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Biomedical subjects

S Sacks

Publications and source records attributed to S Sacks.

At least 19 recordsLinked to original sources
PubMed2005

Prospective registry-based observational cohort study of the long-term risk of malignancies in renal transplant patients treated with mycophenolate mofetil.

This large prospectively conducted observational cohort study examined the risk of lymphoma and other malignancies with mycophenolate mofetil (MMF) in de novo renal transplant recipients. A total of 6751 patients receiving MMF, and an equal number of matched controls receiving non-MMF-based immunosuppression, were identified from two large registries (Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) and Collaborative Transplant Study (CTS)) and followed for 3 years. The primary endpoint was development of lymphoma. Secondary endpoints included development of any malignancy. There was no evidence of any increased risk of developing lymphoma or malignancy with MMF. The risk of developing lymphoma with MMF compared with the non-MMF cohort was not higher in either the CTS registry (relative risk (95% confidence interval); 0.4 (0.17-0.94)) or the OPTN/UNOS registry (1.04 (0.61-1.78)). In the MMF group, there was a trend toward a lower risk of malignancy in both registries (OPTN/UNOS 0.86 (0.69-1.07); CTS 0.79 (0.61-1.02)) and a significant increase in time to malignancy in the CTS dataset (p < 0.026). This study has demonstrated that MMF is not associated with an increased risk of lymphoma or other malignancies post-renal transplant, and may even be associated with a lower risk in some populations.

Adult↗
PubMed2004

Mental disorders and drug abuse in persons living with HIV/AIDS.

This article reviews the literature on the prevalence of mental and substance use disorders among persons living with HIV/AIDS. Drug use, both injection and non-injection, substantially increases the risk for HIV infection. While injection drug users have the highest prevalence rates for HIV, substantially elevated rates of HIV infection are also present among crack cocaine users and individuals with substance use disorders generally. Persons with HIV/AIDS and a mental and/or substance use disorder have highly variable patterns of accessing services. Persons with HIV/AIDS who have a serious mental illness are more highly involved with services than other groups. Most individuals with co-occurring disorders report some involvement with outpatient primary medical care, although ancillary services such as mental health and substance abuse treatment, transportation assistance, and case management improve involvement in medical care. Women with HIV/AIDS and co-occurring mental and substance use disorders experience unique vulnerabilities, particularly those related to exposure to traumatic events. Given the complexity of needs with which triply or multiply diagnosed individuals present, effective treatment programmes are likely to be those that provide some degree of integrated care.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Evaluations of unformulated and formulated dendrimer-based microbicide candidates in mouse and guinea pig models of genital herpes.

Prevention of sexually transmitted infections is a priority in developed and developing countries. One approach to prevention is the use of topical microbicides, and one promising approach is the use of dendrimers, highly branched macromolecules synthesized from a polyfunctional core. Three new dendrimer products developed to provide stable and cost-efficient microbicides were initially evaluated in vitro for anti-herpes simplex virus activity and then in vivo by using a mouse model of genital herpes. From these experiments one product, SPL7013, was chosen for further evaluation to define the dose and duration of protection. Unformulated SPL7013 provided significant protection from genital herpes disease and infection at concentrations as low as 1 mg/ml and for at least 1 h following topical (intravaginal) administration of 10 mg/ml. This compound was then formulated into three vehicles and further evaluated in mouse and guinea pig models of genital herpes infection. In the murine evaluations each of the formulations provided significant protection at concentrations of 10 and 50 mg/ml. Formulated compounds provided protection for at least 1 h at a concentration of 10 mg/ml. From these experiments formulation 2V was chosen for dose ranging experiments using the guinea pig model of genital herpes. The guinea pig evaluations suggested that doses of 30 to 50 mg/ml were required for optimal protection. From these studies a lead compound and formulation (2V of SPL7013) was chosen for ongoing evaluations in primate models of simian immunodeficiency virus and Chlamydia trachomatis infection.

Animals↗
PubMed2000

Service use and cost by mentally ill chemical abusers: differences by retention in a therapeutic community.

