Cutaneous melanoma during pregnancy at the Cancer Center-Institute in Warsaw

Malignant melanoma is a neoplasm which frequency has been increasing rapidly in Poland. The paper describes five cases of patients with cutaneous melanoma coexisting with pregnancy, who have been recently treated in the Department of Soft Tissue/Bone Tumors of M. Sklodowska-Curie Memorial Cancer--Institute of Oncology, Warsaw. All patients presented clinically advanced primary lesions with poor prognosis. In paper recommendations for treatment of women with suspicious cutaneous lesions before or during pregnancy and patients with melanoma planning a pregnancy are presented. The suspicion of melanoma is indication for immediate excisional biopsy by local anesthesia. Further treatment should be performed in tertiary oncological centres. There is no evident clinical data that pregnancy has a significant impact on progression of melanoma. The most important factor influencing prognosis of melanoma is the stage of the disease at the diagnosis. There are no grounds for abortion in pregnant women with melanoma in I/II/III stages.     

N-methyl-2-pyridone-5-carboxamide: a novel uremic toxin?

BACKGROUND: N-methyl-2-pyridone-5-carboxamide (2PY) is one of the end products of nicotinamide-adenine dinucleotide (NAD) degradation. We recently found that serum 2PY concentrations in chronic renal failure (CRF) patients were enhanced to the values, which are potentially toxic. The aim of this study was to determine whether 2PY is an inhibitor of poly(ADP-ribose) polymerase, the nuclear enzyme that is highly involved in variety of physiologic events, including regulation of DNA replication and DNA repair. METHODS: High-performance liquid chromatography (HPLC) was used to determine 2PY and other NAD catabolite concentrations in serum of: nondialyzed patients; patients chronically hemodialyzed; patients after kidney transplantation; and healthy individuals (control group). Moreover, the effect of nicotinamide and 2PY on poly(ADP-ribose) polymerase (PARP-1) in vitro was studied. RESULTS: The serum nicotinamide, 2PY, and 4PY (N-methyl-4-pyridone-3-carboxamide) concentrations are many times elevated in nondialyzed CRF patients when compared with controls. The direct correlations were found between serum 2PY (as well as 4PY and nicotinamide) concentrations and serum creatinine concentration, and negative correlations between serum concentrations of these compounds and creatinine clearance. The concentration of 2PY decreases considerably after hemodialysis (HD) session, but elevates back 48 hours later. It permanently declines after kidney transplantation. Nicotinamide and 2PY significantly inhibit PARP-1 activity in vitro. CONCLUSIONS: Increased serum 2PY concentration, along with a deterioration of kidney function and its toxic properties (significant inhibition of PARP-1 by 2PY), suggest that it could be a novel uremic toxin.     

1H-MR spectroscopy of normal brain tissue before and after postoperative radiotherapy because of primary brain tumors

PURPOSE: Brain metabolism after surgery and postoperative radiotherapy (pRT) because of primary brain tumors was assessed by proton magnetic resonance spectroscopy ((1)H-MRS) in vivo. The study was designed to reveal the impact of pRT on normal brain tissue metabolism, which may potentially help in delineating the target volumes for reirradiated patients. METHODS AND MATERIALS: Spectra of 43 patients ages 16-63 years treated with pRT for primary glial tumors in the Center of Oncology Maria Curie Memorial Institute Branch in Gliwice were analyzed. The control group consisted of spectra acquired for 30 healthy volunteers. All patients were treated with 3D conformal techniques using 6-20 MV photons to total doses of 60 Gy. Spectra were acquired from the control region before pRT and from three uninvolved regions 9-12 months after the end of pRT. Voxels were located in the region of low (<6 Gy), medium (29-39 Gy), and high radiation dose ( approximately 60 Gy). Relative intensities of the signals relating to N-acetyl-aspartate (NAA), choline-based compounds, creatine and phosphocreatine (Cr), mio-Inositol, lactate, and lipids were obtained. RESULTS: The spectra of "normal brain" taken 9 months after pRT are significantly different from those obtained for control volunteers and from the spectra acquired before radiotherapy. The lactate and lipids signals are very strong; however, they are not correlated with absorbed dose. NAA/Cr ratios are significantly lower than before radiotherapy even for the low-dose regions. Differences increase with radiation dose: the NAA/Cr ratio is significantly lower for the regions of brain receiving a high dose of radiation than for the low-dose areas. CONCLUSION: Combined treatment of primary brain tumors (surgery + postoperative radiotherapy) causes alteration of brain metabolism, even in regions of the brain far from the postoperative tumor bed and receiving relatively low total doses of radiation. Single voxel MRS spectroscopy in vivo cannot help in delineating target volumes for secondary irradiation.     

