Leveraging ecological momentary assessment to understand variability in food parenting practices within a low-income racially/ethnically diverse sample of parents of preschoolers.

Children's eating behaviors are shaped significantly by their home food environment, including exposure to food parenting practices. The current study leveraged ecological momentary assessment (EMA) to describe how food parenting practices used to feed preschoolers (n = 116) differed across contextual factors around eating, including type of eating occasion (i.e., meals vs. snacks), day of the week (i.e., weekend vs. weekday), who initiated the meal (parent vs. child), emotional climate of the eating occasion. Parent perceptions of how well the eating occasion went, including how well the child ate and whether the food parenting practices worked as intended were also explored. Parent use of specific food parenting practices, situated within four higher-order domains (i.e., structure, autonomy support, coercive control, indulgent), was found to differ by type of eating occasion; parents engaged in a higher proportion of structure practices at meals than at snacks. Use of specific food parenting practices differed by mealtime emotional climate; parent use of structure and autonomy support was associated with eating occasions described as relaxed, enjoyable, neutral, and fun. Finally, parent perception of how well the child ate differed by use of specific food parenting practices; during eating occasions when parent's felt their child ate "not enough", they used less autonomy support and more coercive control compared to eating occasions where the child ate "enough and a good balance." Leveraging EMA allowed for increased understanding of the variability in food parenting practices and contextual factors. Findings may be utilized to inform the development of larger-scale studies seeking to understand why parents choose specific approaches to feeding their children, as well as the impact of various approaches to child feeding on child health outcomes.

A descriptive assessment of a broad range of food-related parenting practices in a diverse cohort of parents of preschoolers using the novel Real-Time Parent Feeding Practices Survey.

BACKGROUND: Much of the research to-date on food parenting has evaluated typical use of various parent feeding practices via questionnaire. The Real-Time Parent Feeding Practices Measurement survey was developed for use within an Ecological Momentary Assessment (EMA) protocol to capture momentary use of parent feeding practices in real-time. METHODS: This manuscript describes the development of the EMA-based Real-Time Parent Feeding Practices survey and highlights initial descriptive data on the real-time use of 22 individual parent feeding practices (e.g., pressure-to-eat, guided choices, etc.) as reported via EMA by parents of preschool-aged children (n = 116) over a 10-day data collection time period. A total of 3382 eating occasions were reported, with an average of 29.2 reported eating occasions per participant. RESULTS: Results revealed that most participants used a variety of food-related parenting practices day-to-day that span four higher-order domains: structure, autonomy support, coercive control and indulgence. Supportive feeding practices, defined as those from the structure and autonomy support domains, were reported most frequently, with one or more structure behavior (e.g., specific mealtime rules/routines) was used at 88.9% of reported eating occasions and one or more autonomy support behavior (e.g., involvement of the child in meal preparation) was used at 87.3% of eating occasions. While unsupportive feeding practices, defined as practices from within the coercive control (e.g., pressure-to-eat) and indulgent (e.g., anticipatory catering) feeding domains, were reported less frequently, one or more behaviors from each of these domains were still reported at over 25% of all eating occasions. CONCLUSIONS: Results of the current study take a next step towards deepening our understanding of the use of a broad range of food-related parenting practices in real-time. Findings revealed that the vast majority of practices used by parents fall within the structure and autonomy support domains. However, most parents did not exclusively use supportive or unsupportive practices, rather they used a combination of food-related parenting practices across all domains. Future research should continue to explore a broad range of food-related parenting practices and seek to understand how parent approaches to feeding are associated with long-term child outcomes, including dietary intake, food preferences, and eating patterns.

COVID-19 pandemic shifts in food-related parenting practices within an ethnically/racially and socioeconomically diverse sample of families of preschool-aged children.