PURPOSE: Earlier research estimated the incremental costs and outcomes of a modified therapeutic community (modified TC) for mentally ill chemical abusers (MICAs) relative to a treatment-as-usual (TAU) control group. The present study extended the cost analysis by disaggregating the modified TC group into clients who completed the program (completers) and clients who dropped out (separaters). METHODS: Bivariate and multivariate analyses were conducted to estimate differences in treatment and other service costs among completers, separaters, and TAU. Subjects were sequentially assigned to the modified TC (n = 171) or TAU (n = 47), and the analysis period covered 12 months post-baseline. Using a standardized instrument to collect resource use and cost data, the estimated weekly cost per client in the modified TC was $554, with completers showing a larger average cost of treatment ($27,595) than separaters ($9,986). RESULTS: The average TAU subject had a much higher cost for other (non-modified TC) services ($29,795) relative to separaters ($22,048) or completers ($1,986). These findings suggest that, from baseline to the 12-month follow-up, the total cost of modified TC treatment and other services for completers may be slightly lower than the total cost for separaters or TAU subjects. Since the modified TC group had better outcomes than the TAU group, and the completers had better outcomes than the separaters, the modified TC program could be an effective mechanism to reduce the costs of service utilization as well as improve clinical outcomes. IMPLICATIONS: This detailed investigation into service utilization and cost provides policy-makers and program directors with valuable information regarding potentially cost-effective interventions and further underscores the importance of retention in treatment for this vulnerable population.

Adult↗
PubMed2000

Modified therapeutic community for homeless mentally ill chemical abusers: treatment outcomes.

This study compared homeless mentally ill chemical abuser (MICA) clients (n = 342), male and female, sequentially assigned to either of two modified therapeutic community programs (TC1 and TC2) and to a treatment-as-usual (TAU) control group. Follow-up interviews were obtained at 12 months postbaseline and at time F (on average more than 2 years postbaseline) on a retrieved sample of 232 (68%) clients and 281 (82%) clients, respectively. Outcome measures assessed five domains: drug use, crime, HIV risk behavior, psychological symptoms, and employment. Individuals in both modified TC groups showed significantly greater behavioral improvement than TAU at 12 months and time F, and the modified TC2, with lower demands and more staff guidance, was superior to modified TC1. Completers of both TC programs showed significantly greater improvement than dropouts and a subgroup of TAU clients with high exposure (i.e., more than 8 months) to other treatment protocols. The present findings support the effectiveness and longer term stability of effects of a modified TC program for treating homeless MICA clients.

Adult↗
PubMed2000

A clinicopathological study of sinonasal neuroendocrine carcinoma and sinonasal undifferentiated carcinoma.

OBJECTIVE: Sinonasal undifferentiated carcinoma (SNUC) and sinonasal neuroendocrine carcinoma (SNEC) are relatively newly recognized, rare entities requiring further clinicopathological analysis to advance our understanding and determine prognostic distinctions between them. STUDY DESIGN: Retrospective chart review. METHODS: Cases were retrieved from the Copath system. One patient was seen in consultation from an outside institution. Histological and immunohistochemical findings, patient demographics, treatment regimens, and outcomes were analyzed and compared. RESULTS: Ten patients (7 men, 3 women) ranging in age from 17 to 58 years (mean age, 44.7 y) were included. Four patients were classified with SNEC, six as having SNUC. The predominant site was the superior nasal cavity or ethmoids (seven cases), followed by the maxilla (four cases). Disease in four patients was clinically staged as N1 (three with SNUC, one with SNEC), and in six patients as NO (three with SNEC, three with SNUC). Of the nine patients who were treated initially with surgical resection, seven received postoperative radiation therapy alone, one received postoperative radiation and chemotherapy, and one had only limited postoperative chemotherapy. One patient was treated with radiation therapy and chemotherapy alone, without surgical resection. Follow-up was obtained ranging from 6 to 108 months (mean period, 26.4 mo). Three patients died of disease 10, 14, and 41 months, respectively, after diagnosis. Three patients had persistent disease at 6, 9, and 21 months, respectively, two of them with distant metastases. Four patients were disease free after 6, 18, 31, and 108 months, respectively. CONCLUSIONS: SNUC and SNEC are both aggressive tumors, usually presenting in middle age as a nasal mass. Both tumors have the capacity to metastasize locally and distantly, and both can result in poor outcomes. This small series precludes a demographic or prognostic distinction between the two groups.

