Novel mutation in the PANK2 gene leads to pantothenate kinase-associated neurodegeneration in a Pakistani family

Pantothenate kinase-associated neurodegeneration is an autosomal-recessive disorder associated with the accumulation of iron in the basal ganglia. The disease presents with dystonia, rigidity, and gait impairment, leading to restriction of activities and loss of ambulation. The disorder is caused by defective iron metabolism associated with mutations in the PANK2 gene, which codes for the pantothenate kinase enzyme. We report on a mutation screen conducted in two siblings to establish a molecular diagnosis of the disease and a genetic test for the family.     

Discrimination of capsular stage brain abscesses from necrotic or cystic neoplasms using diffusion-weighted magnetic resonance imaging

OBJECT: The authors' aim was to assess the ability of apparent diffusion coefficient (ADC) ratios in distinguishing brain abscesses from cystic or necrotic neoplasms. METHODS: Fifty-three patients with rim-enhancing masses in the brain observed on T1-weighted MR images were included: 26 had abscesses (14 bacterial, six nonbacterial, and six of unknown origin), 11 had glioblastoma multiforme, and 16 had rim-enhancing metastasis. The ADC values, derived from diffusion-weighted imaging, were measured in the most homogeneous portion of the cystic component of the mass. The ADC ratios were calculated by dividing the ADC values from the nonenhancing cystic portion of the mass by the ADC values from contralateral normal-appearing white matter. Lesions were further differentiated based on presence, absence, or incompleteness of a T2 hypointensity rim. The mean (+/- standard deviation) ADC ratios were significantly higher in neoplasms than in abscesses (2.45 +/- 0.91 compared with 1.12 +/- 0:53, p < 0.01). The accuracy of ADC ratios in discriminating abscesses from neoplasms, determined by the area under the receiver operating characteristic curve (Az), was high: 0.91 +/- 0.04 (mean +/- standard error of the mean [SEM]). The threshold of 1.7 was associated with highest efficiency (87%) in discriminating abscesses from neoplasms. If only bacterial abscesses were analyzed compared with neoplasms, the Az increased to 0.96 +/- 0.03 (SEM). Using ADC ratios and T1 rim characteristics, 50 of 53 lesions were correctly classified (efficiency 94.3%). CONCLUSIONS: The accuracy of ADC ratios in discriminating brain abscesses from cystic or necrotic neoplasms is very high and can be further improved using T2 rim characteristics.     

Phenotypic detection of constitutive and inducible clindamycin resistance in clinical isolates of Staphylococcus aureus and coagulase negative Staphylococcus on routine susceptibility plate

Increasing frequency of methicillin resistant Staphylococcus aureus infections and changing patterns in antimicrobial resistance have led to renewed interest in the use of macrolidelincosamide-streptogramin antibiotics. However therapy may fail either due to constitutive or inducible resistance. This study was undertaken to detect different phenotypes including inducible clindamycin resistance in clinical isolates of Staphylococcus aureus and coagulase negative Staphylococcus. Four hundred sixty five Staphylococcus aureus and 84 coagulase negative Staphylococci isolated from different clinical specimens were included in the study. On routine susceptibility testing plate clindamycin (2 microg) disk was placed at a distance of 15mm towards the centre from a peripherally placed erythromycin (15 microg) disk. Fisher exact test was used for statistical analysis. Out of 465 Staphylococcus aureus isolates, 237 (50.96%) were methicillin sensitive (MSSA) and 228 (49.03%) methicillin resistant (MLS(B)c).Over all 118 (25.37%) isolates showed constitutive resistance (MLS(B)c), 70 (15.05%) inducible clindamycin resistance, 143 (30.75%) MS(B) phenotype and 134 (28.81%) were susceptible to both erythromycin as well as clindamycin. Constitutive and inducible resistance to clindamycin were significantly higher in MRSA than MSSA (P=0.0000 and 0.0001 respectively). Out of 84 isolates of coagulase negative Staphylococci, 43 (51.19%) were methicillin sensitive (MSCNS) and 41(48.80%) methicillin resistant (MRCNS). Constitutive MLS(B) resistance was detected in 32 (38.09%), inducible clindamycin resistance 10 (11.90%), MS(B) phenotype 27 (32.14%) and 15 (17.85%) were susceptible to both erythromycin and clindamycin. Performing D test on a routine susceptibility plate saves material, manpower and time as inducible resistance can be reported simultaneously along with other susceptibility results.     

Early chemotherapy in prostate cancer

A considerable proportion of men with clinically localized prostate cancer are not cured by surgery or radiotherapy, and hormone therapy for advanced disease is also not curative. Given the demonstrable efficacy of chemotherapy in hormone-refractory disease, there is an interest in examining the curative potential of chemotherapy when administered early in the natural history of prostate cancer. It is hoped that chemotherapy could be used with hormone therapy and in the adjuvant setting, as is the case in many other solid tumors, in patients with 'high-risk' prostate cancer who are undergoing primary radical prostatectomy or radiotherapy. Early phase clinical trials have shown that using docetaxel as neoadjuvant or adjuvant therapy is safe and feasible. In the neoadjuvant setting, tumor shrinkage, serological response, there is some evidence of pathological downstaging. Several randomized trials are ongoing, and it is anticipated that the results of these studies will help to identify whether the early use of chemotherapy in early prostate cancer is beneficial.     

