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PubMed1999

How to explore the patient with a rising PSA after radical prostatectomy: defining local versus systemic failure.

We report on the various methods used to determine local or distant recurrences in patients with detectable serum prostate-specific antigen (PSA) after radical prostatectomy (RP). Studies show that variables that help predict distant metastases are PSA recurrence less than 2 years following surgery, tumors with Gleason score (GS) greater than 7, and positive seminal vesicles or positive lymph nodes at the time of surgery. In addition, studies in PSA kinetics show that short PSA doubling times, especially less than 6 months, are associated with distant recurrence and better correlated with the pattern and incidence of clinical recurrence than preoperative PSA, specimen GS, or stage alone. Studies show that although positive surgical margins are a significant risk factor for recurrence, only 40% to 50% of patients with positive margins developed an elevated PSA level within 5 years. When suspecting a local recurrence, transrectal ultrasound (TRUS) and TRUS-guided biopsies enhance the relatively inaccurate detection of local recurrence by digital rectal examination and initial prostate fossa biopsies. For distant recurrence, bone scintigrams of patients with a PSA recurrence following RP are only rarely positive and are found to have limited usefulness until the PSA increases to above 30 ng/mL. The role of immunoscintography to differentiate between local and distant recurrence is still evolving and requires further investigation. Further studies are clearly needed to enhance our ability to distinguish local from distant recurrence and to ultimately help guide therapy.

Bone Neoplasms↗

PubMedDate not supplied

Ontogeny of feline temporal lobe epilepsy. III: Spontaneous sleep and arousal disorders in amygdala-kindled kittens.

We report the ontogeny and persistence of sleep and arousal disorders in amygdala-kindled kittens. We also identify procedural differences that may explain discrepancies in the literature on postkindling sleep disorders. The study population consisted of 12 preadolescent kittens kindled between 2.5 and 6.5 months of age, 8 of which were followed to adulthood (> or = 1 year), and 8 unkindled implanted control animals. Sleep and seizure patterns were monitored on 12-24-h polygraphic or split-screen video recordings of EEG and behavioral activity. Kindled kittens displayed spontaneous seizure and interictal sleep anomalies that persisted to adulthood, as follows. As compared with neurosurgical controls, kindled kittens exhibited slow-wave sleep (SWS) and REM sleep insomnia at least 1 year after kindling and 1-5 months after convulsions, regardless of postictal recording delay. Sleep and arousal defects in kindled kittens were similar to but more pronounced than those in kindled adult cats, possibly because kittens spontaneously became epileptic. Detection of postkindling SWS insomnia could be masked by brief scoring epochs (less than the preferred 1-min epoch for cats); recurrent behavioral arousals after kindling frequently aborted 1-min SWS epochs but often did not interrupt 30-s SWS epochs (based on 1-min vs. 30-s minimum duration scoring criteria). Detection of postkindling REM sleep insomnia could be masked in kittens with alternating patterns of REM loss and REM rebound; all these kittens showed periodic bouts of REM onset from waking after kindling. Different data collection and analysis procedures influence detection of sleep and arousal disorders in amygdala-kindled cats when replication of findings is attempted. We conclude that these differences explain some controversies regarding the nature and prevalence of sleep disturbances in the kindling literature in temporal lobe epilepsy (TLE).

Amygdala↗

PubMed2002

Incidence of dementia after ischemic stroke: results of a longitudinal study.

BACKGROUND AND PURPOSE: A number of cross-sectional epidemiological studies have reported that one fourth of elderly patients meet criteria for dementia 3 months after ischemic stroke, but few longitudinal studies of the incidence of dementia after stroke have been performed. We conducted the present study to investigate the incidence and clinical predictors of dementia after ischemic stroke. METHODS: We administered neurological, neuropsychological, and functional assessments annually to 334 ischemic stroke patients (age, 70.4+/-7.5 years) and 241 stroke-free control subjects (age, 70.6+/-6.5 years), all of whom were nondemented in baseline examinations. We diagnosed incident dementia using modified Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition criteria requiring deficits in memory and > or =2 additional cognitive domains, as well as functional impairment. RESULTS: The crude incidence rate of dementia was 8.49 cases per 100 person-years in the stroke cohort and 1.37 cases per 100 person-years in the control cohort. A Cox proportional-hazards analysis found that the relative risk (RR) of incident dementia associated with stroke was 3.83 (95% CI, 2.14 to 6.84), adjusting for demographic variables and baseline Mini-Mental State Examination score. Within the stroke cohort, intercurrent medical illnesses associated with cerebral hypoxia or ischemia were independently related to incident dementia (RR, 4.40; 95% CI, 2.20 to 8.85), adjusting for recurrent stroke, demographic variables, and baseline Mini-Mental State Examination score. CONCLUSIONS: The risk of incident dementia is high among patients with ischemic stroke, particularly in association with intercurrent medical illnesses that might cause cerebral hypoxia or ischemia, suggesting that cerebral hypoperfusion may serve as a basis for some cases of dementia after stroke.

