Reduction in plasma or skin alpha-tocopherol concentration with long-term oral administration of beta-carotene in humans and mice. Beta-carotene is one of the most commonly used compounds in clinical trials of chemopreventive agents in various neoplastic diseases. Animal studies, including our own, have documented that dietary beta-carotene can reduce plasma alpha-tocopherol (vitamin E) levels, but few published studies have examined the clinical or pharmacokinetic ramifications of long-term, high-dose beta-carotene regimens on other fat-soluble vitamins such as alpha-tocopherol. This study was designed to determine the effects of long-term beta-carotene supplementation on plasma concentrations of alpha-tocopherol in normal human subjects and in an experimental C3H/HeN mouse model. In a double-blind study, 45 normal subjects were randomly assigned to receive 0 (placebo), 15, 30, 45, or 60 mg of oral beta-carotene daily for approximately 9 months. Monthly plasma samples were collected. Thirty-five C3H/HeN mice were fed a basal diet with or without beta-carotene and treated topically with or without alpha-tocopherol, except for the control mice, which received UV radiation for 27 weeks from week 3 to week 30. Plasma and dorsal skin samples were taken after 40 weeks and were analyzed for alpha-tocopherol and/or beta-carotene by high-performance liquid chromatography. Long-term dietary beta-carotene administration resulted in statistically significant reductions in levels of alpha-tocopherol in the skin and plasma of UV-irradiated mice. In the human study, the decrease in plasma alpha-tocopherol levels was progressive and significant between 6 and 9 months of beta-carotene dosing in all dosage groups. The greatest decrease was observed during the 9th (last) month of dosing, with a decrease of 40% from baseline. All oral beta-carotene doses (15-60 mg/d), however, resulted in similar decreases in steady-state plasma levels of alpha-tocopherol and in only small differences in beta-carotene plasma levels. Long-term oral administration of beta-carotene decreased steady-state plasma concentrations of alpha-tocopherol. The lack of a significant dose-response effect between doses of beta-carotene and alpha-tocopherol plasma levels is not unexpected, given the small differences in steady-state beta-carotene plasma levels in the four beta-carotene dose groups. Studies are needed to determine how long-term beta-carotene dosing influences tissue distribution of dietary alpha-tocopherol. Careful surveillance for this and other potentially harmful nutrient interactions should become part of all long-term intervention studies.


Screening sigmoidoscopy and colorectal cancer mortality. Sigmoidoscopy may reduce colorectal cancer mortality by identifying both cancers and precursor lesions (including polyps) for treatment; however, evidence regarding the efficacy of this technique as a screening procedure is extremely limited. In the absence of data from randomized controlled trials, we performed a retrospective case-control study to determine if sigmoidoscopy screening is associated with a reduction in colorectal cancer mortality. The medical records of 66 members of the Greater Marshfield Community Health Plan (GMCHP) who died of large-bowel cancer from 1979 to 1988 were reviewed for history of screening for colorectal cancer (case subjects). For comparison, the records of 196 GMCHP members of similar gender, age, and enrollment duration were randomly selected for review (control subjects). History of screening sigmoidoscopy was much less common among case subjects (10%) than among control subjects (30%). Risk for death from colorectal cancer was reduced among individuals having had a single examination by screening sigmoidoscopy (odds ratio = 0.21; 95% confidence interval = 0.08-0.52), compared with the risk for those who never had one. The reduction in risk appeared to be limited to tumors in the rectum and distal colon. Neither fecal occult blood testing nor digital rectal examination was associated with a reduction in colorectal cancer mortality. These results suggest that screening sigmoidoscopy can substantially reduce mortality from cancers of the rectum and distal colon.


Breast cancer risk: effects of estrogen replacement therapy and body mass. Epidemiologic studies have focused on the association between breast cancer risk and a variety of lifestyle and exogenous factors. The purpose of this study was to clarify the effects of alcohol consumption, cigarette smoking, oral contraceptive (OC) use, estrogen replacement therapy (ERT), and body mass on risk of breast cancer. These variables were examined in a case-control study of 604 patients with newly diagnosed breast cancer and 520 control subjects who did not have breast cancer and were frequency matched for age, hospital, and time of diagnosis. These case patients and control subjects were part of an ongoing study of breast cancer by the American Health Foundation and were selected for interview from hospitals in the New York City area from January 1987 through December 1989. The data were analyzed by computation of odds ratios (ORs) for potential risk factors, with adjustment for age at diagnosis and other potential confounding variables and with stratification by menopausal status. We observed positive effects of ERT and high body mass on the risk of postmenopausal breast cancer, particularly when each factor was examined in the absence of the other factor. In lean postmenopausal women, the adjusted summary OR associated with ERT was significantly elevated (OR = 2.0; 95% confidence interval [CI] = 1.1-3.5; P < .01), and there was a statistically significant dose response of breast cancer risk with ERT duration (adjusted ORs = 2.0 for < 5 years and 2.2 for > or = 5 years; positive trend, P < .02). Reciprocally, in women who did not receive ERT, high body mass (Quetelet index > 27) was a significant risk factor for postmenopausal breast cancer (OR = 2.1; 95% CI = 1.3-3.3; P < .02), and the linear trend in risk with increasing body mass was significant (positive trend, P < .02). The strongest effect of body mass occurred in women who were lean at age 18 and gained enough weight to place them in the upper tertile of body mass at the time of diagnosis (OR = 2.6; 95% CI = 1.5-4.6; P < .01). There was no evidence of significant positive associations between breast cancer risk and cigarette smoking, alcohol consumption, or OC use in any subgroup of these women. Our results support the hypothesis that excess adipose deposition heightens breast cancer risk in the postmenopausal years. Furthermore, they underscore the need for continuing investigation of the effects of exogenous estrogens on the development of this malignancy, particularly in lean postmenopausal women.


Characterization of covalent DNA binding of morpholino and cyanomorpholino derivatives of doxorubicin. The doxorubicin analogues cyanomorpholino doxorubicin (MRA-CN) and morpholino doxorubicin (MRA) were synthesized in an attempt to avoid the cardiotoxicity and drug resistance of doxorubicin therapy. MRA-CN forms interstrand DNA cross-links without requiring microsomal metabolic activation in the presence of reduced nicotinamide-adenine dinucleotide phosphate (NADPH) to form a product that alkylates DNA, but MRA requires metabolic activation. Alkylation produces DNA cross-links, which are associated with potentiation of the cytotoxicity of some drugs. Our purpose was to study the DNA binding of MRA-CN and MRA with and without metabolic activation in order to better understand the mechanisms for cross-linking DNA. We used [3H]MRA and [3H]MRA-CN, with the 3H labeled at C-2 and C-6 of the morpholino ring. MRA (10 nM) was incubated with human liver microsomes with or without NADPH to measure DNA binding. In addition, a filter elution assay was used to determine the nature and extent of drug binding to DNA in the human ovarian carcinoma cell line ES-2. We studied the appearance of interstrand cross-links versus total DNA adducts in pBR322 plasmid DNA incubated with 100 nM MRA-CN in cell-free medium and then subjected to denaturation and agarose gel electrophoresis. Regardless of the extracellular concentration of the drug (1-100 nM), 85% of intracellular MRA-CN was covalently bound to DNA, and the total amount of drug bound to DNA was proportional to extracellular drug concentration. No covalent binding of MRA to DNA was found in cells exposed to 10 nM MRA alone for 2 hours. In contrast, 10% of the intracellular drug was bound to DNA if the cells were exposed to MRA preincubated with human liver microsomes and NADPH. The percentage of plasmids containing at least one interstrand cross-link rose from 35% at 15 minutes to 92% at 2 hours. We estimate that eight molecules of MRA-CN were adducted per molecule of pBR322 DNA (or one drug adduct per 545 base pairs), with a minimum of 12% of the adducts forming interstrand cross-links. These results suggest that the carbons at positions 2 and 6 of the morpholino ring of both MRA-CN and the activated metabolite of MRA are retained in the drug-DNA adduct. They also indicate that the formation of interstrand DNA cross-links by MRA-CN is preceded by formation of drug adducts to a single strand of DNA.


Violence as a public health priority for black Americans. This study investigated the extent to which black public health and political leaders believe that reducing violence should be a national public health priority for black Americans when compared with other public health problems such as acquired immunodeficiency syndrome, low birthweight, and access to health care. A survey asking whether violence in the black community is amendable to change and who (or what institutions) should be responsible for the reduction of violence was sent to 427 black health leaders, 326 black mayors, and 467 black legislators. Three hundred twenty responses were returned. Virtually all respondents placed violence as one of the top five, if not the highest, public health priority for black Americans. Health and political leaders differed in their beliefs about whether violence and violence-related behaviors can be ameliorated, and who should bear responsibility for the reduction of violence. While this survey had limitations, more than 300 black public health and political leaders indicated that violence among black Americans should be made a national public health priority. Policy implications are discussed, and a proactive role for the National Medical Association is advocated.


Appendicitis in children: a continuing clinical challenge. This article discusses the findings of a study of pre-adolescent children to determine if the mode of presentation of appendicitis had changed over the past 10 years, if the incidence of perforations decreased with age, and if diagnosis related groups (DRGs) impacted the length of hospital stay. The charts of 42 children under the age of 12 years who were discharged from two inner-city hospitals with a diagnosis of acute appendicitis from 1980 to 1989 were reviewed. There were 20 blacks and 22 whites, 26 males and 16 females with an average age of 7.31 years (range: 2 to 11 years). Over 95% of patients presented with right lower quadrant pain, 78% with guarding, 80% with a positive psoas sign, 93% with a positive Rovsing's sign, and 65% with rectal tenderness. Over 85% of patients had a history of nausea, vomiting, and anorexia. The mean duration of pain was 52.8 hours and the mean temperature was 99.6 degrees F. The mean white blood cell count was 18,176 +/- 4682 for whites versus 14,615 +/- 5459 for blacks. At surgery 15/42 (36%) of patients had a perforation, 11 of whom had positive wound cultures. Escherichia coli was recovered in all 11 of these patients. The average duration of pain in the perforated group was 50.9 hours, and the average age was 7 years. Eleven of these patients had normal bowel sounds on admission. Only 31% of the total cohort had a fecalith identified by pathology. The average postoperative length of stay was 6.5 +/- 2.5 days before the initiation of DRGs and 7.5 +/- 3 days afterward.