This study aimed to evaluate the influence of the COVID-19 pandemic on food parenting practices used by parents of young children. Ecological Momentary Assessment (EMA) was used to evaluate parents' use of coercive, indulgent, structured, and autonomy supportive food parenting practices before and during the COVID-19 pandemic among a diverse racial/ethnic sample (n = 72) of parents of preschool-aged children. The impact of parent and child mood/behavior on use of specific food parenting practices was also evaluated during both time periods. Results revealed that most parents of preschoolers use a variety of food parenting practices, including coercive control, indulgence, structure, and autonomy support practices. The use of structured and autonomy supportive practices, however, decreased during the COVID-19 pandemic. Further, the types of practices used by parents were contextually associated with the mood of the parent as well as child mood. Parent negative mood during COVID-19 was associated with higher levels of coercive control and indulgence and lower levels of structure, whereas child positive child mood was associated with greater use of autonomy supportive practices. These findings suggest that effects of the COVID-19 pandemic on family dynamics around feeding young children include shifts away from theoretically supportive approaches to parenting and highlight the roles of parent and child mood/behavior as potentially important momentary influences on food parenting during this time. Public health practitioners and clinicians working with parents of young children during COVID-19, and in years to come, should consider the potential impact of parental mood and stress, as well as child mood and behaviors. Additional research is needed to better understand how to best help parents maintain supportive feeding practices in the face of challenging situations.

Measurements of Gross α- and ß-Activities of Archived PM2.5 and PM10 Teflon Filter Samples.

The adverse effects of ambient particulate matter (PM) on human health have been well demonstrated, but the underlying properties responsible for its toxicity are still unclear. We hypothesized that particulate radioactivity, which is due to the attachment of radioactive nuclides on particle surfaces, may be responsible for part of PM toxicity. We measured the gross α- and ß-activities for daily PM2.5 and PM10 filters collected at the Harvard Supersite in downtown Boston from 2005 to 2006 and calculated the radioactivities at the time of air sampling retrospectively based on a previously established formula. We examined the relationship between different radioactivities and compared our measurements to those measured at the Boston EPA RadNet Station. The results showed that the majority of PM10 radioactivity is associated with that of PM2.5 samples for both α-activity (98%) and ß-activity (83%). A strong linear relationship was observed between the α- and ß-activities for both PM2.5 [slope = 0.47 (±0.03); p-value < 0.0001] and PM10 [slope = 0.46 (±0.09); p-value < 0.0001] samples. Measurements at the Harvard Supersite and at EPA RadNet sites are highly correlated for both α-activities [slope = 0.17 (±0.02), p-value < 0.0001] and ß-activities [slope = 0.30 (±0.05), p-value < 0.0001]. Additionally, we identified several significant predictors for PM2.5 α-activities. This novel method we developed to measure α- and ß-activities from archived filters will make it possible to assess the retrospective particle radioactivity exposure for future epidemiological studies.

Secondary particles formed from the exhaust of vehicles using ethanol-gasoline blends increase the production of pulmonary and cardiac reactive oxygen species and induce pulmonary inflammation.

BACKGROUND: Ethanol vehicles release exhaust gases that contribute to the formation of secondary organic aerosols (SOA). OBJECTIVE: To determine in vivo toxicity resulting from exposure to SOA derived from vehicles using different ethanol-gasoline blends (E0, E10, E22, E85W, E85S, E100). METHODS: Exhaust emissions from vehicles using ethanol blends were delivered to a photochemical chamber and reacted to produce SOA. The aerosol samples were collected on filters, extracted, and dispersed in an aqueous solutions and intratracheally instilled into Sprague Dawley rats in doses of 700 µg/0.2 ml. After 45 min and 4 h pulmonary and cardiac chemiluminescence (CL) was measured to estimate the amount of reactive oxygen species (ROS) produced in the lungs and heart. Inflammation was measured by differential cell count in bronchoalveolar lavages (BAL). RESULTS: Statistically and biologically significant differences in response to secondary particles from the different fuel formulations were detected. Compared to the control group, animals exposed to SOA from gasoline (E0) showed a significantly higher average CL in the lungs at 45 min. The highest CL averages in the heart were observed in the groups exposed to SOA from E10 and pure ethanol (E100) at 45 min. BAL of animals exposed to SOA from E0 and E85S had a significant increased number of macrophages at 45 min. BAL neutrophil count was increased in the groups exposed to E85S (45 min) and E0 (4 h). Animals exposed to E0 and E85W had increased BAL lymphocyte count compared to the control and the other exposed groups. DISCUSSION: Our results suggest that SOA generated by gasoline (E0), followed by ethanol blends E85S and E85W, substantially induce oxidative stress measured by ROS generation and pulmonary inflammation measured by the recruitment of white blood cells in BAL.

The effects of urban green space and road proximity to indoor traffic-related PM2.5, NO2, and BC exposure in inner-city schools.

