Immunosuppression by chronic exposure to N-nitrosodimethylamine (NDMA) in mice.

Immunosuppression of humoral and cellular responses following chronic oral exposure to 1, 5, 10, and 20 ppm N-nitrosodimethylamine (NDMA) was examined in CD-1 mice. Monitoring of cumulative mortality and the incidence of peritoneal ascites in animals showed an NDMA dose-related mortality and hepatotoxicity. No visible changes in immunological parameters were noted at the 1 ppm NDMA dose. Immunosuppression of immunoglobulin M (IgM) antibody response by NDMA to sheep red blood cells (SRBC) was time-related, dose-related, and could be reversed within 30 d by removal of the chemical from the drinking water. Cellular immune response, monitored by allogeneic stimulation of cells in mixed lymphocyte reaction (MLR), was markedly suppressed by 10 and 20 ppm NDMA. Thus, chronic exposure to NDMA, except for the low-hepatotoxic doses of nitrosamine, resulted in a marked and persistent immunosuppression of cellular and humoral responses in CD-1 mice. In conclusion, chronic exposure to the hepatotoxic (ascite-inducing) doses of NDMA suppressed humoral and cellular immunity. The persistent immunosuppression could be reversed after the removal of NDMA from the drinking water. Although no direct NDMA-related cancer was reported in humans, our data point to a potential epigenetic carcinogenicity of nitrosamines due to chronic immunosuppression.


Metal levels in regrown feathers: assessment of contamination on the wintering and breeding grounds in the same individuals.

Birds are useful indicators of environmental contamination because they are relatively large, conspicuous, top predators in food chains. However, concentrations of contaminants in a bird's tissues reflect the bird's exposure over wide temporal and spatial scales. Birds are most useful as monitors of exposure when these scales are known. In this paper we report concentrations of lead, cadmium, mercury, and selenium in breast feathers of common terns (Sterna hirundo) and roseate terns (S. dougallii) trapped during incubation at breeding colonies in New York and Massachusetts. Terns arrived on the breeding grounds with breast feathers grown on their wintering grounds, and regrew certain feathers that were plucked for analysis. The regrown feathers were themselves plucked, and both sets of feathers were analyzed. For roseate terns at Cedar Beach and common terns at both sites there was a significant increase in mercury levels in the feathers grown on the breeding grounds compared to those grown on the wintering ground. The differences in mercury were far greater at Bird Island than at Cedar Beach. Selenium levels at Cedar Beach were higher for the regrown feathers than the initial feathers for roseate terns, but not for common terns. Lead and cadmium levels were not significantly different at either site for either species. These results suggest that terns are exposed to significantly higher levels of mercury in the northeastern United States than they are in the wintering grounds in South America.


Biochemical toxicology and disposition of Therminol 66 heat transfer fluid after inhalation or after dietary administration to male Sprague-Dawley rats.

The objectives of this study were to determine the disposition of Therminol 66 in rats and to determine the effects of this heat-transfer fluid on liver and kidney microsomal drug-metabolizing enzymes. Therminol 66 was administered to male Sprague-Dawley rats at various doses as either a single oral administration at 0, 100, or 300 mg/kg, or as a single 6-h inhalation exposure at 0 or 350 mg/m3. Animals were killed 48 h after gavage or after termination of inhalation exposure. Additional groups of animals were exposed to Therminol 66 via the diet at 0, 100, 500, or 5000 ppm for 14 d, or via repeated inhalation exposure at 0, 25, 250, or 1200 mg/m3 for 6 h/d for 14 d. These exposure scenarios represent approximately equivalent doses of Therminol 66 by the different routes of administration. No change in body weight was observed after acute oral or inhalation exposure, and little change in body weight was observed in animals administered Therminol 66 via the diet except at the highest dose. There was no change in kidney weight, and liver weights were increased only at the higher doses of Therminol 66. The body weight gain of animals exposed to Therminol 66 via inhalation decreased in a dose-dependent manner over the 2-wk exposure period. Results from the disposition study indicated that Therminol 66 did not appear to accumulate in the tissues examined and did not appear to be extensively absorbed after a single oral dose of 300 mg/kg. The whole-body elimination half-life was approximately 14 h and occurred primarily via the feces. There was no significant induction of hepatic aryl hydrocarbon hydroxylase (AHH) activity after single oral or inhalation exposures to Therminol 66. Ethoxycoumarin O-deethylase (ECOD) was significantly induced only in animals exposed to 350 mg/m3 via inhalation. Repeated dietary and inhalation exposures resulted in AHH and ECOD induction only at the highest doses, and the kidney appeared to be less sensitive than the liver. Animals exposed via inhalation demonstrated a greater hepatic inductive effect than did animals exposed via the diet, which may be due to absorption differences.(ABSTRACT TRUNCATED AT 400 WORDS)


Contrasting respirable quartz and kaolin retention of lecithin surfactant and expression of membranolytic activity following phospholipase A2 digestion.

Respirable-sized quartz, a well-established fibrogenic mineral dust, is compared with kaolin in erythrocyte hemolysis assays after treatment with saline dispersion of dipalmitoyl phosphatidylcholine, a primary phospholipid component of pulmonary surfactant. Both dusts are rendered inactive after treatment, but the membranolytic activity is partly to fully restored after treatment with phospholipase A2, an enzyme normally associated with cellular plasma membranes and lysosomes. Phospholipid-coated dusts were incubated for periods of 2-72 h at a series of applied enzyme concentrations, and the adsorbed lipid species and hemolytic activity were quantitated at each time for both dusts. Surfactant was lost more readily from quartz than from kaolin, with consequent more rapid restoration of mineral surface hemolytic activity for quartz. Interactions of surfactant and mineral surface functional groups responsible for the mineral-specific rate differences, and implications for determining the mineral surface bioavailability of silica and silicate dusts, are discussed.


Distribution of iodine into blood components of the Sprague-Dawley rat differs with the chemical form administered.

It has been reported previously that radioactivity derived from iodine distributes differently in the Sprague-Dawley rat depending on the chemical form administered (Thrall and Bull, 1990). In the present communication we report the differential distribution of radioactivity derived from iodine (I2) and iodide (I-) into blood components. Twice as much radioiodine is in the form of I- in the plasma of animals treated with 125I- compared to 125I2-treated rats. No I2 could be detected in the plasma. With an increase in dose, increasing amounts of radioactivity derived from 125I2-treated animals distribute to whole blood compared to equivalent doses of 125I-, reaching a maxima at a dose of 15.8 mumol I/kg body weight. Most of the radioactivity derived from I2 associates with serum proteins and lipids, in particular with albumin and cholesteryl iodide. These data indicate a differential distribution of radioactivity depending on whether it is administered as iodide or iodine. This is inconsistent with the commonly held view that iodine (I2) is reduced to iodide (I-) before it is absorbed systemically from the gastrointestinal tract.


Induction of transient airway hyperresponsiveness by exposure to 4 ppm nitrogen dioxide in guinea pigs.

In the present study, we investigated (1) whether airway responsiveness to inhaled histamine-aerosol could be induced during 7-d exposure of guinea pigs to 4 ppm NO2 and, if so, (2) whether thromboxane A2 may be involved in such increase. Female Hartley guinea pigs were divided into 6 groups (n = 15/group). Three groups were exposed to filtered air and the other 3 groups were exposed to NO2 for 1, 3, or 7 d (24 h/d). Baseline specific airway resistance (SRaw0) did not change significantly after exposure to 4 ppm NO2 or air. Airway responsiveness was determined 1 wk before the beginning of exposure and on the day of termination of the exposure. Prior to exposure to NO2, the EC200His, the concentrations of inhaled histamine necessary to double SRawNaCl (SRaw after inhalation of 0.9% NaCl), were 1.07 +/- 0.20, 1.30 +/- 0.20, and 1.01 +/- 0.18 mM for the 3 groups later given NO2 for 1, 3, and 7 d, respectively. Following exposure to NO2 for 1, 3, or 7 d, EC200His values were 1.42 +/- 0.25, 0.66 +/- 0.10 (p < .05), and 1.05 +/- 0.22 mM, respectively. These results show that 7-d exposure to 4 ppm NO2 induced a significant increase in airway responsiveness on d 3. Exposure to air had no significant effect on the airway responsiveness. This transient hyperresponsiveness was inhibited by a specific inhibitor of thromboxane synthetase, OKY 046. These results indicated that (1) a lower concentration (4 ppm) of NO2 than that previously reported can induce transient hyperresponsiveness in guinea pigs during appropriate long-term exposure, and (2) thromboxane A2 may play an important role in this transient airway hyperresponsiveness.


Voltage-dependent potassium currents in cultured trout oligodendrocytes.

Ionic currents were recorded in cultured oligodendrocytes from the brain of trout using the whole-cell configuration of the patch-clamp technique. Outward currents were evoked at membrane potentials more positive than -40 mV, which could be separated into two components according to their kinetic parameters and their sensitivity to the holding potential: a fast inactivating current which was completely suppressed by 4-aminopyridine and reduced by tetraethylammonium and a slow steady-state conductance which was similarly sensitive to both potassium channel blockers. The current reversal potential was close to the potassium equilibrium potential. In contrast to mammalian oligodendrocytes but in similarity with cultured Schwann cells, trout oligodendrocytes did not exhibit any inwardly rectifying currents at hyperpolarized membrane potentials.


Novel stage in the oligodendrocyte lineage defined by reactivity of progenitors with R-mAb prior to O1 anti-galactocerebroside.

The developmentally regulated appearance of surface immuno-reactivity of proligodendroblasts [oligodendrocyte progenitors reacting with monoclonal antibodies A007 and O4, but not anti-galactocerebroside (GalC), i.e., A007/O4+GalC-] to monoclonal antibodies R-mAb and O1 was studied both in culture and in vivo. In both cases staining with R-mAb shortly preceded that with O1; that is, a transient population of R-mAb+O1- cells was observed. R-mAb-O1+ cells were not detected. Differential staining with R-mAb and O1 was also noted at the subcellular level. In younger cultures in which R-mAb+ cells were first acquiring O1 immunoreactivity, many of these cells were stained by O1 only on the cell bodies and proximal portions of the processes, whereas in contrast R-mAb stained the whole cell, including the distal portions of the processes. Only in older, more mature R-mAb+ cells did O1 also stain the distal portions of processes. The expression of reactivity to R-mAb and O1 was compared to the proliferative capacity of the cells. Proliferation [assessed by bromodeoxyuridine (BrdU) incorporation] of both R-mAb+ and O1+ cells was negligible both in culture and in vivo. However, treatment of cells in culture with 10 ng/ml basic fibroblast growth factor resulted in an enhancement of proliferation of the R-mAb+ cells. Within the proliferating R-mAb+BrdU+ population, 80% of the cells were O1- (i.e., anti-galactocerebroside negative). These events occur during a critical period of development when A007/O4+ proligodendroblasts begin to become post-mitotic and express surface galactocerebroside.(ABSTRACT TRUNCATED AT 250 WORDS)


Two-site enzyme immunoassay for beta NGF applied to human patient sera.

