Standardized tests of heart rate variability: normal ranges obtained from 309 healthy humans, and effects of age, gender, and heart rate.

The authors undertook this study to determine the effects of age, gender, and heart rate (HR) on the results of cardiac autonomic function tests for measuring heart rate variability (HRV) in a large sample of healthy subjects (n = 309). Conventional tests (deep breathing, maximum/minimum 30:15 ratio), and a standardized 5-minute resting study, including spectral analysis of HR, were used. The main findings included (1) the indices of all tests, except for the ratio of the low- (LF) to high-frequency (HF) spectral power (LF/HF ratio) and HR itself, are inversely related to age in both sexes; (2) the 5-minute spectral bands (except for the LF/HF ratio), the variation coefficient, expiratory-inspiratory ratio during deep breathing, and the maximum/minimum 30:15 ratio are independent of HR; (3) women up to the age of 55 years have a higher resting HR compared with men; (4) young and middle-aged women show a significantly lower LF power and LF/HF ratio compared with age-matched men, whereas no significant gender differences are observed in the absolute HF power. The authors computed age- and gender-dependent normal values for each of the HRV indices studied here and discuss the clinical consequences arising from gender differences in HRV.

Survey of yeast mastitis in dairy herds of small-type farms in the Lublin region, Poland.

The purpose of this study was to isolate fungi from the quarter milk of cow udders in 9 dairy farms. The samples were collected between May 1996 and April 2000 in the Lublin region. Six hundred and four milk samples collected from the quarters of 172 cows with clinical and subclinical mastitis were examined. Milk samples were plated as soon as possible on blood agar (BA), Mac Conkey agar, aesculin-tallium acetate-crystal violet blood agar, and Sabouraud agar with chloramphenicol and gentamicin. Fifty eight (9.6%) of the samples were positive for fungi. All of the fungal isolates were yeasts of the genera Candida, Rhodotorula and Trichosporon. We also isolated Streptococcus agalactiae (4.9%), Str. spp.(6.4%), Staphylococcus aureus (10.4%), coagulase-negative staphylococci-CNS (36.6%), Escherichia coli (3.5%), other microorganisms (2.6%) and no growth (25.8%).

Effects of newer atypical antipsychotics on autonomic neurocardiac function: a comparison between amisulpride, olanzapine, sertindole, and clozapine.

As part of a prospective clinical study investigating the effects of atypical neuroleptics on autonomic neurocardiac function (ANF), serial standardized recordings of conventional electrocardiograms and computer-calculated measurements of 5-minute resting heart rate variability (HRV) were obtained from 51 medication-free inpatients with schizophrenia (DSM-III-R-diagnosed) before and after an average of 14.1 days of treatment with amisulpride 400 mg/day (N = 12), olanzapine 20 mg/day (N = 13), sertindole 12 mg/day (N = 13), or clozapine 100 mg/day (N = 13). Reference values for the HRV data were obtained from a large group of well-matched healthy controls (N = 70). The most important findings were the following: (1) clozapine, olanzapine, and sertindole all prolonged mean frequency-corrected QTc times, which, in the case of sertindole, proved to be significant (Wilcoxon test p <0.05); (2) sertindole and clozapine significantly increased the mean resting heart rate; and (3) only clozapine significantly reduced the parasympathetic resting tone. The results of the HRV studies are discussed considering the in vitro receptor profiles of the atypical neuroleptics under study. Potential implications for the cardiac safety and tolerance of these drugs are also discussed.

Autonomic neurocardiac function in patients with major depression and effects of antidepressive treatment with nefazodone.

