Autografting with Ph-negative progenitors in patients at diagnosis of chronic myeloid leukemia induces a prolonged prevalence of Ph-negative hemopoiesis.

OBJECTIVE: In many patients with chronic myeloid leukemia (CML), a residual population of primitive normal (Ph-negative) progenitors persists despite the marked expansion of the leukemic (Ph-positive) clone. These cells may be found in the blood of patients studied soon after diagnosis or during the period of endogenous hematopoietic recovery that follows myeloreductive therapy. Based on those observations, we have developed a clinical protocol that allows collection of Ph-negative peripheral blood progenitor cells (PBPC) with transplantable hematopoietic regenerative potential. The aim of this study is to examine changes that occur in the percentage of Ph-negative- and Ph-positive-committed progenitor cells and to determine the relationship between changes and clinical outcome. MATERIALS AND METHODS: We followed 15 patients with CML, mobilized and autografted soon after diagnosis with 85%-100% Ph-negative PBPC for a median time of 28 months (range 18-50) after transplant. At 6 months, 1 year, 2 years, and last follow-up, cytogenetic analyses were performed on fresh bone marrow cells and on colony-forming cells (CFC). RESULTS: Autologous transplantation induces a reduction in the proportion of Ph-positive CFC, from 70%-100% to 0%-25% in the majority of patients (78%). After autografting, 8 of 15 patients achieved a long-lasting cytogenetic remission (median, 24 months; range, 21-43) with a Ph-positivity ranging between 0% and 20% at the level of mature mononuclear cells and colony-forming cells (CFC). In some patients, the majority of CFC remained Ph-negative, whereas the majority of the mature cells were Ph-positive. Other patients (5/15) developed cytogenetic relapse (100% Ph-positive), although they were in hematological remission. We found that detection of Ph-positive long-term-culture initiating cells (LTC-IC) in the marrow at diagnosis was the only factor significantly associated with recurrence of the disease (p < 0.01); on the other hand, the number of Ph-negative LTC-IC infused showed a significant correlation with a better outcome (p < 0.03). CONCLUSION: We have shown that a prolonged period of complete or almost complete Ph-negative hemopoiesis can be achieved in patients with CML who undergo autografting with Ph-negative progenitors. Longer follow-up study will be needed to assess whether these changes are associated with improved survival.

Association between drinking water disinfection and somatic parameters at birth.

We conducted an epidemiological study in Liguria, Italy, on the association between somatic parameters at birth and drinking water disinfection with chlorine dioxide and/or sodium hypochlorite. Over 2 years (1988-1989), 676 births at two public hospitals, one in Genoa (548 cases) and another in Chiavari (128 cases) were examined and data regarding both mother and child were obtained from hospital records. Results indicate a higher frequency of small body length (< or = 49.5 cm) and small cranial circumference (< or = 35 cm) in infants born to mothers who drank water treated with chlorine compounds. In particular, the statistical analysis (by simultaneous variance analysis and Scheffé test) indicated that there may be an association between infants with smaller body length and mothers who drank water treated with chlorine dioxide [adjusted odds radio (OR) = 2.0; 95% CI = 1.2-3.3] or sodium hypoclorite (adjusted OR = 2.3; 95% CI = 1.3-4.2) and between infants with smaller cranial circumference and mothers who drank water treated with chlorine dioxide (adjusted OR = 2.2; 95% CI = 1.4-3.9) or sodium hypochlorite (adjusted OR = 3.5; 95% CI = 2.1-8.5). The presence of neonatal jaundice is almost twice as likely (adjusted OR = 1.7; 95% CI = 1.1-3.1) in infants whose mothers drank water treated with chlorine dioxide.

Influence of dietary habits on thyroid status of a nomadic people, the Bororo shepherds, roaming a central African region affected by severe iodine deficiency.

OBJECTIVE: In contrast with the endemic goiter reported in several African countries, the nomadic Bororos of the Central African Republic have an unexpectedly low prevalence of goiter. This study was conducted to elucidate this puzzling observation. DESIGN: Thyroid function and iodine and thiocyanate intakes were evaluated in Bororos and inhabitants of the same area and compared with an Italian population. RESULTS: Urinary iodine concentrations indicated moderate iodine deficiency in the rural people and the Bororos. In the latter, no individual with clinical hypothyroidism was observed. Compared with the reference population, the Bororos had slightly lower thyroxine (T4) and free thyroxine (FT4), slightly increased tri-iodothyronine (T3) and T3/T4 ratio, slightly higher TSH, normal serum thyroglobulin, a prevalence of goiter of 17.1% and a higher urinary thiocyanate. The rural people showed striking differences: lower T4 and FT4, increased T3/T4 ratio, markedly increased TSH and thyroglobulin, a prevalence of goiter of 76.9% and a high urinary thiocyanate, indicating frequent consumption of cassava. A dietary survey indicated that the Bororos ingest large amounts of milk and related products but infrequently eat cassava. CONCLUSION: A minute difference in iodine deficiency between two populations induces totally different patterns of goiter and thyroid function. The reason for such a contrast probably involves differences in diet.

