Weight change and serum lipoproteins in recipients of renal allografts. Hyperlipoproteinemia is common in recipients of renal allografts. In this study, serum lipids and some possible contributing factors--weight gain, weight relative to ideal body weight, daily dose of prednisone, serum creatinine, 24-hour urinary protein, and diabetes mellitus--were assessed in 100 patients. At the end of the first year after transplantation, 57 of the 100 patients had total serum cholesterol concentrations of 240 mg/dl or more--40 of 75 patients without diabetes and 17 of 25 with diabetes. The mean values for weight gain (11.2 kg) and actual weight relative to ideal body weight (19.4 kg) were significantly greater (P = 0.029 and P = 0.01, respectively) in the subgroup of patients without diabetes who had total serum cholesterol values of 240 mg/dl or more at 1 year after transplantation than in those with values of less than 240 mg/dl. The daily dose of prednisone and the serum creatinine levels were similar in these two subgroups. The 24-hour urinary protein measurements were greater at 1 month than at 1 year in both patients with and those without diabetes. Perhaps the initial dietary advice for patients who have undergone renal transplantation should emphasize control of total caloric intake; subsequently, intake of cholesterol and fat can be modified in those patients who have persistent hyperlipoproteinemia.


Fluorescent in situ hybridization: use of whole chromosome paint probes to identify unbalanced chromosome translocations. By identifying structural chromosome anomalies, the clinical cytogenetics laboratory can play a critical role in the diagnosis and treatment of patients with birth defects. Although many new staining techniques have been developed throughout the years to aid in the detection of anomalous chromosomes, some abnormalities still pose a special challenge to cytogeneticists. This difficulty is especially evident in patients with an abnormal chromosome that does not produce a recognizable banding pattern by conventional staining techniques. We describe a recently discovered method of identifying chromosomes by using whole chromosome-specific DNA probes and fluorescent in situ hybridization and provide examples of how this new procedure facilitated the identification of chromosome abnormalities in two patients with multiple birth defects.


Fistulous pseudoaneurysm complicating surgical accessory pathway interruption for Wolff-Parkinson-White syndrome. Pseudoaneurysms of the left ventricle are unusual operative complications that have commonly been associated with replacement of the mitral valve. In this report, we describe a 31-year-old man who was referred to our institution because of atypical chest pain. He had previously undergone three operations for ablation of an accessory pathway because of Wolff-Parkinson-White syndrome. A pseudoaneurysm of the left ventricle was noted on transesophageal echocardiography, biplanar left ventriculography, and ultrafast cine computed tomography of the heart. Elective surgical repair was successful. Although rare, this case demonstrates an unusual but potentially serious complication of surgical treatment of Wolff-Parkinson-White syndrome.


Occult cardiac tamponade detected by transesophageal echocardiography. Transesophageal echocardiography is a safe, minimally invasive procedure that should be considered when the diagnosis of cardiac tamponade is a possibility and when conventional methods fail to provide conclusive diagnostic information. In this report, we describe a 74-year-old man in the intensive-care unit whose condition was unstable postoperatively because of an occult loculated pericardial effusion and cardiac tamponade. Routine noninvasive and invasive monitoring, including hemodynamic monitoring and transthoracic echocardiography, failed to confirm definitively the suspected diagnosis of cardiac tamponade. In addition, because of the hemodynamic instability of the patient, transporting him for definitive tests (such as fast computed tomographic scanning of the mediastinum, which could not be performed at the bedside) for assessment of cardiac tamponade was relatively contraindicated. In our patient, the diagnostic information obtained by transesophageal echocardiography may have been lifesaving.


Efficacy and safety of total parenteral nutrition in pediatric patients. Pediatric patients differ from adult patients because of active musculoskeletal growth and development of visceral organs and because they have a proportionately smaller nutritional reserve, especially premature infants. Measures of outcome of effective nutritional support in pediatric patients who have experienced trauma or medical disease or who have undergone surgical procedures include weight gain, increased height and circumference of the head, increased hepatic synthesis of plasma proteins, immunocompetence, decreased morbidity, improved survival, and fast recovery. If a pediatric patient cannot eat or be tube-fed enterally after 3 days of recovery and support with fluids, parenteral nutrition is indicated. Examples in which this treatment has dramatically decreased morbidity include gastroschisis, short-bowel syndrome, necrotizing enterocolitis, and Hirschsprung's disease. Contraindications to its use include severe congenital (usually genetic) defects and terminal cancer, conditions in which life expectancy and quality of life are severely decreased. The team approach to parenteral and enteral nutrition in pediatric patients is preferred, and stable patients receiving long-term nutritional support, including infants, should be considered for home parenteral nutrition. When administered by protocol, parenteral nutrition is safe in pediatric patients. In properly selected pediatric patients, direct and indirect costs for such therapy may be significantly less than those in adults, and the cost-to-benefit ratio is appreciably higher when life expectancy, parental pleasure, and potential work productivity are considered. Ethical and social issues in initiating and discontinuing parenteral nutrition are best decided during thorough empathic discussions between physicians and parents.


Strategies for prevention of infection after cardiac transplantation. Infection remains a major cause of morbidity and mortality after cardiac transplantation. Most infections occur during the first few months after transplantation. Although late infection does occur, the risk of infection during maintenance immunosuppression is low in the absence of recurrent rejection that necessitates augmentation of suppression of the immune response. Before cardiac transplantation, the risk factors for infectious disease in potential candidates should be assessed. A detailed history of past infections should be elicited, and patients should be screened for the presence of active indolent infection. In addition, potential donors must be thoroughly assessed for organ-transmittable infection. Many common infections that may occur after cardiac transplantation can be prevented with the use of appropriate prophylactic regimens directed toward cytomegalovirus, Toxoplasma gondii, Pneumocystis carinii, and herpes simplex virus. Periodic surveillance serologic tests and cultures after cardiac transplantation facilitate early diagnosis and prompt institution of appropriate therapy.


Pathology of cardiac transplantation: recipient hearts (chronic heart failure) and donor hearts (acute and chronic rejection). Pathologic examination of both the recipient and the donor heart is critical to the success of cardiac transplantation. Idiopathic dilated cardiomyopathy and end-stage ischemic heart disease are still the most common diagnoses for which cardiac transplantation is performed in the United States. After transplantation, the donor heart is susceptible to immunologic (acute and chronic rejection), infectious, and ischemic injury. Other long-term changes, such as hypertrophy of the myocytes and interstitial fibrosis, may also affect the function of the transplanted heart. Periodic endomyocardial biopsies are important for monitoring the status of the transplanted heart. In patients treated with cyclosporine, the clinical signs of rejection may be minimal, and routine biopsy is the only means of detecting early rejection.


Increased plasma concentrations of endothelin in congestive heart failure in humans. Congestive heart failure is characterized by decreased cardiac output and increased peripheral vascular resistance. Endothelin, a peptide found in plasma, is a potent vasoconstrictor. We hypothesized that plasma concentrations of endothelin are increased in humans with congestive heart failure. Plasma samples were obtained from 71 healthy control subjects and 56 patients with congestive heart failure. The mean plasma concentration of endothelin, measured by radioimmunoassay, was 7.1 +/- 0.1 pg/ml in the 71 normal control subjects but 12.6 +/- 0.6 pg/ml in the 56 patients with heart failure (P = 0.001). To evaluate the relationship between circulating endothelin and clinical stage of congestive heart failure, we categorized patients into two groups--those with mild heart failure (New York Heart Association class I or II) and those with severe heart failure (class III or IV). Circulating endothelin in the 24 patients with mild disease was 11.1 +/- 0.7 pg/ml, significantly higher than in normal subjects (P < 0.001). Endothelin in the 32 patients with severe heart failure was 13.8 +/- 0.9 pg/ml, a level significantly higher than that in the group with mild disease (P = 0.029). In the 56 patients with congestive heart failure, a negative correlation was found between plasma concentration of endothelin and left ventricular ejection fraction (r = -0.279; P = 0.037). These data demonstrate that the plasma concentration of endothelin is increased in humans with congestive heart failure and that the level correlates with the severity of disease. Endothelin may have a role in the increased vascular resistance in patients with chronic congestive heart failure.


Colonic tone and motility in patients with irritable bowel syndrome. In this study, our aim was to test the hypothesis that colonic tone is abnormal in patients with irritable bowel syndrome (IBS). We studied eight patients with IBS and eight age-matched asymptomatic control subjects, in whom tone and motility were measured by an electronic barostat and by pneumohydraulic perfusion manometry, respectively. Tone and motility were recorded from the descending colon for a 14-hour period--3 hours awake, 7 hours asleep, 2 hours fasting after awakening, and 2 hours postprandially. In patients with IBS and in healthy subjects, colonic tone decreased by up to 50% during sleep and increased promptly on awakening. Fasting colonic tone (as quantified by the volume in the barostat balloon) in the awake state was not significantly higher in patients with IBS than it was in healthy subjects (125 +/- 13 versus 152 +/- 15 ml; P = 0.19). Tone increased postprandially in both study groups, and the increase was greater in healthy subjects than it was in patients with IBS (P < 0.05). The motility index during fasting was greater in patients with IBS than it was in healthy control subjects (3.2 +/- 0.6 versus 1.6 +/- 0.4; P = 0.05), and the postprandial increase in motility index was greater in the healthy subjects. Preprandially and postprandially, we noted a trend for high-amplitude prolonged contractions to be more frequent in patients with IBS than in healthy subjects. We conclude that colonic tone in patients with IBS showed the same nocturnal and postprandial variations as it did in healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS)


