Enhanced stress-resilience training for surgical trainees.

INTRODUCTION: Core surgical training programmes are associated with a high risk of burnout. This study aimed to assess the influence of a novel enhanced stress-resilience training (ESRT) course delivered at the start of core surgical training in a single UK statutory education body. METHOD: All newly appointed core surgical trainees (CSTs) were invited to participate in a 5-week ESRT course teaching mindfulness-based exercises to develop tools to deal with stress at work and burnout. The primary aim was to assess the feasibility of this course; secondary outcomes were to assess degree of burnout measured using Maslach Burnout Inventory (MBI) scoring. RESULTS: Of 43 boot camp attendees, 38 trainees completed questionnaires, with 24 choosing to participate in ESRT (63.2 per cent; male 13, female 11, median age 28 years). Qualitative data reflected challenges delivering ESRT because of arduous and inflexible clinical on-call rotas, time pressures related to academic curriculum demands and the concurrent COVID-19 pandemic (10 of 24 drop-out). Despite these challenges, 22 (91.7 per cent) considered the course valuable and there was unanimous support for programme development. Of the 14 trainees who completed the ESRT course, nine (64.3 per cent) continued to use the techniques in daily clinical work. Burnout was identified in 23 trainees (60.5 per cent) with no evident difference in baseline MBI scores between participants (median 4 (range 0-11) versus 5 (1-11), P = 0.770). High stress states were significantly less likely, and mindfulness significantly higher in the intervention group (P < 0.010); MBI scores were comparable before and after ESRT in the intervention cohort (P = 0.630, median 4 (range 0-11) versus 4 (1-10)). DISCUSSION: Despite arduous emergency COVID rotas ESRT was feasible and, combined with protected time for trainees to engage, deserves further research to determine medium-term efficacy.

Predictive value of Altmetric score on citation rates and bibliometric impact.

BACKGROUND: Bibliometric and Altmetric analyses provide different perspectives regarding research impact. This study aimed to determine whether Altmetric score was associated with citation rate independent of established bibliometrics. METHODS: Citations related to a previous cohort of 100 most cited articles in surgery were collected and a 3-year interval citation gain calculated. Citation count, citation rate index, Altmetric score, 5-year impact factor, and Oxford Centre for Evidence-Based Medicine levels were used to estimate citation rate prospect. RESULTS: The median interval citation gain was 161 (i.q.r. 83-281); 74 and 62 articles had an increase in citation rate index (median increase 2.8 (i.q.r. -0.1 to 7.7)) and Altmetric score (median increase 3 (0-4)) respectively. Receiver operating characteristic (ROC) curve analysis revealed that citation rate index (area under the curve (AUC) 0.86, 95 per cent c.i. 0.79 to 0.93; P < 0.001) and Altmetric score (AUC 0.65, 0.55 to 0.76; P = 0.008) were associated with higher interval citation gain. An Altmetric score critical threshold of 2 or more was associated with a better interval citation gain when dichotomized at the interval citation gain median (odds ratio (OR) 4.94, 95 per cent c.i. 1.99 to 12.26; P = 0.001) or upper quartile (OR 4.13, 1.60 to 10.66; P = 0.003). Multivariable analysis revealed only citation rate index to be independently associated with interval citation gain when dichotomized at the median (OR 18.22, 6.70 to 49.55; P < 0.001) or upper quartile (OR 19.30, 4.23 to 88.15; P < 0.001). CONCLUSION: Citation rate index and Altmetric score appear to be important predictors of interval citation gain, and better at predicting future citations than the historical and established impact factor and Oxford Centre for Evidence-Based Medicine quality descriptors.

Surgical training rotation design: effects of hospital type, rotation theme and duration.