BACKGROUND: Since there are known adverse health impacts of traffic-related air pollution, while at the same time there are potential health benefits from greenness, it is important to examine more closely the impacts of these factors on indoor air quality in urban schools. OBJECTIVE: This study investigates the association of road proximity and urban greenness to indoor traffic-related fine particulate matter (PM2.5), nitrogen dioxide (NO2), and black carbon (BC) in inner-city schools. METHODS: PM2.5, NO2, and BC were measured indoors at 74 schools and outdoors at a central urban over a 10-year period. Seasonal urban greenness was estimated using the Normalized Difference Vegetation Index (NDVI) with 270 and 1230 m buffers. The associations between indoor traffic-related air pollution and road proximity and greenness were investigated with mixed-effects models. RESULTS: The analysis showed linear decays of indoor traffic-related PM2.5, NO2, and BC by 60%, 35%, and 22%, respectively for schools located at a greater distance from major roads. The results further showed that surrounding school greenness at 270 m buffer was significantly associated (p < 0.05) with lower indoor traffic-related PM2.5: -0.068 (95% CI: -0.124, -0.013), NO2: -0.139 (95% CI: -0.185, -0.092), and BC: -0.060 (95% CI: -0.115, -0.005). These associations were stronger for surrounding greenness at a greater distance from the schools (buffer 1230 m) PM2.5: -0.101 (95% CI: -0.156, -0.046) NO2: -0.122 (95% CI: -0.169, -0.075) BC: -0.080 (95% CI: -0.136, -0.026). These inverse associations were stronger after fully adjusting for regional pollution and meteorological conditions. IMPACT STATEMENT: More than 90% of children under the age of 15 worldwide are exposed to elevated air pollution levels exceeding the WHO's guidelines. The study investigates the impact that urban infrastructure and greenness, in particular green areas and road proximity, have on indoor exposures to traffic-related PM2.5, NO2, and BC in inner-city schools. By examining a 10-year period the study provides insights for air quality management, into how road proximity and greenness at different buffers from the school locations can affect indoor exposure.

Ambient PM2.5 temporal variation and source apportionment in Mbarara, Uganda.

Air pollution is the leading environmental cause of death globally, and most mortality occurs in resource-limited settings such as sub-Saharan Africa. The African continent experiences some of the worst ambient air pollution in the world, yet there are relatively little African data characterizing ambient pollutant levels and source admixtures. In Uganda, ambient PM2.5 levels exceed international health standards. However, most studies focus only on urban environments and do not characterize pollutant sources. We measured daily ambient PM2.5 concentrations and sources in Mbarara, Uganda from May 2018 through February 2019 using Harvard impactors fitted with size-selective inlets. We compared our estimates to publicly available levels in Kampala, and to World Health Organization (WHO) air quality guidelines. We characterized the leading PM2.5 sources in Mbarara using x-ray fluorescence and positive matrix factorization. Daily PM2.5 concentrations were 26.7 µg m-3 and 59.4 µg m-3 in Mbarara and Kampala, respectively (p<0.001). PM2.5 concentrations exceeded WHO guidelines on 58% of days in Mbarara and 99% of days in Kampala. In Mbarara, PM2.5 was higher in the dry as compared to the rainy season (30.8 vs 21.3, p<0.001), while seasonal variation was not observed in Kampala. PM2.5 concentrations did not vary on weekdays versus weekends in either city. In Mbarara, the six main ambient PM2.5 sources identified included (in order of abundance): traffic-related, biomass and secondary aerosols, industry and metallurgy, heavy oil and fuel combustion, fine soil, and salt aerosol. Our findings confirm that air quality in southwestern Uganda is unsafe and that mitigation efforts are urgently needed. Ongoing work focused on improving air quality in the region may have the greatest impact if focused on traffic and biomass-related sources.

Occurrence of microalbuminuria in young people with Type 1 diabetes: importance of age and diabetes duration.

