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Key Points In clinical practice, the level of arterial oxygenation can be measured either directly by blood gas sampling to measure partial pressure (PaO2) and percentage saturation (SaO2) or indirectly by pulse oximetry (SpO2). This review addresses the strengths and weaknesses of each of these tests and gives advice on their clinical use. The haemoglobin–oxygen dissociation curve describing the relationship between oxygen partial pressure and saturation can be modelled mathematically and routinely obtained clinical data support the accuracy of a historical equation used to describe this relationship. Educational Aims To understand how oxygen is delivered to the tissues. To understand the relationships between oxygen saturation, partial pressure, content and tissue delivery. The clinical relevance of the haemoglobin–oxygen dissociation curve will be reviewed and we will show how a mathematical model of the curve, derived in the 1960s from limited laboratory data, accurately describes the relationship between oxygen saturation and partial pressure in a large number of routinely obtained clinical samples. To understand the role of pulse oximetry in clinical practice. To understand the differences between arterial, capillary and venous blood gas samples and the role of their measurement in clinical practice. The delivery of oxygen by arterial blood to the tissues of the body has a number of critical determinants including blood oxygen concentration (content), saturation (SO2) and partial pressure, haemoglobin concentration and cardiac output, including its distribution. The haemoglobin–oxygen dissociation curve, a graphical representation of the relationship between oxygen satur­ation and oxygen partial pressure helps us to understand some of the principles underpinning this process. Historically this curve was derived from very limited data based on blood samples from small numbers of healthy subjects which were manipulated in vitro and ultimately determined by equations such as those described by Severinghaus in 1979. In a study of 3524 clinical specimens, we found that this equation estimated the SO2 in blood from patients with normal pH and SO2 >70% with remarkable accuracy and, to our knowledge, this is the first large-scale validation of this equation using clinical samples. Oxygen saturation by pulse oximetry (SpO2) is nowadays the standard clinical method for assessing arterial oxygen saturation, providing a convenient, pain-free means of continuously assessing oxygenation, provided the interpreting clinician is aware of important limitations. The use of pulse oximetry reduces the need for arterial blood gas analysis (SaO2) as many patients who are not at risk of hypercapnic respiratory failure or metabolic acidosis and have acceptable SpO2 do not necessarily require blood gas analysis. While arterial sampling remains the gold-standard method of assessing ventilation and oxygenation, in those patients in whom blood gas analysis is indicated, arterialised capillary samples also have a valuable role in patient care. The clinical role of venous blood gases however remains less well defined., Understand the role of oximetry in clinical practice and how oxygen delivery, saturation and partial pressure relate http://ow.ly/R05hK

The steady-state basal plasma glucose and insulin concentrations are determined by their interaction in a feedback loop. A computer-solved model has been used to predict the homeostatic concentrations which arise from varying degrees beta-cell deficiency and insulin resistance. Comparison of a patient's fasting values with the model's predictions allows a quantitative assessment of the contributions of insulin resistance and deficient beta-cell function to the fasting hyperglycaemia (homeostasis model assessment, HOMA). The accuracy and precision of the estimate have been determined by comparison with independent measures of insulin resistance and beta-cell function using hyperglycaemic and euglycaemic clamps and an intravenous glucose tolerance test. The estimate of insulin resistance obtained by homeostasis model assessment correlated with estimates obtained by use of the euglycaemic clamp (Rs = 0.88, p less than 0.0001), the fasting insulin concentration (Rs = 0.81, p less than 0.0001), and the hyperglycaemic clamp, (Rs = 0.69, p less than 0.01). There was no correlation with any aspect of insulin-receptor binding. The estimate of deficient beta-cell function obtained by homeostasis model assessment correlated with that derived using the hyperglycaemic clamp (Rs = 0.61, p less than 0.01) and with the estimate from the intravenous glucose tolerance test (Rs = 0.64, p less than 0.05). The low precision of the estimates from the model (coefficients of variation: 31% for insulin resistance and 32% for beta-cell deficit) limits its use, but the correlation of the model's estimates with patient data accords with the hypothesis that basal glucose and insulin interactions are largely determined by a simple feed back loop.

