Modifiable vascular risk factors, white matter disease and cognition in early Parkinson's disease.

BACKGROUND AND PURPOSE: Dementia in Parkinson's disease (PD) is common and disabling. Identification of modifiable risk factors for it is essential. Vascular risk factors (VRFs) may be associated with cognitive decline in early PD. Biomarkers that serve as surrogates of the long-term effect of VRFs on PD are needed. To that end, we aimed to quantitate white matter hyperintensities (WMH) in early PD, measure associations with VRFs and examine relationships between WMH and longitudinal cognition. METHODS: Participants in the Parkinson's Progression Markers Initiative study (141 patients with PD, 63 healthy controls) with adequate baseline structural brain magnetic resonance imaging data were included. Hypertension and diabetes history, and body mass index were combined to create a vascular risk score. WMH were quantitated via automated methods. Cognition was assessed annually with a comprehensive test battery. RESULTS: In the PD group, vascular risk score was associated with WMH for total brain (ß = 0.210; P = 0.021), total white matter (ß = 0.214; P = 0.013), frontal (ß = 0.220; P = 0.002) and temporal (ß = 0.212; P = 0.002) regions. Annual rate of change in global cognition was greater in those with higher vascular risk score (ß = -0.040; P = 0.007) and greater WMH (ß = -0.029; P = 0.049). Higher temporal WMH burden was associated with great decline over time in verbal memory (ß = -0.034; P = 0.031). CONCLUSIONS: In early PD, modifiable VRFs are associated with WMH on brain magnetic resonance imaging. Temporal WMH burden predicts decline in verbal memory. WMH may serve as a surrogate marker for the effect of VRFs on cognitive abilities in PD.

Impact of the operative technique on mid- and long-term results following paediatric heart transplantation.

AIMS: The aim of this study is to evaluate and compare the impact of the bicaval technique versus the biatrial technique (by Lower and Shumway) in paediatric heart transplant patients. Only a few studies investigate this matter regarding the long-term outcome after paediatric heart transplantation. We compared the two surgical methods regarding survival, the necessity of pacemaker implantation. METHODS AND RESULTS: All 134 patients (aged <18 years) - (group-1) biatrial (n = 84), versus (group-2) bicaval (n = 50), who underwent heart transplantation between October 1988 and December 2021, were analysed. Freedom from events were estimated using the Kaplan-Meier method. Potential differences were analysed using the log rank test and Cox proportional hazard models. Mean ± standard deviation: Bypass time (per minutes) was higher in the group 1 as compared with group 2 (P = 0.050). Survival was not significantly different (P = 0.604) in either groups. Eighteen patients required permanent pacemaker implantation in the group 1 and only one patient required it in the group 2 (P = 0.001). CONCLUSIONS: Paediatric heart transplantation using bicaval technique results similar long-term survival compared with the biatrial technique. The incidence of atrial rhythm disorders was significantly higher in the biatrial group, requiring a higher frequency of pacemaker implantation in this group. As a results, the bicaval technique has replaced the biatrial technique in our centre.

Knowledge of the Genetic Information Nondiscrimination act among individuals affected by Huntington disease.

The Genetic Information Nondiscrimination Act (GINA) of 2008 was the first US legislation to address genetic discrimination. We sought to assess understanding of GINA among individuals affected by the autosomal dominant condition, Huntington disease (HD). We conducted a cross-sectional survey of individuals with varying risk of HD to assess their familiarity with GINA. As a control, individuals were surveyed about their familiarity with the Health Insurance Portability and Accountability Act (HIPAA). Those who reported familiarity with GINA were asked about their knowledge of specific provisions of the legislation. The survey was offered to 776 participants and completed by 410 (response rate 53%). Respondents across all groups were less familiar with GINA (41% slightly, somewhat, or very familiar) than with HIPAA (65%; p < 0.0001). Of individuals with or at risk for HD who reported some familiarity with GINA, less than half correctly identified GINA's protections, and less than 15% correctly identified its limitations. Thus, among individuals affected by HD, familiarity with and knowledge of GINA are low. The effectiveness of the legislation may be limited by this lack of knowledge.

Pediatric heart transplantation in infants and small children under 3 years of age: Single center experience - "Early and long-term results".