Nerve growth factor (NGF) supports sympathetic and sensory neurons in the peripheral nervous system and serves functions in the development and maintenance of cholinergic neurons in the basal forebrain. NGF distribution can be studied with the use of a sensitive two-site enzyme immunoassay (EIA). The monoclonal antibody 27/21 to mouse NGF was recently shown to effectively block the activity of both recombinant human NGF and native mouse NGF, and a two-site EIA using monoclonal antibody 27/21 was optimized. We have now applied this assay to examine NGF levels in normal human serum and serum from Parkinson, Alzheimer, and Huntington patients. To further test the specificity of conjugate binding, dilutions of the human sera were preincubated with an excess of monoclonal NGF antibody 27/21 in solution. With this strategy it was possible to completely block the signal obtained using the two-site EIA. Furthermore, we show that recombinant BDNF and NT-3 do not cross-react with monoclonal antibody 27/21 under our conditions. We found low levels of specific NGF immunoreactivity in normal human sera (0.4 +/- 0.1 ng/ml). Significantly lower levels of NGF were found in sera from patients with Parkinson's and Huntington's disease whereas sera from Alzheimer patients showed only slight reductions in the NGF level. Two patients who had received intracerebral NGF infusions (one with Parkinson's and other with Alzheimer's disease) showed significantly elevated serum levels of NGF during the period of infusion. Due to an inhibitory activity in human serum, it was impossible to demonstrate the low levels of NGF activity in the human serum samples using explanted embryonic sympathetic ganglia, even after concentration by pressure dialysis. Thus, the serum levels are below the limit to evoke a response in NGF-sensitive neurons and thus to expect any physiological effect. Nevertheless, the levels measured may be used as indicators in clinical conditions such as Parkinson's and Huntington's disease.


Cell proliferation and protooncogene induction in oligodendroglial progenitors.

Cell proliferation and the expression of the protooncogenes c-fos and c-jun have been examined in the primary cultures of oligodendroglial (OL) progenitor cells in response to phorbol 12-myristate 13-acetate (PMA), serum, insulin, insulin-like growth factor-I (IGF-I), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF). Combined [3H]thymidine autoradiography and immunocytochemistry was used to assess the mitogenic response of O4 (an oligodendrocyte-specific marker)-positive OL progenitors. In addition, the rate of DNA synthesis was measured by the incorporation of [3H]thymidine into acid-precipitable material. It was found that all of the agents tested stimulated DNA synthesis in OL progenitors and induced a rapid increase in c-fos and c-jun protooncogene expression. The induction of c-fos gene expression and DNA synthesis in response to PMA was completely blocked by 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine (H-7), a potent inhibitor of protein kinase C (PKC), thereby suggesting a role for PKC in the control of c-fos expression and cell proliferation in OL progenitors.


Microtubule-associated protein tau is required for axonal neurite elaboration by neuroblastoma cells.

NB2a/d1 neuroblastoma cells constitutively express multiple isoforms of the microtubule-associated protein tau and incorporate this protein into the axonal neurites elaborated during serum deprivation. To examine whether or not tau played an essential role in axonal outgrowth, cells cultured in serum-free medium were treated at 24 h intervals with antisense- and sense-oriented cDNA oligonucleotides (25 or 36 mers that span or are upstream of tau initiation codon) and were simultaneously serum deprived. Oligonucleotide uptake was confirmed by determination of intracellular levels of radiolabeled oligonucleotides. Treatment for 48 h with tau antisense oligonucleotides reversibly inhibited the expression of tau and the number of neurite-bearing cells compared with treatment with sense oligonucleotides. By contrast, tubulin expression was not affected. When cells were treated with antisense oligonucleotide simultaneously with serum deprivation, the initial outgrowth of neurites was unaffected, but continued neurite elongation was prevented. By contrast, neurite outgrowth at 4 h was inhibited when cells were pretreated with tau antisense 24 h before serum deprivation. Furthermore, intracellular delivery of anti-tau antiserum prevented neurite outgrowth and, in cells that had previously been deprived of serum for 24 h, induced retraction of existing neurites. These findings indicate that both the initiation and the continued outgrowth of neurites are dependent on tau and that pre-existing cytoplasmic pools of tau can mediate initial neuritogenesis.


EAE cerebrospinal fluid augments in vitro phagocytosis and metabolism of CNS myelin by macrophages.

Previous studies from this laboratory have shown that CNS myelin is phagocytized and metabolized by cultured rat macrophages to a much larger extent when myelin is pretreated with serum containing antibodies to myelin constituents than when it is left untreated or pretreated with non-specific serum. In this study the effect of cerebrospinal fluid (CSF) from rabbits with experimental allergic encephalomyelitis (EAE) in promoting myelin phagocytosis was examined. Fourteen rabbits were immunized with purified myelin in Freund's complete adjuvant, seven of which developed clinical EAE symptoms. Serum and CSF were collected from EAE and control rabbits, and the CSF was centrifuged to remove cells. Sera and CSF from these rabbits and from Freund's adjuvant-immunized controls and untreated controls were measured for IgG content by radial diffusion assay, their myelin antibody characteristics were analyzed by immunoblots, and the ability of these serum and CSF samples to promote myelin phagocytosis when used for myelin opsonization was examined. The ability of a CSF sample to enhance radioactive myelin uptake and phagocytosis by cultured macrophages as measured by the appearance of radioactive cholesterol ester was linearly proportional to its total IgG titer, and correlated approximately both with clinical symptoms of the animal and the presence of antibody against the myelin constituents myelin basic protein, proteolipid protein, and galactocerebroside. The cholesterol esterification activities of EAE sera correlated to a lesser extent with IgG levels and clinical symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)


The morphological localization and biochemical characterization of a synapsin I-like antigen in the nervous system of Aplysia californica.

Synapsins are a well-characterized class of phosphoproteins found at synapses in the mammalian nervous system. One member of this family, synapsin I, has been extensively studied and shown to associate in a phosphorylation-dependent manner with both small synaptic vesicles and cytoskeletal elements. Though the characteristics of synapsin I suggest an important function in synaptic transmission, its definitive role is still in question. In an effort to find a model system in which to test directly the function of synapsin I, we have looked in the nervous system of the marine mollusc Aplysia californica for synapsin I-like antigens (SILA). Light microscope immunocytochemical studies using polyclonal and monoclonal antibodies to bovine brain synapsin I demonstrate Aplysia SILA in neuronal somata, in the neuropil, and at some identified synapses. Though SILA were exclusively associated with neuronal structures in Aplysia, the pattern of staining suggested that they are not present at all synaptic terminals. This interpretation was corroborated by ultrastructural studies in which SILA were present at some synaptic terminals but absent, or in low abundance, in adjacent terminals. In axons, SILA were associated with vesicles of 120-150 nm diameter, as well as with filamentous structures. Biochemical studies identified small amounts of SILA of 40 and 50 kD molecular weight that are recognized by several antibodies to mammalian synapsin I, and are acid extractable, collagenase-sensitive phosphoproteins; these are criteria used to define synapsin I homologues in other species. Our studies indicate that SILA are present in neurons in Aplysia californica but suggested that they represent only a small percentage of the total protein within the nervous system.


Enhanced permeabilities of cationized-bovine serum albumins at the blood-nerve and blood-brain barriers in awake rats.

Permeability-surface area products (PAs) of the blood-nerve barrier (BNB) and blood-brain barrier (BBB) to 125I-labeled native bovine serum albumin (nBSA, pI approximately 4), and to 2 cationized albumins (cBSA) of differing pI (pI approximately 8 and 11), were quantitatively determined in awake rats, using an i.v. bolus injection technique. Mean PAs of the BNB and BBB to 125I-nBSA, after a circulation time of up to 120 min, were (0.17 +/- 0.23) and (0.09 +/- 0.05) x 10(-5) ml/s.g. wet wt, respectively (n = 12 rats), and were not significantly different from 0 (P greater than 0.05). Mean PAs of the BNB and BBB to 125I-cBSA (pI approximately 8), after circulation time of 12 min, were (1.9 +/- 0.1) and (1.7 +/- 0.1) x 10(-5) ml/s.g wet wt, respectively (n = 8). Significant greater PAs, at both the BNB and BBB to 125I-cBSA (pI approximately 11) [(8.2 +/- 1.8) and (3.0 +/- 0.6) x 10(-5) ml/s.g wet wt, respectively (n = 12)], than both PA's of nBSA and cBSA (pI approximately 8) were found. The accumulation of 125I-cBSA in epi-perineurial tissues also was higher than that of 125I-nBSA, and was related to the degree of cationization. Our results indicate that, as at the BBB, the transfer of cationized serum albumin is enhanced over that of native albumin at the BNB of the mammalian peripheral nerve.


Immunocompetent cell markers in human fetal astrocytes and neurons in culture.

During the past few years, evidence has accumulated that interaction with peripheral immune cells as well as immunoregulatory functions in the central nervous system (CNS) can be played by several types of brain resident cells. Since very little information is available in man, however, we investigated the presence of markers so far considered typical of immunocompetent cells in in vitro cultures of human fetal brain. Immunocytochemistry at the light, scanning, and transmission electron microscopic levels revealed positivity for a very restricted range of macrophage antigens in astrocytes, which, however, were incapable of phagocytosis. In particular, expression of the major histocompatibility complex-class II antigen HLA-DR was observed in the cytoplasm and on the cell surface of GFA-P+ astrocytes and increased with time in culture and cell passages. Among the T-lymphocyte markers tested, Thy.1 and CD4 were positive. Both neurons and astrocytes carried Thy.1 from early cell passages. Noteworthy was the presence of CD4, which serves as the receptor for AIDS virus, in neurons from the first 2 weeks, whereas astrocytes became positive after only 4-6 weeks. Even if most staining was in the cytoplasm, some was exposed on cell surface. Astrocytes were found positive for the B-lymphocyte marker CD21, the cellular receptor for Epstein-Barr virus, whereas CD24 was detected in both neurons and astrocytes. Both antigens are related to B-cell proliferation. Results are in favour of the hypothesis of human brain cells being actively involved in CNS immunological events.


Nerve growth factor receptor gene expression in human peripheral blood lymphocytes in aging.

