Influences of natural menopause on health complaints: a prospective study of healthy Norwegian women.

As a continuation of a cross-sectional study in 1981 involving a representative sample of 1886 women between 45 and 55 years of age, 200 pre-menopausal subjects were selected randomly to take part in a follow-up study. Eighty-seven single measures covering 26 areas of health complaints which have been associated with the menopause in medical textbooks were investigated. A tentative method for relating health complaints at several time points to menopausal status is proposed. A significant number of women reported an increase in vasomotor complaints, vaginal dryness, heart palpitations and social dysfunction following the menopause, although many reported no change or even a reduction in these complaints. On the other hand, a decrease in headache and breast tenderness was noted. No significant differences were observed between the numbers of women reporting an increase or a decrease respectively on any of the other 69 measures (20 complaints), which included anxiety, depression and irritability. Further analyses indicated that the increase in social dysfunction was caused by hot flushes and sweating. This paper raises a number of issues regarding the methodology of longitudinal studies.     

Anterior lumbar fusion using a hybrid interbody graft

Summary This is a radiographic report of 40 patients (20 men, 20 women) who underwent anterior lumbar interbody fusions (73 levels) utilizing a “hybrid” interbody graft composed of femoral cortical allograft (FCA) bone and iliac crest cancellous autograft bone. The average age at surgery was 38 years (range 17–64 years), and follow-up averaged 1.4 years (range 1.0–2.4 years). Nineteen of the patients had undergone previous lumbar surgery. Thirty-two patients (63 levels) underwent anterior fusion combined with some type of posterior fixation, and eight patients (10 levels) had no posterior fixation. Types of posterior fixation included: for 20 patients (36 levels) Steffee variable screw placement fixation, for 10 patients (23 levels) translaminar facet screws (TFS), for 1 patient (3 levels) Knodt rods and for 1 patient (1 level) facet screws. Based on the persistence of lucent lines at the graft-host interface, three patients (one level each) were felt to have non-unions at their latest follow-ups at 1.4, 1.5 and 2.0 years, respectively. Two of these patients had no posterior fixation, and the other had TFS fixation. The overall fusion rate was 96% (70 of 73 levels). The fusion rate for all levels treated with posterior fixation was 98% compared with 75% for those without fixation. Intervertebral disc heights (IVDH) were measured on all films and corrected for magnification with computer assistance. On average, the IVDH was increased postoperatively but returned to preoperative values at follow-up. IVDH loss was independent of the type of instrumentation used. No complications arose from the use of the hybrid graft. Incorporation of the allograft portion of the graft is slow and was felt to be complete in only 7 of the 73 levels at follow-up. We conclude that the hybrid interbody graft technique is a safe and reliable method for performing anterior lumbar interbody fusions and should be combined with some type of posterior fixation. Long-term follow-up will be required to assess the behaviour of the allograft until incorporation is complete.     

Susceptibility to beta-lactam antibiotics and production of beta-lactamase inBacteroides fragilis

Using the agar dilution technique, 231 strains of Bacteroides fragilis, isolated during a 2-year period from human infections, were identified at subspecies level and were tested for susceptibility to 13 beta-lactam antibiotics. The penicillins were benzylpenicillin, ampicillin, carbenicillin, cloxacillin, and the recently described penicillin derivatives cyclacillin, ticarcillin, and PC-904. The following cephalosporin derivatives were tested: cephaloridine, cephalothin, cephalexin, cefamandole and cefuroxime. The cephamycin C derivative cefoxitin was also included in the study. Cefoxitin was the most effective drug tested since more than 80% of the strains were inhibited by 8 microgram/ml or less, and no strain had a minimal inhibitory concentration (MIC) of more than 64 microgram/ml. There was no marked difference in sensitivity among the subspecies with exception of subspecies vulgatus, which was slightly more sensitive to all antibiotics tested. The size of the inoculum was an important factor for obtaining reproducible results in the sensitivity tests. Increased inocula resulted in markedly higher MICs for cephaloridine and cefuroxime. Production of beta-lactamase was performed on all isolates by a chromogenic cephalosporin substrate and about 90% of the strains were found to be beta-lactamase producers.     

Prediction models for insulin resistance in the polycystic ovary syndrome

Women with the polycystic ovary syndrome (PCOS) have a high prevalence of insulin resistance, with consequent increased risk of metabolic diseases later in life. An early metabolic screening would therefore be of clinical relevance. By using stepwise regression analysis on several variables obtained in 72 women with PCOS, we constructed simple and reliable mathematical models predicting insulin sensitivity, as measured by the euglycaemic hyperinsulinaemic clamp. The normal ranges of insulin sensitivity were calculated from 81 non-hirsute, normally menstruating women with normal ovaries, and similar body mass index (BMI) and age as the women with PCOS. Measured variables included BMI, waist and hip circumferences, truncal-abdominal skin folds, circulating concentrations of gonadotrophins, androgens, sex hormone-binding globulin (SHBG), triglycerides, total cholesterol and cholesterol subfractions, fasting insulin, C-peptide and free fatty acids. The three best prediction models included waist circumference, together with insulin (model I: R(2) = 0.77), serum triglycerides (model II: R(2) = 0.65), and the subscapularis skin fold (model III: R(2) = 0. 64). Using reference limits for insulin sensitivity obtained in the 81 normal pre-menopausal women, the models identify insulin resistant women with PCOS. These simple and inexpensive models are potentially useful in clinical practice as an early screening in women with PCOS.     