Aged↗

PubMed2004

Biochemical outcome after radical prostatectomy among men with normal preoperative serum prostate-specific antigen levels.

BACKGROUND: Recent studies have shown that a significant number of men with normal prostate-specific antigen (PSA) levels have prostate carcinoma. Whether malignancies in such men are associated with better outcomes is unclear. The authors compared the risk of biochemical failure after radical prostatectomy (RP) between men with normal PSA levels and men with elevated PSA levels. METHODS: Data were examined from 1582 men who underwent RP between 1988 and 2002 at 1 of 5 equal-access medical centers. Patients were segregated into groups based on serum PSA levels (with stratification according to age-specific reference ranges). Clinical and pathologic characteristics and biochemical outcome data were compared across groups using analyses of variance, log-rank tests, and Cox proportional hazards analysis. RESULTS: Men who had normal PSA levels had significantly fewer high-grade tumors compared with men who had higher PSA levels (P < 0.001). The former group had a significantly decreased incidence of positive surgical margins, extracapsular disease, seminal vesicle invasion, and lymph node involvement (P < 0.001). On multivariate analysis, only serum PSA level (P < 0.001) and biopsy Gleason score (P < 0.001) predicted the time to disease recurrence. When only men with serum PSA levels < 10 ng/mL were examined, PSA level treated as a continuous variable remained a significant predictor of time to biochemical failure (P = 0.02). CONCLUSIONS: Men who had normal PSA levels had significantly fewer high-grade tumors and significantly better biochemical outcomes after undergoing RP compared with men who had elevated PSA levels. Overall, men with normal PSA levels who undergo RP represent a favorable risk group.

Aged↗

PubMed1995

Late pulmonary function following repair of tracheoesophageal fistula or esophageal atresia.

Although tracheoesophageal fistula and esophageal atresia (TEF-EA) are surgically correctable, late respiratory complications have been reported. We administered a respiratory and gastrointestinal symptom questionnaire and performed standard pulmonary function tests (PF T's) and methacholine challenge testing on an unselected group of 25 subjects with TEF-EA who underwent surgery at our institution between 1963 and 1985. Results were compared to predicted normals, as well as 10 sibling controls. While the mean values of lung function test results for the TEF-EA group were within the normal range, they were significantly different from their siblings. Thirteen of the 25 TEF-EA group (52%), but none (0%) of the controls, had abnormal pulmonary function. This was classified as restrictive in 9 (36%), obstructive in 3 (12%), and mixed in 1. In addition, airway hyperreactivity [defined as a positive methacholine challenge (PC20 < or = 8 mg/mL)], was found in 6 of 18 TEF-EA subjects and 4 of the 9 controls who were evaluated. Comparison of TEF-EA subjects with normal and abnormal PFTs showed no difference in the incidence of tracheomalacia, esophageal strictures or dilatation, recurrent pneumonias, or gastroesophageal reflux. The respiratory symptom score in the subjects and controls was similar, and did not correlate with abnormal pulmonary function. The cause of the pulmonary function abnormalities remains unexplained.

Adolescent↗

PubMed2002

Brachytherapy versus radical prostatectomy in patients with clinically localized prostate cancer.

