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Rickettsial diseases of the Far East: new perspectives.

The rickettsial disease of man found only in Asia is mite-borne (scrub) typhus, caused by Rickettsia tsutsugamushi. Unique to southern Japan is a little-known human mononucleosis-like disease caused by Rickettsia sennetsu. In 1981 and 1982, there was a remarkable resurgence in the number of reported cases of mite-borne typhus in Japan after some years of virtual absence. Recent studies of R sennetsu have resulted in its reclassification to the genus Ehrlichia, members of which until now have been exclusively pathogens of animals. The historical background of ecologic investigations, in Malaysia and elsewhere, of these two developments suggest directions for future research.

Animals↗

Evaluation of the effectiveness of guidelines, audit and feedback: improving the use of intravenous thrombolysis in patients with suspected acute myocardial infarction.

OBJECTIVE: To determine the effectiveness of medical audit as a means of improving the use of intravenous thrombolytics in patients with suspected acute myocardial infarction. DESIGN: Time-series analyses of observations in four study hospitals conducting repeated audits and feedback compared to a control hospital. SETTING: Five district general hospitals in North West Thames Region between April 1991 and July 1992. SUBJECTS: 2593 patients admitted as emergencies with a suspected acute myocardial infarction. MAIN OUTCOME MEASURES: Proportion of eligible cases receiving intravenous thrombolytic therapy observed in each audit and proportion of patients in whom this therapy was used appropriately. RESULTS: In the baseline audits, the proportions of eligible cases receiving thrombolytic therapy in the four study hospitals were 94%, 60%, 58% and 57%, and 53% in the control hospital. After three further audits in each study hospital over the subsequent year, the observed proportions had changed to 88% (to 6%), 92% (+32%), 95% (+37%), and 7796 (+20%). Meanwhile the proportion in the control hospital rose to 68% (+15%). The trend over time was significant in the second and third hospitals but not in the other two study hospitals or the control hospital. Reclassification of those cases in which the reliability of the diagnosis was poor altered the extent but not the direction of observed trends. Generally, the appropriateness of use of thrombolytic therapy increased with increasing treatment rates. There was a suggestion, however, that continued auditing in the presence of high treatment rates may have led to a reduction in appropriateness. CONCLUSIONS: medical audit can be an effective means of improving the use of intravenous thrombolytics. It is possible that over auditing may result in greater inappropriate use.

Algorithms↗

Benzodiazepines in Miami-Dade County, Florida driving under the influence (DUI) cases (1995-1998) with emphasis on Rohypnol: GC-MS confirmation, patterns of use, psychomotor impairment, and results of Florida legislation.

Benzodiazepines are central nervous system depressant drugs often detected in biological samples from driving under the influence (DUI) offenders. They are associated with marked psychomotor impairment and represent up to 20% of all Miami-Dade County, Florida DUI urine samples analyzed in our laboratory annually. Flunitrazepam emerged in the mid-1990s as an illegal drug in the U.S. that was predominantly abused recreationally and associated with sexual assaults. Immunoassays for benzodiazepines do not discriminate between different benzodiazepines, and certain metabolites, such as 7-aminoflunitrazepam, react poorly with immunoassay reagents. A simple and sensitive method for the detection and quantitation of major benzodiazepines and metabolites by gas chromatography with mass selective detection is presented. This method was used to confirm benzodiazepines in general and flunitrazepam in particular. Data collected over a three-and-a-half-year period are summarized. Whereas flunitrazepam was present in up to 10% of DUI cases in 1995 and 1996 and had fast become the most frequently encountered benzodiazepine in Miami-Dade County DUI-related urine samples, a dramatic drop in case numbers followed the legal reclassification of the drug as a Schedule I substance in Florida in February 1997. Flunitrazepam was often used alone or in combination with cannabis and cocaine. A recent rise in clonazepam cases coincides with the decrease in flunitrazepam confirmation and may indicate a new trend in the abuse of benzodiazepines in South Florida.

Benzodiazepines↗

Relationship between supercooling point and mortality at low temperatures in Indianmeal moth (Lepidoptera: Pyralidae).