Change in serum cholinesterase activity in Jamaican diabetics. This study investigates the alteration of serum cholinesterase levels in diabetics and its possible relationship to blood glucose, insulin, triglyceride, and cholesterol levels. Fourteen phasic insulin-dependent diabetes mellitus patients were compared with 10 insulin-dependent diabetes mellitus, 10 noninsulin-dependent diabetes mellitus, and 10 normal controls. Each group was matched for age, sex, body mass index, and duration of diabetes. Mean age was 56.7 +/- 2.5 years; mean body mass index, 24.0 +/- 0.8 kg/m2; and mean duration of diabetes, 14.2 +/- 2.2 years. Serum acetylcholinesterase, insulin, triglyceride, and cholesterol levels as well as fasting blood sugar were all assayed using standard techniques. Results suggest an associated increase of serum acetylcholinesterase with triglyceride levels in diabetics and may point to a possible association between increased serum acetylcholinesterase and vascular complications in Jamaican diabetics.


Ethnic distribution of primary central nervous system tumors in Washington, DC, 1971 to 1985. An ethnic analysis was made of 8947 cases of primary central nervous system (CNS) tumors seen at the Armed Forces Institute of Pathology (AFIP), Washington, DC, from 1971 to 1985. Results showed a slightly higher frequency of primary CNS tumors in whites than in blacks with a white:black case ratio of 9:1 against the white:black population ratio in the United States of 7.4:1. Gliomas appeared to be twofold more frequent in whites than in blacks with a white:black case ratio of 12.1:1. However, meningiomas and pituitary adenomas were more common in blacks with a white:black case ratio of 6.7:1 and 4.2:1, respectively. When these results were compared with the results of a previous identical study using similar materials collected at AFIP from 1958 to 1970, the relative paucity of gliomas and higher frequency of meningiomas and pituitary adenomas in American blacks is again confirmed, thus re-emphasizing the importance of genetic factors in the genesis of primary CNS tumors. The remarkable decreasing white:black case ratio of primary CNS tumors as a whole (9:1 compared with 13.7:1) since 1970 probably reflects the socioeconomic improvement of American blacks during the same period.


Sexual behaviors of African-American male college students and the risk of HIV infection. A survey of the rates of sexually transmitted diseases and protective sexual behaviors among a population of African-American male college students demonstrates that although monogamy, avoidance of casual sexual activity, and the avoidance of the use of drugs and alcohol during sexual activity tends to decrease the risk of exposure to human immunodeficiency virus, consistent condom use is the only sexually related behavior that is significantly protective.


Fluoroscopic chest tube insertion and patient care. Catheters and chest tubes may be placed under fluoroscopic control to reduce pleural effusions. This procedure has been adopted as a routine procedure at the UCLA School of Medicine in Los Angeles, California to improve patient care. This technique was modified for the placement of large chest tubes, which can be placed by a radiologist without multiple attempts or complications. Our experience with 2234 patients who underwent this procedure between 1977 and 1990 is described.


Macular degeneration: how big is the problem? Almost every report on macular degeneration begins with a somber reminder that macular degeneration is the single most common cause of blindness in the elderly in the United States and Europe. Almost every report also confirms that there is no known successful approach to slowing, stopping, reversing, or preventing this syndrome. In the light of these devastating statements, it is difficult to explain the paucity of information about the disease process in general and its epidemiologic implications in particular. What little is known deals with prevalence rates; no figures are available regarding the incidence. Additionally, almost without exception, the prevalence numbers are based on the assumption that macular degeneration is a binomial (black and white) problem. However, macular degeneration, like all chronic diseases, exists in a potentially infinite number of shades of gray. Hence, when viewed as an achromatic continuum, macular degeneration is more prevalent than generally believed. Recognizing this disorder earlier invites the greater possibility of a cure or primary prevention.


Painful subacute thyroiditis (de Quervain's thyroiditis). Painful subacute thyroiditis (de Quervain's thyroiditis) usually occurs in association with systemic viral illnesses. This disorder may be manifested in various clinical forms. Primary care physicians must be aware of the clinical features of this disorder to make the correct diagnosis and treat appropriately. Three cases are reported to illustrate the different clinical manifestations of this disorder.


Complications of laparoscopic cholecystectomy. Laparoscopic cholecystectomy with lasers or cautery is a feasible, effective, and worthwhile operative procedure that is subject to morbidity and mortality. There is unequivocal evidence that the complication incidence is directly related to the training and experience of the surgeon, applicability of basic principles of gallbladder and common duct surgery, and preventive measures toward iatrogenic injuries in gallbladder surgery. Continued and sustained investigation in laparoscopic cholecystectomy, technological developments in equipment, and the continued education of the surgeon in the applicability and use of laparoscopic cholecystectomy, intraoperative cholangiography, and choledocholithotomy are essential. At the St Francis Medical Center, Pittsburgh, Pennsylvania 1009 laparoscopic cholecystectomies with lasers or cautery were performed between March 1989 and October 1991. There were 32 (3%) abandoned laparoscopic cholecystectomies with alternative open cholecystectomy. There were six extrahepatic ductal injuries and a complication incidence of 10.9%. The mortality rate was 0.38%. The average length of stay was 2 days. In comparison with standard cholecystectomy, laparoscopic cholecystectomy is a competitive and superior procedure in selected circumstances.


Choroid plexus tumor in a child.

Choroid plexus tumor in a child. A 5-month-old infant is reported who presented with fever, nonspecific symptoms, a rapidly enlarging head, and a regression in motor development. Investigations subsequently confirmed the diagnosis of a choroid plexus papilloma.


Fibular strut grafting for fibrous dysplasia of the femoral neck. When fibrous dysplasia affects the femoral neck, normal bone is replaced by fibro-osseous dysplastic bone that is both mechanically weakened and biomechanically abnormal. Surgical management is recommended for persistent pain, progressive deformity, or impending fracture. Surgical options include curettage and cancellous bone grafting, osteotomy and nail-plate fixation, intramedullary rodding, and cortical bone grafting. We present the case of a patient with a painful, dysplastic lesion of the femoral neck who underwent cortical bone grafting using dual fibular strut grafts. To ensure long-term graft incorporation, the fibular cortical grafts bridged the lesion in the femoral neck and were securely anchored to the normal bone of the lateral femoral cortex and a head of the femur. No supplemental internal fixation was required. The biological basis for success of the fibular strut grafting procedure is that creeping substitution of the cortical graft necrotic bone does not replace the interstitial lamellae, which persist to lend structural support. Fibular strut grafting is an excellent procedure for fibrous dysplasia of the femoral neck.


AIDS/HIV crisis in developing countries: the need for greater understanding and innovative health promotion approaches. Epidemiologic data on morbidity and mortality have shown that the acquired immunodeficiency syndrome/human immunodeficiency virus (AIDS/HIV) epidemic is relatively widespread in the developing countries of the world, especially in the already economically deprived regions of Sub-Saharan Africa. Africa is estimated to have approximately 5 million seropositive individuals, and by the year 2000, this number is expected to include 10 million HIV-infected children. Improved control over this epidemic can only come through a greater understanding of the specifics of the disease and, eventually, the introduction of more effective and innovative health promotion campaigns targeted at medical personnel, traditional healers, families, and persons with AIDS. Comprehensive health promotion campaigns, carefully using mass media strategies in addition to more community-based programs, all operating under "decentralized" AIDS control programs, are reasoned to be the most efficacious approach that African and other developing countries can use to successfully contain the AIDS/HIV epidemic. Given the reality of the following factors: Pattern II (ie, transmission of AIDS via heterosexual sexual activity) is the main mode of HIV transmission in Africa, the traditional dominant roles males have in sexual relations, and the positive relationship between sexually transmitted diseases and AIDS, health promotion campaigns must focus specifically on addressing at-risk culturally related sexual values and behaviors in African communities. Failure to address these and other related factors will certainly lead to an escalation of the AIDS/HIV epidemic in Africa and, therefore, concomitant devastation in the human and societal realms of the region.


Amelioration of nephrotoxicity associated with synthetic oxygen transport media. Use of synthetic oxygen transport media offers the potential advantages of reducing requirements for coadministration of blood products and oxygen at the scene of mass casualty situations. Previous studies have shown perfusions of isolated kidneys with stroma-free hemoglobin (SFH) to be physiological while those with Fluosol-DA (20% FDA) have been associated with low glomerular filtration rate, urinary flow rate, and fractional reabsorption of sodium and potassium (FrNa+ and FrK+). In the present studies, perfusions with SFH/FDA mixtures showed normal glomerular filtration rate, a 50% lower urinary flow rate, and FrNa+ values 3% to 5% higher than SFH controls. Compared with 20% FDA perfusions, nephrotoxic effects of SFH/FDA combinations were moderate. Compared with SFH/FDA mixtures, perfusion with 20% FDA showed lower urinary flow and glomerular filtration rates. Ultrastructural assessment of glomerular filter revealed that FDA emulsion particles were adherent to epithelial podocytes. We conclude that resuscitation with a mixture of SFH and FDA may ameliorate the previously reported nephrotoxicity associated with the use of FDA alone.


A prognostic role for ceruloplasmin in the diagnosis of indolent and recurrent inflammation. Ceruloplasmin is increased in infections, inflammatory diseases, and neoplastic diseases and may be scarcely visible to the naked eye because it imparts a faint green color to the serum. This poses an interesting question as to a possible prognostic role for ceruloplasmin in the diagnosis of persistent or recurrent infection. The clinical course of 50 patients with tainted serum was reviewed retrospectively and ceruloplasmin levels correlated with diagnosis and outcome. Group I consisted of 20 healthy controls with normal ceruloplasmin levels: 35.1 +/- 2.0 mg/dL (range 25 to 45 mg/dL). Group II was made up of 23 surgical patients; 10 of these patients had elevated levels of ceruloplasmin, nine of whom had significant infections (64.2 +/- 3.2 mg/dL), and one patient was on estrogen (73.7 mg/dL). Group III consisted of 27 medical patients; 25 of these patients had elevated levels of ceruloplasmin, 20 of whom had infections (54.1 +/- 2.6 mg/dL), and five had malignancies (61.0 +/- 3.0 mg/dL). Ceruloplasmin levels were consistently elevated in all patients with infections relative to controls (P less than .001) with a variable response in other disease states. Therefore, ceruloplasmin may be useful as a serum marker for indolent or recurrent infections.


Civilian field surgery in the rural trauma setting: a proposal for providing optimal care. Rural trauma presents unique problems for surgical care. While military surgeons are prepared to provide care at or near the scene of battle, civilian literature is devoid of reports for care provided by surgeons at sites of injury occurrences. Although these injuries are infrequent, they are more likely to occur in rural trauma settings. This article describes two cases of extremity injury that required amputation at the scene and presents a proposal for swift mobilization of appropriately trained surgeons to the scene with adequate instrumentation and lighting, which can significantly reduce the morbidity and mortality of these victims.