Inhibition of the development of immediate hypersensitivity by staphylococcal enterotoxin B

We investigated the ability of staphylococcal enterotoxin B (SEB) to modify the immediate hypersensitivity response induced in BALB/c mice following sensitization to ovalbumin (OVA), a response mediated by OVA-reactive Vβ8 T cells. Mice were sensitized by skin painting with OVA every second day over a period of 2 weeks. SEB, a potent activator of Vβ8⁺ T cells, was administered at the same site where OVA was applied (skin of the lower abdomen) following two different protocols. In protocol (A) SEB was injected intradermally 1 day before painting with OVA and on day 7; in protocol B, SEB was injected each time OVA was applied to the skin (eight times). SEB (but not SEA) altered the development of immediate hypersensitivity to OVA, as demonstrated by the reduction in allergen-specific IgE, decreased OVA-specific immediate skin test responsiveness, and prevented the development of increased airways responsiveness after bronchial challenge with OVA. Injections of SEB did not alter the proliferative responses of local draining lymph node cells or spleen mononuclear cells to OVA, indicating that administration of SEB did not inhibit the sensitization to OVA, but shifted the immune response away from an immediate type response (IgE/IgG₁) to IgG_2a, IgG_2b and IgG₃. Although both protocols of SEB treatment did not lead to a major deletion of the Vβ8 T cell population, they did reduce the proliferative response of Vβ8⁺ T cells to OVA. These data indicate that the bacterial toxin SEB is capable of modifying the immediate hypersensitivity response induced by OVA by altering the functional capacity of antigen-reactive Vβ8 T cells.     

Sexual Contact as Risk Factor for Campylobacter Infection,Denmark

Campylobacteriosis is a disease of worldwide importance, but aspects of its transmission dynamics, particularly risk factors, are still poorly understood. We used data from a matched case-control study of 4,269 men who have sex with men (MSM) and 26,215 controls, combined with national surveillance data on Campylobacter spp., Salmonella spp., and Shigella spp., to calculate matched odds ratios (mORs) for infection among MSM and controls. MSM had higher odds of Campylobacter (mOR 14, 95% CI 10–21) and Shigella (mOR 74, 95% CI 27–203) infections, but not Salmonella (mOR 0.2, 95% CI 0–13), and were less likely than controls to have acquired Campylobacter infection abroad (χ² = 21; p<0.001). Our results confirm that sexual contact is a risk factor for campylobacteriosis and also suggest explanations for unique features of Campylobacter epidemiology. These findings provide a baseline for updating infection risk guidelines to the general population.     

Treatment of Burkitt's/Burkitt-like lymphoma in adolescents and adults: a 20-year experience from the Norwegian Radium Hospital with the use of three successive regimens.

BACKGROUND: Burkitt's/Burkitt-like lymphoma (BL/BLL) are highly aggressive lymphomas mainly affecting children and young adults. We report the results in adolescent and adult patients with the use of three successive regimens. PATIENTS AND METHODS: Forty-nine patients aged 15-70 years admitted to the Norwegian Radium Hospital in the period 1982-2001 with a diagnosis of BL/BLL on histological review and who were given chemotherapy with curative intent are included in this analysis. Up to 1987 patients were given doxorubicin-based chemotherapy supplemented with intravenous and intrathecal methotrexate (MmCHOP). From 1987 to 1994, patients who obtained complete remission upon this regimen were consolidated with high-dose therapy with stem-cell support (MmCHOP + HDT). In 1995 we introduced as frontline therapy the German Berlin-Frankfurt-Munster (BFM) regimen. RESULTS: By intention to treat analyses, the progression-free survival rates for patients who received MmCHOP (n=13), MmCHOP + HDT (n=17) or BFM therapy (n=19) are 30.8%, 70.6% and 73.7%, respectively. In the groups of patients who received either the BFM regimen or MmCHOP + HDT, all patients who obtained complete remission upon induction therapy are continuously disease free. There was no treatment-related death. CONCLUSIONS: BL/BLL in adolescents and adults can successfully be treated with 5-day blocks of intensified chemotherapy such as the BFM regimen or CHOP/methotrexate-based chemotherapy consolidated with high-dose therapy. Using the BFM regimen, continuous remissions are obtained without additional myeloablative chemotherapy.     

Immunotherapy for advanced hepatocellular carcinoma: From clinical trials to real-world data and future advances

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated mortality worldwide. HCC is an inflammation-associated immunogenic cancer that frequently arises in chronically inflamed livers. Advanced HCC is managed with systemic therapies; the tyrosine kinase inhibitor (TKI) sorafenib has been used in 1^st-line setting since 2007. Immunotherapies have emerged as promising treatments across solid tumors including HCC for which immune checkpoint inhibitors (ICIs) are licensed in 1^st- and 2^nd-line treatment setting. The treatment field of advanced HCC is continuously evolving. Several clinical trials are investigating novel ICI candidates as well as new ICI regimens in combination with other therapeutic modalities including systemic agents, such as other ICIs, TKIs, and anti-angiogenics. Novel immunotherapies including adoptive cell transfer, vaccine-based approaches, and virotherapy are also being brought to the fore. Yet, despite advances, several challenges persist. Lack of real-world data on the use of immunotherapy for advanced HCC in patients outside of clinical trials constitutes a main limitation hindering the breadth of application and generalizability of data to this larger and more diverse patient cohort. Consequently, issues encountered in real-world practice include patient ineligibly for immunotherapy because of contraindications, comorbidities, or poor performance status; lack of response, efficacy, and safety data; and cost-effectiveness. Further real-world data from high-quality large prospective cohort studies of immunotherapy in patients with advanced HCC is mandated to aid evidence-based clinical decision-making. This review provides a critical and comprehensive overview of clinical trials and real-world data of immunotherapy for HCC, with a focus on ICIs, as well as novel immunotherapy strategies underway.