Concentrations of alpha-Tocopherol after intramammary infusion of Escherichia coli or lipopolysaccharide.

Fifteen Holstein cows were used in a trial involving intramammary challenge to determine the effects of acute clinical mastitis on the concentrations of alpha-tocopherol in milk and plasma and the concentrations of neutrophils in milk and blood. Cows were assigned to one of three experimental groups challenged by intramammary infusion of lipopolysaccharide, Escherichia coli, or sterile phosphate-buffered saline. All quarters infused with lipopolysaccharide or E. coli were diagnosed with clinical mastitis on d 1 and 2 after challenge. Acute inflammation caused by intramammary infusion of lipopolysaccharide or E. coli resulted in increased concentrations of alpha-tocopherol in milk in challenged quarters but had no effect on concentrations of alpha-tocopherol in plasma. Concentrations of alpha-tocopherol in milk and blood neutrophils did not differ among treatment groups. Concentrations of alpha-tocopherol did not differ between milk and blood neutrophils. Approximately 25% of the alpha-tocopherol in milk from glands with clinical mastitis was associated with neutrophils, and < 10% of the alpha-tocopherol in milk from nonmastitic glands was associated with neutrophils. A shift toward sources of alpha-tocopherol other than synthesized milk fat occurred during acute inflammation in the mammary gland.

Knowledge about Alzheimer disease among primary care physicians, psychologists, nurses, and social workers.

Although much of the care of Alzheimer disease (AD) patients and their families is carried out by health professionals who are not specialists in AD or geriatrics, little is known about how knowledgeable these health professionals are about AD. An AD knowledge test was constructed through careful instrument development procedures and then administered through a mail survey. Subjects were 693 individuals, including experts in AD care, generalist health care professionals (primary care physicians, psychologists, social workers, and nurses), nursing students, hospital staff nurses, and assorted health professionals. A 12-item scale with excellent psychometric properties was developed. Experts in AD care performed significantly better than generalist health care professionals on all items. All four groups of generalist health care professionals showed important deficits in fundamental knowledge about AD; for example, only 40% of generalists (vs. 97% of experts) knew that AD is the most common cause of severe memory loss in people over age 65. Results suggest that, although knowledge about assessment and management of AD has increased and has been widely disseminated, many health care professionals remain uninformed about AD. Suggestions for professional education and for use of the UAB AD Knowledge Test for Health Professionals are discussed.

Alzheimer's disease patients and their caregivers: medical care issues for the primary care physician.

Alzheimer's disease (AD) is a common problem with complex challenges in assessment and management for the primary care physician. We present a practical, six-step strategy for physicians to use in AD care, summarized by the acronym ACROSS: assessment of AD, communication of the diagnosis, referral to appropriate community resources, ongoing evaluation, providing solutions to patient and caregiver problems, and maintaining sensitivity to family caregiver issues. The family caregiver of the patient with AD provides the physician with essential diagnostic information and implements physician recommendations for AD care. Advice and support from the physician are essential for the family caregiver to withstand the relentless strain of caring for a loved one with a progressive dementia. We provide practical suggestions for management of common patient and caregiver problems across the stages of AD.

Psychological, social, and health impact of caregiving: a comparison of black and white dementia family caregivers and noncaregivers.

Psychological, social, and health variables were compared in 175 Black and White family caregivers of patients with dementia and 175 Black and White noncaregivers. Caregivers and noncaregivers did not differ within race on demographic variables. Caregiving was associated with increased depression and decreased life satisfaction only in White families. However, caregiving appears to have similar social consequences for Black and White families, including restriction of social activity and increased visits and support by family from outside of the home. Race, but not caregiving, was associated with physical health variables. Methodological issues in comparing well-being in Black and White caregivers, in particular the importance of including noncaregiving comparison subjects are discussed.

What does rCBF-SPECT offer in schizophrenia?

Schizophrenia is a major psychiatric problem common in the younger population. Structural imaging and findings on autopsy have not yet revealed a specific deficit in these patients. Uncertainty in clinical diagnosis based on a set of signs and symptoms is another drawback in the management of this patient population. Regional cerebral blood flow studies (rCBF) using single photon emission computed tomography (SPECT) offers the opportunity to study the underlying phenomenon and to detect the specific functional deficits in schizophrenia.

Use of low molecular weight heparin in pregnancy.