Indianmeal moth, Plodia interpunctella (Hübner), is classified as a freeze-intolerant organism and one of the most cold-tolerant stored-product pests. The objective of this study was to determine the relationship between mortality at low temperatures after minimum exposure and the supercooling point (SCP) for laboratory-reared P. interpunctella at different stages of development. This relationship also was analyzed for field-collected, cold-acclimated fifth instars. Mean SCP of laboratory-reared larvae (i.e., feeding stage) was consistently above approximately -16 degrees C. Mean SCP of laboratory-reared pupae and adults (i.e., nonfeeding stages) and field-collected, cold-acclimated fifth instars was consistently below approximately -21 degrees CP seemed to be the boundary between survival and death for larvae. However, it seemed that a 1-min exposure was not sufficient to cause larval mortality at the SCP. Alternatively, for both pupae and adults, the SCP seemed not to play an important role in their survival at low temperatures, with significant mortality observed at temperatures higher than the mean SCP. Adults were the most susceptible to low temperatures with no survival occurring at -20 degrees C, > 3 degrees C above its mean SCP. Results of this investigation demonstrate that P. interpunctella has a different response to low temperatures depending on stage of development and cold acclimation. Classifying P. interpunctella only as a freeze-intolerant organism disregards the occurrence of prefreeze mortality in this species. Therefore, a reclassification of this species (e.g., chill tolerant or chill susceptible) based on the extent of prefreeze mortality and the temperature and time of exposure at which it occurs is suggested.

Acclimatization↗

SCOP database in 2004: refinements integrate structure and sequence family data.

The Structural Classification of Proteins (SCOP) database is a comprehensive ordering of all proteins of known structure, according to their evolutionary and structural relationships. Protein domains in SCOP are hierarchically classified into families, superfamilies, folds and classes. The continual accumulation of sequence and structural data allows more rigorous analysis and provides important information for understanding the protein world and its evolutionary repertoire. SCOP participates in a project that aims to rationalize and integrate the data on proteins held in several sequence and structure databases. As part of this project, starting with release 1.63, we have initiated a refinement of the SCOP classification, which introduces a number of changes mostly at the levels below superfamily. The pending SCOP reclassification will be carried out gradually through a number of future releases. In addition to the expanded set of static links to external resources, available at the level of domain entries, we have started modernization of the interface capabilities of SCOP allowing more dynamic links with other databases. SCOP can be accessed at http://scop.mrc-lmb.cam.ac.uk/scop.

Animals↗

Reproducibility of electrocardiographic criteria for left ventricular hypertrophy in hypertensive patients in general practice.

Before changes in ECG voltage criteria can be accepted as evidence for changes in LVH, the variability of ECG measurements must be known. Here we report on the results of a study, on the variability of electrocardiographic single lead voltage parameters and (voltage) criteria for left ventricular hypertrophy in hypertensive patients in general practice. Two electrocardiograms were recorded, from 64 patients at an interval of 2 min, to measure the minute-to-minute variability. From 77 patients, two electrocardiograms were recorded at an interval of one week to measure the day-to-day variability. The coefficient of variation of voltage parameters for single leads ranged in the day-to-day group from 9.2% in R/I to 42% in T/V1, and the coefficient of variation for voltage combinations in this group ranged from 10.0% for the Sokolow-Lyon criteria to 13.7% for Gubner-Ungerleider criteria. The reclassification percentages in the day-to-day group ranged from 0% for Gubner-Ungerleider to 17% for Minnesota code criteria. A factor analysis showed that studies which use the Romhilt-Estes score, the Sokolow-Lyon or the Minnesota criteria to detect ECG-LVH are not comparable with studies which use the Cornell or Gubner-Ungerleider criteria.

Aged↗

Does it help to undiagnose angina?

We reported recently the results of re-evaluating a series of 64 patients still experiencing pain originally diagnosed as angina but with normal coronary arteriograms. A musculoskeletal cause for the chest pain was established in 38 and an oesophageal cause in 17 of these patients. We here report these patients' self-assessment of their pain 2 years after this diagnostic reclassification. It is clear that the effects of a diagnosis of angina are not easily rescinded even when the non-cardiac cause of the chest pain is identified.

Angina Pectoris↗

Classification of clinical subsets in psoriatic arthritis.

The classification of PsA is controversial. Two recent papers have suggested new subgroup classifications, however both have served only to expand the controversy. In this study the clinical and radiologic features of 100 patients with PsA are recorded in order to examine possible clinical or radiologic features which may be associated with functional disability and to examine the usefulness of recent reclassification proposals in our patient population. Results indicate that an asymmetric oligoarthritis (AO) pattern of disease is most common occurring in 43%. A symmetric polyarthritis (SP) was present in 33%, and this subgroup had the highest number of erosions and deformities, and a higher proportion of patients with grade III/IV ARA functional disability. While the DIP joints were involved in 46%, predominant DIP joint disease occurred in 16%. As the DIP group had the shortest duration of arthritis, it may be that this group represents recent onset PsA which will evolve into one of the other subgroups. Sacroiliitis was a feature in 14% with predominant spondylitis (SPON) in 4%. Arthritis mutilans (AM) was rare occurring in only 2% of this population, perhaps representing patients with end-stage SP disease. Finally, 2% of patients had features of the synovitis-acne-pustulosis-hyperostosis-osteomyelitis (SAPHO) syndrome. A classification comprising just three subgroups (AO, SP, SPON) is proposed as being of most use clinically though a long-term prospective study is needed for verification.

