Warren L. May

Stroke and severe preeclampsia and eclampsia: a paradigm shift focusing on systolic blood pressure.

OBJECTIVE: To identify important clinical correlates of stroke in patients with preeclampsia and eclampsia. METHODS: The case histories of 28 patients who sustained a stroke in association with severe preeclampsia and eclampsia were scrutinized with particular attention to blood pressures. RESULTS: Stroke occurred antepartum in 12 patients, postpartum in 16. Stroke was classified as hemorrhagic-arterial in 25 of 27 patients (92.6%) and thrombotic-arterial in 2 others. Multiple sites were involved in 37% without distinct pattern. In the 24 patients being treated immediately before stroke, systolic pressure was 160 mm Hg or greater in 23 (95.8%) and more than 155 mm Hg in 100%. In contrast, only 3 of 24 patients (12.5%) exhibited prestroke diastolic pressures of 110 mm Hg or greater, only 5 of 28 reached 105 mm Hg, and only 6 (25%) exceeded a mean arterial pressure of 130 mm Hg before stroke. Only 3 patients received prestroke antihypertensives. Twelve patients sustained a stroke while receiving magnesium sulfate infusion; 8 had eclampsia. Although all blood pressure means after stroke were significantly higher than prestroke, only 5 patients exhibited more than 110 mm Hg diastolic pressures. In 18 of 28 patients, hemolysis, elevated liver enzymes, low platelets syndrome did not significantly alter blood pressures compared with non–hemolysis, elevated liver enzymes, low platelets. Mean systolic and diastolic changes from pregnancy baseline to prestroke values were 64.4 and 30.6 mm Hg, respectively. Maternal mortality was 53.6%; only 3 patients escaped permanent significant morbidity. CONCLUSION: In contrast to severe systolic hypertension, severe diastolic hypertension does not develop before stroke in most patients with severe preeclampsia and eclampsia. A paradigm shift is needed toward considering antihypertensive therapy for severely preeclamptic and eclamptic patients when systolic blood pressure reaches or exceeds 155–160 mm Hg. LEVEL OF EVIDENCE: III

The spectrum of severe preeclampsia: Comparative analysis by HELLP (hemolysis, elevated liver enzyme levels, and low platelet count) syndrome classification☆☆☆★

OBJECTIVE This study was undertaken to explore the spectrum of maternal disease with a triple classification system of HELLP (hemolysis, elevated liver enzyme levels, and low platelet count) syndrome and compare these classes with severe preeclampsia without HELLP syndrome. STUDY DESIGN In this retrospective analytic study the pregnancies of 777 patients with class 1, 2, or 3 HELLP syndrome were compared and contrasted with those of 193 women with severe preeclampsia but without HELLP syndrome. RESULTS Eclampsia, epigastric pain, nausea and vomiting, significant proteinuria, major maternal morbidity, and stillbirth increased as HELLP syndrome worsened from class 3 to class 1. In contrast, headache and diastolic hypertension were more common among the significantly heavier patients with severe preeclampsia without HELLP syndrome. Approximately half of pregnancies complicated by class 1 HELLP syndrome exhibited significant maternal morbidity, compared with only 11% of those complicated by severe preeclampsia without HELLP syndrome. Although a significant trend was apparent in increasing levels of lactate dehydrogenase, aspartate aminotransferase, and uric acid as HELLP syndrome worsened, there was considerable variation within groups. CONCLUSION Laboratory and clinical indices of disease severity in patients with severe preeclampsia or eclampsia generally were highest with class 1 HELLP syndrome and were lowest when HELLP syndrome was absent. Class 3 HELLP syndrome is considered a clinically significant transitional group.

Elevated agonist binding to α2-adrenoceptors in the locus coeruleus in major depression

BACKGROUND Recent postmortem studies demonstrate disrupted neurochemistry of the noradrenergic locus coeruleus (LC) in major depression (MD). Increased levels of tyrosine hydroxylase and decreased levels of norepinephrine transporter implicate a norepinephrine deficiency in the LC in MD. Here we describe a study of alpha2-adrenoceptors in the LC and raphe nuclei of subjects with MD compared with psychiatrically normal control subjects. METHODS The specific binding of p-[125I]iodoclonidine to alpha2-adrenoceptors was measured at multiple levels along the rostrocaudal extent of the LC in postmortem tissue from 14 control and 14 MD subjects. In addition, p-[125I]iodoclonidine binding was measured in the dorsal and median raphe nuclei in the same tissue sections. RESULTS The specific binding of p-[125I]iodoclonidine to alpha2-adrenoceptors was significantly elevated throughout the LC from MD compared with matched control subjects. No significant differences were observed in p-[125I]iodoclonidine binding to alpha2-adrenoceptors in the raphe nuclei comparing MD and control subjects. CONCLUSIONS Given that alpha2-adrenoceptors are upregulated in laboratory animals by treatment with drugs that deplete norepinephrine, our findings implicate a premortem deficiency of brain norepinephrine in the region of the locus coeruleus in subjects with MD.

