Long-term follow-up of patients with candiduria

Candiduria is commonly encountered in hospitalized patients, particularly those with indwelling urinary catheters. While risk factors and therapy are well described in previous studies, little is known about long-term outcomes and recurrence rates of candiduria. We studied 188 patients with candiduria in a retrospective chart review at a single institution from January 1999 to December 2000. Data were collected regarding risk factors and underlying disease, therapy, follow-up cultures until December 2003, and mortality. Ninety-one patients with at least one follow-up culture >1 month after the initial culture (range 2–48) were available for further study. In this group, patients receiving antifungal therapy for asymptomatic candiduria were paradoxically more likely to have subsequent positive urine cultures than patients who never received antifungal therapy. Six patients developed candidemia during follow-up, although in none was this considered to represent a consequence of candiduria. Mortality rate at the end of the follow-up period (mean of 18 months) was 43%, including one death attributed to candidemia. Therapy for candiduria does not appear to reduce candiduria recurrence rates through 48 months of follow-up and little evidence of treatment benefit was identified.     

Altered monocyte function in patients with benign breast disease.

Monocyte migration, lysozyme production and phagocytosis was studied in 34 patients with fibroadenosis, 28 patients with fibroadenoma and 48 healthy female controls. In patients with fibroadenosis and fibroadenoma, monocyte migration and phagocytic activity were significantly reduced when compared to controls (P less than 0.001). Conversely, lysozyme production by monocytes from patients with benign breast disease was significantly higher than in controls (P less than 0.001). In 20 patients with benign breast disease, there was no significant difference in monocyte function before and 3 months after operation. The observed impairment of monocyte function in fibroadenosis and fibroadenoma would not appear to be the result of abnormal blood biochemistry or due to a direct serum inhibitor, but is probably related to an intrinsic cellular defect. Further studies are required to evaluate the significance of impaired monocyte function in the pathophysiology of benign breast disease.     

Long-term follow-up of patients with primary immunodeficiencies

As an example of the need for long-term follow-up by specialty health care to adequately manage immunodeficient patients, we report the case of a patient with Wiskott-Aldrich syndrome who was lost to follow-up for 4 years to the immunology clinic and came back with a neck mass that was diagnosed as B-cell lymphoma. Patients with immunodeficiency are at high risk for the development of malignancy and autoimmune diseases and should be evaluated by a trained specialist with a frequency of not less than every 6 months.     

Natural killer activity in patients with biopsy-proven liver disease.

Most previous studies of lymphocyte-mediated cytotoxicity to animal and human hepatocytes have not taken into account the ability to human lymphoid cells to kill spontaneously cultured cell lines, particularly those of malignant origin (the natural killer or NK effect). We have studied spontaneous killing to a human target (erythromyeloid cell line K562) in patients with biopsy-proven liver disease and from normal controls. Patients with chronic active hepatitis were shown to have a significant reduction in NK activity unrelated to immunosuppressive therapy (P less than 0.01). Other groups showed normal values. These results imply that cytotoxic effectors reported active in chronic liver disease are K cells and not NK cells, with which they share many characteristics, and suggest that a cytotoxic mechanism considered to be of importance in immunosurveillance may be reduced in chronic aggressive hepatitis.     

Long-term follow-up of postmenopausal breast cancer patients following discontinuation of tamoxifen therapy

BACKGROUND: There is a need to evaluate the extent of endometrial pathologies that might develop in postmenopausal breast cancer patients following discontinuation of tamoxifen (TAM) therapy. METHODS: The medical records of 153 postmenopausal breast cancer patients who remained untreated following discontinuation of tamoxifen therapy were evaluated for various clinical features, for endometrial thickness measurements, as detected by transvaginal ultrasonography, and for various endometrial pathologies detected. The last endometrial thickness measurement performed before discontinuation of tamoxifen was compared with endometrial thickness measured following discontinuation of tamoxifen. RESULTS: Patients were followed for 37.5+/-31.3 months. There was a gradual and significant decrement of endometrial thickness measured at the last ultrasonographic study performed before cessation of tamoxifen, compared to that observed in all four ultrasonographic studies performed following discontinuation of tamoxifen (P=0.001). Endometrial thickness gradually and significantly decreased in correlation with the time intervals of the four ultrasonographic studies performed following discontinuation of tamoxifen (P=0.001). Overall, 40 hysteroscopies were performed in 38 (24.8%) patients. No tissue was obtained in 18 (11.8%) patients. Overall endometrial pathologies were diagnosed in 22 (14.4%) patients. Benign endometrial polyps were the most frequent endometrial pathology recovered: 17 (11.1%) patients. No endometrial malignancy was diagnosed. The rate of endometrial pathologies considerably decreased with the extension of time following discontinuation of tamoxifen therapy. CONCLUSIONS: Long-term follow-up of postmenopausal breast cancer patients who remained untreated following discontinuation of TAM therapy did not reveal any malignant endometrial pathology. Only few benign endometrial pathologies were diagnosed, which became fewer in time.     

