Negative pressure wound therapy in cases of spinal surgery and exposed dura: a case-based review.

PURPOSE: Study of negative pressure wound therapy (NPWT) safety for patients with intraoperative exposure of the dura. METHODS: We analyzed the literature on the NPWT usage after spinal surgery in patients with exposure of the dura. We also described our experience of NPWT in 3 pediatric patients with spinal dysraphism. Due to the peculiarities of the anatomy (spina bifida), all of these patients had dural sac exposure during spinal surgery. RESULTS: The reasons for NPWT in all three cases were different. In the first patient with segmental spinal dysgenesis, surgery was complicated by extensive postoperative wound necrosis and the formation of soft tissue deficiency. The second patient with post-myelomeningocele kyphosis had a deficiency of soft tissues during spinal surgery due to a large bedsore at the apex of the deformity. And in the third patient also with post-myelomeningocele kyphosis, NPWT was applied with surgical site infection. In all three cases, NPWT was used when the dura was exposed, without complications and with satisfactory results. The observation period for the patients was 3 years, 2.5 years, and 2 years, respectively. CONCLUSIONS: The usage of NPWT in cases of wound complications in the spinal surgery may be a useful option, which allows saving implants. NPWT is not contraindicated in cases of intraoperative dural exposure if there are no signs of cerebrospinal fluid (CSF) leak.

Prognostic value of survivin expression in Wilms tumor.

PURPOSE: To determine survivin expression patterns in Wilms tumor (WT) and compare it with the expression in normal renal tissue. Also, to analyse cytoplasmic and nuclear survivin expression in relation to histological type, prognostic group and tumor stage. METHODS: Immunohistochemical expression of survivin was analysed in 59 cases of primary WT and in 10 normal kidney specimens, taken from the same patients, but distant from the tumor. RESULTS: 51 out of 59 cases of WT (86.44%) showed decreased cytoplasmic survivin expression and 4 out of 59 cases of WT (6.78%) showed nuclear overexpression of survivin. There was statistically significant difference in the frequency of decreased cytoplasmic expression of survivin in individual components of WT (p=0.005). Decreased cytoplasmic expression of survivin in epithelial, blastemal and stromal component was found significantly more often in low stage WT compared to high stage WT (Fisher exact test, p=0.0002, p=0.002, p=0.002, respectively). There was no statistically significant difference in the frequency of survivin nuclear overexpression between different stages of WT (Fisher exact test, p=0.564), histological types (Fisher exact test, p=0.915), or between different prognostic groups (Fisher exact test, p=1). CONCLUSION: Decreased survivin cytoplasmic expression or nuclear overexpression may be related to favorable prognosis of WT.

Adenovirus-mediated p53 gene transfer in advanced non-small-cell lung cancer.

BACKGROUND: Preclinical studies in animal models have demonstrated tumor regression following intratumoral administration of an adenovirus vector containing wild-type p53 complementary DNA (Ad-p53). Therefore, in a phase I clinical trial, we administered Ad-p53 to 28 patients with non-small-cell lung cancer (NSCLC) whose cancers had progressed on conventional treatments. METHODS: Patients received up to six, monthly intratumoral injections of Ad-p53 by use of computed tomography-guided percutaneous fine-needle injection (23 patients) or bronchoscopy (five patients). The doses ranged from 10(6) plaque-forming units (PFU) to 10(11) PFU. RESULTS: Polymerase chain reaction (PCR) analysis showed the presence of adenovirus vector DNA in 18 (86%) of 21 patients with evaluable posttreatment biopsy specimens; vector-specific p53 messenger RNA was detected by means of reverse transcription-PCR analysis in 12 (46%) of 26 patients. Apoptosis (programmed cell death) was demonstrated by increased terminal deoxynucleotide transferase-mediated biotin uridine triphosphate nick-end labeling (TUNEL) staining in posttreatment biopsy specimens from 11 patients. Vector-related toxicity was minimal (National Cancer Institute's Common Toxicity Criteria: grade 3 = one patient; grade 4 = no patients) in 84 courses of treatment, despite repeated injections (up to six) in 23 patients. Therapeutic activity in 25 evaluable patients included partial responses in two patients (8%) and disease stabilization (range, 2-14 months) in 16 patients (64%); the remaining seven patients (28%) exhibited disease progression. CONCLUSIONS: Repeated intratumoral injections of Ad-p53 appear to be well tolerated, result in transgene expression of wild-type p53, and seem to mediate antitumor activity in a subset of patients with advanced NSCLC.

