Fine-needle, negative-pressure lumbar puncture: a safe technique for collecting CSF.
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Adenoviruses are increasingly recognized pathogens that affect blood and marrow transplant (BMT) recipients. Experiences with 2889 adult BMT recipients were reviewed to study the incidence, clinical spectrum, risk factors for dissemination, response to therapy, and outcome of adenovirus infections. Eight-five patients (3%) were diagnosed by means of culture (n=85) or culture and histopathological examination (n=6). Nine patients had asymptomatic viruria, and 76 had symptomatic infections, which included upper respiratory tract infection (n=20), enteritis (n=18), hemorrhagic cystitis (n=10), pneumonia (n=15), and disseminated disease (n=13). The overall mortality rate was 26%. A higher mortality rate was observed among patients with pneumonia (73%) and disseminated disease (61%). Risk factors for dissemination included receipt of an allogeneic transplant, presence of graft-versus-host disease (GVHD), and receipt of concurrent immunosuppressive therapy. Intravenous ribavirin was not associated with an appreciable benefit among 12 patients who received this treatment. In conclusion, adenovirus infections are an important cause of morbidity and mortality in adult BMT recipients, particularly allogeneic transplant recipients with GVHD who are receiving immunosuppressive therapy. The need for an effective, nontoxic antiviral therapy is apparent.
Donor lymphocyte transfusion has gained considerable interest as adoptive cellular immunotherapy for prevention or treatment of relapse after allogeneic stem cell transplantation. This study was designed to compare the yield of CD3(+), CD3(+)4(+), CD3(+)8(+), CD19(+), CD3(-)56(+)16(+), and CD34(+) cells contained in apheresis products from 61 consecutive non-cytokine treated, human leukocyte antigen (HLA)-matched donors for lymphocyte collection with the corresponding apheresis-derived cell yield from 112 consecutive, HLA-matched donors for blood stem cell collection who received recombinant human granulocyte colony stimulating factor (rhG-CSF, filgrastim) 6 microg/kg every 12 hours until cell collection was completed. Apheresis was started on day 4 or 5 of rhG-CSF treatment. The yield of lymphoid subsets was significantly different in the two sample groups, rhG-CSF treated product yields exceeding untreated product yields by a median of 2.1-fold (range: 1.3-2.6). However, the CD34(+) cell yield in rhG-CSF-treated apheresis products exceeded untreated products by 26-fold. A single untreated apheresis procedure was usually sufficient to collect a target dose of 1 x 10(8)/kg CD3(+) cells. Untreated apheresis products contained a median of 0.2 x 10(6)/kg CD34(+) cells. A potential engraftment dose of > or =0.5 x 10(6) CD34(+) cells per kg of recipient body weight was contained in 16% of 57 untreated apheresis products. One single apheresis performed in a normal, untreated donor provides a sufficient amount of CD3(+) cells for adoptive immunotherapy. Compared with that of an rhG-CSF stimulated apheresis product, the CD34(+) cell count is usually, but not always, below the engraftment dose range. RhG-CSF treatment has little effect on the yield of lymphoid subsets collected by apheresis but is highly selective of the release of CD34(+) cells. This report provides baseline data for studies that will show whether other cytokines such as granulocyte macrophage colony stimulating factor (GM-CSF) and/or Flt-3 Ligand can immunomodulate allotransfusates in vivo to improve the graft-vs.-leukemia (GVL) effect after allogeneic stem cell transplantation, while lowering the incidence and severity of graft-vs.-host disease (GVHD).
BACKGROUND: In sentinel lymph node (SLN) biopsy for breast cancer, many centers use same-day preoperative injection of technetium 99mTc-labeled sulfur colloid and intraoperative injection of blue dye for localization of SLNs. Same-day sulfur colloid injections can be problematic because of the variability in sulfur colloid migration times, which can lead to ineffective use of operating room time, and low SLN-to-background radioactivity ratios. We examined the utility of day-before-surgery injections of high dose 99mTc-labeled sulfur colloid injections. METHODS: The day before surgery, high-dose 99mTc-labeled sulfur colloid was injected peritumorally, and a lymphoscintigram was obtained. Intraoperatively, after injection of blue dye, a gamma probe was used to localize SLNs. Nodes that were stained blue or were highly radioactive were considered SLNs and were removed. RESULTS: Lymphoscintigraphy demonstrated drainage in 107 patients (91%). Transcutaneous localization of the SLN was possible in 104 patients (89%). In three patients, all of whom had no drainage demonstrated on lymphoscintigraphy, no SLN was identified at surgery (97.5% success rate for SLN identification). A mean of 2.3 SLNs per patient were identified. Twenty-five patients (21%) had at least one histologically positive SLN. In 23 of these patients, the positive SLN was the SLN with the most radioactivity, and in the remaining two patients, the positive SLN was both blue-stained and hot. CONCLUSION: Day-before-surgery injection of high-dose 99mTc-labeled sulfur colloid results in high rates of transcutaneous and intraoperative identification of SLNs. The delay between injection and surgery did not appear to promote significant passage of sulfur colloid to second-echelon nodes.
