Fine particulate organic material in the Los Angeles Basin-I: assessment of the high-volume Brigham Young University organic sampling system, BIG BOSS

BACKGROUND AND OBJECTIVE: Acute generalized, widespread bleeding is often related to disseminated intravascular coagulation (DIC), a pathologic process which complicates the clinical course of many diseases and is characterized by huge amounts of thrombin and plasmin within the circulation. The final result is the consumption of platelets, coagulation factors and inhibitors, as well as secondary hyperfibrinolysis, all leading to diffuse hemorrhage and microthromboses. This review article examines the present attitudes to the diagnosis and treatment of overt DIC in clinical practice, emphasizing the importance of an accurate differential diagnosis from some other processes characterized by acute generalized, widespread bleeding. INFORMATION SOURCES: The authors have been working in this field, both at experimental and clinical levels, contributing original papers for many years. In addition, material examined in this review includes articles published in journals covered by MedLine, recent reviews in journals with high impact factor and in relevant books on hemostasis and thrombosis. STATE OF ART AND PERSPECTIVES: DIC is an intermediary mechanism of disease which complicates the clinical course of many well-known disorders. Although the systemic hemorrhagic syndrome is the predominant clinical manifestation, massive intravascular thrombosis frequently occurs contributing to ischemia and associated organ damage, making the mortality rate of this condition high. Current concepts on the pathophysiology, laboratory diagnosis and management of DIC are presented. Complex pathophysiological interrelations make the diagnosis of the etiology of the DIC difficult in clinical practice, although simple tests are useful for identification of patients with the process. Laboratory diagnosis of DIC is mainly based on screening assays, which allow a rapid diagnosis, whereas some other highly sensitive but more complex assays are not always available to routine clinical laboratories. The management of DIC is based on the treatment of the underlying disease, supportive and replacement therapies and the control of the coagulation mechanisms. Although some advances have been achieved, management decisions are still controversial, so that therapy should be highly individualized depending on the nature of the DIC and severity of clinical symptoms. Many syndromes sharing common findings with DIC, such as primary hyperfibrinolysis or thrombotic thrombocytopenic purpura, should be excluded. Finally, new therapeutic approaches to the management of this potentially catastrophic syndrome are required.     

The semantics of addiction: moving beyond expert models to lay understandings

Disseminated intravascular coagulation (DIC) syndromes can be defined as the formation of fibrin deposits within the microcirculation, occurring in definite clinical situations. Their biological counterpart is a consumption coagulopathy. The clinical profiles of DIC have been well known for decades, are multiform and range from latency to overwhelming haemorrhagic diatheses, including also characteristic but rare situations, such as purpura fulminans, acral cyanosis and pictures resembling thrombotic thrombocytopenic purpura or haemolytic-uraemic syndrome. Biological tests of DIC show a consumption coagulopathy, displayed on the standard haemostasis sheet; along with signs of paracoagulation and/or of secondary fibrinolysis (FDP). New tests have recently been introduced: D-dimers are specific and sensible; Antithrombin-III, protein C and alpha 2-antiplasmin also can sometimes be useful. The knowledge of the pathophysiology of DIC has made advances with passing years. Fibrin deposits may be non-occlusive, and indeed they are swiftly removed by a secondary fibrinolysis. Except in very rare situations, such as those leading to a cortical renal necrosis, and perhaps in some ARDS, there is little evidence relating DIC to organ failure syndromes. Moreover, there is no clear relationship between the severity of the consumption coagulopathy and the prognosis. For instance, the mortality is much lower in abruptio placentae, where the coagulopathy is very severe, than in septic shock, where it is usually moderate. In septic shock, the disorders of haemostasis were related initially to a platelet activation, then to an activation of the contact system (releasing kinins and triggering complement cascade), and nowadays to the activation of the extrinsic coagulation system. The treatment of DIC is mainly the treatment of its cause. Indications for heparin therapy should be strictly limited to a few exceptional circumstances. When haemorrhagic diathesis threatens, FPC and/or platelet transfusion may be indicated. Aprotinin can be useful in rare cases of overwhelming secondary fibrinolysis. Trials with antithrombin-III or C1-esterase inhibitors are in progress.     

