A comprehensive study of prescribing, administering and drug handling medication errors in ten wards of a university hospital after implementation of electronic prescribing, clinical pharmacists or medication reconciliation.

Background and aim: Medication errors lead to preventable risks. Preventing strategies such as e-prescribing, clinical pharmacists and medication reconciliation have been implemented in recent years. However, information on long-term medication error rates in routine procedures is missing. Investigations: We aimed to identify predefined medication errors in ten wards of a university hospital where e-prescribing, clinical pharmacists and medication reconciliation have been partially implemented. Patient files were reviewed and routine processes were monitored for drug prescription errors (missing, unclear, outdated information), administration errors (wrong dispensed drugs) and drug handling errors (no light-, moisture-protection, wrong splitting, no separation of drugs, which ought to be taken by an empty stomach). Results: We analyzed 959 prescriptions with 933 solid peroral drugs for 182 patients (98 female, median age 66.5 years [Q25-Q75: 56-78 years]; the median number of drugs was 5 [Q25-Q75: 3-7]). The most frequent prescription error was a not specified drug form (91.1%). The most common administration error was a not adequately provided release dose formulation (72.7%). The lack of light protection for observed photosensitive drugs was the most frequent drug handling error (100%). We found a significantly higher amount of complete drug prescriptions with one of the implemented measurements e-prescribing, medication reconciliation and clinical pharmacists (Fisher's exact test two tailed, each p<0.001; CI 95%). Drug administration errors and drug handling errors were not significantly improved. Among the most frequently involved drug were drugs for acid-related disorders, immunosuppressant, and antineoplastic drugs. Conclusions: In the nearly 1,000 prescriptions and drugs analyzed, medication errors were still common. Various preventive strategies had been implemented in recent years, positively influencing the predefined errors rates.

Use of Second Window ICG in spinal cord biopsy of a mildly contrast-enhancing lesion: Technical note and review of the literature.

INTRODUCTION: Indocyanine green (ICG) is commonly used to visualize cerebral vasculature, particularly in the management of cerebral aneurysms. There have also been attempts to use ICG for visualization of tumors. Injection of ICG followed by immediate fluorescence microscopy is limited by the short time window for imaging and administration and restricted depth of imaging. Second Window Indocyanine Green (SWIG) addresses these issues by allowing for longer contrast times and the imaging of deeper regions of brain tissue. Biopsy of spinal cord lesions is often difficult for a variety of reasons, including the delicate nature of the tissue and differentiating normal from lesional tissue visually, especially in lesions with heterogeneous enhancement. METHODS: In this case report, we describe the use of second window ICG to facilitate the visualization of a spinal cord lesion and subsequent biopsy of the lesion. RESULTS: This patient is a 24-year-old female who had recurrence of a suprasellar germinoma. An MRI of the rest of the neuraxis was performed to assess for the presence of drop metastases. The spinal cord from C2-5 was expanded with areas of patchy enhancement; however, this lesion was asymptomatic. The patient's oncologist requested a biopsy of this lesion to help direct subsequent care of her recurrent germinoma. The day before surgery, the patient had an intravenous injection of ICG dye. She then underwent a C3-5 laminectomy for biopsy of her cervical intramedullary lesion. After opening of the dura, no visible abnormality of the spinal cord could be identified. A Stryker endoscope showed an area of ICG uptake in the cord at approximately the C3-4 level. A midline myelotomy was centered over the ICG demarcated area and several samples were taken for pathology. Final biopsy results determined the lesion to be spinal cord parenchyma with perivascular and intraparenchymal lymphocytes - not consistent with spinal cord tumor or germinoma. CONCLUSION: Second Window ICG is effective in visualizing otherwise visually unremarkable spinal cord lesions. This technology can facilitate biopsy of these lesions and possibly their surgical resection.

Beryllium bis(diazaborolyl): old neighbors finally shake hands.

The synthesis of a linear beryllium bis(diazaborolyl) compound featuring the first non-cluster bond between boron and beryllium has been achieved through the reaction of Yamashita's lithium diazaborolide and BeCl2. In accord with the established chemistry of beryllium, the bonding is polar covalent in character, as determined by structural and spectroscopic analysis, as well as reactivity studies.

