Reporting of paediatric osteoporotic vertebral fractures in Duchenne muscular dystrophy and potential impact on clinical management: the need for standardised and structured reporting.

BACKGROUND: In boys with Duchenne muscular dystrophy (DMD), initiation of bisphosphonate is recommended upon identification of moderate or severe vertebral fractures, even if asymptomatic. Clear radiological reporting is important for consistency of clinical interpretation and management. OBJECTIVES: To audit radiology reports of spine imaging for vertebral fracture assessment in DMD, and assess potential impact on diagnosis and management. MATERIALS AND METHODS: Lateral thoracolumbar spine imaging (71 lateral spine radiographs and 13 lateral dual energy absorptiometry spine image) in 84 boys with DMD performed across two centres. Anonymised radiology reports by paediatric radiologists were circulated to two neuromuscular clinicians and two endocrinologists. Clinicians determined if there was vertebral fracture, no vertebral fracture, or unclear interpretation. Endocrinologists also determined if bisphosphonate was indicated. A single observer (a clinician with expertise in vertebral fracture assessment) performed vertebral fracture assessment in 37 images and re-reported using a structured format. Structured reports were re-circulated to the four clinicians to re-evaluate the degree of concordance in clinical diagnosis of vertebral fracture and treatment decisions with bisphosphonate. RESULTS: The term "fracture" was used in 25/84 (30%) radiology reports and only in 8/43 (19%) with description of vertebral body abnormalities. Fracture grading was included in 7/43 (16%) radiology reports. Diagnostic concordance by the clinicians was noted in 36/84 (43%). Unclear interpretation was noted in 22% to 51% based on radiology reports. No unclear interpretation was noted with structured reports. Complete diagnostic (37/37, 100%) and treatment (37/37, 100%) concordance was noted with the structured reports, whereas complete diagnostic and treatment concordance was noted in only 16/37 (43%) and 17/37 (46%) of the radiology reports, respectively. CONCLUSION: Only a third of radiology reports of spine imaging in DMD explicitly used the terminology "fracture". Grading was only noted in a small percentage. Variability in diagnostic interpretation by clinicians may lead to differing management plans. As identification of vertebral fracture is a trigger for treatment, developing reporting guidelines for paediatric vertebral fracture assessment will improve care. A structured template should be introduced for radiological reporting of paediatric vertebral fracture assessment.

PLA2G6-associated neurodegeneration (PLAN): further expansion of the clinical, radiological and mutation spectrum associated with infantile and atypical childhood-onset disease.

Phospholipase A2 associated neurodegeneration (PLAN) is a major phenotype of autosomal recessive Neurodegeneration with Brain Iron Accumulation (NBIA). We describe the clinical phenotypes, neuroimaging features and PLA2G6 mutations in 5 children, of whom 4 presented with infantile neuroaxonal dystrophy (INAD). One other patient was diagnosed with the onset of PLAN in childhood, and our report highlights the diagnostic challenges associated with this atypical PLAN subtype. In this series, the neuroradiological relevance of classical PLAN features as well as apparent claval hypertrophy' is explored. Novel PLA2G6 mutations were identified in all patients. PLAN should be considered not only in patients presenting with a classic INAD phenotype but also in older patients presenting later in childhood with non-specific progressive neurological features including social communication difficulties, gait disturbance, dyspraxia, neuropsychiatric symptoms and extrapyramidal motor features.

The forkhead transcription factor FOXL2 is expressed in somatic cells of the human ovary prior to follicle formation.

Interactions between germ cells and surrounding somatic cells are central to ovarian development as well as later function. Disruption of these interactions arising from abnormalities in either cell type can lead to premature ovarian failure (POF). The forkhead transcription factor FOXL2 is a candidate POF factor, and mutations in the FOXL2 gene are associated with syndromic and non-syndromic ovarian failure. Foxl2-deficient mice display major defects in primordial follicle activation with consequent follicle loss, and earlier roles in gonadal development and sex determination have also been suggested. However, despite its importance no data presently exist on its expression in the developing human ovary. Expression of FOXL2 mRNA was demonstrated in the human fetal ovary between 8 and 19 weeks gestation, thus from soon after sex determination to primordial follicle development. Expression in the ovary was higher after 14 weeks than at earlier gestation weeks and was very low in the fetal testis at all ages examined. Immunolocalization revealed FOXL2 expression to be confined to somatic cells, both adjacent to germ cells and those located in the developing ovarian stroma. These cells are the site of action of oocyte-derived activin signalling, but in vitro treatment of human fetal ovaries with activin failed to reveal any regulation of FOXL2 transcription by this pathway. In summary, the expression of FOXL2 in somatic cells of the developing human ovary before and during follicle formation supports a conserved and continuing role for this factor in somatic/germ cell interactions from the earliest stages of human ovarian development.