Selective 5-hydroxytryptamine type 3 receptor antagonism with ondansetron as treatment for diarrhea-predominant irritable bowel syndrome: a pilot study. Serotoninergic innervation may contribute to the control of colonic motility and to visceral sensation from the large bowel. Indeed, ondansetron hydrochloride, a selective 5-hydroxytryptamine type 3 receptor antagonist, has been shown to slow colonic transit in healthy volunteers. Thus, we wished to determine whether 5-hydroxytryptamine type 3 receptor blockade slows colonic and small bowel transit in patients with diarrhea-predominant irritable bowel syndrome (IBS) and whether symptoms would be ameliorated with drug therapy. Of 14 patients with well-established IBS who entered a randomized, double-blind, placebo-controlled crossover pilot trial of 4 weeks of treatment with ondansetron, 16 mg three times daily, 11 completed the study. A minimal "washout period" of 4 weeks (median, 7 weeks) separated the two phases of the trial because patients were required to have similar symptoms before both periods of the study. Colonic transit tended to be longer during drug therapy than during the placebo trial, but this difference was not significant. Small intestinal transit and orocecal transit were unchanged by the drug. The integrated and peak postprandial increases in neurotensin, peptide YY, and human pancreatic polypeptide in serum were not significantly different in the drug and placebo periods. After treatment with ondansetron, stool consistency improved significantly; however, stool frequency, stool weight, abdominal pain, and the symptom criteria for IBS were not significantly altered by the drug. The results of this pilot study suggest that the motor effects expected with 5-hydroxytryptamine type 3 receptor blockade (namely, slowed colonic transit) may be diminished in some patients with IBS. The subjective improvement in stool consistency may reflect changes in the perception of defecation.(ABSTRACT TRUNCATED AT 250 WORDS)


Magnetic resonance imaging of facial vascular anomalies. In 36 patients, facial vascular anomalies were studied with 46 magnetic resonance (MR) examinations, 9 angiograms, and 5 computed tomographic scans. All lesions were categorized into classic pathologic groups on the basis of radiologic and pathologic studies, clinical examination, and behavior. Overall, 2 juvenile hemangiomas, 3 capillary malformations (port-wine stains), 18 venous malformations, 9 lymphatic malformations, and 4 arteriovenous malformations were found. MR imaging was superior to computed tomography and angiography for demonstrating the precise anatomic extent of the facial vascular anomalies and their relationship to the adjacent soft tissues but was inferior to computed tomography for demonstrating radiopaque structures such as trophic bone changes and phleboliths. MR imaging was also inferior to angiography in determining the nidus and the exact nature of collateral vascular structures in arteriovenous malformations. MR studies confirmed the clinically suspected diagnosis of facial vascular anomalies and demonstrated typical characteristics for each type of lesion. MR imaging is an ideal initial technique to triage patients with facial vascular anomalies for appropriate management, including observation, endovascular therapy, or surgical excision.


Benign lymphocytic infiltrate of the skin: correlation of clinical and pathologic findings. In a retrospective study of 137 biopsy specimens of skin from 137 patients (69 men and 68 women) that had been obtained between 1972 and 1989 at our institution and that had perivascular and periappendageal lymphocytic infiltrates characteristic of those described as benign lymphocytic infiltrate (BLI), we determined the specificity of the histologic diagnosis and the correlation with clinical data. The final diagnoses, based on clinical and laboratory data and histologic findings, were BLI (59), possible BLI (7), lupus erythematosus (LE) (12), possible LE (7), procainamide-induced LE (1), insect bites (9), possible insect bites (3), polymorphous light eruption (4), lymphocytoma (4), urticaria (4), and indeterminate or miscellaneous diagnoses (27). BLI is a clinical and histologic syndrome that can be heterogeneous in origin. We recommend careful evaluation to exclude other disorders such as LE, polymorphous light eruption, lymphocytoma, and insect bites. Direct immunofluorescence microscopy and immunophenotypic studies may help distinguish BLI from LE.


Balance studies and polymeric glucose solution to optimize therapy after massive intestinal resection. The aim of this study was to determine whether fluid homeostasis could be maintained by using a hypo-osmolar (200 to 221 mosmol/kg), relatively low-sodium (50 to 52 mmol/liter) solution that contained a glucose polymer in a 54-year-old patient with high ileostomy output attributed to short-gut syndrome and resultant prerenal azotemia. Sequential balance studies were performed to assess stool and urinary output, stool fat, and urinary electrolytes initially during intravenous rehydration and subsequently during administration of the necessary fluids and nutrients exclusively by oral supplementation. The additional effects of high-fat and low-fat diet, loperamide hydrochloride, and octreotide acetate were evaluated. When the patient sipped a hypo-osmolar oral rehydration solution while she was awake during the day and received a high dose of loperamide and a 40-g fat, disaccharide-free diet, salt and water homeostasis was maintained. The addition of octreotide did not substantially enhance fluid balance; rather, it increased fecal fat and fluid losses from the small bowel. Thus, hypo-osmolar polymeric glucose solutions maintain fluid homeostasis in patients with the short-gut syndrome. In such patients, simple balance studies are useful for assessing the absorptive capacity of the residual intestine, for developing an optimal individualized treatment, and for eliminating the need for costly, long-term home parenteral nutrition.


Spontaneous coronary arterial dissection and isolated eosinophilic coronary arteritis: sudden cardiac death in a patient with a limited variant of Churg-Strauss syndrome. Isolated eosinophilic coronary arteritis expressed as a limited variant of the Churg-Strauss syndrome (allergic granulomatosis and angiitis) is a rare condition. Equally as rare is the entity of isolated spontaneous coronary arterial dissection associated with eosinophilic arteritis. A 57-year-old woman with a history of asthma and recurrent hypersensitivity (anaphylactoid) reactions to various exogenous allergens was found dead in her home; no premonitory complaints had been noted during the preceding days. Autopsy revealed focal occlusion of the left anterior descending and first diagonal coronary arteries by discrete dissecting hematomas of the media as the cause of sudden and unexpected death. Histologically, the affected arterial wall showed eosinophilic inflammation characteristic of this limited expression of the Churg-Strauss syndrome. To our knowledge, sudden cardiac death caused by arterial dissection in isolated eosinophilic coronary arteritis has not previously been reported.


Mayo Medical Center Brain Injury Outpatient Program: treatment procedures and early outcome data. The rehabilitation of persons with brain injuries has proved challenging; community reintegration is often unsuccessful. Herein we describe our intensive group-oriented outpatient treatment program for persons with brain injury and report outcome data for the graduates of the program thus far. This interdisciplinary program emphasizes the development of cognitive skills, compensation techniques, social skills, emotional adjustment, leisure skills, physical fitness, and health maintenance. Although goals are individually determined, independent living and employment are goals for most participants in the program. Before initial participation, all candidates undergo an extensive 2-day assessment. Typically, a patient remains in the program for approximately 6 months. The specific group treatment approaches used in the program are discussed. Outcome data are assessed with use of the Portland Adaptability Inventory and goal attainment scaling, as well as comparisons of preprogram and postprogram employment status and level of independent living. Our initial results support the conclusion that this comprehensive and integrated treatment program is efficacious in rehabilitating persons with mild to moderate sequelae of brain injury.


Management of patients after cardiac transplantation. During the past decade, the morbidity and mortality associated with cardiac transplantation have decreased dramatically. The current survival for patients who undergo orthotopic cardiac transplantation is 80 to 90% at 1 year and 70 to 80% at 5 years; these results are attributed chiefly to improved immunosuppression and the consequent decrease in infectious illnesses and rejection. Because surgical mortality and technique have not changed appreciably during the past 20 years, improved survival can be ascribed to advances in the medical management of recipients of cardiac transplants. Medical problems frequently encountered in such patients include allograft rejection, allograft vasculopathy, hypertension, renal dysfunction, hyperlipidemia, hyperglycemia, malignant disorders, general surgical disease, and osteopenic bone disease. Hence, the expertise needed for management of patients who undergo cardiac transplantation is not confined to a particular specialty--optimal care necessitates the integrated efforts of a team, including transplant physicians and personnel to provide broad subspecialty and laboratory support. Meticulous management with proactive intervention and minimal effective immunosuppression will prevent or ameliorate many problems and contribute to increased survivorship and improved quality of life. For additional substantive improvement in long-term survival and quality of life for recipients of cardiac allografts, multicenter, prospective, and placebo-controlled clinical investigations will be necessary.


Total lymphoid irradiation: a novel and successful therapy for resistant cardiac allograft rejection. Total lymphoid irradiation (TLI) is a novel type of adjuvant immunosuppression for patients who undergo cardiac transplantation and have refractory allograft rejection during standard immunosuppressive therapy. TLI consists of 6 to 10 fractions of 80 cGy (1 cGy = 1 rad) of irradiation to lymphatic tissues with use of the standard mantle and inverted Y fields. We have used TLI in six patients with biopsy-proven rejection that was refractory to standard treatments, including cyclosporine, azathioprine, antilymphocyte antibodies, and corticosteroids. In five patients, recalcitrant rejection was resolved after completion of TLI, and resolution persisted during long-term follow-up (17 to 30 months; mean, 22.2 months). In each patient, a substantial increase in the CD8 (suppressor T-lymphocyte) subset and elimination of B lymphocytes were demonstrated, findings that also persisted. Side effects were mild and primarily limited to transient leukopenia. In four patients, a readily treated cytomegalovirus reactivation was noted during TLI; thus, a causal relationship was suggested. In recipients of cardiac allografts who have refractory rejection, TLI provides long-lasting amelioration of the rejection profile. This result may be attributable to a relative enhancement of the suppressor T-cell subset and elimination of the B-lymphocyte line. Side effects are minimal, but monitoring for cytomegalovirus activation or reactivation is recommended.


A genetic review of complete and partial hydatidiform moles and nonmolar triploidy. Complete and partial hydatidiform moles are genetically aberrant conceptuses. Usually, complete moles have 46 chromosomes (diploidy), all of paternal origin. Most partial moles have 69 chromosomes (triploidy), including 23 of maternal origin and 46 of paternal origin. Triploidy that involves 23 paternal chromosomes and 46 maternal chromosomes is not associated with molar placental changes and, rarely, can result in a live-born infant with multiple birth defects. Herein we review the mechanisms of fertilization that may produce these unbalanced sets of parental chromosomes and the role of genomic imprinting as a possible explanation for these clinical conditions.


