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Biomedical subjects

M Lefkowitz

Publications and source records attributed to M Lefkowitz.

At least 19 recordsLinked to original sources

A randomized, double-blind, placebo-controlled trial of tegaserod in female patients suffering from irritable bowel syndrome with constipation.

BACKGROUND: Irritable bowel syndrome is a common functional gastrointestinal disorder which affects up to 20% of the population, with a predominance in females. AIM: To evaluate the efficacy and safety of tegaserod in female patients with irritable bowel syndrome characterized by symptoms of abdominal pain/discomfort and constipation. METHODS: In a randomized, double-blind, multicentre study, 1519 women received either tegaserod, 6 mg b.d. (n = 767), or placebo (n = 752) for 12 weeks, preceded by a 4-week baseline period without treatment and followed by a 4-week open withdrawal period. The primary efficacy evaluation was the patient's symptomatic response as measured by the Subject's Global Assessment of Relief. Other efficacy variables included abdominal pain/discomfort, bowel habits and bloating. RESULTS: Tegaserod produced significant (P < 0.05) improvements in the Subject's Global Assessment of Relief and other efficacy variables. These improvements were seen within the first week, and were maintained throughout the treatment period. After withdrawal of treatment, the symptoms rapidly returned. Overall, tegaserod was well tolerated. Diarrhoea was the most frequent adverse event; however, this led to discontinuation in only 1.6% of tegaserod-treated patients. CONCLUSIONS: Tegaserod, 6 mg b.d., produced rapid and sustained improvement of symptoms in female irritable bowel syndrome patients and was well tolerated.

Adult↗

Transdermal fentanyl for chronic pain in AIDS: a pilot study.

This prospective, open-label, before-after trial was designed to compare the efficacy of oral opioids with that of transdermal fentanyl in severe AIDS-related chronic pain, as well as assess barriers, patient satisfaction, and side effects. Thirty-five sequentially selected male and female outpatients with AIDS who were at least 18 years old were enrolled. All had chronic pain requiring continuous treatment with > or = 45 mg/day oral morphine or an equivalent. Eighteen of the patients had a history of chemical dependency. Baseline data were collected while patients received their previously prescribed opioid; assessments were made again after a stable transdermal fentanyl dose (25--300 microg/h) had been maintained for 15 days. Patients completed the International Association for the Study of Pain Classification of Chronic Pain Syndromes questionnaire, the Brief Pain Inventory, and a Satisfaction With Pain Medication questionnaire for assessing pain intensity, relief, and interference with normal functioning. With transdermal fentanyl, pain severity scores decreased significantly, mean pain relief scores increased, and daily functioning measures improved significantly. Most adverse events were mild and unrelated to fentanyl use. Transdermal fentanyl was effective for chronic pain in both chemically dependent and non-chemically dependent patients with AIDS.

Acquired Immunodeficiency Syndrome↗

An alternative algorithm for dosing transdermal fentanyl for cancer-related pain.

Many cancer patients are undermedicated and inappropriately managed for pain, leading to a diminished quality of life. Patients with moderate to severe pain often require opioid analgesics. Recently published guidelines emphasize individualization of opioid treatment to provide the drug and route of administration that meet the needs of the particular patient. Intolerable side effects, ineffective pain relief, or a change in the patient's clinical status can dictate the need for a new pain management regimen. Physicians must be able to readily quantify relative analgesic potency when converting from one opioid to another or from one route of administration to another. Transdermal fentanyl (Duragesic) is an opioid agonist that has been shown to be safe and effective for the treatment of cancer pain. However, clinicians should realize that the manufacturer's recommendations for equianalgesic dosing of transdermal fentanyl may result in initial doses that are too low in some patients, and in a titration period that is too long. Under these circumstances, the patient is likely to experience unrelieved pain. An alternative dosing algorithm that considers both a review of the literature and our combined clinical experience with transdermal fentanyl should help clinicians individualize the treatment of pain.

Administration, Cutaneous↗

Embolization of neurosurgical lesions involving the ophthalmic artery.