Acne Vulgaris↗

Stages I and II non-Hodgkin's lymphomas of Waldeyer's ring and the neck.

In a previous communication we reported our results for patients with localized extranodal presentations of non-Hodgkin's lymphomas of the head and neck who were admitted between 1961-1969. This review describes our larger experience from 1947-1982 in treating 137 Stages I and II Waldeyer's ring patients whose slides were available for reclassification according to the modified Rappaport System. All of these patients were treated definitively as follows: radiotherapy only, 113 patients; radiotherapy and combination chemotherapy, 17 patients; chemotherapy only, seven patients. The overall 5-year survival was 50%. Significant differences were determined for specific subgroups. For patients staged after lymphangiography, the 5-year survival was 67% as compared with 32% for non-lymphangiogram staged patients (p = 0.002). Stage (Ann Arbor) also influenced results. The 5-year survival figure for Stage I was 70% as compared with 42% for Stage II (p = 0.002). The combination of extent of disease in Waldeyer's ring and the status of the neck had a major impact on survival. When the disease was staged according to the TNMAJCC System, the 5-year survivals were: 75% for T1-T2-TX N0; 53% for T1-T2-TX N+; 54% for T3-T4 N0; and 36% for T3-T4 N+. Also, results for tonsil (52%) and base of tongue (66%) disease were better than for disease involving the nasopharynx (39%) or multiple sites (25%). Treatment also influenced survivals and disease-free survivals. The best results were obtained in patients who were treated with radiotherapy and combination chemotherapy. The 5-year survival and disease-free survival figures were 78% and 69%, respectively.

Antineoplastic Agents↗

Changing trends in the diagnosis of sudden infant death.

A study of 114 consecutive cases of unexpected infant death that occurred in South Australia over a 5-year period from January 1994 to December 1998 was undertaken. There were 45 deaths attributed to sudden infant death syndrome (SIDS), 19 to natural causes, 21 to accidents. and 5 to homicides; 24 cases were listed as "undetermined." Although there has been a genuine and continued decline in SIDS numbers in this population, there has also been an increase in the diagnosis of cases of accidental asphyxia due to unsafe sleeping environments and of cases in which the family background and autopsy findings suggested more complex mechanisms. The change in diagnostic profile has followed the introduction of more rigorous clinical history review, death scene examination, and autopsy testing. Thus, although diagnostic outcomes have altered in this population, it is more likely the result of more careful interpretation of the extensive investigations that are now undertaken rather than arbitrary reclassification.

Accidents↗

Spontaneous baroreflex sensitivity and heart rate variability are not superior to classic autonomic testing in older patients with type 2 diabetes.

BACKGROUND: Early detection of cardiac autonomic neuropathy (CAN) permits individual risk stratification. Spontaneous heart rate variability (HRV) and baroreflex sensitivity (BRS) are suggested to be superior to classic autonomic testing in that they detect CAN earlier, with greater reliability, and do not require the patient's undue attention. METHODS: To test that hypothesis, we studied 53 diabetic patients (mean age, 55 years) and 38 age-matched healthy control subjects (HC). Subjects underwent deep breathing, Valsalva maneuver, and orthostatic testing. Each abnormal test was counted as 1 point. A change in systolic blood pressure during standing of more than 10 mm Hg was graded with a single point; a decrease of more than 20 mm Hg received 2 points. A total score of zero was regarded as no CAN (noCAN), a score > or =4 as severe CAN (sCAN), and scores of 1 to 3 as mild CAN (mCAN). Spontaneous BRS was determined using the sequence technique. HRV was calculated as coefficient of variation (CV), high frequency power (HF) and low frequency power (LF). RESULTS: Mean group values for HRV and BRS were: CV = 3.9+/-1.3; 4.0+/-1.3; 2.4+/-1.1; and 1.2+/-0.4; BRS = 8+/-3; 8+/-5; 5+/-2; and 2+/-2 msec/mm Hg for HC n = 38, noCAN n = 15, mCAN n = 26, and sCAN n = 12, respectively. BRS was similar in HC and patients with noCAN. In sCAN, BRS detected only 10 of 12 patients. HRV and BRS did not improve reclassification based on discriminant analysis. CONCLUSION: BRS and HRV did not detect CAN in older diabetic patients better than classic autonomic testing.

