Defining a conceptual framework for near-miss maternal morbidity

Maternal mortality is the major indicator used to monitor maternal health in the United States. For every woman who dies, however, many suffer serious life-threatening complications of pregnancy. Yet relatively little attention has been given to identifying a general category of morbidities that could be called near misses. Characterizing near-miss morbidity is valuable for monitoring the quality of hospital-based obstetric care and for assessing the incidence of life-threatening complications. Cases of near-miss morbidity also provide an appropriate comparison group both for dinical case review and for epidemiologic analysis. This paper presents an initial framework and a process for the definition and identification of near-miss morbidity that minimizes loss of information yet has practical utility. A clinical review team classified 22 of 186 women as near misses and 164 as other severe morbidity. A quantitative score classified 28 women as near misses and 156 as other severe morbidity. Precise classification of near-miss morbidity is the first step in analyzing factors that may differentiate survival from death on the continuum from morbidity to mortality. Ultimately, a methodology for the identification and analysis of near-miss morbidity will allow for integrated morbidity and mortality reviews that can then be institutionalized. The results will serve as important models for other researchers, state health agencies, and regionalized perinatal systems that are engaged in morbidity and mortality surveillance.     

Treatment of experimental autoimmune encephalomyelitis with antisense oligonucleotides against the low affinity neurotrophin receptor

Upregulated expression of the low-affinity neurotrophin receptor (p75) in the central nervous system (CNS) during experimental autoimmune encephalomyelitis (EAE) has recently been demonstrated. To investigate whether p75 plays a role in disease pathogenesis, we adopted a gene therapy approach, utilizing antisense oligonucleotides to downregulate p75 expression during EAE. Phosphorothioate antisense oligonucleotides (AS), nonsense oligonucleotides (NS) or phosphate buffered saline (PBS) were injected daily for 18 days after immunization of SJL/J (H-2s)-mice with myelin proteolipid protein (PLP) peptide 139-151. In the AS group, there was a statistically significant reduction in both the mean maximal disease score (1.85 in the AS, 2.94 in the NS and 2.75 in the PBS-groups, respectively, P < 0.025) and in the cumulative disease incidence ( approximately 60% in the AS group and approximately 90% in the control groups). Histological and immunohistochemical analysis showed reduced inflammation and demyelination, as well as reduced p75 expression at the blood-brain barrier (BBB) in the AS-treated mice in comparison with both control groups. There was no difference, however, in p75 expression on neural cells within the CNS between the three groups of mice. We conclude that p75 could play a proactive role in the pathogenesis of EAE and may exert its effect at the level of the BBB.     

1-(m-chlorophenyl)-biguanide, a potent high affinity 5-HT3 receptor agonist

1-(m-Chlorophenyl)-biguanide (mCPBG) was examined and compared with three 5-HT3 receptor agonists in three 5-HT3 receptor models. mCPBG inhibited [3H]GR67330 binding to 5-HT3 receptors with high affinity (IC50 1.5 nM). mCPBG depolarized the rat vagus nerve with an EC50 one tenth of that for 5-HT (0.05 vs. 0.46 microM); the maximum depolarization was approximately half that for 5-HT. The mCPBG depolarization was potently blocked by the selective 5-HT3 antagonist, ondansetron (pKB 8.6 +/- 0.1). In anaesthetised cats, mCPBG potently evoked the Bezold-Jarisch reflex which was blocked by low doses of ondansetron (10 micrograms/kg i.v.). It is concluded that mCPBG is a potent, high affinity 5-HT3 receptor agonist.     

Changing management of gallstone disease during pregnancy

Background: Symptomatic gallstones may be problematic during pregnancy. The advisability of laparoscopic cholecystectomy (LC) is uncertain. The objective of this study is to define the natural history of gallstone disease during pregnancy and evaluate the safety of LC during pregnancy. Methods: Review of medical records of all pregnant patients with gallstone disease at the University of California, San Francisco, from 1980 to 1996. Results: Of approximately 29,750 deliveries, 47 (0.16%) patients were treated for gallstone disease, including biliary colic in 33, acute cholecystitis in 12, and pancreatitis in two. Conservative treatment was attempted in all patients but failed in 17 (36%) cases. Two patients required combined preterm Cesarean-section cholecystectomy and 10 required surgery in the early postpartum period for persistent symptoms. Seventeen patients required cholecystectomy during pregnancy for biliary colic (10), acute cholecystitis (six), and pancreatitis (one). Three patients were treated with open cholecystectomy. Fourteen patients underwent LC at a mean gestational age of 18.6 weeks, mean OR time of 74 min, and mean length of stay of 1.2 days. Hasson cannulation was utilized in 11 patients. Reduced-pressure pneumoperitoneum (6–10 mmHg) was used in seven patients. Prophylactic tocolytics were used in seven patients, with transient postoperative preterm labor observed in one. There were no open conversions, preterm deliveries, fetal loss, teratogenicity, or maternal morbidity. Conclusions: In past years, symptomatic gallstones during pregnancy were managed conservatively or with open cholecystectomy. LC is a feasible and safe method for treating severely symptomatic patients. Received: 3 April 1997/Accepted: 5 July 1997