Does this patient have acute cholecystitis?

Robert L. Trowbridge, MD; Nicole K. Rutkowski, MD; Kaveh G. Shojania, MD

JAMA. 2003;289:80-86.

Context  Although few patients with acute abdominal pain will prove to have cholecystitis, ruling in or ruling out acute cholecystitis consumes substantial diagnostic resources.

Objective  To determine if aspects of the history and physical examination or basic laboratory testing clearly identify patients who require diagnostic imaging tests to rule in or rule out the diagnosis of acute cholecystitis.

Data Sources  Electronic search of the Science Citation Index, Cochrane Library, and English-language articles from January 1966 through November 2000 indexed in MEDLINE. We also hand-searched Index Medicus for 1950-1965, and scanned references in identified articles and bibliographies of prominent textbooks of physical examination, surgery, and gastroenterology. To identify relevant articles appearing since the comprehensive search, we repeated the MEDLINE search in July 2002.

Study Selection  Included studies evaluated the role of the history, physical examination, and/or laboratory tests in adults with abdominal pain or suspected acute cholecystitis. Studies had to report data from a control group found not to have acute cholecystitis. Acceptable definitions of cholecystitis included surgery, pathologic examination, hepatic iminodiacetic acid scan or right upper quadrant ultrasound, or clinical course consistent with acute cholecystitis and no evidence for an alternate diagnosis. Studies of acalculous cholecystitis were included. Seventeen of 195 identified studies met the inclusion criteria.

Data Extraction  Two authors independently abstracted data from the 17 included studies. Disagreements were resolved by discussion and consensus with a third author.

Data Synthesis  No clinical or laboratory finding had a sufficiently high positive likelihood ratio (LR) or low negative LR to rule in or rule out the diagnosis of acute cholecystitis. Possible exceptions were the Murphy sign (positive LR, 2.8; 95% CI, 0.8-8.6) and right upper quadrant tenderness (negative LR, 0.4; 95% CI, 0.2-1.1), though the 95% CIs for both included 1.0. Available data on diagnostic confirmation rates at laparotomy and test characteristics of relevant radiological investigations suggest that the diagnostic impression of acute cholecystitis has a positive LR of 25 to 30. Unfortunately, the available literature does not identify the specific combinations of clinical and laboratory findings that presumably account for this diagnostic success.

Conclusions  No single clinical finding or laboratory test carries sufficient weight to establish or exclude cholecystitis without further testing (eg, right upper quadrant ultrasound). Combinations of certain symptoms, signs, and laboratory results likely have more useful LRs, and presumably inform the diagnostic impressions of experienced clinicians. Pending further research characterizing the pretest probabilities associated with different clinical presentations, the evaluation of patients with abdominal pain suggestive of cholecystitis will continue to rely heavily on the clinical gestalt and diagnostic imaging.

     

Pigmented villonodular synovitis of the temporomandibular joint: a report of two cases

Pigmented villonodular synovitis is a benign but locally destructive disease that originates in the synovial membranes of the joints. It is a proliferative disorder of unknown etiology, and it is usually monarthric. Approximately 80% of cases involve the knee; the hip, ankle, foot, hand, elbow, and shoulder account for most other cases. Pigmented villonodular synovitis in the temporomandibular joint is rare. When it does occur, its features include preauricular swelling, trismus, and symptoms of temporomandibular joint dysfunction. It can be diagnosed by a combination of the history, clinical examination, characteristic radiologic findings, and fine-needle aspiration or biopsy results. Wide local excision, including the involved bone, and a total synovectomy are advocated because the lesion can recur if it is not adequately excised. We report two new cases of pigmented villonodular synovitis of the temporomandibular joint, and we review the literature on this subject.     

