A case of periodic fever--reevaluation of etiocholanolone fever as an established clinical entity

A case of periodic fever is reported in a 28-year-old male. The patient's clinical and laboratory findings fulfilled diagnostic criteria for etiocholanolone fever (EF). The most crucial endocrine data comprised higher values of both urinary etiocholanolone/androsterone ratio and plasma unconjugated etiocholanolone on febrile days, as compared to the values on afebrile days. However, the author hesitates to promptly diagnose him as EF, because of arguments against EF as an isolated clinical entity, and also because of the presence of auto-antibodies suggestive of an early stage of collagen disease(s). If the patient should develop a florid collagen disease in later clinical course, this case could be another evidence against EF as an established clinical entity, thus a careful follow-up is needed.     

The Brandes-Friesen case reports: how should we interpret the news?

In this issue (see pages 561 to 566 two case reports by Lorne J. Brandes and Linda A. Friesen illustrate a temporal relation between the discontinuation or initiation of therapy with certain non-antineoplastic agents (lithium, carbamazepine and an H1-antihistamine) and the clinical course of cancer. Only an accumulation of similar case reports and the results of epidemiologic and controlled clinical studies will show whether the temporal relation observed in these cases is also a causal one. In the absence of strong, let alone conclusive, evidence that antidepressants or antihistamines promote the growth of tumours in human beings, a recommendation to stop using these medications would be premature. The news about these case reports and about animal studies on the tumour-promoting potential of some antidepressants and antihistamines is likely to spread through the media. The realistic and responsible option for physicians and clinical investigators is to help patients and prospective participants in clinical trials to interpret this information in a balanced and reasonable fashion.     

Exploiting clinical trial data drastically narrows the window of possible solutions to the problem of clinical adaptation of a multiscale cancer model

The development of computational models for simulating tumor growth and response to treatment has gained significant momentum during the last few decades. At the dawn of the era of personalized medicine, providing insight into complex mechanisms involved in cancer and contributing to patient-specific therapy optimization constitute particularly inspiring pursuits. The in silico oncology community is facing the great challenge of effectively translating simulation models into clinical practice, which presupposes a thorough sensitivity analysis, adaptation and validation process based on real clinical data. In this paper, the behavior of a clinically-oriented, multiscale model of solid tumor response to chemotherapy is investigated, using the paradigm of nephroblastoma response to preoperative chemotherapy in the context of the SIOP/GPOH clinical trial. A sorting of the model's parameters according to the magnitude of their effect on the output has unveiled the relative importance of the corresponding biological mechanisms; major impact on the result of therapy is credited to the oxygenation and nutrient availability status of the tumor and the balance between the symmetric and asymmetric modes of stem cell division. The effect of a number of parameter combinations on the extent of chemotherapy-induced tumor shrinkage and on the tumor's growth rate are discussed. A real clinical case of nephroblastoma has served as a proof of principle study case, demonstrating the basics of an ongoing clinical adaptation and validation process. By using clinical data in conjunction with plausible values of model parameters, an excellent fit of the model to the available medical data of the selected nephroblastoma case has been achieved, in terms of both volume reduction and histological constitution of the tumor. In this context, the exploitation of multiscale clinical data drastically narrows the window of possible solutions to the clinical adaptation problem.     

Effect of timing of first clinical mastitis occurrence on lactational and reproductive performance of Holstein dairy cows

Objectives of this study were to determine the influence of timing of first clinical mastitis case occurrence on lactational and reproductive performance in high producing lactating dairy cows during the first 320 days in milk (DIM). Holstein cows, 1001, from two commercial dairy farms in California were retrospectively divided into four treatment groups according to timing of first clinical mastitis case caused by environmental pathogens: control with no recorded clinical cases of mastitis (C; n=501); first clinical mastitis prior to first postpartum AI (MG1; n=250); first clinical mastitis between first postpartum AI and pregnancy diagnosis (MG2; n=147); and first clinical mastitis after diagnosed pregnant (MG3; n=103). Clinical cases of mastitis were identified at every milking by the herd personnel based on abnormal milk or swelling of the mammary gland. A fore sample of milk was aseptically collected from every clinical case for microbiological culture. Mastitis decreased yields of milk, 3.5% fat-corrected milk, and milk components, but the effect was only observed for MG1 and MG2. Cows in the control group had lower linear somatic cell count (SCC) score throughout the lactation. Culling was increased by mastitis, and cows in the mastitis groups left the study earlier than controls. Conception rate at first postpartum AI and pregnancy rate at the end of the study were both decreased by mastitis prior to or after first AI, and MG1 and MG2 cows had extended days open. Furthermore, cows experiencing mastitis during lactation had a higher incidence of abortions. The negative effects of mastitis on reproduction were observed regardless of clinical case being caused by either Gram positive or negative bacteria. Mastitis either prior to or after first postpartum AI impairs lactation performance, increases culling, and decreases reproductive efficiency in high producing Holstein dairy cows.     

