The erythrocyte sedimentation rate in congestive heart failure

BACKGROUND AND METHODS. Physicians have long believed that the erythrocyte sedimentation rate is low in patients with congestive heart failure, but this concept is based on a misinterpretation of the results in a single report published in 1936. To reevaluate this concept in the modern era, we measured the sedimentation rate in 242 patients who were referred for treatment of chronic heart failure. RESULTS. The sedimentation rate was low (less than 5 mm per hour) in only 24 patients (10 percent) but was increased (above 25 mm per hour) in 50 percent. Patients with low or normal sedimentation rates (less than or equal to 25 mm per hour) had more severe hemodynamic abnormalities than patients with elevated rates: lower cardiac index (mean +/- SEM, 1.7 +/- 0.1 vs. 2.0 +/- 0.1 liters per minute per square meter of body-surface area) and higher mean right atrial pressure (mean +/- SEM, 12 +/- 1 vs. 9 +/- 1 mm Hg) (both P less than 0.0001). New York Heart Association functional class IV symptoms were present in 66 percent of the patients with a low or normal sedimentation rate, as compared with 42 percent of those with elevated rates (P less than 0.0001). After one to three months of therapy, patients whose sedimentation rates decreased showed little hemodynamic or clinical response to treatment, whereas both cardiac performance and functional status improved in patients whose rates increased (P less than 0.02 for the comparison between groups). The sedimentation rate was correlated with the plasma fibrinogen level (r = 0.64, P = 0.0025), and changes in the sedimentation rate during treatment were correlated inversely with changes in mean right atrial pressure (r = -0.57, P = 0.0002). During long-term follow-up, patients with low or normal sedimentation rates had a worse one-year survival than patients with elevated rates (41 vs. 66 percent, P = 0.01). CONCLUSIONS. These data indicate that the erythrocyte sedimentation rate is correlated with the severity of illness in patients with chronic heart failure. Because of its lack of discriminatory power, however, the test is of limited value in the clinical management of this disorder.     

A Direct Comparison of the Skin Conductance and Skin Resistance Methods

The purpose of the present study was a direct comparison between simultaneous recordings of skin conductance and skin resistance. Sixty male students received a series of 30 white noise stimuli, while measures were taken continuously from four sites on the palmar surfaces of the fingers. Evaluations were made for response amplitudes, recovery, and for an approximate area measure. Magnitude of reactions and reliabilities were compared using ANOVA procedures. Behavioral concordances were estimated as correlations with the subjects' ratings of stimulus intensities. Conductance and resistance measures do not differ in amplitude, in area, or in strength of their reliabilities and behavioral concordances. No differences in any respect are found between sites. Skin conductance yields significantly (p < .01) shorter recovery times than skin resistance, which is discussed in terms of membrane permeability change.     

Substance P and somatostatin metabolism in sympathetic and special sensory ganglia in vitro

Mechanisms regulating the content of the putative peptide transmitters, substance P and somatostatin, were examined in several neuronal populations in culture. Substance P levels increased more than 25-fold within 48 h in sympathetic neurons in the explanted rat superior cervical ganglion, and remained elevated for 4 weeks. Identity of the peptide was authenticated by combined high pressure liquid chromatography-radioimmunoassay. Veratridine prevented the increase of substance P in vitro, and tetrodotoxin blocked the veratridine effect, suggesting that sodium ion influx and membrane depolarization prevent peptide elevation. Veratridine (or potassium)-induced membrane depolarization released substance P into the culture medium through a calcium-dependent process. Consequently, at least some veratridine effects are attributable to release and subsequent depletion of ganglion peptide. However, the inhibitory effects of veratridine were far greater than could be accounted for by the quantity of peptide released, suggesting a separate influence on net synthesis (synthesis less catabolism) of substance P. Viewed in conjunction with previous in vivo studies, our observations suggest that trans-synaptic impulses, through the mediation of postsynaptic sodium flux, release substance P from sympathetic neurons and also regulate intracellular peptide metabolism. To determine whether the processes regulating substance P in sympathetic neurons reflect generalized mechanisms, a different peptide, somatostatin, was examined in sympathetic neurons; moreover, substance P was examined in a different neuronal population, special sensory neurons in the nodose ganglion. Substance P levels increased significantly in both sympathetic and sensory neurons after explantation, and somatostatin levels increased in sympathetic neurons. In each instance, the increase was dependent upon the presence of the calcium ions. Moreover, these increases were all prevented by veratridine, in a tetrodotoxin-sensitive manner. Our observations suggest that common regulatory mechanisms govern peptide transmitter metabolism in diverse neuronal populations.     

