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Biomedical subjects

K V Shepard

Publications and source records attributed to K V Shepard.

At least 19 recordsLinked to original sources
PubMed1997

Long-term efficacy and safety of dronabinol for acquired immunodeficiency syndrome-associated anorexia.

We studied the effects of long-term (12 months) dronabinol in 94 late-stage acquired immunodeficiency syndrome (AIDS) patients (mean CD4 count of 45/mm3) who previously participated in a 6-week study (placebo versus dronabinol). All patients received dronabinol orally-2.5 mg twice daily (90%) or 2.5 mg once daily (10%). Appetite was measured using a visual analogue scale for hunger (VASH). Dronabinol was associated with consistent improvement in mean appetite. Patients previously treated with dronabinol continued to show improvement in VASH (percent change from baseline of 6-week trial: 48.6-76.1% at each month), whereas those previously treated with placebo exhibited substantial improvement in mean appetite, particularly during the initial 4 months of treatment (48.5-69.9%). Thereafter, dronabinol was associated with a VASH change at least twice baseline. Patients tended toward stable body weight for at least 7 months. Adverse events were primarily related to known central nervous system effects of dronabinol. These data support long-term, safe use of dronabinol for anorexia associated with weight loss in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS.

The effects of dronabinol on appetite and weight were evaluated in 139 patients with AIDS-related anorexia and > or = 2.3 kg weight loss in a multi-institutional study. Patients were randomized to receive 2.5 mg dronabinol twice daily or placebo. Patients rated appetite, mood, and nausea by using a 100-mm visual analogue scale 3 days weekly. Efficacy was evaluable in 88 patients. Dronabinol was associated with increased appetite above baseline (38% vs 8% for placebo, P = 0.015), improvement in mood (10% vs -2%, P = 0.06), and decreased nausea (20% vs 7%; P = 0.05). Weight was stable in dronabinol patients, while placebo recipients had a mean loss of 0.4 kg (P = 0.14). Of the dronabinol patients, 22% gained > or = 2 kg, compared with 10.5% of placebo recipients (P = 0.11). Side effects were mostly mild to moderate in severity (euphoria, dizziness, thinking abnormalities); there was no difference in discontinued therapy between dronabinol (8.3%) and placebo (4.5%) recipients. Dronabinol was found to be safe and effective for anorexia associated with weight loss in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Placebo-blinded study of morphine sulfate sustained-release tablets and immediate-release morphine sulfate solution in outpatients with chronic pain due to advanced cancer.

PURPOSE: This study was conducted to compare the relative analgesic efficacy and safety of an every-4-hour immediate-release oral morphine (IRM) solution with that of an every-12-hour sustained-release oral morphine (SRM) formulation. PATIENTS AND METHODS: This was a double-blind, placebo-blinded, crossover study in 34 adult male and female outpatients with pain due to advanced cancer. Baseline data were collected on day 1. On days 2 and 3, randomly assigned patients received either placebo plus IRM (Roxanol; Roxane Laboratories, Inc, Columbus, OH; 20 mg/mL) at 2, 6, and 10 am, and 2, 6, and 10 pm, or alternatively SRM (Oramorph SR; Roxane Laboratories, Inc; 30 mg) at 10 AM and 10 PM. Patients were then crossed over to the alternate treatment for days 4 through 6. Pain relief was measured using a conventional 100-mm visual analog scale (VAS) and by recording the incidence of breakthrough pain. Information on side effects was obtained from VAS scores for sedation, nausea, anxiety, and depression; by directly questioning the patient as to mental confusion, bowel movements, and laxative use; and from Karnofsky performance status scores. VAS data were analyzed using a linear statistical model. Breakthrough pain data were analyzed using analysis of variance (ANOVA). RESULTS: There were no statistically significant differences between IRM and SRM treatments with respect to VAS pain scores, side effect scores, or incidence of breakthrough pain data. Karnofsky performance scores remained stable for all patients throughout the study. CONCLUSION: It was concluded that every-12-hour administration of SRM and every-4-hour administration of IRM provide similar analgesic effectiveness and side effect profiles in the treatment of chronic pain in cancer patients.

Chemistry, Pharmaceutical↗
PubMed1992

An evaluation of the effect of food on the oral bioavailability of sustained-release morphine sulfate tablets (ORAMORPH SR) after multiple doses.

The effect of food on the oral bioavailability of sustained-release morphine sulfate tablets (ORAMORPH SR; Roxane Laboratories, Inc., Columbus, OH; OSR) was examined in an open-label, randomized, two-period crossover study. Healthy male volunteers received a 30-mg OSR tablet orally every 12 hours for seven doses during both the fasted and fed states. Dosing periods were separated by a 14-day washout. Volunteers in the fasted group received all doses either 2 hours before or after meals. Volunteers in the fed group received all doses immediately after meals. All meals were standardized. Serial blood samples were collected for analysis of plasma morphine concentration by radioimmunoassay. Pharmacokinetic parameters were calculated using plasma concentration data collected after the last dose at 72 hours of each dosing period. The two one-sided t analysis indicated confidence intervals between 80% and 120% for maximum peak plasma concentration (Cmax), AUC72-84hr, Cavg, and Cmin. The relative bioavailability of OSR administered after meals was 90.2% of that administered in the fasted state. As compared with the fasted condition, morphine bioavailability was essentially unchanged when multiple oral doses of 30-mg OSR tablets were given after meals.

