Acquired inhibitor to factor VIII in small cell lung cancer: a case report and review of the literature.

Acquired hemophilia (antibodies or inhibitors to factor VIII) is the most common acquired disease affecting clotting factors. It has been described in association with autoimmune disease, malignancy, dermatologic disorders, in the postpartum period, and with drug interactions. Factor VIII inhibitors have been previously described with lung cancer, three with squamous cell and one with adenocarcinoma. A 54-year-old woman presented with weight loss and shoulder pain. A chest X-ray revealed a right hilar mass, confirmed by computed tomography (CT) scan and biopsy revealed small cell lung cancer. Coagulation panel prior to bronchoscopy showed an increased partial thromboplastin time (aPTT). The presence of factor VIII inhibitor was demonstrated at 5 Bethesda units. The patient was treated with fresh frozen plasma twice for hemorrhagic episodes, and six cycles of chemotherapy were begun with carboplatin and etoposide 16. Eight months after the diagnosis, her aPTT was normal and the factor VIII inhibitor titer was undetectable. This is the first case report of small cell lung cancer and acquired hemophilia. A causal relationship between the malignancy and the presence of factor VIII inhibitors is suggested by the response to therapy.

The pathogenesis of beta(2)-microglobulin-induced bone lesions in dialysis-related amyloidosis.

Dialysis-related amyloidosis (DRA), also referred to as beta(2)-microglobulin amyloidosis (A beta(2)M), is an important cause of morbidity in patients with chronic renal failure and in those who are on dialysis. Although DRA deposits from affected joints have been characterized as a unique amyloid fibril protein, beta(2)M, less is known about the pathologic role of beta(2)M as a mediator of bone and joint disease. Potential mechanisms for beta(2)M pathologic interaction in bone include bone growth factors, cytokines, and advanced glycation end products (AGEs). It appears that DRA is the result of a complex interaction between bone resorption and surrounding tissue destruction culminating in beta(2)M deposition and amyloid formation. More work is required to elucidate the relationship between beta(2)M accumulation and progressive tissue destruction.

A subtherapeutic international normalized ratio despite increasing doses of warfarin: could this be malabsorption?

OBJECTIVE: To describe a case of warfarin resistance apparently caused by malabsorption and to review the literature regarding warfarin resistance. CASE SUMMARY: A 28-year-old renal transplant patient with systemic lupus erythematosus was admitted for upper extremity thrombophlebitis. Resistance to oral warfarin was demonstrated. Potential causes were investigated. The trapezoidal rule was used to compare the area under the curve for intravenous versus oral dosing of warfarin. The usual bioavailability of warfarin should be 100%. In this patient, warfarin bioavailability after oral dosing was 1.5%. Three potential causes, malabsorption (FF), enzymatic degradation (FG), and first-pass extraction in the portal circulation (FH), are discussed. CONCLUSION: This case demonstrates resistance to warfarin presumably caused by malabsorption.

Hypokalemia and metabolic alkalosis: algorithms for combined clinical problem solving.

This article reviews an approach to patients with hypokalemia and metabolic alkalosis using the information obtained from spot urine chloride values, blood pressure determinations, and renin and aldosterone measurements in order to simplify clinical problem solving.

Confronting the communication gap between conventional and alternative medicine: a survey of physicians' attitudes.

CONTEXT: An estimated 60 million Americans use some from of complementary and alternative medicine, though approximately 70% do not tell their physicians about this use. Open communication between conventional medical providers and patients in this area is therefore lacking. OBJECTIVE: To explore the dynamics that could potentially contribute to communication breakdown between physicians and patients over the use of alternative therapies. DESIGN: Mail-in, self-administered questionnaire. PARTICIPANTS: 96 practitioners in primary care and medical subspecialties representing the local county medical society, Stark county, Ohio. MAIN OUTCOME MEASURES: Data were obtained on the following: (1) physicians' level of familiarity with 23 different alternative therapies, (2) the question of whether physicians used the therapies themselves, (3) physicians' assessment of the potential benefits and harm of each therapy, and (4) physicians' response to the prospect of their patients using these therapies. RESULTS: Respondents reported the use of myriad alternative therapies. Only 28%, however, referred patients for alternative therapies. The physicians demonstrated clear preferences for specific therapies (i.e., when asked about benefits, familiarity, and reactions to patient use, they responded differently depending on the therapy). Indication that the doctor-patient relationship might be terminated as a result of alternative therapy use was more common among subspecialists than among primary care practitioners. CONCLUSIONS: Overall, physicians demonstrated an open attitude toward alternative therapies. This finding indicates that patients should disclose their use of alternative therapies to their doctors. Increased referral to alternative healthcare providers may require both ongoing peer-reviewed studies of efficacy and increased physician access to information concerning therapies that have undergone definitive study.

