Biomedical subjects
T Fenton
Publications and source records attributed to T Fenton.
Renal tubular acidosis and osteopetrosis with carbonic anhydrase II deficiency: pathogenesis of impaired acidification.
Renal tubular acidosis with osteopetrosis is an autosomal recessive disorder due to deficiency of carbonic anhydrase II (CAII). A 3.5-year-old Egyptian boy with osteopetrosis and cerebral calcification has a persistent normal anion gap type of metabolic acidosis (plasma pH 7.26) and a mild degree of hypokalemia. A baseline urine pH was 7.0; ammonium (NH4+) excretion was low at 11 mumol/min per 1.73 m2; fractional excretion of bicarbonate HCO3 (FEHCO3) was high at 9% when plasma HCO3 was 20 mmol/l; citrate excretion rate was high for the degree of acidosis at 0.35 mmol/mmol creatinine. Intravenous administration of sodium bicarbonate led to a urine pH of 7.6, a FEHCO3 of 14%, a urine-blood PCO2 difference of 7 mmHg, NH4+ excretion fell to close to nil, and citrate excretion remained at 0.38 mmol/mmol creatinine. Intravenous administration of arginine hydrochloride caused the urine pH to fall to 5.8, the FEHCO3 to fall to 0, the NH4+ excretion rate to rise to 43 mumol/min per 1.73 m2, and citrate excretion to fall to < 0.01 mmol/mmol creatinine. These results show that our patient had a low rate of NH4+ excretion, a low urine minus blood PCO2 difference in alkaline urine, and a low urinary citrate excretion, but only when he was severely acidotic. He failed to achieve a maximally low urine pH. These findings indicate that his renal acidification mechanisms were impaired in both the proximal and distal tubule, the result of his CAII deficiency.
Degree of agreement in plasma fibrinogen among two functional and one immunonephelometric assays.
The purpose of this study was to assess the interchangeability of the nephelometric (immunoassay), von Clauss, and optical (derived) fibrinogen assays. When the nephelometric assay was compared with either of the two functional assays (199 samples) and when the von Clauss and optical methods were compared (879 samples), Pearson and intraclass correlations were .96 to .97. However, there were statistically significant biases (P < .001); the mean ratios of nephelometric to functional assay values were 1.05 to 1.07, and the mean optical to von Clauss assay ratio was 1.05 (data analyzed as logs and expressed as antilogs). The 95% limits of agreement demonstrated that 5% of the ratios for the von Clauss and optical methods were outside the 0.83 to 1.32 range. Analyses restricted to cases with a fibrinogen value of less than 2.0 g/L resulted in somewhat greater biases and higher upper limits of agreement. Laboratorians need more than correlations to make informed judgments regarding the interchangeability of these methods.
Systemic lupus erythematosus presenting as congenital nephrotic syndrome.
A male Caucasian infant developed nephrotic syndrome at 10 weeks of age. He had high titres of antinuclear antibody (ANA) and anti-double-stranded DNA antibody, with hypocomplementaemia, antiplatelet antibodies and anticardiolipin antibodies. There were no detectable antibodies to extractable nuclear antigens (ENA). His mother was consistently seronegative for anti-ENA (anti-Ro) antibodies and ANA. He developed severe, progressive multisystem involvement, however renal function has remained stable. Immunosuppression has been the mainstay of therapy in this rare presentation of systemic lupus erythematosus.
Psychiatric comorbidity in childhood post traumatic stress disorder.
