Development and validation of a procedure for the determination of minoxidil in hair-regrowth formulations using two variants of capillary zone electrophoresis.

A high performance capillary electrophoresis method was developed and validated for purity assessment of minoxidil bulk drug and for determination of minoxidil in Rogaine. The principal use of the method was in analyzing illicit minoxidil-containing hair-regrowth samples. Although validated for Rogaine, the procedure proved equally viable on illicit minoxidil-containing preparations. The developed method fulfilled the goal of providing an orthogonal technique to HPLC for confirmation of the presence of minoxidil in these imitations. The method was validated on two instruments, one utilizing EK injection, the other gravity injection. It is selective for minoxidil, which is separated from known process impurities and the single degradation impurity. Validation figures of merit for linearity/recovery (accuracy) and precision were in accordance with current expectations for method validation.

Free-energy landscape and the critical velocity of superfluid films.

We briefly review some important properties of superfluid flow, especially the problem of critical velocity. We then present new numerical simulation results for a mesoscopic model of superfluids shedding light on the free-energy landscape, the critical velocity and the formation of vortices, which destroy the superflow when the velocity is high.

Induction of anti-mammary cancer immunity by engaging the OX-40 receptor in vivo.

The OX-40 receptor (OX-40R) is a member of the tumor necrosis factor receptor (TNF-R) superfamily that is expressed on activated CD4+ T cells. The OX-40R is a costimulatory molecule that induces CD4+ T cell activation when engaged by its ligand (OX-40 L; found on antigen presenting cells). In human and murine tumors, we have shown upregulation of the OX-40R on CD4+ T cells from tumor-infiltrating lymphocytes (TIL) and tumor-draining lymph node cells (TDLNC) but not on systemic CD4+ T cells, such as peripheral blood lymphocytes (PBL) or splenocytes. In order to examine potentially heightened anti-tumor immunity through enhanced costimulation when engaging OX-40R in vivo, we inoculated mice with a murine mammary cancer cell line (SM1) and then treated with a soluble form of the OX-40 L. Mice injected with a lethal inoculum of SM1 cells were given two intraperitoneal injections (days 3 and 7 post-inoculation) of 100 microg soluble OX-40 L. Seven of 28 treated mice survived the lethal tumor inoculum, as compared to one of 28 control mice, demonstrating a significant survival benefit with treatment (p = 0.0136, log rank analysis). Mice that did not develop tumor by day 90 were rechallenged; all remained tumor-free. Mice were also injected with a second mammary tumor line (4T1) and treated with OX-40L:Ig with similar therapeutic results. Activation of OX-40R+ CD4+ T cells during mammary cancer priming stimulated an antitumor immune response resulting in enhanced survival and protective anti-tumor immunity. These results should have practical applications for treatment modalities for patients with breast cancer.

Medium-throughput pKa screening pharmaceuticals by pressure-assisted capillary electrophoresis.

A fast screening method for the determination of the dissociation constants (pKa) of acidic, basic, and multivalent compounds was developed by using pressure-assisted capillary electrophoresis (PACE). External air pressure was applied to shorten the analysis time. The separation efficiency decreases as air pressure increases. However, it was found that air pressure does not affect the measurement of electrophoretic mobility and pKa significantly when it is less than 2 psi. The method was evaluated in terms of accuracy, precision, and ruggedness by using a set of 48 compounds with literature pKa values ranging from 2 to 10. The difference between the measured pKa values and literature values is less than 0.2 units. The throughput is approximately 20 compounds per day with a 12-point measurement ranging from pH 2.5 to 11. It was demonstrated that this method is applicable for pKa screening of pharmaceuticals with diverse chemical structures.

Long-term prosthodontic follow-up and revisional treatment of patients with cleft lip and palate: case presentation.

PURPOSE: The purpose of this article is to draw attention to the need for regular life-long follow-up care of cleft lip and palate patients to maintain adequate masticatory function, speech, and esthetics, thereby supporting psychosocial function. MATERIALS AND METHODS: Initial and revisional prosthodontic treatments over a period of 32 years in a patient with a bilateral cleft lip and palate are described. RESULTS: Despite an initial dentition of poor health and prognosis and suboptimal patient cooperation, it was possible to arrive at an improved clinical and radiologic state of oral health by the end of the observation period. CONCLUSION: Regular life-long prosthodontic follow-up with adequate maintenance and revisional treatments should be regarded as an essential part of the long-term care for subjects with clefts.

