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A study of 83 Australian adults with spinal cord injuries found that at least 56% had worked at some time post-injury and those who were working when surveyed had done so for an average of close to 10 years. Clerical, office, and administrative occupations proved to be the most suitable. (Author/CR)

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Background: Lactating women undergoing operations under general anesthesia are advised to pump and discard their milk for 24h after the procedure. We determined the kinetics of midazolam elimination in breast milk to ascertain its safety after midazolam administration.Methods: Five lactating women were studied after providing institutionally-approved written informed consent. Patients were premedicated with midazolam, 2 mg IV, 5 min before anesthetic induction with fentanyl, 100 μg IV, and propofol, 2.5 mg/kg IV. Anesthesia was maintained with potent volatile anesthetics. Milk was collected using an electric breast pump before and at 5, 7, 9, 11, and 24h after drug administration. Blood samples were collected before and at regular intervals up to 7h after drug administration. Plasma and milk midazolam concentrations were measured by LC-MS. Midazolam elimination in milk was modelled simultaneously with the plasma kinetics as the cumulative amount of drug in milk just as urinary elimination is modelled, albeit with a delay.Results: Plasma midazolam pharmacokinetics were consistent with those reported by ourselves and others. In 24h of milk collection, only 0.005 (± 0.005)% of the midazolam dose was eliminated in milk, representing 0.009 (± 0.005)% of the midazolam elimination clearance with a pharmacokinetic delay of approximately 9h.Conclusion: The amount of midazolam appearing in breast milk over 24h after administering a single dose is very small and unlikely to affect a healthy term infant.Clinical Pharmacology & Therapeutics (2005) 79, P7–P7; doi: 10.1016/j.clpt.2005.12.021 [ABSTRACT FROM AUTHOR]

The residual effects of neuromuscular blocking agents may persist into the early postoperative recovery period, even when neuromuscular blockade is carefully monitored and reversed in the operating room. Recent data suggest that mild degrees of residual paresis (train-of-four TOF ratios of 0.7-0.9) may be associated with significant impairment of respiratory and pharyngeal muscle function. Therefore, the new gold standard reflecting acceptable neuromuscular recovery is a TOF ratio > or =0.9. Several investigations have demonstrated that many patients continue to arrive in the postanesthesia care unit with TOF ratios <0.7-0.9. Several techniques may be used to reduce the risk of postoperative residual paresis, which include avoidance of long-acting muscle relaxants, use of neuromuscular monitoring in the operating room, routine reversal of neuromuscular blockade at a TOF count of 2-3, and early administration of reversal agents. Careful management of neuromuscular blockade may limit the occurrence of adverse events associated with residual postoperative paralysis. Large-scale outcome studies are needed to clearly define the impact of residual neuromuscular block on major morbidity and mortality in surgical patients.

We have previously shown that a dengue virus type 1 DNA vaccine expressing premembrane (prM) and envelope (E) genes was immunogenic in mice and monkeys and that rhesus monkeys vaccinated with this construct were completely to partially protected from virus challenge. In order to improve the immunogenicity of dengue DNA vaccines, we have evaluated the effect of lysosome targeting of antigens and coimmunization with a plasmid expressing GM-CSF on antibody responses. A dengue virus type 2 candidate vaccine containing prM and E genes was constructed in which the transmembrane and cytoplasmic regions of E were replaced by those of the lysosome-associated membrane protein (LAMP). The modified vaccine construct expressed antigen that was colocalized with endogenous LAMP in lysosomal vesicles of transfected cells, whereas the antigen expressed from the unmodified construct was not. It was hypothesized that targeting of antigen to the lysosomal compartment will increase antigen presentation by MHC class II, leading to stronger CD4-mediated immune responses. Mice immunized with the modified construct responded with significantly higher levels of virus neutralizing antibodies compared to those immunized with the unmodified construct. Coimmunization of mice with a plasmid expressing murine GM-CSF enhanced the antibody response obtained with either the unmodified or the modified construct alone. The highest antibody responses were noted when the modified construct was coinjected with plasmid expressing the GM-CSF gene. These results could form the basis for an effective tetravalent dengue virus DNA vaccine.