Type 2 diabetes is a familial disease and studies of both Caucasian and Japanese families have raised the possibility that a major susceptibility gene is involved. The majority of patients have both beta cell dysfunction and impaired insulin sensitivity but studies of relatives of Type 2 diabetic patients suggest that beta cell dysfunction is an early feature of the disease. Impaired insulin sensitivity, from acromegaly, Cushing's disease or steroid therapy, induces diabetes only in a small proportion of the population, and they may be those who have an inherited cell defect. We postulate that a single beta cell defect gene, on its own, may be insufficient to cause overt diabetes and would lead to life-long glucose intolerance unless associated with other defects such as impaired insulin sensitivity. The nature of such a postulated beta cell defect is uncertain. Whilst it has been reported to be specific to glucose, and not to non-glucose stimuli, this feature may be secondary to hyperglycaemia. The occurrence of islet amyloid in 70-90% of Type 2 diabetic patients, and rarely in the normal population, raises the possibility that amyloid deposition causing disruption of the islet is a factor which might affect beta cell function. Amyloid formation may be a primary abnormality or could be secondary to beta cell dysfunction induced by hyperglycaemia. A major susceptibility gene might predispose a proportion, perhaps 10-15%, of a Caucasian population towards diabetes. The subsequent development of diabetes in a particular patient is likely to depend on many factors including other genetic factors, a sedentary life style and obesity. In different populations different genetic influences may operate, including abnormalities of insulin receptor genes and glucose transporter genes, which may allow a beta cell abnormality to become expressed clinically.

A mathematical model of normal glucose/insulin homoeostasis has been based on the known, experimentally determined responses of the liver and periphery to different glucose/insulin concentrations. Different defects of glucose resistance and insulin resistance have been applied to the model to investigate the degree to which these abnormalities could successfully predict the range of fasting glucose and insulin values found in normal, obese, and diabetic subjects. Modeling glucose resistance or insulin resistance at the liver or the periphery alone did not increase the plasma glucose to levels observed in diabetes, even when associated with marked deficiency of beta-cell function. A defect of either glucose resistance or insulin resistance affecting both periphery and liver allowed a wider range of basal glucose and insulin concentration values, but resulted in unphysiologically low hepatic glucose output: with modeling insulin resistance, hyperglycemia suppressed glucose output, whereas with glucose resistance, raised insulin levels suppressed hepatic glucose output. A wide range of glucose and insulin values, with appropriate basal hepatic glucose output, could only be modeled by insulin resistance at both the liver and periphery with additional glucose resistance at the liver. The modeling results are in accord with investigative studies that suggest secondary hepatic and peripheral glucose resistance in response to hyperglycemia. Modeling provides a systematic means of examining the likely effect of different putative defects in a complex physiological system.

Sir, Digoxin is a commonly used drug in medicine. However, adverse events related to digoxin are one of the most frequent causes for emergency department visits related to medication, especially in older patients.1 The absorption of digoxin from the intestine is between 70% and 90% depending on the type of preparation used e.g. elixir, capsule, etc.2 Digoxin has a large volume of distribution and is concentrated in tissues like myocardium, skeletal muscle and red blood cells. Serum digoxin concentrations correlate best with lean rather than total body weight. Approximately 25% of the digoxin in the plasma is bound to protein.3 There is significant inter-individual variability in therapeutic range, but a generally accepted range is 0.5–2.0 µg/l. Digoxin is eliminated by first-order kinetics. It is primarily (∼70%) excreted unchanged by glomerular filtration and excretion by renal tubules and its excretion is proportional to glomerular filtration rate (GFR). In subjects with normal renal function, digoxin has a half-life of 1.5–2.0 days. The half-life in anuric patients is prolonged to between 3.5 and 5 days.4–7 Digoxin is not effectively removed from the body by dialysis or during exchange transfusion because most of the drug is bound to tissue and does not circulate in the blood.8 The common risk factors for digoxin toxicity are impaired renal function, advanced age and other medications. Co-administration of drugs like p-glycoprotein inhibitors (amiodarone, verapamil, quinidine and ciclosporin) can increase serum digoxin concentration between 20% and 60%.9 Electrolyte disturbances like hypokalaemia and hypomagnesaemia, induced by diuretic agents and hypercalcaemia can also increase digoxin toxicity. Clinical manifestations of digoxin toxicity include a wide range of signs and symptoms and its cardiac effect can be fatal. In life-threatening digoxin toxicity, treatment with digoxin-specific antibody fragments (Fab) is effective and safe.10 Fab is derived from …

