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PubMed1999

Immunogenicity of three Haemophilus influenzae type b protein conjugate vaccines in HIV seropositive adults and analysis of predictors of vaccine response.

HIV-seropositive adults may be at increased risk of infection due to Haemophilus influenzae type b (Hib) as compared with HIV-seronegative adults. Protein conjugate vaccines have been demonstrated to induce protective levels of antibodies against Hib in immunocompetent infants and also in HIV-seropositive infants. In this study we determined the immunogenicity of three protein conjugate Hib vaccines (PRP-D, HbOC, HbNOMP) in 135 HIV-seropositive adults who received one dose of Hib vaccine. Anti-polyribosylribitol phosphate (PRP) antibodies were measured at 0, 1, 3 and 12 months postimmunization by the Farr method. We demonstrate that all three vaccines are highly immunogenic and result in protective (> 1.0 microg/ml) levels of antibody. Overall the anti-PRP antibody level was > 1.0 microg/ml in 26% of patients preimmunization, 91% at both 1 and 3 months, and 79% at 12 months postvaccination. Comparison of responses to the three vaccines over time demonstrated differences in the mean geometric anti-PRP antibody level at 1 month (p=0.03) and the 12 month time points (p=0.03) with lower geometric mean levels in the HbNOMP group, though baseline differences in groups limit the interpretation of these findings. In a univariate analysis of baseline characteristics which predicted poor vaccine response, low total IgG2 levels preimmunization predicted a poor antibody response at 1 month (p < 0.01) and at 12 months (p=0.05), while low CD4 T-cell count predicted poor response at 12 months (p < 0.01). We conclude that all three US licensed protein conjugate Hib vaccines are immunogenic in HIV-seropositive adults, and that baseline CD4 T-cell count and IgG2 levels predict the likelihood of antibody response to vaccine.

Adult↗
PubMed2000

Neurological dysfunction associated with postoperative cerebellar mutism.

BACKGROUND AND OBJECTIVES: The postoperative cerebellar mutism syndrome (CMS) is an unique acute postoperative complication characterized by transient decrease in speech output (often mutism), apathy, irritability as well as global cerebellar dysfunction. As much as 25% of patients undergoing a resection of a cerebellar or IV ventricular tumor may develop such a syndrome. In this retrospective study we characterize the clinical features of the CMS and explore potential etiologic mechanisms. METHODS: We conducted a retrospective analysis of medical records and imaging tests of 8 consecutive patients with the CMS identified through the database of the Children's Hospital and Dana-Farber Cancer Institute, Boston, and compared with a control group of 8 unaffected children undergoing a comparable tumor resection. RESULTS: In contrast to the control group, children in the affected group had marked decrease in speech output and comprehension, apathy and lack of initiative, inattention, persistent eye closure, flaccid hemiparesis and a severe global cerebellar dysfunction. Swallowing difficulties and bowel and bladder dysfunction were also observed. The median duration of the syndrome as judged by the persistence of the communication abnormalities was 4 weeks. The recovery was near complete with exception for a persistent global cerebellar dysfunction. A comparison of CT and MRI scans of children in both groups failed to identify distinguishing features. CONCLUSION: A surgical lesion of the midline cerebellum can cause a complex neurological dysfunction such as the CMS. Thus, we postulate that the cerebellum and its connections function as a 'modulatory system' in control of both motor and non-motor functions, including attention and language.

Akinetic Mutism↗
PubMed2001

MR imaging-guided focused ultrasound surgery of fibroadenomas in the breast: a feasibility study.

PURPOSE: To test the feasibility of noninvasive magnetic resonance (MR) imaging-guided focused ultrasound surgery (FUS) of benign fibroadenomas in the breast. MATERIALS AND METHODS: Eleven fibroadenomas in nine patients under local anesthesia were treated with MR imaging-guided FUS. Based on a T2-weighted definition of target volumes, sequential sonications were delivered to treat the entire target. Temperature-sensitive phase-difference-based MR imaging was performed during each sonication to monitor focus localization and tissue temperature changes. After the procedure, T2-weighted and contrast material-enhanced T1-weighted MR imaging were performed to evaluate immediate and long-term effects. RESULTS: Thermal imaging sequences were improved over the treatment period, with 82% (279 of 342) of the hot spots visible in the last seven treatments. The MR imager was used to measure temperature elevation (12.8 degrees -49.9 degrees C) from these treatments. Eight of the 11 lesions treated demonstrated complete or partial lack of contrast material uptake on posttherapy T1-weighted images. Three lesions showed no marked decrease of contrast material uptake. This lack of effective treatment was most likely due to a lower acoustic power and/or patient movement that caused misregistration. No adverse effects were detected, except for one case of transient edema in the pectoralis muscle 2 days after therapy. CONCLUSION: MR imaging-guided FUS can be performed to noninvasively coagulate benign breast fibroadenomas.