A dengue-2 (DEN-2) DNA vaccine coding for the premembrane and envelope (E) proteins and a recombinant fusion protein containing the B domain of the DEN-2 E protein fused to the maltose-binding protein (MBP) of Escherichia coli both elicited neutralizing antibody in mice. In order to achieve more rapid protective immunity as well as to increase the persistence of neutralizing antibody, we primed mice with the DNA vaccine (D), the recombinant MBP protein (R), or both (RD) given simultaneously, and then boosted twice with either the R (R/R/R or D/R/R) or D (D/D/D or R/D/D) constructs alone or the RD (RD/RD/RD) combination. All of the recombinant protein vaccines were given with alum as an adjuvant. The serum antibody response measured by enzyme-linked immunosorbent assay was highest in D/D/D mice and RD/RD/RD mice. The D/R/R mice showed an intermediate response, and the R/D/D and R/R/R showed the lowest response. The geometric mean (GM) 50% neutralizationtiter (50% plaque reduction neutralization, or PRNT50) was marginally higher for RD/RD/RD mice (891) at 9 months after priming than that for R/R/R mice (724). T he lowest GM PRNT50 titers were seen in the D/D/D mice (33) and R/D/D mice (40), and the D/R/R group had a slightly higher titer (156) than these 2 groups. The predominant antibody subclass for the D/D/D mice was immunoglobulin (Ig) G2a, similar to mice infected with live virus. The R/R/R mice showed an exclusive IgGI antibody response, and the RD/RD/RD response also was predominantly IgGI. The antibody subclass pattern of the R/D/D and D/R/R mice showed a more balanced distribution of both IgG1 and IgG2a. Investigating the neutralizing capacity of antibody subclasses suggested that both IgG1 and IgG2a could neutralize DEN-2 virus. Our observations indicate that the combination RD prime-boost regimen warrants further investigation as a vaccine strategy to prevent dengue infection.

The use of NMB agents for more than 24 to 48 hours in critically ill patients is associated with many potential complications. Neuromuscular-blocking drugs should be used only when their use is essential for optimal patient care. The indications for neuromuscular blockade must be defined clearly, and patients should be evaluated during treatment for the need for continued muscle relaxation. The smallest doses of NMB agents that will accomplish clinical goals should be used. This dosage can be determined through clinical evaluations and peripheral nerve monitoring. It is essential that all patients treated with NMB drugs receive appropriate sedation and analgesia. Myopathies, neuropathies, and alterations of the neuromuscular junction can occur in the ICU setting, and nondepolarizing muscle relaxants seem to be involved in the development of these disorders. Clinicians should be aware of risk factors that may predispose certain patients to neuromuscular complications, including sepsis and the use of high-dose steroids. Neuromuscular-blocking agents should be avoided in these patients if possible. Although not proved, early recognition and treatment of iatrogenic neuromuscular complications may improve patient outcome.

Faster techniques are needed for the early diagnosis of dengue fever and dengue hemorrhagic fever during the acute viremic phase of infection. An isothermal nucleic acid sequence-based amplification (NASBA) assay was optimized to amplify viral RNA of all four dengue virus serotypes by a set of universal primers and to type the amplified products by serotype-specific capture probes. The NASBA assay involved the use of silica to extract viral nucleic acid, which was amplified without thermocycling. The amplified product was detected by a probe-hybridization method that utilized electrochemiluminescence. Using normal human plasma spiked with dengue viruses, the NASBA assay had a detection threshold of 1 to 10 PFU/ml. The sensitivity and specificity of the assay were determined by testing 67 dengue virus-positive and 21 dengue virus-negative human serum or plasma samples. The "gold standard" used for comparison and evaluation was the mosquito C6/36 cell culture assay followed by an immunofluorescent assay. Viral infectivity titers in test samples were also determined by a direct plaque assay in Vero cells. The NASBA assay was able to detect dengue viral RNA in the clinical samples at plaque titers below 25 PFU/ml (the detection limit of the plaque assay). Of the 67 samples found positive by the C6/36 assay, 66 were found positive by the NASBA assay, for a sensitivity of 98.5%. The NASBA assay had a specificity of 100% based on the negative test results for the 21 normal human serum or plasma samples. These results indicate that the NASBA assay is a promising assay for the early diagnosis of dengue infections.