Growth suppression of human leukemic cells in vitro by L-ascorbic acid.

The suppressive effect of L-ascorbic acid on the growth of bone marrow cells from patients with acute nonlymphocytic leukemia was studied using a modified agar culture method featuring daily feeding to allow the growth of leukemic cell colonies. In seven of 28 patients (25%), the numbers of leukemic cell colonies grown in culture were reduced to 21% of control by the addition of L-ascorbic acid (0.3 mM) to the culture medium. Glutathione did not suppress leukemic cell colonies although it has a similar oxidation-reduction potential to that of L-ascorbic acid. The addition of L-ascorbic acid reduced the pH of the medium. However, a comparable reduction of pH by the addition of HCl did not suppress leukemic cell colonies. In simultaneous cultures for leukemic and normal marrow cells, the suppression of leukemic cell colony was noted with a concentration of L-ascorbic acid as low as 0.1 mM (a concentration achievable in vivo), but normal myeloid colonies were not suppressed until the concentration of L-ascorbic acid reached an extremely high level (1 mM). In conclusion, growth of leukemic cells in culture was suppressed by L-ascorbic acid in a substantial proportion of patients with acute nonlymphocytic leukemia. This suppression was a specific effect of L-ascorbic acid and was not due to its oxidation-reduction potential or pH change. Leukemic cells were selectively affected at an L-ascorbic acid concentration attainable in vivo while normal hemopoietic cells were not suppressed.

Improved growth of in vitro colonies in human acute leukemia with the feeding culture method.

Bone marrow cells freshly aspirated from the 10 consecutive untreated adult patients with acute nonlymphocytic leukemia were cultured by 2 different methods: the conventional agar culture method for myeloid colony formation and its modification by daily feeding with culture medium. In 5 patients, colonies grew in much higher numbers (4.7-to 330-fold) with feeding than without. Three patients grew colonies only with feeding. Two of these 3 patients required L-ascorbic acid in the fed medium for colony growth. Colonies did not grow from the remaining 2 patients by any method. In 7 patients the number of colonies grown with feeding were much higher, up to 170 times higher, than were those from normal control marrows, which grew the same number of colonies regardless of feeding or L-ascorbic acid. Peroxidase and Wright's stains indicated the myeloid differentiation of the cells in the leukemic marrow colonies. The leukemic origin of the colonies was proven by chromosomal analysis. The wide range of linearity between the number of cells plated and the number of colonies grown permits quantitative assay of colony-forming leukemic cells. This assay should be valuable for studies of chemotherapy, growth regulation, and differentiation of leukemic cells.

Blinded, randomized, multicenter study to evaluate single administration pegfilgrastim once per cycle versus daily filgrastim as an adjunct to chemotherapy in patients with high-risk stage II or stage III/IV breast cancer.

PURPOSE: This multicenter, randomized, double-blind, active-control study was designed to determine whether a single subcutaneous injection of pegfilgrastim (SD/01, sustained-duration filgrastim; 100 microg/kg) is as safe and effective as daily filgrastim (5 microg/kg/d) for reducing neutropenia in patients who received four cycles of myelosuppressive chemotherapy. PATIENTS AND METHODS: Sixty-two centers enrolled 310 patients who received chemotherapy with docetaxel 75 mg/m(2) and doxorubicin 60 mg/m(2) on day 1 of each cycle for a maximum of four cycles. Patients were randomized to receive on day 2 either a single subcutaneous injection of pegfilgrastim 100 microg/kg per chemotherapy cycle (154 patients) or daily subcutaneous injections of filgrastim 5 microg/kg/d (156 patients). Absolute neutrophil count (ANC), duration of grade 4 neutropenia, and safety parameters were monitored. RESULTS: One dose of pegfilgrastim per chemotherapy cycle was comparable to daily subcutaneous injections of filgrastim with regard to all efficacy end points, including the duration of severe neutropenia and the depth of ANC nadir in all cycles. Febrile neutropenia across all cycles occurred less often in patients who received pegfilgrastim. The difference in the mean duration of severe neutropenia between the pegfilgrastim and filgrastim treatment groups was less than 1 day. Pegfilgrastim was safe and well tolerated, and it was similar to filgrastim. Adverse event profiles in the pegfilgrastim and filgrastim groups were similar. CONCLUSION: A single injection of pegfilgrastim 100 microg/kg per cycle was as safe and effective as daily injections of filgrastim 5 microg/kg/d in reducing neutropenia and its complications in patients who received four cycles of doxorubicin 60 mg/m(2) and docetaxel 75 mg/m(2).

