Lipaemia: causes, consequences and solutions.

The detection of lipaemia in a patient blood sample can be a clinical conundrum as well as an analytical nuisance. With a reported prevalence of 0.7% in all blood samples received for lipid studies its finding has been suggested to be an underappreciated problem [1]. Its presence can have a significant impact on the validity of a number of routine blood tests. The intention of this report is to outline the causes of lipaemia, the clinical and analytical consequences of its presence and some of the tools the laboratory employ to reduce its effects. Both laboratory professionals and clinicians should have an appreciation of the analytical and clinical impact lipaemia may confer on routine biochemistry.

Reduction Formulae for Products of Theta Functions.

In four cases it is already known that the product of two distinct Jacobian theta functions having the same variable z and the same nome q is a multiple of a single Jacobian theta function, with the multiple independent of z. The main purpose of the present note is to show that this property also applies in the remaining two cases.

Purine nucleoside phosphorylase deficiency: a mutation update.

Purine nucleoside phosphorylase (PNPase) deficiency is an autosomal recessive disorder affecting purine degradation and salvage pathways. Clinically, patients typically present with severe immunodeficiency, neurological dysfunction, and autoimmunity. Biochemically, PNPase deficiency may be suspected in the presence of hypouricemia. We report biochemical and genetic data on a cohort of seven patients from six families identified as PNPase deficient. In all patients, inosine, deoxyinosine, guanosine, and deoxyguanosine were elevated in urine, and mutation analysis revealed seven different mutations of which three were novel. The mutation c.770A>G resulted in the substitution p.His257Arg. A second novel mutation c.257A>G (p.His86Arg) was identified in two siblings and a third novel mutation, c.199C>T (p.Arg67X), was found in a 2-year-old female with delayed motor milestones and recurrent respiratory infections. A review of the literature identified 67 cases of PNPase deficiency from 49 families, including the cases from our own laboratory. PNPase deficiency was confirmed in 30 patients by genotyping and 24 disease causing mutations, including the three novel mutations described in this paper, have been reported to date. In five of the seven patients, plasma uric acid was found to be within the pediatric normal range, suggesting that PNPase deficiency should not be ruled out in the absence of hypouricemia.

Time series analysis of the epidemiological transition in Minorca, 1634-1997.

Autoregressive integrated moving average (ARIMA) models provide a powerful tool for detecting seasonal patterns in mortality statistics. The strength of ARIMA models lies in their ability to reveal complex structures of temporal interdependence in time series. Moreover, changes in model parameters provide an empirical basis for detecting secular trends and death seasonality patterns. This approach is illustrated by our analysis of changes in the mortality patterns of the population of the town of Es Mercadal on the island of Minorca between 1634 and 1997. These data reveal a transition from an early mortality pattern requiring a complex ARIMA model that accounts for a strong seasonal death pattern and periodic epidemic-related mortality crises to a much simpler 20th-century pattern that can be described by a simple single-parameter ARIMA model. These same data were also analyzed using standard seasonality tests. The results show that the reduction in the number of parameters required to fit the Es Mercadal mortality data coincides with the epidemiological transition in which the predominant causes of morbidly and mortality shift from infectious to degenerative causes.

Prolactin and macroprolactin: a case report of hyperprolactinaemia highlighting the interpretation of discrepant results.

Immunoassay methods for prolactin detect macroprolactin (i.e. high molecular mass complexes of prolactin) to various degrees. Therefore it is generally assumed that the widely differing results by methods that measure both moieties to a differing extent are due to the presence of macroprolactin. We present a case which challenges such an assumption and suggest that precipitation by polyethylene glycol is the most reliable screen for identifying macroprolactin (and/or interfering antibodies if present).

Interference in immunoassay is an underestimated problem.

The presence of antibodies in some patients' serum has long been known to be a potential source of interference in immunoassays, as shown by numerous case reports. These often appear after the introduction of a new analyte (e.g. troponin) and then decrease in number as the topic becomes exhausted. This highlights the persistent and intrinsic nature of this problem, despite attempts by the manufacturers to compensate for this source of error. However, an explanation of the immunoanalytical basis underpinning these assays could be more effective in raising awareness than intermittent case reports. In this review we have outlined the use of antibodies as reagents, the factors determining how they bind to antigen(s), and the nature of the immune response in order to explain the insidious and unpredictable nature of this form of interference. Studies on the prevalence of interference have yielded values ranging from 0.05 to more than 2%. However, these figures are analyte- and assay-specific, influenced by the study design, and are not therefore generally applicable. It is also highly likely that figures on prevalence and incidence will worsen in the future because of the wider use of monoclonal antibodies as diagnostic and therapeutic tools. Clinical laboratories should be alert to assay interference from antibodies irrespective of its nature, as immunoassays will remain an indispensable analytical tool, unlikely to be replaced in the foreseeable future by a practical alternative.

An integrative approach to mortuary analysis: social and symbolic dimensions of Chumash burial practices.