Adult↗
PubMed1993

Combination chemotherapy in refractory immune thrombocytopenic purpura.

BACKGROUND: Chronic idiopathic thrombocytopenic purpura is a destructive thrombocytopenia caused by an autoantibody. About 80 percent of patients with chronic idiopathic thrombocytopenic purpura have remissions after either corticosteroid therapy or splenectomy. Some patients with resistant disease respond to other agents, but a substantial group are refractory to therapy. METHODS: We used combination chemotherapy to treat 10 patients with refractory immune thrombocytopenia. An average of 6.8 (range, 3 to 10) previous therapies, including corticosteroids and splenectomy, had been unsuccessful in these patients. The patients received from three to eight cycles of therapy consisting of cyclophosphamide and prednisone combined with either vincristine (one patient), vincristine and procarbazine (four patients), or etoposide (six patients, including one patient who received four cycles each containing procarbazine and etoposide). RESULTS: Among the 10 patients, 6 had complete responses (platelet count, > 180,000 per cubic millimeter); of these, 4 patients had responses that persisted for more than 11, 30, 54, or 126 months, 1 had a relapse 9 months after therapy but had a remission with further therapy and remained in remission for 48 months before dying of an unrelated illness, and another relapsed just before her fifth course of therapy. Two patients had partial responses (platelet count, > 50,000 per cubic millimeter); the platelet counts in one remained stable for more than nine months after the end of therapy, and the other patient relapsed. The remaining two patients had no response. Complete responses were associated with a disappearance or marked decrease in the level of platelet-associated autoantibody. CONCLUSIONS: Combination chemotherapy is beneficial in some patients in whom immune thrombocytopenia is refractory to corticosteroids and splenectomy.

Adult↗
PubMed2000

Critical thinking in graduate medical education: A role for concept mapping assessment?

CONTEXT: Tools to assess the evolving conceptual framework of physicians-in-training are limited, despite their critical importance to physicians' evolving clinical expertise. Concept mapping assessment (CMA) enables teachers to view students' organization of their knowledge at various points in training. OBJECTIVE: To assess whether CMA reflects expected differences and changes in the conceptual framework of resident physicians, whether concept maps can be scored reliably, and how well CMA scores relate to the results of standard in-training examination. DESIGN, SETTING, AND PARTICIPANTS: A group of 21 resident physicians (9 first-year and 12 second- and third-year residents) from a university-based pediatric training program underwent concept map training, drew a preinstruction concept map about seizures, completed an education course on seizures, and then drew a postinstruction map. Maps were scored independently by 3 raters using a standardized method. The study was conducted in May and June 1999. MAIN OUTCOME MEASURES: Preinstruction map total scores and subscores in 4 categories compared with postinstruction map scores; map scores of second- and third-year residents compared with first-year residents; and interrater correlation of map scores. RESULTS: Total CMA scores increased after instruction from a mean (SD) preinstruction map score of 429 (119) to a mean postinstruction map score of 516 (196) (P =.03). Second- and third-year residents scored significantly higher than first-year residents before instruction (mean [SD] score of 472 [116] vs 371 [102], respectively; P =.04), but not after instruction (mean [SD] scores, 561 [203] vs 456 [179], respectively; P =.16). Second- and third-year residents had greater preinstruction map complexity as measured by cross-link score (P =.01) than first-year residents. The CMA score had a weak to no correlation with the American Board of Pediatrics In-training Examination score (r = 0.10-0.54). Interrater correlation of map scoring ranged from weak to moderate for the preinstruction map (r = 0.51-0.69) and moderate to strong for the postinstruction map (r = 0.74-0.88). CONCLUSIONS: Our data provide preliminary evidence that concept mapping assessment reflects expected differences and change in the conceptual framework of resident physicians. Concept mapping assessment and standardized testing may measure different cognitive domains. JAMA. 2000;284:1105-1110

California↗
PubMed1996

Magnetic resonance imaging changes after stereotactic radiation therapy for childhood low grade astrocytoma.

