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C Nichols

Publications and source records attributed to C Nichols.

At least 19 recordsLinked to original sources
PubMed1999

The relation of continuing attachment to adjustment in conjugal bereavement.

The role of continuing attachment in adjustment to conjugal loss was examined. At 6 months postloss, 70 midlife bereaved participants were interviewed to assess different forms of continuing attachment. They also engaged in a monologue role-play with their deceased spouse, providing a behavioral measure of grief-related distress. In addition, they completed general and grief-specific symptom inventories at 6 months and again at 14 and 25 months postloss. The results indicated that use of the deceased's possessions to gain comfort was positively correlated with concurrent distress in the role-play and predictive to less of a decrease in grief-specific symptoms over time in a growth curve analysis. In contrast, attachment through fond memories was related to less distress in the role-play. The results, therefore, suggest that whether continuing attachment is adaptive or not depends on its form.

Adult↗
PubMed1998

Formation of zinc protoporphyrin in cultured hepatocytes: effects of ferrochelatase inhibition, iron chelation or lead.

The formation of zinc protoporphyrin in response to lead or iron depletion has previously been investigated in erythroid systems. Because of its possible metabolic role in non-erythroid tissue, we investigated the formation of zinc protoporphyrin in cultured hepatocytes. The effects of lead and inhibitors of ferrochelatase, the iron insertion step of heme synthesis, on the conversion of 5-aminolevulinic acid to zinc protoporphyrin, protoporphyrin and heme were compared in rat and chick embryo hepatocyte cultures. In rat cultures, zinc protoporphyrin was synthesized enzymatically by ferrochelatase, since N-methylmesoporphyrin, an inhibitor of ferrochelatase. caused 40% or greater decreases in both heme and zinc protoporphyrin accumulation and markedly stimulated protoporphyrin accumulation. In addition, chelation of ferrous iron with 2,2'-dipyridyl decreased heme accumulation by 50%, but increased ZPP accumulation by 200%. Zinc protoporphyrin formation in chick embryo hepatocytes required the addition of zinc as well as 5-aminolevulinic acid and apparently was non-enzymatic, since it was not inhibited by N-methylmesoporphyrin nor increased by iron chelation. In the presence of 5-aminolevulinic acid, lead had no effect on zinc protoporphyrin, protoporphyrin or heme accumulation in chick hepatocytes, but decreased all three in rat hepatocytes, with the decrease in protoporphyrin being far greater than that of zinc protoporphyrin or heme. These findings indicate that, in contrast to the effect of lead in erythroid tissue, it did not specifically increase zinc protoporphyrin accumulation or alter iron availability in cultured hepatocytes.

Aminolevulinic Acid↗
PubMed1998

Characterization of a hypermutable strain of Drosophila simulans.

A hypermutable strain of Drosophila simulans that originated from a single spontaneous mutant male was characterized. Seven different mutations were isolated from roughly 100 generations of offspring. The genetic analysis of the viable mutants showed two mutations on the X chromosome, one in the lozenge locus and the other in the ruby gene. The autosomic mutations characterized were a dpp-heldout-like, a blistered-like and a homoeotic dominant mutant with an antenna-to-leg transformation and ectopic eyes that we called Zoinho-napata.

Animals↗
PubMed1998

Clinical applications of chromosome analysis, from fine needle aspiration biopsies, of posterior uveal melanomas.

