Fresh and cryopreserved arterial homografts: immunological and clinical results.

INTRODUCTION: This prospective study defined the immunological and clinical results after fresh and cryopreserved arterial homograft replacement due to graft infection. MATERIALS AND METHODS: Thirty patients who underwent ABO-compatible homograft transplantation were studied for anti-human leukocyte antigen (HLA): antibody production and CD3- and CD4- versus CD8-positive lymphocyte subsets. Nine patients (30%) received immunosuppressive treatment with cyclosporine (1 to 3 mg/kg/d). Immunological studies were performed preoperatively, and early (1, 3, 7 days) and late (1, 3, 6, 12, 24, 36, 48 months) during follow-up. Abdominal computed tomography scans were performed postoperatively at 1, 6, 12, 24, 36, and 48 months of follow-up. RESULTS: Preoperatively, antibodies were not detected. Postoperatively, a progressive increase in percent panel reactive antibodies was observed in all patients 1 month after the transplant. There were no difference between fresh and cryopreserved homografts. The antibody response among patients treated with cyclosporine was less pronounced and delayed. Recipient antibodies were directed against donor-specific antigens. During the immediate postoperative period (1, 3, 7 days) there was a slight increase in CD3- and CD4-positive T lymphocytes and a concomitant decrease in the CD8 subset. Later, CD3 and CD4 progressively decreased and the CD8 set increased. Clinically, no patients had signs of recurrent infection upon late follow-up. Four patients died (13%), but only one death was homograft-related (rupture of the graft). At 2-year follow-up, two patients showed stenotic lesions due to chronic rejection. Clinically, no differences were noted between fresh and cryopreserved homografts, or between patients treated with or without cyclosporine. CONCLUSIONS: Fresh and cryopreserved arterial homografts are immunogenic; they induce a strong anti-HLA antibody response, similar to chronic rejection.

[Cancer of the anus. Analysis of our surgical experience]. / Il cancro dell'ano. Analisi di un'esperienza chirurgica.

BACKGROUND: The different histological varieties of anal cancer due to the presence of different histogenesis tissue can be anatomically distinguished from anal canal tumours by their growth in a periorificial or marginal site. The first appearance of symptoms are common to usual non-tumoral pathologies, but can be ascertained at an early stage using biopsy. Anal cancer can be treated with surgery, conservative or radical treatment, radiotherapy alone and radiochemotherapy with possible surgery. METHODS: Based on the results obtained by radical surgical exeresis due to the frequent spread of tumours to the pelvis and the possibility of metastases in the cava and portal vein, current therapeutic possibilities were analysed in 101 patients with anal cancer undergoing abdominal-perineal surgery. The priority of radiochemotherapy was underlined, reserving the faculty of surgical treatment for cases of large tumours with insufficient penetration. RESULTS: The choice of therapy should be modulated according to its histology, tumour site, increase and grading. Only surgery can ensure long-term results similar to those obtained using surgical treatment of rectal cancer. CONCLUSIONS: For the best results the authors recommend a therapeutic approach which involves some methods used for an early diagnosis.

Squamous-cell carcinoma developing within anal lichen planus: report of a case.

AIM: We present a case of squamous-cell carcinoma developing within perianal lichen planus. This is a chronic or recurrent cutaneous and/or mucosal dermatosis affecting less than 1 percent of the population. Neoplastic degeneration of cutaneous lichen planus is rare; only one case of squamous-cell carcinoma developing within perianal lichen planus has been described up until now in the international literature. CASE REPORT: Our case involved a 68-year-old woman with chronic, long-term lichen planus spreading all over the vulva and perianal region and the mucosa of the anal canal, where squamous-cell carcinoma developed within the perianal lichen planus. Treatment consisted of wide, circular excision of the perianal skin and mucosectomy of the anal canal up to as far as 1 cm above the dentate line. Reconstruction was performed by means of two V-Y bilateral subcutaneous flaps. CONCLUSION: Wide excision was performed not only to remove the squamous-cell carcinoma but also the lichen planus to prevent recurrence of metachronous or synchronous squamous-cell carcinoma. Follow-up at one year after surgery showed no local recurrence of either lichen planus or squamous-cell carcinoma, which suggests that surgical removal should be the therapy of choice for long-term, chronic perianal lichen planus that has proved to be resistant to medical therapy.