Metabolic syndrome in severely obese patients.

BACKGROUND: The authors assessed the prevalence of diabetes, hypertension, dyslipidemia and metabolic syndrome in patients with a high degree of obesity. METHODS: A retrospective investigation was planned in a cohort of obese patients with a wide range of body mass index (BMI) referred to a large University Hospital for weight loss. RESULTS: An increase in prevalence of diabetes and hypertension with increase in the degree of obesity was observed, while the prevalence of dyslipidemia and metabolic syndrome appeared to be independent of the BMI values. CONCLUSION: In severely obese patients a still unknown factor which affects differently glucose and lipid metabolism cannot be excluded.

Ovarian recovery after total body irradiation and allogeneic bone marrow transplantation: long-term follow up of 79 females.

Seventy-nine females undergoing allogeneic BMT following conditioning with total body irradiation (TBI), were prospectively followed between March 1983 and March 1992 with regular gynaecological examinations, including plasma levels of luteinising hormone (LH), follicle stimulating hormone (FSH), 17-beta oestradiol (E2) and pelvic ultrasonography. The end-points of this study were the following: (1) early and late effects of TBI on ovarian function, (2) compliance and results of hormonal replacement therapy (HRT), and (3) predictive events for ovarian recovery. During the first year post-BMT most adult women complained of vasomotor and/or genitourinary tract symptoms. These were associated with decreased E2 and increased LH-FSH plasma levels and a deterioration in their sexual life (94% of sexually active women). Forty-nine adult females were selected to receive systemic hormonal replacement therapy (HRT), consisting of cyclic transdermal oestrogens plus medroxyprogesterone acetate (MPA) or cyclic oral therapy with low doses of conjugated oestrogens and MPA: these patients were selected on the basis of age (< 45 years), absence of medical contraindications or subjective refusal. Compliance and tolerability were overall good: most women (65%) never stopped HRT; this was discontinued in 14 patients for medical reasons and in 3 because of refusal. Forty-three females completed 6 months of HRT: vasomotor symptoms disappeared in 91% of 58 women who previously referred these symptoms. Improvement of genitourinary symptoms was seen both with local and systemic hormonal therapy. However sexual symptoms were reduced in 21 of 26 women (81%) given HRT compared with 8 of 19 (42%) women given local treatment (p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Pancreatic fistula and relative mortality in malignant disease after pancreaticoduodenectomy. Review and statistical meta-analysis regarding 15 years of literature.

This paper analysed the literature published in the last 15 years regarding the onset of pancreatic fistula after pancreaticoduodenectony carried out for tumours in the periampullary region, in the head of the pancreas and in the distal common bile duct. Out of 8370 pancreatic resections we were able to go by only 2684 cases, which showed the type of treatment used in the remaining stump, the rates of leakage and relative mortality. The data collected were analysed statistically using the Cochran test and or the chi 2, evaluating the possible significant difference relative to the various methods of reconstruction. The onset of pancreatic fistrula was found to be statistically more frequent after ligation of the stump than after pancreatico-jejunal anastomosis (p = 0.001). Comparing the pancreatico-jejunal end-to-side anastomosis, to pancreatico-jejunal end-to-end and wirsung-jejunal end-to-side anastomosis the first one had shown a significantly higher rate only for leakage (respectively p = 0.008 and p = 0.010). The occlusion of the wirsung duct with biological substances showed better results compared to ligation (p = 0.001) only as regards onset of the fistula, while the comparison between the occlusion and the three types of anastomosis did not show any statistically difference, except for the pancreatico-jejunal end-to-side anastomosis, in which it was significant only as regards leakage (p = 0.009). The statistical analysis between pancreatico-gastrostomy and pancreatico-jejunal anastomoses indicated that the first technique had a lower morbidity rate than pancreatico-jejunal end-to-side (p = 0.001), pancreatico-jejunal end-to-end (p = 0.010) and wirsung-jejunal end-to-side (p = 0.011). We analysed and compared the results obtained before and after 1975, in order to discover whether was an improvement in the prevnetion or in the treatment of such a complication and its consequences. Furthermore, we tried to establish whether the transanastomotic drainage, the site of the neoplasm, the texture of pancreatic parenchyma and the patient's age could in any way influence the onset and course of the fistula.

