Audit of screening programme for congenital hypothyroidism in Scotland 1979-93

Accepted 30 January 1997
OBJECTIVE—To evaluate the efficiency of the screening programme for congenital hypothyroidism in Scotland and to determine the outcome in the cohort of children with positive testing for thyroid stimulating hormone (TSH).
DESIGN—Establishment of comprehensive database for all Scottish infants with high TSH, detected on Guthrie screening.
SUBJECTS—344 infants born between August 1979 and December 1993 with TSH greater than 40 mU/l on initial Guthrie, or 15-40 mU/l on repeat Guthrie.
MAIN OUTCOME MEASURES—Ages at time of: (a) Guthrie collection, (b) notification of positive result by laboratory, and (c) start of treatment; audit of late diagnosis/missed cases; categorisation of positive cases into definite and probable congenital hypothyroidism, transient TSH elevation, and uncertain status; educational status of children with definite and probable congenital hypothyroidism.
RESULTS—344 positive cases were categorised as having definite (224) and probable (11) congenital hypothyroidism, transient TSH elevation (88), and status uncertain (21). The overall incidence of definite/probable congenital hypothyroidism was 1 in 4400 live births. For the definite/probable groups median age of Guthrie collection was consistently between 6 and 7 days from 1983 onwards but for the whole cohort was later than 10 days in 10.5%. Median age of notification fell from 14days in 1980 to 11 days in 1993. Median age of starting treatment ranged between 11 and 15 days from 1983 onwards. Treatment was delayed in four cases, three due to failed or late Guthrie card submission. Of 149 children with definite/probable congenital hypothyroidism who were of school age, educational status was ascertained in 139 (93%). Only two children (1.4%) were attending special school, one of whom was known to have mild hypothyroidism. Sixteen children (11.5%) were receiving extra help in mainstream education compared with 18% of control children in the Scottish very low birth weight study.
CONCLUSION—The current screening programme is working well, but efficiency could be increased by earlier and more reliable Guthrie collection. A substantial proportion of children picked up on the screening programme have a transient rise in TSH rather than true congenital hypothyroidism. The incidence of special education and learning support in Scottish children with congenital hypothyroidism appears to be no different to that of the general population.

     

Treating nondementia illnesses in patients with dementia

Physicians increasingly are called on to provide primary care for the growing population of people with Alzheimer-type dementia. However, little attention has been paid to the care of nondementia illnesses in this group of patients. To illustrate how presence of dementia can alter the risk-benefit ratio of treatment of a common medical problem, we present a case study in which a patient with dementia developed disastrous adverse effects to a drug commonly used to treat osteoporosis. This case and 2 composite vignettes illuminate how presence of dementia should influence the decision-making process for treatment of nondementia illnesses. We address issues such as decreased decision-making capacity, problems with reporting adverse effects, decreased cognition leading to problems with treatment adherence, and the role of screening and basic questions about acceptable burdens of treatments in patients with limited prognosis. We suggest ways to improve communication with patients with dementia in an effort to minimize complications and improve care, as well as policy changes to include patients with dementia in clinical trials. JAMA. 2000;283:3230-3235     

Treatment of HAART-induced lactic acidosis with B vitamin supplements.

Lactic acidosis, a rare but life-threatening condition is fairly common in HIV-infected individuals. The cause of lactic acidosis appears to stem from the use of HAART, causing mitochondrial dysfunction and the depletion of flavoprotein cofactors necessary for electron transport. Deficiencies of riboflavin or thiamin can contribute to the development of hyperlactic acidemia. Further, the high incidence of liver disease (hepatitis B or C and alcoholic liver disease) in this population predisposes HIV patients to metabolic abnormalities. Supplementation with thiamin or riboflavin, depending on the individual patient's condition, can reduce elevated lactic acid levels.     

What constitutes a true hyperdense middle cerebral artery sign?