BACKGROUND: Anaemia occurs early in the course of diabetes-related chronic kidney disease (CKD). There is little evidence about the prevalence of anaemia in people with diabetes. The aim of this study was to assess the prevalence of anaemia, by stage of CKD, in the general diabetic population. METHODS: Haemoglobin (Hb) was measured on all glycated haemoglobin (HbA1c) samples and the most recent (< 4 months) estimated glomerular filtration rate (eGFR) was obtained. Anaemia (at treatment level) was defined as Hb < 110 g/l or the use of erythropoetic stimulating agents (ESA). RESULTS: Twelve per cent (10-14%) of people had Hb < 110 g/l. The prevalence of anaemia increased progressively with worsening CKD. People with CKD stage 3 accounted for the largest number of people with anaemia; 18% (95% CI 13-24%) had Hb < 110 g/l. Those with eGFR < 60 ml/min/1.73 m2 and not on ESA or dialysis were four (2-7) times more likely than patients with better renal function to have Hb < 110 g/l. The relation between Hb and eGFR became approximately linear below an eGFR of 83 ml/min/1.73 m2, where, for every 1 ml/min/1.73 m2 fall in eGFR, there was a 0.4 (0.3-0.5) g/l fall in haemoglobin. CONCLUSIONS: This study demonstrates that anaemia, at levels where treatment is indicated, occurs commonly in people with diabetes and CKD stage 3 or worse. The screening for anaemia in current diabetes management should be extended.

OBJECTIVE: To determine whether pancreatic B-cell function varies in different populations with similar genetic backgrounds but different environments. RESEARCH DESIGN/METHODS: We compared a specific migrant Gujarati community in the UK (n = 205) with people still resident in the same villages of origin in Gujarat, India (n = 246). Pancreatic B-cell function (HOMA-B) was determined and the influence of age, migration and other factors was explored. RESULTS: As anticipated, there was an age-related decline in log(HOMA-B) in both groups. However, the age-related fall in log(HOMA-B) was more pronounced in the UK than in Gujarat (normalized beta-0.29 vs. -0.14, P for difference = 0.03). The decline of HOMA-B with age persisted after adjustment for body mass index (UK beta = -0.31; Gujarat beta = -0.16, P = 0.015, P < 0.001). There was no significant change in insulin sensitivity (HOMA-S) with age at either site, although insulin sensitivity was lower in the UK. Fasting non-estrified fatty acid (NEFA) levels rose with age in the UK but not in Gujarat (P = 0.003 for difference in gradients). In multiple linear regression analysis, lower log(HOMA-B) was independently associated with higher fasting log(NEFA) levels; normalized beta = -0.24, P < 0.001, age; beta = -0.16, P = 0.005, higher log(insulin-like growth factor binding protein-1); beta = -0.19, P = 0.007 and lower body mass index; beta = 0.26, P = 0.001. This model accounted for 25% of the variability in HOMA-B. CONCLUSIONS: HOMA-B as a measure of B-cell function declines more rapidly with age in the migrant UK group than in Gujarat. This may be a direct consequence of chronically higher NEFA exposure in the UK group.

