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Biomedical subjects

J Neuhaus

Publications and source records attributed to J Neuhaus.

At least 19 recordsLinked to original sources
PubMed2006

CD4+ count-guided interruption of antiretroviral treatment.

BACKGROUND: Despite declines in morbidity and mortality with the use of combination antiretroviral therapy, its effectiveness is limited by adverse events, problems with adherence, and resistance of the human immunodeficiency virus (HIV). METHODS: We randomly assigned persons infected with HIV who had a CD4+ cell count of more than 350 per cubic millimeter to the continuous use of antiretroviral therapy (the viral suppression group) or the episodic use of antiretroviral therapy (the drug conservation group). Episodic use involved the deferral of therapy until the CD4+ count decreased to less than 250 per cubic millimeter and then the use of therapy until the CD4+ count increased to more than 350 per cubic millimeter. The primary end point was the development of an opportunistic disease or death from any cause. An important secondary end point was major cardiovascular, renal, or hepatic disease. RESULTS: A total of 5472 participants (2720 assigned to drug conservation and 2752 to viral suppression) were followed for an average of 16 months before the protocol was modified for the drug conservation group. At baseline, the median and nadir CD4+ counts were 597 per cubic millimeter and 250 per cubic millimeter, respectively, and 71.7% of participants had plasma HIV RNA levels of 400 copies or less per milliliter. Opportunistic disease or death from any cause occurred in 120 participants (3.3 events per 100 person-years) in the drug conservation group and 47 participants (1.3 per 100 person-years) in the viral suppression group (hazard ratio for the drug conservation group vs. the viral suppression group, 2.6; 95% confidence interval [CI], 1.9 to 3.7; P<0.001). Hazard ratios for death from any cause and for major cardiovascular, renal, and hepatic disease were 1.8 (95% CI, 1.2 to 2.9; P=0.007) and 1.7 (95% CI, 1.1 to 2.5; P=0.009), respectively. Adjustment for the latest CD4+ count and HIV RNA level (as time-updated covariates) reduced the hazard ratio for the primary end point from 2.6 to 1.5 (95% CI, 1.0 to 2.1). CONCLUSIONS: Episodic antiretroviral therapy guided by the CD4+ count, as used in our study, significantly increased the risk of opportunistic disease or death from any cause, as compared with continuous antiretroviral therapy, largely as a consequence of lowering the CD4+ cell count and increasing the viral load. Episodic antiretroviral therapy does not reduce the risk of adverse events that have been associated with antiretroviral therapy. (ClinicalTrials.gov number, NCT00027352 [ClinicalTrials.gov].).

AIDS-Related Opportunistic Infections↗
PubMed2005

Comparison of family histories in FTLD subtypes and related tauopathies.

Pedigrees from 269 patients with frontotemporal lobar degeneration (FTLD), including frontotemporal dementia (FTD), FTD with ALS (FTD/ALS), progressive nonfluent aphasia, semantic dementia (SD), corticobasal degeneration, and progressive supranuclear palsy were analyzed to determine the degree of heritability of these disorders. FTD/ALS was the most and SD the least heritable subtype. FTLD syndromes appear to have different etiologies and recurrence risks.

Adult↗
PubMed2005

[Quality requirements for investigational medicinal products. The state authorities' point of view].

The relevant authorities must assess the quality of investigational medicinal products based mainly on the parameters "safety of the persons subject to a clinical study", "adequate reproduction of the drug model defined in the clinical trial authorization", and "reliability of documentation". Of these, the safety of the people subject to a clinical study is of predominant importance. As a consequence, this is the main focus of the authorities. Reliability and integrity of the documentation on investigational medicinal products are important for the assessment of a manufacturing license application. Therefore, this is also subject to the relevant authorities.

Clinical Trials as Topic↗
PubMed2004

[Endoscopic extraperitoneal radical prostatectomy. Results after 300 procedures].

