[Clinical condition of patients with neural tube defects]. / Klinický stav pacientov s defektami neurálnej rúry.

INTRODUCTION: Neural tube defects are the most common congenital anomalies of central nervous system. Their onset is at the embryonic age of 21 to 28 days. Periconceptional administration of folic acid may reduce the occurrence of neural tube defects up to 70%. Clinical features depend on localization of the defect and malformation of central nervous system, as well as on intensive multidisciplinary care in early stages of development. Open defects (meningomyelocele) present with more severe neurological deficiency early after birth. Closed defect manifestation occurs usually later in life with tethered cord syndrome. PURPOSE: This study evaluates clinical status of the patients with neural tube defects, who are followed in the Children's Faculty Hospital in Bratislava. METHODS: Cross-sectional and also retrospective study was conducted by questionnaire that was given to mothers of children with neural tube defect. Data about perinatal and family history, occurrence of hydrocephalus, scoliosis, joint deformities, dysfunction of urinary system and bowel, as well as social care, were collected. Clinical features were statistically evaluated depending on beginning of the defect or locomotion status. RESULTS: 94 patients with mean age of 12.7 years +/- 6.59 SD were included in the study. Patients with open defects had more severe neurological deficiency with hydrocephalus, more common epilepsy, skeleton deformities, wheelchair-dependency, and dysfunction of urinary tract and bowel. Scoliosis and ability of locomotion significantly correlated with higher lever of defect, while hydrocephalus, continence, urinary infections, clean intermittent catheterization, constipation, scoliosis and joint deformities significantly correlated with the ability of locomotion (p < 0.05). CONCLUSION: For patients with neural tube defects, the level of neurological deficiency is the most important prognostic factor for many other clinical characteristics.

Pheochromocytoma-related 'classic' takotsubo cardiomyopathy.

We report a case of a 53-year-old hypertensive male with takotsubo cardiomyopathy in the setting of pheochromocytoma. Pheochromocytoma presenting as takotsubo cardiomyopathy is a recognized but uncommon occurrence with recently increasing number of published cases. We present typical apical ballooning syndrome, with transient left ventricular apical ballooning in contrast to several reports, in which patients with pheochromocytoma-induced cardiomyopathy had so called 'inverted'takotsubo cardiomyopathy. In patients being diagnosed with acute coronary syndrome symptoms without coronary artery stenosis or spasm, and pronounced blood pressure variability, pheochromocytoma-induced takotsubo or 'inverted' takotsubo cardiomyopathy should be kept in mind.

Renal artery aneurysms: presentation of five cases.

We are presenting clinical characteristics, management and follow-up of five consecutive patients with renal artery aneurysm. Renal artery aneurysms are relatively uncommon, they rarely give rise to clinical manifestations and they are usually found incidentally. However with the introduction of Doppler ultrasound, computed tomography (CT) and magnetic resonance (MR) imaging, the diagnosis of renal artery aneurysms became more frequent.

Efficient synthesis of 1alpha-fluoro A-ring phosphine oxide, a useful building block for vitamin D analogues, from (S)-carvone via a highly selective palladium-catalyzed isomerization of dieneoxide to dieneol.

The 1alpha-fluoro A-ring phosphine oxide 1, a useful building block for fluorinated vitamin D analogues, was synthesized from (S)-carvone in 13 synthetic steps, and only five isolations, in 22% overall yield. In the key synthetic step, a highly selective palladium-catalyzed isomerization of dieneoxide 18 to dieneol 20 was achieved using an appropriately selected fluorinated alcohol as a catalytic proton source.

Construct validity of selected Automated Neuropsychological Assessment Metrics (ANAM) battery measures.

The Automated Neuropsychological Assessment Metrics (ANAM) is a computerized library of tests designed to assess neurocognitive functioning across administrations (Kane & Reeves, 1997). This study was designed to examine neuropsychological constructs measured by selected ANAM measures and to compare them with traditional measures putatively assessing similar domains. The sample consisted of 191 outpatients with suspected neurocognitive dysfunction. Correlations and regressions indicated significant relationships between traditional and computerized tests measuring similar constructs. PCA results yielded a three-factor solution: Factor I (Processing Speed/Efficiency), Factor II (Retention/Memory), and Factor III (Working Memory).

The practical synthesis of vitamin D analogs: a challenge for process research.

New, highly-potent vitamin D analogs have increasingly come under consideration for the treatment of a variety of diseases as diverse as psoriasis, diabetes, renal osteodystrophy, osteoporosis, leukemia, cancer (breast, colon, prostate), AIDS and multiple sclerosis. This review will present recent efforts for the development of practical syntheses of these valuable compounds using the synthetically convergent Lythgoe approach.

