Sympathomimetic amines effectively control pain for interstitial cystitis that had not responded to other therapies.

PURPOSE: To further investigate the efficacy of treatment of interstitial cystitis that had been refractory to standard treatment with sympathomimetic amines. METHODS: Dextroamphetamine sulfate sustained release capsules up to 30 mg per day were prescribed in women with refractory painful bladder syndrome/interstitial cystitis in six new cases. The patients were carefully evaluated for relief of symptoms. RESULTS: All six women found marked relief in their painful bladder syndrome in a rather short length of time. The benefit persisted as long as the therapy was maintained. Temporary cessation resulted in prompt return of symptoms, but resumption of sympathomimetic amines again allowed good relief of bladder pain and related symptoms. CONCLUSIONS: Because of very few side-effects and no drug dependence in the dosage used, sympathomimetic amines should be considered for first-line therapy.

Comparative 3D quantitative analyses of trapeziometacarpal joint surface curvatures among living catarrhines and fossil hominins.

Comparisons of joint surface curvature at the base of the thumb have long been made to discern differences among living and fossil primates in functional capabilities of the hand. However, the complex shape of this joint makes it difficult to quantify differences among taxa. The purpose of this study is to determine whether significant differences in curvature exist among selected catarrhine genera and to compare these genera with hominin fossils in trapeziometacarpal curvature. Two 3D approaches are used to quantify curvatures of the trapezial and metacarpal joint surfaces: (1) stereophotogrammetry with nonuniform rational B-spline (NURBS) calculation of joint curvature to compare modern humans with captive chimpanzees and (2) laser scanning with a quadric-based calculation of curvature to compare modern humans and wild-caught Pan, Gorilla, Pongo, and Papio. Both approaches show that Homo has significantly lower curvature of the joint surfaces than does Pan. The second approach shows that Gorilla has significantly more curvature than modern humans, while Pongo overlaps with humans and African apes. The surfaces in Papio are more cylindrical and flatter than in Homo. Australopithecus afarensis resembles African apes more than modern humans in curvatures, whereas the Homo habilis trapezial metacarpal surface is flatter than in all genera except Papio. Neandertals fall at one end of the modern human range of variation, with smaller dorsovolar curvature. Modern human topography appears to be derived relative to great apes and Australopithecus and contributes to the distinctive human morphology that facilitates forceful precision and power gripping, fundamental to human manipulative activities.

Establishment and transformation diminish the ability of fibroblasts to contract a native collagen gel.

Cultures of established and transformed fibroblasts were less able to contract a hydrated collagen gel than normal precrisis cells. Postcrisis fibroblasts from different rodent strains and species underwent a further reduction in contraction ability and either spontaneous or simian virus 40 (SV40) transformation. Human precrisis fibroblasts contracted much more efficiently than two SV40-transformed human lines. Fibroblasts from a patient with Glanzmann's thrombasthenia were intermediate between all other human fibroblasts assayed and the SV40-transformed human lines. The absolute efficiency of contraction was dependent on temperature and serum concentration, but no conditions were found that resulted in equal efficiencies for the three types of cells. Precrisis cells were extremely sensitive to the passage procedures when assayed for collagen contraction.

Dynamic analysis of maxillary perfusion during Le Fort I osteotomy using indocyanine green.

The aim of this study was to evaluate the dynamic perfusion of the maxilla during various stages of a Le Fort I osteotomy using indocyanine green (ICG) dye angiography. This was a retrospective evaluation of patients who underwent a Le Fort I osteotomy. ICG was used to assess perfusion at specific time points during the procedure. Twenty-four patients underwent a Le Fort I osteotomy with dynamic perfusion ICG angiography. Statistically significant differences in perfusion were noted at all three locations assessed between preoperative (T0), post down-fracture (T1), and postoperative (T2) time points. When controlling for mean arterial pressure, statistically significant differences were noted at all three locations assessed between T0 and T1, and between T0 and T2. There were no statistically significant differences in patient age, heart rate, preservation or sacrifice of the descending palatine arteries, or conventional vs. segmental Le Fort I osteotomies across T0, T1, and T2. In conclusion, there was a statistically significant decrease in perfusion, as assessed by intraoperative dynamic angiography, to the anterior maxilla following maxillary down-fracture. Patient age, conventional vs. segmental Le Fort I osteotomy, changes in mean arterial pressure and/or heart rate, and preservation of the descending palatine vessels had no statistically significant effect on perfusion.