Chronic lymphocytic leukemia-associated membranous glomerulopathy: remission with fludarabine.

In some individuals, chronic lymphocytic leukemia (CLL) may be associated with glomerular disease from membranous nephropathy with resultant nephrotic syndrome. CLL is characterized by abnormal immunoregulation with a malignant clonal proliferation of lymphocytes. The association between the abnormal clone and nephrotic syndrome is suggested in some cases by the remission of proteinuria with a reduction in abnormal lymphocyte number after treatment with antineoplastic agents. For the first time, we describe a patient with CLL and associated membranous glomerulopathy whose nephrotic syndrome remitted after treatment with fludarabine, a new purine analogue used in the treatment of refractory CLL.

An approach to clinical acid-base problem solving.

This article demonstrated a systematic approach to acid-base problem solving through the application of the so-called "Rules of Five." This technique was compared with other options for acid-base problem solving, namely, clinicians' use of gestalt or an acid-base map. The superiority of the systematic approach in uncovering triple acid-base disorders was shown.

Sex differences in extracellular and intracellular calcium-mediated vascular reactivity to vasopressin in rat aorta.

In rat thoracic aorta, contractile responses to arginine vasopressin are two-fold higher in females than in males. To determine the roles of extracellular and intracellular Ca2+ in this sexual dimorphism in vascular function, vascular reactivity and Ca2+ channel function were examined in thoracic aortae of male and female rats. In the presence of diltiazem (10 microM), maximal contraction to vasopressin was reduced to a greater extent in male (65+/-2%) than in female aortae (38+/-1%). Maximal contractile responses to KCl and Bay K 8644 were similar in male and female aortae. Sensitivity to KCI was slightly but significantly higher in male than in female aorta; in contrast, sensitivity to Bay K 8644 was nearly three-fold higher in males than in females. Removal of the endothelium enhanced sensitivity to KCl similarly in male and female aortae. In the presence of simvastatin (60 microM; an inhibitor of intracellular Ca2+ release), reactivity to vasopressin was reduced substantially in female (42+/-1%) but unaltered in male aortae. Removal of the endothelium enhanced the inhibitory effect of simvastatin in both female (73+/-2%) and male aortae (41+/-2%). These findings demonstrate that male aortae depend more upon extracellular Ca2+ influx, whereas female aortae depend more upon intracellular Ca2+ release for vasopressin-induced contraction.

A new variant of food poisoning: enteroinvasive Klebsiella pneumoniae and Escherichia coli sepsis from a contaminated hamburger.

For the first time, we report Klebsiella pneumoniae as an enteroinvasive food-borne pathogen transmitted from a hamburger. A 28-year-old previously healthy African-American male ingested a portion of a hamburger from a fast food chain. Symptoms of gastroenteritis rapidly deteriorated to multiorgan failure. Blood and hamburger cultures grew Escherichia coli and Klebsiella pneumoniae. Since Klebsiella had not previously been reported as enteroinvasive, the isolates were compared. Full biochemical profiles, antimicrobial sensitivity, plasmid profile, and toxin assay by DNA hybridization probe were completely concordant. The patient survived the episode of food-borne sepsis. Deliberate or inadvertent employee contamination of food products with feces may be a potential source of life-threatening food-borne illness.

Heparin therapy for myocardial infarction: an unusual trigger for pituitary apoplexy.

A 68-year-old man with coronary artery disease was admitted for chest pain and ventricular tachycardia. After electric cardioversion, therapeutic heparinization was started for myocardial ischemia and nontransmural infarction. On day 3, headache and fever developed, followed by an altered sensorium and hyponatremia. Infectious etiology for the fever was excluded, and results of computed tomography of the brain were normal. Later magnetic resonance imaging (Day 10) demonstrated a pituitary macroadenoma with hemorrhage. Treatment for panhypopituitarism with stress-dose steroids stabilized the patient, and the fever and hyponatremia resolved. Transsphenoidal resection of the pituitary adenoma was performed without incident. This is the first reported case of pituitary apoplexy after heparin anticoagulation for acute myocardial infarction, although chronic anticoagulation in other settings has been reported as a precipitant of apoplexy. The uncommon presentation of a "central" fever and confusion in a patient with previously undiagnosed adenoma posed a diagnostic challenge. Subtle presentations of panhypopituitarism, knowledge of which should lead to suspicion and early diagnosis of pituitary apoplexy, will prevent anticoagulant-induced central nervous system catastrophes and potential fatalities.