PURPOSE: An accurate assessment of prognosis is essential to the clinical assessment of malignancy. In posterior uveal melanoma specific chromosome alterations have been shown to correlate significantly with prognosis; but the procedure is restricted to patients treated surgically, and in consequence has been limited mainly to large tumours. Fine needle aspiration biopsy (FNAB) may provide sufficient material to perform this technique, and allow its use in the in situ assessment of tumours, including small lesions. To determine the feasibility of this approach we have conducted a pilot study using enucleated tumours. METHODS: Ten cases of posterior uveal melanoma were studied. In each instance both a test FNAB and a standard tissue preparation were conducted, and the results compared. FNABS were obtained from enucleated tumours by aspirating cells using a 5 ml syringe with a .25 gauge needle; cells were injected into phosphate-buffered saline, spun down and established in vitro. Conventional short-term cultures were established from tumour tissue samples, which were minced prior to the establishment of cultures. Cytogenetic analysis was performed following standard protocols. RESULTS: Of the 10 cases examined, full chromosome analysis was obtainable from all standard tissue short-term cultures. Cytogenetics was successful from cultures of 6 FNAB, with 2 further FNAB producing partial analyses. No major clonal differences were determined between the two procedures. CONCLUSIONS: Cytogenetic analysis of FNAB appears to be entirely feasible for posterior uveal melanomas, and may permit an accurate in situ assessment of tumours, including small lesions.

Aged↗
PubMed1998

CODE (cisplatin, vincristine, doxorubicin, etoposide) plus granulocyte colony-stimulating factor in advanced non-small-cell lung cancer: a Hoosier Oncology Group phase II trial.

This phase II trial investigated the activity and toxicity of CODE (cisplatin, vincristine, doxorubicin, etoposide) chemotherapy with the addition of granulocyte colony-stimulating factor (G-CSF) in patients who had chemotherapy-naive, advanced, or metastatic non-small-cell lung cancer. Treatment consisted of cisplatin, 25 mg/m2, administered weeks 1 through 9; vincristine, 1 mg/m2, weeks 1, 2, 4, 6, and 8; doxorubicin, 40 mg/m2, weeks 1, 3, 5, 7, and 9; and etoposide, 80 mg/m2 intravenously day 1 and 160 mg/m2 orally, days 2 and 3 on weeks 1, 3, 5, 7, and 9. Granulocyte colony-stimulating factor, 5 microg/kg, was administered subcutaneously on all days that patients were not receiving chemotherapy. From April 1992 through April 1993, 42 patients were entered on study. The principal toxicities were hematologic. Grade 3-4 anemia was seen in 21 patients. Grade 3-4 thrombocytopenia was seen in 9 patients. Grade 3-4 neutropenia occurred in 29 patients. Eight patients experienced a neutropenic febrile episode requiring antibiotics. Nonhematologic toxicities included weight loss and fatigue. Responses were seen in 10 of 42 patients, for an overall response rate of 24% (95% confidence interval, 12%-39%) and a median survival of 7.1 months. The CODE chemotherapy regimen has activity similar to other previously described cisplatin-based regimens, with a significant amount of both hematologic and nonhematologic toxicity. Its continued use in patients who have previously untreated non-small-cell lung cancer cannot be recommended, based on the results of this study.

Adult↗
PubMed1998

Management strategies and outcomes of germ cell tumor patients with very high human chorionic gonadotropin levels.

PURPOSE: To determine the therapeutic results in advanced germ cell tumor (GCT) patients with initial human chorionic gonadotropin (hCG) elevation greater than 50,000 mIU/mL and to document the levels of hCG decline and subsequent plateau and outcome of this patient population. PATIENTS AND METHODS: We conducted a retrospective review of 41 patients who presented to Indiana University (IU) with hCG levels greater than 50,000 mIU/mL between December 1976 and August 1996. All patients had received cisplatin-containing regimens and were monitored with serial hCG levels. RESULTS: Twenty-two of 41 (53.7%) patients continuously show no evidence of disease (NED) and eight additional patients (19.5%) are currently NED with salvage therapy. Only two of 41 patients had a normal hCG level at the start of the fourth and final course of cisplatin combination chemotherapy. Eight additional patients showed normalized hCG levels 1 month later. Seven of these 10 are continuously NED and three are currently NED with salvage therapy. Thirty-one patients had an abnormal hCG greater than 1 month after they completed primary chemotherapy; 15 of these patients (48%) are continuously NED despite no further therapy and five additional patients (16%) are currently NED with salvage therapy. Overall, there was an initial rapid decline in hCG followed by a plateau after the first two courses of therapy. CONCLUSION: Less than 10% of patients who present with hCG levels greater than 50,000 mIU/mL will have a normal hCG at the institution of the fourth and final course of chemotherapy. However, 22 of 41 (53.7%) are continuously NED despite no further therapy. We feel that the optimal strategy for such patients is monthly observation with initiation of salvage therapy if and when there is serologic progression.