Recombinant proteins containing the B domain of dengue virus serotypes 1-4 fused to the maltose binding protein (MBP) of Escherichia coli were evaluated individually and as a tetravalent vaccine candidate in mice. Sera from mice immunized with monovalent DEN-MBP recombinant protein vaccines developed high titers of serotype homologous antibody in the enzyme-linked immunosorbent assay and the plaque-reduction neutralization test. Cross-reactive antibody titers were either several dilutions lower or not detectable. Sera from mice immunized with the tetravalent DEN subunit vaccine neutralized all 4 DEN viruses in the plaque-reduction neutralization test. The neutralizing antibody titers to each individual serotype were significantly greater than any cross-reactive neutralizing antibody titers induced by the monovalent vaccines, providing evidence that the tetravalent DEN recombinant subunit vaccine produced specific neutralizing antibody to all 4 serotypes of dengue virus.

Objective: To investigate the effect of a single, vital capacity breath (vital capacity maneuver [VCM]), administered at the end of cardiopulmonary bypass (CPB), on pulmonary gas exchange in patients undergoing coronary artery bypass graft surgery., Design: Prospective, randomized, double-blind study., Setting: University-affiliated hospital., Participants: Forty patients scheduled for elective coronary artery bypass graft surgery and early tracheal extubation., Interventions: Patients were randomized to 1 of 2 groups. VCM patients received a VCM at the conclusion of CPB. Control patients received no VCM., Measurements and Main Results: Intrapulmonary shunt (Q(S)/Q(T)), arterial oxygenation (PaO2), and alveolar-arterial oxygen gradients (P(A-a)O2) were measured after induction of anesthesia, CPB, intensive care unit (ICU) arrival, and extubation. The duration of postoperative intubation was recorded for each group. Q(S)/Q(T) increased significantly 30 minutes after CPB in the control group (15.7 +/- 1.8% to 27.4 +/- 2.6%; p = 0.01). In the VCM group, a small decrease in Q(S)/Q(T) occurred (16.1 +/- 2.0% to 14.9 +/- 2.0%). After ICU arrival and extubation, no significant difference in Q(S)/Q(T) existed between the 2 groups. With the exception of a higher P(A-a)O2 in the control group at induction of anesthesia, no differences in PaO2 or P(A-a)O2 were present between the 2 groups at any measurement interval. Patients who received a VCM were extubated earlier than the control group (6.5 +/- 2.1 hours v 9.4 +/- 4.2 hours; p = 0.01)., Conclusion: The use of a VCM prevented an increase in Q(S)/Q(T) from occurring in the operating room. Although a VCM did not influence pulmonary gas exchange in the ICU, its application in the operating room appears to exert a beneficial effect on tracheal extubation times after cardiac surgery., (Copyright 2001 by W.B. Saunders Company.)

A DNA vaccine that expresses the premembrane/membrane (prM) and envelope (E) genes of dengue virus serotype-1 was tested for immunogenicity and protection against dengue-1 virus challenge in Aotus nancymae monkeys. The vaccine, in 1 mg doses, was administered intradermally (i.d.) to three monkeys and intramuscularly (i.m.) to three others. For controls, a 1 mg dose of vector DNA was administered i.d. to two monkeys and i.m. to one. All animals were primed and then boosted at one and five months post priming. Sera were collected monthly and analyzed for dengue-1 antibodies by enzyme linked immunosorbent assay (ELISA) and plaque reduction neutralization test (PRNT). Dengue-1 antibodies were detectable in the sera from i.d. and i.m. vaccine inoculated animals one month after the first boost and peaked one month after the second boost. The antibody levels from sera of animals that received the vaccine via the i.d. route were twice those from sera of animals that received the vaccine via the i.m. route. Six months after the second boost all inoculated and two naive monkeys were challenged with 1.25x10(4) plaque forming units (PFU) of dengue-1 virus. Two vaccine immunized animals were protected from viremia while the others showed a reduction in viremia. The mean days of viremia were 1 and 1.3 for the animals that were immunized with the vaccine via the i.d. or i.m. route, respectively vs 4 and 2 mean days of viremia in the animals inoculated with control DNA. Naive animals were viremic for an average of 4 days. All of the three control monkeys that received control DNA inoculum by either the i.d. or i.m. route had an intermittent viremia pattern with one or more negative days interspersed between the positive days. This pattern was not observed in any of the vaccine recipients or the naïve control monkeys. These results demonstrate that DNA immunization is a promising approach for the development of dengue vaccines and that A. nancymae monkeys are suitable for dengue vaccine trials.