In an effort to help physicians offer their patients unbiased advice on the best alternatives for treatment of localized prostate cancer, we present a retrospective comparison of the effectiveness of brachytherapy and radical retropubic prostatectomy in 1305 men with stage T1 and T2 adenocarcinoma of the prostate. Data from 1305 patients treated in our community-based private practice urology group from 1993 to 2002 were reviewed, and patients were classified by initial prostate-specific antigen (PSA) level and risk grouping. Risk grouping was defined by preoperative PSA levels and Gleason scores. We used time to PSA-indicated recurrence as the measure of efficacy. Brachytherapy and radical prostatectomy provided similar responses to treatment (no significant differences given the sample size, length of follow-up, and numerical differences observed) for localized prostate cancers. A prospective study is presently underway to evaluate the respective outcome of these procedures (including incidence of incontinence and impotence), and assess their impact on patient quality of life. The results presented here fail to show any superiority of prostatectomy over brachytherapy with palladium-103 (TheraSeed; Theregenics Corp., Buford, GA) with respect to time until relapse indicated by PSA level increase (> 0.2 ng/mL for prostatectomy and >1.5 ng/mL and rising for brachytherapy). In fact, any differences between treatments favor brachytherapy, particularly for intermediate- and high-risk groups. We conclude that both brachytherapy and prostatectomy should be offered, equally and without bias, to men with stage T1 or T2 organ-confined prostate cancer.

Adenocarcinoma↗

PubMed2005

Total skin-sparing mastectomy without preservation of the nipple-areola complex.

BACKGROUND: We hypothesized that total skin-sparing mastectomy (TSM) including where the skin overlying the nipple and areola is preserved would be oncologically safe and facilitate improved cosmetic reconstruction. METHODS: A review (May 2003 through January 2005) was completed on all procedures that were performed through an inframammary incision or a previous scar with reconstruction using Botox, AlloDerm, and a subpectoral tissue implant. RESULTS: Thirty-one patients had 50 TSMs. Twelve percent (6/50) of TSMs had the skin of the nipple and areola resected: 4 (14% of tumors) because of tumor involvement and 2 (4%) because of skin necrosis. Fourteen percent of patients had other complications: 4% (2/50) had infection and/or flap necrosis and 10% (5/50) had superficial epidermolysis requiring no intervention, for a total complication rate of 18%. Average cosmetic score was 8.5 (range 4 to 10). No recurrences are evident after mean follow-up of 7.9 +/- 5.4 months. CONCLUSION: Our short-term experience suggests that TSM has an acceptable complication rate, is theoretically oncologically safe, and facilitates an improved cosmetic result.

Adult↗

PubMed2003

Clinical evaluation of a self-etching and a one-bottle adhesive system at two years.

OBJECTIVES: The clinical performances of a self-etching adhesive system, Clearfil SE Bond, and a one-bottle adhesive system, Prime&Bond NT, were evaluated in non-carious Class V restorations for a period of two years. METHODS: Ninety-eight restorations were made by one operator for 32 patients. The resin composite used to restore the teeth were Clearfil AP-X and Spectrum TPH for Clearfil SE Bond and Prime&Bond NT, respectively. Two clinicians at the baseline, 6th, 12th and 24th months evaluated the posterior composites according to the modified Ryge criteria's. For this, color match, marginal discoloration, marginal adaptation, recurrent caries, anatomic form, postoperative sensitivity and retention rates were considered. The changes across time and across groups were evaluated statistically. RESULTS: At two years, 88 restorations were reviewed in 28 patients. The retention rates for Clearfil SE Bond were 93 and 91% for Prime&Bond NT. The percentages of the retention rates of both adhesive systems were not found to be different when calculating the failure rates. Recurrent caries, anatomic form and postoperative sensitivity were scored as Alpha for all restorations. Two cases of both adhesive systems showed slight marginal discoloration problems. Three restorations of Prime&Bond NT and one of Clearfil SE Bond had marginal adaptation problems at two years. One case for each adhesive system had slight color change after the same period. CONCLUSION: We can conclude that both adhesive systems tested exhibited very good clinical performance at the end of two years.

Adult↗

PubMed2003

Symptoms of chronic venous disease and association with systemic inflammatory markers.