Inpatient treatment of severe nicotine dependence. The most severely nicotine-dependent patients who have tried traditional treatment programs without success may require maximal intervention to achieve abstinence. In the Clinical Research Center at the Mayo Clinic, we assessed the feasibility of an inpatient treatment program for 24 such subjects, who were hospitalized (in groups of 6) for 2 consecutive weeks. A combination of behavioral, chemical-dependence, and transdermal nicotine-replacement therapy was provided in a smoke-free, protected milieu. Components of the program included group therapy, management of stress, exercise, daily lectures, and supervised activities. The mean age of the 18 women and 6 men was 51.3 years (range, 29 to 69 years). The mean duration of smoking was 33.7 years, and the number of cigarettes smoked per day at the time of admission averaged 33.2. The most frequent tobacco-related medical illnesses were chronic obstructive pulmonary disease, arteriosclerosis obliterans, and coronary artery disease. All subjects but two--each smoked part of a cigarette--remained abstinent from the use of cigarettes while in the Clinical Research Center, and all completed the 2-week inpatient program. The subjects underwent follow-up for 10 weeks after dismissal and were contacted periodically thereafter. At 1 year, 7 of the 24 subjects (29%) had maintained continuous abstinence from smoking, and their self-reported status at 1 year was verified biochemically.


Coexpression of class I major histocompatibility antigen and viral RNA in central nervous system of mice infected with Theiler's virus: a model for multiple sclerosis. Chronic infection of susceptible strains of mice with Theiler's murine encephalomyelitis virus (TMEV) results in central nervous system (CNS) demyelination similar to multiple sclerosis. Demyelination induced by TMEV is mediated, in part, by class I-restricted CD8+ T lymphocytes. For these T cells to function, they must recognize virus-infected CNS targets in the presence of class I major histocompatibility complex (MHC) antigen. Therefore, we studied in vivo expression of class I MHC antigen and viral antigen-RNA in prototypic mouse strains that are susceptible (SJL/J) or resistant (C57BL/10SNJ) to TMEV-induced demyelination. In brains of resistant mice, viral antigen-RNA expression peaked on day 3 after infection and was effectively diminished by day 5 such that few virus-infected cells were ever detected in the spinal cord. In contrast, susceptible mice demonstrated delay in clearance of TMEV from the brain and a subsequent increase and persistence of viral antigen-RNA in the spinal cord for as long as 277 days. Viral infection resulted in "upregulation" of class I MHC expression in the CNS. Class I MHC antigens were expressed as early as 1 day after infection in the choroid plexus of both strains of mice before detection of viral antigen or inflammation. In resistant mice, class I MHC expression predominated in the gray matter of the brain and spinal cord on day 7 after infection but returned to undetectable levels by day 28. In susceptible mice, class I MHC expression in the CNS persisted and was intense in the white matter of the spinal cord throughout chronic infection and demyelination. No class I MHC expression was detected in the CNS of uninfected mice. Coexpression of viral RNA and class I MHC antigen was demonstrated in CNS cells by using simultaneous in situ hybridization and immunoperoxidase technique. These results support the hypothesis that a class I-restricted immune response directed against virus-infected cells may be important in the mechanism of demyelination.


Increasing incidence of pancreatic cancer among women in Olmsted County, Minnesota, 1940 through 1988. To determine trends in the incidence of pancreatic cancer and associated survival, we conducted a population-based study in Olmsted County, Minnesota. From 1940 through 1988, 219 residents of Olmsted County (120 men and 99 women) were diagnosed as having exocrine pancreatic cancer. All patients were Caucasians, and 92% had a histologically confirmed diagnosis. The mean annual adjusted incidence of pancreatic cancer per 100,000 population was 8.5 overall (11.3 for men and 6.6 for women). During the course of the study, the incidence rates increased in women (P < 0.05) and in both genders combined (P = 0.06) but not in men (P = 0.4). The male:female ratio decreased from approximately 2:1 for 1940 through 1949 to 1.5:1 for 1980 through 1988. The incidence was significantly associated with increasing age (P < 0.001) and male gender (P < 0.001) but not calendar period (P = 0.19). The overall median duration of survival was 2.8 months. The 1-year survival rate was only 14%, and no patient lived for more than 55 months after pancreatic cancer was diagnosed. Men and women had similar survival rates. The increased incidence of pancreatic cancer among women may be due in part to the increasing life span of women and the increasing occurrence of pancreatic cancer in the aged.


Spontaneous rupture of the spleen due to infectious mononucleosis. Spontaneous splenic rupture is an extremely rare but life-threatening complication of infectious mononucleosis in young adults. Although splenectomy remains effective treatment, reports of successful nonoperative management have challenged the time-honored approach of emergent laparotomy. On retrospective analysis of our institutional experience with 8,116 patients who had this disease during a 40-year period, we found 5 substantiated cases of atraumatic splenic rupture due to infectious mononucleosis. Four additional cases of suspected splenic rupture were noted. All nine patients were hospitalized and treated (seven underwent splenectomy and two were treated with supportive measures only), and they remain alive and well. In patients with infectious mononucleosis suspected of having rupture of the spleen, a rapid but thorough assessment and prompt implementation of appropriate management should minimize the associated morbidity and mortality. On the basis of review of the medical literature and careful scrutiny of our own experience, we advocate emergent splenectomy for spontaneous splenic rupture in patients with infectious mononucleosis.


Low-dose, time-release nicotinic acid: effects in selected patients with low concentrations of high-density lipoprotein cholesterol. In a retrospective analysis, 63 participants in a cardiac rehabilitation-preventive cardiology program were identified as having low blood concentrations (mean, 34 mg/dl) of high-density lipoprotein cholesterol (HDL-C) and a mean total cholesterol level of 223 mg/dl after 3 months of hygienic measures (aerobic exercise, avoidance of tobacco, diet, and weight loss) designed to increase the HDL-C level. These patients (treatment group) were treated with low-dose, time-release nicotinic acid (mean, 1,297 mg/day) for a mean duration of 7.4 months. All subjects were able to take the drug without intolerable side effects. Fifty-four patients similar to those in the treatment group participated in the same program but were not treated with nicotinic acid (control group). Exercise, diet, body weight, and smoking remained stable throughout the period of observation. For the treatment group, HDL-C levels increased a mean of 18% (+6 mg/dl), total cholesterol concentrations decreased 9% (-20 mg/dl), the ratio of total cholesterol to HDL-C decreased 25% (from 6.8 to 5.1), low-density lipoprotein cholesterol levels decreased 13% (-20 mg/dl), and triglyceride levels decreased 20% (from 165 mg/dl to 132 mg/dl). Aspartate aminotransferase and uric acid concentrations were minimally increased after treatment, and the blood glucose level was unchanged. In the control group, HDL-C levels increased a mean of 8% (+3 mg/dl) and the other blood lipid variables were not improved after a mean of 8.3 additional months of diet and exercise.(ABSTRACT TRUNCATED AT 250 WORDS)


Venous thromboembolism associated with hip and knee arthroplasty: current prophylactic practices and outcomes. Joint registry and hospital data bases for 5,024 total hip and total knee arthroplasties done between 1986 and 1988 at the Mayo Clinic were used to study prophylactic measures and frequency of symptomatic deep venous thrombosis and pulmonary embolism. In virtually all patients, graduated compression stockings were used, with or without another type of prophylaxis. Only 44 of 3,115 patients who underwent hip arthroplasty (1.4%) and 32 of 1,909 patients who underwent knee arthroplasty (1.7%) had definite or probable deep venous thrombosis or pulmonary embolism. Death definitely or possibly attributable to pulmonary embolism occurred in 11 patients who underwent hip arthroplasty (0.35%) and 1 patient who underwent knee arthroplasty (0.05%). Although patients with a history of deep venous thrombosis or pulmonary embolism were more likely to receive warfarin than were patients without such a history, the relative risk of symptomatic deep venous thrombosis or pulmonary embolism in patients who underwent hip arthroplasty and received warfarin postoperatively was approximately half that in patients who received other types of prophylaxis. The risk of death from pulmonary embolism was similarly diminished in the group that received warfarin. The lower rates of these complications in the patients who received warfarin support the prophylactic use of this agent after total hip arthroplasty.


Reye's syndrome in Olmsted County, Minnesota: did it exist before 1963? In this study, our goals were to determine whether Reye's syndrome existed before the first published report of this entity in 1963 and to describe the long-term incidence and trend of this syndrome. Medical and pathologic records and pathologic specimens for Mayo Clinic patients, including those who were residents of Olmsted County, Minnesota, were reviewed through the facilities of the Rochester Epidemiology Project. On review, 12 cases were identified for the period 1920 through 1962; 2 of these cases were in Olmsted County residents. Of the 12 cases identified before 1963, 10 were in patients younger than 5 years of age. In addition to the aforementioned two cases, five others in Olmsted County were diagnosed between 1963 and 1989. Incidence rates were computed for the Olmsted County population. The number of cases and rates per 100,000 persons younger than 18 years of age in that population were 2 cases (0.3) for 1920 through 1962, 4 cases (0.7) for 1963 through 1980, and 1 case (0.4) for 1981 through 1989. Although cases found during the earlier periods may have included disorders that mimic Reye's syndrome, the recommended criteria from the Centers for Disease Control were applied to review of medical records and supported by pathologic findings in the liver. The data showed an age distribution tending toward young patients and no seasonality of occurrence. The incidence rates in Olmsted County, Minnesota, showed an increase for 1963 through 1980 over previous decades, followed by a decrease. The small numbers preclude any conclusion about trends in the incidence rates.


Detection of migratory silicone pseudotumor with use of magnetic resonance imaging. A patient with silicone gel breast implants, who experienced capsular contracture of the left breast that was treated by closed capsulotomy, sought medical attention because of numbness and pain in the left medial forearm and hand. Inflammatory masses subsequently developed in the left anterior axillary and antecubital regions. Magnetic resonance imaging revealed silicone pseudotumors, and mammography confirmed implant rupture and gel extrusion along fascial planes into the axillary region.


