Lack of marital support and poor psychological responses in male cancer patients

A total of 272 men and 252 women with cancer participated in a study of the impact of being married and the presence of spousal support on psychological distress and coping with cancer. All participants underwent a structured interview and completed the Profile of Mood States and the Mental Adjustment to Cancer scale. Multivariate analysis controlling for potentially confounding biomedical and psychosocial variables revealed that unmarried men had significantly higher levels of psychological distress and lower levels of fighting spirit than married men, and that men with spousal support showed higher levels of fighting spirit than men without spousal support. However, no such difference was observed between unmarried and married women or between women with and without spousal support. These findings suggest that being married may play an important role in reducing psychological distress and enhancing fighting spirit of men with cancer, and that being unmarried may be a risk factor for psychological distress and lower fighting spirit for men with cancer.     

Lack of chemokine receptor CCR1 enhances Th1 responses and glomerular injury during nephrotoxic nephritis

During the development of nephrotoxic nephritis (NTN) in the mouse, we find that a variety of chemokines and chemokine receptors are induced: CCR1 (RANTES, MIP-1alpha), CCR2 (MCP-1), CCR5 (RANTES, MIP-1alpha, MIP-1beta), CXCR2 (MIP-2), and CXCR3 (IP-10). Their timing of expression indicated that CXCR2 and CCR1 are probably important in the neutrophil-dependent heterologous phase of the disease, whereas CCR1, CCR2, CCR5, and CXCR3 accompany the subsequent mononuclear cell infiltration characteristic of autologous disease. We therefore assessed the role of CCR1 in NTN using CCR1(-/-) mice. We found that neutrophil accumulation in CCR1(-/-) mice was comparable to that in wild-type animals but that renal recruitment of CD4(+) and CD8(+) T cells and macrophages increased significantly. Moreover, CCR1(-/-) mice developed more severe glomerulonephritis than did controls, with greater proteinuria and blood urea nitrogen, as well as a higher frequency of crescent formation. In addition, CCR1(-/-) mice showed enhanced Th1 immune responses, including titers of antigen-specific IgG2a antibody, delayed-type hypersensitivity responses, and production of IFN-gamma and TNF-alpha. Lastly, using recombinant proteins and transfected cells that overexpressed CCR1, we demonstrated that MIP-1alpha, but not RANTES, bound CCR1 and induced cell chemotaxis. Thus, rather than simply promoting leukocyte recruitment during NTN, CCR1 expression profoundly alters the effector phase of glomerulonephritis. Therapeutic targeting of chemokine receptors may, on occasion, exacerbate underlying disease.     

Lack of effect of desmopressin on ACTH and cortisol responses to ovine corticotropin-releasing hormone in anorexia nervosa

Abstract. Both arginine vasopressin (AVP) and corticotropin-releasing hormone (CRH) are involved in the release of ACTH in man. Desmopressin (DDAVP), a synthetic analogue of AVP, has been shown to have a CRH-like action (able to promote ACTH and cortisol release) in animals but not in normal man. Nevertheless, DDAVP is able to release ACTH and cortisol in ACTH-dependent Cushing's disease. We studied eight anorexia nervosa (AN) patients [as AN is a condition in which chronic activation of the hypothalamic-pituitary-adrenal (HPA) axis is commonly reported] in a refeeding phase of the disease, to evaluate whether, after weight gain, ACTH and cortisol response to ovine corticotropin-releasing hormone (oCRH) [1 μg kg^-1 body weight (BW) i.v.] is restored. We also wanted to ascertain the effect on the HPA axis of 10 μg i.v. DDAVP alone and as pretreatment to oCRH (1 μg kg^-1 BW i.v.)-induced secretion of ACTH and cortisol. We studied six normal women as control subjects. No significant differences in ACTH and cortisol responses to oCRH were found between AN patients and control subjects. DDAVP was not able to stimulate ACTH or cortisol release in AN patients or in control subjects, but in the latter it was able to significantly enhance (P < 0.05) ACTH [area under curve (AUC): 590.0± 104.4 pmol L^-1 120 min^-1 and cortisol (AUC: 28899.0 ± 6935.2nmol L^-1 120 min^-1) responses to oCRH (ACTH AUC: 325.7 ± 101.7 pmol L^-1 120 min^-1, cortisol AUC: 14197.4 ± 2930.0 nmol L^-1 120 min^-1). The present data show that DDAVP does not stimulate ACTH and cortisol in AN patients or, as previously reported, in normal subjects. However, DDAVP is able to enhance ACTH and cortisol release after oCRH administration in normal subjects but not in AN patients. This finding could be due to a down-regulation of hypophyseal DDAVP V3 receptors in AN as a direct consequence of the hypercortisolaemic status usually present.     