BACKGROUND: Major depression (MD) is associated with an augmented risk of cardiovascular mortality. One possible explanation for this association is that MD influences autonomic neurocardiac regulation (ANR). However, previous studies on this subject revealed conflicting results. METHODS: Using an autonomic test battery, which consisted of standardised measurements of heart rate variability (HRV) and blood pressure, we (1) compared ANR between 25 patients with DSM-III-R diagnosed MD and 60 healthy controls, and (2) investigated the autonomic effects of antidepressive treatment with nefazodone. RESULTS: Following multivariate analysis of all tests a significant reduction in HRV could only be shown for the Valsalva ratio amongst the depressives compared to controls. There was a significant inverse correlation between the HRV during deep respiration and both the severity of depression and the duration of the depressive episode. Serial HRV recordings revealed that both the mean resting heart rate and systolic blood pressure significantly decreased after 21 days of nefazodone treatment (average dosage 413 mg/day), whereas after 10 days (average dosage 270.8 mg/day) there were no striking changes compared to the pre-treatment values. During nefazodone treatment no significant changes in parasympathetic tone occurred. LIMITATIONS: ANR was not assessed in a randomised, placebo-controlled fashion. CONCLUSIONS: (1) Patients with MD may suffer from functional disturbances in the interaction between the sympathetic and parasympathetic autonomic tree. (2) The pattern of autonomic changes during treatment suggests that nefazodone induced a dose dependent, serotonergically-mediated down-regulation of the sympathetic tone. This mechanism might be responsible for nefazodone's properties of reducing anxiety.

Vascularized bone marrow transplanted in orthotopic hind-limb stimulates hematopoietic recovery in total-body-irradiated rats.

Hematopoietic recovery after bone marrow transplantation (BMT) is reported to be slow with long-lasting immune deficiency. This may be attributable to lack of a proper microenvironment for hematopoietic cell proliferation and differentiation. We have designed a model in which complete hematopoietic reconstitution of lethally irradiated rats can be achieved by vascularized bone marrow transplantation (VBMT) in an orthotopic hind-limb graft. The aim of the study was to investigate the process of repopulation of bone marrow cavities and peripheral blood of irradiated rats after VBMT and, in particular, to follow the contribution of grafted BM cells and residual recipient BM cells in hematopoietic regeneration. Lewis hind-limbs were transplanted orthotopically to totally irradiated (8 Gy) syngeneic sex-mismatched recipients (VBMT). In the control group 8 x 10(7) BM cells in suspension were injected intravenously (BMCT). After 10 days BM and peripheral blood (PB) cells were collected from the recipient. For cell subset analysis cytomorphological evaluation of BM smears and flow cytometry of PB cells were performed. Additionally, PCR was performed using specific primers for rat Y chromosome (sex-determining region Y-Sry) to detect male (donor or recipient) cells in sex-mismatched BM graft recipients and the products were analyzed by electrophoresis. VBMT brought about much faster replenishment of nucleated cells in BM and PB than did BMCT. Cytometry analysis of PB cells revealed more lymphocytes in VBMT than in BMCT recipients. The amount of donor DNA of bands corresponding to Y-Sry was also higher in PB cells of VBMT than of BMCT recipients. The presence of host DNA was observed in PB cells of VBMT rats but was not detected in PB population of BMCT recipients. VBMT is highly effective in hematopoietic reconstitution of irradiated recipients. The fast cell maturation and repopulation may be due to the presence of stromal cells transplanted in a normal spatial relationship with donor hematopoietic cells in hind-limb graft. Self renewal of radioresistant host cells was seen after VBMT but not after BMCT.

Primary structure of fox (Vulpes vulpes) proinsulin based on sequence studies of pancreatic peptides and cDNA.

Insulin and C-peptide were extracted and purified from fox (Vulpes vulpes) pancreas using gel filtration, ion-exchange chromatography and HPLC. Chromatographic data for the insulin, as well as for its oxidized and carboxymethylated chains proved it to be identical to that of polar fox (Alopex lagopus) and dog. The sequence analysis of a peptide which was assumed to be the corresponding C-peptide revealed that it comprises 23 amino acid residues and is identical to the C-peptide fragment isolated from dog pancreas: it differs from polar fox C-peptide by a single substitution (Asp-->Glu). mRNA was isolated from pancreatic tissue and cDNA was obtained by reverse transcription. A polymerase chain reaction was performed using gene-specific primers to obtain a DNA fragment corresponding to part of fox proinsulin. DNA sequencing revealed 100% identity to dog proinsulin at the protein level, although some amino acids were encoded by different codons. The total sequence of proinsulin was deduced from these results.