Thrombosis and hemorrhage in oncology patients

As outlined in this review, patients with cancer may harbor many alterations of hemostasis. These are multifaceted and must be considered when trying to control hemorrhage or thrombosis in cancer patients. Also, hemorrhage or thrombosis is often the final fatal event in many patients with metastatic solid tumor or hematologic malignancies. Patients with malignancy present a major clinical challenge in this new era of oncologic awareness and more aggressive care, which has led to prolonged survival for patients and a longer time frame during which these complications may develop. Therefore, these complications are occurring more commonly. It is important to realize that these alterations of hemostasis exist and must be approached in a sequential and logical manner with respect to diagnosis; only in this way can responsible, efficacious, and rational therapy be delivered to patients. By far the most common alteration of hemostasis in malignancy is that of hemorrhage associated with thrombocytopenia, either drug-induced, or radiation-induced, or from bone marrow invasion. Hemorrhage resulting from DIC, however, is also quite common and may present as hemorrhage, thrombosis, thromboembolus, or any combination thereof. Many antineoplastic drugs and radiation therapy may lead to or significantly enhance hemorrhage in patients with malignancy. Thrombosis, also commonly seen in patients with malignancy, is often a manifestation of low-grade DIC. When approaching the patient with malignancy and either hemorrhage or thrombosis, all the potential defects in hemostasis must be considered, defined from the laboratory standpoint, and treated in as precise and logical manner as possible.     

Conservative therapy in thoracic outlet syndrome. Literature review and pathogenetic considerations

Due to the broad clinical presentation and the lack of generally accepted diagnostic criteria, thoracic outlet syndrome (TOS) is a disputed diagnosis. Various surgical techniques have been described and investigated as treatment for TOS, whereas only a few studies have reported the outcome after a conservative approach. Based on the literature, the pathophysiology of TOS and the impact of conservative therapy are discussed. Our personal experience has shown that after early diagnosis and implementation this treatment is a safe and valuable therapeutical option in TOS based on the correction of a postural and functional disturbance of the upper thoracic aperture underlying the pathogenic process. Successful conservative treatment may also be considered as further diagnostic evidence for TOS.     

The millennium criteria for the diagnosis of atopic dermatitis

Atopic dermatitis forms an active area of basic and clinical research, where important new knowledge about genetics and immunopathogenesis has surfaced over the past years, and where simultaneous development of new and innovative therapies is under way. However, the inclusion of any patient in an atopic dermatitis study, whether it is on its genetics, pathogenesis or therapy, requires a diagnosis which is irrefutable. Since there is no simple and also no complicated laboratory procedure to reach a diagnosis of atopic dermatitis, different sets of clinical criteria have been developed for the purpose of making the diagnosis uniformly in different studies as well as in different study centers. The most commonly used are Hanifin and Rajka's set of diagnostic features, which have major and minor clinical criteria to be fulfilled in order to establish a diagnosis of atopic dermatitis. Recent developments in the immunology of atopy have clearly established the major abnormality in this syndrome, the preferential production of allergen-specific IgE. In this contribution, it is suggested that the presence of such antibodies in a given patient should be a mandatory criterium for the diagnosis of atopic dermatitis. Such a diagnostic test however establishes a diagnosis of atopic syndrome, not atopic dermatitis. Thus, for atopic dermatitis we have to rely, for the time being, on additional clinical criteria. The clinical features described in the literature are critically evaluated, and it is suggested that in addition to the mandatory presence of allergen-specific IgE, 2 of 3 principal criteria (pruritus, typical morphology and distribution, chronic or chronically relapsing) should be present for such a diagnosis. Finally, the minor features originally described by Hanifin and Rajka and later evaluated by others are revised and divided over 4 subcategories; a) related to subclinical eczema; b) related to dry skin; c) extra skin folds; and d) ophthalmological pathology. They are suggested to be used as additional criteria only, needed when clinical suspicion is high but the new mandatory and principal diagnostic criteria described here are inconclusive. For study purposes, we suggest that the mandatory and principal criteria are sufficient. They are now evaluated and validated in ongoing atopic dermatitis treatment studies.     

An unusual presentation of Fitz-Hugh-Curtis syndrome

A case of Fitz-Hugh-Curtis syndrome masquerading as a perforated peptic ulcer is presented. The pathophysiology, clinical presentation, differential diagnosis, and management of this syndrome are discussed.     