Characteristics of high-risk adolescent outpatients with treponemal antibody. This study analyzes variables associated with syphilis infection among adolescents attending a public medical clinic in the District of Columbia. All adolescent clinic patients found to have Treponema pallidum antibody from June 1, 1989 through June 1, 1990 were included in the study. Medical records were reviewed for the following data: age, sex, presence or absence of court jurisdiction over the patient, chief complaint, concurrent infections, and the clinical stage of syphilis. The study population included 52 patients. The results revealed that male patients carry a higher risk of remaining undetected because only one third acknowledged any complaints prior to examination. This cohort study illustrates the predilection of syphilis for the indigent and underserved. Moreover, it highlights that insidious disease in adolescents is often unsuspected and undetected until routine screening tests are performed.


Extracorporeal shock wave lithotripsy for radiolucent stones. Eleven patients with radiolucent urinary calculi were treated with shock wave lithotripsy. Nine of these patients experienced successful fragmentation of their stones and subsequent spontaneous passage of the calculi fragments. The majority of the stones were composed of uric acid alone or a mixture of uric acid and calcium oxalate. One stone with metabolites of triamterene also fragmented well. Uric acid calculi can be treated successfully with shock wave lithotripsy using adequate visualization by contrast injection.


Risk factors for neuroleptic malignant syndrome. Neuroleptic malignant syndrome, a rare and potentially fatal complication of antipsychotic drugs, is poorly understood. Equally poorly understood are the risk factors of neuroleptic malignant syndrome. Long-term and parenteral treatment with high doses of neuroleptic drugs are implicated as risk factors for the syndrome. Recently, attention has been drawn to the frequency of neuroleptic malignant syndrome in patients treated with a combination of haloperidol and lithium. This article reports a case in which the patient's risk factors for neuroleptic malignant syndrome included not only haloperidol and lithium but also a predisposition to substances of abuse.


Prevalence of Lyme disease infection in Oklahoma. Even though Lyme disease probably existed in Oklahoma prior to 1975 when the disease was first reported in Connecticut and even though ecological conditions favor a high prevalence, an unexpectedly low rate was evidenced in both a serological survey and the number of cases reported to the Oklahoma State Department of Health. Lyme disease does not appear to pose a significant public health threat in Oklahoma at the present time; however, the the presence of all the necessary factors for transmission and the rapidly increasing number of cases reported in nearby areas merits continued surveillance in this state. The need for consistent case definition is discussed.


Mortality in the slave and white populations of Natchitoches Parish, Louisiana, 1850. A review of mortality from the 1850 census mortality schedules of Natchitoches Parish, Louisiana has provided a snapshot of the health conditions of African-American slaves. The cause of death was abstracted from the mortality schedule and categorized according to the ninth revision of the Manual of the International Classification of Diseases. Children under the age of 9 accounted for 44% of the total mortality. Sixty-four percent of all deaths recorded occurred in the slave population. Sixty-two percent of the slave deaths occurred in the male population. Leading causes of death were helminthiasis, whooping cough, fever, cholera, and pneumonia. Reports of mortality due to Cachexia Africana (dirt eating) among slaves are discussed.


Reevaluation of dioxin bioconcentration and bioaccumulation factors for regulatory purposes. Bioconcentration factors (BCF) or bioaccumulation factors (BAF) reported for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin) in aquatic environments encompass a wide range of values, from less than 1000 to 189,000 l/kg. These values are based on concentrations of TCDD in various environmental media including water, sediment, or food. Under the Federal Water Pollution Control Act and its enabling regulations (40 CFR 100-140, 400-470), point source discharge limits are established so that the nominal receiving water concentration will not exceed the water quality criterion. To be consistent with this regulatory process, the water quality criterion should also be calculated using an accumulation factor that is based on a nominal water concentration. The regulatory process for developing a water quality criterion for TCDD requires the selection of a BAF that describes the relationship between the source to be regulated and the fish tissue concentration.


In vitro embryotoxicity of petroleum creosote monitored via mouse preimplantation embryo culture. A mouse preimplantation embryo culture system was utilized to characterize the in vitro embryotoxicity of petroleum creosote (PC), a complex mixture of aliphatic and polycyclic aromatic hydrocarbons. ICR mouse embryos, collected on d 3.5 of gestation (blastocyst stage), were exposed for 1 h to varying concentrations of petroleum creosote in serum-supplemented culture medium. Parallel embryo cultures were exposed to PC in medium supplemented with rodent hepatic S9 microsomal fractions to monitor the role of bioactivation in PC-induced embryotoxicity. Embryos were subsequently cultured in control medium for 72 h and observed for viability as well as specific, time-dependent developmental end points--hatching and attachment to the culture dish at 48 h, and trophoblastic outgrowth with a distinct inner cell mass at 72 h. Embryonic viability varied in inverse proportion to PC concentration. Petroleum creosote caused embryolethal effects at concentrations of 33 micrograms/ml of culture medium and 54 micrograms/ml. Embryotoxicity was not observed at 22 micrograms/ml. Culture supplementation with rodent hepatic S9 fractions did not modify, either qualitatively or quantitatively, the embryotoxicity of PC in vitro. These findings implicate PC as a prenatal toxicant and support environmental and human health concerns regarding PC exposure from PC-containing chemical waste sites.


Performance of an aquatic multispecies system in evaluating the effects of a model microbial pest control agent on nontarget organisms. A recirculating multispecies test system was developed in conjunction with a study of the fate and persistence of a model microbial pest control agent on non-target marine and freshwater organisms. The basic unit of the system was a 113-I glass aquarium with vertical biological filters in the center of the aquarium, such that two compartments were formed. This allowed the sequestration of predator and prey species within the same system. Organisms from six phyletic groups were subjected to a genetically altered strain of Pseudomonas putida for 15-29 d in either artificial seawater or fresh water. The system was able to maintain the animals for these periods with a minimum of maintenance. Additionally, the system design lent itself to disinfection, dismantling, and rebuilding between experiments with a minimum of labor, and has potential for longer-term studies.


Procedure for evaluating changes in respiratory symptoms of experimentally asthma-induced guinea pigs by a personal computer. An automated system was developed for evaluating changes in respiratory symptoms in guinea pigs over a long period with a personal computer. The data on breathing curves obtained with a body plethysmograph were analyzed to determine respiratory rate, expiration/inspiration ratio, ventilation ratio, and other parameters. With this system, respiratory changes in guinea pigs, such as increase or decrease of respiratory rate, expiration/inspiration ratio, and ventilation ratio, and death of animals could be easily observed. Investigation of delayed respiratory response to Candida albicans in sensitized guinea pigs and of the effects of SO2 or NO2 exposures on its response was carried out using this system. Respiratory changes in delayed respiratory response were mostly increased respiration rate and succeeding expiratory prolongation being noted just before death. In the influences of SO2 or NO2 exposure on delayed respiratory response, increase of respiratory rate in NO2 and expiratory and inspiratory prolongation in SO2 were found. This system should prove useful for evaluating changes in respiratory symptoms due to toxic agents, medicines, and air pollutants in small animals.


Selected pesticide residues and metabolites in urine from a survey of the U.S. general population. Residues of toxic chemicals in human tissues and fluids can be important indicators of exposure. Urine collected from a subsample of the second National Health and Nutrition Examination Survey was analyzed for organochlorine, organophosphorus, and chlorophenoxy pesticides or their metabolites. Urine concentration was also measured. The most frequently occurring residue in urine was pentachlorophenol (PCP), found in quantifiable concentrations in 71.6% of the general population with an estimated geometric mean level of 6.3 ng/ml. Percent quantifiable levels of PCP were found to be highest among males. Quantifiable concentrations of 3,5,6-trichloro-2-pyridinol (5.8%), 2,4,5-trichlorophenol (3.4%), para-nitrophenol (2.4%), dicamba (1.4%), malathion dicarboxylic acid (0.5%), malathion alpha-monocarboxylic acid (1.1%), and 2,4-D (0.3%) were found, but at much lower frequencies. No quantifiable levels of 2,4,5-T or silvex were found. Preliminary analyses showed an apparent relationship between residue concentration and two measures of urine concentration (osmolality and creatinine). A large segment of the general population of the United States experienced exposure to certain pesticides, including some considered biodegradable, during the years 1976-1980.


Acute toxicity, distribution, and metabolism of 2,4,6-trinitrophenol (picric acid) in Fischer 344 rats. Picric acid (2,4,6-trinitrophenol) is widely used in industry, by the military, and as a research/clinical chemistry reagent. Characterization of the toxicity of this chemical has been limited. Thus the acute toxicity, distribution, and metabolism of picric acid were investigated using Fischer 344 rats. The LD50 for picric acid following oral dosing of male and female rats was established as 290 and 200 mg/kg, respectively. Blood gas analysis indicated severe acidosis during acute intoxication. Metabolism of picric acid was limited to reduction of nitro groups to amines. Metabolites isolated from urine included N-acetylisopicramic acid (14.8%), picramic acid (18.5%), N-acetylpicramic acid (4.7%), and unidentified components (2.4%). Approximately 60% of the parent picric acid was excreted unchanged. The plasma half-life for picric acid was 13.4 h with a gut absorption coefficient (ka) of 0.069 h-1. Twenty-four hours following oral administration of [14C]picric acid (100 mg/kg), the primary depots of radioactivity (per gram tissue basis) were blood, spleen, kidney, liver, lung, and testes. Respective tissue/blood ratios were 0.37, 0.31, 0.28, 0.26, and 0.22. All other tissue assayed had partition ratios < 0.20, with brain and adipose tissue having the least amount of radioactivity. Tissue/blood ratios were essentially maintained over a 48-h postadministration period. Binding (in vitro) of [14C]picric acid to plasma proteins (whole blood preparations) demonstrated both high- and low-affinity binding sites, with dissociation constants of 3.18 x 10(-6) and 2.85 x 10(-4) M, respectively. The findings of this investigation provide information on the acute toxicity, metabolism, and distribution of picric acid, which can be used in risk assessment analyses and in the design of subchronic and chronic toxicity tests.