Hypercholesterolemia after chemotherapy for testis cancer.

PURPOSE: The study was designed to determine prospectively the prevalence of fasting serum lipid abnormalities in patients who were treated with cisplatin-based chemotherapy for germ cell tumors. We unexpectedly had demonstrated hypercholesterolemia in 20 of 30 nonfasting patients in a prior study of long-term toxicity of chemotherapy for germ cell tumors. The present study was designed to explore this phenomenon further. PATIENTS AND METHODS: Seventeen unselected patients with biopsy-proven germ cell tumors, who underwent cisplatin-based chemotherapy and who had no prior history of cardiac disease nor known hypercholesterolemia, were studied. In addition to the standard staging tests, blood was drawn for a pretreatment fasting lipid screen, which included cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and apolipoproteins A1, B, and (a). Repeat samples were drawn 24 hours after the administration of cisplatin and at intervals of 6 to 24 months after the completion of treatment. RESULTS: Seven of 17 patients (41%) had higher than desirable levels of total serum cholesterol and low-density lipoprotein cholesterol. Two of them had normal levels before treatment, four had preexisting hypercholesterolemia that increased further, and one patient had an elevated pretreatment level that did not alter. Absolute increases in serum cholesterol were noted in 14 of 17 patients. No consistent patterns of change beyond the reference ranges were found for other serum lipids. CONCLUSIONS: We have confirmed our initial observation that serum cholesterol increases in patients who received cisplatin-containing chemotherapy regimens for germ cell tumors. Further studies will be necessary to define whether other lipid abnormalities occur and the biologic significance of these findings.

Phase I trial of subcutaneous recombinant macrophage colony-stimulating factor: clinical and immunomodulatory effects.

PURPOSE: Recombinant human macrophage colony-stimulating factor (rM-CSF) has been demonstrated to control the growth, differentiation, and function of mononuclear phagocytes. Preclinical studies have indicated antitumor effects, and therefore a phase I trial of rM-CSF in patients with malignancy was initiated. The toxicity and hematologic and immunologic effects were investigated. PATIENTS AND METHODS: rM-CSF was administered as a subcutaneous injection on days 1 through 5 and 8 through 12. Cycles were repeated every 28 days. Cohorts of four to seven patients received rM-CSF at dose levels from 0.1 to 25.6 mg/m2/d. Forty-two patients received 88 cycles of rM-CSF. All patients had metastatic solid tumors refractory to standard therapy. RESULTS: The toxicity of rM-CSF was mild. Dose-limiting toxicity included thrombocytopenia (two patients) and iritis (one patient) occurring at a dose of 25.6 mg/m2/d. Hematologic studies demonstrated dose-related monocytosis occurring routinely at doses > or = 3.2 mg/m2/d, and thrombocytopenia. Immunologic studies demonstrated enhanced secretion of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1 beta) by monocytes after in vitro stimulation with lipopolysaccharide, and increased expression of TNF-alpha mRNA at higher rM-CSF dose levels. Pharmacokinetic studies demonstrated that the systemic clearance rate of M-CSF increases during week 1 of therapy, resulting in lower blood levels of M-CSF during the second week of therapy. CONCLUSION: rM-CSF can be safely administered to patients, and has biologic activity on peripheral-blood monocytes.

Intravenous administration of recombinant human macrophage colony-stimulating factor to patients with metastatic cancer: a phase I study.

