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Biomedical subjects

M R Thomas

Publications and source records attributed to M R Thomas.

At least 109 records · Page 6Linked to original sources

Incorporation of deuterium-labeled fatty acids into human milk, plasma, and lipoprotein phospholipids and cholesteryl esters.

Fatty acid metabolism and the contribution of dietary fatty acids to milk cholesteryl ester (CE) and phospholipid (PL) were investigated in normal lactating mothers. The approach used was to feed mixtures of triglycerides containing deuterium-labeled palmitic acid (16:0-2H2), oleic acid (18:1-2H6), and linoleic acid (18:2-2H4). Milk and plasma samples were collected for 72 hr. Triglyceride (TG), CE, and PL fractions from milk, plasma, and lipoprotein were isolated and analyzed by gas-liquid chromatography and mass spectrometry. Data for the milk CE and PL fractions showed a definite selectivity for incorporation of 16:0-2H2 and 18:1-2H6 relative to 18:2-2H4. Based on the ratios of the deuterated fatty acids incorporated into the milk CE and PL samples, their incorporation times and isotopic enrichment data, it appears that these fatty acids are supplied mainly by the TG derived from chylomicrons and very low density lipoproteins. Plasma and lipoprotein CE data showed a progressive increase in 18:2-2H4 content, with 16:0-2H2 and 18:1-2H4 remaining relatively constant over the collection period. Plasma and lipoprotein PL data showed a higher rate for incorporation of 18:2-2H4 than 16:0-2H2 and 18:1-2H6 over the course of the sampling period. Comparison to previous data from adult males indicates lactation does not have a major effect on the general metabolism of these fatty acids. An increase with time in the isotopic enrichment of 18:2-2H4 in the plasma and lipoprotein CE and PL samples was observed which is consistent with in vitro selectivities reported for lecithin:cholesterol acyltransferase and phosphatidylcholine acyltransferase.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholesterol Esters↗

Role of recombinant interferon alpha 2 and cimetidine in patients with advanced malignant melanoma.

Following recent reports suggesting that the addition of cimetidine to interferon may enhance response rates in patients with metastatic malignant melanoma, we have completed a Phase II study of the use of recombinant alpha 2 interferon and cimetidine in patients with advanced malignant melanoma and who had progressive disease following interferon therapy alone. We observed two partial responses, no complete responses, and two patients had stable disease. Toxicity encountered was analogous to that of interferon alone. We conclude that the additional of cimetidine to alpha interferon is not beneficial in the treatment of advanced metastatic malignant melanoma.

Antineoplastic Combined Chemotherapy Protocols↗

Infused and ingested labeled lysines: appearance in human-milk proteins.

Incorporation of two labeled forms of lysine into human-milk proteins was studied in fasted lactating subjects to determine whether highly labeled proteins could be produced for subsequent nutritional studies and whether the kinetics of milk synthesis could be studied in humans with stable isotope techniques. Five subjects, maintained on formula diets, received L-[13C1]lysine (27 mumol/kg) as an IV bolus and L-[15N2]lysine (27 mumol/kg) as an oral bolus 4 h postprandially. Milk samples were collected at 30, 45, 90, 150, 240, and 360 min. Tracer lysine levels in the hydrolysate of unfractionated milk protein were determined by gas chromatography-mass spectrometry isotope ratiometry. After a delay of at least 45 min, significant labeling of milk protein was detected and reached a maximum at 150 min with cumulative percent does recovery over 6 h of 0.5%. Human-milk proteins can be labeled for nutritional investigations and in vivo kinetics of milk protein synthesis can be studied with stable isotope techniques.

Administration, Oral↗

Psychiatric diagnoses in patients with psychogenic dizziness or severe tinnitus.

Psychiatric assessments were made of patients with psychogenic dizziness (N = 17) and severe tinnitus (N = 24) using the Structured Clinical Interview for DSM-III-R (SCID). The psychogenic dizziness group had a high prevalence of psychiatric disorders (100%), the majority being anxiety disorders (94%), particularly diagnoses in the panic-agoraphobic cluster (76%). The severe tinnitus group had a lower prevalence of psychiatric disorders (63%) with a predominance of mood disorders (46%). Those tinnitus patients with no hearing loss tended to have more diagnoses per patient and more anxiety disorders than those with hearing loss. Although this was not a random sampling of these patients populations, the results are of sufficient magnitude to warrant further studies. The implications of the results are discussed in terms of treatment and future research.