Adolescent↗
PubMed1999

Do antepartum herpes simplex virus cultures predict intrapartum shedding for pregnant women with recurrent disease?

OBJECTIVE: To examine antenatal screening as a predictor of intrapartum shedding of herpes simplex virus (HSV) and to determine its usefulness in guiding the appropriate route of delivery for patients with recurrent HSV in pregnancy. METHODS: A population of 198 pregnant women with a history of recurrent genital HSV were cultured in the last weeks of their pregnancy by specially-trained personnel and intrapartum by their delivering attendants. RESULTS: Of cultures from a total of 906 antenatal visits, 17% were culture positive, with an asymptomatic shedding rate of 3.4%. Asymptomatic shedding occurred in 12.6% of women. Over the 8-week antepartum period, viral culture-positivity rates for each visit ranged from 11% to 19.5%. This provided an expected delivery culture-positivity rate of 15.3%. However, actual intrapartum viral culture positivity occurred in only three of 191 women (1.5%; P < 0.001). Because previous studies have suggested antepartum culture positivity fails to predict intrapartum viral shedding, evaluations, including cultures, as well as predictive values for subsequent culture positivities, were determined under the supervision of an infectious disease specialist. Under these conditions, positive predictive values were 59% when the interval between visits was 2 days, but only 19% when days between visits were >2 (P < 0.0001). No cases of neonatal herpes were seen in this population, although cesarean deliveries were performed in 31% of the patient population, with genital herpes as the indication for 56% of those. CONCLUSIONS: Antepartum serial screening by viral culture is not predictive of an infant's risk of intrapartum viral exposure when conducted at weekly intervals. However, more frequent assessments of patients can be predictive of an infant's exposure risk to HSV; for patients with frequent recurrent disease near term or primary infection in pregnancy, frequent late antepartum screening may be appropriate.

Adolescent↗
PubMed1999

Absence of MHC class II gene expression in a patient with a single amino acid substitution in the class II transactivator protein CIITA.

We investigated the underlying genetic defect in an immunodeficient patient who presented with recurrent bacterial infections in his late twenties and demonstrated a transcriptional defect in major histocompatibility complex (MHC) class II regulation. Transient heterokaryon analysis implicated functional loss of CIITA, the MHC class II transactivator protein, and in support of this MHC class II antigen expression was restored by stable transfection with the wild-type molecule. A single amino acid substitution, phenylalanine to serine, in the COOH-terminal portion of the CIITA sequence correlated with reduced transcription of both classical (HLA-DP, -DQ, and -DR) and nonclassical (HLA-DM and -DO) class II genes. The long survival of the patient, although remarkable, was not associated with partial CIITA function as evidenced by residual MHC class II expression. These data define at high resolution a region of CIITA that is essential for function in both professional and nonprofessional antigen presenting cells and which could potentially constitute a target for therapeutic intervention by novel factors with a propensity to downregulate MHC class II antigen expression.

Adult↗
PubMed1999

New developments in the epidemiology, natural history and management of genital herpes.

The prevalence of genital herpes is increasing in several populations worldwide. Factors that may be contributing to this increase include greater numbers of sexual partners, the high frequency of asymptomatic infections, poor use of safe sexual practices, and possibly the decreased incidence of childhood oral herpes simplex virus infection. Transmission occurs via skin-to-skin or mucous membrane contact during periods of viral shedding when lesions are present but may also occur when the patient is unaware of the lesions or when lesions are not clinically apparent. This has important implications for strategies to prevent transmission of the disease. The introduction of the antiherpes agent, acyclovir, and more recently famciclovir and valacyclovir, facilitates the management of genital herpes. Treatment of first-episode genital herpes reduces the severity and duration of symptoms, time to lesion healing, and cessation of viral shedding. Episodic treatment of recurrences as they occur may be of benefit to some patients. Daily suppressive therapy significantly reduces the frequency of recurrences and asymptomatic viral shedding. Accordingly, patients who experience frequent or severe recurrences, those particularly troubled by their disease, and those who wish to reduce the frequency of asymptomatic infection generally prefer suppressive therapy. The possibility that suppressive therapy may have an impact on transmission of the disease is currently under investigation. Antiviral treatments have important implications for public health and may help reduce the psychological and psychosocial impact of genital herpes on individual patients.

