Calciphylaxis – a topical overview

'Calciphylaxis', a calcification syndrome associated with ischaemic cutaneous necrosis, is acquired naturally in humans in disease states. It is a life and limb-threatening complication, usually observed in patients with renal disease and secondary hyperparathyroidism, but known to occur in the absence of renal or parathyroid disease. The reported mortality rate, which ranges from 60-80%, relates to wound infection, sepsis and organ failure. It is a small-vessel vasculopathy, which is estimated to occur in about 4% of haemodialysis patients. Clinically, violaceous, reticulate areas of cutaneous necrosis and eschar may be evident, particularly in the extremities. In addition to the clinical picture, a raised calcium phosphorous product, an elevated parathyroid hormone level, radiographic evidence of vessel and soft-tissue calcification and the finding of mural calcification affecting small arteries and arterioles on histopathology help to confirm the diagnosis of this entity which generally has a poor prognosis. A high index of suspicion and an active multidisciplinary management approach, with rigorous attention to wound care and prevention of sepsis, are vital in the management of these patients. In this overview, we discuss the pathophysiology, clinical features and associations, risk factors, diagnosis and management issues relating to calciphylaxis.     

Assessment of cardiovascular autonomic function.

Autonomic assessment has played an important role in elucidating the role of the autonomic nervous system in diverse clinical and research settings. The techniques most widely used in the clinical setting entail the measurement of an end-organ response to a physiological provocation. The non-invasive measures of cardiovascular parasympathetic function involve the analysis of heart rate variability while the measures of cardiovascular sympathetic function assess the blood pressure response to physiological stimuli. Prolonged tilt-table testing, with or without pharmacological provocation, has become an important tool in the investigation of a predisposition to neurally mediated (vasovagal) syncope. Frequency domain analyses of heart rate and blood pressure variability, microneurography, occlusion plethysmography, laser Doppler imaging and flowmetry, and cardiac sympathetic imaging are currently research tools but may find a place in the clinical assessment of autonomic function in the future.     

THERAPEUTIC PROGRESS IN INTENSIVE CARE SEDATION AND ANALGESIA PART II—DRUG SELECTION

In part I of this review the principles governing the uses of analgesics and sedatives in the ITU were considered. In part II we shall review the drugs available considering first, symptomatic therapy and secondly, regional analgesia.     

Variables that affect the expansion rate and outcome of small abdominal aortic aneurysms

Seventy-three patients with small (less than 6 cm in diameter) abdominal aortic aneurysms (AAAs) were selected for nonoperative management and followed up with sequential ultrasound size measurements. Fifty-four men and 19 women, 51 to 89 years of age (mean 70 years), had an initial mean AAA size of 4.1 cm (anteroposterior) x 4.3 cm (lateral) diameter, with a calculated elliptic cross-sectional area of 14.3 cm2. After a mean of 37 months of follow-up, AAA area increased at a mean rate of 20% per year (3 cm2 yr; 0.4 to 0.5 cm/yr diameter). Expansion rate was not affected by initial aneurysm size. During follow-up, only 3 patients (4%) required urgent operation (1 died), 26 patients (36%) died of non-AAA causes, and 26 patients (36%) underwent elective AAA repair because of progressive size increase (1 died). Elective operations were performed at the rate of 10% per year, when mean AAA size had increased to 22 cm2 (5.1 cm in diameter). Multiple regression analysis of clinical parameters available at presentation indicated that subsequent elective AAA repair was predicted by younger age at diagnosis and larger initial aneurysm size. As anticipated, patients who underwent surgery had more rapid aneurysm expansion (5.3 cm2/yr) compared with patients who did not undergo surgery (1.6 cm2/yr; p less than 0.05). This difference was caused by more rapid expansion during later follow-up intervals among patients selected for operation and was not predicted by the change in aneurysm size observed during initial ultrasonographic follow-up. Final aneurysm size was predicted by initial size, duration of follow-up, and both systolic and diastolic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

A noninvasive method of predicting pulmonary-capillary wedge pressure.