Adult↗

Malignant melanoma--profile of an epidemic.

Cutaneous malignant melanoma is occurring in epidemic proportions in the United States. To provide a profile of persons at risk and the epidemiologic features of malignant melanoma, we reviewed the records of 325 patients with cutaneous malignant melanoma seen at the University of Colorado Health Sciences Center between 1973 and 1983. Most patients had fair skin, brown or blonde hair, blue or green eyes, and had difficulty in suntanning. The majority of melanomas (72%) developed in preexisting nevi. In women, melanomas were most common on the extremities, and in men they occurred most frequently on the trunk, head or neck. The most frequently noted depth of invasion was Clark's level IV. At diagnosis, most of the patients (77%) were at stage I. We conclude that malignant melanoma constitutes a major disease problem in the western United States that is largely preventable with appropriate physician and patient education.

Adolescent↗

Metastatic disease in patients with newly diagnosed malignant melanoma.

In patients with stage I Clark's level III and IV malignant melanoma (MM), recurrence rates of 30-60% can be expected after resection of the primary lesion. If metastatic disease could be detected early and treated in such patients, survival might be prolonged. Ninety patients (37 males and 53 females) with newly diagnosed, resected stage I cutaneous MM, levels III and IV, were evaluated for metastatic disease at diagnosis using a physical examination; CBC; SMA 18; chest films; brain computed tomography (CT) scan; and radioisotope liver, spleen, and bone scans. Forty-four patients had level III and 46 had level IV melanomas ranging in thickness from 0.65 to 4.5 mm. None of these 90 patients was found to have metastatic disease. Such tests are not useful and can be replaced by a history and physical examination with substantially improved cost effectiveness.

Humans↗

Mercury pulmonary emboli following intravenous self-injection.

The attempted intravenous injection of metallic mercury resulted in multiple mercury pulmonary emboli. Few of the abnormalities of respiratory or renal function reported previously were demonstrated. In particular the isotope ventilation/perfusion scan was unhelpful in confirming the diagnosis. Extravasation of mercury at the injection site produced a severe local inflammatory reaction and in the presence of toxic blood mercury levels surgical excision was undertaken. The blood mercury levels fell significantly but remain elevated within the toxic range to date. This may be due to the continued absorption of embolized mercury. The long-term effects of chronically elevated blood mercury levels is unknown.

Adult↗

Effects of increased dietary calcium intake upon the calcium and bone mineral status of lactating adolescent and adult women.

We studied the effectiveness of an increased calcium (Ca) diet in preventing bone mineral loss in lactating adolescent mothers. Three groups of lactating women were studied: 15 control adolescents consuming their usual Ca diet (900 mg/d), 21 experimental adolescents consuming a high-Ca diet (greater than 1600 mg/d), and 12 adults. At 2 and 16 wk postpartum, serum calcium, phosphate, magnesium, albumin, alkaline phosphatase, vitamin D, parathyroid hormone (PTH), and calcitonin (CT) were determined. Bone mineral analyses were performed by photon absorptiometry. By 16 wk the control adolescent group had a 10% decrease in bone mineral content (BMC) and increased PTH and CT. The experimental adolescent and adult groups had no significant change in BMC during the study. There was a positive correlation (r = 0.45, p less than 0.01) between dietary Ca intake and BMC in all adolescents. Data suggest that bone loss during lactation in adolescents may be prevented with adequate dietary Ca intakes.

Adolescent↗

Alterations in piglet small intestine after cholesterol deprivation.