OBJECTIVES: The 'hyperdense MCA sign' refers to an appearance of increased attenuation of the proximal middle cerebral artery (MCA) that is often associated with thrombosis of the M1 MCA segment and may be the only diagnostic feature on computed tomography early after ischaemic stroke. False positives are recognized, and correct recognition of this sign has, therefore, assumed greater importance with the advent of thrombolytic therapy for stroke. We sought to define objective criteria for hyperdensity of the MCA. METHODS: Brain computed tomographs obtained by a standard protocol in a neuroradiology department were analyzed by a single observer. All consecutive scans reported as exhibiting a hyperdense MCA were compared to controls reported as having normal scans. Ovoid regions of interest were placed over the vessels and cerebral cortices, and the attenuation in Hounsfield units (HU) measured. Absolute attenuation and ratios of one side to the other were compared. RESULTS: MCA attenuation was unrelated to age in cases (n = 18) and controls (n = 80). The mean MCA attenuation was greater in the affected MCA of cases as compared with controls [54.0 HU (99% confidence interval CI 46.7-61.2) vs. 41.3 HU (99% CI 39.7-43.0); p < 0.00001]. Cases were subdivided into true and false positives by the ratio of denser:less dense MCA (within or without the 95% prediction interval for controls). In all true positives, the MCA ratio was > 1.2. 9 of 10 true positives had acute ischaemic stroke; 1 patient had herpes simplex encephalitis, but had MCA attenuation within the 95% CI for controls. False positives had mature cerebral infarction or non-ischaemic pathologies. The ratio of MCA attenuation to adjacent cerebral cortex was significantly higher in both true and false positives than in controls. CONCLUSIONS: Hyperdense MCAs associated with acute ischaemic stroke can be distinguished from normal vessels and false positives by measurement of absolute attenuation of affected and normal vessels: an absolute density of >43 HU and a MCA ratio of >1.2 defined hyperdensity and excluded all other pathologies. Confirmation in other centres is required.     

选择性头部降温对胎羊缺血性脑损伤纹状体神经元凋亡和星形胶质细胞增殖的影响

目的研究选择性头部降温对缺血性脑损伤胎羊纹状体神经元凋亡和星形胶质细胞增殖的影响。方法胎羊于妊娠117~124d时通过双侧颈动脉阻塞30min造成双侧脑缺血损伤,损伤后将胎羊随机分为:损伤组(n=10)、2h低温组(损伤后2h开始亚低温治疗,n=7)和6h低温组(损伤后6h开始亚低温治疗,n=8),另设正常对照组(n=5)。通过冷循环水进行选择性头部降温,取脑组织用免疫组化法检测胎羊纹状体caspase-3(半胱天冬氨酸酶-3),GFAP(胶质纤维酸性蛋白)和PCNA(增殖细胞核抗原)的表达。结果①纹状体神经元凋亡:正常对照组中,caspase-3表达极少(11.00±13.77),损伤组caspase-3免疫阳性细胞为177.70±48.69,明显增加(P=0.000),损伤后2h治疗组(54.14±39.44,P=0.000)和损伤后6h治疗组(122.43±52.36,P=0.017)均能减少caspase-3免疫阳性细胞。②纹状体星形胶质细胞增殖:与正常对照组(163.40±21.98)相比,缺血性脑损伤组的GFAP免疫阳性细胞明显增多(433.25±66.69,P=0.000),损伤后2h开始亚低温治疗(219.50±35.31,P=0.000)和损伤后6h开始亚低温治疗(272.50±86.20,P=0.000)均能减少GFAP免疫阳性细胞。③纹状体PCNA阳性细胞的表达:在正常对照组中,PCNA免疫阳性细胞较少,为153.40±12.46,缺血性脑损伤组的PCNA免疫阳性细胞明显增多(353.70±45.60,P=0.000),损伤后2h开始亚低温治疗(187.14±26.26,P=0.000)和损伤后6h开始亚低温治疗(230.25±67.46,P=0.000)均能减少PCNA免疫阳性细胞。结论亚低温可以抑制纹状体神经元的凋亡和星形胶质细胞的增殖,该作用可能为选择性头部降温的脑保护作用机制之一。