BACKGROUND. The noninvasive prediction of pulmonary-capillary wedge pressure (PCWP) is important for the recognition and treatment of a variety of cardiovascular disorders. The response of the arterial pressure to the Valsalva maneuver has been shown to correlate with the PCWP. We therefore devised a noninvasive method to measure this pressure response at the bedside and correlated these measurements with the PCWP measured directly with a pulmonary-artery catheter. METHODS. Simultaneous, blinded, noninvasive measurements of the ratio of the final amplitude to the initial amplitude of the pulse wave form during the stress phase of the Valsalva maneuver (pulse-amplitude ratio) and direct measurements of the PCWP were obtained in 20 clinically stable patients and in 14 clinically unstable patients who were receiving vasoactive agents, 12 of whom also had endotracheal tubes in place. RESULTS. Using linear regression analysis, we found that the pulse-amplitude ratio strongly correlated with the measured PCWP over a range of base-line values from 4 to 32 mm Hg for the 20 clinically stable patients (R2 = 0.80) and the 14 clinically unstable patients (R2 = 0.85). The method also correctly predicted changes in the PCWP after the administration of nitroglycerin or furosemide and after expansion of the intravascular volume (R2 = 0.79). CONCLUSIONS. These preliminary data indicate that a simple noninvasive method can accurately predict the PCWP and changes in the PCWP in response to medical therapy.     

Factors associated with hypertension in Nigerian civil servants

BACKGROUND. Study of hypertension in segments of West African populations in transition toward Westernization may lead to better understanding of the high risk for hypertension among Westernized blacks. METHODS. Five hundred fifty-nine urban civil servants, ages 25-54, were recruited from six ministries of Bendel State, Nigeria. Blood pressure, physical measurements, urinary protein and glucose, fasting blood glucose, and demographic data were collected at the workplace. Subjects were classified as senior staff (professionals or administrators) or junior staff (non-administrators). RESULTS. Among 172 male senior staff, the age-adjusted rate of hypertension (diastolic blood pressure > or = 90 mm Hg, systolic blood pressure > or = 140 mm Hg, or on an antihypertensive medication) was 43% and occurrence rose dramatically from 21 to 63% across age groups 25-34 to 45-54, respectively. Among 266 male junior staff, the age-adjusted rate of hypertension was 23%, and occurrence did not rise with age. Logistic regression showed that body mass index (kg/m2), age, alcohol drinking, and being senior staff were all independently related to hypertension in men. On the other hand, the age-adjusted rate of hypertension in 121 women was 20% and was significantly related only to body mass index. CONCLUSION. Male urban civil servants appeared to have a risk for hypertension similar to that of U.S. black males. Age, body mass index, alcohol drinking, and other unidentified factors related to higher socioeconomic status were strong determinants of hypertension in this population.     

Activity of vasoactive intestinal peptide and serotonin in the paraventricular nucleus reflects the periodicity of the endogenous stimulatory rhythm regulating prolactin secretion.

PRL secretion in the female rat is regulated by an endogenous stimulatory rhythm (ESR) of prolactin-releasing factors of hypothalamic origin which has a bimodal periodicity with distinct nocturnal (N) and diurnal (D) phases. The N phase reaches peak magnitude by 0300 h and the D phase reaches peak magnitude by 1700 h. This rhythm was first unmasked in ovariectomized rats by correctly timed injection of a dopamine antagonist. OT, vasoactive intestinal peptide (VIP), and serotonin (5-HT) are differentially involved in generating the ESR. Pharmacological studies suggest that OT is the neurohormone and VIP and 5-HT are neuromodulators which act to stimulate OT release. Recently, we reported that activity of OTergic neurons in the paraventricular nucleus (PVN) and OT concentrations in the anterior pituitary mirror the periodicity of the ESR. The present experiments were conducted to determine if VIP and 5-HT activity in the hypothalamus also mirrors the periodicity of the ESR. Push-pull cannulae were surgically implanted in the PVN of ovariectomized female rats. Following recovery, push-pull perfusion was conducted from either 0600-1400 h, 1400-2200 h, or 2200-0600 h. VIP was measured in perfusates by RIA. There was no difference in VIP pulse frequency between rats perfused during the three periods studied. However, animals perfused from 2200-0600 h had significantly greater pulse amplitude as compared to rats at either 0600-1400 h or 1400-2200 h. Activity of 5-HTergic neurons in the hypothalamus was studied by estimating the turnover of 5-HT 10 min following the injection of pargyline. Hypothalamic nuclei were dissected using Palkovits' punch technique and 5-HT concentration assayed by HPLC in conjunction with electrochemical detection. Turnover of 5-HT was estimated by calculating the slope of the accumulation of 5-HT over 10 min at differing times of day using least squares regression analysis. There was a distinct diurnal rhythm of 5-HT accumulation in the PVN. Rats killed at 1700 h had significantly greater slopes of 5-HT accumulation in the PVN than rats killed at either 0300 or 1200 h. Similarly, there was a diurnal rhythm of 5-HT turnover in the suprachiasmatic nucleus. Rats sampled at either 1200 or 1700 h had significantly greater slopes of 5-HT accumulation in the suprachiasmatic nucleus than rats sampled at 0300 h. There was no diurnal rhythm of 5-HT turnover evident in either the median eminence or the supraoptic nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)