Mammalian cells require cholesterol for normal cell function. This requirement can be fulfilled by endogenous biosynthesis or by extracellular supplementation. Infants fed with human milk receive greater quantities of cholesterol than those fed commercial formulas. Whether this lack of cholesterol in commercial formulas poses a threat to normal neonatal cell function is not known. We compared small intestinal microvillus membrane fluidity, hydrolase activities, protein concentration, permeability to nonabsorbable markers, and weight gain in neonatal piglets receiving restricted intake of isocaloric formulas containing either normal amounts of cholesterol (145 mg/dl) or very low levels of cholesterol (less than 2 mg/dl). Using the fluorescent probe, diphenylhexatriene, and fluorescence polarization, microvillus membranes from cholesterol deprived piglets demonstrated higher fluidities than did microvillus membranes from animals fed normal concentrations of cholesterol. Cholesterol-deprived animals, even though their caloric intake was similar to cholesterol-fed animals, demonstrated a net weight loss per animal whereas the cholesterol-fed animals demonstrated a weight gain. These results demonstrate that in a pig model on a restricted intake, cholesterol deprivation alters the biophysical properties of the microvillus membrane.

Animals↗

Calcium intake and bone density of lactating women in their late childbearing years.

Researchers have shown through epidemiological surveys that osteoporosis results in hip, vertebra, or long bone fractures in at least 10% of women over 50 years of age. The primary objective of this study was to determine calcium intake and bone mineral content in lactating women in their later childbearing years. Eight lactating women over 37 years of age were compared with eight nulliparous women to determine differences in dietary intake of energy, protein, vitamin D, calcium, and phosphorus. Anthropometric measurements, bone density measurements, serum calcium, serum phosphate, and serum alkaline phosphatase measurements were made at 2 weeks and 6 weeks postpartum. Intakes of protein, vitamin D, and calcium were significantly lower in the diets of control women. No significant differences were found in biochemical analysis (except for a significantly lower serum phosphorus in the control group of women), bone density, nutrition assessment, or physical assessment between lactating and control groups. Thus, when dietary calcium intake is greater than the RDA for lactating women, bone mineral content is not affected during the first 6 weeks of lactation.

Adult↗

Human lactation: maternal transfer of dietary triglycerides labeled with stable isotopes.

A stable isotope tracer method was utilized to measure quantitatively the secretion of diet-derived fatty acids (FA) into human milk. A mixture of [2H6]tripalmitin, [2H18]-triolein, and [2H12]trilinolein was administered to three healthy, lactating women 22 to 30 years of age. Milk and blood samples were collected sequentially for 72 hr. The FA composition and concentration of total plasma, lipoprotein, and milk triglycerides were determined by gas-liquid chromatography (GLC) and the isotopic enrichment was determined by gas-liquid chromatography-mass spectrometry (GLC-MS). There were no statistically significant differences in mammary secretion of the individual fats, either by a single individual or between subjects. The mean secretion of fat by one breast was 5.11 +/- 1.26% of the dose (CV = 25%). There was a significant 6.0-hr delay between peak occurrence of the tracer in plasma and its occurrence in milk. The lipids are transported to the mammary gland primarily by the chylomicron and very low density lipoprotein triglycerides.

Adult↗

Treatment of metastatic malignant melanoma with recombinant interferon alpha 2.

Fifty-nine patients with metastatic malignant melanoma were entered into a phase II trial of recombinant alpha-2 interferon given in a dosage of 10 million IU/M2 subcutaneously three times per week for one year. Forty-five of these were evaluable for response. Of five evaluable patients with ocular primaries, none responded to interferon treatment. Four of 40 patients (10%) with cutaneous primaries achieved complete remission, and 6 further patients (15%) had partial remissions for a combined response rate of 25%. Two patients remain in complete remission 15+ and 32+ months after starting treatment. Responses were limited to subcutaneous, lymph node and lung metastases. The treatment schedule was well tolerated with the majority of patients receiving more than 70% of their predicted doses. Flu-like symptoms were the most common side effect. No evidence of cumulative toxicity was seen. We conclude that interferon is an active agent in metastatic malignant melanoma of cutaneous origin and that further trials are indicated.

Adult↗

Recovery of blood and bone marrow stem cells following intense chemotherapy and autologous bone marrow transplantation.