Life-threatening complications of impacted common bile duct lithiasis. A case report.

Impacted common bile duct (CBD) lithiasis poses therapeutical challenges and repeated attempts of removal may result in life-threatening complications. CASE REPORT. A 45 year-old female patient was admitted in emergency for right upper quadrant abdominal pain and jaundice. Clinical, lab data, abdominal ultrasound (US) and cholangio-MRI established the diagnosis of acute cholecystitis and obstructive jaundice due to distal CBD lithiasis. Endoscopic retrograde colangiopancreatography (ERCP) confirmed the presence of a distal CBD stone but extraction failed. The patient was operated on and surgical procedure consisted of cholecistectomy, intraoperative cholangiography and a side-to-side choledocho-duodenal anastomosis was performed because all attempts to extract the stone through choledocotomy or duodenotomy and enlargement of endoscopic shincterotomy failed. The postoperative course was endangered by a severe pancreatitis, a massive upper digestive bleeding and portal vein thrombosis that responded to conservative management in the intensive care unit. The patient was discharged after 34 days in good clinical condition and approximately 9 months later was readmitted electively for an incisional hernia. Apart from this, physical examination, lab tests and imagistic studies were normal; the patient was operated and rapidly discharged in good condition. In conclusion, the management of CBD lithiasis may be a serious challenge both for interventional endoscopists and surgeons and require a concerted team effort.

Low proliferative rate of invasive node-negative breast cancer predicts for a favorable outcome: a prospective evaluation of 669 patients.

This study was designed to compare outcome in terms of disease-free survival (DFS) in women with histologically negative axillary lymph nodes and documented low proliferative rate cancer to other well-defined prognostic factors including type of adjuvant treatment. Between 1988 and 1998, we studied 669 patients with invasive node-negative breast cancer up to 5 cm in size and low proliferative rate measured by flow cytometry to determine S-phase fraction (SPF) or by histochemistry (Ki67/MIB1). At a median follow-up of 53 months, 5-year DFS for the entire group was 94% and did not differ significantly by type of systemic adjuvant treatment: none (133 patients, 95% DFS), tamoxifen (441 patients, 94% DFS), or chemotherapy with doxorubicin and cyclophosphamide (95 patients, 92% DFS). In a multivariate prognostic factor analysis, only tumor size was significant; 5-year DFS was 96% for T1N0 cancer versus 89% for T2N0 cancer (P = 0.01). We have prospectively confirmed that a low rate of proliferation as measured by SPF or MIB1 determination confers an excellent prognosis in invasive node-negative breast cancer up to 5 cm in size, regardless of adjuvant treatment.

Comparison of titanium and stainless steel, Greenfield vena caval filters.

The standard stainless steel Greenfield filter (SGF) requires a 24F-sized carrier system, and its insertion percutaneously has been associated with local venous thrombosis. To facilitate both percutaneous and operative insertion, a titanium model of the Greenfield filter (TGF) has been developed that allows use of a 12F-sized carrier system. Mechanical comparison of the SGF and TGF devices shows that both withstand extensive flexion stress, but the TGF has greater endurance (52 gm at 20 mm travel) than the SGF (48 gm at 5 mm travel). Measurement of lateral forces for fixation shows comparable force (4.5 gm) at 22 mm for each device but greater force for the TGF at diameters more than 22 mm to its resting diameter of 38 mm. The TGF also withstands crevice corrosion in hydrochloric acid and ferric chloride better than the SGF. Animal studies in 20 sheep show comparable fixation of both devices with no added thrombogenicity of the TGF. Thrombus capture and resolution studies after 14 days in dogs show comparable effectiveness, and histologic examination of the venae cavae show similar inflammatory cell reaction and fibrosis with no foreign body reaction for either metal. Both the SGF and the TGF demonstrate durability and effective filtration of thrombi, with the TGF having the added advantages of ease of insertion and potential improved fixation in larger cavae.

Outpatient laparoscopic lumbar discectomy: description of technique and review of first twenty-one cases.

