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PubMed2005

A retrospective chart review of the clinical effects of atypical antipsychotic drugs on glycemic control in institutionalized patients with schizophrenia and comorbid diabetes mellitus.

BACKGROUND: The association between schizophrenia and onset of type 2 diabetes mellitus (DM) is well documented. It is unclear whether this association is due to inherent risk factors in individuals with schizophrenia or to treatment with antipsychotic drugs, particularly atypical antipsychotic agents. OBJECTIVES: The goals of this retrospective, observational study were the following: (1) to determine whether adequate glycemic control could be achieved in patients with schizophrenia and comorbid DM who were undergoing treatment with atypical antipsychotic drugs, (2) to identify inherent risk factors that may affect glycemic control in this patient population, and (3) to consider the possibility that combined medication and inherent risk factors may affect glycemic control. METHODS: This was a retrospective, observational chart review that evaluated institutionalized patients in a New Jersey mental institution with concurrent diagnoses of schizophrenia and type 1 or 2 DM who were being treated with atypical antipsychotic agents (ie, olanzapine, risperidone, clozapine, or quetiapine) and were referred by their hospital internists to a weekly, half-day, in-hospital DM clinic. All patients with initial and end-point data for the efficacy measure (ie, change in glycosylated hemoglobin [HbA(1c)]) were included in the analysis. Mixed-effects linear and least-squares models were used to test whether a specific comorbidity had an effect on the change in HbA(1c) adjusted for the duration of the observation. RESULTS: A total of 72 patients met entry criteria. Among the 38 patients with baseline and end-point data (20 treated with olanzapine and 18 treated with risperidone), mean (SD) HbA(1c) decreased from 8.21% (2.4%) to 7.62% (1.7%). The only baseline demographic characteristic or comorbidity that predicted significant worsening in the adjusted HbA(1c) change was hepatitis (P = 0.003). CONCLUSIONS: Using appropriate, aggressive antidiabetic therapy, glycemic control was achieved in this group of patients with schizophrenia and comorbid DM who were treated with atypical antipsychotic agents.

Adult↗
PubMed2005

Comparison of late toxicity between continuous low-dose-rate and pulsed-dose-rate brachytherapy in cervical cancer patients.

PURPOSE: To compare survival and severe late radiation toxicity between patients who received continuous low-dose-rate (LDR) brachytherapy (BT) and pulsed-dose-rate (PDR) BT for cervical cancer. METHODS AND MATERIALS: A retrospective review of cervical cancer patients who underwent primary radiotherapy with or without concurrent cisplatin was performed. Late Grade 3 or worse toxicities were assessed using the National Cancer Institute Common Toxicity Criteria. The study endpoints were overall and disease-free survival and the probability of severe late toxicity. RESULTS: A total of 109 patients (65.7%) received LDR BT and 57 (34.3%) received PDR BT. Seventy patients received concurrent chemotherapy with cisplatin. The 3-year overall survival and disease-free survival rate was 70% and 57% for the LDR group and 82% and 70% for the PDR group, respectively (p = 0.25 and p = 0.19). The 3-year probability rate for late Grade 3 or worse toxicity was 7.4% for LDR BT patients and 7.6% for PDR BT patients, respectively (p = 0.69) and 6.9% and 7.6%, respectively, for concurrent chemotherapy vs. none (p = 0.69). CONCLUSION: No difference was found in severe late toxicity, overall survival, or disease-free survival between the LDR and PDR groups.

Adult↗
PubMed2004

Cataract surgery with the AlphaCor artificial cornea.