Administration, Oral↗
PubMed1992

A controlled study of sustained-release morphine sulfate tablets in chronic pain from advanced cancer.

The purpose of this double-blind crossover study was to determine whether a sustained-release morphine sulfate (SRMS) tablet given orally every 12 hours could adequately replace immediate-release morphine sulfate solution (IRMS) given orally every 4 hours in hospitalized patients with chronic pain from advanced cancer. Of 33 patients entered, 27 completed the study and were included in the efficacy and safety analysis. Patients were initially randomized to receive either 30-mg SRMS tablets every 12 hours or IRMS at the same mg/24 hours dose, every 4 hours. After 2 days, a crossover was performed, and patients received the alternate treatment for 3 days. Pain and side effects were assessed using a standard 100 mm visual analogue scale (VAS). There were no statistically significant differences between the two treatment groups for mean VAS pain scores or scores for sleepiness, nausea, depression, and anxiety. The incidence of breakthrough pain was similar for both treatment groups, as was the incidence of confusion and constipation. The results demonstrated that SRMS is a safe, effective analgesic preparation for patients who require oral opioids for cancer pain. The data also support the conclusion that sustained-release morphine tablets administered every 12 hours can replace an immediate-release morphine solution administered every 4 hours.

Chronic Disease↗
PubMed1991

Sensitive and specific radioimmunoassays for opiates using commercially available materials. I: Methods for the determinations of morphine and hydromorphone.

Sensitive and specific radioimmunoassay (RIA) methods for the analysis of morphine and hydromorphone in human plasma samples using commercially available materials were developed. The limit of quantitation was 0.3 ng/mL of plasma for morphine and 50 pg/mL of plasma for hydromorphone. An extraction step preceding the RIA quantitatively removed morphine, leaving 99% morphine-3-glucuronide (M3G) and 95% hydromorphone-3-glucuronide (H3G) in the aqueous phase. The specificity of the morphine RIA method for the analysis of clinical samples was confirmed by HPLC quantitation. The antiserum used in the hydromorphone RIA method cross reacted slightly with H3G at 0.66%. However, analysis of clinical samples using the direct versus the extraction RIA showed that the extraction step was necessary for the specific determination of hydromorphone in pharmacokinetic studies. After extraction, only 0.033% of the H3G present in plasma samples would be observed as interference for the free hydromorphone. The RIA methods were shown to be accurate and reproducible with almost 100% recovery of morphine and hydromorphone. They offer convenient alternatives to chromatographic methods for pharmacokinetic studies.

Antibody Specificity↗
PubMed1991

Recent clinical experience with dronabinol.

Dronabinol, delta-9-tetrahydrocannabinol in sesame oil, has been used for several years as an antiemetic for patients receiving cancer chemotherapy. In combination studies with prochlorperazine, enhancement of efficacy, as measured by duration of episodes of nausea and vomiting and by severity of nausea, has been found. The incidence of psychotropic effects from dronabinol appears to be decreased by concomitant administration of prochlorperazine. In open pilot studies, dronabinol caused weight gain in seven of ten patients with symptomatic HIV infection. In both HIV and cancer patients, dronabinol improved appetite at a dose which was well tolerated for chronic administration.

Antineoplastic Agents↗
PubMed1991

Thrombotic thrombocytopenic purpura treated with plasma exchange or exchange transfusions.

Of 40 patients with thrombotic thrombocytopenic purpura, 17 were treated with plasma exchange, 15 with exchange transfusions, and 6 with both types of therapy. One patient died before being treated and another patient was seen but not treated. Plasma exchange was performed daily for a mean of seven exchanges per patient. The replacement fluid during plasma exchange was fresh frozen plasma in all cases. The complete response rates for each type of treatment were as follows: 88% for plasma exchange (15 patients), 47% for exchange transfusions (7 patients), and 67% for exchange transfusions and plasma exchange (4 patients). Clinical and laboratory factors were examined for any statistically significant association with therapy response. Treatment with plasma exchange was statistically the initial factor most strongly associated with prognosis. Paresis, paresthesias, seizures, mental status change, and coma showed no association with response to treatment. Some of the laboratory factors that did not show significant association with treatment response were the initial creatinine, hemoglobin, platelet count, lactate dehydrogenase, and total bilirubin. This study supports the hypothesis that plasma exchange has significantly improved the prognosis of patients with thrombotic thrombocytopenic purpura. These patients should be treated aggressively regardless of the severity of their symptoms.

