CHOLEDOCHOLITHIASIS—Correlation of Preoperative with Operative and Postoperative Data to Enhance Diagnostic Insight

One hundred cases of common bile duct explorations were reviewed in an attempt to obtain information that might give insight into the diagnosis and definitive treatment of choledocholithiasis. Fifty of the hundred patients had common duct stones. Correlations were made between the incidence of choledocholithiasis as proved at operation, and the following factors: Kind and number of choledochal exploratory criteria used, the clinical diagnosis of common duct stones, and the pathologic features of gallbladders removed.The incidence of stones was statistically related to aging.The most frequent choledochal exploratory criteria were common duct dilatation or thickening (63 cases) and history of jaundice (50 cases).The most reliable single criterion in “diagnosing” common duct stones was palpable common or hepatic duct stones, the diagnosis having been correct in 15 of 17 such cases.The most reliable combination of criteria was a history of jaundice, plus palpable stones, with correct diagnosis in all such cases.The clinical diagnosis of choledocholithiasis was correct in only 17 per cent of cases.The correlation of the incidence of common duct stones with the degree of gallbladder disease—that is, acute or chronic—did not provide information that might be helpful in diagnosing choledocholithiasis.The incidence of proven retained common duct stones was 3 per cent, the non-fatal postoperative complication rate was 21 per cent and operative mortality was 1 per cent.     

Is Early Tuberculosis Death Associated with Increased Tuberculosis Transmission?

Introduction

Tuberculosis (TB) is now a relatively uncommon disease in high income countries. As such, its diagnosis may be missed or delayed resulting in death before or shortly after the introduction of treatment. Whether early TB death is associated with increased TB transmission is unknown. To determine the transmission risk attributable to early TB death we undertook a case-control study.

Methods

All adults who were: (1) diagnosed with culture-positive pulmonary TB in the Province of Alberta, Canada between 1996 and 2012, and (2) died a TB-related death before or within the first 60 days of treatment, were identified. For each of these “cases” two sets of “controls” were randomly selected from among culture-positive pulmonary TB cases that survived beyond 60 days of treatment. “Controls” were matched by age, sex, population group, +/- smear status. Secondary cases of “cases” and “controls” were identified using conventional and molecular epidemiologic tools and compared. In addition, new infections were identified and compared in contacts of “cases” that died before treatment and contacts of their smear-matched “controls”. Conditional logistic regression was used to find associations in both univariate and multivariate analysis.

Results

“Cases” were as, but not more, likely than “controls” to transmit. This was so whether transmission was measured in terms of the number of “cases” and smear-unmatched or -matched “controls” that had a secondary case, the number of secondary cases that they had or the number of new infections found in contacts of “cases” that died before treatment and their smear-matched “controls”.

Conclusion

In a low TB incidence/low HIV prevalence country, pulmonary TB patients that die a TB-related death before or in the initial phase of treatment and pulmonary TB patients that survive beyond the initial phase of treatment are equally likely to transmit.     

I Choose,Therefore I Like: Preference for Faces Induced by Arbitrary Choice

Behavioral choice alters one’s preference rather than simply reflecting it. This effect to fit preferences with past choice, is known as “choice-induced preference change.” After making a choice between two equally attractive options, one tends to rate the chosen option better than they initially did and/or the unchosen option worse. The present study examined how behavioral choice changes subsequent preference, using facial images for the choice options as well as blind choice techniques. Participants rated their facial preference for each face, and chose between two equally preferred faces and subsequently rated their facial preference. Results from four experiments demonstrated that randomly chosen faces were more preferred only after participants were required to choose “a preferred face,” (in Experiment 1) but not “an unpreferred face,” (in Experiment 2) or “a rounder face” (in Experiment 3). Further, preference change was still observed after participants were informed that choices were actually random (in Experiment 4). Our findings provide new and important implications characterizing the conditions under which random choice changes preference, and show that people are tempted to make a biased evaluation even after they know that they did not make the choice for themselves.     