PURPOSE: We recorded symptoms reported by patients with chronic venous disease (CVD) of the leg and correlated these with systemic inflammatory markers. METHODS: This was an observational study in a cohort of 132 adult patients with CVD attending the vascular clinic of a teaching hospital. Patients were excluded in whom recent surgery, illness, or concomitant medication may have influenced measurements of systemic inflammatory mediators. Patients with CEAP clinical stages C(2) to C(5) only were considered for inclusion in the study. CEAP clinical stage was established for each patient, and duplex ultrasound scanning was used to assess extent of venous disease in the lower limbs. Blood was taken from a foot vein, and the following inflammatory mediators were measured with enzyme-linked immunosorbent assay: von Willebrand factor, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, soluble (s)E-selectin, sP-selectin, L-selectin, VEGF, and cytokines interleukin (IL)-1 alpha, IL-1 beta, IL-6, and tumor necrosis factor-alpha. Symptoms were recorded by patients using a visual analog scale (VAS) for the symptoms of pain, cramps, heaviness, paresthesia, and feeling of swelling. RESULTS: The greatest VAS symptom scores were observed in the less severe disease stages: C(2) median pain score, 2.8 units (interquartile range [IQR], 0.1-5); C(3), 4.5 (IQR, 3.4-5.5), C(4), 0.5 (IQR, 0-3.0); C(5), 0 (IQR, 0-4). Symptom scores were similar in patients with primary and recurrent venous disease after previous surgery and in patients with superficial venous reflux and deep venous reflux. No correlation was found between the measurements of inflammatory mediators and the symptoms assessed with the VAS. CONCLUSION: We found no correlation between symptoms reported by patients and the internationally agreed clinical stages of venous disease of C(2) to C(5). Neither was there any correlation between levels of inflammatory mediators and patient symptoms. Symptoms reported by patients with CVD cannot be explained by anatomic distribution of venous disease in the lower limb veins or by the systemic inflammatory response in venous disease.

Biomarkers↗

PubMed1997

Intra-arterial carboplatin chemotherapy for brain tumors: a dose escalation study based on cerebral blood flow.

PURPOSE: To perform in intra-arterial dose escalation study of carboplatin based on hemispheric blood-flow estimation in patients with recurrent malignant glioma. The primary purpose was to determine the maximally tolerated intra-arterial dose. METHODS AND PATIENTS: Methods included: 1) selective intra-arterial delivery performed with modern microcatheters, 2) pulsatile infusion, and 3) dosage based on local cerebral blood-flow estimation (middle cerebral artery 60%, anterior cerebral artery 20%, posterior cerebral artery 15%, and anterior choroidal artery 5% of the hemispheric blood-flow). The deliveries were performed above the ophthalmic artery in the anterior circulation, or above the anterior inferior cerebellar arteries in the posterior circulation. The doses were escalated from 200 mg/hemisphere at 50 mg increments. Twenty-one patients were studied (14 with glioblastoma multiforme, five anaplastic astrocytoma, one aggressive low-grade glioma, one metastasis). Patients had recurrent glioma limited to one hemisphere and Karnofsky score of 50 or greater. Concomitant therapies were allowed. RESULTS: Carboplatin was escalated to a dose of 1400 mg/hemisphere. One patient had a permanent neuromotor decline. The predominant toxicity was hematopoietic. The median time to tumor progression was 22 weeks, median survival 39 weeks, and the response rate 70% (50% SD and 20% PR) of 19 patients. CONCLUSIONS: Hemispheric blood-flow estimation allowed us to escalate the dose of intra-arterial carboplatin to twice what was previously considered safe. Responses compared favorably to previous studies. Further studies are needed to determine if this method will provide improved and durable responses.

Adult↗

PubMed1993

Impact of stromal sensitivity on radiation response of tumors.