Immunohistochemical analysis of primary breast tumors and tumor-draining lymph nodes by means of the T-cell costimulatory molecule OX-40.

OBJECTIVES: The OX-40 receptor (OX-40R/CD134) is expressed primarily on activated CD4(+) ("helper") T cells. We have previously reported the presence of OX-40(+) T cells in head and neck cancer and melanoma, where they appear to be restricted to tumor compartments (primary tumor infiltrating lymphocytes [TILs] and draining lymph node cells) and therefore may represent the tumor antigen-specific CD4(+) T cells. METHODS: In order to determine the degree of OX-40R expression, and any relationship with the presence of tumor cells (lobular and/or infiltrating ductal carcinoma), 45 archived paraffin-embedded breast primary tumors and their associated draining (axillary) lymph nodes were retrospectively analyzed using standard immunohistochemical techniques. RESULTS: Seven of 45 primary tumors (16%) and 7 of 29 with lympocytic infiltrates (24%) were noted to have elevated levels of OX-40R(+) lymphocytes within the tumor specimens, including 2 of 4 specimens thought to have only "pure" ductal carcinoma in situ (DCIS). No OX-40R(+) lymphocytes were noted in normal breast tissue. Twenty-one (43%) patients had axillary metastases at the time of resection. High levels of OX-40R expression was seen in 9 (45%) of these 21 axillary node specimens, whereas no such staining was seen in the node-negative specimens (P <0.001). Furthermore, in a patient thought to be without axillary disease, several subcapsular single-cell metastases were retrospectively discovered near a lone cluster of OX-40R(+) lymphocytes. In general, visual inspection showed OX-40R(+) T cells to be in close proximity to tumor and often in direct contact with metastatic cells. CONCLUSIONS: The OX-40R is upregulated on lymphocytes within tumor draining lymph nodes, and these lymphocytes are specifically localized around tumor deposits. These data imply that OX-40R immunostaining may be useful for both determination of occult involvement of lymph nodes by tumor and for identification of potential candidates for future OX-40 based immunotherapy.

Engagement of the OX-40 receptor in vivo enhances antitumor immunity.

The OX-40 receptor (OX-40R), a member of the TNFR family, is primarily expressed on activated CD4+ T lymphocytes. Engagement of the OX-40R, with either OX-40 ligand (OX-40L) or an Ab agonist, delivers a strong costimulatory signal to effector T cells. OX-40R+ T cells isolated from inflammatory lesions in the CNS of animals with experimental autoimmune encephalomyelitis are the cells that respond to autoantigen (myelin basic protein) in vivo. We identified OX-40R+ T cells within primary tumors and tumor-invaded lymph nodes of patients with cancer and hypothesized that they are the tumor-Ag-specific T cells. Therefore, we investigated whether engagement of the OX-40R in vivo during tumor priming would enhance a tumor-specific T cell response. Injection of OX-40L:Ig or anti-OX-40R in vivo during tumor priming resulted in a significant improvement in the percentage of tumor-free survivors (20-55%) in four different murine tumors derived from four separate tissues. This anti-OX-40R effect was dose dependent and accentuated tumor-specific T cell memory. The data suggest that engagement of the OX-40R in vivo augments tumor-specific priming by stimulating/expanding the natural repertoire of the host's tumor-specific CD4+ T cells. The identification of OX-40R+ T cells clustered around human tumor cells in vivo suggests that engagement of the OX-40R may be a practical approach for expanding tumor-reactive T cells and thereby a method to improve tumor immunotherapy in patients with cancer.

The influence of alveolar bone grafting on the orthodontic and prosthodontic treatment of patients with cleft lip and palate.

The introduction of mixed dentition bone grafting of alveolar clefts means that the alveolar process can be fully restored, permitting adjacent teeth to migrate or be orthodontically moved into the grafted bone. Thus a complete dental arch can be obtained without prosthodontics in the great majority of patients. In addition, oral-nasal fistulae are closed, mucosal recesses eliminated (facilitating oral hygiene) and the long-term periodontal health of the teeth adjacent to the former cleft is improved. Alveolar bone grafting with subsequent orthodontic treatment, together with advances in dental materials, have contributed substantially to the care of patients with alveolar clefts, reducing the need for prosthodontic procedures and allowing completion of the dental treatment at an earlier age.

A definition of prosthetic dentistry.