OBJECTIVE: The purpose of this study was to examine the psychiatric comorbidity between children presenting with Post Traumatic Stress Disorder (PTSD) and traumatized children not developing this disorder. DESIGN: One-hundred and seventeen severely maltreated children were examined for evidence of PTSD. Analyses probed for diagnostic relationship, between PTSD and other formal diagnoses on The Diagnostic Interview for Children and Adolescents, Revised Version (DICA-CR). PARTICIPANTS: All children presented before a juvenile/family court due to severe child maltreatment and psychological trauma. These children had been ordered removed from parental custody due to the trauma suffered by the child. For the purposes of analyses, this entire group of maltreated and traumatized children were dichotomized into a PTSD group and a non-PTSD group. Thirty-five percent (41 of 117) of the children met strict DICA criteria for PTSD. MEASUREMENTS: The children were examined by means of a structured clinical interview. The Diagnostic Interview for Children and Adolescents, revised version (DICA-Child-R), along with a more general psychiatric interview. The DICA-Child-R responses provided the only determination of whether the children met formal PTSD criteria. Data gathering on the sample also included a comprehensive review of risk factors for the development of PTSD, including demographics, and type(s) of trauma suffered. RESULTS: Findings revealed that the PTSD diagnosis was significantly correlated with: 1. Attention Deficit Hyperactivity Disorder (ADHD) 2. Other anxiety disorders 3. Brief Psychotic Disorder or Psychotic Disorder NOS 4. The presence of suicidal ideation 5. A trend toward mood disorders. There were no differences between the two samples on measures of age, race, and family income. CONCLUSIONS: Pediatric PTSD is a severe psychiatric disorder. In this study, PTSD was statistically related to other formal psychiatric diagnoses. The investigators attended to the issues relating to true comorbidity versus inaccurate diagnosis secondary to symptom overlap between different conditions. Applying strict criteria, the results suggest that the presence of PTSD in children confers a substantial likelihood of other formal diagnosis. Moreover, the symptom of suicidal ideation was overrepresented among PTSD subjects. Given these additional conditions, more extensive evaluation and specialized, multi-modal treatment should be considered in children presenting with PTSD.
Persistence of pediatric post traumatic stress disorder after 2 years.
One-hundred and fifty-six children were randomly evaluated at an inner-city juvenile/family court. These children were removed from their parent's custody subsequent to a finding of severe child maltreatment. From our original sample of 156 children, 62 met strict criteria for Post Traumatic Stress Disorder (PTSD). Fifty-two of these 62 were successfully recruited and participated in the 2 year re-examination. Each PTSD diagnosis was conferred by the Diagnostic Interview for Children and Adolescents (DICA). From our sample of 52 PTSD children re-examined after 2 years, 17 (32.7%) retained the full PTSD diagnosis, while 67.3% did not meet criteria.
Early developmental history and pediatric posttraumatic stress disorder.
OBJECTIVE: To determine which factors from the early developmental histories of maltreated children are associated with the risk of developing posttraumatic stress disorder (PTSD). DESIGN: Retrospective cohort analytic study. SETTING: A county juvenile/family court (not a criminal court). SAMPLE: The sample consisted of 117 severely maltreated children, aged 5 to 12 years, whose maltreatment was so severe that they were removed from parental custody. Forty-one (35%) of these children met criteria of the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, for PTSD. MAIN OUTCOME MEASURES: Individual developmental and temperament-independent variables were used to compare children with PTSD and the maltreated children who did not reach PTSD inclusion criteria. The child's PTSD status was the primary dependent variable. RESULTS: Variables representing the three factors from the early developmental history, along with markers for sex and race (black vs other), were entered into a logistic regression, with PTSD status as the outcome variable. Indicators of five different types of child maltreatment were also entered as predictors, to control for previously discovered effects associated with the type of trauma suffered by the children. This analysis disclosed that, while we controlled for the other predictors, one of the developmental factors remained statistically significant, one was marginally significant (P = .07), and one made no contribution toward predicting the probability of PTSD. Sex did not make a significant contribution to the logistic model, but being black continued to be associated with a lower probability of developing PTSD. CONCLUSIONS: We conclude that PTSD may be caused by factors discernible in the first year of life that leave a maltreated child vulnerable to this disorder. These include birth weight less than 2.25 kg, jaundice, vomiting, diarrhea, infections, sleep problems, frequent crying, poor weight gain, fussiness, jumpiness, and distress when moved. The seemingly protective effect of being black was an unexpected, although provocative, finding whose interpretation will require further investigation.
Maternal and child posttraumatic stress disorder in cases of child maltreatment.