Lack of effect of isometric handgrip exercise on the responses of the carotid sinus baroreceptor reflex in man

1. The change in arterial pressure and heart rate resulting from alteration of carotid sinus transmural pressure by a median--34 mmHg and +33 mmHg by means of a variable-pressure neck chamber was tested in seven male volunteer subjects, at rest and during exertion of 35, 45 and 65% of maximum voluntary handgrip. 2. During 60 s of 35 and 45%, and during 30 s of 65%, of maximal voluntary handgrip there was virtually no alteration of the response of blood pressure to alteration carotid sinus transmural pressure. 3. The bradycardic response to increase in carotid sinus transmural pressure was reduced at various times after the commencement of handgrip at 45 and 65% of maximum voluntary contraction. 4. It is concluded that a reduction in arterial baroreceptor reflex sensitivy does not play an important role in the initiation of the increase in arterial blood pressure and heart rate caused by isometric exercise. 5. The hypothesis is advanced that some of the cardiovascular changes in exercise may result from elevation of the central 'set point' for blood pressure.     

Lack of tacrolimus-induced cardiomyopathy

BACKGROUND: Hypertrophic cardiomyopathy (HCM) has been reported in pediatric transplant patients receiving tacrolimus. It is unclear whether tacrolimus is associated with HCM in adult transplant recipients. OBJECTIVE: To determine the prevalence of HCM in noncardlac adult transplant patients receiving tacrolimus. METHODS: A retrospective analysis of nonheart transplant recipients who received tacrolimus at our institution from January 1982 to April 1996 was conducted. Patients with left-ventricular hypertrophy (LVH) defined as a posterior or septal wall thickness > or = 1.3 cm by echocardiography (ECHO) were independently evaluated. RESULTS: There were 3609 patients who met entry criteria including 2257 liver, 1333 kidney, and 19 other organ transplants. Of the 502 patients who had undergone ECHOs after transplantation, 171 had LVH. The etiology of LVH was categorized as valvular disease (36%), hypertensive disease (29%), ischemic heart disease (17%), or multifactonal (15%). There were six patients in whom, after detailed chart review, no underlying cause of LVH was evident. Five of these patients had HCM, representing an overall prevalence of 0.1% in the entire group of tacrolimus-treated patients, and 1% in patients referred for ECHO. CONCLUSIONS: The prevalence of HCM in our tacrolimus-treated adult transplant population is similar to that reported in general population studies. These data suggest that tacrolimus is not a risk factor for HCM in adult transplant recipients.     

Lack of methemoglobinemia with flutamide

OBJECTIVE: To determine whether the nonsteroidal antiandrogenic drug flutamide is a clinically relevant inducer of methemoglobinemia in patients with prostatic cancer. METHODS: Fifty consecutive outpatients with prostatic cancer stage D2 entered the study (age 71.1 +/- 7.3 y). Five patients were lost to follow-up; the remaining 45 patients received the recommended oral dose of flutamide 250 mg three times daily. Total hemoglobin (Hb) and methemoglobin (Met-Hb) concentrations were measured on varying days using an ultraviolet/visible-spectrophotometric method with an intra- and interday variability < 8%. In 12 patients, Met-Hb was analyzed before initiating flutamide therapy and after therapy was begun. RESULTS: On average, 2.6 venous blood samples per patient were analyzed with a mean Met-Hb concentration of 1.9% of total Hb. Mean concentrations of > or = 3% were detected in only six patients (13%). The data from 12 patients evaluated before and after initiating flutamide therapy were without significantly different changes. During the study period, no clinical signs of methemoglobinemia were reported or observed. CONCLUSIONS: This study found no clinically relevant increase of Met-Hb concentrations in elderly patients with prostatic cancer during chronic treatment with flutamide. However, clinicians should be aware of the very rare possibility of flutamide-induced methemoglobinemia.     

Lack of Nephrotoxicity of Intravenous Dimethylsulfoxide

Abstract

Intravenous dimethylsulfoxide (DMSO) was used to treat seven patients with stable spinal cord injuries. Because of drug-associated hemoglobinemia and hemoglobinuria, the patients were studied for subtle evidence of renal tubular dysfunction by serial measurements of urinary beta-2-microglobulin excretion. No increases in tubular protein excretion or decreases in glomerular filtration rate were observed following short-term infusions of 10-40% DMSO. It is concluded that there is no significant short-term nephrotoxicity from intravenous DMSO.     

Lack of homology among potexvirus RNAs

Representative cDNAs prepared against each of five different potexvirus RNAs were annealed to these and other viral RNAs to assess the extent to which these viruses might be related. In all cases, the cDNA hybridized to completion with its homologous RNA but failed to cross-hybridize significantly to any other viral RNA. Partial hybridization was detected when the cDNA of one virus was annealed to the RNA of a distinct strain of the same virus. We conclude that despite their morphological similarities, members of the potexvirus group have diverged substantially in nucleotide sequence.