Current aspects of Turner syndrome

Recent progress in the clinical, genetic and therapeutic knowledges of Turner's syndrome are presented. The quality of life of Turner's syndrome can be much improved by early treatment with recombinant human growth hormone which significantly increases the patient's final height, and appropriate oestrogenic therapy at pubertal and adult ages. However, this requires an early diagnosis. Consequently, a karyotype must be performed in every girl with delayed growth, even in the absence of clinical features of the Turner's syndrome.     

Hypernatremia and hypertonic syndromes

Hypernatremia is the most common cause of hypertonicity in small animal medicine. Despite this fact, severe hypernatremia is an uncommon clinical entity in dogs and cats. The causes of hypernatremia are excessive water loss and increased sodium intake. Clinical signs are most often related to CNS dysfunction. Severe hypernatremia should be considered a life-threatening situation and treated as such. Initial fluid therapy should be given with care according to the rate of onset of hypernatremia, as deterioration of the animal's condition is a common sequela. The determination of the cause of hypernatremia and the treatment can be both challenging and rewarding. The other notable hypertonic syndrome in small animal medicine is hyperosmolar nonketotic diabetes mellitus. Judicious management of this disease with fluid therapy and insulin is the standard therapy. An understanding of the pathophysiology is essential to their diagnosis and appropriate medical management.     

Chronic fatigue syndrome

A great concern is recently given to the chronic fatigue syndrome in the Czech Republic. Unfortunately, published data allow us to state neither the etiologic agent nor the pathophysiology of the disease. Although many authors published various laboratory abnormalities, these changes are inconstant and do not allow to state a diagnosis of the chronic fatigue syndrome by a single laboratory test, and effective therapy is not known either. Psychotherapy, and in some cases antidepressants, are recommended by some authors to alleviate patient's symptoms. Neither immunological nor antiviral therapy showed positive results in controlled trials and are not generally used in most centers.     

Akathisia

The syndrome of akathisia typically consists of a subjective component, e.g. inner restlessness and an urge to move, and observable symptoms such as restless legs and inability to sit still. In most cases akathisia is caused by neuroleptics. There are several subtypes of akathisia according to the time of onset in the course of neuroleptic treatment. In clinical routine extrapyramidal motor disturbances are often underestimated or misinterpreted. As far as akathisia is concerned, differential diagnosis of restlessness or of repetitive movement patterns may be problematic. Non-compliance and impulsive behaviour are regarded as possible complications of akathisia, but systematic investigations are lacking. The pathophysiology of akathisia is not clear, but it probably differs from other pharmacologically induced motor disturbances. If warrantable, the first step in akathisia treatment is dose-reduction of the causing agent. Anticholinergic drugs, benzodiazepines, and beta-receptor blockers may be effective. Clinical assessment and survey of the patient's behaviour, e.g. during occupational therapy and group therapy is important for an early diagnosis of akathisia so that complications may be minimised.     

Immunohistochemistry of secretory particles (''vesiculosomes'') from the epithelium of bovine seminal vesicles and ampulla of the vas deferens

Several syndromes involving antiphospholipid antibodies have been described in the literature. Although the varied clinical manifestations have been well delineated, the vascular pathophysiology in patients with these antibodies remains unclear. Vascular damage is often described as a vasculopathy; however, several case reports have described an associated vasculitis. We report two patients with manifestations of antiphospholipid antibody syndrome (APLS) and concurrent vasculitis. The first patient, a 42-year-old man, presented with abdominal pain and fevers. The second patient, a 39-year-old man, presented with fever and testicular pain. Both were ultimately felt to have polyarteritis nodosa associated with APLS. Their complicated hospital courses and difficulties we encountered in diagnosing and treating them are discussed. The literature describing other cases of vasculitis associated with antiphospholipid antibody syndrome is reviewed. Whether the presence of antiphospholipid antibodies favors the development of vasculitis or vice versa is not clear. Further studies are needed to address this question and to determine optimal therapeutic regimens in these critically ill patients.     