Surveillance of depleted uranium exposed Gulf War veterans: health effects observed in an enlarged "friendly fire" cohort.

To determine clinical health effects in a small group of US Gulf War veterans (n = 50) who were victims of depleted uranium (DU) "friendly fire," we performed periodic medical surveillance examinations. We obtained urine uranium determinations, clinical laboratory values, reproductive health measures, neurocognitive assessments, and genotoxicity measures. DU-exposed Gulf War veterans with retained metal shrapnel fragments were excreting elevated levels of urine uranium 8 years after their first exposure (range, 0.018 to 39.1 micrograms/g creatinine for DU-exposed Gulf War veterans with retained fragments vs 0.002 to 0.231 microgram/g creatinine in DU exposed but without fragments). The persistence of the elevated urine uranium suggests ongoing mobilization from the DU fragments and results in chronic systemic exposure. Clinical laboratory outcomes, including renal functioning, were essentially normal. Neurocognitive measures showing subtle differences between high and low uranium exposure groups, seen previously, have since diminished. Sister chromatid exchange frequency, a measure of mutation in peripheral lymphocytes, was related to urine uranium level (6.35 sister chromatid exchanges/cell in the high uranium exposure group vs 5.52 sister chromatid exchanges/cell in the low uranium exposure group; P = 0.03). Observed health effects were related to subtle but biologically plausible perturbations in central nervous system function and a general measure of mutagen exposure. The findings related to uranium's chemical rather than radiologic toxicity. Observations in this group of veterans prompt speculation about the health effects of DU in other exposure scenarios.

Incidence and clinical relevance of RET proto-oncogene germline mutations in pheochromocytoma patients.

BACKGROUND: Autosomal dominant cancer syndrome--multiple endocrine neoplasia type 2 (MEN 2), may exist more often than expected in patients with pheochromocytoma. Germline mutations identified recently in MEN 2 can be revealed by genetic screening. OBJECTIVE: To evaluate the frequency of RET (rearranged during transfection) mutations in patients with pheochromocytoma. DESIGN AND METHODS: We genetically screened germline mutations in the RET proto-oncogene and clinically re-evaluated patients with pheochromocytoma. A pentagastrin test and other biochemical studies were performed in all patients. SETTING: Department of Internal Medicine and Hypertension, The Medical University of Warsaw, Warsaw, Poland and the Department of Nephrology and Hypertension, Albert Ludwigs University, Freiburg, Germany. PARTICIPANTS: Seventy seven unselected patients with pheochromocytoma (19 men, 58 women, mean age: 51.55 +/- 1.5 years; pheochromocytoma confirmed histopathologically) out of 162 diagnosed and treated in the years 1957-1998 in the Department of Internal Medicine and Hypertension in Warsaw, Poland. The other 85 patients did not respond to the written invitation. MAIN OUTCOME MEASURES: The finding of RET mutations and diagnosis of MEN 2 in patients with pheochromocytoma. RESULTS: Genetic testing revealed germline mutations in the RET proto-oncogene in six patients (7.8%). All carriers had mutation of exon 11, codon 634: TGC to CGC. In four patients with this mutation, medullary thyroid carcinoma (MIC) was diagnosed and in three cases, surgically treated. Biochemical parameters: parathormone 31.88 +/- 2.87 pg/ml, calcitonin: 0 min 0.23 +/- 0.14 ng/ml; 2 min 0.49 +/- 0.21 ng/ml; 5 min 0.48 +/- 0.21 ng/ml, metoxycatecholamines: 601.62 +/- 42.71 microg/24h, epinephrine: 1.94 +/- 0.17 microg/24h, norepinephrine 13.96 +/- 1.3 microg/24h, carcinoembryonic antigen (CEA) 9.94 +/- 4.3 ng/ml. Ambulatory blood pressure monitoring (ABPM): systolic blood pressure (SBP): 116 +/- 1.9 mmHg, diastolic blood pressure (DBP): 73.7 +/- 0.9 mmHg. Clinical, biochemical and imaging procedures did not reveal any recurrence of pheochromocytoma in the 77 patients studied. CONCLUSIONS: Patients with pheochromocytoma should be genetically screened for mutations of the RET proto-oncogene. These patients should undergo clinical screening for MEN 2. In addition, genetic studies can be useful for the screening of the families of the carriers.

Health effects of depleted uranium on exposed Gulf War veterans.

