Enuresis and more.

We describe Pervasive Refusal Syndrome, an important but rare, debilitating condition that may present to paediatric services. Although previous reports have described improvement seen with care delivered in the mental health setting, we have demonstrated treatment predominately delivered in a paediatric ward environment associated with successful recovery.

Sensitivity of host-seeking nymphal lone star ticks (Acari: Ixodidae) to immersion in heated water.

Host-seeking nymphal Amblyomma americanum (L.) (Acari: Ixodidae) were placed into heated water, and their survival or their torpidity was recorded as a function of exposure time. Exposures were determined that either kill the nymphs or affect their mobility. All nymphs died when exposed for a minute or more to a temperature > 51 degrees C. Nearly all nymphs remained motionless for a period of time when exposed for 3 min to a temperature > 44 degrees C.

The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial.

BACKGROUND: The international standard radiotherapy schedule for early breast cancer delivers 50 Gy in 25 fractions of 2.0 Gy over 5 weeks, but there is a long history of non-standard regimens delivering a lower total dose using fewer, larger fractions (hypofractionation). We aimed to test the benefits of radiotherapy schedules using fraction sizes larger than 2.0 Gy in terms of local-regional tumour control, normal tissue responses, quality of life, and economic consequences in women prescribed post-operative radiotherapy. METHODS: Between 1999 and 2001, 2215 women with early breast cancer (pT1-3a pN0-1 M0) at 23 centres in the UK were randomly assigned after primary surgery to receive 50 Gy in 25 fractions of 2.0 Gy over 5 weeks or 40 Gy in 15 fractions of 2.67 Gy over 3 weeks. Women were eligible for the trial if they were aged over 18 years, did not have an immediate reconstruction, and were available for follow-up. Randomisation method was computer generated and was not blinded. The protocol-specified principal endpoints were local-regional tumour relapse, defined as reappearance of cancer at irradiated sites, late normal tissue effects, and quality of life. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN59368779. FINDINGS: 1105 women were assigned to the 50 Gy group and 1110 to the 40 Gy group. After a median follow up of 6.0 years (IQR 5.0-6.2) the rate of local-regional tumour relapse at 5 years was 2.2% (95% CI 1.3-3.1) in the 40 Gy group and 3.3% (95% CI 2.2 to 4.5) in the 50 Gy group, representing an absolute difference of -0.7% (95% CI -1.7% to 0.9%)--ie, the absolute difference in local-regional relapse could be up to 1.7% better and at most 1% worse after 40 Gy than after 50 Gy. Photographic and patient self-assessments indicated lower rates of late adverse effects after 40 Gy than after 50 Gy. INTERPRETATION: A radiation schedule delivering 40 Gy in 15 fractions seems to offer rates of local-regional tumour relapse and late adverse effects at least as favourable as the standard schedule of 50 Gy in 25 fractions.

The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial.

BACKGROUND: The international standard radiotherapy schedule for breast cancer treatment delivers a high total dose in 25 small daily doses (fractions). However, a lower total dose delivered in fewer, larger fractions (hypofractionation) is hypothesised to be at least as safe and effective as the standard treatment. We tested two dose levels of a 13-fraction schedule against the standard regimen with the aim of measuring the sensitivity of normal and malignant tissues to fraction size. METHODS: Between 1998 and 2002, 2236 women with early breast cancer (pT1-3a pN0-1 M0) at 17 centres in the UK were randomly assigned after primary surgery to receive 50 Gy in 25 fractions of 2.0 Gy versus 41.6 Gy or 39 Gy in 13 fractions of 3.2 Gy or 3.0 Gy over 5 weeks. Women were eligible if they were aged over 18 years, did not have an immediate surgical reconstruction, and were available for follow-up. Randomisation method was computer generated and was not blinded. The protocol-specified principal endpoints were local-regional tumour relapse, defined as reappearance of cancer at irradiated sites, late normal tissue effects, and quality of life. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN59368779. FINDINGS: 749 women were assigned to the 50 Gy group, 750 to the 41.6 Gy group, and 737 to the 39 Gy group. After a median follow up of 5.1 years (IQR 4.4-6.0) the rate of local-regional tumour relapse at 5 years was 3.6% (95% CI 2.2-5.1) after 50 Gy, 3.5% (95% CI 2.1-4.3) after 41.6 Gy, and 5.2% (95% CI 3.5-6.9) after 39 Gy. The estimated absolute differences in 5-year local-regional relapse rates compared with 50 Gy were 0.2% (95% CI -1.3% to 2.6%) after 41.6 Gy and 0.9% (95% CI -0.8% to 3.7%) after 39 Gy. Photographic and patient self-assessments suggested lower rates of late adverse effects after 39 Gy than with 50 Gy, with an HR for late change in breast appearance (photographic) of 0.69 (95% CI 0.52-0.91, p=0.01). From a planned meta-analysis with the pilot trial, the adjusted estimates of alpha/beta value for tumour control was 4.6 Gy (95% CI 1.1-8.1) and for late change in breast appearance (photographic) was 3.4 Gy (95% CI 2.3-4.5). INTERPRETATION: The data are consistent with the hypothesis that breast cancer and the dose-limiting normal tissues respond similarly to change in radiotherapy fraction size. 41.6 Gy in 13 fractions was similar to the control regimen of 50 Gy in 25 fractions in terms of local-regional tumour control and late normal tissue effects, a result consistent with the result of START Trial B. A lower total dose in a smaller number of fractions could offer similar rates of tumour control and normal tissue damage as the international standard fractionation schedule of 50 Gy in 25 fractions.