BACKGROUND: Entrants into UK surgical specialty training undertake a 2-year programme of core surgical training, rotating through specialties for varying lengths of time, at different hospitals, to gain breadth of experience. This study aimed to assess whether these variables influenced core surgical trainee (CST) work productivity. METHODS: Intercollegiate Surgical Curriculum Programme portfolios of consecutive CSTs between 2016 and 2019 were examined. Primary outcome measures were workplace-based assessment (WBA) completion, operative experience and academic outputs (presentations to learned societies, publications and audits). RESULTS: A total of 344 rotations by 111 CSTs were included. Incremental increases in attainment were observed related to the duration of core surgical training rotation. The median number of consultant-validated WBAs completed during core surgical training were 48 (range 0-189), 54 (10-120) and 75 (6-94) during rotations consisting of 4-, 6- and 12-month posts respectively (P < 0·001). Corresponding median operative caseloads (as primary surgeon) were 84 (range 3-357), 110 (44-394) and 134 (56-366) (P < 0·001) and presentations to learned societies 0 (0-12), 0 (0-14) and 1 (0-5) (P = 0·012) respectively. Hospital type and specialty training theme were unrelated to workplace productivity. Multivariable analysis identified length of hospital rotation as the only factor independently associated with total WBA count (P = 0·001), completion of audit (P = 0·015) and delivery of presentation (P = 0·001) targets. CONCLUSION: Longer rotations with a single educational supervisor, in one training centre, are associated with better workplace productivity. Consideration should be given to this when reconfiguring training programmes within the arena of workforce planning.

ANTECEDENTES: Los residentes de especialidades quirúrgicas del Reino Unido realizan un período troncal de formación quirúrgica de 2 años, en el que rotan por diversas especialidades durante periodos de tiempo variables y en diversos hospitales, a fin de conseguir una experiencia amplia. Este estudio tuvo como objetivo evaluar si estas variables influyeron en la productividad de los residentes durante el período troncal (core surgical trainee, CST). MÉTODOS: Se examinaron los inventarios de los programas del Intercollegiate Surgical Curriculum Programme (ISCP) de CST consecutivos entre 2016 y 2019. Las variables principales fueron la puntuación final del Workplace-Based Assessment (WBA), y la actividad quirúrgica y académica (presentaciones a sociedades académicas, publicaciones y auditorías) realizadas. RESULTADOS: Se incluyeron 344 rotaciones de 111 CST. Se constataron mejores resultados en relación con la duración de la rotación de CST. La mediana (rango) de la puntuación de los supervisores en las WBA fue de 48 (0'189), 54 (10'120) y 75 (6'94) (P < 0,001) en las rotaciones a los 4, 6 y 12 meses, respectivamente. El número de intervenciones (como cirujano principal) fue de 84 (3'357), 110 (44'394) y 134 (56'366) (P < 0,001) y de presentaciones a sociedades científicas fue de 0 (0-12), 0 (0- 14) y 1 (0-5) (P = 0,012). No hubo relación entre el tipo de hospital o la especialidad y la productividad en el lugar de trabajo. El análisis multivariable identificó la duración de la rotación como único factor independientemente relacionado con la puntuación de la WBA (P = 0,001), la finalización de la auditoría (P = 0,015) y el número de presentaciones realizadas (P = 0,001). CONCLUSIÓN: Las rotaciones de periodos de tiempo largos con un solo supervisor y en un solo centro se asocian con una mejor productividad en el lugar de trabajo. Debería tenerse en cuenta este factor al reconfigurar los programas de capacitación desde el punto de vista laboral.

Proof of surgical publication prowess: prospective observational study of factors associated with surrogate markers of academic reach.