Nerve growth factor (NGF) has a modulating effect on immune function, which may occur as a consequence of binding to the NGF receptor (NGF-R). To determine if mRNA for the gene coding for p75NGFR (low affinity NGF-R) is present in lymphocytes, Northern blot analysis of mRNA from human peripheral blood lymphocytes (PBL) and purified T lymphocytes was initiated using cDNA probe for human p75NGFR. p75NGFR mRNA was present in PBL and T lymphocytes, and the mRNA in response to phytohemagglutinin stimulation showed maximum levels at 14 hr of stimulation. p75NGFR mRNA content when analyzed in PBL and T cells from volunteers of various ages showed that p75NGFR mRNA expression does not change with the age of the cell donor.


Effect of dark rearing on the volume of visual cortex (areas 17 and 18) and number of visual cortical cells in young kittens.

The surface area, total volume, and total number of neurons of areas 17 and 18 in one hemisphere of dark-reared (DR), dark-reared and light-exposed (DRL), and normally reared (NR) kittens were studied at the age of 6 weeks. The thickness of the visual cortex was lower by 13% and 11% (area 17) and by 17% and 16% (area 18) in DR and DRL groups, respectively, when compared with similar cortical areas in NR kittens. The surface area values of area 17 were nearly the same in DR and DRL kittens, both being, however, 37% smaller than in NR animals. The surface area of area 18 was significantly smaller than that of area 17 in each group, and was also lower in DR (by 27%) and DRL (by 21%) groups when compared with the NR group. As a consequence of dark rearing, the numerical density of cortical neurons in area 17 amounted to about double of the value observed in normally reared kittens and was also significantly higher in area 18. The numerical density of nerve cells of DRL kittens fell between the DR and NR groups. The total cortical volume of area 17 was similar in DR and DRL groups but it was by 46% (DR) and by 44% (DRL) smaller than in NR kittens. In each experimental group, the total volume of area 18 was significantly smaller than that of area 17. The cortical volume of area 18 was also smaller than in the NR group by 39% and 34% in DR and DRL groups, respectively. In DR and NR kittens, the total numbers of neurons in areas 17 (DR = 26.4 million, NR = 25.7 million) and 18 (DR = 8.5 million, NR = 9.0 million) were essentially similar. In the DRL groups a significantly smaller number of cortical neurons was found both in area 17 (21.5 million) and in area 18 (6.8 million). It is concluded that, in spite of considerable differences in the cortical thickness, surface area, numerical density, and total cortical volume, the absolute numbers of neurons in area 17 and 18 of visually deprived (DR) and NR kittens do not differ at 6 weeks of age. The main deficit in cortical organization following dark rearing, therefore, appears to be confined mainly to the neuropil, as a result of an underdevelopment of neuronal processes and of depressed synaptic organization.(ABSTRACT TRUNCATED AT 400 WORDS)


The effect of the new trauma DRGs on reimbursement.

Reimbursement for trauma care based on prospective payment has not been satisfactory. The Health Care Financing Administration introduced four new Multiple Significant Trauma (MST) DRGs in 1991 with the intention of covering patients who have had at least two body sites injured. To determine the effect if any on reimbursement, a sample of patients who were assigned the new DRGs over a 5-month period were analyzed. The analysis compared the calculated reimbursement for these 49 patients based on their total accumulated charges, DRG weights, and the average Medicare dollar blend along with the additional weight factor specific for the study facility. This analysis was compared with an additional analysis determining the reimbursement performed on the same patient sample but with DRG weights determined from DRGs derived from the 1989 DRG GROUPER/FINDER. During the 5-month study period, 5.5% of the patients discharged from the hospital has sustained at least one injury covered by ICD-9-CM codes. Of these, 49 (3.9%) were classified into one of the four new MST DRGs. The majority of patients were male (75.5%), the mean age was 31.8 years, and the total charges accumulated were $1,809,192.23. The calculated DRG-based reimbursement was $1,183,495.40, or 65.5% of the total charges. In the second part of the study, using the DRGs available in 1989 for the same sample of patients, the DRG-based reimbursement was $691,437.72, or only 38.2% of the accumulated charges.(ABSTRACT TRUNCATED AT 250 WORDS)


Invalidation of the APACHE II scoring system for patients with acute trauma.

The APACHE II scoring system has been promulgated as a useful tool in the assessment of the severity of injury and prognosis for acutely ill patients. The physiologic basis for stratification is weighted toward older patients with chronic medical conditions. Recently, the APACHE II system has been proposed as a method for determining diagnosis related group (DRG) reimbursement for individual trauma patients. The present study applied the APACHE II scoring system to 280 patients with blunt or penetrating trauma who had documented systolic blood pressure < 90 mm Hg. Fifty-seven (20%) died of their injuries within the first 24 hours. APACHE II scores were recorded both in the emergency room (ED) and at 24 hours following admission. Injury Severity Scores (ISS), Revised Trauma Scores (RTS), and TRISSCAN were calculated. The APACHE II (n = 223) recorded at 24 hours (2.5 +/- 0.2) was significantly less than that recorded in the ED (6.6 +/- 0.3, p < 0.05, Mann-Whitney analysis). Using regression analysis, there was no correlation between APACHE II and ISS if recorded in the ED (r2 = 0.06) or 24 hours following admission (r2 = 0.08). APACHE II also demonstrated a poor correlation with the length of hospital stay (r2 = 0.03 [ED], = 0.19 [24 hours]). Whereas APACHE II may be helpful in defining severity of disease among patients with acute-on-chronic medical conditions, the classification lacks an anatomic component, which is essential to assess the magnitude of acute injury in patients who are typically otherwise healthy.


The management of gunshot wounds to the face.

Treatment principles for penetrating neck trauma are well described yet few exist for facial injuries. To help delineate these issues, we viewed our recent experience with gunshot wounds to the face. Since 1986 we have treated 100 patients with such injuries. Their mean age was 28.9 years (range, 12-77 years). There were 89 male patients and 11 female patients. Ninety-six patients were considered stable on initial examination. Yet 35 patients required urgent airway control in the ED; only two needed a surgical airway. Emergency angiography was performed in 37 patients; 19 vascular injuries were identified. Eleven required therapy for vascular injuries, five by neck exploration and six by embolization. In 15 patients the trajectory suggested an intracranial injury, i.e., across the base of the skull. Although 14 of 16 patients were awake and alert at examination, head CT scans demonstrated serious intracranial pathologic processes in 9 patients. Sixty-seven patients sustained bony injury, 19 patients a significant nonvascular soft-tissue injury, and 38 patients a significant neurologic injury (26 peripheral, one spinal and 20 cerebral injuries). Ultimately, 44% of all patients required some surgical treatment and 25% had a complication from their injury. Six patients died, three of CNS injury, one of exsanguination, and two of sepsis. The bony, soft tissue, nervous, and vascular anatomy make the management of gunshot wounds to the face challenging. Although initially stable, many patients require early airway control and urgent work-up for vascular and intracranial injuries. Early subspecialty input is helpful in delineating the often complex injury pattern and planning an optimal management strategy.


Utilization of trauma-related deaths for organ and tissue harvesting.

A randomized retrospective analysis of patients who suffered trauma-related deaths over 36 months (May 1987-April 1990) was performed to study their utilization as candidates for organ and tissue harvesting. There were a total of 108 patients: 79 males, 29 females. The average age was 46.2 years; 38 (36%) of these patients were 65 years of age or older. Over 50% of fatalities were the result of motor vehicle crashes. There were 61 potential tissue donors. Forty-three were lost without documentation of a request for organ procurement. There were 23 patients with potentially salvageable organs: one candidate was lost without documentation of a request for organ procurement. Twenty-eight (26%) of the patients had support withdrawn; 16 were 65 years old or older. Brain death protocol was instituted in 17 (20%); organs were obtained from 70% of these patients. Reasons for failure of procurement after request by a physician included family refusal in seven cases, cardiopulmonary arrest during brain death protocol in two cases, and religious bias in one candidate. Twelve patients were organ donors: 10 patients were tissue donors. We conclude that the greatest source of underutilization lies in the failure to request tissue for harvesting, since there were no isolated tissue donors. Pertinent information should be more widely distributed to physicians regarding candidacy for tissue donation. Further consideration of the adequacy of organs or tissue in relation to the candidates' age should be given, since patients aged 65 years and older can be a significant source of potential donor candidates.(ABSTRACT TRUNCATED AT 250 WORDS)


Could the oxygen cost of breathing be used to optimize the application of pressure support ventilation?

Pressure support ventilation (PSV) is a new ventilator modality that augments spontaneous inspiratory pressure with selected levels of positive airway pressure. There is presently considerable interest in its use in the management of critically ill, ventilator-dependent patients. The optimal method for application has not yet been established. This study investigated the effects of PSV on the oxygen cost of breathing (OCOB), a clinically applicable technique for quantitating the work of breathing. The OCOB and other bedside variables of pulmonary function were measured during PSV in ventilator-dependent patients where weaning was limited by an inability to sustain respiratory work. Nine studies were performed in 8 patients in the surgical intensive care unit. The OCOB, tidal volume (VT), respiratory rate (RR), and minute ventilation (VE) were measured at various levels of pressure support. The OCOB was calculated from the difference in oxygen consumption (VO2) during mechanical and spontaneous ventilation both at CPAP and with PSV. With increasing levels of PSV, the OCOB was observed to steadily decrease from 22% to 8% (p < 0.001). There were also statistically significant increases in VT and decreases in RR. VE appeared not to be influenced. The results of this study suggest that the bedside measurement of the OCOB may be an accurate, simple, and reproducible method of titrating the level of applied pressure support in order to optimize respiratory work.


Continuous pulse oximetry and the diagnosis of pulmonary embolism in critically ill trauma patients.

The diagnosis of pulmonary embolism (PE) may be difficult to establish in trauma patients, particularly those who are unresponsive or mechanically ventilated. Based on a prior retrospective study, we hypothesized that patients monitored by continuous pulse oximetry who experienced a 10% or greater sudden sustained drop in arterial oxygen saturation (SaO2) without a change in static lung compliance (Cst) were most likely to have had a PE. We followed SaO2 in 972 patients admitted to our trauma ICU during the 18-month period ending in December 1990. Forty-eight patients (5%) with SaO2 changes, but no Cst changes, were evaluated for suspected PE using pulmonary arteriography (PA). Of these, 21 (44%) had a positive PA study. All patients with a positive PA had either clear chest roentgenograms or no change in underlying pulmonary pathologic processes. Of the remainder, 26 had evidence of a new pathologic entity on chest roentgenograms and only one patient had a SaO2 decrease, no change in Cst, and a negative PA. All mechanically ventilated trauma patients should have SaO2 monitored continuously. Patients with a > 10% drop in Sao2 with no change in Cst and no new roentgenographic chest findings should undergo PA. Based on our experience, this approach would yield a sensitivity, specificity, and predictive value of 100%, 99.9%, and 95%, respectively, for the diagnosis of clinically significant PE.


Venous injuries of the lower extremities and pelvis: repair versus ligation.