Thrombotic thrombocytopenic purpura in 166 pregnancies: 1955-2006

A review of pregnancy-associated thrombotic thrombocytopenic purpura (TTP) in 166 pregnancies was undertaken using 92 English-language publications from 1955 to 2006. Initial and recurrent TTP presents most often in the second trimester (55.5%) after 1-2 days of signs/symptoms; postpartum TTP usually occurs following term delivery. TTP with preeclampsia (n = 28) exhibits 2-4 times higher aspartate aminotransferase (AST) values and lower total lactate dehydrogenase (LDH) to AST ratios (LDH to AST ratio = 13:1), compared with TTP without preeclampsia (LDH to AST ratio = 29:1). Maternal mortality is higher with initial TTP (26% vs 10.7%), especially with concurrent preeclampsia (44.4% vs 21.8%, P < .02). Although maternal mortality with TTP has substantially declined when plasma therapy is utilized, delay of diagnosis and therapy for initial TTP confounded by preeclampsia/hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome remains a significant maternal-perinatal threat. Rapid and readily available laboratory testing to quickly diagnose TTP and HELLP syndrome/preeclampsia is desperately needed to improve care.

Early risk assessment of severe preeclampsia: Admission battery of symptoms and laboratory tests to predict likelihood of subsequent significant maternal morbidity

OBJECTIVE This study was undertaken to investigate the utility of an admission battery of findings and laboratory data in the discrimination of patients with severe preeclampsia with or without HELLP (hemolysis, elevated liver enzyme levels, and low platelet count) syndrome at high risk for development of significant maternal morbidity. STUDY DESIGN The clinical and laboratory findings at hospital admission for 970 patients with severe preeclampsia with or without HELLP syndrome were studied retrospectively to develop parameters associated with low, moderate, and high risks for the subsequent development of significant maternal morbidity involving the hematologic and coagulation, cardiopulmonary, and hepatorenal systems. RESULTS Nausea and vomiting and epigastric pain are independent risk factors for complicated severe preeclampsia. Results of a panel of tests with values including lactate dehydrogenase level >1400 IU/L, aspartate aminotransferase level >150 IU/L, alanine aminotransferase level >100 IU/L, uric acid level >7.8 mg/dL, serum creatinine level >1.0 mg/dL, and 4+ urinary protein by dipstick can be used to discriminate the patient at high risk for significant maternal morbidity. Concentrations of lactate dehydrogenase, aspartate aminotransferase, and uric acid above these cut points have the strongest predictive value and are risk additive with worsening thrombocytopenia. CONCLUSION The presence of nausea and vomiting, epigastric pain, or both in association with admission laboratory values that are in excess of the cutoffs for lactate dehydrogenase, aspartate aminotransferase, and uric acid concentrations or for all 6 tests is predictive of high risk of morbidity for the patient with severe preeclampsia. These factors are independent of and additive with the rising maternal risk associated with decreasing platelet count.

Maternal benefit of high-dose intravenous corticosteroid therapy for HELLP syndrome

OBJECTIVE We compared maternal outcomes for patients with HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome treated with or without high-dose corticosteroids to ameliorate maternal disease. STUDY DESIGN An analysis of data for patients with HELLP syndrome (platelets, <or=100,000/microL; lactate dehydrogenase level, >or=600 IU/L; aspartate aminotransferase and/or alanine aminotransferase level, >or=70 IU/L) who were treated during the 7-year epochs before and after the clinical trials in 1992 and 1993 demonstrated maternal benefit with high-dose dexamethasone. RESULTS Corticosteroid use increased from 16% (39/246 patients) for fetal indication from 1985 to 1991 to 90% (205/228 patients) for maternal-fetal indications from 1994 to 2000. Significantly reduced composite maternal disease from 1994 to 2000 was evidenced by improvements in laboratory parameters, disease progression to class 1 HELLP syndrome, the degree of hypertension, the need for antihypertensive therapy, the use of transfusion, and the presence of maternal morbidity (P<.05). Indices of postpartum recovery also were shortened significantly (P<.001). CONCLUSION Routine early initiation of high-dose intravenous corticosteroids for patients with HELLP syndrome significantly lessened maternal disease, reduced maternal morbidity, and expedited recovery.