Investigations in the use of mice exposed to mycotoxins as a model for growing pigs. A series of experiments was conducted to determine the feasibility of using mice to screen for possible dietary mycotoxin interactions before testing them with swine. Selected mycotoxins, deoxynivalenol (DON) and T-2 toxin, were fed to young mice, alone and in combination. The severity of effects on body weights caused by DON (0-20 mg DON/kg diet) was more pronounced in a dose-related manner when the animals were exposed to contaminated diets starting at 21 d of age than at 28 d (Experiment 1) as reflected in the analysis of variance. The relative variance among diets after 7 d was twice as great for the younger than for the older mice. In both age groups, the weight gain response was linear, similar to that seen in growing swine. In Experiment 2, a significant (p < .05) diet type x DON interaction for food consumption evident after 7 d, indicated that the effect of DON depended on the type of diet (freeze-dried vs. regular mash). There was no difference in food efficiency between diet type, but a strong dose-dependent effect due to DON was observed. When DON and T-2 toxin were fed together to young mice, a significant (p < .001) linear decrease in weight gain and food consumption was observed after 7 d on the contaminated diet as the toxin concentration increased.


Ovine urinary metabolites of ethoxyquin. Metabolites of ethoxyquin (EQ, 1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline) in the urine of sheep and rats were separated and identified by gas chromatography-mass spectrometry (GC-MS). Sheep were given diets containing EQ or EQ.HCl (0.5% of total diet) and urine samples were collected for the first 24 h and for another 24-h period after 12 d of feeding. Rats were given EQ/corn oil (0.08 g EQ/d/rat) orally for 7 d and urine samples were collected at ambient temperature for a 24-h period following 6 d of dosing. The urine samples were extracted with ethyl acetate at pH 5, and the concentrated extracts were analyzed by GC-MS. Ethoxyquin was identified in all sheep urine samples collected during the first 24 h of feeding, and EQ and hydroxylated EQ were identified in all urine samples collected after 12 d of feeding. In contrast, EQ, hydroxylated EQ, and dihydroxylated EQ were identified in urine collected from rats fed EQ for 7 d.


Interaction of multiple nuclear proteins with the promoter region of the mouse 68-kDa neurofilament gene. Four brain-specific, DNase I hypersensitive sites (HSS) have been mapped to the 5' flanking region of the mouse 68-kDa neurofilament gene. These sites are contained within a 1.7-kb sequence that confers neuronal specificity of expression of this gene in transgenic mice. To identify DNA sequences that might be involved in gene regulation, the HSS situated near the promoter region has been analyzed by gel mobility shift assays and DNase I footprinting to investigate protein binding sequences. Of particular interest are two footprints localized to a 9-nucleotide sequence that flanks both the light and medium neurofilament gene in mouse and to a sequence that demonstrates partial homology to several promoter regions, including element-1, a motif required for neuron specificity in Drosophila. A prominent footprint was also detected at a sequence that contains a near-perfect palindrome centered at a PstI restriction site.


Molecular cloning of a novel mRNA using an antibody directed against synaptic glycoproteins. It has been suggested by a number of investigators that glycoproteins may play a role in the development and/or maintenance of synapses in the mammalian CNS. For many synaptic glycoproteins, however, little precise structural or functional information is available. In an effort to isolate probes specific to individual glycoproteins, we have screened a rat brain cDNA expression library with a mixed polyclonal antibody directed against concanavalin A-binding synaptic junctional glycoproteins. Using this approach, we have previously reported the cloning of SC1, a putative extracellular matrix glycoprotein found in adult brain (Johnston et al., Neuron 2:165-176, 1990). We now report the cloning and characterization of a second novel cDNA, which has been designated SC2. Northern blots show that this cDNA recognizes a 1.2-kb mRNA that is present throughout postnatal development in the rat. It is expressed at high levels in brain and is also found at lower levels in several other tissues. In situ hybridization suggests that the SC2 mRNA is strongly expressed by many types of neurons. Sequence data reveals a single open reading frame in the cDNA, encoding a putative hydrophobic protein with a calculated molecular weight of 36.1 kDa. Sequence analysis reveals some similarity between SC2 and 5 alpha-reductase, a microsomal membrane protein important in testosterone metabolism.


Analysis of promoter activity and 5' genomic structure of the neural cell adhesion molecule L1. To gain insight into the molecular mechanisms underlying the regulation of expression of the neural cell adhesion molecule L1 and into the exon-intron structure of the L1 gene, a genomic clone from the mouse was characterized. The clone was identified by screening an EMBL3 library with an L1-specific cDNA probe and comprises approximately 15 kb, in which the first 2,206 nucleotides of the coding region are included. Of the 5 of 6 immunoglobulin (Ig)-like domains sequenced, all are encoded by 2 exons, with the first exon being smaller than the second. The exon encoding the signal peptide is separated from a mini-exon containing 15 bp by a large intron, approximately 2.6 kb in length, whereas the other introns are smaller, with the coding information for the Ig-like domains 3-5 clustered in a 1,643-bp-long fragment with introns only 110-217 bp in length. The 5' upstream region of the clone comprises 5 kb, with the first 112 bp lying upstream to the coding sequence and containing a start site for transcription. No consensus sequence for a TATA box was found. Consensus DNA sequences for the binding of the gene products of Hox 1.3, engrailed and bicoid, are localized upstream to the transcription start site. A 1,262-bp fragment containing part of the first exon showed promoter activity in neuroblastoma cells, but hardly in L cells and not in CHO cells, indicating that this fragment is sufficient for neural cell directed promoter activity.


Immunohistochemical and biochemical analysis of N-cadherin expression during CNS development. The expression of the calcium-dependent adhesion molecule N-cadherin during chick embryo central nervous system (CNS) development was examined by immunohistochemistry and electrophoresis and immunoblotting. During histogenesis, N-cadherin is expressed at high levels in a uniform fashion in many regions of the CNS. However, during later stages of development, expression becomes restricted to the ependymal cells lining the ventricular system and in the choroid plexus. This down-regulation was confirmed by both immunohistochemical and biochemical techniques. The program of expression lags behind in the cerebellum in concert with the delayed development of this region of the brain. A high level of N-cadherin was found to be expressed in the brainstem and spinal cord floorplate, while a low level was detected at the optic nerve head. The results indicate that while, in general, the program of N-cadherin expression is similar in the retina and the brain, certain structures unique to the eye and brain express locally high or low levels of this adhesion protein.


Secretion of apolipoprotein E by an astrocytoma cell line. Apolipoprotein (apo) E is a predominant protein in developing mammalian brain and in damaged peripheral nerve. Of particular interest is the observation that astrocytes in the central nervous system cease to produce apoE after nerve damage, whereas an increase in apoE production results after peripheral nerve injury. Differences in the response to injury with regard to the production of apoE may be related to dissimilarities in the abilities of the central and peripheral nervous systems to regenerate. As there are few data concerning the regulation of apoE gene expression in extrahepatic tissues, we employed a human astrocytoma cell line (CCF-STTG1) as a model to study apoE production in astrocytes. CCF-STTG1 cells secreted apoE constitutively in serum-free media. Cholesterol added to the media as cholesterol:phospholipid liposomes (2-100 micrograms/ml) or as human plasma LDL increased the amount of apoE secreted into the media, but had little or no effect on the relative abundance of apoE mRNA. By contrast, the commercially available triglyceride-phospholipid emulsion Intralipid added at dilutions of 1:50 to 1:500 caused a total inhibition of apoE secretion by the cells, but again, little change was noted in the relative abundance of apoE mRNA. Insulin (5 micrograms/ml) caused a 45-55% reduction in the amount of apoE secreted by the astrocytoma cells. Glucagon (5 micrograms/ml), on the other hand, did not increase apoE secretion, and apoE mRNA concentrations were not affected by either hormone treatment. ApoE was secreted from the astrocytoma cells associated with particles of plasma VLDL to IDL and HDL size. After feeding the cells with 20 micrograms/ml cholesterol as cholesterol:phospholipid liposomes, an increased proportion of apoE was secreted associated with the larger VLDL to IDL size particles, with a concomitant decrease in the proportion associated with the smaller HDL-size particles. When cells were incubated with 5 micrograms/ml insulin, most of the apoE was associated with the HDL-size particles. When cholesterol:phospholipid liposomes were added in the presence of insulin virtually all of the secreted apoE was found associated with the VLDL to IDL size particles. In summary, the regulation of apoE production in CCF-STTG1 cells in many respects resembles that of other cells, including hepatocytes. However, it is clear that there remain to be identified cell specific factors which regulate apoE production in astrocytes. The CCF-STTG1 cell line promises to provide a suitable model to investigate these questions.


Advances in the use of the fluorescent probe fura-2 for the estimation of intrasynaptosomal calcium. Fura-2 has been used to measure intracellular Ca2+ with great success in a variety of cell and subcellular preparations, including synaptosomes. There is, however, a great deal of variability in the reported estimates of resting intrasynaptosomal Ca2+ ([Ca2+]i). Fura-2 AM is highly lipophilic and passes readily across the plasma membrane into the cytoplasm, where it is de-esterified and trapped. The lipophilicity of fura-2, however, promotes the formation of micelles in aqueous media, which may impede the passage of the probe across cell membranes. Our results suggest that some of the variability in the reported [Ca2+]i estimates may be related to fura-2 de-esterification and loading efficiencies. The use of the nonionic detergent pluronic F-127 is recommended to prevent the formation of fura-2 micelles. The use of a detergent is not always an acceptable practice, however, especially in studies in which detergent-lipid interactions may influence membrane parameters. We found that fatty acid free bovine serum albumin (BSA) (0.25%) greatly increases the intrasynaptosomal concentration of the probe, resulting in a significant increase in the signal-to-noise (S/N) ratio. The mechanism appears to be independent of effects of BSA on synaptosomal integrity and directly related to the prevention of fura-2 micelle formation, as evidenced by light spectroscopic scattering measurements. Thus, BSA appears to keep the probe in a form that crosses the synaptic plasma membrane more readily. The effectiveness of BSA in improving the loading of fura-2 into synaptosomes was comparable to the detergent pluronic F-127, making it possible to measure [Ca2+]i without compromising membrane integrity.


Laminin and its neurite outgrowth-promoting domain in the brain in Alzheimer's disease and Down's syndrome patients. Immunocytochemistry, radioimmunoassay, immunoblotting, Northern analysis, and polymerase chain reaction (PCR) technique were applied to investigate the distribution of laminin and its neurite outgrowth domain in brains of neuropathologically verified cases of Alzheimer's disease and Down's syndrome. New antibodies against a neurite outgrowth domain of laminin were characterized and were used in localization of this peptide antigen in the human brain. Laminin was found as large punctate deposits in all plaques in the affected brains. Laminin synthesis was increased as assessed by RNA blotting and immunoblotting, and glial cells were heavily immunoreactive with antibodies for a neurite outgrowth-promoting peptide antigen of the B2 chain of laminin. This peptide antigen not only was produced by glial cells but also was deposited in the brain tissue. As this peptide antigen promotes neurite outgrowth at low concentrations, and is specifically neurotoxic at high concentrations, it may play a synergistic role with other molecules in inducing the sprouting and neurodegeneration occurring in brains of patients with either Alzheimer's disease or Down's syndrome.