PURPOSE: To review the outcomes of AlphaCor artificial cornea (Argus Biomedical Pty Ltd.) implantation concurrent with or subsequent to cataract surgery. SETTING: Nonrandomized multicenter clinical trial. METHODS: AlphaCor devices were implanted under an approved protocol. Extracapsular cataract extraction with intraocular lens implantation was concurrently performed in 5 cases; an additional case had a displaced cataractous lens removed after severe blunt trauma subsequent to AlphaCor implantation. RESULTS: Cataract surgery was difficult because the view was restricted and residual soft lens matter was retained. There was an increased incidence of postoperative complications (eg, melt, glaucoma) in cataract cases compared with noncataract AlphaCor cases. The mean best corrected visual acuity was worse in cases with cataract than in cases without. CONCLUSIONS: The technique for cataract surgery in AlphaCor cases needs to be refined. Imaging studies performed postoperatively may help ascertain whether soft lens matter remains so additional antiinflammatory medication can be considered. Melting appears to be preventable by topical medroxyprogesterone 1% therapy.

Adult↗
PubMed2006

Aspiration rate following chemoradiation for head and neck cancer: an underreported occurrence.

BACKGROUND AND PURPOSE: We would like to assess the prevalence of aspiration before and following chemoradiation for head and neck cancer. PATIENTS AND METHODS: We reviewed retrospectively the Modified Barium Swallow (MBS) in 63 patients who underwent concurrent chemotherapy and radiation for head and neck cancer. MBS was performed prior to treatment to determine the need for immediate gastrostomy tube placement. MBS was repeated following treatment to assess the safety of oral feeding prior to removal of tube feeding. All patients were cancer free at the time of the swallowing study. No patient had surgery. Dysphagia severity was graded on a scale of 1-7. Tube feedings were continued if patients were diagnosed to have severe aspiration (grade 6-7) or continued weight loss. Patients with abnormal swallow (grade 3-7) received swallowing therapy following MBS. RESULTS: Before treatment, there were 18 grade 1, 18 grade 2, 9 grade 3, 8 grade 4, 3 grade 5, 3 grade 6, and 4 grade 7. Following chemoradiation, at a median follow-up of 2 months (1-10 months), one patient had grade 1, eight patients had grade 2, nine patients had grade 3, eight patients had grade 4, 13 patients had grade 5, seven patients had grade 6, and 11 patients had grade 7. Six patients died from aspiration pneumonia (one before, three during, and two post-treatment), and did not have the second MBS. Overall, 37/63 (59%) patients developed aspiration, six of them (9%) fatal. If we excluded the 10 patients who had severe aspiration at diagnosis and the six patients who died from pneumonia, the prevalence of severe aspiration was 33% (21/63). CONCLUSIONS: Aspiration remained a significant morbidity following chemoradiation for head and neck cancer. Its prevalence is underreported in the literature because of its often silent nature. Diagnostic studies such as MBS should be part of future head and neck cancer prospective studies to assess the prevalence of aspiration, and for rehabilitation.

Aged↗
PubMed2005

Rectus abdominis myocutaneous and myoperitoneal flaps for neovaginal reconstruction after radical pelvic surgery: comparison of flap-related morbidity.

PURPOSE: To compare flap-specific complications of rectus abdominis myocutaneous (RAM) and myoperitoneal (RAMP) flap neovagina reconstructions performed concurrently with radical pelvic procedures. MATERIALS AND METHODS: Retrospective single institution chart review of all patients with RAM or RAMP flap neovaginal reconstructions performed on a Gynecologic Oncology service, 1988-2003. Analysis for associations with flap-specific morbidity was performed. RESULTS: Neovaginal reconstructions comprised 32 RAM and 7 RAMP flaps. Twenty-two (69%) RAM patients underwent total pelvic exenteration compared to 1 (14%) RAMP patient (P < 0.013). Overall, 33 (85%) of the patient population had previously been treated with radiation. Flap-specific complications developed in 12 (32%) RAM versus 4 (57%) of the RAMP patients (P > 0.1). Donor site complications and incisional hernias were increased in RAMP patients (both P < 0.03), with trends for increasing risk of vaginal stricture/stenosis and superficial wound separations (both P < 0.1). Complete vaginal stenosis developed in only 1 (3%) RAM versus 3 (43%) RAMP patients. Furthermore, 3 RAMP patients developed complete stenosis when the vaginal defect was circumferential and involved >65% of the vagina while this did not occur in 22 similar RAM patients (P < 0.0005). Only patients with partial longitudinal defects maintained vaginal patency after RAMP flap. Fifteen (58%) of 26 patients surviving >12 months reported coitus, with no significant difference between the groups. CONCLUSIONS: When there is circumferential loss of the upper 2/3 of the vagina. RAMP flaps are not suitable for neovaginal reconstruction after radical pelvic surgery because of an increased risk of vaginal stenosis compared to RAM flaps. Patients with partial longitudinal vaginal defects, however, may have successful neovaginal reconstruction with RAMP flaps.

