Gliomas in families.

Gliomas in families. This is a descriptive study of 19 families with glial tumors. Twelve were identified prospectively from 178 consecutive, unrelated adults and children with newly diagnosed gliomas seen at a regional cancer center between 01 Jan 89 and 31 Mar 91 (6.7%). There were 45 affected members (42 confirmed); 30 males, 15 females, ages 4 months-78 years (median, 44.5 years; mean, 38.9 years). Two families had four affected members, three families had three, and the others two. All confirmed tumors were supratentorial and all, save one, contained an astrocytic element. Three additional members of two families had other brain or neuroectodermal tumors. These families were not unusually cancer prone and did not appear to have neurofibromatosis, tuberous sclerosis, or colonic polyposis. There was no consistent pattern of inheritance.


Symptomatic dystonia: clinical profile of 46 Brazilian patients. Dystonia is a syndrome characterized by sustained muscle contraction, provoking twisting and repetitive movements or abnormal postures. It may be classified according to etiology, as idiopathic or symptomatic. We studied 122 Brazilian patients with a dystonic syndrome. Of these, 46 (37.7%) had symptomatic dystonia. The most frequent cause was tardive dystonia (34.8%) followed by perinatal cerebral injury (30.4%). Other causes were stroke (13.0%), encephalitis (6.5%) and Wilson's disease (4.3%). Cranial trauma, mitochondrial cytopathy and psychogenic, were the least frequent causes with one patient in each category. The etiology in two patients could not be established. Perinatal cerebral injury and postencephalitic dystonia were seen in the younger age group, while post-stroke and tardive dystonia were seen in the older age group.


The role of magnetic resonance imaging in acute transverse myelitis. Eighteen adult patients presenting with acute transverse myelitis (ATM) were evaluated using magnetic resonance imaging. Only 7 had abnormal scans showing an area of increased signal intensity within the cord solely on T2 weighted images; T1 weighted images were normal. The MRI abnormality did not correlate with the cause of the transverse myelitis, the extent of maximum neurological deficit, or the prognosis. A scan performed more than 5 days after the onset of disease was most likely to be positive. Even though the prognostic value of MRI in ATM may be limited, it remains a valuable technique for ruling out other causes of noncompressive spinal cord lesions, such as hemorrhage, vascular malformation, or tumor.


Changes in the bacterial flora of the upper and lower respiratory tracts and bronchoalveolar lavage differential cell counts in feedlot calves treated for respiratory diseases. Serial nasopharyngeal swab and bronchoalveolar lavage cultures were used to estimate changes in the bacterial flora of the respiratory tracts of calves during the first month after arrival in the feedlot. Bronchoalveolar lavage (BAL) differential cell counts served to evaluate pulmonary inflammatory changes during this period. Two groups of calves were studied, one consisting of clinically normal controls (n = 60), the other, of cases (n = 59) which received treatment for respiratory disease (penicillin +/- trimethoprimsulfadoxine). A variety of organisms, including Pasteurella multocida, Pasteurella haemolytica, Haemophilus somnus, Mycoplasma bovis and Mycoplasma bovirhinis, were present in the upper and lower airways of both groups during the postarrival period. With the exception of M. bovis, an overall decline in the prevalence of these organisms was observed during the course of the study. In cases, there was a marked decrease in the number of Pasteurella spp. and H. somnus isolates immediately following treatment. For the Pasteurella spp., however, this effect was shortlived as they often appeared to recolonize the respiratory tract within eight days of terminating antimicrobial therapy. Treatment did not appear to affect the frequency of isolating M. bovis. Its prevalence, in both groups of calves, increased to levels approaching 100% during the course of the study. All Pasteurella spp. isolates were tested for susceptibility to several commonly used antimicrobials. Resistance was only evident among P. haemolytica isolated from cases and in every instance this was to a combination of penicillin, ampicillin and tetracycline. Significantly more isolates were resistant after treatment than before. There were BAL differential cell count abnormalities indicative of inflammation in both cases and controls.(ABSTRACT TRUNCATED AT 250 WORDS)


Age distribution of animals persistently infected with bovine virus diarrhea virus in twenty-two Danish dairy herds. The objectives of this study were to compare the age distribution of animals persistently infected (PI) with bovine virus diarrhea virus (BVDV) in 12 herds with clinical BVD compared to ten herds without clinical BVD and to examine the incidence of PI calves born after the oldest PI animal. Blood samples from all animals were tested for bovine virus diarrhea virus and antibodies. In five herds, blood samples were obtained from calves born after the whole herd had been tested. All calves born by PI dams were also blood tested. In herds with clinical BVD the median age of PI animals was 248 days and in herds without clinical BVD the median age was 144 days. There was no significant difference between the age of PI animals in herds with clinical BVD compared to herds without clinical BVD (p = 0.48) suggesting similar epidemiology of the occurrences of PI animals in the two herd categories. Thereafter, all herds were used to study the incidence of PI animals. A total of 129 PI animals were found. In ten herds with 72 PI animals the age range of PI animals was more than six months. In these herds 26.3% of the PI animals were born within the first two months after birth of the oldest PI animal, no PI animals were born 2- less than 6 months, 52.7% were born 6- less than 14 months, 6.9% were born 14- less than 22 months and 13.9% (all born by PI dams) were born later than 22 months after the oldest PI animal.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of Pasteurella haemolytica leukotoxic culture supernatant on bovine neutrophil aggregation. Pasteurella haemolytica A1 leukotoxic culture supernatant was evaluated for its ability to cause aggregation of bovine peripheral neutrophils. Neutrophils were isolated by a hypotonic lysis method and incubated with zymosan-activated plasma (ZAP), leukotoxic culture supernatant, antileukotoxin serum, calcium and magnesium-free media, p-bromophenacyl bromide and protein kinase C inhibitors. Aggregation was evaluated by changes in infrared light transmittance. Leukotoxic culture supernatant caused neutrophils to aggregate, and this effect was significantly removed by preincubation with antileukotoxin serum. Aggregation to ZAP and leukotoxin was dependent on the presence of extra-cellular calcium. Activation of protein kinase C by phorbol myristate acetate induced aggregation which was reduced by staurosporine; however, aggregation to leukotoxin did not involve protein kinase C activation. Phospholipase A2 inhibition did not alter the aggregation response to ZAP or to leukotoxin. The in vitro measurement of neutrophil aggregation induced by the leukotoxin of P. haemolytica reflects cytoskeletal and other activation events that may contribute to the intense inflammatory process which this organism induces in the lungs of cattle.


Relaxin is not associated with poor milk yield in the postpartum sow. Porcine relaxin (pRXN) titers were measured in 109 plasma samples drawn between 24 and 120 h post-partum from good (n = 34), and poor (n = 25) milking sows and from sows (n = 12) exhibiting overt signs of hypogalactia located on six swine farms in Ontario. Mean plasma pRXN titers among the three groups at 24 h post-partum were not significantly different although there was considerable variation. By 48 h however, the pRXN titers had declined markedly in all groups and between 72 and 120 h, pRXN was cleared from the plasma of all sows examined except one hypogalactic animal that had a titer of 1.13 ng/mL at 96 h. These results suggest that, although pRXN may be identifiable in the corpora lutea during the puerperium, it does not contribute to either hypogalactia or poor lactational performance in sows. The data also encourage the view that pRXN could be used at farrowing without deleterious effects on suckling.


Development of a model ribosomal RNA hybridization assay for the detection of Sarcocystis and other coccidia. Two regions of the primary structure of the small subunit rRNA of Sarcocystis muris bradyzoites were compared with nucleotide sequences of S. gigantea, Toxoplasma gondii, Plasmodium berghei and Mus musculus and used to design genus- and species-specific probes for the detection and identification of coccidia. Total cellular RNA of purified S. muris, S. cruzi, T. gondii and Eimeria nieschulzi and coccidia-infected tissues of mouse, ox, sheep and pig, were assayed using twenty-base oligomers labelled with 32P. Hybridization occurred at temperatures ranging from 21 degrees C to 41 degrees C or 51 degrees C. One probe detected only S. muris and another successfully hybridized to several members of coccidia, including S. muris, S. cruzi, T. gondii and E. nieschulzi. One ng of total cellular RNA was sufficient to yield detectable hybrids in slot blot assays. The excellent sensitivity suggests that rRNA-based probes are capable of detecting individual parasites, and can assay low levels of coccidial infections not detectable by other methods. The results of this study show that it is possible to customize the specificity of rRNA-based probes for diagnostic, epidemiological or taxonomic purposes.


The effect of dietary sodium on right ventricular failure-induced ascites, gain and fat deposition in meat-type chickens. Experiments were carried out using various levels of sodium (Na+) from NaCl or NaHCO3 to determine: 1) the level of Na+ required to induce ascites alone or in combination with cold temperature and 2) the effect of Na+ on weight gain and fat deposition in broiler chickens. In experiment 1, there were no cases of ascites using levels of Na+, from NaCl at 0.14% to 0.44% in the feed from day 3 or using added Na+, from NaCl at 0.0% to 0.12% in the water from day 3 with a level of 0.14% in the feed. There was no significant difference in 21 or 42 day body weight, feed conversion, or right ventricle:total ventricle (RV:TV) ratio between treatment groups. Day 3 to 4 body weight gains were significantly increased in all treatment groups with added Na+ (p less than 0.01). In experiment 2, with levels of added Na+, from NaCl, at 0.0% to 0.12% in the water with a level of 0.20% in the feed there were two cases of ascites, one at day 7 and one at day 40 at the 0.12% level. There were no significant differences in body weight at days 21 or 42 or in the RV:TV ratios between groups. Feed conversions were improved (p less than 0.01) with the lowest and highest levels of Na+ and a significant increase in day 3 to 4 body weight gain, with increasing Na+ in all treatment groups, was observed.(ABSTRACT TRUNCATED AT 250 WORDS)


Epidemiological studies of congo red Escherichia coli in broiler chickens. This prospective cohort study was designed to confirm the association between Congo red binding Escherichia coli (CREC) and E. coli air sacculitis in commercial broilers. It was also designed to evaluate CREC as an air sacculitis risk factor and to explore the CREC relationship to other air sacculitis risk factors (poultry house temperature, air-ammonia levels, and presence of other diseases). In addition, this study was used to assess a possible role of the broiler-breeder flocks and hatchers in the spread of CREC air sacculitis. Congo red E. coli-associated airsacculitis risk was based on CREC exposure of the chicks in the hatchers. Breeder flocks with greater than 30 CREC colonies/plate from hatcher air sampling tests were placed in the high risk group; flocks with less than five CREC colonies/plate were placed in the low risk group. Increased risks of death due to air sacculitis (RR = 2.26), and increased death rates due to CREC air sacculitis (RR = 9.45) in high-risk flocks, identified CREC as an important air sacculitis risk factor. The attributable risk percent of CREC airsacculitis from hatcher exposure of CREC was 89.4%, pointing to the hatcher as the source of CREC infection. The association of specific broiler-breeder flocks to high levels of CREC in the hatchers, and subsequent air sacculitis, suggests that the broiler-breeders are the ultimate source of CREC.