Mental health and substance use among self-employed lawyers and pharmacists.

BACKGROUND: Self-employed workers experience occupational stress and may suffer from various mental health disorders. AIMS: To assess the mental health, substance use and risk factors for psychological distress in a sample of self-employed lawyers and pharmacists. METHODS: A cross-sectional study, using self-completion postal questionnaires, of lawyers and pharmacists. The General Health Questionnaire-28 (GHQ-28) was used as a measure of current mental health, and some additional questions evaluated alcohol, tobacco and psychotropic drug use and somatic morbidity. A multiple regression model was used to analyse the respective impact of the different risk factors on psychological suffering. RESULTS: A total of 1282 lawyers and 1153 pharmacists participated representing response rates of 36 and 35%, respectively. According to the GHQ-28 score, the rate of psychological distress was high in the sample overall, especially in lawyers (52 versus 47% in pharmacists, P < 0.05). According to the mean number of drinks per day, 16% of the lawyers and 13% of the pharmacists reported alcohol misuse, and lawyers were twice as likely as pharmacists to smoke (26 versus 13%, P < 0.001). Higher GHQ-28 scores were associated in lawyers with female gender, being widowed or divorced, smoking and using anxiolytic medication and in pharmacists with being younger, smoking, alcohol abuse and anxiolytic and hypnotic use. CONCLUSIONS: In our sample of these self-employed groups, both pharmacists and lawyers reported a high rate of psychological distress.

The use of the GORE® TIGRIS® Vascular Stent with dual component design in the superficial femoral and popliteal arteries at 6 months.

AIM: The aim of this study was to collect procedural and clinical data assessing safety and performance of the GORE® TIGRIS® Vascular Stent, a novel dual component stent, made of a nitinol wire frame combined with a fluoropolymer-interconnecting structure. METHODS: This retrospective analysis included 32 consecutive patients (20 men, mean age 72.8 years) with 40 atherosclerotic femoropopliteal lesions (occlusions in 5%) who underwent angioplasty and implantation of a GORE® TIGRIS® Vascular Stent. The patients were scheduled for follow-up at 3, 6 and 12 months after stent implantation for Duplex ultrasound and assessment of Rutherford Becker class (RBC) and Ankle-Brachial Index (ABI) RESULTS: The mean implanted stent length was 62.3 mm (range 30-100 mm). Procedural success (residual stenosis <30%) was achieved in 100% of the lesions. At 6 months 2 restenosis in 2 patients were observed, resulting in a cumulative primary patency rate (±standard error) of 91.7±8.0%. Between baseline and 6 months the ABI increased from 0.65±0.18 to 0.96±0.12 (P<0.0001) and the median of RBC increased from 3 to 1.5 (P<0.0005). No stent thrombosis was found. CONCLUSION: In this retrospective collection of patients all lesions could be successfully treated with this novel hybrid TIGRIS stent. These preliminary results show promising primary patency rates at 6 months. In addition, significant improvements were observed in symptom classification and hemodynamics.

[Hysterical mutism]. / Le mutisme hystérique.

BACKGROUND: Conversion disorders comprise many clinical pictures, including hysterical mutism. Hysterical mutism has emerged as a clinical entity that remains difficult to diagnose, and whose treatment is poorly codified. Hysterical mutism is a disorder of the vocal function without changing the integrity of the body, resulting in loss of voice. Identified at all times, hysterical mutism entered the medical field in the late nineteenth century, under the direction of Jean-Martin Charcot (Salpêtrière School). Since then, although the disorder has emerged as a clinical entity, it remains little known. METHOD: A systematic review of the literature. We performed electronic literatures search of relevant studies using Medline, SUDOC, and BIUM. Search terms used were mutism, functional aphonia, conversion disorder, hysteria. RESULTS: The epidemiology of hysterical mutism is difficult to assess. The first limitation is the lack of consensensual diagnostic criteria. An estimate of its frequency may be advanced through registries consultation of otolaryngology-head and neck surgery. Through a literature review, emerges a rare disorder, about 5% of functional dysphonia. The sex-ratio is in favour of women. Regarding age of onset of disorder, functional aphonia mainly concerns adults with an average around the age of 30-40 years. The onset of the disorder typically involves a sudden onset and a recent stressful event. The duration of the disorder is difficult to specify. It appears that this dysfunction is rapidly reversible and that the majority of patients are in remission of this disorder within three months. The recurrence of dysfunction seems to be frequent. The existence of psychiatric comorbidity did not appear to be the rule. The natural history of this disorder is not known making it tricky to evaluate the efficiency of therapeutic approaches. CONCLUSION: Today the term hysterical mutism does not appear as an entity in either international classification. It belongs to the category of conversion disorder in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). Identified as a medical entity described by the school of the Salpêtrière, this disorder has raised little interest. The medicalization of the condition remains difficult because of the importance of stigma associated with it, which contributes to the rejection rather than support of patients with mutism. To better understand this disorder and improve the care of patients who suffer, renewed interest is warranted.