Chest Radiographic Patterns and the Transmission of Tuberculosis: Implications for Automated Systems

BackgroundComputer-aided detection to identify and diagnose pulmonary tuberculosis is being explored. While both cavitation on chest radiograph and smear-positivity on microscopy are independent risk factors for the infectiousness of pulmonary tuberculosis it is unknown which radiographic pattern, were it detectable, would provide the greatest public health benefit; i.e. reduced transmission. Herein we provide that evidence.Objectives1) to determine whether pulmonary tuberculosis in a high income, low incidence country is more likely to present with “typical” adult-type pulmonary tuberculosis radiographic features and 2) to determine whether those with “typical” radiographic features are more likely than those without such features to transmit the organism and/or cause secondary cases.MethodsOver a three-year period beginning January 1, 2006 consecutive adults with smear-positive pulmonary tuberculosis in the Province of Alberta, Canada, were identified and their pre-treatment radiographs scored by three independent readers as “typical” (having an upper lung zone predominant infiltrate, with or without cavitation but no discernable adenopathy) or “atypical” (all others). Each patient’s pre-treatment bacillary burden was carefully documented and, during a 30-month transmission window, each patient’s transmission events were recorded. Mycobacteriology, radiology and transmission were compared in those with “typical” versus “atypical” radiographs.FindingsA total of 97 smear-positive pulmonary tuberculosis cases were identified, 69 (71.1%) with and 28 (28.9%) without “typical” chest radiographs. “Typical” cases were more likely to have high bacillary burdens and cavitation (Odds Ratios and 95% Confidence Intervals: 2.75 [1.04–7.31] and 9.10 [2.51–32.94], respectively). Typical cases were also responsible for most transmission events—78% of tuberculin skin test conversions (p<0.002) and 95% of secondary cases in reported close contacts (p<0.01); 94% of secondary cases in “unreported” contacts (p<0.02).ConclusionAs a group, smear-positive pulmonary tuberculosis patients with typical radiographic features constitute the greatest public health risk. This may have implications for automated detection systems.     

“HIDDEN” ALCOHOLICS—Medical Implications of Undiscovered Addiction

“Hidden alcoholics”—those who drink surreptitiously to keep their addiction secret—far out-number the overt habitues of skid rows. The former rather than the latter should be considered “typical” alcoholics. Even though they have severe problems, they maintain fairly good employment stability and stability in marriage. Yet they steadily deteriorate.Often “hidden” alcoholics go to physicians because of symptoms referable to alcoholism but contrive to conceal their addiction and so make diagnosis difficult. Hence, physicians observing certain kinds of symptoms that cannot be attributed to a readily observable or demonstrable pathologic change should make searching inquiry as to the patient''s drinking habits. For not until the proper diagnosis is made in such cases can there be hope of effective treatment.     

Cumulative Sum Analysis for Experiences of a Single-Session Retrograde Intrarenal Stone Surgery and Analysis of Predictors for Stone-Free Status

Introduction

This study investigated the learning curve of a single-session retrograde intrarenal surgery (RIRS) in patients with mid-sized stones. Competence and trainee proficiency for RIRS was assessed using cumulative sum analysis (CUSUM).

Materials and Methods

The study design and the use of patients'' information stored in the hospital database were approved by the Institutional Review Board of our institution. A retrospective review was performed for 100 patients who underwent a single-session RIRS. Patients were included if the main stone had a maximal diameter between 10 and 30 mm. The presence of a residual stone was checked on postoperative day 1 and at one-month follow-up visit. Fragmentation efficacy was calculated “removed stone volume (mm³) divided by operative time (min)”. CUSUM analysis was used for monitoring change in fragmentation efficacy, and we tested whether or not acceptable surgical outcomes were achieved.

Results

The mean age was 54.7±14.8 years. Serum creatinine level did not change significantly. Estimated GFR and hemoglobin were within normal limits postoperatively. The CUSUM curve tended to be flat until the 25th case and showed a rising pattern but declined again until the 56th case. After that point, the fragmentation efficacy reached a plateau. The acceptable level of fragmentation efficacy was 25 ml/min. Multivariate logistic regression analyses showed that stone-free rate was significantly lower for cases with multiple stones than those with a single stone (OR = 0.147, CI 0.032 – 0.674, P value  = 0.005) and for cases with higher number of sites (OR = 0.676, CI 0.517 – 0.882, P value  = 0.004).

