Bilateral occurrence of pheochromocytoma in patients with the multiple endocrine neoplasia syndrome type 2A (Sipple's syndrome)

Two kindreds with the multiple endocrine neoplasia type 2A syndrome were studied. Of one of these we examined 150 members, 20 of whom were treated with thyroidectomy for medullary carcinoma and nine with bilateral adrenalectomy for pheochromocytoma. Of the second kindred 59 members were examined, seven of whom were thyroidectomized and seven treated with bilateral adrenalectomy. Pheochromocytomas were invariably found on both sides, even in four cases in which the adrenals on one side appeared to be completely normal, not only at preoperative roentgenologic examination but also on inspection during the operation. The microscopic finding of micronodules and a cluster of abnormal medullary cells identical with those found in pheochromocytomas in one of the apparently normal adrenals represents a first stage in the development of diffuse medullary hyperplasia as well as nodular hyperplasia. This is in accordance with the fact that in the MEN type 2A syndrome pheochromocytomas are always multicentric and multiple in origin. On the basis of these findings we conclude that all patients with the MEN 2A syndrome who show symptoms and signs of active pheochromocytoma should be subjected to bilateral adrenalectomy, even when one or both of the adrenals appear to be normal at roentgenologic investigation.     

Autologous stem cell transplantation for HIV-associated lymphoma.

Is peripheral stem cell mobilization followed by autologous stem cell transplantation (ASCT) feasible in patients with human immunodeficiency virus (HIV)- associated lymphoma (HIV-L)? Studies have demonstrated that, in the HIV- negative (HIV(-)) setting, ASCT may improve lymphoma-free survival in high-risk non-Hodgkin lymphoma (NHL) or relapsed Hodgkin disease (HD) and NHL. Given the poor prognosis of HIV-L with conventional chemotherapy, this dose-intensive approach was explored. Nine patients with HIV-HD or NHL mobilized a median of 10.6 x 10(6) CD34(+) cells/kg and engrafted after ASCT. CD4 counts recovered to pretransplantation levels and HIV viral loads were controlled in patients compliant with antiretroviral therapy. Seven of 9 patients remain in remission from their lymphoma at a median of 19 months after transplantation. Thus, patients with HIV-L on antiretroviral therapy can engraft following ASCT. Prolonged lymphoma remissions, without significant compromise of immune function, can be seen, suggesting that ASCT can be used in selected patients with HIV-L.     

A study of the morbidity,mortality and long-term survival following radical cystectomy and radical radiotherapy in the treatment of invasive bladder cancer in Yorkshire

OBJECTIVES: To study the morbidity of radical cystectomy and radical radiotherapy in the treatment of patients with invasive carcinoma of the bladder and to report the long-term survival following these treatments. PATIENT AND METHODS: 398 patients with invasive carcinoma of the bladder treated between 1993 and 1996 in the Yorkshire region were studied. Of 398 patients studied, 302 patients received radical radiotherapy and 96 underwent radical cystectomy. A retrospective review of patients' case notes was performed to construct a highly detailed database. Crude estimates of survival differences were derived using Kaplan-Meier methods. Log-rank tests (or, where appropriate, Wilcoxon tests) were used to test for the equality of these survivor functions. These functions were produced as all-cause survival. The proportional hazards regression modelling was used to assess the impact of definitive treatment on survival. A backwards-stepwise approach was used to derive a final predictive model of survival, with likelihood ratio tests to assess the statistical significance of variables to be included in the model. RESULTS: The patients undergoing radiotherapy were significantly older (mean age: 71 years versus 66 years), but no difference was identified in the distribution of American Society of Anaesthesiologists (ASA) grades in the two treatment groups. The stage distribution of cases in the treatment groups was not significantly different. Significant treatment delays were observed in both treatment groups. The median time from being seen in the clinic to transurethral resection of bladder tumour (TURBT) and subsequent radical treatment (cystectomy or radiotherapy) was 4.3 and 9 weeks, respectively. Age was the most significant independent factor accounting for treatment delays (p < 0.001). The 30-day and 3-month treatment-associated mortality for radical cystectomy and radiotherapy was 3.1% and 8.3% and 0.3% and 1.65%. Of the patients who received radiotherapy, 57 (18.8%) were subsequently subjected to a salvage cystectomy. For these 57 patients, 30-day and 3-month mortality after the salvage cystectomy were 8.8% and 15.7%. Gastrointestinal complications were the major source of early morbidity after primary and salvage cystectomy. Bowel leakage occurred in 3% following radical and 8.7% after salvage cystectomy. Bowel complications (leakage and obstruction) were the major cause of death following salvage cystectomy. No specific cause was predominant in those undergoing radical cystectomy with intestinal anastomotic leakage and urinary leakage accounting for one death each. Exacerbation of co-morbid conditions accounted for the remaining causes of mortality. Urinary leakage occurred in 4% following both forms of cystectomy. Recurrent pyelonephritis and intestinal obstruction were responsible for the majority of complications in the follow-up period. Bladder and gastrointestinal complications accounted for the majority of complications following radical radiotherapy. Some degree of irritative bladder and rectal were noted commonly. Severe bladder problems, which rendered the bladder non-functional or required surgical correction, occurred in 6.3% of patients. 2.3% of patients underwent surgery for bowel obstruction related to radiotherapy induced bowel strictures. Following radiotherapy, 43.6% of patients had a recurrence in the bladder at varying intervals post-treatment. Of these, 40% had > or =T2 disease. The 5-year survival following radiotherapy (with or without salvage cystectomy) was 37.4% while 36.5% of patients were alive 5 years after radical cystectomy. There was no statistically significant difference in the overall 5-year survival figures between the two primary treatments. Tumour stage, ASA grade and sex were the only independent predictors of 5-year survival on multivariate analysis. CONCLUSIONS: This retrospective regional study shows that there is no significant difference in the 5-year survival of patients with invasive bladder cancer treated with either radical radiotherapy or radical cystectomy. All forms of radical treatment for bladder cancer are associated with a significant treatment-associated morbidity and mortality. Gastrointestinal complications were responsible for the majority of complications. The treatment-associated mortality at 3 months was two- or three-fold higher than the 30-day mortality; emphasising its importance as an indicator of the true risks of cystectomy. The clinical T stage, the sex and the ASA grade of the patient were the only independent predictors of survival. The data in this series suggests that radical radiotherapy and radical cystectomy should be both considered as valid primary treatment options for the management of invasive bladder cancer.     