The electronic structure of the full- and half-Heusler alloys have been studied by ab-initio calculations using full potential augmented plane-wave-method (FLAPW). It was shown that obtained equilibrium lattice parameters and magnetic moments agree well with available experimental data. The influence of vacancies on the electronic structure and magnetic properties of Ni 2-x MnGa and Co 2-x ZrSn is analyzed.

Increased state funding in all sectors of research is now being advocated in the name of a new economic theory called Endogenous Growth Theory (EGT). Here, Terence Kealey and Aram Rudenski (Cambridge University, UK) argue that this new model of scientific funding, devised by Stanford economist Paul Romer in 1990, is inherently flawed--as was the model before it--and will not lead to economic prosperity as governments hope.

Gilbert’s syndrome is a benign condition causing hyperbilirubinemia, which is also a symptom of liver or hemolytic disease. A genetic test may be possible for Gilbert’s syndrome because an associated gene defect has been isolated. Here we present a mathematical analysis of the use of this test in excluding harmful causes of hyperbilirubinemia. The effectiveness of the test depends on a low prevalence and high penetrance of the gene defect and a low prevalence of harmful hyperbilirubinemia. If the gene defect has a 12% prevalence and 10% penetrance, then the prevalence of harmful hyperbilirubinemia needs to be

To the Editors: The emergency management of hypoxaemic patients requires clinicians to avoid the hazard of dangerous hypoxaemia due to under-treatment with oxygen, whilst also avoiding the hazards of hypercapnic respiratory failure (iatrogenic hypercapnia) and oxygen toxicity, which may be caused by over-treatment with oxygen. In the past, many clinicians acted cautiously by giving high concentrations of oxygen to all potentially hypoxaemic patients and a culture evolved that “more is better”. However, since the 1960s, it has been known that some patient groups, particularly those with chronic obstructive pulmonary disease (COPD), are especially vulnerable to uncontrolled oxygen therapy and a recent randomised study showed that mortality in this patient group was doubled when high-concentration oxygen was used compared with controlled oxygen therapy [1–4]. It has also been demonstrated that hyperoxaemia is associated with increased mortality in patients with stroke, and in survivors of cardiac resuscitation and critically ill patients in the intensive care unit (ICU) [5–7]. The British Thoracic Society (BTS) guidelines for emergency oxygen use recommend a target oxygen saturation range of 94–98% for most emergency medical patients and a lower target range of 88–92% for those at risk of hypercapnic respiratory failure …

Anaemia occurs early in the course of diabetes-related chronic kidney disease (CKD). There is little evidence about the prevalence of anaemia in people with diabetes. The aim of this study was to assess the prevalence of anaemia, by stage of CKD, in the general diabetic population.Haemoglobin (Hb) was measured on all glycated haemoglobin (HbA1c) samples and the most recent (4 months) estimated glomerular filtration rate (eGFR) was obtained. Anaemia (at treatment level) was defined as Hb110 g/l or the use of erythropoetic stimulating agents (ESA).Twelve per cent (10-14%) of people had Hb110 g/l. The prevalence of anaemia increased progressively with worsening CKD. People with CKD stage 3 accounted for the largest number of people with anaemia; 18% (95% CI 13-24%) had Hb110 g/l. Those with eGFR60 ml/min/1.73 m2 and not on ESA or dialysis were four (2-7) times more likely than patients with better renal function to have Hb110 g/l. The relation between Hb and eGFR became approximately linear below an eGFR of 83 ml/min/1.73 m2, where, for every 1 ml/min/1.73 m2 fall in eGFR, there was a 0.4 (0.3-0.5) g/l fall in haemoglobin.This study demonstrates that anaemia, at levels where treatment is indicated, occurs commonly in people with diabetes and CKD stage 3 or worse. The screening for anaemia in current diabetes management should be extended.