OBJECTIVES: We analyzed the early and long-term survival after ABO-compatible heart transplantation in children under 3 years of age from 1991 to 2021 at our center. This retrospective and descriptive study aimed to identify serious adverse events associated with mortality after pediatric heart transplantation. PATIENTS AND METHODS: 46 patients with congenital heart failure (37%) in end-stage heart failure have undergone a pediatric heart transplantation. Primary outcome of interest was survival at follow-up time. RESULTS: Median (IQR) follow-up time (y), age (y), body-weight (kg) and BMI (kg/cm2) were 13.2 (5.7-19.5), 0.9 (0.2-2.0), 6.8 (4.3-10.0) and 14.2 (12.3-15.7). Twenty-four (52%) patients were male. 15 patients (33%) had a single ventricle physiology. At 30- days survival rate was 94 ± 4%. Survival rate at 1, 5, 10 and 15 years post HTx was 87 ± 5%, 84 ± 6%, 79 ± 6% and 63 ± 8%. One child underwent re-transplantation after 4 years, and another one after 11 years - in both cases due to graft failure. Higher early mortality in patients under 3 months of age and in patients with single ventricle physiology. Transplant free survival at 15 years was in children with cardiomyopathy better (71 ± 10%) than in those with congenital heart disease (50 ± 13%). One or more previous heart surgeries prior to HTx (n = 21) were associated to more mortality. CONCLUSION: Pediatric heart transplantation has acceptable long-term results and is still the best therapeutic option in children with end-stage cardiac failure. Underlying anomalies and single ventricle physiology, age below 3 months had a significant impact on survival.

The influence of processing factors and non-atopy-related maternal and neonate characteristics on yield and cytokine responses of cord blood mononuclear cells.

RATIONALE: Several studies have evaluated the associations between cord blood cellular responses and atopic diseases in children, but the results of these studies are inconsistent. Variations in blood processing factors and maternal and infant characteristics are typically not accounted for and may contribute to these inconsistencies. METHODS: Cord blood samples were obtained from 287 subjects participating in the Childhood Origins of ASThma project, a prospective study of children at high risk for the development of asthma/allergies. Mononuclear cells were stimulated with phytohaemagglutinin (PHA), phorbal myristate acetate/ionomycin or a suspension of killed staphylococcus, and IFN-gamma, IL-10 and IL-13 were quantitated by ELISA. Cell yields and cytokine production were related to processing factors and maternal and infant characteristics. RESULTS: The strongest relationships between independent variables and cell yield or cytokine responses occurred with the season of birth. The highest median cell yields were seen in fall, and the lowest in summer (difference of 47%, P=0.0027). Furthermore, PHA-induced IL-5 and IL-13 responses were approximately 50% higher in spring and summer than in fall or winter (P<0.0001). Clots in the cord blood samples were associated with a reduced median cell yield (42% reduction, P<0.0001), and an increased PHA-induced IL-10 secretion (27% increase, P=0.004). CONCLUSIONS: These data suggest that season of collection, and to a lesser extent clotting in samples, affect cord blood mononuclear cell yield and cytokine responses. Careful documentation and analysis of processing and environmental variables are important in understanding biological relationships with cytokine responses, and also lead to greater comparability among studies using these techniques.

Structure-activity relationships of somatostatin analogs in the rabbit ileum and the rat colon.

UNLABELLED: Somatostatin increases absorption of electrolytes and inhibits diarrhea in patients with endocrine tumors and short bowel syndrome. In an attempt to develop a gut-specific somatostatin analog, each amino acid in the somatostatin molecule was replaced with L-alanine, deleted, or substituted with its D-isomer. The potency of each analog to stimulate ion transport in the rabbit ileum was then determined using the modified Ussing chamber technique. The results were compared to the ability of each analog to inhibit the stimulated release of growth hormone from cultured rat anterior pituitary cells and to inhibit the arginine-stimulated release of insulin and glucagon in the rat in vivo. Analogs that showed gut selectivity were then tested for their ion transport properties in the rat colon. RESULTS: (a) Substitution with L-alanine or deletion of the amino acid at position 6, 7, 8, or 9 and deletion of Threonine(10)-produced analogs with significantly reduced ion transport properties to <4% of somatostatin's action. The substitution also markedly reduced the ability of the compounds to inhibit the release of growth hormone, insulin, and glucagon. (b) Selectivity of intestinal ion transport was achieved by any one of the following alterations: L-alanine substitution at Phenylalanine(11), deletion of Phenylalanine(11), substitution with D-lysine at Lysine(4), or substitution with L-alanine at Lysine(4). These compounds had intestinal ion transport properties of 52, 34, 139, and 94%, respectively, while demonstrating little or no inhibition of growth hormone, insulin or glucagon release. CONCLUSIONS: (a) Phenylalanine(6), Phenylalanine(7), Tryptophan(8), and Lysine(9) are required for the ion transport and other biologic actions of somatostatin, whereas Threonine(10) serves as an essential spacer. (b) Alteration at Phenylalanine(11) or Lysine(4) yields analogs that are selective for ion transport in the rabbit ileum and rat colon. These findings should be taken into consideration when developing a gut-specific somatostatin analog that can be useful in the treatment of diarrhea.