Antiviral Agents↗
PubMed1999

Modified therapeutic community for homeless mentally ill chemical abusers: emerging subtypes.

This paper is one of a series reporting on a clinical field trial evaluating the efficacy of the modified therapeutic community (TC) approach for the treatment of homeless mentally ill chemical abusers (MICAs). The social and psychological characteristics of the treatment sample were described in an earlier paper; the purpose of the present report was to categorize subtypes of homeless MICA clients to predict with greater accuracy their treatability in modified TCs. An index that consistently correlated with treatment-relevant variables was identified for each of three dimensions; Homelessness (residential instability), Mental Illness (current severity), and Substance Abuse (current substance abuse/dependence diagnosis). These indices yielded distributions that captured the variability in the sample with respect to a number of variables, including drug use, criminality, human immunodeficiency virus (HIV) risk (sexual behavior), psychological status, and motivation. Bivariate and multivariate analyses showed that the indices were not strongly related to demographic variables such as race/ethnicity, age, or gender, but were significantly associated with baseline drug use, criminal activity, HIV risk (sexual behavior), psychological symptoms, and motivation and readiness. These findings indicate that, even among those admitted to residential treatment for substance abuse, homeless MICA clients are not homogeneous; rather, subgroup differences emerge among the indices of homelessness, mental illness, and substance abuse. The efficacy of treatment in modified TCs for these subgroups will be assessed in subsequent papers examining the relationships among the three indices, client retention, and outcomes during and subsequent to residential treatment.

Diagnosis, Dual (Psychiatry)↗
PubMed1999

Modified therapeutic community for mentally ill chemical abusers: outcomes and costs.

Several studies have established that the personal and social consequences of substance abuse are extensive and costly. These consequences are frequently compounded by mental illness. Although interventions that target mentally ill chemical abusers (MICAs) present several challenges, the potential benefits of successful interventions are significant. This article presents outcomes and costs of a modified therapeutic community (TC) intervention for homeless MICAs. Outcomes at follow-up are compared with those for a control group of homeless MICAs receiving standard services in a "treatment-as-usual" (TAU) condition. Annual economic costs for the modified TC and the average weekly cost of treating a single client are estimated. Treatment and other health service costs at 12 months postbaseline are compared for modified TC and TAU clients. The results of this study indicate that, suitably modified, the TC approach is an effective treatment alternative for homeless MICAs, with the potential to be highly cost-effective relative to standard services.

Cost-Benefit Analysis↗
PubMed1999

Sequential assignment and treatment-as-usual. Alternatives to standard experimental designs in field studies of treatment efficacy.

Psychosocial treatment research studies encounter obstacles to random assignment (RA). Used together, two procedures offer an alternative to the standard RA design. First, sequential assignment (SA) may create less opposition from administration, staff, and clients. SA operates on the principle that limited bed availability, a common treatment consideration in the field, determines assignment of clients to conditions. Second, treatment-as-usual (TAU) represents an alternative type of control condition. Some clients on the waiting list will, before a slot opens up and they enter an experimental condition, be absorbed into the existing treatment system, in which the amount and type of treatment they receive can vary widely. Substituting SA and TAU for the standard RA design may introduce methodological impurities including certain limited biases.

Bias↗
PubMed1998

Carpal tunnel syndrome: validation of an interview questionnaire on occupational exposure.

The objectives of this study were 1) to summarize in a clinically meaningful way information on occupational risk factors for carpal tunnel syndrome (CTS), and 2) to test a questionnaire on risk factors that could be used by physicians with their patients. For the two objectives, a systematic literature review was performed and synthetized graphically, and a questionnaire was developed and administered to 238 patients who underwent release surgery for CTS. Patients were classified in four groups according to the incidence rate of CTS surgery in their occupation. Answers to the questionnaire on exposure to risk factors for CTS were compared between these four groups with the hypothesis that the group with the highest incidence would report the highest exposure. The results showed that questioning workers on the amount of force required to perform tasks that are "especially demanding" for the wrists or hands is both useful clinically and valid to be used by the clinician to make a judgement on the occupational nature of CTS. Repetitiveness and segmental exposure to vibrations or to cold are potentially useful and will need further validation. There is no evidence at present that posture or motion of the wrists is potentially useful to describe occupational exposure when questioning patients with CTS.