AIMS: To determine the occurrence of microalbuminuria in young people with Type 1 diabetes mellitus followed prospectively for 2 years and to relate the presence of persistent elevations in urinary albumin excretion (UAE) to age, diabetes duration, puberty and other factors. METHODS: During a 2 year period, random urine samples were obtained from 471 patients, aged 8-18 years (mean +/-sd 12.9 +/- 2.3 years) with Type 1 diabetes duration 5.6 +/- 3.0 years, as part of routine clinical care. Urine albumin and creatinine concentrations were measured in 1310 samples (median, 3 samples per patient) and the albumin:creatinine ratio was calculated (in micrograms albumin per milligram creatinine). Height, weight, blood pressure (BP), glycated haemoglobin (HbA(1c)), blood glucose monitoring frequency and Tanner staging were collected from patients' medical records. RESULTS: Twenty-three per cent of patients had one or more sample with elevated UAE (> or =20 microg/mg) and 9.3% had persistent elevations (> or =2 samples > or =20 microg/mg). Those with and without persistent microalbuminuria did not differ significantly in age, diabetes duration, z-score for body mass index, pubertal status or BP percentile. Ten per cent of children <13 years old and 9% of children > or =13 years old had persistent microalbuminuria. Persistent microalbuminuria was significantly associated with diabetes duration only in older children (duration 0.5-3 years, 4%; 4-6 years, 8%; > or =7 years, 14%; P = 0.02, trend test). Mean HbA(1c) over the 2 years was 8.7 +/- 1.2%. In a logistic regression model, mean HbA(1c) was the only significant predictor of persistent microalbuminuria (odds ratio 1.3, 95% confidence interval 1.0-1.6, P = 0.05). CONCLUSIONS: Microalbuminuria in older children with Type 1 diabetes is likely to be clinically significant. In younger children, it may reflect functional, reversible renal changes. Longitudinal analysis is needed to confirm the probable transient nature of microalbuminuria in young patients with Type 1 diabetes.

Intramural ("small vessel") coronary artery disease in hypertrophic cardiomyopathy.

Many patients with hypertrophic cardiomyopathy have signs and symptoms of myocardial ischemia and dysfunction. Although hypertrophy and increased left ventricular pressure can account for such abnormalities, altered small intramural coronary arteries have also been described in such patients. To determine the prevalence and extent as well as the clinical relevance of abnormal intramural coronary arteries, a histologic analysis of left ventricular myocardium obtained at necropsy was performed in 48 patients with hypertrophic cardiomyopathy (but without atherosclerosis of the extramural coronary arteries) and in 68 control patients with either a normal heart or acquired heart disease. In hypertrophic cardiomyopathy, abnormal intramural coronary arteries were characterized by thickening of the vessel wall and a decrease in luminal size. The wall thickening was due to proliferation of medial or intimal components, or both, particularly smooth muscle cells and collagen. Of the 48 patients with hypertrophic cardiomyopathy, 40 (83%) had abnormalities of intramural coronary arteries located in the ventricular septum (33 patients), anterior left ventricular free wall (20 patients) or posterior free wall (9 patients); an average of 3.0 +/- 0.7 abnormal arteries were identified per tissue section. Altered intramural coronary arteries were also significantly more common in tissue sections having considerable myocardial fibrosis (31 [74%] of 42) than in those with no or mild fibrosis (31 [30%] of 102; p less than 0.001). Abnormal intramural coronary arteries were also identified in three of eight infants who died of hypertrophic cardiomyopathy before 1 year of age. In contrast, only rare altered intramural coronary arteries were identified in 6 (9%) of the 68 control patients (0.1 +/- 0.05 abnormal arteries per section; p less than 0.001) and those arteries showed only mild thickening of the wall and minimal luminal narrowing. Moreover, of those patients with abnormal intramural coronary arteries, such vessels were about 20 times more frequent in patients with hypertrophic cardiomyopathy (0.9 +/- 0.2/cm2 myocardium) than in control patients (0.04 +/- 0.02/cm2 myocardium). Hence, abnormal intramural coronary arteries with markedly thickened walls and narrowed lumens are present in increased numbers in most patients with hypertrophic cardiomyopathy studied at necropsy and may represent a congenital component of the underlying cardiomyopathic process.(ABSTRACT TRUNCATED AT 400 WORDS)

Circulating anticoagulant in the procainamide-induced lupus syndrome.

An elderly man with procainamide hydrochloride-induced lupus syndrome had a circulating anticoagulant against factor XI and a biologic false-positive (BFP) test result for syphilis. This was not associated with hemorrhagic problems. The activity of the circulating anticoagulant and the BFP disappeared within days following discontinuation of procainamide and the administration of corticosteroids.

Adrenal crisis in the setting of high-dose ketoconazole therapy.

