Molecular Characterization of Mycoplasma pneumoniae Isolates in the United States from 2012 to 2018.

Mycoplasma pneumoniae is a major cause of community-acquired pneumonia. There are limited data in the United States on the molecular epidemiological characteristics of M. pneumoniae We collected 446 M. pneumoniae-positive specimens from 9 states between August 2012 and October 2018. Culture, antimicrobial susceptibility testing, P1 subtyping, and multilocus VNTR (variable-number tandem repeats) analysis (MLVA) were performed to characterize the isolates. Macrolide-resistant M. pneumoniae (MRMp) was detected in 37 (8.3%) specimens. P1 subtype 2 (P1-2) was the predominant P1 subtype (59.8%). P1 subtype distribution did not change significantly chronologically or geographically. The macrolide resistance rate in P1 subtype 1 (P1-1) samples was significantly higher than that in P1-2 (12.9% versus 5.5%). Six P1-2 variants were identified, including two novel types, and variant 2c was predominant (64.6%). P1-2 variants were distributed significantly differently among geographic regions. Classical P1-2 was more frequent in lower respiratory tract specimens and had longer p1 trinucleotide repeats. Classical P1-2 was most common in MRMp (35.7%), while variant 2c was most common in macrolide-susceptible M. pneumoniae (67.5%). Fifteen MLVA types were identified; 3-5-6-2 (41.7%), 4-5-7-2 (35.3%), and 3-6-6-2 (16.6%) were the major types, and four MLVA clusters were delineated. The distribution of MLVA types varied significantly over time and geographic location. The predominant MLVA type switched from 4-5-7-2 to 3-5-6-2 in 2015. MLVA type was associated with P1 subtypes and P1-2 variant types but not with macrolide resistance. To investigate the M. pneumoniae genotype shift and its impact on clinical presentations, additional surveillance programs targeting more diverse populations and prolonged sampling times are required.

Macrolide-Resistant Mycoplasma pneumoniae in the United States as Determined from a National Surveillance Program.

There are sparse data to indicate the extent that macrolide-resistant Mycoplasma pneumoniae (MRMp) occurs in the United States or its clinical significance. Between 2015 and 2018, hospitals in 8 states collected and stored respiratory specimens that tested positive for M. pneumoniae and sent them to the University of Alabama at Birmingham, where real-time PCR was performed for detection of 23S rRNA mutations known to confer macrolide resistance. MRMp was detected in 27 of 360 specimens (7.5%). MRMp prevalence was significantly higher in the South and East (18.3%) than in the West (2.1%). A2063G was the predominant 23S rRNA mutation detected. MICs for macrolide-susceptible M. pneumoniae (MSMp) were ≤0.008 µg/ml, whereas MICs for MRMp were 16 to 32 µg/ml. Patients with MRMp infection were more likely to have a history of immunodeficiency or malignancy. Otherwise, there were no other significant differences in the clinical features between patients infected with MRMp and those infected with MSMp, nor were there any differences in radiographic findings, hospitalization rates, viral coinfections, the mean duration of antimicrobial treatment, or clinical outcomes. There was no significant change in MRMp incidence over time or according to age, sex, race/ethnicity, or status as an inpatient or an outpatient. Patients with MRMp were more likely to have received a macrolide prior to presentation, and their treatment was more likely to have been changed to a fluoroquinolone after presentation. This is the first national surveillance program for M. pneumoniae in the United States. Additional surveillance is needed to assess the clinical significance of MRMp and to monitor changes in MRMp prevalence.

Growth inhibition by nitrocompounds of selected uric acid-utilizing microorganisms isolated from poultry manure.

