Nutritional and genetic contributions to serum cholesterol concentration in a children's follow-up study

In the Finnish multicentre study of cardiovascular risk in young Finns in 1980, 1983 and 1986, 2429, 2052 and 1841 9 to 18-year-old children and adolescents participated. In 1980, subjects of eastern origin living in the west had, despite their western diet, higher serum cholesterol concentrations than subjects both residing in and originating from the west. In males, eastern origin increased the eastlwest difference in serum cholesterol concentrations. Between 1980 and 1986 the mean serum total cholesterol of the study cohorts decreased by 5.5% and simultaneously the east/west differences in serum cholesterol concentrations disappeared in boys. The study suggests that genetic background is a separate factor determining serum total cholesterol level, but with declining serum cholesterol concentrations the effect of the genetic factor does not become manifest.     

Control of Gonadotropin Secretion by Steroid Hormones in Male Castrates: Site of Oestradiol Action

Four normal healthy castrated male transsexuals who were not on hormone therapy for at least 4 months volunteered for this study. Each subject received 3 infusions at weekly intervals--the first consisting of LHRH alone, the second of LHRH and oestradiol and the third of oestradiol alone. Venous blood samples were collected at 20-minute intervals 1 hour before the start and during the whole period of infusion. Plasma concentrations of FSH, LH and oestradiol were measured by radio-immunoassay. On an average, 100 micrograms of LHRH enhanced the area under the LH secretion curve by 177% and under the FSH curve by 68%. Oestradiol had a differential effect on the endogenous secretion of LH and FSH, suppressing them by 53% and 18%, respectively. Similarly, the LHRH-stimulated release of LH was significantly inhibited to a greater extent (42%) than that of FSH (23%, P less than 0.05; paired t test). Such an observation and in the light of our acceptance of the single releasing hormone theory, suggests that the differential actions of oestradiol on the secretions of FSH and LH are due to mechanisms residing in the pituitary.     

Double aneuploidy. Turner-Down syndrome.

Double aneuploidy involving Down and Turner syndromes is a rare occurrence. Of the six patients reported to have combined Down and Turner syndromes, four fundamentally different forms of chromosome mosaicism have been noted and all have been mosaic with respect to monosomy X. Reported here is the first example of a Turner-Down patient in whom there is no X mosaicism. The different forms of the double aneuploidy cannot be explained by any single combination of nondisjunctional errors. The clinical findings in these patients and the several mechanisms of nondisjunctional error that may account for the observed forms of aneuploidy are reviewed and discussed.     

Bile duct injuries during laparoscopic cholecystectomy: a collective experience of four teaching hospitals and results of repair

BACKGROUND: Laparoscopic cholecystectomy has been performed in Singapore since 1990 and, up until the end of 1997, a total of 4445 procedures had been performed in the four major teaching hospitals. Although bile duct injuries were thought to have increased following the introduction of laparoscopic cholecystectomy, there have been no reviews done on the incidence of these injuries in the Singapore context. METHODS: The present retrospective review aimed to audit the rate of bile duct injuries in the four major teaching hospitals in Singapore and to document the results of management of these injuries. RESULTS: Of the 4445 procedures performed, there were 19 (0.43%) cases of bile duct injuries. These involved the common hepatic duct (n = 8), common bile duct (n = 10), and the right hepatic duct (n = 1). The underlying gall bladder pathology included non-inflamed gall bladders (n = 10), acute cholecystitis (n = 4), Mirrizzi's syndrome (n = 3) and mucocele of the gall bladder (n = 2). Transection of the duct accounted for the majority of the injuries. Eleven bile duct injuries were identified at the time of operation. These were primarily repaired over a T tube (n = 4) or by a bilio-enteric bypass (n = 7). The remainder were diagnosed at a median of 7 days (range: 1-556 days) after surgery with a presentation of jaundice or pain. These were repaired by bilio-enteric anastomosis (n = 7) and closure over a T tube (n = 1). Three patients developed strictures subsequently, two following bilio-enteric repair after delayed diagnosis and one following immediate primary repair over a T tube. One patient developed intrahepatic stones and required a left lateral segmentectomy. CONCLUSIONS: The experience of a 0.43% bile duct injury rate is comparable to the best results from most large series in the West. Inflammation at Calot's triangle is an important associated factor for injury. Early recognition and prompt repair affords good results, and hepaticojejunostomy is recommended as the repair of choice.     

Management of Hirschsprung's disease with reference to one-stage pull-through without colostomy

BACKGROUND/PURPOSE: The authors evaluated the safety and benefits of 1-stage pull-through in comparison with staged repair of Hirschsprung's disease under circumstances prevailing in a developing country. METHODS: Forty-nine patients were treated for Hirschsprung's disease during a 7-year period between January 1991 and March 1998 at our institution, which is a tertiary referral center. Nine patients were excluded from the study, and the medical records of the remaining 40 patients were reviewed. RESULTS: Eighteen patients including 7 neonates underwent 1-stage pull-through, and 22 patients underwent staged correction. There was no mortality for patients undergoing one-stage treatment, but there was 1 death caused by anastamotic leak after a 2-stage repair. There was no substantial difference in the incidence of complications (38.8% v 45.45%) and the need for additional surgical procedures (33.5% v 45.45%) between the 2 groups. Seventy-one percent after 1-stage treatment and 80% after staged treatment had a satisfactory functional result, and the incidence of incontinence was 14% and 10%, respectively. Overall, the incidence of postoperative enterocolitis was low (7.5%). CONCLUSIONS: One-stage correction of Hirschsprung's disease is a safe procedure in all age groups. It offers economical and social advantages to families in developing countries. Benefits of 1-stage treatment include avoidance of multiple operations, elimination of complications associated with a colostomy, shorter duration of hospital stay, and completion of treatment at an earlier age. It is advisable to continue postoperative anal dilatation for a minimum period of 6 months to 1 year to reduce the incidence of enterocolitis.     