Expression of a Drosophila melanogaster acetylcholine receptor-related gene in the central nervous system.

We isolated Drosophila melanogaster genomic sequences with nucleotide and amino acid sequence homology to subunits of vertebrate acetylcholine receptor by hybridization with a Torpedo acetylcholine receptor subunit cDNA probe. Five introns are present in the portion of the Drosophila gene encoding the unprocessed protein and are positionally conserved relative to the human acetylcholine receptor alpha-subunit gene. The Drosophila genomic clone hybridized to salivary gland polytene chromosome 3L within region 64B and was termed AChR64B. A 3-kilobase poly(A)-containing transcript complementary to the AChR64B clone was readily detectable by RNA blot hybridizations during midembryogenesis, during metamorphosis, and in newly enclosed adults. AChR64B transcripts were localized to the cellular regions of the central nervous system during embryonic, larval, pupal, and adult stages of development. During metamorphosis, a temporal relationship between the morphogenesis of the optic lobe and expression of AChR64B transcripts was observed.

Cell lines containing and expressing the human herpesvirus 6A ts gene are protected from both H-ras and BPV-1 transformation.

Human herpesvirus 6A (HHV-6A) strain U1102 was previously shown to contain a 1473 bp transformation suppressor gene (ts) (Araujo et al., 1995). Ts inhibited transformation of NIH3T3 cells by H-ras and transcription of the H-ras and human immunodeficiency type 1 (HIV-1) promoters in transient transfection experiments. In the current study, stable NIH3T3 cell lines expressing ts protein were established by transfection with pRc-ts containing the ts gene under the control of the Rous sarcoma virus (RSV) long terminal repeat (LTR) and a neomycin selectable marker. Selected cell lines contained approximately one to two copies per cell of intact ts sequences, expressed ts protein and grew at approximately the same rate as parental NIH3T3 cells. These cell lines were protected from H-ras transformation while parental and NIH3T3 cells containing the ts gene cloned in the antisense orientation were not. Expression of the chloramphenicol acetyl transferase (CAT) gene under the control of the EJ-H-ras promoter was also suppressed in the ts cell lines but not when the CAT gene was under the control of the murine osteosarcoma virus LTR or human cytomegalovirus immediate early promoter. When NIH3T3 cell lines expressing ts protein were established by infection with the retrovirus, LNCts, the cells expressed ts protein and were protected from H-ras transformation. Furthermore, bovine papillomavirus type 1 (BPV-1) transformation was also suppressed in cells co-transfected with BPV-1 plus ts and in ts expressing cell lines transfected with BPV-1. The BPV-1 p89 and p2443 promoters were down-regulated in 3T3-ts lines. Because the human papillomavirus type 16 (HPV-16) p97 promoter has similarity to the BPV-1 p89 promoter, the ability of ts to suppress p97 was also tested. Like the H-ras and BPV-1 promoters, HPV-16 p97 was down-regulated in 3T3-ts lines. The data indicate the utility of ts against H-ras, BPV-1 and HPV-16 promoters and their respective oncogenes.

A transforming fragment within the direct repeat region of human herpesvirus type 6 that transactivates HIV-1.

HHV-6 infection has been associated with several malignancies including non-Hodgkin's lymphoma and Hodgkin's disease by the presence of high antibody titer and/or the presence of HHV-6 DNA. To understand their oncogenic potential, SalI restriction fragments from HHV-6 strain U1102 were transfected into NIH3T3 cells to assess transforming ability. A 3.9-kbp SalI-L DNA fragment spanning the junction of the direct repeat left (DRL) and unique long segment (UL) regions of HHV-6 induced foci of morphologically altered cells. The SalI-L transformed NIH3T3 focal lines induced tumors in nude mice within 2 weeks. The retention of HHV-6 specific DNA observed in SalI-L transformed cells and their tumor-derived lines suggest a possible maintenance function. Since both HHV-6 infection as well as transforming fragments from other DNA viruses have been shown to transactivate the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR), SalI-L was examined for transactivation activity. SalI-L up-regulated HIV-1 LTR CAT 10-15 fold in both monkey CV-1 and human T Jurkat cells. The further study of the SalI-L transforming fragment exhibiting transactivation of HIV-1 LTR will elucidate whether these two activities are encoded by a single gene and will aid in the understanding of the interaction between HHV-6 and HIV-1 as it relates to progression of AIDS and/or AIDS-related malignancies.

