Tuberous sclerosis complex and Wolff-Parkinson-White syndrome

This report highlights the association between tuberous sclerosis and Wolff-Parkinson-White syndrome. Ten patients with concurrent diagnoses of Wolff-Parkinson-White syndrome and tuberous sclerosis were identified. Wolff-Parkinson-White syndrome presented early in life, nine cases being diagnosed in the first year. Eight of the 10 cases were male. In eight cases, the syndrome was associated with supraventricular tachycardias, and in nine with cardiac rhabdomyomata. One child died from cardiac failure secondary to obstruction of the left ventricular outflow tract by a rhabdomyoma. Five of nine survivors showed resolution of Wolff-Parkinson-White syndrome on follow up. The accessory pathway was localised in nine patients from surface electrocardiograms: six children had left sided pathways and three had right sided pathways.     

Creatinine related reference ranges for urinary homovanillic acid and vanillylmandelic acid at 6 months of age

The relationship between homovanillic acid (HVA), vanillylmandelic acid (VMA), and creatinine in the urine of 6 month old babies has been studied and reference ranges in the form of centiles constructed for HVA and VMA against creatinine. Over 10,000 urine samples were collected from babies in four health districts in the north of England. HVA and VMA concentration, either independently or when divided by creatinine concentration, were dependent upon the absolute concentration of creatinine in the sample. After adjustment for creatinine significant differences in the mean concentration of HVA were found between sexes. No such differences were found for VMA. HVA and VMA were also found to be age dependent. Centiles were constructed using a procedure which makes no distributional assumptions about the data. The net effect of utilising these centiles was to increase the predictive value of a positive screening test from 20% to 40% without any increase in the false negative rate.     

Renal transplantation and osteoporosis

A cross sectional study assessed the bone mineral density (BMD) of 20 young adult patients who received a renal transplantation in childhood. The BMD of the lumbar spine, mainly trabecular bone, and of the total body, mainly cortical bone, were measured and expressed as an SD score. Fourteen patients (70%) had a BMD SD score of the lumbar spine below -1, of whom six patients were below -2. Fifteen patients (75%) had a BMD SD score of the total body below -1, of whom seven patients were below -2, Both trabecular and cortical bone appeared to be involved in the osteopenic process. The cumulative dose of prednisone was inversely correlated to both lumbar spine and total body BMD SD score. In a multiple regression analysis the cumulative dose of prednisone appeared to be the only factor with a significant effect on BMD SD score. Most young adult patients who had received a renal transplantation in childhood had moderate to severe osteopenia. Corticosteroid treatment played a major part in the development of osteopenia in these patients.     

Involvement of deprivation and environmental lead in neural tube defects: a matched case-control study

OBJECTIVE: To analyse the prevalence of neural tube defects in small geographical areas and seek to explain any spatial variations with reference to environmental lead and deprivation. SETTING: The Fylde of Lancashire in the north west of England. DESIGN: Cases were ascertained as part of a prospective survey of major congenital malformations in babies born in the Fylde to residents there between 1957 and 1981. A matched case-control analysis used infants with cardiovascular system, alimentary tract, and urinary system malformations as controls. Conditional logistic regression was used to assess the effects of more than 10 micrograms/l lead in drinking water and the Townsend deprivation score. RESULTS: The prevalence of neural tube defects in 1957-73 was higher in Blackpool, Fleetwood, and North Fylde, whereas the three control groups showed no significant spatial variation. In 1957-81 mothers living in electoral wards with either a higher proportion of houses with more than 10 micrograms/l lead in the water or a higher deprivation score had a greater risk of having a baby with a neural tube defect. For spina bifida and cranium bifidum alone, this was also true. For anencephaly, deprivation was less important although the effect of lead was still seen. In some neural tube defects, lead may act independently of other possible factors associated with deprivation. It seemed unlikely that lead levels changed significantly during the survey. The percentage of houses with 10 micrograms/l or more of lead in the water in 1984-5 was similar to that found in Great Britain 10 years previously. CONCLUSION: There is evidence to suggest that lead is one cause of neural tube defects, especially anencephaly. This could link the known preventive actions of hard water and folic acid. Calcium is a toxicological antagonist of lead. One cause of a deficiency of folic acid is impaired absorption secondary to zinc deficiency, which may be produced or exacerbated by lead.     