Conclusions

The statistical analysis of RIRS learning experience revealed that 56 cases were required for reaching a plateau in the learning curve. The number of stones and the number of sites were significant predictors for stone-free status.     

Canadian Applicants to Medical Schools in Canada for 1965-66

An examination of applicants to Canadian medical schools for 1965-66 revealed that 4660 applications were received by the 12 schools for approximately 900 places available; 2852 of these were from Canadians, but because many applicants applied to more than one school, these 2852 applications represented only 1767 individuals. Evaluations made by the schools concerning the acceptability of these applicants showed that only 36 persons rated as “acceptable” by one or more schools failed to gain admission to any Canadian school for 1965-66. Furthermore, 66 “marginal” applicants were accepted, as were 130 multiple applicants who were rated as “acceptable” by one school but “marginal” and/or “unacceptable” by one or more other schools. Of the 464 multiple applicants, only 40% received the same evaluation from all schools to which they applied. If those multiple applicants who were rated as acceptable by all schools to which they applied are added to single applicants rated as acceptable, the pool of these clearly acceptable candidates (40% of all Canadian applicants) is sufficient only to fill 78% of places available. It was thus concluded that it is erroneous to speak of a surplus of well-qualified Canadian applicants at the present time.     

INITIAL CARE OF ACUTE BACK INJURIES

The mechanism of injury to the back should be obtained with the utmost accuracy and set down in the history as a separate paragraph under that heading. This is usually best obtained by questioning and requestioning the patient during the course of the examination. A history of any previous back affections should also be obtained at the first visit.The detailed examination of the back is not complete without a general physical examination.X-ray studies should be done immediately in all cases in which the injury has been caused by direct violence or forceful indirect violence (as in “jackknife” injury).Terms such as “disc disease,” “ruptured intervertebral disc” and various others that convey a similar meaning should not be used as the initial diagnosis and should be withheld until such a diagnosis is definitely established.The plan of treatment may include a period in hospital or of rest at home, or it may be carried out with the patient ambulatory. Corsets and braces should be prescribed only when they are to serve a definite function and the same can be said of physiotherapy.     

Uniform binding and negative catalysis at the origin of enzymes

Enzymes are well known for their catalytic abilities, some even reaching “catalytic perfection” in the sense that the reaction they catalyze has reached the physical bound of the diffusion rate. However, our growing understanding of enzyme superfamilies has revealed that only some share a catalytic chemistry while others share a substrate‐handle binding motif, for example, for a particular phosphate group. This suggests that some families emerged through a “substrate‐handle‐binding‐first” mechanism (“binding‐first” for brevity) instead of “chemistry‐first” and we are, therefore, left to wonder what the role of non‐catalytic binders might have been during enzyme evolution. In the last of their eight seminal, back‐to‐back articles from 1976, John Albery and Jeremy Knowles addressed the question of enzyme evolution by arguing that the simplest mode of enzyme evolution is what they defined as “uniform binding” (parallel stabilization of all enzyme‐bound states to the same degree). Indeed, we show that a uniform‐binding proto‐catalyst can accelerate a reaction, but only when catalysis is already present, that is, when the transition state is already stabilized to some degree. Thus, we sought an alternative explanation for the cases where substrate‐handle‐binding preceded any involvement of a catalyst. We find that evolutionary starting points that exhibit negative catalysis can redirect the reaction''s course to a preferred product without need for rate acceleration or product release; that is, if they do not stabilize, or even destabilize, the transition state corresponding to an undesired product. Such a mechanism might explain the emergence of “binding‐first” enzyme families like the aldolase superfamily.     