Salmonella enteritidis and other Salmonella in laying hens and eggs from flocks with Salmonella in their environment. Seven Canadian layer flocks with Salmonella enteritidis in their environment were investigated to determine the numbers of hens infected with S. enteritidis, the localization of S. enteritidis in organs of infected hens and the numbers of S. enteritidis-infected eggs produced by two affected flocks. By a microagglutination test (MAT) using S. pullorum antigens, these flocks had more seropositive hens (mean 51.9 +/- 16.9%) than two Salmonella-free flocks (mean 13.0 +/- 4.2%). Culture of tissues of 580 hens (433 seropositive) from the seven flocks detected 26 (4.5%) S. enteritidis-infected hens from two flocks. In one flock, 2/150 hens were infected with S. enteritidis phage type (PT) 8, which was confined to the ceca, and no Salmonella spp. were isolated from 2520 eggs (one day's lay). In the second flock, where 24/150 hens were infected with S. enteritidis PT13, extraintestinal infection was found in nine hens and involved the ovaries and/or oviduct in two hens. Salmonella enteritidis PT13 was isolated from one sample of egg contents and from one sample of cracked shells from among 14,040 eggs (one day's lay) from this flock. The overall prevalence of S. enteritidis-contaminated eggs from the two flocks with infected hens was less than 0.06%. Other Salmonella spp. isolated were S. heidelberg from 58 hens (10%), and S. hadar, S. mbandaka and S. typhimurium from one hen (0.2%) each. The MAT with antigens of S. pullorum had a sensitivity of 81% and a specificity of 24% for detecting S. enteritidis-infected hens.(ABSTRACT TRUNCATED AT 250 WORDS)


Use of bacitracin in the prevention and treatment of experimentally-induced idiopathic colitis in horses. Ten healthy ponies from a single herd were found by repeated fecal culture to be free of Salmonella species and Clostridium cadaveris. In a preliminary study, four ponies administered a single oral dose of 10 mg/kg lincomycin did not develop idiopathic colitis when the drug was administered alone. Four other ponies were administered 10 mg/kg lincomycin by stomach tube together with 0.45 L of colonic content from a horse with idiopathic colitis induced earlier by lincomycin alone. Two of the four ponies were treated with 25 g oral zinc bacitracin premix (110 g/kg active ingredient) 24 h later. Forty-two hours after inoculation the two untreated ponies had severe signs of idiopathic colitis and were euthanized. Postmortem findings were typical of idiopathic colitis. The two treated ponies had milder illness but the more severely affected was also euthanized; the other was retreated at 42 h with bacitracin pre-mix and again 12 h later. Its illness and diarrhea resolved over the next 24 h. Clostridium cadaveris was isolated in large numbers from the cecum of the euthanized ponies and their cecal content contained mouse lethal and guinea pig dermonecrotic, but not cytotoxic, activity. Enterotoxins of Clostridium perfringens and Clostridium difficile could not be demonstrated. No toxin could be demonstrated in culture supernatants of C. cadaveris or in supernatants of cecal contents treated with ethanol prior to culturing in anaerobically incubated broth. No Salmonella spp. were isolated. A further two ponies were administered 10 mg/kg lincomycin orally with 0.45 L colonic content from a horse with idiopathic colitis, as described.(ABSTRACT TRUNCATED AT 250 WORDS)


Pathology of morbillivirus infection in striped dolphins (Stenella coeruleoalba) from Valencia and Murcia, Spain. During the summer and fall of 1990 hundreds of striped dolphins (Stenella coeruleoalba) died in the Spanish Mediterranean as a result of morbillivirus infection. A pathological investigation was carried out on dolphins from Valencia and Murcia which were among the first to die in the epizootic. The dolphins were in poor body condition and pneumonia was the main necropsy finding. Microscopic lung lesions characterized by necrosis of bronchial and bronchiolar epithelium and infiltration of alveoli with macrophages, lymphocytes, neutrophils and multinucleated syncytia were seen in most dolphins. Cytoplasmic and nuclear eosinophilic viral inclusions were present in bronchial and bronchiolar epithelium and in syncytia. Focal granulomatous inflammation associated with nematodes was also present. Brain lesions included diffuse degeneration and necrosis of neurons, microgliosis, perivascular cuffing, formation of syncytia and focal demyelination. Cytoplasmic and nuclear eosinophilic inclusions were present in neurons and glial cells. There was severe lymphoid necrosis and depletion of spleen and lymph nodes and syncytia also occurred in lymph nodes. Biliary and transitional epithelium contained nuclear and cytoplasmic eosinophilic inclusions. Immunoperoxidase staining using monoclonal antibodies to phocine distemper virus confirmed the presence of morbillivirus antigens in lung and brain. The distribution and severity of lesions in striped dolphins are similar to those of distemper in seals, harbor porpoises and terrestrial mammals. The formation of syncytia in the lung and brain may be a useful pathological indicator of morbillivirus infection and may be used in the investigation of pinniped and cetacean strandings in North America.


Liposomes targeted to deliver antisecretory agents to jejunal mucosa. The B subunit of cholera toxin has been covalently attached to the surface of liposomes made from a mixture of phosphatidylethanolamine, phosphatidylcholine and cholesterol. Adenylate cyclase inhibitors and chloride conductance inhibitors were encapsulated within the liposomes. These "targeted" liposomes were used to study the combined effects of this novel delivery system, and a limited number of possible antisecretory agents, on net fluid flux into the pig jejunum. A state of net secretory fluid flux was induced in isolated jejunal loops in weanling pigs by adding theophylline or cholera toxin to the lumen of the isolated loops. There was no reduction in net fluid secretion when liposome suspensions without encapsulated secretory inhibitors were added to fluid in the lumen of loops treated with theophylline. There was also no reduction in net fluid secretion when miconazole, alpha-phenylcinnamate or 5 nitro-2-(3-phenethylamino)benzoate were encapsulated within targeted liposomes added to isolated jejunal loops. The net fluid flux induced by exposure of jejunal loops to theophylline was significantly reduced by adding targeted liposomes containing 2'-deoxy-3'-AMP. The reduction involved a reversal of net secretory fluid flux to an absorptive value. The net fluid secretory response to treatment of loops with cholera toxin was also inhibited by treating loops with targeted liposomes containing 2'-deoxy-3'-AMP. However, the reversal of secretion was less complete for secretion induced by cholera toxin than for secretion induced by theophylline. The reduced antisecretory efficacy versus cholera toxin was not improved by encapsulating higher concentrations of 2'-deoxy-3'-AMP.(ABSTRACT TRUNCATED AT 250 WORDS)


The effects of thiamin on lead metabolism: organ distribution of lead 203. The effect of thiamin on the organ distribution of lead was evaluated in CD-1 mice exposed intragastrically or intraperitoneally to a single dose of lead acetate (100 micrograms) containing 100 microCi lead 203. They were treated with either thiamin (25 or 50 mg/kg body weight), calcium ethylenediaminetetraacetic acid (CaEDTA) (50 mg/kg body weight), or combinations of thiamin and CaEDTA. The whole body retention and the organ distribution of lead 203 varied depending upon the route of lead administration, dose of thiamin and the specific treatment combination. Thiamin (25 or 50 mg/kg) treatment increased the whole body retention of both intragastric and intraperitoneal lead by approximately 10% in each instance. Calcium ethylenediaminetetraacetic acid, either alone or in combination with thiamin (50 mg/kg) reduced the whole body retention of lead by as much as 14% regardless of route of lead exposure. The relative retention of lead by the liver, kidney and spleen was greater in mice exposed to lead by the intragastric route. Regardless of route, CaEDTA in the combined treatment reduced the relative retention of lead in both the liver and kidney, whereas thiamin alone only reduced the retention of lead in the kidney. The results of this study indicate that thiamin in combination with CaEDTA alters the distribution and retention of lead in a manner which may have therapeutic application as it relates to chelation therapy.


Enhanced adherence of Pasteurella multocida to porcine tracheal rings preinfected with Bordetella bronchiseptica. Adherence of 25 isolates of Pasteurella multocida to porcine tracheal rings was evaluated. Results indicated that adherence was not related to the isolate's origin, capsular or somatic types, dermonecrotoxin production or hemagglutination activity. The effect of a preinfection with Bordetella bronchiseptica on the colonization by P. multocida was then studied. On rings infected with P. multocida alone, bacteria initially adhered to the epithelium, but within a few hours, the level of colonization decreased progressively. On rings preinfected with B. bronchiseptica, or pretreated with a cell-free B. bronchiseptica culture supernate (or filtrate), a high level of P. multocida colonization was maintained for at least 24 hours. Results indicate that B. bronchiseptica appears to facilitate upper respiratory tract colonization by P. multocida by a process which involves a low molecular weight (less than or equal to 1000) heat-stable substance, possibly the tracheal cytotoxin.