Human herpesvirus 6 (HHV-6) ORF-1 transactivating gene exhibits malignant transforming activity and its protein binds to p53.

The 357 amino acid open reading frame 1 (ORF-1), also designated DR7, within the SalI-L fragment of human herpesvirus 6 (HHV-6) exhibited transactivation of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) promoter and increased HIV-1 replication (Kashanchi et al., Virology, 201, 95-106, 1994). In the current study, the SalI-L transforming region was localized to the SalI-L-SH subfragment. Several ORFs identified in SalI-L-SH by sequence analysis were cloned into a selectable mammalian expression vector, pBK-CMV. Only pBK/ORF1 transformed NIH3T3 cells. Furthermore, cells expressing ORF-1 protein produced fibrosarcomas when injected into nude mice, whereas control cells, expressing either no ORF-1 protein or C-terminal truncated (after residue 172) ORF-1 protein, were not tumorigenic. Western blot analysis of proteins extracted from the tumors revealed ORF-1 protein. Additional studies indicated that ORF-1 was expressed in HHV-6-infected human T-cells by 18 h. Co-immunoprecipitation experiments showed that ORF-1 protein bound to tumor suppressor protein p53, and the ORF-1 binding domain on p53 was located between residues 28 and 187 of p53, overlapping with the specific DNA binding domain. Functional studies showed that p53-activated transcription was inhibited in ORF-1, but not in truncated ORF-1, expressing cells. Importantly, the truncated ORF-1 mutant also failed to cause transformation. Analysis of several human tumors by PCR revealed ORF-1 DNA sequences in some angioimmunoblastic lymphadenopathies, Hodgkin's and non-Hodgkin's lymphomas and glioblastomas. The detection of ORF-1 sequences in human tumors, while not proof per se, is a prerequisite for establishing its role in tumor development. Taken together, the results demonstrate that ORF-1 is an HHV-6 oncogene that binds to and affects p53. The identification of both transforming and transactivating activities within ORF-1 is a characteristic of other viral oncogenes and is the first reported for HHV-6.

Toward the validation of RDC schizoaffective disorder.

The Research Diagnostic Criteria (RDC) for schizoaffective disorder were applied to a clinic population of 71 patients with bipolar I disorder. Twenty-five patients were found to meet RDC criteria for schizoaffective disorder. The RDC-positive group were found to be the most psychotic patients and had a younger age at onset and admission to the clinic that the RDC-negative group. They had also had their conditions diagnosed more frequently as schizophrenic by referring physicians. There was no difference, however, between the two groups on many other variables, including clinical, family history, drug response, and laboratory studies. We conclude that our bipolar I population cannot be further subdivided into meaningful clinical entities using the RDC criteria for schizoaffective disorder.

Cooperation between CR1 (CD35) and CR3 (CD 11b/CD18) in the binding of complement-opsonized particles.

We analyzed the binding of sheep erythrocytes bearing C3b (EC3b) to cells transfected with human complement receptors. EC3b bound avidly to cells expressing CR1 but failed to bind to cells expressing CR3. In the presence of factor I, the binding of EC3b, to CR1 was transient. Primary monocytes and cotransfected cells expressing both CR1 and CR3 mediated a stable resetting of EC3b, even in the prolonged presence of factor I. This stable adhesion was dependent on the presence of CR3, because blocking CR3 with mAb resulted in the factor I-dependent release of erythrocytes from these cells. A model is proposed in which these two complement receptors cooperate in a unique manner. These results suggest that the stable adhesion of complement-opsonized particles to cells expressing CR1 and CR3 is actually a dynamic molecular process in which an important function of leukocyte CR1 is to generate the ligands for CR3.

The Sleep-Wake Activity Inventory: a self-report measure of daytime sleepiness.

