Autonomic Nervous System Function and Essential Hypertension: Individual Response Specificity With and Without Beta-Adrenergic Blockade

The aim of the present research was to study individual response specificity in 22 male patients having essential hypertension (HT) and to compare these patients with age-matched male normotensive controls (NT). Four stimuli, letter identification, mental arithmetic, cold pressor and isometric exercise, were administered while recordings were made of: systolic and diastolic blood pressures, heart rate, respiration, forearm and hand blood flows, and skin conductance level and fluctuations. After each session urine samples were collected and epinephrine and norepinephrine levels were analyzed. Twelve subjects in the HT group were given beta-adrenergic blocking agents and retested 1 to 21 months (X?= 12 months) after the first session. Each response was standardized, using NT as the reference group. Intraclass correlations were computed to evaluate whether HT males reacted with a more consistent hierarchy of responses than did NT. Intraclass correlations were significantly higher among the patients than in the control group, regardless of whether the blood pressure response was included or excluded in the computation of the intraclass correlations. Thus, we conclude that male HT patients show more individual response specificity than NT controls. Beta-adrenergic receptor antagonists reduced levels of cardiovascular activity and attenuated reactivity but did not affect amount of specificity. Thus, intraclass correlations provide unique and useful information, since they are not related to blood pressure reactivity or to urinary catecholamine levels, nor affected by beta-adrenergic blockade.     

A behavioral analysis of chest pain in patients suspected of having coronary artery disease

A group of 83 men and women who had been referred to Johns Hopkins Hospital for cardiac catheterization for evaluation of chest pain and possible coronary artery bypass surgery were assessed behaviorally for their chest pains. During the approximately 2-week period between clinical evaluation and catheterization, the patients completed self-report forms about their chest pains. Patients completed one form for each episode of chest pain. Referring physicians also completed a form about the patients "typical" chest pain. The data were analyzed in terms of the antecedents, concomitants, and consequences of the chest pain, and patients' reports were compared to physicians' judgments. Major findings were as follows: 1) Antecedents--most episodes occurred while the patient was at home at times when his mood was one of contentment. 2) Concomitants--the average patient reported fewer than one episode per day which persisted for about 4 min and was rated as 36 on a scale of 0 to 100. The most common physical symptoms accompanying the episode were breathlessness and weakness, and the most common pain sensations were reported to be pressing or aching. There was no consistency among patients either in primary location or path of radiation of the pain. Duration of pain did not correlate significantly either with sensation or symptoms; however, severity rating did correlate with symptoms and sensations. 3) Consequences--most episodes were self-treated with nitroglycerin or rest. Patients typically returned to their ongoing activities; however, there were a number of interactions between the likelihood of returning to ones ongoing activity and the antecedents of the episodes. 4) The referring physicians significantly overestimated the frequency and severity of their patients' episodes; furthermore, they were selective in their abilities to identify correctly the antecedents or concomitants associated with their patients' pain--e.g., they were reliable in their judgments about subjects who had sleep-related episodes; however, they were inaccurate in characterizing the typical sensations or symptoms reported by their patients. It is suggested that a behavioral analysis may enable a physician to characterize his patient's chest complaints better, and perhaps also may facilitate the differentiation between chest complaints indicative of coronary artery disease and chest complaints of a noncoronary origin.     

Learned control of heart rate during exercise in patients with borderline hypertension

Summary Twelve patients with borderline hypertension [⩽21.33/12.6, ⩾18.6/12.0 kPa (⩽160/ 95; ⩾ 140/90 mm Hg)] participated in an experiment aimed at testing whether they could learn to attenuate heart rate while exercising on a cycle ergometer. Six experimental (E) subjects received beat-to-beat heart-rate feedback and were asked to slow heart rate while exercising; six control (C) subjects received no feedback. Averaged over 5 days (25 training trials) the exercise heart-rate of the E group was 97.8 bt min⁻¹, whereas the C group averaged 107 bt min⁻¹ (P=0.03). Systolic blood pressure was unaffected by feedback training. Generally, changes in rate-pressure product reflected changes in heart-rate. Oxygen consumption was lower in the E than in the C group late in training. We conclude that neurally mediated changes associated with exercise in patients with borderline hypertension can be brought under behavioral control through feedback training.     

A Mott cell hybridoma

A hybridoma is described that exhibits all the characteristic features of Mott cells. It has spherules (Russell bodies) in the cytoplasm made up of dilated rough endoplasmatic reticulum and containing condensed immunoglobulin (λ₁ light chains). Some of the cells appear to be very fragile, and free spherules are often found on cell smears. Cells with the Mott cell characteristics are still able to divide, but they do not secrete immunoglobulin. Hybridomas of this kind should be useful for determining the place of the Mott cell within the scheme of B cell differentiation.     

The LHRH antagonist cetrorelix: a review

In those clinical situations in which an immediate and profound suppression of gonadotrophins is desired, LHRH agonists have the disadvantage of producing an initial stimulatory effect on hormone secretion. Therefore, the use of GnRH antagonists which cause an immediate and dose-related inhibition of LH and FSH by competitive blockade of the receptors is much more advantageous. One of the most advanced antagonist produced to date is Cetrorelix, a decapeptide which has been shown to be safe and effective in inhibiting LH and sex-steroid secretion in a variety of animal species and in clinical studies as well. Clinical trials in patients suffering from advanced carcinoma of the prostate, benign prostate hyperplasia, and ovarian cancer are currently in progress and have already shown the usefulness of this new treatment modality. In particular, the concept that a complete suppression of sex-steroids may not be necessary in indications such as uterine fibroma, endometriosis and benign prostatic hyperplasia represents a promising novel perspective for treatment of these diseases. Following completion of phase III trials in controlled ovarian stimulation for IVF regimens, Cetrorelix was given marketing approval and, thus, became the first LHRH antagonist available clinically.     

