimental nephron, in the absence of changes in systemic and renal hemodynamics. During proximal MIJ, ET–1 may have reached the macula densa during the time preceding the beginning of collection and interruption of the delivery of fluid to the distal nephron. ET–1 directly stimulates fractional and absolute volume reabsorption along the proximal tubule. Proximal secretion and/or filtration of ET–1 could represent a physiological mechanism to activate the tubuloglomerular feedback, eliciting a response opposite to that triggered by systemic and intrarenal infusion.
Effects of Renal Arterial Endothelin-1 and Endogenous Endothelins on Regional Kidney Blood Flow and Renal Antihypertensive Mechanisms in Anesthetized Rabbits
Authors: Weekes Simon R. , Madden Anna C. , Bergström Göran , Anderson Warwick P. , Evans Roger G.
Published: April 2003

To determine how endothelins affect regional kidney blood flow and responses to increased renal artery pressure (RAP), an extracorporeal circuit was established to control RAP independent of the mean systemic arterial pressure (MAP). RAP was first set at ∼65 mm Hg, and endothelin-1 (1 ng/kg/min for 30 min then 0.4 ng/kg/min) or vehicle was infused into the renal artery, or the ETA/ETB antagonist TAK-044 (3 mg/kg plus 3 mg/kg/h) or vehicle was administered intravenously. RAP was then progressively increased in steps from ∼65 to ∼160 mm Hg. When RAP was ∼65 mm Hg, endothelin-1 increased renal vascular resistance (RVR, 72%), and reduced cortical (CBF, 26%) but not medullary blood flow (MBF). TAK-044 reduced MAP (12%) and RVR (15%) and increased CBF (21%) but not MBF. When RAP was increased, renal blood flow (RBF), glomerular filtration rate, and urine and sodium excretion increased, while MAP fell. These responses were unaffected by endothelin-1. TAK-044 potentiated the increases in RBF and reductions in MAP in response to increased RAP, but did not affect urine and sodium excretion. Plasma renin activity was reduced by endothelin-1 and increased by TAK-044. Thus, both exogenous and endogenous endothelins reduce CBF but not MBF, and reduce plasma renin activity, but neither affect pressure natriuresis.
Elevated Salt and Nitrate Levels in Drinking Water Cause an Increase of Blood Pressure in Schoolchildren
Authors: Pomeranz Avishalom , Korzets Ze’ev , Vanunu Daniel , Krystal Haim , Wolach Baruch
Published: April 2003

Aim: To assess the influence on blood pressure in schoolchildren, of elevated sodium (Na+) and nitrate (NO–3) levels in the drinking water. Methods: The blood pressure was recorded in three groups of age- and weight-matched schoolchildren (fourth and fifth graders) ingesting differing Na+ and NO–3 concentrations with their drinking water. Group 1 (n = 452) imbibed high-Na+, high-NO–3 water (196 and 49 mg/l, respectively); group 2 (n = 418) consumed low-Na+, high-NO–3 water (25 and 49 mg/l, respectively) and group 3 (n = 86) drank low-Na+, low-NO–3 water (35 and 25 mg/l, respectively). The chloride (Cl–) concentrations varied in parallel to those of Na+. Results: Systolic blood pressure (SBP) and mean arterial pressure (MAP) were significantly increased in group 1 versus groups 2 and 3 (115.6 ± 12.2 and 86.4 ± 9.6 mm Hg vs. 111.1 ± 11.6 and 83 ± 8.3 and 107 ± 8.8 and 81 ± 7.2 mm Hg, respectively, p < 0.05). The SBP in group 2 was also significantly higher than in group 3 (111.1 ± 11.6 vs. 107 ± 8.8 mm Hg; p < 0.05). Conclusions: Elevated Na+ (and possibly Cl–) in combination with high NO–3 concentrations in drinking water leads to an increase of SBP and MAP in fourth and fifth graders. The effects of Na+ (and/or Cl–) and NO–3 on SBP and MAP appear to be additive, yet independent of each other.
Effect of Tubal and Pelvic Pathology on Uterine Receptivity and Success in Intracytoplasmic Sperm Injection
Authors: Alrayyes Samer , Fakih Hasan , Khan Iqbal
Published: April 2003

Objective:To evaluate the effect of pelvic pathology on pregnancy outcome of couples with male factor infertility undergoing intracytoplasmic sperm injection (ICSI) and tubal embryo transfer (TET). Design: Clinical study of patients who underwent ICSI for poor sperm parameters. Setting: Tertiary care academic center. Patients: Twenty-six women with normal pelvis (group A) were matched according to age, stimulation protocol, number of transferred embryos, and number of cycles with 26 patients treated for stage 1 endometriosis (group B), and 26 patients with pelvic disease and at least one patent tube (group C). Main Outcome Measure: Pregnancy/cycle, pregnancy/patient, implantation rate and miscarriage rate. Results: Patients with normal pelvis undergoing ICSI and those with treated mild endometriosis demonstrated significantly better embryo implantation and miscarriage rates than ICSI patients with minimal tubal disease. Ongoing pregnancy rate was 50% for patients with normal pelvis and treated endometriosis groups and 30% for women with tubal pathology. The miscarriage rate of patients with tubal disease (33%) was significantly higher than that of the other two groups (14%). Conclusion: Treated mild endometriosis does not affect the outcome in ICSI patients undergoing TET when compared to women with normal pelvic findings, but the presence of tubal disease might affect the pregnancy outcome.
The Δccr-5 Mutation in the CCR-5 Chemokine Receptor Gene Conferring Resistance to Human Immunodeficiency Virus Type 1: Frequency in Kuwait
Authors: Voevodin Alexander , Samilchuk Elena , Dashti Suhaila
Published: April 2003

