A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies.

Microtubule severing enzymes implement a diverse range of tissue-specific molecular functions throughout development and into adulthood. Although microtubule severing is fundamental to many dynamic neural processes, little is known regarding the role of the family member Katanin p60 subunit A-like 1, KATNAL1, in central nervous system (CNS) function. Recent studies reporting that microdeletions incorporating the KATNAL1 locus in humans result in intellectual disability and microcephaly suggest that KATNAL1 may play a prominent role in the CNS; however, such associations lack the functional data required to highlight potential mechanisms which link the gene to disease symptoms. Here we identify and characterise a mouse line carrying a loss of function allele in Katnal1. We show that mutants express behavioural deficits including in circadian rhythms, sleep, anxiety and learning/memory. Furthermore, in the brains of Katnal1 mutant mice we reveal numerous morphological abnormalities and defects in neuronal migration and morphology. Furthermore we demonstrate defects in the motile cilia of the ventricular ependymal cells of mutants, suggesting a role for Katnal1 in the development of ciliary function. We believe the data we present here are the first to associate KATNAL1 with such phenotypes, demonstrating that the protein plays keys roles in a number of processes integral to the development of neuronal function and behaviour.

Gene-environment interaction influences attachment-like style in mice.

Attachment styles are established soon after birth and form the basis for a healthy psychological life during adulthood. Here, we investigated whether genetic background (i.e. isogenic strains: C57BL/6N and BALB/c) and parent-of-origin (i.e. reciprocal hybrids) epigenetic effects influence attachment-like styles in mice. We discovered that a specific genetic and epigenetic assortment exerts a role on the development of a secure or insecure attachment-like style. In particular, when biological mothers raise their pups, the attachment-like style is mainly secure, independently of the genetic background. However, when foster mothers raise pups, the attachment-like style can be either secure or insecure, depending on the particular genetic background, and this effect is paternally transmitted. Finally, we observed that secure attachment-like in mice leads to greater sociability during adulthood, while insecure attachment-like leads to reduced sociability. Our study sheds light on gene-environment interactions that shape the attachment-like style early in development and pave the way for a healthy psychological life.

Reaching and grasping phenotypes in the mouse (Mus musculus): a characterization of inbred strains and mutant lines.

Skilled movements, such as reaching and grasping, have classically been considered as originating in the primate lineage. For this reason, the use of rodents to investigate the genetic and molecular machinery of reaching and grasping has been limited in research. A few studies in rodents have now shown that these movements are not exclusive to primates. Here we present a new test, the Mouse Reaching and Grasping (MoRaG) performance scale, intended to help researchers in the characterization of these motor behaviors in the mouse. Within the MoRaG test battery we identified early phenotypes for the characterization of motor neurone (Tg[SOD1-G93A](dl)1Gur mice) and neurodegenerative (TgN(HD82Gln)81Dbo transgenic mice) disease models in addition to specific motor deficits associated with aging (C3H/HeH inbred strain). We conclude that the MoRaG test can be used to further investigate complex neuromuscular, neurological, neurodegenerative and behavioral disorders. Moreover, our study supports the validity of the mouse as a model for reaching and grasping studies.

Emergence of Candida parapsilosis as the predominant species causing candidemia in children.

An increase in the rate of isolation of Candida parapsilosis, relative to other Candida species, in our children's hospital led us to analyze the clinical and epidemiological variables associated with candidemia. We sought to determine if these variables are different for patients infected with C. parapsilosis. All episodes of candidemia occurring over a 7-year period were analyzed retrospectively. Of 81 episodes in 80 patients, 35 (43%) were in neonates, and 46 (57%) were in nonneonates. C. parapsilosis was isolated in 40 episodes (49%). C. parapsilosis was significantly more likely than non-C. parapsilosis species to be associated with prematurity (P = .001), presence of a central venous catheter (P = .002), and use of total parenteral nutrition (P = .03). C. parapsilosis has emerged as the predominant species in our children's hospital. The mortality rate associated with candidemia in children is lower than previously reported and may be associated with the high rate of isolation of C. parapsilosis.