[Phantom rectum after Miles' operation]. / Il retto fantasma dopo intervento di Miles.

The authors observed symptoms relating to the existence of a phantom rectum, a phenomenon about which little is still known, in 233 cases (32.1%) in a series of 724 patients undergoing amputation of the abdomino perineal rectum due to malignant neoplasm. The genesis of this phenomenon is attributed to an abnormal reactivity of the cortical and thalamic projection areas with greater response to stimuli from the stump or aspecific visceral stimuli, or even stimuli from the adjacent cortical regions. The psychodynamic aspects linked to the patient's need to develop a different body awareness should not be underestimated; this has to integrate a new anatomic reality, such as colostomy in the place of the anorectum, entailing the relinquishment of the previous body scheme. Prevention and treatment of phantom rectum, which is painful in 27% of cases, is essential for a correct operating technique, adequate psychotherapeutic support, the patient's active participation in a reeducation programme for colostomy management. It should not be forgotten that painful phantom rectum, especially with late onset, may be diagnostically significant as an indicator of the recurrence of neoplastic pathology, sometimes allowing diagnosis to be anticipated by several months. This underlines the importance of carrying out a careful postoperative clinical, biohumoral and radiological control in these patients, including pelvic CT. In the authors' experience of 233 patients suffering from phantom rectum, it was possible to document the presence of neoplastic recidivation in 30 cases (12.8%) using pelvic CT. In these cases, symptoms appeared after a disease-free interval of 26.3 months (range 3-75 months), whereas the presence of phantom rectum without recidivation is usually described in the first 2 months after surgery.

[Surgery of anal fistulas]. / La chirurgia delle fistole anali.

The authors report a study on 120 patients with anal fistula (111 males and 9 females). The average age was 44.3 years (median 44, SD +/- 14.807). 64.1% of patients had an intersphincteric fistula, 23.3% hanal transphincteric fistula, 1.6% a suprasphincteric fistula, 7.5% a horseshoe fistula and the 3.3% an extrasphincteric fistula. We treated 14 patients (11.66%) with direct surgical treatment. The other 106 had various types of treatment depending on the localisation and the involvement of the anorectal sphincter. We had 11 cases (9.1%) of complications, such as recurrence in 5 patients (4.1%) transitory incontinence in 2 cases (1.6%) and finally postoperative bleeding in 3 patients (2.5%).

[Rubber band ligation of hemorrhoids. Our experience]. / La legatura elastica delle emorroidi. Nostra esperienza.

The authors present their series of rubber band ligation of hemorrhoids performed from 1991 to 1994 in the Unità di Colon Proctologia of Modena, that is located in the Second Division of Surgery of the Surgical Department of Modena University. In that period 158 patients were treated. Age range was between 17 and 93 years old, and patients were affected by II and III degree of hemorrhoids. The complications verified were: 14 cases of recurrence (8.8%), 2 cases of severe bleeding, no case of perineal sepsis or urinary retention. Other complications of less importance were 89 cases of pain (56.3%), not severe bleeding in 23.41% of patients. Results show that this method of treatment of hemorrhoids, used by experts, is the first choice treatment of this pathology.

Vertical subcutaneous pedicle flaps for posterior perineal reconstruction. Report of three cases.

PURPOSE: Loss of a certain amount of cutaneous tissue of the perineal region may be remedied by first intention with creation of cutaneous flaps, thus preventing second intention healing. METHODS: We present three emblematic cases in which the posterior perineal region was reconstructed by means of vertical subcutaneous pedicle flaps, subsequent to cutaneous tissue loss after surgery for extensive condilomas or neoplastic pathologies. RESULTS: Tissue loss was repaired by means of a V-Y type vertical subcutaneous pedicle flap, constructed laterally of the extirpation zone and advanced in a median direction. In all cases, no ischemia or infection of flaps occurred; sphincteral continence and long-term aesthetic results have proved to be satisfactory. CONCLUSIONS: Vertical pedicle subcutaneous flaps are well vascularized, extremely mobile, and easy to perform and have no serious postoperative complications.

Sepsis-bacteraemia and other infections due to non-opportunistic bacterial pathogens in a consecutive series of 788 patients hospitalized for HIV infection.

