A questionnaire survey on the usage of low protein staple foods by people with phenylketonuria in Scotland.

BACKGROUND: There is scarce evidence available with respect to an evaluation of the role of low protein staple foods (LPSF) in the management of phenylketonuria (PKU). The present study explored beliefs, acceptability and issues around the use of LPSF by people with PKU or their carers. METHODS: A semi-anonymous questionnaire was posted to 178 people with PKU in Scotland (104 children, aged 2-17 years, and 74 adults). Questions explored were: the type and amount of LPSF ordered; perceptions on use and usefulness of LPSF; acceptability of the LPSF sensory properties (i.e. taste, smell, texture, appearance); support for the supply and use of LPSF; and comments from primary healthcare professionals regarding dispensing and prescription. RESULTS: Eighty-two individuals responded (46% response rate): 97% perceived that LPSF were useful for PKU management; more than 85% reported that LPSF were important for phenylalanine control, satisfying appetite, and diet variety. The most common LPSF ordered were pasta/rice/cous cous, flour, biscuits and bread. Fifty percent of respondents ordered <51% of the recommended unit allowance of LPSF. The sensory properties of LPSF were well perceived. Forty-nine percent (n = 39) had received a comment from primary healthcare staff regarding the prescription or dispensing of LPSF; 59% (n = 23) received negative comments, the majority of which came within general practitioner surgeries. CONCLUSIONS: There is a positive attitude and perception on the use and usefulness of LPSF in the management of PKU. Issues with respect to the supply and provision of LPSF within primary health care may indicate poor communication between specialists and primary healthcare professionals or a lack of scientific evidence demonstrating their clinical effectiveness.

A preliminary trial of the effect of recombinant human growth hormone on short-term linear growth and glucose homeostasis in children with Crohn's disease.

BACKGROUND: It is unclear whether recombinant human growth hormone (rhGH) improves linear growth in children with Crohn's disease (CD). AIMS: To investigate the effects of rhGH on height velocity (HV) and glucose homeostasis over a 6-month period. DESIGN AND SETTING: Randomized controlled trial in two tertiary children's hospitals in 22 children with inflammatory bowel disease amongst whom 21 had CD. Duration of disease from diagnosis and number of acute relapses requiring either exclusive enteral nutrition or therapeutic dose of oral prednisolone were similar in the treatment and control groups. INTERVENTION: Either rhGH (0·067 mg/kg per day) as daily subcutaneous injections (rhGH group; n, 11) or no rhGH, (Ctrl; n, 11) for 6 months. MAIN OUTCOME MEASURE: Percentage change in HV after 6 months in the two groups. Auxology, puberty, skeletal age, disease factors, treatment and glucose homeostasis were also assessed. RESULTS: Median HV increased from 4·5 (range, 0·6, 8·9) at baseline to 10·8 (6·1, 15·0) cm/year at 6 month (P = 0·003) in the rhGH group, whereas in the Ctrl group, it was 3·8 (1·4, 6·7) and 3·5 cm/year (2·0, 9·6), respectively (P = 0·58). Median percentage increase in HV after 6 months in the rhGH group was 140% (16·7, 916·7) compared with 17·4% (-42·1%, 97·7%) in the Ctrl group (P < 0·001). There were no significant differences in disease activity and proinflammatory cytokines at baseline and 6 months in both groups and change in bone age for chronological age was also similar in the two groups. In the rhGH group, fasting insulin increased from 4·0 (2·0, 11·0) to 7·0 mU/l (2·0, 16·0) (P = 0·02), whereas in the Ctrl group, it was 3·0 (1·2, 12·7) and 3·8 mU/l (2·1, 7·0) (P = 0·72), respectively. CONCLUSIONS: Although this pilot trial shows that rhGH can improve short-term linear growth in children with CD, the clinical efficacy of this therapy needs to be further studied in longer-term studies of growth, glucose homeostasis and disease status.

Therapeutic effect of a topical CCR2 antagonist on induced alveolar bone loss in mice.

