A novel BK channel-targeted peptide suppresses sound evoked activity in the mouse inferior colliculus.

Large conductance calcium-activated (BK) channels are broadly expressed in neurons and muscle where they modulate cellular activity. Decades of research support an interest in pharmaceutical applications for modulating BK channel function. Here we report a novel BK channel-targeted peptide with functional activity in vitro and in vivo. This 9-amino acid peptide, LS3, has a unique action, suppressing channel gating rather than blocking the pore of heterologously expressed human BK channels. With an IC50 in the high picomolar range, the apparent affinity is higher than known high affinity BK channel toxins. LS3 suppresses locomotor activity via a BK channel-specific mechanism in wild-type or BK channel-humanized Caenorhabditis elegans. Topical application on the dural surface of the auditory midbrain in mouse suppresses sound evoked neural activity, similar to a well-characterized pore blocker of the BK channel. Moreover, this novel ion channel-targeted peptide rapidly crosses the BBB after systemic delivery to modulate auditory processing. Thus, a potent BK channel peptide modulator is open to neurological applications, such as preventing audiogenic seizures that originate in the auditory midbrain.

Putative calcium-binding domains of the Caenorhabditis elegans BK channel are dispensable for intoxication and ethanol activation.

Alcohol modulates the highly conserved, voltage- and calcium-activated potassium (BK) channel, which contributes to alcohol-mediated behaviors in species from worms to humans. Previous studies have shown that the calcium-sensitive domains, RCK1 and the Ca(2+) bowl, are required for ethanol activation of the mammalian BK channel in vitro. In the nematode Caenorhabditis elegans, ethanol activates the BK channel in vivo, and deletion of the worm BK channel, SLO-1, confers strong resistance to intoxication. To determine if the conserved RCK1 and calcium bowl domains were also critical for intoxication and basal BK channel-dependent behaviors in C. elegans, we generated transgenic worms that express mutated SLO-1 channels predicted to have the RCK1, Ca(2+) bowl or both domains rendered insensitive to calcium. As expected, mutating these domains inhibited basal function of SLO-1 in vivo as neck and body curvature of these mutants mimicked that of the BK null mutant. Unexpectedly, however, mutating these domains singly or together in SLO-1 had no effect on intoxication in C. elegans. Consistent with these behavioral results, we found that ethanol activated the SLO-1 channel in vitro with or without these domains. By contrast, in agreement with previous in vitro findings, C. elegans harboring a human BK channel with mutated calcium-sensing domains displayed resistance to intoxication. Thus, for the worm SLO-1 channel, the putative calcium-sensitive domains are critical for basal in vivo function but unnecessary for in vivo ethanol action.

Environmental modulation of microcystin and ß-N-methylamino-L-alanine as a function of nitrogen availability.

The most significant modulators of the cyanotoxins microcystin and ß-N-methylamino-L-alanine in laboratory cyanobacterial cultures are the concentration of growth-medium combined nitrogen and nitrogen uptake rate. The lack of field studies that support these observations led us to investigate the cellular content of these cyanotoxins in cyanobacterial bloom material isolated from a freshwater impoundment and to compare these to the combined nitrogen availability. We established that these toxins typically occur in an inverse relationship in nature and that their presence is mainly dependent on the environmental combined nitrogen concentration, with cellular microcystin present at exogenous combined nitrogen concentrations of 29 µM and higher and cellular BMAA correlating negatively with exogenous nitrogen at concentrations below 40 µM. Furthermore, opposing nutrient and light gradients that form in dense cyanobacterial blooms may result in both microcystin and BMAA being present at a single sampling site.

Differential regulation of synapsin phosphorylation by monocular deprivation in juveniles and adults.