Although most archaeologists recognize that valuable information about the social lives of ancient people can be obtained through the study of burial practices, it is clear that the symbolic nature of burial rituals makes interpreting their social significance a hazardous enterprise. These analytical difficulties can be greatly reduced using a research strategy that draws upon the strengths of a broad range of conceptually and methodologically independent data sources. We illustrate this approach by using archaeological data from cemeteries at Malibu, California, to explore an issue over which researchers are sharply divided: when did the simple chiefdoms of the Chumash Indians first appear in the Santa Barbara Channel area? First we establish the social correlates of Chumash burial practices through the comparison of historic-period cemetery data, ethnohistoric records, and ethnographic accounts. The resulting understanding of mortuary symbolism is then used to generate hypotheses about the social significance of prehistoric-period Malibu burial patterns. Finally, bioarchaeological data on genetic relationships, health status, and activity are used to independently test artifact-based hypotheses about prehistoric Chumash social organization. Together, these independent data sources constitute strong evidence for the existence of a ranked society with a hereditary elite during the late Middle period in the Santa Barbara Channel area.

Birth seasonality in the early Spanish-Mexican colonists of California (1769-1898).

The pattern of birth seasonality in California's early Spanish-Mexican colonists between 1769 and 1898 was reconstructed using genealogical data for progeny of 657 marriages. The monthly distribution of the 3,824 births in this sample shows a strong seasonal pattern, with spring and fall peaks (corresponding to peaks in conceptions during July and February) and a low point in October. This seasonal reproductive pattern is the result of a complicated set of interactions among environmental, physiological, and cultural variables. California's strongly developed winter rainfall pattern and the 19th-century agricultural cycle clearly influenced the seasonal pattern of marriages and births in this agrarian society. Several historical processes interacted with these environmental and economic factors to transform the seasonal birth pattern of the early colonists. Through time the birth pattern becomes less variable and the birth maximum shifts from spring to early winter. This appears to be, at least in part, a result of changes in labor patterns and an increase in average parity. These data suggest a multifactorial explanation for birth seasonality, in which the timing of conceptions and births is influenced by both environmental and socioeconomic factors.

Age and sex-related variation in hyoid bone morphology.

Although the relationship between hyoid bone shape and fracture pattern figures prominently in forensic investigations of strangulation, few quantitative data exist on age and sex differences in hyoid morphology. An image analysis system was used to take a series of 30 measurements on digitized radiographs of 315 hyoid bones from people of known age and sex. The degree of fusion of the greater cornua to the hyoid body was also recorded. Statistical analysis of these data shows that there is a continuous distribution of hyoid bone shapes and the most bones are highly symmetrical. Based on smaller samples, previous researchers have suggested that non-fusion is more common in women than in men. In contrast, our data suggest that men and women have similar non-fusion rates. Analysis of sexual dimorphism shows that the greatest length differences are in the greater cornua. There are also significant sex differences in hyoid shape. For example, the distal ends of the greater cornua of women are significantly longer than those of men.

Brief communication: gender and sex: vive la difference.

The distinction prevalent in the social sciences between the terms sex and gender is a useful one and ought to be preserved. Sex refers to the anatomical or chromosomal categories of male and female. Gender refers to socially constructed roles that are related to sex distinctions. Use of these terms as synonyms is becoming increasingly frequent in physical anthropology, especially among bioarchaeologists and primatologists. A failure to make the distinction between gender and sex is analytically incapacitating in a field such as physical anthropology, whose strength lies in the integration of biological and cultural information.

Extended mortality benefit of early postinfarction reperfusion. GUSTO-I Angiographic Investigators. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries Trial.

BACKGROUND: Reperfusion therapy for myocardial infarction, understood to reduce mortality by preserving left ventricular function, was initially expected to provide increasing benefits over time. Surprisingly, large controlled thrombolysis trials demonstrated maximum benefit at 4 to 6 weeks with no subsequent increased treatment advantage. Such studies, however, compared groups by assigned treatment, not physiological effectiveness. METHODS AND RESULTS: We calculated 2-year survival differences among 2431 myocardial infarction patients according to early infarct artery patency and outcome left ventricular ejection fraction using Kaplan-Meier curves. Hazard ratios for significant survival determinants were derived from Cox regression models. Two-year vital status (minimum, 688 days) was determined in 2375 patients (97.7%). A substantial mortality advantage for early complete reperfusion (Thrombolysis in Myocardial Infarction [TIMI] grade 3) and for preserved ejection fraction occurred beyond 30 days. The unadjusted hazard ratio for the TIMI 3 group compared with lesser grades at 30 days was 0.57 (95% confidence interval [CI], 0.35 to 0.94) and 30 days to > or = 688 days was 0.39 (95% CI, 0.22 to 0.69). Consequently, early TIMI 3 flow was associated with approximately a 3 patient per 100 mortality reduction the first month with an additional 5 lives per 100 from 30 days to 2 years. For ejection fraction >40% compared with < or = 40%, the unadjusted hazard ratio was 0.25 (95% CI, 0.16 to 0.37) at 30 days and 0.22 (95% CI, 0.15 to 0.33) after 30 days through 2 years (lives saved, approximately 9 and 11 per 100, respectively). CONCLUSIONS: Successful reperfusion and myocardial salvage produce significant mortality benefits that are amplified beyond the initial 30 days.