Diagnostic Alternatives Used by Veterinary Surgeons for the Recording of Udder Diseases in the Norwegian Health Card System for Cattle

A questionnaire, in which 7 cases of udder disease were described, was distributed to 890 veterinarians in Norway. They were requested to classify the cases according to the diagnostic alternatives listed in the Norwegian Health Card System for Cattle (NHCSC). The NHCSC recordings are used for progeny testing of bulls, for disease monitoring, and for research purposes. The aim of this study was to evaluate the quality of the recordings for udder diseases. The questionnaire was answered by 633 veterinary surgeons. Four cases of clinical mastitis (CM) with abnormal secretion as well as other clinical signs of inflammation were correctly classified as CM by almost 100% of the veterinary surgeons. A cow in the final stage of lactation, showing no clinical signs except for clots in the milk, was considered not to be a clinical case by more than 25% of the veterinary surgeons. A typical case of subclinical mastitis (SM) was reported as SM by 83% of the veterinary surgeons, and as CM by 16%. A subclinical case with a recent history of clots in the secretion was classified as SM by 66% of the veterinary surgeons, but almost 40% either reported CM as their sole diagnosis or considered the case to be CM in combination with SM. Of the clinical cases, those exhibiting marked local signs of inflammation and a systemic reaction were correctly classified as acute clinical mastitis (ACM) by 96%–98% of the veterinary surgeons. In the NHCSC, the diagnostic alternatives for cases of CM are ACM and chronic clinical mastitis (CCM). One case, for which the diagnosis subacute clinical mastitis was appropriate according to standard definitions, was classified as CCM by 66%), and as ACM by 6%. Based on the information given in the questionnaire, the diagnosis for 2 of the clinical cases could have been either ACM or CCM, and for both cases each of these 2 alternatives was reported by more than 43% of the veterinary surgeons. A teat lesion, which was present together with ACM in one cow, was reported by 91% of the veterinary surgeons.     

自身免疫性肝炎合并慢性布鲁菌病1例并文献复习

目的探讨自身免疫性肝炎合并布鲁菌感染时的临床特征、诊断及其治疗等特点。方法回顾性分析我院确诊的1例自身免疫性肝炎合并慢性布鲁菌感染患者的临床特点、相关指标的检测结果并结合文献报道进行总结。结果患者临床表现缺乏特异性。血培养和血清抗体检测呈阳性,C-反应蛋白(CRP)可见升高而降钙素原(PCT)变化不明显。结论布鲁菌病不能仅从临床表现来鉴别和诊断,更不能因为缺少流行病学资料而否定。自身免疫性肝炎患者的CRP水平对急性炎症的敏感性会降低,但仍可以作为疗效判断的参考指标。应适度增加疗程,定期复查,以更好的控制慢性布鲁菌感染。     

A Human Case of Hymenolepis diminuta in a Child from Eastern Sicily

We report a case of Hymenolepis diminuta infection in a 2-year-old child living in a suburban area of Catania, Italy. This case was initially referred to us as Dipylidium caninum infection, which was not cured after being treated twice with mebendazole. However, by analyzing the clinical presentation and stool samples we arrived to the diagnosis of H. diminuta infection. The case presented with atypical allergic manifestations which had never been reported as clinical features of symptomatic H. diminuta infection; remittent fever with abdominal pain, diffuse cutaneous itching, transient thoracic rash, and arthromyalgias. The patient was treated with a 7-day cycle of oral niclosamide, which proved to be safe and effective. This case report emphasizes that a correct parasitological diagnosis requires adequate district laboratories and trained personnel. In addition, we recommend the importance of reporting all H. diminuta infection cases, in order to improve knowledge on epidemiology, clinical presentation, and treatment protocols.     