Adult↗
PubMed2003

Humoral rejection in cardiac transplantation: risk factors, hemodynamic consequences and relationship to transplant coronary artery disease.

BACKGROUND: Acute cellular rejection is the mechanism of most immune-related injury in cardiac transplant recipients. However, antibody-mediated humoral rejection (HR) has also been implicated as an important clinical entity following orthotopic heart transplantation. Humoral rejection has been reported to play a role in graft dysfunction in the early post-transplant period, and to be a risk factor for the development of transplant coronary artery disease. Some involved in transplantation pathology doubt the existence of clinically significant humoral rejection in cardiac allografts. Those who recognize its existence disagree on its possible role in graft dysfunction or graft coronary artery disease. In this study, we report clinical features of patients with the pathologic diagnosis of HR at our institution since July 1997, when we began systematic surveillance for humoral rejection. METHODS: We reviewed medical records of patients with the pathologic diagnosis of HR without concurrent cellular rejection between July 1997 and January 2001. Diagnosis was based on routine histology ("swollen cells" distending capillaries, interstitial edema and hemorrhage) and immunofluorescence (capillary deposition of immunoglobulin and complement with HLA-DR positivity), or immunoperoxidase staining of paraffin-embedded tissue (numerous CD68-positive macrophages and fewer swollen endothelial cells distending capillaries). RESULTS: A total of 44 patients (4 to 74 years old) showed evidence of HR without concurrent cellular rejection at autopsy or on one or more biopsies. Although females comprised only 26% of our transplant population, 23 patients (52%) with HR were female. A positive peri-operative flow cytometry T-cell crossmatch was observed in 32% of HR patients compared with 12% of controls (p = 0.02). Hemodynamic compromise consisting of shock, hypotension, decreased cardiac output/index and/or a rise in capillary wedge or pulmonary artery pressure was observed in 47% of patients at the time of diagnosis of HR. Six patients (5 females) died (14% mortality) with evidence of HR at or just before autopsy, 6 days to 16 months after transplantation. The incidence of transplant coronary artery disease was 10% greater at 1 year, and 36% greater at 5 years, in patients with HR when compared with non-HR patients. CONCLUSIONS: Humoral rejection was associated with acute hemodynamic compromise in 47% of patients, and was the direct cause of death in 6 patients (13%). Humoral rejection is a clinicopathologic entity with a high incidence in women and is associated with acute hemodynamic compromise, accelerated transplant coronary artery disease and death.

Adult↗
PubMedDate not supplied

Overview of male reproductive pathology.

An understanding of form and function is important for examination of the male reproductive tract. A basic understanding of spermatogenesis and hormonal function in the reproductive tract is essential for the pathologists in this evaluation. Gross and histologic reproductive changes need to be distinguished from normal variation and correlated with the reproductive status of the animal. This is especially important when correlating histologic changes with organ weight and other reproductive parameters, such as seminal analysis data. Sexual maturity of animals and tissue handing can impact interpretation. Sexual immaturity of preclinical safety animals can present challenges for accurate identification of compound-related changes. Likewise, proper handling of unfixed reproductive tissues and appropriate selection of a fixation protocol are important in avoiding artifacts that may interfere with the microscopic evaluation. The histopathology technician needs to recognize testicular landmarks that allow for correct orientation at trimming so the pathologist can assess not only the morphology of seminiferous tubules but also the outflow tract. For the most effective evaluation of the male reproductive tract, the testes and epididymides should be examined concurrently. Although the term "staging" is often used inappropriately, the pathologist should review testicular tissues in a "stage-aware" manner. This article reviews gross and histologic changes of the male reproductive tract as well as tissue orientation and fixation to assist in accurate interpretation of potential treatment-related changes in male reproduction.