The overall objective of this study was to evaluate the potential ability of nitrocompounds to reduce ammonia volatilization by inhibiting uric acid-utilizing microorganisms. Experiment I was conducted to evaluate the effects of nitrocompounds on the growth of uric acid-utilizing microorganisms isolated from poultry manure during six-hour incubation. There were five treatments: (1) control, (2) 50 mM nitroethane, (3) 50 mM nitroethanol, (4) 50 mM nitropropanol, and (5) 50 mM nitropropionic acid. Optical density values of nitrocompounds were significantly lower than that of control at two, four, and six hours. Plate counts of uric acid-utilizing microorganisms after six-hour incubation exhibited that nitrocompounds greatly reduced the growth of these microorganisms except for the nitroethane (P < 0.05). The nitropropanol and nitropropionic acid treatments showed significantly higher inhibitory effects compared to the nitroethanol. Experiments II and III were conducted to evaluate inhibitory effects of nitrocompounds on growth of uric acid-utilizing microorganisms compared to non-nitrocompounds such as ethanol, propanol, and propionic acid. Experiments II and III consisted of seven treatments: (1) control, (2) nitroethanol, (3) nitropropanol, (4) nitropropionic acid, (5) ethanol, (6) propanol, and (7) propionic acid. The incubation times of Experiments II and III were 6 and 24 h, respectively. The nitrocompounds were significantly more successful in inhibiting growth of uric acid-utilizing microorganisms compared to those non-nitrocompounds. These results suggest that nitrocompounds exhibit potential to reduce ammonia volatilization in poultry manure by inhibiting growth of uric acid-utilizing microorganisms.

Time course of recovery of adrenal function in children treated for leukemia.

OBJECTIVE: Many protocols for treating children with early B-cell lineage acute lymphoblastic leukemia use 28 consecutive days of high-dose glucocorticoids during induction therapy. We prospectively studied the effects of this therapy on adrenal function. STUDY DESIGN: Ten children with early B-cell lineage acute lymphoblastic leukemia were evaluated by cosyntropin (corticotropin (1-24)) stimulation testing before initiation of dexamethasone therapy and every 4 weeks thereafter until adrenal function returned to normal. RESULTS: All 10 patients had normal adrenal function before dexamethasone treatment and insufficient adrenal responses 24 hours after completing therapy. Each child felt ill for 2 to 4 weeks after completing therapy. Although 7 patients recovered normal adrenal function after 4 weeks, 3 patients did not have normal adrenal function until 8 weeks after discontinuing therapy. Statistically significant differences in both basal and corticotropin-stimulated cortisol levels were noted when comparing tests performed at baseline, 24 hours after completing therapy, and 4 weeks after completing therapy. CONCLUSION: High-dose dexamethasone therapy, a standard treatment for early B-cell acute lymphoblastic leukemia, can cause adrenal insufficiency lasting more than 4 weeks after cessation of treatment. This problem might be avoided by tapering doses of glucocorticoids and providing supplemental glucocorticoids during periods of increased stress.

Delayed methotrexate clearance in a patient with sickle cell anemia and osteosarcoma.

A 15-year-old girl with homozygous sickle cell anemia (HbSS) and osteosarcoma is described. Delayed clearance of methotrexate (MTX) after the second course of high-dose MTX (HDMTX) led to the development of renal and hepatic toxicities. Rescue was accomplished with high-dose leucovorin, intravenous carboxypeptidase G2, and thymidine. Although the renal and hepatic abnormalities resolved, focal tonic-clonic seizures developed, accompanied by abnormal brain imaging. Four weeks after this episode, all clinical and biochemical abnormalities resolved. Preexistent end-organ damage associated with HbSS may compromise the ability to deliver high-dose chemotherapy with curative intent in patients with malignant disease.

Phase I and pharmacokinetic trial of aminopterin in patients with refractory malignancies.

PURPOSE: Aminopterin (AMT) is a potent folate analog that is no longer in routine clinical use. Because of laboratory data that suggests improved metabolism of AMT versus methotrexate (MTX) in lymphoblasts, we developed a phase I trial to determine the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacokinetic profile of AMT. PATIENTS AND METHODS: Twenty patients with refractory malignancies were treated. The starting dose of AMT was 2.5 mg/m2 every 12 hours for two doses weekly: the dose of AMT was decreased and leucovorin (LV) rescue was added after the DLT was observed. Pharmacokinetics were performed after both intravenous (i.v.) and oral AMT administration. RESULTS: Mucosal toxicity was dose-limiting and resulted in the need for a dose reduction (dose level 2: AMT 2 mg/m2 every 12 hours for two doses weekly) and, subsequently, the addition of scheduled LV rescue (dose level 3: AMT 2 mg/m2 every 12 hours for two doses followed by LV 5 mg/m2 orally every 12 hours for two doses, starting 24 hours after the second dose of AMT). The mean areas under the curve (AUC) for the i.v. (n = 14) and oral (n = 13) doses were 1.20 +/- 0.09 (SE) and 1.05 +/- 0.14 micromol x h/L respectively. The half-life was 3.64 +/- 0.28 hours and the oral bioavailability in 12 matched subjects was 83.5% +/- 8.3%. One patient with endometrial adenocarcinoma achieved a complete response (CR) and remains on therapy at 11+ months. Seven patients had stable disease (SD) for 8 weeks or greater, which included one patient with a metastatic nerve sheath tumor who was stable for 9 months. CONCLUSION: We conclude that AMT has good oral bioavailability and that, when given on a q12 hour x two weekly schedule, the MTD is 2 mg/m2 with delayed LV rescue.