BACKGROUND: Ultrasonography is increasingly used to evaluate the nodal status of breast cancer patients and specialized positioning permits assessment of the infraclavicular fossa. However, the incidence and significance of infraclavicular (level III) adenopathy detected sonographically in locally advanced breast cancer (LABC) has not been defined. METHODS: The study population consisted of 146 LABC patients registered in a prospective trial of induction chemotherapy between 1991 and 1996. All patients underwent ultrasound imaging before and after chemotherapy. Median follow-up was 32 months. RESULTS: Forty-two of 146 patients (29%) had suspicious infraclavicular adenopathy; all 42 had additional positive axillary lymph nodes by ultrasound. Disease-free and overall survival for the patients with suspicious infraclavicular adenopathy was significantly worse compared with patients without this feature; disease-free survival 50% versus 68% (P = 0.112); overall survival 58% versus 83% (P = 0.026). CONCLUSIONS: Nearly one third of LABC patients will have infraclavicular lymph node involvement by ultrasound imaging; this finding is a significant adverse prognostic feature, and we recommend that infraclavicular nodal evaluation become a routine component of the sonographic workup of breast cancer patients, particularly if lower axillary lymph nodes appear involved.
NaCl detection thresholds were determined for 12.5- and 50-mm(2) lingual areas at four anterior tongue locations in eight subjects using a device that allowed for accurate temporal and spatial presentation of tastants to small regions of the anterior tongue. The locations, all on the right side of the tongue, were the tongue tip, an area 1.7 cm posterior to the tongue tip, and regions 1.7 and 3.4 cm posterior to the tip along the tongue's lateral margin. Stimulus duration was 0.75 s. Thresholds were established using a two-alternative forced-choice single-staircase procedure, and the number of fungiform papillae at each stimulation site was counted with the aid of videomicroscopy. NaCl thresholds were lower for the 50-mm(2) than the 12.5-mm(2) stimulation area at all target sites, and were directly related to papillary number among and within the stimulated regions. For a given number of papillae, thresholds were lower within the 12.5-mm(2) than within the 50-mm(2) stimulation region, likely reflecting taste bud density and activation of common afferent pathways. The tongue tip was more sensitive than any other tongue region, and the lateral margins were seemingly more sensitive than the lingual centrum. Large individual differences in taste sensitivity and tongue papilla numbers were noted, and some subjects were insensitive to the highest tastant concentrations at the nontip loci. This study empirically demonstrates that NaCl detection sensitivity varies across discrete regions of the anterior tongue and is related to the relative number and density of fungiform papillae.
OBJECTIVES: To determine the efficacy of immediate bedside or office percutaneous, trans-thyroidal injections of a bioabsorbable gelatin material (Gelfoam, Upjohn Co., Kalamazoo, MI) to decrease the risk of aspiration resulting from acute vocal fold immobility. STUDY DESIGN: Retrospective review of patients presenting with acute vocal fold immobility and aspiration or high aspiration risk at an urban, tertiary care university hospital. METHODS: All patients were evaluated by videostroboscopy, functional endoscopic evaluation of swallowing (FEES), and objective voice measures. Patients with acute vocal fold immobility and evidence of aspiration on history or FEES were given the option of medialization by Gelfoam injection. Injections were performed percutaneously in the office or at the bedside under laryngoscopic guidance. FEES was repeated after injection to verify improvement in aspiration. RESULTS: Eleven patients underwent Gelfoam injection for treatment of aspiration and vocal fold immobility. All were significantly improved on post-injection FEES study. All patients were returned to an oral diet, avoiding the need for long-term enteral access. CONCLUSION: Percutaneous Gelfoam injections is a rapid, temporary solution to the common problem of aspiration resulting from acute vocal fold immobility.
Localization and quantitation of 2-nitroimidazole drug binding in low pO2 tumors is a technique that can allow the assessment of hypoxia as a predictive assay. EF5 [2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl) acetamide] is such a drug, and it has been shown to be predictive of radiation response in rodent tumors. Using fluorescence immunohistochemical techniques, we provide data on the presence, distribution, and levels of EF5 binding as a surrogate for hypoxia in human head and neck and uterine cervix squamous cell cancers (SCCs). Six patients with SCC were studied. Four patients had head and neck tumors, and two had uterine cervix cancers. The incubation of fresh tissue cubes in EF3 under hypoxic conditions ("reference binding") demonstrated that all tumors were capable of binding drug, and that this binding varied by a factor of 2.9-fold (174.5-516.1) on an absolute fluorescence scale. In the five patients treated at the lowest drug doses (9 mg/kg), in situ binding was quantitatable. For all six patients, the maximum rate of in situ binding varied by a factor of 6.7 between the lowest and highest binding tumor (24.8-160.3) on an absolute fluorescence scale. In tumors with high binding regions, intratumoral heterogeneity was large, extending from minimal fluorescence (<1%) up to 88.6% of reference binding. In tumors with minimal binding, there was little intratumoral heterogeneity. These studies demonstrate substantial heterogeneity of in situ binding between and within individual squamous cell tumors.