Adult↗
PubMed1997

Mechanical stretch induces vascular permeability factor in human mesangial cells: mechanisms of signal transduction.

Hemodynamic abnormalities have been implicated in the pathogenesis of the increased glomerular permeability to protein of diabetic and other glomerulopathies. Vascular permeability factor (VPF) is one of the most powerful promoters of vascular permeability. We studied the effect of stretch on VPF production by human mesangial cells and the intracellular signaling pathways involved. The application of mechanical stretch (elongation 10%) for 6 h induced a 2.4-fold increase over control in the VPF mRNA level (P < 0.05). There was a corresponding 3-fold increase in VPF protein level by 12 h (P < 0. 001), returning to the baseline by 24 h. Stretch-induced VPF secretion was partially prevented both by the protein kinase C (PKC) inhibitor H7 (50 microM: 72% inhibition, P < 0.05) and by pretreatment with phorbol ester (phorbol-12-myristate-13 acetate 10(-)7 M: 77% inhibition, P < 0.05). A variety of protein tyrosine kinase (PTK) inhibitors, genistein (20 microg/ml), herbimycin A (3.4 microM), and a specific pp60(src) peptide inhibitor (21 microM) also significantly reduced, but did not entirely prevent, stretch-induced VPF protein secretion (respectively 63%, 80%, and 75% inhibition; P < 0.05 for all). The combination of both PKC and PTK inhibition completely abolished the VPF response to mechanical stretch (100% inhibition, P < 0.05). Stretch induces VPF gene expression and protein secretion in human mesangial cells via PKC- and PTK-dependent mechanisms.

Capillary Permeability↗
PubMed1997

Modified therapeutic community for mentally ill chemical "abusers": background; influences; program description; preliminary findings.

This paper briefly surveys the literature that addresses the problem of co-occurring mental and "substance abuse disorders." It discusses several convergent influences on the development of modified therapeutic community (TC) approaches. The paper describes in some detail the modified TC program for mentally ill chemical "abusers" (MICAs). The paper also summarizes research data that establish positive retention rates and significant in-treatment change to support the effectiveness of the modified TC and to underscore the limited effect of treatment-as-usual approaches. Treatment approaches must be comprehensive, multidimensional, of relatively long duration, and must systematically address the interrelated problems of mental illness and substance use.

Comorbidity↗
PubMed1996

Detection of viral DNA to evaluate outcome of antiviral treatment of patients with recurrent genital herpes.

Culture of infectious virus, PCR amplification of viral DNA, and the appearance of genital skin lesions were used as markers to study the course of a recurrence of genital herpes in 40 patients treated with famciclovir or placebo. The highest frequency of patients with skin lesions occurred within the first 36 h following the onset of a recurrence, which also corresponded to the peak in the production of virus. While the timing of the peak in skin lesions was independent of the type of treatment, the frequency of lesions and the release of virus at the lesion site were both reduced by famciclovir treatment. Furthermore, patients receiving this antiviral agent showed a more rapid recovery time and a shorter period during which viral DNA could be detected at the lesion. PCR and then Southern blot hybridization greatly enhanced our ability to detect herpes simplex virus at the lesion site. This procedure proved to be of greater diagnostic value in assessing genital herpes than the standard culture method currently used. In addition, PCR was more sensitive in evaluating treatment effectiveness.

2-Aminopurine↗
PubMed1995

Therapeutic community methods in methadone maintenance (Passages): an open clinical trial.

A non-random open clinical trial was conducted to determine whether a day-treatment program based on modified therapeutic community (TC) methods (Passages) produced better treatment outcomes for heroin addicts than did standard methadone maintenance therapy. Altogether, 327 methadone clients at two clinic sites were studied: 115 Passages members, and 212 comparison subjects. Compared to non-Passages clients, clients who voluntarily joined and remained in Passages for at least 6 months exhibited significantly larger reductions in cocaine use, heroin use, needle use, criminal activity, and psychological dysfunction. The present findings suggest that TC-oriented enhanced day-treatment can help methadone clients recover from drug abuse and adopt a prosocial lifestyle.

Adult↗