Predictability of reformatted computed tomography for pre-operative planning of endosseous implants

OBJECTIVES: To determine the reliability of reformatted 2D-CT for pre-operative planning of implant placement. METHODS: One hundred consecutive partially or fully edentate patients underwent 2-D reformatted CT pre-operative planning and subsequent implant placement. The number, site and size of the implants, the available bone height and anatomical complications were recorded. The pre-operative planning and the outcome at surgery were compared statistically using a percentage agreement and Kendall's correlation coefficient. RESULTS: Agreement between the pre- and intra-operative data was good for the number of implants (60%) and the selected sites (70%). From a total of 416 implants planned, 21 implants could not be placed because of intra-operative findings. Agreement was relatively poor for implant size (44%) and anatomical complications (46%). Kendall's correlation coefficient was highest for the number of implants (0.80) and implant sites (0.81). It was much lower for implant sizes (0.51) and did not reach significance for anatomical complications (0.09). CONCLUSIONS: Reformatted 2D-CT is reliable for the pre-operative assessment of the number and sites of implants in the jaws. It is less predictable for the implant size needed and poor for anatomical complications.     

Differential effects of injections of anti-mu and anti-delta monoclonal antibodies on B-cell populations in adult mice: regulation of xenoreactive natural antibody-producing cells

BACKGROUND: The depletion of differential B cell and xenoreactive natural antibodies (XNA) by anti-delta and anti-mu injections was analyzed in adult mice. Sequential treatment with anti-delta and then anti-mu induces a complete depletion of B cells and XNA and represents a potential approach to induce xenograft tolerance. METHODS: Adult mice were injected with anti-mu, anti-delta, anti-delta then anti-mu, or control isotype monoclonal antibodies from day 0 to day 14. The different B-cell populations were analyzed by FACS and immunohistology. Ig production was tested by ELISA. XNA were analyzed by FACS. RESULTS: Anti-mu injections induced a depletion of IgMhigh, immature B cells, marginal zone B cells, and B1 cells and an increase of IgG-XNA production. Anti-delta injections induced mature conventional IgDhigh B-cell depletion and increased IgM-XNA production. Interestingly, sequential injections of anti-delta then anti-mu induced a depletion of immature B cells, mature B cells (MZ, B2, and B1), and XNA. CONCLUSIONS: These results demonstrate that mature B-cell depletion in adult mice can be obtained by mAb injections and depends on the surface immunoglobulin cross-linking threshold. Indeed, anti-mu mAb depleted IgMhigh B cells (MZ and B1) and anti-delta, IgDhigh B cells (B2). The differential B-cell suppression shows that conventional B cells are responsible in the IgG-XNA production and MZ and B1 cells in the IgM-XNA production. Sequential repeated injections of anti-delta then anti-mu mAb depleted all B-cell populations and suppressed the whole XNA production.     

Bilateral cystoid macular edema following successful treatment of AIDS-associated CMV retinitis

Background: Cystoid macular edema (CME) in AIDS patients with inactive cytomegalovirus (CMV) retinitis is an uncommon but potentially sight-threatening complication. The pathogenesis of CME in these patients is unclear. This study tries to identify possible risk factors by analyzing the charts of five patients. Methods: Ten eyes of 5 patients that finally developed CME were followed for an average of 18 months. The initial retinal lesions, their response to antiviral treatment, the development of CME, and the patients' immune status were prospectively monitored. Results: CMV retinitis was diagnosed at a median CD4+ count of 3 cells/mm³ (range 0–11). All eyes responded to the initial systemic anti-viral treatment. At the onset of CME, CMV retinitis was controlled by antiviral maintenance therapy in all patients [ganciclovir (n = 2), cidofovir (n = 2), foscarnet (n = 1)]. The median time between diagnosis of CMV retinitis and onset of CME was 11.5 months (range 5–24). Development of CME was associated with significant visual loss: acuity ranged from 0.05 to 0.7 when CME was first noticed, compared to 0.8–1.25 at diagnosis of CMV retinitis. Duration of inflammation, size or zone of retinal necrosis did not favor the development of CME, neither did the antiviral therapy. A weak correlation of CME development and immune status (expressed as increase of CD4+ cells) was found. Due to systemic corticosteroids CME resolved. Conclusions: CME is a new visual threat to AIDS-patients with CMV retinitis whose immune status improved under the latest combined antiretroviral therapy. Therapy with oral corticosteroids may positively influence this condition.      