We describe a patient with type I diabetes mellitus and hypothyroidism who developed frank adrenocortical insufficiency while receiving a high-dose ketoconazole therapy for keratitis caused by Acanthamoeba species. While impaired cortisol responses to corticotropin and mildly symptomatic hypoadrenalism have been described previously with ketoconazole therapy, to our knowledge, this case represents the first documented article of an actual adrenal crisis associated with this drug. Two reasons are postulated for the development of this complication in our patient: high-dose ketoconazole therapy given in divided doses during the day, and a possibly impaired central response to stress because of hypothyroidism. Our article points to the need to monitor patients treated with high-dose ketoconazole for adrenal insufficiency, particularly if associated illnesses are present that may impair an adequate stress response.

Effect of 40-cm segment umbilical cord milking on hemoglobin and serum ferritin at 6 months of age in full-term infants of anemic and non-anemic mothers.

OBJECTIVE: To assess the effect of early clamping and milking of a 40-cm umbilical cord LUCM (long umbilical cord and milking) on hemoglobin (Hb) and serum ferritin concentrations at 6 months of age and to evaluate whether the effect is different in infants of anemic and non-anemic mothers. STUDY DESIGN: Eligible term-infants of anemic (maternal Hb<11.0 g dl(-1)) and non-anemic mothers (Hb ⩾11.0 g dl(-1)) were randomized to LUCM or control groups (N=100 each). In the LUCM group, the umbilical cord was clamped at 40-cm length and milked. The control group had the cord clamped at 5 cm and not milked. Neonatal morbidities until discharge and Hb and serum ferritin at 6 months of age were compared. Effects in infants of anemic and non-anemic mothers were compared. RESULT: Compared with infants of non-anemic mothers, cord Hb was similar (14.50±1.90 g dl(-1) vs 14.67±1.73 g dl(-1)), but cord ferritin lower (85.8±55.4 ng ml(-1) vs 119.4±58.5 ng ml(-1), P<0.01) in infants of anemic mothers. Mean Hb concentration at 6 months was 9.60±1.42 g dl(-1) in the LUCM group and 9.07±1.10 g dl(-1) in the control group (P=0.004). Mean serum-ferritin concentration at 6 months was 113.9±43.8 ng ml(-1) in the LUCM group and 70.8±39.5 ng/ml in the control group (P<0.001). The effectiveness of LUCM did not vary with the maternal anemia status. CONCLUSION: Keeping the umbilical cord long and milking may be an effective method for improving Hb and iron stores at 6 months of age in term-infants.

Dawn simulation compared with a dim red signal in the treatment of winter depression.

In a randomized, parallel design, 19 patients with winter depression were treated with either a week of a white 1.5-hr dawn simulation peaking at 250 lux or a week of a red, 1.5-hr dawn signal peaking at 2 lux. The subjects were told that they would receive either a white or red dawn reaching in intensity that would be dimmer than standard bright light treatment. At the end of both the baseline week and the treatment week subjects were blindly assessed with the Hamilton Rating Scale for Depression (HDRS). Analysis of covariance was used to compare the two dawn treatments. The white, 1.5-hr, 250 lux dawn simulation resulted in significantly (p < 0.05) lower HDRS scores compared to the red, 1.5-hr, 2 lux dawn. This is the second controlled study which indicates that dawn simulation is an effective treatment for winter depression.

Dermatologic manifestations of infections in immunocompromised patients.

Thirty-one immunocompromised patients (22 renal allograft recipients, 5 patients receiving chronic corticosteroid therapy, and 4 patients undergoing chemotherapy for acute leukemia) with significant dermatologic infection, excluding typical cellulitis and herpesvirus infections, were retrospectively identified over a 12-year period. Of these 31 patients, 15 (48%) had infection restricted to their skin, 6 (19%) appeared to have primary cutaneous infection that spread hematogenously to other parts of the body, 2 (6%) had infections of adjoining nasal tissue that spread to contiguous skin, and 8 (26%) appeared to have disseminated systemic infection that spread to the skin. In six of the eight patients with apparent secondary skin involvement, the development of the cutaneous lesion was the first clinical indication of disseminated infection. Eleven immunocompromised patients (35%) with bacterial infection of the skin or subcutaneous tissue were identified. These patients could be divided into three categories: leukemic patients with bacteremic gram-negative infection metastasizing to the skin (3 cases), renal transplant recipients with recurrent staphylococcal infection on and around the elbow ("transplant elbow") or streptococcal sepsis from a site of cellulitis (5 cases), and immunocompromised patients with opportunistic bacterial infection due to Nocardia asteroides or atypical mycobacteria (3 cases). Seventeen immunocompromised patients (55%) with fungal infection of the skin or subcutaneous tissue were identified. These included 12 patients with opportunistic fungal infection (Cryptococcus neoformans, 4 cases; Aspergillus species, 3 cases; Paecilomyces, 2 cases; Rhizopus species, 2 cases; and Candida tropicalis, 1 case) and 5 patients with extensive, confluent cutaneous dermatophyte infections. One patient with protothecosis and two patients with extensive papillomavirus infection were identified. Of these latter two cases, one had his immunosuppression discontinued, with clearing of his extensive warts; the other had confluent warts of the face and neck that subsequently underwent malignant degeneration to squamous cell carcinoma while chronic immunosuppressive therapy was continued.(ABSTRACT TRUNCATED AT 400 WORDS)

