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.

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.

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 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.

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.

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.

Documentation of recent fetal demise with simultaneous maternal and fetal heart rate monitoring.

A case of recent fetal demise with maternal-fetal electrocardiogram (ECG) signal conduction is presented. Diagnosis and graphic documentation of fetal demise were made by comparison of heart tracings obtained from the maternal precordium and from the fetal scalp. Combined monitoring is suggested as a diagnostic procedure and as a method of graphic documentation.

Association of portal hypertension and ruptured splenic artery aneurysm in pregnancy.

Spontaneous rupture of a splenic artery aneurysm is a rare, usually catastrophic event complicating pregnancy. Among risk factors for splenic artery aneurysm in nonpregnant patients is portal hypertension. The third case of rupture of splenic artery aneurysm in a patient with portal hypertension is reported, and previous reports are reviewed. In each of these cases the portal hypertension was due to hepatic cirrhosis. A previously unreported association between portal hypertension in pregnancy and rupture of a splenic artery aneurysm is presented.

Acute effect of cigarette smoking on the fetal heart nonstress test.

A major limitation in the use of the nonstress test (NST) has been the high frequency of nonreactive NSTs in the absence of fetal distress. Exogenous factors causing loss of fetal heart rate reactivity (FHRR) have not been fully evaluated, although it has previously been shown that chronic smokers have an increased incidence of nonreactive NSTs in the absence of fetal distress. A group of chronically smoking high-risk pregnant women at 31 to 44 weeks' gestation was studied to determine if the acute effects of smoking caused the NST to become nonreactive. After a reactive NST was obtained, each patient smoked 1 cigarette and the effects of the fetus were observed. Twenty-six studies were performed on 25 patients. A transient mild elevation of baseline fetal heart rate was noted after smoking in several studies; however, no significant change was found in FHRR, indicating that the acute effects of smoking a single cigarette are not responsible for the increased incidence of nonreactive NSTs in smokers.

Bleomycin, vinblastine, and cis-platinum in the treatment of advanced endodermal sinus tumor.

The endodermal sinus tumor has traditionally been associated with an exceedingly poor prognosis. Three women with advanced pure endodermal sinus tumors were treated with a combination of bleomycin, vinblastine, and cis-platinum (VBC). Serum alpha-fetoprotein levels were monitored for all patients during and after therapy, and in each case the alpha-fetoprotein returned to normal range, correlating with complete clinical remission. Second-look laparotomy was negative for tumor in each case. Two patients have had no overt sign of recurrence 12 months after cessation of therapy. The third patient had post-treatment elevation of alpha-fetoprotein levels, and eventually was found to have recurrent tumor 6 months after chemotherapy was stopped. The VBC combination, previously found effective in testicular germ cell tumors, is also effective in ovarian germ cell tumors.

Pregnancy-related rupture of arterial aneurysms.

Over 50 per cent of ruptured arterial aneurysms in women under the age of 40 are pregnancy-related. The hemodynamic and endocrine changes of pregnancy appear to be the cause of arterial alterations which may lead to new aneurysm formation and/or weakening of preexisting aneurysms. The most commonly reported arteries to have aneurysms rupture during pregnancy are the aorta, cerebral arteries, splenic artery, renal artery, coronary artery, and ovarian artery. In many instances, the rupture of an arterial aneurysm will initially simulate other less serious disease processes, thus delaying the correct diagnosis until a catastrophic event occurs. Early diagnosis and treatment of a ruptured arterial aneurysm are imperative in order to give optimal chances of survival to the mother and fetus.

The ultrastructure of the thin loop limbs of the mouse kidney.