[Detection, identification and visualization of the recurrent laryngeal nerve during thyroidectomy--still a surgical dilemma]. / Hledání, identifikace a vizualizace nervus laryngeus recurrens pri tyreoidektomii--stálé chirurgické dilema.

OBJECTIVE: Based on their on experience the authors express their opinion on routine detection and visualization of the NLR during radical surgery of the thyroid gland. They describe standard and alternative steps of surgery leading to protection of the recurrent nerve. MATERIAL AND METHODS: The authors evaluated a group of 735 patients operated during the last thirty nine months which comprised 87% total thyroidectomies, 11.6% total lobectomies, the remainder were almost total operations. The number of visualized nerves was 1367. RESULTS: Unilateral temporary damage of the NLR leading to temporary pareses of the vocal cords was recorded in 19 patients, i.e. 1.39%, bilateral transient paresis in one case, i.e. 0.07%. Permanent damage of one vocal cord after severing of the NLR occurred in 11 patients, i.e. 0.8%, bilateral lesions of the vocal cords were not recorded. CONCLUSION: There are no extensive statistics of thyroid operations without reports on damage of the NLR. With the increasing number of radical operations of the gland also the number of departments increased which recommend unequivocally to seek and visualize the NLR. The authors results support this point of view. They use most frequently a modification of Wang's method and consider as the smallest extent of visualization of the NLR the distance between the branching of the inferior thyroid artery and the entry of the NLR into the larynx.

Comparison of information processing technologies.

OBJECTIVE: To examine the type of information obtainable from scientific papers, using three different methods for the extraction, organization, and preparation of literature reviews. DESIGN: A set of three review papers was identified, and the ideas represented by the authors of those papers were extracted. The 161 articles referenced in those three reviews were then analyzed using 1) a formalized data extraction approach, which uses a protocol-driven manual process to extract the variables, values, and statistical significance of the stated relationships; and 2) a computerized approach known as "Idea Analysis," which uses the abstracts of the original articles and processes them through a computer software program that reads the abstracts and organizes the ideas presented by the authors. The results were then compared. The literature focused on the human papillomavirus and its relationship to cervical cancer. RESULTS: Idea Analysis was able to identify 68.9 percent of the ideas considered by the authors of the three review papers to be of importance in describing the association between human papillomavirus and cervical cancer. The formalized data extraction identified 27 percent of the authors' ideas. The combination of the two approaches identified 74.3 percent of the ideas considered important in the relationship between human papillomavirus and cervical cancer, as reported by the authors of the three review articles. CONCLUSION: This research demonstrated that both a technically derived and a computer derived collection, categorization, and summarization of original articles and abstracts could provide a reliable, valid, and reproducible source of ideas duplicating, to a major degree, the ideas presented by subject specialists in review articles. As such, these tools may be useful to experts preparing literature reviews by eliminating many of the clerical-mechanical features associated with present-day scientific text processing.

Pescadillo, a novel cell cycle regulatory protein abnormally expressed in malignant cells.