PURPOSE: A more precise and up-to-date definition of prosthetic dentistry is warranted. The aim of the present review is to present a new core definition of the discipline on the basis of a discussion of existing definitions. MATERIALS AND METHODS: Clinical textbooks in prosthetic dentistry and dental implantology, as well as medical and dental glossaries were reviewed. RESULTS: Two main categories of definitions of prosthetic dentistry were identified: first, definitions that emphasized the technologic aspects of the discipline, i.e., the fabrication of prostheses; and second, definitions that incorporated some reference to the objectives or aims of prosthetic treatment, i.e., the restoration of one or more aspects of oral function. Slightly more than half of the citations contained such aim-related references, and this aspect tended to be most pronounced in recent publications. CONCLUSION: The following definition is ventured: prosthodontics is the discipline of dentistry concerned with the consequences of congenital absence or acquired loss of oral tissues and with the methods for and assessment whether more good than harm is done by inserting artificial devices made from alloplastic materials.

Synthesis filterbank with low hardware complexity for subband image coding.

Different algorithms are evaluated and optimizations are performed to obtain a filterbank for subband coding of images especially suited for very large scale integration (VLSI) implementation. Based on a filterbank consisting of two finite impulse response (FIR) filters combined with an 8-point discrete cosine transform (DCT), we investigate how the quantization of filter coefficients and twiddle factors in different algorithms affects the quality of the filterbank. It is found that a DCT based on a Stasinksi (1989) algorithm with twiddle factors of only 5 b together with FIR filter coefficients of 10 b gives a filterbank with high coding gain, no blocking artifacts, and limited ringing. The VLSI complexity is comparable to that of DCT transforms.

A long-term study of transverse stability of maxillary teeth in patients with unilateral complete cleft lip and palate.

The aim of this study was to investigate the long term post-treatment transverse stability of the maxillary dental arch in subjects with unilateral complete cleft lip and palate (UCLP) treated by the Harvold/Bøhn method of orthodontic expansion and prosthodontic retention. The treatment of 22 consecutive patients, primarily operated on during the period 1957-60, was completed at a mean age of 18.1 years by the provision of a fixed partial retention prosthesis across the cleft using the cleft side central incisor and canine only as abutment teeth. The cleft side lateral incisor was missing in each case. Dental casts were made at the time of abutment preparation and at six subsequent times with the final observation 13.5 years after treatment completion. Measurements of any shift in the transverse position of cleft side and non-cleft side canines, premolars and first molars were made on standardized photographs of the casts. A constructed anteroposterior palatal line served as 'midline' reference. A mean reduction of width at the final observation, as recorded from the palatal surface to the reference line, was for the cleft side canine: -0.4 mm, the premolar immediately distal to the prosthesis and the first molar: both -1.2 mm. The corresponding mean width reductions on the noncleft side were: canine -0.9 mm, premolar -1.2 mm, first molar -1.6 mm. The rate of movement towards the midline decreased linearly with In(time) for all variables (P < 0.02) but for the cleft side canine.

The effect of alveolar bone grafting on the prosthodontic/reconstructive treatment of patients with unilateral complete cleft lip and palate.

This study compared the effect that the introduction of mixed dentition alveolar bone grafting and subsequent orthodontic treatment has had on the prosthodontic/reconstructive habilitation of patients with unilateral cleft lip and palate. Two groups, each consisting of 40 consecutive patients with unilateral cleft lip and palate, were compared at the end of their dental treatment. In the group treated prior to the advent of bone grafting, all subjects received a fixed partial prosthesis in the cleft area, and a total of 87 abutment teeth were prepared for complete coverage crowns. In contrast, in the group of patients for whom the alveolus was restored by bone grafting, it was possible to obtain a complete dental arch without prosthodontic intervention in 36 patients (90%). Thirteen subjects in the bone grafting group had the crown anatomy of anterior teeth modified using resin composite or resin-bonded porcelain veneers. Two patients had a premolar transplanted to the anterior region of the dental arch. On average the dental treatment was completed 3 years earlier in the bone grafting group. Thus, alveolar bone grafting with subsequent orthodontic treatment, together with advances in dental materials, have markedly reduced the need for prosthodontic procedures and have also allowed the completion of the dental treatment at an earlier age.

Psychosocial adjustment in Norwegian adults who had undergone standardised treatment of complete cleft lip and palate. II. Self-reported problems and concerns with appearance.