Adolescent↗
PubMed1997

Aortic changes in experimental renal failure: hyperplasia or hypertrophy of smooth muscle cells?

Cardiovascular complications are a well-known feature of chronic renal failure. Increased wall thickness of intramyocardial arterioles and elastic (aorta) and peripheral (mesenteric) arteries is seen even after normalization of blood pressure. It is currently unknown whether such increases result from hyperplasia of vascular smooth muscle cells, hypertrophy, or a combination of both or from an increase in aortic extracellular matrix. Using a recently developed unbiased stereological technique (the dissector), we investigated the aortas of subtotally nephrectomized rats and sham-operated controls after perfusion fixation. We determined aortic wall thickness, cross-sectional area of aortic media, total number of vascular smooth muscle cells per unit aortic length (1 mm), mean cell and nuclear volumes, volume density of elastic fibers, extracellular matrix, vascular smooth muscle cells, and total volumes of these structures per unit of aortic length (1 mm). Blood pressure was not significantly increased in subtotally nephrectomized rats. In contrast, wall thickness, cross-sectional media, total number of aortic vascular smooth muscle cells, and volume of extracellular matrix including collagen were significantly increased after subtotal nephrectomy, whereas cellular hypertrophy was only modest and an increase in elastic fibers did not occur. In conclusion, increased aortic wall thickness in experimental renal failure results primarily from an increase in aortic extracellular matrix. In addition, however, proliferation of aortic vascular smooth muscle cells resulting in cell hyperplasia also contributed to aortic wall thickening to a minor degree. It appears that aortic wall thickening is caused by secretory stimulation of the proliferating vascular smooth muscle cells, resulting in increased matrix production. The nature of the underlying stimulus requires further investigation.

Animals↗
PubMed1997

Granulocyte-macrophage colony-stimulating factor/interleukin-3 fusion protein versus granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for non-Hodgkin's lymphoma: results of a randomized double-blind trial.

PURPOSE: A phase III trial to compare PIXY321 with granulocyte-macrophage colony-stimulating factor (GM-CSF) following high-dose therapy and autologous bone marrow transplant (ABMT) was conducted to evaluate the time to hematopoietic recovery. PATIENTS AND METHODS: One hundred seventy-seven patients with non-Hodgkin's lymphoma (NHL) receiving ABMT were randomized to receive either PIXY321 750 micrograms/m2/d divided into two subcutaneous (SC) doses or GM-CSF 250 micrograms/m2/d as a 2-hour intravenous (IV) infusion starting on day 0 post-ABMT for a maximum of 28 days. RESULTS: The median time to reach an absolute neutrophil count (ANC) > or = 500/microL in the PIXY321 group was 17 days versus 19 days in the GM-CSF group (P = .07) and the median time to reach platelet transfusion independence in the PIXY321 group was 25 days versus 23 days in the GM-CSF group (P = .30). The toxicity profiles of the two agents appeared to be equivalent with the exception of more patients in the PIXY321 group with a rash (64%) compared with the GM-CSF group (48%) (P = .028). A logistic regression model identified the use of a non-total-body irradiation (TBI) regimen and/or receipt of unpurged marrow and a body-surface area greater than 2.0 m2 as predictive of faster neutrophil engraftment, and those three factors, as well as the receipt of < or = two prior chemotherapy regimens as predictive for rapid platelet engraftment. CONCLUSION: There was a trend toward a slight improvement in neutrophil engraftment post-ABMT with the PIXY321 administered by an SC route compared with GM-CSF administered by an IV route. However, no differences could be identified between the two agents with respect to the time to platelet transfusion independence. Patient, regimen, and graft characteristics were most predictive of the engraftment tempo.

