Differences in the Nature and Kinetics of the Ethanol-related Circulating Cytotoxic Proteins in Normal Subjects and Patients with Alcohol-induced Cirrhosis

The kinetics and nature of the nondialyzable cytotoxic activity which appeared in the serum after the consumption of 1.2 g ethyl alcohol per kilogram body weight over 45 min was studied in six healthy volunteers and eight patients with histologically proven alcohol-related cirrhosis of the liver. Whereas the cytotoxic activity in the dialyzed serum showed a single peak with a maximum value 8 hr after the start of ethanol consumption in the healthy volunteers, it showed two peaks with maximum values at 2 and 8 hr in the patients with cirrhosis. Studies of the fractions obtained by Sephacryl-S-300 gel filtration of the 2-hr postalcohol serum samples revealed substantial cytotoxic activity in the fractions containing both the albumin peak and the IgG peak in the patients with cirrhosis and only in the fractions containing the albumin peak in the healthy volunteers. Experiments with pure IgG preparations obtained from prealcohol and 2-hr postalcohol sera by chromatography on Q-Sepharose Fast Flow anion-exchange resin showed considerable cytotoxic activity in the preparations from the patients with cirrhosis and little or no cytotoxic activity in those from the healthy volunteers. Thus, the early peak of the biphasic serum cytotoxicity curve seen after ethanol consumption by patients with cirrhosis appeared to be caused by the development of a substantial cytotoxic activity in the IgG molecules during the first 2 hr.(ABSTRACT TRUNCATED AT 250 WORDS)     

Does a predisposition to the metabolic syndrome sensitize women to develop pre-eclampsia?

OBJECTIVE: This study aimed to identify those factors in the non-pregnant state that distinguished women who developed pre-eclampsia from those who had normotensive pregnancies. DESIGN AND SETTING: This was a retrospective analysis of anthropometry, blood pressure, biochemical and haematological variables in 62 women with pre-eclampsia and 84 normotensive pregnant women who took part in studies of the pathophysiology of pre-eclampsia. Pregnant volunteers were seen, after admission to hospital or in the outpatient clinic, and followed-up at 6 weeks and 6 months post-partum in the outpatient clinic or their home. Participants Proteinuric pre-eclampsia was defined as blood pressure > or = 140/90 mmHg with proteinuria of at least 300 mg/24 h after 20 weeks gestation, in women with no history of hypertension and whose blood pressure returned to normal levels by 6 months post-partum. Normotensive pregnancy was defined as blood pressure < 130/90 mmHg without proteinuria. MAIN OUTCOME MEASURES: The primary outcome measures were blood pressure, body mass index (BMI), triglycerides, total cholesterol, low density lipoprotein (LDL) and high density lipoprotein cholesterol and markers of severity of pre-eclampsia. RESULTS: Regardless of parity, women with pre-eclampsia had elevated BMI before, during and after pregnancy compared with women who had normotensive pregnancies. Triglycerides were significantly elevated in women who had pre-eclampsia both before and after delivery, while total and LDL cholesterol were elevated significantly at both visits after delivery. Systolic and diastolic blood pressure, which by definition were elevated antepartum in women with pre-eclampsia, remained higher at post-partum visits compared with women who had normotensive pregnancies. Women with pre-eclampsia reported a greatly increased frequency of both maternal hypertension and pre-eclampsia. Markers of severity of pre-eclampsia, which normalized by 6 months postpartum, included plasma creatinine, uric acid, albumin, endothelin 1 and urinary protein, 2,3, dinor-6-keto-PGF1alpha, blood platelet and neutrophil counts. CONCLUSION: The relative elevation of blood pressure, BMI and lipids in the non-pregnant state are features of the metabolic syndrome and may be important sensitizing factors contributing to the pathogenesis of pre-eclampsia. A familial predisposition to pre-eclampsia may operate partly through these mechanisms.     

Is proteinuric pre-eclampsia a different disease in primigravida and multigravida?