Clinical education in two-year colleges: cost-benefit issues.

Allied health program directors and administrators need to be aware of the costs and benefits of their clinical training programs to assure continued availability of training facilities for students. In a pilot study, program directors and administrators who are members of the National Network of Health Career Programs in Two-year Colleges (NN2) were surveyed concerning items to include in a cost-benefit-analysis tool, intangible and tangible costs and benefits of clinical education programs, and evaluation of a tool to analyze costs and benefits. Surveys were sent to 138 NN2 members, with 58 responding. Clinical sites were primarily in independent hospitals or health care systems. Most programs had preceptor-to-student ratios of 1:1-1:2, with few students being paid for clinical work. The respondents identified costs as staff time, materials and supplies, equipment, and others. Benefits were orientation and recruitment savings; increased professionalism, job satisfaction, and work quality of staff; ability to maintain and upgrade staff skills and knowledge; and student assistance with clinical coverage. Few programs were required to perform cost analysis. Allied health clinical education programs continue to depend on the willingness of health care facilities to accept students for clinical training.

Multidisciplinary team dynamics in the production of problem-based-learning cases in issues related to older adults.

Two important goals in allied health education are to prepare future allied health professionals to function as members of interdisciplinary teams and to increase their awareness of issues related to the growing older adult population. The responsibility for achieving these goals rests on the faculty and administrators of allied health education programs, who may not themselves be proficient in either of these domains. A multidisciplinary team of health educators and administrators was brought together to produce six problem-based learning (PBL) cases related to older adults. Members of the team represented a variety of disciplines in health care, diverse philosophies of educational development, a variety of roles in allied health education, and differing levels of knowledge of issues related to older adults--parameters similar to those found in the members of an interdisciplinary healthcare team. The methods by which this multidisciplinary group functioned and the dynamics in attaining the goals of the project are presented.

Sensitive reversed-phase liquid chromatographic determination of fluoride based on its ternary systems with zirconium(IV) or hafnium(IV) and 2-(5-bromo-2-pyridylazo)-5-diethylaminophenol.

Optimum conditions for the direct reversed-phase LC determination of fluoride based on the ternary M-(F-)-(5-Br-PADAP) complexes [M = ZrIV or HfIV and 5-Br-PADAP = 2-(5-bromo-2-pyridylazo)-5-diethylaminophenol] were evaluated. Chromatographic separation was performed with C18 end-capped column with an eluent consisting of acetonitrile-water (85 + 15 v/v) mixture of pH 4.0 +/- 0.3 (flow rate 1 ml min-1), and the eluate was monitored spectrophotometrically at lambda max = 585 nm. The calibration curves were linear over a wide range of fluoride concentrations: from 1 to 110 and 150 ng ml-1 for the ZrIV-(F-)-(5-Br-PADAP) and HfIV-(F-)-(5-Br-PADAP) systems, respectively (using a 20 microliters loop). Under such conditions the detection limits were 0.8 and 0.7 ng ml-1, respectively, and the quantification limit is 1.0 ng ml-1 for both methods. When a 100 microliters loop was used, the limits of both detection and quantification in the method based on the zirconium system were 0.2 ng ml-1. Using the proposed method, fluoride was determined directly in tap water, saliva and an anti-cancer agent for prostatic cancer (Leuprolid).

[Conservative treatment of cerebral arteriovenous malformations. Follow-up study of 31 cases]. / Leczenie zachowawcze naczyniaków tetniczo-zylnych mózgu. Badanie katamnestyczne 31 przypadków.