The rodent visual cortex retains significant ocular dominance plasticity beyond the traditional postnatal critical period. However, the intracellular mechanisms that underlie the cortical response to monocular deprivation are predicted to be different in juveniles and adults. Here we show monocular deprivation in adult, but not juvenile rats, induced an increase in the phosphorylation of the prominent presynaptic effecter protein synapsin at two key sites known to regulate synapsin function. Monocular deprivation in adults induced an increase in synapsin phosphorylation at the PKA consensus site (site 1) and the CaMKII consensus site (site 3) in the visual cortex ipsilateral to the deprived eye, which is dominated by non-deprived eye input. The increase in synapsin phosphorylation was observed in total cortical homogenate, but not synaptoneurosomes, suggesting that the pool of synapsin targeted by monocular deprivation in adults does not co-fractionate with excitatory synapses. Phosphorylation of sites 1 and 3 stimulates the release of synaptic vesicles from a reserve pool and increases in the probability of evoked neurotransmitter release, which may contribute to the strengthening of the non-deprived input characteristic of ocular dominance plasticity in adults.

Exposure to chrysotile asbestos associated with unpacking and repacking boxes of automobile brake pads and shoes.

Industrial hygiene surveys and epidemiologic studies of auto mechanics have shown that these workers are not at an increased risk of asbestos-related disease; however, concerns continue to be raised regarding asbestos exposure from asbestos-containing brakes. Handling new asbestos-containing brake components has recently been suggested as a potential source of asbestos exposure. A simulation study involving the unpacking and repacking of 105 boxes of brakes (for vehicles ca. 1946-80), including 62 boxes of brake pads and 43 boxes of brake shoes, was conducted to examine how this activity might contribute to both short-term and 8-h time-weighted average exposures to asbestos. Breathing zone samples on the lapel of a volunteer worker (n = 80) and area samples at bystander (e.g., 1.5 m from worker) (n = 56), remote area (n = 26) and ambient (n = 10) locations collected during the unpacking and repacking of boxes of asbestos-containing brakes were analyzed by phase contrast microscopy and transmission electron microscopy. Exposure to airborne asbestos was characterized for a variety of parameters including the number of boxes handled, brake type (i.e. pads versus shoes) and the distance from the activity (i.e. worker, bystander and remote area). This study also evaluated the fiber size and morphology distribution according to the International Organization for Standardization analytical method for asbestos. It was observed that (i) airborne asbestos concentrations increased with the number of boxes unpacked and repacked, (ii) handling boxes of brake pads resulted in higher worker asbestos exposures compared to handling boxes of brake shoes, (iii) cleanup and clothes-handling tasks produced less airborne asbestos than handling boxes of brakes and (iv) fiber size and morphology analysis showed that while the majority of fibers were free (e.g. not associated with a cluster or matrix), <30% were respirable and even fewer were of the size range (>20 microm length) considered to pose the greatest risk of asbestos-related disease. It was found that average airborne chrysotile concentrations (30 min) ranged from 0.086 to 0.368 and 0.021 to 0.126 f cc(-1) for a worker unpacking and repacking 4-20 boxes of brake pads and 4-20 boxes of brake shoes, respectively. Additionally, average airborne asbestos exposures (30 min) at bystander locations ranged from 0.004 to 0.035 and 0.002 to 0.011 f cc(-1) when 4-20 boxes of brake pads and 4-20 boxes of brake shoes were handled, respectively. These data show that a worker handling a relatively large number of boxes of brakes over short periods of time will not be exposed to airborne asbestos in excess of its historical or current short-term occupational exposure limits.

Assessment of potential human health risks posed by benzene in beverages.