The predictive value of electrodiagnostic studies in carpal tunnel syndrome

In recent years, electrodiagnostic studies have become an expected component in the work up and evaluation of carpal tunnel syndrome. We conducted a retrospective review of 460 carpal tunnel decompressions to determine whether the accuracy of diagnosis and the prediction of therapeutic outcome could be related to the positivity and severity of findings on preoperative electrical studies. The 349 patients (460 hands) were divided into two groups: group 1 consisted of hands with the clinical diagnosis of carpal tunnel syndrome but with normal electrodiagnostic studies (n = 62); in group 2 the hands had a clinical diagnosis of carpal tunnel syndrome with confirmatory electrodiagnostic studies (n = 398). The number and distribution of signs and symptoms of carpal tunnel syndrome were not statistically different between these two groups. There was not a statistically significant difference in the success rate of surgery or the incidence of complications. The similarities between these two groups suggests that the distinction between them (the positivity of electrodiagnostic studies) is an artificial one and that the clinical diagnosis of carpal tunnel syndrome is sufficient to predict the presence of the disease, as well as outcome of surgery. On the basis of these data, strict adherence to electrodiagnostic studies to confirm the diagnosis will exclude 13 percent of the patients with legitimate carpal tunnel syndrome from receiving appropriate therapy.     

Clinical and laboratory indices that enhance the diagnosis of postural tachycardia syndrome

OBJECTIVE: To identify clinical and laboratory indices that improve the diagnosis of the postural tachycardia syndrome (POTS). DESIGN: We assessed associations of orthostatic intolerance by using multivariate regression analysis. MATERIAL AND METHODS: We evaluated autonomic symptoms and autonomic function in 30 patients with POTS, 30 patients with mild orthostatic intolerance, and 19 age- and gender-matched control subjects. Indices of parasympathetic and sympathetic functions were analyzed on the basis of (1) autonomic function tests (head-up tilt), (2) oscillations at respiratory and nonrespiratory frequencies (0.01 to 0.09 Hz) in R-R interval and blood pressure (Wigner distribution), and (3) deterministic component (rescaled range analysis). RESULTS: The four clinical and laboratory indices that independently supported the diagnosis of POTS are as follows: (1) orthostatic heart rate during the first minute of head-up tilt, (2) autonomic deficit (adrenergic autonomic score), (3) loss of spectral powers in R-R interval during head-up tilt at the fifth minute, and (4) severity of orthostatic dizziness, fatigue, palpitations, and shortness of breath. CONCLUSION: Enhancing the sensitivity and specificity of the diagnosis of POTS should be possible by using these four indices. A hyperadrenergic state and distal neuropathy, affecting adrenergic sympathetic cardiovagal fibers, seem to be involved in the pathophysiology of POTS. Certain features suggest brain-stem dysregulation.     

Diagnosis and management of gastroesophageal reflux in infants and children

Use of histamine blockers, proton pump inhibitors, and prokinetic drugs, along with traditional antacids, has become standard therapy for gastroesophageal reflux (GER) in symptomatic adults. Response to this therapy is assessed to confirm the diagnosis of GER, and is often advocated as the best way to establish the causes and effects of the disease. It is well documented that reflux occurs throughout the life span. However, the incidence in children is difficult to estimate, requiring interpretation of behavior and symptoms in nonverbal and atypical presentations. Unfortunately, the diagnosis of GER in children is often made after the development of complications such as aspiration pneumonia, esophagitis, or ulcers. Early recognition and intervention by primary care providers is necessary to prevent such serious complications of untreated GER. This article presents the pathophysiology and clinical manifestations of GER. Diagnosis in children is discussed, and recommendations for empiric therapy, including conservative measures and drug therapies, are presented.     

Antineutrophil cytoplasmic antibody (C-ANCA) levels in relation to the treatment of Wegener's granulomatosis