A retrospective study was carried out to evaluate the incidence, etiology and role of non-opportunistic bacterial infections in a series of 788 consecutive HIV-infected patients hospitalized during the last 7 years; 71.9% of patients were i.v. drug addicts, 15.6% homo-bisexual men, 7.4% heterosexuals, 2.7% haemophiliacs and 2.4% children with vertically-acquired infection. According to the CDC classification of HIV infection, 71 patients were classified as CDC I-II, 148 as CDC III, and 569 (72.2%) as CDC IV. Diagnosis of bacterial infection was based on signs and symptoms, in association with the isolation of microorganisms consistent with the clinical picture. Two hundred and nineteen patients out of 788 (27.8%) (4 in CDC group I-II, 34 in CDC III and 181 in CDC IV), presented one or more episodes of non-opportunistic bacterial infection. The morbidity of these infections showed a significant correlation with the progression of HIV disease (CDC III vs. CDC I-II [p < 0.003] and CDC IV vs. CDC III [p < 0.05]), but no significant relation was found with age, sex or type of risk for HIV infection. The most frequent clinical picture was sepsis/bacteraemia (33.3%), followed by respiratory tract (23.8%), and genitourinary tract (20.8%) infections. A total of 399 bacterial pathogens were isolated in 303 different episodes of infection: 211 (52.9%) were gram-positive and 188 gram-negative, with Staphylococcus aureus (69 isolations), Staphylococcus epidermidis (50), and Pseudomonas spp. (48) as the major pathogens. Sepsis/bacteraemia was the most frequent clinical picture associated with growth of gram-positive pathogens, while detection of gram-negative bacteria appeared more significantly related with genitourinary or respiratory tract localizations. Bacterial infections in hospitalized HIV-infected patients, even though rarely life-threatening, need particular attention because of the high incidence and recurrence rate, the wide aetiological and clinical spectrum, the frequent microbial associations and the strict relationship with the progression of HIV disease.

In vitro immunotoxicity of +/- 2'-deoxy-3'-thiacytidine, a new anti-HIV agent.

The present study compares the in vitro effect of (+/-)-2'-deoxy-3'-thiacytidine (BCH 189) a new synthetic anti-HIV-1 dideoxynucleoside, with 3'-azido-3'-deoxythymidine (AZT) on the immune function of lymphocytes from 10 normal and 12 HIV-1+ patients (CDC II and III). The effect of different doses of BCH 189 and AZT was analysed in vitro on: (i) T cell proliferation after stimulation with concanavalin A (Con A) or anti-CD3 MoAb; (ii) B cell proliferation and immunoglobulin production after stimulation with pokeweed mitogen (PWM); (iii) cytokine production (IL-2, IL-6, GM-CSF, tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) from lymphocytes stimulated with anti-CD3 MoAb or phytohaemagglutinin (PHA). BCH 189 inhibited the proliferation of B and T lymphocytes from normal and HIV+ subjects less than AZT; even if lymphocytes from HIV+ (CDC III) subjects produced higher levels of IL-6 and TNF-alpha, neither BCH 189 nor AZT molecule interfered with cytokine release. Immunoglobulin production from B lymphocytes was inhibited only by a high concentration (50 microM) of BCH 189 or AZT. These results show that BCH 189 affects lymphocyte proliferation in vitro less than AZT, and support its use in clinical trials in HIV-infected patients.

Recombinant alpha-interferon 2b in the treatment of HIV-related thrombocytopenia.

OBJECTIVE: To assess the efficacy and the mechanism of action of alpha-interferon (alpha-IFN) in the treatment of HIV-related thrombocytopenia. METHODS: Thirteen HIV-positive subjects [nine men and four women with severe thrombocytopenia (platelets, < or = 30 x 10(9)/l)] were treated with alpha-IFN 2b alone at a dose of 3 x 10(6) U three times a week for 5 weeks. Haematological parameters, platelet kinetic and bone-marrow myeloid progenitor cultures [megakaryocyte colony-forming units (CFU-MK); granulocyte macrophage CFU (CFU-GM) and erythroid burst-forming units (BFU-E)] were evaluated before and after treatment in responsive subjects. RESULTS: Seven out of 13 subjects showed a partial response (platelets, 50-149 x 10(9)/l) after alpha-IFN 2b therapy. Platelet survival as evaluated by 111In-oxine significantly increased, while platelet turnover showed a slight but not statistically significant increase after treatment. The growth of bone-marrow myeloid progenitor cells decreased after alpha-IFN 2b therapy, again without statistical significance. CONCLUSION: alpha-IFN 2b may increase the platelet count in HIV-positive subjects with severe symptomatic thrombocytopenia by prolonging platelet survival. The immunomodulatory and antiviral action of this drug may be responsible for prolonged platelet survival.

