Subglottic cysts: The Great Ormond Street experience in 105 patients.

PURPOSE: The aim of the study was to assess the contemporary presentation and management of subglottic cysts and make recommendations on the treatment of these patients. METHODS: Retrospective case series of 105 patients between October 1999 and November 2017 from a paediatric teaching hospital. RESULTS: Ninety-one percentage (n = 96) had a history of prematurity, with a mean gestation of 27.2 weeks (SD ± 4.1). A history of intubation was found in 99% (n = 104) of cases [median 18 days (range = 1-176)]. Presenting symptoms were: Stridor 57.1%, (n = 60), difficult intubation 14% (n = 15), recurrent croup 11.4% (n = 12), failed extubation 7.6%, (n = 8), hoarseness/weak cry 10.5% (n = 10). Ninety percentage (n = 94) underwent intervention for management of SGCs with 86% (n = 81) treated with cold steel marsupialisation and 14% (n = 13) with CO 2 laser. Recurrent cysts occurred in 56% (n = 53) of cases. Treatment modality did not affect recurrence (p = 0.594 Δ). Sixty-six percentage (n = 69/105) of patients had one or more concurrent airway pathology at MLB. Most frequent was subglottic stenosis 47% (n = 49), with 16% (n = 8) subsequently requiring open reconstructive airway surgery. Mean duration of follow-up was 47.6 months (SD ± 38.3). CONCLUSION: SGC are an uncommon, reversible cause of upper airway obstruction and should be considered in the list of differential diagnoses in patients with a history of prematurity and perinatal intubation, presenting with stridor. While concurrent SGS is common, adequate symptom improvement in such cases may be achieved with SGC removal alone. Management is by surgical marsupialisation. Recurrence and additional airway pathologies are common and may necessitate longer-term treatment in centres with paediatric airway expertise.

Adverse effects of anti-epileptics in trigeminal neuralgiform pain.

BACKGROUND: Side effects of anti-epileptic drugs (AEDs) have not been adequately documented in trigeminal neuralgia and its variants. The aim of this observational cross-sectional study was to compare the A-B Neuropsychological Assessment Schedule (ABNAS), which measures cognitive side effects to the Adverse Events Profile (AEP), which looks at a broader range of side effects, and to investigate drug/dosage relationships with questionnaire scores to help determine a point at which a drug change would be indicated. METHODS: One hundred five patients were recruited from a facial pain clinic, over a 10-month period. Self-complete questionnaire scores were compared between patients using different AEDs. RESULTS: A-B Neuropsychological Assessment Schedule score correlated well with AEP indicating that cognitive side effects were a significant burden. Toxic range on the ABNAS was estimated to occur when scores were >43/72 (95% CI: 37.4-48.6). Polytherapy is weakly associated with the higher scores. Oxcarbazepine dosage was found to linearly correlate with AEP and ABNAS scores, better than carbamazepine dosage. Memory alteration was least common with lamotrigine and oxcarbazepine, and there was less association between fatigues with oxcarbazepine/pregabalin. CONCLUSION: Anti-epileptic drugs have significant side effects. The ABNAS questionnaire is a useful tool along with the AEP to recognize and monitor AEDs' side effects and to help to adjust medications to optimal dosage.

Differential binding affinity of mutated peptides for MHC class I is a predictor of survival in advanced lung cancer and melanoma.

Background: Cancer mutations generate novel (neo-)peptides recognised by T cells, but the determinants of recognition are not well characterised. The difference in predicted class I major histocompatibility complex (MHC-I) binding affinity between wild-type and corresponding mutant peptides (differential agretopicity index; DAI) may reflect clinically relevant cancer peptide immunogenicity. Our aim was to explore the relationship between DAI, measures of immune infiltration and patient outcomes in advanced cancer. Patients and methods: Cohorts of patients with advanced non-small-cell lung cancer (NSCLC; LUAD, n = 66) and melanoma (SKCM, n = 72) were obtained from The Cancer Genome Atlas. Three additional cohorts of immunotherapy treated patients with advanced melanoma (total n = 131) and NSCLC (n = 31) were analysed. Neopeptides and their clonal status were defined using genomic data. MHC-I binding affinity was predicted for each neopeptide and DAI values summarised as the sample mean DAI. Correlations between mean DAI and markers of immune activity were evaluated using measures of lymphocyte infiltration and immune gene expression. Results: In univariate and multivariate analyses, mean DAI significantly correlated with overall survival in 3/5 cohorts, with evidence of superiority over nonsynonymous mutational and neoantigen burden. In these cohorts, the effect was seen for mean DAI of clonal but not subclonal peptides. In SKCM, the association between mean DAI and survival bordered significance (P = 0.068), reaching significance in an immunotherapy-treated melanoma cohort (P = 0.003). Mean DAI but not mutational nor neoantigen burden was positively correlated with independently derived markers of immune infiltration in both SKCM (P = 0.027) and LUAD (P = 0.024). Conclusions: The association between mean DAI, survival and measures of immune activity support the hypothesis that DAI is a determinant of cancer peptide immunogenicity. Investigation of DAI as a marker of immunologically relevant peptides in further datasets and future clinical studies of neoantigen based immunotherapies is warranted.