The purpose of this study was to examine the rates of posttraumatic stress disorder (PTSD) among a sample of severely maltreated children and their mothers, and to investigate the age of onset of documented maltreatment in these children. The sample consisted of 109 pairs of women and their children who were before a juvenile/family court due to maltreatment of sufficient severity to warrant removal of the child from parental custody. Children were examined using the PTSD Section of the Diagnostic Interview for Children and Adolescents, Revised 6th Version (DICA-6-R). The PTSD Module of the Structured Clinical Interview for DSM-III-R (SCID) was administered to all mothers. Clinical psychiatric interviews were also administered to all children and mothers. From the sample of 109 cases, 15.6% of the mothers met SCID criteria for a current presentation of PTSD, while 36.7% had a past history of PTSD. Of the 109 evaluated children, 35.8% met current DICA criteria for PTSD. Posttraumatic stress disorder is significantly overrepresented in the children of mothers diagnosed with PTSD (p = .001). The average age of maltreatment onset was 46.4 months among the children diagnosed as PTSD, and was 61.3 months in the group of seriously maltreated children who did not develop PTSD (p = .038). The onset of maltreatment is significantly earlier among children whose mothers meet PTSD criteria than among other maltreated children (p = .025). Intergenerational transmission of violence and developmental effects of traumatic experiences upon the young child are discussed.
Management training for pathology residents. I. Results of a national survey.
The professional activities of anatomic and clinical pathologists involve, to a large extent, management issues. To evaluate the management training received by pathology residents, the authors surveyed pathology residency training programs in the United States. Responses were collected from 138 of 187 programs (73.8% response rate). Of the 138 programs, 61 reported that they had a formal training program in management, with an average of 26.8 +/- 4.9 (standard error) hours/year devoted to this discipline. Directors of 64.5% of the programs felt that management training should be expanded. Lectures were used in 61% of the programs, some in combination with case studies. Elements of training in fiscal management were present in 52.8% of the programs, and the presence of fiscal management training was associated significantly with a greater number of hours spent in management training (P < .001). Training in traditional laboratory management and quality control was included in 91.5% of the programs. The principles of total quality management were discussed in only 31.7% of the programs, but 80.6% of the programs encouraged residents' participation in departmental or institutional total quality management activities. These data indicate that there are major differences in the quality of and emphasis on management training for pathology residents in the United States.
Schoolchildren with HIV infection: a survey of the nation's largest school districts.
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Conference on advances in AIDS vaccine development--1993. Report of Perinatal Intervention Working Group.
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Child maltreatment and the development of posttraumatic stress disorder.
OBJECTIVE--The purpose of this study was to compare the relative effects of various forms of maltreatment on the development of posttraumatic stress disorder (PTSD) in children. DESIGN--Children were randomly selected from a population of court-involved maltreated children. The children were then assigned to a PTSD group and a non-PTSD group on the basis of their responses to a structured interview. SETTING--A juvenile/family court in a large urban area. PARTICIPANTS--This study examined 101 children who were before a juvenile/family court because of severe child maltreatment. All children had been removed from parental custody as a result of the maltreatment. INTERVENTIONS--None. MEASUREMENTS AND RESULTS--Structured clinical psychiatric interviews were administered to each child and each parent, and all court records were reviewed. The major analyses assessed the extent to which the presence and duration of the most common types of severe maltreatment were associated with a diagnosis of PTSD. Thirty-nine children met criteria for PTSD. Those who were sexually maltreated and those who witnessed family violence had a much greater likelihood of developing PTSD than did those whose histories of maltreatment did not include these types of events. The duration of emotional abuse (psychological terror) also proved to be a significant factor in discriminating children diagnosed as having PTSD from other severely maltreated children. CONCLUSIONS--These findings delineate factors implicated in the cause of PTSD. Moreover, they provide information that will enable the protective service community to screen more effectively for PTSD among maltreated children.
Discordance between effects of anti-ischemic therapy on ambulatory ischemia, exercise performance and anginal symptoms in patients with stable angina pectoris. The Angina and Silent Ischemia Study Group (ASIS).