BACKGROUND AND OBJECTIVE: Chemokines are known to regulate leukocyte trafficking, recruitment and infiltration in periodontal diseases. The study objective was to determine the effect of an experimental oral/topical chemokine (C-C motif) receptor 2 (CCR2)-antagonist treatment on alveolar bone loss in a mouse model of Porphyromonas gingivalis-induced periodontitis. MATERIAL AND METHODS: Balb/C mice (n = 41) were randomly assigned to four groups. Group 1 was infected by P. gingivalis applied orally/topically for 5 wk. Group 2 was also infected and then treated with vehicle (aqueous methylcellulose) for an additional 4 wk. Group 3 was infected and orally/topically treated with CCR2 antagonist (10 mg/kg). Group 4 served as a noninfected, nontreated control group. Mice received intraperitoneal injections of Alizarin (30 mg/kg) and calcein (20 mg/kg) three times from the last day of infection to determine mineral deposition, reflecting bone dynamics. Mandibles were analysed by morphometry and confocal fluorescence microscopy. RESULTS: Alveolar bone loss was compared among groups using Tukey's test, and bone formation was qualitatively observed. Infected mice showed significantly greater alveolar bone loss than noninfected control animals (group 1 vs. 4, p < 0.01). Vehicle-treated mice (group 2) showed the largest area of alveolar bone loss (p < 0.01), while mice treated with the CCR2 antagonist showed the smallest area of alveolar bone loss and were similar to the control group (group 3 vs. 4, p = 0.14). Qualitative analysis of fluorescent dye uptake indicated increased bone formation in CCR2-antagonist-treated mice, suggesting an improved bone repairing process. CONCLUSION: The results suggested that treatment with CCR2 antagonist inhibited alveolar bone loss and improved bone formation in this model. These data support further evaluation of CCR2 antagonist as a therapeutic target for the development of new treatment modalities on bacterially induced alveolar bone resorption.

The growth hormone insulin-like growth factor 1 axis in children and adolescents with inflammatory bowel disease and growth retardation.

CONTEXT: There is scarce knowledge about the growth hormone (GH) insulin-like growth factor-1 (IGF1) axis in children & adolescents with inflammatory bowel disease (IBD) and growth retardation. OBJECTIVE: To describe the pattern of GH and IGF1 secretion in children & adolescents with IBD. DESIGN: A retrospective review of 28 patients (23 M) of IBD (25 Crohn's Disease and three Ulcerative Colitis) and growth retardation who had investigation of the GH/IGF-1 axis. Height velocity (HV) and serum IGF1 were converted to standard deviation score (SDS); to account for delayed puberty in girls over 11 years and boys over 12 years, HV and serum IGF1 SDS were adjusted for bone age. RESULTS: Median (range) age and Ht SDS at the time of endocrine evaluation was 14.3 years (7.7,17.0) and -2.0(-3.6,-0.9), respectively. Median HVSDS over the prior 12 months was -2.2(-7.7,2.8). Median peak serum GH on insulin tolerance test (ITT) was 5.8 mcg/l (1.3, 24.0), and median serum IGF1 SDS was -0.9(-3.1, 0.1). Five of 28 (18%) had a peak serum GH of >12 mcg/l. Overall, four had biochemical evidence of functional GH deficiency (peak GH < 3 mcg/l and IGF1 SDS < 0) and 11 children had biochemical evidence suggesting GH resistance (peak GH > 6 mcg/l and IGF1 SDS < 0). However, only one child had a peak serum GH > 6 mcg/l and a very low IGF1 SDS of <-2.0. There was a negative association between peak serum GH and Ht SDS (r = -0.49, P = 0.008), but there was no association with HV and there was no association between IGF1 SDS and Ht or HV SDS. IGF1 SDS showed a negative association with erythrocyte sedimentation rate (r = -0.41, P = 0.04). CONCLUSION: Growth retardation in children and adolescents with IBD is commonly associated with a range of biochemical abnormalities ranging from functional GH deficiency to GH resistance. In these children, poor relationship between systemic markers of growth and height velocity point to an important role of growth factors at the target organ level in modulating growth in children with IBD. The value of assessing the GH/IGF-1 axis and whether it predicts subsequent response to growth-promoting therapy requires further exploration.