From Theory to Practice: Measuring end-of-life communication quality using multiple goals theory.

OBJECTIVES: To describe how multiple goals theory can be used as a reliable and valid measure (i.e., coding scheme) of the quality of conversations about end-of-life issues. METHODS: We analyzed conversations from 17 conversations in which 68 participants (mean age=51years) played a game that prompted discussion in response to open-ended questions about end-of-life issues. Conversations (mean duration=91min) were audio-recorded and transcribed. Communication quality was assessed by three coders who assigned numeric scores rating how well individuals accomplished task, relational, and identity goals in the conversation. RESULTS: The coding measure, which results in a quantifiable outcome, yielded strong reliability (intra-class correlation range=0.73-0.89 and Cronbach's alpha range=0.69-0.89 for each of the coded domains) and validity (using multilevel nonlinear modeling, we detected significant variability in scores between games for each of the coded domains, all p-values <0.02). CONCLUSIONS: Our coding scheme provides a theory-based measure of end-of-life conversation quality that is superior to other methods of measuring communication quality. PRACTICE IMPLICATIONS: Our description of the coding method enables researches to adapt and apply this measure to communication interventions in other clinical contexts.

Prenatal diagnosis of orofacial clefts: association with maternal satisfaction, team care, and treatment outcomes.

OBJECTIVE: Prenatal diagnosis of an orofacial cleft is thought to allow mothers greater opportunity to become prepared for the special needs of an infant with a cleft and plan for the care of their child. Using a population-based sample, we determined which children were more likely to be diagnosed prenatally, and whether early diagnosis was associated with maternal satisfaction and treatment outcomes. DESIGN: Interviews were completed with 235 (49% of eligible) mothers of children ages 2 to 7 with orofacial clefts initially enrolled in the National Birth Defects Prevention Study from the Arkansas, Iowa, and New York sites. Maternal satisfaction with information, support, and treatment outcomes was compared between women who received a prenatal diagnosis and those who did not. RESULTS: Of 235 infants with clefts, 46 (19.6%) were identified prenatally. One third of mothers were somewhat or not satisfied with information provided by medical staff. Satisfaction did not vary by timing of the diagnosis. Infants diagnosed prenatally were no more likely to have received care provided by a recognized multidisciplinary cleft team (76%) than were infants diagnosed at birth (78%). Speech problems and facial appearance as rated by the mother did not vary by timing of the diagnosis. CONCLUSIONS: Timing of the cleft diagnosis did not alter maternal satisfaction with information, whether care was provided by a designated cleft team, or maternal perception of facial appearance or speech. Further research should determine whether prenatal diagnoses alter maternal anxiety or influence postnatal morbidity.

WFDC1/ps20 is a novel innate immunomodulatory signature protein of human immunodeficiency virus (HIV)-permissive CD4+ CD45RO+ memory T cells that promotes infection by upregulating CD54 integrin expression and is elevated in HIV type 1 infection.