Pasteurella multocida infections. Report of 34 cases and review of the literature.

Pasteurella multocida, a small, gram-negative coccobacillus , is part of the normal oral flora of many animals, including the dog and cat. P. multocida is the etiologic agent in a variety of infectious disease syndromes. We have reported 34 cases of infection caused by P. multocida and have reviewed the English literature. P. multocida infections may be divided into three broad groups: 1. Infections resulting from animal bites and scratches : The most common infections caused by P. multocida are local wound infections following animal bites or scratches . Cats are the source of infection in 60 to 80% of cases and dogs in the great majority of the remainder. Local infections are characterized by the rapid appearance of erythema, warmth, tenderness, and frequently purulent drainage. The most common local complications are abscess formation and tenosynovitis. Serious local complications include septic arthritis proximal to bites or scratches , osteomyelitis resulting from direct inoculation or extension of cellulitis, and the combination of septic arthritis and osteomyelitis, most commonly involving a finger or hand after a cat bite. 2. Isolation of P. multocida from the respiratory tract: The isolation of P. multocida from the respiratory tract must be interpreted differently than its isolation from other systemic sites. Most commonly P. multocida found in the respiratory tract is a commensal organism in patients with underlying pulmonary disease, but serious respiratory tract infections including pneumonia, empyema, and lung abscesses may develop. Most patients with respiratory tract colonization or infection have a history of animal exposure. 3. Other systemic infections: P. multocida is recognized as a pathogen in a variety of systemic infections including bacteremia, meningitis, brain abscess, spontaneous bacterial peritonitis, and intra-abdominal abscess. P. multocida often acts as an opportunistic pathogen with a predilection for causing bacteremia in patients with liver dysfunction, septic arthritis in damaged joints, meningitis in the very young or elderly, and pulmonary colonization or invasion in patients with underlying respiratory tract abnormalities.(ABSTRACT TRUNCATED AT 400 WORDS)

Overview of fluoroquinolone safety.

The safety of the fluoroquinolone antimicrobial agents is reviewed, discussing documented and potential clinical and laboratory adverse effects and drug-drug interactions. In prospective, randomized, double-blind clinical trials comparing fluoroquinolones to nonquinolone drugs or placebo, the fluoroquinolones were not significantly different (22 studies) or were superior (5 studies) to comparison agents but were only rarely more toxic (2 studies). Adverse effects included mild gastrointestinal toxicities and less common but more problematic central nervous system toxicities. Clinically important interactions occurred with coadministration of antacids and all fluoroquinolones and with theophylline and enoxacin and to a lesser extent ciprofloxacin and pefloxacin but not other fluoroquinolones. Potential adverse effects such as cartilage damage, DNA damage, teratogenicity, and crystalluria, while of concern, have not as yet been shown to be of clinical importance. Therapy of bacterial infections in children and adolescents is relatively contraindicated, but growing clinical experience with treatment of these patients has not so far revealed serious bone or cartilage toxicity. The fluoroquinolones thus far have exhibited a favorable safety profile, but our clinical experience is still limited, and monitoring for as yet unappreciated toxicities is warranted.

Comparative pharmacokinetics of ofloxacin and ciprofloxacin.

Review of publications in which the pharmacokinetics of ofloxacin and ciprofloxacin were compared directly indicates that although similar in many respects, these fluoroquinolones exhibit three differences that may be important clinically. First, ofloxacin is more completely absorbed, achieves higher peak serum concentrations, and has a longer terminal elimination half-life, which result in a fivefold greater area under the curve than that of ciprofloxacin when similar doses are orally administered. Ofloxacin's more favorable pharmacokinetic profile seems to compensate at least in part for the greater activity of ciprofloxacin against gram-negative bacilli in vitro. Second, ofloxacin is eliminated almost entirely via the kidneys, whereas ciprofloxacin is eliminated via both the kidneys and non-renal routes. This suggests that ciprofloxacin may be preferable for patients with variable renal function, whereas ofloxacin may be preferable for patients receiving dialysis because of the need for less frequent administration. Third, concomitant use of ciprofloxacin with either theophylline or caffeine decreases elimination and thereby results in elevated serum concentrations of these methylxanthine derivatives. Because ofloxacin does not cause clinically significant alterations in the pharmacokinetics of either theophylline or caffeine, it may be preferable for patients using these concomitantly.