Pulsatile masses surrounding vascular prostheses: real-time US color flow imaging

A prospective evaluation of color flow mapping and real-time ultrasound was performed to determine if pseudoaneurysms could be distinguished from other causes of masses surrounding vascular grafts of the lower extremities. Twelve palpable pulsatile masses were imaged. Diagnoses were confirmed at angiography (n = 11), computed tomography (n = 7), aspiration biopsy (n = 5), and operative intervention (n = 6). A swirling pattern of blood flow was seen in six of seven cases of pseudoaneurysm. Lack of flow signals was noted in four of the five collections representing hematoma (n = 2) or infection (n = 2). The seventh case was later shown to be an infected, thrombosed pseudoaneurysm. The single false-positive diagnosis was made early in the series when the flow signals detected were due to transmitted arterial pulsations. The authors conclude that color Doppler flow imaging is useful in the differential diagnosis of pulsatile masses associated with prosthetic grafts. Prosthetic graft pseudoaneurysms have a specific appearance of swirling blood flow arising from a wide neck and are distinguishable from traumatic or iatrogenic pseudoaneurysms of the native vascular tree.     

Pulmonary histiocytosis X: comparison of radiographic and CT findings

The authors retrospectively evaluated radiographs, computed tomographic (CT) scans, and results of pulmonary function tests (when available) for 17 patients with biopsy-proved pulmonary histiocytosis X. In 11 patients, high-resolution CT was used. In 12 patients, CT demonstrated cystic air spaces, usually less than 10 mm in diameter. In three of these 12, cysts were the only abnormality, but in six others, nodules (usually less than 5 mm in diameter) were also present. Two patients had only nodules and one, only emphysema. CT showed that many lesions that appeared reticular on plain radiographs were actually cysts. CT showed no central or peripheral concentration of lesions, but it did reveal that many small nodules were distributed in the centers of secondary lobules around small airways. CT findings correlated better with the diffusing capacity (rho = -0.71) than did the plain radiographic findings (rho = -0.57). Thus, CT was better than radiography at showing the morphology and distribution of lung abnormalities.     

Introduction of H-2Dd determinants into the H-2Ld antigen by site-directed mutagenesis