Understanding why human immunodeficiency virus (HIV) preferentially infects some CD4(+) CD45RO(+) memory T cells has implications for antiviral immunity and pathogenesis. We report that differential expression of a novel secreted factor, ps20, previously implicated in tissue remodeling, may underlie why some CD4 T cells are preferentially targeted. We show that (i) there is a significant positive correlation between endogenous ps20 mRNA in diverse CD4 T-cell populations and in vitro infection, (ii) a ps20(+) permissive cell can be made less permissive by antibody blockade- or small-interference RNA-mediated knockdown of endogenous ps20, and (iii) conversely, a ps20(low) cell can be more permissive by adding ps20 exogenously or engineering stable ps20 expression by retroviral transduction. ps20 expression is normally detectable in CD4 T cells after in vitro activation and interleukin-2 expansion, and such oligoclonal populations comprise ps20(positive) and ps20(low/negative) isogenic clones at an early differentiation stage (CD45RO(+)/CD25(+)/CD28(+)/CD57(-)). This pattern is altered in chronic HIV infection, where ex vivo CD4(+) CD45RO(+) T cells express elevated ps20. ps20 promoted HIV entry via fusion and augmented CD54 integrin expression; both of these effects were reversed by anti-ps20 antibody. We therefore propose ps20 to be a novel signature of HIV-permissive CD4 T cells that promotes infection in an autocrine and paracrine manner and that HIV has coopted a fundamental role of ps20 in promoting cell adhesion for its benefit. Disrupting the ps20 pathway may therefore provide a novel anti-HIV strategy.

Reduction in newborns with discharge coding of in utero alcohol effects in the United States, 1993 to 2002.

OBJECTIVE: To determine whether use of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for fetal alcohol effects has declined during the past 10 years among hospitalized newborns in the United States. DESIGN: Trends in use of the ICD-9-CM code 760.71, "alcohol affecting the fetus," among newborns from 1993 through 2002 were compared with trends in self-reported drinking during pregnancy and maternal diagnoses of alcohol abuse during childbirth. SETTING: Sampled short-term, nonfederal general and specialty hospitals. PARTICIPANTS: Infants born from 1993 to 2002 in the United States who were included in the Healthcare Cost and Utilization Project databases. MAIN OUTCOME MEASURES: Documentation of ICD-9-CM code 760.71 among newborns, self-reported drinking during pregnancy, and diagnoses of maternal alcohol abuse during childbirth from 1993 through 2002. RESULTS: The prevalence of the ICD-9-CM code 760.71 for alcohol affecting the fetus, as documented in the discharge record of newborns, declined from 0.73 (95% confidence interval, 0.56-0.92) per 1000 live births in 1993 to 0.17 (95% confidence interval, 0.13-0.20) per 1000 live births in 2002. Rates declined concurrently with those of self-reported alcohol consumption during pregnancy and diagnoses of maternal alcohol abuse during childbirth. CONCLUSIONS: Use of the ICD-9-CM code for alcohol affecting the fetus among newborns declined 75% throughout 10 years. Results may be due to decreases in drinking during pregnancy, decreases in disclosure of alcohol use by the mother, or more selective use of the discharge code. National hospital discharge databases may allow cost-effective monitoring of public health interventions that address rare conditions of the fetus and newborn.

Hospitalizations of newborns with folate-sensitive birth defects before and after fortification of foods with folic acid.

CONTEXT: The prevalence of neural tube defects is reduced in populations of women who receive folic acid supplementation. Since 1998, grain products in the United States have been fortified with folic acid. Fortification may have additional benefits by reducing the national prevalence of newborn hospitalizations for other folate-sensitive birth defects. OBJECTIVE: Our purpose with this work was to compare rates of hospitalizations of newborns with folate-sensitive birth defects before and after implementation of fortification of grains. METHOD: National hospital discharge data from the Healthcare Cost and Utilization Project were used to compute rates of newborn hospitalizations for selected birth defects per 10,000 live births in the United States. Newborn hospitalization rates involving congenital anomalies recognizable at birth were analyzed for 5 years before fortification of grains and 5 years after fortification. Additional analyses compared changes in newborn hospitalization rates for birth defects by race/ethnicity, income, insurance status, and region of the country. RESULTS: Newborn hospitalization rates for spina bifida decreased 21% from 1993-1997 to 1998-2002. Newborn hospitalization rates also decreased for anencephaly (20%) and limb-reduction defects (4%). Decline in hospitalizations for spina bifida occurred more often among Hispanic newborns (33%) than among white (13%) or black (21%) newborns. Decline in limb-reduction defects was seen primarily among blacks (11%). Findings using hospitalization data were similar to recent reports using birth defect surveillance systems with the exception of findings for orofacial clefts and conotruncal heart defects. No reductions were noted in newborn hospitalizations for these anomalies. CONCLUSIONS: Results from this ecological study fail to demonstrate substantial declines in newborn hospitalizations beyond those anticipated from a reduction in neural tube defects. The society-wide impact of the fortification program on birth defects and other health conditions should continue to be monitored.

