Humoral hypercalcemia of malignancy in squamous cell carcinoma of the skin: parathyroid hormone--related protein as a cause.

The second most common cause of hypercalcemia is humoral hypercalcemia of malignancy (HHM), a condition associated with increased mortality. Although hypercalcemia is usually seen in squamous cell cancers, only 13 cases have been described in association with squamous cell skin cancer, and only 5 of these had characteristics of HHM. We report a case of hypercalcemia due to squamous cell skin cancer confined to the chest wall in a 67-year-old semi-comatose patient. Aggressive treatment with intravenous fluid hydration, furosemide, and etidronate corrected the hypercalcemia. A thorough workup ruled out bone metastasis and confirmed increased parathyroid-related protein, the hallmark of HHM. After regaining consciousness, the patient refused further therapy and subsequently died.

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.

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.

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.

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.

Postoperative acute pulmonary edema: a rare presentation of pheochromocytoma.

A 39-year-old white female underwent an uneventful vaginal hysterectomy for dysfunctional bleeding. Evaluating a mild aortic insufficiency murmur preoperatively an echocardiogram revealed normal left ventricular wall motion and function. Postoperatively the patient developed severe abdominal pain, acute hypertension (200/100 mmHg), and sinus tachycardia. Within minutes she decompensated into acute pulmonary edema. ECG demonstrated acute ST segment elevation in the precordial leads consistent with acute infarction. Emergency left heart catheterization showed normal coronary vessels with severe left ventricular dysfunction. An abdominal ultrasound was obtained, revealing a right adrenal mass. Plasma epinephrine was 334, norepinephrine 34,543 pg/ml; urine epinephrine 45, urine norepinephrine 2,137 micrograms/24 hours. She was started on prazosin and nifedipine sustained release with good blood pressure control. Four days later, an echocardiogram demonstrated the left ventricular wall motion reverting to normal. The adrenal tumor was subsequently resected successfully. Acute pulmonary edema causing dilated cardiomyopathy is a rare complication of pheochromocytoma that has been seldomly reported. A progressive fatal course is common: reversibility and survival depend on identifying and removing the pheochromocytoma.

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.

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.

Spontaneous vertebral artery dissection as a complication of autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) may be associated with a variety of cardiovascular complications, including intracranial saccular aneurysms. In ADPKD, intracranial saccular aneurysms tend to rupture more frequently and earlier than the sporadic variety with a tendency to cluster in families. In contrast, dissecting intracranial aneurysms are rarely associated with either intracranial saccular aneurysms or ADPKD. We describe an ADPKD-1 patient whose course was complicated by a spontaneous dissection of a vertebral artery aneurysm. This particular patient had previously experienced three episodes of ascending aortic dissection with cystic medial necrosis. Intracranial vascular and aneurysmal dissection may occur in select ADPKD patients with familial clusters.

Remission of nephrotic range proteinuria in type I diabetes. Collaborative Study Group.

The present study assessed the extent to which remission of nephrotic-range proteinuria occurred in patients with Type I diabetes enrolled in the Captopril Study, a placebo controlled multicenter clinical trial of captopril therapy in diabetic nephropathy. Of the 409 patients recruited into the Captopril Study, 108 had nephrotic-range proteinuria (> 3.5 g/24 hr) at entry in the Study (baseline). This group was the subject of the present study. Remission of nephrotic-range proteinuria was defined as follows: (1) Onset of the remission was taken as the date when proteinuria was first noted to be < or = 1.0 g/24 hr. (2) The reduction in proteinuria had to be sustained for a minimum of six months and until the end of the Captopril Study. (3) During the remission, the average of all 24 hour proteinuria measurements could not exceed 1.5 g. (4) Decline in renal function could not explain the reduced proteinuria. That is, the patient's serum creatinine during the entire period of observation in the Captopril Study had to remain at less than a doubling of the baseline serum creatinine. Remission of nephrotic-range proteinuria occurred in 7 of 42 patients assigned to captopril (16.7%, mean follow-up 3.4 +/- 0.8 years) and in 1 of 66 patients assigned to placebo (1.5%, mean follow-up 2.3 +/- 1.1 years; P = 0.005, comparing remission rate in captopril vs. placebo-treated patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Aspergillus discitis with acute disc abscess.

