The recent emergence of a highly related virulent Clostridium difficile clade with unique characteristics.

OBJECTIVES: Clostridium difficile is a major global human pathogen divided into five clades, of which clade 3 is the least characterized and consists predominantly of PCR ribotype (RT) 023 strains. Our aim was to analyse and characterize this clade. METHODS: In this cohort study the clinical presentation of C. difficile RT023 infections was analysed in comparison with known 'hypervirulent' and non-hypervirulent strains, using data from the Netherlands national C. difficile surveillance programme. European RT023 strains of diverse origin were collected and whole-genome sequenced to determine the genetic similarity between isolates. Distinctive features were investigated and characterized. RESULTS: Clinical presentation of C. difficile RT023 infections show severe infections akin to those seen with 'hypervirulent' strains from clades 2 (RT027) and 5 (RT078) (35%, 29% and 27% severe CDI, respectively), particularly with significantly more bloody diarrhoea than RT078 and non-hypervirulent strains (RT023 8%, other RTs 4%, p 0.036). The full genome sequence of strain CD305 is presented as a robust reference. Phylogenetic comparison of CD305 and a further 79 previously uncharacterized European RT023 strains of diverse origin revealed minor genetic divergence with >99.8% pairwise identity between strains. Analyses revealed distinctive features among clade 3 strains, including conserved pathogenicity locus, binary toxin and phage insertion toxin genotypes, glycosylation of S-layer proteins, presence of the RT078 four-gene trehalose cluster and an esculinase-negative genotype. CONCLUSIONS: Given their recent emergence, virulence and genomic characteristics, the surveillance of clade 3 strains should be more highly prioritized.

Secondary abdominal pregnancy in a Jehovah's Witness.

A 35-year-old woman, gravida 2, para 1, aborta 0, arrived at our emergency department with abdominal pain of more than 2 weeks' duration. Diagnostic pelvic ultrasonography confirmed a 16-week intra-abdominal pregnancy. Hemoglobin level was 6.9 mg/dL, and hematocrit value was 20.1%. The patient refused blood transfusion on religious grounds. Laparotomy revealed 2,000 mL of blood in the abdomen and a live fetus, with the placenta attached to the omentum and the serosal surface of the right fallopian tube. Postoperative hemoglobin level was 2.8 mg/dL. The patient was transferred to another facility for hyperbaric oxygen therapy, where she subsequently died. Abdominal pregnancy is rare, but has high fetal and maternal mortality rates. Our patient's case was complicated, since she was a Jehovah's Witness and refused lifesaving treatment on religious grounds. Serious medical decisions were made, while respecting the autonomy of the patient.

Elastin and collagen degradation products in urine of smokers with and without chronic obstructive pulmonary disease.

It has been hypothesized that emphysema results from damage to the elastic fiber network of the lungs as a result of elastase-antielastase imbalance. We used a new assay for urinary desmosine (DES) and isodesmosine (IDES), specific markers for the degradation of mature crosslinked elastin, and hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP), specific markers for the degradation of mature crosslinked collagen, in order to examine elastin and collagen degradation in relation to current cigarette smoking and the presence of chronic obstructive pulmonary disease (COPD). The study sample consisted of 22 never-smokers (NSM group), 13 current smokers without airflow obstruction (SM group), and 21 patients with COPD (COPD group), including both current and former smokers. The relation between the creatinine-height index and FEV1 was used to correct for possible loss of muscle mass and decreased excretion of creatinine in the COPD group. Mean urinary excretion of elastin-derived crosslinks in the COPD group (DES, 11.8 +/- 5.1 [mean +/- SD]; IDES, 11.3 +/- 5.0 micrograms/g creatinine) and in the SM group (DES, 11.0 +/- 4.2; IDES, 10.2 +/- 2.5 micrograms/g creatinine) was significantly higher than in the NSM group (DES, 7.5 +/- 1.4; IDES, 6.9 +/- 1.3 micrograms/g creatinine). In multivariate analysis, current smoking and the presence of COPD were significantly and independently associated with higher urinary excretion of elastin degradation products, and there was no significant interaction between current smoking and the presence of COPD.(ABSTRACT TRUNCATED AT 250 WORDS)

Onset of menses in two adult patients with Prader-Willi syndrome treated with fluoxetine.

Prader-Willi syndrome (PWS) is characterized by hypotonia at birth, hypogonadism, early childhood obesity, and mental deficiency. Hypogonadotropic hypogonadism is a major characteristic of patients with PWS, and it is speculated to be due to hypothalamic insufficiency. Two adult female patients with PWS and no prior history of menses are presented. Both of these patients were treated with fluoxetine for psychopharmacologic management of obsessive features in the form of food preoccupation and hyperphagia or for compulsive behaviors in the form of severe self-injurious behaviors. The two female patients with PWS who had primary amenorrhea developed vaginal bleeding believed to be menses following at least 6 months of treatment with fluoxetine. Mature hypothalamic function is characterized by pulsatile release of gonadotropin-releasing hormone (GnRH) in a critical range of frequency and amplitude. Central nervous system neurotransmitters may modify GnRH secretion. Fluoxetine specifically inhibits the reuptake of serotonin which may impact the hypothalamic-pituitary-ovarian system in female patients with PWS.