OBJECTIVES: We sought to define the extent to which the therapeutic efficacy of three single-drug regimens on ambulatory ischemia paralleled efficacy on other clinical manifestations of ischemia, specifically exercise test performance and anginal symptoms. BACKGROUND: Some studies have shown that the presence and severity of ambulatory ischemia are predictive of anginal symptoms and exercise test performance, whereas other studies have not. Less is known about effects of antianginal treatment and whether response to therapy for one clinical manifestation reflects therapeutic responses for other clinical manifestations. METHODS: We studied 50 patients in the Angina and Silent Ischemia Study who had documented coronary disease, an exercise test positive for ischemia, the presence of ambulatory and asymptomatic ischemia on ambulatory electrocardiographic (ECG) Holter monitoring and stable anginal symptoms. Patients received maximally tolerated doses of sustained release propranolol (mean 293 mg/day), sustained release diltiazem (mean 350 mg/day), nifedipine (mean 79 mg/day) and placebo, each for 2-week periods in a double-blind, crossover fashion. Patients' responses to treatment were assessed by 48-h ambulatory ECG monitoring, exercise test (standard Bruce protocol) and diaries of angina. Levels of efficacy for each agent and for each clinical measure were compared using Spearman correlation analysis. RESULTS: With placebo there was no correlation among the frequency of ischemic episodes by ambulatory ECG monitoring, exercise time to 1.0-mm ST segment depression or frequency of anginal episodes. Furthermore, for a given patient the efficacy of each active medication in reducing ambulatory ischemia was not correlated with response in anginal symptoms or exercise test performance (r = -0.21 to 0.24, p = NS). Within each of these clinical measures, efficacy of one drug was more strongly correlated with efficacy of another drug (r = 0.64 to 0.81 for ambulatory ischemia, 0.48 to 0.56 for exercise test performance and 0.16 to 0.54 for anginal symptoms). CONCLUSIONS: Different measures of ischemia, specifically ambulatory ischemia assessed by ambulatory ECG monitoring, exercise performance on exercise test and anginal symptoms, are independent. Efficacy for each clinical end point must be assessed separately when considering response to drug treatment.
Subsets of ambulatory myocardial ischemia based on heart rate activity. Circadian distribution and response to anti-ischemic medication. The Angina and Silent Ischemia Study Group (ASIS)
BACKGROUND: Identification of whether episodes of ambulatory ischemia are caused by increases in myocardial oxygen demand or to episodic coronary vasoconstriction in patients with stable coronary disease may be important to guide selection of optimal anti-ischemic therapy and to gain insight into mechanisms responsible for adverse cardiac events. METHODS AND RESULTS: Mean minute heart rate activity during ambulatory ECG (AECG) monitoring was determined for 50 patients treated with propranolol, diltiazem, nifedipine, or placebo in a randomized, double-blind, crossover trial. Periods of heart rate increases of various magnitudes and durations and starting at various baseline heart rates on each therapy were identified throughout each 48-hour AECG recording, and the proportion of these periods associated with an ischemic episode was determined. The circadian variation of ischemic episodes categorized by the presence or absence of an increase in heart rate was analyzed. Eighty-one percent of ischemic episodes were preceded by an increase in heart rate > or = 5 beats per minute. The likelihood of developing ischemia associated with a heart rate increase was proportional to the magnitude and duration of the heart rate increase and the baseline heart rate before the increases in heart rate: likelihood ranged from 4% when the heart rate increased 5-9 beats per minute and lasted < 10 minutes to 60% when the heart rate increased > or = 20 beats per minute and lasted > or = 40 minutes. The likelihoods of developing ischemia based on changes in the heart rate variables were similar for each of the therapies. Propranolol therapy significantly reduced the magnitude and duration of heart rate increase and the baseline heart rate compared with therapy with placebo, diltiazem, or nifedipine (P < .001). Ischemic episodes associated with a heart rate increase displayed a daytime peak, whereas ischemia occurring without a heart rate increase occurred evenly throughout the day. Propranolol reduced the proportion of heart rate-related ischemic episodes and increased the proportion of non-heart rate-related episodes compared with placebo (P < .02), and nifedipine exerted the opposite effect (P = .005). Multivariate analysis indicated that the probability of developing ischemia was strongly associated with heart rate variables and was unaffected by time of day. CONCLUSIONS: Most episodes of ambulatory ischemia are associated with a preceding period of increased heart rate. The likelihood of developing ischemia is predicted by heart rate variables and unaffected by time of day. Anti-ischemic efficacy is generally a result of the medication's efficacy in reducing heart rate variables. A minority of ischemic episodes are not associated with preceding periods of increased heart rate, may be caused by episodic coronary vasoconstriction, and are more effectively reduced by nifedipine than propranolol.