BACKGROUND: In the UK, general surgery higher surgical trainees (HSTs) must publish at least three peer-reviewed scientific articles (as first, second or corresponding author) to qualify for certification of completion of training (CCT). This study aimed to identify the factors associated with success in this arena. METHODS: Deanery rosters supplemented with data from the Intercollegiate Surgical Curriculum Programme, PubMed and ResearchGate were used to identify the profiles of consecutive HSTs. Primary outcomes were publication numbers at defined points in higher training (speciality training year (ST) 3-8); secondary outcomes were the Hirsch index and ResearchGate scores. RESULTS: Fifty-nine consecutive HSTs (24 women, 35 men) were studied. The median publication number was 3 (range 0-30). At least three published articles were obtained by 30 HSTs (51 per cent), with 19 (38 per cent) of 50 HSTs achieving this by ST4 (of whom 15 (79 per cent) had undertaken out of programme for research (OOPR) time) and 24 (80 per cent) by ST6. Thirteen HSTs (22 per cent) (ST3, 6; ST4, 4; ST5, 2; ST8, 1) had yet to publish at the time of writing. OOPR was associated with achieving three publications (24 of 35 (69 per cent) versus 6 of 24 (25 per cent) with no formal research time; P = 0·001), higher overall number of publications (median 6 versus 1 respectively; P < 0·001), higher ResearchGate score (median 23·37 versus 5·27; P < 0·001) and higher Hirsch index (median 3 versus 1; P < 0·001). In multivariable analysis, training grade (odds ratio (OR) 1·89, 95 per cent c.i. 0·01 to 3·52; P = 0·045) and OOPR (OR 6·55, 2·04 to 21·04; P = 0·002) were associated with achieving three publications. CONCLUSION: If CCT credentials are to include publication profiles, HST programmes should incorporate research training in workforce planning.

ANTECEDENTES: En el Reino Unido, para obtener el título de especialista (certification of completion of training, CCT), los residentes de cirugía general durante la etapa de formación específica (higher general surgical trainees, HST) deben publicar, al menos, tres artículos científicos en revistas con sistema de revisión por pares (peer review) (como primer o segundo autor o como autor para la correspondencia). Este estudio tuvo como objetivo identificar los factores asociados con el éxito en este aspecto. MÉTODOS: Se identificaron las reseñas de HST consecutivos, mediante datos propios de cada institución y del Intercollegiate Surgical Curriculum Programme, PubMed y ResearchGate. La variable principal fue el número de publicaciones en puntos definidos de la etapa de formación específica (ST3-8); las variables secundarias fueron los índices de Hirsch y las puntuaciones de ResearchGate. RESULTADOS: Se analizó la actividad científica de 59 HST consecutivos (24 mujeres, 35 varones). La mediana del número de publicaciones fue de 3 (rango 0-33). Treinta HST (50,8%) lograron >3 publicaciones; 19 (38,0%) lo lograron en ST4 (78,9% durante el período de investigación al margen del programa de formación quirúrgica (Out of Programme Research (OOPR)), y 24 (80,0% de la totalidad de la cohorte) en ST6. Trece HST (22,0%) no habían publicado ningún trabajo hasta el momento de la redacción de este artículo (6 ST3, 4 ST4, 2 ST5 y 1 ST8). El OOPR se asoció con la consecución de las 3 publicaciones (68,6% versus 25,0%, P = 0,001), con un mayor número de publicaciones (mediana 6 versus 1, P < 0,001), con puntuaciones ResearchGate más elevadas (23,37 versus 5,27, P < 0,001) e índices de Hirsch más altos (3 versus 1, P < 0,001). En el análisis multivariable, el año de residencia (razón de oportunidades, odds ratio, OR 1,890, i.c. del 95% 0,014-3,522, P = 0,045) y el OOPR (OR 6,545, i.c. del 95% 2,037-21,036, P = 0,020) se asociaron con la consecución de las tres publicaciones. CONCLUSIÓN: Si la CCT exige un número de publicaciones, los programas de los HST deberían incorporar formación en investigación dentro de la actividad laboral habitual.

Variations in competencies needed to complete surgical training.

Background: This study aimed to analyse the degree of relative variation in specialty-specific competencies required for certification of completion of training (CCT) by the UK Joint Committee on Surgical Training. Methods: Regulatory body guidance relating to operative and non-operative surgical skill competencies required for CCT were analysed and compared. Results: Wide interspecialty variation was demonstrated in the required minimum number of logbook cases (median 1201 (range 60-2100)), indexed operations (13 (5-55)), procedure-based assessments (18 (7-60)), publications (2 (0-4)), communications to learned associations (0 (0-6)) and audits (4 (1-6)). Mandatory courses across multiple specialties included: Training the Trainers (10 of 10 specialties), Advanced Trauma Life Support (6 of 10), Good Clinical Practice (9 of 10) and Research Methodologies (8 of 10), although no common accord was evident. Discussion: Certification guidelines for completion of surgical training were inconsistent, with metrics related to minimum operative caseload and academic reach having wide variation.