Blood-brain barrier and blood volume imaging of cerebral glioma using functional CT: A pictorial review

Five cases of cerebral glioma are presented here that illustrate the benefit of functional CT imaging of blood-brain barrier permeability and cerebral blood volume. Functional CT uses Patlak analysis of a single location dynamic sequence to extract physiological information that is useful clinically in the assessment of cerebral gliomas. Functional CT offers distinct advantages over other functional modalities including clearer delineation of tumour, tumour grading, measurement of tumour activity and monitoring response to therapy.     

Nuclear forms of parathyroid hormone-related peptide are translated from non-AUG start sites downstream from the initiator methionine

PTH-related peptide (PTHrP), normally a secreted protein, exerts at least part of its biological functions via intracrine actions at the level of the cell nucleus/nucleolus. To gain insight into the mechanism whereby this peptide accesses the cytosol for subsequent nuclear import, we characterized its nuclear forms. In transfected COS-1 cells, three nuclear PTHrP species were produced, which were larger than the mature form of the protein but smaller than prepro-PTHrP and comprised both the amino- and carboxyl-terminal regions of the peptide. This suggested that nuclear PTHrP proteins contain part of the prepropeptide and likely arise from alternate initiation of translation at downstream non-AUG codons within the signal sequence. Transient expression of two PTHrP forms, one in which the unique initiator ATG was mutated to a noninitiator ATC codon, and another encompassing an engineered N-linked glycosylation site, generated peptides of size comparable to nuclear PTHrP proteins. These were inefficiently targeted to the ER, bypassed ER transit, and exclusively localized to nucleoli. Using a polyclonal antiserum against the pro-region of PTHrP, nuclear PTHrP species were shown to harbor the propeptide sequence. Hence, our data argue that nuclear PTHrP forms result from translation initiated at alternate, internal codons. This may constitute the first example of translation initiation at downstream non-AUG codons in a mammalian protein.     

Low grade fibromyxoid sarcoma of the falciform ligament: a case report

Background  

Low grade fibromyxoid sarcomas (LGFMS) are very rarely seen. They commonly arise from deep soft tissues of the lower extremities. Very few cases of intra-abdominal location have been reported.     

Early prophylactic inhaled beclomethasone in infants less than 1250 g for the prevention of chronic lung disease

OBJECTIVE:

Inflammation plays an important role in the development of chronic lung disease (CLD), which has become a major cause of morbidity in surviving infants less than 1250 g at birth. The authors hypothesized that the progression of this inflammation and, therefore, the establishment of CLD would be decreased with the use of early prophylactic inhaled corticosteroids. Short, and long term respiratory and neurodevelopmental outcomes were also examined.

DESIGN:

A double-blind, randomized placebo controlled trial.

SETTING:

Level-III neonatal intensive care unit.

POPULATION STUDIED:

Sixty infants less than 1250 g at birth, diagnosed with respiratory distress syndrome and requiring ventilatory support at 72 h of age were enrolled in the study.

INTERVENTION:

Infants enrolled received either placebo or beclomethasone diproprionate by a metered dose inhaler, which was used in-line with the ventilator circuit while the infant was ventilated and then via a spacer until 28 days of age.

RESULTS:

Thirty infants were given beclomethasone and 30 were given placebo. There were two deaths in each group. Among the surviving infants, the frequency of moderate-to-severe CLD was 17% in each study group. Mean time to extubation was not different for beclomethasone compared with placebo at 16.4 and 12.5 days (P=0.12), respectively. The requirement for intravenous corticosteroids was lower in the beclomethasone-treated group (RR 0.67, 95% CI 0.43 to 1.04), although this difference was not statistically significant. The incidence of growth failure, infection and intraventricular hemmorhage did not differ between the two groups. Long term outcomes were not different with respect to the incidence of respiratory re-admissions, cerebral palsy, developmental delay, blindness or deafness.