Long-term follow-up of patients with extracardiac valved conduits

Seventeen patients having extracardiac valved conduits placed between the right ventricle and pulmonary artery were followed for 7 to 87 months postoperatively (mean, 42 months), at the Heart Institute, Kenritsu Amagasaki Hospital, Japan. There were no late deaths in the study group. Three conduits have been replaced, all because of conduit stenosis. In two-dimensional echocardiographic examinations, commissural fusion and calcification of the valve were noted in 6 out of 16 xenograft valved conduits. Mechanical valve immobility was found in one patient. Neointimal peel of the dacron graft was noted in 6 out of 17 cases, and marked left ventricular deformity in the short axis view was found in 6. Late cardiac catheterization was done in 6 patients who were suspected of having valve failure and right ventricular hypertension by two-dimensional echocardiography. All 6 of these patients showed a high pressure gradient between the pulmonary artery and right ventricle and also had elevated right ventricular pressure. In conclusion, two-dimensional echocardiography is a simple, non-invasive and very accurate method for detecting conduit stenosis and valve failure. An echocardiographic series should be performed for a long-time postoperatively because obstructions of valved conduits may be progressive, and an operation may be advisable in order to prevent the development of advanced right ventricular hypertrophy and deterioration.     

Long-term follow-up in patients with intra-Hisian atrioventricular block

Long-term follow-up was performed in patients with intra-Hisian atrioventricular (AV) block who were implanted with permanent pacemakers. Subjects were 14 consecutive patients (3 men and 11 women, 65.4±9.7 [SD] years old), who exhibited intra-Hisian block at the time of pacemaker generators were replaced due to battery depletion. Electrophysiological examinations were performed at both the initial implantation and pacemaker replacement. The mean duration from the initial implantation to the replacement was 9.4±4.3 years. All patients had severe symptoms such as syncope, dizziness, or dyspnea, and these symptoms were relieved by pacemaker implantation. Seven patients had complete AV block, and the other seven had advanced or paroxysmal AV block at the time of implantation. Seven patients, who had advanced AV block at the time of implantation, developed complete AV block. Five of the seven patients who had complete AV block at the time of implantation remained in complete AV block, one patient had advanced AV block, and one patient of complete AV block increased significantly from 50% to 93% during the two electrophysiological examinations (P<0.05). A mean heart rate of 40.3±7.5 beats/min was observed during complete AV block. At the time of implantation, two patients were misdiagnosed as having AH block, and the other two patients were misdiagnosed as having HV block. In conclusion, intra-Hisian AV block gradually developed from advanced or paroxysmal AV block into complete AV block. Because the diagnosis of intra-Hisian block is sometimes difficult, we should always consider the possibility of intra-Hisian block in patients with severely symptomatic AV block.     

Early treatment of Menkes disease with parenteral Cooper-Histidine: Long-term follow-up of four treated patients

We report on the long-term clinical course of 4 boys with Menkes disease, treated from early infancy with parenteral copper-histidine, with follow-up over 10–20 years. Three of the 4 had male relatives with a severe clinical course compatible with classical Menkes disease. As a consequence of early treatment, our patients have normal or near-normal intellectual development, but have developed many of the more severe somatic abnormalities of the related disorder, occipital horn syndrome, including severe orthostatic hypotension in 2. In addition, 1 boy developed a previously unreported anomaly, namely, massive splenomegaly and hypersplenism as a consequence of a splenic artery aneurysm. Previously reported molecular studies in 2 of these patients had shown gene defects which would have predicted a truncated and probably nonfunctional gene product. Despite the favorable effects on the neurological symptoms, parenteral copper treatment for Menkes disease should still be regarded as experimental. The development of more effective treatments must await a more precise delineation of the role which the Menkes protein plays in intracellular copper trafficking. Am. J. Med. Genet. 76:154–164, 1998. © 1998 Wiley-Liss, Inc.     