Antecedentes: Este estudio se propuso analizar el grado de variación relativa en las competencias específicas de la especialidad que se requieren para obtener el certificado de haber completado la formación (Certification of Completion of Training, CCT) por el Joint Committee for Surgical Training (JCST) del Reino Unido. Métodos: Se analizaron y compararon las guías del organismo regulador relacionadas con las competencias en habilidades quirúrgicas, tanto operatorias como no operatorias, requeridas para el CCT. Resultados: Se demostró una amplia variación entre especialidades en el número mínimo requerido del cuaderno de casos (mediana 1.201; rango 60­2.100), operaciones índices (13; 5­55), evaluaciones basadas en procedimientos (18; 7­60), publicaciones (2; 0­4), comunicaciones para determinar asociaciones (0; 0­6) y auditorias (4; 1­6). Los cursos obligatorios entre las distintas especialidades incluían: formación de los formadores (10 de 10 especialidades), apoyo vital avanzado en traumas (6/10), buena práctica clínica (9/10) y metodologías clínicas (8/10), aunque era evidente que no existía un acuerdo común. Conclusión: Las directrices sobre la certificación para completar la formación quirúrgica eran inconsistentes, con una amplia variación en los números relativos a los mínimos casos operados y objetivos académicos alcanzados.

Role of Anti-Carbamylated Protein Antibodies Compared to Anti-Citrullinated Protein Antibodies in Indigenous North Americans With Rheumatoid Arthritis, Their First-Degree Relatives, and Healthy Controls.

OBJECTIVE: Rheumatoid arthritis (RA) is characterized by the presence of autoantibodies, including seropositivity for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs). In addition, antibodies to carbamylated proteins (anti-CarP) are present in patients with RA and are associated with joint damage. This study was undertaken to assess the presence of anti-CarP antibodies in indigenous North Americans (First Nations [FN] populations) with RA compared to their at-risk first-degree relatives (FDRs) and healthy controls. METHODS: Anti-CarP IgG and ACPAs (specifically, anti-cyclic citrullinated peptide [anti-CCP] antibodies) were measured by enzyme-linked immunosorbent assay in the sera of FN patients with RA (n = 95), their unaffected FDRs (n = 109), and healthy FN controls (n = 85). Antibodies to additional citrullinated peptides were measured using a multiplex ACPA array, and the number of peptides recognized was reported as an ACPA score. Groups were compared using the chi-square test and Mann-Whitney U test. Associations between RA and seropositivity for RF, ACPAs, and anti-CarP antibodies were determined by logistic regression. RESULTS: Anti-CarP antibodies were more frequent in FN patients with RA (44.3%) compared to FDRs (18.3%) and FN controls (4.7%) (both P < 0.0001 versus RA). Moreover, anti-CarP antibodies were more frequent in FDRs than in FN controls (P = 0.008). The ACPA score was higher in anti-CCP-positive FN patients with RA than in anti-CCP-positive FN FDRs (median score 7 [interquartile range (IQR) 7] versus median score 1 [IQR 4]; P = 0.04). The association with RA was strongest when all 3 autoantibodies (RF, anti-CCP, and anti-CarP) were present in the patients' serum (odds ratio 194, 95% confidence interval 23-1,609, P < 0.0001). CONCLUSION: Anti-CarP antibodies are prevalent in FN patients with RA and also more common in their at-risk FDRs compared to healthy controls. The results indicate an association of RF, ACPAs, and anti-CarP with RA that is strongest when all 3 autoantibodies are present. These findings may provide new insights into the evolution of autoimmunity in preclinical RA.