A candidate DNA vaccine expressing dengue virus type 1 pre-membrane and envelope proteins was used to immunize rhesus macaques. Monkeys were immunized intramuscularly (i.m.) or intradermally (i.d.) by three or four 1 mg doses of vaccine, respectively. Monkeys that were inoculated i.m. seroconverted more quickly and had higher antibody levels than those that were inoculated i.d. The sera exhibited virus-neutralizing activity, which declined over time. Four of the eight i.m.-inoculated monkeys were protected completely from developing viraemia when challenged 4 months after the last dose with homologous dengue virus. The other four monkeys had reduced viraemia compared with the control immunized monkeys. The i.d. -inoculated monkeys showed no reduction in viraemia when challenged with the virus. All vaccinated monkeys showed an anamnestic antibody response, indicating that they had established immunological memory. Vaccine-induced antibody had an avidity index similar to that of antibody induced by virus infection; however, no clear correlation was apparent between antibody avidity and virus neutralization titres.

Dengue virus (DV), an arthropod-borne flavivirus, causes a febrile illness for which there is no antiviral treatment and no vaccine. Macrophages are important in dengue pathogenesis; however, the initial target cell for DV infection remains unknown. As DV is introduced into human skin by mosquitoes of the genus Aedes, we undertook experiments to determine whether human dendritic cells (DCs) were permissive for the growth of DV. Initial experiments demonstrated that blood-derived DCs were 10-fold more permissive for DV infection than were monocytes or macrophages. We confirmed this with human skin DCs (Langerhans cells and dermal/interstitial DCs). Using cadaveric human skin explants, we exposed skin DCs to DV ex vivo. Of the human leukocyte antigen DR-positive DCs that migrated from the skin, emigrants from both dermis and epidermis, 60-80% expressed DV antigens. These observations were supported by histologic findings from the skin rash of a human subject who received an attenuated tetravalent dengue vaccine. Immunohistochemistry of the skin showed CD1a-positive DCs double-labeled with an antibody against DV envelope glycoprotein. These data demonstrate that human skin DCs are permissive for DV infection, and provide a potential mechanism for the transmission of DV into human skin.

Study Objectives: To prospectively assess the impact of a liberalized preoperative fasting policy on operating room (OR) utilization., Study Design: Prospective cohort study involving data collection before and after a change in nil per os (NPO) policy., Setting: Academic teaching hospital., Patients: 5,420 consecutive outpatients and AM admissions., Interventions: Data collection was done on all adult patients who presented to our OR suite over two 15-week periods. During the first 15-week period, patients were instructed to drink no liquids after midnight (control group, n = 2,646). In the second 15-week period, patients were allowed to consume unlimited clear fluids until 2 to 3 hours prior to surgery (study group, n = 2,774)., Measurements and Main Results: We found no difference between the control and study groups in the number of cases cancelled (0 in each group) or delayed (8 vs. 9; relative risk [RR] = 1.07, 95% confidence interval [CI] = 1.000 to 1.148) due to noncompliance with fasting guidelines. There was no difference between the groups in the number of cases of aspiration (0 in each group). In the control group, significantly more episodes of regurgitation were noted (12 vs. 9; RR = 0.715, 95% CI = 0.535 to 0.955) and more rapid-sequence/awake intubations were performed (119 vs. 51; RR = 0.409, 95% CI = 0.306 to 0.546) than in the study group., Conclusions: Liberalizing a preoperative fasting policy and allowing patients to consume unrestricted clear fluids up until 3 hours before their scheduled time of surgery did not affect their compliance with fasting requirements. No increase in cancellations or delays of surgical procedures due to inappropriate oral intake was observed.

