Graft vasculopathy in clinical hand transplantation.

Allogeneic hand transplantation is now a clinical reality. While results have been encouraging, acute rejection rates are higher than in their solid-organ counterparts. In contrast, chronic rejections, as defined by vasculopathy and/or fibrosis and atrophy of skin and other tissues, as well as antibody mediated rejection, have not been reported in a compliant hand transplant recipient. Monitoring vascularized composite allograft (VCA) hand recipients for rejection has routinely involved punch skin biopsies, vascular imaging and graft appearance. Our program, which has transplanted a total of 6 hand recipients, has experience which challenges these precepts. We present evidence that the vessels, both arteries and veins may also be a primary target of rejection in the hand. Two of our recipients developed severe intimal hyperplasia and vasculopathy early post-transplant. An analysis of events and our four other patients has shown that the standard techniques used for surveillance of rejection (i.e. punch skin biopsies, DSA and conventional vascular imaging studies) are inadequate for detecting the early stages of vasculopathy. In response, we have initiated studies using ultrasound biomicroscopy (UBM) to evaluate the vessel wall thickness. These findings suggest that vasculopathy should be a focus of frequent monitoring in VCA of the hand.

Saccade dysfunction associated with chronic petrol sniffing and lead encephalopathy.

BACKGROUND: In chronic petrol sniffers, recent exposure to high levels of leaded petrol may give rise to a lead encephalopathy characterised by tremor, chorea, ataxia, hyperreflexia, convulsive seizures, and death. Neurological abnormalities associated with lead encephalopathy involve the cortex, basal ganglia, cerebellum, and brain stem. OBJECTIVE: To use saccadic eye movement tasks as an experimental tool to determine which CNS changes are associated with chronic petrol sniffing and which with a history of lead encephalopathy, and to what extent these changes are reversible. METHODS: Saccade function was assessed in chronic petrol sniffers with a history of lead encephalopathy (encephalopathic sniffers), chronic petrol sniffers who had never suffered lead encephalopathy (chronic sniffers), individuals who had sniffed petrol in the past but had not done so for more than six months (ex-sniffers), and individuals who had never sniffed petrol (non-sniffers). RESULTS: Chronic sniffers showed increased latency of visually guided saccades and antisaccades and increased antisaccade errors which suggested cortical and basal ganglia dysfunction. These abnormalities returned to normal in ex-sniffers. Encephalopathic sniffers showed the same abnormalities as chronic sniffers but with greater severity and additional saccadic signs including dysmetria, gaze evoked nystagmus, and saccade slowing which usually indicate cerebellar and brain stem dysfunction. CONCLUSIONS: Chronic petrol abuse is associated with cortical and basal ganglia abnormalities that are at least partially recoverable with abstinence. Additional long term cerebellar and brain stem abnormalities are associated with lead encephalopathy.

Case-control study of the association between kava use and pneumonia in eastern Arnhem and Aboriginal communities (Northern Territory, Australia).

Pneumonia causes significant morbidity and mortality in Aboriginal populations in Australia's Northern Territory (NT). Kava, consumed in Arnhem Land since 1982, may be a risk factor for infectious disease including pneumonia. A case-control study (n = 115 cases; n = 415 controls) was conducted in 7001 Aboriginal people (4217 over 15 years). Odds ratios (OR) were calculated by conditional logistic regression with substance use and social factors as confounders. Pneumonia was not associated with kava use. Crude OR = 1.26 (0.74-2.14, P = 0.386), increased after controlling for confounders (OR = 1.98, 0.63-6.23, P = 0.237) but was not significant. Adjusted OR for pneumonia cases involving kava and alcohol users was 1.19 (0.39-3.62, P = 0.756). In communities with longer kava-using histories, adjusted OR was 2.19 (0.67-7.14, P = 0.187). There was no kava dose-response relationship. Crude ORs for associations between pneumonia and cannabis use (OR = 2.27, 1 18-4.37, P = 0.014) and alcohol use (OR = 1.95, 1.07-3.53, P = 0.026) were statistically significant and approached significance for petrol sniffing (OR = 1.98, 0.99-3.95, P = 0.056).