BACKGROUND: Stereotactic radiotherapy (SRT) is fractionated radiotherapy delivered under stereotactic guidance to produce highly focal and precise therapy. We studied the incidence of imaging changes that can mimic tumor progression after completion of SRT for childhood low grade astrocytoma. METHODS: Between June 1992 and September 1994, we prospectively treated 28 children with low grade astrocytomas with SRT. The patients ranged in age from 2 to 22 years (median: 10 yrs) and none had received prior radiation therapy or radiosurgery. Routine fractionation was employed (180-200 centigray[cGy]) to a total dose of 5220-6000 cGy over 5 to 6 weeks. All of the patients underwent initial and follow-up magnetic resonance imaging (MRI) according to protocol. RESULTS: Median clinical follow-up for the 28 patients was 24 months (range, 5-32 mos) with a median radiographic follow-up of 15 months (range, 3-26 mos). Fifteen patients had reduction in tumor size, one patient had stable disease. Twelve patients (43%) developed increased size of the lesion, increased signal intensity or enhancement, cysts or cavitations, and an increase in edema or mass effect on follow-up MRI. Most of these changes occurred between 9 and 12 months after the start of SRT and resolved or decreased by 15 to 21 months. All but one patient had normal or stable neurologic examinations. CONCLUSIONS: Treatment-related MRI changes are common after conventionally fractionated schedules using stereotactic radiation techniques for patients with low grade astrocytomas. These changes can be distinguished from tumor progression by their transient nature as well as the general absence of clinical symptoms.

Adolescent↗
PubMed1989

Prospective study of amikacin versus netilmicin in the treatment of severe infection in hospitalized patients.

PURPOSE: Four previous studies comparing netilmicin and amikacin have yielded inconclusive results concerning efficacy and rates of nephrotoxicity and ototoxicity. For this reason, we conducted a prospective, randomized, controlled trial of the two drugs in the treatment of hospitalized patients with severe infection. PATIENTS AND METHODS: A total of 202 patients were enrolled in the study; 100 received netilmicin and 102 received amikacin. Concomitant antimicrobials were restricted to metronidazole and benzylpenicillin. Peak and trough aminoglycoside levels were assayed within the first 36 hours and at least every 72 hours thereafter. A full blood cell count, serum electrolytes, creatinine, bilirubin, and liver enzymes were measured before therapy, weekly thereafter, and within 48 hours after the discontinuation of therapy. Nephrotoxicity and ototoxicity were assessed in patients. A standard agar dilution procedure was used to determine minimal inhibitory concentrations. RESULTS: No significant pretreatment differences were found between the two groups. Patients in the amikacin group responded significantly better to treatment than did patients in the netilmicin group (90% versus 79%; p less than 0.05). A notable finding was the markedly inferior response rate of Pseudomonas aeruginosa infections to netilmicin as compared with amikacin (13 of 24 with a favorable response compared with 25 of 26). No significant difference in ototoxicity was found, whereas nephrotoxicity appeared to be significantly less with amikacin (4% versus 12%, p less than 0.05). Although amikacin seemed less nephrotoxic than netilmicin, this may have been related to the significantly greater number of patients with initial renal dysfunction who received netilmicin. CONCLUSIONS: Amikacin appears to be significantly more efficacious than netilmicin for the treatment of P. aeruginosa infections, especially those in non-urinary tract sites. There is no apparent difference between the two drugs in terms of ototoxicity.

Acute Disease↗
PubMed1991

Infection in the myelodysplastic syndromes.