Two easy-to-use commercial diagnostic assays, a dipstick enzyme-linked immunosorbent assay (ELISA) (Integrated Diagnostics, Baltimore, Md.) and an immunochromatographic card assay (PanBio, Brisbane, Australia) were evaluated for detection of immunoglobulin M (IgM) antibody to dengue virus with an in-house IgM antibody capture microplate ELISA as a reference assay. The dipstick ELISA was based on the indirect-ELISA format using dengue 2 virus as the only antigen and enzyme-labeled goat anti-human IgM antibody as the detector. The total assay time was 75 min. The immunochromatographic card assay was based on the antibody capture format and separately measured both anti-dengue virus IgM and IgG in the same test. Colloidal-gold-labeled anti-dengue virus monoclonal antibody bound with dengue virus 1 to 4 antigen cocktail was the detector, and anti-human IgM and IgG were the capture antibodies. The total assay time was <10 min. Sera from 164 individuals classified as either anti-dengue virus IgM positive (94) or anti-dengue virus IgM negative (70) in the reference microplate ELISA with a dengue virus 1 to 4 antigen cocktail were tested in the two commercial assays. The dipstick ELISA missed 7 of 94 positive samples, for a sensitivity of 92.6%, while the immunochromatographic card assay missed two positive samples, for a sensitivity of 97.9%. Of the 70 negative samples, four were false positive by the dipstick ELISA and two were false positive in the immunochromatographic card assay, resulting in specificities of 94.3 and 97.1%, respectively. Both commercial assays provide sensitive and specific detection of anti-dengue virus IgM antibody and could prove useful in settings where the microplate ELISA is impractical.

During the past year, we have seen the continuing spread of antimicrobial drug resistance in important gastrointestinal pathogens. Typhoid fever seen in the United States was multidrug resistant, but still susceptible to quinolones. The mechanism of quinolone resistant typhoid in Vietnam was better elucidated. Treatment failures in enterobacteriaceae treated with quinolones suggest that the minimum inhibitory concentration break point for resistance should be lowered. Evidence is mounting that ciprofloxacin and ofloxacin may be safely used to treat serious infections in children. Cefixime showed some promise in treating shigellosis in an open labeled trial. Decreased gastric acid secretion was associated with cholera but not dysentery. Phase 1 trials of vaccines for cholera and enterotoxigenic Escherichia coli showed promise. The antifungal drug, clotrimazole, demonstrated ability to inhibit secretory diarrhea in laboratory studies. Nitazoxanide demonstrated efficacy in both protozoan and helminthic infections in humans, including fascioliasis.

New drugs are needed for preventing drug-resistant Plasmodium falciparum malaria. The prophylactic efficacy of azithromycin against P. falciparum in malaria-immune Kenyans was 83%. We conducted a double-blind, placebo-controlled trial to determine the prophylactic efficacy of azithromycin against multidrug-resistant P. falciparum malaria and chloroquine-resistant Plasmodium vivax malaria in Indonesian adults with limited immunity. After radical cure therapy, 300 randomized subjects received azithromycin (148 subjects, 750-mg loading dose followed by 250 mg/d), placebo (77), or doxycycline (75, 100 mg/d). The end point was slide-proven parasitemia. There were 58 P. falciparum and 29 P. vivax prophylaxis failures over 20 weeks. Using incidence rates, the protective efficacy of azithromycin relative to placebo was 71.6% (95% confidence interval [CI], 50.3-83.8) against P. falciparum malaria and 98.9% (95% CI, 93.1-99.9) against P. vivax malaria. Corresponding figures for doxycycline were 96.3% (95% CI, 85.4-99.6) and 98% (95% CI, 88.0-99.9), respectively. Daily azithromycin offered excellent protection against P. vivax malaria but modest protection against P. falciparum malaria.