Adolescent↗
PubMed1997

Dentistry and hypertension.

The author monitored the systolic and diastolic blood pressure, or BP; mean arterial pressure, or MAP; and heart rate, or HR, of hypertensive and normotensive patients once each minute during dental procedures. He found statistically significant differences in the means of the initial five and final five systolic BP and diastolic BP, MAP and HR readings. Exceptions were the HR in 18- to 45-year-old normotensive patients and the systolic BP in hypertensive patients. The author concluded that the time at which BP is monitored during a dental procedure may be significant.

Adolescent↗
PubMed1997

2-Chlorodeoxyadenosine as initial therapy for advanced low grade lymphomas.

In order to evaluate efficacy and safety of 2-chlorodeoxyadenosine (2-CdA) as primary therapy of low grade non Hodgkin's lymphoma, a phase II trial of 2-CdA was initiated in patients with previously untreated advanced low grade lymphoma. Fourteen previously untreated patients with stage III and IV low grade lymphoma were enrolled. Patients received 2-CdA 0.1 mg/kg/d by continuous infusion for 7 days every 28 days, for 1-6 cycles of therapy (median 3.5). Results showed one complete response and nine partial responses for an overall response rate of 75%. Until now there have only been three responding patients who have had progressive disease, with a median follow-up time of 18 months. The major toxicity was bone marrow suppression and nine patients stopped therapy prior to a planned six cycles because of prolonged cytopenias, primarily thrombocytopenia. Fifteen of 50 cycles of therapy were associated with neutropenic febrile episodes and there was one septic death secondary to Listeriosis. It seems from this small group of patients that 2-CdA is an active agent in previously untreated low grade lymphoma. Myelosuppression is cumulative and limits the number of cycles of therapy which can be given. Future exploration of different doses or schedules of this active agent is warranted.

Adult↗
PubMed1996

Serum progesterone and human chorionic gonadotrophin measurements in the evaluation of ectopic pregnancy.

We evaluated the clinical usefulness of measuring the serum concentrations of human chorionic gonadotrophin (HCG) and progesterone to distinguish between early viable and nonviable pregnancies. We investigated 110 women with clinical symptoms of abnormal pregnancy. A single HCG measurement did not clearly distinguish between ectopic and failing intrauterine pregnancies; an HCG value below 3,000 IU/L, together with a serum progesterone below 40 nmol/L, predicted abnormal pregnancy outcome in 97% of women (positive predictive value: 91%; negative predictive value: 95%). Serum HCG value above 3,000 IU/L or progesterones above 40 nmol/L, discriminated between an ongoing pregnancy and an abnormal pregnancy in 87% women (positive predictive value: 95%; negative predictive value: 91%) and provided reassurance of an ongoing pregnancy. Our results suggest that a combination of serum progesterone and HCG measurements provide clinically useful biochemical information which enhances the prediction of pregnancy outcome.

Chorionic Gonadotropin↗
PubMed1996

Arteriolar wall thickening, capillary rarefaction and interstitial fibrosis in the heart of rats with renal failure:the effects of ramipril, nifedipine and moxonidine.