Objective: The homozygous deletion of 32 nucleotides in the CCR-5 gene (Δccr-5) confers resistance to macrophage-tropic HIV-1. The aim of this study was to determine the frequency of Δccr-5 in populations residing in Kuwait. Methods: A polymerase chain reaction (PCR) test for Δccr-5 has been developed. The specificity of the test has been proved by direct sequencing of the PCR products amplified from individuals homozygous for the wild-type allele and from Δccr-5/wild-type heterozygotes. Results: Among 353 healthy individuals residing in Kuwait (270 Kuwaiti citizens and 83 Bedouins) tested for the Δccr-5 mutation, 8 heterozygotes have been identified, 4 in each group. No homozygotes for the Δccr-5 deletion have been found. The frequency of the Δccr-5 allele in Kuwaiti nationals and Bedouins residing in Kuwait is 0.74 and 2.4%, respectively. Conclusion: The Δccr-5 mutation is present in populations residing in Kuwait, though its frequency is quite low and can hardly influence the pace of HIV-1 spreading in Kuwait.
Epidemic Hysteria: School Outbreaks 1973–1993
Authors: Sirois François
Published: April 2003

Objective: Increased reporting of outbreaks has brought more familiarity with the syndrome but no more accurate knowledge about the nature and mechanisms of such episodes. As it has become an area for an expanding field of competitive explanations, the review is intended to find any additional epidemiological cues and any clarification about methods of investigating such outbreaks. Methods: The retrieval of data was organized upon a choice to have a homogeneous sample rather than a comprehensive one. Newspapers and sociological sources were left out. A Medline search with cross-referencing was conducted to select the outbreaks limited to the standard school type. Reports were examined from two points of view: the descriptive epidemiological parameters and the mode of reporting the outbreaks. Results: Forty-five episodes were studied. A historic shift in the manifest presentation is apparent: larger groups are involved for a shorter time. A period at risk has been identified: the last 2 months of the school calendar. The peak age of affected children is 12. A downward age spread is present in 14/20 episodes where suitable information is provided. Methods of reporting were classified into four categories: descriptive (n = 24), public health reports (n = 7), case-control (n = 7), case study (n = 7). Diagnosis of exclusion for environmental contamination is still a prevalent mode of reporting but does not make the outbreak intelligible. Conclusion: (1) A two-step approach is suggested: a simple environmental check for short and uneventful outbreaks; an intensive case study for any episode with long duration or recurrence. (2) Two hypotheses for future testing are proposed: a hypothesis of arousal, probably of a benign, age-specific, and sexual nature, in short simple cases; a hypothesis of conflict in the long or recurrent ones.
Lung Function and Severity of Mitral Stenosis
Authors: Nour Mahmoud M. , Shuhaiber Hani , Yousof Abdul Mohsen
Published: April 2003

Objective: To correlate the degree of severity in patients with rheumatic mitral stenosis to pulmonary function data and to their respiratory symptoms. Methods: Pulmonary function and the MCR questionnaire on respiratory symptoms were made in 43 patients with simple mitral stenosis (SMS), and 79 patients with advanced mitral stenosis scheduled for valve replacement surgery (MVR). Results: All the patients in the two groups had restrictive and obstructive patterns. They had reduced forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), peak expiratory flow rate, maximal flow after exhalation of 75, 50 and 25% of FVC and single-breath carbon monoxide diffusing capacity (DLCO) and increased total airway resistance, resistance during expiration, and residual volume (RV). The SMS group tended toward more normal values. The MVR group had lower values for all the parameters, specially FVC, FEV1, DLCO and higher RV. The MVR group had a significantly higher prevalence of cough, phlegm and acute chest illness than the SMS group. Conclusion: The study confirmed the restrictive and obstructive pattern of pulmonary dysfunction in patients with rheumatic mitral stenosis which related with the severity of mitral stenosis and with respiratory symptoms.
Enteral Versus Parenteral Feeding: The Avoidance of Systemic Infection in the Critically Ill
Authors: Finck Christine M. , Torelli Giovanni F. , Meguid Michael M. , Varma Madhu , Evangelista Rebecca
Published: April 2003

The critically ill patient very often presents with systemic evidence of infection including tachypnea, tachycardia and hypo-hyperthermia; this may lead to sepsis syndrome and subsequent multisystem organ failure. In order to manage this clinical condition, nutritional supportive therapy is very often required. The choice between enteral and parenteral nutrition is not always straightforward. Early enteral nutrition seems to exert beneficial effects, although parenteral nutrition is often easier to administer, and thus is the treatment of choice. There are only few prospective, randomized, controlled trials comparing the two methods of intervention therapy. Parenteral nutrition seems to be associated with mechanical, metabolic and septic complications, while enteral nutrition, which is associated with similar complications, prevents gastrointestinal mucosal atrophy, attenuates the injury stress response, maintains immunocompetence, and preserves normal gut flora. This literature review focuses on the role played by these two methods of nutritional support therapy in the development of systemic infections. This review will also analyze possible mechanisms of action and future therapeutic strategies.
Diagnosis of Cytomegalovirus Infection by the Detection of Early Antigen (pp65) in Leukocytes of Kidney Transplant Patients
Authors: Pacsa A.S. , El-Shazly A. , Gupta R.K. , Johny K.V. , Nampoory M.R.N. , Tarek S. , Gadalla N. , Essa S.
Published: April 2003