Aspects of social and psychological adjustment were investigated in a sample of 233 Norwegian adults 20-35 years old with repaired complete cleft lip and palate (CLP); in 126 the cleft was on the left, in 45 on the right, and in 62 it was bilateral. All subjects received a standardised regimen of care from the Oslo cleft palate team. The study, based on response to a questionnaire, partly copied a national survey of social and economic life in the Norwegian population. Adults with complete clefts were compared with a large control sample of the same age. The purpose of this paper is to describe the occurrence of common psychological problems among subjects with CLP. Anxiety, depression, and palpitations were reported about twice as often by subjects with CLP compared with controls, and these psychological problems were strongly associated with concerns about appearance, dentition, speech, and desire for further treatment. These findings suggest that there is an impaired level of psychological wellbeing among subgroups of subjects with clefts.

Psychosocial adjustment in Norwegian adults who had undergone standardised treatment of complete cleft lip and palate. I. Education, employment and marriage.

Aspects of social and psychological adjustment were investigated in a sample of 233 Norwegian adults 20-35 years old with repaired complete cleft of the lip and palate (CLP); in 126 the cleft was on the left, in 45 on the right, and in 62 it was bilateral. All subjects received a standardised regimen of care from the Oslo cleft palate team. The investigation, based on response to a questionnaire, partly replicated a national survey of social and economic life in the population, so that adults with complete clefts could be compared with a large control sample of the same age. This report covers education, employment, and marriage. The results confirm previous findings that there are few differences in educational attainment and employment between adults with CLP and other people. Fewer with CLP marry, and when they marry they do so later in life, particularly if the CLP is bilateral. Income seemed to be lower among married men and single women with CLP than among the control population.

On the optimality of nonunitary filter banks in subband coders.

This paper investigates the energy compaction capabilities of nonunitary filter banks in subband coding. It is shown that nonunitary filter banks have larger coding gain than unitary filter banks because of the possibility of performing half-whitening in each channel. For long filter unit pulse responses, optimization of subband coding gain for stationary input signals results in a filter bank decomposition, where each channel works as an optimal open-loop DPCM system. We derive a formula giving the optimal filter response for each channel as a function of the input power spectral density (PSD). For shorter filter bank responses, good gain is obtained by suboptimal half-whitening responses, but the impact on the theoretical coding gain is still highly significant. Image coding examples demonstrate that better performance is achieved using nonunitary filter banks when the input images are in correspondence with the signal model.

Nasal stenosis after operations on the nose: expansion and subsequent maintenance of the nasal airway. Case report.

Nasal stenosis after operations on the nose may cause respiratory problems. We have re-established the patency of the nasal airway by controlled expansion of the nostril and nasal vestibule in seven patients. The airway was subsequently maintained with an individually adapted retention tube which was used intermittently as necessary.

Periodontal condition in adult patients with unilateral complete cleft lip and palate.

The periodontal condition, as expressed by plaque accumulation, gingival bleeding, and pocket depth formation, was registered in relation to maxillary teeth in 50 subjects with systematically treated unilateral complete cleft lip and palate (UCLP). Their treatment had been completed at a mean age of 19.5 years when a fixed partial denture was inserted in the cleft area. The mean interval between completion of the treatment and the present investigation was 9.5 years. Generally, the periodontal condition in relation to abutment and nonabutment teeth seemed to be in accordance with that seen in the general population, implying that the condition was poorer in relation to abutments as compared with nonabutment control teeth. Indirect evidence indicated that this was caused by the adverse effects of prosthodontic treatment rather than by the anatomic deviations created by the repaired cleft.

Destruction of the soft palate and nose by tertiary 'benign' syphilis. A case report.

A case of untreated tertiary syphilis involving the soft palate and nose is described and the treatment is outlined. In view of the rising incidence of acquired syphilis the clinician should bear this disease in mind whenever atypical lesions are encountered.

The reliability of clinical evaluation of some characteristics in complete prosthetics.

The aim of this investigation was to study intra-assessor reliability and the relationship between individual and simultaneous evaluations when retention and stability of complete prostheses and the condition of the residual ridges were clinically assessed according to defined criteria. Further, inter-assessor reliability and the reliability of simultaneous evaluations were studied by evaluating the condition of the residual ridge on two occasions. Nine patients and three prosthodontists participated. Generally, the reliability levels were low and individual deviations from the simultaneous evaluations were common.