Health effects of kava use in an eastern Arnhem Land Aboriginal community.

BACKGROUND: Heavy kava use in Aboriginal communities has been linked to various health effects, including anecdotes of sudden cardiac deaths. AIMS: To examine associations between kava use and potential health effects. METHODS: A cross-sectional study was carried out within a kava-using east Arnhem Land Aboriginal community in tropical northern Australia. One-hundred-and-one adults who were current, recent or non-users of kava were enrolled in March 2000. Main outcome measures were physical, anthropometric, biochemical, haematological, immunological and neurocognitive assessments. RESULTS: Kava users more frequently showed a characteristic dermopathy (P<0.001). They had increased levels of gamma-glutamyl transferase and alkaline phosphatase (P<0.001). Lymphocyte counts were significantly lower in kava users (P<0.001). Fibrinogen, plasminogen activator inhibitor-1 and neurocognitive tests were not different between kava use categories. IgE and IgG antibodies were elevated across the whole group, as were C-reactive protein and homocysteine. CONCLUSIONS: Kava use was associated with dermopathy, liver function abnormalities and decreased lymphocytes. If kava continues to be used by Aboriginal populations, monitoring should focus on the health consequences of these findings, including a possible increase in serious infections. The interaction between kava, alcohol and other substances requires further study. Although markers of cardiovascular risk are increased across the population, these were not higher in kava users, and this increase may be linked to the large infectious pathogen burden reflective of the socioeconomic disadvantage seen in many remote Aboriginal communities.

Factors affecting phantom scores at annual mammography facility inspections by the U.S. Food and Drug Administration.

RATIONALE AND OBJECTIVES: The authors performed this study to evaluate the factors affecting phantom image score at the annual inspection of mammography facilities. MATERIALS AND METHODS: In 1997, three U.S. Food and Drug Administration (FDA)-trained inspectors performed inspections of all mammography facilities in North Carolina. All federal and state inspection data were collected and evaluated by using linear regression analysis. Factors affecting the American College of Radiology phantom scores were assessed. RESULTS: Phantom score was affected by inspector identity, view box luminance, and optical density. All of these factors had a statistically significant effect on mass score (P < .05). Inspector identity yielded a statistically significant effect on speck group score, fibril score, and total score. Luminance yielded a statistically significant effect on both speck group score and total score. CONCLUSION: Phantom scoring should be automated to allow for more consistent interobserver scoring. In addition, radiology facilities can improve the likelihood of receiving a passing phantom score by reducing the ambient light and increasing the view box luminance in the location where the images are evaluated and the phantom is scored routinely. Radiologists should also consider increasing phantom and clinical image optical density to allow for improved phantom testing outcomes.

Has the mammography quality standards act affected the mammography quality in North Carolina?

OBJECTIVE: The United States Food and Drug Administration implemented federal regulations governing mammography under the Mammography Quality Standards Act (MQSA) of 1992. During 1995, its first year in implementation, we examined the impact of the MQSA on the quality of mammography in North Carolina. MATERIALS AND METHODS: All mammography facilities were inspected during 1993-1994, and again in 1995. Both inspections evaluated mean glandular radiation dose, phantom image evaluation, darkroom fog, and developer temperature. Two mammography health specialists employed by the North Carolina Division of Radiation Protection performed all inspections and collected and codified data. RESULTS: The percentage of facilities that met quality standards increased from the first inspection to the second inspection. Phantom scores passing rate was 31.6% versus 78.2%; darkroom fog passing rate was 74.3% versus 88.5%; and temperature difference passing rate was 62.4% versus 86.9%. CONCLUSION: In 1995, the first year that the MQSA was in effect, there was a significant improvement in the quality of mammography in North Carolina. This improvement probably resulted from facilities' compliance with federal regulations.

Comparison of zafirlukast (Accolate) absorption after oral and colonic administration in humans.