Identification of the in vivo promoters of bacteriophages S13 and phi X174 and measurement of their relative activities.

Regions of bacteriophages phi X174 and S13 that contain putative promoter sequences were amplified by the polymerase chain reaction (PCR) and cloned into the reporter vector pKO-1. Assays of galactokinase activity revealed in vivo promoter activity in those constructs containing the promoter sequences with transcription initiation (+1) sites at nucleotide positions 45, 982, 1823, and 5211. These were identical in location to sequences with in vitro promoter activity and to the three known promoters PA, PB, and PD. P5211 is the location of a new, fourth, promoter. A site with a +1 position at nucleotide 4876, previously shown to initiate RNA synthesis in an in vitro run-off transcription assay, had no in vivo promoter activity. To investigate whether flanking sequences had effects on promoter activity, restriction fragments of phi X174 and S13 that encompass the in vivo promoters were cloned into the reporter vector pKO-1. The PA and P5211 promoter constructs showed dramatic effects with increases in activity of up to 7 times that shown with the PCR-generated promoter constructs. The phi X174 PB promoter construct had a 50% decrease in activity compared with the PCR-generated PB clone. While the data showed that in most instances promoter activity is affected by the flanking sequences in which the promoter is embedded, no general pattern correlating flanking sequences and promoter activity could be discerned. Additional evidence that the promoter sequence regions were active in vivo promoters was obtained by S1 nuclease mapping experiments. Initiation of RNA synthesis was shown at positions 45, 982, and 5211.

Pediatric primary gram-negative nosocomial bacteremia: a possible relationship with infusate contamination.

OBJECTIVE: To evaluate the potential contribution of "extrinsic" contamination of intravenous fluids in hospital bacteremia and infection. DESIGN: Prospective cross-sectional survey of infusate contamination, December 1992 to December 1993. SETTING: A pediatric department (1,500 admissions per year) in a general, urban teaching hospital, serving low-income patients. SAMPLES AND PATIENTS: Infusate samples (0.5 to 1.0 mL) from the injection port used by the staff were taken for cultures from all febrile or septic patients in hospital wards. At least four samples were taken each day; if no febrile or septic patients were available, other patients were sampled at convenience. RESULTS: A 6.8% positive culture rate (87 contaminates in 1,277 infusates) was obtained, without significant differences among the wards. Gram-negative organisms were recovered from 56 samples (62.9%), mainly of the tribe Klebsielleae (56.1%). Coagulase-negative staphylococci were isolated in 30 samples (33.7%). There was no significant difference between the febrile-septic group and the asymptomatic group in the rate of infusate contamination (P = .59). In eight patients, the same organisms were recovered from infusate and blood culture. The overall bacteremia rate was 2.5 per 100 discharges. CONCLUSIONS: Compared to previous reports, higher infusate contamination rates and different organisms (mainly gram-negative) were observed. In hospitals of underdeveloped countries, nosocomial infection control frequently is disregarded. Infusate contamination may be common and could lead to gram-negative bacteremia. In such settings, it seems advisable to perform surveillance studies to identify infusate contamination, because a single infusate contamination could be a signal for an epidemic.