We assessed the clinical significance of cANCA in relation to the diagnosis and follow-up of Wegener's granulomatosis patients using NephroScholor C-ANC, the ELISA kit for the detection of cANCA. The NephroScholor C-ANC test for cANCA was revealed to be useful for the diagnosis of Wegener's granulomatosis, but slightly less sensitive than the indirect immunofluorescence assay using human neutrophils, which has been in widespread use for the detection of ANCAs. With NephroScholor C-ANC, the cANCA titer can be estimated conveniently and expressed quantitatively. When conventional immunosuppressive therapy with prednisolone and cyclophosphamide was applied, the patients' symptoms subsided as the cANCA titer decreased, and thus it also seemed useful for the follow-up of Wegener's granulomatosis patients. However, a rising ANCA titer during the course of the disease was not always correlated with the occurrence of a relapse as previously reported. Based on these findings, it is not recommended that treatment be changed immediately because of elevation of the ANCA titer alone, and it never seemed too late to increase immunosuppressive therapy, even after a clinical exacerbation was observed. Several treatments other than the conventional immunosuppressive therapy have often been applied for our patients, especially in the limited type of this disease, and these treatments, including sulfamethoxazole-trimethoprim alone, low-dose prednisolone alone, and cyclophosphamide alone, have often been useful. We conclude that the choice of therapy must depend on the severity or the condition of the individual patient, and this therapeutic policy should reduce unnecessary side effects of potentially toxic drugs.     

The scorpion envenoming syndrome

The pathophysiology of the scorpion envenoming syndrome is reviewed with emphasis on the body systems commonly affected. Concepts of the mechanisms underlying venom action, as can be explained by the recently discovered effects on ionic channels, are discussed. The results of clinical analysis of cases of scorpion sting victims and animal experiments with scorpion envenomation supporting these concepts are presented. The pharmacokinetic characteristics of scorpion venoms and their correlation to the magnitude of toxic effects are presented in relation to the potentials of therapeutic intervention. The pharmacological basis of the therapeutic usefulness and toxicities of the drugs commonly used in the treatment of scorpion envenoming is also projected. Finally, the results of a successful nation-wide clinical study with serotherapy of scorpion envenoming are presented and evaluated.     

The hemostatic system function of patients with severe forms of diphtheria

Hemostasis of 100 patients with severe diphtheria infection was studied throughout the disease. The patients were found to have marked procoagulant, anticoagulant and fibrinolytic disorders. Antithrombogenic activity of the vascular wall was also abnormal. The above impairments correlated with the symptoms severity and are interpreted as DIC syndrome which ran subclinically or as hemorrhagic syndrome. The majority of the patients underwent a hyperhypocoagulant phase of DIC syndrome.     

Immunosuppressive therapy of vasculitis: current aspects and perspectives

Vasculitides are a set of serious diseases of unknown aetiology with various immunopathogenetic mechanisms, characterized by inflammation and necrosis of the vessel wall with consequent lumen obliteration. They may be primitive or associated with other diseases, have heterogeneous clinical manifestations and different degrees of severity which may be related to the localization of the interested vessels. Although in the last years many classifications have been proposed, a standardized nomenclature of vasculitides is unquestionably still needed to facilitate the diagnosis and management of patients with the disease. Steroids and immunosuppressant are the conventional therapy, whereas other therapeutic strategies are reserved for the refractory vasculitides to conventional therapies or for intolerant recipients to cytotoxic drugs. New approaches are represented by monoclonal antibodies and drugs which could be effective in the treatment of the trigger factors which activate the immunopathological mechanisms. Current data suggest that, rather than pursuing the idea of a single therapy for vasculitides, an oncological model of combined therapy, to induce both the disease control and maintenance of remission, might be adopted. An improvement of our knowledges on the mechanisms underlying the different entities associated to standardized criteria of activity and remission of disease will lead to an improvement of our therapeutic strategies.     

Habitual dependence on modern imaging modalities: the new golem

Modern imaging techniques have been taking over our medical life, but none denies the progress that has followed introduction of modern imaging modalities. For the generation of younger physicians who entered the profession after the introduction of these techniques, use of US, CT, MRI and the like is natural and often applied. But the patient is not computerized and medicine is far from being a pure science. 3 cases of common surgical problems are presented in which excessive use of diagnostic modalities resulted in unnecessary operations, thus leading to unnecessary morbidity. In these days of soaring medical expenses, many unnecessary imaging and laboratory studies are done for reasons of "defensive" medicine. It is important to fortify the position of clinical diagnosis, but making clinical decisions without requiring expensive and sometimes misleading imaging studies significantly reduces costs. Admittedly, courage and firm professional backbone are required to face a lawyer or a judge and say: "This CT or US study would not have changed my clinical decision; it would have made no positive contribution to it, and might even have mislead me." This paper comes to remind physicians of the importance of clinical diagnosis and the need to develop and rely on primary medical skills. Machines and laboratory tests are aids to diagnosis, they do not make the diagnosis.