Secretion of alpha-hemolysin by bovine mammary isolates of Staphylococcus aureus. A total of 262 strains of Staphylococcus aureus isolated from the mammary gland of dairy cows were examined for the production of alpha-hemolysin. Strains were cultured in a liquid medium of casein hydrolysate and yeast extract in an atmosphere of 7% (v/v) CO2 in air. The assay consisted of a dot immunoblotting technique employing bacterial culture supernatants and a mouse monoclonal antibody specific for alpha-hemolysin. Ninety-four percent (247) of 262 strains were positive for alpha-hemolysin by this method, when cultured in the laboratory. This figure is compared with those obtained in previous studies which typically based their results on the hemolytic patterns of isolates on blood agar plates.


Canadian National Breast Screening Study: 2. Breast cancer detection and death rates among women aged 50 to 59 years. To evaluate the efficacy of annual mammography over and above annual physical examination of the breasts and the teaching of breast self-examination among women aged 50 to 59 on entry. Individually randomized controlled trial. Fifteen urban centres in Canada with expertise in the diagnosis and treatment of breast cancer. Women with no history of breast cancer and no mammography in the previous 12 months were randomly assigned to undergo either annual mammography and physical examination (MP group) or annual physical examination only (PO group). The 39,405 women enrolled from January 1980 through March 1985 were followed for a mean of 8.3 years. Derived from the participants by initial and annual self-administered questionnaires, from the screening examinations, from the patients' physicians, from the provincial cancer registries and by record linkage to the Canadian National Mortality Data Base. Expert panels evaluated histologic and death data. Rates of referral from screening, rates of detection of breast cancer from screening and from community care, nodal status, tumour size and rates of death from all causes and from breast cancer. Over 85% of the women in each group attended the screening sessions after screen 1. The characteristics of the women in the two groups were similar. Compared with the Canadian population the participants were more likely to be married, have fewer children, have more education, be in a professional occupation, smoke less and have been born in North America. The rate of screen-detected breast cancer on first examination was 7.20 per 1000 in the MP group and 3.45 per 1000 in the PO group, more node-positive tumours were found in the MP group than in the PO group. At subsequent screens the detection rates were a little less than half the rates at screen 1. During years 2 through 5 the ratios of observed to expected cases of invasive breast cancer were 1.28 in the MP group and 1.18 in the PO group. Of the women with invasive breast cancer through to 7 years, 217 in the MP group and 184 in the PO group had no node involvement, 66 and 56 had one to three nodes involved, 32 and 34 had four or more nodes involved, and 55 and 46 had an unknown nodal status. There were 38 deaths from breast cancer in the MP group and 39 in the PO group. The ratio of the proportions of death from breast cancer in the MP group compared with those in the UC group was 0.97 (95% confidence interval 0.62 to 1.52). The survival rates were similar in the two groups. Women whose cancer had been detected by mammography alone had the highest survival rate. The study was internally valid, and there was no evidence of randomization bias. Screening with yearly mammography in addition to physical examination of the breasts detected considerably more node-negative, small tumours than screening with physical examination alone, but it had no impact on the rate of death from breast cancer up to 7 years' follow-up from entry.


Canadian National Breast Screening Study: 1. Breast cancer detection and death rates among women aged 40 to 49 years. To evaluate the efficacy of the combination of annual screening with mammography, physical examination of the breasts and the teaching of breast self-examination in reducing the rate of death from breast cancer among women aged 40 to 49 years on entry. Individually randomized controlled trial. Fifteen urban centres in Canada with expertise in the diagnosis and treatment of breast cancer. Women with no history of breast cancer and no mammography in the previous 12 months were randomly assigned to undergo either annual mammography and physical examination (MP group) or usual care after an initial physical examination (UC group). The 50,430 women enrolled from January 1980 through March 1985 were followed for a mean of 8.5 years. Derived from the participants by initial and annual self-administered questionnaires, from the screening examinations, from the patients' physicians, from the provincial cancer registries and by record linkage to the Canadian National Mortality Data Base. Expert panels evaluated histologic and death data. Rates of referral from screening, rates of detection of breast cancer from screening and from community care, nodal status, tumour size, and rates of death from all causes and from breast cancer. Over 90% of the women in each group attended the screening sessions or returned the annual questionnaires, or both, over years 2 to 5. The characteristics of the women in the two groups were similar. Compared with the Canadian population, the participants were more likely to be married, have fewer children, have more education, be in a professional occupation, smoke less and have been born in North America. The rate of screen-detected breast cancer on first examination was 3.89 per 1000 in the MP group and 2.46 per 1000 in the UC group; more node-positive tumours were found in the MP group than in the UC group. During years 2 through 5 the ratios of observed to expected cases of invasive breast cancer were 1.26 in the MP group and 1.02 in the UC group. Of the women with invasive breast cancer through to 7 years, 191 and 157 women in the MP and UC groups respectively had no node involvement, 55 and 43 had one to three nodes involved, 47 and 23 had four or more nodes involved, and 38 and 49 had an unknown nodal status. There were 38 deaths from breast cancer in the MP group and 28 in the UC group. The ratio of the proportions of death from breast cancer in the MP group compared with those in the UC group was 1.36 (95% confidence interval 0.84 to 2.21). The survival rates were similar in the two groups. The highest survival rate occurred among women whose cancer had been detected by mammography alone. The study was internally valid, and there was no evidence of randomization bias. Screening with yearly mammography and physical examination of the breasts detected considerably more node-negative, small tumours than usual care, but it had no impact on the rate of death from breast cancer up to 7 years' follow-up from entry.


Prevalence of antibody to human T-cell lymphotropic virus type I/II in people of Caribbean origin in Toronto. To estimate the prevalence of antibody to human T-cell lymphotropic virus type I/II (anti-HTLV-I/II) in people from an HTLV-I/II-endemic area (the Caribbean) living in a nonendemic region (Canada). Cross-sectional household survey. Households in Toronto in 1989. A modified quota sampling method was used to recruit subjects of Caribbean origin as well as other Canadians. Of 2900 people invited to participate in the study 1323, 743 of Caribbean origin, were interviewed about their background and possible exposure to HTLV-I/II. Blood samples were analysed for anti-HTLV-I/II by means of an enzyme-linked immunoassay, the result being confirmed by the Western blot technique and radioimmunoprecipitation assay. The samples were also analysed for antibody to human immunodeficiency virus (anti-HIV) and hepatitis B surface antigen (HBsAg) and for surrogate markers of non-A, non-B hepatitis. A total of 853 blood samples (64.5%) were analysed, 483 (56.6%) from subjects of Caribbean origin. The proportion of subjects who agreed to give a blood sample was similar for the Caribbean and non-Caribbean strata. Eleven subjects, all of Caribbean origin (2.3% of the Caribbean stratum), were confirmed to be positive for anti-HTLV-I/II. There were no significant differences between the antibody-positive and antibody-negative subjects with respect to sex, age, racial origin or residence in the Caribbean for at least 22 years. All anti-HTLV-I/II-positive subjects were negative for anti-HIV and HBsAg, and four (36.4%) were positive for antibody to HBsAg and to hepatitis B core antigen. Except for origin, an association between antibody positivity and other factors could not be demonstrated. The findings suggest that blood donor screening might include place of origin in addition to the usual lifestyle or behavioural factors. However, the need to ensure safety of transfusion must be balanced against the need for participation of all groups in the blood transfusion program.


Attitudes about cancer and knowledge of cancer prevention among junior high students in Calgary, Alberta. Results from a survey of junior high students conducted in preparation of curriculum materials on cancer prevention are reported. Students in the survey (n = 246) consider cancer to be a serious disease, not particularly amenable to treatment, and caused by many things. About half the students mentioned avoiding tobacco use as important in preventing cancer. However, 27% were unable to identify any ways to avoid getting cancer. Specific knowledge of dietary practices recommended to reduce cancer risk was poor, with fewer than 10% of students mentioning high fibre or low fat as important dietary habits. Knowledge of factors related to skin cancer was better, with 53% of students mentioning avoiding sun exposure as a way to reduce the risk of skin cancer. The majority of students (71%) wanted more information about cancer. The results from the survey indicate a need for cancer-prevention materials in the school curriculum.


Rural high school students' knowledge, attitudes and behaviours related to sexually transmitted diseases. High school students are at high risk for contracting sexually transmitted diseases (STDs). A sample of 69 rural high school students from the province of Alberta, Canada were surveyed regarding their knowledge, attitudes and behaviours related to STDs to ascertain whether they differ from urban students. Results indicate that rural and urban high school students are similar in terms of knowledge about STDs, attitudes towards their prevention and also in terms of sexual behaviours. As with other studies, behaviours lagged behind knowledge and attitudes with reported condom use low. Sexual decision making was influenced mainly by the peer group. Males and females were mainly influenced by the same factors which include the willingness of their partner, the behaviours of their friends and family, concern about contracting a STD. These data emphasize the need to implement primary prevention programs for high school aged youth in rural as well as urban settings.


Hospital response protocols for child sexual abuse and sexually transmitted diseases in children. Hospitals are significant portals of entry to the health care system for children who have been sexually abused. Hospital staff have the opportunity to investigate, intervene in and prevent the cycle of abuse. Accordingly, several Canadian hospitals have standardized responses to meet the needs of the sexually abused child; however, the prevalence of protocols and the degree of standardization across the country have not been documented. A survey of hospitals in Canada indicated that 46% of hospitals that treated children had a response protocol for child sexual abuse and only 17% had a response protocol for sexually transmitted diseases in children. Protocols were more likely to be in place in hospitals that were accredited, specialized in paediatrics, were designated as teaching facilities for medicine, nursing and social work, and had more than 200 beds. In hospitals without protocols, staff were often not convinced of their need or desirability.