PURPOSE: To determine the incidence, characteristics, and outcome of infection in patients with myelodysplastic syndromes (MDS) and risk factors that may lead to infection. PATIENTS AND METHODS: We reviewed infections that occurred in 86 consecutive patients with MDS who received care from 1968 to 1986 at a university-affiliated Veterans Affairs Medical Center. Time lines charting the course of each patient with MDS were created and included infections, MDS subgroup at the time of presentation and at the time of each infection, peripheral neutrophil counts, and therapies for MDS. RESULTS: Infections occurred at a rate of nearly one per patient year of observation. Infection rates were associated with MDS subgroup as follows: refractory anemia with or without ringed sideroblasts (RA +/- RS) less than refractory anemia with excess blasts (RAEB) less than RAEB in transformation (RAEB-T). The group of RA +/- RS patients who had erythroid abnormalities but minimal or no dyspoiesis of other cell lines had the lowest rate of infections. Infection rates were higher in patients with less than or equal to 1,000 neutrophils/microL blood than in patients with greater than 1,000 neutrophils/microL blood for each classifiable MDS subgroup. Neutrophil concentration and MDS subgroup were independent risk factors for infection in patients with MDS. Bacterial pneumonias and skin abscesses were the most common infections. Infection was the most common cause of death during MDS, accounting for 64% of deaths, and was more common than transformation to acute leukemia as a cause of death. CONCLUSION: Infection is a common, life-threatening problem in patients with MDS. Neutropenia and MDS subgroup are each risk factors for infection. Clinicians should aggressively evaluate patients with fever and MDS for infection, especially pneumonia and skin infections.

Adult↗
PubMed1996

Prophylactic antibiotics for the prevention of early infection in multiple myeloma.

PURPOSE: Patients with multiple myeloma are at increased risk for bacterial infection. During the first 2 months of initial chemotherapy the rate of infection is twice that experienced during the remainder of the disease course. As many as one-third of these early infections are fatal, and many more prevent adequate administration of chemotherapy. This study was designed to determine whether the morbidity and mortality of early infection can be prevented by prophylactic administration of trimethoprim-sulfamethoxazole (TMP-SMX). PATIENTS AND METHODS: Eligible patients about to begin chemotherapy for multiple myeloma were randomly assigned to prophylaxis for 2 months or to no prophylaxis (control). Antibiotic prophylaxis consisted of TMP-SMX 160/800 mg orally every 12 hours administered for the first 2 months of initial chemotherapy. All patients were observed for infection for 3 months after the start of chemotherapy. RESULTS: Of 57 patients entered into the study, 54 were evaluable, representing 13.1 patient-years of observation. The 28 TMP-SMX patients and 26 control patients were comparable in terms of chemotherapy regimen, age, gender, stage, and bone marrow function. Bacterial infection during the 3-month study period occurred in 11 control patients but in only 2 patients assigned TMP-SMX (P = 0.004). Eight severe infections occurred in controls compared with 1 in a TMP-SMX patient (P = 0.010) leading to 4 and 1 infection deaths, respectively (P = not significant). Severe infections included 5 pneumonias (3 with sepsis), 2 urinary tract infections with complicating pneumonia or sepsis, 1 diverticulitis with perforation, and 1 staphylococcal scalded skin syndrome. None of the 4 nonbacterial infections was severe. The rate of bacterial infection was 2.43 per patient-year for controls and 0.29 per patient-year for the TMP-SMX group (P = 0.001). Toxicity (skin rash 6 patients, nausea 1 patient) was not life-threatening but required discontinuation of TMP-SMX in 25% of patients. CONCLUSION: Administering TMP-SMX for the first 2 months of initial chemotherapy is effective, inexpensive prophylaxis for early bacterial infection in multiple myeloma.

Aged↗
PubMed1999

Study of cavernosal arterial anatomy using color and power Doppler sonography: impact on hemodynamic parameter measurement.