Lateral plantar nerve injury following steroid injection for plantar fasciitis.

A 41 year old man presented with pain and numbness affecting the lateral aspect of his foot after a steroid injection for plantar fasciitis. Examination confirmed numbness and motor impairment of the lateral plantar nerve. The findings were confirmed by electromyographic studies. The anatomy of the lateral plantar nerve and correct technique for injection to treat plantar fasciitis are discussed.

High rates of multiple antibiotic resistance in Streptococcus pneumoniae from healthy children living in isolated rural communities: association with cephalosporin use and intrafamilial transmission.

OBJECTIVE: Streptococcus pneumoniae is one of the most clinically significant pathogens with emerging antibiotic resistance. We performed a surveillance study in isolated rural populations of healthy children to estimate the prevalence of pneumococcal resistance and to contrast factors that predict pneumococcal carriage with those that specifically predict resistant pneumococcal carriage. METHODS: The study was conducted in 1998 in 2 rural communities in Utah. Families were recruited directly for participation through community canvassing. Surveillance nasopharyngeal cultures were obtained from children who were younger than 8 years. Antibiotic usage and information on other potential risk factors were obtained from questionnaires and local pharmacy records. Resistance was determined by testing isolates for susceptibility to penicillin, cefaclor, trimethoprim-sulfamethoxazole, erythromycin, ceftriaxone, and trovafloxacin. Selected resistant isolates were characterized further by serotyping, pulsed field gel electrophoresis, and Southern blot with DNA probes specific for the pneumococcal lytA gene and for antibiotic resistance genes. RESULTS: In April 1998, surveillance nasopharyngeal cultures were obtained from 368 children aged

Probabilistic linkage of computerized ambulance and inpatient hospital discharge records: a potential tool for evaluation of emergency medical services.

STUDY OBJECTIVES: Emergency medical services (EMS) is an important part of the health care system. The effect of EMS on morbidity, mortality, and costs of illness is difficult to evaluate because hospital information is not available in out-of-hospital databases. We used probabilistic linkage to create such a database from ambulance and inpatient data and demonstrate the potential for linkage to facilitate evaluation of EMS responses resulting in hospital admission. METHODS: Statewide ambulance and inpatient hospital discharge records were available for 1994 through 1996. Ambulance records indicating admission to the emergency department or hospital (165,649 records) were linked to inpatient hospital records indicating emergency admission (146,292 records) by using probabilistic linkage. Out-of-hospital data (dispatch code, treatments rendered, and ages), linkage rates, and inpatient data (discharge status, charges, length of stay, and payer category) were analyzed. RESULTS: We linked 24,299 (14.7%) ambulance events to inpatient hospital discharges. If we had used exact linkage methods, we would have only linked 14,621 record pairs, a loss of nearly 40%. Linkage rates were relatively constant between years (approximately 15%) but differed by ambulance dispatch codes. Out-of-hospital dispatch codes with high linkage rates included breathing problems (22.6%), chest pain (21.5%), diabetic problems (16.9%), drowning incidents (14.9%), falls (19.2%), strokes (32.8%), and unconsciousness or fainting episodes (16.1%). Linkage to the hospital record provided access to hospital outcome data. Inpatient mortality was 6.8%. Survivors were discharged home (60.7%), transferred to other acute-care facilities (3.6%) or intermediate-care facilities (23.3%), or discharged with home health care provision (4.9%). The median length of stay was 3 days, and median charges were $6,620; total inpatient charges were $286,737,067. CONCLUSION: Probabilistic linkage enables ambulance and hospital discharge records to be linked together and potentially increases our ability to critically evaluate EMS by providing access to hospital-based outcomes. Such evaluation will be further improved by linking to ED, other outpatient, and other public health data sources.

Shoulder belts in motor vehicle crashes: a statewide analysis of restraint efficacy.