Aged↗

The role of desmin and N-cadherin in effusion cytology: a comparative study using established markers of mesothelial and epithelial cells.

The objective of the present study was to analyze the role of the mesothelial markers desmin and N-cadherin in the diagnostic panel of serous effusions. A total of 181 pleural and peritoneal effusions consisted of 101 cases cytologically diagnosed as malignant (89 carcinomas, 12 mesotheliomas), 78 benign, and 2 inconclusive specimens. All specimens were immunostained using 11 antibodies, against epithelial membrane antigen, Ber-EP4, carcinoembryonic antigen, E-cadherin, CA 125, N-cadherin, desmin, calretinin, p53, vimentin, and CD45. After evaluation of immunocytochemistry results, 110 specimens were diagnosed as malignant (98 carcinomas, 12 mesotheliomas) and 71 as benign (56 cellular, 15 paucicellular). The presence of desmin was detected in benign mesothelial cells in 47 of 56 (84%) reactive cellular specimens compared with 1 of 12 (8%) malignant mesotheliomas and 2 of 98 (2%) carcinomas. N-cadherin was expressed in 48 of 56 (86%) reactive cases, 12 of 12 (100%) mesotheliomas, and 47 of 98 (48%) carcinomas. In carcinomas, N-cadherin expression was most often seen in ovarian carcinoma but was also found in other carcinomas. Calretinin, an established marker of mesothelial cells, was detected in 52 of 56 (93%) reactive specimens, 11 of 12 (93%) mesotheliomas, and 3 of 98 (3%) carcinomas. Evaluation of staining results led to reclassification of six malignant specimens as benign, whereas 17 cases diagnosed as benign and the two diagnosed as inconclusive were classified as malignant. In conclusion, desmin appears to be a promising marker for the distinction between reactive mesothelium and malignant epithelial cells in terms of both specificity and sensitivity, and its complementary use with calretinin is recommended. Unlike calretinin, it may also prove valuable for the distinction between benign and malignant mesothelial cells. N-cadherin does not have a role in the distinction between mesothelial and epithelial cells. However, it may prove useful in the characterization of carcinomas of unknown origin. As has previously been shown, a significant number of diagnoses that are based on morphologic examination alone are modified after the use of a broad antibody panel.

Adolescent↗

Scrub typhus and tropical rickettsioses.

PURPOSE OF REVIEW: Recent developments in molecular taxonomic methods have led to a reclassification of rickettsial diseases. The agent responsible for scrub typhus (Orientia tsutsugamushi ) has been removed from the genus Rickettsia and a bewildering array of new rickettsial pathogens have been described. An update of recent research findings is therefore particularly timely for the nonspecialist physician. RECENT FINDINGS: An estimated one billion people are at risk for scrub typhus and an estimated one million cases occur annually. The disease appears to be re-emerging in Japan, with seasonal transmission. O. tsutsugamushi has evolved a variety of mechanisms to remain viable in its intracellular habitat. Slowing the release of intracellular calcium inhibits apoptosis of macrophages. Subsets of chemokine genes are induced in infected cells, some in response to transcription factor activator protein 1. Cardiac involvement is uncommon and clinical complications are predominantly pulmonary. Serious pneumonitis occurred in 22% of Chinese patients. Dual infections with leptospirosis have been reported. Standardized diagnostic tests are being developed and attempts to improve treatment of women and children are being made. Of the numerous tick-borne rickettsioses identified in recent years, African tick-bite fever appears to be of particular importance to travellers. The newly described flea-borne spotted fever caused by Rickettsia felis may be global in distribution. SUMMARY: Rash and fever in a returning traveler could be rickettsial and presumptive doxycycline treatment can be curative. Recent research findings raise more questions than answers and should stimulate much needed research.

Animals↗

Dysautonomia and neurocardiogenic syncope.

Syncope in childhood is a common problem. In most children, syncope is benign, secondary to a disturbance in autonomic control of heart rate and blood pressure. It is increasingly evident that neurally mediated syncope is a heterogeneous group of conditions, necessitating a reclassification of autonomic disorders. New entities, such as postural orthostatic tachycardia and cerebral vasoconstrictive syncope, are recognized. The key to the diagnosis of syncope is a careful history. Tilt testing can be useful when the history is unclear. Unfortunately tilt test protocols vary, affecting specificity and sensitivity. The mainstay of therapy is reassurance. If symptoms are troublesome, Fludrocortisone and B-blockers remain the favored drugs. The efficacy of Midodrine and Serotonin Uptake Inhibitors is currently under review. Cardiac pacing is effective for those patients with severe episodes and demonstrated asystole. It is not known whether pacing would be effective for the majority who have neurally mediated syncope without significant bradycardia.