In experimental renal failure, increased intramyocardial arteriolar wall thickness, reduced myocardial capillary density, and increased cardiac interstitium are found. The extent to which such alterations can be modified by therapeutic interventions has not been investigated to date. The purpose of this study was to examine the effects of Ramipril, Nifedipine and Moxonidine on these structural changes. Sham-operated and subtotally nephrectomized (SNX) 300-g male Sprague-Dawley rats (N = 7 to 11) were left untreated (N = 9) or treated with Ramipril (0.5 mg/kg body wt per day; N = 7), Nifedipine (30 mg/kg body wt per day; N = 9), or Moxonidine (10 mg/kg body wt per day; N = 8) for 8 wk. After perfusion fixation, heart and aorta were examined by stereological techniques. Aortic wall thickness was significantly higher in SNX than in sham-operated control rats and was similarly lowered by all three interventions. In contrast, the wall thickness of intramyocardial arterioles was significantly higher in SNX; this was prevented by Ramipril and Nifedipine, but not by Moxonidine. Intramyocardial capillary length density (Lv) was significantly lower and interstitial volume density (Vv) significantly higher in untreated SNX. Reduction of capillary length density was completely prevented by Moxonidine and in part by Ramipril. The increase in cardiac interstitial volume density was completely prevented by Ramipril and was partially prevented by Moxonidine or Nifedipine treatment. The following conclusions can be drawn from the results: (1) all agents normalize aortic wall thickness, but only calcium channel blockers and angiotensin-converting enzyme (ACE) inhibitors prevent intramyocardial arteriolar wall thickening: (2) intramyocardial arteriolar wall thickening, capillary rarefaction, and expansion of the cardiac interstitium are seen in SNX even after lowering the blood pressure to subnormal levels; i.e., changes in systemic blood pressure cannot completely explain the altered vascular structure in renal failure; (3) the effects of Ramipril, Nifedipine, and Moxonidine on cardiovascular structures in experimental renal failure are not completely accounted for by their hemodynamic actions.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Effect of ramipril, nifedipine, and moxonidine on glomerular morphology and podocyte structure in experimental renal failure.

BACKGROUND: Experimental renal failure causes structural alterations of the kidney. It is still unresolved how these changes are modified by antihypertensive treatment. Purpose of the study. To examine the effects of different antihypertensive agents (ramipril, nifedipine, moxonidine) mainly on glomerular geometry, cell number, cell morphology, and capillarization, in a subtotal nephrectomy model of renal failure. MATERIAL AND METHODS: Sham-operated male SD rats and subtotally nephrectomized (SNX) ad libitum-fed rats were examined. Groups of 8-10 SNX rats were left untreated or were treated with ramipril (0.5 mg/kg b.w. per day), nifedipine (20 mg/kg b.w. per day) or moxonidine (10 mg/kg b.w.per day) respectively. After perfusion fixation the kidneys were examined using stereological techniques. RESULTS: Systolic blood pressure (by tail plethysmography) was 110+/-13 mm Hg in sham-op and 119+/-9 in SNX. It was effectively and comparably reduced below normal values by ramipril (89+/-11 mmHg), nifedipine (98+/-23 mmHg) and moxonidine (92+/-11 mmHg). The glomerulosclerosis index (SI) was significantly increased in SNX versus sham-op; it was similarly decreased by ramipril and moxonidine but less so by nifedipine. Vascular damage (preglomerular vessels) was reduced by all treatments whereas tubulointerstitial damage was signficantly reduced only by ramipril and moxonidine. Mean glomerular tuft volume was increased in SNX compared to sham-op. controls and was normalized only by ramipril treatment. Glomerular cells were differentially affected the three antihypertensive agents. After subtotal nephrectomy an increase in podocyte volume and mesangial cell number per glomerulus was noted. Nifedipine, and to a lesser extent ramipril, prevented mesangial cell hyperplasia. In contrast, only the ACE inhibitor ramipril, but not nifedipine or moxonidine prevented podocyte abnormalities, particularly podocyte hypertrophy. CONCLUSIONS: (i) Despite comparable reduction in systolic blood pressure, different classes of antihypertensive agents had diverse effects on renal damage in subtotally nephrectomized rat. This observation is consistent with specific, non-hemodynamic actions of anti-hypertensives. (ii) Glomerular and tubulointerstitial damage are prevented by treatment with ACE inhibitors and antisympathotonic agents, but not with the calcium antagonist nifedipine. In contrast, renal vascular changes were also prevented by nifedipine. (iii) Only ACE inhibitors effectively inhibited podocyte hypertrophy and mesangial cell hyperplasia. Whether the superior effect of ACE inhibitors on glomerulosclerosis is related to inhibition of glomerular growth and podocyte hypertrophy as well as preservation of podocyte structure, or whether these findings are merely a passive reflection of greater efficacy, remains unresolved.