Die pH-Aktivitätsspektren der sauren proteolytischen Enzymaktivitäten von Harn und Serum

Zusammenfassung 1. Die p_H-Abhängigkeit der sauren proteolytischen Enzymaktivitäten von Harn und Serum wurde mit Hämoglobin und Casein als Substraten mittels zweier unabhängiger analytischer Methoden im Bereich von p_H 0,9–4,4 untersucht. Die p_H-Aktivitätskurven von Harn und Serum wiesen hinsichtlich der Form, der Lage und der Ausprägung von Aktivitäts-Maxima deutliche Unterschiede auf. Die mittlere Aktivität der Seren betrug etwa ein Drittel der mittleren proteolytischen Aktivität der Harne.2. Die saure proteolytische Enzymaktivität des Harnes wurde durch Zusatz einer Heparin-Präparation gehemmt. Das Maximum der Hemmung lag zwischen p_H 2,2 und 3,0.3. Die saure proteolytische Enzymaktivität des Harnes zeigte sich bei p_h 3,50 alkalistabiler als diejenige bei p_H 2,15.4. Die Befunde werden im Hinblick auf die Theorie einer exogen-endogenen Partition der Enzyme des Gastrointestinaltraktes und die Heterogenität der sauren gastrointestinalen Proteasen diskutiert. Es wird geschlossen, daß die Bestimmung einer renalen Protease-Clearance wegen fehlender Zuordnungsmöglichkeit der proteolytischen Enzymaktivitäten von Harn und Serum zu bestimmten Enzymen bzw. Proenzymen noch nicht möglich ist.     

Serotonin transporter binding in Tourette Syndrome

Recent studies provided evidence for an involvement of the dopaminergic system in the pathophysiology of Tourette Syndrome (TS). However, little is known about possible impairment of other neurotransmitter systems. In obsessive-compulsive disorder (OCD), a common comorbidity in TS, it is suggested that the serotonergic system plays a major role in the pathogenesis. We, therefore, used [I-123]2[beta]-carbomethoxy-3[beta]-(4-iodophenyl)tropane ([123I]beta-CIT) and single photon emission computed tomography (SPECT) to investigate serotonin transporter (SERT) binding capacity in 12 patients with TS with various degrees of associated obsessive compulsive behaviour (OCB) and 16 age-matched healthy controls. Binding ratios in TS patients not receiving serotonin reuptake inhibitors (SSRI) (n=8) were significantly reduced compared to age-adjusted ratios from normal controls (2.8 versus 3.2, p=0.003). Treatment with SSRI resulted in a significant reduction of SERT availability. Performing linear regression analysis for this small group, SSRI-free patients indicated trends for a negative correlation between [123I]beta-CIT binding on SERT and OCB (r=-0.78, p=0.023) as well as complex motor tics (r=-0.68, p=0.064). In healthy controls, but not in the TS group, we found an age-related decline in SERT binding capacity (0.28% decrease per year, p=0.038). Our data are in agreement with previous results suggesting an impairment of the serotonergic system in TS. It can be speculated that the reduction in SERT binding capacity is associated with the degree of comorbid OCB.     

Neuronal colonic dysplasia associated with short-segment Hirschsprung's disease. A possible cause of therapeutic failure

We describe two cases of short-segment Hirschsprung's disease associated with neuronal colonic dysplasia. The recurrence of postoperative symptoms of bowel obstruction may be due to the combined occurrence of these two disorders.     

Severe combined immunodeficiency with B lymphocytes: in vitro correction of defective immunoglobulin production by addition of normal T lymphocytes.