Epidemiology and control of vancomycin-resistant enterococci in an adult and children's hospital.

BACKGROUND: The incidence of vancomycin-resistant enterococci (VRE) has reached endemic proportions in many medical centers. To initiate an effective infection control program, an understanding of the epidemiologic attributes of the genus in medical facilities is imperative. METHODS: We studied 138 consecutive cases of VRE from April through December 1995. We created a database to analyze the risk factors for patients in both an adult hospital and a children's hospital and screened all specimens, submitted for routine microbiologic analysis, for VRE. RESULTS: One hundred twenty-three cases (89%) occurred in the adult acute care hospital, and 15 (11%) occurred in the children's hospital. Eighty patients (58%) were colonized with VRE, and 58 (42%) had an infection with VRE. Eighty-three percent of all the cases of VRE were nosocomially acquired. The majority of cases occurred in the medical service. Urine was the most important clinical specimen infected or colonized. Prior use of an antibiotic, other than vancomycin, was the most important risk factor for all nosocomial cases, followed by prior vancomycin use for surgical patients and residence in a unit with other patients infected with VRE for the medical service. Direct admission from another hospital was the most important risk factor for community-acquired cases. Special microbiologic screening of cultures yielded 48% of all VRE identified. Enterococcus faecium was the predominant resistant isolate recovered. CONCLUSIONS: The control of VRE in the hospital setting is difficult for several reasons. Almost half of all patients carrying VRE would not have been identified without special microbiologic screening efforts, as would patients, admitted from the community, who are already colonized with VRE. Controlling antibiotic use both in the hospital and the community is basic for controlling these organisms. Continuous education of all staff about VRE and other nosocomially significant organisms is the key to controlling the spread of these bacteria.

The challenge of vancomycin-resistant enterococci: a clinical and epidemiologic study.

BACKGROUND: Vancomycin-resistant enterococci have been recovered with increasing frequency from hospitalized patients. Risk factors, mode of nosocomial transmission, extent of colonization in hospitalized patients, and treatment options for these organisms have not been completely delineated. METHODS: We studied 53 patients (group A) with vancomycin-resistant enterococci isolated from various clinical specimens and also surveyed for vancomycin-resistant enterococci in stool specimens submitted for Clostridium difficile toxin assays (group B). Stool specimens submitted for identification of bacterial pathogens and stool specimens from hospital employees were also analyzed for vancomycin-resistant enterococci. RESULTS: Seventy-six isolates of vancomycin-resistant enterococci were recovered in group A. Five of these patients harbored vancomycin-resistant enterococci on admission. Fifty-three of 289 group B stool specimens submitted for C. difficile toxin assays yielded vancomycin-resistant enterococci. Cephalosporins and vancomycin were the most common antimicrobial agents received by both groups of patients. Enterococcus faecium isolates were more resistant than Enterococcus faecalis isolates to antimicrobial agents. All isolates exhibited high-level aminoglycoside resistance and were not beta-lactamase producers. There were at least 15 different molecular clones of E. faecium and three of E. faecalis. Vancomycin-resistant enterococcal bacteremia was associated with a 100% in-hospital mortality rate. CONCLUSIONS: Multidrug-resistant and vancomycin-resistant enterococci have become important nosocomial pathogens that are difficult to treat. Vancomycin-resistant enterococcal bacteremia was associated with a poor prognosis. We found a high rate of colonization in patients with suspected C. difficile toxin colitis. Judicious use of vancomycin and broad-spectrum antibiotics is recommended, and strict infection control measures must be implemented to prevent nosocomial transmission of these organisms.

Vancomycin-resistant Enterococcus faecium in hospitalized children.

OBJECTIVE: Determine the epidemiology and risk factors for colonization with vancomycin-resistant Enterococcus faecium. DESIGN: Survey; case-control study. SETTING: Children's hospital. PATIENTS: Pediatric oncology patients. INTERVENTION: Contact isolation, restriction of vancomycin prescribing. RESULTS: There was a high prevalence of colonization with vancomycin-resistant enterococci among pediatric oncology patients. The length of hospitalization and the administration of vancomycin and other intravenous antibiotics was associated with colonization. Prevention of colonization was associated with restriction of vancomycin use and contact isolation. CONCLUSIONS: Vancomycin use may predispose to colonization with vancomycin-resistant E faecium. Vancomycin-resistant E faecium may be nosocomially spread. Contact isolation and restriction of vancomycin use may prevent spread of vancomycin-resistant E faecium.