Effects of aging and food restriction on the trigeminal ganglion: a morphometric study. A quantitative morphometric study of the rat trigeminal ganglion was conducted to determine the changes that occur with aging. All measurements were tracked from young to old age in two rat groups simultaneously. One group was fed ad libitum, the other was maintained on restricted food intake from 6 weeks on. Immunocytochemical and radioimmunoassay techniques were used to study the neuron group that produces the peptide, CGRP and to compare it with the CGRP-negative neuron group. We observed that in the trigeminal ganglion, soma diameters and nucleus diameters of all neurons, whether CGRP positive or negative, increased modestly with age; so did total ganglion weight. Food restriction delayed, but did not prevent the increases in neuron diameters. No significant changes occurred as a function of age in the total number of neurons per ganglion, the ratio of CGRP positive to CGRP negative neurons and ganglion content of CGRP. Food restriction did not affect the parameters that remained constant with age. These findings are in contrast to the marked inhibitory effect of food restriction on age-related increase in thyroid calcitonin, a hormone that is encoded by the same gene as CGRP.


Age-related changes in concentrations of vasopressin in the central nervous system and plasma of the male Wistar rat. The results of studies on the influence of age on concentrations of vasopressin (VP) in blood plasma and hypothalamic and extrahypothalamic brain sites have not been unequivocal. Studies on extrahypothalamic concentrations of VP in the aging rat have used two age groups only and have mainly provided semiquantitative data. For these reasons we determined, by radioimmunoassay, the concentrations of vasopressin in thirteen brain structures and in the plasma of 3-, 10-, 20- and 28-month-old male Wistar rats. Age-related decreases in VP concentrations were found in the pituitary gland, hypothalamus, thalamus, midbrain, medulla oblongata, amygdala and pineal gland, while an increase was noted in plasma. Decreases in the concentration of VP in the amygdala and pineal gland occurred between 3 and 10 months of age and probably represent developmental changes. In the pituitary, thalamus, midbrain, medulla oblongata and plasma, differences in the concentration of VP were also found between 10-month-old and older animals and are probably related to aging. The finding of increased plasma VP concentrations in aged animals agrees with the notion that neuronal function does not necessarily decline with age and suggests that neurons may even be activated. Age-related changes in VP concentrations were not observed in the other structures examined. It has been reported that the VP innervation of a number of brain structures depends on testosterone. Despite reports to the contrary VP concentrations do not generally decline in these structures with aging.


Dissociation kinetics of the uterine estrogen receptor-estradiol complex are unaltered in aging C57BL/6 mice. Several, though not all, estrogen-dependent phenomena show reduced responsiveness to estradiol (E2) during aging. One factor contributing to this reduced sensitivity could be an increase in the dissociation rate of the estrogen receptor-hormone complex. We therefore studied the effect of aging on the dissociation rate of 3HE2 from the uterine cytosolic estrogen receptor (ER) of C57BL/6 mice that had been ovariectomized 48 h earlier. Measurements were made at 28 degrees C at two concentrations of cytosol. In dilute cytosol ([ER] = 0.01 nM) the dissociation of ER-3HE2 displayed a single phase, first order profile which did not differ among young (4-6 month), middle-aged (15-18 month) and old (23-30 month) mice. In more concentrated cytosol ([ER] = 2 or 6 nM) the dissociation of ER-3HE2 displayed a biphasic first order profile that consisted of an initial rapidly dissociating phase followed by a more slowly dissociating phase. There was no effect of age on the dissociation rate constant (K) of either the rapid (K-1) or slow (K-2) phase. Shortening the time allotted for the concentrated cytosol to equilibrate with 3HE2 before measuring the dissociation rate reduced the fraction of the receptor hormone complex that dissociated in the slow phase, but, once again, the dissociation profiles did not differ between age groups. These results indicate that uterine ER dissociation kinetics remain unaltered in middle-aged and old mice and are therefore unlikely to play a role in the attenuated responsiveness to estrogen during aging.


Expression of c-fos, c-jun and jun B in peripheral blood lymphocytes from young and elderly adults. The expression of c-fos, c-jun and jun B proto-oncogenes was studied in phytohemagglutinin (PHA) activated peripheral blood lymphocytes (PBL) from young and aged humans. Specific mRNAs for c-fos and c-jun were detectable within 30 min after cell activation and reached maximal levels within 2 h. Both c-fos and jun B mRNAs decreased to pre-activation levels within 6 h, while c-jun mRNA remained elevated. In PHA-activated PBL, no age-related differences were observed in c-fos or jun B mRNA expression. However, c-jun mRNA levels decreased significantly (1.73 +/- 0.08 vs. 1.16 +/- 0.09 arbitrary units, P < 0.01, young vs. old) in PBL from elderly individuals activated with PHA. Because previous work has demonstrated that T cells from elderly individuals may display normal proliferative responses when activated via the anti-CD2 pathway, c-jun and jun B mRNA expression was also studied in anti-CD2-activated purified T cells. No age-related differences were found in the expression of either of these two proto-oncogenes by anti-CD2 activated T cells. These results suggest that the decreased IL-2 production and proliferative response displayed by PHA-activated PBL from elderly adults may be related to age-related changes in c-jun mRNA expression and in the ratio of c-fos to c-jun mRNA.


Effect of physical activity stress on the phagocytic process of peritoneal macrophages from old guinea pigs. The different stages of the phagocytic function in peritoneal macrophages from old guinea pigs (27 +/- 3-months-old) were studied before, immediately after and 24 h after being subjected to physical activity stress (swimming until exhaustion) which raised the blood levels of corticosterone. The phagocytosis of opsonized Candida albicans was stimulated immediately after physical activity. No modifications in adherence, chemotaxis, ingestion of inert particles, or microbicide capacity, measured by nitroblue tetrazolium (NBT) reduction, were found. At 24 h, when no stress could be shown by corticosterone analysis, the phagocytosis of opsonized C. albicans remained stimulated and chemotaxis was increased while ingestion of inert particles and microbicide capacity remained unchanged. The adherence, however, was at a smaller level. No correlations were found between the corticosterone levels and the status of the phagocytic process of peritoneal macrophages.


Influence of age on stereoselective pharmacokinetics and metabolism of hexobarbital in the rat. The influence of age on stereoselective pharmacokinetics and in vitro metabolism of R- and S-hexobarbital was studied in the rat. After intravenous administration of the racemate, the plasma concentrations of S-hexobarbital are markedly lower than those of R-hexobarbital. For S-hexobarbital the half-life is somewhat shorter and the volume of distribution and plasma clearance is higher than for its antipode. For both enantiomers an increase in AUC and half-life, and a decrease in clearance are observed with aging. These changes occur mainly between the 3rd and the 12th month and are slightly more pronounced for R- than for S-hexobarbital, as appears from the S/R ratios. The volume of distribution shows no changes with aging. In vitro disappearance rate in 3-month-old rats is significantly higher for S- than for R-hexobarbital. There is for both enantiomers an increase in disappearance rate in 12-month-old rats as compared to younger or older rats, but this is significant only for the R-enantiomer. There are pronounced differences in the kinetics and metabolism of both hexobarbital enantiomers; changes with aging occur, but are only slightly and not always significantly more important for R- than for S-hexobarbital.


Changes with aging and physical exercise in ascorbic acid content and proliferative response of murine lymphocytes. Ascorbic acid content and lymphoproliferative response to phytohemagglutinin were measured in lymphocytes from axillary nodes, spleen and thymus of young (15 +/- 2 weeks) and old (60 +/- 5 weeks) BALB/c mice. Ascorbic acid content in lymphocytes from spleen and thymus was found to be significantly higher and the lymphoproliferative response in the three immunocompetent organs significantly lower in old mice as compared to young mice. Moreover, young and old BALB/c mice were required to maintain a swimming activity until exhaustion (exhaustive exercise) or 90 min of swimming each day for a total of 20 days (continuous exercise). In both young and old mice the stress produced by exhaustive exercise and confirmed by the existence in serum of significantly increased levels of corticosterone compared to controls, caused a significant decrease in ascorbic acid content as well as in lymphoproliferative response. Continuous exercise, characterized by the presence in serum of significantly decreased levels of corticosterone compared to controls, produced the most significant decrease in ascorbic acid content from young and old murine lymphocytes. Moreover, this exercise resulted in a significant increase in lymphoproliferative response. Our results suggest that aging results in an increase in the ascorbic acid content of lymphocytes accompanied by a decline in the lymphoproliferative response in old BALB/c mice.


Age-related changes in antioxidant enzyme activities are region and organ, as well as sex, selective in the rat. Enzyme activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were determined in the liver as well as several specific brain regions of young and old Fischer-344 rats of both sexes. In the liver of male rats, activities of CAT as well as Mn-SOD were lower, while activities of Cu Zn-SOD were higher in old (30-month-old) rats than in young (7-month-old) ones. Activities of total SOD as well as GSH Px were comparable for young and old male rat livers. In contrast to male rats, in female rat livers, activities of CAT were significantly higher in old (28-months-old) rats, while activities of Mn-SOD were slightly (but significantly) higher in old rat livers. In old male rats, activities of Mn-SOD were significantly higher than in young males in several specific regions of the brain (the substantia nigra (s. nigra), striatum, hippocampus) but lower in the cerebellum. In particular, SOD activities in s. nigra, striatum and hippocampus in old male rats were several fold higher than corresponding values in young male rats. Activities of Cu Zn-SOD were generally unchanged with age. Activities of CAT as well as GSH-Px (both Se-dependent and non-Se-dependent forms) were also relatively unaffected by age. In female rat brains, activities of Mn-SOD as well as those of others all remained mostly unaffected by aging, although there was a general tendency of slightly higher activities in most cerebral regions for Mn-SOD in old female rats. Thus, age-related changes of these antioxidant enzymes in the liver and brain are markedly sex dependent and some enzyme activities (such as CAT in the liver) change in an opposite direction with age. Changes of Mn-SOD in the brain were markedly region-specific in male rats. Results suggest that the significance of the changes of these antioxidant enzyme activities during aging needs to be carefully interpreted, taking into consideration the fact that changes are markedly variable depending on sex as well as the organs and brain regions examined.