The concordance between serum anti-Mullerian hormone and testosterone concentrations depends on duration of hCG stimulation in boys undergoing investigation of gonadal function.

BACKGROUND: In boys undergoing investigation of gonadal function, the relationship between a single measurement of serum anti-Mullerian hormone (AMH) and hCG stimulated serum testosterone is unclear. AIM: The aim of the study was to assess concordance between serum AMH and testosterone concentrations following hCG stimulation of two different durations. METHODS: Samples from 284 children (M : F, 154 : 130) with a median age of 8 years (10th, 90th centiles, 0.25, 14) were used to establish an AMH reference range. Clinical data were reviewed in boys undergoing investigation of gonadal function and who had an AMH measurement and a hCG stimulated (3-day or 3-week) (n = 26) testosterone. Of these 26 boys, 11 had combined genital anomalies, whereas the rest had conditions such as isolated hypospadias, undescended testes or microphallus. Normal testosterone response to hCG stimulation was defined as a level greater than 3.5 nmol at day 4 and 9.5 nmol/l at day 22. RESULTS: In the reference group, the 5th centile AMH for boys below 1 year was 215 pmol/l and between 1 and 8 years 180 pmol/l. The 95th centile for girls for these respective age groups was 30 pmol/l and 25 pmol/l. In those cases where serum testosterone concentrations were available at day 1, day 4 and day 22 of the 3 week-hCG test, five cases had a normal serum testosterone at day 4 and three cases only showed such a response by day 22. In those where serum AMH was less than 180 pmol/l, a poor testosterone response of less than 3.5 nmol was observed in approximately seven of eight (88%) cases with a 3-day hCG stimulation test or the 3-week test. An AMH of greater than 180 pmol/l was associated with a normal testosterone response at day 4 in 10 out of 15 (67%) cases and at day 22 in eight of 11 (73%) cases. However, a low serum testosterone concentration of less than 3.5 nmol after the 3-day hCG test was only associated with a likelihood of a low AMH in three of eight (37%) cases. With the 3-week hCG test, a low day 22 testosterone of 9.5 mmol/l or less was associated with a low AMH of 180 pmol/l or less in four of seven (57%) cases. CONCLUSION: In boys undergoing investigation of gonadal function, the concordance between AMH and testosterone is better at day 22 than day 4. A normal AMH may provide useful information on overall testicular function but does not exclude the need for an hCG stimulation test.

Best practice in primary care pathology: review 6.

This sixth best practice review examines four series of common primary care questions in laboratory medicine: (1) laboratory monitoring in hypertension and heart failure abnormalities; (2) markers of inflammatory joint disease; (3) laboratory investigation of chronic diarrhoea; and (4) mumps and chickenpox. The review is presented in question-answer format, referenced for each question series. The recommendations represent a precis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by Medline Embase searches to identify relevant primary research documents. They are not standards but form a guide to be set in the clinical context. Most are consensus based rather than evidence based. They will be updated periodically to take account of new information.

Hirano body filaments contain actin and actin-associated proteins.

Hirano bodies are eosinophilic, rod-shaped intraneuronal inclusions whose frequency increases with age and with Alzheimer's disease. To investigate their composition and possible relationship to the neuronal cytoskeleton, we employed immunocytochemistry and immunoelectronmicroscopy by using antisera to cytoskeletal proteins. The presence of actin, alpha-actinin, vinculin and tropomyosin was demonstrated diffusely throughout the Hirano body. The presence of these proteins supports the contention that Hirano bodies are derived from an abnormal organization of the neuronal cytoskeleton. The staining of Hirano bodies with fluorescent labelled phalloidin, a probe with a unique affinity for F-actin, indicates that the actin in Hirano bodies is in the F-state. Results of high voltage electron microscopy on 1.0 and 0.5 micron sections confirm the purely filamentous nature of Hirano bodies. These findings suggest that the mechanism of formation of Hirano bodies is different from that of the neurofibrillary tangle, another characteristic intraneuronal inclusion seen in Alzheimer patients.