PURPOSE: Recombinant human macrophage colony-stimulating factor (M-CSF) has been shown to stimulate specifically macrophage lineage differentiation in vitro and to induce cells capable of antitumor activity alone or in combination with an antibody. The administration of M-CSF to mice has demonstrated antitumor therapeutic effects in vivo. Therefore, a phase I trial of M-CSF administration to patients with metastatic cancer was undertaken. PATIENTS AND METHODS: M-CSF was given by intermittent intravenous bolus infusion every 8 hours for 7 days; the treatment cycle was repeated once after a week of rest. Cohorts of three patients underwent dose escalation from 10 to 100,000 micrograms/m2/d; 23 patients received 27 courses of M-CSF administration. All patients had metastatic solid tumors refractory to conventional therapy, including renal cell carcinoma (RCC) (nine), melanoma (seven), and colorectal carcinoma (seven). RESULTS: Treatment-related toxicity was minimal; five patients developed transient signs of ocular or periorbital inflammation, with iridocyclitis as the most severe manifestation. At the highest doses, platelet counts decreased with therapy (but remained > 100,000/mm3) and the absolute monocyte count increased during the course of therapy. Only at 30,000 and 100,000 micrograms/m2/d was treatment limited because of toxicity (iritis and malaise). Pharmacokinetic studies demonstrated up to a 1,000-fold increase in circulating serum M-CSF after bolus infusion; half-life varied from 1 to 6 hours. Complete regression of mediastinal adenopathy and multiple pulmonary metastases were observed in one patient with RCC. CONCLUSION: Recombinant M-CSF can be administered safely to patients with metastatic cancer at doses that demonstrate biologic activity.

A phase I trial of recombinant human macrophage colony-stimulating factor by rapid intravenous infusion in patients with refractory malignancy.

Twenty patients with advanced cancer for which there was no effective standard therapy or whose disease was refractory to standard therapy were treated with recombinant macrophage colony-stimulating factor (rM-CSF). The rM-CSF was administered by intravenous bolus infusion for 5 consecutive days every other week for 2 treatment weeks. The doses administered ranged from 30 to 33,000 micrograms/m2/day. There was no intrapatient dose escalation. There were minimal to no systemic side effects seen, except for acute dyspnea noted in three patients. The dyspnea was felt to be related to the rate of infusion and did not recur in one patient given additional rM-CSF at a slower infusion rate. The major hematologic effect seen was a mild decrease in platelet count, which began to recover while the patients continued to receive the rM-CSF. The clearance of rM-CSF was dose dependent. Lower doses resulted in a saturable mechanism felt to represent cellular uptake. Clearance at higher doses demonstrated both a first-order mechanism at high serum rM-CSF concentrations, representing renal clearance, as well as a saturable mechanism at low serum concentrations. The maximum mean serum half-life was reached at dose levels of greater than or equal to 3,690 micrograms/m2 and was in the range of 234-258 min. By this route of administration, rises in absolute monocyte count were slight and seen only at doses of greater than or equal to 450 micrograms/m2 during the second therapy week. The maximum tolerated dose was not reached in this study because of lack of availability of rM-CSF.

The influence of reduced liver blood flow on the pharmacokinetics and pharmacodynamics of recombinant tissue factor pathway inhibitor.

OBJECTIVES: Recombinant tissue factor pathway inhibitor (rTFPI) has been shown to be an effective treatment in animal models of sepsis and is under investigation for human use. Reduced liver blood flow during septic shock may substantially alter the pharmacokinetics of rTFPI because clearance of rTFPI approaches liver blood flow. The aim of this study was to examine the effect of exercise-induced reduction in liver blood flow on the pharmacokinetics and pharmacodynamics of rTFPI. METHODS: This was a two-way, open-label, randomized crossover study in eight healthy male volunteers. The subjects in both treatment groups received a continuous intravenous infusion of rTFPI (0.2 mg/kg/h) concurrently with intravenous sorbitol (50 mg/min) for 4 hours. Sorbitol was used as a biomarker for liver blood flow. The subjects were randomized to remain supine or to exercise on a bicycle ergometer for 30 minutes starting at the beginning of the third hour of the infusion. RESULTS: Exercise reduced liver blood flow (mean +/- SEM) from 1.44 +/- 0.06 L/min to 0.40 +/- 0.03 L/min. The average clearance of rTFPI decreased from 0.73 +/- 0.04 L/min in the supine position to 0.25 +/- 0.02 L/min during exercise. This decrease in rTFPI clearance resulted in an 80% (95% confidence interval [CI], 60% to 102%) increase in plasma rTFPI levels during exercise. The average maximal prothrombin time and activated partial thromboplastin time values during exercise were 1.4 (95% CI, 0.4 to 2.5) and 4.4 (95% CI, 2.7 to 6.1) seconds higher compared with the supine steady-state level. CONCLUSIONS: Reduction in liver blood flow by exercise markedly increased rTFPI concentrations and induced a slight but variable prothrombin time and activated partial thromboplastin time increase at the rTFPI dose studied.

Supplementation with vitamin C and N-acetyl-cysteine increases oxidative stress in humans after an acute muscle injury induced by eccentric exercise.