A recent study by the U.S. Food and Drug Administration (FDA) indicated that some beverages contained benzene at levels above the federal drinking water standard of 5 parts per billion (ppb). In tests conducted by the FDA, Crystal Light Sunrise Classic Orange (CLSCO) was reported to contain benzene levels as high as 87.9 ppb. The purpose of the present study was to better characterize benzene concentrations in CLSCO and to quantify potential human health risks. Twenty-eight samples of CLSCO were obtained from retail stores in Houston, Tex., U.S.A. The mean benzene concentrations in 16 oz original and new formulation bottles were 90 and 0.18 ppb, respectively, while 64-oz bottles contained an average of 3.38 ppb. A variety of exposure scenarios were evaluated to determine potential health risks using both deterministic and probabilistic techniques. In the deterministic analyses, upper bound point estimate cancer risks ranged from 5.4E-6 to 8.7E-8, while hazard indices (HI) ranged from 0.28 to 0.00104. Probabilistic analyses were conducted to develop more realistic cancer risk estimates. In these analyses, the 50th and 95th percentile cancer risk estimates were 3.7E-6 and 8.0E-6, and the 50th and 95th percentile hazard indices were 0.19 and 0.42, respectively. In conclusion, all cancer risk estimates and noncancer hazards met the typical health risk benchmarks established by the U.S. regulatory agencies (1E-4 to 1E-6 for cancer and hazard indices less than 1.0).

Eradicating Listeria monocytogenes from fully cooked franks by using an integrated pasteurization-packaging system.

Surface pasteurization by applying steam or hot water before or after packaging of processed foods may be used to eliminate pathogens such as Listeria monocytogenes from ready-to-eat meat and poultry products. Surface pasteurization treatment with a mixture of pressurized steam and hot water was integrated into a continuous vacuum-packaging system to reduce L. monocytogenes from fully cooked franks. The franks (2.54 cm diameter by 15.24 cm length) were surface inoculated to contain up to 6 log CFU/cm2 L. monocytogenes. The inoculated franks were treated at 121 degrees C for 1.5 s in an arrangement of six franks per packaging chamber followed by immediate vacuum sealing of the top films of food packages in the same unit. A 3-log CFU/cm2 reduction of L. monocytogenes on fully cooked franks was obtained using the integrated pasteurization-packaging system. The pasteurization depth was 1.27 mm below the surfaces of the franks. This process provides a commercially applicable means of ensuring food safety by effectively eradicating L. monocytogenes from ready-to-eat meat and poultry products at the very last possible step of food packaging before reaching retail consumers.

Physical properties of cream reformulated with fractionated milk fat and milk-derived components.

Emulsifying properties of milk-derived components influence the physical characteristics of reformulated creams. Fractionated butter oils with different melting ranges (low-melt: 10 to 25 degrees C; medium-melt: 25 to 35 degrees C) were recombined into fluid dairy systems using skim milk, or sweet buttermilk and butter-derived aqueous phase to manufacture 20% milk fat creams. Separation temperature (49 degrees C or 55 degrees C) in obtaining emulsifying components was examined for its effect on physical properties of pasteurized reformulated creams. Rate of creaming, viscosity, feathering, and sensory characteristics of reformulated and natural creams stored at 3.3 degrees C were evaluated over a 13-d period. Creaming rate of reformulated and natural creams was unaffected by formulation and was most influenced by duration of storage. Melting characteristics of butter oils influenced viscosity at some shear rates. With the exception of natural cream, all formulations were consistent in apparent viscosity during the 2-wk storage period. All creams feathered in a pH range of 4.70 to 5.20 and were classified as moderately stable to slightly unstable. All reformulated and natural creams met sensory quality specifications with the exception of creams formulated with skim milk and lower melting range butteroil. Creams formulated with buttermilk, butter-derived aqueous phase, and lower-melting range butter oil most closely mimicked natural creams with regard to sensory quality and viscosity.

Acyclovir suppression to prevent recurrent genital herpes at delivery.

OBJECTIVE: To determine if suppressive acyclovir near term decreased the frequency of clinical recurrences at delivery in women with recurrent genital herpes simplex virus (HSV) infection. METHODS: We conducted a prospective, double-blind, randomized trial in 234 women with recurrent genital herpes. Women with genital infection of any frequency were enrolled. Patients received either suppressive oral acyclovir 400 mg three times daily or an identical placebo after 36 weeks' gestation. Clinical lesions were identified, and HSV cultures were obtained at delivery. The frequencies of clinical and subclinical HSV recurrences at delivery were evaluated. RESULTS: Six percent of patients treated with acyclovir, and 14% of patients treated with placebo had clinical HSV at delivery (p = 0.046). No patients in the acyclovir group had positive HSV cultures, compared with 6% of placebo-treated patients (p = 0.029). There was no significant difference in subclinical HSV shedding in the acyclovir group (0%) compared with the placebo-treated group (3%) (p = 0.102). CONCLUSIONS: Suppressive acyclovir therapy significantly decreased the incidence of clinical genital herpes and the overall incidence of HSV excretion at delivery in patients with previous herpes infection.