Wet-chemical synthesis and consolidation of stoichiometric bismuth telluride nanoparticles for improving the thermoelectric figure-of-merit.

Bismuth telluride nanoparticles (NPs) have been synthesized using a low-temperature wet-chemical approach from bismuth(III) oleate and tri-n-octylphosphine telluride. The size and shape of the NPs can be controlled by adjusting the temperature, reaction time, and nature of the surfactants and solvents. Aromatic hydrocarbons (toluene, xylenes) and ethers (phenyl- and benzyl-ether) favor the formation of stoichiometric Bi2Te3 NPs of platelike morphology, whereas the presence of oleylamine and 1-dodecanethiol yields Bi-rich Bi2Te3 spherical NPs. XRD, IR, SEM, TEM, and SAED techniques have been used to characterize the obtained products. We show that the surfactants can be efficiently removed from the surface of the NPs using a two-step process employing nitrosonium tetrafluoroborate and hydrazine hydrate. The surfactant-free NPs were further consolidated into high density pellets using cold-pressing and field-assisted sintering techniques. The sintered surfactant-free Bi2Te3 showed electrical and thermal properties comparable to Bi2Te3 materials processed through conventional solid state techniques, and greatly improved over other nanostructured Bi2Te3 materials synthesized by wet-chemical approaches.

Evaluating systemic lupus erythematosus patients for lung involvement.

INTRODUCTION: We set out to determine the frequency of respiratory symptoms, abnormal lung function, and shrinking lung syndrome (SLS) among patients with systemic lupus erythematosus (SLE) and to determine correlates of SLS. METHODS: Consecutive adult patients who fulfilled the American College of Rheumatology classification criteria for SLE were enrolled. Demographics, clinical, and serologic characteristics were recorded; all patients underwent pulmonary function tests (PFT) and had either a chest X-ray or computed tomography scan. SLS was defined as dyspnea with restrictive lung physiology (defined as a forced vital capacity (FVC) <80% predicted in the absence of obstruction) who did not have any evidence of interstitial lung disease on chest imaging; controls were symptomatic patients with no restrictive physiology and the absence of interstitial changes on chest imaging. RESULTS: Sixty-nine out of 110 (63%) patients had respiratory symptoms, 73 (66%) patients had abnormal lung function, and 11 (10%) patients met the definition for SLS. In a multivariate model controlling for disease duration, a history of pleuritis, modified American College of Rheumatology total score, seropositivity for dsDNA and RNP antibodies, increased disease duration (odds ratio (OR) = 1.2; 95% confidence interval (CI) of 1.0-1.3, p = 0.04), seropositivity for anti-RNP (OR = 24.4; 95% CI of 1.6-384.0, p = 0.02), and a history of serositis were significantly associated with SLS when compared with symptomatic controls. CONCLUSION: Respiratory symptoms, abnormal lung function, and SLS are common in SLE. Clinicians should consider evaluation for SLS among symptomatic patients with long-standing disease and a history of pleuritis.

Non-HLA genes modulate the risk of rheumatoid arthritis associated with HLA-DRB1 in a susceptible North American Native population.

Most of the genetic risk for rheumatoid arthritis (RA) is conferred by 'shared epitope' (SE), encoding alleles of HLA-DRB1. Specific North American Native (NAN) populations have RA prevalence rates of 2-5%, representing some of the highest rates estimated worldwide. As many NAN populations also demonstrate a high background frequency of SE, we sought to determine whether other genetic factors contribute to disease risk in this predisposed population. RA patients (n=333) and controls (n=490) from the Cree/Ojibway NAN population in Central Canada were HLA-DRB1 typed and tested for 21 single-nucleotide polymorphisms (SNPs) that have previously been associated with RA, including PTPN22, TRAF1-C5, CTLA4, PADI4, STAT4, FCRL3, CCL21, MMEL1-TNFRSF14, CDK6, PRKCQ, KIF5A-PIP4K2C, IL2RB, TNFAIP3, IL10-1082G/A and REL. Our findings indicate that SE is prevalent and represents a major genetic risk factor for RA in this population (82% cases versus 68% controls, odds ratio=2.2, 95% confidence interval 1.6-3.1, P<0.001). We also demonstrate that in the presence of SE, the minor allele of MMEL1-TNFRSF14 significantly reduces RA risk in a dominant manner, whereas TRAF1-C5 increases the risk. These findings point to the importance of non-HLA genes in determining RA risk in a population with a high frequency of disease predisposing HLA-DRB1 alleles.