The lifespans of H-2 congenic mice differ significantly. The B10.AKM (H-2m) strain has a median survival time (MST) of 15 months, whereas the B10.BR (H-2k) strain has an MST of 24 months. It was previously shown that B10.AKM mice at 13-15 months of age have immunological function comparable to those of B10.BR mice at 22-26 months of age. These functions include: a low proliferative response, reduced levels of intracellular calcium release [Ca2+]i, and an increase in the frequency of memory helper T-cells (CD4+ CD44hiCD45RBlo). In this report similar deficiencies were demonstrated in B10.AKM mice at 2-4 months of age and show that activated spleen NK1.1+CD4+ T (NKT) cells from young B10.AKM mice produce a significantly higher level of IL-4 but a lower level of IFN-gamma as compared to NKT cells from B10.BR mice of the same age. Also, the cytotoxic activity of natural killer (NK) cells from spleens of young (2-4 months) as well as adult (12-16 months) B10.AKM mice is significantly lower (P < 0.01) than that of NK cells from B10.BR mice. These findings suggest that the NKT activity in young B10.AKM mice is a factor for the early onset of immune dysfunction leading to a shorter lifespan.
BACKGROUND: Cephalic tetanus is a rare form of the tetanus caused primarily by wounds or other infectious processes involving the head and neck. This condition frequently progresses to the generalized form of tetanus with the attendant risks and complications. METHODS: A case report of a young female who developed an unusual form of tetanus after a tongue piercing is presented here. We discuss this disorder as it applies to the contemporary caregiver with a focus on its presentation and recognition. RESULTS: A delay in diagnosis of 13 days from presentation occurred. The patient had a slow, uneventful but incomplete recovery course. She never developed significant airway compromise, nor did she demonstrate any evidence of hemodynamic instability but continued to have right facial weakness up to 6 months after discharge. CONCLUSIONS: A few factors were identified that contributed to the significant delay in diagnosis. The unusual nature of the disease and a lowered index of suspicion on the part of the initial caregivers were probably the major causes. Fortunately, no major adverse sequelae resulted from the delay. However, if this case heralds the onset of a rise in the incidence of tetanus, early recognition and diagnosis would seem essential to avoid much of the morbidity and mortality associated with the disease.
BACKGROUND: Specimen radiography is an important part of breast conservation surgery for ductal carcinoma in situ (DCIS). The objective of this study was to determine whether mastectomy specimen radiography could help in obtaining negative resection margins in patients with DCIS undergoing skin-sparing mastectomy (SSM) with immediate breast reconstruction (IBR). METHODS: Of 95 patients treated at our institution with SSM and IBR for DCIS, 35 had specimen radiography. The mastectomy specimen was first examined grossly and then inked, serially sectioned, and sent for radiographic assessment. Tissue slices containing calcifications were identified for pathologic evaluation. Additional tissue was excised if tumor was found near the inked margins or if calcifications were found near the radiographic margins. RESULTS: Of the 35 patients who had specimen radiography, the radiographic margins were free of calcifications in 30 patients (86%); of these patients, the margins on the final histologic examination were free of tumor in 27 and within 1 mm in 3. The other five patients (14%) had calcifications close to the radiographic margin; four underwent an intraoperative re-excision, but the margin for one of those four patients was still positive on final histologic examination. Margins were found to be negative by both mastectomy specimen radiography and histology in 77% of the patients. Of the 95 patients with DCIS, three patients (3%), none of whom had specimen radiography, developed local recurrences. One of these was successfully re-treated, one died as a result of synchronous distant metastases, and one was lost to follow-up. At a median follow-up time of 3.7 years, 93 patients (98%) were alive and free of disease. CONCLUSIONS: Intraoperative radiography of mastectomy specimens may be useful for assessing margin status and for identifying the location of microcalcifications within tissue slices.