Objective: Cytomegalovirus (CMV) infection is a frequent complication of kidney transplantation contributing substantially to morbidity and mortality. Early diagnosis of the infection is essential to implement an effective antiviral therapy. This study is aimed at establishing the CMV antigenemia assay for the diagnosis of CMV infection, and for monitoring the effectiveness of ganciclovir therapy in kidney recipients in Kuwait. Methods: Leukocyte-enriched fractions of 215 blood specimens from 92 kidney recipients were processed for the detection of CMV-specific protein (pp65) by using a commercial kit (Incstar Corp., USA). Plasma fractions were also tested for the presence of CMV IgM antibodies, and selected samples (n = 15) were processed for virus isolation in MRC-5 diploid cell culture. Results: Regarding symptomatic (n = 35) and asymptomatic patients (n = 57) the assay showed an 86% positive and a 79% negative predictive value, compared to the 55% and 70% values, respectively, for CMV IgM antibodies. The number of positive cells was parallel with the severity of symptoms. Using a cutoff level of >5 antigen-positive leukocytes/50,000 cells, the assay reached 93% positive and 96% negative predictive values. There was a very good agreement between the assay and virus isolation. Ganciclovir therapy could be monitored effectively with the assay, and in 11 symptomatic patients treated with ganciclovir, a prompt decrease in the number of antigen-positive cells was noted. Conclusion: The CMV antigenemia assay is a valuable tool for the early diagnosis of symptomatic CMV infection and monitoring antiviral therapy in kidney transplant patients.
Acute Splenic Infarctionfollowing Air Tr avel in a Child with Hb SD Disease
Authors: Adekile AdekunleD. , Al-Harbashy HossamA. , Kalaoui Malak , Gharbawy Fatma
Published: April 2003

Objective: The relative hypoxia, dehydration and immobility associated with air travel predispose sickle cell disease patients to acute splenic crises; however we are not aware of previous reports involving children with Hb SD. Clinical Presentation: We report on a previously healthy 2-year-old Kuwaiti girl who developed a sudden onset of severe abdominal pain while traveling on a commercial jet aircraft. This was followed by vomiting and fever. On examination in the emergency room she was very irritable with abdominal tenderness maximal over the left hypochondrium. The spleen was palpable 7 cm below the costal margin, and abdominal ultrasonography and CAT scan confirmed a diagnosis of acute splenic infarction. Hematological investigations showed that the patient was a compound heterozygote for Hbs S and D. Intervention: The patient was managed with intravenous fluids and analgesics and made a full recovery. Conclusion: Acute splenic infarction should be considered in the differential diagnosis of a sudden onset of abdominal pain associated with air travel in patients with Hb SD.
Double Aneuploidy: 48,XXY,+18 in a Bedouin Boy
Authors: AI-Awadi S.A. , AI-Naggar R.L. , Tayel S.M. , Uma R.
Published: April 2003

Objective: This study describes a case of double aneuploidy (48,XXY,+18), makes genotype-phenotype correlation of the case and compares it with those in the literature. This study throws more light on the origin of double aneuploidy. Methods: Clinical examination, skeletal survey, echocardiography, cranial ultrasonography and chromosomal examination of a peripheral blood sample using GTG-type of banding were performed. Results: Clinical examination of the 25-day-old boy showed craniofacial dysmorphic features suggestive of trisomy 18, ventricular septal defect and complicated postnatal events leading to his neonatal death. Skeletal survey demonstrated absence of ossification centers of the epiphyses of long bones. Cranial ultrasonography revealed bilateral ventriculomegaly with thin cerebral cortex. Chromosomal analysis showed 48,XXY,+18 karyotype with no evidence of mosaicism. Conclusion: In the very few reported cases of double aneuploidy involving autosomes and sex chromosomes the clinical manifestations of the sex chromosome abnormality are usually missing. Double aneuploidy reflects a more serious segregation defect of meiosis than simple nondisjunction, and is not simply the result of the rare coincidence of paternal and maternal nondisjunction.
Glomerulonephritis in Children: Experience from the Kuwait Renal Centers
Authors: El-Reshaid K. , Kapoor M.M. , Nampoory M.R.N. , Madda J.P. , Jawad N. , Johny K.V.
Published: April 2003