Adrenaline cells of the rat adrenal cortex and medulla contain renin and prorenin.

The distribution and content of renin in Sprague-Dawley (SD) and transgenic (mREN-2)27 rats (TG) were compared to further define the cellular basis and function of the adrenal renin-angiotensin system. Antibody binding (to rat and mouse renin protein and prosequence) was visualised in serial paraffin sections using an avidin-biotin peroxidase technique. Chromaffin and adrenaline cells were identified by tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase immunoreactivity, respectively. In SD zona glomerulosa (ZG), renin and its prosequence localised to small steroid cells while in homozygous (receiving lisinopril) and heterozygous (untreated) TG, steroid cells labelled in all cortical zones. In addition, throughout the cortex of each strain, large polyhedral adrenaline chromaffin cells occurring singly or in small groups and occasionally in rays labelled for renin and prosequence. Similar large adrenaline cells immunolabelled for all antisera in medulla while other cells were only TH-positive. Total adrenal renin content was 53 times higher in heterozygous transgenics than SD rats and was mainly (74%) prorenin. In SD, 37% of cortical renin was prorenin but in adrenal medulla only active renin was detected. Thus, from present and previous work both renin and prorenin occur not only in mitochondrial dense bodies of the ZG, but also in secretory granules of adrenaline chromaffin cells in both cortex and medulla implying in situ synthesis and paracrine functions.

Autoimmune hypothyroidism in a patient with generalized resistance to thyroid hormone.

Generalized resistance to thyroid hormone is a rare condition; affected individuals have elevated serum levels of free thyroxine and free triiodothyronine with inappropriately normal or slightly elevated levels of thyrotropin, yet are generally clinically euthyroid. However, responsiveness to thyroid hormone varies from tissue to tissue, and some patients may benefit from treatment with exogenous hormone. We have described the case of a patient with this disorder who initially had a mildly elevated serum thyrotropin level and was clinically euthyroid but in whom symptomatic autoimmune hypothyroidism subsequently developed. The serum free thyroxine level, although diminished from its previously elevated value, remained within the normal range. The patient required substantial doses of levothyroxine to return basal and stimulated TSH to their prior levels. Criteria for the treatment of adults with this disorder have not been firmly established. This case suggests that one indication for thyroid hormone supplementation may be the presence of high-titer serum antithyroid antibodies in patients who initially have mildly elevated thyrotropin values; they could be at increased risk for progression to overt hypothyroidism.

Empty sella resulting from the spontaneous resolution of a pituitary macroadenoma.

Recent studies suggest that the infarction of a pituitary adenoma may be a frequent cause of an empty sella turcica. However, to date, evidence of such progression has been largely speculative. We present the case of a patient with a pituitary macroadenoma that underwent spontaneous involution resulting in an empty sella, as documented by serial magnetic resonance imaging scans. A brief review of the proposed causes of primary empty sella, with emphasis on pituitary necrosis, is provided.

Tuberculosis in a small semi-rural county.

Tuberculosis cases in a semi-rural county of western Maryland have been reviewed in an attempt to identify high-risk groups at which tuberculosis control efforts could be targeted. Although the cases were concentrated to some extent among nonwhites, older persons, and unmarried city residents, it appears that a general approach will be needed, emphasizing greater collaboration of health departments with the medical profession and a general health education approach to the public.

The prolactin-inducible protein (PIP/GCDFP-15) gene: cloning, structure and regulation.