Morphological differentiation and proteoglycan synthesis regulate Alzheimer amyloid precursor protein processing in PC-12 and human astrocyte cultures. A morphologically differentiated strain of rat pheochromocytoma (PC-12H) metabolically labeled with [35S]methionine and incubated with a phorbol ester displayed reduced 140-kDa and increased 15 kDa bands relative to cells incubated without phorbol ester after immunoprecipitation with antisera elicited by the C-terminal peptide of the Alzheimer amyloid precursor protein (APP). These bands correspond to glycosylated full length APP and a C-terminal fragment previously reported by Anderson et al. (Neurosci. Lett. 120:126-128, 1991) to result from a cleavage within the amyloidotic A4 region of APP, which releases a 120 kDa extracellular fragment. The 15 kDa fragment, not immunoprecipitated with an antisera elicited by the N-terminal portion of A4 amyloid, is nonamyloidogenic. Incubation of these cells with p-nitrophenylxyloside, known to inhibit proteoglycan formation, also increased this nonamyloidogenic cleavage of APP. In contrast to these results, an undifferentiated low passage PC-12-L strain constitutively displayed rapid nonamyloidogenic APP cleavage. Incubation of PC-12-L with phorbol ester did not affect the relative abundance of 140 or 15 kDa bands. Growth of PC-12-L with 7 S NGF or dibutyryl cAMP resulted in increased morphological differentiation and decreased APP cleavage which was now phorbol-inducible. Similar analyses of dividing and senescent human astrocytes and normal and F-AD fibroblasts indicate 5-fold lower rates of mid-A4 APP cleavage. Phorbol esters decreased the 140 kDa APP band without affecting the intensity of the 15 kDa band in these cells.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of a discrete dorsal forebrain lesion in the rat on the expression of neuronal and glial-specific genes: induction of calmodulin, NF-L, SC1, and GFAP mRNA. The influence of a localized tissue injury on the expression of genes encoding specific neuronal and glial proteins was examined using in situ hybridization. A pronounced induction of neuron-specific calmodulin (CaM) mRNA was evident within cells proximal to the wound site by 2 hours following a cortical lesion in rats. By 12 hours postlesion, intense signal corresponding to CaM mRNA was found to extend 1 mm from the wound site. Changes in the expression of mRNA encoding two additional neuronal proteins, the 68 kilodalton neurofilament protein and the extracellular matrix protein, SC1, were also evident at 12 hours following the cortical injury. Of the two glial proteins examined, a dramatic elevation in levels of mRNA for glial fibrillary acidic protein (GFAP) was observed at the wound site by 12 hours postlesion. This intense labeling corresponding to GFAP mRNA was evident in the ipsilateral glial limitans and hippocampus as well as in the contralateral glial limitans. In contrast, the pattern of labeling for the beta-subunit of the S100 protein did not differ from that of control animals at either of the postlesion intervals examined. This study identifies four genes, CaM, GFAP, SC1, and NF-L, which are induced following a localized cortical injury and which encode mRNA species enriched in specific cell-types in the central nervous system.


A decision analysis of traumatic splenic injuries. We created a decision analysis model of the nonsurgical management of traumatic splenic injuries to clarify the risk of hospital survival, overwhelming postsplenectomy infection (OPSI) deaths, and transfusion-related deaths. We reviewed 72 cases of splenic injury at our institution to identify our transfusion requirements for successful observation (0.5 units), observation failure (1.0 units), and surgical splenic management (1.6 units). Using our model and baseline probabilities determined from the literature, we compared the nonsurgical management of splenic injuries with immediate laparotomy and found an increase in hospital survival with observation, but an over two-fold increase in the risk of transfusion-related death. The OPSI deaths were not markedly different between the two strategies. Overall, we found decision analysis useful in identifying important variables such as the probability of nontherapeutic laparotomy death or missed injury, and in clarifying the risk of the nonsurgical management of splenic injuries with regard to transfusion-related deaths and OPSI deaths.


Improved outcome with hypotensive resuscitation of uncontrolled hemorrhagic shock in a swine model. Recent animal studies have shown that aggressive saline infusion may produce significant mortality in models of moderately severe (20-30 mL/kg) uncontrolled hemorrhage. The postulated mechanism is an increase in hemorrhage that accompanies restoration of normal blood pressure. Although aggressive saline infusion and restoration of blood pressure appear indicated when hemorrhage is potentially lethal (40-45 mL/kg), we hypothesized that the attempt to restore blood pressure with aggressive saline infusion would not improve survival. This study used a swine model of severe uncontrolled hemorrhagic shock to compare the effects of resuscitation to mean pressures of 40 and 80 mm Hg. Twenty-four immature swine, each with a surgical steel aortotomy wire in place, were bled rapidly from a femoral artery catheter to a mean arterial pressure (MAP) of 30 mm Hg. The aortotomy wire was then pulled, producing a 4-mm aortic tear and free intraperitoneal hemorrhage. When the pulse pressure decreased to 5 mm Hg, saline infusion was begun at 6 mL/kg/minute and continued as needed to maintain the following endpoints: group I (MAP = 40 mm Hg), group II (MAP = 80 mm Hg), and group III (no resuscitation). After a maximum saline infusion of 90 mL/kg, the infusate was changed to shed blood at 2 mL/kg/minute. Data were compared using analysis of variance and Fisher's exact test. One-hour survival was 87.5%, 37.5%, and 12.5% for groups I, II, and III, respectively. Intraperitoneal hemorrhage for the three groups was 8.2 mL/kg, 39.9 mL/kg, and 6.7 mL/kg. The amount of saline infused was 55.8 mL/kg in group I and 90 mL/kg in group II.(ABSTRACT TRUNCATED AT 250 WORDS)


Prospective evaluation of preoperative fluid resuscitation in hypotensive patients with penetrating truncal injury: a preliminary report. Although intravenous (IV) fluid therapy is routinely prescribed for hypotensive injury victims, there are concerns that elevating the blood pressure before hemorrhage is controlled may be detrimental. This is a preliminary report of an ongoing randomized study designed to evaluate the effect fluid resuscitation, delayed until surgical intervention, has on the outcome for hypotensive victims of penetrating truncal injury. In the first year, 300 consecutive patients with gunshot or stab wounds to the trunk who had a systolic blood pressure of 90 mm Hg or less were entered into the study. Patients were excluded from the outcome analysis because of death at the scene or minor injury not requiring surgical intervention. The remaining study patients were randomized into (1) an immediate resuscitation group (n = 96) for whom IV fluid resuscitation was initiated in the ambulance and in the emergency center before surgical intervention, or (2) a delayed resuscitation group (n = 81) for whom IV fluid resuscitation was delayed until the time of surgical intervention. The two study groups were found to be well balanced with respect to anatomic injury severity, pretreatment vital signs, survival probability, and preoperative treatment times. There were no significant differences in the rate of survival to hospital discharge (immediate resuscitation group, 56%; delayed resuscitation group, 69%). There were no significant differences in the rate of postoperative complications. Further study is necessary to determine if it is advantageous to delay fluid resuscitation until surgical intervention.


Prospective validation of criteria, including age, for safe, nonsurgical management of the ruptured spleen. One hundred twelve cases of blunt splenic rupture were prospectively entered (October 1987-October 1991) into surgical or nonsurgical management groups using these criteria for the nonsurgical group: hemodynamic stability+age less than 55 years+CT scan appearance of grade I, II, or III injury+absence of concomitant injuries precluding abdominal assessment+absence of other documented abdominal injuries. All ages were included and AAST injury scaling was used. Patients were grouped from the trauma room. The surgical treatment group included 66 patients (49 splenectomies, 17 splenorraphies). These patients were generally older and more severely injured, required more transfused blood, and a longer ICU stay. The nonsurgical group included 46 patients with 33 older than 14 years. There were 3 patients over the age of 55 years inappropriately included in this group, and nonsurgical therapy failed in all three. Statistical analysis (chi 2) showed that more splenic injuries were observed and more spleens were saved with these criteria applied prospectively compared with a previous retrospective series in the same institution. Our series had a success rate of 93%, and validates the criteria used for safe, nonsurgical management of the ruptured spleen and adds a new criterion: a maximum age of 55 years.


Physician review improves hospital DRG reimbursement in injury. This was a prospective study of all DRG reimbursed trauma patients discharged during an 11-month period. Initial DRGs were assigned by hospital coding specialists (HCS). A surgeon (SURG) subsequently reviewed each chart and assigned DRGs to maximize reimbursement. The data for 244 patients were: age = 36.5 years, Trauma Score (TS) = 13.8, Injury Severity Score (ISS) = 16.9, and length of stay (LOS) = 10.3 days. Total charges for the 244 patients were $4,261,208 with an initial HCS projected reimbursement of $1,687,963. The SURG review resulted in a total projected reimbursement of $1,956,476, an increase of $268,513 in revenue (p less than 0.001). Charges correlated strongly with LOS and ISS. The HCS-coded and SURG-coded reimbursements also correlated positively with LOS and ISS, but to a lesser extent. The SURG review of DRG assignment improved hospital reimbursement for the injured patients. However, this reimbursement fell well below hospital billings.


Blunt colonic injury--a multicenter review. During the past decade there has been a shift in the management of injuries of the colon to primary repair without a protective diverting colostomy. Unfortunately, reports concerning this practice contain relatively few patients with blunt trauma and it is unclear whether the principles established for penetrating injury should be applied in the setting of blunt colon injury. A retrospective review of 54,361 major blunt trauma patients admitted to nine regional trauma centers from January 1, 1986, through December 31, 1990, was conducted. Statistical analysis of the data collected regarding 286 (0.5%) of these patients who suffered colonic injury revealed: (1) injury to the colon is found in more than 10% of patients undergoing laparotomy following blunt trauma; (2) available diagnostic modalities are unreliable in detecting isolated colonic pathology; (3) primary repair of full-thickness injuries or resection and anastomosis may be safely performed without diversion; (4) gross fecal contamination is the strongest contraindication to primary repair. Further, delay of surgery, shock, and the timing of antibiotic administration were not associated with significantly increased morbidity.