Quantitative analysis of facial soft tissue perfusion during hypotensive anesthesia using laser-assisted indocyanine green fluorescence angiography.

The aim of this study was to quantitatively evaluate the efficacy of induced hypotensive anesthesia in decreasing facial soft tissue perfusion during orthognathic surgery using laser-assisted indocyanine green fluorescence angiography. This retrospective study involved the evaluation of 16 patients who underwent orthognathic surgery. Data collection included facial tissue perfusion of the bilateral cheeks and chin at normotension and with pharmacologically induced hypotensive anesthesia. There were statistically significant differences in the facial tissue perfusion at normal and depressed levels of blood pressure (P<0.001). This study used an objective measure to demonstrate the long-standing belief that hypotensive anesthesia is efficacious in reducing tissue perfusion in the surgical field. The data suggest that pharmacologically depressing the level of mean arterial pressure by 18% may result in a 41-52% decrease in facial soft tissue perfusion. This study reports a novel method of quantitative analysis.

Ability of the xid gene to prevent autoimmunity in (NZB X NZW)F1 mice during the course of their natural history, after polyclonal stimulation, or following immunization with DNA.

F1 hybrid offspring of New Zealand Black mothers and New Zealand White fathers [(NZB X NZW)F1] female mice develop antibodies to single-stranded (ss) and native DNA, immune complex glomerulonephritis, massive proteinuria, and premature death with renal failure. By a series of matings, congenic (NZB X NZW)F1 . xid/xid mice were prepared. These mice were different from (NZB X NZW)F1 mice in having the X chromosome-linked immune deficiency gene, xid, in homozygous form. Such congenic (NZB X NZW)F1 . xid/xid females failed to develop antibodies to single-stranded or native DNA. They also failed to develop fatal renal disease as measured by proteinuria, glomerular histology, glomerular immunofluorescence, and survival. To control for unknown genetic factors, studies were performed with littermates that were derived by mating NZB . xid/+ females with NZW . xid/Y males such that the resulting offspring were either (NZB X NZW)F1 . xid/xid (and therefore "defective") or (NZB X NZW)F1 . xid/+ [phenotypically like (NZB X NZW)F1]. In these and in additional studies, mice were housed in the same cages and identified by ear tagging so as to avoid possible environmental variations from cage to cage. In these studies, xid/xid mice failed to develop the characteristic signs of autoimmunity, whereas the controls did. Similar results were also obtained with (NZW X NZB)F1 xid/xid mice compared with (NZW X NZB)F1 xid/+ mice. The effect of xid/xid upon (NZB X NZW)F1 mice was further investigated by assessing responses to immunization and polyclonal B cell activation in vivo. The xid/xid mice failed to produce anti-ssDNA following immunization with ssDNA complexed to a protein carrier in fluid form or even emulsified in adjuvant. Finally, the xid/xid mice failed to produce antiDNA in response to multiple injections of the polyclonal activator, bacterial lipopolysaccharide (LPS), or the polyclonal activator, polyribose inosinic acid . polyribose cytidylic acid. However, the xid/xid mice were neither generally hyporesponsive nor unable to recognize LPS because they made normal antibody responses following immunization with LPS to which multiple trinitrophenyl groups were chemically attached. We conclude from these studies that xid/xid, which is known to cause the deletion of a B cell subset, has a profound affect upon (NZB X NZW)F1 mice, rendering them insusceptible to the naturally occurring autoimmune disease characteristic of (NZB X NZW)F1 mice, and preventing them from producing antibodies to DNA despite purposeful immunization and polyclonal B cell activation. These results force a reevaluation of previous concepts regarding the mechanisms by which xid/xid might interfere with the development of autoimmunity, and a consideration of therapeutic implications.

Induction of c-Ha-ras gene expression by double-stranded RNA and interferon requirement.