Healthy communications: producing a health report (Infowatch) for monitoring and promoting health in local communities. In order to bridge the gap between producers and users of community health data, we have developed a standardized format to provide a simple, comprehensive approach to the communication of epidemiologic data at the local level. Infowatch follows a series of format and style rules selected to enhance readability. The four-page format is divided into six sections: introduction and scope; "results" presented as charts, figures and text; policy implications (through consultation with community groups); methodological summary; references for self-study; and, invitation for reader feedback. An editorial committee comprising experts and representatives from local interest groups ensures that the data presented are relevant and of high quality. The content of each Infowatch issue varies depending on community priorities. Infowatch is distributed to 3,000 people, including representatives from health-related, academic, governmental and non-governmental agencies. Five areas assess qualitatively the impact of Infowatch: reader, media, policy, education, and solicited responses. Overall, response from all categories has been favourable with evidence of infiltration into policy.


Health behaviours in a Canadian community college sample: prevalence of drug use and interrelationships among behaviours. This study investigated the prevalence of drug use among a Canadian college sample and the covariation of drug taking and other health-related behaviours. A representative sample of students at a community college in Alberta were interviewed using telephone surveys, mail-in questionnaires and face-to-face interviews. Data was collected on drug, alcohol and caffeine use, cigarette smoking, eating habits, sleep habits and exercise. While use of illicit drugs did not appear to be widespread, alcohol appeared to be a primary substance abuse problem for a minority of subjects. Factor analysis indicated that the various health habits did not form one dimension of health-related behaviours. Four separate factors emerged: abusive drinking, eating habits, a drug use factor (caffeine intake, smoking, cannabis and hallucinogen use), and exercise levels. Findings are discussed in terms of their implications for future research, treatment and intervention.


The hepatitis B immunization strategy in Nova Scotia: is it effective? Since 1987, both hepatitis B disease and hepatitis B vaccine utilization have increased dramatically in Nova Scotia. We present a review of hepatitis B vaccine utilization relative to the occurrence of disease in Nova Scotia. In the two regions with the highest incidence rates, cases have been increasingly associated with lifestyle-related risk factors. Vaccine utilization was primarily for occupational risks. The current provincial hepatitis B immunization strategy is to recommend immunization to targeted high-risk groups. This strategy was judged to be ineffective. The cost of the vaccine is the most important deterrent for adopting an expanded or universal immunization strategy. The pooling of hepatitis B vaccine orders across Canada is suggested as a means to effect significant reductions in the cost of vaccine. Provincial programs would then be able to expand coverage to include populations at immediate risk and youngsters prior to the start of high-risk activity.


[Organization of prehospital emergency care in Canada: Elements of international and interprovince comparisons]. Out of a comparative research conducted on the training of first respondents to car crash injuries, this paper identifies four major factors influencing the way in which a country designs its prehospital emergency system. The paper also discusses elements pertaining to the organization of these systems in Canada and presents relevant interprovincial variations.


Aspects of preventive health care for older persons. Preventive health care for older persons is considered in terms of primary, secondary and tertiary prevention and examples of relevant services are provided both from Canada and from other countries. Three areas of concern are identified, namely communication, quality assurance and funding. It is suggested that various approaches used in other countries, such as Home Visitor Programs, be examined and more generally that comparisons with health care services in other countries be carried out, particularly with respect to evaluations and possible economic steering effects.


Recent trends in morbidity and mortality rates for abdominal aortic aneurysms. To examine recent trends in mortality and morbidity rates from aortic aneurysms among Canadian seniors. Retrospective study. Men and women age 65 years or older who were hospitalized in Canada with a primary diagnosis of aortic aneurysm or whose underlying cause of death was aortic aneurysm. Unlike other circulatory diseases which have shown marked declines, mortality and morbidity rates from aortic aneurysms have remained constant over the last 10 years. Risks for male seniors are 4-5 times greater than for females. Since mortality and morbidity from aortic aneurysms have not decreased and screening offers potential benefits, costs and benefits of screening need to be quantified.


Preparing health professionals for a collaborative health promotion role. Practitioners and educators must consider whether or not the curriculum offered in a university setting by our health professional schools prepares the potential practitioner for work in the multisectorial, interdisciplinary milieu that has been recommended by The Alma Ata Declaration, the Epp Health Promotion document and the Ottawa Charter. I describe a final-year course in Community Health Nursing that is being offered by Dalhousie University School of Nursing. The course is open to generic and post-registration nurses. The course, based on adult learning principles, used a collaborative community development approach. The curriculum was designed to give baccalaureate student nurses the experience of participating in collaborative health promotion directed towards the strengthening of a community. Student, faculty, preceptor and service-based coordinators' evaluation of the two-year implementation of the course is described in the paper.


Diabetes-related lower extremity amputations in Ontario: 1987-88 experience. Lower extremity amputee rates were estimated for diabetic persons living in Ontario. The rates were specified for age, sex and six Health Regions. The 1987-88 Hospital Records Institute database supplied the information regarding the amputations and the prevalence of diabetes in Ontario was estimated from age/sex specific diabetic rates of the U.S. The crude amputee rate for Ontario is 40 amputees/year/10,000 diabetics and the amputation rate is 44 amputations/year/10,000. These rates are lower than the 101 amputees/year/10,000 reported in the U.K. and are reasonably close to those of the U.S. (59.7 amputations/year/10,000). Age and sex Standardized Morbidity Ratios indicated that Region 1 and 6 have significantly higher and Region 2 significantly lower amputee rates than the Province. There is an almost two-fold difference between the highest and the lowest DRLEA rates of the six regions. (Range: 60-30). These results should be interpreted with caution, since actual prevalence rates of diabetes are not available.


Health promotion through healthy public policy: the contribution of complementary research methods. The focus of the "new public health" is moving from the level of individuals to the level of organizations, communities, and broader social policies. Traditional quantitative methods which are appropriate at the level of individual behaviour change, require adaptation and refinement when sociopolitical change becomes the mechanism for health promotion. Because of their training and experience, health services researchers and health educators, especially psychologists, are understandably resistant to making necessary methodologic changes. Well-designed and carefully conducted qualitative studies, using techniques such as ethnographic interviews, participant observation, case studies, or focus group activities, are required to complement quantitative approaches. These studies can fill gaps where quantitative techniques are suboptimal or even inappropriate. Hard qualitative techniques can also support soft quantitative methods. Their utility in process evaluation is now beyond dispute. Recent work at the New England Research Institute is used to illustrate the role of qualitative research in the evaluation of health promotion through planned sociopolitical change.


Bureaucratic logic in new social movement clothing: the limits of health promotion research. This paper discusses theoretical, methodological and political problems in the field of health promotion research. It argues that these problems result from a partial and contradictory appropriation of the discourse of new social movements. Politically, the health promotion movement is largely confined within the state, rather than the expression of a social movement against the state. The direction of health promotion research and policy is, therefore, caught in the bureaucratic logic of "trapped administrators", and results in contradictory emphases on problems like the development of "health promotion indicators", which show little result in informing a broader but coherent conceptualization of health, let alone in effecting change in health policy and outcomes. Such political problems reflect parallel confusions about theory and methodology. Theoretically, the field relies heavily on a critique of bio-medical science, but fails to move beyond a rhetorical outline of an alternative to systematic arguments about what promotes health. In this regard, the literature on health promotion remains unaware of important conceptual developments in the social sciences, relies on imprecise specifications of major constructs like community empowerment, and has no conception of the state. Methodologically, the literature is influenced by contradictory epistemological tendencies which reflect a positivist inspiration (as in the search for indicators) and an anti-positivist emphasis on agency and social change through the collective action and the discursive reconstitution of social identity, value and meaning. In regard to these questions, this paper is critical of observers who suggest that the way ahead is to embrace post-modern research strategies.(ABSTRACT TRUNCATED AT 250 WORDS)


Feminist methods in health promotion research. This paper describes and discusses the traditional social scientific approach to health promotion research, details some of its methods of data collection and analysis, outlines some of the principles of feminist methods of research particularly as these provide a critical analysis of traditional methods and concludes with a feminist critique of a typical and influential health promotion document, the Active Health Report (1985).


Building a methods bridge between public policy analysis and healthy public policy. The literature has only begun to consider what research is needed to support the development and implementation of healthy public policy initiatives. To date, a consistent methodological approach is recommended: multiple methods (document analysis and key informant interviews supplemented by quantitative data) with an aim toward understanding the perspective of key policy stakeholders. Currently, these methods are not the mainstay of policy analysis which is often driven more by a preference for technique (e.g., cost-benefit analysis) than by underlying epistemology or theory. Yet the explicit values of healthy public policy (intersectoral policy-making, public participation, etc.) suggest the importance of paying greater attention to epistemological and theoretical principles when making methodological choices.


Host resistance and the immune system.

Host resistance and the immune system. Elderly persons are more susceptible and vulnerable to many infections compared with young adults. This phenomenon can be attributed to a decline in host defense mechanisms, particularly altered immune function. The effects of aging on T- and B-lymphocyte function; antigen-presenting cells, natural killer cells, and granulocytes; and organ-specific host resistance are discussed in this article.


Learning to 'walk our talk': the implications of sociological theory for research methodologies in health promotion. In recent formulations of the concept of health promotion, such as Achieving Health for All and the Ottawa Charter, emphasis is clearly placed on comprehensivity and the integration of individual and social determinants of health, broadly defined. This paper is premised on the observation that despite evidence of a paradigm shift in the way we talk about health promotion at a conceptual level, we have yet to properly articulate a 'new' research methodology to accompany the 'new' health promotion. The paper has three main sections. First, some of the limitations and contradictions that separate the rhetoric of health promotion from its current operationalization in research practice are discussed. In asserting the inherent links between theory, methodology and method, the need for a new research paradigm is demonstrated. In the second section, seven key issues derived from the literature on sociological theory are identified and discussed in terms of their implications for choosing a new research methodology for health promotion. In the third section it is suggested that using these issue areas as a 'decision map' leads to the selection of a preferred strategy which brings together both interpretive and critical perspectives to bear on our understanding of social reality as it affects health. Elements of both of these approaches and the nature of their potential complimentarity are considered. Throughout these deliberations the reader is encouraged to consider the potentially conservative or activist orientations that alternate methodologies imply, and to critically evaluate how these mesh with the emerging rhetoric of fostering empowerment that is the cornerstone of the 'new' health promotion.