BACKGROUND: The impact of axillary node dissection on breast cancer survival is unclear. Limited axillary surgery has been proposed but may increase regional recurrence rates. Optimal management for axillary recurrence is poorly understood. METHODS: Axillary recurrences were initial treatment failure sites in 44 of 4,255 breast cancer patients (1%) seen at M.D. Anderson Cancer Center, 1982 to 1992. RESULTS: Twenty-one patients (48%) had early stage disease (0, I, II) at diagnosis. With 70.8 months median follow-up, complete control of axillary recurrence was achieved in 31 patients (71%). Distant metastases developed in 50% and were more likely with uncontrolled axillary recurrences. Failure to receive multimodality therapy and failure to undergo surgery for the recurrence correlated with resistant axillary disease. CONCLUSIONS: Axillary recurrence from breast cancer is uncommon but may follow any stage of disease. One half of affected patients develop distant metastases. Durable disease control is best achieved with multimodality therapy including a surgery component.
Acute (invasive) fungal rhinosinusitis is an aggressive and potentially lethal complication of insulin dependent diabetes, as well as immunosuppression from chemotherapy and bone marrow transplant. The goal of this article is to describe methods to help with the diagnosis and treatment of sinusitis prior to developing this state of immune-compromise. This will help eliminate a significant risk factor for these patients that can lead to serious morbidity and ultimately mortality.
OBJECTIVES: Acoustic neuromas (ANs) comprise 6% of intracranial tumors. Population and autopsy studies have widely divergent estimates of AN incidence. With widespread use of MRI, asymptomatic ANs will be identified, which should improve estimates of the prevalence of this tumor. METHODS: The reports of all brain MRI scans during a 5-year period were retrospectively searched for the diagnosis of AN. MRIs obtained because of a suspicion of AN were discarded, leaving only the unsuspected ANs. RESULTS: A total of 24, 246 MRI studies were performed during this time period. Seventeen patients had unsuspected ANs. Eight tumors were smaller than 1 cm, 6 were between 1 and 2 cm, and 3 were 2 cm or larger. For all MRI scans, we found 7.0 unsuspected ANs per 10,000 brain MRI studies (0. 07%). CONCLUSION: The true prevalence of AN is likely greater than the 10 per million per year previously reported. This implies that there may be a larger number of asymptomatic ANs than previously suspected.
Paradoxical vocal fold motion is a rare disorder in which adduction of the folds occurs on inspiration. The disorder presents with signs of airway obstruction and often airway distress, so proper diagnosis by the otorhinolaryngologist is critical to subsequent management. We present a retrospective review of 10 patients with the diagnosis of paradoxical vocal fold motion seen over a 6-year period. Eight patients were females, and 6 required an acute airway intervention at presentation; 3 patients eventually underwent tracheotomy for respiratory decompensation. Six patients had a prior diagnosis of asthma, and this was determined to contribute to their respiratory status. Five patients were treated with botulinum toxin and 2 with flexible nasolaryngoscopic biofeedback, which improved the outcome. A review of the literature confirms a female predominance of patients presenting with paradoxical adduction and airway distress, often with a history of asthma and psychopathology. Our experience with botulinum toxin and biofeedback suggests that these procedures are viable treatment options in the management of patients with this disorder.
The purpose of this study was to determine the early efficacy and toxicity of a new multimodality organ-preservation regimen for locally advanced, resectable oropharyngeal squamous cell carcinoma (SCC). Patients with T3-4N0-3M0 or T2N2-3M0 oropharyngeal SCC were eligible for this Phase II study. Patients needed the physiologic reserve for surgery and technically resectable tumors. Induction carboplatin (area under the curve = 6) and paclitaxel (200 mg/m2) x 2 cycles (q21 days) were given. Objective responders received definitive radiotherapy (XRT), 70 Gy/7 weeks with concurrent weekly paclitaxel. Initially, the dose of paclitaxel was 50 mg/m2/week; because of mucosal toxicity it was reduced to 30 mg/m2/week. Patients with N2-3 disease received post-XRT neck dissection and 2 more cycles of "adjuvant" chemotherapy. In the first 22 patients, the neutropenic fever rate was 27%. Although there has been no grade IV-V toxicity from induction therapy, grade II-III toxicity resulted in an unacceptable delay in starting XRT in 14% of patients. The response rate to induction chemotherapy was 91%. Grade III mucositis occurred in all patients during concurrent chemoradiotherapy. One patient died of pneumonia during concurrent chemoradiotherapy after receiving 26 Gy and 3 doses of paclitaxel 50 mg/m2. No dose-limiting toxicity occurred in 15 patients treated with concurrent paclitaxel 30 mg/m2/week. Actuarial overall survival at 18 months is 82%; local-regional control is 86%. To date, distant metastases have not developed in any patients. This regimen has intense but acceptable acute toxicity. The maximum tolerated dosage of weekly paclitaxel during standard continuous-course XRT is confirmed to be 30 mg/m2/week. The treatment efficacy of this regimen (response rate and short-term local-regional and distant control) is encouraging. Accrual continues to obtain long-term toxicity, efficacy, and quality-of-life data.
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