[Carcinoid tumors of the appendix. Review of the literature and two case reports]. / I tumori carcinoidi dell'appendice. Analisi della letteratura e presentazione di due casi.

Gastrointestinal carcinoids are infrequent but at the same time hardly rare tumours. They are often chance findings but, as is clearly reported in the literature, their potential malignancy should not be overlooked. They are most commonly localised in the appendix. The authors describe two case reports of carcinoid tumours of the appendix, one of which was diagnosed during left hemicolectomy due to Crohn's disease and the other during acute appendicitis. Prognostic and therapeutic problems are discussed in the light of the most recent literature.

Elevated plasma levels of vasoactive intestinal peptide in AIDS patients with refractory idiopathic diarrhoea. Effects of treatment with octreotide.

OBJECTIVE: To evaluate plasma levels of vasoactive intestinal peptide (VIP) in AIDS patients with refractory idiopathic diarrhoea, and to assess the role of treatment with octreotide. PATIENTS: Three AIDS patients were evaluated for severe watery diarrhoea of 2-6 months' duration, which was complicated by weight loss, weakness, and fluid and electrolyte abnormalities. They had not shown a significant response to several regimens of empirical antimicrobial chemotherapy, or symptomatic antidiarrhoeal treatment. METHODS: A complete diagnostic examination, including repeated microbiological evaluation and radiological, ultrasonographic, endoscopic and histological examination, was performed. Plasma levels of VIP were determined by radioimmunoassay and compared with concentrations in a group of healthy subjects. RESULTS: Since no clinically significant results were obtained from standard diagnostic evaluation and empirical therapeutical attempts, idiopathic refractory diarrhoea was diagnosed. Plasma concentrations of VIP were moderately elevated in all three subjects examined, with levels of 11.5, 17.5 and 9.5 pmol/l (values < 8.8 pmol/l in the control group). One patient received 50-100 micrograms octreotide three times daily subcutaneously for 6 months, resulting in complete resolution of diarrhoea and significant improvement in body weight and quality of life, together with a reduction in VIP concentration to within normal values. CONCLUSIONS: Although the somatostatin analogue octreotide has been used successfully in the management of both infectious and non-infectious AIDS-related diarrhoea, gastrointestinal neuroendocrine function and circulating humoral mediators of diarrhoea have not hitherto been investigated extensively in HIV-infected subjects. Our data on the association of idiopathic secretory diarrhoea and elevated plasma VIP levels provide a possible pathophysiological rationale for identifying AIDS patients whose refractory diarrhoea may be more responsive to octreotide treatment.

Abdominal lymphadenopathy detected by ultrasonography in HIV-1 infection: prevalence and significance.

By using abdominal ultrasonography (UlS), deep nodes were detected in 41 of 85 (48%) HIV-1 positive subjects, most of them heroin addicts, but in none of 85 healthy HIV-negative controls. Computerized tomography, performed in 10 cases of lymphadenopathy, invariably confirmed the UlS findings. Prevalence [asymptomatic carriers: 8/15 (53%); PGL patients: 8/18 (44%); ARC: 13/27 (48%); AIDS: 12/25 (48%)], number, size, and site of deep nodes were comparable among the different CDC groups. No correlation was found between abdominal and superficial lymphadenopathy. Median serum concentrations of gammaglobulins (g/dl) and IgG (mg/dl) were higher in patients with than without deep nodes (2.25 vs 1.87 and 2540 vs 1900, respectively) (p < 0.01) as well as in cases with than without superficial nodes (2.15 vs 1.80 and 2340 vs 1941, respectively) (p < 0.05). Abdominal lymphadenopathy occurred during all stages of HIV infection even in asymptomatic carriers: this should be considered in the differential diagnosis of UlS-detected deep nodes. Enlargement of either deep or superficial nodes seems to reflect a state of polyclonal B cell activation.