PURPOSE: This study characterized the gastrointestinal (GI) absorption of zafirlukast after oral and colonic administration in humans. METHODS: Five healthy subjects received zafirlukast solution (40 mg) orally and via an oroenteric tube into the colon in a randomized, crossover fashion. Two additional subjects were dosed into the distal ileum. Serial blood samples were obtained and plasma concentrations were quantitated by HPLC. RESULTS: Mean +/- SD pharmacokinetic parameters after oral vs. colonic administration were: AUC infinity of 2076 +/- 548 vs. 602 +/- 373 ng x h/mL, respectively, and Cmax of 697 +/- 314 vs. 194 +/- 316 ng/mL, respectively. Mean colon:oral AUCalpha and Cmax were 0.29 and 0.30, respectively. Median tmax values were 2.0 and 1.35 hr after oral and colonic administration. First-order absorption rate constants (Ka and Kac) were estimated from a two-compartment model with first-order elimination. Kac:Ka was <0.5 in 4 of the 5 subjects dosed in the colon. CONCLUSIONS: Zafirlukast was absorbed at multiple sites in the GI tract. The rate and extent of zafirlukast absorption was less after colonic than oral administration. Zafirlukast was significantly absorbed in the distal ileum. This study demonstrated that gamma scintigraphy, digital radiography, and fluoroscopy can be used to track the movement and confirm the location of the oroenteric tube in the GI tract.

Effects of processing conditions on mammographic image quality.

RATIONALE AND OBJECTIVES: Any given mammographic film will exhibit changes in sensitometric response and image resolution as processing variables are altered. Developer type, immersion time, and temperature have been shown to affect the contrast of the mammographic image and thus lesion visibility. The authors evaluated the effect of altering processing variables, including film type, developer type, and immersion time, on the visibility of masses, fibrils, and speaks in a standard mammographic phantom. MATERIALS AND METHODS: Images of a phantom obtained with two screen types (Kodak Min-R and Fuji) and five film types (Kodak Min-R M, Min-R E, Min-R H; Fuji UM-MA HC, and DuPont Microvision-C) were processed with five different developer chemicals (Autex SE, DuPont HSD, Kodak RP, Picker 3-7-90, and White Mountain) at four different immersion times (24, 30, 36, and 46 seconds). Processor chemical activity was monitored with sensitometric strips, and developer temperatures were continuously measured. The film images were reviewed by two board-certified radiologists and two physicists with expertise in mammography quality control and were scored based on the visibility of calcifications, masses, and fibrils. RESULTS: Although the differences in the absolute scores were not large, the Kodak Min-R M and Fuji films exhibited the highest scores, and images developed in White Mountain and Autex chemicals exhibited the highest scores. CONCLUSION: For any film, several processing chemicals may be used to produce images of similar quality. Extended processing may no longer be necessary.

Neurological and cognitive abnormalities associated with chronic petrol sniffing.

Substance abuse through the deliberate inhalation of petrol (petrol sniffing or gasoline sniffing) is prevalent in inner-urban and remote rural communities. Although acute toxic encephalopathy is a well-documented consequence of petrol sniffing, the neurological and cognitive effects of chronic petrol sniffing are unknown. A structured neurological examination and the Cambridge Neuropsychological Test Automated Battery (CANTAB) were used to assess neurological and cognitive function in 33 current-sniffers (individuals who had sniffed petrol for >6 months), 30 ex-sniffers (individuals who had sniffed petrol in the past but had abstained for 6 months) and 34 matched non-sniffers (individuals who had never sniffed petrol). No subject was, or had been, encephalopathic from petrol sniffing and all were residing in their community. Blood lead and hydrocarbon levels and information about petrol sniffing behaviour were obtained from each subject. When compared with non-sniffers, current-sniffers showed higher rates of abnormal tandem gait, rapid alternating hand movements, finger to nose movements, postural tremor, bilateral palmomental reflexes and brisk deep reflexes. Cognitive deficits occurred in the areas of visual attention, visual recognition memory and visual paired associate learning. Ex-petrol sniffers showed higher rates of abnormal tandem gait and bilateral palmomental reflexes and cognitive deficits in the areas of visual recognition memory and pattern-location paired associate learning. Blood lead levels and length of time of petrol sniffing correlated significantly with the magnitude of neurological and cognitive deficits. Blood hydrocarbon levels were not related to neurocognitive deficits, although this may have been due to methodological difficulties in obtaining hydrocarbon levels. These results suggest that subtle neurological and cognitive abnormalities do occur in individuals who abuse petrol but who do not have acute toxic encephalopathy and that the severity of these abnormalities is reduced with abstinence.