During the last decade laparoscopy has become the standard technique in the urologist's armamentarium due to constant technological advancements and refinements. Laparoscopic radical prostatectomy (LRPE), although technically demanding and associated with a considerable learning curve, has become the operative procedure of choice for patients with clinically localized prostate cancer in selected and specialized urologic centers around the globe. However, a major drawback of LRPE is the transperitoneal route of access to the extraperitoneal organ of the prostate. The principal disadvantages of LRPE are potential intraperitoneal complications. Endoscopic extraperitoneal radical prostatectomy (EERPE) is a further advancement of minimally invasive surgery as it overcomes the limitations of LRPE by the strictly extraperitoneal route of access. Based on our growing experience with this procedure we introduce several technical modifications, improvements, and refinements including a nerve-sparing, potency-preserving approach (nEERPE) in an effort to further improve this minimally invasive procedure. We report our short-term follow-up results after 300 procedures. The mean operative times were 115 min without and 150 min with lymph node dissection, in total 140 min (range: 60-260 min). There was no conversion and the transfusion rate was 1.3%. There were three early reinterventions (two bleeding and one hematoma) and five late reinterventions (four symptomatic lymphoceles and one colostomy due to a rectal fistula). Pathological stage was pT2a in 54 patients (18%), pT2b in 87 patients (29%), pT3a in 115 patients (38.3%), pT3b in 40 patients (13.3%), and pT4 in 4 patients (1.3%). Positive surgical margins were found in 9.2% (13/141) of patients with pT2 tumor and 30.3% (47/155) of patients with pT3 tumor. The mean catheterization time was 6.9 days. Six and twelve months postoperatively 86.3 and 89.6% of the patients were completely continent; 9.2% of patients needed 1-2 pads per day and 4.5 and 1.2% of patients needed more than 2 pads per day, respectively. Short-term oncological and functional results of EERPE are at least as favorable as in LRPE while operative times are shorter and complication rates are low. EERPE is a technical advancement because it combines the advantages of a totally extraperitoneal access with the advantages of a minimally invasive procedure.

Adult↗
PubMed2004

Is the rhesus monkey (Macaca mulatta) comparable to humans? Histomorphology of the sphincteric musculature of the lower urinary tract including 3D-reconstruction.

The physiology of the muscle systems of the human lower urinary tract is still not known in detail. To study the functional basics of this complex organ system, experiments are often performed in animal models including rhesus monkeys. To apply the results of animal model studies to the humans, a clear knowledge of the comparative anatomy of both species is necessary. However, detailed comparative studies of the lower urinary tract of the rhesus monkey and the humans are lacking. Accordingly, a detailed study on the sphincteric musculature of the lower urinary tract of the rhesus monkey was performed in order to demonstrate anatomical correspondences and differences between both species. The lower urinary tract anatomy was investigated in 18 male and female rhesus monkeys (Macaca mulatta) by serial sections. Immunohistochemical staining methods were used to differentiate striated and smooth musculature. Three-dimensional reconstructions were performed in order to demonstrate the topographical anatomy of the different muscle systems. In both man and male rhesus monkeys, a urethral sphincter muscle exists independent of the pelvic floor musculature, with a smooth and a striated muscular part. A urinary diaphragm (diaphragma urogenitale) does neither exist in the rhesus monkey nor in the human. In contrast to women, a striated muscle encircles the urethra and vagina together in the female rhesus monkey. A vesical sphincter muscle, found in the human bladder outlet, does not exist in the rhesus monkey.

Animals↗
PubMed2002

Increased sensitivity to 4-chloro-m-cresol and caffeine in primary myotubes from malignant hyperthermia susceptible individuals carrying the ryanodine receptor 1 Thr2206Met (C6617T) mutation.

Malignant hyperthermia (MH) is an autosomal-dominant disorder of skeletal muscle, triggered by volatile anaesthetics and depolarizing muscle relaxants. The causative defect lies in the control of Ca(2+) release from the sarcoplasmic reticulum in skeletal muscle. Numerous mutations have been detected in the ryanodine receptor 1 (RyR1) gene, but so far an MH-causative role has only been confirmed for 16 human RyR1 mutations. In this report we show that myotubes derived from individuals carrying the RyR1 Thr2206Met (C6617T) mutation have an abnormal response of the intracellular calcium concentration to 4-chloro-m-cresol and to caffeine. Satellite cells were obtained from muscle biopsies of patients referred for diagnosing MH. The intracellular calcium concentration in response to 4-chloro-m-cresol and to caffeine was investigated by fluorescence calcium imaging. In myotubes the half-maximal activation concentration (EC(50)) for 4-chloro-m-cresol was reduced from 203 micro m (wild type) to 98 micro m (Thr2206Met), and for caffeine from 3.8 mm to 1.8 mm. From the reduction of EC(50) we conclude that the RyR1 Thr2206Met mutation is pathogenic for MH.

Amino Acid Substitution↗
PubMed2001

Breast cancer risk in women with abnormal cytology in nipple aspirates of breast fluid.