There has been no investigation to determine if the widely used over-the-counter, water-soluble antioxidants vitamin C and N-acetyl-cysteine (NAC) could act as pro-oxidants in humans during inflammatory conditions. We induced an acute-phase inflammatory response by an eccentric arm muscle injury. The inflammation was characterized by edema, swelling, pain, and increases in plasma inflammatory indicators, myeloperoxidase and interleukin-6. Immediately following the injury, subjects consumed a placebo or vitamin C (12.5 mg/kg body weight) and NAC (10 mg/kg body weight) for 7 d. The resulting muscle injury caused increased levels of serum bleomycin-detectable iron and the amount of iron was higher in the vitamin C and NAC group. The concentrations of lactate dehydrogenase (LDH), creatine kinase (CK), and myoglobin were significantly elevated 2, 3, and 4 d postinjury and returned to baseline levels by day 7. In addition, LDH and CK activities were elevated to a greater extent in the vitamin C and NAC group. Levels of markers for oxidative stress (lipid hydroperoxides and 8-iso prostaglandin F2alpha; 8-Iso-PGF2alpha) and antioxidant enzyme activities were also elevated post-injury. The subjects receiving vitamin C and NAC had higher levels of lipid hydroperoxides and 8-Iso-PGF2alpha 2 d after the exercise. This acute human inflammatory model strongly suggests that vitamin C and NAC supplementation immediately post-injury, transiently increases tissue damage and oxidative stress.

Effect of posture on vital capacity.

The influence of some extreme body postures on vital capacity (VC) was examined in young adult humans. Two postures required full support of body weight by the arms: arms up, hanging from a bar, and arms down with hands gripping parallel bars. Three involved muscles that flex and extend the trunk: a partial sit-up position while supine and nearly maximal spinal extension and flexion while standing. Changes at the inspiratory and expiratory volume extremes were recognized by having the subjects do two VC efforts: the first standing and the second in the posture in question while continuing to breathe on the spirometer. Control observations in which the second of a VC pair was performed in an unstressed posture allowed correction for the influence of rebreathing. The changes in corrected VC were small, the greatest being an average reduction of approximately 8% in the partial sit-up position. During full support of body weight by the arms, the VC was slightly increased due to a significant increase in the inspiratory extreme and no change in the expiratory extreme. Spinal extension produced small increases in lung volume at both extremes with no significant change in VC, whereas spinal flexion did not influence the upper extreme but did increase lung volume at the lower extreme. The changes are discussed in terms of trunk muscle action.

Exposure-based safety evaluation of recombinant human macrophage colony-stimulating factor (M-CSF) in cynomolgus monkeys.

The safety of M-CSF was assessed in cynomolgus monkeys in an intravenous dosing regimen. Exposure (AUC0-24) multiples (monkey vs human) were calculated using the no observable adverse effect level (NOAEL) observed in this study and correlated with known M-CSF-induced toxicities in a previous continuous intravenous infusion (civ) study in monkeys. M-CSF was administered by daily intravenous infusion (2 h) to cynomolgus monkeys (2/sex/ group) at 0.1, 0.3, 0.7, and 1.0 mg/kg/day, for 28 consecutive days. Control animals (2/sex) received placebo. The 0.7 mg/kg/day group was held for an additional 4-week recovery period. Criteria evaluated included physical observations, ophthalmoscopy, electrocardiography, body weight, food consumption, clinical pathology, antibody formation, pharmacokinetics, necropsy, organ weights, and histopathology. The only effect previously seen in monkeys after intravenously administered M-CSF occurred in animals in the 0.7 and 1.0 mg/kg/day groups. They exhibited a slight decrease in platelets between days 4 and 12 with subsequent recovery. No effects related to M-CSF administration were evident in macroscopic or microscopic evaluations and there was no evidence of anti-M-CSF antibody production. M-CSF at all dose levels was completely eliminated within each dosing interval with no accumulation. Clearance of M-CSF was enhanced during the first week of dosing, but returned to baseline clearance levels by day 27. This dosing regimen was shown to be remarkably free of toxicities noted in a previous monkey study where M-CSF was given by civ at similar daily doses. At the high dose, which was considered to be the NOAEL, the AUC0-24 was 40-fold greater than the AUC0-24 in clinical trials where 2.0 mg/m2 was administered by a daily 2-h infusion.

The pharmacological selectivity of three NMDA antagonists.