Lewy bodies contain epitopes both shared and distinct from Alzheimer neurofibrillary tangles.

Most of the identified constituents of the filamentous inclusions characteristic of the neurodegenerative diseases of aging are derived from the cytoskeleton. This study was undertaken to define immunocytochemically the cytoskeletal constituents of the filamentous cytopathologic marker of idiopathic Parkinson disease, the Lewy body (LB). An array of antibodies specific to neurofilaments, tubulin, microtubule associated proteins (tau, MAP1 and MAP2) and Alzheimer neurofibrillary tangles (NFT) were used to immunostain sections containing LB. All the antibodies to tubulin, MAP1 and MAP2 and the majority of the antibodies to neurofilaments and NFT recognized LB. The two monoclonal antibodies to NFT that recognize LB also react with ubiquitin, which has been identified in NFT. The prominent NFT component, tau, is apparently not incorporated into LB. These findings suggest that the presence of tau might not be a prerequisite to the formation of abnormal filaments. Therefore, although LB contain elements of neurofilaments, microtubules and ubiquitin, as do other abnormal neuronal filaments, they are distinct in composition. These distinctive and shared features may provide useful insights regarding the mechanisms underlying the formation of filaments in LB as well as those of other neuronal inclusions.

Lipid and lipoprotein concentrations in pregnancies complicated by intrauterine growth restriction.

Previous studies have shown that in preeclampsia, plasma lipids climb substantially above levels seen in normal pregnancies. Such lipid changes may play a role in the endothelial damage characteristic of preeclampsia. Pregnancies complicated by intrauterine growth restriction (IUGR), without preeclampsia, have similar placental pathology to preeclampsia despite the absence of the maternal systemic manifestations of hypertension and proteinuria. The aim of this study was to perform a cross-sectional study of lipid and lipoprotein concentrations in the third trimester, from normal pregnancies, and those complicated by IUGR without preeclampsia. Our hypothesis was that, in contrast to the exaggerated lipid changes seen in preeclampsia, lipid and lipoprotein concentrations in IUGR would be similar to those of matched healthy pregnant controls. Fasting blood samples for lipids and lipoprotein fractions were taken in the third trimester, from eight women with IUGR; and eight women with uncomplicated pregnancies, matched as a group for age, booking weight, parity, and gestational age at sampling. There were no significant differences (P > 0.05) in the median concentrations of triglyceride, high-density lipoprotein, and very-low-density lipoprotein 1 (VLDL1), between cases and controls. However, women with IUGR pregnancies had significantly lower cholesterol [4.95 mmol/L (3.35-7.10) vs. 7.47 (5.75-8.45); median (range) for IUGR patients and controls, respectively; P < 0.01], low-density lipoprotein (LDL)-cholesterol [2.45 mmol/L (0.95-3.60) vs. 4.25 (3.35-5.60); P < 0.01], VLDL2 mass [59.0 mg/dL (37-87) vs. 103.0 (64-168); P < 0.01], intermediate-density lipoprotein mass [56.0 mg/dL (31-110) vs. 125.6 (91-157); P < 0.01], and total LDL mass [221.0 mg/dL (104-237) vs. 380.3 (267-534); P < 0.01]. In addition, it was noteworthy that, with respect to LDL-cholesterol and total LDL mass, there was little or no overlap in the ranges of concentrations measured between cases and controls. Because VLDL2 and intermediate-density lipoprotein are the synthetic precursors to LDL in the circulation, their significantly lower median concentrations imply a failure of appropriate LDL synthesis in IUGR pregnancies. Whatever the mechanism, if our results are confirmed in larger studies and longitudinal investigations, then LDL-cholesterol measurements (when LDL-cholesterol fails to rise appropriately or is low in the third trimester) may be of use in identifying mothers with, or at risk of, a pregnancy complicated by IUGR.

Central nervous system complications of thermal burns. A postmortem study of 139 patients.