Animals↗
PubMed1992

Adenovirus infection in pediatric liver transplant recipients.

A retrospective review of adenoviral infection in pediatric liver transplant recipients was done at Children's Hospital of Pittsburgh to define its epidemiology and clinical importance. Medical records of patients with adenovirus were reviewed and data collected regarding clinical course, microbiologic studies, biopsy results, immunosuppression, concurrent infections, and outcome. Of 484 liver transplant recipients, 49 had 53 episodes of adenoviral infection. The most common sites of adenoviral infection were the liver, lung, and gastrointestinal tract. Serotypes 1, 2, and 5 were recovered most often; type 5 was commonly associated with hepatitis. Invasive adenoviral infection occurred in 20 children, leading to death in 9. Median time from transplantation until isolation of adenovirus was 25.5 days. This timing suggests either reactivation or donor-associated transmission. Prospective studies using molecular epidemiologic techniques will be helpful in evaluating transmission patterns of adenovirus in this population.

Adenovirus Infections, Human↗
PubMed1984

Carotid endarterectomy in patients with asymptomatic intracranial aneurysm.

The patient with symptomatic extracranial carotid artery disease who, on angiography, is found to have a coexisting intracranial aneurysm presents a therapeutic dilemma. Relief of the carotid stenosis, with a potential increase in cerebral blood pressure, might increase the risk of aneurysm rupture. Conversely, repair of the aneurysm may be hazardous because of the low flow imposed by the carotid stenosis, particularly in the event of perioperative hypotension. We reviewed 19 patients treated with 20 carotid endarterectomies in the face of concurrent asymptomatic intracranial aneurysm. There were no instances of aneurysm rupture during the operation or the 30 days following operation. The literature reported to date consists of a total of 20 patients with only one incidence of aneurysm rupture in the postoperative period. We conclude that carotid endarterectomy is unlikely to precipitate rupture of an intracranial aneurysm during the operation or postoperative period.

Aged↗
PubMed2001

New developments in the use of tricyclic antidepressants for the management of pain.

In recent years, tricyclic antidepressant drugs have experienced a resurgence in their use as valuable pharmacological tools in the treatment of pain. Along with the evolution in our understanding of their analgesic mechanisms of action, there have been concurrent breakthroughs regarding their indications for use and modes of administration. This review focuses on recent advances in our understanding of how antidepressant drugs exert their antinociceptive effects, and new developments regarding their clinical application.

Journal Article↗
PubMed1996

Possible interaction between cyclosporine and glibenclamide in posttransplant diabetic patients.

The possible occurrence of a kinetic interaction between cyclosporine A and glibenclamide was assessed by reviewing data of six posttransplant diabetic patients who received the two drugs concurrently. Coadministration of the two drugs resulted in a 57% increase in the steady-state plasma cyclosporine levels despite normal hepatic and renal functions in the patients. This elevation in cyclosporine level is possibly due to an interaction between the two drugs resulting from an inhibition of CYP3A4-mediated metabolism of cyclosporine by glibenclamide. This observation calls for a closer monitoring of cyclosporine plasma levels during concomitant administration of these two drugs in this group of patients.

Adult↗
PubMedDate not supplied

Patients with chronic hepatitis C--who should not be treated?