Malignant tumors in the head of the pancreas and the periampullary region. Diagnostic and prognostic aspects.

This paper analyzes the value of ultrasonography (US), computerized tomography (CT) and endoscopic retrograde cholangiopancreatography (ERCP) to establish the location, nature and resectability of carcinomas of the pancreatic head and of the periampullary region. The prognostic importance of certain pathological factors in relation to survival was also evaluated. As regards the site of origin, 112 cases with carcinoma were classified as follows: 56 pancreatic, 32 ampullary, 10 common bile duct, and 14 undefined. Papillary tumors were more accurately defined by ERCP compared to CT+US (p = 0.033), whereas CT was less accurate than US+ERCP (p = 0.05). No significant differences were found in pancreatic and common bile duct tumors. Pathological confirmation was obtained with ERCP in 54 cases (46% pancreatic, 69% papillary and 50% common bile duct). In the remaining 58 patients (including 1 chronic pancreatitis) the diagnosis was confirmed with percutaneous or intraoperative biopsy. Tumor extent was better defined by US+CT. In 42 resected patients the final pathological examination revealed an error of preoperative staging in 79% pancreatic, 59% papillary, and 83% common bile duct tumors. Tumor size, nodal status, perivascular, capsular and portal vein infiltration proved to be significant prognostic factors for pancreatic tumors. Stepwise regression identified tumor size, capsular infiltration and perivascular invasion as the most important covariates for survival. Ulceration, papillary histotype, pancreas and Oddi muscle infiltration, grading, perineural, lymphatic and vascular involvement were found to be significant in papillary tumors. The Cox proportional hazard model showed that pancreatic, Oddi muscle, perineural infiltration, and histologic type respectively represent a relative risk of 5.93, 107.36, 21.31, 20.61. The limited number of cases of common bile duct primary did not allow us to carry out statistical analysis on these tumors.

Long-term outcome of children and adolescents with anorexia nervosa: study of comorbidity.

Eighty-seven children and adolescents with anorexia nervosa, admitted to the Gaslini Department of Child Neurology and Psychiatry between 1976 and 1990, were followed up after a mean of 9.6 years. Outcome measures included the Morgan Russell Outcome Schedule as modified by Jeammet. Outcome was good in 43 (53%) cases, intermediate in 27 (34%) cases, and negative in 11 (14%) cases. No deaths occurred. Based on the Jeammet assessment schedule, the most significant items predicting outcome were insight; sexual, familial, and social relationships; and mental state. Gender of patients and early disease onset did not seem to be predictive measures. Poor outcome was associated with a severe initial clinical picture and length of in-patient treatment. In regard to comorbidity, mood and personality disorders seemed to be negative prognostic indicators, whereas anxiety disorders did not show prognostic value.

Epilepsy associated with infantile hemiparesis: predictors of long-term evolution.

To study the evolution of epilepsy associated with infantile hemiparesis (IH) in relation to age and identification of factors predictive of pharmacoresistance. Thirty-four children with epilepsy and associated IH were followed for a period of 13 years and 3 months (range 5-19 years). All the patients underwent clinical evaluation and EEG, CT and/or MRI. Disease course was evaluated from the time of diagnosis of epilepsy to end of follow-up by differentiating the cases with severe pharmacoresistance from those with favourable outcome. Several possible prognostic factors were identified predicting evolution toward intractable epilepsy. Univariate statistical analysis by calculating odds ratio (OR) with 95% confidence interval (CI) and multivariate analysis by logistic regression were performed. Eleven cases presented severe epilepsy evolving toward pharmacoresistance; duration of epilepsy was always longer than 8 years. Twenty-three cases (seven with severe epilepsy and 16 with mild epilepsy) evolved toward remission; in these patients epilepsy duration was shorter (2-7 years) and a complete remission was obtained within 12 years of age. Significant prognostic factors associated with pharmacoresistance included: non-vascular causes, cortical lesions, mixed and frequent seizures during the first two years of epilepsy. Our results show that surgical treatment could be considered in cases with unfavourable prognostis factors.

Prognostic indicators of local recurrence in patients operated for rectal cancer.