Objective: To study the clinical, pathological, and epidemiological features of childhood steroid-refractory idiopathic glomerulonephritis (SRIGN), i.e., nephrotic syndrome, which failed an 8-week course of prednisone, and secondary forms of glomerulonephritis (GN) in Kuwait. Methods: Data on these two forms of GN were collected retrospectively from the records of children attending the two renal centers of Kuwait between January 1, 1990, and December 31, 1996. Results: During the 7 years, a total of 80 children were diagnosed to have GN, 56 of whom were Kuwaiti nationals. In the latter group, 34 children had SRIGN. Hence, the calculated annual incidence rate of Kuwaiti children with both GNs was 3.1 per million and that for SRIGN was 1.9 per million children. Histologically, 22 (65%) of these patients had minimal change, 5 (16%) focal segmental, 2 (6%) non-IgA mesangioproliferative, and 1 membranous GN. Congenital nephrotic syndrome, membranoproliferative GN, and GN secondary to parasitic infestations or microbial infections were not seen in the Kuwaiti children, and nephrotic syndrome secondary to IgA glomerulopathy was diagnosed in 1 patient only. Aggressive autoimmune diseases such as systemic lupus erythematosus (SLE) and vasculitis were common. Seven patients had SLE which accounted for 44% of secondary GN and for 14% of all the patients included in the study, while 3 patients were found to have vasculitis. Interestingly, only 3 of the 13 patients with SLE and vasculitis presented with rapidly progressive GN. Conclusions: The pattern of renal disease associated with SRGN in Kuwaiti children is different from that reported from neighboring countries and other Arab states. The homogeneity of the population studied, lack of endemic infections or parasitic infestations, and genetic predisposition may have been the underlying factors. Furthermore, the high incidence of the insidious kidney-limited disease associated with SLE and vasculitis is another feature which indicates a more aggressive diagnostic approach in the management of GN in our area.
The Etiology of Female Breast Cancer
Authors: Sharpe Colin , Boivin Jean-François
Published: April 2003

Considerable knowledge has been acquired about the determinants of female breast cancer. A positive family history among first-degree relatives is associated with an increased risk of breast cancer, as is a past history of benign proliferative breast disease. Risk increases with decreasing age at menarche, and with increasing age at first full term pregnancy and at menopause. Pregnancy is followed by a short-term increase in risk, followed by a long-term decrease. Risk increases with age. Evidence that environmental determinants are involved comes from the study of migrant populations: migrants assume the risk of breast cancer prevalent in their new environment, arguing against the hypothesis that risk is determined solely by genetic mechanisms. The best understood environmental determinant is ionizing radiation: it increases risk in a dose-dependent fashion. While ecologic studies of diet supported the hypothesis that high fat intake increases risk, cohort and case-control studies have yielded conflicting evidence, casting doubt on this hypothesis. However, weight gain during adult life is associated with an increased risk. Some drugs increase risk, specifically exogenous oestrogens and ethanol. The anti-oestrogen tamoxifen reduces risk. Recent evidence shows that both passive and active exposure to tobacco smoke is associated with an increased risk of breast cancer. Some women may be more susceptible to the effects of tobacco smoke on a genetic basis. Undoubtedly, other environmental determinants of breast cancer will be discovered.
Febrile Neutropenia in Patients with Acute Leukemia with Long-Term Central Venous Access in Kuwait: Microbial Spectrum, Outcome and Catheter Management
Authors: Al Bahar Soad , Pandita Ramesh , Bavishi Ketan , Savani Bipin
Published: April 2003

Objective: This study was conducted to investigate the microbial spectrum, outcome and catheter management in febrile neutropenic acute leukemia patients with long-term central venous access, at a single center in Kuwait. Methods: One hundred and thirty-three febrile neutropenic episodes in 64 adult acute leukemia patients with long-term central venous access encountered at the Kuwait Cancer Control Centre were studied. The frequency of clinically documented infections, microbiologically documented infections, fevers of unknown origin and catheter-related infection was determined. Response to treatment and the need for catheter removal were studied. Results: In the 133 febrile neutropenic episodes, clinically documented infections, microbiologically documented infections and fever of unknown origin occurred in 12.8, 30.8 and 56.4%, respectively. Thirty-two episodes of catheter-related infections were encountered. Gram-positive and gram-negative infections occurred in equal frequency. Escherichia coli and methicillin-resistant Staphylococcus aureus were the most frequent organisms. Of all episodes, 87.2% responded to antibiotics and 11 episodes required removal of the catheter. Of the clinically documented infections, 76.5% of the episodes responded to treatment without catheter removal. Of the microbiologically documented episodes, 68.3% were treated successfully without removal of the catheter. One hundred percent of the episodes of fever of unknown origin responded to a broad spectrum of antibiotics, without catheter removal. Conclusion: Gram-negative and gram-positive infections occur in equal frequency in febrile neutropenic acute leukemia patients with long-term central venous catheters. E. coli and methicillin-resistant S. aureus are the most frequent organisms and the majority of the episodes are curable by antimicrobial therapy without the removal of the catheter.
Evaluation of the WHO Clinical Case Definition of AIDS in the Indian Context: Suggesting a Prediction Rule
Authors: Kaushik P. , Pandey R.M. , Pande J.N.
Published: April 2003

Objective: To test the statistical significance of the existing World Health Organization (WHO) clinical case definition for the diagnosis of acquired immunodeficiency syndrome (AIDS) in areas where diagnostic resources are limited in India, and frame a prediction rule that is sensitive and specific for the clinical diagnosis of AIDS. Methodology and Results: In a case-load study, we evaluated the WHO clinical case definition of AIDS in 162 patients, the training set (58 seropositives) at the All India Institute of Medical Sciences, New Delhi. This definition had a sensitivity of about 29%, specificity of about 29%, positive predictive value of about 19% and negative predictive value of about 42%. We analyzed the clinical data of these 162 patients using stepwise logistic regression analysis. Generalized lymphadenopathy, oropharyngeal candidiasis, presumptive esophageal candidiasis, herpes zoster in the last 5 years and a total lymphocyte count of less than 1,000 × 109/l emerged as important predictors. A prediction rule for the diagnosis of AIDS in the Indian context was then developed empirically using the coefficients of these predictors. We further tested the rule prospectively in 50 patients, the test set (11 seropositives) and found it to have a sensitivity of 81.8%, specificity of 97.4%, positive predictive value of 90%, and a negative predictive value of 95%. Conclusion: The WHO definition was not significant statistically for clinical use in India. The new prediction rule may help in AIDS surveillance in India.
Incidence of Primary Central Nervous System Cancers in South and East Netherlands in 1989–1994
Authors: van der Sanden Gitty A.C. , Schouten Leo J. , van Dijck Jos A.A.M. , van Andel Joke P. , Coebergh Jan-Willem W.W.
Published: April 2003