The purpose of our study was to evaluate the impact of shoulder belt use on motor vehicle crash ejection, morbidity and mortality. We analyzed motor vehicle crash records linked to hospital inpatient data for front seat occupants of passenger cars in Utah between 1994 and 1996 (n = 103,035). Stochastic simulations were used to adjust for possible seatbelt misclassification. There were 276 (0.3%) occupants coded as using only a shoulder belt. The adjusted odds of ejection for shoulder only belted occupants was higher compared to lap-shoulder belted (odds ratio (OR) = 18.9; 95% confidence interval (CI) = 15.1, 25.1) and lap only belted occupants (OR = 4.3; 95% Cl = 2.9, 7.7). There was no difference in the odds of ejection for an occupant using a shoulder belt only and an occupant using no seatbelt (OR = 1.1; 95% CI = 1.0, 1.3). Occupants using a shoulder belt only were more likely to sustain a fatal or hospitalizing injury than lap-shoulder belted (OR = 2.3; 95% Cl = 1.9, 3.0), and lap only belted occupants (OR = 1.8; 95% CI = 1.3, 2.7), while controlling for other covariates. Occupants using only a shoulder belt had the same odds of a fatal or hospitalizing injury as unbelted occupants (OR = 1.1; 95% Cl = 0.9, 1.4). Average hospital inpatient length of stay, charges and injury severity scores were similar for all restraint types. These results stress the need for the use of a lap belt in conjunction with the shoulder belt.

Intragenic suppressors of an OmpF assembly mutant and assessment of the roles of various OmpF residues in assembly through informational suppressors.

We employed two separate genetic approaches to examine the roles of various OmpF residues in assembly. In one approach, intragenic suppressors of a temperature-sensitive OmpF assembly mutant carrying a W214E substitution were sought at 42 degrees C, or at 37 degrees C in a genetic background lacking the periplasmic folding factor SurA. In the majority of cases (58 out of 61 revertants), the suppressors mapped either at the original site (position 214) or two residues downstream from it. In the remaining three revertants that were obtained in a surA background, an alteration of N230Y was located 16 residues away from the original site. The N230Y suppressor also corrected OmpF315 assembly at 42 degrees C in a surA(+) background, indicating that the two different physiological environments imposed similar assembly constraints. The specificity of N230Y was tested against five different residues at position 214 of mature OmpF. Clear specificity was displayed, with maximum suppression observed for the original substitution at position 214 (E214) against which the N230Y suppressor was isolated, and no negative effect on OmpF assembly was noted when the wild-type W214 residue was present. The mechanism of suppression may involve compensation for a specific conformational defect. The second approach involved the application of informational suppressors (Su-tRNA) in combination with ompF amber mutations to generate variant OmpF proteins. In this approach we targeted the Y40, Q66, W214, and Y231 residues of mature OmpF and replaced them with S, Q, L, and Y through the action of Su-tRNAs. Thus, a total of 16 variant OmpF proteins were generated, of which three were identical to the parental protein, and two variants carrying W214Q and Y231Q substitutions were similar to assembly-defective proteins isolated previously (R. Misra, J. Bacteriol. 175:5049-5056, 1993). The results obtained from these analyses provided useful information regarding the compatibility of various alterations in OmpF assembly.

Type 2 diabetes mellitus in Canada's first nations: status of an epidemic in progress.

This review provides a status report on the epidemic of type 2 diabetes mellitus that is affecting many of Canada's First Nations. We focus on the published literature, especially reports published in the past 2 decades, and incorporate data from the Aboriginal Peoples Survey and the First Nations and Inuit Regional Health Survey. We look at the extent and magnitude of the problem, the causes and risk factors, primary prevention and screening, clinical care and education, and cultural concepts and traditional knowledge. The epidemic of type 2 diabetes is still on the upswing, with a trend toward earlier age at onset. Genetic-environmental interactions are the likely cause. Scattered intervention projects have been implemented and evaluated, and some show promise. The current health and social repercussions of the disease are considerable, and the long-term outlook remains guarded. A national Aboriginal diabetes strategy is urgently needed.

Radiographic scoring method for the assessment of the severity of nutritional rickets.