Many surgeons advocate repair of venous injuries to prevent the sequelae of venous ligation. Since 1986, we have treated 74 patients with 79 venous injuries of the lower extremity or pelvis. There were 68 men and six women with a mean age of 29.2 years (range, 16-62 years). The mechanisms of injury were gunshot wounds in 61 patients, stab wounds in 11 patients, and shotgun wounds and blunt trauma in one patient each. Forty-eight injuries were treated by ligation; 31 injuries were treated by repair. Repairs included two interposition grafts, eight end-to-end repairs, 16 venorrhaphies, and five vein patches. In addition, we developed a venous injury staging system (VIS), which ranged from grade I (less than 50% laceration) to grade IV (complete interruption with soft-tissue injury). Patient age, mechanism, location of injury, associated injuries, and incidence of arterial injury were not different between the patients treated by ligation and those treated by repair. Patients treated with venous ligation had a greater VIS (mean, 3.45 vs. 2.0), a greater incidence of shock (71% vs. 39%), and higher transfusion requirements (9.23 vs. 4.82 units). Postoperative morbidity rates were identical, however. There was no increase in the need for fasciotomy in patients treated with venous ligation. Eighty-six percent of the patients treated by ligation were totally free of edema at discharge. The others had only mild edema that did not interfere with daily activities at discharge and follow-up. Ligation is a safe alternative to repair in patients with injuries to the lower extremities or pelvis.(ABSTRACT TRUNCATED AT 250 WORDS)


Trauma center closures: a national assessment.

A 1990 national survey of 66 closed trauma centers across 14 states was conducted to ascertain the factors that prompted closure. Data from 44 facilities, or 67% of the centers identified, indicate that inadequate financing and physician participation were commonplace. The findings support the work of other investigators and demonstrate that uncompensated care, inadequate reimbursement, high operating costs, and lack of physician support all adversely affect trauma care in both urban and suburban settings.


On-scene helicopter transport of patients with multiple injuries--comparison of a German and an American system.

Hospital-based helicopter services from a German (GER) and an American (AMR) university-affiliated trauma center were reviewed. All patients with multiple injuries transported via helicopter from the scene to the trauma centers during a 1-year period were included. The patients were comparable regarding mechanism of injury, age, flight times, mean ISS, ISS distribution, and number of severe injuries per body region (patients with AIS score > 3 for head, thorax, and abdomen). Overall mortality was 21 of 221 (9.5%) for GER and 21 of 186 (11.3%) for AMR (NS). Survivor-based TRISS analysis yielded Z statistics of +2.459 for GER (p < 0.025) and +1.049 for AMR (NS). M statistics were 0.89 for GER, 0.874 for AMR; the W statistic +1.35 for GER. There were nine unexpected survivors (Ps < 0.50) for GER and six for AMR. There was a significantly higher (p < 0.01) number of early deaths (< 6 hours) in AMR (12; ISS = 56) than in GER (four; ISS = 64). Analysis of the prehospital data demonstrated significant differences in the mean volume of IV fluids infused: 1800 mL, GER; 825 mL, AMR (p < 0.05); rate of intubation: 82 of 221 (37.1%) GER; 24 of 186 (13.4%) AMR (p < 0.001); and thoracic decompressions: 20 of 221 (9.1%) GER; 1 of 186 (0.5%) AMR (p < 0.001). Prehospital care in the GER system is directed on scene by a trauma surgeon member of the flight crew compared with a nurse/paramedic team with remote medical control in the AMR system.(ABSTRACT TRUNCATED AT 250 WORDS)


Initial and subsequent hospital costs of firearm injuries.

To provide economic, epidemiologic, and clinical data on initial and subsequent hospitalizations for firearm injuries. Nonconcurrent prospective study; data obtained by medical records review. Public university teaching hospital, designated a level I trauma center. Two hundred fifty persons first hospitalized for firearm injuries at UC Davis Medical Center, Sacramento, between January 1, 1984, and June 30, 1985, and followed by medical records review to June 30, 1989. The aggregate hospital charge for 250 firearm injuries, exclusive of professional fees, was $3,745,496, of which 80% was borne directly or indirectly by public funds. The charge for initial hospitalizations was $3,297,506. Mean and median initial charges per case were $13,190 and $5,996 respectively; range, $787-$494,152. The five patients with charges over $100,000 accounted for 33% of all charges; 36% of all patient days were attributable to the eight patients with hospitalizations lasting more than 30 days. Thirty-one patients were rehospitalized a total of 71 times; charges for rehospitalization totaled $447,990. Three fourths of all charges resulted from handgun injuries. The costs for hospital treatment of firearm injuries are substantial. Avoiding prolonged hospitalization may be helpful in controlling these costs, but will be difficult to achieve. Primary prevention of firearm injuries may be the most effective cost-control measure.


Differential effects of cyclo-oxygenase and thromboxane synthetase inhibition on ventilation-perfusion relationships in acid aspiration-induced acute lung injury.

Cyclo-oxygenase metabolites are important regulators of pulmonary vascular and airway tone and may act to regulate ventilation-perfusion (VA/Q) relationships. Hypoxemia that follows aspiration of gastric acid is associated with increased venous admixture, and plasma levels of thromboxane (TX) B2 and 6-keto-PGF2 alpha are increased after experimental acid-induced acute lung injury. The present study was designed to determine the effects of cyclo-oxygenase metabolites on VA/Q relationships in canine acid aspiration. Eighteen anesthetized dogs received 0.2 mL/kg 0.1 N HCl intratracheally; six were pretreated with ibuprofen (IBU), a cyclo-oxygenase inhibitor, 12.5 mg/kg IV, and six other dogs received OKY-046 (OKY), a TX synthetase inhibitor, 0.5 mg/kg IV. The remaining six animals (ACID) served as controls. Continuous distributions of ventilation and perfusion were evaluated with the multiple inert gas elimination technique. Within 30 minutes, acid injury resulted in significant (p < 0.05) decreases in PaO2 from baseline values by 44.7 +/- 5.4 and 47.6 +/- 4.8 mm Hg in the ACID and OKY groups, respectively. Although decreased, the change in PaO2 of 21.0 +/- 4.8 mm Hg in IBU animals was significantly (p < 0.05) attenuated in comparison with the other groups. Ibuprofen increased pulmonary vascular resistance, attenuated perfusion to shunt and low VA/Q areas, and reduced ventilation to unperfused areas for the first 2 hours after acid injury (all p < 0.05), whereas OKY exacerbated hypoxemia and VA/Q inequality.(ABSTRACT TRUNCATED AT 250 WORDS)


Lethal Staphylococcus aureus-induced shock in primates: prevention of death with anti-TNF antibody.

A successful experimental treatment for gram-positive sepsis to our knowledge has not been achieved. The objectives of this study were to develop a nonhuman primate model of lethal gram-positive sepsis employing the micro-organism Staphylococcus aureus and to determine the efficacy of treatment using monoclonal antibody (MAb) to tumor necrosis factor alpha (TNF). The antibody was administered intravenously, 15 mg/kg, 30 minutes after the beginning of a 2-hour infusion of S. aureus, 4 x 10(10) colony forming units/kilogram. The baboons infused with S. aureus demonstrated the release of the cytokines TNF and interleukin-6 (IL-6), but endotoxin was not observed in the plasma at any time. Treatment with antibody to TNF abolished the rise in serum TNF levels and reduced the increased levels of IL-6. Treatment with MAb to TNF prevented multiple organ failure and achieved permanent (> 7 day) survival of all baboons.


Pulmonary damage after intramedullary femoral nailing in traumatized sheep--is there an effect from different nailing methods?

Stabilization of femoral shaft fractures is a controversial issue in the management of patients with multiple trauma. Intramedullary nailing usually is preferred primarily; in recent years, however, pulmonary complications (e.g., ARDS) have been reported that were attributed to the reaming procedure. To study the effects of different nailing methods in a model of severe trauma, hemorrhagic shock and lung contusion were created at day 1 in sheep prepared by the method described by Staub. After recuperation (day 3) the animals in the study group (group 1) underwent intramedullary nailing of a closed femur without prior reaming; group 2 was treated with reaming and nailing according to AO standards. The reaming procedure led to an acute increase of pulmonary arterial pressure only in group 2 (19.8 +/- 2.1 to 31.0 +/- 4.6 mm Hg). Pulmonary triglyceride levels increased at parallel time points from 18.27 +/- 2.3 to 33.04 +/- 7.37 mg/dL only in group 2. Stimulatory capacity of polymorphonuclear leukocytes (PMNL) increased in the study group and decreased in controls (group 1: 2.652 +/- 0.23 x 10(6) cpm to 3.387 +/- 1.34 x 10(6) cpm; group 2: 2.699 +/- 0.34 x 10(6) cpm to 2.460 +/- 0.187 x 10(6) cpm). Intramedullary nailing caused an increase of lung capillary permeability in both groups; in the study group less damage was seen (group 1: 0.390 +/- 0.0006 to 0.354 +/- 0.011; group 2: 0.391 +/- 0.0004 to 0.336 +/- 0.015; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Cost and complications during in-hospital transport of critically ill patients: a prospective cohort study.

We prospectively studied transport of a group of 100 surgery/trauma patients and a matched control group in the ICU. APACHE II scores for the two groups were 23 +/- 6 and 20 +/- 8. During transport both groups had ECG, heart rate, blood pressure, and oxygen saturation continuously monitored. We also determined the cost and results of transport for those patients requiring diagnostic testing. There were six diagnostic tests performed: CT scan of the abdomen (39%), CT scan of the head (31%), CT scan of the chest (8%), CT scan of the cervical spine (4%), angiography (14%), and tomography (4%). Average transport time was 74 +/- 16 minutes with a range of 20-225 minutes. Physiologic changes defined as a BP +/- 20 mm Hg, heart rate +/- 20 beats/min, respiratory rate +/- 5 breaths/min, or oxygen saturation +/- 5% for 5 minutes duration occurred in 66% of transported patients and 60% of ICU patients. There were no differences in arterial blood gas levels before and during transport. In 39% of transports, the results of diagnostic testing produced a change in patient management within 48 hours. Abdominal CT scanning and angiography were associated with the highest percentage of tests leading to a management change (51% and 57%). The average charge to the patient was $612.00 and the average cost to the hospital $452.00. Our results suggest that while physiologic changes are frequent during transport, they are also frequent in ICU patients as a consequence of the severity of illness.(ABSTRACT TRUNCATED AT 250 WORDS)


An evaluation of provider-related and disease-related morbidity in a level I university trauma service: directions for quality improvement.