Digoxin cardiotoxicity in aging anesthetized F344 rats. It is generally accepted that the sensitivity to toxic effects of digitalis increases with advancing age; however, the relative contribution of pharmacokinetics and pharmacodynamics to this aging-related change is presently unknown. The current study was designed to determine if senescence affects digitalis tolerance in an animal model and if observed changes are mediated by altered cardiac or autonomic nervous system responsiveness. Male, F344 rats of three age groups (4, 14 and 25 months) were anesthetized and infused intravenously with digoxin at a rate of 880 micrograms/kg per min. Two separate anesthetic regimens were employed: (a) an age-adjusted dose of urethane in spontaneously breathing animals (AR1); and (b) a non-age-adjusted dose of alpha-chloralose plus urethane in mechanically ventilated rats (AR2). Heart rate, EKG and arterial blood pressure were monitored continuously; baroreceptor reflex function was estimated before and 10 min following the start of digoxin infusion by examining the response to bilateral carotid occlusion. The infusion time required for digoxin-induced AV-dissociation was significantly reduced by senescence in rats anesthetized by AR1. However, doses of digoxin required to elicit ventricular extrasystoles and death were not significantly different among age groups in this anesthetized model and serum digoxin levels did not differ at the time of cardiac arrest. Similarly, AR2 animals showed a significant aging-related decrease in the time to AV-dissociation. However, in contrast to AR1, animals in AR2 displayed an aging-associated increase in the doses of digoxin required to produce ventricular arrhythmias and cardiac arrest. Thus, results suggest that aging in the F344 rat may, by pharmacodynamic mechanisms, promote the sensitivity to digoxin-induced AV-dissociation but not to ventricular arrhythmias or cardiac arrest.


Using the Gompertz-Strehler model of aging and mortality to explain mortality trends in industrialized countries. Mortality trends in industrialized countries are characterized by declines in vascular disease (ischemic heart disease and stroke) and rises in cancers and degenerative diseases. These trends are typically analyzed by examining each disorder in isolation using the perspective of genetic and environmental influences. However, longitudinal Gompertzian analysis and the Gompertz-Strehler model of aging and mortality as modified by Lestienne suggest that age-specific mortality rates, for both general and disease-specific mortality, are an interrelated deterministic function of aggregate genetic, environmental and competitive influences. Consequently, evolving mortality trends and patterns appear to be influenced by three factors (with deterministic competition being the third factor), rather than just two factors (genetic and environmental) as commonly depicted.


Age related rejoining of broken chromosomes in human leukocytes following X-irradiation. One theory of aging is that the ability to repair DNA or chromosome damage decreases with age. This study made use of a method which allows the measurement of chromatid repair in interphase nuclei, the technique of premature chromosome condensation. The number of excess chromosome fragments per cell remaining after 24 h of incubation at 37 degrees C was determined and used as a measure of the ability of leukocytes to repair. The leukocytes from male donors of several ages were used and the cells from older donors showed greater residual damage and, therefore, less repair.


Age related alterations in the response of the pial arterioles to adenosine in the rat. To evaluate the effects of aging on vasoreactivity of pial arterioles to adenosine and barium chloride, an hydraulically intact cranial window preparation was developed in the rat. The microvasculature of anesthetized 3- and 24-month-old Fischer-344 rats was studied during superfusion with artificial cerebrospinal fluid with and without test agents and results determined by videomicroscopy techniques. In both cohorts, the response of pial arterioles to adenosine was both dose and vessel size dependent: arteriolar dilation increased with increasing concentrations of adenosine and at any given concentration the percent increase in diameter was greater in the smaller vessels. During adenosine superfusion the absolute changes and percent increase in vessel caliber were greater in the young rats. Arteriolar vasoconstriction due to barium chloride was vessel size dependent but there were no significant differences in response between young and aged rats. The results indicated an attenuated cerebrovascular response in aged rats to adenosine, but not to barium chloride. This may be due to a difference in the mode of action in these two compounds. Venules did not respond to adenosine at any concentration.


Effects of phorbol myristate and ionomycin on in vitro growth of aged Peyer's patch T and B cells. The proliferative responses of Peyer's patch (PP) T cells from aged BALB/c mice to concanavalin A (Con A) are considerably reduced, as compared to those of the young (P < 0.001). This reduced reactivity of aged T cells could be partly, but not entirely, corrected by interleukin 2 (IL-2) (P < 0.001). PP T cells from aged mice responded synergistically to a protein kinase C (PKC) activator, phorbol myristate acetate (PHA), plus a calcium ionophore, ionomycin, at much lower concentrations than to Con A (P < 0.001); however, the maximal proliferative response still remained nearly at 8/10th of the young (P < 0.01) and higher levels of PMA (but not of ionomycin) were required (P < 0.001). Addition of IL-2 restored the diminished response to the levels of the young T cells (P < 0.05), but that of Con A did not (P > 0.05). The proliferative responses of PP B cells to lipopolysaccharide (LPS) do not differ from those of the young (P > 0.05), but the spontaneous proliferation of aged (unstimulated) B cells is enhanced nearly twofold versus that of the young (P < 0.001). Like the PP T cells, PP B cells from aged mice also responded synergistically to PMA plus ionomycin but to a lesser degree than those of the young under the same stimulation (P < 0.01). Their maximal proliferation required higher levels of PMA, but not of ionomycin and was also diminished (P < 0.01), compared to that of the young. B cell stimulatory co-factors, IL-4 and IL-6, failed to affect the response of aged and young B cells to PMA plus ionomycin (P > 0.05), whereas LPS remediates the reduced response of aged B cells to PMA plus ionomycin. Thus, T and B cells from senescent PP demonstrate an impaired proliferative responsiveness via the Ca-dependent PKC pathway. A T cell mitogen and B cell stimulatory cytokines did not alter this activation pathway, once optimally stimulated. Whereas, T cell stimulatory cytokine IL-2 and B cell mitogen LPS could restore the age-associated decline of the corresponding lymphocyte subsets, T and B cells, in activation of the Ca-dependent pathway. The altered transmembrane signal transduction appears to be intrinsically defective in these aged PP T and B cells.


Difference in response of hepatic glutathione S-transferase activities to protein-free diet between young and old C57/BL male mice. Responses of hepatic glutathione S-transferase (GST) activities to protein-free diet (PFD) and normal diet (ND) refeeding were compared for young (6-month-old) and old (22-month-old) C57/BL male mice. Enzyme activities toward 1-chloro-2,4-dinitrobenzene (CDNB) were not significantly different between young and old rat livers in the basal condition without diet manipulation. When animals were fed PFD for 1 week, GST activities toward CDNB significantly declined in both age groups in comparison to respective basal values, but there was no significant difference in activities between the two age groups after a 7-day PFD. When they were refed with ND for 2 days (on day 2 of ND), the activities in young mice rose to a level significantly higher than the corresponding basal value. In contrast, in old animal livers, the activity slightly but further tended to decline on day 2 of ND. Activities in old rat livers returned to the basal level on day 5 of ND, while activities in young animal livers that increased to levels higher than basal levels due to the overshoot returned to the basal level on day 7 of ND. Enzyme activities toward 1,2-dichloro-4-nitrobenzene (DCNB) were significantly higher in young rat livers than in old ones at the basal period. However, enzyme activities also overshot the basal level on day 2 of ND after 7-day PFD in young mouse livers, while in old mouse livers the activities were lowest on this day. Activities returned to the basal level on day 7 of ND in both age groups. Thus, the greatest difference in enzyme activities between young and old mouse livers for both substrates was observed on day 2 of ND after 7-day PFD, rather than at either the basal period or immediately after 7-day PFD. The results essentially agree with our previous findings on female C57/BL mice as well as female Fischer-344 rats, suggesting that the age-induced changes in the GST system become clearly manifest after diet manipulation of PFD followed by ND refeeding, rather than in values during a basal period without diet manipulation, regardless of sex or species of animal.


Assigning appropriateness ratings for diagnostic upper gastrointestinal endoscopy using two different approaches. Methods that combine information in the medical literature with expert clinical judgment are needed to determine the appropriateness of use of a procedure. The purpose of this study is to better understand the reliability and construct validity of this process by comparing ratings of appropriateness for diagnostic upper gastrointestinal endoscopy that were developed using different approaches by two independent groups. Both the RAND/UCLA Health Services Utilization Study (HSUS) and the American Society for Gastrointestinal Endoscopy (ASGE) combined scientific data with expert physician judgment to rate the appropriateness of specific clinical indications for the use of upper gastrointestinal endoscopy. This study applies the ratings developed by each group to a nationally representative sample of 1,585 endoscopies performed on people 65 years of age and older in 1981. HSUS developed indications that could be used to rate all 1,585 procedures; ASGE indications were less comprehensive and applied to 70% (n = 1,115) of procedures. Of those rated by both groups, appropriateness category ratings agreed for 94% of the procedures. However, the procedures not rated by ASGE were unevenly distributed across HSUS appropriateness ratings. Twelve percent of procedures rated as appropriate by HSUS were not rated by ASGE, but 80% of procedures rated as equivocal by HSUS and 73% rated as inappropriate by HSUS were not rated by ASGE, for those procedures rated by both approaches there was good agreement; however, a more explicit and comprehensive method may be required if equivocal and inappropriate use of a procedure is to be identified.


Adherence to screening flexible sigmoidoscopy in asymptomatic patients. The purpose of this study was to assess patient adherence to physician-recommended screening flexible sigmoidoscopy. In the setting of a family practice residency program, adherence rates in asymptomatic patients (N = 333, age > or = 50 years) were compared among a Usual Care Group; an Intervention Group that received educational materials and a phone reminder; and a Continuity Group, which had longstanding continuity with a single physician. Data from mailed questionnaires (N = 180) were used to examine the associations of demographic factors and attitudes with adherence. Adherence was 30.3% overall, with a nonsignificant increase in the Intervention Group compared with the Usual Care Group. In a pooled analysis of the Usual Care and Continuity Groups, the half of the sample with the highest continuity had a significantly higher adherence rate than the rest of the sample (45%; P < 0.001). In a discriminant analysis (78% correct classification, P < 0.001) two history variables (family history of cancer; family history of colon problems), one measure of continuity (number of physician visits), one demographic variable (lower household income), and two attitudinal factors (perception of how painful flexible sigmoidoscopy would be; perception of how well the physician explained its importance) made statistically significant contributions to the prediction of adherence. Results of the study show that screening flexible sigmoidoscopy is acceptable to asymptomatic patients, and that continuity is likely to have a positive impact on adherence. Because attitudes offer the potential for modification, we suggest that physicians reassure patients that flexible sigmoidoscopy is not unduly painful and discuss with patients individually its importance to their health.