PURPOSE: We report on color and power Doppler ultrasound to study cavernosal arterial anatomy, and evaluate the impact of vascular anatomy on the measurement of hemodynamic parameters. MATERIALS AND METHODS: Cavernosal arterial anatomy of 42 patients with erectile dysfunction was evaluated using color and power Doppler ultrasound. A computerized waveform analysis was used to measure peak systolic velocity, end diastolic velocity and resistive indexes at various sites, including the penile crura, and proximal mid and distal penile shaft. Hemodynamic parameters were measured in each artery in cases of bifurcated or multiple cavernosal arteries. RESULTS: A total of 80 corpora were adequately evaluated. We observed a single artery without major proximal branches in 37 corpora, a single artery with major proximal branches in 17, bifurcated arteries in 15, 2 cavernosal arteries in 4 and marked arterial tortuosity in 1. In 6 corpora the main cavernosal artery arose from the superficial dorsal artery. The peak systolic velocity was highest at the proximal and decreased progressively at the distal site. The peak systolic velocity plus or minus standard deviation at the mid shaft averaged 69.3+/-30.0% of that at the proximal penile shaft. Of the 15 corpora with bifurcated arteries 67% had a 40% or greater difference in peak systolic velocity between the branches. Complete or partial occlusion of the cavernosal artery was identified in 3 corpora, and a dramatic difference in peak systolic velocity proximal and distal to the stenotic area was demonstrated. CONCLUSIONS: Cavernosal arterial anatomy is variable and hemodynamic parameters differ at various sites of measurement. Parameters should be measured at a consistent proximal site to obtain a reliable assessment. Variations in vascular anatomy and cavernosal artery pathology should be considered when interpreting color Doppler sonography and before penile vascular surgery.

Adult↗
PubMed2001

Children with headache suspected of having a brain tumor: a cost-effectiveness analysis of diagnostic strategies.

OBJECTIVE: To assess the clinical and economic consequences of 3 diagnostic strategies-magnetic resonance imaging (MRI), computed tomography followed by MRI for positive results (CT-MRI), and no neuroimaging with close clinical follow-up-in the evaluation of children with headache suspected of having a brain tumor. Three risk groups based on clinical variables were evaluated. MATERIALS AND METHODS: A decision-analytic Markov model and cost-effectiveness analysis was performed incorporating the risk group prior probability, MRI and CT sensitivity and specificity, tumor survival, progression rates, and cost per strategy. Outcomes were based on quality-adjusted life year (QALY) gained and incremental cost per QALY gained. RESULTS: For low-risk children with chronic nonmigraine headaches of >6 months' duration as the sole symptom (prior probability of brain tumor 0.01%), no neuroimaging with close clinical follow-up was less costly and more effective than the 2 neuroimaging strategies. For the intermediate-risk children with migraine headache and normal neurologic examination (prior probability of brain tumor 0.4%), CT-MRI was the most effective strategy but cost >$1 million per QALY gained compared with no neuroimaging. For high-risk children with headache of <6 months' duration and other clinical predictors of a brain tumor such as an abnormal neurologic examination (prior probability of brain tumor 4%), the most effective strategy was MRI, with cost-effectiveness ratio of $113 800 per QALY gained compared with no imaging. CONCLUSION: Our analysis suggests that MRI maximizes QALY gained at a reasonable cost-effectiveness ratio in children with headache at high risk of having a brain tumor. Conversely, the strategy of no imaging with close clinical follow-up is cost saving in low-risk children. Although the CT-MRI strategy maximizes QALY gained in the intermediate-risk patients, its additional cost per QALY gained is high. In children with headache, appropriate selection of patients and diagnostic strategy may maximize quality-adjusted life expectancy and decrease costs of medical workup.

Adult↗
PubMed1998

Hemodynamic patterns of pharmacologically induced erection: evaluation by color Doppler sonography.