As the number of preventable trauma-related deaths plateaus as a result of trauma system development, new directions for quality improvement in trauma care must come from analyzing morbidity with standardized methods to establish thresholds for provider-related and disease-specific complications. To establish such thresholds and determine priorities for improvements in quality all trauma patients who died, who were admitted to the ICU or OR, who were hospitalized for more than 3 days, or who were interfacility transfers to an academic trauma service, were concurrently evaluated for 1 year. All complication events were defined, reviewed, tabulated, and classified using 135 categories of complications. These categories were subdivided into provider-specific and disease-specific complications. Provider-related complications were classified as justified or unjustified to allow identification of events with a potential for improvement. A total of 1108 patients were admitted (mean ISS, 17); there were 97 deaths. Three potentially preventable deaths were identified, 857 complication events were identified, and 285 provider-related complications were responsible for errors with potential for improvement in 59 events (21%). Disease-specific morbidity was primarily related to infection; pneumonia accounted for 36% of all infectious complications and systemic infection for only 8.6% of infectious complications. Organ failure and other major systemic complications occurred in 2%-8% of patients. This type of analysis forms the basis on which to determine thresholds of provider-specific and disease-specific morbidity in a trauma hospital and serves as a guide to direct efforts toward continuous quality improvement.


A study of recovery in trauma patients.

Although the majority of trauma patients are discharged home rather than to a rehabilitation facility, the timeliness of their return to function (RTF) has received little study. The present prospective study attempted to identify those factors that would predict delayed RTF. The study group consisted of patients admitted to a level I trauma center for at least 24 hours, who were of working age (18-64 years), who passed a cognitive screening examination, and who were discharged home. Demographic data and psychological profiles were collected on all participants. Patients were followed by telephone at approximately 1 1/2, 3, and 6 months after discharge. Five hundred seventy patients were entered into the study; complete follow-up data were available for 441. Statistical methods were modeled after survival analysis using a proportional hazards multiple regression to identify variables prognostic of RTF time. This type analysis is independent of time, providing a "risk" of RTF at any point in time after the injury. It also allowed the calculation a relative hazards ratio (RHR), which quantifies the impact of a prognostic variable on RTF time. Injury Severity Score (ISS) and age were found to be associated with RTF (p < 0.0001 for each). After correcting for ISS and age, five additional factors were found to be associated with RTF. Higher educational level and living in a non-family household were associated with faster RTF. Less than 100% income replacement by disability income, pre-injury hostility, and litigation related to the injury were associated with slower RTF. There were a number of other demographic, work-related, and psychosocial factors that were not related with RTF.(ABSTRACT TRUNCATED AT 250 WORDS)


Management of trauma and emergency surgery in space.

Trauma may cause morbidity or mortality in expeditionary spaceflight settings. Physiologic and mechanical changes related to microgravity may increase susceptibility to and complicate the management of injuries in spaceflight. Limited surgical experience in microgravity suggests that special apparatuses and techniques will be needed to maintain the stability of patients, surgeons, and equipment, and to control fluids. A prototype microgravity surgical workstation and suction unit and modifications of standard procedures were devised to address these needs. Using these devices and methods and selected surgical supplies during repeated 25-second intervals of microgravity generated by parabolic arc flight, the "ABCs" of trauma management, limb traction and immobilization, and minor surgical procedures were performed in flight and problems were identified. Convincing "qualification" of spaceflight surgical equipment and protocols will require evaluations in continuous microgravity. As on Earth, the major determinant of emergency surgical care in spaceflight may be the presence or absence of a well-trained surgeon.


Duplex ultrasonography versus arteriography in the diagnosis of arterial injury: an experimental study.

Duplex ultrasonography (DUS) and arteriography (ART) were evaluated using an experimental model of arterial trauma in order to determine the accuracy of DUS compared with ART and to define the characteristic ultrasonographic features of arterial injuries. Occlusions (n = 19), blunt injuries (n = 24), lacerations (n = 25), arteriovenous fistulae (n = 13), or no injuries (sham, n = 19) were surgically created in the femoral and carotid arteries of 25 dogs. Following closure of the incisions, DUS was performed and interpreted by a staff vascular surgeon without knowledge of the presence or type of injury. Biplane selective ART was evaluated by an independent staff radiologist. Although DUS and ART were equally accurate in evaluating arterial injuries, DUS was more sensitive (90.1% +/- 3.3% versus 80.2% +/- 4.4%, p = 0.002) and better at identifying lacerated arteries (p = 0.01). However, ART had greater specificity (94.7% +/- 5.1% versus 68.4% +/- 10.7%, p = 0.04) and was more accurate for identifying normal arteries (p = 0.04). The validity of DUS increased in the latter half of the study, thus demonstrating a learning curve. Duplex ultrasonography was a more sensitive screening modality than ART for evaluating arterial injuries in our experimental model, thereby supporting its use in clinical trials to evaluate its accuracy, reliability, and cost effectiveness in the trauma setting. Furthermore, management decisions can be based on the specific type of injury, pathologic condition of the arterial wall, and hemodynamic factors identified by DUS. Clinically occult arterial injuries can be followed by repeat DUS to define the natural history of these injuries.


Sagittal liver transection--an injury from improperly worn shoulder harness seatbelts: a report of two cases.

We have identified two cases which exemplify the typical injury caused by the under-the-arm placement of a shoulder harness (without the associated lap belt) in frontal collisions, namely, fatal liver laceration in the sagittal plane. Trauma care personnel should be alert for this type of rapidly fatal abdominal injury that occurs even in low-speed impacts. A prominent warning label on these belts regarding proper placement and the need for use of the associated lap belt may be appropriate.


Effect of chronic hypoxia on fibronectin in plasma, bronchoalveolar lavage fluid and liver of rats.

The present study was undertaken to measure fibronectin (FN) concentration in plasma and bronchoalveolar lavage fluid (BALF) with an enzyme linked immunosorbent assay (ELISA) method, to observe the distribution of FN in liver with an immunohistochemical stain method and to investigate the effect of chronic normobaric hypoxia on them in experimental rats. The results showed that chronic hypoxia caused a significant decrease in plasma FN concentration while BALF FN concentration and the distribution of FN in the liver were not significantly affected, suggesting that the change in FN in the lower respiratory tract can not be reflected by the change in plasma FN concentration and that the decrease in plasma FN concentration can not be attributed to the change in liver FN secretion. The decrease in plasma FN concentration may lead to a decrease in the defence ability of the body and may contribute to the development of hypercoagulability observed in some patients with chronic hypoxia.


Analysis of the biocompatibility of magnetic porous tricalcium phosphate ceramics in rat femurs.

A new biomaterial, magnetic porous tricalcium phosphate ceramics (MPTCP), may be used for repairing defects in bones as a substitute for bone grafting. This study was designed to examine its biocompatibility and the systemic toxicity. The ceramic sections, approximately 15.3 mg, were implanted into both proximal femurs of 10 male and 10 female albino SW rats. An equal number of male and female animals served as sham-operated controls. Implantation of MPTCP ceramics in rat femurs had no deleterious effects on body weight, organ/body weight ratio, and on blood, liver and kidney functions. Plasma levels of inorganic phosphorus were significantly elevated in rats implanted with MPTCP ceramics. Alkaline phosphatase values in plasma in the experimental group were equal to those in the control group. Photomicrographs, radiographs and scanning electron photomicrographs of the rat femurs implanted with MPTCP ceramics demonstrated excellent bone association with implants and growth of some new bone into MPTCP ceramics. In conclusion, MPTCP ceramics are biocompatible and suitable for the reconstruction of bones.


Effects of dietary oils on pulmonary vascular reactivity and chronic hypoxic pulmonary hypertension in rats.

The effects of dietary oils on pulmonary vasoreactivity and chronic hypoxic pulmonary hypertension were assessed in rats fed on soybean oil (SO), pig oil (PO), soybean oil plus pig oil (SP) or a regular diet (HC) started two months before the onset of chronic normobaric hypoxia (10 +/- 0.5% O2 ventilation, 8 h per day, for 14 days). The mean pulmonary arterial pressure and pulmonary vasoreactivity to acute hypoxia were higher in the SO group than in the PO, SP and HC groups. Hypertrophy of the right ventricle in the SO group was more serious as well. Blood viscosity and hematocrit were augmented by chronic hypoxic in SO, PO, PS and HC groups, but no significant differences were found among them. The findings suggest that dietary soybean oil can potentiate hypoxic pulmonary vasoconstriction, and thereby promote the development of pulmonary hypertension and right ventricular hypertrophy.


Prognostic significance of DNA flow cytometry in non-Hodgkin's lymphoma.

A series of cases of non-Hodgkin's lymphoma (NHL) were studied by morphology and flow cytometry. The DNA analysis was performed by applying a trypsin digestion method to archival paraffin-embedded samples. DNA aneuploid tumors constituted 47.4% of the total cases, and the frequency in the intermediate and the high malignant grade groups (51.9%, 76.8%) were significantly higher than that of the low grade group (17.6%; P less than 0.05). The S phase fraction (SPF) increased significantly with a high histological malignant grade (P less than 0.005). The mean SPF values of the low, intermediate and high grade lymphomas were 6.5 (0.6-18.8)%, 13.5 (3.2-37.3)% and 23.4 (4.4-41.4)%, respectively. Differences in ploidy status were not associated with survival rate. The survival rate of the cases with high SPF value in all cases of our series and low grade group of NHLs tended to become lower (P = 0.1 and 0.08, respectively). These results suggest that the flow cytometric analysis of DNA content should be a useful means for prediction of prognosis in non-Hodgkin's lymphoma.


Effect of cigarette smoking on hypoxic pulmonary vasoconstriction and its relation to animal species and period of smoking.

The alteration in hypoxic pulmonary vasoconstriction (HPV) induced by cigarette smoking was studied in Wistar rats, piglets and in humans. The percentage change of pulmonary vascular resistance (delta PVR%) and the amplitude of the systolic wave in impedance pneumorheogram (delta H%) were used to estimate the strength of HPV. It was observed that immediately after acute cigarette smoking, HPV in rats increased (delta PVR% from 55.0 +/- 15.6% to 102.3 +/- 12.4%), which is mainly mediated by leukotrienes (LTs); whereas HPV in piglets decreased (delta PVR% from 65.2 +/- 12.5% to 55.9 +/- 9.8%), which is mainly mediated by beta-adrenergic receptors, and HPV in humans also increased (delta H% from 20.6 +/- 2.6% to 31.1 +/- 4.1%), in which prostaglandins and leukotrienes may play the role of mediators. However, after one-month cigarette smoking, the HPV in rats fell significantly (delta PVR% 11.4 +/- 1.6%). An increase in synthesis of vasodilative prostaglandins and a decrease in leukotrienes synthesis may be the contributing factors to this alteration in HPV.


The chelating-resin modified electrode and its application in the detection of copper in human samples.

A new kind of carbon paste electrodes modified by chelating resin was prepared for detection of trace amount of copper in human hair. As the ion exchange between chelating resin and cupric ions and the coordination reaction on the modified electrode take place at the same time, this method has high sensitivity and good selectivity. The detection limit is 6 x 10(-9) mol/L. The average percentage of recovered copper is 108 +/- 8.3% and the variant coefficient (CV) 7.7%.