Computer graphics of SEM images facilitate recognition of chromosome position in isolated human metaphase plates.

There is general agreement that at the time of mitosis chromosomes occupy precise positions and that these positions likely affect subsequent nuclear function in interphase. However, before such ideas can be investigated in human cells, it is necessary to determine first the precise position of each chromosome with regard to its neighbors. It has occurred to us that stereo images, produced by scanning electron microscopy, of isolated metaphase plates could form the basis whereby these positions could be ascertained. In this paper we describe a computer graphic technique that permits us to keep track of individual chromosomes in a metaphase plate and to compare chromosome positions in different metaphase plates. Moreover, the computer graphics provide permanent, easily manipulated, rapid recall of stored chromosome profiles. These advantages are demonstrated by a comparison of the relative position of group A-specific and groups D- and G-specific chromosomes to the full complement of chromosomes in metaphase plates isolated from a nearly triploid human-derived cell (HeLa S3) to a hypo-diploid human fetal lung cell.

[Pediatric nosocomial bacteremia. Potential usefulness of culturing infusion liquids]. / Bacteriemia nosocomial pediátrica. Utilidad potencial del cultivo de los líquidos de infusión.

Hospital-acquired bacteremia is a common cause of morbidity and mortality, mainly in pediatric units. In a 25 month retrospective study, we analyzed the blood cultures from the Hospital General Regional of the city of Leon, Guanajuato State, Mexico, in order to establish the causal agents of nosocomial bacteremia and infer some associations with contaminated intravenous infusion fluids. In addition we performed a two month study to culture the flasks and intravenous tubing used in our infusions. Five hundred and fifty one blood cultures drawn from August 1990 to September 1992 were analyzed. A total of 135 (24.5%) were positive, most of them (51.8%) with strains of the Klebsielleae tribe (SKT) (Klebsiella, Enterobacter, Serratia). The global incidence of bacteremia in the two year period was 4.3%. In the infusion study, 230 intravenous fluids were cultured, with 68 isolates (30%) most from the SKT tribe. A final consideration is made on the role that inadequate management of intravenous liquids could play in the development of endemic and epidemic nosocomial bacteremia in our hospital, and the eventual utility of making cultures of the i.v. liquids.

[Surveillance of therapy with aminoglycosides at a specialized hospital]. / Vigilancia de terapia con aminoglucósidos en un hospital de especialidades.

Aminoglycosides (AG) are excellent antibiotics against gram-negative bacilli infections, but their use implies potential ototoxicity and nephrotoxicity if an excessive dosage is prescribed. In this study we evaluated 105 episodes of AG treatment in 104 patients hospitalized in a specialty hospital in the city of Leon, Mexico. In each case a basal serum creatinine, weight and age were recorded. A single serum AG assay per episode of treatment was done. Either amikacin or gentamicin were one the AG prescribed. Prior to AG administration only 54 treatment episodes (51%) had a before treatment creatinine assay. The initial creatinine clearance showed normal values in 43% (23/54 episodes) and it was altered (below 80 mL/min) in 31 (57%) of the episodes. In the 31 cases with an altered renal function only 15 (48%) underwent dosage adjustment. In summary the AG were prescribed in excess in 54% (29/54) of the episodes. The serum AG levels within toxic range were observed in 11 episodes. These results suggest that in our hospital AG treatment is not adequately done and monitored.

[The seroepidemiology of rubella in a female population of reproductive age in León, Guanajuato]. / Seroepidemiología de la rubéola en una población femenina en edad fértil de León, Guanajuato.

In order to assess the seroepidemiology of protective antibodies against rubella among women from León, Guanajuato, Mexico, a prospective study was done. The sample consisted in 176 serum samples from urban and rural women at reproductive age, drawn from June 1990 to June 1991. Samples were tested by the classic hemagglutination inhibition method, titers of 1:8 or higher were considered as positive. Global positivity was 71 per cent (125 sera). Seropositivity did not increase with women's age; the lowest values were seen at the rural zones (58.9%). This survey showed a lower seropositivity than the previously reported in Mexico, and confirms data from new official studies. With this information authors suggest that the utility and viability of a national vaccination program should be reviewed and propose that it could be risky that individual clinicians to recommend children vaccination because the lack of coordination could increase adult cases of rubella.