Relevance of routine admission electrocardiograms for psychiatric patients.

OBJECTIVE: To make clinically relevant recommendations for electrocardiogram (ECG) testing among psychiatric patients, the study examined the practice of ordering ECGs for this population. METHODS: The records of 4,045 patients consecutively admitted for psychiatric care to seven community teaching hospitals over one year were examined. The frequency of ECG orders was documented, and abnormal ECG results were grouped into two categories: relevant to psychiatric treatment (ischemia or conduction defects) and incidental to treatment (minor abnormalities and screening abnormalities). For those with abnormalities, additional cardiac follow-up data were recorded. Associations between ECG results and patients' characteristics were analyzed. RESULTS: ECGs were performed for 2,857 (71 percent) of first admissions, of which 2,225 (78 percent) showed neither relevant nor screening abnormalities. Eighteen percent of those tested had relevant abnormalities, most commonly a first-degree atrioventricular block or some evidence of a myocardial infarction. ECG screening abnormalities were found for another 4 percent, primarily left ventricular hypertrophy (3 percent), but no follow-up occurred for 46 percent of these patients. Among patients under 40 years of age, 8 percent had relevant abnormalities, and 3 percent had screening abnormalities. Among patients without apparent cardiac risk, 10 percent had relevant and 3 percent had screening abnormalities. More than half the patients who had a second or third admission during the year had a repeat ECG, even when previous ECGs were normal. CONCLUSIONS: Routine ECG is not an effective treatment or screening tool in this population, and substantial cost savings could result from more selective testing, particularly among young patients, those at low risk, and those with repeat admissions.

Nephrologists' subjective attitudes towards end-of-life issues and the conduct of terminal care.

Decisions which determine the duration and outcome of terminal care should be influenced by patient autonomy. Studies suggest, however, that end-of-life decision-making is more complex than a single principle and that physicians may be responsible for selected aspects of terminal care independent of patient choice. To study how nephrologists' perceptions toward end-of-life issues may affect decision-making, we anonymously surveyed 125 of them. The study employed the straightforward terminology of "hastening death" rather than adopting the ambiguous term "euthanasia" or the narrow term "assisted suicide." Subjective physician profiles demonstrated that nephrologists who are less comfortable with dying patients were significantly less likely to report that they omitted life-prolonging measures (p = 0.02) and more likely to report that they would not initiate measures in order to hasten death even were it legal (p = 0.04). Ninety-eight percent of nephrologists reported omissions in terminal care with patient knowledge and 80% without patient knowledge. In contrast, forty-three percent of the nephrologists said that were it to become legal to initiate measures in order to hasten death, they would "never" do so. The ethical framework utilized for discontinuation of dialysis decisions incorporated medical benefit (cancer as criterion, 48%; multisystem complications, 84%; dementia 79%) and quality of life criteria. Twenty-five percent of nephrologists admitted difficulty with advance directives if the directives clashed with heir beliefs. ESRD end-of-life decision-making in the USA may be altered by the subjective characteristics of nephrologists. In particular, nephrologists' level of discomfort with patient mortality is linked with their reported management of terminal patients.

Enterovesical fistula presenting as life-threatening normal anion gap metabolic acidosis.

Enterovesical fistula is a rare complication of a variety of inflammatory and neoplastic diseases. It usually presents with pneumaturia, fecaluria, urinary tract infections, or irritable bladder symptoms in the setting of either diverticulitis or malignancy. For the first time, we describe a patient with an enterovesical fistula who presented with a life-threatening normal anion gap metabolic acidosis. The direction of flow through the fistula, ie, bladder to intestine, was contingent on a spastic bladder and was responsible for the atypical presentation.

Geriatric renal function: estimating glomerular filtration in an ambulatory elderly population.