Infections in elderly persons. An altered clinical presentation. The high prevalence, morbidity, and mortality of infectious diseases in the geriatric population mandates that clinicians caring for older patients become better acquainted and familiar with the special and unique characteristics and features of this common clinical problem. Only through such awareness and understanding will clinical outcomes, functional capacity, and quality of life be improved in the elderly population.


Pneumonia.

Pneumonia. Pneumonia is one of the most serious infections in elderly persons. For example, individuals with nursing-home acquired pneumonia requiring hospitalization have a mortality rate of approximately 40%. In the frail, elderly patient, the clinical manifestations may be very nonspecific and consist only of confusion and falls; these individuals often may not present with either fever or cough. Sputum is frequently not available for culture in this population, and chest radiography for pneumonia may be confounded by underlying pulmonary or cardiac disease. Antibiotic therapy for pneumonia in older patients must often be empirical.


Program evaluation within a health promotion framework. Program evaluation can assist in assessing the conceptualization, design, implementation and utility of health promotion action. Evaluation of health promotion, with multiple strategies combining individual, social and policy action, lends itself to an evaluation-as-politics paradigm. Consideration of the interests of all major stakeholders, use of a series of related studies, and a commitment to multiple methods and multiple perspectives characterize this paradigm. Simple, practical research that is adequate for answering relevant questions is required. The program evaluator is not a neutral, scientific observer--he/she is a participant in the political arena along with other stakeholder groups. A model of the areas of interest in evaluation of health promotion, some potential evaluation questions, and a health promotion impact evaluation model are presented to emphasize unique aspects involved in evaluation of health promotion action. The evaluator can take a proactive role and challenge problems in conception and implementation of health promotion action. He/she can advocate for health promotion.


Institutional ethnography: explicating the social organization of professional health practices intending client empowerment. Institutional enthnography uses traditional ethnographic procedures grounded in an analytic approach for explicating the social organization of knowledge. I illustrate the theory and method by describing my experience and analysis-to-date in a study of the social organization of knowledge in mental health, day program occupational therapy in Atlantic Canada. I emphasize the research standpoint within everyday experience. From this point, the researcher explicates (through description) how (micro) social relations, i.e. everyday actions, speech and documentation, are embedded in the (macro) practices of "institutions" such as mental health services. I summarize data management procedures including use of ETHNOGRAPH. Analysis-to-date is showing how the organization of mental health day programs both constrains and creates potential for occupational therapists enabling client empowerment.


Vaccinations.

Vaccinations. Tetanus-diphtheria toxoid, influenza virus vaccines, and pneumococcal vaccine are recommended for older persons in the United States by the Centers for Disease Control. But most high-risk older persons remain unvaccinated, despite experiencing relatively high rates of tetanus, influenza-related complications, and pneumococcal disease, and having available effective, safe, and low-cost vaccines. Strategies for improving these vaccination rates require an intensive approach focused on (1) identifying older persons with high-risk conditions, (2) improving the delivery of vaccines, (3) improving the acceptance of vaccines by older persons, and (4) establishing mandatory immunization programs.


Tuberculosis.

Tuberculosis. In the United States, the incidence of tuberculosis (TB) is higher in elderly persons than in any other segment of the population, except in HIV-infected persons. The diagnosis of TB, however, is all too often not considered in geriatric patients. Although elderly nursing home residents are at a greater risk for TB than the aging population in the community setting, the majority (80%) of active TB cases in elderly persons occur in community dwellers. The diagnosis, treatment, and prevention of TB are reviewed in this article.


Fungal infections.

Fungal infections. Increased travel and outdoor leisure activities place the elderly individual at risk for infection with the endemic mycoses, histoplasmosis, blastomycosis, coccidioidomycoses, and sporotrichosis. Elderly patients who are immunosuppressed are at risk for infection with the opportunistic fungi such as Candida and Aspergillus. In this article, the clinical manifestations and the approach to diagnosis are discussed. The use of antifungal agents that are currently available to treat severe fungal infections also are reviewed.


A critical perspective on research and knowledge development in health promotion. The paper addresses four issues that pervaded conference deliberations: the relevance of qualitative approaches to research, the importance of community participation in the research process, the need to broaden the disciplinary base of health promotion, and the possibilities for a critical research perspective. The paper suggests why the idea of qualitative methods is so appealing to health promotion researchers, and what may prevent such methods from living up to the expectations held of them. The emphasis on community participation in research expresses an attempt to make research more relevant and accountable, but it also may inhibit the theoretical grounding of research, and create strain between pragmatic and scientific interests. The field of health promotion is inherently multidisciplinary, but it remains unclear if and how different disciplines can be effectively combined or integrated. The relative absence of critical thought at the conference is noted, and the authors argue that a critical perspective is needed in both "research of" and "research for" health promotion.


Fourth generation evaluation, the paradigm revolution and health promotion. The author argues that two events are inextricably linked:first, the increasing disenchantment with the conventional paradigm for conducting science, and second, the changing conceptions of health. With respect to the latter, medical professionals are increasingly moving away from disease as an indicator of health and moving toward conceptions of wellness, and away from a cure model and toward a prevention model. The paper demonstrates what the new inquiry paradigm looks like and what its synergisms are with newer constructions of human health, and finally concludes with additional problems which must be noted.


Urinary tract infection.

Urinary tract infection. Urinary tract infections are the most common bacterial infections experienced by elderly patients. These infections are often asymptomatic, although on occasion they produce discomfort for selective older patients (particularly those with obstructive uropathy), and present a risk for bacteremia, septic shock, adult respiratory distress syndrome, and death. The limited available data suggest that there are major differences with regard to pathogenesis, microbiology, clinical features, laboratory abnormalities, and therapy between young and elderly women who develop symptomatic pyelonephritis. There is a need to provide a standard antibiotic prophylaxis program to those elderly patients with specific cardiac conditions who are scheduled to undergo urinary procedures.


Accessing community development research methodologies. This paper is a perspective on the strengths and weaknesses of community development research offered to health promoters by a community development insider. The author provides her rationale for the opinion that no research paradigm other than the qualitative one satisfies the naturalistic context of either community development or health promotion, including inquiry into concepts such as community health, community wellbeing, community competence and community self-reliance. Attention is drawn to key aspects of the community development process with relevance to health promoters which are largely undertheorized, including clarity about the central issue of the nature of the interaction among learning, action and change. Finally, the paper specifies three implications of the naturalistic paradigm for either research or practice. These include academic prejudice against qualitative research from some quarters, the limitations of all research paradigms for some questions, and essential uncertainties of naturalistic inquiry.


Catheter-associated bacteriuria.

Catheter-associated bacteriuria. Catheter-associated bacteriuria is the most common nosocomial infection in both acute and long-term care facilities. Complications include fever, bacteremia, acute pyelonephritis, urinary stones, chronic renal inflammation, and death. Catheter-associated bacteriuria can be postponed by maintaining the closed nature of the catheter system. Postponement may become prevention of bacteriuria if the catheter is removed as soon as possible.


Infections in the nursing home.

Infections in the nursing home. Infections are a common cause of morbidity and mortality in nursing home patients. A variety of factors predispose these patients to infections. Infections commonly encountered among these patients include pneumonia, urinary tract infections, tuberculosis, and gastrointestinal and skin infections. Preventive measures and infection control techniques offer protection to both patients and employees.


Infected pressure and diabetic ulcers.

Infected pressure and diabetic ulcers. Infected pressure and diabetic ulcers are encountered frequently by clinicians caring for the geriatric population. These infections are polymicrobial and are often complicated by sepsis syndrome and osteomyelitis. Together, these infections account for significant morbidity and mortality in elderly persons. A team approach to management is essential for the clinician, and efforts should focus primarily on prevention.


Methicillin-resistant Staphylococcus aureus infection. Elderly patients with chronic illnesses are at increased risk of becoming colonized or infected with methicillin-resistant Staphylococcus aureus (MRSA). Therapeutic choices for the treatment of MRSA have been limited by the ever-expanding resistance of organisms and drug toxicity. In hospitals, the MRSA carrier state has been associated with increased risk of infection and possible dissemination of the organism to other patients. The epidemiology of MRSA and its significance in long-term care have been less well defined. Isolation procedures and steps to contain or eradicate MRSA should be accommodated to the individual needs of the facility and its resources.


Peritonitis.

Peritonitis. Intraperitoneal infections or inflammatory disease in elderly patients are a diagnostic challenge that will be encountered with increasing frequency in the aging population of the United States. Diagnostic clues are not overt and frequently appear late in the course of the disease. Confusion and subtle changes in clinical status are important signals. A high index of suspicion is required to initiate diagnostic procedures. Therapy will frequently be modified not only to the disease process but also to the patient to incorporate concepts of minimally invasive procedures. The advent of laparoscopic surgery may be a great advance in the diagnosis and treatment of intra-abdominal crisis in geriatric patients. It also may make elective surgery conform more to the goals of the geriatric patient and thus prevent the high morbidity and mortality associated with emergency surgery in this age group.


Bacterial meningitis.

Bacterial meningitis. Meningitis remains a significant health problem for the older adult population. Although the overall incidence of this disease has decreased in the United States, the incidence of meningitis in the elderly population is increasing. Additionally, the recognition of meningitis in the older adult may be more difficult because the usual symptoms and signs are neither as specific nor as sensitive as they are in a younger population. Newer antibiotics have provided better therapeutic approaches to some of the organisms responsible for this disease, and newer methods of therapy beyond antibiotics hold the promise of altering the unacceptably high morbidity and mortality.


Infective endocarditis.

Infective endocarditis. This article examines the presentation, diagnosis, and treatment of infective endocarditis in elderly persons. Special problems that cause complications and mortality to be higher in older patients than younger patients also are discussed. Areas of active debate and research are mentioned, including the use of diagnostic echocardiography, treatment of specific bacterial species, sources of iatrogenic endocarditis, and antibiotic prophylaxis.