The addition of double-stranded RNA (dsRNA) to NIH 3T3 cells led to an increase in the RNA levels of c-Ha-ras. The double-stranded configuration was required for the increase in c-Ha-ras mRNA levels, as heat-denatured dsRNA and single-stranded RNA did not have any effect. Nuclear run-on transcription experiments indicated that the increase in c-Ha-ras mRNA levels stimulated by dsRNA was due to transcriptional activation of the gene. The induction of c-Ha-ras gene expression by dsRNA was inhibited by anti-beta interferon antibodies, suggesting that interferon might mediate the induction.

Augmentation of the infraorbital rim in orthognathic surgery.

Mid-face augmentation via a Le Fort I osteotomy is a commonly performed operation. Advancement of the upper jaw and associated structures (nose, lower cheek areas) can certainly improve function as well as facial aesthetics and harmony. Often, in patients with severe mid-face deficiency, hypoplasia of the maxilla extends all the way up to the infraorbital rims. The receding infraorbital rim contributes to the negative vector of the globes. In patients with this level of mid-face hypoplasia, while advancing the maxilla at the Le Fort I level satisfies all of the requirements for orthognathic surgery, the deficient infraorbital rim remains unchanged and can actually accentuate the negative vector of the globes. This article explains our approach in augmentation of the deficient infraorbital rim using alloplastic silicone implants at the time of a Le Fort I osteotomy.

Overexpression of PTEN/MMAC1 and decreased activation of Akt in human papillomavirus-infected laryngeal papillomas.

Laryngeal papillomas are benign, human papillomavirus-induced hyperplastic tumors of the respiratory tract. They are characterized by overexpression of the epidermal growth factor receptor, constitutive activation of mitogen-activated protein kinase, a low proliferative rate, and defects in differentiation. We have now found that phosphoinositol 3-kinase (PI 3-K) activity is significantly increased in papilloma tissue. However, phosphorylated Akt (also known as protein kinase B), a downstream effector of PI 3-K, is reduced when compared with normal tissue. The ratio of activated Akt to total Akt is much lower in papillomas than in normal laryngeal tissue, suggesting decreased Akt activation. PTEN/ MMAC1 is a tumor suppressor that dephosphorylates phosphatidylinositol 3,4,5-triphosphate, an intermediate in the PI 3-K/Akt signaling pathway. We have found that PTEN protein is overexpressed in laryngeal papillomas when compared with normal laryngeal tissues. On the basis of reverse transcription-PCR analysis, PTEN mRNA is more abundant in papillomas, suggesting transcriptional up-regulation. We postulate that negative regulation of the PI 3-K/Akt pathway by PTEN may modulate the effects of the hyperactive epidermal growth factor receptor/mitogen-activated protein kinase pathway, contributing to the low proliferation and dysfunctional differentiation of laryngeal papillomas.

Laryngeal papilloma cells have high levels of epidermal growth factor receptor and respond to epidermal growth factor by a decrease in epithelial differentiation.

Laryngeal papillomas are benign epithelial tumors caused by human papillomaviruses. These tumors are characterized by hyperplasia of the spinous layer and abnormal differentiation. Many tumor cell lines over-express the epidermal growth factor (EGF) receptor on their surface, and EGF regulates normal cell growth. We have asked about the relationship of the EGF receptor and EGF response in laryngeal papilloma cells. Papilloma cells showed markedly greater immunohistochemical staining for the EGF receptor, compared to uninfected cells. Both cell types showed a 2-3-fold increase in nuclei incorporating bromodeoxyuridine when EGF was present. Removal of EGF from papilloma cells cultured on collagen rafts permitted normal stratification and differentiation, as determined by synthesis of keratin 13. Inclusion of EGF induced abnormal differentiation with minimal expression of keratin 13. Uninfected laryngeal cells cultured on rafts in the presence of EGF synthesize keratin 13 in all suprabasal cells. EGF reduced both human papillomavirus RNA levels in the papilloma cells and expression of a reporter gene linked to the human papillomavirus 11 enhancers and E6 promoter in uninfected cells. These results suggest that the phenotype of papillomas is induced, in part, by EGF binding to the abundant EGF receptors.