Falciparum malaria is one of the most common infectious illnesses in the world and can progress rapidly to coma and death in the nonimmune patient. The presentation is nonspecific, so blood smears must be made and read quickly. Proper therapy requires taking into account drug resistance, recognizing the signs of severe malaria, and proper treatment for complications. Long-sleeved clothing, bed nets, insecticides, and chemoprophylaxis can help prevent malaria, but the infection must be suspected in any traveler returning from an endemic area. This article reviews epidemiology, diagnosis, treatment, and prevention of falciparum malaria in the temperate zone.

A Plasmodium vivax-like human malaria parasite was recently identified from Madang, a holoendemic malarious region in Papua New Guinea. The complete nucleotide sequence of the circumsporozoite (CS) protein gene of this parasite is presented here. The CS protein of this parasite has an 11-mer repeat sequence and is different from the other known CS protein genes of human malaria parasites. However, it is identical to the CS protein gene of a monkey malaria parasite, Plasmodium simiovale. This P. vivax-like malaria parasite was found in Sepik, another malarious region of Papua New Guinea, and in Brazil, Indonesia, and Madagascar. No pure isolate of this parasite was identified. Specific oligonucleotide probes were used to determine relative proportion of the P. vivax-like parasite in P. vivax (type 1 and type 2) mixed field isolates. Compared with P. vivax or Plasmodium falciparum, the circumsporozoite protein of P. vivax-like parasites showed markedly less polymorphism.

Objective: To compare the safety and efficacy of loperamide plus ciprofloxacin with those of ciprofloxacin alone in the treatment of bacillary dysentery., Design: Double-blind, placebo-controlled, randomized clinical trial., Setting: Hospital in Thailand., Participants: Eighty-eight adults with dysentery seeking medical care between November 1990 and February 1992. Patients who had received prior antibiotics or antimotility drugs were excluded., Intervention: All 88 patients with dysentery were treated with ciprofloxacin, 500 mg twice daily for 3 days. Forty-two of these patients were randomly assigned to receive loperamide, a 4-mg initial dose followed by 2 mg after every loose stool (as many as eight caplets [16 mg] daily), and 46 were randomly assigned to receive placebo., Measurements: Stools were collected daily until resolution of diarrhea and again after 10 days. The time to passage of the last unformed stool, number of unformed stools, and symptoms were recorded after treatment., Results: Shigella or enteroinvasive Escherichia coli (53%), Vibrio parahaemolyticus (16%), and Salmonella (7%) were the most common bacterial enteric pathogens identified in 88 patients with dysentery. In patients infected with Shigella or enteroinvasive E. coli, the median duration of diarrhea was 19 hours (25th to 75th percentiles, 6 to 42 hours) for those receiving loperamide plus ciprofloxacin compared with 42 hours (21 to 46 hours) for those receiving ciprofloxacin alone (P = 0.028). The median number of diarrheal stools for those receiving ciprofloxacin and loperamide was 2.0 (1 to 5 stools) compared with 6.5 (2 to 9 stools) for those receiving ciprofloxacin alone (P = 0.016). None of the participants had a temperature greater than 38 degrees C after 24 hours of treatment. None of the patients was infected with the same bacterial enteric pathogen more than 1 day after receiving treatment., Conclusions: Loperamide decreases the number of unformed stools and shortens the duration of diarrhea in dysentery caused by Shigella in adults treated with ciprofloxacin.

Detection of Shigella organisms and enteroinvasive Escherichia coli (EIEC) by polymerase chain reaction (PCR) was evaluated in 20 patients with dysentery before and in 17 of the 20 after treatment with ciprofloxacin. DNA sequences coding for IpaH antigen, a multiple copy sequence found on the chromosome, and the invasion plasmid locus (ial) was detected after DNA amplification in 13 stools from patients from whom shigellae or EIEC were isolated but not in 21 nondysenteric stools containing other enteric bacteria. Although shigellae or EIEC were not isolated from any patient with dysentery after ciprofloxacin treatment, IpaH and ial sequences were found after PCR amplification in 7 patients after treatment with ciprofloxacin. IpaH sequences alone were detected in 4 patients; DNA augmentation of IpaH in stools in a specific way to identify Shigella or EIEC infection in persons from whom cultures cannot be obtained promptly after the onset of diarrhea or who have received antibiotics.