OBJECTIVE: A number of anteriorly located cranial base and extracranial lesions receive their vascular supply wholly or in part from the ophthalmic artery, and embolization of the ophthalmic artery can be helpful in the management of these lesions, either as the primary treatment or as an adjunct to surgery. We present situations in which the embolization of lesions involving the ophthalmic artery was performed to effect a partial or total cure of the lesion. METHODS: Twelve patients underwent a total of 15 embolization attempts on lesions involving the ophthalmic artery. Four patients had arteriovenous malformations of the orbit, four had dural arteriovenous fistulae, two had orbital meningiomas, one had a planum sphenoidale meningioma, and one had a juvenile nasal angiofibroma. In each case, a Tracker No. 18 microcatheter (Target Therapeutics, Inc., Fremont, CA) was navigated into the ophthalmic artery using a steerable guidewire and digital road mapping. Embolic agents included polyvinyl alcohol particles ranging from 350 to 1500 microm in diameter, 2-mm platinum microcoils, and n-butyl-cyanoacrylate. In 12 of 15 cases, lidocaine and amytal provocation tests were conducted before any attempt at embolization to assess the role of the ophthalmic artery in vision. RESULTS: Embolization was successfully performed in the 14 situations in which it was attempted. Positive results of two lidocaine/amytal tests were noted. In one case, embolization was not attempted. In the other case, a larger caliber embolic agent (2-mm platinum coils) was used. A single transient decrease in visual acuity lasting 4 days was the only embolization-related complication. CONCLUSION: Proper case selection, judicious use of embolic agents, and use of provocative testing can result in safe embolization of lesions supplied by the ophthalmic artery.

Adolescent↗

Pain management guidelines: implications for managed care--a roundtable discussion.

One of the most important concerns of patients with cancer, particularly those with metastatic disease, is "Will I be in constant pain?" This is a similar concern voiced by patients with late-stage human immunodeficiency virus infection. The management of chronic pain has enormous implications on a patient's ability to function and on his or her quality of life. In June 1996, Medical Interface convened a panel of experts in Chicago to discuss pain management therapies, guidelines, and how these issues will affect, and be affected by, the managed care environment.

Acquired Immunodeficiency Syndrome↗

Aggressive angiomyxoma: a clinicopathologic study of 29 female patients.

BACKGROUND: Aggressive angiomyxoma is an uncommon mesenchymal tumor that preferentially involves the pelvic and perineal regions of females. Since its initial description in 1983, approximately 65 cases have been reported in the English literature. METHODS: The clinical and pathologic features of 29 cases of aggressive angiomyxoma were evaluated in a review of archival material from the Armed Forces Institute of Pathology (1960-1992). Histochemical stains for mucosubstances and immunohistochemistry (avidin-biotin complex method) were utilized to characterize the neoplasms further. RESULTS: All patients were females, between 16 and 70 years (median; 34 years). The soft tissues of the pelvis, perineum, vulva, buttock, retroperitoneum, and inguinal regions were involved. The majority of the tumors were > or = 10 centimeters in greatest dimension. Follow-up ranging from 8 to 198 months (mean, 93 months; median, 95 months) was available for 22 patients. Eight patients developed recurrent tumor, from 10 months to 7 years after the initial resection. No patient developed metastases and there were no tumor related deaths. Histologically, the neoplasms were sparsely to moderately cellular and predominantly composed of bland, relatively nondescript. stellate and spindled cells embedded in a loosely collagenized matrix with scattered vessels of varied caliber. A few cases contained some tumor cells with more abundant eosinophilic cytoplasm that raised the possibility of focal smooth muscle differentiation. The tumor matrix was no more than weakly reactive for mucosubstances; thus, while glycosaminoglycans are present to a limited extent, edema fluid appears to be a major component of the noncollagenous stroma. The neoplastic cells were at least focally immunoreactive for desmin (22/22), smooth muscle actin (19/20), muscle specific actin (16/19), vimentin (17/17), CD34/QBEND-10 (8/16), and estrogen (13/14) and progesterone (9/10) receptor. All of the examined tumors were negative for S100 protein (20/20). Ki67 (MIB1) immunoreactivity was present in <1% of the tumor nuclei in all 16 cases tested. CONCLUSIONS: Aggressive angiomyxoma is a distinctive, locally aggressive, mesenchymal tumor that appears to be relatively site specific and has a peak incidence in females in the fourth decade of life. There is a strong propensity for local recurrence but metastatic disease has not been reported. Since the first evidence of recurrence may be many years after the initial resection, long term follow-up is required. The neoplastic cells of aggressive angiomyxoma exhibit fibroblastic and myofibroblastic features and appear to be hormonally influenced. The possibility that the progenitor cell has a capacity for smooth muscle differentiation is raised.