Pancreatic mucinous noncystic (colloid) carcinomas and intraductal papillary mucinous carcinomas are usually microsatellite stable.

Pancreatic mucinous noncystic (colloid) carcinomas (MNCC) differ from the usual ductal adenocarcinomas in their mucin expression profile and share with many extrapancreatic mucinous carcinomas the expression of MUC2. Because mucinous carcinomas are frequently associated with mutations of the DNA mismatch repair genes, causing them to exhibit the so-called mutator phenotype, we decided to investigate whether MNCCs of the pancreas are characterized by microsatellite instability (MSI). Twelve carcinomas with a mucinous phenotype (8 mucinous noncystic carcinomas, 3 intraductal papillary-mucinous carcinomas with an invasive muconodular component, and 1 ductal adenocarcinoma with an extensive mucinous noncystic component) and 11 ductal adenocarcinomas were immunostained with monoclonal antibodies to the mismatch repair gene products hMLH1, hMSH2, and hMSH6. For MSI analysis, DNA was isolated from microdissected tissue, and five primary microsatellites (BAT 25, BAT 26, D5S346, D17S250, and D2S123) were analyzed. MSI was diagnosed in case a novel allele was found, compared with the normal tissue. The criterion for LOH was a 75% signal reduction. All carcinomas tested exhibited nuclear expression of mismatch repair gene products, except for one MNCC that also showed MSI at the molecular level. The data suggest that pancreatic carcinomas with a mucinous phenotype (MUC2+/MUC1-) do not appear to normally exhibit mutations in the mismatch repair genes and therefore differ in their carcinogenesis from those in other organs.     

Serum immunoglobulin G antibody to Porphyromonas gingivalis in rapidly progressive periodontitis: titer, avidity, and subclass distribution.

Porphyromonas gingivalis is a suspected pathogen in rapidly progressive periodontitis (RPP). We have determined the anti-P. gingivalis serum immunoglobulin G (IgG) isotype response and avidity and the subclass titer distributions for 30 RPP patients and 30 age-, sex-, and race-matched healthy subjects by using enzyme-linked immunosorbent assay technology. Patients and control subjects were classified as seropositive if their total IgG response to P. gingivalis was twofold or more than the median response in healthy subjects. The predominant antibody responses for both patients and healthy subjects were IgG2 and IgG3, with a subclass order of IgG2 greater than IgG3 greater than IgG1 greater than IgG4. The avidity of the IgG response was highest for the seropositive healthy subjects and was no different between seronegative and seropositive RPP patients. The subclass antibody responses did not depend on gender, and there were no correlations between titer, avidity, or subclass with disease severity in the RPP patients as measured by pocket depth or bone loss on dental X rays. The seronegative RPP patients exhibited antibody responses that were greater than the responses of seronegative healthy subjects for all four subclasses, while the seropositive RPP patients had higher IgG1 and IgG4 levels than seropositive healthy subjects. These findings are consistent with the hypothesis that both carbohydrate and protein antigens are important in the IgG response to P. gingivalis. The relative predominance of IgG2, a subclass which lacks strong complement fixation and opsonic properties, and the low avidity of patient anti-P. gingivalis IgG antibodies suggest that humoral responsiveness to infection with P. gingivalis may be ineffective in clearing this organism.     

Combining EL4-B5-based B-cell stimulation and phage display technology for the successful isolation of human anti-Scl-70 autoantibody fragments

Scl-70 is the major antigen recognised by autoantibodies in the sera of patients with systemic sclerosis (SSc). The autoantibodies that specifically react with Scl-70 are highly characteristic of the disease and represent valuable markers for the diagnosis of SSc. We describe a novel strategy for cloning autoantibody fragments starting with a small blood sample from an SSc patient. B cells isolated from the collected peripheral blood mononuclear cells (PBMCs) were cultured in vitro using the EL4-B5 system. Anti-Scl-70 IgG-producing cells were pooled for RNA preparation followed by the generation of phagemid libraries of approximately 10(7) independent single-chain Fvs (scFvs). The screening of these libraries by phage display allowed us to isolate four anti-Scl-70 scFvs following three rounds of biopanning. About 10 times more starting blood material was needed to generate scFv libraries of similar size from PBMCs of an SSc patient and only two anti-Scl-70 scFvs were isolated after three rounds of phage selection. Together, this work shows that functional autoantibody fragments can be advantageously cloned after in vitro expansion of B cells. The isolated anti-Scl-70 autoantibody fragments represent useful tools for calibrating SSc diagnostic assays.     

The use of successive blood-pressure measurements to estimate blood-pressure variability

Multiple daily, self-determined blood-pressure measurements were obtained from 254 hypertensive patients for 1 month. In an effort to establish a practical and reliable technique for estimating blood-pressure variability, standard deviations from three (at one time of day) or nine (throughout the day) successive self-determinations were compared with a reference value, taken to be the standard deviation for the entire month (252 determinations per subject). Neither the standard deviation of three measures taken on one occasion nor that of nine measures taken throughout the day correlated well with the reference value (average R₃=.21 for SBP, .20 for DBP; average R₉=.39 for SBP, .38 for DBP). However, when a sample consisting of 12 measures (taken three at a time, at the same time of day, weekly for 4 weeks) was used, the average correlation rose to .60 for SBP and .54 for DBP. Thus, it appears that 12 samples taken in this way provide a reliable estimate of the standard deviation for an entire month, and it is suggested that this sampling technique also would enhance the reliability of conclusions drawn from assessments of the prognostic value of blood-pressure variability.