We report a retrospective, clinicopathologic study of 139 patients who died during treatment of a severe burn. Fifty-three percent of the patients had central nervous system (CNS) complications-infections, cerebral infarcts and hemorrhages, metabolic encephalopathies, central pontine myelinolysis, and cerebral trauma. Children and adults were equally affected. Sixteen percent of the patients had a CNS infection. Candida species, Staphylococcus aureus and Pseudomonas aeruginosa caused almost 80% of them. S. aureus and candida caused cerebral microabscesses and septic infarcts. P. aeruginosa caused meningitis and infarcts due to meningitis. CNS infections arose as a result of spread from a systemic source. The major risk factors for CNS infection were an extensive burn, S. aureus endocarditis, and a burn wound infection due to candida or P. aeruginosa. Patients with burns of less than 30% of the surface area of their body, those without a systemic infection, and those in the first week after their burn were at low risk. Eighteen percent of the patients had cerebral infarcts. In almost half the patients, the infarcts were caused by septic arterial occlusions or other complications of the burn, viz, disseminated intravascular coagulation (DIC) and septic shock. In only one-third of the patients were infarcts due to atherosclerosis, atrial fibrillation, or other causes prevalent in the general population. Intracranial hemorrhages were only one-fifth as frequent as infarcts and were due to DIC and thrombocytopenia, caused by bacteremia. Diagnosis during life was difficult, because the neurologic picture of focal cerebral lesions and meningitis was indistinguishable from that of metabolic encephalopathies, and because many patients had more than 1 neurologic complication. However, our results suggest that a clinical approach that includes analysis of risk factors for CNS infection, cerebral imaging, examination of cerebrospinal fluid, and tests for DIC can lead to a neurologic and microbiologic diagnosis in most patients.

Matching-to-sample deficits in patients with senile dementias of the Alzheimer and Lewy body types.

Using a computerized matching-to-sample task, nonverbal visual recognition memory was studied in two groups of patients suffering from senile dementia of the Alzheimer type or the recently described senile dementia of the Lewy body type. The patients' cognitive abilities had been shown to be similar according to a number of standard psychometric tests. The two groups did not differ with respect to simultaneous matching-to-sample performance, although both were impaired relative to control. The group with senile dementia of the Lewy body type was severely impaired, relative to the group with senile dementia of the Alzheimer type, when delays (delayed matching to sample) were introduced. The findings suggest that short-term mnemonic processes, mediated by temporal lobe structures, could be more severely affected in senile dementia of the Lewy body type.

Anaplastic astrocytoma mimicking metastatic carcinoma.

A case of anaplastic astrocytoma mimicking a metastatic carcinoma is presented. This rare type of astrocytoma with epithelial features is compared to cases reported in the literature, and the importance of staining brain tumor biopsies for glial fibrillary acidic protein is emphasized.

Mechanisms of partial renal infarct hypertension.

Contributions of both the renin-angiotensin and immune systems to the aetiology of renal infarct hypertension were examined in Sprague-Dawley rats. Partial renal infarction was produced by ligating and sectioning two out of three branches of the left renal artery. The right kidney remained intact. Renal infarction resulted in rapid development of stable hypertension. One week following infarction, the plasma renin activity (PRA) increased more than threefold. However, PRA returned to control levels 4 weeks after infarction. Chronic immunosuppressive therapy with cyclophosphamide at most only attenuated the development of renal infarct hypertension associated with this transient renin elevation. However, cyclophosphamide prevented the later maintenance phase of the hypertension, and could also completely reverse established infarct hypertension. Activation of the renin-angiotensin system plays a role in the onset of partial renal infarct hypertension, but an intact immune system is required for maintenance of the hypertension. It is hypothesized that immunological reactions against renal tissue maintain renal infarct hypertension.

Immune system dysfunction contributes to the aetiology of spontaneous hypertension.

