In vitro activity of minocycline against respiratory pathogens from patients with cystic fibrosis.

Our objective was to determine the in vitro activity of minocycline against isolates of Burkholderia cepacia (BC), Stenotrophomonas maltophilia (SM), and Pseudomonas aeruginosa (PA) cultured from the respiratory tract of patients with cystic fibrosis (CF). Cultures of BC, SM, and PA were isolated in a hospital bacteriology laboratory from the sputum or oropharyngeal cultures obtained from patients attending a Cystic Fibrosis Center, and were prospectively tested for in vitro sensitivity to minocycline by Kirby-Bauer disk diffusion. From January 1994 to July 1995, 116 cultures from 61 patients had at least one of the three pathogens; 9/61 (15%) patients had an isolate of BC, and 7/9 (78%) had an initial isolate sensitive to minocycline, of which 3 were sensitive only to minocycline; 2 cultures were resistant to all antibiotics. Four of 7 patients with BC were treated with minocycline; 3 patients developed resistant isolates 3-13 months after therapy. Five of 61 patients (8%) had an isolate of SM: 4/5 (80%) of these isolates were sensitive to minocycline, of which 1 was sensitive only to minocycline. Fifty-five of 61 patients (90%) had at least one PA isolate, with 112 morphotypes recovered from 90 cultures: 40/112 morphotypes (36%) were sensitive to minocycline, 65 (58%) were resistant, and 7 (6%) were intermediate in sensitivity. We conclude that the marked in vitro activity of minocycline against BC and SM isolated from patients with CF suggests that minocycline may have an adjunct role in the antimicrobial therapy of multidrug resistant, respiratory pathogens in CF.

Spontaneous in vivo reversion to normal of an inherited mutation in a patient with adenosine deaminase deficiency.

Somatic mosaicism in genetic disease generally results from a de novo deleterious mutation during embryogenesis. We now describe a somatic mosaicism due to the unusual mechanism of in vivo reversion to normal of an inherited mutation. The propositus was an adenosine deaminase-deficient (ADA-) child with progressive clinical improvement and unexpectedly mild biochemical and immunologic abnormalities. Mosaicism due to reversion was evidenced by absence of a maternally transmitted deleterious mutation in 13/15 authenticated B cell lines and in 17% of single alleles cloned from blood DNA, despite retention of a maternal 'private' ADA polymorphism linked to the mutation. Establishment of significant somatic mosaicism following reversion to normal could modify any disorder in which revertant cells have a selective advantage.

The absorption and effect of dietary supplementation with omega-3 fatty acids on serum leukotriene B4 in patients with cystic fibrosis.

The substitution of omega-3 (n-3) fatty acids for omega-6 (n-6) fatty acids generates eicosanoids with diminished inflammatory effects. As the lungs of patients with cystic fibrosis (CF) are in a state of chronic inflammation in which increased amounts of eicosanoids are found, n-3 supplementation may reduce this level of inflammation and result in clinical improvement. The absorption and clinical effects of n-3 vs. n-6 fatty acids in CF were measured in a prospective, randomized, double-blind, crossover study in which 14 patients with CF (age: 6-16 years, mean 10.5 years; baseline Shwachman-Brasfield scores: 41-88, mean 76.7) received 6 weeks of n-3 ethyl ester concentrate from menhaden oil (100-131 mg/kg/day, mean 112.8) or n-6 fatty acids from safflower oil (102-132 mg/kg/day, mean 113.3), followed by a washout period of 6 weeks, and then 6 weeks of the other supplement. Analysis by gas chromatography showed that n-3 supplementation resulted in increased eicosapentaenoic acid (20:5n-3) in platelet phospholipids, from 0.14 to 2.16%, P < 0.05 and in increased docosahexaenoic acid (22:6n-3), from 1.33 to 3.72%, P < 0.05. Clinical effects were evaluated at weeks 0, 6, 12, and 18, and analyzed for differences among the n-3, n-6, and washout periods. No adverse effects were reported or observed. No statistically significant differences were found (ANOVA, P > 0.05) in Shwachman-Brasfield scores, sweat test, weight change, or forced expiratory volume and flow (FEV1, FEF25-75%, and FVC) percentiles. Tumor necrosis factor was not measurable in any serum sample. Serum leukotriene B4 (LTB4) levels were significantly reduced by n-3 fatty acids, mean reduction (-177 pg/mL) compared to n-6 fatty acids (+63 pg/mL) P < 0.05. These results show that both n-3 fatty acids are absorbed and incorporated into platelet phospholipids in patients with CF and reduced serum LTB4. No significant clinical differences or adverse effects were found.

Pediatric clerkship performance in diverse community clinical settings.