Effect of pancreatico-biliary secretions and GI transit time on the absorption and pharmacokinetic profile of ranitidine in humans.

PURPOSE: Ranitidine plasma concentration vs. time profiles and the extent of ranitidine absorption were examined in the presence and absence of pancreatico-biliary secretions in order to elucidate factors which may contribute to secondary peaks after oral ranitidine administration. METHODS: Ranitidine solution (300 mg) was administered to 4 fasting healthy subjects via an indwelling small-bore oroenteric tube located approximately 16 cm distal to the pylorus On 3 consecutive days, subjects randomly received ranitidine alone (control), ranitidine 10 min after 0.04 micrograms/kg IV cholecystokinin (CCK) sufficient to cause gall bladder emptying into the duodenum, and ranitidine 30 min after inflation of an occlusive duodenal balloon located approximately 10 cm distal to the pylorus to prevent pancreatico-biliary secretions from reaching the dosing port or beyond. Small bowel transit time (SBTT; min) was measured by breath H2. Serial blood samples, obtained over 12 hours in each treatment, were analyzed by HPLC to determine ranitidine AUC0-12 (ng*h/mL), as well as Cmax (ng/mL) and Tmax (min) of the first and subsequent peaks, if subsequent peaks were observed. RESULTS: Ranitidine AUC0-12 and Cmax were not altered significantly by treatments; treatment effects on SBTT varied. Secondary peaks were observed in subjects #1 and #3 during the control treatment and subjects #2 and #4 during the CCk treatment. No secondary peaks were observed in any subject during the balloon treatment, and Tmax1 was delayed. CONCLUSIONS: Results support the hypothesis that pancreatico-biliary secretions (present in the intestinal lumen during control or CCK treatment) and gastrointestinal transit time may influence the occurrence of secondary peaks in ranitidine concentration vs. time profiles.

Educational outreach to mammography facility staff to assist with compliance with the Mammography Quality Standards Act in rural North Carolina.

RATIONALE AND OBJECTIVES: The purpose of this project was to develop and evaluate an educational program targeted at mammography facilities in rural areas of North Carolina that were having difficulty complying with the 1992 Mammography Quality Standards Act (MQSA). MATERIALS AND METHODS: Fourteen facilities deemed at risk for closure under MQSA were identified by state inspection personnel. Problems at the facilities were evaluated by a radiologist, a physicist-educator, and a radiation physicist through a written survey, review of phantom and clinical images, and a site visit. Individual advice and instruction were provided on-site by the physicist-educator, with written materials provided in follow-up. A repeat site visit was made 4-6 months after the initial visit. RESULTS: Of 51 problems identified at the 12 institutions that completed the program, 35 (69%) were corrected. All facilities that had failing phantom scores at the inspection prior to the intervention had passing scores at the inspection after the intervention. There was a statistically significant increase in the sum of the phantom scores for the facilities offered this intervention compared with those not offered it (P = .03). CONCLUSION: This educational program improved mammography quality at participating facilities.

Resource requirements to develop a large, remote aboriginal health service: whose responsibility?

In 1994 the Commonwealth funded studies to establish and develop Aboriginal health services. One such study was undertaken in 1995 at Maningrida, Northern Territory: to identify the health-service needs of the population and consider community management structures; to identify Northern Territory expenditure for primary health care; and to provide a three- to five-year development budget. Approximately 2100 Aboriginal residents in the region used the service, including 750 living on 24 outstations within 75 km. Nearly 40 per cent were aged under 15 years. Childhood morbidity was high, with children under two averaging 1.4 hospital admissions per year. The age pyramid reflected premature adult mortality from the third decade of life. Service providers identified inadequate staffing and infrastructure as barriers to service development. Community consultations emphasised the need for resident doctors, improved outstation services and aged and respite care, local training for Aboriginal health workers and housing for staff. These developments would require per capita primary health care expenditure ($872) to be doubled. Aboriginal people in remote areas are disadvantaged through Commonwealth Grants Commission funding formulae and lack of Medicare access. As the sole funding source, the Northern Territory spends over $1.83 million per year providing health services at Maningrida. Additionally, the study proposed that the Commonwealth spend $1.96 million a year over five years on staffing and infrastructure. Local Aboriginal organisations also agreed to allocate resources for health service development. Ineffective implementation, lack of clarification of government responsibilities and funding shortfalls remain barriers to developing remote Aboriginal health services.