Utilization review savings at the micro level. Utilization review (UR) programs have become an integral part of efforts to contain health care costs for private health insurers, employers, and health care organizations. While some studies have measured the overall performance of these programs, important information in the prior level of the health care utilization has not been used in estimating the effectiveness of the program for micro units (e.g., employer groups). In this article, the authors present a model to determine how the impact of the hospital UR program on health care utilization for specific groups varies with historical use patterns. The estimation approach used in this article can be used to determine the effect of UR for specific employer groups without having to rely on the average effectiveness measures for all. Claims obtained from Aetna Health Plans provided data for more than 5,300 employer accounts covering approximately 580,000 employees, 44% of whom had the UR program sometime during the period 1987 to 1990. Because of regression to the mean, UR savings were greater for units with higher prior use and smaller for units with lower use. In addition to prior use, the size of the group also determined the extent of regression to the mean. Groups with smaller number of enrollees had greater potential to save from the UR because of UR's ability to reduce the outliers.


Analyzing communication in medical consultations. Do behavioral measures correspond to patients' perceptions? When analyzing relationships between physician-patient communication and medical outcomes, researchers typically rely on quantitative measures of behavior (e.g., frequencies or ratios) derived from observer-coding of transcripts, audiotapes, or videotapes. Interestingly, rarely have researchers assessed whether quantitative measures of communication (e.g., the physician's information giving) correspond to patients' perceptions of physicians' communication (e.g., informative). This investigation of 115 pediatric consultations examined this issue and yielded several notable findings. First, less satisfied parents received more directives and proportionally less patient-centered utterances from physicians than did more satisfied parents. Second, findings were mixed regarding the degree to which behavioral measures related to analogue measures of parents' perceptions. For example, the doctors' use of patient-centered statements was predictive of parents' perceptions of physicians' interpersonal sensitivity and partnership building, but the amount of information physicians provided parents was unrelated to judgments of the doctors' informativeness. Third, with some important exceptions, relationships between behavioral measures and parents' evaluations did not vary for parents differing in education and anxiety about the child's health. Finally, behavioral measures in the form of frequencies tended to be better predictors of parents' perceptions than were measures in the form of proportions. Implications are discussed.


The effects of consultation on over-the-counter medication purchasing decisions. This article examines factors that predict changes in consumer purchasing decisions of nonprescription medications. Variables corresponding to factors in Andersen's behavioral model are measured, in addition to data regarding characteristics of the 17 pharmacy consultants who provided counseling services. One thousand seven hundred and thirteen consumers in five stores in southern California were provided consultation during a 6-month period, resulting in 25.4% of the patients purchasing a different drug than intended when entering the pharmacy, 1.3% being referred to a physician, and 13.4% not purchasing any over-the-counter medication at all. Logistic regression techniques demonstrated that one enabling variable (availability of generic medications), and four need factors (the discussion of clinical issues, short encounters, cough and cold products, and vitamin products) were significant predictors of the consumer's decision to purchase a different product than intended. Consultant characteristics (introversion, external locus of control) were also important predictors, but opposite the expected direction. Consumers who received information from female consultants were more likely to change their purchasing decisions.


An overview of the development and refinement of the Resource-Based Relative Value Scale. The foundation for reform of U.S. physician payment. Responding to distortions in payment rates between services, policymakers in the United States have sought a systematic and rational foundation for determining physician fees. One such approach to paying physicians, the Resource-Based Relative Value Scale (RBRVS), determines fees by measuring the relative resource costs required to produce them. On January 1, 1992, the Medicare program implemented a new payment system for physician services based on the RBRVS. This article provides a brief history of the RBRVS and a summary of the methods and data used to derive it. This overview represents the culmination of 6 years of research by the Harvard RBRVS study team and provides a road map to the study's concepts and definitions. The overview also provides a context for the articles in this issue that describe five major studies undertaken since 1988. The study's overall results are presented in the last article of the series.


Predicting the work of evaluation and management services. Physicians, carefully adhering to the definitions of Physicians' Current Procedural Terminology (CPT) billing codes, used the same CPT codes to denote evaluation and management services that varied widely in work and used different codes for services whose work was the same. As payment shifted to the Medicare Fee Schedule, it was important that the coding system be redefined so that codes consistently reflect the resource costs of these services. Redefining these codes for a resource-based payment system required an understanding of how verifiable predictors relate to physician work. Using data obtained from the Resource-Based Relative Value Scale (RBRVS) study regarding 377 services surveyed among physicians in 31 specialties, multiple regression analyses of the relationship of different variables to the mean values of work were performed. Intraservice time, which accounted for 90% of the variance, was the most important predictor of intraservice work. Specification of time, which previously had not been an element in the definitions of CPT codes for evaluation and management services, was useful in refining these codes so that their value corresponds more closely to resource costs. Other predictors of work were site of service or visit type, patient status (new/initial, established/subsequent), and referral status (consultation, nonconsultation).


Small-group judgment methods for determining resource-based relative values. National telephone surveys used in the Resource-Based Relative Value Scale Study produce reliable and valid relative values of work, but phone surveys are expensive and time consuming. We evaluated three small-group processes as alternatives. We compared national survey work estimates for 38 surgical services to those generated by panels of 11 and 19 highly qualified general surgeons using 1) single-round mail survey; 2) Delphi multiple-round ratings; and 3) modified Delphi with face-to-face discussion. Single-round mail-survey ratings were closest to the national survey; average differences were 11.0% and 12.6%. Delphi feedback led to increased differences: typical values differed by 14.6% and 15.2%. Face-to-face discussion led to still further divergence (21.0%). Single-round mail survey of a small number of experts provides relative work values that compare more favorably to those of the national survey than those obtained from Delphi multiple-round ratings or modified Delphi with face-to-face discussion.


Physician and practice characteristics, frequency of performance, and the Resource-Based Relative Value Scale. The Resource-Based Relative Value Scale is based in part on the ratings of the work of services obtained from a random sample of physicians in a specialty. Ratings are used without regard to board-certification or other characteristics of the physician, or to the physician's experience with the service. Critics have suggested that all physicians may not be equally qualified to rate the work of services. Using data obtained from the Resource-Based Relative Value Scale surveys and analyzed using multiple regression methods, the authors found that physician and practice characteristics explain, at most, a small fraction of the variation in ratings of work. Any increase in the precision of the work scale obtained by adjusting physicians' work ratings according to physicians' characteristics could be achieved at lower cost by a slight increase in sample size. Associations between frequency of performing a service and ratings of work are about as likely to be in one direction as another. Most of the differences between estimates of work, excluding and including physicians who have not performed a service, are less than 2% in absolute value, and all are less than 10%. Estimates of work using ratings of physicians in the upper half in frequency of performance are usually within 10% of estimates using other ratings. Even if the observed associations are not due to chance, the potential improvement in accuracy of estimates of work appears too small to justify using data on frequency of performance.


Incorporating practice costs into the Resource-Based Relative Value Scale. Practice costs (not including liability insurance costs) account for approximately 41% of the payment for medical and surgical services in the Medicare Fee Schedule. Unlike the portion of the fee schedule that compensates physicians for their work, the practice cost portion of the Medicare Fee Schedule is not resource-based; it is based instead on historical charges. As a result, physicians can recover their practice costs in less time and with less effort (measured in work relative value units) by performing invasive procedures and tests than by providing evaluation and management services. The Physician Payment Review Commission has proposed, in some detail, a method for incorporating practice costs into the Medicare Fee Schedule. The method involves allocating indirect costs on the basis of physician work plus direct costs. We find, using their own analytical framework, that indirect costs should rather be allocated on the basis of time. But to better serve the goal of incentive neutrality, and to make practice cost payments more equitable, the payment a physician receives for practice costs should be based not on service mix and volume, but on characteristics of the physician's practice more closely related to practice costs: for example, whether the physician has an office, or whether the physician practices alone or in a group.


Results and impacts of the Resource-Based Relative Value Scale. On January 1, 1992, the Health Care Financing Administration implemented the 1989 legislation reforming the Medicare payment system for physicians' services. The cornerstone of the new payment reform is the Medicare Fee Schedule (MFS), which is based on the Resource-Based Relative Value Scale (RBRVS). In this article, the major findings of the RBRVS study and its impacts on physician payment are summarized. The authors report the impacts of a RBRVS-based fee schedule on Medicare fees and physicians' income if it were fully implemented, assuming budget neutrality and absence of volume changes in services. Under this scenario, fees for evaluation and management services increase by 15% to 45%, while fees for invasive services and diagnostic tests decrease by 20% to 30%. These changes increase the Medicare income of family practitioners by more than 30% while decreasing the income of most surgical specialties by 10% to 20%.


Understanding the Medicare Fee Schedule and its impact on physicians under the final rule. On January 1, 1992, the Medicare program unveiled a new method for paying physicians known as the Medicare Fee Schedule (MFS). The new fee schedule is a complex system of administrative pricing based on the resource inputs used in producing physician services. The MFS consists of three parts: 1) a Relative Value Scale, which assigns to each medical service a value relative to all other services; 2) a conversion factor, which converts the relative values into dollars; and 3) a geographic adjustment factor, which adjusts payments based on geographic differences in the cost of producing physician services. In this article, the following are addressed: how the relative values were determined; how the geographic adjustment factor was constructed; and how the conversion factor was calculated. In addition, balance billing limits and the Medicare Volume Performance Standards (MVPS) are described. Computer simulations of the impact of the MFS on payments to physicians are presented. The authors found that the MFS will 1) redistribute payments away from surgeons, radiologists, and other procedure-based specialties toward the primary care specialties; 2) redistribute payments away from urban areas toward rural areas; and 3) redistribute payments away from invasive procedures and diagnostic tests toward evaluation and management services. The authors conclude with a discussion of the future refinements of the MFS, its applicability to other payers, and whether it will accomplish its intended purposes.