Infective diseases during pregnancy and their teratogenic effects.

TORCH group infections (toxoplasmosis, others, rubella, cytomegalovirus, herpes) are the most serious infectious diseases during pregnancy due to the seriousness of possible embryo-fetal lesions. Rates of transmission and degree of the damage on the product of conception have been described as well as congenital malformation pictures and neonatal illness still observed following to Toxoplasma, HSV, VZV, CMV and Rubella virus infections. Too often, it is very hard to discriminate between primary and recurrent infections in pregnancy, notwithstanding the possible implications. Since at present, neither effective vaccines nor resolutive therapies are available against viral infections, the main means against infection of the foetus still remains the prevention of infections in the pregnant woman.

[Thoracic lymphoma and AIDS]. / Lymphome thoracique et SIDA.

During the past 4 years, 122 patients with AIDS and 20 with thoracic lymphoma associated to AIDS were observed. There were 18 cases of non-Hodgkin's lymphoma, mostly at a high grade and a high b-cell stage (Burkitt's or Burkitt-like lymphoma) (16 cases). This prevalence reflects the general increase in the number of neoplasms secondary to immunosuppression, which goes along with the improvement of prevention and the control of opportunistic infections. Out of these 20 lymphomas in AIDS, 5 (25%) produced thoracic lesions; in 4 cases, the initial site of the disease was in a thoracic site. The frequency of such expressions is greater that reported in the literature. The radiological appearances are atypical relative to the classical signs of lymphoma in the general population, with predominantly nodular forms (60%) or peripheral, fast-growing masses that are likely to invade the thoracic wall. Isolate lymph node invasion is possible, as well as pleural effusion. Though not pathognomonic, this appearance is highly suggestive of lymphoma in AIDS (LDS) in HIV-positive patients. In all patients with pulmonary lymphoma, CT showed bilateral lesions in a greater number than plain radiography had shown, with morphological and CT appearances that allowed a correct approach of the diagnosis and an appropriate choice of the site of biopsy.

Anti-hepatitis C virus antibodies amongst Italian homo-bisexual males.

The authors report on an anti-hepatitis C virus antibody (HCV Ab) prevalence (6.9%) in 622 homo-bisexual males from Northern Italy, voluntarily attending an HIV and STDs screening program in the period 1984-89. The anti-HCV antibody prevalence shows a significant correlation with: i) presence of serological markers for HBV (O.R. = 3.12, 95% C.I. = 1.53-6.52) and HIV (O.R. = 12.09; C.I. = 6.52-22.52) infection; ii) a stable relationship with an anti-HCV antibody positive partner (O.R. = 7.79; 95% C.I. = 2.50-23.90); iii) more than twenty different male partners per year (O.R. = 2.55; 95% C.I. = 1.17-5.66). These data demonstrate the existence of a sexual transmission of HCV among homosexuals. This route might contribute in maintaining endemic levels of HCV infection in the homo-bisexual population and it might represent an important way of spreading the virus in the general population too.

Detection of circulating p24 antigen-positive CD4+ cells during HIV infection by flow cytometry.

OBJECTIVES: To determine the amount of circulating CD4+ cells positive for intracellular p24 antigen during HIV infection, and to correlate the results with clinical, virological and therapeutic parameters. METHODS: Data were obtained from 24 anti-HIV-negative subjects (controls) and 47 anti-HIV-positive patients classified according to clinical diagnosis, serum p24-antigen assay results, and antiretroviral treatment with zidovudine, using a modified flow cytometric assay for the detection of intracellular HIV p24 antigen (p24-FCA) in circulating CD4+ lymphocytes. RESULTS: The proportion of CD4+ lymphocytes positive for p24-FCA correlated well with HIV infection (1.685 +/- 1.902 versus 0.160 +/- 0.152 in controls; P < 0.001) and clinical progression [Centers for Disease Control (CDC) stage II: 1.310 +/- 1.187; CDC stage III 1.145 +/- 1.442; CDC stage IVA/C2: 2.335 +/- 2.112; CDC stage IVC1: 2.066 +/- 2.420]. The percentage of CD4+ cells positive for HIV p24-FCA was inversely correlated with an absolute peripheral blood CD4+ lymphocyte count (Spearman's rank correlation = -0.324; P < 0.05). However, there was no statistically significant difference between patients in presence (n = 27; 1.938 +/- 2.095) or absence (n = 20; 1.343 +/- 1.594) of serum p24 Ag. The variable linked most strongly to the detection of intracellular p24 in anti-HIV-positive patients was zidovudine treatment: the proportion of p24-FCA-positive CD4+ lymphocytes was significantly lower (0.825 +/- 0.910) in the treated patients (n = 25) than in the untreated patients (n = 22; 2.662 +/- 2.248; P < 0.001). CONCLUSIONS: Our results suggest that CD4+ p24 Ag-FCA is a rapid and easy test for the identification of the proportion of CD4+ lymphocytes with intracellular p24 Ag, and that it could be more appropriate than serum p24 Ag assay in evaluating disease progression and efficacy of antiretroviral treatment.