The efficacy and safety of the cytobrush during pregnancy.

The safety and efficacy of abrasive cytology, using the cytobrush, were evaluated in 300 pregnant patients. When compared to conventional cytology obtained with a cotton-tipped applicator there was no difference in adverse pregnancy events. Smear adequacy (containing endocervical cells) was statistically (P less than 0.01) and clinically increased from 21 to 86%. The use of abrasive cervical cytology was associated with a twofold increase in the incidence of abnormal smears.

Split course interstitial brachytherapy with a source shift: the results of a new technique for salvage irradiation in recurrent inoperable cervical lymphadenopathy greater than or equal to 4 cm diameter in 23 patients.

Between June 1981 and December 1986, 23 patients with prior irradiation of the neck for epithelial ENT tumors underwent salvage irradiation for isolated recurrent inoperable cervical lymphadenopathy greater than or equal to 4 cm. The initial irradiation had delivered 45-80 Gy to the cervical lymph nodes. Split course interstitial brachytherapy was used with a source shift in an attempt to decrease treatment complications. The first and second course of the split course implants delivered 35 Gy and 30 Gy at a 1 month interval. The active lines of the second implant were placed parallel to and in between the position of the lines of the first implant. Three patients did not receive the second implant (one death, one disease evolution, one necrosis). For the patient who died between the first and second implants the local control rate could not be determined. The immediate overall local control rate was 73% (16/22) with a later recurrence rate of 62% (10/16), but only in three cases was recurrence within the treated volume (19%-3/16). The local control rate was better (3/9) if the initial lymphadenopathy was greater than or equal to 4 cm less than or equal to 6 cm but worse (3/13) in those with initial lymphadenopathy greater than 6 cm. Survival of these patients overall was poor with 26% survival at 1 year and 13% at 2 years. Tolerance overall was acceptable with tissue necrosis occurring in 36.5% of cases including those with initial skin involvement. If these cases were excluded the necrosis rate was only 15.5%. In this patient population with inoperable recurrent cervical lymphadenopathy in whom a further dose of external irradiation is not possible interstitial brachytherapy should be considered. Our technique of implantation, split over two sessions with a source shift, is practicable with an acceptable toxicity. It may be used even after high dose external beam irradiation and in large volumes of disease, and it gives better results than classical brachytherapy.

Evaluation of obstetric ultrasonography at the first prenatal visit.

A prospective study was performed on 1000 consecutive patients to assess the value of ultrasonography at first prenatal visit. Significant ultrasonographic findings were noted in more than one third of the patients. A discrepancy between ultrasonography and menstrual dating was the most frequently noted abnormality, occurring in 27%; 59% of those would not have been discovered on initial physical examination. Other frequently noted abnormalities included missed abortion (5.7%) and twins (1.6%). The frequency of abnormalities on the initial laboratory studies recommended by the American College of Obstetricians and Gynecologists was evaluated and found to be significantly less than the frequency of clinically important ultrasonographic findings, ranging from 4.0% for positive urine cultures to 0.2% for positive serologic tests. Unexpected findings on physical examination, excluding assessment of pregnancy dating on the basis of uterine size, were even less frequent, occurring in 2.1% of the patients. It is concluded that obstetric ultrasonography at the time of the first prenatal visit is better than physical examination in evaluating the status of the pregnancy and should be considered for all patients.

Funic reduction for the management of umbilical cord prolapse.

The current management of umbilical cord prolapse centers on attempts to alleviate the pressure of the presenting part on the cord while preparation for cesarean section is being made. A 10-year experience in which there were vigorous attempts to accomplish safe vaginal delivery after the diagnosis of umbilical cord prolapse is presented. Eight cases of umbilical cord prolapse occurred, a frequency of 1 in 277 deliveries (0.37%), all of which had a normal immediate neonatal outcome. Vaginal delivery was accomplished in seven patients (87.5%); diagnosis was made in two of them when delivery was imminent. Five patients were more remote from delivery and had successful funic reduction (manual replacement of the prolapsed cord). Funic reduction is proposed as a potentially beneficial initial step in the management of umbilical cord prolapse.

Differential expression of c-myc and H-ras oncogenes in Barrett's epithelium. A study using colorimetric in situ hybridization.