Bacterial resistance to the quinolone antimicrobial agents.

Bacterial resistance to the newer quinolones occurs less frequently than to the older analogue nalidixic acid. Single-step mutations conferring greater than eightfold increases in minimal inhibitory concentration occur at frequencies of less than 10(-10) for many bacterial species and at 10(-8) for Pseudomonas aeruginosa. Passage on increasing concentrations of quinolones, however, results in highly resistant strains of many species. Chromosomal mutations have been shown to produce two mechanisms of resistance, alterations in the A subunit of the target enzyme, DNA gyrase, and decreased drug accumulation associated with altered porin outer membrane proteins and pleiotropic resistance. For some mutants reduced accumulation appears to depend on active quinolone efflux across the inner membrane. Resistance developing during quinolone therapy of infections has been infrequent to date and reported most often with P. aeruginosa and Staphylococcus aureus, and at sites with poor quinolone penetration or foreign bodies. Resistance should be monitored, and the means for limiting its development studied.

Infection in the renal transplant recipient.

The incidence of infection in the renal transplant patient is directly related to the net immunosuppressive effect achieved and the duration of time over which this therapy is administered. A second major factor in the causation of infections in this population is the nosocomial hazards to which these patients are exposed, ranging from invasive instrumentation to environmental contamination with Aspergillus species, Legionella pneumophila, Pseudomonas aeruginosa and other microbial pathogens. Careful surveillance is necessary to identify and eliminate such nosocomial sources of infection. The major types of infection observed can be categorized according to the time period post-transplant in which they occur: postsurgical bacterial infection in the first month after transplantation; opportunistic infection, with cytomegalovirus playing a major role, and transplant pyelonephritis in the period one to four months post-transplant; and a mixture of conventional and opportunistic infections in the last post-transplant period. Conventional infection in this late period occurs primarily in patients with good renal function who are receiving minimal immunosuppressive therapy; opportunistic infection occurs primarily in patients with poor renal function who are receiving higher levels of immunosuppression.

Mechanisms of action of and resistance to ciprofloxacin.

Ciprofloxacin and other newer quinolone antimicrobial agents exhibit increased potency and decreased frequency of spontaneous bacterial resistance in comparison with older analogues such as nalidixic acid. New and published observations on the mechanisms of action of and resistance to ciprofloxacin in Escherichia coli are presented and discussed. Genetic and biochemical studies have identified the A subunit of the essential bacterial enzyme DNA gyrase as a target of ciprofloxacin and other quinolones. For a series of quinolones, inhibition of purified DNA gyrase correlated with antibacterial activity. The bactericidal activity of ciprofloxacin and ofloxacin is, in contrast to that of certain other quinolones, somewhat less affected by rifampin and cell starvation, suggesting the existence of a site of drug action in addition to DNA gyrase. The frequency of selection of spontaneous single-step resistance mutants of E. coli was more than 100-fold lower with ciprofloxacin than with nalidixic acid. Strains highly resistant to ciprofloxacin could, nevertheless, be selected by serial passage on drug-containing agar. Two mutations contributing to this high level of resistance were analyzed. One, designated cfxA, conferred a 16-fold increase in drug resistance and mapped in a location consistent with a gyrA mutation; similar increases in resistance to ciprofloxacin were seen with gyrA mutations selected for resistance to other quinolones. The other mutation, cfxB, conferred pleiotropic resistance to ciprofloxacin, tetracycline, and chloramphenicol and appeared to be an allele of the multiple antibiotic resistance gene marA. The mutation cfxB was associated with a decreased amount of porin outer membrane protein OmpF, suggesting that drug permeation may occur in part through this channel. In summary, the A subunit of DNA gyrase is a target of ciprofloxacin and other quinolones. Ciprofloxacin resistance appears to occur both by mutation in this target and by alteration of drug permeation through the outer membrane of the cell.