Long-term follow-up of antiretroviral-naive HIV-positive patients treated with nevirapine

This article reports on the extended follow-up of 125 antiretroviral (ARV)-naive patients treated with nevirapine (NVP) in the United Kingdom. The patients have been observed for a median of 1.8 years after starting NVP (range, 4 days-2.7 years). Baseline CD4 counts and HIV RNA levels were 210 (interquartile range, 130 - 335) cells/mm3 and 4.86 (range, 4.52-5.26) log10 copies/ml, respectively. Eleven patients (9.0%) developed a rash thought to be related to NVP, of whom 4 permanently discontinued NVP. Twenty-four months after starting NVP, RNA levels had dropped by a median of 2.32 log10 copies/ml and CD4 counts increased by a median of 143 cells/mm3. In all, 96 patients had at least one viral load measured <500 copies/ml, a median of 2.8 months after starting NVP. RNA levels rebounded >500 copies/ml in 37 of these patients, on average 2 years after initial response. In conclusion, in ARV-naive patients, NVP is generally well tolerated and long-term response rates are good.     

Pathologic features of breast cancers in women with previous benign breast disease

To compare pathologic features of the cancers arising after different types of benign breast disease (BBD), we reviewed the invasive breast cancer slides of 169 women with a previous benign biopsy result. Lesions were categorized previously as nonproliferative, proliferative without atypia, or atypical hyperplasia. Pathologic features of the cancers were evaluated without knowledge of the previous BBD category. Estrogen and progesterone receptor immunohistochemistry was performed on available tissue blocks. The median times between a benign result and cancer were 100, 124, and 92 months for women with nonproliferative lesions, proliferative lesions without atypia, and atypical hyperplasia, respectively. Cancers in the 3 groups did not differ significantly in tumor size, axillary lymph node status, or histologic grade, and there was no significant difference in the distribution of histologic types of breast cancer. Lymphatic vessel invasion, extensive intraductal component, and hormone receptor status did not differ among BBD categories. The pathologic features of breast cancers that develop in women with a previous benign biopsy result do not vary according to the histologic category of the previous BBD.     

Long-term follow-up of a patient with neonatal form of Gaucher disease

Gaucher disease is the most common of the lysosomal storage diseases. It presents a wide phenotypic continuum, in which one may identify the classically described phenotypes, including type 1 form with visceral involvement, type 2 acute neuropathic early-infantile form, and type 3 subacute neuronopathic form. At the most severe end there is the perinatal form with onset in utero or during the neonatal period. The very few reported cases of neonatal onset Gaucher disease presented high and early mortality, due to neurological or visceral involvement, including liver failure. We report our experience treating a patient with the neonatal form of Gaucher disease who presented at birth with thrombocytopenia, hepatosplenomegaly and cholestasis. Despite early enzyme replacement therapy, liver disease was progressive. Liver biopsy showed hepatocellular giant-cell transformation, a nonspecific finding consistent with inflammation. The lack of response to enzyme replacement therapy and the microscopic findings suggested that mechanisms apart from substrate accumulation and Gaucher cells may play a role in the hepatic pathogenesis in Gaucher disease. An attempt to use corticosteroids at the age of 3 months resulted in a dramatic improvement in liver function and resulted in long-term survival. The patient is alive and 2 years old at this writing. Our case suggests that inflammatory processes may be important in the early pathogenesis of Gaucher disease and that early use of corticosteroids may open the way to a new therapeutic approach.     

Vascular infiltration in benign breast disease.

Infiltration of the walls of blood vessels by mammary epithelium was found in two cases of sclerosing adenosis. Survey of a series of cases of sclerosing adenosis and severe epitheliosis revealed a 10 per cent incidence of vascular infiltration. Usually only a single vein was involved but in the propositus an artery and two veins were infiltrated. The findings highlight the infiltrative propensities of sclerosing adenosis, already recognised as infiltrating nerve sheaths. The vascular lesions appear to be benign structurally and this is borne out by the clinical behaviour.     

Elastosis in benign and malignant breast disease

Elastosis, the presence of clumps of elastic fibers, is known to occur frequently in association with breast carcinoma. To test the hypothesis that the degree of elastosis increases progressively in fibrocystic disease with the severity of epitheliosis (epithelial hyperplasia, papillomatosis; widely believed to be the only premalignant component of fibrocystic disease) and increases further with intraductal and infiltrating duct carcinoma, breast tissue stained for elastic fibers from 84 women in the fifth decade of life was studied. Fourteen cases were evaluated in each of six disease categories: fibrocystic disease without epitheliosis; fibrocystic disease with epitheliosis, graded subjectively as mild, moderate, or severe (based on the degree of epithelial hyperplasia); intraductal carcinoma; and infiltrating duct carcinoma of the breast. Periductal elastosis and stromal elastosis were graded on a scale of 0 to 4 (absent to massive). The grades of both periductal elastosis and stromal elastosis were compared with those for the six disease categories ranked by increasingly advanced disease. The results indicate that the grades of periductal elastosis (Spearman rank correlation coefficient [R] = 0.54; P less than 0.001) and stromal elastosis (R = 0.75; P less than 0.001) increase progressively with the severity of breast disease.     