Adolescent↗

Atypical apocrine adenosis of the breast: a clinicopathologic study of 37 patients with 8.7-year follow-up.

BACKGROUND: Apocrine metaplasia is occasionally superimposed on sclerosing adenosis (apocrine adenosis) in breast biopsies, and cytologic atypia is sometimes present (atypical apocrine adenosis). The long term risk of patients developing breast carcinoma subsequent to the diagnosis of this lesion is unknown. METHODS: Atypical apocrine adenosis was defined as apocrine adenosis with enlarged nucleoli and a greater than threefold variation in nuclear area. Lesions with recognizable cytoarchitectural patterns of intraductal carcinoma were excluded. Surveillance, Epidemiology and End Results (SEER) data were used as the reference population for calculations of relative risk. RESULTS: Thirty-seven women with atypical apocrine adenosis had a mean follow-up of 8.7 years. Four patients developed invasive ductal carcinoma of the breast (3 ipsilateral, 1 contralateral) after a mean of 5.6 years. The relative risk of developing carcinoma was 5.5 (95% confidence interval [CI], 1.9-16). All patients who developed carcinoma were older than age 60 at the time of breast biopsy showing atypical apocrine adenosis, and carcinoma developed at a mean age of 70 years. In the older than 60 years age group (11 patients), the relative risk of developing carcinoma was 14 (95% CI, 4.1-48). CONCLUSIONS: Atypical apocrine adenosis confers an increased risk of developing breast carcinoma in women older than age 60, and the risk in younger women is probably low. Some cases of atypical apocrine adenosis may represent in situ apocrine carcinomas that are difficult to diagnose because of the absence of the usual architectural features of intraductal carcinoma.

Adult↗

Primary diffuse large B-cell lymphoma of the breast. A clinicopathologic study of 31 cases.

Primary non-Hodgkin's lymphoma of the breast is a rare neoplasm for which survival data vary among the reported studies. Thirty-one cases of diffuse large B-cell lymphoma of the breast, which had been seen in consultation from 1973 to 1985 at our institution, were reviewed. This represents the largest number of lymphomas of this histologic subtype reported to date in the English literature. Histologic examination and immunophenotypic analysis were performed and the results were correlated with clinicopathologic data. The patient population consisted of 29 females and 2 males with a mean patient age of 58.2 years. At the time of diagnosis, 26 patients had unilateral involvement (16 left, 10 right), and 5 had bilateral disease. Mean tumor size was 3.8 cm. Histologically, all cases showed a diffuse large B-cell lymphoma as classified by the Revised European-American Classification of Lymphoid Neoplasms (R.E.A.L Classification). Immunophenotypic studies on paraffin sections confirmed a B-cell lineage in every case. The majority of patients received chemotherapy and/or radiation therapy. The median survival was 36 months, confirming that this neoplasm has a poor prognosis.

Adult↗

Pain management for the AIDS patient.

The relief of pain in persons with HIV disease, while similar to other patient populations such as cancer patients, has some unique aspects. Pain must be a focus, and a priority, of care in persons with HIV disease along with treatment of the underlying HIV infection and the complications of immune compromise. Pain in patients with AIDS is very prevalent and often undertreated. Pain contributes to psychological and functional morbidity in AIDS. At the present time, the guidelines developed for treatment of cancer pain are used in patients with HIV disease, with the recognition that neuropathic pain should be treated differently from nociceptive pain. A multidisciplinary approach to pain management is optimal; however, consultations with pain specialists are adequate for management of pain in most patients, including those with HIV disease. Approaches to management of pain in patients with HIV disease are: Localize and characterize pain Work up possible etiologies Rule out infections and malignancies Be aware of multiple etiologies Explore the psychological/emotional contribution to pain Perform a thorough history and physical examination including medication history, history of substance use/abuse, and neurological and psychological assessments Treat the medical and psychological causes of pain Use appropriate pain medications in adequate doses Consult specialists in pain management, when necessary.