Economic and clinical factors have placed an increasing emphasis on minimally invasive surgical treatment of lumbar disc herniations. Percutaneous posterolateral techniques have been used increasingly over the last seven years but have definite technical limitations related to location of the disc herniation and its size. Dissatisfaction with percutaneous posterolateral lumbar discectomy (PPLD) led the senior author to explore the possibility of an anterior approach. Preliminary work included a "hands on" laparoscopy course and assisting experienced laparoscopists in the operating room. Before authorization from the Palomar Medical Center Investigational Review Board was obtained, dissection of the prevertebral space was performed in a human volunteer and a two level discectomy on a recently deceased patient was carried out in the operating room. The first operation was performed on February 4, 199I. Early in the series, patient selection was identical to that of percutaneous posterolateral discectomy, namely a soft posterolateral herniation contained within the posterior longitudinal ligament (PLL). As experience was gained, indications were expanded to include larger disc herniations. A description of the technique and our experience with the initial 21 consecutive cases form the basis of this report.

Performance by spring and fall-calving cows grazing with full, limited, or no access to toxic Neotyphodium coenophialum-infected tall fescue.

Replacing toxic, wild-type Neotyphodium coenophialum-infected tall fescue (E+) with nontoxic, N. coenophialum-infected tall fescue (NE+) has improved cow performance, but producer acceptance of NE+ has been slow. The objective was to compare performance by spring- and fall-calving cows grazing either E+ or NE+ at different percentages of the total pasture area. Gelbvieh×Angus crossbred cows (n=178) were stratified by BW and age within calving season and allocated randomly to 1 of 14 groups representing 5 treatments for a 3-yr study: i) Fall-calving on 100% E+ (F100); ii) Spring-calving on 100% E+ (S100); iii) Fall-calving on 75% E+ and 25% NE+ (F75); iv) Spring-calving on 75% E+ and 25% NE+ (S75); and v) Spring-calving on 100% NE+ (SNE100). Groups allocated to F75 and S75 grazed E+ until approximately 28 d before breeding and weaning, then were then moved to their respective NE+ pasture area for 4 to 6 wk; those allocated to F100, S100, and SNE100 grazed their pastures throughout the entire year. Samples of tall fescue were gathered from specific cells within each pasture at the time cows were moved into that particular cell (∼1 sample/mo). Blood samples were collected from the cows at the start and end of the breeding season. Stocking rate for each treatment was 1 cow/ha. Forage IVDMD, CP, and total ergot alkaloid concentrations were affected (P<0.05) by the treatment×sampling date interaction. Hay offered, cow BW, and BCS at breeding, end of breeding, and at weaning were greater (P<0.05) from fall-calving vs. spring-calving. Cow BW at weaning was greater (P<0.05) from F75 and S75 vs. F100 and S100. The calving season×NE+ % interaction affected (P<0.05) calving rates. Preweaning calf BW gain, actual and adjusted weaning BW, ADG, sale price, and calf value at weaning were greater (P<0.05) from fall-calving vs. spring-calving and from SNE100 vs. S75 except for sale price which was greater (P<0.05) from S75 vs. SNE100. Cow concentrations of serum prolactin at breeding and serum NEFA at the end of breeding were affected (P<0.05) by the calving season×NE+ % interaction. Serum Zn and Cu concentrations from cows were affected (P<0.05) by calving season. A fall-calving season may be more desirable for cows grazing E+, resulting in greater calving rates, cow performance, and calf BW at weaning, whereas limited access to NE+ may increase calving rates, serum prolactin, and NEFA concentrations during certain times in the production cycle, particularly in spring-calving cows.

Myasthenia gravis associated with thymoma and toxic multinodular goiter. A case report.

Adequate antithyroid drug treatment or surgery usually generates remission of myasthenia gravis (MG) in patients with thymus hyperplasia associated with Graves' hyperthyroidism. The case of a 46-year-old woman diagnosed with MG based on the clinical picture, anticholinesterase drug test and positive electromyography (EMG) is presented. The cervico-thoracic computer tomography revealed a compressive nodular goiter and normal antero-superior mediastinum and led to the diagnosis of MG secondary to the hyperthyroidism. An uneventful total thyroidectomy was performed, but postoperatively the MG symptoms worsened. TC99m tetrofosmin scintigraphy revealed an area of hyperfixation in the antero-inferior mediastinum, suggestive for thymoma, as confirmed by a repeated thoracic CT scan. Following a longitudinal sternotomy, a well incapsulated tumor of approximately 6/5 cm located in the antero-inferior mediastinum was found and an extensive thymomectomy was performed. The postoperative course was uneventful and the patient was discharged 9 days later with complete remission of myasthenia. The pathology report of the specimen revealed a mixt thymoma or AB thymoma after Muller-Hermelink and WHO classification, with invasive capsular foci corresponding to Masaoka II stadium. In conclusion, scintigraphy proved to be useful in the diagnosis and decision making of a thymoma.