The clinical course of 31 patients with conservatively treated intracranial arteriovenous malformations (AVM's) was followed-up. The average follow-up period was 8.2 years, 75% of patients were followed up for more than 5 years. The initial symptom was intracranial bleeding in 21 patients (68%), seizure in 5 (16%), neurological deficit in 2 (6.5%), headache in 2 (6.5%) and intracranial hypertension in 1 (3%). The prognosis was more favourable for patients presenting with seizures than for patients presenting with haemorrhage. Patients in the haemorrhage group had 29% incidence of haemorrhage causing 14% mortality in this group. Of the 31 patient's 20 (64.5%) had a good clinical outcome, 4 (13%) had a fair outcome and 2 (6.5%) poor, 5 patients died, with one not due to AVM. There was no correlation between pregnancy and bleeding.

[Central neurocytoma of the right parietal and occipital lobe. Case report]. / Nerwiak zwojowokomórkowy osrodkowy w placie ciemieniowym i potylicznym prawej pólkuli mózgu. Opis przypadku.

Central neurocytoma is a rare tumour of the CNS. It typically occurs in intraventricular location in young adults. The authors describe central neurocytoma in a 17-year-old woman, which was situated unusually for this type of tumour in the brain parenchyma. In this paper radiological and histopathological picture is presented.

Alcoholism, peripheral neuropathy (PNP) and cardiovascular autonomic neuropathy (CAN).

In contrast to diabetic autonomic neuropathy, cardiovascular autonomic neuropathy (CAN) in long-term alcoholics has been studied rarely. Using both standardized bedside tests and computer-assisted analysis of heart rate variability (HRV), we prospectively compared autonomic neurocardial function between 35 strictly selected, detoxified alcoholics (DSM-III-R), and 80 well matched healthy controls. Evidence for a potential CAN was found in 25.7% of all the alcoholics studied and in 41% of those with clinically manifest PNP (n=22). Overall, our results demonstrated a significant association between the presence of a CAN and peripheral neuropathy (PNP) amongst chronic alcoholics (chi-square test P<0.05); there was no evidence of a CAN in any of the alcoholics without a clinically manifest PNP. The CAN was characterized by a dissociated appearance of parasympathetic and sympathetic disorders. Our findings provide reason to suspect that the total lifetime dose of alcohol and the duration of alcohol dependence are the most important factors contributing to the pathogenesis of both PNP and sympathetic dysfunction. As is the case with diabetics, computer-assisted measurements of HRV including spectral analysis appear to be far superior to conventional bedside tests for detecting evidence of cardiovagal dysfunction in long-term alcoholics.

Improved autonomic neurocardial balance in short-term abstinent alcoholics treated with acamprosate.

Standardized investigations on resting heart rate variability (HRV) should provide more information on acamprosate's human pharmacodynamic properties because acamprosate interacts with several neurotransmitter systems which are also involved in maintaining autonomic neurocardiac balance. We performed HRV measurements prospectively in 69 healthy controls and 19 chronic alcoholics to prove the hypotheses that: (1) compared to healthy controls, chronic alcoholics show disturbances in neurocardiac vagal function; and (2) in alcoholics, acamprosate treatment (6-8 days) should further decrease parasympathetic activity if acamprosate interacts with central gamma-aminobutyric acidA receptors in vivo. Cardiovagal dysfunction was initially present in 21% of the alcoholics. After treatment. however, their neurocardiac sympathetic-parasympathetic balance improved significantly.

Peptide-specific antibodies as probes of the topography of the Ca2+-binging motifs in alphaIIbbeta3.

Antibodies against synthetic peptides corresponding to four Ca2+-binding motifs of the alphaIIb subunit have been obtained and used as molecular probes to analyze the topography of the alphaIIbeta3 complex. The specificity of the antibodies has been characterized by ELISA and Western immunoblotting in terms of binding capacity and affinity to the isolated alphaIIbbeta3 and its alphaIIb subunit. Our data suggest that: (a) all four Ca2+-binding motifs of the alphaIIb are partially exposed on the surface of the intact molecule and accessible to antipeptide antibodies. However, they are not in close vicinity to the ligand recognition domain since the antibodies do not produce complete inhibition of platelet aggregation. (b) The conformation of amino acid stretches which form the second Ca2+-binding motif of alphaIIb is particularly dependent upon the presence of cation, and this region undergoes significant conformational alterations upon Ca2+ expulsion.

