Plasma levels and vascular effects of vasopressin in patients undergoing coronary artery bypass grafting.

OBJECTIVE: Recent studies have suggested that endogenous vasopressin (AVP) acts as a spasmogen during coronary artery bypass grafting (CABG). Given that AVP could induce vasospasm in the grafted vessel, we assessed the release of this peptide during and after CABG, and explored ways of counteracting its contractile effect on the internal mammary artery (IMA). METHODS: Plasma levels of AVP were determined by radioimmunoassay in 16 patients before, during and after CABG. Using isometric force recording techniques, we also investigated the mechanisms involved in the contractile effect of AVP in ring preparations of IMA specimens taken from 95 patients. RESULTS: Plasma AVP levels peaked after the start of cardiopulmonary bypass (CPB) and correlated well with serum osmolality (Pearson's r=0.9490; P<0.0001; n=16). An inverse correlation was observed between plasma AVP levels recorded at this stage and the maximal contraction induced in vitro by AVP in vascular rings from the same patients (Pearson's r=-0.6968; P<0.01; n=16). No change in the AVP response was produced by endothelium removal, exposure to the NO precursor (3 x 10(-4)M L-arginine), inhibition of nitric oxide (NO) synthase (3 x 10(-5) M L-NAME) or soluble guanylate cyclase (3 x 10(-6) M 1H-[1,2,4]oxadiazol [4,3,-alpha]quinoxalin-1-one (ODQ)), removal of the superoxide anion (100 U/ml superoxide dismutase (SOD) plus 1200 U/ml catalase) or hydroxyl radical (10(-4) M deferoxamine), or specific alpha1 - (10(-6) M prazosin) or endothelin (10(-5) M bosentan) receptor antagonism. In contrast, adenylate cyclase activation (3 x 10(-8) M forskolin) reduced the contractile response to AVP, while prostanoid synthesis (3 x 10(-6) M indomethacin) inhibition and blockade of Ca2+ -activated potassium channels (KCa) (10(-3) M tetraethylammonium (TEA)) enhanced AVP contraction. Age, gender and smoking also modified the AVP response. CONCLUSION: Our findings suggest a role for AVP as a modulator of vascular tone in human IMA. The effect of AVP is dependent on prostanoids and Ca2+ -activated K+ channels, so its dysfunction in pathophysiological cardiovascular processes could mean that AVP, among other factors, produces vasospasm in IMA grafts.     

Effect of Zinc or S-Adenosyl-l-methionine on Long Term Administration of Low Doses of Lead to Rats

Two alternatives for the treatment of lead intoxication, administration of zinc or a thiol donor, S-adenosyl-L-methionine (SAM), were analysed. Rats were exposed to lead (Pb)-acetate (60 mg/1) in drinking water during 90 days; one group also received SO₄Zn in water (40 mg/l), while another received both Pb and SAM (5 mg/24 hr intraperitoneally. Erythrocytic δ-aminolaevulinic dehydratase (ALA-D) activity was significantly reduced (P<0.001) both in rats receiving Pb alone and in rats receiving Pb and each of the other two treatments. The high erythrocytic uroporphyrinogen synthetase (URO-S) activity noticed in Pb administered rats, was significantly (P< 0.001) reduced in animals treated either with zinc or with SAM. Hepatic ALA-D activity tended to decrease while renal enzyme activity was not modified by the low level Pb exposure used in this work. Interestingly, SAM treated rats in both tissues exhibited significantly (P<0.01) higher activities of the enzyme. It is argued that SAM treatment causes a surplus of thiols that allows the full expression of ALA-D catalytic activity.     

Further characterization of morphologically defined typical and atypical CLL: a clinical, immunophenotypic, cytogenetic and prognostic study on 390 cases

We analysed a group of 390 patients, diagnosed with chronic lymphocytic leukaemia (CLL). Cases were subclassified as morphologically typical and atypical CLL according to the criteria of the FAB proposal. Typical CLL cases were mostly diagnosed at a low-risk stage (Binet A/Rai 0), required no immediate treatment and expected a long survival; atypical CLL cases mostly presented at a more advanced risk stage (Binet B/Rai I–II), usually required immediate treatment and their survival was shorter. Moreover, clinical staging was of prognostic significance in typical but not in atypical cases.   In typical CLL, del(11q) was the most common chromosomal abnormality (21%) whereas in atypical CLL trisomy 12 was found in about 65% of the cases documented with an abnormal karyotype. Although chromosomal abnormalities were associated with a poor survival in typical CLL, they are of no prognostic significance in atypical CLL.   Based on these data, we conclude that subtyping CLL by morphology enables the identification of two groups of cases, each characterized by a specific clinical presentation, different cytogenetic abnormalities and prognostic parameters. We speculate that these two groups may represent two related, but different, diseases with different prognostic parameters and a different survival.     