BACKGROUND: We previously showed that women with abnormal cytology in breast fluid obtained by nipple aspiration had an increased relative risk (RR) of breast cancer compared with women from whom fluid was not obtained and with women whose fluid had normal cytology. This study extends the follow-up in the original study group (n = 4046) and presents the first follow-up for a second group of women (n = 3627). METHODS: We collected nipple aspirate fluid from women in the San Francisco Bay Area during the period from 1972 through 1991, classified the women according to the most severe epithelial cytology observed in fluid specimens, and determined breast cancer incidence through March 1999. We estimated RRs for breast cancer using Cox regressions, adjusting for age and year of study entry. All statistical tests were two-sided. RESULTS: For women in the first and second study groups, the median years of follow-up were 21 years and 9 years, respectively, and breast cancer incidences were 7.8% (285 cases in the 3633 women for whom breast cancer status could be determined) and 3.5% (115 of 3271), respectively. Compared with women from whom no fluid was obtained, whose incidences of breast cancer were 4.7% (39 of 825) and 3.3% (65 of 1950) for those in group 1 and group 2, respectively, incidences and adjusted RRs were 8.1% (34 of 422), with RR = 1.4 (95% confidence interval [CI] = 0.9 to 2.3), and 0% (0 of 31), respectively, for those with unsatisfactory aspirate specimens and 8.2% (148 of 1816), with RR = 1.6 (95% CI = 1.1 to 2.3), and 3.1% (25 of 811), with RR = 1.2 (95% CI = 0.8 to 2.0), respectively, for those with normal cytology in aspirates. Compared with women from whom no fluid was obtained, incidences and adjusted RRs for women in group 1 with epithelial hyperplasia and atypical hyperplasia in aspirates were 10.8% (52 of 483), with RR = 2.4 (95% CI = 1.6 to 3.7), and 13.8% (12 of 87), with RR = 2.8 (95% CI = 1.5 to 5.5), respectively, while those for women in group 2 were 5.5% (25 of 457) and 0% (0 of 22), respectively, with a combined RR = 2.0 (95% CI = 1.3 to 3.3). CONCLUSION: The results obtained with the newly followed women independently confirmed previous findings that women with abnormal cytology in nipple aspirates of breast fluid have an increased risk of breast cancer.

Adolescent↗
PubMed2001

[Anatomic principles of urinary incontinence].

The morphological fundamentals of urinary continence are still subject to controversy. This was the reason for a renewed examination of the sphincter musculature of the lower urinary tract. This study included 50 male and 15 female autopsy specimens. The organs of the lower urinary tract including the neighboring organs had been removed in their entirety and histologically reprocessed en bloc as a complete series of sections. We were able to demonstrate that the internal sphincter or m. sphincter vesicae is represented as a circular, distinct structure which elliptically embraces the internal urethral orifice. Lamellas of the detrusor are not involved in the formation of the internal sphincter. In females and males, the external sphincter consists of a striated and a smooth muscular part (m. sphincter urethrae transversostriatus et glaber). In transverse sections, the muscle has a horseshoe shape. It is completely separated by connective tissue from the musculature of the pelvic floor. A deep transverse perineal muscle does not exist. The histological findings were used for the construction of a digital three-dimensional model of the anatomy of the lower urinary tract. Computer animations of the model with integrated original histologies were generated and stored as a computer video on a CD-ROM attached to this journal.

Computer Simulation↗
PubMed2001

The prehospital treatment of status epilepticus (PHTSE) study: design and methodology.

Status epilepticus is a neurological emergency that is typically first encountered and managed in the prehospital environment. Although aggressive pharmacological treatment of status epilepticus is well established in the emergency department and hospital settings, the relative risks and benefits of active therapy for status epilepticus in the prehospital setting are not known. The Prehospital Treatment of Status Epilepticus (PHTSE) study is a prospective, randomized, double-blind, placebo-controlled study designed to address the following aims: (1) to determine whether administration of benzodiazepines by paramedics is an effective and safe means of treating status epilepticus in the prehospital setting and whether this therapy influences longer-term patient outcome, (2) to determine whether lorazepam is superior to diazepam for the treatment of status epilepticus in the prehospital setting, and (3) to determine whether control of status epilepticus prior to arrival to the emergency department influences patient disposition. The initial phase of the PHTSE study began in January 1994 and was completed in February 1999 after the successful enrollment of 205 patients into the three treatment arms. In this paper, we describe the rationale for the conceptualization of the study and details of the study design and methodology, and emphasize some aspects of study implementation that are unique to research involving the emergency medical system.

Adult↗
PubMed2001

Comparative anatomy of the male guinea-pig and human lower urinary tract: histomorphology and three-dimensional reconstruction.