Acyclovir suppression to prevent clinical recurrences at delivery after first episode genital herpes in pregnancy: an open-label trial.

OBJECTIVE: To continue evaluation of the use of acyclovir suppression in late pregnancy after first episode genital herpes simplex virus (HSV) infection, using an open-label study design. METHODS: Ninety-six women diagnosed with genital herpes for the first time in the index pregnancy were prescribed suppressive acyclovir 400 mg orally three times daily from 36 weeks until delivery in an open-label fashion. Herpes cultures were obtained when patients presented for delivery. Vaginal delivery was permitted if no clinical recurrence was present; otherwise a Cesarean delivery was performed. Neonatal HSV cultures were obtained and infants were followed clinically. Rates of clinical and asymptomatic genital herpes recurrences and Cesarean delivery for genital herpes were measured, and 95% confidence intervals were calculated. RESULTS: In 82 patients (85%) compliant with therapy, only 1% had clinical HSV recurrences at delivery. In an intent to treat analysis of the entire cohort, 4% had clinical recurrences (compared with 18-37% in historical controls). Asymptomatic shedding occurred in 1% of women without lesions at delivery. Two of the four clinical recurrences were HSV-culture positive. No significant maternal or fetal side-effects were observed. CONCLUSIONS: In clinical practice the majority of patients are compliant with acyclovir suppression at term. The therapy appears to be effective at reducing clinical recurrences after a first episode of genital herpes complicating a pregnancy.

Relationship issues of women with breast cancer.

This in-depth, qualitative pilot study explored the impact of breast cancer on specific dimensions of the relationships and roles of women. It included interaction within the partner relationship as well as with family, friends, and colleagues. Data were obtained by individual and group interviews from 10 women with a diagnosis of breast cancer and 5 male partners. Both partnered and single women participated. There were four major findings seldom discussed in the literature, which have important implications for preventive intervention. First, partner relationships troubled before the diagnosis as well as those characterized by mutual caring faced challenges and negative changes. Second, in an effort to protect each other, communication within the partner dyad became less open, and there were changes in the usual manner of conflict resolution. Third, unpartnered women appeared to be more vulnerable to problems of negative adjustment, largely because of relationship issues. Fourth, participants confirmed the need for a comprehensive intervention to facilitate coping with issues relative to relationships, intimacy, and sexuality. Although the sample was small, in-depth data were obtained that provide a basis for specific areas in which further empirical investigation is needed, and they indicate that preventive intervention may well be warranted.

Predictive value of serial middle cerebral and renal artery pulsatility indices in fetuses with oligohydramnios.

OBJECTIVE: To determine if unexplained changes in the amniotic fluid index or pulsatility indices of the fetal renal, middle cerebral, or umbilical artery are predictive of perinatal outcome in pregnancies complicated by oligohydramnios. METHODS: Changes in amniotic fluid measurements and fetal vessel velocimetry in patients with oligohydramnios were evaluated for correlation with fetal outcome. Fourteen fetuses with oligohydramnios underwent serial sonography evaluating the amniotic fluid index and fetal middle cerebral, renal, and umbilical velocimetry. Matched controls and neonatal outcomes were obtained. RESULTS: Change in amniotic fluid index and in renal artery pulsatility index were inversely correlated. Change in the middle cerebral artery pulsatility index was different in infants with normal outcome compared to infants with adverse outcome CONCLUSIONS: Serial velocimetry of the middle cerebral artery may identify fetuses with oligohydramnios at risk for adverse outcomes.

The relationship between rates of HVc neuron addition and vocal plasticity in adult songbirds.

