Multicenter phase II study of Nordic fluorouracil and folinic acid bolus schedule combined with oxaliplatin as first-line treatment of metastatic colorectal cancer.

PURPOSE: This Nordic multicenter phase II study evaluated the efficacy and safety of oxaliplatin combined with the Nordic bolus schedule of fluorouracil (FU) and folinic acid (FA) as first-line treatment in metastatic colorectal cancer. PATIENTS AND METHODS: Eighty-five patients were treated with oxaliplatin 85 mg/m(2) as a 2-hour infusion on day 1, followed by a 3-minute bolus injection with FU 500 mg/m(2) and, 30 minutes later, by a bolus injection with FA 60 mg/m(2) every second week. The same doses of FU and FA were also given on day 2. RESULTS: Fifty-one of 82 assessable patients achieved a complete (n = 4) or partial (n = 47) response, leading to a response rate of 62% (95% CI, 52% to 72%). Nineteen patients showed stable disease, and 12 patients had progressive disease. Thirty-eight of the 51 responses were radiologically confirmed 8 weeks later (confirmed response rate, 46%; 95% CI, 36% to 58%). The estimated median time to progression was 7.0 months (95% CI, 6.3 to 7.7 months), and the median overall survival was 16.1 months (95% CI, 12.7 to 19.6 months) in the intent-to-treat population. Neutropenia was the main adverse event, with grade 3 to 4 toxicity in 58% of patients. Febrile neutropenia developed in seven patients. Nonhematologic toxicity consisted mainly of neuropathy (grade 3 in 11 patients and grade 2 in another 27 patients). CONCLUSION: Oxaliplatin combined with the bolus Nordic schedule of FU+FA (Nordic FLOX) is a well-tolerated, effective, and feasible bolus schedule as first-line treatment of metastatic colorectal cancer that yields comparable results compared with more complex schedules.     

Inframalleolar bypass in limb salvage. Late results

STUDY OBJECTIVE: The objective of this retrospective study was to report the long-term results of distal revascularization at the ankle in patients with critical ischemia. PATIENTS AND METHODS: From January 1989 to November 1999, 50 inframalleolar bypasses were performed in 49 patients (35 males and 14 females with a mean age of 75 years [range: 51 to 95 years]). Twenty-five patients (50%) were diabetics. All patients presented with critical ischemia of the lower limb. Distal anastomosis was performed at the retromalleolar posterior tibial artery in 28 cases (56%), pedal artery in 20 cases (40%) and distal fibular artery in two cases (4%). Bypasses were performed using a greater saphenous vein (n = 38), a cryopreserved arterial allograft (n = 9), or a PTFE graft (n = 2). A composite graft with greater saphenous vein and arterial allograft was performed in two cases. RESULTS: There were two early postoperative deaths. One patient presented a blow-out of the distal anastomosis that required bypass ligation and subsequent leg amputation. Early thrombosis of the graft occurred in four cases, leading to major amputation in three cases. No patients were lost to follow-up and mean follow-up was 26.7 months (range: 1 to 86 months). Graft thrombosis occurred in 15 patients and led to amputation in 6 cases. Bypass graft patency rate was 72% and 61% at 1 year and 3 years, respectively, yielding a 80% limb salvage rate at 3 years. The 3-year actuarial survival rate was 53%. CONCLUSION: Inframalleolar bypasses are a valuable tool in patients with critical ischemia. The lower limb salvage rate is satisfactory in this elderly population. Based on this experience, angiography with good run-off and, when necessary, a surgical approach to verify patency of the arteries at the ankle should always be performed before undertaking a major amputation.     

Short-term exposure to stone minerals used in asphalt affect lung function and promote pulmonary inflammation among healthy adults

ObjectiveStone minerals are a partially ignored environmental challenge but a significant contributor to urban air pollution. We examined if short-term exposure to two stone minerals – quartz diorite and rhomb porphyry – commonly used in asphalt pavement would affect lung function, promote pulmonary inflammation, and affect bronchial reactivity differently.MethodsOur randomized crossover study included 24 healthy, non-smoking young adults exposed to the stone minerals quartz diorite, rhomb porphyry, and control dust (lactose). Exposure occurred in an exposure chamber, in three separate 4-hour exposure sessions. Fractional exhaled nitric oxide (FeNO) and lung function were monitored before exposure, then immediately following exposure, and 4 and 24 hours after exposure. In addition, methacholine was administered 4 hours following exposure, and exhaled breath condensate (EBC) was collected before exposure, then immediately and 4 hours after exposure. EBC was analyzed for pH, thiobarbituric acid reactive substances (TBARS), intercellular adhesion molecule 1 (ICAM-1), interleukin-6 (IL-6), IL-10, P-Selectin, surfactant protein D (SP-D), and tumor necrosis factor-α (TNF-α).ResultsOur results showed significantly elevated concentrations of FeNO after exposure to quartz diorite compared to rhomb porphyry, suggesting that quartz diorite is more likely to trigger pulmonary inflammation after short-term exposure. Moreover, short-term exposure to rhomb porphyry was associated with a modest but statistically significant decline in forced vital capacity (FVC) compared to quartz diorite.ConclusionThese results emphasize that using stone material in asphalt road construction should be reconsidered as it may affect lung inflammation and lung function in exposed subjects.     