A small group of Gulf War veterans possess retained fragments of depleted uranium (DU) shrapnel, the long-term health consequences of which are undetermined. We evaluated the clinical health effects of DU exposure in Gulf War veterans compared with nonexposed Gulf War veterans. History and follow-up medical examination were performed on 29 exposed veterans and 38 nonexposed veterans. Outcome measures employed were urinary uranium determinations, clinical laboratory values, and psychiatric and neurocognitive assessment. DU-exposed Gulf War veterans with retained metal shrapnel fragments are excreting elevated levels of urinary uranium 7 years after first exposure (range 0.01-30.7 microg/g creatinine vs 0.01- 0.05 microg/g creatinine in the nonexposed). The persistence of the elevated urine uranium suggests on-going mobilization from a storage depot which results in a chronic systemic exposure. Adverse effects in the kidney, a presumed target organ, are not present at this time, though other effects are observed. Neurocognitive examinations demonstrated a statistical relationship between urine uranium levels and lowered performance on computerized tests assessing performance efficiency. Elevated urinary uranium was statistically related to a high prolactin level (>1.6 ng/ml; P=0.04). More than 7 years after first exposure, DU-exposed Gulf War veterans with retained metal fragments continue to excrete elevated concentrations of urinary uranium. Effects related to this are subtle perturbations in the reproductive and central nervous systems.

An exploration of the construct validity of the Heaton memory tests.

The Heaton techniques for assessing memory differ from most other memory measures by employing the combination of learning trials, repeated exposure to test stimuli, and 4-hour recall measures. The present study was designed to explore the relationship between the Heaton Story and Figure memory procedures, the California Verbal Learning Test (CVLT), and measures of attention, word fluency, and spatial perception. Data from 126 individuals were analyzed. Three separate factor analyses were performed that examined measures of attention, learning, and recall. Each revealed a three-factor solution accounting for 71, 70, and 72% of the variance, respectively. Regression analyses supported the visual components of Figure Memory and the verbal components of Story Memory obtained in the factor analyses. Overall, the findings supported the independence of the Heaton Memory procedures and the role of spatial factors in performance of Figure Memory. Additionally, both Figure and Story Memory shared variance with the CVLT, supporting the validity of both procedures as memory measures.

Persistent dissection of carotid artery in patients operated on for type A acute aortic dissection--carotid ultrasound follow-up.

Over a period of 5 years, 124 patients were operated on at the National Institute of Cardiology in Warsaw for acute aortic dissection, 27 of whom died. The 97 patients discharged from the hospital were included in the present analysis. The age of the patients ranged from 25 to 73 years with a mean of 50+/-10 years. Ultrasound examination of carotid arteries was performed with the patient lying on his back using a Toshiba 340A color Doppler system with a linear array probe of 7.5 MHz. Of the 97 patients examined, 15 (15%) had a dissection of at least one of the common carotid arteries (CCA). Two had Marfan syndrome. In 11 patients the dissection involved the right common carotid artery and in four it involved both the left and right common carotid arteries. The flow in the true lumen of CCA and ICA was preserved in all patients and the degree of narrowing ranged from 30 to -70%. Only one of the 15 patients with CCA dissection had an ipsilateral neurological deficit which was already present before the aortic aneurysm operation. Ultrasound follow-up was performed in all patients with the CCA dissection found on first examination. The mean duration of follow-up was 21 months. In 14 patients the degree and extent of the dissection as well as the narrowing of the true lumen was comparable, and in one patient the false channel closed spontaneously. During follow-up there were no new major neurological events despite the persistence of the CCA dissection with different degrees of narrowing of the true lumen. Doppler ultrasound examination of the carotid arteries can supply additional information about the extent of the dissection, and help to assess the flow in the persisting 'double channel' common carotid artery during the follow-up of patients.

Temperature coefficient of membrane currents induced by noxious heat in sensory neurones in the rat.