Radiographic changes of rickets are well characterized, but no method of grading the severity of these changes has been in general use. Consequently, it is difficult to compare objectively or follow radiographic improvement. We prospectively evaluated the utility and reproducibility of a scoring method for measuring the severity of rickets. A 10-point score for radiographs of wrists and knees was devised to assess the degree of metaphyseal fraying and cupping and the proportion of the growth plate affected. The score progresses in half point increments from zero (normal) to 10 points (severe). Four trained physicians independently scored radiographs on two separate occasions from 67 children with active rickets. A broad representation of mean radiographic scores was moderately correlated with alkaline phosphatase (r = 0.58). Interobserver correlation of radiographic scores was 0.84 or greater for all observer pairs and intraobserver correlation was 0.89 or greater for each observer. Researchers and clinicians should find the score useful to assess objectively the severity of rickets.

Distinctive emergency department usage for injury for workers' compensation cases in Utah in 1996.

To compare emergency department services paid by worker's compensation (WC) with services paid by other payers, a state database of 72,747 emergency department visits for injured adults (ages 21 to 54) in 1996 in Utah was analyzed. WC visits accounted for 21.6% (15,704) of all adult injury visits. The mean emergency department charge for WC visits was $282, and the admission rate was 17 per 1000 visits. The mean charge for other payers was $334, and the admission rate was 43 per 1000 visits. Differences were also found between these groups for Injury Severity Scores and diagnoses. In summary, WC emergency department usage was associated with less severe injuries than was emergency department usage for other payers in Utah in 1996.

A comparison of calcium, vitamin D, or both for nutritional rickets in Nigerian children.

BACKGROUND: Nutritional rickets remains prevalent in many tropical countries despite the fact that such countries have ample sunlight. Some postulate that a deficiency of dietary calcium, rather than vitamin D, is often responsible for rickets after infancy. METHODS: We enrolled 123 Nigerian children (median age, 46 months) with rickets in a randomized, double-blind, controlled trial of 24 weeks of treatment with vitamin D (600,000 U intramuscularly at enrollment and at 12 weeks), calcium (1000 mg daily), or a combination of vitamin D and calcium. We compared the calcium intake of the children at enrollment with that of control children without rickets who were matched for sex, age, and weight. We measured serum calcium and alkaline phosphatase and used a 10-point radiographic score to assess the response to treatment at 24 weeks. RESULTS: The daily dietary calcium intake was low in the children with rickets and the control children (median, 203 mg and 196 mg, respectively; P=0.64). Treatment produced a smaller increase in the mean (+/-SD) serum calcium concentration in the vitamin D group (from 7.8+/-0.8 mg per deciliter [2.0+/-0.2 mmol per liter] at base line to 8.3+/-0.7 mg per deciliter [2.1+/-0.2 mmol per liter] at 24 weeks) than in the calcium group (from 7.5+/-0.8 [1.9+/-0.2 mmol per liter] to 9.0+/-0.6 mg per deciliter [2.2+/-0.2 mmol per liter], P<0.001) or the combination-therapy group (from 7.7+/-1.0 [1.9+/-0.25 mmol per liter] to 9.1+/-0.6 mg per deciliter [2.3+/-0.2 mmol per liter], P<0.001). A greater proportion of children in the calcium and combination-therapy groups than in the vitamin D group reached the combined end point of a serum alkaline phosphatase concentration of 350 U per liter or less and radiographic evidence of nearly complete healing of rickets (61 percent, 58 percent, and 19 percent, respectively; P<0.001). CONCLUSIONS: Nigerian children with rickets have a low intake of calcium and have a better response to treatment with calcium alone or in combination with vitamin D than to treatment with vitamin D alone.

PIP: A randomized, double-blind, controlled trial was conducted to compare the efficacy of calcium, vitamin D, and a combination of both in the treatment of nutritional rickets among Nigerian children. Subjects included 123 Nigerian children with the deformity characteristics of rickets. For each child who was enrolled, a parent or guardian was asked to recruit a control child with the same sex, age, weight, and who had no clinical signs of rickets. Children with rickets were under treatment for 24 weeks with vitamin D (600,000 U intramuscularly at enrollment and at 12 weeks), calcium (1000 mg daily), or a combination of both. Then the serum calcium and alkaline phosphates were measured and a 10-point radiographic score was used to assess the response to the 24-week treatment. The results revealed a low dietary calcium intake in children with rickets and in control children. Children under vitamin D treatment appeared to have a small increase in the mean serum calcium concentration when compared to children under calcium treatment or a combination of both vitamin D and calcium. A greater proportion of children in the calcium and combination-therapy groups than in the vitamin D group reached the combined end point of a serum alkaline phosphates concentration of 350 U/liter or less and radiographic evidence of nearly complete healing of rickets. Overall, compliance ranged from 92% to 96% across the three groups. Since Nigerian children with rickets had low calcium intake, treatment should focus on dietary supplementation with calcium or a combination of calcium and vitamin D.