Using a culture model of glial tumorigenesis, we identified a novel gene that was up-regulated in malignant mouse astrocytes following the loss of p53. The gene represents the murine homologue of pescadillo, an uncharacterized gene that is essential for embryonic development in zebrafish. Pescadillo is a strongly conserved gene containing unique structural motifs such as a BRCA1 C-terminal domain, clusters of acidic amino acids and consensus motifs for post-translational modification by SUMO-1. Pescadillo displayed a distinct spatial and temporal pattern of gene expression during brain development, being detected in neural progenitor cells and postmitotic neurons. Although it is not expressed in differentiated astrocytes in vivo, the pescadillo protein is dramatically elevated in malignant human astrocytomas. Yeast strains harboring temperature-sensitive mutations in the pescadillo gene were arrested in either G(1) or G(2) when grown in nonpermissive conditions, demonstrating that pescadillo is an essential gene in yeast and is required for cell cycle progression. Consistent with the latter finding, DNA synthesis was only observed in mammalian cells expressing the pescadillo protein. These results suggest that pescadillo plays a crucial role in cell proliferation and may be necessary for oncogenic transformation and tumor progression.

Medical management and adjuvant therapies in spinal metastatic disease.

Metastatic spinal tumors are an increasingly common and difficult problem encountered by neurosurgeons and orthopedic surgeons. To improve therapies and increase life expectancy for patients with tumors such as those of the breast and prostate, a global, systematic approach is required to maximize the preservation of neurological function, maintenance of spinal stability, and relief of pain, all with the ultimate goal of improved functional capacity and quality of life (QOL). Although radiotherapy and surgery are still the primary therapeutic options, several new adjuvant therapies initially implemented to control pain more effectively have also been shown to reduce overall skeleton-related complications (pathological fractures and hypercalcemia) and may ultimately improve and extend QOL. This more global approach to spinal metastases also includes optimizing each patient's overall medical condition and potential for healing (that is, nutrition), as well as avoiding potential complications associated with metastatic disease (such as deep vein thrombosis), including excessive blood loss in the case of renal metastasis. A thorough knowledge and understanding of these therapeutic adjuvants is required to optimize care and to respond to our increasingly medically knowledgable patient population whose access to prevalent medical information has been increased because of the internet.

Trypanosoma cruzi: the development of estrus cycle and parasitemia in female mice maintained with or without male pheromones.

Female BALB/c or C57B1/6 mice, kept in small groups of three or five animals with or without male odor, all had a similar progesterone and corticosterone level, mean number of estrus and duration of estrus cycle. However, if males were kept in the same room, the mean duration of the estrus cycle was longer for both strains; and C57B1/6 females had a significantly higher number of estrus than BALB/c mice and showed a tendency to synchronize the estrus cycle within a group. After infection of females of both mouse strains with vector-derived metacyclic trypomastigotes of Trypanosoma cruzi, anestrus with intense phlegm production occurred during the acute phase of infection and this was positively correlated with higher parasitemia. Within individual groups of BALB/c mice, the female with the relatively highest corticosterone and progesterone level had the lowest parasitemia. In groups kept separate from male pheromones, one or two females in each group developed high parasitemias.

Use of structural allografts in spinal osteomyelitis: a review of 47 cases.

OBJECT: The use of structural allografts in spinal osteomyelitis remains controversial because of the perceived risk of persistent infection related to a devitalized graft and spinal hardware. The authors have identified 47 patients over the last 3.5 years who underwent a surgical decompression and stabilization procedure in which fresh-frozen allografts were used after aggressive removal of infected and devitalized tissue. The patients subsequently underwent 6 weeks of postoperative antibiotic therapy (12 months for those with tuberculosis [TB]). METHODS: Follow-up data included results of serial clinical examinations, radiography, laboratory analysis (erythrocyte sedimentation rate and white blood cell count), and clinical outcome questionnaires. Of the original 47 patients (14 women and 33 men, aged 14-83 years), 39 were available for follow up. The average follow-up period at the time this article was submitted was 17 +/- 9 months (median 14 months, range 6-45 months). In the majority of cases (57%), a Staphylococcus species was the infectious organism. Predisposing risk factors included intravenous drug abuse (IVDA), previous surgery, diabetes, TB, and concurrent infections. During the follow-up period only two patients suffered recurrent infection at a contiguous level; both had a history of IVDA and one also had a chronic excoriating skin condition. No other recurrent infections have been identified, and no patient has required reoperation for persistent infection or allograft/hardware failure. CONCLUSIONS: It is the authors' opinion that the use of structural allografts in combination with aggressive tissue debridement and adjuvant antibiotic therapy provide a safe and effective therapy in cases of spinal osteomyelitis requiring surgery.