1. Membrane currents induced by noxious heat (Iheat) were studied in cultured dorsal root ganglion (DRG) neurones from newborn rats using ramps of increasing temperature of superfusing solutions. 2. Iheat was observed in about 70 % of small (< 25 microm) DRG neurones. At -60 mV, Iheat exhibited a threshold at about 43 C and reached its maximum, sometimes exceeding 1 nA, at 52 C (716 +/- 121 pA; n = 39). 3. Iheat exhibited a strong temperature sensitivity (temperature coefficient over a 10 C temperature range (Q10) = 17.8 +/- 2.1, mean +/- s.d., in the range 47-51 C; n = 41), distinguishing it from the currents induced by capsaicin (1 microM), bradykinin (5 microM) and weak acid (pH 6.1 or 6.3), which exhibited Q10 values of 1.6-2.8 over the whole temperature range (23-52 C). Repeated heat ramps resulted in a decrease of the maximum Iheat and the current was evoked at lower temperatures. 4. A single ramp exceeding 57 C resulted in an irreversible change in Iheat. In a subsequent trial, maximum Iheat was decreased to less than 50 %, its threshold was lowered to a temperature just above that in the bath and its maximum Q10 was markedly lower (5.6 +/- 0.8; n = 8). 5. DRG neurones that exhibited Iheat were sensitive to capsaicin. However, four capsaicin-sensitive neurones out of 41 were insensitive to noxious heat. There was no correlation between the amplitude of capsaicin-induced responses and Iheat. 6. In the absence of extracellular Ca2+, Q10 for Iheat was lowered from 25.3 +/- 7.5 to 4. 2 +/- 0.4 (n = 7) in the range 41-50 C. The tachyphylaxis, however, was still observed. 7. A high Q10 of Iheat suggests a profound, rapid and reversible change in a protein structure in the plasma membrane of heat-sensitive nociceptors. It is hypothesized that this protein complex possesses a high net free energy of stabilization (possibly due to ionic bonds) and undergoes disassembly when exposed to noxious heat. The liberated components activate distinct cationic channels to generate Iheat. Their affinity to form the complex at low temperatures irreversibly decreases after one exposure to excessive heat.

Reliability of length measurements in full-term neonates.

OBJECTIVE: To describe and compare the intra- and interexaminer reliability of four techniques for measuring length in full-term newborns and to determine whether the different techniques yield significantly different measurements. DESIGN: A descriptive study, describing the intra- and interexaminer reliability of four length measurement techniques: crown-heel, supine, paper barrier, and Neo-infantometer. The nurses were blind to their own and to the other nurse's measurements. The order of the nurses and the order in which the measurements were obtained was randomized. SETTING: Mothers' rooms in a university hospital. PARTICIPANTS: Thirty-two healthy full-term newborns. INTERVENTIONS: Length measurements using four different length techniques were obtained twice each by two experienced neonatal nurses. MAIN OUTCOME MEASURES: To measure the intra- and interexaminer reliability, the following statistics were calculated: mean absolute differences, standard deviations, technical error of measurement; percentage less than .5 and 1.0 cm, and percentage of error. RESULTS: Intra- and interexaminer differences were significantly larger when examiners used the crown-heel measurement technique. Although the intra- and interexaminer reliability of length measurements obtained with the supine, paper barrier, and Neo-infantometer techniques did not differ significantly, the amount of error in these measurements was large. CONCLUSIONS: Measurements obtained using the crown-heel technique are significantly less reliable than measurements obtained using the supine, paper barrier, or Neo-infantometer techniques.

Total synthesis of 25-hydroxy-16,23E-diene vitamin D3 and 1 alpha,25-dihydroxy-16,23E-diene vitamin D3: separation of genomic and nongenomic vitamin D activities.

Separation of genomic and nongenomic vitamin D activities was achieved by structural modification of 1,25-dihydroxy vitamin D3 by introduction of 16 and 23E double bonds. The modified compound 3, lacking a 1 alpha-hydroxy group, exhibits only nongenomic activity. Its 1 alpha-hydroxy relative 4 expresses fully both genomic and non-genomic activities. A total synthesis of analogues 3 and 4 is described.

Clinical evaluation of 24 h ambulatory monitoring of blood pressure under various environmental conditions (home and work versus hospital).

OBJECTIVE: To assess the effects of activity and environment on the spontaneous changes in 24 h blood pressure monitoring (BPM) and how these factors influenced the diagnosis of white-coat hypertension in the hypertensive subjects. PATIENTS AND METHODS: We examined 44 white-collar workers with untreated, uncomplicated mild hypertension, mean age 35 years, twice using 24 h BPM: on the day of natural activity, at home and at work (work-day 24 h BPM); and on the fourth day of hospitalization (hospital-day 24 h BPM). RESULTS: The mean value of blood pressure during activity period in hospital (hospital-day blood pressure) wqas significantly lower than that for ambulatory monitoring day (work-day blood pressure; 132/82 versus 138/85 mmHg). For work-day 24 h BPM the mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) from the period 0800-1600 h were substantially higher than the values from 1600-2300 h; for hospital-day 24 h BPM the mean SBP and DBP from two parallel activity periods did not differ significantly. The average office blood pressure of outpatients was 147.9 mmHg for SBP and 92.4 mmHg for DBP. Using the same threshold value of work-day and hospital-day blood pressures < 135/85 mmHg, the prevalence of white-coat hypertension was higher during a hospital day than it was on the work day. Basing our analysis of work-day 24 h BPM, white-coat hypertension was diagnosed in 28% of patients; basing our analysis on hospital-day 24 h BPM it was diagnosed in 49% of patients. mean night SBP and DBP at home and at hospital did not differ significantly. The correlation coefficients for relationship between home-night and hospital-night blood pressures were higher than those for work-day and hospital-day blood pressures (0.6 versus 0.44 for SBP; 0.63 versus 0.56 for DBP).CONCLUSIONS: Modification of the environmental conditions during activity period of men with mild hypertension causes an essential change in values and rhythm of blood pressure during this period, but does not influence the mean night blood pressure. Disregarding this fact during clinical interpretation of the results of 24 h BPM, especially with this group of patients, might be the main cause of a significant mistake in diagnosing white-coat hypertension.