The guinea-pig is often used for experimental studies in urology. However, the anatomy of the lower urinary tract of the guinea-pig is poorly described in the literature. The structure and function of the lower urinary tract, i.e. continence, micturition and sexual function, are closely related to the gross anatomy of the pelvis and the fine structure of the musculature. We investigated the anatomy and histomorphology of the lower urinary tract by serial sections in male guinea-pigs and compared it to that in humans. Immunohistochemical stainings for alpha-smooth muscle cell actin were used to differentiate between smooth and striated muscles. By using whole pelvic preparations, including all internal organs preserved in their in situ location for three-dimensional reconstruction, we developed three-dimensional models, which elucidate the spatial relationship of all muscular structures and can help to deduce functional aspects of lower urinary tract function. In the guinea-pig, most of the muscles found in humans can be demonstrated in comparable location and extension. However, the structure of the prostate and the existence of the so-called coagulation glands define a significant difference in the morphology of the prostatic urethra.

Animals↗
PubMed2001

Repair of inguinal hernias using the mesh technique during extraperitoneal pelvic lymph node dissection.

PURPOSE: This article describes our experience of using a totally extraperitoneal approach for endoscopic pelvic lymphadenectomy and inguinal hernia repair with the mesh technique in one procedure. MATERIALS AND METHODS: A total of 52 patients underwent modified pelvic lymph node dissection for the staging of prostate cancer. Eight of them had hernia defects; 1 was recurrent. Five patients with direct and 3 patients with indirect inguinal hernias were treated by totally extraperitoneal hernia repair with the placement of a mesh measuring at least 10 x 15 cm (prolene mesh with incision and flap). RESULTS: The mean duration of the lymphadenectomy itself was decreased from 150 min (first 20 patients) to 70 min (n = 21-52). The mean additional procedure time for hernioplasty was 15 min. The overall lymph node-positive rate was 9.6%. The complication rate was 7.7%. Four patients developed symptomatic lymphoceles, 1 of whom developed deep venous thrombosis. No complications occurred which were attributed to hernia repair. Morbidity did not rise, and hospitalization time did not increase for the patients who underwent hernioplasty. There were no recurrences or neuralgias on follow-up up to 2 years. CONCLUSIONS: By avoiding entry into the peritoneal cavity, the extraperitoneal approach obviates intra-abdominal complications (ileus, bowel injury, peritonitis) in both techniques. The extraperitoneal approach for pelvic lymph node dissection allows concomitant inguinal hernia to be repaired with low morbidity and within an acceptable operating time.

Aged↗
PubMed2001

Comparative anatomy of the male guinea-pig and human lower urinary tract: histomorphology and three-dimensional reconstruction.

The guinea-pig is often used for experimental studies in urology. However, the anatomy of the lower urinary tract of the guinea-pig is poorly described in the literature. The structure and function of the lower urinary tract, i.e. continence, micturition and sexual function, are closely related to the gross anatomy of the pelvis and the fine structure of the musculature. We investigated the anatomy and histomorphology of the lower urinary tract by serial sections in male guinea-pigs and compared it to that in humans. Immunohistochemical stainings for alpha-smooth muscle cell actin were used to differentiate between smooth and striated muscles. By using whole pelvic preparations, including all internal organs preserved in their in situ location for three-dimensional reconstruction, we developed three-dimensional models, which elucidate the spatial relationship of all muscular structures and can help to deduce functional aspects of lower urinary tract function. In the guinea-pig, most of the muscles found in humans can be demonstrated in comparable location and extension. However, the structure of the prostate and the existence of the so-called coagulation glands define a significant difference in the morphology of the prostatic urethra.

Anatomy, Comparative↗
PubMed2000

The efficacy of medical abortion: a meta-analysis.

Multiple clinical studies demonstrate the efficacy of medical abortion with mifepristone or methotrexate followed by a prostaglandin analogue. However, assessing predictors of success, including regimen, is difficult because of regimen variability and a lack of direct comparisons. This meta-analysis estimates rates of primary clinical outcomes of medical abortion (successful abortion, incomplete abortion, and viable pregnancy) and compares them by regimen and gestational age. We identified 54 studies published from 1991 to 1998 using mifepristone with misoprostol (18), mifepristone with other prostaglandin analogues (23), and methotrexate with misoprostol (13). Data abstracted from studies included regimen details and clinical outcomes by gestational age. We found that efficacy decreases with increasing gestational age (p<0.001), and differences by regimen are not statistically significant except at gestational age > or =57 days. For gestations < or =49 days, mean rates of complete abortion were 94-96%, incomplete abortion 2-4%, and ongoing (viable) pregnancy 1-3%. For gestations of 50-56 days, the mean rate of complete abortion was 91% (same for all regimens), incomplete abortion 5-8%, and ongoing pregnancy 3-5%. For > or =57 days, success was lower for mifepristone/misoprostol (85%, 95% confidence interval 78-91%) than for mifepristone/other prostaglandin analogues 95% (CI 91-98%, p = 0.006). For mifepristone/misoprostol, using > or =2 prostaglandin analogue doses seems to be better than a single dose for certain outcomes and gestational ages. We conclude that both mifepristone and methotrexate, when administered with misoprostol, have high levels of success at < or =49 days gestation but may have lower efficacy at longer gestation.