The efficacy of intravenous droperidol in the prehospital setting.

Droperidol is used for sedating combative patients in the emergency department (ED). We performed a randomized, prospective, double-blind study to evaluate the efficacy of droperidol in the management of combative patients in the prehospital setting. Forty-six patients intravenously received the contents of 2-cc vials of saline or droperidol (5 mg). Paramedics used a 5-point scale to quantify agitation levels prior to and 5 and 10 min after administration of the vials. Twenty-three patients received droperidol and 23 received saline. At 5 min, patients in the droperidol group were significantly less agitated than were patients in the saline group. At 10 min, this difference was highly significant. Eleven patients in the saline group (48%) required more sedation after arrival in the ED versus 3 patients (13%) in the droperidol group. We conclude that droperidol is effective in sedating combative patients in the prehospital setting.

A new high frequency polymorphism in the HER-2/neu oncogene in normal tissue and breast tumors.

The HER-2/neu (erbB-2) oncogene, if amplified and/or overexpressed in breast and ovarian cancers, is associated with a poor prognosis. Employing direct DNA sequencing, we have discovered and sequenced an 80 base pair intron from human placenta which contains an A to G polymorphism. This polymorphism lends itself to restriction fragment length polymorphism analysis of the PCR product spanning this intron. All three genotypes, homozygous A, heterozygous, and homozygous G appear in normal control populations and breast tumors. Also, no difference was seen between the polymorphic form found in five breast cancers and the corresponding normal tissue.

Cartilage-cell-containing tumours of the pelvis: a radiological review of 40 patients.

Cartilage-cell-containing tumours of the pelvis are responsible for a quarter of all primary bone lesions in this site. Benign tumours are uncommon but when present have classical radiological appearances similar to those described elsewhere. Only the rarest, chondromyxoid fibroma, may cause difficulty in diagnosis. Seventy-three per cent of cartilage-cell tumours are malignant and are either chondrosarcoma or chondroblastic osteosarcoma. Chondrosarcoma occurs after the second decade of life, usually with a longer history, and may be categorised as either a secondary peripheral or primary central tumour, each having typical radiological features. Chrondroblastic osteosarcoma tends to occur in younger patients with a shorter clinical history and is almost exclusively situated adjacent to a sacroiliac joint, producing purely lytic, sclerotic or mixed patterns of bone destruction. Experience suggests that computed tomography is the single most valuable further examination, since the pelvis is a complex structure with confusing overlying soft-tissue artefacts. This technique may indicate both the route and choice of optimal biopsy site.

Discrimination learning of delinquent boys as a function of reinforcement contingency and delinquent subtype.

Previous research has demonstrated the effectiveness of contingency management as a means of behavioral resocialization with delinquent boys on an individual basis. The present study was designed to examine and clarify systematically verbal and token reward and/or punishment. The principal findings of the study were: (1) Neurotic subjects performed at the highest level for punishment, at the lowest level for reward, and at an intermediate level for a combination of reward and punishment, regardless of verbal or token contingency modality. (2) Psychopathic subjects performed best for the joint verbal reward and punishment contingency, but they did not learn over trials for the joint token reward and punishment contingency. Their performance was undifferentiated at asymptote under the separate verbal and token reward or punishment contingencies. (3) Neurotic subjects performed at a significantly higher level than did psychopathic subjects for verbal and token punishment, while psychopathic subjects performed at a significantly higher level than neurotic subjects for verbal and token reward.