In a controlled study of 15 pregnant patients undergoing therapeutic termination of pregnancy, seven received subcutaneously 5,000 anti-FXa units of low molecular weight (LMW) heparin 15 and 3 h prior to the termination, and eight patients acted as controls. Paired maternal and fetal blood samples were taken (before or immediately after the termination) for assay of heparin activity by a chromogenic anti-FXa method sensitive to levels of 0.02 anti-FXa U/ml. LMW heparin was detected in all maternal samples of the test patients but was not detected in any of the fetal samples. The use of LMW heparin as a thromboprophylactic agent was then evaluated in 11 patients who were known to have a severe thromboembolic tendency, had suffered recurrent miscarriages and had responded poorly to conventional anticoagulation (oral anticoagulant, conventional heparin). All patients receiving LMW heparin in thromboprophylactic doses completed uneventful pregnancies and gave birth to healthy babies (three for the first time) without complication. Bone density scans performed in all patients shortly after the delivery showed normal mineral mass. We conclude that LMW heparin does not cross the placental barrier, and in addition offers satisfactory antithrombotic protection for both maternal and placental circulation. In addition, this study provides preliminary data from 11 patients suggesting LMWH may not give rise to maternal osteoporosis, a finding that now needs further investigation.

Quantification of regional cerebral blood flow (rCBF) using 99Tcm-HMPAO and SPECT: choice of the reference region.

The effects of the choice of the reference region in determining the relative regional cerebral blood flow (rCBF) using 99Tcm-hexamethylpropylene amine oxime (HMPAO) single photon emission tomography (SPECT) have been studied in order to establish or exclude it as a cause of inconsistencies in these studies. Relative rCBF was estimated by normalizing the regional count densities to two reference regions, the cerebellum and the whole slice, in 35 patients with Alzheimer's disease (AD), 25 patients with chronic schizophrenia (SCH) and the same number of matched normal volunteers. The statistical significance of the differences in rCBF between patients and their matched normals varied in the two sets of rCBF data. Smaller differences were highly significant while some larger differences were of less significance with whole slice normalization. The results suggest that the choice of reference region is one of the causes resulting in discrepancies in the results from various centres. The need to use a standard reference region is indicated.

Morphologic (CT) and functional (rCBF-SPECT) correlates in Alzheimer's disease.

Thirty-five patients with a clinical diagnosis of probable Alzheimer's disease underwent computed tomography (CT) and regional cerebral blood flow (rCBF) studies using single photon emission computed tomography (SPECT). Two sets of images in each subject were scored for the extent of structure and function changes. Thirty-four of 35 patients had various degrees of atrophy on CT, 33 of whom also had perfusion deficits of varying severity. One patient with normal CT had perfusion deficits, and another patient with a normal perfusion pattern had changes on CT. Regional perfusion deficits on SPECT were seen with and without associated changes on CT. Correlations were studied between CT and SPECT scores using Spearman's rank correlation coefficients. While regional scores on CT and SPECT did not significantly correlate, the total and left hemisphere scores on two sets of images showed fair correlations (r = 0.425 and r = 0.535, respectively, P less than 0.01). The correlations between cognitive performance in patients as assessed on Mini-Mental State Examination (MMSE) and CAM-COG and perfusion scores were highly significant while CT scores showed lower correlations. These findings suggest that the relationship between structural and functional changes in Alzheimer's disease is not straightforward and that the extent of changes in function as assessed by regional cerebral blood flow studies is a reliable measure of deficits in cognitive function.

Patterns of regional cerebral blood flow in Alzheimer's disease.

Regional cerebral blood flow was assessed in 35 patients with Alzheimer's disease and the same number of matched normal volunteers. Images were scored for regional perfusion deficits. Mildly demented patients had parietal and temporal perfusion deficits, often unilateral. Moderate to severely demented patients had bilateral temporal and parietal perfusion deficits. All severely demented patients also had involvement of both occipital regions. Frontal lobe deficits were seen in 14 patients. Left cortical perfusion deficits were more severe than the right cortical perfusion deficits in general. Patients with early onset of the disease showed left frontal deficits, more often, however, the total perfusion deficit scores in early and late onset groups were not statistically significant. Also, the cognitive performance scores were not statistically significant in these two groups. These results suggest a stage-dependent reduction in regional cerebral blood flow in patients with Alzheimer's disease.

Assessment of gall bladder dynamics, cholecystokinin release and the development of gallstones during octreotide therapy for acromegaly.

The development of gallstones is a well recognized complication of therapy with the long-acting somatostatin analogue, octreotide in patients with acromegaly. A group of nine acromegalic patients was treated with octreotide at doses of 300-600 micrograms daily for 8 months and the changes in fasting and post-prandial cholecystokinin release, and gall bladder motor function (determined by a radiosotopic technique) were assessed at regular intervals. In addition the development of any gallstones was determined by serial ultrasonography. Fasting cholecystokinin levels showed no significant change over 6 months, whereas the post-prandial levels demonstrated a significant decrease (p less than 0.01) during therapy, yet remained significantly higher than fasting levels. Twenty-four hours after commencing therapy gall bladder ejection fraction was decreased by 57 +/- 23 per cent and gall bladder ejection rate decreased by 63 +/- 19 per cent compared to the pretreatment values, whereas after 6 months' therapy a marked reduction in gall bladder ejection fraction (greater than 35 per cent) and gall bladder ejection rate (greater than 40 per cent) persisted in only four of nine patients. Three of these four patients with persistently impaired gall bladder motor function were subsequently shown to have developed either gallstones or biliary sludge during the course of therapy. We conclude that treatment with octreotide is associated with an impaired post-prandial release of cholecystokinin in all acromegalic patients, but gallstones only develop in those patients who, in addition, have evidence of a persistently impaired gall bladder motor response to cholecystokinin.