Presence of human papillomavirus type 16 related sequences in verrucous carcinoma of the larynx.

Verrucous carcinoma of the larynx clinically resembles laryngeal papilloma in that both are wart-like masses on the vocal cords and may be characterized by multifocality and recurrence. Human papillomavirus (HPV) infection is an etiological factor in laryngeal papilloma, and recent evidence implicates HPV in squamous neoplasias. To determine whether HPV is also associated with verrucous carcinoma of the larynx, we analyzed tissue specimens from six patients with verrucous carcinoma of the larynx by Southern and DNA dot blot hybridization for HPV DNA. From three patients, specimens of normal laryngeal epithelium were also studied. All tissues showed evidence of HPV sequences related but not identical to HPV-16. They were negative for HPV-11. In contrast, four squamous cell carcinomas of the larynx and three normal laryngeal tissues were negative for HPV DNA. Histological sections of the six verrucous lesions were found to contain koilocytosis. Immunoperoxidase staining for HPV capsid antigens was negative in all these cases. The consistent and specific association of HPV with the verrucous carcinomas in this report suggests the possibility of a pathogenic involvement.

Elevation of the epidermal growth factor receptor and dependent signaling in human papillomavirus-infected laryngeal papillomas.

Laryngeal papillomas are benign tumors caused by human papillomaviruses types 6 and 11. This study addressed alterations in levels of signal transduction from the epidermal growth factor receptor (EGFR) in papillomas and cultured papilloma cells compared to normal tissue and cells. Mitogen-activated protein kinase (MAPK) was activated to a greater extent, phosphotyrosine was more abundant, and EGFR was overexpressed in laryngeal papillomas compared to normal laryngeal epithelium by Western blot analysis. The EGFR was 3 times more abundant in cultured papilloma cells than in normal laryngeal cells by Scatchard analysis and Western blot, without gene amplification or an increase in steady-state levels of mRNA. Following stimulation with EGF, a significant portion of the EGFR was recycled to the surface in papilloma cells, whereas in normal cells, it was not. Tyrosine kinase activity and activation of MAPK was more responsive to epidermal growth factor stimulation in papilloma cells than in uninfected primary laryngeal cells. PD153035, a specific inhibitor of the EGFR, and an EGFR-specific antibody that blocks ligand binding completely abrogated basal MAPK activation by endogenous ligands in laryngeal papilloma cells. These results demonstrated that infection of laryngeal epithelium by low-risk human papillomaviruses elevates the EGFR by posttranslational mechanisms, increasing its responsiveness to ligand-mediated activation. They also showed that MAPK activation in laryngeal papillomas depends upon ligand-mediated EGFR stimulation.

Primary delayed onset craniosynostosis in a child demonstrated by serial computed tomography imaging.

Primary delayed onset craniosynostosis is a rarely reported phenomenon. The unique case of a 2-year-old boy who had computed tomography (CT) scans performed 20 months apart demonstrating the post-gestational development of sagittal suture craniosynostosis is presented. The otherwise healthy male initially presented to the emergency department at age 7 months with soft tissue swelling over his left parietal region secondary to a fall. A CT scan revealed a possible left parietal skull fracture without intracranial pathology and patent cranial sutures with a normocephalic calvarial configuration. Twenty months later, his paediatrician referred the boy to the craniofacial service for evaluation of progressive dolichocephaly. A new CT scan showed complete fusion of the sagittal suture with resultant biparietal narrowing, frontal bossing, and occipital prominence. The patient subsequently underwent uncomplicated frontoparietal craniotomy with calvarial vault reconstruction. Prior reports in the literature of cases of non-syndromic primary delayed onset craniosynostosis all lack 'pre-synostosis' CT imaging that proves post-birth patency of the cranial sutures. This case report documents CT demonstrating true primary delayed onset craniosynostosis.

Anterior leaflet procedures during mitral valve repair do not adversely influence long-term outcome.