About 2,000 patients with primary CNS cancers, as defined by the ICD-O, were registered in four adjacent cancer registries in South and East Netherlands in 1989–1994, covering a population of more than 5 million people. About 85% of the patients were registered through pathological laboratories, concentrated in four centers for neurosurgery. Patients with a clinical-radiological diagnosis only (about 50% in the age-group of 75 years and older) were mainly identified through medical records of hospitalized patients. World-standardized incidence rates of 6.5 and 4.4 per 100,000 person-years for males and females, respectively, were similar to those reported in other European cancer registries. Eighty-five percent of histologically verified primary CNS cancers were of glial origin, 6% were lymphomas and 4% embryonal tumors. Gliomas were mainly of astrocytic (about 85%) and oligodendroglial or mixed type (about 10%). Without additional review most astrocytic tumors could be classified into high-grade (70–75%) and low-grade astrocytomas (20–25%). Different grading systems were used for gliomas, but the dichotomy of astrocytomas according to differentiation grade seemed to correspond well with the definition of the WHO. Age-specific incidence rates for low-grade astrocytomas were remarkably constant. The incidence of high-grade astrocytomas increased sharply with age and declined after the age of 70, whereas the incidence of clinically diagnosed tumors continued to increase. Male/females-ratios were relatively high for these tumor types (1.6–1.7). We conclude that the registration of primary CNS cancers in the Netherlands may be almost complete and valid for gliomas, embryonal tumors and lymphomas.
Hypotheses Concerning Roles of Dietary Energy, Cured Meat, and Serum Tocopherols in Adult Glioma Development
Authors: Schwartzbaum Judith A. , Fisher JamesL. , Goodman Joseph , Octaviano D’dra , Cornwell DavidG.
Published: April 2003

We conducted a pilot study to determine whether: (1) high levels of energy intake increase glioma risk; (2) the previously observed relationship between cured meat consumption and glioma risk can be attributed to confounding by energy intake, and (3) α-tocopherol modifies caloric intake and γ-tocopherol modifies cured meat consumption. We identified 40 age-sex-race matched glioma sets, and obtained serum vitamin C and α- and γ-tocopherol levels for 23 of these sets. Glioma risk increased with quartile of total dietary energy adjusted for fat, protein, and nitrite-containing meat consumption (odds ratio = 1.0, 2.7, 5.8, 8.2; p value for trend test = 0.02). Although positive associations between individual cured meats and glioma risk decreased when adjusted for caloric intake, the small sample size makes it difficult to interpret the results. Serum α-tocopherol appeared to modify the effect of calories and serum γ-tocopherol may modify the effect of cured meat on glioma risk. While the observed interaction is predicted by experimental research, our findings are based on small numbers. Larger studies are needed to further evaluate our preliminary findings.
A Nationwide Cohort Study on Creutzfeldt-Jakob Disease among Human Growth Hormone Recipients
Authors: Wientjens D.P.W.M. , Rikken B. , Wit J.M. , Hofman A. , Stricker B.H.Ch.
Published: April 2003

Objective: In 1991, a Dutch patient who had been treated from 1963 to 1969 with human-derived growth hormone died of Creutzfeldt-Jakob disease (CJD). This study was performed to investigate whether among other Dutch human growth hormone recipients there were clinically suspected cases of iatrogenic CJD. Methods: In a retrospective cohort study, all patients (n = 564) treated with human-derived growth hormone before May 1985 and recorded in the Dutch National Growth Registry were followed up until January 1995 for a clinical diagnosis of CJD. For this purpose, all human growth hormone recipients were linked to a database of the Foundation for Health Care Information comprising hospital discharges with a clinical diagnosis of iatrogenic CJD. Linkage of the two databases was performed on the basis of date of birth and gender. Subsequently, verification of patient’s name and initials of the positively matched pairs took place. Results: Linkage provided 37 positively matched pairs concerning 29 individual patients. After verification, no name from the hospital discharge records corresponded to the names of the human growth hormone recipients. Conclusion: The follow-up of 564 Dutch human growth hormone recipients, who had been treated with human growth hormone until 1985 did not establish any clinically suspected case of iatrogenic CJD. Future cases, however, can still emerge due to the potentially long incubation period of prion diseases.
Lateral Hypothalamus Modulates the Intrinsic Splenic Natural Killer Cell Activity in Rats
Authors: Iimori Hirofumi , Kawamura Noriyuki , Wenner Marcus , Murakami Masato , Yamamoto Hiroshi
Published: April 2003