BACKGROUND/AIMS: To identify subgroups of patients at high risk of local relapse after curative surgery for rectal cancer. METHODOLOGY: Thirty-five variables of 216 patients observed from January 1987 to December 1995 were retrospectively analyzed according to univariate and multivariate methods. Median follow-up was 38 months. RESULTS: High and moderate grade (P = 0.0001), Size > or = 5 cm (P = 0.013), lymph nodes involvement (P = 0.002) and patients with locally advanced rectal cancer underwent extensive surgery and postoperative radiation significantly increased local relapse; whereas surgical procedure and experience of surgeons had no influence. CONCLUSIONS: The above-mentioned prognostic factors of rectal cancer that show a risk of local relapse 2- to 3.5-times higher than comparative conditions could be useful in identifying subgroups of patients at high risk for local recurrence. These patients should undergo a careful selection according to risk factors of relapse in order to increase local control of disease performing "optimal" primary surgery, effective postoperative radiation and tailored follow-up.

Analysis of the distribution and genetic variability of viral isolates in a cohort of HCV-positive hepatopathic patients.

The genotyping of the hepatitis C virus (HCV) by viral nucleic acids sequencing allows accurate epidemiological evaluation of a cohort of patients suffering from HCV-related chronic hepatopathy. The identification of viral isolates, which can be generally associated with hepatic damage or, vice versa, which are more responsive to pharmacological treatment, might enhance clinical interest on the nature of the infecting genotypes. We, therefore, draw attention to those viral genotypes that are characterised by significantly high or altered viremic and enzymatic levels.

Interpretation and diagnostic implications of an immunoblotting (INNOLIA) test for HCV serology.

The association analysis of antibodies versus HCV, carried out with INNOLIA test, prevented a clear determination of the existence of specific serological patterns. In this respect, it may be of interest to monitor the immune response to the non-structural genomic regions (NS3, NS4, NS5). The INNOLIA kit is reliable, but susceptible to improvement in terms of specificity, sensitivity and biological standardization.

Role of viral isolate in the etiopathogenetic determinism of HCV infection: diagnostic and epidemiological evaluation.

HCV genotyping by nucleic acid sequencing emphasizes the difficulties involved in carrying out a more precise determination of the infectant viral population, probably due in part to the finding of still unknown isolates. Signs of heterogeneity in the genotype composition of the viral quasi-species and its evolutionary dynamism over time, together with the role played by some, more potentially aggressive, isolates in causing hepatic damage, encourage a more in-depth study of such topics.

[Pain in Guillain-Barré syndrome]. / Il dolore nella sindrome di Guillain-Barré.

The clinical features of pain were analysed in 31 children with Guillain-Barré Syndrome. Pain may be considered characteristic of childhood GBS. Pain, various painful sensations and dysaesthesias must be emphasised in the early diagnosis of GBS. An attempt was made to identify the meanings of early pain (preceding or accompanying the onset of weakness), late pain, mild or severe sensory symptoms or signs and the role played by triggering or perpetuating factors. Only the application of a diagnosis-therapeutic protocol for childhood GBS, that pays particular attention to the problem, will suggest satisfactory answers to research.

Alexithymia and body weight in obese patients.

The authors evaluated severely obese patients to determine whether being far different in body shape from the accepted standard may cause obese people to develop alexithymic personality traits. They evaluated the food- and weight-related attitudes in obesity surgery patients and in long-term follow-up of those who had previously had biliopancreatic diversion (BPD) for obesity. One quarter of the obese patients had alexithymic characteristics without any modification following stable weight loss, a rate of alexithymia similar to that observed in the nonclinical population. Furthermore, the frequency of alexithymia and the patients' scores on the Toronto Alexithymia Scale were similar in obese and post-BPD individuals. The authors concluded that being obese by itself does not influence the presence of alexithymic personality traits. However, they suggest that the improvement in food-related and weight-related attitudes following stable weight loss may be different in alexithymic and in nonalexithymic obese patients.

[Eating behavior and energy expenditure]. / Comportamento alimentare e spese energetiche.

The relationships between the resting energy expenditure (REE), measured by indirect calorimetry, and eating behavior, assessed by the "Three Factor Eating Questionnaire" were evaluated. The study was carried out in a group of healthy never-obese subjects and in two groups of formerly obese people, who have maintained a normal weight for more than two years. The subjects of the first formerly obese group had brought their body weight to normal by dieting. The second one comprised subjects following biliopancreatic diversion for obesity (BPD) in the long term, who maintain a normal weight because of the intestinal malabsorption due to the operation regardless of food consumption. In comparison with the other subjects, significantly higher cognitive restraint score values were observed in the post-diet subjects. Furthermore, a negative significant correlation between cognitive restraint and REE was found in the non operated subjects, while such correlation was not present in the BPD subjects. Therefore, in normal people cognitive restraint has to be considered to be related to behavioral-cognitive factors rather than biologically driven by energy requirements.