A comparative study of the effects of cadmium on microsomal mixed-function oxidase activities between kidney cortex and liver.

The effects of cadmium and phenobarbital (PB) administration on the activities of microsomal mixed-function oxidase (MFO) in rat kidney cortex and liver were studied. Five indices, including cytochrome P-450 contents, aniline hydroxylase, NADPH-cytochrome c reductase, aminopyrine N-demethylase and 7-ethoxycoumarin O-deethylase activities, were assayed. By comparison, it was found that PB could induce MFO activities in kidney cortex microsomes and liver microsomes, both hepatic and renal microsomal MFO were decreased by the ip injection of CdCl2, and Cd2+ could markedly decrease the phenobarbital induction to hepatic and renal microsomal MFO activities with the exception of NADPH-cytochrome c reductase in kidney cortex microsomes.


Association between allotypes of complement components C2, BF, C4 of HLA class III and cerebral stroke.

Allotypes of C2, BF and C4 in 58 patients with cerebral stroke (CS) and 110 normal control individuals in Guangzhou district were determined. The results show that there is a significant association between BF*F and CS.


A study of calcium ion-selective PVC membrane electrode based on neutral carrier N,n,n',n'-tetracyclo-3-oxapentanediamide (correction of oxapetanediamide).

A calcium ion-selective PVC membrane electrode based on neutral carrier n,n,n',n'-tetracyclohexyl-3-oxapetanediamide, using di-(2-ethylhexyl)phthalate as the plasticizer and potassium tetrakis (4-chlorophenyl) borate as the additive is reported in this paper. The ion selective membrane consists of 1 wt% of the Ca2+ selective ligand, 65 wt% of the plasticizer, 1 wt% of the additive and 33 wt% of poly (vinyl chloride) powder. The electrode has the linear response range of 2.0 x 10(-7)-10(-1) mol/L with the Nernstian slope of 28 mV/decade at 25 degrees C and the detection limit of 2.0 x 10(-8) mol/L. The response time of the calcium ion-selective electrode is as the concentration of calcium ion is rapidly shifted from 10(-5) to 10(-4) mol/L. The potential stability and reproducibility are good. The free calcium in blood serum was determined by the calcium ion-selective electrode with satisfactory results.


The preadministration of activated charcoal and aspirin absorption.

There is little information describing the effects of activated charcoal preadministration on drug absorption. This study was undertaken to determine the effect of activated charcoal preadministration at two different times on aspirin absorption. Fifteen volunteer subjects completed three study phases: 1) 975 mg aspirin alone, 2) 975 mg aspirin 30 min after 10 g activated charcoal, and 3) 975 mg aspirin 60 min after 10 g activated charcoal. Urine was collected for 48 h after the initiation of each study phase, and total aspirin recovery determined by HPLC. The aspirin recovery was 88.8% +/- 4.5% for the control phase, and 84.8% +/- 9.4% (Phase 1) and 85.8% +/- 12.6% (Phase 2) for the activated charcoal treatments (p > 0.05). These results suggest that activated charcoal administered 30 and 60 min prior to drug ingestion has little effect on drug absorption. Further studies of the effect of charcoal preadministration on the absorption of other drugs may provide useful information regarding factors important in determining activated charcoal efficacy.


Ethylene glycol poisoning: experiences from an epidemic in Sweden.

In 1987 two lethal adult cases of accidental ethylene glycol poisoning were given spectacular attention in the Swedish mass media. This resulted in an epidemic of intentional ethylene glycol poisonings. In addition to six cases related to alcohol abuse, another 30 severe suicidal poisonings were reported to the Swedish Poison Information Centre in five months. The clinical course and outcome in these 36 severe cases are reviewed. The primary clinical manifestations were metabolic acidosis, CNS disturbances and kidney damage with circulatory failure in the most severe cases. Mortality was 17%. Fragmentation of the normal striation in heart cells was found in two of the fatal cases and severe brain damage in all fatal poisonings. The degree of acidosis but not the serum ethylene glycol level correlated with both kidney damage and outcome. Treatment included ethanol, correction of the metabolic acidosis and dialysis. Four patients with serum ethylene glycol concentrations of 10-20 mmol/L (620-1240 mg/L) but with no or minimal metabolic acidosis were treated with ethanol alone; none of these patients developed renal damage.


Acute intoxication by endosulfan.

The authors report six patients with acute endosulfan intoxication. The symptoms of nausea, vomiting, headache, and dizziness began 2.7 +/- 0.5 h after ingestion; in four cases the patients had been hospitalized but were asymptomatic. All had severe metabolic acidosis with high anion gap and hyperglycemia; five of six had decreased blood platelets. Three patients had pulmonary aspiration, and five required mechanical ventilation. The one fatality followed acute renal failure, disseminated intravascular coagulation, thrombi in the pulmonary arteries and aorta, and cardiogenic shock. In this patient the blood endosulfan was 2.85 mg/L versus a mean of 0.48 mg/L in the survivors.


The effects of histamine administered in fish samples to healthy volunteers.

The effects of histamine administered in samples of fish to eight healthy volunteers (4 females and 4 males), aged 21-30 years, were studied. The subjects were given 0, 45 and 90 mg of histamine that had been metabolized from histidine by photobacteria in the fish and 90 mg of histamine added to fresh fish, for breakfast. The subjects were observed during 6 h after breakfast. Special attention was paid to clinical symptoms, blood pressure and ECG. The pH of the gastric contents was recorded continuously from 5 min before to 6 h after the meal. Blood samples to measure the histamine concentration were taken at intervals during 24 h after breakfast. Two of the subjects showed effects (facial flushing, headache) that could be attributed to the ingestion of histamine. No significant changes were observed in the blood pressure and ECG. The pH of the gastric fluids did not decrease significantly. The histamine concentration in plasma correlated closely with the histamine dose ingested (p < 0.001, r = 0.996). The Cmax of the dose of 90 mg did not differ statistically significant from the Cmax of the dose of 90 mg histamine added to unspoiled fish.


Review of parenteral sulfite reactions.

Sulfiting agents are commonly used in parenteral emergency drugs, including epinephrine, dexamethasone, dobutamine, dopamine, norepinephrine, phenylephrine, procainamide, and physostigmine. Published anaphylactic or asthmatic reactions have been associated with sulfited local anesthetics, gentamicin, metoclopramide, doxycycline, and vitamin B complex. The reactions differ from those caused by foods, in that they have a rapid onset, have no predilection for steroid-dependent asthmatics, and do not always coincide with a positive oral challenge. The mechanism is unknown, but may involve a dose-related reaction with disulfide bonds on sympathetic and parasympathetic receptor membranes. Patients with a history of positive oral challenge to 5-10 mg of sulfite may be at increased risk of developing a reaction to parenteral sulfites. Despite documentation of sensitivity, sulfites should not be withheld from patients experiencing a life-threatening emergency. Non-sulfited alternatives are often available, and should be used preferentially.


Cocaine exposure in utero: perinatal development and neonatal manifestations--review.

The question of whether cocaine exposure in utero increases the risk of major structural malformations remains controversial. Most animal studies have demonstrated that cocaine can have a teratogenic effect. The ultimate association between cocaine exposure and fetal development must be inferred from human data. The relative effects of cocaine exposure, exposure to other illicit drugs and alcohol and deficient prenatal care are difficult to assess. Little specific information is available about the amount, duration, and timing of cocaine use during the nine months of pregnancy. Unlike the case with many other teratogens, cocaine exposure at any point in pregnancy can result in some abnormality. The extent of damage and the organ involved depend on the particular stage of morphogenesis. A large scale prospective human study is needed to confirm the suggested teratogenic effects. Since it involves an illicit drug such a study is obviously difficult to perform.


Seizure with hyponatremia in a child prescribed desmopressin for nocturnal enuresis.

We report a case of hyponatremia associated with a grand mal seizure in a 28 month-old child after intra-nasal desmopressin administration for high fluid intake with nocturnal enuresis. In view of the temporary symptomatic action and the seriousness of certain side-effects of desmopressin we recommend that desmopressin be used with caution in childhood enuresis.


Fatal systemic poisoning after skin exposure to monochloroacetic acid.

Little information is available on the toxicity of monochloroacetic acid. We report the case of a 38 year-old man who was splashed with an 80% monochloroacetic acid solution on 25-30% of his body surface. In addition to epidermal and superficial dermal burns, features of systemic poisoning occurred within a few hours including disorientation, agitation, cardiac failure and coma. He later developed severe metabolic acidosis, rhabdomyolysis, renal insufficiency and cerebral edema, and died due to uncal herniation on d 8. The 4 h post exposure plasma monochloroacetic acid concentration was 33 mg/L confirming skin absorption. In addition to its corrosive action, monochloroacetic acid probably blocks the tricarboxylic acid cycle (Kreb's cycle) and may also react with sulfhydryl groups in enzymes, causing severe tissue damage in energy-rich organs.


The changes of gasoline compounds in blood in a case of gasoline intoxication.

A 44 year-old man, found in his gasoline vapor filled car, died of multiple organ failure on d 9. Blood samples from d 2-7 were analyzed by gas chromatography/mass spectrometry. The estimated half-lives of gasoline, toluene, ethylbenzene, m,p-xylene, and o-xylene were 16.9, 21.4, 27.5, 32.8, and 25.8 h respectively. The estimated initial gasoline concentration in blood was 247 micrograms/ml.


Improvement of sexual behavior in aged rats by p-chlorophenylalanine and methysergide.

The effects of methysergide, a serotonin antagonist, and p-chlorophenylalanine (PCPA), a serotonin synthesis blocker on the sexual behavior of intact old male rats at 19-23 months of age and female rats at 17-18 months of age were studied. Female rats with prolonged vaginal cornification and a lordosis quotient (LQ) of less than 50%, and male rats displaying no ejaculation were selected as experimental animals. The receptivity of aged female rats, but not the approach behavior to males nor proceptivity was improved by PCPA or methysergide. The LQ of intact aged female rats in non-exit tests was improved by the i.p. administration of 50 mg/kg B.W. of PCPA 2 to 4 hours prior to the sexual behavior test or 3 mg/kg B.W. of methysergide 4 hours prior to the test. Total mount frequency and mount latency of intact aged male rats were improved by the administration of methysergide (3 mg/kg B.W.), while total mount frequency and intromission latency were improved by the administration of PCPA (20 mg/kg B.W. for 4 days). The present results together with the finding from our previous study suggest that the increase of serotonin (5-HT) activity per se plays an important role in the decline of receptivity of aged female rats and the copulatory activity of aged male rats.


Molecular characterization of R-plasmids pST1 and pST2 from Salmonella typhimurium S24.