STUDY DESIGN: Aspergillus osteomyelitis of the vertebral body and disc space is rare. This report discusses a case that occurred in an immunosuppressed 29-year-old man and reviews the pertinent medical literature. OBJECTIVES: To review the management and treatment of Aspergillus osteomyelitis of the vertebral body and disc space. SUMMARY OF BACKGROUND DATA: The patient presented with acute neurologic compromise resulting from L5-S1 discitis and a large epidural soft tissue component secondary to the Aspergillus infection. RESULTS: The patient underwent aggressive surgical debridement along with treatment with amphotericin B and had a complete clinical recovery. CONCLUSIONS: The authors recommend a combined medical-surgical approach in most cases of vertebral Aspergillus osteomyelitis. Early surgery with vigorous surgical debridement along with antifungal treatment seems to yield a good outcome.

Using chart reviews to assess residents' performances of components of physical examinations: a pilot study.

PURPOSE: To evaluate chart review as a method of assessing residents' performances of physical examinations in an ambulatory care setting. METHOD: In 1992, nurse authors at the Affiliated Hospitals at Canton of the Northeastern Ohio Universities College of Medicine assessed whether 22 internal medicine residents performed ten components of the physical examination by interviewing patient volunteers immediately after the patients' examinations. A total of 89 patient interviewees were included in the analysis; these patients were all new outpatients who had been scheduled for initial visits to obtain complete histories and physical examinations. Charts for the same patients were then retrospectively reviewed. The residents and faculty were blinded to both the chart reviews and the interviews. Statistical methods used were Pearson correlational analysis and variance-component analysis. RESULTS: The interviews and chart reviews showed 81% agreement in component performance. Completeness of the physical examination (whether measured by chart review or interview) did not correlate with other standard methods of resident evaluation, and completeness did not show a significant association with characteristics of the residents and patients. Two of the 22 residents assessed were identified as having completeness scores so low as to be unsatisfactory. CONCLUSION: That residents were identified as failing to perform examination components suggests that chart reviews, especially when independently verified by patient interviews, may be a useful evaluation tool for identifying inadequate performance of components of the physical examination and may identify the need for remediation.

End of life issues in ESRD. A study of three decision variables that affect patient attitudes.

The substantial end-stage renal disease (ESRD) mortality rate reflects an older population, worsening comorbidity, and increased cardiovascular disease. Advance directives in ESRD may simplify issues such as cardiopulmonary resuscitation (CPR) and dialysis discontinuation. However, ESRD patients with advance directives may change their mind or allow surrogate leeway for override of end-of-life decisions. Three decision variables (requesting CPR, discontinuation of dialysis with depression, or discontinuation with dementia) were studied in 141 ESRD patients through a 47 item questionnaire. Duration of dialysis (> or = 4 years) (P = 0.002) and prior CPR experience (P = 0.02) increased the probability of refusing CPR by 12 times. The use of surrogates and substituted judgement for dialysis discontinuation with depression was more likely in women (P = 0.0006) and in patients with higher levels of education (P = 0.003). The odds of deciding to discontinue given dementia were three times greater for hemodialysis than peritoneal dialysis patients (P = 0.03). Eighty-three percent of the patients requested that physicians periodically check with them to determine if their advance directives had changed. The authors conclude that advance directives may assist ESRD patients, families, and staff with end-of-life decisions. Three end-of-life decision variables are significantly affected by duration and type of dialysis, previous CPR, gender, and level of education.

Eosinophils in urine revisited.