This study aimed to identify if the clinical features of proteinuric pre-eclampsia or the biochemical markers of endothelial dysfunction associated with this syndrome are altered according to parity in a direction that would suggest a different pathophysiology. Groups of 27 primigravid and 35 multigravid women with pre-eclampsia (defined as blood pressure >140/90 mmHg and 2+ proteinuria) were studied ante-partum, and at 6 weeks and 6 months post-partum. Clinical markers of severity of pre-eclampsia, including blood pressure, markers of renal, hepatic and coagulatory function, and biochemical markers of endothelial dysfunction were measured. Fetal outcome was assessed by birthweight and birthweight percentile. Ante-partum systolic blood pressure was 10 mmHg higher in the primigravida, and this difference was independent of age and anti-hypertensive medication. Analysis of systolic blood pressure before and after delivery showed the primigravid women to have elevated systolic blood pressure over the whole time period (P<0.01). The primigravid women had more severe hepatic dysfunction, with elevated aspartate aminotransferase levels, but plasma creatinine, proteinuria, platelet counts and haematocrit were similar, indicating that renal and coagulatory function and plasma volume were affected to the same extent in the two groups and were independent of parity. Birthweight was similar in the two groups, and the percentage of infants weighing less than the 10th centile for gestation was also similar. Biochemical markers of endothelial dysfunction, assessed by measuring the urinary prostacyclin metabolite 2, 3-dinor-6-oxo-prostaglandin F(1alpha) and plasma endothelin 1, did not differ according to parity. There were no differences in a number of other biochemical markers of pre-eclampsia, including plasma albumin, uric acid, triacylglycerol, and total, low-density lipoprotein and high-density lipoprotein cholesterol. Basophil, monocyte and lymphocyte counts were elevated before delivery in primigravid women with pre-eclampsia. The differences in lymphocyte counts persisted post-partum. Further studies are required to clarify the role, if any, of monocytes, basophils and lymphocytes in the pathophysiology of pre-eclampsia. In conclusion, the elevated systolic blood pressure and raised aspartate aminotransferase levels observed in primigravida suggest a more severe form of pre-eclampsia. The lack of differences in birthweight and other biochemical and endothelial markers of severity of pre-eclampsia do not suggest a different pathophysiology; however, the persistently higher white cell counts in the primigravid pre-eclamptics are of interest, and might reflect differences in immune responses in the two groups. We suggest that studies of the pathophysiology of pre-eclampsia should include multigravida, as long as there is adequate post-partum follow-up to exclude underlying disease.     

Bone stimulators for fusions and fractures

Even though a complete understanding of electrical responses of bone has not been fully obtained, useful data toward this end have been gathered. The development of devices that use what is known about the bone's electrophysiologic properties has impacted patient care. Many health care professionals remain skeptical about the effects of electrical stimulation in bone healing. Therefore, further research is needed to help the practitioner formulate a more educated opinion on this form of therapy.     

Influence of the central nucleus of the amygdala on the content of corticotropin-releasing factor in the median eminence

The central nucleus of the amygdala possesses numerous neurons containing corticotropin-releasing factor (CRF). This study demonstrates a striking decrease of the CRF-like immunoreactivity in the median eminence at both 1 and 2 weeks after bilateral lesions of the amygdaloid central nucleus. Lesion of the amygdaloid central nucleus did not alter the neurophysin-like immunoreactivity in the internal zone of the median eminence, indicating the integrity of the efferent neurophysin-containing fibers of the supraoptic and paraventricular hypothalamic nuclei. However, there was a concomitant decrease of neurophysin and CRF-like immunoreactivity in the external zone of the median eminence. These results substantiate the hypothesis that the amygdaloid central nucleus can influence the content of CRF-like material in the median eminence via a multisynaptic pathway involving the synthesis of CRF at the level of the paraventricular nucleus of the hypothalamus. The exact mechanism by which lesion of the amygdaloid central nucleus influences the CRF content in the median eminence remains to be determined.     

Bone densitometry of excised vertebrae; Anatomical relationships

Summary Bone mineral density (BMD) was determined in 32 excised vertebrae using three methods: (1) dual-energy quantitative computed tomography (QCT), (2) dual-photon absorptiometry (DPA) with 153-Gd in an anteriorposterior projection and (3) scanning slit X-ray absorptiometry (SSXA) in both AP and lateral projections. The QCT region-of-interest in the anterior vertebral body had a lower density than that of the total trabecular portion of the body, but was highly correlated to this larger region (r=0.96; SEE=8 mg/cm³). The anterior QCT region also correlated moderately with BMD from DPA (r=0.77; SEE=18 mg/cm³). Measurements of the vertebral body in lateral projection were less well correlated (r=0.5–0.7) to QCT densities. Both the anterior QCT region (r=0.81; SEE=18 mg/cm³) and the BMD from DPA (r=0.86; SEE=16 mg/cm³) were similarly predictive of density of the integral vertebral body. Differences among densitometric methods on the spine depend on the projection used and the region examined.     

INCREASES IN URINARY KALLIKREIN ACTIVITY AND PROSTANOID SYNTHESIS AFTER DIETARY POTASSIUM SUPPLEMENTATION

1. To determine whether increasing dietary potassium alters kallikrein activity or prostaglandin synthesis, 77 women participated in a 3 week screening to assess their dietary potassium intake. Forty-four normotensive women whose dietary potassium was less than 60 mmol/day were allocated randomly to one of two groups who took either 80 mmol/day KCl (Slow-K, Ciba Geigy) or matching placebo for the first or second of two 4 week periods. 2. Significant increases in urinary kallikrein excretion (P less than 0.01), and urinary 6-keto-PGF1 alpha (P less than 0.01) were observed during potassium supplementation. These changes occurred without alterations in urine volume or sodium excretion. 3. It is suggested that potassium-induced changes in urinary 6-keto-PGF1 alpha may reflect increased renal and possibly vascular synthesis of prostacyclin. These increases may be mediated by increased plasma potassium stimulating kallikrein synthesis, leading to bradykinin-induced activation of phospholipase A2. Enhanced kallikrein/kinin and prostacyclin formation could contribute to the blood pressure lowering effect of potassium reported in hypertensive subjects.