The purpose of this study was to develop a valid multidimensional self-report measure of sleepiness. There were 554 subjects who completed the inventory. The structure of the Sleep-Wake Activity Inventory (SWAI) was derived from principal components analysis. The independent predictive strength of the factors was assessed by forward stepwise regression analysis with the average sleep latency on the Multiple Sleep Latency Test (MSLT) as the dependent variable. The scores on each of the factors were also compared by the level of sleepiness determined by the MSLT (pathological, diagnostic gray area, and normal). Factor analysis showed the existence of six factors on the SWAI (Excessive Daytime Sleepiness [EDS], Psychic Distress, Social Desirability, Energy Level, Ability to Relax and Nocturnal Sleep). The EDS factor was the best predictor of average MSLT. It was also able to differentiate pathological levels of sleepiness from both the diagnostic gray and normal levels of sleepiness. EDS factor scores were sensitive to changes in sleep physiology as improved scores followed normalization of sleep-disordered breathing. The SWAI was shown to be easy to complete, have a multi-dimensional structure, have a EDS factor useful in the prediction of average MSLT scores, be sensitive to differential levels of sleepiness, and change as a result of effective treatment.

Sleep disturbance and psychiatric disorders: a longitudinal epidemiological study of young adults.

In a longitudinal epidemiological study of young adults, we estimated the association between sleep disturbance and psychiatric disorders, cross-sectionally and prospectively. A random sample of 1200 was drawn from all 21-30-year-old members of a large health maintenance organization (HMO) in Michigan; 1007 were interviewed in 1989 and 979 were reinterviewed in 1992. Lifetime prevalence of insomnia alone was 16.6%, of hypersomnia alone, 8.2%, and of insomnia plus hypersomnia, 8%. The gender-adjusted relative risk for new onset of major depression during the follow-up period in persons with history of insomnia at baseline was 4.0 (95% confidence interval [CI] 2.2-7.0) and in persons with baseline history of hypersomnia, 2.9 (95% CI 1.5-5.6). When history of other prior depressive symptoms (e.g., psychomotor retardation or agitation, suicidal ideation) was controlled for, prior insomnia remained a significant predictor of subsequent major depression. Complaints of 2 weeks or more of insomnia nearly every night might be a useful marker of subsequent onset of major depression.

Psychometric evaluation of daytime sleepiness and nocturnal sleep onset scales in a representative community sample.

BACKGROUND: The public health importance of daytime sleepiness as a risk factor for accidents, interpersonal problems, and decreased productivity has been recognized. However, epidemiologic research on this topic has been limited by the reliance on laboratory measures (i.e., the Multiple Sleep Latency Test-MSLT). Two scales, daytime sleepiness and nocturnal sleep onset, have been identified from the self-report Sleep-Wake Activity Inventory (SWAI) in a clinic sample and validated against the MSLT. This study evaluates the replicability of the two scales in a population sample and assesses potential thresholds in scale scores that distinguish normal from pathologic levels of daytime sleepiness and difficulty falling asleep. METHODS: The sample consisted of 2181 subjects 18-45 years old in the Detroit metropolitan area. All sleep characteristic information covered the 2 weeks prior to interview. Split-half sample factor analyses were conducted to assess replicability of the results. Distribution of scale scores and their relation to construct validity variables were used to evaluate possible thresholds. RESULTS: A two-factor model appeared to best account for the variation among the 12 items from the SWAI. The two factors accounted for 50% of the variance in both split-half sample analyses. The revised eight-item daytime sleepiness and two-item nocturnal sleep onset scales showed good and fair internal consistency respectively across both split-half samples. There appeared to be a "natural break" in daytime sleepiness scale scores that was associated with a substantial and consistent change in number of hours slept. No breaks appeared in nocturnal sleep onset scores. CONCLUSIONS: This study replicated the results of the clinic-based study and suggested a potentially useful diagnostic threshold for self-report excessive daytime sleepiness. Epidemiology of sleep depends on the ability to move from the laboratory to population surveys in reliable and valid ways. Development of self-report is a step in that direction.

Psychopathology among children of manic-depressive patients.

Twenty-seven individuals with bipolar illness were interviewed concerning their children who were between the ages of 6 and 18 years. The structured interview included items concerning the behavior of the child during the previous year, as well as items concerning events which may have affected the child. Of 49 children, 4 were considered to have an affective disorder and 18 were considered to have an undiagnosed disorder. A child was more likely to have a disorder if the natural parents were divorced. This difference was significant. When the child was living with both natural parents, the presence of a mental illness in the nonproband parent did not increase the likelihood of illness in the child. This difference was significant. The presence of illness in the child did not seem to be related to the severity of bipolar illness in the proband parent.

The reliability of the diagnostic features in patients with narcolepsy.