The finding of eosinophils in the urine has been suggested to be useful in establishing the diagnosis of acute interstitial nephritis (AIN). The diagnostic accuracy of this test has not yet been defined. It is the purpose of this study to define the specificity, sensitivity, and the predictive positive and negative values for the presence of eosinophils in the urine. One hundred forty-eight patients with pyuria were tested for the presence or absence of urinary eosinophils. In this group consecutively admitted to the hospital with WBC in the urine, 4% of patients had urinary eosinophilia of greater than 1 eosinophil per 100 cells. Since none of this group had the diagnosis of AIN, the false positive rate was 4% and the specificity was 96%. In a selected group of patients in which the diagnosis of AIN was suspected by a nephrology consultant, urinary eosinophils were found in 6 of 15 patients with a confirmed diagnosis of AIN but were also found in 10 of 36 patients with another renal diagnosis. The sensitivity for eosinophiluria was 40% and the specificity was 72% with a positive predictive value of only 38%. We conclude that eosinophiluria is not an accurate test for the diagnosis of AIN. The false positive and negative rates are too high to confirm an AIN diagnosis.

A kindred exhibiting cosegregation of an overlap connective tissue disorder and the chromosome 16 linked form of autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a disorder of adult onset manifested by bilaterally enlarged cystic kidneys frequently associated with progressive renal failure. The mutated gene (PKD1) responsible for 85 to 95% of cases has been localized to a small segment on the distal tip of the short arm of chromosome 16. A clinical spectrum of heritable connective tissue disorders that remain unclassifiable under the present nosology but that contain elements of the Marfan's syndrome have previously been described. The genetic localization and molecular basis of such overlap connective tissue disorders (OCTD) have not been elucidated. In this report, a kindred in which ADPKD and OCTD appear to cosegregate is described. The connective tissue phenotype in this family includes aortic root dilation, aortic and vertebral artery aneurysms with dissection, and aortic valve incompetence, as well as pectus abnormalities, pes planus, joint laxity, arachnodactyly, scoliosis, dolichostenomelia, and high arched palate. ADPKD was manifest primarily as bilateral renal cysts with or without renal failure. The DNA of all living family members was studied with markers recognizing polymorphic loci flanking the PKD1 region (3'HVR and O90a), as well as markers from the loci of chromosomes 15 and 5, associated with fibrillin genes FBN1 and FBN2, respectively. In this kindred of 20 family members traced through five generations, cosegregation of ADPKD and the OCTD phenotype was observed in 12 of 12 meioses and 3 of 3 phase known. Both markers for PKD1 were tightly linked to both ADPKD and OCTD, whereas there was no evidence for linkage with either fibrillin locus. In this family, the ADPKD and OCTD mutations are genetically linked. The presence of OCTD with ADPKD identifies a group of patients at significantly greater risk for sudden death from aortic root and other vascular aneurysmal dissection and rupture.

Reversible acute renal failure as an atypical presentation of ischemic nephropathy.

Ischemic nephropathy (IN) is defined as a clinically significant reduction in glomerular filtration rate in patients with hemodynamically significant obstruction to renal artery flow in a solitary functioning kidney or with bilateral renal artery stenosis (RAS). Ischemic nephropathy typically has a subacute to chronic course that may lead to end-stage renal disease. Acute anuric renal failure, which occurs less commonly with IN, is usually associated with moderately severe hypertension and has been attributed to certain risk factors: angiotensin-converting enzyme inhibition, a reduction in blood pressure secondary to antihypertensives or volume contraction, and exposure to contrast media. We present a series of six patients with IN and acute, anuric renal failure without either moderately severe hypertension or the previously defined risk factors. Of these six patients, four had RAS in a solitary kidney and two were found by ultrasound to have disparity in kidney size and bilateral RAS. Within 1 week of surgery, three patients developed renal failure that did not involve the kidney(s) responsible for the anuria and thus mimicked postoperative acute renal failure. Creatinine levels pre-anuria (1.2 to 2.1 mg/dL), during renal failure (5.0 to 12.8 mg/dL), and postrecovery (1.6 to 2.8 mg/dL) showed recovery of renal function, with renal artery bypass in four patients (sustained at 1 year). Two patients refused surgery and are on chronic dialysis. Acute renal failure in IN may occur postoperatively or spontaneously, and emergent intervention (ultrasound, angiography, angioplasty, and/or surgery) in this setting may lead to the correction of RAS and preservation of renal function.