Factors Associated with Long-Term Complications after Repair of Mandibular Fractures

Educational Objective: At the conclusion of this paper, the participants should be able to identify, compare, and discuss the natural history of complications of mandible fractures and repair.

Preeclampsia-associated Hepatic Hemorrhage and Rupture: Mode of Management Related to Maternal and Perinatal Outcome

This article is a critical review of the obstetric literature concerning preeclampsia-associated hepatic hemorrhage to develop guidelines conducive to optimal maternal and perinatal outcomes. An English literature search was performed for reports of hepatic hemorrhage or hepatic rupture in pregnancy during 1960 to 1997. Data were analyzed by Statmost packages using ANOVA, Chi-square, and Fishers exact tests. One hundred forty-one patients with hepatic rupture/hemorrhage were reported. The three most common presenting findings were epigastric pain, hypertension, and shock. With rare exception, patients had evidence of preeclampsia. Diagnosis was elusive and most frequently accomplished at laparotomy. When utilized, ultrasound and computed tomography (CT) were helpful diagnostic modalities. Maternal survival was highest in the arterial embolization treatment group. Maternal and perinatal survival improved considerably during the study interval. Route of delivery did not seem to impact survival rates. It was concluded that the application of ultrasound and CT for diagnosis and the use of hepatic artery embolization for treatment of hepatic hemorrhage/rupture seem to be beneficial management options for this rare event.

Hippocampal volume and total cell numbers in major depressive disorder

Neuroimaging consistently reveals smaller hippocampal volume in recurrent or chronic major depressive disorder (MDD). The underlying cellular correlates of the smaller volume are not clearly known. Postmortem tissues from 17 pairs of depressed and control subjects were obtained at autopsy, and informant-based retrospective psychiatric assessment was performed. Formalin-fixed left temporal lobes were sectioned (40 μm), stained for Nissl substance, and every 60th section selected throughout the entire hippocampus. Total volume of the hippocampal formation was calculated, and total numbers of pyramidal neurons (in hippocampal fields CA1, CA2/3, hilus), dentate gyrus (DG) granule cells, and glial cells were estimated stereologically. While hippocampal volume in all MDD subjects was not significantly smaller versus control subjects, in recurrent/chronic MDD, total volume decreased with duration of depressive illness (r = -0.696, p < 0.026). There was no significant difference between MDD and controls in total number or density of pyramidal neurons/granule cells or glial cells in CA1, CA2/3, hilus, or DG. However, CA1 pyramidal neuron density increased with duration of illness in recurrent/chronic MDD (r = 0.840, p < 0.002). Granule cell (r = 0.971, p < 0.002) and glial cell numbers (r = 0.980, p < 0.001) increased with age in those taking antidepressant medication (n = 6). Increasing DG granule cell and glial cell numbers with age in antidepressant-treated subjects may reflect proliferative effects of antidepressant medications. Decreasing total volume and increasing CA1 pyramidal neuron density with duration of illness in recurrent/chronic MDD lends support to the neuropil hypothesis of MDD.

Gender-specific decrease in NUDR and 5-HT1A receptor proteins in the prefrontal cortex of subjects with major depressive disorder.

A variety of studies have documented alterations in 5-HT1A receptor binding sites in the brain of subjects with major depressive disorder (MDD). The recently identified transcription factor, nuclear deformed epidermal autoregulatory factor (NUDR/Deaf-1) has been shown to function as a transcriptional modulator of the human 5-HT1A receptor gene. The present study was undertaken to document the regional and cellular localization of NUDR in the human prefrontal cortex and to examine the levels of NUDR and 5-HT1A receptor protein in prefrontal cortex of female and male depressed and control subjects. NUDR immunoreactivity was present in neurons and glia across cortical layers and was co-localized with 5-HT1A receptor immunoreactive neurons. NUDR immunoreactivity as measured by Western blot was significantly decreased in the prefrontal cortex of female depressed subjects (42%, p=0.02) and unchanged in male depressed subjects relative to gender-matched control subjects. Similarly, 5-HT1A receptor protein level was significantly reduced in the prefrontal cortex of female depressed subjects (46%, p=0.03) and unchanged in male depressed subjects compared to gender-matched control subjects. Reduced protein expression of NUDR in the prefrontal cortex of female subjects with MDD may reflect a functional alteration in this transcription factor, which may contribute to the decrease in 5-HT1A receptors observed in the same female subjects with MDD. In addition, the gender-specific alterations in cortical NUDR and 5-HT1A receptor proteins could represent an underlying biological mechanism associated with the higher incidence of depression in women.