Cooperating elephants mitigate competition until the stakes get too high

Cooperation is ubiquitous in the animal kingdom as it aims to maximize benefits through joint action. Selection, however, may also favor competitive behaviors that could violate cooperation. How animals mitigate competition is hotly debated, with particular interest in primates and little attention paid thus far to nonprimates. Using a loose-string pulling apparatus, we explored cooperative and competitive behavior, as well as mitigation of the latter, in semi-wild Asian elephants (Elephas maximus). Our results showed that elephants first maintained a very high cooperation rate (average = 80.8% across 45 sessions). Elephants applied “block,” “fight back,” “leave,” “move side,” and “submission” as mitigation strategies and adjusted these strategies according to their affiliation and rank difference with competition initiators. They usually applied a “fight back” mitigation strategy as a sanction when competition initiators were low ranking or when they had a close affiliation, but were submissive if the initiators were high ranking or when they were not closely affiliated. However, when the food reward was limited, the costly competitive behaviors (“monopoly” and “fight”) increased significantly, leading to a rapid breakdown in cooperation. The instability of elephant cooperation as a result of benefit reduction mirrors that of human society, suggesting that similar fundamental principles may underlie the evolution of cooperation across species.

This study shows that in a task requiring coordinated pulling, elephants compete for access to food but work to mitigate competition in order to maintain cooperation. If the cost of competition becomes too high, however, cooperation breaks down entirely. This behavior mirrors that seen in humans and other great apes, suggesting that certain cooperative mechanisms are not unique to primates.     

Utility and Limitation of Cumulative Stone Diameter in Predicting Urinary Stone Burden at Flexible Ureteroscopy with Holmium Laser Lithotripsy: A Single-Center Experience

Purpose

To retrospectively assess the clinical utility in ureteroscopy (URS) planning of cumulative stone diameter (CSD), which does not account for stone width or depth, as a predictor of URS outcome and compare it with stone volume.

Materials and Methods

Patients with renal stones treated at a single institute by flexible URS were retrospectively evaluated. To assess the clinical utility of CSD, relationships between stone-free (SF) status and stone burden (CSD and volume) were analyzed using the area under the receiver operating characteristics (AUROC) curve. To identify stone number impact on CSD, the AUROC of CSD divided by stone number was evaluated. Correlation coefficients of CSD and stone volume were also calculated for groups by stone number.

Results

In cases with CSD <20.0 mm, CSD and stone volume revealed equal ability to predict SF status. In cases with CSD ≥20.0 mm, stone volume showed higher predictive ability. The ROC curves for cases with ≥4 stones showed that CSD was less predictive of SF status than stone volume. The correlation coefficients of CSD and stone volume by stone number were 0.922 for 1 stone, 0.900 for 2–3 stones, and 0.661 for ≥4 stones.

Conclusions

In cases with CSD ≥20.0 mm or ≥4 stones, we should evaluate stone volume for a more predictive stone burden, and pretreatment non-contrast CT seems sufficient. In cases with CSD <20.0 mm or 1–3 stones, CSD was as valid a predictor of preoperative stone burden as stone volume, so preoperative kidney-ureter-bladder (KUB) films may be sufficient.     

A Re-Examination of the History of Etiologic Confusion between Dengue and Chikungunya

Contrary to the perception of many researchers that the recent invasion of chikungunya (CHIK) in the Western Hemisphere marked the first episode in history, a recent publication reminded them that CHIK had prevailed in the West Indies and southern regions of the United States from 1827–1828 under the guise of “dengue” (DEN), and that many old outbreaks of so-called “dengue” actually represented the CHIK cases erroneously identified as “dengue.” In hindsight, this confusion was unavoidable, given that the syndromes of the two diseases—transmitted by the same mosquito vector in urban areas—are very similar, and that specific laboratory-based diagnostic techniques for these diseases did not exist prior to 1940. While past reviewers reclassified problematic “dengue” outbreaks as CHIK, primarily based on manifestation of arthralgia as a marker of CHIK, they neither identified the root cause of the alleged misdiagnosis nor did they elaborate on the negative consequences derived from it. This article presents a reconstructed history of the genesis of the clinical definition of dengue by emphasizing problems with the definition, subsequent confusion with CHIK, and the ways in which physicians dealt with the variation in dengue-like (“dengue”) syndromes. Then, the article identifies in those records several factors complicating reclassification, based on current practice and standards. These factors include terms used for characterizing joint problems, style of documenting outbreak data, frequency of manifestation of arthralgia, possible involvement of more than one agent, and occurrence of the principal vector. The analysis of those factors reveals that while some of the old “dengue” outbreaks, including the 1827–1828 outbreaks in the Americas, are compatible with CHIK, similar reclassification of other “dengue” outbreaks to CHIK is difficult because of a combination of the absence of pathognomonic syndrome in these diseases and conflicting background information.     