Three N-methyl-D-aspartate (NMDA) antagonists (+/-)2-amino-5-phosphonopentanoate (AP5), 3-((+/-)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) and ((+/-)-5-methyl-10,11-dihydro-5H-dibenzo(a.d.)cyclohepten-5,10- imin e maleate) (MK-801) have been tested for selectivity against depolarization of motoneurones induced by carbachol, 5-hydroxytryptamine, noradrenaline and substance P in isolated immature rat spinal cord preparations. AP5 (400 microM) and CPP (50 microM) gave mean dose-ratios, for antagonism against NMDA, of 103 +/- 14.9 S.E.M. (eight preparations) and 34.1 +/- 1.9 S.E.M. (14 preparations). MK-801 (1 and 10 microM) was the most potent of the three antagonists yielding dose ratios greater than 100 after 120 min treatment. MK-801 potentiated responses induced by 5-hydroxytryptamine and noradrenaline given dose-ratios of 0.22 +/- 0.16 S.E.M. and 0.20 +/- 0.06 S.E.M., respectively (four preparations). The three antagonists produced no significant antagonism of the non-amino acid agonists (four preparations for each agonist) when dose-ratios against NMDA were at least 40. The observations support the use of these antagonists as tools to identify sites of excitatory amino acid-mediated transmission.

Cerebral maturation in premature infants: quantitative assessment using MR imaging.

BACKGROUND AND PURPOSE: The assessment of whether brain development is at an appropriate level for age has become an integral part of clinical MR reporting, although few studies have quantitatively defined the developmental changes occurring in premature infants. We have developed a simple scoring system to assess four parameters of cerebral maturation--myelination, cortical folding, glial cell migration, and germinal matrix distribution--to determine the total maturation score (TMS). The aim of this study was to validate this scoring system in a large population of preterm infants across a range of gestational ages. METHODS: A retrospective analysis was conducted of MR images acquired over a 3-year period with an identical imaging protocol. Infants born more than 14 days before the imaging examination and those with a clinical or radiologic history suggestive of neuroabnormality were excluded from the study. The TMS was derived by consensus. Interobserver agreement was evaluated by using the Bland-Altman plot. RESULTS: Images from 134 infants (23-41 weeks' gestational age) were evaluated. The TMS was significantly related to the postmenstrual age of the infant, with the mean TMS for each age group increasing with advancing postmenstrual age. Interobserver agreement was found to be high (mean difference in score = 0.07, SD = 0.56). CONCLUSION: This scoring system provides a standardized method for assessing cerebral maturation in the premature infant. The TMS is easy to calculate from standard MR images, is reproducible, and can help detect changes occurring within a postnatal age of a few weeks.

MR features of developing periventricular white matter in preterm infants: evidence of glial cell migration.

PURPOSE: MR imaging of the brain is increasingly used in the investigation of the newborn, but little information is available on the normal appearance of the developing brain. We scanned a series of newborn infants in an attempt to define the normal appearance of developing periventricular white matter and to assess how pathologic conditions may modify this appearance. METHODS: Sixty-eight newborn infants, median postmenstrual age (PMA) 34 weeks (range, 24 to 42 weeks), were subdivided into two groups: group A (n = 33), which included those with normal clinical and sonographic examinations, and group B (n = 35), which contained those with evidence of neuroabnormality detected prior to the MR study, either clinically or by cerebral sonography. Images were acquired in two planes on a 1.5-T imager using turbo spin-echo pulse sequences. RESULTS: Symmetric periventricular bands of reduced signal intensity were noted in the frontal periventricular white matter on T2-weighted images in 98% of group A infants and in 97% of group B infants. The number of bands was inversely related to PMA. The reduction in number of bands with increasing PMA was delayed in group B infants. CONCLUSION: The uniform appearance of periventricular bands in a population of healthy infants and their relationship to the infants' maturity is consistent with the results of previous histologic studies. These studies demonstrate the presence of migrating glial cells within the periventricular white matter of infants beyond 20 weeks' gestation, when neuronal migration to the cortex is complete. We postulate that the bands seen on T2-weighted images represent groups of migrating glial cells, providing a further marker of cerebral maturation.

A prospective comparison of central and peripheral vein access for parenteral nutrition in the newborn.