Spontaneously hypertensive rats (SHRs) have a depressed T lymphocyte system, especially a reduced activity of the suppressor T cells, and it has been postulated that an auto-immune defect may be important in the aetiology of hypertension in these rats. In an earlier study we demonstrated that chronic immunosuppressive therapy prevents approximately 50% of the hypertension in the SHR. In the present study, an attempt was made to correct the immune imbalance by implanting thymic tissue from normotensive rats into SHRs. Weekly thymic implants from Wistar donor rats into 16-week-old SHRs produced a maximal reduction (P less than 0.05) in the tail-cuff pressure, after 4 weeks, to a level of 156 +/- 2.3 mmHg (n = 8) in thymus-implanted SHRs versus 189 +/- 2.5 mmHg (n = 6) in sham-implanted SHRs. Also, neonatal thymic implants delayed development of spontaneous hypertension and attenuated the final hypertensive state. Mean arterial pressure averaged 186 +/- 2.8 mmHg in 22-week-old, neonatally sham-implanted SHRs, while it was reduced (P less than 0.05) to 164 +/- 4.2 mmHg in the neonatally thymus-implanted SHRs at this time. The thymic implants had little effect on total T cell, helper T cell or suppressor T cell counts. However, the antihypertensive effect of the thymic implants was associated with a substantial increase in the blastogenic responsiveness of suppressor T cells from the SHRs. These results support the hypothesis that immunological dysfunction plays an important role in the aetiology of spontaneous hypertension.

Immunohistochemical recognition of ethylnitrosourea induced rat brain microtumors by anti-Leu 7 monoclonal antibody.

This immunocytochemical study was undertaken to clarify the histogenesis of ethylnitrosourea-induced rat brain tumors. The tumors induced in offspring of Sprague-Dawley rats injected with ethylnitrosourea on day 18 of gestation were used in these experiments. Controls consisted of pregnant Sprague-Dawley rats similarly injected with saline alone. Both microtumors (less than 1 mm) and macrotumors were examined immunocytochemically. The cells present in both macro- and microtumors were reactive with anti-Leu 7, an antibody which recognizes oligodendrocytes. Intermixed with, but distinct from the tumor cells were glial fibrillary acidic protein positive cells morphologically identical to astrocytes found in other areas distant to tumors in the treated animals, and in controls. These data suggest that both early and late tumors are oligodendrogliomas, not astrocytomas or mixed gliomas, and that the cell of origin of the tumor is the oligodendrocyte rather than an uncommitted stem cell as previously suggested.

Method for assessment of laboratory turnaround times: comparison before, during, and after analysis.

AIMS: To establish a mechanism to examine the components of turnaround time in a representative cross-section of laboratory users; and to identify potential areas for improvement. METHODS: Information was collected manually from result reports received by eight laboratory users: three wards in the main hospital, four GP practices, and one local psychiatric hospital. This was combined with data from the departmental computer files to create a spreadsheet detailing different time points in the processing of a specimen, from venepuncture to receipt of result report. RESULTS: At the main hospital, 80% of samples arrived within two hours of venesection and 95% by four hours; 75% of samples were analysed within two hours; 85% of results arrived in the wards within six hours of printing, although 12% took more than 18 hours to arrive; median overall time six hours. At the satellite (psychiatric) hospital, all samples arrived within seven hours of venesection; 45% were analysed within two hours--the rest the following morning; there were highly variable post-analytical times, minimum 18 hours, maximum 122 hours; the median overall time was 69 hours. Twenty five per cent of samples from GPs took more than 20 hours to arrive; 75% were analysed within two hours, the rest took over 18 hours--waiting overnight; the post-analytical times were highly variable, minimum 22 hours, maximum 122 hours; the median overall time was 50 hours. CONCLUSIONS: The method is easily repeatable and demonstrates the need for local improvement in the post-analytical period. Although specific to the individual data handling system for one laboratory, this method may be used as a basis for other laboratories in pathology disciplines to undertake a representative assessment of turnaround times for different groups of laboratory users.

Laboratory turnround time: closing the loop.