Electrical stimulation of the lateral hypothalamus (LH) in rats increased splenic natural killer (NK) cell activity, whereas electrical ablation of the LH decreased it. However, the percentage of NK cells, as detected by the anti-NKR-P1 monoclonal antibody, in the spleen did not change significantly. These results suggest that the LH does not modulate the splenic NK cell activity by increasing the NK cell number but by increasing the intrinsic NK cell activity itself.
Cellular Signaling Mechanisms for Stimulation of Growth Hormone Secretion and Growth Hormone Primary Transcripts by Immunosuppressant Agents, FK506 and Cyclosporin A, in Cultured Rat Pituitary Cells
Authors: Ohye Hidemi , Sato Makoto , Murao Koji , Matsubara Shuji , Tokuda Masaaki , Takahara Jiro
Published: April 2003

Although an immunosuppressant, FK506, has been known to stimulate growth hormone (GH) release from rat somatotropes, the cellular signaling mechanism is unknown. In the present study, intracellular signaling pathways were investigated for FK506- and cyclosporin A (CsA)-induced GH release in cultured rat anterior pituitary cells. Northern and Western blot analysis revealed that the FK506-binding protein (FKBP12) and the CsA-binding protein (cyclophilin A) exist at the mRNA and protein level in the rat anterior pituitary tissue. FK506 and CsA increased GH release in a dose-dependent manner and inhibited calcineurin (CaN) activity in the cultured pituitary cells. The third immunosuppressant, rapamycin (RP), inhibited the FK506-induced GH release, although RP alone had no effect. Protein kinase A (PKA) inhibitors, H-89 and HA-1004 and EGTA blocked FK506- and CsA-induced GH release. TGF-β did not alter basal GH release, but inhibited FK506-induced GH release. GH primary transcripts were increased by FK506, and the effects were blocked by H-89 and HA-1004. These results suggest that the immunosuppressants, FK506 and CsA, stimulate GH release by inhibiting CaN activity which results in the activation of the PKA system in the rat somatotropes. TGF-β receptors might be involved in FK506-induced GH release as a separate pathway. FK506 also stimulates GH primary transcripts via a PKA-dependent mechanism in a manner similar to its effects on GH release.
Endotoxin-Stimulated Release of Cytokines by Cultured Cells from the Murine Neurohypophysis: Role of Dexamethasone and Indomethacin
Authors: Hansen Erik W. , Malling Dorte , Christensen Jens D.
Published: April 2003

It is well established that many cell types produce inflammatory cytokines and we were interested to see whether cells in the neurohypophysis had this ability. This study examines the effect of lipopolysaccharide (LPS) on cytokine production in cultured murine neural lobe (NL) cells. Cells were cultured from the neurohypophysis of mice not older than 5 days and the experiments were performed after 12 days in culture. The majority of cells in culture were immunoreactive for glial fibrillary acidic protein, indicating that the cells were pituicytes. Cytokines were measured in 24-hour samples using commercial ELISA kits. Cells growing in a medium free of endotoxin released 94.3 ± 6.6 pg IL-6/NL/24 h (mean ± SEM, n = 21). The release of interleukin-6 (IL-6) was reversible and increased concentration dependently with LPS in the concentration range of 0.1–1 ng/ml. The addition of 1 ng/ml LPS increased the IL-6 release 12-fold to a maximum value of 1,134 ± 85.5 pg IL-6/NL/24 h (mean ± SEM, n = 6). No trace of interleukin-1β (IL-1β) (<3 pg/NL/24 h) or tumor necrosis factor-α (<10 pg/NL/24 h) was detected after LPS stimulation. We examined the effect of dexamethasone (10–6 M) and indomethacin (10–4 M) on the release of IL-6 in submaximally stimulated cells. Dexamethasone inhibited the unstimulated and the LPS-stimulated release of IL-6 by 70 and 81%, respectively. Indomethacin had no influence on the release, and it is concluded that cyclooxygenase is not involved in the response. A close association exists between the membrane of the neurosecretory endings and the pituicytes in the neurohypophysis. This naturally raises the question as to whether IL-6 might reflect a physiological connection between the two cell types.
Reward Linked to Increased Natural Killer Cell Activity in Rats
Authors: Wenner Marcus , Kawamura Noriyuki , Ishikawa Toshio , Matsuda Yoshihiro
Published: April 2003

In rats splenic natural killer (NK) cell activity was found to be significantly higher following chronic uncontrollable electrical stimulation of the lateral hypothalamus in fully conscious rats, compared to sham-operated rats. In a pre-test study, all rats had demonstrated that the electrode site had self-stimulating properties, which supports the possibility that the experience of reward may be implicated in NK cell activity augmentation.
Maternal Exposure to the Synthetic Cannabinoid HU-210: Effects on the Endocrine and Immune Systems of the Adult Male Offspring
Authors: del Arco Ignacio , Muñoz Raúl , Rodríguez de Fonseca Fernando , Escudero Leticia , Martín-Calderón Jose Luis , Navarro Miguel , Villanúa María Angeles
Published: April 2003