Effects of varying the expression level of recombinant human mGlu1alpha receptors on the pharmacological properties of agonists and antagonists

1. Different expression levels of the human type 1alpha metabotropic glutamate (mGlu1alpha) receptor were obtained in transfected Chinese hamster ovary cells using an isopropyl beta-D-thiogalactopyranoside (IPTG) inducible system. Expression of mGlu1alpha receptors could not be detected using immunoblotting or immunocytochemical approaches in non-induced cells, however, controlled expression could be induced following IPTG addition in a time- and concentration-dependent manner. 2. In induced cells (100 microM IPTG, 20 h) the agonists L-quisqualate or 1-aminocyclopentane-1S,3R-dicarboxylic acid stimulated large increases in [3H]-inositol (poly)phosphate (in the presence of Li+) and inositol, 1,4,5-trisphosphate levels. 3. Induction with 1-100 microM IPTG allowed the receptor density to be increased incrementally and this not only resulted in an increase in the maximum response to L-quisqualate, 1-aminocyclopentane-1S,3R-dicarboxylic acid and (S)-3,5-dihydroxy-phenylglycine, but also in an increase in the respective potencies of each agent to activate phosphoinositide hydrolysis. 4. The intrinsic activity of the partial agonist 1-aminocyclopentane-1S,3R-dicarboxylic acid dramatically increased with increasing receptor expression. 5. The activities of the competitive mGlu1alpha receptor antagonists (S)-alpha-methyl-4-carboxyphenylglycine and (S)-4-carboxy-3-hydroxyphenylglycine for inhibition of the effects of L-quisqualate or (S)-3,5-dihydroxyphenylglycine were found to be independent of the receptor expression level. 6. When the mGlu1alpha receptor was expressed at very high levels, no evidence for receptor constitutive activity could be detected, and none of the antagonists tested revealed either any intrinsic activity or negative efficacy. 7. These data demonstrate that both the potency and efficacy of mGlu1alpha receptor agonists are influenced by expression level, whilst mGlu1alpha receptor antagonist activities are independent of expression level.     

Hemorrhagic fevers: few clues after 25 years

There is a high prevalence of Ebola antibodies found in the Kenya population, related to geographical area and season, although the clinical disease was never found and the virus was not isolated. A field study was carried out in 7 hospitals in western Kenya, 1986 -1987 (including surveillance studies in suspect areas), to intensify collection and transport of samples, testing facilities, patient observation with record keeping and follow-up. This study involved 1109 admitted patients with fever and/or bleeding, 155 contacts of haemorrahagic fever antibody (Hfab) patients, and 916 people in suspect areas. Respectively 160,44 and 80 persons were found Hfab positive mainly to Ebola, using an indirect immunofluorescent assay. From 676 viral cultures no virus was isolated. A relationship between antibody titres and ecological factors, social habitat, age, sex or season was not found. The non-specificity of IF testing was demonstrated by: 1) the disagreement between the results of two reference laboratories; 2) the unpredictability of the titre conversation course; and 3) by proving a significant cross-reactivity with Borrelia burgdorferii antibodies, Plasmodium falcparum antibodies and Salmonella typhi antibodies. Renewed testing in 1995 of 90 positive sera (with low titres) showed 19 sera to be positive by Elisa (2 in Zaire, 1 in Sudan, 9 in Reston and 7 in Cote d'Ivoire) from which 4 were confirmed by IFI 2 in Reston and 2 in Cote d'Ivoire. These findings are more proof that non-human virulent strains of Filoviridae, especially Ebola virus, are around in Kenya.     

The influence of δ9-Tetrahydrocannabinol on intraocular pressure in the anaesthetized cat

⁹-Tetrahydrocannabinol (⁹-THC) was injected both intravenously and into the brain stem via the left vertebral artery. Contrary to results obtained with clonidine, neither the fall in intraocular pressure (IOP), nor the arterial hypotension induced by ⁹-THC, were enhanced after the central administration of the drug. For clonidine, a central mechanism underlying the ocular hypotensive effect has recently been proposed. This suggestion is based upon the enhanced fall in IOP after central administration of clonidine. The pontomedullary area is considered to be the main initial target of this drug. Obviously, the IOP-lavering mechanism of ⁹-THC is different from that of clonidine.     

Quality control of surgical technique in a multicenter, prospective, randomized, controlled study on the surgical treatment of gastric cancer.