Adenine reutilization as a cause of increased ATP concentration in erythrocytes of patients with chronic renal failure

Abnormalities of adenine nucleotide metabolism are observed in erythrocytes of patients with chronic renal failure (CRF) and the elevated ATP concentration is the most impressive one. In humans, adenine and/or adenosine reutilization is the only source of purine moiety used to erythrocyte adenine nucleotide synthesis. In the present study we have focused on the role of adenine as a substrate for the intraerythrocyte ATP production. 10 patients with CRF and 10 healthy volunteers (control group) were included into the study. Using HPLC, the measurements were performed in plasma and erythrocyte extracts. We observed a few fold higher adenine concentration in both plasma and erythrocytes of patients with CRF when compared with control group. There was also elevated an intraerythrocyte ATP concentration in the studied group of patients. Moreover, we have found a positive correlations between a) plasma creatinine concentration and plasma adenine concentration, b) plasma creatinine concentration and erythrocyte adenine concentration, c) plasma adenine concentration and intraerythrocyte ATP concentration. It appears that increased adenine reutilization could be a principle reason of the increased ATP synthesis in erythrocytes of patients with CRF.     

Gender differences in rat neuropathic pain sensitivity is dependent on strain

It is well recognized that gender differences play a major role in pain sensitivity, pain report, analgesic efficacy and prevalence of certain chronic pain disorders. In the present study we sought to determine whether male or female rats of two different outbred strains (Sprague-Dawley and Holtzman) experienced differential pain sensitivity after the same mononeuropathy lesion. Following baseline mechanical allodynia testing, rats of each sex and strain underwent an L5 spinal nerve transection. Mechanical allodynia using 2 and 12 g von Frey filaments was assessed at days 1, 3, 5, 7, and 10 post surgery. There were no statistically significant differences in allodynia between gender in the Holtzman strain or between strains. However, mechanical allodynia was significantly greater in female Sprague-Dawley rats as compared with males following a spinal nerve transection. These data suggest that the choice of rat gender and strain should be considered in experimental neuropathic pain studies, especially in the assessment of potential analgesics.     

Neurologic complications in Wegener's granulomatosis

Nervous system involvement is relatively frequent in Wegener's granulomatosis (WG). It may be difficult to differentiate between the primary central nervous system involvement and complications secondary to concomitant arterial hypertension, renal insufficiency and iatrogenic effects of immunosuppressive therapy. The crucial role in the assessment of intracranial pathology may be ascribed to the diagnostic imaging techniques: magnetic resonance imaging (MRI), computed tomography (CT) and cerebral blood flow imaging utilising the single photon emission computed tomography (SPECT). SPECT may prove superior sensitivity to MRI. It may be especially useful in differentiating central nervous system involvement in WG with secondary changes of other origin.     

Analysis of a rapid, simple, and inexpensive technique used to obtain platelet-rich plasma for use in clinical practice

The use of platelet-rich plasma (PRP) has become more generally accepted, and implant dentists are using PRP more frequently to promote the healing of oral surgical and/or periodontal wounds. Critical elements of PRP are thought to be growth factors contained within the concentrated platelets. These growth factors are known to promote soft-tissue healing, angiogenesis and osteogenesis. We present a rapid, simple, and inexpensive methodology for preparing PRP using the Cliniseal centrifuge method. This study demonstrates that platelets are concentrated approximately 6-fold without altering platelet morphology. Further we demonstrate that key growth factors, platelet-derived growth factor BB (PDGF-BB), transforming growth factor B (TGF-B1), vasculature endothelial growth factor (VEGF), and epidermal growth factor (EGF) are present in comparable or higher concentrations than those reported with the use of other techniques. Prolonged bench set time (>3 hours) after centrifugation resulted in decreased concentration of TGF-B1 but not decreased concentration of PDGF-BB, VEGF, or EGF. This study confirms the molecular aspects of PRP obtained using this inexpensive and efficient methodology.