Linfoma esplénico presentado como pancreatitis aguda en una paciente de 84 años: reporte de un caso

A case is presented of an 84 year-old woman who was admitted to the Emergency Department due to an episode of non-calculous acute pancreatitis. In the aetiological study, the presence of a splenic lymphoma was documented, which had a compressive effect on the pancreas. After resolving the symptoms, she was scheduled for a splenectomy with a good technical result. At six months after admission the patient was in an excellent clinical and functional condition. This case highlights the unusual clinical presentation of this haematological disease, and the need to evaluate all the available therapeutic options in selected elderly patients.     

Splenic lymphoma presenting as acute pancreatitis in an 84 year-old patient. A case report

A case is presented of an 84 year-old woman who was admitted to the Emergency Department due to an episode of non-calculous acute pancreatitis. In the aetiological study, the presence of a splenic lymphoma was documented, which had a compressive effect on the pancreas. After resolving the symptoms, she was scheduled for a splenectomy with a good technical result. At six months after admission the patient was in an excellent clinical and functional condition. This case highlights the unusual clinical presentation of this haematological disease, and the need to evaluate all the available therapeutic options in selected elderly patients.     

Improved performance on high-dimensional survival data by application of Survival-SVM

MOTIVATION: New application areas of survival analysis as for example based on micro-array expression data call for novel tools able to handle high-dimensional data. While classical (semi-) parametric techniques as based on likelihood or partial likelihood functions are omnipresent in clinical studies, they are often inadequate for modelling in case when there are less observations than features in the data. Support vector machines (svms) and extensions are in general found particularly useful for such cases, both conceptually (non-parametric approach), computationally (boiling down to a convex program which can be solved efficiently), theoretically (for its intrinsic relation with learning theory) as well as empirically. This article discusses such an extension of svms which is tuned towards survival data. A particularly useful feature is that this method can incorporate such additional structure as additive models, positivity constraints of the parameters or regression constraints. RESULTS: Besides discussion of the proposed methods, an empirical case study is conducted on both clinical as well as micro-array gene expression data in the context of cancer studies. Results are expressed based on the logrank statistic, concordance index and the hazard ratio. The reported performances indicate that the present method yields better models for high-dimensional data, while it gives results which are comparable to what classical techniques based on a proportional hazard model give for clinical data.     

Clinical importance of the genus Trichoderma. A review

Opportunistic fungal infections have been observed with increasing frequency in recent years in immunocompromised patients. Several data were published in the last decade about the clinical importance of the filamentous fungal genus Trichoderma, indicating that Trichoderma strains--besides their agricultural and biotechnological importance--may be potential opportunistic pathogens in immunocompromised hosts as well. This review is going to summarize the clinical case reports about Trichoderma infections, and to discuss the information available on the antifungal susceptibility and on the ecophysiological, enzymological and systematic aspects of clinical Trichoderma isolates.     

Biosimilars clinical development program: confirmatory clinical trials: a virtual/simulated case study comparing equivalence and non-inferiority approaches

As part of long term commitment of the Biologicals and Vaccines Committee (B&V) of the International Federation of Pharmaceutical Manufacturers and Association (IFPMA) to provide expert input to the WHO on their recently finalized GUIDELINES ON EVALUATION OF SIMILAR BIOTHERAPEUTIC PRODUCTS (SBPs), and in response to WHO's request, the IFPMA B&V prepared a clinical case study at a recent WHO workshop in Seoul, Korea. The case study, presented by Mark Fletcher on behalf of B&V, involved a model scenario for a clinical efficacy trial to support the approval of a Similar Biotherapeutic Product (SBP) as part of the required comparative clinical program against a Reference Biotherapeutic Product (RBP). A key goal was to understand and illustrate key clinical and statistical principles, and considerations described in the WHO Guidance for regulatory authorities when designing and implementing WHO guidelines and post-approval regulatory oversight for SBPs. Using this model SBP/RBP pair, an interactive discussion was carried out among the workshop participants on the pros and cons of using equivalence vs. non-inferiority designs to assess the two products' similarity. Through discussion of the case, the complexity of demonstrating similar efficacy and safety of a SBP vs. RBP for biotherapeutic products is outlined and discussed in the context of the key principles laid out in the recently published WHO GUIDELINES ON EVALUATION OF SIMILAR BIOTHERAPEUTIC PRODUCTS (SBPs). The exercise illustrates the need for a case-by-case approach when interpreting clinical data from SBP dossiers to adequately assure similar efficacy and safety of SBPs for any studied indication.     