Chloroquine has been the treatment of choice for vivax malaria for more than 40 years. Lately, several case-reports have suggested the emergence of resistance to chloroquine in Plasmodium vivax in Papua New Guinea and Indonesia. We undertook prospective treatment and prophylaxis trials of chloroquine in children and adults with vivax malaria living in Irian Jaya (Indonesia New Guinea). 46 villagers with P vivax parasitaemia were treated with chloroquine by mouth (25 mg base/kg body weight divided over 3 days) and followed up for 14 days. Parasitaemia cleared initially but recurred within 14 days in 10 (22%) subjects. All recurrences were in children younger than 11 years, 7 of whom were younger than 4 years; the failure rate among children under 4 was 70%. 7 of the patients with recurrences were given a second course of chloroquine. In all, the infections initially cleared but recurrent parasitaemia developed in 5 (71%) within 14 days. Whole-blood chloroquine concentrations were consistently above those previously shown to cure P vivax blood infections (90 micrograms/L whole blood). Subjects whose initial infections cleared and who had no parasitaemia on day 14 received weekly prophylaxis with chloroquine. Despite the presence of expected blood chloroquine concentrations, P vivax parasitaemia developed in 9 of 17 subjects receiving prophylaxis during 8 weeks of follow-up (median time to parasitaemia 5.3 weeks). Chloroquine can no longer be relied upon for effective treatment or chemoprophylaxis of P vivax blood infections acquired in this part of New Guinea.

Cocaine abuse is common among parturients with an incidence of 11.8 to 20%. Myocardial infarction is a rare and lethal event during pregnancy with an incidence of 1 in 10,000 pregnancies. We present the anaesthetic management of a parturient of 36 wk gestation who suffered a myocardial infarction nine hours before delivery which was temporally related to "crack" cocaine use. The patient's cardiovascular system became unstable following cocaine use, and she required mechanical ventilatory support and pharmacologic stabilization guided by invasive haemodynamic monitoring. This patient survived a non-Q wave myocardial infarction, but the prognosis of peripartum myocardial infarction remains poor with a mortality rate of 30-40% which is increased if the infarction occurs in the third trimester or postpartum period. The optimal mode and timing of delivery after myocardial infarction is unresolved. The association between cocaine use and myocardial infarction was first described in 1982, and cocaine remains unique among local anaesthetics in its ability to compromise the cardiovascular system through both sympathomimetic effects and vasoconstrictive effects on coronary arteries. Because of the prevalence of substance abuse, cocaine use should be considered in the differential diagnosis of sudden cardiovascular compromise in parturients.

To determine the efficacy of loperamide given with long- and short-course quinolone therapy for treating traveler's diarrhea, 142 US military personnel were randomized to receive a single 750-mg dose of ciprofloxacin with placebo, 750 mg of ciprofloxacin with loperamide, or a 3-day course of 500 mg of ciprofloxacin twice daily with loperamide. Culture of pretreatment stool specimens revealed campylobacters (41%), salmonellae (18%), enterotoxigenic Escherichia coli (ETEC, 6%), and shigellae (4%). Of the participants, 87% completely recovered within 72 h of entry. Total duration of illness did not differ significantly among the three treatment groups, but patients in the 3-day ciprofloxacin plus loperamide group reported a lower cumulative number of liquid bowel movements at 48 and 72 h after enrollment compared with patients in the single-dose ciprofloxacin plus placebo group (1.8 vs. 3.6, P = .01; 2.0 vs. 3.9, P = .01). While not delivering a remarkable therapeutic advantage, loperamide appears to be safe for treatment of non-ETEC causes of traveler's diarrhea. Two of 54 patients with Campylobacter enteritis had a clinical relapse after treatment that was associated with development of ciprofloxacin resistance.