This study determined the test-retest reliability of the polysomnographic findings in narcolepsy. The diagnosis of narcolepsy was based on clinical symptoms and polysomnographic signs. Control subjects were screened before participation and were split based on their screening multiple sleep latency test (MSLT) into high- and low-MSLT groups. Subjects completed two polysomnographic evaluations with at least 5 days between laboratory tests. Narcoleptics had lower sleep efficiencies and high stage 1% when compared to the low MSLT control group. They had more awakenings and less stage 2% than the control groups. Narcoleptics had a shorter latency to 1 when compared to the high-MSLT group but comparable to that of the low-MSLT group. Narcoleptics had a higher number of sleep-onset rapid eye movement periods (SOREMPs) than both control groups. The MSLT scores were stable across the two evaluations and showed a statistically significant correlation. Twenty-eight of the 30 narcoleptic subjects had two or more SOREMPs on reevaluation. None of the controls had multiple SOREMPs. Thus, multiple SOREMPs were shown to be a reliable finding in patients with narcolepsy.

HLA DR2 in narcolepsy with sleep-onset REM periods but not cataplexy.

To determine the association of HLA DR2 in patients with narcolepsy without cataplexy, a case-control study was performed. Patients receiving the diagnosis of narcolepsy without cataplexy had excessive daytime sleepiness (EDS) and polysomnographic findings consistent with narcolepsy but no clinical evidence of cataplexy. Of 28 patients identified, 12 agreed to return for HLA typing. Respondents did not differ from nonrespondents in demographic, clinical, or sleep laboratory data. The comparison group was 503 individuals, those 30 years and older, on the Michigan Kidney Transplant Registry. The odds ratio obtained from logistic regression indicated a strong association between narcolepsy without cataplexy and HLA DR2. To control for potential confounding variables, multivariate models were constructed to explore the joint effects of HLA DR2 and each one of the covariates (age, sex, and race), their possible combinations, and the effect of all three covariates. The odds ratios decreased minimally and the association between the disease and HLA DR2 remained significant.

Dynamic and biochemical responses to single and repeated doses of clonidine during dynamic physical activity.

Beta-adrenoceptor blockade increases serum K, which may be related to renin inhibition, hypoaldosteronism, and exercise-induced skeletal muscle release of serum K. We report on the dynamic and biochemical response to clonidine (C) after single (S) 0.2-mg and repeated (R) 0.1-mg bid doses of C to six normal subjects at rest, 2 hr after dosing and immediately before dynamic physical activity (DPA) on a treadmill, and at peak activity and 2 hr after DPA. Blood pressure (BP), heart rate (HR), plasma renin concentration (PRC), aldosterone (ALD), serum K, epinephrine (E), and norepinephrine (NE) were measured in standing subjects before and 2 hr after placebo or C (S or R), at peak DPA, and 2 hr after exercise. K, BP, and HR were also determined during all stages of DPA. Results show a parallel rise in K at peak over rest after C (S or R) and after placebo. NE, E, and PRC decreased after 1 wk of C (P less than 0.01), but the fall of ALD was only slight. The fall in NE at rest suggested a relationship to the decrease in systolic BP and rate pressure product after 1 wk on C. With DPA there is a normal yet smaller increase in systolic BP and also a smaller rise in HR with S- and R-dose C. There is no adverse rise in K in C-treated subjects during DPA.

Biochemical and dynamic responses to single and repeated doses of methyldopa and propranolol during dynamic physical activity.

Our purpose was to describe changes in potassium disposition with antirenin antihypertensives during dynamic physical activity in normal subjects receiving methyldopa and propranolol. Before the study, 2 hr after dosing and coincident with immediate preexercise on treadmill (at graded increases of exercise), and 2 hr after exercise, blood was sampled for determination of potassium, renin, aldosterone, and catecholamine levels. Blood pressure and heart rate were measured. The results demonstrate no greater increase in potassium after single or multiple doses of methyldopa than after placebo. After the first dose of propranolol there was a greater rise in potassium over that with placebo, but it was not observed after multiple doses, which may be related to the low doses. There were minor, but significant, changes in norepinephrine, renin, and systolic pressure with multiple-dose methyldopa and in renin, heart rate, and systolic and diastolic pressure with propranolol. Overall, the adrenergic responses to exercise win methyldopa and propranolol were biochemically altered rather than functionally impaired. The latter is related to dose and the underlying age and state of health of our subjects. Methyldopa (or clonidine) may be useful in patients with hypertension who exercise and are predisposed to pertubations in potassium disposition.