BACKGROUND: Irradiation of tumors causes the death of both parenchymal tumor cells as well as normal tissue stromal cells (e.g., endothelium, connective tissue). However, it has been difficult to distinguish the contributions to overall tumor response after irradiation from the two compartments. The development of the severe combined immunodeficient (SCID) mouse provides a model in which the contribution of stromal cell responses to ionizing radiation to overall tumor response can be defined, because its normal tissue cells are extremely radiosensitive. Therefore, the results of irradiation of tumors in radiation-sensitive (SCID) and radiation-resistant hosts can be compared, and the contribution of the normal tissue stroma clarified. PURPOSE: Our purpose was to investigate the effects of radiation-induced stromal cell damage on tumor cell death, using tumor growth delay (GD) and local control (complete and permanent regression of the irradiated tumor) as end points. METHODS: Tumor GD and local control experiments were performed in SCID, athymic, and C3H mice. Sixty SCID and 60 nude mice for each of three human tumor cell lines (HGL9, HSTS26, HCT15) and for each of five murine cell lines (FSC1, FSC2, FSM1, FSM2, E01) and 60 SCID and 60 C3H mice for the FSa2 spontaneous C3H sarcoma were studied. Neoplasms were produced by injection of 10(6) cells from in vitro tissue cultures into the flanks of donor mice; after tumors had grown, experimental neoplasms were produced by transplanting 2- to 3-mm fragments into recipient mice. Animals were randomly assigned to various groups when tumors reached average volumes of 120 mm3. Graded, single-dose x irradiations (15-115 Gy, dose rate about 7 Gy/min) were given under acutely hypoxic conditions. Tumors were scored one to two times per week until recurrence. RESULTS: The x-ray doses needed to achieve local control in 50% of the animals (tumor control doses, TCD50) ranged from 45.1 to 58.0 Gy for human tumors and from 36.3 to 114.0 Gy for murine tumors. On average, the TCD50 values in SCID mice were only about 3.5% lower than values in nude or C3H mice. The amount of GD defined at 66% of the TCD50 for the various groups was, however, 27% longer in the SCID mice (P = .004). CONCLUSIONS: While the three-fold higher radiation sensitivity of the normal tissue stromal cells in the SCID mice did not alter the percentage of tumors controlled by x irradiation in the SCID mouse hosts as compared with other hosts, there appear to be significant differences in GD. Radiation-induced stromal cell damage does not significantly contribute to tumor cell death; however, it can prolong the interval of tumor regression.

Animals↗

PubMed2000

A randomized controlled trial of rubber band ligation versus infra-red coagulation in the treatment of internal haemorrhoids.

OBJECTIVE: Despite the presence of numerous non-surgical therapies for the treatment of haemorrhoids, none of these therapies has clearly been proven to be superior. The effectiveness and patient tolerance of rubber band ligation (RBL) and infra-red coagulation (IRC) in the treatment of haemorrhoids was assessed. DESIGN: Prospective randomized trial. SETTING: Academic hospital (tertiary care). PARTICIPANTS: A total of 133 consecutive patients (73 males, 60 females, mean age 48 years (range 19-82)) with internal haemorrhoids, and without concomitant anorectal disease, were randomized to rubber band ligation (RBL, n = 65) or infra-red coagulation (IRC, n = 68). INTERVENTIONS: Rubber band ligation or infra-red coagulation was performed in one or more sessions with four-week intervals until symptoms had resolved. Treatment outcome and side-effects were assessed after each treatment session and one month after the last treatment by proctological examination and a questionnaire, including a pain score (visual analogue scale from 0 to 10). Recurrence of complaints was assessed by telephone questionnaire [mean follow-up of 19.2 months (SD 7.8)]. RESULTS: Treatment outcome was assessed in 124 patients (60 RBL, 64 IRC). The mean number of treatment sessions was 1.6 (SD 0.9) for both therapies. For RBL, 58 patients (97%), and for IRC, 59 patients (92%) were symptom-free or had satisfactorily improved. Only third-degree haemorrhoids seemed to respond better to RBL (five of five patients symptom-free) than to IRC (two of four patients symptom-free). Pain following treatment was more common and more severe after RBL (VAS 5.5 +/- 3.7) than after IRC (VAS 3.3 +/- 3.3, P= 0.018). The telephone questionnaire was answered by 105 patients. Nine of 50 patients (18%) treated with RBL and 11 of 55 patients (20%, P= 0.81) treated with IRC had experienced symptomatic relapse to pre-treatment levels. CONCLUSIONS: Infra-red coagulation and rubber band ligation are equally effective in the treatment of haemorrhoids. The rate and severity of pain is higher after rubber band ligation. Infra-red coagulation should be the first-line treatment for haemorrhoids.