Trypanosoma cruzi: skin-penetration kinetics of vector-derived metacyclic trypomastigotes.

In order to investigate the natural route of infection of nude and normal BALB/c mice with Trypanosoma cruzi via the skin, a drop of vector faeces/urine containing metacyclic trypomastigotes was placed onto the puncture site of a bite from Triatoma infestans. The periods of exposure, i.e. until removal of flagellates from the skin, and the time elapsed until surgical removal of the skin around the puncture were varied. After 15 min of exposure, T. cruzi developed in all nude mice without surgery, and in four of 10 mice if the puncture region of the skin was removed directly after exposure. In a shaved puncture region, 5 min of exposure were sufficient to infect all normal BALB/c mice without surgery and one of four mice with direct removal of the puncture region. Longer periods of exposure or time until removal of the skin only sometimes resulted in higher infection rates. Prepatent periods and the development of parasitaemia varied irrespective of the period of exposure or the period until skin removal at the puncture site. The importance of these findings is that they clearly prove that T. cruzi can rapidly invade the host via the puncture site of the bite of the vector and that at least some parasites are immediately transported away from this site.

Expression of the lung resistance protein predicts poor outcome in patients with multiple myeloma.

Expression of the lung resistance protein (LRP) is associated with resistance to various anticancer drugs including melphalan and, therefore, may affect the clinical outcome in multiple myeloma (MM). To determine the clinical significance of LRP, we have compared LRP expression in bone marrow plasma cells with clinical parameters including response to chemotherapy and survival of previously untreated patients with MM (n = 72). LRP expression immunocytochemically assessed by means of the LRP-56 monoclonal antibody was positive (> or =10% staining plasma cells) in 44 (61%) samples. There was no correlation between LRP expression and age, sex, type of the paraprotein, serum creatinine, stage, beta2-microglobulin, serum lactate dehydrogenase, or C-reactive protein. However, LRP expression was more frequently observed in patients with a p53 deletion than in those without such a deletion (P = 0.01). The overall response rate for all of the patients evaluable for response to induction chemotherapy (n = 58) was 67%. The response rate was 87% for patients without LRP expression but only 54% for patients with LRP expression (P = 0.01). Kaplan-Meier analysis revealed that patients with LRP expression had a shorter overall survival (median, 33 months) than those without LRP expression (median not reached; P = 0.04). These data show that LRP expression is an important marker for clinical drug resistance and predicts a poor outcome in MM.

Examining the immune response in sentinel lymph nodes of mice and men.

Recently, it was recognized that an immune response develops along one of two major pathways. One leads to a destructive immune response (type 1), while the alternative leads to a nondestructive immune response (type 2). Our studies in animal models suggest that therapeutic vaccines induce a tumor-specific type 1 immune response while ineffective vaccines induce a type 2 response. These results have led us to examine the immune response in sentinel lymph nodes draining tumor vaccines of patients entered onto clinical trials for melanoma, breast and renal cell cancer.

Androgens alter the cytokine profile and reduce encephalitogenicity of myelin-reactive T cells.

Adoptive transfer of proteolipid protein 139-151-specific T cell lines was used to examine the role of androgens in regulating T cell cytokine secretion and the severity of experimental autoimmune encephalomyelitis (EAE) in the SJL mouse. In this study, we found that T cells from female mice transferred more severe EAE than T cells from male mice and that gender differences in clinical disease were due, at least in part, to differences in donor T cell cytokine secretion. T cell lines were selected from proteolipid protein 139-151-immunized female SJL mice in the presence or absence of exogenous androgens. Androgen-selected T cell lines secreted less IFN-gamma and more IL-10 than untreated cell lines. Clinical disease induced by the adoptive transfer of androgen-selected T cell lines was less severe than disease induced with untreated T cell lines. Furthermore, androgen treatment of naive TCR transgenic T cells, during their first encounter with Ag, resulted in a shift in the balance of Th1/Th2 cytokines. This phenotype was maintained during subsequent stimulations in the absence of androgen. These results suggest that androgen present in the lymphoid microenvironment during the induction of an immune response can alter the development of effector T cells and may play an important role in governing gender differences in the immune response and susceptibility to autoimmune disorders.