We used site-directed mutagenesis to localize serologically defined (s) and CTL (c)-defined alloantigenic determinants to discrete amino acid sequences of a murine MHC class I antigen. Based on the prediction that amino acid position 63-73 of the H-2Dd antigen forms s-allodeterminants, the H-2Ld gene was mutated in a sequential fashion to replace codons for amino acid positions 63, 65, 66, 70, and 73 with those of the H-2Dd amino acids. Epitopes of the mutant antigens expressed in L-cells were examined by the binding of a series of mAbs specific for the H-2Dd antigen. The mutant antigen M66 had substitutions at residues 63, 65, and 66, and resulted in the acquisition of a number of H-2Dd-specific s-epitopes. Mutant M70 had an additional substitution at residue 70, which led to the gain of multiple additional H-2Dd s-epitopes. Together, more than half of all the relevant H-2Dd s-epitopes were mapped into amino acid position 63-70 of the H-2Dd molecule, which was expressed in the mutant H-2Ld gene. The final mutation at residue 73 (M73) caused no new epitope gains, rather, a few Dd s-epitopes acquired by the preceding mutations were lost. All of the H-2Ld-specific s-determinants were retained in the mutant molecules, as were H-2Dd s-determinants specific for the alpha-2 or alpha-3 domains. Changes of these residues affected c-determinants defined by CTL. Anti-H-2Dd CTL cultures and an anti-H-2Dd CTL clone recognized the mutant H-2Ld molecules, M66 and M70. Some CTL clones generated against the Q10d molecule, which has an identical sequence to H-2Dd between residues 61 and 73, failed to recognize native H-2Dd or Ld but did crossreact with mutant Ld. While bulk-cultured anti-H-2Ld CTL cultures reacted strongly against M73, bulk-cultured H-2Ld restricted anti-vesicular stomatitis virus CTL did not. Finally, at the clonal level two of three anti-H-2Ld CTL clones lost reactivity with some or all of these mutant molecules. From these results we conclude that a stretch of amino acids from position 63 to 70 of the alpha-1 domain controls major s- and c-antigenic sites on the H-2Dd antigen and c-sites on H-2Ld antigen.     

New universal precaution aspiration tray

A new tray has been designed for use during procedures involving needles and other sharp objects. The tray includes a foam adhesive pad, marked into 10 sections, into which the sharp objects can be placed point first. After the procedure, the objects can be safely withdrawn by their handles and then discarded. The tray has been used in more than 250 procedures.     

Diagnostic CT scans: assessment of patient, physician, and radiologist awareness of radiation dose and possible risks

PURPOSE: To determine the awareness level concerning radiation dose and possible risks associated with computed tomographic (CT) scans among patients, emergency department (ED) physicians, and radiologists. MATERIALS AND METHODS: Adult patients seen in the ED of a U.S. academic medical center during a 2-week period with mild to moderate abdominopelvic or flank pain and who underwent CT were surveyed after acquisition of the CT scan. Patients were asked whether or not they were informed about the risks, benefits, and radiation dose of the CT scan and if they believed that the scan increased their lifetime cancer risk. Patients were also asked to estimate the radiation dose for the CT scan compared with that for one chest radiograph. ED physicians who requested CT scans and radiologists who reviewed the CT scans were surveyed with similar questions and an additional question regarding the number of years in practice. The chi(2) test of independence was used to compare the three respondent groups regarding perceived increased cancer risk from one abdominopelvic CT scan. RESULTS: Seven percent (five of 76) of patients reported that they were told about risks and benefits of their CT scan, while 22% (10 of 45) of ED physicians reported that they had provided such information. Forty-seven percent (18 of 38) of radiologists believed that there was increased cancer risk, whereas only 9% (four of 45) of ED physicians and 3% (two of 76) of patients believed that there was increased risk (chi(2)(2) = 41.45, P <.001). All patients and most ED physicians and radiologists were unable to accurately estimate the dose for one CT scan compared with that for one chest radiograph. CONCLUSION: Patients are not given information about the risks, benefits, and radiation dose for a CT scan. Patients, ED physicians, and radiologists alike are unable to provide accurate estimates of CT doses regardless of their experience level.     

Exploring frontal asymmetry using functional near-infrared spectroscopy: a preliminary study of the effects of social anxiety during interaction and performance tasks

Preliminary studies examining brain function associated with social anxiety suggest the possibility of right-sided prefrontal activation associated with phobic stimulation. Although most existing neuroimaging techniques preclude participants from engaging in ecologically valid social tasks during assessment, functional near-infrared spectroscopy (fNIRS) is a promising new technique that permits such assessment. The present study investigated the utility of the fNIRS procedure and explored frontal asymmetry during in vivo social challenge tasks among female undergraduate students who scored in top and bottom percentiles on a social anxiety screening measure. Results revealed that participants in both groups experienced a significant increase in concentration of blood volume and oxygenated hemoglobin in the right hemisphere compared to the left hemisphere while giving a speech. Non-hemispheric effects were also observed. In addition, the high anxiety group showed a non-significant trend toward greater right frontal activity than the low anxiety group. This study highlights the utility of the fNIRS device in successfully assessing real-time changes in cerebrovascular response as a function of naturalistic social behavior, and supports the potential utility of this technology in the study of the neurophysiology of social anxiety.     

Electrocardiographic changes associated with isolated right ventricular infarction

Isolated infarction of the right ventricle is an extremely rare entity. A patient is described with diffuse interstitial lung disease who developed ST segment elevation in inferior and anterior leads on a routine electrocardiogram and at autopsy was found to have an isolated right ventricular infarct involving approximately 70% of the right ventricular circumference without involvement of the left ventricle and septum. This case illustrates that isolated right ventricular infarction in the presence of cor pulmonale and right ventricular hypertrophy can produce an injury current in the limb and precordial leads of the electrocardiogram which mimics that seen in typical transmural infarction of the left ventricle.