To determine the role of c-myc and H-ras in progressive, dysplastic Barrett's mucosa (BM), and the usefulness of these oncogenes as markers for dysplastic lesions at high risk for malignant transformation, sequential formaldehyde solution-fixed, paraffin-embedded biopsy specimens that were obtained from 12 patients with BM were evaluated by in situ hybridization with the use of biotinylated complimentary DNA probes. Nine of the patients were taken from a previous prospective study. Four of these nine patients had dysplasia, and adenocarcinoma had developed in two of them; five had nondysplastic BM only. Two additional patients had adenocarcinoma, but their initial biopsy specimens had revealed dysplasia. One additional patient had intermediate-grade dysplasia. The intensity of oncogene expression was quantified by computerized color-image analysis. Enhanced c-myc expression of approximately equal intensity was consistently observed in all grades of dysplasia and carcinoma. H-ras was also consistently expressed in higher grades of dysplasia and carcinoma but not in low-grade dysplasia. Neither c-myc nor H-ras expression was detected in nondysplastic BM. The expression of H-ras in dysplastic BM appears to be a helpful marker for identifying which dysplastic lesions will progress to carcinoma.

Continuous or interrupted fascial closure: a prospective evaluation of No. 1 Maxon suture in 402 gynecologic procedures.

During a 14-month period of using a long-term absorbable suture (No. 1 Maxon), 402 patients were entered into a prospective, randomized trial of fascial closure. Patients were randomized between a continuous closure (201 patients) and an interrupted en bloc (201 patients) technique. Each patient was subjected to a preoperative and intraoperative protocol for wound management. There were no acute wound failures. Wound infection rates and risk of hernia were not apparently affected by closure technique.

Single-dose antibiotic prophylaxis for patients undergoing extended pelvic surgery for gynecologic malignancy.

The comparative efficacy of single-dose antibiotic prophylaxis was retrospectively evaluated in 116 patients undergoing extended pelvic surgical procedures with curative intent. During the 24-month period, other important variables such as surgeon's experience, duration of preoperative hospitalization, preoperative preparation, method of hair removal, suture type, suture size, use of drains, use of cautery, and abdominal closure were controlled. The overall surgical site infection rate was 4.3% after radical hysterectomy with lymphadenectomy and 4.5% after total hysterectomy with lymphadenectomy. In this clinical situation the use of a single dose of antibiotic prophylaxis theoretically decreases cost and patient exposure and appears to be as efficacious as a multiple-dose regimen.

Immunocytochemical study of ras and myc proto-oncogene polypeptide expression in the human menstrual cycle.

The human endometrium is a unique and dynamic tissue model system characterized by cyclic processes of cellular proliferation, differentiation, and menstrual desquamation. Both the glandular epithelial and stromal mesenchymal components work in synchronous response to the mitogenetic effect of estradiol and the antimitogenetic effect of progesterone. Mechanisms whereby estradiol and progesterone exert their effects are not completely understood. This study was undertaken to evaluate the expression and localization of the polypeptide products of the ras and myc proto-oncogenes sequentially during the menstrual cycle. Sixteen endometrial biopsy specimens were evaluated. Immunocytochemical quantitation of ras and myc expression was done by use of color image analysis (CoreScan). There was no cyclic variation in the ras polypeptide product, but the expression of myc polypeptide was low in the secretory phase and high in the proliferative phase.

Immunocytochemical study of transforming growth factor expression in benign and malignant gliomas.

Immunocytochemical studies using polyclonal antibodies to epidermal growth factor (EGF) and transforming growth factor (TGF) alpha and beta were performed on 20 cases of human gliomas. EGF immunoreactive material was detected in both benign and malignant glial tumors. In addition, EGF immunoreactive material was detected in normal brain. TGF-beta was detected in both benign and malignant tumors, but was not detected in normal brain. In contrast, TGF-alpha was highly conserved in its expression, occurring predominantly in malignant compared with benign or normal brain tissue (P less than 0.0001). In malignant gliomas, glioblastomas contained 76% TGF-alpha reactivity (immunoreactive product), and anaplastic types contained 85% reactivity. Benign gliomas contained only 13% TGF-alpha reactivity. These findings support the role of TGF-alpha as an oncoprotein marker in brain neoplasms.