Central venous parenteral nutrition (PN) is frequently used in preterm infants. Although central venous catheters (CVC) permit reliable delivery of hypertonic solution, they may be associated with more serious complications than when a peripheral venous infusion is used. The aim of this randomised prospective study was to compare complications of central versus peripheral venous access using Silastic catheters identical expect for intravascular length. Eighty such devices were inserted, 38 central (CVC), 42 peripheral (PVC). Catheter life was not significantly different between groups: median (range) CVC 10d (2-25); PVC 7d (1-22) with no difference in overall complication rate. Although peripherally sited catheters tended not to function for as long as CVCs, they offer a useful alternative to central venous catheterisation.

Magnetic resonance imaging of the infant brain: anatomical characteristics and clinical significance of punctate lesions.

OBJECTIVE: To describe the magnetic resonance imaging (MRI) characteristics of punctate brain lesions in neonates (number, appearance, distribution, and association with other brain abnormalities) and to relate them to neurodevelopmental outcome. METHODS: A retrospective analysis was performed of 110 MRI brain scans from 92 infants admitted in 1998 to the neonatal intensive care unit. Results of routine neurodevelopmental follow up (1998-2001) in those infants with punctate brain lesions were analysed. RESULTS: Punctate lesions were observed in 15/50 preterm and 2/42 term infants. In the preterm group, the number of lesions was < 3 in 20%, 3-10 in 27%, and > 10 in 53%. In 14/15 the lesions were linearly organised and located in the centrum semiovale. Other brain abnormalities were absent or minor--that is, "isolated" punctate lesions--in 8/15 and major in 7/15. In the term group, punctate lesions were organised in clusters and no other brain abnormalities were observed. Isolated punctate lesions were observed in 10/17 infants, and a normal neurodevelopmental outcome was seen in 9/10 (mean follow up 29.5 months). One infant showed a slight delay in language development. In the infants with associated brain lesions (7/17, mean follow up 27.5 months), outcome was normal in only two subjects. CONCLUSIONS: Punctate lesions are predominantly seen in preterm infants, are usually linearly organised, and border the lateral ventricles. Isolated punctate lesions may imply a good prognosis, because most of these subjects have a normal neurodevelopmental outcome so far.

Exact sampling from nonattractive distributions using summary states.

Propp and Wilson's method of coupling from the past allows one to efficiently generate exact samples from attractive statistical distributions (e.g., the ferromagnetic Ising model). This method may be generalized to nonattractive distributions by the use of summary states, as first described by Huber. Using this method, we present exact samples from a frustrated antiferromagnetic triangular Ising model and the antiferromagnetic q=3 Potts model. We discuss the advantages and limitations of the method of summary states for practical sampling, paying particular attention to the slowing down of the algorithm at low temperature. In particular, we show that such slowing down can occur in the absence of a physical phase transition.

The functions of medical care.

Medical care has several important functions other than restoring or maintaining health. These other functions are assessment and certification of health status, prognostication, segregation of the ill to limit communication of illness, and helping to cope with the problems of illness--the caring function. Medical care serving these "paracurative" functions may legitimately be given indepedently, without associated curing or preventive intent of the provider of care. Although such services do not result in benefits to health, such as extension of life or reduction of disability, they do have other valued outcomes, outcomes not measurable as a gain in personal health status. For example, caring activities may result in satisfaction, comfort, or desirable affective states, even while the patient's health status deteriorates during an incurable illness. The physician's approach to patients, the economist's analysis of the benefits of health services, the planner's decisions about health programs, the evaluator's judgments about the quality of care, or the patient's expectations about treatment are strongly influenced by his assumptions about the purpose of medical care or the proper outcome of the process. When the health worker assumes that the only useful outcome is health, he may consider the paracurative services to be ineffective, inefficient, or undesirable. In contrast, when he recognizes and understands the paracurative functions of medical care, he may better perform his function in the medical care system.

A cardiac arrest and a second-hand report.

KIE: A resident was ordered to discontinue resuscitation procedures on a 65-year-old man who had suffered cardiac arrest. A chaplain's assistant and a nurse had alerted the primary physician to the spouse's statements that her husband did not want his life prolonged by extraordinary means. A lack of communication among all the parties aggravated the conflicts in this case in which the patient was unable to state his desires, the resident and physician found out about his wishes second-hand, and only the chaplain's assistant spoke about the issue with the wife. Physicians are urged to take the initiative in discussing resuscitation with patients and/or family members as soon as potentially terminal situations arise. Other health personnel should participate in decisions about emergency care. In cases where such communication has not occurred, a resident should not stop resuscitative efforts without more information about the patient's wishes.^ieng