The clinical utility of computed tomographic scanning and neurologic examination in the management of patients with minor head injuries. The evaluation and management of patients with minor head injury (MHI: history of loss of consciousness or posttraumatic amnesia and a GCS score greater than 12) remain controversial. Recommendations vary from routine admission without computed tomographic (CT) scanning to mandatory CT scanning and admission to CT scanning without admission for selected patients. Previous reports examining this issue have included patients with associated non-CNS injuries who confound the interpretation of the data and affect outcome. We hypothesized that patients with MHI and no other reason for admission with normal neurologic examinations and normal CT scans would have a negligible risk of neurologic deterioration requiring surgical intervention. To validate this hypothesis we studied 2766 patients with an isolated MHI admitted to seven trauma centers between January 1, 1988, and December 31, 1991. There were 1898 male patients and 868 female patients; injury was blunt in 99%. A neurologic examination and a CT scan were performed on 2166 patients; 933 patients had normal neurologic examinations and normal CT scans and none required craniotomy; 1170 patients had normal CT scans and none required craniotomy; 2112 patients had normal neurologic examinations and 59 required craniotomy. The sensitivity of the CT scan was 100%, with positive predictive value of 10%, negative predictive value of 100%, and specificity of 51%. The use of CT alone as a diagnostic modality would have saved 3924 hospital days, including 814 ICU days, and $1,509,012 in hospital charges. Based on these data, we believe that CT scanning is essential in the management of patients with MHI and that if the neurologic examination is normal and the scan is negative patients can be safely discharged from the emergency room.


Pitfalls in the use of color-flow duplex ultrasound for screening of suspected arterial injuries in penetrated extremities. We compared color-flow duplex ultrasonographic scanning (CFD) to arteriography in 67 patients who sustained 75 penetrating injuries to the extremities without obvious arterial injury. There were 72 negative and three (4.0%) positive CFD studies and no failed attempts. With arteriography as the "gold standard," CFD had a specificity of 99% and a sensitivity of 50%, positive and negative predictive values of 66% and 97%, and an accuracy of 96%. Small pseudoaneurysms were missed in an axillary and an aberrant radial artery, and a genicular artery pseudoaneurysm was misread as originating from the popliteal artery. Cautious interpretation of negative studies appears warranted, particularly in the axilla and in bifurcated arteries. Extremity arteries should be completely imaged to rule out aberrant anatomy. Questionable studies should be confirmed arteriographically. With these caveats, color-flow duplex scanning may be useful for screening extremities with penetrating injuries thought to harbor occult arterial injuries.


The deleterious effects of intraoperative hypotension on outcome in patients with severe head injuries. Prehospital or admission hypotension doubles the mortality for patients with severe head injury (SHI = Glasgow Coma Scale score less than or equal to 8). To our knowledge no study to date has determined the effects of intraoperative hypotension [IH: systolic blood pressure (SBP) less than 90 mm Hg] on outcome in patients with SHI. This study examined 53 patients who had SHI and required early surgical intervention (surgery within 72 hours of injury). All patients were initially normotensive on arrival. There were 17 patients (32%) who developed IH and 36 (68%) who remained normotensive throughout surgery. The mortality rate was 82% in the IH group and 25% in the normotensive group (p less than 0.001). The duration of IH was inversely correlated with Glasgow Outcome Scale using linear regression (R = -0.30; p = 0.02). Despite vigorous fluid resuscitation in the IH group, additional pharmacologic support was used in only 32%. These data suggest that IH is not uncommon after SHI (32%) and that it does have a significant effect on patient outcome.


Impact of minimal injuries on a level I trauma center. Overtriage (i.e.; transport of patients with minimal injuries to a trauma center) has been accepted as necessary to avoid missing clinically significant injuries. We reviewed our experience with 344 patients (ISS less than or equal to 4) who were admitted to a level I trauma center during a 2-year period. The trauma team was activated for 209 patients (TA), and emergency department referrals accounted for 135 (ED). One hundred seventy-three patients (TA = 64%, ED = 36%) met American College of Surgeons' Committee on Trauma (ACSCOT) field triage criteria (FTC). Mechanism of injury, especially ejection from a motor vehicle, was the most frequently utilized FTC indicator. We found no differences between the TA and ED groups relative to Trauma Score, Glasgow Coma Scale score, Injury Severity Score, length of stay, or ICU days. Mean total costs were higher for the TA group than for the ED group. The TA group had a higher nursing acuity level than the ED group. Compliance with FTC yields an inherent overtriage of minimally injured patients; however, noncompliance with FTC compounds the overtriage rate. Failure to comply with FTC is costly, labor intensive, and may represent misuse of the trauma system. We propose continual re-education of prehospital personnel, increased responsibility of all hospitals in the trauma center catchment area, and protocols for "downstaging" trauma resuscitation in minimally injured patients.


Routine pelvic x-ray studies in awake blunt trauma patients: a sensible policy? To evaluate the usefulness of routine pelvic x-ray films in the resuscitation of blunt trauma victims, 1395 patients were prospectively evaluated over a 13-month period. Of these, 810 (58%) were awake with Glasgow Coma Scale scores greater than or equal to 13 and were enrolled into the study. A history, with directed questions regarding pelvic pain, a clinical examination of the pelvis, and an anterior-posterior pelvic x-ray film (APPX) were obtained for each patient. Thirty-nine patients (5%) had fractures identified on the x-ray films. Of these patients with radiographically identified fractures, 34 (87%) complained of pain and had positive results on clinical examination, two (5%) either complained of pain or had positive results on examination and three (8%) had neither complaint of pain nor positive examination results. Of the 771 patients without fractures 743 (96%) lacked pain complaints or positive examination results. The likelihood of fracture was greatest in patients with complaints of pain and positive examination results (65%) followed by patients with either complaint of pain or positive examination results (16%). Only three (0.4%) of the 743 patients having no complaints of pain and a negative clinical examination had fractures diagnosed roentgenographically. These were minor fractures that did not affect the clinical course. Total charges incurred to diagnose pelvic fractures in this low-yield patient group were $88,028. We conclude that the practice of obtaining a screening APPX is not necessary or cost-effective in the management of awake blunt trauma patients who do not complain of pain and who have normal pelvic physical examination results.


Base deficit stratifies mortality and determines therapy. To determine the association of base deficit with mortality and other factors affecting mortality. Retrospective review. Tertiary care center. Consecutive samples of 3791 trauma patients admitted with an arterial blood gas sample taken in the first 24 hours. Age, injury mechanism, head injury, shock (systolic blood pressure less than 90 mm Hg), Revised Trauma Score, TRISS probability of survival Ps, and mortality. Most (3038) patients (80.1%) exhibited a base deficit. Base deficit, age, injury mechanism, and head injury were associated with mortality using logistic regression. Age less than 55 years, no head injury, and a base deficit of -15 mmol/L were associated with 25% mortality. Age greater than or equal to 55 years with no head injury or age less than 55 years with a head injury and a base deficit of -8 mmol/L were associated with a 25% mortality. When shock was added to the model, all factors remained significant, and base deficit was supplemental to blood pressure. Base deficit also added significantly to the Revised Trauma Score and TRISS measurements. The base deficit is an expedient and sensitive measure of both the degree and the duration of inadequate perfusion. It is useful as a clinical tool and enhances the predictive ability of both the Revised Trauma Score and TRISS.


Analysis of organ procurement failure at an urban trauma center and the impact of HIV on organ procurement at a regional transplantation center. A 42-month experience with 100 patients with fatal head injuries was analyzed to identify areas of organ procurement failure. Thirty-six patients were ineligible for organ donation. Reasons for exclusion included advanced age (7), sepsis (16), hepatitis (1), systemic illnesses (3), and HIV infection or risk (9). Resuscitation failure (17 patients) and late deaths from failed support (16 patients) left 31 potential donors. Of the 30 families asked to donate, 17 consented (56.7%). Annual consent rates were 25%, 71%, 75%, and 67%. Efforts to improve organ procurement should focus on resuscitation and physiologic support of potential donors. To assess the impact of HIV infection or risk on organ procurement, a 3-year experience of the regional transplantation center (RTP) was reviewed. Of 1,714 referrals to the RTP from 102 hospitals, 1,120 were from trauma centers. The incidence of rejection because of HIV risk or infection was significantly higher in the trauma center group than in the group from non-trauma centers, 17.2% versus 10.2% (p less than 0.004). A similar difference was noted between metropolitan and suburban hospitals (p less than 0.0001). Hepatitis risk was comparable, 3.9% vs. 3.2%. The risk of HIV infection is emerging as a factor limiting organ donation at urban trauma centers.


Associated aortic rupture-pelvic fracture: an alert for orthopedic and general surgeons. Blunt trauma patients with pelvic fractures have been shown to have a two-fold to five-fold increased risk of aortic rupture compared with the overall blunt trauma population. A retrospective review was performed to determine whether the relationship between aortic rupture and pelvic fracture could be further delineated using a pelvic fracture classification based on mechanism of injury. Of 4,157 consecutive blunt trauma patients, 371 (8.9%) had pelvic fractures, 34 (0.8%) had ruptured thoracic aortas and 12 had both injuries. When pelvic fractures were classified according to vector of force, 10 of 12 (83%) aortic ruptures occurred in patients with an anterior-posterior compression fracture pattern, an incidence of aortic rupture eight times greater than that of the overall blunt trauma population. There was no increased incidence of aortic rupture among patients with any other pelvic fracture pattern. We conclude that the previously reported association between aortic rupture and pelvic fracture can be further specified to include, predominantly, those patients with an anterior-posterior compression fracture pattern.


Percutaneous tracheostomy/gastrostomy in brain-injured patients--a minimally invasive alternative. Tracheostomy and gastrostomy are frequent adjunctive procedures required in the management of patients with severe brain injuries to facilitate neurorehabilitation. We therefore evaluated the use of two minimally invasive surgical procedures, percutaneous tracheostomy (PT) and percutaneous endoscopic gastrostomy (PEG), in 27 patients with severe brain injuries. The mean age was 41 +/- 4 years, and 23 (85%) were men. All patients were intubated, and 19 (70%) required mechanical ventilator support on the day of PT/PEG. The endotracheal tubes had been in place for 1 to 21 days (mean, 8.7 +/- 0.8). All patients were stable from their acute brain injury; 13 had intracranial pressure (ICP) monitors in place. The Seldinger technique, as described by Ciaglia, was employed for PT. Following PT, a PEG was inserted by a modification of the Sachs-Vine "push" technique. We were uniformly successful in placing these access tubes. Complications were minor and not clinically significant. Three of 13 patients (23%) with ICP monitors had a transient rise in ICP related to PT and one of these patients developed local subcutaneous emphysema. Another patient experienced a mild cellulitis at the tracheostomy site. Of note, there were no PEG-related complications. In conclusion, PT and PEG are readily learned, minimally invasive procedures. In our experience with patients with severe brain injuries combined PT/PEG is a uniformly safe alternative to gain long-term access to the airway and gut.