To evaluate the effect of lymph node dissection on gastric cancer patients operated upon with curative intent, we are carrying out a multicenter, prospective, randomized, controlled study in the Netherlands. The trial compares conventional gastrectomy to gastrectomy with extended lymph node dissection. In the first four months, a Japanese supervisor attended all the extended surgery and instructed many Dutch surgeons, including the eight consulting surgeons; since then, all extended gastrectomies have been attended by one of the consulting surgeons. The study coordinator attended all conventional cases. This assured that the quality of the extended surgery was as good as the Japanese standard, of which excellent results have been reported. To achieve this quality control, randomization before surgery was obligatory for practical reasons. Curability assessment at laparotomy, however, is done quite objectively with histological proof, except for the judgement of irresectability. Although this has resulted in many non-curative cases being randomized but subsequently not given the allocated surgery, the sample size should be sufficient to allow analysis according to randomization or the initial "intention to treat." This is the first protocol for a multicenter trial in surgical oncology to have such excellent surgical quality control and to assure a quality as high as that in the original report with uniformity in the level of technique. In studies comparing surgical techniques, it is vital that attention should be given to surgical quality control, otherwise survival rates may show little improvement and fail to make any impact on surgical practice.     

The conduct of in vitro and in vivo drug-drug interaction studies: a Pharmaceutical Research and Manufacturers of America (PhRMA) perspective.

Current regulatory guidances do not address specific study designs for in vitro and in vivo drug-drug interaction studies. There is a common desire by regulatory authorities and by industry sponsors to harmonize approaches, to allow for a better assessment of the significance of findings across different studies and drugs. There is also a growing consensus for the standardization of cytochrome P450 (P450) probe substrates, inhibitors and inducers and for the development of classification systems to improve the communication of risk to health care providers and to patients. While existing guidances cover mainly P450-mediated drug interactions, the importance of other mechanisms, such as transporters, has been recognized more recently, and should also be addressed. This article was prepared by the Pharmaceutical Research and Manufacturers of America (PhRMA) Drug Metabolism and Clinical Pharmacology Technical Working Groups and represents the current industry position. The intent is to define a minimal best practice for in vitro and in vivo pharmacokinetic drug-drug interaction studies targeted to development (not discovery support) and to define a data package that can be expected by regulatory agencies in compound registration dossiers.     

Methylated DNA collected by tampons--a new tool to detect endometrial cancer.

This proof of principle study aimed to define a new and simple strategy for detection of endometrial cancer using epigenetic markers. We investigated DNA isolated from vaginal secretion collected from tampon for aberrant methylation of five genes (CDH13, HSPA2, MLH1, RASSF1A, and SOCS2) using MethyLight in 15 patients with endometrial cancer and 109 patients without endometrial cancer. All endometrial cancer patients revealed three or more methylated genes, whereas 91% (99 of 109) of the patients without endometrial cancer had no or fewer than three genes methylated in their vaginal secretion. The methods developed in this study provide the basis for a prospective clinical trial to screen asymptomatic women who are at high risk for endometrial cancer.     

The Dutch normal-pressure hydrocephalus study. How to select patients for shunting? An analysis of four diagnostic criteria

BACKGROUND: Comparison of the predictive value of four "diagnostic tests" for the outcome of shunting in patients with normal-pressure hydrocephalus (NPH). METHODS: Ninety-five NPH patients who received shunts were followed for 1 year. Gait disturbance and dementia were quantified by an NPH scale and handicap by a modified Rankin scale. Primary outcome measures were differences between the preoperative and last scores on both the NPH scale and the modified Rankin scale. Clinical and computed tomographic (CT) findings typical of NPH, absence of cerebrovascular disease, and a resistance to outflow of cerebrospinal fluid (CSF) >/= 18 mmHg/ml/minute were designated as a positive test outcome; clinical and CT findings compatible with NPH, presence of cerebrovascular disease, and an outflow resistance < 18 mmHg/ml/minute as a negative test outcome. RESULTS: For each of the four tests the percentage of patients classified as improved was significantly greater for those with positive than with negative test results. Measurement of CSF outflow resistance was the only significant prognostic factor for the improvement ratio in NPH scale and CT in the modified Rankin scale according to multivariate logistic regression analysis. The accurate predictive value of the combination of typical clinical and CT findings was 0.65, that of the positive test results of outflow resistance, clinical and CT findings was 0.74. CONCLUSION: The best strategy is to shunt NPH patients if their outflow resistance is >/= 18 mmHg/ml/minute or, when the outflow resistance is lower, if their clinical as well as their CT findings are typical of NPH.