Salmonella typhimurium S24 was isolated in September 1986 at Kaohsiung Medical College Hospital, Kaohsiung, Taiwan, from a patient suffering from gastroenteritis during an outbreak of salmonellosis. Two conjugative R-plasmids have been isolated from Escherichia coli K-12 14R525, which was mated with S. typhimurium S24. The two R-plasmids found in S. typhimurium S24 belong to two different incompatibility (Inc) groups: the 130-kilobase IncFI plasmid pST1 and the 56-kb IncN plasmid pST2. These two R-plasmids of pST1 and pST2 together mediate resistance to multiple antibiotics in S. typhimurium S24. By DNA probes hybridization, plasmid pST1 was shown to carry an enteric type II chloramphenicol acetyltransferase (CAT) gene, a class C tetracycline resistance (TetR) gene and a type III dihydrofolate reductase (DHFR) gene, all of which confer resistance to chloramphenicol, tetracycline, and trimethoprim respectively. A Richmond's type III beta-lactamase gene was located on each plasmid of pST1 and pST2. beta-lactamases specified by both plasmids pST1 and pST2 conferred high level resistance to amoxicillin, carbenicillin, piperacillin, sulbenicillin, ticarcillin in addition to ampicillin. A novel aminoglycoside 6'-N-acetyltransferase [AAC(6')] was demonstrated on plasmid pST2. This AAC(6') enzyme modified kanamycin, amikacin, dibekacin, tobramycin, gentamicin, netilmicin, sisomicin, butirosin and ribostamycin.


Carcinoma of the external auditory canal and middle ear.

Fifty-three patients with carcinoma arising in the external auditory canal and/or middle ear seen at Veterans General Hospitals, Taipei and Taichung in the period between January 1970 and December 1988 were retrospectively reviewed. There were 49 males and 4 females. Their ages ranged from 5 to 80 years, the average being 58 and the median 59 years. In 10 patients the primary site of the tumor was located in the middle ear, in 32 patients it was the external auditory canal, and in the remaining 11, both areas. The most common cancer which occurred in this area was the squamous cell type, accounting for 85% of our cases. The majority of patients had an otorrhea history with duration from 6 months to more than 40 years. Nine patients received surgery alone, 8 irradiation alone, 31 a combination of surgery and radiotherapy. Initial complete regression of the tumor was noted in 100% of the combined therapy group. This was better than surgery (56%) or irradiation alone (60%). Bleeding and infection caused by surgery, and osteonecrosis caused by radiation were the most frequent and severe complications. The actual 5-year survival rate was 33%. Life table analysis showed that only the extent of the disease affected survival significantly. The 5-year survival rates were 23% and 51% for advanced and early stages respectively (p < 0.05). Combined therapy resulted in better local control and survival than operation or radiotherapy alone, but the benefit did not reach a significant level (p = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)


[Pattern shift visual evoked potentials in diabetes mellitus].

Functional exploration of the optic pathways with pattern shift visual evoked potentials (PSVEP) has been rapidly accepted as a non-invasive method of investigation of diabetics. For this article, we conducted the PSVEPs study on 46 cases of NIDDM and 13 cases of IDDM. The peak latency, interpeak latency and evoked amplitude of P100 were analyzed in each case. For further correlation, the motor and sensory nerve conduction velocities of the median nerve, blood sugar, serum HbA1c, and duration of DM were measured simultaneously. Two nondiabetic control groups which matched the age and sex of the NIDDM and IDDM groups were used for comparison. In the IDDM group, the results showed prolongation of all peak and interpeak latencies (IPL) except the peak latency of N75 on the right side. The P100 amplitude was reduced as compared with the age-matched young control group. The interocular P100 latency difference (ILD) was not statistically significant between the IDDM group and the age-matched control group. The results of the NIDDM group revealed prolongation of all peak latencies and IPLs. The P100 amplitude and ILD showed no statistically significant difference between NIDDM and the age-matched control group. The prolongation of N 75 peak latency exhibited a linear correlation with duration, HbA1c and median nerve SNCV.


[Interdigestive and postprandial pancreatic exocrine secretion and cholecystokinin release in dogs].

Interdigestive and postprandial pancreatic exocrine secretion and cholecystokinin (CCK) release were investigated in 5 mongrel dogs with chronic gastric and pancreatic fistulas in this study. The rapidly exaggerated postprandial pancreatic exocrine secretions were shown to be directly correlated to the rapid CCK release after meal. Corresponding to the previous studies, in the interdigestive state, pancreatic exocrine secretion showed cyclic changes which would be abolished by intravenous administration of atropine sulfate. However, we failed to demonstrate any significant correlation between plasma CCK levels and periodic pancreatic exocrine secretions during the interdigestive state through CCK radioimmunoassay. Furthermore, intravenous administration of atropine sulfate did not change the plasma CCK levels significantly in the interdigestive state. Having reviewed the literature, we thought that the periodic pancreatic exocrine secretion during the interdigestive state might be related to motilin release and cholinergic enteropancreatic reflex.


[Surgical management of blunt liver trauma].

From 1986 to 1990, 46 patients with blunt liver trauma were hospitalized and operated on in Kuang Tien General Hospital. Included were 33 males and 13 females with a mean age of 31 years (range: 2 to 62). The mean duration of the follow-up was 43 months. We classified the severity of liver injury with the liver injury scale which was published by the Organ Injury Scaling (O. I. S.) Committee of the American Association for the Surgery of Trauma (A. A. S. T.) in 1989. According to the operative findings, the liver injury of the 46 cases were classified as follows: grade I 4 cases, grade II 18 cases, grade III 16 cases, grade IV 2 cases, grade V 4 cases, and grade VI 2 cases. Among the patients, 4 cases were treated with drainage. Four cases underwent simple repair. Twenty-seven cases were treated with repair and drainage. Three cases underwent debridement and selective ligation of bleeding vessels. Four cases underwent partial resection of liver, and 3 cases required repair of the inferior vena cava. One case was packed with gauze for hemostasis. The mortality rate was 15.2%, and the morbidity rate 30.3%. The most frequent postoperative complications related to the hepatic injury in the patients who survived the initial operation were wound infection (8.7%), intra-abdominal abscesses (6.5%), pancreatitis (6.5%), pulmonary infection (4.3%), and small bowel obstruction (4.3%).


Familial spontaneous pneumothorax-report of seven cases in two families.

Spontaneous pneumothorax usually occurs sporadically in healthy young adults, who tend to be tall and thin. The usual cause is rupture of small subpleural bullae found in the apex of the upper lobe. Familial spontaneous pneumothorax is a rare condition. With a review of the English literature from 1921 to 1991, only 59 families with 135 cases have been reported. A genetic background has been suggested, but the actual mode of inheritance is still unknown. Relationships between the HLA haplotype A2B40, the alpha1-antitrypsin phenotype and the occurrence of spontaneous pneumothorax have been proposed, but are still controversial. We present 7 patients in 2 families with 13 episodes of spontaneous pneumothorax. Neither congenital defect, alpha1-antitrypsin deficiency nor the described A2B40 HLA haplotype could be found in our patients. We propose that there are no such factors existed in these patients. Further study is required to determine if any genetic marker is linked to familial spontaneous pneumothorax.


Field validation of the Tallstick in marginal communities in Nicaragua.

The Tallstick is a new, simplified anthropometric field tool which allows immediate visual interpretation of height-for-age. This tool was field tested in community-based programmes in Managua, Nicaragua, and the rural community of Los Zarzales, screening 1004 children aged 0-60 months for nutritional stunting. Overall sensitivity and specificity analysis comparing HAZ scores and Tallstick results revealed that the Tallstick correctly identified 83-85 per cent of severely stunted children (HAZ < -2.5) and two-thirds of those with HAZ of -2 and below. It also had good positive predictive value for the mildly stunted. As a screening tool for low weight-for-age, the Tallstick performed better than arm circumference. The best of the community volunteers trained with the Tallstick could use it as well as their trainers. Progressive stunting was found in the 280 children in the sample who did not receive any form of milk. The advantages of the Tallstick for community-level screening and the importance of sustained linear growth are discussed.


Deletion analysis of DMD/BMD children in Singapore using multiplex polymerase chain reaction (PCR) technique.

Twenty-three children suffering from Duchenne/Becker muscular dystrophy (DMD/BMD) in Singapore were analysed using the multiplex polymerase chain reaction (PCR) technique. Deletions were found in 14 cases. One rare case of total deletion of all nine exons was observed. This is the first DMD/BMD deletion analysis on South East Asian children. This technique for screening deletions was informative in 61 per cent of the local cases and would be useful for rapid diagnosis of deletion cases of DMD/BMD.


Breastfeeding promotion in Kenya: changes in health worker knowledge, attitudes and practices, 1982-89.

In 1982, a study of health worker knowledge, attitudes and practices with respect to breastfeeding was undertaken in Kenya. A breastfeeding promotion campaign ensued, in which training of health workers was a major component. In 1989, the impact of this campaign was evaluated through a survey examining changes in health worker knowledge, attitudes and practices. The survey showed that considerable improvements in knowledge and substantial improvements in hospital practices have occurred, although none of these could be attributed to any single element of the breastfeeding promotion programme. Particularly undesirable practices which were common in 1982, such as separation of mother and baby, formula feeding and use of bottles have virtually disappeared from Kenyan hospitals. Recommendations regarding future programme directions are made.


Rutter's Behaviour Scale (B2) for children (Teacher's Scale): validation and standardization for use on Nigerian children.

Nigerian teachers were asked to place the children in their classes in either of two groups: Group I, comprising children of normal behaviour, and Group II, children who, in their opinion, had significant behavioural problems. Validity of the teachers' grouping was confirmed, using as reference measure the findings from traditional psychological assessment of the children. The teachers then completed the Rutter Child Behaviour Questionnaire (Teachers' Scale) for the same children. The children's scores on the Rutter Scale were matched against the teacher's grouping, the aim being to identify the Rutter Score that separates the children into two 'behaviour' groups that agree most closely with the teachers' own grouping. Results show that this was achieved at the Rutter Score of 10 (k = 0.66). Children scoring 10 or more on the Rutter scale appeared mostly in Group II, while those scoring less than 10 were mostly in Group I. Rutter's scale was also found to be a highly valid instrument for identifying Nigerian children with behavioural problems. It is recommended that Nigerian children scoring > or = 10 on Rutter's Behaviour Questionnaire (Teacher's Scale), should be regarded as children with behavioural disorder. This is one point higher than the score of > or = 9 recommended for British children.


Detecting malnutrition at age 6-12 months: international comparisons of arm circumference v. standard anthropometry.