Central and peripheral adaptations after 12 weeks of exercise training in post-coronary artery bypass surgery patients.

PURPOSE: Training adaptations in patients with coronary artery disease (CAD) have been reported previously, but little is known about central and peripheral adaptations in those recovering from coronary artery bypass graft surgery (CABG). The purpose of this study was to examine the effects of 12 weeks of endurance exercise training on exercise performance and left ventricular and peripheral vascular reserve in a group of uncomplicated CABG patients. METHODS: Thirty-one patients were recruited and began training 8 to 10 weeks after uncomplicated CABG. Patients underwent progressive exercise training consisting of walking and jogging, at 75% to 80% maximal oxygen intake (VO2max). Measures of left ventricular function included ejection fraction (EF), ventricular volumes, and the pressure volume ratio, an index of contractility. Peak ischemic exercise calf blood flow and vascular conductance was determined using strain-gauge plethysmography. Maximal oxygen intake and submaximal blood lactate concentration also was determined. RESULTS: A significant improvement in VO2max (1497 +/- 60 mL/min versus 1691 +/- 71 mL/min) was observed after training. This change was accompanied by an increase in the EF during submaximal exercise (60 +/- 3% versus 63 +/- 2% at 40% VO2max; 61 +/- 3% versus 64 +/- 3% at 70% VO2max) (P < 0.05), and the change in EF from rest to exercise (delta EF). No changes were observed for ventricular volumes during exercise, although there was a trend for a higher stroke volume at 70% VO2max. A significant increase (18%) was observed for peak ischemic exercise calf blood flow and vascular conductance. In addition, submaximal blood lactate concentration was lower after training. CONCLUSIONS: These data indicate that exercise training for 12 weeks in patients recovering from CABG can elicit significant improvements in functional capacity that, for the most part, are secondary to peripheral adaptations, with limited support for improvement in left ventricular function.

Radical transurethral resection and chemotherapy in the treatment of muscle-invasive bladder cancer: a long-term follow-up.

OBJECTIVE: To evaluate the treatment of patients with muscle-invasive bladder cancer (T2-T4a) by radical transurethral resection (TUR) and cisplatin-methotrexate systemic chemotherapy. PATIENTS AND METHODS: Fifty patients with transitional cell carcinoma (TCC) of the bladder (nine T2, 36 T3 and five T4a) were treated by 'complete' TUR of the bladder tumour followed by 2-6 cycles of cisplatin (70 mg/m2) and methotrexate (40 mg/m2) chemotherapy. The median (range) tumour size was 3 (1-7 cm). In six patients, attempted TUR at the dome of the bladder led to intraperitoneal perforation; the tumour was excised by partial cystectomy in these patients. The latest follow-up results from 57 patients treated by radical TUR and methotrexate alone, reported previously, are included. RESULTS: At the first evaluation cystoscopy immediately after completing chemotherapy, 38 patients were tumour-free, eight had persistent muscle-invasive TCC and four had Ta, T1+CIS disease. With an overall median follow-up of 47 months, 10 additional patients relapsed with muscle-invasive carcinoma in the bladder after a median interval of 15.6 months; three patients developed Ta, T1 tumours, three Ta, T1 + CIS, and six CIS only. Six of the 10 recurrent invasive tumours were at the same site, but four were at a different site in the bladder. Although during follow-up 12 patients developed superficial recurrence that required endoscopic treatment, the bladder was preserved (free of muscle-invasive cancer) in 37 of 50 patients. In 30 of these 37, this was achieved with no need for salvage radiotherapy or cystectomy. Six patients died from metastatic TCC with no tumour in the bladder. CONCLUSION: In this selected group of patients, muscle-invasive bladder cancer was controlled by TUR and systemic chemotherapy, preserving normal bladder function in 60% of patients without apparently comprising overall survival.