OBJECTIVE: To determine whether multiple and diverse clinical settings and resources in a pediatric clerkship result in satisfactory performance by medical students and affect their choice of a pediatric residency after graduation. DESIGN: Retrospective study 1985 through 1990. SETTING: Medical students in a pediatric clerkship in a medical school that is part of a land grant university where the clinical curriculum is conducted in six geographically distinct communities. MAIN OUTCOME MEASURE: (1) Three performance criteria including: multiple choice final examination score, clinical performance evaluations by preceptors, and formal evaluation of patient written records. (2) Students matching with a pediatric or combined internal medicine/pediatric residency. RESULTS: Of 499 students 92.8% successfully passed all three criteria with no statistically significant differences between communities. A smaller percentage of students (15.2%) (community range, 6 to 18.5%) entered straight or combined pediatric residencies, whether or not a pediatric residency was present in the community. CONCLUSIONS: Medical students can achieve satisfactory competency in pediatric clerkships offered in diverse clinical settings, and choose pediatric residency training whether or not they are exposed to a pediatric residency during their clerkship. A problem-based learning curriculum does not hinder selecting pediatrics as a career choice.

Spontaneous pneumothorax in common pulmonary vein atresia.

Common pulmonary vein atresia is a rare congenital anomaly that is rapidly fatal unless immediately recognized and corrected by surgical intervention. This article describes three neonates who died with the diagnosis soon after birth. In the constellation of presenting clinical features in each case, the occurrence of early spontaneous pneumothorax was particularly noteworthy. This sign may well be a helpful physiologic marker within the context of suspected congenital heart disease associated with severe pulmonary venous obstruction.

Fatal respiratory syncytial virus pneumonitis in a previously healthy child.

Respiratory syncytial virus (RSV) is a cause of significant morbidity and mortality in infants and children with an immunocompromised status or a congenital heart disease. The following case describes a 6 8/12-year-old, previously normal child who had a fatal interstitial pneumonitis caused by RSV. Documentation of RSV as the etiologic agent and documentation of her immune status are presented. In light of recent advances in the rapid diagnosis and treatment of RSV, this virus should be considered in children with an unusual interstitial pneumonitis regardless of their known immunologic status.

Mucus-stimulating activity in the sera of patients with cystic fibrosis: demonstration and preliminary fractionation.

The ciliated, mucus-secreting urn cell complex (UCC) is found swimming in the coelomic cavity of the marine invertebrate Sipunculus nudus. This cell complex, which can be maintained in suspension cultures, responds to various stimuli by hypersecreting mucus in the form of a cohesive mucus "tail." This tail can be measured and expressed as a multiple of "urn cell diameters." Using this bioassay, heated sera from 35 patients with cystic fibrosis (CF), 29 patients who were obligate heterozygotes for the CF gene, and 42 controls with a variety of diseases were tested. Control sera yielded a mean (+/- S.D.) mucus tail length of 2.5 (+/-2.3); CF sera yielded a mean mucus tail length of 7.5 (+/- 2.9), (P < 0.0005), and obligate heterozygote sera yielded a mucus tail length of 6.2 (+/- 2.1), (P < 0.0005). These responses were reproducible with different UCC suspensions from the same Sipunculus, as well as from different Sipunculi. In addition, sera from 3 CF patients and 3 controls were chromatographed on protein A-Sepharose. The bound IgG fraction was then washed with 8 M urea and subsequently eluted with 1 M acetic acid. Pooled dialyzed, lyophilized fractions were assayed as coded samples in the UCC assay. Mucus-stimulating activity as measured by mucus tail length per mg protein was greatest in the fractions eluted with 8 M urea. The 8 M urea fractions from 3 CF sera were 2.8 to 5.5 times as active as fractions from 3 control sera. The UCC assay can quantitatively measure mucus-stimulating activity in CF serum. This activity appears to be associated with a serum fraction which can be dissociated from IgG.

Defective activation of the third component of complement in the sera of newborn infants.

The activation of the terminal complement components, C3--9, plays an important role in the host's defense against infection. In the present study, the ability of bacteria to activate the third component of complement (C3) in newborn serum was examined. A variety of bacteria were incubated in test sera at 37 degrees C for 30 min and the percent of available C3 that was activated was measured. Using one strain of Escherchia coli (no. 3), 32% (mean) of the available C3 was activated in sera from 18 newborns, as compared to 85% in sera from their mothers and 79% in sera from 13 normal adults (P less than 0.005). In contrast, using another strain of E. coli (N70), the percent of C3 activated in newborn sera (83%) was the same as in sera from their mothers (81%) or in sera from normal adults (73%). The defective activation of C3 in newborn sera by E. coli was not related to the presence of the K1 antigen. Newborn sera were also challenged with other bacterial species and the activation of C3 was deficient when tested with klebsiellae, but not with staphylococci or streptococci. The defect in newborn sera appeared to be due to a deficiency of a serum factor rather than to the presence of an inhibitor.

Haemophilus influenzae as a cause of Brodie's abscess in an infant.

Brodie's abscess is a form of subacute osteomyelitis which is defined by a particular constellation of clinical, radiological and pathological features. Its occurrence in infants is extremely rare. This case documents just such an occurrence. To our knowledge, the pathogen Haemophilus influenzae has not been previously recognized as a cause of Brodie's abscess in particular or subacute osteomyelitis in general. The clinical presentation and diagnostic pitfalls which may be encountered in this age group are discussed.