The thin limbs of the loops of Henle in the mouse kidney have been investigated by conventional electron microscopy. Resulting from light microscopic investigations, a distinction in the epithelia of short and long loops can be demonstrated. Ultrastructurally, the thin limbs (descending) of short loops are composed of a uniformly thin and simple epithelium. In contrast, long loops (thin descending and ascending) are composed of three different epithelial types which are representative of a distinctly more complex epithelial system. Two epithelial types were observed in the thin descending limbs of long loops and the third type was observed in the ascending thin limbs. Based upon these findings it is suggested that the thin descending limbs of short and long loops of Henle in the mouse kidney cannot perform the same functions in the renal concentrating mechanism.

The structural organization of the kidney of the desert rodent Psammomys obesus.

The architecture of the desert rodent Psammomys obesus has been studied by means of standard histologic procedures and by single nephron injections. As other rodent kidneys (rat, mouse), the Psammomys kidney consists of two types of nephrons, 66% short looped and 34% long looped nephrons. The cortex is composed of 4 to 5 layers of glomeruli, which lie closely put together, the glomeruli often touch each other. The superficial and the midcortical glomeruli give rise to short looped neophrons, the juxtamedullary to long looped nephrons. In the strongly developed medulla the inner stripe shows the most striking pattern. It consists of two distinct compartments, that of the giant vascular bundles and that of the interbundle regions. The giant vascular bundles consist of about 8 to 14% arterial vasa recta and 39 to 47% venous vasa recta; furthermore they include the thin descending limbs of the short loops of Henle which amount to 44 to 51% of the bundle structures. The tubules of the interbundle regions surround the bundles in a regular pattern. The inner zone is almost completely surrounded by the renal pelvis; the long broad papilla protrudes into the ureter. The thin descending limbs of short looped nephrons traverse the inner stripe inside the giant vascular bundles. Leaving the bundles they turn back within the inner stripe; their ascending limbs lie in the interbundle region. Both limbs of the long loops of Henle run in the interbundle region, together with the ascending limbs of the short loops and the collecting ducts. The long loops penetrate deeply the inner zone. Many bends are found near the tip of the papilla. The renal pelvis has a very specialized form. It penetrates the inner stripe with many complexely shaped extensions, which surround the giant vascular bundles. Large parts of the bundles with their thin walled structures are thus separated from the pelvic urine only by a single layer of cuboidal epithelium. The possible functional importance of the described specializations of the Psammomys kidney (giant vascular bundles, large inner zone, special shape of the renal pelvis) for the urine concentrating and urea recyclng mechanisms is discussed.

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.

[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.

[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.

Female predominance of immigration to the United States since 1930: a first look.

PIP: Immigration patterns in the US in the last 50 years have defied the conventional wisdom that most international migrants are young, working-age males. Since 1930 more than 1/2 of all immgrants to the US have been women, and 2/3 have been women or children. Data show that the persistently large number of marriages of foreign-born or native-born US residents to alien women, coupled with increasing government regulation of immigration and a strong policy bias against the seperation of spouces and children, has resulted in the preponederance of women and children in immigration since 1930. The shift in the sex and age distribution of immgrants in the US in 1930 can also be attributed to the effectiveness of the 1924 quota laws in drastically reducing the enormous influx of immigrants from southern and eastern Europe, when the remaing flow was dominated by wives and children. Traditional sex role behavior has played a significant role in determining both the level and patterns of immigration to the US--while large inflows of economically motivated males induced 2nd flows of women and children before 1930, the 1940s saw the flow of foreign-born wives and children of US servicemen in the wake of Korean and Vietnam wars. An analysis of the Immigration and Naturalization Service data tapes for the 3.6 million fiscal 1972-79 arriving immigrants shows that almost 1/4 are children under 15. Except in this age group, females outnumber males in all other age groups. While immigrants are predictably younger than the US born population regardless of sex, immigrant women are more likely to be married than men, and both are more likely to be married than their US born peers. Immigrant women are substantially less likely to report labor market experience than immigrant men. Unlike US workers, immigrants tend to cluster at the top or bottom of the occupational scale, regardless of sex. Immigrant women are also clustered in the sterotypical female dominated occupations.^ieng