Adrenergic beta-Antagonists↗

Buckling and hydraulic mechanisms in orbital blowout fractures: fact or fiction?

Since the first description of orbital blowout fractures, there has been much confusion as to their etiology. Two principal mechanisms have been proposed to explain their production, the buckling and the hydraulic mechanisms caused, respectively, by trauma to the orbital rim and the globe of the eye. The aim of this study was to evaluate both mechanisms qualitatively and quantitatively. Our protocol used intact cadavers, quantifiable intraocular pressure, variable and quantifiable force, and quantifiable bone strain distribution with strain gauge analysis. One orbit of each cadaver was used to simulate each of the two mechanisms, allowing direct comparison. Fractures produced by the buckling mechanism were limited to the anterior part of the orbital floor, with strain readings reaching up to 3756 microepsilon. Posteriorly, strain did not exceed 221 microepsilon. In contrast, hydraulic-type fractures were much larger, involving anterior and posterior parts of the floor as well as the medial wall of the orbit. Here, strain exceeded 3756 microepsilon in both parts of the floor. Furthermore, we have demonstrated that the average energy required to fracture the orbital floor by the buckling mechanism is 1.54 J, whereas an average energy of 1.22 J is needed to produce this fracture by the hydraulic mechanism. Our results suggest that efforts to establish one or another mechanism as the primary etiology are misplaced. Both mechanisms produce orbital blowout fractures, with different and specific characteristics. We believe this provides the basis for our reclassification of such fractures.

Biomechanical Phenomena↗

Polycystic ovary syndrome: a single gene mutation or an evolving set of symptoms.

Polycystic ovary syndrome is one of the most common endocrinopathies among women. Nevertheless, there is no one single acceptable definition for this syndrome, its pathophysiology is not completely understood and its etiology remains an enigma. Several studies have examined the genetic basis of polycystic ovary syndrome with varying results, probably caused by the different criteria used to define the syndrome. These studies, together with studies that deal with reclassification of polycystic ovary syndrome, are described in the following review. Furthermore, a simplified alternative approach to this symptom complex is proposed.

Female↗

The cerebral palsied hip.

Controversy exists regarding the role of pelvic obliquity in hip dysplasia and cerebral palsy. Earlier authors noted such a relationship but did not confirm its existence by scientific study. The current study confirms the association of pelvic obliquity to hip dysplasia in spastic cerebral palsy. At presentation of subluxation or dislocation before surgery, 80 patients were indexed into 5 body alignment types. Reclassifications were performed with passage of time to study the natural history and effects of surgery. Hip dysplasia was found in all cases to be consistent with the forces related to pelvic obliquity.

Cerebral Palsy↗

Classification of chronic radiation sickness cases using neural networks and classification trees.

Chronic radiation sickness is a deterministic radiation health effect observed among the Mayak Production Association workers in Russia. In this study, unsupervised neural networks were used to cluster hematological measurements in a subset (n = 88) of the Mayak Production Association population while excluding from the analysis the radiation dose and the historical clinical diagnosis. Clusters of observations that had lower average leukocyte and thrombocyte counts were labeled "affected" and those having higher average blood cell counts were labeled "unaffected." The class (cluster) membership for each individual was used subsequently as a dependent variable in a classification tree model in order to identify significant features of the underlying classification model. After re-classification of cases using this method, the results showed a better data separation between the blood cell counts for affected vs. unaffected groups compared to those based on historical classification, and a greater difference between group means for differential blood counts was observed than for the historical diagnosis. The reclassification of diagnostic groups changed the group mean radiation doses. The geometric means (and 95% CL) of cumulative radiation dose equivalent from external exposures, based on the historical diagnosis, are 0.31 (0.0035, 3.4) vs. 1.7 (0.0007, 18) Sv. After clustering and classification tree analyses, the group geometric means were 0.78 (0.0014, 8.6) vs. 1.5 (0.0007, 17) and 0.82 (0.0013, 9.0) vs. 1.4 (0.0008, 16) Sv, using (respectively) whole blood cell counts or differential counts as the independent variables. The approach presented here is useful as a diagnostic aid for both retrospective analyses and in the event of future radiation accidents.

Chronic Disease↗