Preventable complications and death from multiple organ failure among geriatric trauma victims. We reviewed 374 consecutive trauma patients over age 65 years to determine (1) if the emergency room Trauma Score (TS) could predict mortality, thereby improving ICU triage, and (2) the frequency of preventable complications in patients who died (n = 31). Fifty-two percent of deaths (n = 16) occurred in patients with TS = 15 or 16. Multiple organ failure/sepsis (MOF/S) was the most common cause of death overall (42%) and was also the most frequent cause of death in patients with a TS = 15-16 (63%). Nonsurvivors in the TS = 15-16 subgroup were older (80.9 +/- 2.0 vs. 74.9 +/- 0.5 years, p less than 0.02) and had greater ISSs (15.8 +/- 3.7 vs. 8.0 +/- 0.4, p = 0.001) than survivors. Patients with a TS less than 15 suffered high overall mortality (45%). Preventable complications contributed to mortality in 32% of all deaths and in 62% of MOF/S deaths. Aggressive care to prevent avoidable complications may improve survival in elderly trauma victims.


Acute stabilization of the cervical spine by halo/vest application facilitates evaluation and treatment of multiple trauma patients. The management of acute cervical spine injuries has traditionally used bed-based skeletal traction until all non-neurologic injuries have been evaluated. This treatment method substantially hinders the ability to transport patients and to perform imaging studies and surgical procedures. In contrast, early application of a halo/vest apparatus provides immediate cervical stabilization and facilitates the diagnostic work-up and treatment of the patients with multiple injuries. The records of all 78 patients admitted from February 1988 through June 1991 who had acute cervical spine fractures, subluxations, or both with a risk of instability were reviewed. All patients were treated with halo/vests and no patient deteriorated neurologically following halo/vest application. Twenty-nine patients (37%) had a total of 55 associated injuries including long bone/pelvic fractures in 17, thoracic injuries in 13, closed head injuries in 11, facial fractures in 6, noncontiguous spinal fractures in 5, and abdominal injuries in 3. The mean injury Severity Score (ISS) was 18 (range, 9-54). While in the halo/vest, 43 patients (55%) had a total of 99 diagnostic studies completed and 46 patients (59%) had a total of 76 surgical procedures performed. There were 35 neurosurgical procedures on 32 patients and 41 non-neurosurgical surgical procedures on 24 patients. Over the past year, 20 of 21 patients (95%) had their halo/vest placed in the emergency department. The data demonstrate that many diagnostic and surgical procedures need to be performed on patients with unstable cervical spine injuries.(ABSTRACT TRUNCATED AT 250 WORDS)


Nutritional assessment using a pulmonary artery catheter. To determine if oxygen consumption (VO2) derived from the Fick equation (FE) can be used to determine energy expenditure (EE), 29 paired indirect calorimetry (IC) and FE VO2 determinations were obtained. The Weir equation was used to calculate EE from the FE VO2 value. There was a strong correlation between the methods (r = 0.82, p less than 0.001). Mean EE by IC and FE was 2460 +/- 539 and 2372 +/- 787 kcal/day, respectively, a difference of 88 +/- 467 kcal/day. A single IC determination is often used to guide nutrition for several days. To evaluate this practice, FE and IC determinations were repeated in 8 patients. There was a 19% difference in EE between initial and follow-up IC, which was identical to the mean difference between paired FE and IC measurements. FE can be used to estimate EE, and is as accurate as using a single IC reading to predict EE on subsequent days.


The disparity between hypothermic coagulopathy and clotting studies. Hypothermic patients commonly develop coagulopathy, but the effects of hypothermia on coagulation remain unclear because clinical laboratories routinely perform clotting tests only at 37 degrees C. Measurements of activated partial thromboplastin times (APTT), prothrombin times (PT), and thrombin times (TT) were performed on plasma from normothermic and hypothermic rats at a range of temperatures (25 degrees-37 degrees C) to assess the effects of hypothermia on apparent clotting factor levels and clotting factor activities. In general, clotting times were more severely prolonged when test temperatures were hypothermic than when body temperatures were hypothermic. Indeed, little to no prolongation resulted from body hypothermia alone. These findings reveal the observed disparity between clinically evident hypothermic coagulopathy and near-normal clotting studies. Clotting studies performed at 37 degrees C will not confirm hypothermic coagulopathy. These results indicate that the appropriate treatment for hypothermia-induced coagulopathy is rewarming rather than administration of clotting factors.


The role of laparoscopy in abdominal trauma. Thirty-nine hemodynamically stable trauma patients were evaluated prospectively by laparoscopy before planned celiotomy. Laparoscopy was performed using a forward-viewing laparoscope connected to two high-resolution video monitors. The mechanism of injury was blunt trauma in eight, stab wounds (SWs) in 16, and gunshot wounds (GSWs) in 15. Laparoscopy correctly identified the presence of an intraperitoneal injury in 26 patients. Six other patients had retroperitoneal injuries, five of which were seen on laparoscopy. The remaining seven patients had no demonstrable intraperitoneal or retroperitoneal injuries, did not undergo celiotomy, and were observed without morbidity. In comparison with findings at surgery, laparoscopy identified injuries to the liver in eight of ten, to the diaphragm in three of three, to the colon in two of three, to the stomach in three of three, to the kidney in one of one, to the spleen in none of three, and to the small bowel in none of four patients. Visualization of the spleen was achieved in only one patient. The extent of the hemoperitoneum was underestimated from the laparoscopic examination in all nine patients with greater than 750 mL of peritoneal blood, four of whom had undetected active bleeding. Laparoscopy was performed easily in all patients and there were no complications associated with its use. In conclusion, the absence of an intra-abdominal injury was correctly identified with laparoscopy in 11 patients and laparoscopy may decrease the need for celiotomy in selected patients. However, the inability to "run the small bowel," visualize the spleen, and evaluate hemorrhage limits the utility of laparoscopy in determining which patients with laparoscopically visualized injuries will require celiotomy.


An analysis of the relationship between fluid and sodium administration and intracranial pressure after head injury. Severe head injury is the leading cause of traumatic death. When a severe head injury is combined with hypotension the mortality doubles. The use of asanguineous salt solutions to maintain blood pressure, however, may contribute to cerebral swelling and intracranial hypertension. For this reason, restrictions of fluids (FLD) and sodium (Na) have been advocated. To our knowledge, however, there are no clinical data to support this recommendation. We hypothesized that in adult patients sustaining severe head injuries (Glasgow Coma Scale score less than or equal to 8) with or without associated injuries: (1) FLD balance and total Na administered during the initial 72 hours of hospital admission are positively and significantly correlated with each other, and (2) total FLD, FLD balance, and total Na administration during the initial 72 hours are significantly and positively correlated with changes in ICP and adverse outcome. We retrospectively studied 40 adult trauma patients with severe head injuries. We found a significant correlation between total Na and FLD balance (R2 = 0.54; p less than 0.05). However, we found no significant correlation between total FLD and maximum ICP (R2 = 0.081), ICP score (R2 = 0.01), or outcome (R2 = 0.066), no significant correlation between FLD balance and maximum ICP (R2 = 0.000), ICP score (R2 = 0.000), or outcome (R2 = 0.01), and no significant correlation between total Na and maximum ICP (R2 = 0.000), ICP score (R2 = 0.001), or outcome (R2 = 0.02). We conclude that Na and FLD administration are not independent determinants of ICP during the initial 72 hours after brain injury.


Monoethylglycinexylidide production parallels changes in hepatic blood flow and oxygen delivery in lung injury managed with positive end-expiratory pressure. Mechanical ventilation with high levels of positive end-expiratory pressure (PEEP) decreases hepatic blood flow (HBF) and hepatic oxygen delivery (HO2D). Noninvasive methods of detecting decreased HBF might prevent hepatic ischemia and dysfunction. Monoethylglycinexylidide (MEGX) is a hepatic metabolite of lidocaine, used clinically to determine graft function following hepatic transplantation. In order to test the hypothesis that MEGX production would be affected by changes in hepatic hemodynamics associated with lung injury, 12 dogs were instrumented with femoral and pulmonary artery catheters. Splenectomy was performed and the portal and hepatic veins cannulated. The hepatic artery and portal vein were encircled with flow probes. Lung injury was induced in six animals (INJURED group) with oleic acid (0.08 mL/kg) and 10 cm H2O PEEP was added to correct subsequent shunt. Levels of MEGX were measured 15 minutes after injection of intravenous lidocaine (1 mg/kg). Levels of HBF, HO2D, and MEGX were measured at BASELINE, after lung injury (INJURY time point), and after addition of PEEP (PEEP time point). CONTROL animals (n = 6) were studied at the same time points but without lung injury or PEEP. Hepatic blood flow and hepatic oxygen delivery were significantly decreased after lung injury and further decreased after PEEP. Levels of MEGX were unchanged in the CONTROL group but were significantly reduced by lung injury and PEEP in the INJURED group. Decreased MEGX production may be a useful clinical indicator of reduced hepatic flow and oxygen supply in critical illness.


Thalamic hand: a late onset sequela of stroke and its influence on physical function after rehabilitation: two cases report. Thalamic hemorrhage or infarction is one of the common causes of stroke. People who suffer from this type of cerebrovascular disease may develop thalamic syndrome which includes sensory disturbance, motor deficit and psychological problems. In this report, we introduce two cases of thalamic hemorrhage followed up for more than a half year after stroke. Delayed rigidity and choreodystonic type of involuntary movement over their paretic hand developed gradually. The metacarpophalangeal joints of the affected hand were kept flexed and the proximal and distal interphalangeal joints became extended. Thalamic hand is demonstrated in the appended pictures. Once the patient develops a thalamic hand, activities of daily living will be affected due to poor hand performance despite of high motor recovery stage. Early recognition and proper rehabilitation program for the patients with thalamic hand are emphasized.


