[Health care and infective aspects in patients affected by common variable immunodeficiency assisted in the Lazio Regional Authority Reference Centre for Primary Immunodeficiencies]. / Aspetti infettivologici ed assistenziali di pazienti con Immunodeficienza Comune Variabile afferenti al Centro di Riferimento della Regione Lazio per le Immunodeficienze Primitive.

Common variable immunodeficiency (CVID) is a chronic condition characterised by a predominant defect of humoral immunity. In most cases the diagnosis of CVID is made during adulthood; the main clinical features of CVID are chronic and relapsing infections (mainly of respiratory and gastroenteric tracts). CVID patients may also develop neoplastic and autoimmune diseases. In our centre (the Regional Centre for Primary Immunodeficiencies of the Lazio Regional Authority) we administered a 23-item questionnaire to 60 patients with CVID undergoing substitutive therapy with intravenous immunoglobulins (IVIG) about their demographic characteristics, time of clinical onset, time of diagnosis of CVID, clinical features, IVIG doses and administration intervals, and self-assessment of health status. In addition, the clinical history of all patients was reviewed, and the levels of serum IgG, IgA and IgM were evaluated and compared with the pre-therapy serum concentration. Moreover, an analysis of the treatment costs was performed. At onset, 67.2% of patients presented recurrent respiratory infections, and 50% had infections of the lower respiratory tract; 39.6% of the patients had gastroenteric infections. Most patients (57%) had recurrent infections of at least 2 of the respiratory, gastroenteric and/or urogenital tracts. In 37.9% of the group the diagnosis of CVID was made in less than 2 years after the beginning of symptoms, but in many cases (22.4%) the diagnosis took more than 10 years. 93% of patients are treated with a dose of IVIG between 6 and 15 g per administration, with intervals between 2 and 3 weeks. The review of patients'clinical history showed that 43% of patients have had respiratory infections during the follow-up in our Centre, 43% have splenomegaly (3% were also subjected to splenectomy) and 18.3% have autoimmune diseases. The mean concentration of IgG before the beginning of IVIG therapy was 235 mg/dl, while during the follow-up it was 664 mg/dl. Given the long time often required for diagnosis, general physicians and specialists should be better informed in order to make diagnosis swifter. The substitutive therapy with IVIG is effective in preventing recurrent infections and complications. A thorough follow-up is important for diagnosing neoplastic and autoimmune complications; in addition, immunologic analysis of peripheral blood and bone marrow are useful in identifying subgroups of patients with more severe clinical features. Finally, in selected patients, treatment costs may be controlled by modifying the dosage of IVIG or the intervals between administrations.

Early catheter removal in 100 consecutive patients undergoing radical retropubic prostatectomy.

OBJECTIVES: To investigate the outcome of 100 consecutive patients selected for early catheter removal after radical retropubic prostatectomy (RRP), where urethral catheter drainage is used routinely for 2-3 weeks. PATIENTS AND METHODS: The study included 129 consecutive patients with clinically localized prostate cancer who underwent RRP. Catheters were removed in the clinic (with no radiographic studies) 8-9 days after RRP provided there was no evidence of urine leak, pelvic haematoma, rectal injury or severe obesity. The follow-up (mean 21 months) results were available for 118 patients, 100 of whom were candidates for early catheter withdrawal. Their records were reviewed for evidence of complications, including urinary retention, anastomotic stricture formation and urinary incontinence. RESULTS: Urinary retention developed in two of the 100 patients, requiring simple catheter replacement. Nine patients developed bladder neck contracture requiring dilatation or incision. No patients developed anastomotic disruption, urinary tract infection or pelvic abscess. At the mean follow-up of 21 months, 76% of patients were continent and did not require pads; 19% of patients had mild stress urinary incontinence requiring the use of 4 pads/day. CONCLUSION: With appropriate patient selection as described, catheters can be removed in the clinic (with no radiographic studies) 8-9 days after RRP, with no increased incidence of complications, including anastomotic stricture, retention or incontinence.

Characterization of ureteral dysfunction in an experimental model of congenital bladder outlet obstruction.