Growth faltering, which may herald protein-energy malnutrition (PEM) usually begins between ages 6 and 12 months. However, arm circumference (AC or MUAC) has mainly been used to screen for PEM between 12 and 60 months of age, when AC is age-independent. This study of 378 infants aged 6-12 months in Pakistan, Nepal, Sierra Leone, and Papua New Guinea showed that a cut-off 12.5 cm AC selects infants < 80 per cent weight-for-age (WA) with 76 per cent sensitivity and 90 per cent specificity. Of the 378 infants studied 131 (35 per cent) had WA < 80 per cent and 126 (33 per cent) had AC < 12.5 cm. Weight-for-length agreed less well with AC. The inter-regional prevalence range of AC < 12.5 cm was 29-40 per cent, while the WA < 80 per cent range was 27-45 per cent. When AC is plotted against age, a flat 'plateau' (slope = 0.04) shows age-independence between 6 and 12 months in these 378; this contrasts to the 10 per cent AC increase in European reference populations. Because this AC plateau parallels the WA plateau seen between 6 and 12 months of age in most developing nations, AC < 12.5 cm may provide a simple and valid screening test for early PEM in this crucial age bracket. Conformatory studies elsewhere are indicated.


Use of hepatitis B vaccine alone or in combination with hepatitis B immunoglobulin for immunoprophylaxis of perinatal hepatitis B infection.

The efficacy of hepatitis B vaccine alone or in combination with immunoglobulin in neonates born to HBsAG positive mothers was investigated. Twenty-four infants were given three doses (at 0, 1, 2 months) of the vaccine alone, while 27 infants were given hepatitis B immunoglobulin (HBIG) and three doses of the vaccine. Fifty-eight infants born to HBsAg positive mothers who did not agree for vaccination or could not come for follow-up constituted the control group. The overall seroprotection rates (anti-HBS levels > or = 10 IU/l) were almost similar in both the groups at 6 months (81 and 76 per cent, respectively). However, the seroprotection rates in babies born to HBeAg positive mothers were better with combination of HBIG and vaccine (71 v. 57 per cent, respectively). It was also observed that seroprotection rates in babies born to anti-HBe positive mothers were even better (100 and 90 per cent in vaccine alone and combination group, respectively). No chronic carrier was detected in babies born to anti-HBe positive mothers.


Women's work in agriculture and child nutrition in Tanzania.

This paper examines the food related work that women are doing, and the possible effect on child feeding and nutritional status. Women's participation in food production may have positive as well as negative consequences for child nutrition. On the one hand, it may augment the total amount of food procured, while on the other, it may give women less time for child care and feeding. The data show that women are using less time in cooking and children are fed less often during the peak labour seasons. However, a profound and conclusive negative effect of mother's agricultural work on child nutritional status could not be shown. This finding is explained by various compensatory mechanisms employed by the mothers which may buffer the negative effect of the women's time constraints. The norm of feeding children at the maximum only three times a day was seen as the major contributing factor to child malnutrition. According to the women, this feeding frequency was seen as the maximum possible taking into account their heavy work in agricultural production.


Prenatal growth curves corrected for certain genetic and environmental factors.

Factor analysis for non-orthogonal data was done to assess the straight and interaction effects of certain genetic and environmental factors on birth weight. While the interaction effects did not assume any significance, straight effects of gestational age, parity, mother's weight, and sex were significant in influencing the birth weight. Mother's height and socio-economic status of the family had no significant effect on birth weight. Step-up multiple regression analysis showed that contribution to the total variance explained (R2 x 100 = 29.7 per cent) in birth weight was about 15, 7, 5, and 2 per cent, respectively, from gestational age, parity, mother's weight, and sex of the baby. Correction of the mean weight curve was done by successive graphic approximation method and residuals were further minimized.


Gastric residuals in preterm babies.

The gastric residual (GR) volume was measured in 50 healthy preterm babies, 38 appropriate-for-dates (AFD), and 12 small-for-dates (SFD) with gestational age of 28-36 weeks. The mean basal 4-hour gastric residual (B4 GR) volume was 2.8 +/- 0.63 ml in parenterally fed babies. There was a marked decrease in the residuals from 20.7 +/- 15.2 per cent (mean +/- SD) on day 4 to 8.6 +/- 4.3 per cent on day 7 (P < 0.001). Of the 27 infants fed with expressed breastmilk (EBM), mean GR was 24.4 +/- 10.2 per cent in supine and 12.8 +/- 4.3 per cent in prone position (P < 0.01). Twenty-one babies nursed in the prone position showed a mean GR volume of 12.8 +/- 4.3 per cent with EBM and 13.6 +/- 2.7 per cent with milk formula. No difference was noted in the gastric residuals of AFD v. SFD babies. No linear correlation was found between increase in abdominal girth and GR. However, if the increase in abdominal girth was at least 2 cm or more, a GR of 23 per cent or more was observed. This should be taken as warnings to reduce or withhold oral feeds.


Vertical jumping height and horizontal overhead throwing velocity in young male athletes.

The purpose of this study was to examine the effects of calendar and skeletal age, anthropometric dimensions, training history and their interactions on vertical jumping height and horizontal overhead throwing velocity in a cross-section of 318 young male athletes (age range 9-16 years) participating in cross-country skiing (n = 70), basketball (n = 40), apparatus gymnastics (n = 19), ice hockey (n = 50), track and field (n = 89) and wrestling (n = 50). Vertical jumping height was measured with four different loads held on the shoulders and then interpolated for loads representing 0 and 40% body mass. Horizontal overhead throwing velocity using both hands was determined for seven balls of different weights and then interpolated for weights representing 1 and 5% body mass. Both vertical jumping height and overhead throwing velocity were found to increase (P < 0.01) from the skeletally youngest to the oldest cohort when the effects of body height and mass were controlled. The inter-event comparisons did not reveal statistically significant differences in respect of vertical jumping height. Also in the overhead throwing tests, the inter-event differences were small, although the analysis of variance revealed statistically significant (P < 0.001) differences for the skeletal age cohorts of 13 and 14 years. While the quantity of training had no effect on vertical jumping height, it explained the results in the overhead throwing test. The effects of training on vertical jumping and horizontal overhead throwing among adolescent athletes were considered to be small, while maturational processes and anthropometric development followed by increase in calendar age were deemed to be of greater importance.


Ventilation and blood lactate increase exponentially during incremental exercise.

This study examined whether the ventilatory (V) compensation for metabolic acidosis with increasing O2 uptake (VO2) and CO2 output (VCO2) might be more in accord with the theoretical expectation of a progressive acceleration of proton production from carbohydrate oxidation rather than a sudden onset of blood lactate (BLa) accumulation. The interrelationships between V, VO2, VCO2 and BLa concentration, [BLa], were investigated in 10 endurance-trained male cyclists during incremental (120 +/- 15 W min-1) exercise tests to exhaustion. Regression analyses on the V, VCO2 and [BLa] vs VO2 data revealed that all were better fitted by continuous Y = A.exp.[B.VO2] + C rate laws than by threshold linear rate equations (P < 0.0001). Plots of V vs VCO2 and [BLa] were also non-linear. Ventilation increased as an exponential V = 27 +/- 4.exp.[0.37 +/- 0.03.VCO2] function of VCO2 and as a hyperbolic function of [BLa]. In opposition to the 'anaerobic (lactate) threshold' hypothesis, we suggest these data are more readily explained by a continuous development of acidosis, rather than a sudden onset of BLa accumulation, during progressive exercise.


Morphological proportionality in elite age group North American divers.

The purpose of this investigation was to describe the morphological parameters that characterize elite age group divers. Comparisons are made to normative age group data from the Coquitlam Growth Study and the constancy of important characteristics from age group to age group is examined. Data were collected on 27 male and 28 female elite divers who participated in the 1990 North American Age Group Diving Championships. Body build, body composition and skinfold corrected diameters were determined from 36 anthropometric parameters and analysed by ANOVA, t-test and Phantom z-scores procedures. All age groups except the 14- to 15-year-old males were significantly (P < or = 0.05) shorter than their norms but recorded higher androgyny index values. The estimated relative muscle mass increased significantly (P < or = 0.05) with age for males at all ages (40.8-46.3%). The 16- to 18-year-old females had a significantly (P < or = 0.05) larger relative muscle component compared to the younger age groups (40.1-38.4%). When normalized for height, active tissue development of the extremities was comparable between the sexes except in the forearm. The results indicate that at all age levels short stature is an important characteristic for divers. Analysis of regional active tissue development provides further insight into sport-specific prerequisites for success at elite levels.


The biomechanics of the discus throw: a review.

This review provides an evaluation of published scientific literature (mostly that in English or German) which has reported quantitative data relating to the biomechanics of the discus throw. This is done by considering the two stages of the throw--the launch (the movements in the circle) and the discus flight. To ascertain the optimal release characteristics of the discus to maximize the distance thrown, the results of those studies which have addressed this problem by simulating the flight of the discus are evaluated. To assess the merit of this literature, a detailed evaluation of studies of the aerodynamics of discus flight is also undertaken in this review. These results are compared with measured release conditions from filmed discus throws. The greater part of the review seeks to establish the technique of the thrower within the circle necessary to achieve an optimum release. Thus, the discus throwing technique is discussed in relation to the results of cinematographic data, and the extremely limited number of force platform and electromyographic studies. An evaluation of experimental procedures and the reporting of experimental errors, particularly for the cinematographic studies, is included. Consideration is also given to some of the more descriptive, coaching literature where points are raised which serve to highlight important biomechanical aspects of throwing technique. It is concluded that not enough relevant and reliable biomechanical data currently exist to answer many of the important questions about the technique of the discus throw, and some future research directions to help overcome this are recommended.


The "twin peak" sign: reliable evidence of dichorionic twinning.

In twin pregnancies with a single placental zone, the presence of a triangular projection of placental tissue beyond the chorionic surface, extending between the layers of the intertwin membrane, has provided reliable evidence that there are two fused placentas (dichorionic, diamniotic) rather than a single shared placenta (monochorionic, diamniotic). This observation, dubbed the "twin peak" sign, was identified in 15 twin pregnancies, all proven to be dichorionic at birth, and in five triplet pregnancies, all proven to be trichorionic. This finding is produced by proliferating chorionic villi growing into the potential space between the two layers of chorion in the intertwin membrane. The single chorion of a monoplacental twin pregnancy serves as an intact barrier, preventing villi from growing between the two amniotic layers. A decision sequence incorporating the use of the twin peak sign is described for determining the type of twinning that has occurred.


The variable appearances of fetal gallstones.

Only four cases of fetal gallstones have been reported previously, which implies that this condition is rare. Gallstones in children have been reported more frequently, and it may be that some of these are present in fetal life. Over a 12 month period in this department, seven cases of gallstones or sludge were seen within the fetal gallbladder. The variable appearances of fetal cholelithiasis are described and the possible causes discussed. Fetal gallstones may not be as rare as indicated by the paucity of cases in the literature.