[Comparative study of the survival of gastric B-cell lymphoma of mucosal origin with respect to lymph node lymphoma of similar histology]. The differences in clinical presentation, morphology, phenotype and genetic changes between lymphomas originating in the gastrointestinal tract and the lymph nodes justified the proposal of a system of specific classification for lymphomas originating in lymphoid tissue associated to mucosa (MALT). Nevertheless, there is no conclusive evidence that the types of lymphoma defined as such have a different clinical evolution with respect to the lymph nodes lymphomas. With the aim of analyzing this problem a clinical follow up of 33 patients with primary gastric lymphomas (high and low grade) was compared with the results of a group of 99 lymphomas of the lymph nodes was carried out with classification according to the criteria of Kiel classification and the proposal by Isaacson et al for MALT lymphomas. Survival obtained by the Kaplan-Meier method was compared by the Mantel-Haenzel test. The results obtained showed that all gastric lymphomas have a less aggressive evolution than those of lymph node origin (p < 0.01). This significant statistical difference was also observed when lymphomas of similar histology were compared. Similarly, the subgroups of large cell lymphoma (p < 0.05) and small cells (p < 0.01) differ with respect to lymphomas of similar histology and of lymph node origin. In contrast with the results expected, no significant difference was observed between the two main groups of lymphomas of high and low grade mucosal origin. The analysis of the results supports the convenience of a system of specific classification for lymphomas of mucosal origin. Nevertheless, the specific existence of groups of high and low grade lymphomas is questioned since the probability of survival between both subgroups does not show statistically significant differences.


[Primary gastrointestinal lymphoma: a study of 25 cases]. The digestive tract constitutes the most frequent localization of the extranodular non Hodgkin's lymphoma. The chief clinical and histological characteristics were analyzed as were the evolution and response to treatment of 25 patients diagnosed with primary gastrointestinal lymphoma (PGIL) in one center over a period of eight years. To establish the diagnosis of PGIL the Dawson criteria were used and the state was determined by the Ann-Arbor classification modified by Musshoff. To histologically classify of the PGIL the Working Formulation was followed. The influence of the clinical, histological characteristics and the state of the obtention of complete remission (CR), the survival free period of the disease (SFD) and global survival (GS) were analyzed. The mean age of the series was 56 years (standard deviation 15 years) (12 males). The most frequent localization was gastric followed by the small intestine and the large intestine. Abdominal pain and weight loss were the most frequent clinical manifestations in the PGIL, regardless of its site. In 12 patients the PGIL was of an intermediate grade of malignancy, 8 were of low grade and 5 of high grade. The state was IE in 11 patients, IE1 in 9 and IIE2 in 5. The most used treatment was radical surgery followed by polychemotherapy. Complete remission was obtained in 15 patients and 2 recurred. The foreseen SFP at 7 years was 69% of the cases and GS was 53%. In IE state patients was most frequently obtained and GS was also more prolonged in these patients. In the present series the gastric localization of patients with primary gastrointestinal lymphoma was more frequent than intestinal localization. The HNL of intermediate and high grades of malignancy predominated those of low grade. The prognosis of patients with primary gastrointestinal lymphoma in a IE state was more favorable than the remaining patients. In turn, surgery constituted a good option in the initial treatment of patients with primary gastrointestinal lymphoma.


[Sudden cardiac death in the counties of Girona]. Data on sudden cardiac death in Spain in scarce. Mortality rates from sudden cardiac death occurring in six counties of Girona (including urban, industrial, and rural areas) between October 1987 and September 1988 were assessed. From a total of 1,573 deaths in residents of the studied area aged between 25 and 74 years, 222 cases with a suggestive diagnosis of sudden cardiac death were selected. Data that confirmed the diagnosis and the time elapsed from the initial clinical symptoms and death were obtained by inquiring physicians who signed the death certificates, relatives or witnesses and by reviewing the hospital records. Of a total of 137 deaths of cardiac origin, there were 107 cases of sudden cardiac death (which occurred within 24 hours after the onset of symptoms). The mortality rate of sudden death of cardiac origin was 37.5 per 100,000 inhabitants, that was significantly higher among men (67.8 in men and 15.4 in women). The mortality rate showed a statistically significant increase in the older age groups (28.4 per 100,000 inhabitants in the age group of 45-54 years, 69 in the group of 55-64 years, and 129.7 in the group of 65-74 years). Death occurred within the first hour after the onset of symptoms in 59 patients, 17 of whom were admitted to a hospital. Only 35% of the total 107 patients were treated in hospital. Mortality rate of sudden cardiac death in Girona is low. Few patients dying from sudden cardiac death could have medical care.


[Bacterial peritonitis in cirrhosis. Prospective study of 80 episodes]. The high incidence, recognition of the different variants and the important changes introduced in the methods of diagnosis of bacterial peritonitis of cirrhotic patients led the authors to study this entity according to the most up to date and standardized criteria. The clinical-epidemiological, biological and bacteriological characteristics of 80 episodes of ascitic fluid infection (AFI) were studied. Diagnostic paracentesis was performed in all the patients and were evaluated according to a prospective study protocol. The patients with AFI were classified into three groups: 1) spontaneous bacterial peritonitis (SBP) (761 episodes); 2) secondary bacterial peritonitis (BP) (5 cases); and 3) bacteriascitis (BA) (4 episodes). The clinical manifestations were not specific, with absence of abdominal pain and fever in 9% of the cases. There were no clinical differences between the variants of AFI. The ascitic fluid culture was positive in 80% of the cases of SBP while it was only so in 9% of the Gram stain. Most of the cases of peritonitis were caused by Gram negative bacilli (77%), predominantly E. coli (64%). The culture was positive in 100% of the cases of BP, generally being polymicrobian, and Gram stain was positive in 67% of the cases. The inflammatory response of the ascitic fluid in the different variants of AFI was gradual, being lower in BP and nul in BA. In 52 episodes of SBP (73.8%) the infection was cured. In the group of SBP all the patients died without having resolved the peritonitis (p < 0.001). Forty-four patients (62%) with BP were discharged from hospital. A multivariate logistic regression analysis demonstrated that from a total of 32 variables analyzed, only the absence of fever (p < 0.0001), the presence of advanced hepatic encephalopathy (p < 0.0001), the presence of leukocytosis, serum bilirubin higher than 137 mumol/l, urine sodium levels lower than 10 mmol/l, the level of LDH in ascitic fluid higher than 2 microKat/l and ascitic fluid culture positivity had independent prognostic value. Infection of ascitic is a frequent entity. Although its variants are clinically indifferentiable, there are clear biochemical, bacteriological and evolutive differences. The mortality of ascitic fluid infection remains high. Its prognosis fundamentally depends of the degree of evolution of the hepatopathy and the severity of the peritoneal infection.


[Immunologic prognostic parameters in infection by the human immunodeficiency virus]. To evaluate the use of quantitative and functional immunologic parameters as prognostic markers of infection by the human immunodeficiency virus (HIV). The number of CD4 and CD8 lymphocytes, the CD4/CD8 ratio, the percentage of interleukin 2 (IL-2) receptors, the response to phytohemaglutinin (PHA) and the production of interferon tau (IFN-tau), were analyzed in 85 patients with HIV infection: 14 with acquired immunodeficiency syndrome (AIDS) (stage IV), 16 with persistent generalized adenopathies (stage III), and 55 asymptomatic patients (stage II). Similarly, a control group of 35 blood donors with negative HIV serology was studied. Over a period of 30 months, 17 patients (5 of stage III and 12 of stage II) evolved to stage IV. In a multivariate analysis the decrease in the number of CD4 lymphocytes in stage II and the decrease in the production of IFN-tau in stage II and III were the parameters associated with progression to stage IV. The decrease in the production of interferon tau in patients with infection by the human immunodeficiency virus in stage II and III as well as the decrease in the number of CD4 lymphocytes in stage II are prognostic factors associated with the evolution to stage IV of the infection.


[Comparative study of human cutaneous sensitivity to 2 and 5 international units of the PPD RT 23 tuberculin with Tween 80]. The aim of this study was to know whether the human reaction to the Mantoux test with 5 UT of PPD RT 23 is similar to that achieved with the same test but with 2 UT of the same substance. A simultaneous double Mantoux test was used at doses of 2 UT and another of 5 UT of the same trade mark of tuberculin PPD RT 23 with Tween 80 in 2,575 individuals. The subjects were distributed into two different groups of different ages, taking into consideration the possible presence of BCG vaccination. The doses of 5 UT produced a greater number of tuberculin positive individuals and a greater diameter of induration of reaction than that of the doses of 2 UT in both groups and with significant statistical differences. One hundred ninety-six (7%) subjects were tuberculin positive with 5 UT and negative with 2 UT. The reactions produced by the Mantoux test with 5 and 5 UT PPD RT were different since the two doses are not bioequivalent.


[Clinical application of the biological variability data of the thyroid hormones]. The selection of laboratory tests with greater effectiveness for identifying patients with thyroid disorders (sensitivity) from non affected subjects (specificity) is, at present, under discussion. The study of biological variation can contribute to point out the laboratory tests with greater effectiveness. Total blood was collected daily for five consecutive days from 25 healthy volunteers, which maintaining their usual life style all over the period. The biological coefficients of variation--within and between--subject, the individuality indexes and the critical differences between consecutive results are estimated. The effect of pulsatility over the results obtained is also discussed. The most effective laboratory test for the diagnosis of thyroid disorders is TSH, with the precaution of doing a second analysis if the first result falls close to either the lower or higher reference range limits. The best laboratory tests for the monitoring of hypo- and hyperthyroidism are total T4 and free T4, in which a critical difference between consecutive results higher than 15% indicates a significant change in the patient status.