OBJECTIVE: Serum testosterone measurement is an integral part of the endocrine assessment of men. Little is known about its variation in relation to migration. We examined within a South Asian group the effect of migration to the UK on androgen levels. DESIGN: Circulating testosterone and SHBG concentrations were measured in 97 Gujarati men resident in India and in 79 men from the same villages of origin living in Birmingham, UK. Free testosterone was calculated by Vermeulen's method. Insulin sensitivity (HOMA-S) was determined from paired fasting plasma intact insulin and glucose values. RESULTS: Circulating testosterone was significantly lower in UK Gujarati men (17.2 nmol/l [15.7-18.7]) vs. Indian Gujarati men (21.7 [20.0-23.5]) (P = 0.0002) (age-adjusted median [95% CI]). There was no difference by migration status in circulating free testosterone. Sex hormone binding globulin (SHBG) levels were lower in UK migrants (16.8 nmol/l [15.5-18.1]) than in nonmigrants (21.9 nmol/l [20.5-23.3]) (P < 0.0001). Testosterone level correlated positively with insulin sensitivity (HOMA-S) (rho 0.16, P = 0.04). In multivariate analysis, total testosterone was independently and positively associated with logSHBG (normalized beta (beta) = 0.29, P = 0.002) and independently and negatively with waist circumference (beta = -0.19, P = 0.04), in a model also including height, age, migration status, leptin and fasting insulin. CONCLUSION: Lower circulating testosterone in UK Gujarati men and its association with markers of insulin sensitivity suggest a profound influence of body composition change with migration on testosterone levels. The lower SHBG in this group restores parity in free testosterone. Account should be taken of SHBG in interpreting testosterone levels in men, as well as in women.

AIMS/HYPOTHESIS: IGFs and their binding proteins are increasingly recognised as important in understanding the pathogenesis of cardiovascular disease. Low IGFBP-1, particularly coupled with low IGF-I, is associated with increased cardiovascular risk. In relation to structural and regulatory parallels between IGFBP-1 and - 2 we have now examined the hypothesis that IGFBP-2 may be a marker for cardiovascular risk. METHODS: Fasting IGFBP-2, IGFBP-1, IGFBP-3, IGF-I, IGF-II, insulin, C-peptide, glucose, lipids, NEFAs, and HbA1c were measured in a cohort of 163 patients with type 2 diabetes. Individuals were categorised according to the presence or absence of the metabolic syndrome. RESULTS: Patients with the metabolic syndrome had a lower IGFBP-2 concentration. Low circulating IGFBP-2 was associated with elevated fasting glucose (rho = - 0.23, p = 0.003). IGFBP-2 correlated negatively with triglycerides (rho = - 0.19, p = 0.01) and LDL-cholesterol (rho = - 0.20, p = 0.01), and positively with insulin sensitivity (HOMA-S) (rho = 0.26, p = 0.02). Multivariate logistic regression demonstrated that low IGFBP-2 was independently associated with an increased risk of the metabolic syndrome (OR 0.31 [95 % CI 0.11 - 0.90]; p = 0.03). IGFBP-3 did not differ according to the presence or absence of metabolic syndrome. CONCLUSION/INTERPRETATION: Low IGFBP-2 is associated with multiple cardiovascular risk factors similarly to IGFBP-1. Such associations were not apparent for IGFBP-3. Lack of marked prandial regulation of IGFBP-2, in contradistinction to IGFBP-1, may make IGFBP-2 a more robust biomarker for identification of insulin-resistant individuals at high cardiovascular risk in epidemiological studies.PMID: 16915540 [PubMed - indexed for MEDLINE]

Background: Direct (non-extracted) testosterone immunoassays may give spuriously high results in women. The presumed interferents may be removed if testosterone is extracted into an organic phase before being measured. We aimed to clarify possible causes and effects of interference in testosterone measurement in women. Methods: Women who had a blood sample referred to Hope Hospital Clinical Biochemistry laboratory for measurement of serum testosterone concentration over a six-month period were studied. Clinical and treatment data were recorded. A difference (direct-minus-extracted testosterone) of less than 1.0 nmol/L was used to define a group with low interference. A difference of 2.5 nmol/L or more was used to define a group with significant interference. Results: The distribution of interference in 1271 serum samples from female patients was unimodal. There were no group differences in clinical presentation or treatment. The median degree of interference was 1.4 nmol/L. In 42 female patients with varying degrees of interference, identified on routine assay, regression analysis showed strong association between dehydroepiandrosterone sulphate (DHEA-S) and interference (direct-minus-extracted testosterone) ( r = 0.77, P Conclusions: Given that DHEA-S is present in very variable amounts in blood, it is possible that even with a low cross reactivity, DHEA-S or one of its metabolites significantly interferes in the testosterone assay when at higher concentrations.