Adult↗

PubMed2006

Significance of micrometastases in pelvic lymph nodes detected by real-time reverse transcriptase polymerase chain reaction in patients with clinically localized prostate cancer undergoing radical prostatectomy after neoadjuvant hormonal therapy.

OBJECTIVE: To clarify the significance of micrometastases in pelvic lymph nodes in patients treated by radical prostatectomy (RP) for prostate cancer after neoadjuvant hormonal therapy (NHT). PATIENTS AND METHODS: The study included 52 patients with clinically localized prostate cancer who received NHT followed by RP. The expression of prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) in 989 lymph nodes isolated from the 52 patients were assessed by a fully quantitative real-time reverse-transcriptase polymerase chain reaction (RT-PCR). We regarded specimens in which either PSA or PSMA mRNA were positive as showing the 'presence of micrometastasis'. Lymph node specimens were also stained immunohistochemically with an antibody against PSA. RESULTS: Pathological examinations detected tumour cells in 11 lymph nodes from four patients, and real-time RT-PCR further identified micrometastasis in 40 lymph nodes from 19 patients with no pathological evidence of nodal involvement. The presence of micrometastatic cancer cells was confirmed by immunohistochemical staining in 19 lymph nodes from 11 patients with pathologically negative nodes. The presence of micrometastases was significantly associated with other conventional prognostic variables, including the pretreatment serum PSA level, biopsy Gleason score and surgical margin status. The biochemical recurrence-free survival rate in patients with no micrometastasis was significantly higher than that in those with micrometastasis. Furthermore, multivariate analysis identified the presence of micrometastasis as an independent factor predicting biochemical recurrence. CONCLUSIONS: Although residual foci of atrophic prostate cancer cells in resected lymph nodes after NHT can be difficult to diagnose by routine pathological examination, the present results show the usefulness of quantitative real-time RT-PCR targeting PSA and PSMA genes for detecting micrometastatic tumour foci in pelvic lymph nodes from patients with localized prostate cancer treated by NHT followed by RP. Furthermore, the present findings suggest that micrometastases in pelvic lymph nodes might be, at least partly, important in the development of biochemical recurrence in some patients undergoing RP after NHT.

Androgen Antagonists↗

PubMed2005

Adult living donor versus deceased donor liver transplantation: a 6-year single center experience.

No long-term (>3 years) prospective comparison of adult-to-adult living donor liver transplantation (A2ALLTx) to adult deceased donor liver transplantation (ADDLTx) has been reported. This is a prospective, IRB approved, 6-year comparison of A2ALLTx to ADDLTx. Data include: age, gender, ethnicity, primary liver disease, waiting time, pretransplant CTP/MELD score, cold ischemia time (CIT), perioperative mortality, acute and chronic rejection, graft and patient survival, charges and post-transplant complications. In 6 years, 202 ADDLTx (74.5%) and 69 A2ALLTx (25.5%) were performed at VCUHS. Hepatitis C virus (HCV) was the most common reason for transplantation in both groups (48.1% vs. 42%). Data regarding overall patient and graft survival, monetary charges and retransplantation rates were similar. Comparison of patient/graft survivals, retransplantation rates in patients with and without HCV were not statistically different. A2ALLTx patients had less acute rejection (11.5% vs. 23.9%) and more biliary complications (26.1% vs. 11.4%). Overall, A2ALLTx is as durable a liver replacement technique as the ADDLTx. Patients with A2ALLTx were younger, had lower MELD scores, less acute rejection and similar histological HCV recurrence. Biliary complications were more common in A2ALLTx but were not associated with increased graft loss compared to ADDLTx.

Adult↗

PubMed2006

Evaluation of BRCA1 and BRCA2 mutation prevalence, risk prediction models and a multistep testing approach in French-Canadian families with high risk of breast and ovarian cancer.