[Brain tumor and imminent premature labor: a case report]. / Guz mózgu a zagrozenie porodem przedwczesnym. Opis przypadku.

A pregnant woman with cerebral tumour of right hemisphere is reported. In the 30th week of pregnancy intracranial pressure was increased and imminent premature delivery were diagnosed. The patient was operated on for cerebral tumour and immediately after this cesarean section was performed. We conclude that in this case neurosurgical operation followed by cesarean section saved the life of the mother and child.

Antiovulatory antagonists of LHRH related to antide.

We report 104 analogues of the potent antiovulatory antagonist of LHRH, N-Ac-D-Nal-D-Cpa-D-Pal-Ser-Lys(Nic)-D-Lys(Nic)-Leu-Ilys-Pro-D-Ala- NH2, Antide. We replaced the Nic group in Antide with other acyl substituents to modulate size, hydrophilicity or basicity of the molecule, we also replaced the Lys residues with shorter basic amino acids, and made cyclic 5/6 analogues as well as position 5 or 6 dimers. We substituted Ilys8 with other alkyl groups and acyl derivatives. When injected in 0.1% DMSO in water in a typical antiovulatory (AO) assay. Antide gives six rats ovulating out of eight (6/8) at 2 micrograms, 4/8 at 4 micrograms, and in the histamine release assay (HRA). ED50 is > 300 micrograms/ml; [Lys(N-Isobutyl)8]Antide gave 2/8 at 2 micrograms/rat; [Lys (8-Qis)5]Antide gave 1/8 at 1 microgram, and 0/8 at 2 micrograms, and in the HRA ED50. 22 micrograms/ml; [D-Lys(8-Qis)5]Antide gave 4/8 at 1 microgram and 0/8 at 2 micrograms, and in the HRA, ED50 was 27 micrograms/ml; [Lys(8-Qic)8] gave 5/8 at 1 microgram 1/8 at 2 micrograms/ [Lys(2-Pyc)6]Antide gave 3/8 at 1 microgram, and 0/8 at 2 micrograms, and in the HRA ED50 was 116 micrograms/ml; [D-Lys (2-Pyc)5]Antide gave 5/8 at 1 microgram and in the HRA, ED50 was 100- > 300 micrograms/ml; [Lys(2-Pyc)5.D-Lys(2-Pyc)6]Antide gave 2/8 at 1 microgram. The substitutions of the Nic groups of Antide at Lys5 or D-Lys6 with 8-Qis or with 2-Pyc groups seem to give highly potent antiovulatory antagonists of LHRH and constitute significant new leads to generate potent antiovulatory compounds endowed with moderate or low histamine release.

Systematic substitution of an oxytocin antagonist with D-amino acids: unexpected high antagonistic potency of the D-Cys6-substituted analogue.

We report twelve analogues (1-12) of [Pmp1,D-Trp2,Arg8]oxytocin, PA (parent antagonist), (Pmp = beta,beta-pentamenthylene-beta-mercaptopropionic acid), which is a potent antagonist (pA2 = 7.77) of the uterotonic effect of oxytocin (OT) in rats. The analogues were designed by replacement of each optically active amino acid residue at positions 3-8 in PA with a D-amino acid. Analogues 1-8, featuring D-amino acids in the ring portion, were weaker antagonists than PA or were inactive. Unexpectedly, replacement with D-Cys6 gave analogue 9, pA2 = 8.29, which is more than 3 times as potent as PA, and replacement with D-Pen6 gave analogue 10, pA2 = 7.98, also more potent than PA. Replacement with D-Pro7 and D-Arg8 gave analogues 11 and 12, which are approximately equipotent or somewhat more potent than PA. These data suggest that neither the orientation of the tail sequence with respect to the plane of the ring portion of an antagonist nor the configuration of individual amino acids in the tail sequence may be critical for preservation of antagonism to the uterotonic action of OT. In the antidiuretic assay, analogues 9 and 12 were very weak partial agonists and had estimated pA2 = < 6.3 and < 5.6, respectively. Analogue 9 constitutes an interesting lead for the future design of OT antagonists with different molecular requirements than those featuring L-Cys6 as a substituent.