Vertical transmission of human immunodeficiency virus type 1. Prognostic value of IgA antibody to HIV-1 polypeptides during pregnancy.

In a retrospective study of 31 pregnant women infected with human immunodeficiency virus type 1 (HIV-1), nine (29%) infants presented unequivocal signs of HIV-1 infection (persistent p24 antigenemia and/or positive virus isolation). All serum samples obtained from the others, during pregnancy and on delivery, were studied for specific antibody (IgA) production by immunoblotting analysis to establish a possible link between the presence of a defined antibody class and mother-to-child viral transmission. The majority (16 of 22) of HIV-1-seropositive mothers who delivered uninfected children showed IgA antibody to low-molecular-weight HIV-1 polypeptides during pregnancy. Among those who delivered infected babies, only one showed a weak IgA reactivity to HIV-1 during pregnancy. Thus, our results suggest that immunoblotting study of IgA may be a diagnostic adjunct to predict the risk of mother-to-child HIV-1 transmission.

Recombinant interleukin-2 (rIL-2) in acquired immune deficiency syndrome (AIDS): preliminary report in patients with lymphoma associated with HIV infection.

In an ongoing phase II study, 12 patients with lymphoma and HIV infection were treated with zidovudine (ZDV) and recombinant interleukin-2 (rIL-2) to evaluate if this association may produce beneficial effect on the immunologic status and the outcome of lymphoma. The protocol included daily doses of rIL-2 at 6 MIU/m2 over 5 days in c.i. per week for a total 4 courses; ZDV was associated at 600 mg/d in the period under study. An improved CD4 count, exceeding 2- to 4-fold the basal count, was obtained in patients with a basal CD4 number greater than 100/microliters accompanied by a significant increase of NK and LAK activity (p less than 0.001). From the clinical point of view the reduction of tumor manifestation was proportional to CD4 basal number; 2 patients from those with CD4 greater than 100/microliters obtained a complete remission after rIL-2 and ZVD. The p24 antigen, taken as parameter of viral replication, remained invariably negative after rIL-2 and ZDV in patients already negative and became negative in 1 patient previously positive. Our conclusion is that the association of rIL-2 and AZT is safe and useful in patients with lymphoma and HIV infection.

[Monitoring of several hematological parameters of the erythroid series in patients with HIV infection treated with zidovudine]. / Monitoraggio di alcuni parametri ematologici della serie eritroide in pazienti con infezione da HIV in trattamento con zidovudina.

Haematologic toxicity is the most common adverse effect related to long-term administration of zidovudine (AZT). We evaluated the kinetics of modifications of some haematologic parameters of erythroid series in 65 patients with HIV infection treated with AZT for a mean duration of 7.6 +/- 4.7 months (13 of them with a previous diagnosis of AIDS, 34 with ARC, 18 asymptomatic or with LAS/PGL), in order to correlate the observation and the evolution of these laboratory changes with the onset of severe anaemia. The development of macrocytosis occurs in a large majority of AZT-treated subjects, in spite of folate and vitamin B12 supplementation; the monitoring of erythrocytes distribution according to cellular volume and cellular haemoglobin concentration makes it possible to early recognize the occurrence of modification in erythropoiesis. There is no correlation between an elevated mean corpuscular volume and the development of severe anaemia (Hb less than or equal to 9 g/dl) in an individual patient; a fall in the reticulocyte count appears to be the earliest peripheral blood sign of the development of bone marrow toxicity.