Acquired Immunodeficiency Syndrome↗

The effects of nonsteroidal anti-inflammatory drugs on blood pressures of patients with hypertension controlled by verapamil.

BACKGROUND: Nonsteroidal anti-inflammatory drugs may attenuate the antihypertensive effects of diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, central alpha-agonists, and other vasodilators. Their effects on the antihypertensive efficacy of calcium channel blockers are inadequately studied in small numbers of patients but appear to be minimal. METHODS: A three-phase, randomized, double-blind, placebo-controlled multicenter study included 162 patients aged 18 to 75 years with essential hypertension. After diastolic blood pressure was controlled to 90 mm Hg or less with once-daily verapamil hydrochloride, patients received ibuprofen, naproxen, or placebo matching capsules for 3 weeks, and blood pressure, heart rate, weight, and adverse effects were evaluated. A general linear model with 95% confidence intervals was used to compare each nonsteroidal anti-inflammatory drug treatment group with the placebo group. RESULTS: No significant differences in sitting, standing, or supine blood pressure were noted with naproxen or ibuprofen compared with placebo. The percentages of patients in each treatment group with increases of 10 mm Hg or more in either systolic or diastolic blood pressure were similar. Statistically significant increases in weight were seen with both nonsteroidal anti-inflammatory drug therapies. Changes in pulse rate were not significant. The incidence of adverse effects was similar across all three treatment groups. CONCLUSIONS: The addition of naproxen or ibuprofen to the treatment of hypertensive patients in whom blood pressure is controlled by once-daily verapamil does not cause an increase in blood pressure. Verapamil may therefore offer considerable advantages in maintaining control of blood pressure in patients who regularly receive nonsteroidal anti-inflammatory drug therapy.

Adolescent↗

Additive effects of verapamil and enalapril in the treatment of mild to moderate hypertension.

A factorial design was applied in this multicenter, double-blind, placebo-controlled trial of the calcium-channel blocker verapamil and the ACE inhibitor enalapril to assess the hypotensive effects of the combination compared with monotherapy, to evaluate safety, and to determine the effects on quality of life (QOL) of both drugs, alone and in combination. The study consisted of a 3 x 2 factorial design wherein 186 men and women with a sitting diastolic blood pressure (BP) of between 95 mm Hg and 114 mm Hg, after a 4-week placebo washout, were randomized to one of six treatment groups for 4 weeks of active treatment. Monotherapy with both 240 mg verapamil and 10 mg enalapril reduced systolic and diastolic BP to a similar extent and significantly more than placebo. The 240 mg verapamil + 10 mg enalapril combination was additive for both systolic and diastolic blood pressure; 120 mg verapamil + 10 mg enalapril was additive for systolic BP only. The total number of adverse events reported was similar for all six treatment groups. QOL scores were unchanged from baseline and not different between treatment groups. The combination of 240 mg verapamil and 10 mg enalapril was significantly more effective at reducing BP than either drug alone; this additivity of effect was not linked to a higher rate of adverse experiences or to a deterioration in QOL. Thus, combination therapy at lower doses may offer an alternative treatment option to higher dose monotherapy.

Adult↗

A pilot, open-labelled, phase II study using oral ribavirin in the treatment of patients with chronic active hepatitis B.