Ten minute radiopharmaceutical test in biliary atresia.

To provide an objective rapid means of excluding extrahepatic biliary atresia (atresia), a hepatic index was devised from the ratio of the net hepatic to cardiac distribution of 99mTc diisopropyl iminodiacetic acid or methylbrom iminodiacetic acid between 2.5 and 10 minutes after injection. The hepatic index was compared with subjective assessment of abdominal scintigraphy performed repeatedly over 24 hours. In 22 infants with hepatitis the hepatic index ranged from 5.03 to 14.9, one having no excretion on scintiscan. In 26 infants with atresia the index ranged from 0.49 to 4.26 and in two with paucity of intralobular bile ducts it was 1.85 and 3.69. None of these infants had excretion apparent on scintiscans. Similarly, low hepatic indices occurred in four infants with liver dysfunction but pigmented stools, three of whom had no excretion apparent on scintiscans. These preliminary studies suggest that a hepatic index of greater than 5 is much more rapid and as specific in excluding atresia as repeated abdominal scintigraphy.

Normal volunteer studies with modified 99Tcm tin colloid.

99Tcm tin colloid, modified by the addition of various amounts of the surfactant Pluronic F68 was evaluated as a new liver imaging agent in normal adult male volunteers. The relative amounts taken up in the liver and spleen were measured by two quantitative methods with a view to establishing the most useful technique. The changes in biodistribution resulting from mechanical shaking during preparation of the colloids and in vitro ageing of the preparations were assessed. The pharmacokinetics of uptake into liver and spleen of the various formulations tested were independent of Pluronic F68 content. However, at low levels of Pluronic F68 the liver:spleen ratio decreased as the colloid preparation was aged before use. At high levels of Pluronic F68 there was increased background activity. An optimum formulation was identified combining low background activity with a stable pattern of biodistribution independent of preparation age.

Studies of insulin-like growth factor -I and -II by specific radioligand assays in umbilical cord blood.

Somatomedin concentrations in human umbilical sera (n = 206) were measured using a specific radioimmunoassay for insulin-like growth factor (IGF)-I and a specific radioreceptor assay for IGF-II following acid-ethanol extraction of the sera to remove the somatomedin binding proteins. IGF-I concentrations were lower (P less than 0.001) than adult values and correlated with gestational age (P less than 0.001) and birth weight (P less than 0.0001). Multiple regression analysis demonstrated that both birth weight expressed independently of gestational age as the standard deviate score (P less than 0.0001) and gestational age (P less than 0.002) had effects on umbilical cord IGF-I concentrations. IGF-II concentrations were similar to adult values and did not correlate with gestational age, birth size or IGF-I values. IGF-II concentrations were higher (P less than 0.005) in male than female fetuses. These data support a role for IGF-I in influencing fetal growth and suggest the independent regulation of the secretion of IGF-I and II in the perinatal period. These was no evidence to suggest a distinct perinatal form of somatomedin.

The prelaparotomy diagnosis of extrahepatic biliary atresia.

The diagnostic accuracy of laboratory investigations in the prelaparotomy differentiation between extrahepatic biliary atresia (EHBA) and intrahepatic disease (IHD) was assessed in 86 consecutive infants presenting with conjugated hyperbilirubinaemia. Forty five infants had EHBA and 41 IHD. The mean serum bilirubin concentration, gamma-glutamyltranspeptidase (GGT) activity, and the GGT/aspartate transaminase (AST) ratio were appreciably higher in infants with EHBA than in those with IHD. In infants with IHD, however, serum bilirubin concentrations were in the EHBA range in 19 (47%), as were GGT values in 29 (71%), and GGT/AST ratios in 33 (80%). In individual patients neither increasing nor decreasing GGT values were of diagnostic importance. Failure of biliary excretion of 99Tcm-p-Butyl-ida occurred in 29 of 30 (97%) patients with EHBA but also in 22 of 23 (67%) with IHD. In all 5 patients with IHD associated with alpha 1 antitrypsin deficiency these 4 investigations gave results in the EHBA range. Liver biopsy specimen interpretation, correct in 38 of 42 infants with EHBA, gave an overall accuracy of diagnosis of 86%: the results of 3 further biopsies were equivocal. In 33 of 40 infants with IHD bile duct obstruction was excluded; the remaining 7, including 4 with alpha 1 antitrypsin deficiency, showed equivocal changes. Faecal excretion of 131I rose bengal faecal excretion was less than 10% in 36 of 37 patients with EHBA and in 9 of 26 with IHD, giving an overall accuracy of diagnosis of 84%. In patients in whom genetic disorders, such as alpha 1 antitrypsin deficiency had been excluded, interpretation of liver biopsy specimens together with 131I rose bengal faecal excretion remain the most accurate means of identifying those who need surgery for EHBA and of avoiding unnecessary laparotomy in infants with IHD.