162 HIV-1 infected pregnant women and vertical transmission. Results of a prospective study.

BACKGROUND: Aim of this paper is to describe the changes over a 16-year period of the characteristics and management of HIV infected pregnant women. METHODS: Prospective study: analysis of data obtained from 162 women and 176 infants. Factors evaluated included: maternal socio-demographic level, immunological and virological parameters, antiretroviral therapy, mode of delivery, pregnancy outcome and babies follow-up. RESULTS: The proportion of women with heterosexual acquisition of infection has increased significantly from 13.5% in 1985-1989 to 47.1% in 1996-2001 (p<0.0005, Fisher's exact test), while the proportion acquiring HIV through injecting drugs has declined. Mean CD4 cell count at delivery was 535 x 106/l (+/-522.3 x 106/l). In 1990, 50% of mothers received antiretroviral therapy, rising significantly to 87.5% in 2000. The elective cesarean section was introduced in 1998 and its rate has increased to 75% in 2000. The vertical transmission rate changed from 9.5% in 1985-1989 to 14.3% in 1996-2000 (this difference was not statistically significant, Fisher's exact test). CONCLUSIONS: Social characteristics of the HIV-infected women have changed since the mid-1980s: in recent times women are having children at increasingly older ages and are more likely to know that they are HIV infected when they become pregnant. Antiretroviral therapy, elective caesarean delivery and avoidance of breastfeeding can reduce transmission of HIV, but the vertical transmission rate was unaffected by their use in our study and it remains high in comparison with rates reported from other studies.

[The use of n-3 fatty acids in chronic juvenile arthritis]. / Impiego degli acidi grassi n-3 nell'artrite cronica giovanile (ACG).

Juvenile Chronic Arthritis (JCA) is a chronic disease still lacking of a complete therapeutic solution. Therapy traditionally used consists of non steroidal anti-inflammatory drugs and in some selected cases of gold salt and immuno-suppressive agents. Recently it has been described the possibility of a dietary supplementation of n-3 fatty acids in addition to conventional pharmacotherapy. The aim of our study is to demonstrate the real efficacy of this dietary supplementation on JCA symptoms. The group of 16 patients treated, compared to a control group of 16 patients, has shown a significative decrease of CRP.

[Double-blind controlled comparison of placebo and paracetamol in patients with G-6-PD deficiency]. / Confronto in doppio cieco controllato tra placebo e paracetamolo in soggetti carenti di G-6-PD.

In this study are reported 17 patients with G-6-PD deficiency. These subjects have been studied with double-blind trial between placebo and Paracetamol, looking for the possible hemolysis induced from drug in these children with G-6-PD deficiency. Hemolysis had been valued by various hematological parameters (Hb, erythrocyte count, reticulocytosis, bilirubinemia, haptoglobin, hemopexin, and survival of erythrocytes marked with Cr). The results (8 cases with placebo and 9 cases with paracetamol) demonstrate that paracetamol have not induced hemolysis in these G-6-PD deficient subjects.

[Normotest in the early neonatal period]. / Ii normotest nel periodo neonatale precoce.

The aim of this study is the behavior of Normotest (NT) values in newborns in the first 4 days of life. The study has been carried out between January, 1982, and December, 1984, at the Department of Child Health and Neonatal Medicine - School of Medicine - University of Genoa. The number of infants tested was 1320. 694 were males and 626 females, 529 preterm (G.A. less than 37 weeks) and 791 full term babies. Infants have been tested from one to five times in the first four days of life, with the first evaluation within 12 hours of life. 1215 newborns (92%) presented NT values greater than 20%, 105 babies (8%) had NT below 20% in at least one evaluation, and received Vitamin K1 (0.5 mg/kg i.m.) as prophylaxis, being thereafter excluded from this study. Among the neonate with NT greater than 20%, 426 babies have been considered, who had, at least, three evaluations in the first four days of life. 288 (68%) of the 426 newborns, had not important disease, while 138 (32%) were sick neonates; of these babies 88 (64%) had respiratory distress syndrome and 50 (36%) had an infectious condition. The mean of NT values of the 426 newborns decreased from the first (33.84%) to the 2nd day (32.72%), with a following increment in 3rd (35.29%) and 4th day of life (39.01%). Newborns with gestational age (G.A.) less than 34 weeks showed significantly lower values than newborns with G.A. between 34-37 weeks and those with G.A. greater than 37 weeks. No newborn with NT values greater than 20% either received vitamin K or showed symptoms of haemorrhagic disease in early or later neonatal period.