BACKGROUND: Ribavirin is a synthetic purine nucleoside with demonstrated antiviral activity against several DNA and RNA viruses. OBJECTIVES: An open-labelled pilot study to evaluate the safety and effect of ribavirin in the treatment of patients with chronic active hepatitis B (CAH-B). STUDY DESIGN: 24 CAH-B patients were treated with oral ribavirin 1200 mg daily in 3 divided doses for 4 weeks. Biochemical and virological parameters were monitored at regular interval during and after treatment. RESULTS: The serum hepatitis B e antigen (HBeAg) and HBV DNA measured by dot-blot hybridization were positive in all patients before treatment. At the end of 4 weeks of therapy, the HBV DNA levels decreased in 15 (63%) patients and became undetectable in 1 (4%) of these individuals. The mean HBV DNA decreased from 288+/-78 pg/ml at baseline to 219+/-79 pg/ml at the end of the 4 weeks of treatment (p = 0.046). Eight weeks after cessation of treatment, HBV DNA was undetectable in 10 (42%) patients, and the mean HBV DNA was 46+/-23 pg/ml (p < 0.01 when compared to mean baseline value). Seven (29%) patients seroconverted from HBeAg positive to anti-HBe positive but no patients lost hepatitis B surface antigen (HBsAg) during the 8 weeks of follow-up. At the end of 4 weeks of ribavirin treatment, serum levels of alanine aminotransferase (ALT) decreased in all but 1 patient; only 1 patient normalized serum ALT at this time. The mean serum ALT decreased significantly from 416+/-72 IU/l at baseline to 179+/-35 IU/l at the end of 4 weeks of treatment (p = 0.001). Eight weeks after cessation of therapy, the mean serum ALT value was 151+/-32 IU/l (p < 0.001 when compared to mean baseline value) and 5 (21%) patients normalized serum ALT at this time. During ribavirin treatment, the main side effect was a decrease in the hemoglobin level which returned to the pretreatment level in each instance within 2 months after discontinuance of therapy. CONCLUSIONS: Results of this pilot study indicated that oral ribavirin was well tolerated in CAH-B patients and resulted in lowering of serum ALT and HBV DNA values. A randomized controlled trial is needed to fully evaluate the beneficial effects of ribavirin in CAH-B patients.

Journal Article↗

Adenosarcoma of the uterine cervix: a clinicopathological study of 12 cases.

The clinical and pathologic features of 12 cervical adenosarcomas from the files of the Armed Forces Institute of Pathology are described. The patients ranged in age from 13 to 67 years (mean 37). The majority (58%) presented with abnormal bleeding. All tumors were located in the cervix and consisted of soft, tan, polypoid or papillary masses ranging in size from 1.5 to 4.5 cm. Microscopically, they showed a biphasic pattern with mesenchymal and epithelial components. There was a characteristic stromal condensation below the epithelial surface and around glandular structures. The cytologic atypia of stromal cells was 1+ in three, 2+ in five, and 3+ in four. The mitotic activity ranged from four to 28 (mean 7.0) mitotic figures per 10 high-power fields. One neoplasm contained cartilage and one striated muscle. Myometrial invasion was present in three. Treatment consisted of hysterectomy in nine patients and excisional biopsy in three. Two patients received radiotherapy; one before surgery and the other after hysterectomy. Two were treated with chemotherapy. Follow-up ranged from 9 months to 18.8 years. Nine patients were alive and well with no evidence of recurrent tumor at postoperative intervals of 0.8-18.8 years. One patient died 1 year after diagnosis with intraabdominal metastasis. One developed a recurrent tumor. This study demonstrates a favorable prognosis for patients with cervical adenosarcoma. Similar to patients with uterine adenosarcoma, prognosis is mostly affected by the presence of deep myometrial invasion.

Adenosarcoma↗

Intraductal (intracystic) papillary carcinoma of the breast and its variants: a clinicopathological study of 77 cases.

The clinical and pathological features of 77 cases of intraductal (intracystic) papillary carcinoma (IPC) of the breast are reported. It should be recognized as an intraductal carcinoma variant and distinguished from invasive papillary carcinoma. Intraductal papillary carcinoma remains a difficult diagnosis as there are four different epithelial growth patterns any of which may predominate. Low grade nuclear features occur in one third of cases, a so-called "stratified spindled cell" epithelial proliferation with bland morphology occurs in one quarter of cases, and a dimorphic population of malignant cells, which may in part be confused with myoepithelial cells, occurs in one quarter of cases. The 77 cases studied were from the 10-year interval 1970 to 1979. The effect on prognosis of cytoarchitectural features, duct wall and stromal invasion, and associated intraductal carcinoma were evaluated. The contribution of immunohistochemistry to the diagnosis using antibodies to smooth muscle actin, S-100 protein, and CAM 5.2 was examined. The 10-year survival rate was 100%, and the 10-year disease-free survival rate was 91%. Mastectomy had been performed in 72% of patients. Three of the patients developed metastases; two were alive with tumor and one died of other causes. Six patients had local recurrence in the chest wall; one was alive without disease, two were alive with tumor, and three died of other causes. An associated intraductal carcinoma of usual nonnecrotic or comedo type was present in 40% of all cases. When IPC recurred or metastasized, it did so as invasive papillary carcinoma in six of seven cases. Stromal invasion was found in 13 patients. Local recurrence developed in two of these. Invasion was not seen in any of the three patients who developed metastases. However, this may be a function of sampling as there was an average of 5.2 tumor sections per case. Patients with low grade tumors had no recurrence or metastasis, and in the absence of invasion may be treated by local excision. Patients with higher grade tumors have an increased risk of recurrence and metastasis.