Isolation of hydroxylysyl pyridinoline, a mature collagen crosslink from neonatal rat aorta smooth muscle cell cultures.

Hydroxylysyl pyridinoline (HP) is a nonreducible collagen crosslink derived from three posttranslationally modified lysyl residues. Neonatal rat aorta smooth muscle cell cultures (NNRSMC) produce mg amounts of insoluble collagen. The purpose of the present study was to evaluate the capability of NNRSMC to produce collagen containing HP crosslinks. Cultures were pulsed with [14C]-lysine and then chased for five weeks. Insoluble collagen was prepared by digestion of the cell layer material with porcine pancreatic elastase and trypsin. After acid hydrolysis and cation-exchange chromatography, purified HP was isolated by reversed phase ion-paired chromatography. The material eluting from the HPLC was monitored continuously at 295 nm and the ultraviolet absorption spectrum was recorded every 21 msec. The ultraviolet spectrum of the HP peak was virtually identical to that of standard HP run on the HPLC. The HP exhibited a homogeneity of 97.3% when the ultraviolet spectrum of the apex of the peak was compared with the spectra of the shoulders of the peak. The radioactive HP also exhibited the expected fluorescence emission spectrum. We calculate a mean of 0.40 +/- 0.03 nmol HP/nmol collagen in the three experiments as compared with reported values of 0.57 +/- 0.1 for rabbit aorta. This is the first report of cell culture biosynthesis of chemically measurable amounts of HP. Using such pulse-chase techniques one can study the maturation of intermediate collagen crosslinks into HP. HP can also be used as a marker to study the metabolism of mature collagen molecules during normal and pathologic states.

Graduate medical education in the United States.

The annual surveys of residency programs on which this statistical report is based have had a 95% or higher rate of response for the past five years. The number of accredited programs increased in 1986, primarily as a result of the accreditation of subspecialty programs in internal medicine. The largest number of programs is found in general internal medicine, followed by family practice, general surgery, and obstetrics/gynecology. More than one fifth of the programs are located in the Middle Atlantic region of the United States, with the largest number in the state of New York. The number of positions offered by accredited programs has increased as a result of the increase in the number of specialties with accredited programs. The number of GY-1 positions projected in the fall to be offered the following July has not increased significantly over the past three years. The reader is cautioned that the "number of positions offered" is affected by many factors and is subject to frequent change throughout the year. The number of residents on duty in ACGME-accredited programs increased in 1986 as a result of the increase in number of programs. However, the number of GY-1 residents on duty has decreased by 7% since 1984. This decrease is largely accounted for by the number of FMGs in GY-1 positions, a 21% decrease since 1984. This is especially evident in number of US citizen FMGs in GY-1 positions, a 38% decrease in the same time period. The specific factors that have caused the decrease in number of GY-1 FMG residents are not known at this time. One explanation might be a hesitation on the part of program directors to appoint new FMGs. Another factor could be the lower pass rate of US citizen FMGs on the FMGEMS, one qualification for appointment to an ACGME-accredited program. The number and percentage of women in residency programs continues to increase as it has over the past several years. For example, in 1977 women accounted for only 15% of residents; in 1986 they were 27% of residents on duty. Although female residents are found in nearly all disciplines, two thirds of them are training in family practice, internal medicine, obstetrics/gynecology, pediatrics, or psychiatry.(ABSTRACT TRUNCATED AT 400 WORDS)

The incidence of cone epiphyses and ivory epiphyses of the hand in Nigerian children.

Radiographs of the left hand of 594 children from Ibadan, Nigeria were inspected for skeletal anomalies to determine differences in the incidence of cone and ivory epiphyses for the rich and poor children and differences in incidence for four hemoglobin types. Ivory epiphyses ovvurred more often in children in the lower socio-economic class and children with hemoglobin AA. The cone epiphyses observed in Hb SS children were primarily a result of bone infarcts, while cones in children of other hemoglobin types appeared to be normal variants. The incidence of ivory epiphyses was higher in the Nigerian children than in American black children in the Ten-State Nutrition Survey. The incidence of cone epiphyses was much lower than those reported for other normal populations.

Effect of maternal smoking on hemoglobins and hematocrits of the newborn.

PIP: The progeny of smokers had higher 48-hour hemoglobin and hematocrit levels than that of nonsmokers in this study, based on 10,399 clinically-normal term white infants. This effect could not be accounted for by 1) per capita income; 2) maternal pre-pregnancy weight or maternal stature; or 3) placental weight/birth-weight ratio, and was found to be proportionately related to the level of maternal smoking. The response of the progeny in utero to maternal smoking during pregnancy clearly is an increase in 1) red cell volume suggesting oxygen deprivation during gestation, and 2) hemoglobin concentration; consequently the progeny are likely to enter the postnatal period with a larger fetal iron reserve. This result is considered nutritionally relevant.^ieng

Paradoxical bilateral asymmetry in bone size and bone mass in the hand.

Among 227 chronic renal disease patients, micrometer caliper radiogrammetric measurements of the second metacarpal at midshaft showed the right metacarpal to be larger (with greater bone area) and with a greater cortical area than the left second metacarpal, both in 208 right-handed individuals and in 19 left-handed individuals. This direction of asymmetry was individually characteristic of the majority of individuals, whether right-handed, left-handed or ambidextrous.