Links between phytoplankton and bacterial community dynamics in a coastal marine environment.

Bacteria and phytoplankton dynamics are thought to be closely linked in coastal marine environments, with correlations frequently observed between bacterial and phytoplankton biomass. In contrast, little is known about how these communities interact with each other at the species composition level. The purpose of the current study was to analyze bacterial community dynamics in a productive, coastal ecosystem and to determine whether they were related to phytoplankton community dynamics. Near-surface seawater samples were collected in February, May, July, and September 2000 from several stations in the Bay of Fundy. Savin et al. (M.C. Savin et al., Microb Ecol 48: 51-65) analyzed the phytoplankton community in simultaneously collected samples. The attached and free-living bacterial communities were collected by successive filtration onto 5 microm and 0.22 microm pore-size filters, respectively. DNA was extracted from filters and bacterial 16S rRNA gene fragments were amplified and analyzed by denaturing gradient gel electrophoresis (DGGE). DGGE revealed that diversity and temporal variability were lower in the free-living than the attached bacterial community. Both attached and free-living communities were dominated by members of the Roseobacter and Cytophaga groups. Correspondence analysis (CA) ordination diagrams showed similar patterns for the phytoplankton and attached bacterial communities, indicating that shifts in the species composition of these communities were linked. Similarly, canonical CA revealed that the diversity, abundance, and percentage of diatoms in the phytoplankton community accounted for a significant amount of the variability in the attached bacterial community composition. In contrast, ordination analyses did not reveal an association between free-living bacteria and phytoplankton. These results suggest that there are specific interactions between phytoplankton and the bacteria attached to them, and that these interactions influence the composition of both communities.

[Chronic renal insufficiency: 1) adaptation of nephron function in chronic renal insufficiency and 2) progression of chronic renal insufficiency]. / Hronicna insuficijencija bubrega: 1) prilagodjavanje funkcije nefrona u hronicnoj insuficijenciji bubrega i 2) progresija hronicne insuficijencije bubrega.

In chronic renal insufficiency resulting from destruction of the vast majority of nephrons, the surviving nephrons adapt their functions to the conditions of vigorous haemodynamic and osmolar overloads. They acquire an appropriate behaviour to preserve the principal renal functions and to achieve the balance of inner space. In the long period of time, similarly as in healthy people. Glomerulotubular balance as well as tubuloglomerular balance distinguish the remaining nephron function, while autoregulation of perfusion pressure along the glomerulus rapidly vanishes. All three regulation mechanisms are characteristic of the nephron function under physiologic conditions. Intense work of the remaining nephrons in chronic renal failure is under the high level controls of the group of hormones, among them are rennin-angiotensin system, arginine-vasopressin and atrial natriuretic peptide playing very important and particular roles. Comparison of different published studies emerge the idea that chronically increased arginine-vasopressin levels in chronic renal failure could block the autoregulation of blood flow and hydraulic pressure in glomeruli, which together with other mediator actions give high and fluctuating tense within remaining glomeruli, during every single cardiac cycle. It is probably the main event in the further course of kidney disease progression resulting in definite damage of the overloaded nephrons. Angiotensin II is one of reliably recognised mediators of unfavourable outcome in the process of nephron adaptation in chronic renal failure. Knowing the pathophysiologic processes in the remaining functionally adapted nephrons in chronic renal insufficiency determines a more adequate therapeutic approach in these patients.

Mucosal iron transport by rat intestine.

Using highly sensitive 2-site immunoradiometric assays, we examined the relationship between iron absorption from closed intestinal loops and transferrin and ferritin concentrations in isolated duodenal mucosal cells. As in prior studies, mucosal ferritin correlates inversely with iron absorption and directly with body iron stores as measured by the concentration of nonheme iron in liver. Mucosal transferrin, on the other hand, varies directly with both the total mucosal uptake of radioiron and the proportion of this radioiron transferred from the mucosa to the carcass. The highest correlation with iron absorption was observed with the transferrin-ferritin ratio in isolated mucosal cells. These results suggest that there are two functionally distinct iron-binding compartments in the duodenal mucosa. One is a strong compartment, ferritin, and the other is a transport compartment, transferrin. Control of iron absorption by the intestinal mucosa is closely tied to the balance between these two intracellular iron compartments.