BackgroundThe insulin-like growth factor (IGF) system is implicated in the pathogenesis of diabetes and cardiovascular disease.ObjectiveWe report the effects of total energy intake on the IGF system in two populations with markedly different dietary macronutrient intake and cardiovascular event rate.Design, subjects and settingDietary macronutrient intake was measured in a specific Gujarati migrant community in Sandwell, UK (n = 205) compared with people still resident in the same villages of origin in India (n = 246). Fasting IGF-I, IGF-binding protein (IGFBP)-1 and IGFBP-3, insulin and glucose (0 and 2-hour) were measured.ResultsTotal energy and total fat intake were higher in UK migrants, as were IGFBP-3 and IGF-I (mean (95% confidence interval): 145.9 (138.1–153.6) vs. 100.9 (94.6–107.3) ng ml-1; F = 76.6, P < 0.001). IGFBP-1 was lower in UK migrants (29.5 (25.9–33.0) vs. 56.5 (50.6–62.5) μg l-1; F = 48.4, P < 0.001). At both sites, IGF-I correlated positively with total energy (Spearman's ρ = 0.45, P < 0.001) and total fat (ρ = 0.44, P < 0.001) as did IGFBP-3 with total energy (ρ = 0.21, P < 0.05) and fat (ρ = 0.26, P < 0.001). Conversely, in Indian Gujaratis, IGFBP-1 fell with increasing total energy (ρ = -0.27, P < 0.001) and fat intake (ρ = -0.26, P < 0.01) but not in UK Gujaratis. Multiple linear regression modelling showed that increasing quartiles of fat intake were associated with higher IGF-I (β = 0.42, P = 0.007) independent of age, body mass index, plasma insulin, fatty acids and 2-hour glucose.ConclusionIn these genetically similar groups, migration to the UK and adoption of a different diet is associated with marked changes in the IGF system, suggesting that environmental factors profoundly modulate serum concentrations and actions of IGFs.

Insulin resistance is implicated in the pathogenesis of polycystic ovarian syndrome (PCOS). Insulin-sensitizing agents are increasingly used in the treatment of infertility and hirsutism in PCOS. However, not all women with PCOS are insulin-resistant.To assess the degree of insulin resistance within a clinic population of women referred for treatment of oligomenorrhoea or infertility.We evaluated 25 consecutive PCOS outpatients referred for treatment of menstrual dysfunction/infertility and a matched control group. All underwent a standard oral glucose tolerance test (OGTT) with serial insulin measurements. Insulin sensitivity was calculated using homeostasis model assessment (HOMA).Five of the 25 clinic patients had abnormal glucose handling (two had previously unknown type 2 diabetes and three had impaired glucose tolerance). Fasting and 2-h insulin levels were significantly higher in the PCOS women. Mean HOMA-S (insulin sensitivity) was even lower for PCOS women with normal GTT status (mean (95% confidence interval): 0.53 (0.34-0.72)) than for controls (0.94 (0.84-1.04)) (F = 4.2, p0.001). HOMA-B (pancreatic beta-cell function) was nearly tripled for normal GTT status PCOS women at 273 (205-342) versus 105 (70-139) for controls (F = 6.8, p0.001).The results suggest a role for routine measurement of HOMA-S in identifying women with PCOS with insulin resistance with a view to targeting them with insulin-sensitizing agents.