Salbutamol: tablets, inhalational powder, or nebuliser?

A study was carried out to ascertain the most effective method of giving salbutamol. Seventeen children with severe asthma received active salbutamol (4 mg via a nebuliser, 400 micrograms as an inhalational powder, or a 4 mg tablet) together with complementary placebos on a double-blind, triple-dummy randomly allocated basis. The bronchodilatation effect was assessed by measuring the peak expiratory flow rate. The bronchodilatation effect was greatest when patients received nebulised salbutamol (p less than 0.05) but lasted longest when they received the tablet (p less than 0.0001); the onset of the effect was rapid with all forms of administration. These results indicate that nebulised salbutamol gives the best relief in severe asthma; in less severe cases, however, a regimen combining the inhalational powder and tablets is sufficient and more convenient.

Gaseous trace analysis using pulsed photoacoustic Raman spectroscopy.

A new method for trace analysis of gases, based on the pulsed photoacoustic Raman spectroscopy (PARS) technique, is described. The method has been applied to the analysis of mixtures of CH(4) in N(2), CO(2) in N(2), and N(2)O in N(2) at concentrations near 1 ppm. The apparatus used is described in some detail. Means of improving the method's sensitivity as well as sensitivity-limiting processes are evaluated. The analytical capabilities of this technique are compared with both direct (IR) absorption and other Raman techniques such as CARS and stimulated Raman gain spectroscopy (SRGS).

Hepatobiliary imaging: a comparison of 99Tcm-dihydrothioctic acid and 99Tcm-pyridoxylidene glutamate in the non-jaundiced patient.

A comparison of two hepatobiliary imaging agents, 99Tcm-dihydrothioctic acid (99Tcm-DHT) and (99Tcm-pyridoxylidene glutamate (99Tcm-PG) has been carried out in 44 non-jaundiced patients. Thirty-one patients were admitted for investigation of upper abdominal pain and 13 patients were volunteers who were undergoing treatment for unrelated conditions. Satisfactory liver images were obtained with both agents in patients without liver disease, but they were inferior to those seen after 99Tcm-sulphur colloid. 99Tcm-PG produced clearer images of the gall-bladder and bile ducts than 99Tcm-DHT. Non-visualization of the gall-bladder was interpreted as gall-bladder disease; in patients with inflammatory gall-bladder disease no gall-bladder image was seen (nine 99Tcm-DHT, nine 99Tcm-PG). The gall-bladder was also not demonstrated in two of the volunteers' group (one 99Tcm-DHT, one 99Tcm-PG), nor was a gall-bladder seen in five patients whose abdominal pain was not due to acute cholecystitis. Despite this, there was agreement between the results of imaging and oral cholecystography in 21 out of 22 subjects. 99Tcm-PG is non-toxic, cheap and rapidly excreted by the liver into the bile. A 99Tcm-PG scan would be useful when rapid diagnosis is required in suspected acute cholecystitis when conventional contrast radiology is unlikely to be of value.

Hepatobiliary imaging: the use of 99Tcm-pyridoxylidene glutamate scanning in jaundiced adults and infants.

99Tcm-pyridoxylidene glutamate (99Tcm-PG) scans have been carried out in 24 jaundiced adults (mean total bilirubin 255 mumol/l and 11 infants with prolonged obstructive jaundice (mean total bilirubin 165 mumol/l). Absence of radioactivity in the gut was interpreted as complete biliary obstruction which was the cause of jaundice in ten adults and six infants. Using this criterion occlusion or patency of the bile ducts was correctly determined in 21 adults and eight infants. False-negative gut images were found in one adult and two infants, and three scans were inconclusive (two adults, one infant). The scan was unable to show details of the site of obstruction or pathology but the technique was simple and atraumatic and was safely performed in patients with serious complications, e.g. renal failure, coagulation defects, septicaemia. In infants the 99Tcm-PG scan compared well with the 131I rose bengal faecal excretion test and with liver biopsy in the investigation of prolonged obstructive jaundice. Repeat scans in infants with biliary atresia were used to assess postoperative bile drainage. It is suggested that 99Tcm-PG scanning is useful screening test in difficult cases of jaundice. It is especially useful in frail patients, and patients with complications.