Decreased histamine release by luteinizing hormone-releasing hormone antagonists obtained upon translocation of the cationic amino acid from position 8 to position 7.

We report analogues of N-Ac-D-Nal-D-Cpa-D-Pal-Ser-Lys(Pic)-D-Lys(Pic)-Leu-Ilys-Pro-D-Ala- NH2, the parent antagonist (PA), which is a potent antagonist of LHRH. To simplify future radioactive labeling we prepared N-Ac-D-Nal-D-Cpa-D-Pal-Ser-Lys(Pic)-D-Lys(Pic)-Leu-Arg-Pro-D-Ala-NH2 (4), [Arg8]PA, which had good activity in the antiovulatory assay (AOA). Other analogues were designed at first by substituting with Arg at positions 5, 6, 7, 9, and 10, and Trp or Leu at position 8. Subsequent analogues were prepared in attempts to improve the AOA of the initial ones. Substitutions with Arg9 or Arg10 led to analogues 1-3 with no AOA activity at 5 micrograms/rat. However, substitution with Arg7 gave 9, [Arg7,Leu8]PA, with significant activity in the AOA at 5 micrograms/rat and borderline activity at 2.5 micrograms/rat, and substitution with Ilys7 gave 13, [Ilys7,Leu8]PA, with borderline activity at 2 micrograms/rat, both analogues showing much weaker activity than PA in the histamine release assay (HRA) and therefore being potentially safer. Substitutions with D-Arg6 or Arg5 led to analogues with either good AO activity at 5 micrograms/rat (analogue 7) or with borderline activity at 5 micrograms/rat (analogue 8), although both were more potent than 6 in the HRA. Combinations of Ilys or Arg at positions 7 and 8 led to 10 and 11, both of which were tested at 2 micrograms/rat and found to have either good AO activity (analogue 10) or borderline activity (analogue 11) but unsuitably potent in HR. Substitutions using Ilys7 and neutral amino acids at position 8 led to 14-17 which were inactive in the AOA. Of great significance is the substitution with Arg7 yielding analogue 9, which was much safer in the HRA than analogue 4, [Arg8]PA. Analogues 9 and 13, featuring substitutions with the Arg7-Leu8 or Ilys7-Leu8 sequences were even safer than PA or 6 in the HRA. Analogue 12, [D-Trp3,Tyr5,D-Arg6,Arg7,Leu8]PA, featuring the Arg7-Leu8 sequence, had much lower potency in the HRA than [D-Trp3,Tyr5,D-Arg6,Leu7,Arg8]PA, which has the normal Leu7-Arg8 sequence. Ilys7 together with neutral amino acids at position 8 led to analogues 14-17 which were also very weak (safer) in the HRA, with the smaller amino acids Ala8 and Abu8 being the weakest of all analogues prepared.(ABSTRACT TRUNCATED AT 400 WORDS)

[Clinical analysis of 27 cases of primary lymphoma of the central nervous system]. / Analiza kliniczna 27 pierwotnych chloniaków osrodkowego ukladu nerwowego.

Clinical analysis of 27 patients with primary central nervous system lymphoma--Out of 4397 patients with intracranial neoplasms treated in the Department of Neurosurgery Medical Academy in Poznan between years 1956-1990, 27 patients i.e. 0.6% had primary central nervous system lymphoma. The patients age ranged from 15 to 63 years. In most patients the tumour was located in the temporo-parietal region. All patients were treated surgically, and then some received radio and/or chemotherapy. In spite of combined therapy the results of treatment are unsatisfactory, the median survival time is between 2 and 4 months.