Abortifacient Agents↗
PubMed2000

Barriers to timely prenatal care among women with insurance: the importance of prepregnancy factors.

OBJECTIVE: This study, designed to avoid methodologic limitations of previous research, aimed to identify the important noninsurance barriers to timely prenatal care. METHODS: We identified a subsample of a cross-sectional statewide representative postpartum survey conducted in California during 1994-1995, focusing on 3071 low-income women with Medi-Cal or private coverage throughout pregnancy. RESULTS: Twenty-eight percent of those women had untimely care, although only 6% were unaware of their pregnancies during the first trimester. Controlling for numerous sociodemographic factors; knowledge, attitudes, beliefs, and behaviors; stressful life circumstances; and logistic obstacles that might deter seeking or receiving care, the following risk factors for untimely care were significant and experienced by more than one fifth of women: unwanted or unplanned pregnancy (affecting 43% and 66% of women, respectively), no regular provider before pregnancy (affecting 22% of women), and no schooling beyond high school (affecting 76% of women). Transportation problems, affecting 8% of women, appeared to be the only significant logistic barrier to timely care. CONCLUSION: Improving timeliness of prenatal care among low-income women with third-party coverage is likely to require broad social and health policies that focus on factors affecting women before pregnancy. Assistance with transportation could contribute to more timely care for some low-income women, but programs focusing primarily on other noninsurance barriers during pregnancy might not substantially improve the timeliness of care, at least among low-income women with third-party coverage.

California↗
PubMed2000

Risk-based selection of respirators against infectious aerosols: application to anthrax spores.

This article presents two methods for estimating infection risk among individuals wearing air-purifying respirators against airborne pathogens, with the overall aim of selecting appropriate respiratory protection. Necessary data inputs are the parameters for the ambient pathogen concentration distribution, the respirator penetration distribution, and the infectious dose distribution, along with the breathing rate, duration of a respirator use period, and the number of use periods. The first method assumes that the pathogen does not exhibit a cumulative dose effect, whereas the second accounts for a cumulative dose effect. The methods are illustrated with hypothetical scenarios involving Bacillus anthracis (anthrax) spores. Available data suggest that anthrax spores would exhibit a cumulative dose effect for multiple exposures occurring close in time, as would likely affect personnel responding to a bioterrorist release. The analysis shows that failure to account for a cumulative dose effect when present leads to underestimating infection risk. Three types of air-purifying respirators are compared for their predicted efficacy in reducing the risk of inhalation anthrax. Although uncertainty analyses are not performed, a general conclusion is that a full-facepiece powered air-purifying respirator would be the best air-purifying device for responding to an anthrax spore release. Because such respirators would not prevent all personnel from inhaling an infectious dose, it would be advisable for users not previously vaccinated against anthrax to receive post-exposure prophylactic therapy.

Adult↗
PubMed1997

Familial and personal medical history of cancer and nervous system conditions among adults with glioma and controls.

The causes of glioma, the most common type of primary malignant brain tumor, are poorly understood. This study compared the personal and first-degree familial medical histories of 462 adults newly diagnosed with glioma in the San Francisco Bay Area between August 1, 1991, and March 31, 1994, with those of 443 controls who were frequency-matched on age, sex, and ethnicity. Cases and controls had equivalent personal histories of cancers other than brain cancer and most nervous system conditions, but they differed significantly regarding histories of epilepsy, seizures, or convulsions 3 or more years prior to diagnosis (odds ratio = 3.3, 95% confidence interval (CI) 1.4-7.9), chickenpox (odds ratio = 0.4, 95% CI 0.3-0.6), and shingles (odds ratio = 0.5, 95% CI 0.3-0.8). Four cases (less than 1%) and no controls had known genetic disorders (three had neurofibromatosis and one had tuberous sclerosis). Cases and controls had similar family histories of cancer and seizures. However, the odds ratio for a validated family history of primary brain tumor was 2.3 (95% CI 1.0-5.8). These results suggest that although family history of any cancer probably is not an important risk factor for adult glioma, a family history of brain tumors may play a role. Variation in exposure to or biologic response to common viral infections might play a greater role in the etiology of adult glioma than family history.

Adult↗