CONCLUSIONS:

Early treatment with inhaled beclomethasone diproprionate did not reduce the incidence of CLD or decrease the duration of mechanical ventilation. The decrease in intravenous corticosteroid use was not statistically significant. Long term outcome was not affected.     

Real Time-PCR HBV-DNA Analysis: Significance and First Experience in Armed Forces

Background

HBV DNA quantitation is used extensively world wide for the diagnosis and monitoring of treatment of Hepatitis B virus (HBV) infection. However, it has still to be popular in India. The aim of this study was to quantitate HBV – DNA by Real time – PCR method in Hepatitis B and in immuno-compromised patients, to compare the results with HBeAg detection and to monitor the response to therapy of chronic Hepatitis B patients to antivirals.

Methods

Ninety one serum samples of Hepatitis group of patients (all HBsAg positive), 41 samples from immuno-compromised patients (all HBsAg negative) and 49 patients of Chronic Hepatitis B group (all HBsAg positive) were the subjects of this first ever study in Armed Forces. Twenty serum samples from healthy volunteers and non-hepatitis B patients served as negative controls. The amplification detection was carried out in a Rotor-Gene 2000-sequence detector

Results

Amongst Hepatitis B group, 33% (30/91) of the samples were positive for HBV-DNA and 26% (24/91) of samples were positive for HBeAg. In the immuno-compromised group of patients 14.6% (6/11) of samples were positive for HIV-DNA and 9.7% (4/41) were positive for HBeAg. Of the Chronic Hepatitis B patients on treatment, all (100%) were positive by HBV-DNA, whereas 29/49 (59.2%) were positive by HBeAg before treatment. After treatment with antivirals, 06/49 (12.2%) were positive by both tests and 11/49 (22.5%) were positive only by HBV-DNA. 32/49 (65.3%) patients became negative serologically after therapy.

Conclusion

HBeAg status did not necessarily reflect HBV-DNA level in the serum, as 10/91 (11%) in the Hepatitis B group, 2/41 (4.9%) in the immuno compromised group and 20/49 (40.8%) patients in the Chronic Hepatitis B group were positive for HBV-DNA but negative for HBeAg. HBV-DNA was not found to be positive amongst any of the negative controls. Real time – PCR is a sensitive and reproducible assay for HBV-DNA quantitation and may be started in Armed Forces referral centers in the near future.Key Words: Real time – PCR, Chronic Hepatitis B, HBV – DNA, Antivirals     

SUBACUTE HEPATIC FAILURE-A CLINICAL PROFILE

A combined experience of 37 cases of subacute hepatic failure encountered in five major gastroenterology centres over a period of ten years is discussed. Majority (65%) were males with average age of 38 years. Maximum (54%) were in 5th decade. Jaundice (100%), abdominal distention (38.7%), swelling feet (64%), fever (54%), abdominal pain (54%), exhaustion (78.3%) were the major presenting features. Jaundice and ascites were present in all cases. Pedal oedema (78.3%), hepatomegaly (54%), splenomegaly (32.4%) and encephalopathy (27%) were the other important clinical features. Hypoalbuminemia and prolonged prothrombin time were significant laboratory findings in addition to hyperbilirubinemia and elevated ALT and AST. Hbs Ag was detected in 46%. Major complications encountered were renal failure (48.7%), spontaneous bacterial peritonitis (43.2%), other infections (43.2%), encephalopathy (43.2%) and upper gastrointestinal bleed (22%). 54% died during stay in hospital. To conclude subacute hepatic failure is potentially fatal condition.KEY WORDS: Subacute hepatic failure, HBsAg, Jaundice