Reliability and validity of rigid lift and pelvic leveling device method in assessing functional leg length inequality.

Clinicians commonly include an assessment of leg length inequality (LLI) as a component of a musculoskeletal examination. Little research is available, however, documenting reliability and validity of clinical methods for assessing LLI. The purpose of this study was to determine the reliability and validity of assessing functional LLI using a pelvic leveling device. Subjects were 19 women and 13 men between the ages of 18 and 55 who reported having a diagnosed or suspected LLI. Clinical determination of LLI was made by placing rigid lifts under the suspected shorter lower extremity until the leveling device indicated that the iliac crests were level. This measurement was made twice by one investigator and once by a second investigator. Standing radiographic measurements of LLI using rigid lifts were used to establish validity of the clinical method. Intraclass correlation coefficients [ICC(2,1)] and absolute difference values were computed to assess reliability and validity. The mean absolute difference between the two clinical measurements of LLI by the same investigator was 0.29 cm (+/- 0.52), with an ICC = 0.84. The mean absolute difference between clinical measurements of LLI by the two investigators was 0.49 cm (+/- 0.46), with an ICC = 0.77. The ICC and mean absolute difference reflecting agreement between radiographic measurements and clinical measurements of LLI was 0.64 and 0.58 cm (+/- 0.58), respectively, for one investigator and 0.76 and 0.55 cm (+/- 0.37), respectively, for the second investigator. The intratester reliability, intertester reliability, and validity assessments included instances in which paired observations disagreed regarding which lower extremity was the shorter lower extremity. Factors that may be associated with the unacceptable reliability and validity of the clinical assessment method include asymmetric positioning of the ilia, body composition of the patient, and design of the clinical instrument. The authors discuss clinical implications related to assessment of LLI.

An evaluation of unleaded petrol as a harm reduction strategy for petrol sniffers in an aboriginal community.

OBJECTIVE: In mid 1989, leaded petrol was replaced by unleaded petrol to reduce lead toxicity in petrol sniffers in Maningrida, a remote Aboriginal community in Northern Australia. RETROSPECTIVE REVIEWS: Hospital admissions between 1987 and 1992 due to petrol sniffing were compared for Maningrida and a community using only leaded petrol. RESULTS: Admissions from Maningrida decreased significantly following introduction of unleaded petrol (chi 2 on 2df = 22.25, p < 0.001). Lead and hydrocarbon exposures were also compared for three groups from Maningrida (27 sniffers using only unleaded petrol; 15 exsniffers and 13 nonsniffers) and 24 individuals admitted to hospital for petrol sniffing related illness from other communities using only leaded petrol. Median blood lead levels for hospitalized sniffers (using only leaded petrol). Maningrida sniffers (using only unleaded petrol), exsniffers and nonsniffers were 5.06, 1.87, 1.24 and 0.17 microM/L respectively. There were significant differences between blood lead level, delta-aminolevulinic acid dehydratase activity, and free erythrocyte protoporphyrin for sniffers of leaded and unleaded petrol, whereas these indices were not significantly different for current sniffers and exsniffers in Maningrida. Hydrocarbons were only detectable in the blood of active sniffers (toluene < or = 0.5 micrograms/mL; benzene < or = 0.17 micrograms/mL blood; n-hexane not detected). CONCLUSIONS: The elimination of tetraethyl lead from petrol resulted in a significant decrease in hospitalization of petrol sniffers.

Evaluation of strategies used by a remote aboriginal community to eliminate petrol sniffing.