Sepsis.

Sepsis. Septic shock is associated with a very high mortality in elderly patients. This is likely due to the age-related anatomic and physiologic changes and the presence of comorbid diseases. Medical management of patients with septic shock consists of antibiotics, fluids, vasopressors, and careful monitoring. Judicious use of antiendotoxin monoclonal antibodies may be a beneficial adjunctive therapy.


Antimicrobial therapy.

Antimicrobial therapy. Antibiotic dosing is not influenced by age as much as by the weight loss and loss of renal function that occurs with advanced age. The chronic diseases that afflict the frail, elderly person, however, exert a profound influence on the types of infections and the variety of organisms that must be considered in empiric therapy choices. Safety, efficacy, and cost favor the choice of broad-spectrum oral antimicrobials or the newer quinolones for initial treatment of moderately severe, urinary, respiratory, or skin and soft-tissue infections. When parenteral empiric therapy is needed, the third-generation cephalosporins are preferable to multi-drug or narrow-spectrum regimens. To avoid adverse reactions, the frail, elderly patient generally should be given somewhat lower doses at longer dose intervals compared with younger patients.


Clozapine in the treatment of refractory schizophrenia: Canadian policies and clinical guidelines. Clozapine is an atypical neuroleptic agent that has recently become available in Canada with potential clinical efficacy in the treatment of refractory schizophrenia, and in patients with schizophrenia neurologically intolerant to conventional neuroleptics. Although it causes few extra-pyramidal symptoms, the drug has a number of other adverse effects including a risk of agranulocytosis in one to two percent of all patients. Because of this, the use of the drug is permitted only if the white blood count is monitored weekly. The monitoring system, outlined in this article, requires a coordinated effort between clinical staff, pharmacy, laboratory and the Clozaril Support and Assistance Network. Clinical guidelines are proposed, detailing the indications and contraindications for treatment and the pharmacokinetics, dosing, adverse effects, and drug interactions with clozapine. In addition, the economics, government policies and implications for future research are considered. Although there are administrative and clinical difficulties associated with its use, clozapine represents an advance in therapeutic research. Patients and family members will be inquiring about the drug and may deserve a trial. This article aims to inform Canadian mental health professionals about the safe and beneficial use of clozapine.


Victims of violence: aspects of the "victim-to-patient" process in women. This paper is an overview of aspects of the victim-to-patient process which reflects the interrelationship between mental health and mental disorder, particularly of women who suffer the sexual assault, sexual abuse, or wife assault. Knowledge of the psychological processes and symptoms aids diagnosis, modifies treatment and the process of recovery following acts of violence.


[Dysmorphophobia (body dysmorphic disorder)]. This article reviews the historical and terminological origins of dysmorphophobia from Herodotus to today. It explains the differences pointed out by many authors, including the DSM-III-R, between body dismorphic disorder and delusional disorder somatic type, which are referred to as monosymptomatic hypochondriacal psychoses in Europe. Epidemiological data, clinical characteristics and outcome are discussed. Explicative theories and neurobiological, developmental and analytical aspects of body image are presented. The association between body dismorphic disorder and other disorders is analyzed, and treatment possibilities are discussed. The authors suggest that body dismorphic disorder be classified with obsessive compulsive disorder, whatever the intensity of symptomatology, rather than with somatoform or delusional disorder, and treated with serotonin uptake inhibitors or neureptics that have been proven to be effective for the treatment of this disorder, such as pimozide.


Social risk factors for borderline personality disorder: a review and hypothesis. A number of behaviours associated with borderline personality disorder (including attempted suicide, suicide, substance abuse, and antisocial behaviour) are on the increase among the young. The common factor in these disorders is impulsiveness. Evidence is reviewed suggesting that social disintegration reduces the threshold of impulsive behaviours. It is proposed that this is the mechanism through which social risk factors effect the prevalence and morbidity of borderline personality. A number of ways of testing this hypothesis are suggested.


Correlates of sexual abuse in women with anorexia nervosa and bulimia nervosa. Of 184 female outpatients meeting the DSM-III-R criteria, for anorexia nervosa, bulimia nervosa, or anorexia nervosa with bulimia, approximately 25% reported previous sexual abuse. Furthermore, previous sexual abuse was associated with greater psychological disturbance, measured by the Eating Disorder Inventory and Eating Attitudes Test. Sexual functioning did not differ among women who did or did not report sexual abuse. This finding suggests that sexual abuse or its correlates may affect severity rather than type of eating disorder.


Psychiatric services: a survey of nursing homes and homes for the aged in Ontario. A survey was conducted to determine perceptions and attitudes of psychiatric services available to nursing homes and homes for the aged across Ontario. A questionnaire was sent by mail to medical and nursing directors separately. Thirty-six point eight percent of responders reported that the nursing home residents never receive psychiatric care, and 88.2% of responders estimated the total psychiatric care received by all of their residents per month was five hours or less. Almost three-quarters of the responders stated that they require more psychiatric services. Significantly more nursing directors than medical directors wanted more psychiatric services. Southwestern Ontario, followed by Northern Ontario, had the least perceived availability of a visiting psychiatrist. Perceived availability was greatest in larger urban areas and least in rural areas. The mean percentage of residents perceived to have psychiatric or behavioural problems was 30.5%, while the mean percentage perceived to require psychotropic medication was 37.4%. Physical aggression, wandering and agitation were identified as the behavioural problems of greatest concern to staff. When a visiting psychiatrist is not available, residents sometimes have to travel long distances for psychiatric evaluation. Planning is required to facilitate and encourage the development of efficient and effective psychiatric services for long term care facilities for the elderly.


Assessing the "criminalization" of the mentally ill in Canada. This paper is an overview of the conceptual and methodological problems encountered trying to assess the hypothesis that the mentally ill, as a consequence of deinstitutionalization, are being "criminalized". Generalizations are difficult to make, in large part because most of the studies are American and do not fit well into the Canadian scene. Relevant Canadian findings are reviewed and compared to the US data. There is some evidence that Canadian patients may be diverted from the criminal justice system more often than in the US, where there are fewer resources. However, this conclusion must be tempered by the fact that Canadian surveys have found high rates of mental disorder among prison and jail inmates.


Depression and level of functioning in patients with rheumatoid arthritis. This study examined the degree to which depression is related to physical and psychosocial dysfunction. The Beck Depression Inventory and the Sickness Impact Profile were administered to 34 patients with rheumatoid arthritis. Information on the demographic variables (age and employment status) and medical status variables (duration of disease and functional classification) were collected for each patient. Regression analyses revealed that depression was an important predictor of total, physical and psychosocial sickness-related behavioural dysfunction. The proportion of variance attributed to depression was moderate to large and was significant even after controlling for important demographic and medical status variables. These results suggest that depression is an important factor to be considered when evaluating the clinical significance of physical and psychosocial dysfunction in patients with rheumatoid arthritis.


Adult children of alcoholics in treatment programs for anxiety disorders and substance abuse. Studies of the first-degree relatives of patients with alcoholism and anxiety disorders have identified a significant overlap of these disorders. Forty percent of the patients in an outpatient anxiety disorder program were adult children of alcoholics (ACOA), a proportion similar to that found in the substance abuse program. The ACOAs in both programs were younger, had higher co-dependency scores and were younger when they had their first psychiatric contact than the controls. The adult children of alcoholics who had anxiety disorders were more likely to be female and their alcoholic parents were less likely to have had psychiatric antecedents to alcoholism. Aside from substance abuse, similarities in sociodemographic variables and the impact of the parents' alcoholism were noted, reinforcing the hypothesis that vulnerabilities to anxiety disorders and alcoholism overlap.


Intensive early exposure to geriatric psychiatry in residency training: impact on career choice and practice. The authors examined the impact of intensive early exposure to geriatric psychiatry on the career choice of trainees. All psychiatrists who had completed a six month inpatient rotation on a general hospital psychogeriatric unit as part of their first year of residency were interviewed three to 12 years later with a questionnaire designed to elicit practice patterns, prior interest in geriatrics, and the major influences of the rotation. Nine of 16 trainees had spent more than 50% of their time since graduation treating elderly patients. Those surveyed who were not practicing geriatrics spontaneously reported positive influences of the rotation on psychiatry training in general. The nature of geriatric psychiatry and the clinical issues, as well as the supervisors and educational activities were rated as the most important influences of the rotation. Early experience in psychogeriatrics seems valuable for subspecialty recruitment as well as general psychiatry training.


[Community services and quality of life: a study of the impact in a remote region]. This longitudinal study with a matched comparison group was conducted in Abitibi, an area in North-West Quebec. Its goal was to observe the impact of community support services on the quality of life of long term psychiatric patients living in a remote area. A cohort of 47 subjects, living in a small town with a comprehensive network of community support services, was compared with a similar group living in a neighbouring city with only outpatient services. The satisfaction with life domains scale developed by Andrews and Withey and adapted by Baker and Intagliata was used at four times during the study. According to the results, the subjective perception of the quality of life in the two groups is comparable, even though the objective conditions are less favorable for the group participating in the community support program. The highest ratings were given to the place of residence, the neighborhood and its commodities; the lowest ratings were given to their love life and financial situation. One can observe a stability of the measures of quality of life over time and for the two groups. The perceptions of the sample living in a remote area are much more favorable than the ones of a comparable group living in the Montreal area. These results are discussed in a double perspective: the role of community support services in the daily life of people who are having severe and persistent problems of mental health, and the interest of measures of quality of life.


A treatment approach for patients in midlife. A treatment concept is described based on phase of life developmental theory for certain middle-aged patients encountered in a general hospital setting that--of a midlife crisis unit. Theoretical considerations on the rationale for setting up a midlife crisis unit, a brief description of a pilot unit of this nature during its first year of operation and several clinical vignettes illustrating typical presenting situations are discussed.