The decision to treat a patient with chronic hepatitis C (CHC) is based on what is known about the risk factors for developing liver cirrhosis or hepatocellular carcinoma, as well as on conditions that contraindicate therapy or impair therapy effectiveness. Several factors, including age, treatment side effects, disease severity, concurrent diseases and life conditions, may render treatment decisions more difficult. This review focuses on identifying CHC patients who should not receive treatment.

Age Factors↗
PubMedDate not supplied

Do qualifiers of ASCUS distinguish between low- and high-risk patients?

OBJECTIVE: To evaluate the qualification of a Pap smear classified as atypical squamous cells of undetermined significance (ASCUS) favor reactive or neoplasia as recommended by the Bethesda System. STUDY DESIGN: The smears from 105 concurrent patients with a cytologic diagnosis of ASCUS not otherwise qualified were reviewed and subclassified as ASCUS favor reactive, low grade squamous intraepithelial lesion (LSIL) or high grade squamous intraepithelial lesion (HSIL) based on the Bethesda System criteria. The cervical biopsy diagnoses were correlated. RESULTS: Of the 105 cases classified as ASCUS, 37 were subclassified as favor reactive, 51 as favor LSIL and 17 as favor HSIL on cytologic review. In the ASCUS favor reactive group, 19 (51%) had reactive changes on biopsy, 17 (46%) had cervical intraepithelial neoplasia (CIN) 1, and 1 (2%) had CIN 3. A total of 48% patients had CIN. In the favor LSIL group, there was CIN 1 in 28 cases (55%), CIN 2 or 3 in 12 (23%) and benign changes in 11 (22%) on biopsy. Seventy-eight percent had CIN. In the 17 cases classified as ASCUS favor HSIL group, all had CIN. CONCLUSION: Of the total 105 cases of ASCUS, 71% had CIN, 29% had reactive changes on follow-up biopsies, and 48% of patients in the ASCUS favor reactive group had CIN. Qualifiers of ASCUS have questionable utility in patient management.

Adolescent↗
PubMed2000

Phase II studies of the glycine antagonist GV150526 in acute stroke : the North American experience. The North American Glycine Antagonist in Neuroprotection (GAIN) Investigators.

BACKGROUND AND PURPOSE: GV150526, a selective glycine site antagonist, reduces infarct volume in rats with focal cerebral ischemia. Safety and efficacy in humans with acute stroke are being investigated. We sought to further explore the safety, pharmacokinetics, and preliminary outcome of GV150526 treatment in patients with a clinical diagnosis of acute stroke. METHODS: Two trials were conducted in North America. The North American Glycine Antagonist in Neuroprotection trial (GAIN 1) (GLYA2001; United States only) was designed as a sequential dose escalation study. GAIN 2 (GLYA2005; United States and Canada) was designed to further assess the safety of the highest dose tolerated in GAIN 1. Both trials were randomized (2:1), double-blind, and placebo controlled. Treatment was started within 12 hours of symptom onset; patients with both ischemic stroke and primary intracerebral hemorrhage were included in both trials. RESULTS: The dose escalation study (GAIN 1) completed 3 dosing tiers. Enrollment was suspended before escalation to the fourth tier because of laboratory reports of transiently elevated bilirubin levels in a concurrent European study that employed the dose targeted for this tier. After review by an independent safety committee of the worldwide safety data, the second study (GAIN 2) commenced. One hundred nine patients were randomized and dosed with study drug, either an 800-mg loading dose followed by 200 mg every 12 hours for 3 days of GV150526 or placebo. The incidence of serious adverse events was similar in the drug and placebo groups. Mild irritation at the infusion site and symptoms suggestive of mild and reversible altered mentation were reported more frequently in the GV150526 group than in the placebo group. Hyperbilirubinemia was reported in 6% of GV150526-treated patients compared with 3% of placebo-treated patients. Outcome at 4 weeks after stroke was better in GV150526-treated patients, but the studies were not powered to show statistical significance, and the baseline neurological deficits in the GV150526-treated patients were less severe. CONCLUSIONS: These preliminary studies suggest that GV150526 is well tolerated by patients with suspected acute stroke. Further pivotal studies testing the efficacy and safety of GV150526 in acute stroke are ongoing.