OBJECTIVE: To evaluate the success of strategies--including replacing petrol with aviation gasoline (avgas) in the fuel supply, and employment and skills-training programs targeting young people--in reducing petrol sniffing at Maningrida, an isolated Aboriginal community in northern Australia. METHODS: A follow-up study of 13 Aboriginals who were non-sniffers, 15 who were ex-sniffers and 27 who were petrol sniffers in 1992 was conducted by questionnaire in 1994, 20 months after intervention strategies were commenced; 11 non-sniffers, 11 ex-sniffers and 18 petrol sniffers, respectively, participated. MAIN OUTCOME MEASURES: Petrol-sniffing status, changes in employment status, blood lead levels of the participants, and community crime statistics. RESULTS: After intervention strategies in Maningrida, petrol sniffing ceased, with related crime falling markedly. Employment increased significantly among petrol sniffers, from 7% to 63% (chi 2 = 11.53; df = 1; P < 0.001). Only two petrol sniffers were reported to have continued petrol sniffing elsewhere. Apart from one of these individuals, who had recently returned to Maningrida, blood lead levels fell significantly in those with a history of petrol sniffing, indicating they had not continued to sniff avgas, which contains lead additives (0.8 g/L). CONCLUSIONS: While avgas introduction was a key element in eliminating petrol sniffing, its apparent lack of success as a single intervention elsewhere indicates the importance of widespread community resolve against petrol sniffing and the development of coordinated employment strategies in successfully eliminating the practice and reducing associated social disruption.

The efficacy of chelation therapy and factors influencing mortality in lead intoxicated petrol sniffers.

BACKGROUND: The use of chelating agents to treat patients with petrol sniffing encephalopathy has been controversial, since alkyllead additives in petrol are not chelatable. A high mortality has also been reported in hospitalised petrol sniffers. AIMS: (i) Evaluate the efficacy of chelating agents in mobilising lead for excretion and lowering blood lead; (ii) Review factors contributing to mortality in hospitalised petrol sniffers. METHODS: All males chelated between 1992-1993 were studied (n = 20). Blood and urinary lead were measured daily before and during chelation then twice weekly until discharge. Parenteral calcium disodium edetate (EDTA) and dimercaprol (BAL) were administered together, every six hours for five days, seven patients subsequently received oral D-penicillamine until discharge. Clinical details were reviewed for eight patients with petrol sniffing encephalopathy who died between 1990-1994. RESULTS: Urinary lead excretion substantially increased during parenteral chelation (median excretion = 113 microM/5 days, compared with pre-chelation excretion = 1.1 microM/day). Median blood lead concentration fell from 4.83 microM/L (pre-chelation) to 1.91 microM/L (post-chelation). D-Penicillamine did not appear to increase urinary lead excretion appreciably. All eight deaths followed sepsis; five from complications of aspiration pneumonia. CONCLUSIONS: Airway maintenance and management are crucial for survival in these patients. In the short-term, parenteral chelation was effective in mobilising lead for excretion and reducing blood lead in encephalopathic petrol sniffers and was comparable to cases of inorganic lead intoxication. However, as in the treatment of inorganic lead intoxication, the long-term efficacy of chelation for petrol sniffers remains controversial. Prevention strategies against petrol sniffing at a community level are recommended.

Patterns of petrol sniffing and other drug use in young men from an Australian Aboriginal community in Arnhem Land, Northern Territory.

Petrol sniffing and use of other drugs were examined among 48 males aged 13-32 years resident in a remote Aboriginal community in Arnhem Land. The study group consisted of 13 non-sniffers, 13 ex-sniffers and 22 current sniffers. Unemployment was highest among those with a history of petrol sniffing. Employment and family influence emerged as major reported reasons for individuals stopping petrol sniffing. The findings of the study suggest that strategies to reduce petrol sniffing should not only focus on education, employment, skills training and recreation, but should further encourage Aboriginal communities to utilize family relationships to dissuade young people from the practice. Unlike ex-sniffers and current sniffers, non-sniffers tended to be abstainers from tobacco, kava and alcohol. Of the selected study group, 52% smoked >or=25 cigarettes per day. On the basis of the research findings, the local community Council has implemented employment, skills training and recreation strategies to reduce petrol sniffing in this age group. A reduction in tobacco consumption in both adults and young people has also been targeted through health education programmes developed by the community health clinic and the school.