Lack of association between level of Plasminogen Activator Inhibitor-1 and estimates of tumor angiogenesis in early breast cancer

Plasminogen Activator Inhibitor type-1 (PAI-1) is involved in tumor invasion and progression. High levels of PAI-1 are associated with poor prognosis in breast cancer, and PAI-1 has been shown to play a role in angiogenic processes. Since estimates of tumor angiogenesis may predict poor prognosis we studied the relationship between PAI-1 and estimates of angiogenesis in breast cancer. Tumor tissue specimens from 438 breast cancer patients were included. Median follow-up was 10.3 years. Protein levels of PAI-1 were measured using an ELISA. Angiogenesis scores were performed using a Chalkley grid. Median PAI-1 level was 0.70 ng/mg protein (range, 0 - 90 ng/mg protein) and median Chalkley count was 5.00 (range, 2.67 - 12.00). Chalkley counts were not correlated with PAI-1. In univariate analysis both increasing PAI-1 and increasing Chalkley counts evaluated as continuous parameters were significantly associated with poor disease-specific survival with RR 1.04 (95% CI 1.02 - 1.07) (p<0.0001) and RR 1.11 (95% CI 1.01 - 1.22) (p=0.04), respectively. High tertiles of PAI-1 were borderline significantly correlated with poor disease-specific survival (p=0.06), whereas high tertiles of Chalkley counts were significantly associated with poor disease-specific survival (p=0.004). Combining low/low versus high/high tertiles of Chalkley counts and PAI-1 showed actuarial 10-year survival rates of 82% versus 52% (p=0.004). High N-stage (p<0.0001), grade (p<0.0001) and increasing levels of PAI-1 (p=0.009) were independent markers of death from breast cancer. This study confirms high PAI-1 or high Chalkley counts as markers of poor prognosis in breast cancer patients, and suggests that the prognostic impact of PAI-1 is independent of its supposed involvement in tumor angiogenesis.     

Survival after elective surgery for colonic cancer in Denmark

Aim Total mesorectal excision (TME) has been shown to improve the outcome for patients with rectal cancer. In contrast, there are fewer data on complete mesocolic excision (CME) for colonic cancer. Method Data from the National Colorectal Cancer Database were analysed. This includes about 95% of all patients with colorectal cancer in Denmark. Only patients having elective surgery for colonic cancer in the period 2001–2008 were included. Overall and relative survival analyses were carried out. The study period was divided into the periods 2001–2004 and 2005–2008. Results 9149 patients were included for the final analysis. The overall 5‐year survival rates were 0.65 in 2001–2004 and 0.66 in 2005–2008. The relative 5‐year survival rates were also within 1% of each other. None of these comparisons was statistically significant. Conclusion Survival following elective colon cancer surgery has been almost unchanged since 2001.     

Topical 5-aminosalicylic acid versus prednisolone in ulcerative proctosigmoiditis

The therapeutic efficacy of a slightly acidic, buffered suspension of 1000 mg 5-aminosalicylic acid (Pentasa^®) was compared with that of 25 mg prednisolone following daily rectal administration to outpatients with mild to moderate proctosigmoiditis. The study was carried out as a randomized, double-blind trial in seven gastroenterological departments. A total of 123 patients were included of whom 114 completed the study (53 5-aminosalicylic acid, 61 prednisolone). The patient population was representative for the disease as it ordinarily appears in medical outpatient clinics. After 14 days, patients in total remission discontinued the treatment, while the rest were treated for another two-week period. Improvement or remission was seen in 77% of the 5-aminosalicylic acid-treated patients and in 72% of the prednisolone-treated patients (P>0.05). More than half the patients requiring prolonged treatment benefited from it, which points to an advantage of extended therapy. Side effects were few and mild. It is concluded that the applied suspension of 5-aminosalicylic acid is at least as efficient as prednisolone for topical treatment of patients with slightly to moderately active proctosigmoiditis.The group includes: Vibeke Binder, MD, Stig Bondesen, MD, Olaf Bonnevie, MD, Knud Christian Christensen MD, Lisbeth Ambrosius Christensen, MD, Poul Danø, MD, Hans Draminsky Petersen, MD, Troels Havelund, MD, Eigill F. Hvidberg, MD, Oli Jacobsen, MD, Karin Ladefoged, MD, Karsten Lauritsen, MD, Laurits Stærk Laursen, MD, Jørgen Rask-Madsen, MD, Sten Nørby Rasmussen, MD, German Sanchez, MD, Poul Schlichting, MD, Ulrik Tage-Jensen, MD, Mogens Vilien, MD, Johann Wandall, MD.