Use of the Beck Anxiety and Depression Inventories for Primary Care with Medical Outpatients.

The effectiveness of the Beck Anxiety (BAI-PC) and Depression (BDI-PC) Inventories for Primary Care for discriminating 56 primary care patients with and without revised, third edition Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) diagnosed anxiety and mood disorders was studied. The Anxiety and Mood modules from the Primary Care Evaluation of Mental Disorders (PRIME-MD) were used to establish diagnoses. The coefficient alphas for the BAI-PC and BDI-PC were, respectively, .90 and .88. A BAI-PC cutoff score of 5 and above yielded the highest clinical efficiency (82%) with 85% sensitivity and 81% specificity for identifying patients with and without panic, generalized anxiety, or both disorders, whereas a BDI-PC cutoff score of 6 and above afforded the highest clinical efficiency (92%) with 83% sensitivity and 95% specificity for detecting patients with and without major depressive disorders. The use of these instruments to screen primary care patients before conducting extensive diagnostic evaluations with them was discussed.

[Evaluation of selected parameters of zinc metabolism in patients with primary hypertension]. / Ocena wybranych parametrów gospodarki cynkowej u chorych z pierwotnym nadcisnieniem tetniczym.

UNLABELLED: The aim of the study was to investigate the role of zinc (Zn) in essential hypertension (EH). PATIENTS AND METHODS: Material of the study consisted of 31 patients (12 female, 19 male) with mild and moderate EH and 20 healthy persons (NT) (7 female, 13 male). Erythrocyte (ZnE) and serum (ZnS) zinc as well as 24 hour urinary zinc excretion (ZuU) were assessed in both groups. Zn parameters were measured by atomic absorption spectrophotomery. RESULTS: ZnS was lower and ZnE was higher in EH (p < 0.001) than in normotensives. ZnU did not differ between EH and NT. ZnE and ZnS negatively correlated with age in NT but not in EH, ZnU negatively correlated with age only in EH. BP positively correlated with ZnS in EH but not in NT. In both groups negative correlations were found between BP and ZnU. CONCLUSIONS: 1. Zinc probably plays a role in pathogenesis of essential hypertension.

Internal structure of the MMPI-2 Addiction Potential Scale in alcoholic and psychiatric inpatients.

Recently, Weed, Butcher, McKenna, and Ben-Porath (1992) introduced two new scales for assessing alcohol and drug abuse with the Minnesota Multiphasic Personality Inventory-2 (MMPI-2; Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989): the Addiction Potential Scale (APS), an empirically derived measure similar to the MacAndrew Alcoholism Scale (MAC; MacAndrew, 1965), and the Addiction Acknowledgement Scale. Like the MAC, the APS was designed to identify the personality dimensions associated with substance abuse. Although there has been evidence to support the discriminative validity of the APS among samples of abusers, nonabusers, and psychiatric inpatients (Greene, Weed, Butcher, Arrendondo, & Davis, 1992; Weed et al., 1992), there has been no attempt to determine the personality dimensions tapped by the APS. Thus our study investigated the internal complexities of the APS. Using MMPI-2 protocols from a sample of alcoholic and psychiatric inpatients, we subjected the APS to a principal components analysis with subsequent varimax rotation. Both qualitative and quantitative methods were used to name the components that were identified. Five components consistently emerged across settings: Satisfaction/Dissatisfaction with Self, Powerlessness/Lack of Self-Efficacy, Antisocial Acting-Out, Surgency, and Risk-Taking/Recklessness, Clinical advantage gained from a knowledge of the internal structure of the APS was illustrated using 6 patients from the alcoholic sample. A rational approach to validating the empirical structure of the APS was discussed as a potential avenue for future research.