OBJECTIVES: This study was done to assess the impact of anterior mitral leaflet reconstructive procedures on initial and long-term results of mitral valve repair. BACKGROUND: It has been suggested that involvement of the anterior leaflet in mitral valve disease adversely affects the long-term outcome of mitral valve repair. Our policy has been to aggressively repair such anterior leaflets with procedures that include triangular resections in some cases. METHODS: From June 1979 through June 1993, 558 consecutive Carpentier-type mitral valve repairs were performed. The anterior mitral leaflet and chordae tendineae were repaired in 156 patients (mean age 58 years). The procedures included anterior chordal shortening in 78 patients (50%), anterior leaflet resections in 44 (28%), resuspension of the anterior leaflet to secondary chordae in 42 (27%) and anterior chordal transposition in 27 (17%). Concomitant cardiac surgical procedures were performed in 75 patients (48%). RESULTS: The operative mortality rate was 2.5% (2 of 81) for isolated mitral valve anterior leaflet repair and 3.8% (6 of 156) for all mitral valve anterior leaflet repair. Freedom from reoperation at 5 and 10 years was, respectively, 89.7% (n = 160) and 83.4% (n = 24) for the entire series of 558 patients, 91.9% (n = 51) and 81.2% (n = 10) for patients with anterior leaflet procedures, 88.8% (n = 109) and 84.4% (n = 14) for patients without anterior leaflet procedures and 91.7% (n = 118) and 88.9% (n = 18) for patients without rheumatic disease. Logistic regression showed that rheumatic origin of disease (odds ratio 2.99), but not anterior leaflet repair, increased the risk for reoperation. CONCLUSIONS: These results demonstrate that expansion of mitral valve techniques to include anterior leaflet disease yields immediate and long-term results equal to those seen in patients with posterior leaflet disease.

Potential language and attentional networks revealed through factor analysis of rCBF data measured with SPECT.

We used changes in regional cerebral blood flow (rCBF) to disclose regions involved in central auditory and language processing in the normal brain. rCBF was quantified with a fast-rotating, single-photon emission computerized tomograph (SPECT) and inhalation of 133Xe. rCBF data were obtained simultaneously from parallel, transverse slices of the brain. The lower slice was positioned to include both Broca's and Wernicke's areas. The upper slice included regions generally regarded by neurobehaviorists as less related to primary auditory or linguistic functions. We presented three types of auditory stimuli to ten healthy, young volunteers: (a) diotically presented Danish speech, (b) dichotic word stimulation, and (c) white noise. Wilcoxon's signed ranks sum test revealed increased rCBF in language-related areas of cortex, viz., Wernicke's area and its right-sided homologous area as well as in Broca's area (left hemisphere), when subjects listened to narrative speech, compared to white noise (baseline). No significant rCBF differences were detected with this test during dichotic stimulation vs. white noise. A more sophisticated statistical method (factor analysis) disclosed patterns of functionally intercorrelated regions. The factor analysis reduced the highly intercorrelated rCBF measures from 28 regions of interest to a set of three independent factors. These factors accounted for 77% of the total variation in rCBF values. These three factors appeared to represent statistical analogues of independent brain networks involved in (I) auditory/linguistic, (II) attentional, and (III) visual imaging activity.

Depressive response to physostigmine challenge in borderline personality disorder patients.

The purpose of this study was to examine the relationship between mood and hormonal responses to cholinergic challenge with physostigmine in order to assess cholinergic system responsiveness in borderline personality disorder (BPD) patients, other non-BPD personality disorder patients, and normal controls. Thirty-four personality disorder patients, 10 of whom met criteria for BPD and 24 of whom met criteria for other, non-borderline, personality disorders, and 11 normal controls participated in a double blind, placebo controlled physostigmine challenge paradigm. The Profile of Mood States depression subscale (POMS-D) self report measure was obtained at baseline and following the physostigmine or placebo infusions. A repeated measures ANOVA of POMS-D scores in placebo and drug conditions indicated a significantly greater depressive response in the total cohort of personality disorder patients than in the normal comparison group (p < 0.05). However, the depressive response to physostigmine was significantly greater in BPD patients, but not other personality disorder patients, compared to normal controls (p < 0.05). There was a correlation between the peak placebo-corrected depressive response to physostigmine and a group of BPD traits related to affective instability but not a group of BPD traits related to impulsivity. There was no correlation in any group between mood response to physostigmine and changes in plasma cortisol, prolactin, or growth hormone, or to nausea or other side effects following physostigmine infusion. These data suggest that there is an association between BPD and acute depressive responses to physostigmine challenge, and that the cholinergic system may be involved in the regulation of affect in Axis II disorders.