Necrotizing pneumonia, massive necrosis of lung tissue, is a serious, often fatal, complication of lobar pneumonia. Four children 1.3 to 7.5 yr of age were hospitalized with bacteremic pneumococcal pneumonia. All of them were acutely ill on presentation with arterial desaturation, and they developed anemia and thrombocytosis. Two patients had pleural effusion requiring drainage. A chest CT scan revealed segmental or lobar pulmonary liquification, which led to the diagnosis of necrotizing pneumonia. This finding could be demonstrated early in the course of the disease. Subsequently, all of the patients developed cavitating lesions. With adequate antipneumococcal therapy and/or chest tube drainage, all of the patients recovered completely; however, clinical improvement was prolonged: fever lasted 9 to 20 days, and length of hospitalization was 12 to 26 days. Contrary to that in adults, complete recovery is anticipated in children with bacteremic necrotizing pneumococcal pneumonia, and no invasive investigations are required.

In order to obtain data on the prevalence and incidence of herpes virus type 2 (HSV(2)) infection in selected populations of women and to identify groups that might benefit from routine prenatal screening, an epidemiological study was conducted during the period 1984-1990, which showed HSV(2) seroprevalence to be 2.8%. Due to the worldwide increase of over 30% of HSV(2) infection in the past two decades, a second study was performed during the period 1 January 1998-31 December 1999. Four different population groups were studied: 172 children aged 6 months to 17 years (group 1), 716 adults, men and women aged 18-95 (group 2), 200 women aged 30-67 who participated in the first survey and were re-examined in 1999 in the second survey (group 3), and a prevalence group of 155 parturient women from six different delivery rooms (group 4). Among the healthy 716 males and females HSV(2) seroprevalence was 4.5%. When analyzed by subgroup, HSV(2) seroprevalence rose from 2.3% in the 18-30 years subgroup to 6.5% in the 30-50 years subgroup and to 7.3% in the 51-70 years subgroup, and then declined to 2.4% after age 70 years. In the 200 women re-examined, HSV(2) seroprevalence was 7.7% with a 0.55% HSV(2) sero incidence per annum. In the prevalence group HSV(2) seroprevalence was 4.5%. Sera from the 1223 participants of all four groups were also screened for HSV(1) infection. HSV(1) antibody was present in 22% of children aged 6 months-1 year, in 60% at 21 years and in 87% at age 70 years. The data support the conclusion that in Israel there is no justification for routine prenatal HSV(2) screening in the healthy female population.

Rapid emmetropization is described in pediatrically normal infants from 9 months of age during the following year. The infants, obtained from various categories of the Cambridge population screening program, provided a broad range of refractive errors. The large group of 254 nonanisometropic infants studied allowed the mean rate of change and dependence on the initial refraction value to be determined. Refraction was measured by cycloplegic retinoscopy. Rapid emmetropization changes occurred in the following refractive components: mean spherical equivalent (MSE), astigmatism magnitude, the horizontal astigmatism component, the infant's most positive meridian, and the infant's most negative meridian. The MSE and astigmatism rates of change (diopters/year), were highly dependent on their respective initial powers (r = -0.61 and r = -0.76). The percentage weighted mean proportional rate of change for MSE was -30% (SE 4%) and for astigmatism magnitude it was -59% (SE 14%). There was much individual variation, with some exhibiting fast emmetropization and others not. The MSE and astigmatism changes, however, were almost independent of each other. The refractive errors of the most positive and most negative meridians emmetropize because they are both derived from the MSE and half the astigmatism. With-the-rule astigmatism was more prevalent than against-the-rule astigmatism at 9 months of age, and with-the-rule astigmatism exhibited a significantly greater proportional rate of change. The relationship of emmetropization and refractive screening is considered. A new component "MOMS" is introduced, the maximum ocular meridional separation, when both eyes are considered. Thus incorporating astigmatism and anisometropia may be a good single indicator of conditions associated with later amblyopia. The almost independent emmetropization of the MSE and astigmatism components is an important result to consider in theories of emmetropization, refractive screening, clinical prescribing, and the evaluation of infants in treatment trials.