Aged↗
PubMedDate not supplied

Rupture of the round window membrane.

A case of sudden deafness due to rupture of the round window membrane is presented. Nineteen similar cases have previously been reported in the literature. In a review of these twenty patients, it is noted that a history of concurrent physical effort or barotrauma was present in eighteen. This supports the view that the injury is produced by pressure changes acting either along the cochlear aqueduct (the explosive route) or, directly on the middle ear structures (the implosive route). At operation, the rupture may be difficult to see, and a separate leak from the oval window may be present. The timing of any surgical intervention is important. The authors recommend that this should be deferred for one week after the onset of symptoms, as the fistula may heal spontaneously. If no definite improvement has occurred at the end of this time, then tympanotomy should be undertaken during the next week.

Adult↗
PubMedDate not supplied

Peer victimization and psychosocial adjustment in children: current knowledge and future directions.

Childhood peer victimization is the experience of being a target of peers' aggressive behavior. Peer victimization is a common occurrence and has been concurrently and prospectively linked to significant psychological distress. This paper provides a review of the extant literature on the relationship between peer victimization and psychosocial adjustment in nonclinical and pediatric populations. Clinical applications of this literature, as well as directions for future study, are presented.

Aggression↗
PubMed1998

Epileptic seizures progressing into nonepileptic conversion seizures.

BACKGROUND: Epileptic and nonepileptic seizures can occur in the same patient, but usually occur at different times. In 1885, Gowers suggested that minor seizures can elaborate into hysterical seizures, but the concurrence of epileptic and nonepileptic seizures is not well documented. METHODS: We reviewed all patients with nonepileptic seizures documented with video-EEG recordings at our center to identify those with temporally associated epileptic seizures. RESULTS: Four patients were identified in whom video-EEG-documented epileptic seizures were temporally associated with nonepileptic seizures. In one woman, the nonepileptic event followed an absence seizure. Given the high frequency of absence seizures, the occurrence of the nonepileptic seizure may have been coincidental. In three patients, the seizures were partial and arose from right frontotemporal regions. In these patients, epileptic seizures were infrequent. CONCLUSIONS: Epileptic and nonepileptic seizures can be temporally related, and in patients with partial seizures, there may be a pathophysiologic relation in which ictal changes facilitate the development of conversion symptoms. Ictal activation or disinhibition of emotions or impulse control may contribute to these nonepileptic events.

Adult↗
PubMed1992

Glucuronidation of drugs. A re-evaluation of the pharmacological significance of the conjugates and modulating factors.

Glucuronides of drugs are considered to be generally inactive and rapidly eliminated. Therefore, these metabolites are often not taken into account in evaluating drug effects. The present review describes examples of both direct and indirect contributions of glucuronides to net drug effects. Multiple lines of evidence indicate that morphine-6-glucuronide has analgesic activity. This compound has a high affinity to the mu-receptor, is capable of penetrating the blood/brain barrier and is a potent analgesic after administration to patients. Indirect activity of glucuronides may consist of a systemic cycle in which an active parent compound is derived from the glucuronide by enzymatic action. Such systemic cycling has been demonstrated for clofibric acid. In addition, some acyl glucuronides are subject to intramolecular rearrangement and the resulting metabolites are resistant to beta-glucuronidase. Covalent protein binding of glucuronides by different mechanisms may contribute to drug toxicity and immune responses. If glucuronides are accepted as potential modifiers of net drug action it is important to determine what factors modulate disposition of these compounds. Therefore, the later section of this review describes glucuronidation under different pathophysiological conditions. Examples for alterations of the rate and/or extent of glucuronidation by concurrent diseases processes, age and coadministration of other drugs are provided.

Age Factors↗