The androgen and prolactin responsive prolactin-inducible protein (PIP)/gross cystic disease fluid protein (GCDFP-15) is expressed in benign and malignant human breast tumors and in such normal exocrine organs as sweat, salivary and lacrimal glands. In this paper we report the cloning and structure of the human gene, and describe potential mechanisms involved in its regulation by hormones. The entire PIP gene, 7 kb long, was found in a single recombinant phage clone. The gene has 4 exons ranging from 106 bp to 223 bp in length. Nuclear run-on experiments utilizing PIP genomic fragments to detect nascent PIP transcripts revealed that both androgen and prolactin increased transcription of the PIP gene. Neither hormone had any effect on the stability of PIP precursor RNA or mature mRNA. Therefore the PIP gene is an excellent model by which to study the molecular events associated with the actions of prolactin and androgen in the regulation of gene expression in mammalian cells.

Altered alpha-mannosidase isoenzymes in the liver in hepatic cirrhosis.

Homogenates of liver from cases of hepatic cirrhosis due to alpha 1-antitrypsin deficiency (PiZZ) alcoholism were analyzed for their content of various lysosomal enzymes. Also determined were the specific activities of lactate dehydrogenase, glutamate-oxaloacetate transaminase, glutamate-pyruvate transaminase, and creatine phosphokinase in the extracts of liver from cases of both kinds of hepatic cirrhosis: all of these activities were within the range of control values. Similarly, the specific activities of the following lysosomal hydrolases were unremarkable: acid phosphatase, beta-mannosidase, beta-fucosidase, beta-glucuronidase and beta-glucosidase. Hexosaminidase specific activity was increased twofold in livers from the cases of cirrhosis due to alpha 1-antitrypsin deficiency. The specific activity of alpha-mannosidase (measured at pH 4.5) in homogenates of livers from PiZZ individuals with cirrhosis and those with alcoholic cirrhosis was increased two- to four-fold. Chromatography of the high-speed supernatant fraction from homogenates of livers of cirrhotic and noncirrhotic individuals on columns of DEAE-cellulose resolved alpha-mannosidase activity into two components: under the conditions employed, acid pH optimum (pH 4.5) alpha-mannosidase did not bind to the resin, whereas intermediate pH optimum (pH 5.5) alpha-mannosidase could be eluted with 0.1 mol/l NaCl. Liver from one case of (PiZZ) alpha 1-antitrypsin deficiency and emphysema, without demonstrable cirrhosis, was found to contain normal levels of both acid alpha-mannosidase and intermediate alpha-mannosidase. However, cases of cirrhosis due to alpha 1-antitrypsin deficiency contained twice as much acid alpha-mannosidase and only one third to one fourth as much intermediate alpha-mannosidase as controls. The deficiency in hepatic intermediate alpha-mannosidase was also observed in 5 of 5 cases of alcoholic cirrhosis.

Determination of serum acid and alkaline phosphatase using 4-methylumbelliferyl phosphate.

The present report compares the performance of several colorimetric substrates presently employed in clinical laboratories for the determination of serum acid and alkaline phosphatase with that of the fluorogenic phosphatase reagent 4-methylumbelliferyl phosphate. Acid and alkaline phosphatase assays were performed on reference hospital populations in Nigeria and the United States. The results of both acid and alkaline phosphatase determinations indicate that the coefficient of variation is smaller for the fluorometric assay than for the colorimetric methods that employ either phenyl phosphate or p-nitrophenyl phosphate as the substrate. Furthermore, serum acid phosphatase determinations using 4-methylumbelliferyl phosphate identified increased serum enzyme levels in 6/6 cases of prostatic carcinoma and 9/9 cases of Gaucher's disease. The occurrence of elevated serum alkaline phosphatase levels in 24/24 cases involving liver and bone disease was also confirmed by the fluorometric alkaline phosphatase assay. In addition, sera from eight patients with the connective tissue disease, osteogenesis imperfecta, were found to contain normal levels of acid and alkaline phosphatase by the fluorometric assays. From these results it appears that the sensitive and rapid fluorometric assay procedures can be readily employed in the clinical pathology laboratory for the determination of serum acid and alkaline phosphatase levels.