Adult↗

Pain in hospitalized patients with AIDS: analgesic and psychotropic medications.

OBJECTIVE: We undertook this study to evaluate the use of analgesic and psychotropic medication in acquired immunodeficiency syndrome (AIDS) patients with pain and to determine whether our previous findings of a high prevalence of pain in patients with AIDS who were hospitalized could be replicated. Additional factors related to pain were evaluated, such as death during hospital stay, i.v. drug abuse, and length of hospital stay. DESIGN: One hundred thirty-nine medical charts randomly selected from 1 year of hospital admissions of patients with AIDS were reviewed in a systematic manner for pain, prescription of analgesic and psychotropic medication, patient demographics, and disease characteristics. RESULTS: Sixty-one percent of the charts reviewed had at least one note of nonprocedural pain. Sixty-eight percent of pain patients were prescribed a nonnarcotic (most commonly acetaminophen), and 44% a narcotic. Sixty-two percent of pain patients were prescribed a psychotropic medication. Patients with pain were significantly more likely to receive an analgesic as well as psychotropic medication, particularly a sedative-hypnotic, than patients without pain. Having pain was not significantly related to other factors such as i.v. drug abuse except for length of hospital stay. Most of the previous study findings were replicated with the notable exception of the rate of prescription of psychotropics as well as acetaminophen, which increased substantially in this study. CONCLUSIONS: Although pain is a prevalent problem in hospitalized AIDS patients, narcotics as well as antidepressants appear to be underutilized. It is suggested that medical education regarding pain management in AIDS patients is an important first step in a more aggressive approach.

Acquired Immunodeficiency Syndrome↗

Management of postherpetic neuralgia.

Postherpetic neuralgia is a perplexing disorder in which pain develops as a result of herpes zoster. It is a common cause of neuropathic pain and may render its effects especially on the elderly and immunocompromised. Once established, postherpetic neuralgia is resistant to most treatment modalities and can lead to much despair. Many therapeutic approaches have been attempted through the years, most with varying results. This review describes clinical manifestations including allodynia, hyperaesthesia and anaesthesia. It also reviews pharmacologic and non-pharmacologic treatment modalities including a review of anaesthetic nerve blocks, neurostimulation, acupuncture and surgical techniques.

Acupuncture Analgesia↗

Epithelioid stromal cells in lymphocytic mastitis--a source of confusion with invasive carcinoma.

Fourteen examples of lymphocytic mastitis (LM) with epithelioid stromal cells characterized by formation of a palpable, hard breast mass composed of a predominantly lobulocentric lymphocytic infiltrate, stromal fibrosis, and an unusual stromal infiltrate of epithelioid cells are presented. The epithelioid cells were so prominent and abundant that the possibility of an infiltrating carcinoma was raised in three cases, and a fourth case was misinterpreted as a granular cell tumor. Interestingly, eight of the 12 women and the only male patient had long standing, insulin dependent diabetes mellitus (IDDM), whereas two had IDDM and hypothyroidism, one had hypothyroidism alone, and one had systemic lupus erythematosus. Contrary to the conclusions in a recent report, our findings indicate that these mammary changes are not exclusive to patients with IDDM, and may also occur in nondiabetic patients particularly those with autoimmune disorders. The morphologic features of the epithelioid stromal cells which have been mistaken for infiltrating carcinoma are emphasized; immunohistochemical and ultrastructural findings favoring their myofibroblastic nature are presented.

Actins↗