BACKGROUND AND OBJECTIVE: In clinical settings with fixed resources allocated to predictive genetic testing for high-risk cancer predisposition genes, optimal strategies for mutation screening programmes are critically important. These depend on the mutation spectrum found in the population under consideration and the frequency of mutations detected as a function of the personal and family history of cancer, which are both affected by the presence of founder mutations and demographic characteristics of the underlying population. The results of multistep genetic testing for mutations in BRCA1 or BRCA2 in a large series of families with breast cancer in the French-Canadian population of Quebec, Canada are reported. METHODS: A total of 256 high-risk families were ascertained from regional familial cancer clinics throughout the province of Quebec. Initially, families were tested for a panel of specific mutations known to occur in this population. Families in which no mutation was identified were then comprehensively tested. Three algorithms to predict the presence of mutations were evaluated, including the prevalence tables provided by Myriad Genetics Laboratories, the Manchester Scoring System and a logistic regression approach based on the data from this study. RESULTS: 8 of the 15 distinct mutations found in 62 BRCA1/BRCA2-positive families had never been previously reported in this population, whereas 82% carried 1 of the 4 mutations currently observed in > or =2 families. In the subset of 191 families in which at least 1 affected individual was tested, 29% carried a mutation. Of these 27 BRCA1-positive and 29 BRCA2-positive families, 48 (86%) were found to harbour a mutation detected by the initial test. Among the remaining 143 inconclusive families, all 8 families found to have a mutation after complete sequencing had Manchester Scores > or =18. The logistic regression and Manchester Scores provided equal predictive power, and both were significantly better than the Myriad Genetics Laboratories prevalence tables (p<0.001). A threshold of Manchester Score > or =18 provided an overall sensitivity of 86% and a specificity of 82%, with a positive predictive value of 66% in this population. CONCLUSION: In this population, a testing strategy with an initial test using a panel of reported recurrent mutations, followed by full sequencing in families with Manchester Scores > or =18, represents an efficient test in terms of overall cost and sensitivity.

Adolescent↗

PubMed1987

Cleft lip with or without cleft palate: identification of sporadic cases with a high level of genetic predisposition.

Previous studies have suggested that asymmetry for certain bilaterally represented features may be an indicator of genetic predisposition to cleft lip with or without cleft palate and may therefore be of value in the individual assessment of recurrence risk, particularly for sporadic cases. An asymmetry score has been devised that may be of use in identifying those with a high level of genetic predisposition. Stepwise logistic regression selected nine variables that together correctly classified 85% of familial cleft patients and unrelated non-cleft controls. Applying the same regression equation to sporadic cases, 26% fell into the range occupied by the majority of familial patients, suggesting that these had a high level of genetic predisposition.

Adolescent↗

PubMed2003

Systemic infection, interleukin 1beta, and cognitive decline in Alzheimer's disease.

Activated microglia, the resident macrophages of the brain, are a feature of Alzheimer's disease. Animal models suggest that when activated microglia are further activated by a subsequent systemic infection this results in significantly raised levels of interleukin 1beta within the CNS, which may in turn potentiate neurodegeneration. This prospective pilot study in Alzheimer's disease subjects showed that cognitive function can be impaired for at least two months after the resolution of a systemic infection and that cognitive impairment is preceded by raised serum levels of interleukin 1beta. These relations were not confounded by the presence of any subsequent systemic infection or by baseline cognitive scores. Further research is needed to determine whether recurrent systemic infections drive cognitive decline in Alzheimer's disease subjects through a cytokine mediated pathway.

Aged↗

PubMed2002

Combined pharmacotherapy and psychotherapy as maintenance treatment for late-life depression: effects on social adjustment.

OBJECTIVE: This study examined the effects of maintenance treatment for late-life depression on social adjustment. The authors hypothesized that elderly patients recovering from depression would have better social adjustment with medication and interpersonal psychotherapy than with medication or psychotherapy alone. METHOD: Patients aged 60 and older recovering from recurrent major depression were randomly assigned to one of four treatments: nortriptyline and interpersonal psychotherapy, nortriptyline and clinic visits, placebo and psychotherapy, or placebo and clinic visits. The Social Adjustment Scale was administered every 3 months until illness recurrence. Combined treatment was compared to monotherapy on scores over 1 year among patients who remained in recovery (N=49). RESULTS: Patients receiving nortriptyline and interpersonal psychotherapy maintained social adjustment, which declined in those receiving monotherapy. CONCLUSIONS: Treatment of late-life depression with nortriptyline and psychotherapy is more likely to maintain social adjustment than treatment with either alone. Combination therapy improves not only duration but quality of wellness.

Age Factors↗