Natural and synthetic cannabinoid receptor agonists have been described to exert profound effects on both the neuroendocrine integration and the functional responses of the immune system. In the present study, Wistar rats were exposed to the highly potent cannabinoid agonist HU-210 (1, 5 and 25 μg/kg) during gestation and lactation and the ensuing effects on several endocrine and immune parameters of the adult male offspring were analyzed. Perinatal exposure to HU-210 partially affected the distribution of lymphocyte subpopulations in the spleen and peripheral blood. The major changes observed occur after maternal exposure to the 25 μg/kg dose of HU-210. There was a reduction in the T-helper subpopulation in the spleen and a dose-related decrease in the rate of Thelper/Tcytotoxic in peripheral blood lymphocytes. Concanavalin-A and lipopolysaccharide-induced proliferation were normal in all the groups tested. In the same animals, perinatal exposure to HU-210 did not affect basal levels of growth hormone, IGF-1, prolactin, or follicle-stimulating hormone. Basal values of luteinizing hormone were elevated in animals given the 1 μg/kg dose of HU-210. Corticosterone levels were reduced in the animals exposed to the higher dose of HU-210 during gestation and lactation. These animals exhibited a decreased responsiveness of the hypothalamo-pituitary-adrenal (HPA) axis to the stimulation with a single injection of HU-210 (20 μg/kg, i.v.) at adult ages, which may reflect the onset of long-lasting tolerance to the HPA-activating properties of cannabinoids. The opposite pattern of response was found in the animals given the 1 μg/kg dose, in which a sensitization of the corticosterone response to acute HU-210 was observed. The present work reveals that maternal exposure to cannabinoids results in minor changes in the development of the immune system, but may induce long-lasting alterations in the functional status of the HPA axis.
Effects of the IL-1 Receptor Antagonist on the IL-1- and Endotoxin-Induced Activation of the HPA Axis and Cerebral Biogenic Amines in Mice
Authors: Dunn Adrian J.
Published: April 2003

Endotoxin (lipopolysaccharide, LPS) and interleukin-1 (IL-1) are known to activate the hypothalamo-pituitary- adrenocortical (HPA) axis, as well as brain norepinephrine (NE) and indoleamine metabolism. Because LPS administration is known to induce the synthesis and secretion of IL-1, it has been proposed that IL-1 is the endogenous mediator of the response to LPS. This proposal has been tested using various antagonists of IL-1 with varied results. Therefore we have re-examined this question using a wide range of doses of the interleukin-1- receptor antagonist protein (IL-1ra) at various times after intraperitoneal LPS. The results indicate that IL-1ra at doses more than adequate to prevent responses to exogenously administered IL-1β, failed to significantly attenuate the increases in plasma ACTH and corticosterone and the cerebral catecholamine and indoleamine responses induced by intraperitoneal LPS in mice. IL-1ra was also ineffective when plasma ACTH and corticosterone were measured at longer times after LPS, although some trends towards attenuations were occasionally observed at 4 or 6 h. The latter is consistent with the time course of IL-1 induction by LPS. Intracerebroventricular administration of IL-1ra attenuated the endocrine and neurochemical responses to intraperitoneal IL-1β. However, intracerebroventricular IL-1ra failed to antagonize the HPA and neurochemical responses to intraperitoneal administration of LPS or to intravenous IL-1β. In all of these experiments, there were very close parallels between the HPA and the neurochemical responses, especially that of NE. We conclude that IL-1 does not mediate the HPA or the neurochemical responses to intraperitoneal LPS, although it may contribute in a minor way to the late HPA responses. However, IL-1 within the CNS may contribute to the responses to intraperitoneal IL-1, but not to intraperitoneal LPS or intravenous IL-1.
The Role of Local Induction of Tumor Necrosis Factor by LPS within a Subcutaneous Air Pouch in the Development of a Febrile Response in Guinea Pigs
Authors: Roth Joachim , Störr Birgit , Martin Dave , Voigt Karlheinz , Zeisberger Eugen
Published: April 2003

In rats, fever can be induced by injection of bacterial lipopolysaccharide (LPS) into a subcutaneous air pouch. This febrile response is in part dependent on the local action of interleukin-1β within the pouch. In the present study, we tried to find out if this model of fever induction can be applied in guinea pigs and if the local LPS-induced formation of tumor necrosis factor-α (TNF-α) participates in the development of the febrile response. A dose of 100 μg/kg LPS was injected into a subcutaneous air pouch along with solvent (0.9% saline), or 100 mg/kg pentoxifylline, or 1 mg/animal soluble 55-kD TNF receptor (referred to as TNF-binding protein, TNF bp). The mean LPS-induced concentration of TNF in the lavage of the air pouch (measured 60 min after injection) was 17,765 pg/ml in animals injected with LPS and solvent. This value was reduced to 7,631 pg/ml if pentoxifylline was injected along with LPS into the pouch. If LPS was injected along with TNF bp, no bioactive TNF was detected in the lavage of the air pouch. Simultaneously, TNF was measured in blood plasma. Circulating concentrations of TNF were about 5–8% of the values detected in the lavage of the air pouch (mean values: 1,366 pg/ml in response to LPS plus solvent; 377 pg/ml in response to LPS plus pentoxifylline; no circulating TNF at all in response to LPS plus TNF bp). These data indicated a small spill-over of TNF from the air pouch into the circulation. Neither the reduction of local TNF formation in the air pouch by pentoxifylline nor the complete neutralization of TNF within the pouch by TNF bp resulted in a significant attenuation of the febrile response induced by injection of LPS into the subcutaneous air pouch. If there were an activation of cutaneous nerves to induce fever by a local formation of cytokines within the air pouch, TNF would not represent a likely candidate to be responsible for such a neural stimulation.
Activation of the Adrenocortical Axis by Surgical Stress: Involvement of Central Norepinephrine and Interleukin-1
Authors: DeKeyser Freda G. , Leker Ronen R. , Weidenfeld Joseph
Published: April 2003