Preoperative Chemotherapy Alone and Combined with Preoperative Radiotherapy in Small-Size Breast Cancer

Abstract: Breast conservation surgery is an effective and safe treatment for many breast carcinomas. It may be possible to further limit the extent of resection (or expand the indication for breast conservation) by the application of preoperative chemotherapy and radiotherapy. We explored the feasibility of this in a pilot study.
Seventy-three patients (mean age 48, 63% premenopausal) with confirmed breast cancer, less than 2.5 cm, received chemotherapy (Group A) or chemotherapy plus radiotherapy (Group B) prior to limited resection (tumorectomy). Axillary dissection was always performed. Results: In 6/31 (19%) Group A and 17/42 (40%) Group B patients the tumor was not palpable after preoperative treatment, with complete pathological remission in 1 and 3 cases respectively. Histologic grading, mitosis, cellular alteration, and cellularity evaluations indicated a consistently greater therapeutic effect with chemoradiotherapy than with chemotherapy alone.
In conclusion, radiotherapy appears useful in the preoperative treatment of breast cancer and its use in association with various drug combinations should be further explored.     

Heritability of myopic refractive errors in identical and fraternal twins

The existence of a visual feedback control of eye growth in humans is controversal, as the contributions of genetic and environmental factors are still unknown. To evaluate the heritability of refractive defects, we measured ocular refraction in 19 monozygote and 20 dizygote twin pairs (mean age 5 years). Monozygosity was ascertained by a common chorion, similarity of somatic traits, and identical dermatogliphes and was confirmed in myopes by blood marker diagnosis. Ocular refractive defects and axial length were evaluated by eye-loplegic autorefractometry and biometry. By comparing identical and fraternal twins heritability of refractive defects was estimated to be 0.08–0.14; this low value indicates that the observed variability in refractive errors is nongenetic in origin. Three monozygote pairs were anisomyopic; differences between eyes in identical twins were related to the increased axial length of myopic eyes. In one eye, myopia was attributed to visual deprivation induced by a congenital cataract, while in five eyes it was correlated directly to the degree of astigmatic defects. The discordant axial length observed in monozygote twins is nongenetic. In agreement with previous findings reported in the literature, it is proposed that visual impoverishment of retinal images may play an early regulatory role in postnatal eye growth.Deceased     

Cisplatin-associated anaemia in patients with solid tumours

We have reviewed the incidence of cisplatin-induced anaemia in patients affected with solid tumours treated with at least three courses of first-line cisplatincontaining regimens. In our experience, a low percentage (5%) of patients required transfusions of red blood cells. We think it is of the utmost importance to adopt uniform criteria in monitoring and treatment of patients at risk of developing cisplatin anaemia and to identify subsets of patients to eventually treat with erythropoietin.     

Botulinum toxin and neuromotor rehabilitation: An integrated approach to idiopathic cervical dystonia.

Currently, the best treatment option for idiopathic cervical dystonia (ICD) is injection of botulinum toxin (BTX) into the affected muscles, whereas rehabilitative approaches have given disappointing results. We evaluated whether the association of an ad hoc rehabilitative program may improve the clinical efficacy of BTX treatment in a single-center, cross-over, controlled study. Forty patients with ICD were randomly assigned to two different treatment groups: (1) BTX type A (BTX-A) plus a specific program of physical therapy (BTX-PT) or (2) BTX-A alone (BTX-0). Patients in the BTX-PT group showed a longer duration of the clinical benefit (118.8 vs. 99.1 days) and needed a lower dose of BTX at reinjection (284.5 vs. 325.5 units). In addition, they showed more marked reductions in their disability in activities of daily living (-9.7 vs. -4.85 points) and subjective pain (-13.35 vs. 6.95 points) scores. Association of BTX-A therapy with a specific program of physical therapy may improve ICD treatment outcome.     

The clinical phenotypes of juvenile bipolar disorder: toward a validation of the episodic-chronic-distinction.

BACKGROUND: Recent research has addressed the issue of subtyping juvenile bipolar disorder (JBD). Accordingly, we set out to find out, in a naturalistic sample of bipolar children and adolescents with mania and mixed mania, whether the most useful subtyping should be based on clinical features (elated vs. irritable) or course (episodic vs. chronic). METHODS: We studied 136 patients, 81 male patients (59.6%) and 55 female patients (40.4%), mean age 13.5 +/- 2.9 years, meeting the DSM-IV diagnosis of bipolar disorder, assessed by a structured clinical interview (Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version [K-SADS-PL]). RESULTS: Regarding course, 77 patients (56.6%) had an episodic course and 59 patients (43.4%) had a chronic course. Patients with chronic course were significantly younger, had an earlier onset of JBD, and presented a more frequent comorbidity with disruptive behavior disorders. According to the prevalent mood disturbance, 75 patients (55.1%) showed an elated and 61 patients (44.9%) showed an irritable mood. Elated mood was more frequent in patients with episodic course, whereas irritable mood was more frequent in the patients with chronic course. CONCLUSIONS: These findings suggest that chronic versus episodic course may be a putative differential feature. Further validation of such a distinction would require prospective studies, temperament evaluation, gender and neurobiologic approaches, and differential psychopharmacologic assignment and response.