In adulthood, songbird species vary considerably in the extent to which they rely on auditory feedback to maintain a stable song structure. The continued recruitment of new neurons into vocal motor circuitry may contribute to this lack of resiliency in song behavior insofar as new neurons that are not privy to auditory instruction could eventually corrupt established neural function. In a first step to explore this possibility, we used a comparative approach to determine if species differences in the rate of vocal change after deafening in adulthood correlate positively with the extent of HVc neuron addition. We confirmed previous reports that deafening in adulthood changes syllable phonology much more rapidly in bengalese finches than in zebra finches. Using [(3)H]thymidine autoradiography to identify neurons generated in adulthood, we found that the proportion of new neurons in the HVc one month after labeling was nearly twice as great in bengalese than in zebra finches. Moreover, among the subset of HVc vocal motor neurons that project to the robust nucleus of the archistriatum, the incidence of [(3)H]thymidine-labeled neurons was nearly three times as great in bengalese than in zebra finches. This correlation between the proportion of newly added neurons and the rate of song deterioration supports the hypothesis that HVc neuron addition may disrupt stable adult song production if new neurons cannot be "trained" via auditory feedback.

Prospects for control of herpes simplex virus disease through immunization.

Herpes simplex viruses (HSVs) can cause a variety of infections, including genital herpes. Despite effective antiviral therapy, HSV infections remain a significant worldwide public health problem. Vaccines offer the best hope for controlling spread and limiting HSV disease. This article discusses the pathogenesis and immunobiology of mucocutaneous HSV infections, summarizes the spectrum of diseases caused by HSV, and provides a review of the field of HSV vaccine research. This article also discusses what might be realistically expected of a vaccine intended for control of genital herpes and explores the question of whether a vaccine that is effective in controlling genital HSV disease might also be effective in controlling nongenital HSV disease. The efficacy of such vaccines for the full spectrum of HSV disease will eventually determine the timing and targeting of immunization, ranging from selective immunization in preadolescence to universal childhood immunization as part of the routine childhood regimen.

Variation in food selection among lambs: effects of basal diet and foods offered in a meal.

In studies of behavior and nutrition, we typically determine nutritional needs and formulate diets for the average member of the herd, not for specific individuals within a herd. Nevertheless, variation among individuals could affect productivity of the group if the diet diverges too much from what individuals at the extremes prefer to eat. Thus, it is important to determine the degree to which individuals within a group vary in their food preferences when offered alternatives. Our first objective was to determine the degree to which lambs differed in preference for foods high in energy (barley) or protein (alfalfa) (Exp. 1). When we offered lambs barley and alfalfa for ad libitum consumption for 25 d, individuals varied in the amounts of barley (range: 221 to 991 g/d) and alfalfa (range: 51 to 558 g/d) they consumed (P < .0001). At one extreme, individuals preferred a diet of 6% alfalfa and 94% barley; at the other extreme, individuals preferred a diet of 70% alfalfa and 30% barley. Our second objective was to determine whether lambs from Exp. 1 compensated, when fed a basal diet that was lower in alfalfa than they preferred, by ingesting foods higher in alfalfa when offered a meal (Exp. 2). Lambs were ranked according to the percentage of alfalfa (range from 6 to 70%) and barley (range from 94 to 30%) they ate during Exp. 1 and then assigned alternately to two treatments: 1) basal diet with similar proportions of alfalfa and barley consumed ad libitum (preferred diet) or 2) basal diet with 10% less alfalfa than consumed ad libitum (low-alfalfa diet). We then conducted three trials in which lambs fed the different basal diets were offered a meal for 15 min/d for 2 d of two foods that differed in barley and alfalfa. During Trial 1, when we offered barley and alfalfa, lambs in both groups preferred barley (138 g) to alfalfa (46 g) (P < .05). During Trial 2, when the test foods (barley and alfalfa) were diluted with grape pomace (20%), lambs fed the preferred basal diet ate more barley (116 vs 64 g) and less alfalfa (48 vs 87 g) than lambs fed the low-alfalfa basal diet (P < .05). During Trial 3, when we offered a food high in barley (80% barley and 20% pomace) and a food high in alfalfa (70% alfalfa, 14% cornstarch, and 16% pomace), lambs fed the preferred basal diet ate more of the high-barley food (124 vs 73 g) and less of the high-alfalfa food (45 vs 98 g) than lambs fed the low-alfalfa basal diet (P < .05). Collectively, these results illustrate that lambs varied greatly in their preferences for foods that differ in energy (barley) and protein (alfalfa), and that when their preferred basal diet was altered, lambs compensated by ingesting food that complemented their basal diet during a daily meal. The addition of grape pomace in Trials 2 and 3 reduced the protein content of the high-barley and high-alfalfa foods such that the high-barley food was only marginally adequate to meet needs compared with the high-alfalfa food. Lambs fed the low-alfalfa basal diet compensated by eating more of the high-alfalfa food than lambs fed the preferred basal diet.