PURPOSE: Penile erection is achieved through hemodynamic mechanisms that can be assessed best with color flow imaging and Doppler waveform analysis. We performed dynamic studies using computer assisted analysis to assess the hemodynamic patterns of pharmacologically induced erection. MATERIALS AND METHODS: A total of 73 color Doppler ultrasound studies was performed in 66 patients with erectile dysfunction. Various blood flow parameters, including peak systolic velocity, end diastolic velocity, mean flow rate, resistive index and artery diameter, were observed continuously and recorded frequently for about 30 minutes after intracorporeal injection of papaverine/phentolamine/prostaglandin E1 mixture. A computerized Doppler waveform analysis of 3 curves or greater was performed for each recording to minimize error. A second injection was administered if the first injection failed to induce a rigid erection. Status of the erection was observed and recorded throughout the study. A computerized graph was generated for each corpus. RESULTS: After intracorporeal injection the time to reach normal or peak velocity varied from 1 to 24 minutes. Among 146 corpus units in 73 color Doppler ultrasound studies we observed the following hemodynamic patterns: I-normal maximal peak systolic velocity (35 cm. per second or greater), sustained; Ia-end diastolic velocity 0 or less with complete erection response (19 units); Ib-end diastolic velocity greater than 0 or incomplete erection response (14 units); II-normal maximal peak systolic velocity (35 cm. per second or greater), transient; IIa-end diastolic velocity 0 or less with complete erection response (21 units); IIb-end diastolic velocity greater than 0 or incomplete erection response (12 units); III-borderline maximal peak systolic velocity (30 to 35 cm. per second); IIIa-end diastolic velocity 0 or less with complete erection response (10 units); IIIb-end diastolic velocity greater than 0 or incomplete erection response (8 units); IV-low maximal peak systolic velocity (less than 30 cm. per second); IVa-end diastolic velocity 0 or less with complete erection response (24 units); and IVb-end diastolic velocity greater than 0 or incomplete erection response (38 units). CONCLUSIONS: Erection is a complex and dynamic process. A new classification of hemodynamic patterns is presented that aids in assessing and interpreting more thoroughly blood flow parameters to stratify more precisely the hemodynamic patterns of erectile dysfunction.

Adult↗
PubMed1994

Stereotactic radiotherapy for pediatric and adult brain tumors: preliminary report.

PURPOSE: Stereotactic radiotherapy is a new modality that combines the accurate focal dose delivery of stereotactic radiosurgery with the biological advantages of conventional radiotherapy (1.8-2.0 Gy/day using 25-30 fractions). The modality requires sophisticated treatment planning, dedicated high-energy linear accelerator, and relocatable immobilization devices. We report here our early experience using stereotactic radiotherapy for intracranial neoplasms. METHODS AND MATERIALS: Between June 1992 and September 1993, we treated 82 patients with central nervous system lesions using stereotactic radiotherapy, delivered from a dedicated 6 MV stereotactic linear accelerator. A head fixation frame provided daily relocatable setup using a dental plate for all patients over 8 years of age. A modified head frame, which does not require a mouthpiece, was used for children requiring anesthesia. The patients ranged in age from 9 months to 76 years. Thirty-three patients were children less than 21 years of age. Selection criteria for the protocol included: (a) focal, small (< 5 cm) radiographically distinct lesions known to be radiocurable (pituitary adenoma, craniopharyngioma, meningioma, acoustic neuroma, pilocytic astrocytoma, retinoblastoma), and (b) lesions located in regions not amenable to surgery or radiosurgery such as the brain stem or chiasm. Standard fractionation and conventional doses were delivered. Patients with low-grade astrocytoma, oligodendroglioma, or ependymoma were treated using a dose escalation regime consisting of conventional doses plus a 10% increase. RESULTS: Although follow-up is 16 months (range 3-16 months), posttreatment radiographic studies in 77 patients have been consistent with changes similar to those found after conventional radiation therapy. To date, reduction of up to 50% of the original volume has been noted in 19 out of 77 patients, and 4 patients had a complete response, 2 with dysgerminoma, and 1 each with astrocytoma and retinoblastoma. In 56 patients disease was either stable or the follow-up was too short for evaluation. While the follow-up is relatively short, there have been no in-field or marginal recurrences. The only unexpected radiographic findings were in three patients with pilocytic astrocytomas, who developed asymptomatic edema in the treatment volume. Accuracy in daily fractionation was excellent. In over 2000 patient setups with 41,000 scalp measurements, reproducibility was found to be within 0.41 mm (median) of baseline readings, allowing for precise immobilization throughout the treatment course. The treatment in all cases was well tolerated with minimal acute effects. Our stereotactic radiotherapy facility can provide fractionated therapy for 10-12 patients a day efficiently and accurately. CONCLUSIONS: The treatment and relocatable stereotactic head frames were well tolerated with minimal acute effects. No long-term sequelae have been noted, although the observation period is short. To fully define the role of stereotactic radiotherapy, we are conducting prospective studies to evaluate neurocognitive and neuroendocrine effects. We expect that this innovative approach will make a significant impact on the treatment of intracranial neoplasms, particularly in children.

Adolescent↗