The management of a case of treatment-resistant paraphilia with a long-acting LHRH agonist. A patient with multiple paraphilias who had been treated for several years with sex drive reducing agents (cyproterone acetate and medroxyprogesterone acetate) with little effect on sexual activity or fantasy was offered treatment with long-acting leuprolide acetate, on LHRH agonist. This produced a marked decrease in all reported sexual thoughts and activities with no significant side-effects.


Are too many children being treated with methylphenidate? A survey was conducted of the use of methylphenidate in British Columbia during a six month period to determine if a disproportionate number of children are being treated with methylphenidate for hyperactivity. The data obtained do not indicate a problem regarding the diagnosis of attention deficit hyperactivity disorder in children. However, the data pertaining to adults indicate that the reasons stated for prescribing methylphenidate are controversial in a significant number of cases.


Evolving misidentification syndromes and facial recognition deficits. In this paper, the authors report the case of a 33 year old man with several misidentification delusions involving the self. Evidence suggests that one type of misidentification delusion may evolve into another type. Neuropsychological testing further suggests that misidentification delusions may be associated with subtle abnormalities in facial recognition abilities and with non dominant cerebral compromise.


Post-traumatic stress disorder: an overview. An overview of post-traumatic stress disorder, including a brief historical survey, and its epidemiology, nosology, etiology, clinical presentation, treatment, prognosis as well as a short vignette, highlights the fact that this disorder prevails in times of war and peace. Early intervention is emphasized as the key to successful treatment. The timeliness for Canadian mental health professionals to review this disorder is also mentioned.


Augmentation of valproate with lithium in a case of rapid cycling affective disorder. Rapid cycling affective disorder is characteristically unresponsive to conventional interventions. In bipolar rapid cycling affective disorder, the manic episodes may be controlled with either neuroleptics or electroconvulsive therapy, but the depressive episodes are highly intractable. This report describes the successful treatment of a patient with a bipolar rapid cycling affective disorder using a combination of valproic acid and lithium carbonate.


Significance of glutathione S-transferase-pi as a tumor marker in patients with oral cancer. The authors analyzed the clinical usefulness of glutathione-S-transferase-pi (GST-pi) as a tumor marker in patients with oral cancer. GST-pi levels in plasma of 61 patients with oral squamous cell carcinomas, 65 patients with benign oral diseases, and 78 healthy subjects were investigated with the sandwich enzyme-immunoassay (EIA) system. Elevated GST-pi levels in plasma were observed in patients with oral cancer, but patients with benign oral diseases had normal GST-pi levels. More than 70% of patients with Stage III or IV oral cancer and more than 50% of those with Stage I and II disease had elevated levels of GST-pi in plasma. Elevated levels of GST-pi in plasma were also discovered in most patients with tumor recurring after surgery before recurrence was detected clinically. GST-pi also was found to be a useful marker for evaluating the response to chemotherapy, for monitoring postoperative tumor resectability or tumor burden, and for predicting the recurrence of tumor in patients with oral cancer. GST-pi is considered to be a useful aid for early diagnosis, predicting tumor extent, and determining parameters of treatment efficacy and prognosis for oral cancer.


Long-term treatment results of postoperative radiation therapy for advanced stage oropharyngeal carcinoma. The authors report the long-term treatment results for advanced stage base of tongue (BOT) and tonsillar fossa (TF) carcinomas treated with surgery and postoperative radiation therapy (RT) at Memorial Sloan-Kettering Cancer Center. Between 1973 and 1986, 51 patients with squamous cell carcinoma of the BOT (n = 31 patients) and TF (n = 20 patients) were treated with surgery plus RT. Indication(s) for RT included: advanced disease (Stage T3/T4, 34 patients [66%]); close or positive margins (33 patients, 64%) and multiple positive neck nodes (43 patients, 84%). The 7-year actuarial local control rates for BOT and TF lesions were 81% and 83%, respectively. Local control was achieved in 17 of 18 (94%) patients with T3 lesions, and 12 of 16 (75%) patients with T4 lesions. Among patients with positive or close margins who received postoperative doses of 60 Gy or more, the long-term control rate was 93%. The presence of a treatment interruption had a negative effect on the local control rates. The actuarial control among patients who required a treatment break was 64%; for those not requiring interruption of their treatment, the actuarial control was 93% (P = 0.05). At 7 years, the overall survival for all patients was 52%, and the disease-free survival was 64%. The actuarial incidence of neck failure was 21% and 18% for BOT and TF, respectively. The likelihood of having distant metastasis at 7 years for all patients was 30%. The actuarial incidence of having a second malignancy was 35% for patients with BOT disease. Second malignancy was not observed among patients with TF lesions. The authors conclude that surgery and postoperative RT can provide excellent long-term, disease-control rates for patients with advanced BOT and TF tumors. However, current strategies for BOT lesions have been directed at tongue preservation without surgery.


Auditory brain stem responses in patients after radiation therapy for nasopharyngeal carcinoma. The study evaluated the incidence and severity of brain stem myelopathy occurring after radiation exposure in a cohort of patients who received external radiation exposure for nasopharyngeal carcinoma (NPC). Brain stem function was investigated by auditory brain stem responses (ABR). Four of 21 patients who could be examined had aberrations in ABR. Three patients showed highly abnormal ABR, with no distinctive patterns or peaks. Two of these patients also showed clinical symptoms of brain stem dysfunction, including multiple palsies in cranial and peripheral nerves, whereas the third patient had no clinical signs of brain stem disorders. The fourth patient had minor conduction delays in ABR. The remaining group of 17 patients who could be examined had ABR latency and transmission times similar to those of the control group. None of these patients had neurologic symptoms. Dose-response analysis showed that patients who received radiation doses of 59 Gy or less to the brain stem had normal ABR, whereas four of six patients who received a dose of 68 Gy had manifest or subclinical brain stem dysfunction. The results emphasize the importance of protecting the brain stem from high-dose radiation when possible. The results also demonstrate the usefulness of ABR as a supplement to the clinical examination of patients with possible myelopathy occurring after radiation exposure.


Bone infarct-associated osteosarcoma.

Bone infarct-associated osteosarcoma. Reported is a patient with an osteosarcoma arising in a medullary infarct of the humerus. Infarct-associated sarcoma (IAS) of bone is rare. In a collective review of 50 cases reported in the medical literature, only 37 were fully documented. Including our patient, 26 men and 12 women, ranging in age from 18 to 82 years (mean, 53.4 years) have been reported. Black patients appeared to be disproportionately represented, accounting for 36% of the group. In most patients, there was no known cause for the infarct, whereas in the remainder, the most common underlying condition was a prior dysbaric event or alcoholism. Approximately 75% of the patients had multiple bone infarcts. The femur was involved in 21 patients, the tibia in 14, the humerus in 2, and the radius in 1. Among 40 sarcomas in these patients, 7 (18.4%) were osteosarcomas, and 29 (72.5%) were malignant fibrous histiocytomas. The survival rate in patients with IAS is poor: 5 of the 7 patients with osteosarcoma (71%) and 20 of the 31 other patients (65%) died of tumor. Eight patients are alive and well, all for longer than 5 years.


The association of erythrocytosis and chronic lymphocytic leukemia. The authors report the clinical course of three patients with well-documented chronic lymphocytic leukemia (CLL) and concomitant erythrocytosis. Associated disorders included immune cytopenias, Hashimoto struma and Richter syndrome. Durable complete remissions of CLL have occurred in two patients. Inasmuch as a chance association of these two relatively rare hematologic disorders is unlikely, the available information suggests that a pluripotent stem cell with the capacity to differentiate into lymphoid and erythroid pathways is the most attractive hypothesis.


Molecular genetic, cytogenetic, and immunohistochemical characterization of alveolar soft-part sarcoma. Implications for cell of origin. Alveolar soft-part sarcoma is a rare tumor of uncertain histogenesis. The authors report a patient who was studied using immunohistochemistry, cytogenetic analysis, and molecular probes for MyoD1 and MYCN (N-myc proto-oncogene). By immunoperoxidase, the tumor was focally positive for vimentin, neuron-specific enolase, and S-100 protein but negative for muscle-specific actin, desmin, and low-molecular-weight keratin. Direct chromosome analysis of primary tumor cells using G-banded preparations yielded two clonally abnormal lines: one demonstrated trisomy 47,XX+5; the other demonstrated 46,XX,1p-,17q+. Expression of the MYCN RNA was detectable at a low level, and MYCN was single copy at the DNA level. Expression of the myogenic molecular marker MyoD1 was not detected by Northern blotting analysis. This is the first detailed study to address the molecular biology and tumor cytogenetics of alveolar soft-part sarcoma. The results of this study indicate a neurogenic origin for this unusual tumor and fail to provide support for the notion of a myogenic origin.


Primary non-Hodgkin malignant lymphoma of the breast. An immunohistochemical study of seven patients and literature review of 152 patients with breast lymphoma in Japan. The breast is rarely a primary site for extranodal malignant lymphoma. Most reported primary non-Hodgkin malignant lymphomas of the breast (PBL) are of B-cell phenotype. Histologic and immunohistochemical analyses of seven patients with PBL and a statistical analysis of 152 patients with PBL reported in the Japanese literature were performed. Malignant lymphoma could not be predicted preoperatively with clinical and radiologic findings; breast carcinoma, fibroadenoma, and phyllodes tumor were the preoperative diagnoses. All patients were women; they ranged in age from 31 to 80 years (mean, 57.6 years). The right breast was involved initially in five patients. In four, only the breast was involved (Stage I), whereas in three, the ipsilateral axillary lymph nodes (Stage II) were involved at diagnosis. According to the Working Formulation, all patients belonged to the intermediate grade and were classified as having diffuse large cell (five patients) or mixed (two patients) lymphoma. Immunophenotypic analysis revealed that all patients had B-cell lymphoma. No patients had lymphoepithelial lesions, which is the characteristic feature in categorizing a lymphoma as a mucosa-associated lymphoid tissue (MALT) lymphoma. A statistical analysis of the patient reported in the Japanese literature has divided PBL into two types: a bilateral type that affects younger women and a unilateral type that has a broad age distribution, but preponderantly occurs in older women. The age and stage at diagnosis were significant prognostic factors in predicting the survival time, but the location and size of the tumor at initial presentation, histopathologic type, terminal leukemic manifestation, and treatment modality were not. This study indicates that most PBL are diffuse large cell lymphoma of B-cell phenotype and that the age and stage at diagnosis are significant prognostic factors.