In elderly individuals, serum creatinine may remain normal as glomerular filtration rate (gfr) declines. Therefore, the estimation of glomerular filtration utilizing mathematical models incorporates age as an important variable. In order to adjust drug dosages and diagnose renal disease earlier in the elderly, a variety of such simplified estimates of gfr have been applied. Unfortunately, no estimator is as accurate as the cumbersome gold standards (e.g. inulin or iothalamate clearance) and the reliability of each may vary with the particular clinical setting. The purpose of this study was to critically evaluate three commonly used estimators of gfr-i.e., creatinine clearance (CC), Cockroft-Gault (CG), and 100 over serum creatinine (100/SC)-comparing them to iothalamate clearance (IC) in a group of healthy ambulatory geriatric subjects (n = 41; ages 65-85). IC declined 1 ml/min per year of age in our sample. CC demonstrated a similar decline, a correlation of 0.83 with IC, and moderate error relative to IC of 17% at the mean (standard error [SE] = 12.3). In contrast, 100/SC correlated only 0.56 with IC, demonstrated a large positive bias (41 ml/min), and showed no age-related decline. An age correction to 100/SC similar to that utilized in the CG formula was clearly necessary. Despite the age and weight correction used in the CG formula, we found the estimates from it to be inaccurate (correlation = 0.5; SE = 23.8). A simpler age-corrected formula (Est. IC = 1/2 [100/SC] + 88-age) was derived and proved significantly superior to CG in our ambulatory geriatric sample, but still exhibited enough error (SE = 16.4) to question its clinical utility. It appears that serum creatinine based estimates of gfr in the elderly may not provide accurate results.

Severe tinea barbae due to Trichophyton verrucosum infection in dairy farmers.

Trichophyton verrucosum infection, which is acquired from the hide of dairy cattle, is the cause of tinea barbae, a severe pustular eruption on the face and neck. We present the cases of five patients, three of whom had severe pustular tinea barbae and two of whom had eruptions of the forearms. All five patients were dairy farmers. On physical examination, all five patients were afebrile and did not appear toxic. Peripheral leukocyte counts of the three patients with pustular tinea barbae were normal. Gram stain and bacterial cultures of the draining pustules were negative in all three cases. Potassium hydroxide preparation showed hyphae, and cultures yielded T. verrucosum in all three cases. Four patients received therapy with fluconazole, and one received therapy with griseofulvin; in all cases, the lesions healed. T. verrucosum can cause pustular tinea barbae in farmers that may be mistaken for a Staphylococcus aureus infection by clinicians, including infectious disease experts. The answer to a simple question, "Are you a dairy farmer?", may suggest the diagnosis of T. verrucosum in the proper clinical setting.

Pylephlebitis: a case report and review of outcome in the antibiotic era.

Pylephlebitis or septic thrombophlebitis of the portal vein, a precursor of hepatic abscesses, is an extremely rare and frequently fatal complication of diverticulitis. The following report describes a patient presenting with pylephlebitis and complicated diverticulitis. Diagnosis was confirmed by computed tomography. The patient had a favorable outcome with medical and surgical therapy, prompting us to evaluate historical treatment of pylephlebitis.

Testosterone causes direct relaxation of rat thoracic aorta.

Several recent studies have provided evidence that gonadal steroid hormones can exert acute (nongenomic) effects on both neural and vascular tissues. This study examines the acute effects of testosterone (T) on vascular reactivity of the rat thoracic aorta. Aortic rings from male Sprague-Dawley (SD) rats with (+ENDO) and without (-ENDO) endothelium were prepared for isometric tension recording. In (+ENDO) male aortae precontracted with phenylephrine (PE), T produced dose-dependent relaxation from 25 microM (30.3 +/- 7.1%) to 300 microM (99.4 +/- 0.4%), whereas T vehicle (< or = 0.5% ethanol) had no effect. Pretreatment of (+ENDO) aortae with T (50 microM; 10 min) attenuated subsequent contractile responses to PE. Both maximal contraction and sensitivity to PE were reduced by T. Pretreatment of (+ENDO) aortae with both T and N omega-nitro-L-arginine methyl ester (250 microM) reversed in part the attenuating effects of T alone; however, both maximal response and sensitivity to PE were still reduced compared to control rings (without T or N omega-nitro-L-arginine methyl ester). Pretreatment of (-ENDO) aortae with T reduced sensitivity to PE, but had no effect on maximal contraction. T pretreatment (50 microM; 10 min) of both (+ENDO) female SD aortae and (+ENDO) male testicular-feminized rat aortae reduced maximal contraction and sensitivity to PE in both groups to a similar extent as in (+ENDO) male SD aortae. These data suggest that T has a direct vasodilating effect on the rat aorta, which involves endothelium-dependent (enhanced NO release) and -independent mechanisms and is gender- and intracellular androgen receptor-independent.