[Can a prostatic adenocarcinoma simulate an acute myocardial infarction?]. The assay for the MB isoenzyme of creatine kinase is widely used in the diagnosis of acute myocardial infarction. Patients with metastatic carcinoma of the prostate may have an elevated serum creatine kinase BB fraction, which by immunoinhibition method may be read mistakenly as creatine kinase MB. We report the case of a patient with a history of myocardial injury, chest pain, total CK above of reference range and CK-MB isoenzyme, determinated with an immunoinhibition technique, larger than 100% of enzymatic activity of total CK, that was carrier of a prostatic adenocarcinoma in stage D2. We comment the diseases in which the CK-BB fraction may be elevated, discuss the laboratory methods for the determination of creatine kinase isoenzymes, and revised, briefly, the properties of the new immunoassays, that measure mass concentration of creatine kinase MB, in the diagnosis of acute myocardial infarction.


[Serum lipoprotein (a) levels during treatment with LDL apheresis for homozygous familial hypercholesterolemia]. Due to the double atherogenic and antifibrinolytic action of lipoprotein (a) (Lp [a]) and its predictive value of cardiovascular disease in hypercholesterolemic patients, we document in the present work the changes in Lp (a) levels of a patient with homozygous familial hypercholesterolemia after one year of LDL-apheresis treatment. A child with LDL-receptor deficiency under weekly LDL-apheresis treatment with dextran-sulfate columns. Serum samples were taken in basal conditions (pre-apheresis) and post-apheresis, as well as from the perfusion system to evaluate the lipoprotein retention capacity of the columns. Samples were processed for Lp (a) determination by ELISA with polyclonal antibodies. When the treatment was initiated, the patient's Lp (a) serum levels were very high (997 mg/l), and they reduced progressively with the apheresis sessions. After one year of treatment, maximum Lp (a) concentration is only slightly higher than 400 mg/l, whereas minimum Lp (a) concentration is lower than 50 mg/l. Dextran-sulfate columns in the apheresis system retain every lipoprotein containing apo B, including LDL and Lp (a), with high affinity and high capacity in such a way that the treatment of three-fold the plasma volume of the patient results in an 85% decrease of Lp (a) levels. After each LDL-apheresis treatment, there is a progressive increase in Lp (a) concentration. The analysis of these data allowed the estimation of the fractional catabolic rate of Lp (a) in the patient, which was 0.08 pools/day. Simultaneous treatment with lovastatin (20 mg/day) did not alter this parameter or Lp (a) serum concentration. After one year of weekly LDL-apheresis treatment, the patient's average Lp (a) serum concentration is lower than 300 mg/l, which is below the risk threshold level. Therefore, apheresis with dextran-sulfate columns is a very effective treatment for the reduction of both LDL and Lp (a) serum concentrations in homozygous familial hypercholesterolemia.


[Ferrokinetic studies in the initial evaluation of idiopathic myelofibrosis: results in 18 patients]. Since there is no effective treatment for idiopathic myelofibrosis (IM) the determination of possible factors which are involved in the appearance of anemia in this disease may be important from a practical point of view. The results of the initial ferrokinetic study analyzed in 18 patients with IM included plasma clearance (T1/2) and globular incorporation (U max) of 59Fe in addition to the uptake of 59Fe in the sacrum, spleen and liver in 16 patients. The clinical-hematologic and histologic data of the different groups of patients identified according to the results of the study were compared. Three ferrokinetic patterns were observed: 1) normal or increased erythropoiesis (8 patient), 2) inefficient erythropoiesis (7 patients), and 3) aplastic pattern (3 patients). The only difference observed between the three groups was the existence of lower levels of Hb and reticulocytes in the subjects with aplastic type pattern. In contrast, although there was an inverse correlation between the medullar and extramedullar uptake of iron (p = 0.018) no relation was observed between the latter and the size of the spleen or liver. The results obtained in this study indicate that IM behaves heterogeneously from a ferrokinetic point of view.


[Haemophilus influenzae pulmonary infection in patients infected with the human immunodeficiency virus]. Haemophilus influenzae has frequently been identified as the etiologic agent in pneumonias of patients with the human immunodeficiency virus (HIV) infection. The experience of the authors is reviewed and the significance of isolating this microorganism in respiratory samples commented upon. The clinical, radiological and microbiological data of patients with HIV infection in whom H. influenzae was identified in blood, lung tissue, or samples of the lower respiratory tract obtained by fibrobronchoscopy were retrospectively evaluated. Twenty cases were diagnosed with 75% presenting bilateral lung infiltration. In 70% the isolation sample was that of bronchoalveolar lavage. In 40% of the total another microorganism was identified in coinfection with H. influenzae, of which Mycobacterium tuberculosis was the most frequent. Thirty-five percent of the cases presented antecedents of one or several previous pulmonary infections. H. influenzae infection was not observed with either concomitant or previous infections in 20% of the patients. A high frequency of pneumonias by Haemophilus influenzae with bilateral radiologic presentation have been found. H. influenzae is frequently demonstrated as in coinfection with other agents. The role that this microorganism has in pulmonary infection of patients with HIV infection is not clearly defined.


[Cost-effectiveness study of prevaccination screening tests in vaccination against hepatitis B in hospital health professionals]. The aim of this study was to know the cost-effectiveness of a vaccination program of hospital personnel against hepatitis B as compared to vaccination strategy with previous screening tests versus vaccination without screening. The costs of the process of vaccination with and without previous screening tests for hospital personnel (first year residents = MIR R1 and staff doctors) was calculated taking, not only the cost of the vaccinations, but also the costs of withdrawal, injection, antibody determination and the displacement costs of the subject into account. In the case of a MIR-R1, the cost of vaccination without previous screening is 12,492 pesetas, with the cost for a staff doctor being 15,092 pesetas. The vaccination strategy with previous antibody screening tests is only profitable with prevalences of 28.77% of positivity in the case of MIR-R1 and 29.55% in staff doctors. This study defends the elimination of previous antibody screening tests in vaccination against hepatitis B since the legal obligation of previous screening tests is no longer applicable. Moreover, vaccination is practically innocuous and prevaccination screening tests are only profitable with prevalences os seropositivity higher than 28% in the case of MIR-R1 and 29.55% in the case of staff doctors which are ciphers much higher than those of the prevalence of seropositivity normally found among Spanish hospital personnel.


[Contribution of magnetic resonance imaging in the early diagnosis of epidural metastasis]. Vertebral bone metastases represent the most frequently affected region within the skeleton. They are of important relevance because of the risk of medullar compression. The diagnosis of medullar canal invasion is of particular interest in order to prevent neurological dysfunction. A prospective study was carried out to detect the frequency and degree of invasion of the spine. Twenty-eight patients were studied (13 males and 15 females), with a median age of 61 years (range 35-85), with cancer diagnosis and vertebral bone metastases, and local or radicular pain, without signs or symptoms suggesting myelopathy. Neurological, physical examination, radiological study (anteroposterior and lateral) and magnetic resonance imaging (MRI) study was performed in all patients to detect medullar canal invasion. Local pain was present in 43% of patients (n = 12), and radicular in 57.1% (n = 16). The most frequent radiologic vertebral involvement was thoracic (46.4%), with 71% of vertebral body collapse. MRI showed epidural space invasion in 75% of patients (n = 21), with a degree superior to 50% in 43%. The beginning of vertebral pain in a patient with cancer diagnosis, with evidence of bone invasion after radiological study, represents a major indicator to perform a MRI study to detect epidural involvement.


[Effects of captopril on left ventricular morphology and function in essential arterial hypertension]. The presence of diastolic dysfunction in a hypertensive patient is not necessarily associated to the existence of left ventricular hypertrophy. The aim of this study was to determine whether the reduction of the left ventricular mass in hypertensive patients treated with captopril is accompanied by an improvement of the diastolic filling indexes. Nineteen patients with essential hypertension were studied before and after one year of treatment with captopril. Different morphological indexes and diastolic function of the left ventricle were evaluated by mode M and Doppler echography. The indexes of left ventricular mass diminished significantly with treatment with captopril. The thickness of the ventricular walls diminished with treatment although not significantly. No significant modification was observed in the indexes of diastolic function (quotient of speed of protodiastolic filling/speed of telediastolic filling and time of deceleration of transmitral fluid during diastole) following the treatment period. Diminution of the left ventricular mass induced by captopril in hypertensive patients is not accompanied by an improvement in ventricular filling. It is suggested that myocardial hypertrophy is not responsible for diastolic dysfunction of arterial hypertension.


[Acute transverse myelitis and primary antiphospholipid syndrome]. The case of a 39 years old woman with acute transverse myelitis manifested as a syndrome of the anterior spinal artery is presented. Etiologic investigation diagnosed a primary antiphospholipid syndrome because of the finding of significantly high titers of anticardiolipin antibodies discarding the presence of systemic lupus erythematosus for the lack of sufficient diagnostic criteria. The association between both clinical pictures is infrequent.


[Multifocal motor neuropathy after administration of gangliosides]. A case of a 38 years-old male with motor neuropathy with multifocal conduction blocks following the administration of ganglioside therapy is reported. There was generalized weakness without areflexia and normal parameters of the spinal fluid, including protein values. Electrophysiological data showed multiple conduction blocks with normal nerve conduction velocities. Antibodies against asialo-GM1 gangliosides were present in the cerebrospinal fluid. There could be a relationship between the ganglioside administration and the development of an immune-mediated neuropathy. Several cases of demyelinating polyradiculoneuritis after ganglioside treatment have been reported. If this association is confirmed, the apparent lack of toxicity of gangliosides should be reconsidered.


Spinally-mediated antinociception is induced in mice by an adenosine kinase-, but not by an adenosine deaminase-, inhibitor. Relative involvement of adenosine deaminase and adenosine kinase in antinociception induced by endogenous adenosine was investigated. Antinociception induced by 5'-amino 5'-deoxyadenosine (5'-ADAdo; an adenosine kinase inhibitor) and deoxycoformycin (dCF; an adenosine deaminase inhibitor) administered i.t. was determined using the mouse tail-flick assay. Dose- and time-dependent antinociception was observed following i.t. administration of 5'-ADAdo, but not dCF. Antinociception induced by 5'-ADAdo was reversed by coadministration i.t. of theophylline, an adenosine receptor antagonist, in a dose-dependent manner. These data provide preliminary evidence that adenosine kinase plays a more significant physiological role than adenosine deaminase in the regulation of adenosine involved in spinally-mediated antinociception.