A 6 1/2-month-old male with severe combined immunodeficiency (SCID) had a low percentage and number of T cells (11%; 241/mm3) and a high percentage and number of B cells (52%; 1187/mm3) and null cells (37%; 868/mm3). In vitro studies were performed to determine if this child's primary defect involved differentiation of both T and B lymphocytes or if failure of B lymphocytes to differentiate into immunoglobulin producing cells was secondary to T lymphocyte abnormalities. Immunoglobulin production by lymphocytes in response to polyclonal mitogens (pokeweed mitogen and foetal calf serum) was measured by pulse-labelling cells with 3H-leucine and then precipitating cytoplasmic and secreted immunoglobulins with polyvalent anti-human immunoglobulin and S. aureus (Cowan strain I) protein A. The patient's lymphocytes did not synthesize immunoglobulins in vitro in response to mitogens. They did not suppress synthesis of immunoglobulins by normal lymphocytes. However, addition of normal purified T cells, which themselves did not synthesize immunoglobulins, enabled the patient's B lymphocytes to become immunoglobulin synthesizing and secreting cells. Gamma, mu, and light chains were secreted. This suggests that the primary abnormality was in the T-cell axis at the level of lymphoid stem cells or prothymocytes and that failure of B lymphocytes to become immunoglobulin-producing cells was secondary to this defect.     

OH Radical-induced chemical reactions of polynucleotide complexes

Poly(A + U), the 1:1 complex of poly(riboadenylic acid), poly A, and poly(ribouridylic acid), poly U, at pH 8 and self-complexed poly A at pH 4 exist as double helices in dilute aqueous solution. These complexes exhibit a similar behavior as native calf thymus DNA upon irradiation with 16 MeV electron pulses. Thus time resolved Rayleight light scattering measurements showed that crosslinking and double strand breakage can be clearly separated, the former proceeding faster than the latter. The extent to which the two processes occur depends on the ionic strength of the solution. At ionic strenghts exceeding 10 ^?1 mol/l crosslinking is the dominant process indicating that h_crit, the critical length between two single strand breaks for the accomplishment of double strand breaks, is strongly reduced. The investigation of complexes of poly A and Mg²⁺ ions revealed that the destruction of salt bridges is the rate determining process for the decrease of the light scattering intensity due to mainchain scission. This implies that life-times of salt bridges can be determined.     

Detection of methicillin-resistant Staphylococcus aureus and simultaneous confirmation by automated nucleic acid extraction and real-time PCR

A molecular assay for the simultaneous detection of a Staphylococcus aureus-specific gene and the mecA gene, responsible for the resistance to methicillin in staphylococci, was evaluated. The assay included an automated DNA extraction protocol conducted with a MagNA Pure instrument and real-time PCR conducted with a LightCycler instrument. The performance and robustness of the assay were evaluated for a suspension of methicillin-resistant S. aureus (MRSA) strain with a turbidity equivalent to a McFarland standard of 0.5, which was found to be the ideal working concentration. The specificity of the new molecular assay was tested with a panel of 30 gram-negative and gram-positive bacterial strains other than MRSA. No cross-reactivity was observed. In a clinical study, 109 isolates of MRSA were investigated. All clinical MRSA isolates gave positive results for the S. aureus-specific genomic target, and all but one were positive for the mecA gene. In conclusion, the new molecular assay was found to be quick, robust, and laborsaving, and it proved to be suitable for a routine molecular diagnostic laboratory.     

Depressive symptoms and disability in acute and chronic back pain patients

Depression and level of disability are evaluated in acute and chronic low back pain (LBP) patients. To assess the possibility that some somatic symptoms are confounded with pain, the items of the Beck Depression Inventory arc divided into a cognitive-affective and somatic subscale. The sample consisted of 37 chronic LBP patients. 41 acute LBP patients, and 28 healthy participants. The level of disability was assessed by the Oswestry Low Back Pain Disability Questionnaire. Chronic LBP patients, but not acute LBP patients, have more depressive symptoms than controls. Additionally, chronic LBP patients report more somatic symptoms of depression (e.g.. emo ltional and self disturbance complaints) than cognitive-affective symptoms. Finally, correlation statistics reveal significant relations between the level of disability and depression scores. Whereas chronic patients show a significant correlation between the somatic subscale and level of disability, in acute patients the cognitive-affective subscale is significantly related to the level of disability. The findings suggest careful consideration of whether somatic symptoms of depression are related to pain when using self-report measurements of depression in pain patients. The separation of cognitive-affective and somatic symptoms of depression to evaluate pain problems seems appropriate.