Marriage patterns of California's early Spanish-Mexican colonists (1742-1876).

Marriage patterns of California's eighteenth and nineteenth century Spanish-Mexican families are analysed using data from genealogies and mission records. A shortage of women among the military based colonists led to an unusual marriage pattern with a large age differential between husbands and wives. The average age at marriage was 18.4 years for women and 28.4 years for men. Spatial mobility was high for both sexes, particularly for men. More husbands than wives were born in Mexico. The Monterey presidial district of central California was the birthplace of a disproportionate number of husbands and the southern California districts were a source of wives. The transition between a founding population predominantly composed of Mexican immigrants and a population of native-born Californians occurred at the beginning of the nineteenth century.

Skeletal evidence for child abuse: a physical anthropological perspective.

Analysis of the skeletal remains of abused children can prove challenging for forensic pathologists and radiographers who are inexperienced in the direct examination of bones. In such cases, radiographically invisible skeletal lesions that document a history of trauma can often be identified by a physical anthropologist with appropriate osteological experience. This is illustrated by cases in which skeletal remains of four murdered children and a mentally handicapped adult produced evidence of antemortem trauma and perimortem injuries that was critical in developing murder cases against the assailants. In these cases, well-healed areas of subperiosteal new bone formation were identified that were below the threshold of radiographic detection. Such injuries provide strong evidence for a history of physical abuse.

Normalizing acute care: a day hospital/crisis residence alternative to inpatient hospitalization.

Normalization is the use of culturally valued means to enable people with disabilities to live culturally valued lives. In this article, the authors describe an effort to bring normalization practices to acute psychiatric care. They describe a day hospital/crisis respite diversion program that serves as an alternative to acute inpatient hospitalization and sketch the research project that fostered it. The authors argue that a day hospital/ crisis respite provides effective clinical care comparable to inpatient hospitalization but achieves greater potential for recovery through a normalizing philosophy and practice. An implication of this finding is that such programs based on the principle of normalization may be both cost effective as well as more empowering for patients.

Modification of Monte Carlo codes for use with sharply peaked phase functions.

Monte Carlo and approximate radiative transfer equation solutions predict different amounts of scattering for large aerosols. A new Monte Carlo scattering algorithm alleviates this discrepancy.

Elevated plasma adrenocorticotropin (ACTH) with adrenal hyperplasia: a new factor in ACTH regulation?

We report a patient with Cushing's syndrome in whom the etiology of the hypercortisolemia could not be definitely established despite extensive biochemical investigations. Results included raised basal serum cortisol, plasma ACTH, and urinary free cortisol; failure to suppress even a paradoxical rise in serum cortisol after dexamethasone (1 mg overnight, 2, 8, and 16 mg/day); and a definite but not exaggerated rise in 11-deoxycortisol after metyrapone. After iv CRF, plasma ACTH rose from 22 to 30 pmol/L. Abdominal computed tomographic scanning showed adrenal hyperplasia; the presence of an adrenal adenoma, although suspected, was not established. An unusual finding was the presence in the urine of large amounts of 21-deoxycortisol metabolites, including 3 alpha,11 beta,17 alpha-trihydroxy-5 beta-pregnan-20-one and 5 beta-pregnane 3 alpha,11 beta,17 alpha,20 alpha-tetrol. On the basis of preoperative biochemical/radiological findings, a provisional diagnosis of ACTH-dependent Cushing's syndrome associated with autonomous bilateral adrenal hyperplasia was made. Incomplete bilateral adrenalectomy was performed; adrenal hyperplasia was histologically confirmed, but no tumor was found. However, ACTH was measured 1) just before operation when the patient was receiving treatment with metyrapone, and 2) postoperatively when the patient was receiving steroid replacement only, and on these occasions ACTH levels were lower than during the initial investigations. Pituitary scans before and after adrenalectomy were similar, offering no evidence of pituitary infarction. We propose that abnormal production of 21-deoxycortisol contributed to the aberrant regulation of ACTH and cortisol in this case, providing an example of a previously unreported cause of hypercortisolemia.

Cranial injuries as evidence of violence in prehistoric southern California.

Crania from the Channel Island area of southern California were examined for evidence of traumatic injuries. Well-healed depressed fractures in the outer table of the cranial vault are common in skeletal remains from the northern Channel Islands (18.56% n = 598) but rare in those from the mainland coast (7.5% n = 146). This prevalence of traumatic injuries among the islanders may be a result of intense competition over resources in a geographically circumscribed environment. The frequency of cranial injuries increases significantly between the early and late prehistoric periods on the Channel Islands. This temporal variation appears to reflect changes in patterns of violence associated with population growth and environmental instability.