Prevention of perinatal herpes: prophylactic antiviral therapy?

So what is the take-home message from these studies? The first question, about fetal and neonatal safety, appears to be answered positively. With more than 1,812 infants reported to have been exposed to varying amounts and duration of maternal acyclovir suppression, there has not been any apparent, short-term adverse fetal or neonatal effect. Use of acyclovir in infants, even in those that are premature, is very well tolerated, with a wide margin of safety. In addition, the pharmacokinetics studies by Frenkel et al and Kimberlin et al, as well as the animal studies, suggest that maternal use of acyclovir may actually provide a prophylactic and therapeutic benefit to an infant who is exposed to HSV. The second question, as to whether acyclovir suppression would simply change symptomatic outbreaks into asymptomatic ones, also appears to have some answers. The information provided by Wald et al indicated that acyclovir suppression actually decreases asymptomatic shedding, along with decreasing clinical recurrences. Because asymptomatic shedding seems to be similar in pregnant and nonpregnant patients, it would be reasonable to assume that asymptomatic shedding also would be decreased at delivery in pregnant women with HSV infection. This supposition is supported by the data from the randomized trials and cohort studies that demonstrated a lower than expected asymptomatic shedding rate. As yet, however, there has been no randomized trial in pregnant women that has had an adequate sample size to confirm this on a statistically significant basis. The third question, whether acyclovir suppression would lower the frequency of symptomatic recurrences at parturition, reducing the need for cesarean in these patients, has answers as well, although they may not be as clear cut as one would like. Women who experience their first genital herpes outbreak while they are pregnant seem to benefit from acyclovir suppression, with both a decrease in the risk of clinical recurrences at delivery and a decreased need for cesarean delivery. This is well documented by a randomized trial and other cohort studies. Acyclovir's efficacy in patients who have a history of genital herpes infections antedating their pregnancy is less clear. The data appear to indicate a clinically important decrease in the likelihood of symptomatic reactivations at the time of delivery, although the sample sizes in the randomized studies have been too small to draw a statistically significant conclusion one way or the other. Unfortunately, a definitive trial for this group of women may never be done. Assuming a 13% recurrence risk at the time of delivery and a 50% decrease in recurrences with the use of acyclovir, 652 women would have to complete the study to achieve a power of 80%. Conducting the study at the largest, single institution, prenatal center in the United States, Scott et al were only able to enroll 222 women during a period of 6 years. Likewise, Brocklehurst et al terminated their trial early because of recruitment difficulties. They enrolled only 63 women during a period of 4 years using two different sites in the United Kingdom. Unless a multicenter trial is conducted or a meta-analysis performed on the available data, we will probably have to be content with the data as it now stands. With valacyclovir and famciclovir now available, it is unlikely that any further work will be done with acyclovir. Information from the valacyclovir trials, however, may reach statistical significance because of changes in the study design that will allow smaller sample sizes to reach adequate power. Famciclovir treatment holds promise because of its longer intracellular half-life, but until concerns about potential mutagenicity are resolved and more information on its efficacy for suppressive therapy becomes available, it should not be considered for maternal suppressive therapy. Acyclovir appears to be effective, at least in some cohorts, and is probably safe for the fetus. (AB

Prevention of herpes simplex virus infection and latency by prophylactic treatment with acyclovir in a weanling mouse model.