Long-term follow-up of patients with AIDS on maintenance therapy for toxoplasmosis

To assess potential interactions of multiple drug regimens administered to patients with AIDS for toxicity and efficacy, we reviewed the charts of 35 patients on maintenance therapy for toxoplasmosis. Seven relapses of toxoplasmosis occurred in 6 of 35 (17 %) patients, and seven episodes of pneumocystosis occurred in 6 of 35 (17 %) patients. Four relapses of toxoplasmosis and 5 relapses of pneumocystosis were seen in 20 patients treated with pyrimethamine/clindamycin; 2 relapses of toxoplasmosis and 2 relapses of pneumocystosis were seen in 11 patients treated with pyrimethamine alone, and 1 relapse of toxoplasmosis was seen in 13 patients treated with pyrimethamine/sulfadiazine. Adverse effects were related to pyrimethamine in 10 patients, to clindamycin in 7 patients, and to sulfadiazine in 8 patients. These results must be compared with those of prospective trials to determine the efficacy and safety of various maintenance regimens.     

Long-term follow-up of Japanese patients with chronic hepatitis B treated with interferon-alpha

The long-term usefulness of interferon-alpha (IFN-alpha) in chronic hepatitis B remains controversial. To investigate the long-term efficacy of IFN-alpha therapy in chronic hepatitis B, 62 Japanese patients, including 27 patients treated with IFN-alpha (IFN group) and 35 patients without antiviral therapy matched by age and sex as controls (control group), were followed up for 2-14 years. At entry, the serum alanine aminotransferase (ALT) level in the IFN group was significantly higher than that in the control group (238.6+/-250.1 vs. 142.3+/-152.1 IU/l, P < 0.05). The prevalence of genotype C was 89%, with no difference between the two groups (93 vs. 86%). There was no significant difference in the presence of the precore mutation or the dual core promoter mutations between the IFN and control groups (37 vs. 46%, 74 vs. 66%). After long-term follow-up, the rate of sustained HBeAg seroconversion was comparable in the two groups (33 vs. 31%). Normalization of serum ALT level was seen in 44% of the IFN group and 51% of the control group, with no difference. There was also no difference in the percentage of cases with loss of serum HBV-DNA by PCR assay between the two groups (33 vs. 29%). During follow-up, two patients of the control group and three patients of the IFN group developed cirrhosis, and one of the IFN- treated patients progressed to hepatocellular carcinoma. The results of this long-term follow-up study showed that no benefit of IFN-alpha treatment was detectable during long-term follow-up in Japanese patients with chronic hepatitis B.     

Long-term follow-up of laparoscopic splenectomy in patients with immune thrombocytopenic purpura

Laparoscopic splenectomy (LS) has been reserved for intractable and relapsing immune thrombocytopenic purpura (ITP) despite medical treatment. With further experiences of LS in ITP, we investigated long term outcomes of LS, especially newly developed morbidities, and tried to find predictive factors for favorable outcomes. From August 1994 to December 2004, fifty-nine patients whose follow-up period was more than 12 months after LS were investigated. After a long-term follow-up (median 54 months, range 12.5-129 months), a complete response (CR) was found in 28 patients (47.5%), partial response in 24 (40.7%), and no response in 7 (11.9%). The relapse rate during follow-up periods was 15.2%. The rapid response group (p=0.017), in which the platelet count increased more than twice of the preoperative platelet count within 7 days after LS, relapsing after medical treatment (p=0.02), and the satisfactory group as the initial result of LS (p=0.001) were significant for predicting CR in univariate analysis, but only the initial satisfactory group was an independent predictive factor for CR in multivariate analysis (p=0.036, relative risk=6419; 95% CI, 1.171-35.190). Infections were the most frequent morbidities during the follow-up period, which were treated well without mortality. LS is a safe and effective treatment modality for ITP. Active referral to surgery might be required, considering complications and treatment results related to long-term use of steroid-based medications.