Habilitation of Patients with Congenital Malformations Associated with Thalidomide: Surgery of Limb Defects

The deformities commonly seen in “thalidomide babies” are described. These vary from relatively uncomplicated radial-ray defects to complete phocomelia of all four extremities. It is suggested that the care of these children is best carried out in a clinic accustomed to dealing with juvenile amputee problems. A plea is made for very early fitting of upper-extremity prostheses (at approximately three months of age) in cases of unilateral upper-limb deficiencies. A “bucket” for sitting should be supplied for children with quadrilateral phocomelia to sit in when they reach seven or eight months of age. Children with severe upper-limb malformations will be candidates for some form of externally powered prostheses.     

Psychological Antecedents to Conception Among Abortion Seekers

At a university hospital, 642 women seeking induced abortion for an unwanted pregnancy were surveyed before the procedure regarding their perception of what psychological and behavioral factors, if any, played a role in their becoming pregnant: 35 percent said they had had intercourse during what they believed was a “safe period”; 33 percent believed that they had experienced a contraceptive failure; 29 percent indicated fear of side effects influenced their use of a contraceptive method; 27 percent and 21 percent, respectively, indicated that they had thought pregnancy “couldn''t happen to me” or had “put the thought of pregnancy out of my mind.” The women''s responses indicated that a number of additional attitudes, beliefs, and behaviors were also important and that for any individual woman at least three or four factors had often combined in a dynamic sequence to greatly increase her risk of pregnancy. The implications of the findings for educational and counseling programs are discussed.     

Chorioamnionitis and Patent Ductus Arteriosus: A Systematic Review and Meta-Analysis

Background

Chorioamnionitis has recently been reported as a risk factor for various neonatal diseases, including cerebral palsy, bronchopulmonary dysplasia, and necrotizing enterocolitis, but its effect on patent ductus arteriosus (PDA) is unclear. We performed a systematic review and meta-analysis to evaluate the effect of chorioamnionitis on PDA.

Methods

We searched PubMed, EMBASE, Cochrane Library, and KoreaMed databases using the terms: “intrauterine infection” or “maternal infection” or “antenatal infection” or “chorioamnionitis” or “placenta inflammation” or “placenta pathology” or “neonatal outcome” or “neonatal morbidity” or “PDA or patent ductus arteriosus” or “ductus arteriosus,” and “prematurity” or “very low birth weight infant.” Studies were included if they were randomized controlled trials, case–control studies, or cohort studies that included information relating to chorioamnionitis and PDA.

Results

Among 1,571 studies, a total of 23 studies (17,708 cases) were included in the meta-analysis to analyze the relationship between chorioamnionitis and PDA, except one study that only included PDA requiring surgical ligation. The association between chorioamnionitis and PDA was statistically significant (odds ratio [OR] 1.43; 95% confidence interval [CI] 1.19, 1.72; P < 0.0001). In subgroup analysis, clinical chorioamnionitis was not associated with PDA (OR 1.28; 95% CI 1.00, 1.64, 1.790; P = 0.05), whereas histologic chorioamnionitis (OR 1.54; 95% CI 1.10, 2.15; P = 0.01) and chorioamnionitis diagnosed from both clinical and histologic findings (OR 1.75; 95% CI 1.07, 2.86; P = 0.03) showed significant associations with PDA. Chorioamnionitis did not increase the risk of PDA requiring surgical ligation (OR 1.23; 95% CI 0.69, 2.17; P = 0.48), and antenatal steroid use reduced the risk of PDA (OR 0.62; 95% CI 0.42, 0.90; P = 0.01) after chorioamnionitis.

Conclusions

The results from this meta-analysis support an association between maternal chorioamnionitis and PDA in offspring.     