Effects of diuretic therapy on the development of tolerance during continuous therapy with nitroglycerin.
OBJECTIVES: This study examined the effects of concurrent diuretic therapy on the hemodynamic responses to short-term and sustained therapy with transdermal nitroglycerin. BACKGROUND: Sodium retention and plasma volume expansion occur during therapy with nitroglycerin and may play a role in the loss of nitroglycerin effects during sustained therapy. METHODS: Twenty-two normal male volunteers were treated for 1 week with either hydrochlorothiazide and amiloride (50 + 5 mg) (n = 11) or placebo (n = 11) in a randomized, double-blind fashion. All 22 subjects then received continuous transdermal nitroglycerin (19 +/- 1 mg/24 h) for 5 to 7 days. RESULTS: On the first and last day of transdermal nitroglycerin therapy, standing heart rate, systolic blood pressure and hematocrit values were assessed at 8, 9 and 10 AM and 12 noon. Heart rate and blood pressure responses to sublingual nitroglycerin (0.6 mg) were also evaluated before and after sustained transdermal nitroglycerin therapy. A significant loss of the hemodynamic effects of transdermal and sublingual nitroglycerin occurred during sustained therapy in both the diuretic and placebo therapy groups. In both groups, transdermal nitroglycerin therapy was associated with a significant decrease in hematocrit that persisted for the entire treatment period. CONCLUSIONS: These results suggest that diuretic therapy does not prevent plasma volume expansion or the loss of hemodynamic effects during sustained transdermal nitroglycerin therapy. The persistent decrease in hematocrit suggests that plasma volume expansion plays a role in the attenuation of nitrate effects. It also provides evidence of continued vascular activity of nitroglycerin despite loss of systemic hemodynamic effects.
Psychiatric diagnoses of maltreated children: preliminary findings.
The study sample consists of 96 children (61 maltreated, 35 controls) between 5 and 10 years of age. The two groups of subjects were compared on diagnoses as determined by the administration of the Diagnostic Interview for Children and Adolescents, Revised 6th Version (DICA-6-R) as well as clinical DSM-III-R diagnoses. Children who had suffered maltreatment exhibited significantly greater incidences of attention deficit hyperactivity disorder, oppositional disorder and post-traumatic stress disorder diagnoses than did controls, on both child and parent DICA interviews. The children's interviews revealed that maltreated children present with a significant incidence of psychotic symptomatology as well as personality and adjustment disorders. Conversely, conduct and mood disorders emerged as significant factors in the parent interviews, with the maltreated group showing significantly greater incidence of these diagnoses.
Psychiatric diagnoses of abusive mothers. A preliminary report.
The Structured Clinical Interview for DSM-III-R diagnoses of 54 mothers who had maltreated their children were compared with those of 37 controls. The maltreatment group showed a significantly greater incidence of both current and past diagnoses. Maltreating mothers exhibited a significantly greater incidence of current mood disorder, alcohol abuse, and personality disorder than did controls. The results indicate that past abuse of cocaine, alcohol, other substances and past mood disorders were significantly more prevalent among the maltreatment sample than among controls. Mothers who had maltreated their children were significantly more likely to have histories of posttraumatic stress disorder than were controls.
Senior-Loken syndrome. Case reports of two siblings and association with sensorineural deafness.
Two siblings with Senior-Loken syndrome are described. The need for a full evaluation of renal function and hearing in children with a retinal dystrophy is emphasised.