Traumatic tension pneumocephalus--intracerebral pneumatocele: a case report. An 18-year-old Chinese man, suffering from head injury in a motorcycle accident, with right traumatic frontal intracerebral hemorrhage and frontal bone fractures, underwent emergency craniotomy with evacuation of hematoma at a local out-patient clinic and three months later, he suffered from CSF rhinorrhea. Headache, nausea and vomiting developed a week prior to admission. Tension pneumocephalus was diagnosed by computed tomography (CT) scan and plain skull X-ray. The fistula tract of the ethmoid sinus was investigated by radioisotope albumin (RISA) cisternography. The patient subsequently underwent emergency craniotomy for decompression. During the operation, we found that the intracerebral pneumatocele in the right frontal lobe communicated with the ipsilateral ethmoidal sinus, through which extracranial air ingressed and CSF egressed. This pneumatocele was unroofed and the fistula was temponaded by pericranial muscles and the Gelfomas sealed by tissue glue. Finally duraplasty was performed. Follow-up CT scan revealed that pneumocephalus subsided and the patient was cured of CSF rhinorrhea on discharge. As a surgical emergency, tension pneumocephalus can be successfully treated only by early diagnosis and early treatment.


[Bleeding secondary duodenal diverticulum: a rare late complication following nephrolithotomy]. Secondary duodenal diverticula are due primarily to traction upon that section from some other cause such as ulcer, cholecystitis and so forth. It accounts for 1.6 to 20% of all duodenal diverticula. Numerous reports of gastrointestinal hemorrhage from duodenal diverticula have appeared in the literature. But massive UGI bleeding due to secondary duodenal diverticulum, caused by nephrolithotomy, was a rare late complication. Here we present a case of a 63-year-old male patient who underwent a right side nephrolithotomy 10 and 8 years previously, then developed massive UGI bleeding suddenly. Pre-operative UGI series and gastroscopy showed chronic duodenal ulcer and duodenal diverticulum at second section where much blood clot was noted. In time, a successful operation was performed. This complication of secondary duodenal diverticulum was rare, so consideration regarding management and surgical approach was discussed.


Intravenous dipyridamole technetium-99m MMI myocardial perfusion scintigraphy for detection of coronary artery disease. To evaluate the efficacy of stress technetium-99m MMI (N-2-methoxy-2-methyl propyl isonitrile) myocardial perfusion scintigraphy (Tc-99m MMI) using intravenous dipyridamole for detection of coronary artery disease (CAD), we collected 66 cases (53 men, 13 women, aged 40-79 years old) between Sept. 1990 and Oct. 1991. The cases were divided into two groups: group I involving 44 patients received coronary arteriography (CAG) examination without previous percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG); group II embracing 22 patients received no CAG examination but all were suffering from old myocardial infarction (MI) evidenced by history and electrocardiography (ECG). All cases underwent Tc-99m MMI planar and single photon emission computed tomography (SPECT) both on intravenous dipyridamole stress and separate day rest tests. Of the 44 group I patients receiving both Tc-99m MMI and CAG, 35 (79.5%) were positive and 7 (16%) were negative by both tests and another 2 (4.5%) were positive by CAG only. Of those positive by both tests, 21 (60%) suffered from identical coronary arterial involvement, including 13 one-vessel disease, 5 double-vessel disease and 3 triple-vessel disease. Of group II patients, 14 suffered from old inferior wall (IW) MI, 6 from old anterior or anteroseptal wall (AW) MI, 1 from old lateral wall (LW) MI and another 1 from combined old anterior and lateral wall (ALW) MI by ECG. Of the 14 patients with IWMI by ECG, all suffered from right coronary artery (RCA) disease but 7 (50%) of them from multivessel disease (MVD) by Tc-99m MMI. 5 of the 6 patients with AWMI by ECG suffered from left anterior descending coronary artery (LAD) disease, but 3 of them from MVD by Tc-99m MMI. Both patients with LWMI and ALWMI by ECG suffered from triple-vessel disease by Tc-99m MMI. The sensitivity of Tc-99m MMI in detecting CAD in group I was 95%, the specificity was 100%. The sensitivity for detection of individual coronary artery disease in LAD, left circumflex coronary artery (LCX) and RCA was 96%, 45% and 89% in this order and the respective specificity was 94%, 100% and 88%. In group II the sensitivity was 95%. The overall sensitivity of intravenous dipyridamole Tc-99m MMI for detection of CAD in groups I and II was 95%; specificity was 100% and accuracy was 95%. In conclusion, stress Tc-99m MMI using intravenous dipyridamole is a valuable method for evaluation and detection of CAD.


Quantitative measurement of muscle and subcutaneous fat thickness in newborn by real-time ultrasonography: a useful method for site and depth evaluation in vaccination. In order to quantify muscle thickness and choose the appropriate site for intramuscular injection of vaccines in neonates, we used ultrasonography to measure muscle and subcutaneous fat thickness of anterolateral mid-thigh, upper outer quadrant of buttock and middle area of deltoid in fifty full term (group 1) and thirty low birth weight (group 2) infants. A Hitachi EUB40 real-time scanner and a 5 MHz transducer was used in the study. We delineated the normal distribution of muscle and subcutaneous fat thickness in mid-thigh, buttock and deltoid areas of full term and low birth weight infants. There was no significant difference between male and female infants in the two groups. Muscle and subcutaneous fat thickness in the thigh area was 11.8 +/- 1.9 mm and 3.8 +/- 0.4 mm, respectively, in group 1; 8.6 +/- 1.7 mm and 2.7 +/- 0.5 mm in group 2. Figures in the buttock area were 10. 1 +/- 1.5 mm and 3.7 +/- 0.5 mm in group 1, 6.9 +/- 1.2 mm and 2.7 +/- 0.7 mm in group 2; and in the deltoid area were 5.2 +/- 0.7 mm and 3.4 +/- 1.5 mm in group 1 and 3.8 +/- 0.8 mm and 2.3 +/- 0.6 mm in group 2. There was significant logarithmic correlation between muscle thickness and body weight (r = 0.6, 0.8, 0.6) and muscle thickness and body length (r = 0.4, 0.6, 0.6) in thigh, buttock and deltoid areas of the low birth weight infants. In contrast, there was significant logarithmic correlation only between buttock muscle and body weight (r = 0.5) in the full term infants.(ABSTRACT TRUNCATED AT 250 WORDS)


Reconstruction of the severely deficient acetabulum with the bipolar prosthesis and allo-autograft. We reviewed the clinical results and radiographs of four patients who had revision of the acetabular component of a failed total hip arthroplasty with a bipolar socket supplemented by autoallograft to reconstruct massive bony defect. These patients were followed up from twelve to seventeen months. The clinical score was assessed by a modified d'Aubigne's rating score that assigned a maximum of 18 points. The preoperative clinical score ranged from 1 to 5 points (mean: 3.25 points). The postoperative score improved to a range of 13-17 points (mean: 15.25 points). Of the hips examined, nearly all were pain-free. The largest possible bipolar cup was used with solid structural allografting augmented by morseled cancellous autograft. These have been uniformly trouble-free with acetabular reconstitution. Cup migration was minimal or none. The follow-up periods were short and some migration is probably to be anticipated in the future. Although this technique was originally conceived as part of a staged procedure, it seemed as a definitive procedure yielding acceptable results for dealing with a severely deficient acetabulum. Larger series and longer periods of follow-up are demanded to support this assertion.


[The management of sinus tracts of dental origin]. The purpose of this study was to evaluate the results of conservative endodontic therapy of 86 fistulous cases of dental origin at the Department of Conservative Dentistry, Kaohsiung Medical College Hospital. Approximately 60% (52/86) endodontically treated teeth, with a minimum recall period of 6 months, were evaluated for success or failure. The results are as follows: (1) The overall success rate was 82.7% (43/52) fistulous cases. There was no significant statistical difference between male and female patients. (2) There was a better success rate with cases over a 2-year recall period than with cases under a 2-year recall period, but there was no significant statistical difference between these two groups. (3) Cases with periapical pathosis less than 5 mm in diameter, had a better success rate than those with periapical pathosis larger than 5 mm in diameter, but there was no significant statistical difference between these two groups. (4) There was a 79.1% (34/43) success rate in non-surgically treated cases, and a 66.7% success rate (6/9, excluding three successfully retreated cases which had been originally treated with a non-surgical technique) in surgically treated cases.


[Histological study of the change of pulp tissue during shedding of the deciduous tooth]. To understand the pulp change of root resorption of human deciduous teeth from a histological point of view, one hundred and twenty specimens were collected for study. The teeth (caries-free) were extracted for occlusal reason or because they exhibited various degrees of mobility and discomfort. The extent of root resorption was classified into five grades: Res. i, Res. 1/4, Res. 1/2, Res. 3/4 and Res. Co., according to Moorrees et al. and Haavikko. All teeth were fixed in 10% formalin (pH 7.2) immediately after extraction for 3-7 days. They were then decalcified for 14 days in 5% formic acid-sodium citrate, sectioned serially at 7 microns and stained with hematoxylin and eosin, Masson's stain, and silver impregnated stain. All sections were examined under a light microscope. The results obtained were as follows: 1. While the root was resorbed more than one half way, some normal pulp was replaced by the connective tissue as in inflammation. Internal resorption could be seen. 2. By the time deciduous root resorption was essential as complete, normal pulp tissue was no longer present. 3. Because the nerve degenerated during initial tooth resorption, there was no evidence that deciduous root resorption was under nervous control. 4. The present observation suggests that in addition to odontoclasts, several other cells such as fibroblast-like cells and macrophages, were actively involved in root resorption during the shedding of deciduous teeth.


Types of dementia in Taiwan--a prospective study. We prospectively investigated 100 consecutive inpatients with suspected dementia to evaluate the relative frequency of various types of dementia in a general hospital of Taiwan. Dementia was confirmed in 86 cases (86%) according to the dementia criteria of the third revised edition of the Diagnostic and Statistical Manual of Mental Disorders and Clinical Dementia Rating Scale (greater than or equal to 1). In contrast to the western developed countries, vascular dementia (VD) (35%) was the leading type of dementia, followed by Alzheimer's disease (AD) (27%), mixed VD and AD (MIX) (14%), and other degenerative diseases (10%). Ten cases (11.6%) of potentially treatable dementia were identified and 8 of 10 had good improvement after appropriate treatment. There were significant age differences among patients with MIX, AD and VD (p less than 0.01). Those with MIX were the oldest (72.12 +/- 9.4) followed by AD (69.70 +/- 8.52) and VD (64.81 +/- 9.12). Males were slightly predominant in this series (male:female = 50:36). A comprehensive clinical investigation including laboratory tests, electroencephalography and CT are necessary in the assessment of demented patients in order to make correct etiological diagnoses which lead to appropriate treatment or management of this terrifying syndrome.