Single-source outbreak of Candida tropicalis complicating coronary bypass surgery.

Candida tropicalis was isolated from the sternal wounds of eight coronary bypass patients from 18 to 89 days postoperatively; infections were limited to soft tissue in five patients but involved the sternum in three patients. Analysis of surgery records implicated one individual as the potential source of the yeast; this was confirmed by microbiological studies of fingertips and nasopharynx cultures of all personnel in contact with these patients. Only the suspect nurse, then acting as a scrub nurse and not as a circulator, infected the eight patients. Her removal from the cardiac team terminated the cluster outbreak.

Central catheter infections: single- versus triple-lumen catheters. Influence of guide wires on infection rates when used for replacement of catheters.

A prospective study was conducted over six months to determine if triple-lumen catheters were associated with a higher rate of infection than single-lumen catheters. A total of 502 central intravascular catheters were prospectively collected from 362 consecutive patients in the adult intensive care units. Semiquantitative and broth cultures were performed on distal and proximal catheter segments, with peripheral blood culture specimens drawn in febrile patients. The overall infection rate for the 502 catheters was 11.8 percent or 2.2 infections per 100 days at risk. The infection rates were: single-lumen lines, 8 percent; triple-lumen lines, 32 percent; and triple-lumen pulmonary artery catheters, 12 percent. When corrected for time at risk, the triple-lumen lines and the triple-lumen pulmonary artery catheters had the same rate of infection, which was three times greater than that of the single-lumen catheters. After correction for confounding variables such as the presence of diabetes mellitus, the use of hyperalimentation, the degree of illness, dialysis, or ultrafiltration, and the use of a guide wire to place a replacement line over a pre-existing one, the risk of infection remained significantly higher for triple-lumen than for single-lumen catheters. The use of a guide wire to place a new line over an old one also was associated with a trend towards an increased risk of infection.

Microbiology of indwelling central intravascular catheters.

Indwelling central-line catheters (n = 502) from 362 patients in intensive care units were analyzed prospectively. The skin site, 6-cm-distal and -proximal subcutaneous segments of the catheter, exudates, and blood were cultured. Semiqualitative roll plate cultures of the catheter segments were followed by broth cultures and examined for 72 h. All isolates were identified, and susceptibilities were determined. Line infections, defined clinically, yielded 22 different microbial species; 10 different species were recovered from colonized lines. Of the Staphylococcus epidermidis isolates recovered, 39% occurred singly and 21% occurred in combination with other microorganisms; Enterococcus faecalis, S. hominis, and Pseudomonas aeruginosa were next in frequency of isolation. Line infections also yielded other staphylococci, viridans group streptococci, several members of the family Enterobacteriaceae, acinetobacters, anaerobic bacteria, Candida spp., and Aspergillus fumigatus. While S. epidermidis was also the most frequent isolate among the line colonizers, different species and different frequencies of isolation were found among this group. The study showed that the distal catheter segment broth culture was the best predictor of clinical line infections; in addition, gram-negative bacteria were isolated only from the catheters of patients with overt infections.

Clinical laboratory and epidemiological investigations of a Streptococcus pyogenes cluster epidemic in a newborn nursery.

Streptococcus pyogenes, nontypable with available M antisera, T type 12, and reactive in the serum opacity test, produced various lesions in 10 newborn infants during a 2-month period. All infants except one were discharged from the nursery before overt disease manifestations. Colonization studies of newborn infants showed a streptococcal carrier rate of 19% (27 of 140). Only 1 of 154 staff members yielded the same streptococcus from the throat, but it could not be implicated as the source for the outbreak. Cohorting of infants and chlorhexidine gluconate hand washing by staff members helped in terminating this cluster epidemic.