PURPOSE: Ureteral dysfunction is a significant sequela of congenital bladder outlet obstruction. However, the structural and functional alterations associated with ureteral dysfunction are not well defined. A model of fetal bladder obstruction in sheep was used to characterize the changes in ureteral smooth muscle, extracellular matrix (ECM) and functional properties in response to bladder outlet obstruction. MATERIALS AND METHODS: Partial bladder outlet obstruction was created in fetal sheep at gestational age 95 days via placement of a metal ring around the proximal urethra as well as ligation of the urachus. Ureters were harvested at 109 and 135 days (full term = 140 days) to determine the relative composition of smooth muscle, ECM and urothelium by morphometric analysis and to measure DNA and protein concentrations. Ureteral tissue from 135 day gestation obstructed and control sheep was harvested and immediately placed in Krebs solution. Smooth muscle strips (2-3 mm. x 7-8 mm.) were suspended in organ baths. The frequency and amplitude of spontaneous ureteral contractions was as well as the response to electric field stimulation (EFS) were determined. RESULTS: Bladder outlet obstruction caused a significant increase in ureteral weight, smooth muscle mass and total ECM at both 109 and 135 days gestation. Total ureteral DNA was greater in obstructed compared with sham ureters at 135 days gestation. Obstructed ureters demonstrated greater amplitude and frequency of spontaneous contractions as well as more pronounced response to EFS when compared to sham ureters. CONCLUSIONS: The fetal ureter responds to bladder obstruction with smooth muscle hyperplasia and hypertrophy which is associated with increased spontaneous activity and augmented response to EFS. ECM content is markedly increased indicating a shift in the balance of connective tissue synthesis and degradation. Congenital post-obstructive ureteral dysfunction therefore appears to be the result of dysregulated smooth muscle cell growth and altered ECM homeostasis producing abnormal ureteral contractility.

Metastatic merkel cell tumor to bladder presenting as an encroachment tumor with gross hematuria.

Merkel cell carcinoma is an uncommon and aggressive tumor of neuroendocrine and epithelial origin. A case of metastatic Merkel cell tumor with hematuria secondary to invasion into the bladder is presented. This is the second reported case of metastatic Merkel cell tumor to the bladder and the first published cystoscopic image of such a lesion.

Clinicopathological characteristics of prostatic adenocarcinoma in men with atypical prostate needle biopsies.

PURPOSE: Atypical or nondefinitive diagnoses comprise 1.5 to 10% of all prostate needle biopsies and many men with atypical biopsy have carcinoma on rebiopsy. We characterize the clinical and pathological features of these men and the tumors, and compare them to those of other men who had more than 1 biopsy. MATERIALS AND METHODS: All prostate needle biopsies done at our institution between 1989 and 1996 on men with a followup biopsy were reviewed and the clinicopathological features were correlated. RESULTS: A total of 343 men had more than 1 biopsy during this period. Of the biopsies 64 were atypical and followup (repeat biopsy) was available for 59. Men with an atypical diagnosis were more likely to have carcinoma (34%) and to be diagnosed subsequently earlier (270 days) than those with an initial negative diagnosis (22%, 603 days). No significant differences were noted in patient age, results of digital rectal examination, initial or followup serum prostate specific antigen, subsequently identified tumor size or Gleason score on needle biopsy or at resection. Although on review as many as 38% of the original atypical foci could be reclassified, this reclassification did not significantly change the results of rebiopsy. CONCLUSIONS: Men with an atypical diagnosis on prostate biopsy are significantly more likely to have carcinoma on rebiopsy than men with an initial negative diagnosis, and the second biopsy should be performed at a significantly shorter interval. The tumors that are subsequently identified in these men are similar to those identified in men without an atypical biopsy.

Long-term pulmonary toxicity of multiagent chemotherapy including bleomycin and cyclophosphamide in osteosarcoma survivors.

PURPOSE: To assess long-term pulmonary effects of multiagent chemotherapy, we studied serial pulmonary function tests (PFTs) of 35 children with osteosarcoma up to 12 years after diagnosis. PATIENTS AND METHODS: We analyzed 84 sets of PFTs from 35 patients diagnosed with osteosarcoma between 1981 and 1991. They received bleomycin, cyclophosphamide, methotrexate, doxorubicin, cisplatin, and actinomycin D over 9-12 months and we performed PFTs from 3 days to 152 months after diagnosis. Time period I included 36 PFTs (43%) performed between 1 and 5 months from diagnosis, time period II included 20 PFTs (24%) performed between 8 and 12 months from diagnosis, and time period III included 28 PFTs (33%) performed between 12 and 119 months from diagnosis. Total lung capacity (TLC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and carbon monoxide diffusing capacity (DLCO) were analyzed. Maximal respiratory pressures and arterial blood gases were measured to assess muscle weakness and gas exchange, respectively. Mean differences in PFTs were compared among the three time periods and between time period pairs. RESULTS: All mean PFT values showed significant differences among time periods. Significant decline in DLCO; (P=.012), TLC (P=.020), and FEV1 (P=.028) between time periods I and II were noted followed by a trend towards recovery between time periods II and III. Time periods I and III were not significantly different from one another. Mean PFTs performed after 2 years of diagnosis were not different from mean PFTs performed from diagnosis at 2 years. CONCLUSION: This dosage regimen of multi-agent chemotherapy for osteosarcoma patients caused a transient, but significant, decline in PFTs within 8-12 months after administration but appears to cause no significant long-term pulmonary function abnormalities.