Animals↗
PubMed1994

Hypopyon uveitis in patients with acquired immunodeficiency syndrome treated for systemic Mycobacterium avium complex infection with rifabutin.

OBJECTIVE: Iridocyclitis has been identified as a dosage-dependent side effect in patients with the acquired immunodeficiency syndrome (AIDS) who are treated for Mycobacterium avium complex (MAC) infection with systemic rifabutin. We reviewed cases of acute hypopyon uveitis occurring in patients with AIDS to establish whether there was an association. DESIGN: Retrospective case series. SETTING: Outpatient clinic and inpatient hospital-based ophthalmology referral practice and infectious disease specialty service. PATIENTS: Seven patients with AIDS, aged 10 to 40 years, presenting with acute unilateral hypopyon mimicking infectious endophthalmitis. MAIN OUTCOME MEASURES: Findings from complete ophthalmological evaluation and ancillary laboratory testing. RESULTS: At the time of presentation, all seven patients were receiving treatment for MAC infection with rifabutin (dosage range, 300 to 600 mg/d) and clarithromycin. Results of microbiological investigations in five patients were negative. Iridocyclitis became bilateral in all seven patients, and hypopyon developed in the contralateral eye in five of seven patients. Hypopyon resolved rapidly with intensive topical corticosteroid therapy. Residual inflammation responded to topical corticosteroids with or without reduction of the rifabutin dosage. CONCLUSIONS: Concomitant use of rifabutin, clarithromycin, and fluconazole may precipitate hypopyon uveitis in patients with AIDS being treated for MAC infection.

AIDS-Related Opportunistic Infections↗
PubMed1992

Effect of one-legged exercise on the strength, power and endurance of the contralateral leg. A randomized, controlled study using isometric and concentric isokinetic training.

The purpose of this investigation was to study the effect of one-legged exercise on the strength, power and endurance of the contralateral leg. The performance of the knee extensor and flexor muscle of 20 healthy young adults (10 men and 10 women) was first tested by Cybex II+ and 340 dynamometers. Then 10 subjects were chosen at random to train using one leg three times a week for 7 weeks whilst the other 10 served as controls. During the 8th week, the tests were repeated. Both quadriceps and hamstring muscles of the trained subjects showed a cross-transfer effect from the trained limb to the untrained side. This concerned the strength and power, as well as endurance characteristics of these muscles. The average change in peak torque of the quadriceps muscle was +19% (P less than 0.001) in the trained limb, +11% (P less than 0.01) in the untrained limb and 0% in the control limbs. In hamstring muscles the changes were +14% (P less than 0.01), +5% and -1%, respectively. Concerning muscle endurance (work performed during the last 5 contractions in the 25-repetition test) the corresponding changes were +15% (P less than 0.01), +7% (P less than 0.01), and -1% in quadriceps muscle, and +17% (P less than 0.05), +7%, and -3% in hamstring muscles. The average strength benefit in the untrained limb was +36% (hamstring muscles) and +58% (quadriceps muscle) of that achieved in the trained limb. Untrained hamstring muscle showed better benefits in the endurance parameters than in strength or power parameters, while in the quadriceps muscle this effect was reversed. A positive relationship was observed between the changes (greater improvement in the trained limb resulted in greater improvement in the untrained limb) (hamstring muscles: r = 0.83, P less than 0.001, quadriceps muscle: r = 0.53, P less than 0.001). In endurance parameters, this relationship was almost linear while in the strength and power parameters the results were more in favour of a curvilinear relationship with limited benefit.

Adult↗