Presence of a p53 gene deletion in patients with multiple myeloma predicts for short survival after conventional-dose chemotherapy.

In multiple myeloma (MM), previous studies showed that mutations of the p53 gene are rare events in patients with newly diagnosed disease, but it is not known whether deletions of p53 are of any significance in MM. To address this question, we used interphase fluorescence in situ hybridization (FISH) with a DNA probe specific for the p53 locus at 17p13 and investigated bone marrow plasma cells from 72 patients with MM (59 patients = 81.9% before therapy). By FISH, deletions of p53, which were found to be predominantly monoallelic, were detected in 32.8% and 54.5% of patients with newly diagnosed and relapsed MM, respectively. Karyotypes from six of the patients with a p53 deletion by FISH showed a structural abnormality of 17p in only one of them. Additional FISH studies including a distal-17p probe (specific for the D17S34 locus) provided evidence for an interstitial deletion on 17p resulting in loss of p53 hybridization signals in myeloma cells. Among all 59 patients with newly diagnosed MM, presence of a p53 deletion was associated with stage III (P = .054), but not with other laboratory and clinical parameters. Patients with a p53 deletion had significantly shorter survival time compared with those without a deletion, both from the time of diagnosis (median 13.9 v 38.7 months; P < .0001) and from the time of initiation of induction treatment consisting of conventional dose chemotherapy (median 15.9 months v median not reached at 38 months; P < .0002). On stepwise multivariate regression analysis, presence of a p53 deletion was the most significant independent parameter predicting for shortened survival (P = .002). We conclude that a p53 gene deletion, which can be identified by interphase FISH in almost a third of patients with newly diagnosed MM, is a novel prognostic factor predicting for short survival of MM patients treated with conventional-dose chemotherapy.

Correlation of thrombosis with increased platelet turnover in thrombocytosis.

There are no readily applicable methods to routinely assess thrombosis risk and treatment response in thrombocytosis. Reticulated platelets (RP) define the most recently released platelets in the circulation, and the RP% has been shown to estimate platelet turnover in thrombocytopenic states. We examined whether increased RP values were associated with thrombotic complications in thrombocytosis. Platelet count, RP%, and absolute RP count were measured at presentation in 83 patients with chronic or transient thrombocytosis, 46 patients with deep vein (DVT) or arterial (ART) thrombosis and normal platelet counts, and 83 healthy controls with normal platelet counts. Chronic thrombocytosis patients presenting with thrombosis (n = 14) had significantly higher RP% (14.7% +/- 10. 1%, mean +/- SD) than asymptomatic chronic thrombocytosis patients (n = 23, RP% = 3.4% +/- 1.8%), healthy controls (3.4% +/- 1.3%), DVT patients (n = 21, 3.8% +/- 2.1%), or ART patients (n = 25, 4.5% +/- 4.1%, P < .05 for all comparisons). Chronic thrombocytosis patients with thrombosis also had significantly higher absolute RP counts than asymptomatic chronic thrombocytosis patients (98 +/- 64 x 10(9)/L [range, 54 to 249 x 10(9)/L] v 30 +/- 13 x 10(9)/L [range, 11 to 51 x 10(9)/L]; P = .0004), whereas healthy controls, DVT, and ART patients had similarly low absolute RP counts (6 +/- 6 x 10(9)/L, 9 +/- 7 x 10(9)/L, and 11 +/- 7 x 10(9)/L, respectively; P > .49). The RP% and absolute RP counts remained significantly higher in chronic thrombocytosis patients with thrombosis when patients were further subdivided into primary myeloproliferative disorders versus secondary thrombocytosis. Similarly elevated RP percentages and absolute counts were also noted in transient thrombocytosis patients with thrombosis (n = 6, 11.5% +/- 4.4% and 90 +/- 46 x 10(9)/L, respectively) when compared with asymptomatic transient thrombocytosis patients (n = 40, 4.5% +/- 2.7% and 35 +/- 16 x 10(9)/L, respectively) and to all control groups (P < .05 for all comparisons). In addition, 7 of 8 thrombocytosis patients who were studied before developing symptoms of thrombosis had elevated absolute RP counts compared with only 1 of 63 thrombocytosis patients who remained asymptomatic. Follow-up studies in seven chronic thrombocytosis patients showed that successful aspirin treatment of symptomatic recurrent thrombosis significantly reduced the RP% from 17.1% +/- 10.9% before therapy to 4.8% +/- 2.0% after therapy; absolute RP counts decreased from 102 +/- 67 x 10(9)/L to 26 +/- 10 x 10(9)/L (P < .01 for both). We conclude that thrombosis in the setting of an elevated platelet count is associated with increased platelet turnover, which is reversed by aspirin therapy. Measurement of reticulated platelets to assess platelet turnover may be useful in evaluating both treatment response and thrombotic risk in thrombocytosis.