OBJECTIVE: Acyclovir is an antiviral agent that inhibits acute herpes simplex virus replication and decreases the frequency of reactivation, but it is not currently used to prevent primary disease or the establishment of latency. The purpose of this study was to reexamine the efficacy of acyclovir in preventing acute and latent herpes simplex virus infection. STUDY DESIGN: Mice were infected by footpad inoculation with 2 viral recombinants that express beta-galactosidase. Half of each group was treated prophylactically with intraperitoneal acyclovir and then given acyclovir in the drinking water. Four days after infection, the dorsal root ganglia were removed, fixed, and stained, and the number of cells expressing beta-galactosidase were counted. RESULTS: Compared with placebo, prophylactic acyclovir completely inhibited acute viral replication as evidenced by the absence of beta-galactosidase activity (P < .001) and significantly decreased the number of neurons harboring latent infection (P = .01). CONCLUSION: Acyclovir prophylaxis prevented acute and reduced latent ganglionic infection with herpes simplex virus in a weanling mouse model.

Cost-effectiveness of acyclovir suppression to prevent recurrent genital herpes in term pregnancy.

The objective of this paper is to determine whether acyclovir suppression provides a greater cost savings over no medical therapy in the management of recurrent genital herpes (HSV) in pregnancy. Estimates of the risk of HSV recurrence and cesarean delivery rates in acyclovir-treated and -untreated patients and frequency of neonatal acyclovir treatment were derived from literature reviews, prospective surveillance, and practices at our institution. Estimates of costs were derived from average hospital and outpatient clinic charges at our institution. Calculations were run separately for four different groups of patients: women whose first diagnosis of genital herpes occurred during the pregnancy, women whose diagnosis antedated pregnancy and who had infrequent recurrences, women whose diagnosis antedated pregnancy and had frequent recurrences, and all women with a history of genital herpes regardless of timing of diagnosis or frequency of recurrences. Suppressive acyclovir treatment of all term pregnant women with a history of genital herpes resulted in an estimated savings of $183.00 per patient or $36,600,000 per year. Women with their first episode of herpes diagnosed during pregnancy or with frequent recurrences benefitted even more, achieving a savings of $455.00 and $391.00 per patient, respectively. Assuming that prenatal acyclovir treatment is safe for the fetus, utilizing this management for all patients with recurrent HSV in pregnancy could immediately save $183 per patient. On a national level, this translates to $36,600,000 per year just in reduced obstetrical costs. If indirect costs associated with cesarean deliveries had been included in these calculations, the estimated savings would be even more substantial.

Postpartum endometritis caused by herpes simplex virus.

BACKGROUND: Herpes simplex virus (HSV) is rarely the causative agent of endometritis and is usually found in association with pelvic inflammatory disease. Only one case of postpartum HSV endometritis has been reported. CASES: We describe two cases of herpes simplex postpartum endometritis. Neither patient had genital HSV lesions noted at the time of delivery. The first case developed after a preterm cesarean delivery in an 18-year-old primipara. She had persistent puerperal fever despite broad-spectrum anti-microbial treatment. The second case was a 16-year-old primipara whose vaginal delivery was complicated by severe postpartum endometritis. Vulvar and endometrial cultures were positive for HSV alone in both patients. Both infants died from disseminated HSV infection. CONCLUSION: Herpes simplex virus can cause clinical postpartum endometritis.

Perinatal herpesvirus infections. Herpes simplex, varicella, and cytomegalovirus.

The herpesvirus infections (herpes simplex, varicella, and cytomegalovirus) create many dilemmas when encountered during pregnancy. This article reviews the epidemiologic diagnosis and management of perinatal herpesvirus infections. A review of possible future trends is also included.