Antibiotic resistance in hospitals: a ward‐specific random effect model in a low antibiotic consumption environment

Association between previous antibiotic use and emergence of antibiotic resistance has been reported for several microorganisms. The relationship has been extensively studied, and although the causes of antibiotic resistance are multi‐factorial, clear evidence of antibiotic use as a major risk factor exists. Most studies are carried out in countries with high consumption of antibiotics and corresponding high levels of antibiotic resistance, and currently, little is known whether and at what level the associations are detectable in a low antibiotic consumption environment. We conduct an ecological, retrospective study aimed at determining the impact of antibiotic consumption on antibiotic‐resistant Pseudomonas aeruginosa in three hospitals in Norway, a country with low levels of antibiotic use. We construct a sophisticated statistical model to capture such low signals. To reduce noise, we conduct our study at hospital ward level. We propose a random effect Poisson or binomial regression model, with a reparametrisation that allows us to reduce the number of parameters. Inference is likelihood based. Through scenario simulation, we study the potential effects of reduced or increased antibiotic use. Results clearly indicate that the effects of consumption on resistance are present under conditions with relatively low use of antibiotic agents. This strengthens the recommendation on prudent use of antibiotics, even when consumption is relatively low. Copyright © 2012 John Wiley & Sons, Ltd.     

Caries decline before fluoride toothpaste was available: earlier and greater decline in the rural north than in southwestern Norway

The purpose of this study was to evaluate factors related to caries in 6–17-year-olds in 2 groups of Norwegian counties between 1966 and 1983. The average number of surfaces filled and permanent teeth extracted due to caries declined in the 4 northern counties from 1967. An increase was recorded in the 7 southwestern counties until 1971, then a decline. In the 1960s significantly more surfaces were filled and teeth extracted in the north compared to the southwest. Based on intra-county comparisons, the decline in surfaces treated was greater in the north between 1967 and 1983; 5.4 ± 0.4 vs 3.7 ± 0.7, P < 0.01. The averages were 1.9 surfaces treated in the north and the southwest in 1983. Higher infant mortality, lower percentage of people with completed senior secondary education, and more inhabitants per doctor and per dentist in the north indicate a less favorable situation than in the southwest. School-based fluoride programs had been implemented in both groups from the mid-1960s and around 60% participated when fluoride toothpaste became freely marketed in 1971. More fluoride programs and more fluoride tablets were available to children in the north; this may indicate a preventive attitude among dentists. The decline of caries started at different times in different parts of Norway. In the rural north with the most unfavorable situation, the decline was greater and started years before fluoride toothpaste came on to the market. The early decline may partly be ascribed to the school-based fluoride programs, the continued decline to several factors.     

Tuberculose mammaire : à propos de quatre cas à l’hôpital d’instruction des armées Omar Bongo Ondimba (HIAOBO) de Libreville (Gabon)

Mammary tuberculosis is a rare localization of extra pulmonary tuberculosis. Its frequency increases proportionally with the HIV pandemic. We report four cases of breast tuberculosis diagnosed in the general medicine department of HIAOBO including two with positive HIV serology. It is necessary to know this extra pulmonary form/feature as the differential diagnosis with breast tumors is sometimes difficult     

Immune‐mediated diseases and microbial exposure in early life

The non‐communicable disease pandemic includes immune‐mediated diseases such as asthma and allergy, which are likely originating in early life where the immature immune system is prone to alterations caused by the exposome. The timing of exposure seems critical for the developing immune system, and certain exposures may have detrimental effects in the earliest life, but no or even beneficial effects later. The human microbiome and infections are candidates as intermediary in the interaction between the host and the environment. The evidence seems inconsistent as infections as well as particular colonization patterns in neonates drive both short‐term and long‐term asthma symptoms, while, on the other hand, the composition of the microbiome in early life may protect against asthma and allergy in later life. This apparent contradiction may be explained by a deeper disease heterogeneity than we are currently able to discriminate, and in particular, the indiscriminate lumping together of different diseases into one atopic disease category. Also, the microbiome needs a differentiated understanding, considering balance between microbial groups, diversity and microbial genetic capability. Furthermore, the effects of the microbial exposure may only affect individuals with certain susceptibility genes. Few of the observations have been replicated, and publication bias is likely. Therefore, we are still far from understanding, or having proved, causal effects of the human microbiome. Still, the microbiome–gene interaction is a fascinating paradigm that fosters exiting research and promises a breakthrough in the understanding of the mechanisms driving asthma, allergy and eczema, and potentially also other immune‐mediated non‐communicable diseases.