AIMS: To institute recommendations from a laboratory turnround time study; to evaluate audit methods; and to quantify improvements achieved. METHODS: Changes to result report distribution and specimen delivery were affected by posting results directly from the laboratory followed by the introduction of a twice daily courier service. Improvements were evaluated by repeating the turnround time audit described in an earlier report. Pre-, peri- and post-analytical turnround times were compared before and after changes had been instituted. RESULTS: Directly posting general practitioner (GP) results increased the percentage of reports which reached their destination within one and two days after they were generated from 13 to 29% and from 68 to 82%, respectively. Pre- and postanalytical times were superimposable before and after posting was started. Corresponding improvements to the satellite hospital service were from 25 to 78% and from 60 to 82%, respectively. The courier service shortened the median total turnround time from 50 to nine hours for GPs and from 69 to 18 hours for the satellite hospital. Fifty three per cent of GP reports and 21% of satellite hospital reports arrived on the same day as the sample was taken: 99% and 94%, respectively, had arrived by the next day. The number of analytically "old" samples which arrived the day after they had been taken, thus invalidating many results, fell from 25 to 3%. CONCLUSIONS: These audits of laboratory turnround time have been used to present a valid case for changes to laboratory transport and to quantify the improvements achieved. They produce consistent and repeatable results, which may also be used to monitor future performance, to assess further changes and to establish the cost-effectiveness of resources used.

Audit of an emergency biochemistry service.

AIM: To examine a model for the evaluation of appropriateness of testing in an emergency biochemistry laboratory. METHODS: A model was devised in which incoming emergency test requests were categorised as appropriate or inappropriate. Explicit criteria were used to define eight minor categories, which were chosen to reflect accurately current working practice within the hospital and laboratory. Five junior medical staff each undertook a prospective 24 hour assessment, during which time all incoming requests were monitored and categorised according to these criteria. Concordance between monitors was evaluated before and during assessments. RESULTS: Of 509 requests, 384 (75%) were appropriate and 125 (25%) were inappropriate according to the criteria used to define categories. Inappropriate requests fell into three main groups: preoperative samples (43.2% (54/125) of all inappropriate requests), missed routine samples (33.6% (42/125)) and accelerated (priority) analyses (16% (20/125)). Various other reasons accounted for the remaining 7.2% (9/125). CONCLUSION: This model may be used to obtain valid information about current clinical and laboratory practice. Strategies to reduce the number of inappropriate requests have been identified in order to reserve the emergency service for situations of true need.

Splenectomy and the induction of murine colon cancer.

The influence of a functional spleen on induction and growth of cancer is unknown. Both beneficial and detrimental results have been observed in tumor-bearing hosts following splenectomy. We examined the effect of splenectomy, splenic autotransplantation, and splenic preservation on the induction and growth of 1,2-dimethylhydrazine (DMH)-induced murine colon cancer. Following splenectomy there was a significant increase in malignant tumors but no increase in benign tumors. To rule out the possibility that splenectomy increased the carcinogenicity of DMH by decreasing the capacity for DNA repair in colon cells, the units of 06-alkylguanine DNA alkyltransferase were measured in tumor-free and malignant colon tissue from both splenectomized and control rats. This repair protein was chosen because it is known to protect cells from the mutagenic effects of methylating agents. There was no significant difference in the alkyltransferase activity of tumor-free colon vs malignant tumor or between treatment regimens. Thus, the ability of the spleen to protect rats from the induction of malignant colon tumors induced by DMH is most likely due to preservation of immunologic surveillance in the host.

Effects of muramyl dipeptide and core body temperature on peritoneal bacterial clearance.

To examine the interaction between muramyl dipeptide (MDP) and core body temperature in murine peritonitis, 120 Sprague-Dawley rats were randomized to receive either 0, 1, or 4 micrograms/g body weight of MDP. Twenty-four hours later a sublethal intraperitoneal inoculation of Escherichia coli was given after core body temperature regulation at 32 degrees C to 40 degrees C, which was maintained for 30 minutes. Killing of the rats at 1, 3, or 6 hours later allowed evaluation of peritoneal white blood cell and bacterial counts. Results demonstrated that MDP (independent of core body temperature) caused an increased peritoneal white blood cell response at one and six hours and an increased peritoneal bacterial clearance at three hours. Increasing core body temperature adversely affected peritoneal bacterial clearance. High-dose MDP was clearly significant in acceleration of peritoneal bacterial clearance. No interaction between MDP and core body temperature was seen.