Adrenal myelolipoma in the cottontop tamarin (Saguinus o. oedipus)

Two cases of myelolipoma in the cottontop tamarin (Saguinus o. oedipus) were found unequivocally within the adrenal gland, supporting an earlier suggestion that the adrenal gland was the possible origin of a juxtarenal myelolipoma in the same species. In the present study a 30-mm-diameter myelolipoma was present in the adrenal gland in case 1, whereas in case 2 the myelolipoma was only detected on histological examination. In case 1, changes in the adrenal gland were considered to be of minor clinical significance, whereas in case 2 the myelolipoma was an incidental finding.     

1例原发性脾脏结核病例的临床与实验室检验分析

本文报道1例罕见的原发于脾脏的结核病例,该病例以发热起病,免疫功能正常,无明确肺部病灶,最终根据脾脏切除术后病理学结果及腹腔脓液分枝杆菌培养阳性确诊。分析临床表现及诊断方法,有助于提高临床医生对此类病例的认识与重视。     

Influenza Outbreak during Sydney World Youth Day 2008: The Utility of Laboratory Testing and Case Definitions on Mass Gathering Outbreak Containment

Background

Influenza causes annual epidemics and often results in extensive outbreaks in closed communities. To minimize transmission, a range of interventions have been suggested. For these to be effective, an accurate and timely diagnosis of influenza is required. This is confirmed by a positive laboratory test result in an individual whose symptoms are consistent with a predefined clinical case definition. However, the utility of these clinical case definitions and laboratory testing in mass gathering outbreaks remains unknown.

Methods and Results

An influenza outbreak was identified during World Youth Day 2008 in Sydney. From the data collected on pilgrims presenting to a single clinic, a Markov model was developed and validated against the actual epidemic curve. Simulations were performed to examine the utility of different clinical case definitions and laboratory testing strategies for containment of influenza outbreaks. Clinical case definitions were found to have the greatest impact on averting further cases with no added benefit when combined with any laboratory test. Although nucleic acid testing (NAT) demonstrated higher utility than indirect immunofluorescence antigen or on-site point-of-care testing, this effect was lost when laboratory NAT turnaround times was included. The main benefit of laboratory confirmation was limited to identification of true influenza cases amenable to interventions such as antiviral therapy.

Conclusions

Continuous re-evaluation of case definitions and laboratory testing strategies are essential for effective management of influenza outbreaks during mass gatherings.     

The use of SMS 201-995 (somatostatin analogue) in insulinomas. Additional case report and literature review

A 76-year-old man, a known case of insulinoma, was well controlled for 11 days on 50 micrograms SMS 201-995 every 12 h; clinical recovery was immediate with normalization of blood sugars and C-peptide levels. The potential value of this new drug in the management of insulinomas is illustrated by this case and by 11 additional case reports which are reviewed. A rise in C-peptide levels during treatment without concomitant hypoglycaemia might be the first indication of a loss of control.     

Multiple Bilateral Pulmonary “Fungus Balls” in an Immunocompetent Patient Unsuitable for Surgical Treatment: Efficacy of Azoles Treatment

Data guiding management of pulmonary mycetomas are based on uncontrolled trials and case reports. Surgical resection represents a definitive treatment associated with high mortality and sometimes not feasible due to clinical conditions. We report a case of an immunocompetent patient with multiple pulmonary mycetomas, suggestive for probable chronic aspergillosis, in which surgery was contraindicated. The patient experienced a good response to long-term oral voriconazole therapy with remarkable clinical and radiological improvement at three-month follow-up. In cases of probable chronic aspergillomas, when surgery is contraindicated, long-term antifungal therapy with voriconazole seems to be a valid alternative option.     

以中枢神经系统症状为首发表现的干燥综合征1例并文献复习

目的:探讨干燥综合征累及中枢神经病变的临床表现及诊断、鉴别诊断、治疗。方法:报告中国人民解放军第175医院1例累及中枢神经病变的干燥综合征患者的临床资料并复习相关文献,对其临床表现、诊断、容易混淆的鉴别诊断及治疗进行分析。结果:1例累及中枢神经病变的干燥综合征患者经治疗病情好转出院。结论:累及中枢神经病变的干燥综合征,尤其以中枢神经系统症状为首发表现者,极易误诊为多发性硬化,遇可疑病例应及时完善检查,避免因忽视其它系统症状而导致漏诊和误诊,影响患者的预后。     

Another case of 9P-syndrome.

This paper discusses the value of an International Repository of Chromosomal Abnormalities and Variants as a means of communication and case finding. A further case of 9p- is described. The clinical and cytogenetic findings confirm the existence of a clinical entity which in many respects is the opposite of the 9p trisomy syndrome.