Exchange Transfusion, Whole Blood↗
PubMed1989

Metastases to pineal gland.

Metastases to the pineal gland is an uncommon event. Bronchogenic carcinomas are the most frequent source of the primary lesion. A case of small cell carcinoma of the lung with solitary metastases to the pineal gland is reported; the literature is reviewed.

Brain Neoplasms↗
PubMed1988

Peripheral small cell undifferentiated carcinoma of the lung. Clinicopathologic features of 17 cases.

Seventeen cases of resectable peripheral small cell undifferentiated carcinoma of the lung were studied (average size, 2.1 cm; range, 0.9-3.5 cm). The carcinomas exhibited predominantly mixed intermediate and fusiform/spindle subtypes; in seven carcinomas there were at least some foci of oat cell subtype. There was no histologic evidence of typical carcinoid tumor. Seven cases were fixed in solutions appropriate for immunohistologic study; these exhibited prominent neuron-specific enolase activity but less prominent and more variable staining for the carcinoembryonic antigen and cytokeratins. All 17 cases were deemed resectable and had no clinical or radiologic evidence of metastasis. Seven (41%) patients died with recurrent and/or metastatic carcinoma (average survival, 1.7 years); five of these patients had carcinomas with at least some foci of oat cell foci subtype.

Adult↗
PubMed1988

Acute leukemia occurring after radiotherapy and chemotherapy with a nitrosourea, PCNU.

Secondary acute leukemias can occur in patients who have been treated with chemotherapy. Several reports have shown that treatment with nitrosoureas can result in secondary leukemia, but this is the first report implicating the investigational drug PCNU as a cause. This case is unique because of the cytogenetic findings, the short latency period between the chemotherapy and the diagnosis of leukemia, and the successful treatment of the leukemia with high-dose cytarabine (ara-C).

Adenocarcinoma↗
PubMed1987

Hepatitis in patients receiving intraarterial chemotherapy for metastatic colorectal carcinoma.

Fifty-one patients with metastatic colorectal carcinoma confined to the liver received intraarterial chemotherapy through the hepatic artery via a subcutaneous pump. The chemotherapy consisted of sequential 14-day infusions of floxuridine (FUDR) and dichloromethotrexate (DCMTX) or a 14-day infusion of FUDR and bolus mitomycin (MMC). Twenty-four patients (47%) developed hepatitis with an elevation of hepatic serum transaminase (serum glutamic oxaloacetic transaminase, SGOT, or serum glutamic-pyruvic transaminase, SGPT). The median time to develop hepatitis was 11 weeks after initiation of chemotherapy. The morphologic effects of chemotherapy were evaluated in eight patients with hepatitis. All the patients with hepatitis had normalization of the serum transaminases after temporary cessation of chemotherapy. There was a trend toward a greater chance of remission in patients who developed hepatitis. Sixty-seven percent of the patients with a therapeutic response had hepatitis, whereas only 33% of the patients without a response had hepatitis. However, this difference was not statistically significant. The occurrence of hepatitis was not related to FUDR dose, drug program (FUDR-DCMTX vs. FUDR-MMC), pump flow rate, hepatic arterial anatomy, sex, or age of the patients.

Bilirubin↗
PubMed1986

Liver pathology following hepatic arterial infusion chemotherapy. Hepatic toxicity with FUDR.

The authors reviewed the liver histopathology and the clinical features of eight patients with liver metastases from colorectal cancer who were treated by hepatic arterial infusion chemotherapy (HAIC) via an implantable pump (Infusaid). Before HAIC, these patients had no evidence of hepatitis, and results of liver biopsies performed on three patients showed only minor morphologic alterations. All the liver tumors responded to HAIC, but all patients developed hepatitis. Clinical findings included nausea, vomiting, abdominal pain and jaundice. Serum transaminases, alkaline phosphatase and bilirubin levels were increased. Clinical observations suggested that 5-fluoro-2'-deoxyuridine (FUDR), the predominant drug given, was the hepatotoxic agent. Toxic effects were hepatocyte necrosis, steatosis, cholestasis, central vein sclerosis, and alterations in the portal triad. In addition, central vein lesions like those in veno-occlusive disease, and micronodular cirrhosis resembling that induced by alcohol, were encountered. Although individual susceptibility to FUDR appeared to vary, portal triad fibrosis was present in all eight cases and, together with central vein sclerosis and cirrhosis, appeared to be related to the dose and duration of HAIC.

Adult↗
PubMed1986

Bilateral solid renal masses in a young man.

Bilateral solid renal masses presenting in a young patient in the absence of systemic manifestations or genetic abnormalities, such as Von Hippel-Lindau's disease, are difficult diagnostic challenges. Primary renal lymphomas are exceedingly rare. More commonly, renal involvements are caused by lymphoma in the retroperitoneal area. It is important for a urologist to be aware of this diagnostic possibility, since unnecessary removal of a kidney and extensive surgery may be avoided, and because appropriate staging can be performed at exploration.

Adult↗