Hospital cluster epidemic with Morganella morganii.

A cluster epidemic of 13 Morganella morganii infections involving 11 patients occurred over a 3-month period in 1977. This epidemic was unusual in that it involved four services and five hospital floors. The outbreak was effectively terminated when strict asceptic techniques were reinforced.

Nosocomial urinary-tract infections in a skilled nursing facility.

Fifty-five documented infections reported from an admission unit of a large skilled nursing facility (SNF) during a five-month period were analyzed. Of these, 45 (82 percent) were urinary-tract infections (UTIs), chiefly asymptomatic bacteriuria. Sixty-three percent of the UTIs were acquired in the SNF, and the remainder were acquired during the preceding stay in a general hospital. Statistically, Proteus species infections were more common among the SNF-acquired UTIs, whereas Pseudomonas aeruginosa infections were the most common among the hospital-acquired UTIs. The following recommendations are made: 1) for previously hospitalized elderly patients in whom urinary-tract sepsis develops soon after admission to an SNF, treatment should start with an antibiotic active against Pseudomonas aeruginosa while the results of cultures are pending; 2) symptomatic lower urinary-tract infections caused by SNF-acquired Proteus species should be treated with nalidixic acid or trimethoprimsulfamethoxazole; 3) the term "nosocomial infection" should be broadened to include infections acquired in long-term care institutions; and 4) infection surveillance should be started in selected long-term care institutions for the elderly as part of an expanded National Nosocomial Infections Survey.

Studies of the surgical scrub.

A study comparing the relative efficacy of a five versus a ten minute surgical scrub was carried out using random sampling of personnel scrubbing for routine scheduled hospital surgical procedures. Scrubbing for five minutes was found to be equally as effective as scrubbing for ten minutes. Betadine was compared to pHisoHex as a scrubbing agent and found to be statistically more effective in degerming the skin following a five minute scrub. As a result of this study, a routine preoperative surgical scrub of five minutes' duration, using Betadine as the scrubbing agent, is recommended.

Wound infection. Acute versus chronic cholecystitis.

Wound infection in 239 patients who underwent cholecystectomy were analyzed retrospectively. Seventeen per cent of the patients with acute cholecystitis had wound infection compared with 8.9 per cent of patients with chronic cholecystitis. Bacteriology of wound infections revealed Staphylococcus aureus in 76.4 per cent of the chronic cholecystitis group and in 12.5 per cent of the acute cholecystitis group. Wound infection in the acute cholecystitis group involved gram-negative rods predominantly. Organisms were isolated from bile culture in 71.4 per cent of acute cholecystitis patients compared with 59.6 per cent of chronic cholecystitis patients. Of patients with positive bile cultures 11.3 per cent had wound infections compared with 6.8 per cent of patients with negative bile cultures. The most common organisms isolated from bile cultures with resultant wound infections were S epidermis, S aureus, and Klebsiella sp. Wound infection after cholecystectomy for chronic cholecystitis arises from external sources and not contaminated bile. Antibiotic therapy should be directed accordingly.

Wound infection: a prospective study of 7519 operations.

Wound infection was prospectively studied in 7,519 consecutive operations after preoperative classification as clean, clean-contaminated, and infected. The overall infection rate was 3.9 per cent. Clean, 3.2 per cent; clean-contaminated, 4.4 per cent; contaminated, 12.4 per cent; infected, 16.2 per cent. Wound infection was not seasonally related or dependent on changes in house staff. In clean cases, the predominant role of Staphylococcus aureus (37%) has been superceded by enterococci (44%). In clean-contaminated cases, enterococci (43.5%) were the most common, followed by Escherichia coli (40.0%). In contaminated wounds, E. coli was most common (40.0%). The infected case category grew mixed flora (E. coli, 82 per cent; enterococci, 54 per cent, and Pseudomonas aeruginosa, 43 per cent). Nosocomial organisms were important only in the contaminated (14%) and infected (43%) categories. Antibiotic therapy before cultures are available should include agents with activity against enterococci as well as S aureus, and E. coli in clean cases.