In the present study, we examined the mechanisms involved in the activation of the adrenocortical axis following surgical stress. Adult male rats underwent surgical laparotomy or craniotomy under ether anesthesia while control rats were only ether-anesthetized. Four hours following laparotomy or craniotomy, serum adrenocorticotropin (ACTH) and corticosterone (CS) were significantly increased and returned to almost basal levels after 24 h. Laparotomy also caused a significant depletion of corticotropin-releasing hormone (CRH-41) in the median eminence (ME). Pretreatment with dexamethasone 50 μg/kg completely abolished the pituitary-adrenal response while pretreatment with type II corticosteroid receptor antagonist caused a significant hypersecretion of both ACTH and CS and inhibited the effect of dexamethasone. The response to laparotomy was markedly attenuated in rats injected with 6-hydroxydopamine into the paraventricular nucleus (PVN) which significantly depletes norepinephrine (NE) PVN content. Intracerebroventricular injection of interleukin-1 receptor antagonist (IL-1ra) also inhibited the pituitary-adrenal response to laparotomy. The results suggest that (1) surgical stress activates the hypothalamo-pituitary-adrenal (HPA) axis via a mechanism which involves the release of CRH from the ME and NE input to the PVN; (2) the adrenocortical response is sensitive to the negative feedback of glucocorticoids via the mediation of type II glucocorticoid receptors, and (3) central IL-1 may be a mediator in the HPA axis response to surgical stress.
The Effect of the Repeated Administration of the Compound 3,4-Methylenedioxymethamphetamineon the Response of Rats to the5-HT2A,C Receptor Agonist (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)
Authors: Granoff Martin I. , Ashby Jr. Charles R.
Published: April 2003

In this study, we examined the effect of the 5-HT2A,C receptor agonist (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) on locomotor activity and the head twitch response in rats by the repeated (twice daily for 4 days) subcutaneous administration of 0.9% saline (1 ml/kg) or (±)-3,4-Methylenedioxymethamphetamine (MDMA) (20 mg/kg), a compound that selectively destroys serotonergic nerve terminals. There was no difference between the MDMA- and saline-treated rats regarding the (±)-DOI-induced (0.625, 1.25 or 2.5 mg/kg, i.p.) increase and decrease in the head twitch response and horizontal locomotor activity, respectively. Overall, repeated MDMA does not alter the behavioral response of rats to (±)-DOI.
Obsessive-Compulsive Symptom Exacerbation Following Cortisone Treatment
Authors: Grabe Hans-Jörgen , Freyberger Harald Jürgen , Maier Wolfgang
Published: April 2003

We here report a case of obsessive-compulsive symptom exacerbation during cortisone therapy in an adult patient without organic brain disorder. Possible clinical and pathophysiological considerations are discussed.
Inflationary Tendencies in Judging the Yield of Depression Research
Authors: van Praag H.M.
Published: April 2003

The mood around mood disorders is one of optimism. Progress in diagnosis and treatment is generally felt to be considerable. Zeitgeist rests on convictions. In this case the main supporting convictions are the following: depression is a very frequent disorder and its diagnosis has improved greatly; we dispose of more or less specific agents to control depression: biological psychiatric research made great strides, particularly in the field of affective disorders; new antidepressants are properly tested before being clinically introduced. Each of these convictions is critically analysed. It is concluded that each of these claims is either a half-truth or not true. Apparently reality awareness and reality testing are out of balance. This harms the prospects of research, particularly biological research. Ways to avoid the stalemate are discussed.
Gender-Related Seasonality of Human Platelet Phenolsulfotransferase Activity
Authors: Marazziti Donatella , Palego Lionella , Rossi Alessandra , Cassano Giovanni Battista
Published: April 2003

This study focused on the investigation of the possible effect of gender and season on the activity of the thermolabile and thermostable forms of platelet phenolsulfotransferase (PST) in a group of 23 healthy, drug-free volunteers of both sexes. The results showed a different seasonal profile of PST activity in men and women: in men, PST seasonal rhythms revealed a shallow profile with higher values in both the spring and summer than in the autumn. Conversely, in women, the PST seasonality showed a profile consisting overall of a main peak in the summer. Also, significant gender-dependent correlations were found between the photoperiod length and PST values. Our findings should stimulate further investigation into gender-dependent molecular mechanisms underlying the regulation of the metabolism of endogenous and xenobiotic agents, such as monoamines and phenols, which are the substrates of PST.
Acute and Chronic Effects of Caffeine on Performance, Mood, Headache, and Sleep
Authors: James Jack E.
Published: April 2003

Despite being the most widely consumed psychoactive substance in the world, there is considerable confusion regarding the effects of caffeine. This study examined objective indices of performance, and self-reported mood, headache, and sleep in 36 healthy male and female habitual caffeine consumers exposed to a pattern of moderate intake. A double-blind placebo-controlled cross-over design with counterbalancing was employed in which all subjects participated in four experimental conditions involving the ingestion of placebo or caffeine 3 times daily for 6 days followed by a 7th (challenge) day of placebo or caffeine ingestion. No evidence was found that caffeine improved performance, either in the context of acute or habitual use. On the contrary, performance was found to be significantly impaired when caffeine was withdrawn abruptly following habitual use. Participants reported feeling more alert and less tired following acute ingestion of caffeine, but feeling less alert in conjunction with chronic exposure to the drug. In addition, caffeine withdrawal was associated with reported increasses in frequency and severity of headache, and with reports of sleeping longer and more soundly.