Tertiary Hyperparathyroidism

In our first 200 cases of primary hyperparathyroidism confirmed by operation 12 were also shown to have a long history either of a malabsorption syndrome or of chronic renal-glomerular failure. We consider that they first went through a phase of secondary hyperparathyroidism, during which one or more of the glands became autonomous adenamata. This then produced the biochemical changes of “primary” hyperparathyroidism, necessitating excision of the adenoma. This condition is best described as “tertiary” hyperparathyroidism. The transition from secondary to tertiary hyperparathyroidism occurred in four of the 12 patients while under our observation. We think the same process can be traced retrospectively in the other eight cases. The concept of tertiary hyperparathyroidism may help to explain the high incidence of other diseases in association with primary hyperparathyroidism.The behaviour of the parathyroid glands provides a valuable model for the investigation of tumour formation in man. All states occurred in our patients with primary hyperparathyroidism, from normal through hyperplasia to adenoma formation and finally to parathyroid carcinoma.     

On the validation of crystallographic symmetry and the quality of structures

In 2008, Zwart and colleagues observed that the fraction of the structures deposited in the PDB alleged to have “pseudosymmetry” or “special noncrystallographic symmetry” (NCS) was about 6%, and that this percentage was rising annually. A few years later, Poon and colleagues found that 2% of all the crystal structures in the PDB belonged to higher symmetry space groups than those assigned to them. Here, I report an analysis of the X-ray diffraction data deposited for this class of structures, which shows that most of the “pseudosymmetry” and “special NCS” that has been reported is in fact true crystallographic symmetry (CS). This distinction is important because the credibility of crystal structures depends heavily on quality control statistics such as R_free that are unreliable when they are computed incorrectly, which they often are when CS is misidentified as “special NCS” or “pseudosymmetry”. When mistakes of this kind are made, artificially low values of R_free can give unjustified confidence in the accuracy of the reported structures.     

MEASLES ENCEPHALITIS—A Successful Method of Treatment with Typhoid Vaccine

During a 12-year period 50 patients with measles encephalitis were treated with typhoid vaccine—45 of them not until they were in a vegetative state. There were no deaths in the treated cases. All except one were clinically normal after treatment was ended. Late in the series it became apparent that after the clinical normal is attained and the electroencephalogram becomes normal, treatment should still be continued until the cortex has been “challenged” repeatedly and the electroencephalogram shown to remain normal.The “shock” element in the treatment with typhoid vaccine was prevented by anticipating and circumventing the unfavorable reactions to the vaccine.It may take 20 to 50 treatments or more with typhoid vaccine to return a patient to normality. Each individual is different and responds in a different period of time.     

Association between Mouth Breathing and Atopic Dermatitis in Japanese Children 2–6 years Old: A Population-Based Cross-Sectional Study

As mouth breathing is associated with asthma and otitis media, it may be associated with other diseases. Therefore, this population-based cross-sectional study evaluated the association of mouth breathing with the prevalences of various diseases in children. Preschool children older than 2 years were included. A questionnaire was given to parents/guardians at 13 nurseries in Tokushima City. There were 468 valid responses (45.2%). We defined a subject as a mouth breather in daytime (MBD) if they had 2 or more positive items among the 3 following items: “breathes with mouth ordinarily,” “mouth is open ordinarily,” and “mouth is open when chewing.” We defined subjects as mouth breathers during sleep (MBS) if they had 2 or more positive items among the following 3 items: “snoring,” “mouth is open during sleeping,” and “mouth is dry when your child gets up.” The prevalences of MBD and MBS were 35.5% and 45.9%, respectively. There were significant associations between MBD and atopic dermatitis (odds ratio [OR]: 2.4, 95% confidence interval [CI]: 1.4–4.2), MBS and atopic dermatitis (OR: 2.4, 95% CI: 1.3–4.2), and MBD and asthma (OR: 2.2, 95% CI: 1.2–4.0). After adjusting for history of asthma and allergic rhinitis; family history of atopic dermatitis, asthma, and allergic rhinitis; and nasal congestion; both MBD (OR: 2.6, 95% CI: 1.3–5.4) and MBS (OR: 4.1, 95% CI: 1.8–9.2) were significantly associated with atopic dermatitis. In preschool children older than 2 years, both MBD and MBS may be associated with the onset or development of atopic dermatitis.