Synthesis of some phosphonates with antiherpetic activity.

Several keto phosphonates, phosphonoacetates , and dialkyl phosphonates containing (aryloxy)aryl groups were synthesized and evaluated for antiherpteic activity. Two of the most active compounds, 12 and 16, were evaluated topically in the mouse vaginal model against herpes simplex virus (HSV) type 2. Compound 16 exhibited an increased survival rate, as well as increased survival time. Evaluation of 16 in the guinea pig skin test against HSV-2 produced a reduction in virus titer, as well as in mean vesicle score.

Antiviral activity of some beta-diketones. 3. Aryl bis(beta-diketones). Antiherpetic activity.

A series of bis(beta-diketones) was synthesized and tested in vitro for antiviral actitity against herpes simplex type 2. Two parameters which were studied in an effort to optimize activity were the nature of the aryl group and the length of the alkyl bridge. One of the more active compounds, 4,4'-[(1,4-phenylenedioxy)bis(6,1-hexanediyl)]-bis[3,5-heptanedione] (6), was evaluated more extensively and found to inhibit the cytopathic effect in tissue culture of herpes simplex virus type 1 as well as type 2. Compound 6 was evaluated in vivo topically against herpes simplex type 1 in experimentally induced skin infections in guinea pigs. A topical treatment with 2% of 6 in a vanishing cream base, administered 24 h postinfection applied five times daily for 4 days, significantly reduced the number and size of herpetic vesicles.

The dup(3)(p25 leads to pter) syndrome: a case with holoprosencephaly.

We report a patient with dup(3p) syndrome with holoprosencephaly. This infant is compared with 17 others reported previously with banding studies. In 72% of cases the duplication derived from a mother with a balanced translocation; 78% of affected individuals are males. The most common anomalies are characteristic facial changes, congenital heart defects, and hypoplasia of male genitalia. Holoprosencephaly has not been reported before in the dup(3p) syndrome.

Minimally invasive versus sternotomy approaches for mitral reconstruction: comparison of intermediate-term results.

BACKGROUND: This study compares intermediate-term outcomes of mitral valve reconstruction after either the standard sternotomy approach or the new minimally invasive approach. Although minimally invasive mitral valve operations appear to offer certain advantages, such as reduced postoperative discomfort and decreased postoperative recovery time, the intermediate-term functional and echocardiographic efficacy has not yet been documented. METHODS: From May 1996 to February 1999, 100 consecutive patients underwent primary mitral reconstruction through a minimally invasive right anterior thoracotomy and peripheral cardiopulmonary bypass and Port-Access technology (Heartport, Inc, Redwood City, Calif). Outcomes were compared with those for our previous 100 patients undergoing primary mitral repair who were operated on with the standard sternotomy approach. RESULTS: Although patients were similar in age, the patients undergoing the minimally invasive approach had a lower preoperative New York Heart Association classification (2.1 +/- 0.5 vs 2.6 +/- 0.6, P <.001). There was one (1.0%) hospital mortality with the sternotomy approach and no such case with the minimally invasive approach. Follow-up revealed that residual mitral insufficiency was similar between the minimally invasive and sternotomy approaches (0.79 +/- 0.06 vs 0.77 +/- 0.06, P =.89, 0- to 3-point scale); likewise, the cumulative freedom from reoperation was not significantly different (94.4% vs 96.8%, P =.38). Follow-up New York Heart Association functional class was significantly better in the patients undergoing the minimally invasive approach (1.5 +/- 0.05 vs 1.2 +/- 0.05, P <.01). CONCLUSIONS: These findings demonstrate comparable 1-year follow-up results after minimally invasive mitral valve reconstruction. Both echocardiographic results and New York Heart Association functional improvements were compatible with results achieved with the standard sternotomy approach. The minimally invasive approach for mitral valve reconstruction provides equally durable results with marked advantages for the patient and should be more widely adopted.