Two cases of esophageal carcinoma metastatic to the pineal region with a review of the literature.

BACKGROUND: Metastasis to the pineal region is rare, and there are no previously reported cases of esophageal carcinoma metastatic to the pineal region. CASE DESCRIPTION: We now present two cases of solitary esophageal carcinoma metastatic to the pineal region. In each case there was no evidence of disease progression at the primary site at the time of presentation, and neurologic symptoms were the first indication of recurrent disease. Both patients underwent infratentorial/supracerebellar resection of the pineal lesions and were subsequently referred for radiation therapy. CONCLUSIONS: These two cases emphasize that metastatic disease must be a likely differential consideration in a patient with a CNS lesion and a history of previous malignancy, even if the lesion is in an unusual location.

Bone resorption in multiple myeloma and in monoclonal gammopathy of undetermined significance: quantification by urinary pyridinium cross-links of collagen.

To quantify osseous breakdown in multiple myeloma (MM), monoclonal gammopathy of undetermined significance (MGUS), and benign osteoporosis, we measured urinary levels of pyridinium cross-links of collagen in 50 patients with newly diagnosed and untreated MM, 40 patients with MGUS, 40 untreated patients with osteoporotic vertebral fractures, and 64 healthy adults. Ion-paired, reverse-phase high-performance liquid chromatography (HPLC) was used to measure total urinary excretion of pyridinoline (h-PYD) and deoxypyridinoline (h-DPD). Urinary excretion of free immunoreactive deoxypyridinoline (i-DPD) was determined with an enzyme immunoassay. MM patients had significantly (P < .0001) higher levels of h-PYD, h-DPD, and i-DPD than the healthy adults, patients with MGUS, or patients with osteoporosis. The MGUS and osteoporosis groups presented with elevated (P < .05) levels of urinary pyridinium cross-links when compared with healthy controls. In 20 MM patients who subsequently received chemotherapy, the percent changes in i-DPD did not correlate with the changes in the monoclonal protein. In one of three patients experiencing a transition of initial MGUS into stage I MM, i-DPD increased above the upper limit of the normal range. In 13 patients with stable MGUS, i-DPD remained normal in repeated measurements. Based on the upper limits of the normal range, the sensitivity of urinary pyridinium cross-links in stage I and II MM was low (<50%), but it was between 78% (h-DPD) and 93% (i-DPD) in stage III MM. Specificity in patients with MGUS was between 87% (h-PYD) and 97% (h-DPD). In conclusion, determining the urinary excretion of pyridinium cross-links seems to be a promising noninvasive and thus easily repeatable method for evaluating the actual degree of osseous breakdown. Although measurement of pyridinium cross-link levels is not useful in discriminating patients with MGUS from early-stage myeloma patients, determination of i-DPD levels may contribute importantly to clinical guidance, since increased i-DPD levels seem to identify patients who are particularly likely to benefit from osteoclast-inhibiting drugs such as bisphosphonates. The fact that in a number of patients paraprotein concentrations and i-DPD levels did not change in parallel but instead diverged strongly after chemotherapy might explain the observation that bone lesions sometimes progress even in patients who achieve complete remission.