Endolymphatic sac tumour: a rare cause of recurrent vertigo

Endolymphatic sac tumour occurring in a 32-year-old man presenting with Meniere's like symptoms of recurrent vertigo, hearing loss and tinnitus is described. Magnetic resonance imaging and computed tomography showed a vascular bone tumour centred over the retrolabyrinthine aspect of the temporal bone where the endolymphatic sac was located. Surgical excision via a translabyrinthine approach was performed. Endolymphatic sac tumours are rare papillary adenocarcinomas that arise from the endolympatic sac. It can be mistaken both on radiology and histology for other tumours such as paragangliomas, renal or papillary thyroid carcinoma metastases. Surgical excision is the treatment of choice but sacrifice of the auditory and facial nerve may be needed in advanced cases to achieve tumour clearance.     

Usefulness of the Audit of Diabetes-Dependent Quality-of-Life (ADDQoL) questionnaire in patients with diabetes in a multi-ethnic Asian country

INTRODUCTION: Asia will be at the forefront of the current epidemic of diabetes mellitus. Quality of life (QOL) is an important outcome measure in the assessment of diabetes care. However, few QOL instruments are culturally suitable for use in Asian countries. The Audit of Diabetes-Dependent Quality-of-Life (ADDQoL) questionnaire is a third-generation individualised QOL instrument. Individualised instruments such as the ADDQoL have the potential to be useful and less costly alternatives to computerised adaptive testing (CAT), which may not be practical in developing countries. OBJECTIVE: To evaluate and validate the ADDQoL questionnaire in English-speaking patients with diabetes in Singapore, a multi-ethnic Asian country. METHODS: The ADDQoL and EQ-5D were administered to English-speaking respondents with type 1 or 2 diabetes (aged > or =18 years) recruited from a tertiary acute-care referral hospital by convenience sampling. The usefulness of the key design features of the ADDQoL were assessed by measuring the number of zero-importance responses, the change in item ranking with and without weighting for importance, and the frequency of utilisation of the 'not applicable' (NA) options. The acceptability, factor structure and internal consistency (Cronbach's alpha) of the ADDQoL were also assessed. Data were subjected to unforced factor analysis with oblimin rotation and then the condition was set to force a one-factor solution. The validity of the ADDQoL was tested with the following hypotheses: those with moderate or severe problems on the EQ-5D would have worse ADDQoL average weighted impact (AWI) scores than those with a perfect health rating on the EQ-5D; those with better Present QOL scores on the ADDQoL would have better EQ-5D utility and visual analogue scale (VAS) scores; on the ADDQoL, AWI scores would correlate better with diabetes-dependent QOL than with Present QOL scores; and female respondents, those who required insulin or had longer duration of known diabetes would have worse ADDQoL AWI scores (known-group validity). RESULTS: We analysed data from 152 respondents (49% Chinese, 34% Indian; 45% female; mean age 52 years, range 18-80; mean duration of known diabetes 10 years, range 0-62). There were few missing data. Weighted scoring and NA options were shown to be necessary, thus supporting the usefulness of individualised health-related QOL measures. Factor structure of the ADDQoL was supported and internal consistency was high (alpha = 0.94). All hypotheses were fulfilled except for one that was partially fulfilled; respondents with longer duration of known diabetes did not report worse ADDQoL AWI scores. CONCLUSIONS: The ADDQoL is culturally appropriate, valid, reliable and well accepted among Singaporean patients with diabetes. Individualised measures such as the ADDQoL allow one to obtain precise score estimates and may offer developing countries a useful alternative to CAT.     

Lack of somatic mutations in EGFR tyrosine kinase domain in hepatocellular and nasopharyngeal carcinoma

Activating EGFR somatic mutations have been shown to predict treatment response to small molecules targeting the EGFR intracellular tyrosine kinase domain. Recent work on cell-lines and animal models had demonstrated an inhibitory effect of EGFR tyrosine kinase inhibitors in hepatocellular and nasopharyngeal carcinoma, and clinical trials in these tumour types are ongoing. There are few data on the presence or prevalence of EGFR mutations in hepatocellular and nasopharyngeal carcinomas. We studied exons 18-21 of the EGFR gene from 100 hepatocellular and 102 nasopharyngeal carcinomas, and found no exonic mutations of potential significance. Alternative mechanisms may be important for the observed activity of small molecule EGFR tyrosine kinase inhibitors in hepatocellular and nasopharyngeal carcinomas.