Treatment plans for black and white women with stage II node-positive breast cancer. The National Cancer Institute Black/White Cancer Survival Study experience. The National Cancer Institute Black/White Cancer Survival Study began patient accrual in 1985 and was designed to investigate factors that might contribute to the observed racial differences in survival for cancer of the breast, uterine corpus, colon, and bladder. To determine whether there were racial differences in treatment in a clinically homogeneous set of patients, 305 (25%) of the 1222 women in this study with Stage II node-positive (N+) breast cancer were evaluated. Patient characteristics for blacks and whites were similar for age, metropolitan area of residence, tumor size, extent of nodal involvement, and steroid receptors. Differences in histologic findings, tumor grade, and nuclear atypia were observed. Blacks had a higher frequency of comorbid conditions, especially hypertension (P < 0.00001). Fewer blacks underwent breast-conserving surgery (P = 0.004). In a multivariate analysis, race was no longer a significant factor in the selection of primary treatment, but education and metropolitan area of residence remained significant. Blacks and whites received similar postoperative systemic therapy, with combination chemotherapy (cyclophosphamide, methotrexate, and 5-fluorouracil) and tamoxifen, the most common cytotoxic and endocrine therapies used. The National Cancer Institute consensus statement concerning adjuvant therapy for breast cancer was published in the middle of the 2-year period that study cases were accrued, and treatment plans in this study generally agreed with consensus guidelines. Should survival differences in black and white patients with Stage II N+ disease in this study be found, they are unlikely to be attributable to differences in initial or postoperative treatment.


Randomized adjuvant trial to evaluate the addition of tamoxifen and PSK to chemotherapy in patients with primary breast cancer. 5-Year results from the Nishi-Nippon Group of the Adjuvant Chemoendocrine Therapy for Breast Cancer Organization. A randomized adjuvant trial was conducted from October 1982 to January 1985 to evaluate the addition of tamoxifen (TAM) to combination chemotherapy with perioperative mitomycin C (MMC) and ftorafur (FT) for patients with estrogen receptor (ER)-positive tumors and the addition of PSK, a biologic response modifier, to MMC+FT chemotherapy for patients with ER-negative tumors in operable Stage IIA, IIB, and IIIA cancer. The doses used were 20 mg of oral TAM daily, 600 mg of oral FT daily, and 3 g of oral PSK daily for 2 years. Intravenous MMC (13 mg/m2) was given on the day of operation. A total of 967 patients were entered and randomized by stratification based on ER status and staging (1978 International Union Against Cancer [UICC] criteria at the time of trial execution). Of 967 patients, 914 (94.5%) were evaluable. At 5-year follow-up, significant prolonged overall survival (OS) and relapse-free survival (RFS) times were seen with the addition of TAM in patients with ER-positive and Stage IIIA T3N0 cancer (1987 UICC-American Joint Committee on Cancer [AJCC] criteria); however, no significant survival benefit from TAM was seen in patients with ER-positive and Stage IIA T2N1 cancer. There was no significant difference between regimens, with or without PSK, in patients with ER-negative disease. Results of subset analyses suggested a benefit from TAM in postmenopausal patients with ER-positive and Stage IIA T2N1 cancer and a benefit from PSK in patients with node-negative, ER-negative, and Stage IIA T2N1 cancer. The 5-year results of the current trial showed a survival advantage by the addition of TAM to chemotherapy in patients with ER-positive and Stage IIIA T3N0 cancer.


Phase III trial of cyclophosphamide versus cyclophosphamide, doxorubicin, and methotrexate in hormone-refractory prostatic cancer. A Hoosier Oncology Group study. Between August 1984 and November 1989, the Hoosier Oncology Group conducted a Phase III study comparing cyclophosphamide (CTX) with cyclophosphamide, doxorubicin, and methotrexate (CAM) in patients with hormone-refractory metastatic prostatic cancer to determine whether the addition of doxorubicin and methotrexate to the cyclophosphamide regimen conferred any survival advantage. One hundred three patients were registered and randomized, 99 were evaluable for response, and all were evaluable for survival results. All had histologically confirmed metastatic prostatic cancer and had not responded to hormonal therapy. Fifty-three patients received CTX alone, and 50 received CAM. Seventy-one patients (69%) had evaluable disease, and 32 (31%) had measurable disease. There were no complete responses and only four (13%) partial responses in the patients with measurable disease. There was no difference in overall survival time between the two treatment arms in either patients with a Karnofsky performance status (KPS) of 80-100 (median survival, 9.0 versus 9.5 months; P = 0.93) or in those with a KPS of 50-70 (median survival, 5.0 versus 6.0 months; P = 0.51). There was no difference in overall time to progression between the two treatment arms (median time to progression; 4.4 versus 6.2 months; P = 0.07). Toxicity was tolerable in both regimens. It was concluded that there was no survival advantage to CAM over CTX alone. New chemotherapeutic agents with greater activity against prostatic cancer must be identified.


Lipid-associated sialic acid, squamous cell carcinoma antigen, carcinoembryonic antigen, and lactic dehydrogenase levels as tumor markers in squamous cell carcinoma of the head and neck. Circulating tumor markers are valuable adjuncts in the management of several malignant lesions, including germ cell tumors and adenocarcinomas of the breast, colon, prostate, and ovary. However (to the authors' knowledge), currently, no serologic markers have been shown to have prognostic value for patients with squamous cell carcinomas of the head and neck (SCCHN). Novel and existing markers were evaluated prospectively in patients with SCCHN: The levels of lipid-associated sialic acids (LASA), squamous cell carcinoma circulating antigen (SCC-Ag), carcinoembryonic antigen (CEA), and lactic dehydrogenase (LDH) were evaluated in 52 patients: 42 with active measurable SCCHN and 10 with no clinical evidence of active disease after treatment (NED). In patients with active disease, LASA, SCC-Ag, CEA, and LDH were elevated in 71%, 33%, 27%, and 18%, respectively, and in seven patients with distant metastasis (M1) in 100%, 86%, 57%, and 33%, respectively. None of the markers were elevated in the NED group. The incidence and magnitude of LASA and SCC-Ag elevations correlated with the extent of disease (active disease versus NED, Stage III versus IV, T0-3 versus T4 primary lesions, M0 versus M1). LDH and CEA elevations correlated primarily with the presence of distant metastases. LASA appears to be a promising sensitive marker of SCCHN, followed in decreasing order of sensitivity by SCC-Ag, CEA, and LDH. Additional study to evaluate the specificity of LASA and its correlation with tumor response to therapy is warranted.


"Locked-in syndrome" after intrathecal cytosine arabinoside therapy for malignant immunoblastic lymphoma. A 22-year-old man with malignant immunoblastic lymphoma had "locked-in" syndrome within 48 hours of receiving a single (100 mg) dose of intrathecal cytosine arabinoside (ara-C) in conjunction with intravenous ara-C, cisplatin, and doxorubicin. Eight hours after therapy, the patient had central hypoventilation and blurred vision that progressed to blindness within 3 hours. During the next 10 hours, he became completely quadriplegic but remained intermittently alert and was able to respond to commands by eye or head movements. Radiographic studies showed necrosis of the medulla and swelling of the entire spinal cord. The patient persisted in a locked-in state until his death 3 weeks later, after removal of life support systems. Autopsy confirmed extensive necrosis of the lower medulla, optic chiasm, cranial nerves I and IV, and spinal cord. This case was unusual for its severity. The temporal relationship to ara-C instillation favors a toxic idiosyncratic response to chemotherapy. The authors advocate caution when bolus intrathecal and intravenous ara-C are administered to a patient within a short time of each other.


Phase III double-blind comparison of intravenous ondansetron and metoclopramide as antiemetic therapy for patients receiving multiple-day cisplatin-based chemotherapy. Ondansetron hydrochloride is a selective serotonin subtype 3 (5HT3) receptor antagonist that has been shown to be an effective antiemetic in patients receiving cisplatin chemotherapy. This double-blind study compared the safety and efficacy of intravenous ondansetron with metoclopramide in patients receiving a 4- or 5-day regimen of cisplatin (20-40 mg/m2/day) combination chemotherapy. Forty-five patients were enrolled, and efficacy of the drug therapy could be studied for all 45. Patients were randomly assigned (1:1) to receive three daily intravenous doses of either 0.15 mg/kg ondansetron or 1 mg/kg metoclopramide. All patients were monitored daily for the number of emetic episodes (vomiting or retching), severity of nausea, adverse events, and laboratory safety parameters. Seven (30%) patients who received ondansetron had no emetic episodes throughout the entire study period compared with two (9%) who received metoclopramide (P = 0.077). The greatest difference in antiemetic efficacy was seen on day 1, when 18 (78%) patients who received ondansetron had no emetic episodes compared with 3 (14%) patients who received metoclopramide (P < 0.001). Significantly fewer antiemetic treatment failures (more than five emetic episodes or withdrawal from the study) occurred with patients given ondansetron (9%) than with those given metoclopramide (50%) during the entire study period (P = 0.002). The most commonly reported adverse event associated with ondansetron therapy was headache (controlled with acetaminophen), whereas diarrhea and restlessness were the most commonly reported adverse events associated with metoclopramide therapy. Extrapyramidal symptoms were judged to have occurred in 13 patients who received metoclopramide and 1 patient who received ondansetron. However, the patient who received ondansetron subsequently was judged to have had an anxiety attack. In patients with low or normal baseline transaminase values, a greater percentage who received ondansetron had transient increases as great as twice the upper limit of normal in aspartate transaminase (5% versus 0%) and alanine transaminase (17% versus 6%) than those who received metoclopramide. Ondansetron is superior to metoclopramide as antiemetic therapy for multiple-day cisplatin-based chemotherapy.