Sixteen patients with advanced (stage III) malignant melanoma were treated with escalating doses of intravenous BCNU and melphalan starting at 400 and 35 mg/m2, respectively, and escalating to 1,000 and 110 mg/m2, respectively, combined with autologous marrow transplantation. The duration of granulocytopenia and time to granulocyte recovery was similar in all groups regardless of chemotherapy dose. Platelet recovery was delayed in patients receiving the highest doses of chemotherapy. This study showed that bone marrow colony-forming units in culture took as long as 6 months to recover. This was adequate to bring peripheral blood counts to normal but not to pretreatment levels. These studies indicate that autologous bone marrow transplantation is beneficial in enhancing short-term recovery, but may not be beneficial in the long-term hematopoietic recovery.

Agranulocytosis↗

Lysine and protein metabolism in young women. Subdivision based on the novel use of multiple stable isotopic labels.

A multitracer stable isotope study of lysine kinetics was carried out in fasted adult female volunteers to determine whether a multicompartmental model that partitions protein synthesis and breakdown into at least two types of tissue components can be constructed from plasma and breath data. Five female subjects, maintained on formula diets, received L-[13C1]lysine (27 mumol/kg) as an i.v. bolus and L-[15N2]lysine (27 mumol/kg) as an oral bolus 4 h postprandially. Plasma and breath samples were collected for 6 h. On an alternate day, subjects received NaH13CO3 (10 mumol/kg) as an i.v. bolus and breath samples were collected for 6 h. Plasma tracer lysine levels were determined by gas chromatography-mass spectrometry isotope ratiometry, and breath 13CO2 levels were measured by mass spectrometric gas isotope ratiometry. The tracer data could be fitted to a mammillary multicompartmental model that consisted of a lysine central compartment and slow- and fast-exchanging peripheral compartments containing 37, 38, and 324 mumol/kg, respectively. The rates of lysine oxidation, incorporation into protein, and release by protein breakdown were 21, 35, and 56 mmol/kg/h, respectively, in the fast-exchanging compartment, whereas the rates of protein synthesis and breakdown in the slow compartment were both 53 mmol/kg/min. These values corresponded to a whole-body lysine flux of 106 mmol/kg/h. The kinetic parameters were in excellent agreement with reported values obtained by constant-infusion methods. The measurements indicated that it will be possible to detect changes in amino acid pool sizes and protein synthesis and breakdown associated with the mobilization of protein stores from plasma and breath measurements in multitracer stable isotope experiments.

Administration, Oral↗

Depression: medical interface with psychiatry and treatment advances.

A number of advances, primarily pharmacologic, have occurred in recent years in the treatment of depression. Some of the recent advances relating to neurotransmitters and other neuropsychiatric factors believed to be related to depression are discussed, including how antidepressants may affect these systems. Some more recently recognized or often overlooked side effects of antidepressants are also discussed, as well as differential side effect profiles. The second generation antidepressants are critiqued and are generally believed to be no better than many of the first generation antidepressants. The usefulness of and indications for tricyclic serum levels and standard neuroendocrine tests for depression are summarized. Recent findings regarding lithium, including augmentation, and monoamine oxidase inhibitors, especially for atypical depressions with panic symptoms, are included, as is the use of psychostimulants, especially for medically ill patients who cannot take other antidepressants.

Adult↗

Oncologic emergencies in primary care. Five malignancy-associated conditions to watch for.

Acute problems requiring emergency management may occur in association with malignancy. The most common are superior vena cava syndrome, compression of the spinal cord or cauda equina, hypercalcemia, tumor lysis syndrome, and fever in the neutropenic patient. Successful management requires that the physician be aware of the potential for such an emergency in a cancer patient and give priority to treatment, based on clinical evidence and a few essential studies, over definitive diagnosis.

Bacterial Infections↗

Teaching psychiatry to primary care internists.

Many patients who seek the care of primary care physicians are suffering from a wide variety of psychiatric disorders. Primary care physicians should become skilled in interviewing techniques and basic psychiatric differential diagnosis, management, and treatment approaches for some types of psychiatric disorders and learn to regularly consult with and make referrals to psychiatrists when appropriate. Psychiatrists should play a very active role in the education of primary care specialists. This should include observation of the physician interviewing patients with different types of psychiatric disorders in addition to didactic teaching and supervision on topics such as psychopharmacology. With mutual collaboration between primary care interests and psychiatrists the patients of both groups of physicians should receive better care and continuing education of both may occur through an ongoing dialogue.

Humans↗