Analysis of the hepatic functional reserve, portal hypertension, and prognosis of patients with human immunodeficiency virus/hepatitis C virus coinfection through contaminated blood products in Japan.

BACKGROUND: As the survival of human immunodeficiency virus (HIV)-infected individuals has improved due to the widespread use of antiretroviral therapy, the mortality rate due to hepatitis C virus (HCV)-related liver disease has increased in HIV/HCV-coinfected patients. AIM: The aims of this study were to establish the appropriate therapeutic strategy for HIV/HCV-coinfected patients by evaluating the liver function, including the hepatic functional reserve and portal hypertension, and to investigate the prognosis of HIV/HCV-coinfected patients in Japan. PATIENTS AND METHODS: In addition to regular liver function tests, the hepatic functional reserve of 41 patients with HIV/HCV coinfection was evaluated using the indocyanine green retention rate and liver galactosyl serum albumin-scintigraphy. The data for 146 patients with HIV/HCV coinfection through blood products were extracted from 4 major HIV centers in Japan. In addition to liver function tests, the platelet counts (PLT) were evaluated as a marker of portal hypertension. RESULTS: In spite of the relatively preserved general liver function test results, approximately 40% of the HIV/HCV-coinfected patients had an impaired hepatic functional reserve. In addition, while the albumin and bilirubin levels were normal, the PLT was <150,000/µL in 17 patients. Compared with HCV mono-infected patients with a PLT <150,000/µL, the survival of HIV/HCV-coinfected patients was shorter (HCV, 5 years, 97%; 10 years, 86% and HIV/HCV, 5 years, 87%; 10 years, 73%; P < .05). CONCLUSION: These results must be taken into account to establish an optimal therapeutic strategy, including the appropriate timing of liver transplantation in HIV/HCV-coinfected patients in Japan.

A case report and epidemiological investigation of axillary lymph node abscess caused by Corynebacterium ulcerans in an HIV-1-positive patient.

A human immunodeficiency virus-1 (HIV-1)-positive male undergoing antiretroviral therapy was diagnosed with an axillary lymph node abscess caused by Corynebacterium ulcerans, and an environmental survey revealed that the patient's cat as the source of infection.

Influence of menopause on mandibular bone quantity and quality in Japanese women receiving dental implants.

SUMMARY: The purpose of this study was to evaluate the effect of menopause on bone mineral density and bone width of the mandible. Results indicate that menopause affects the bone quality and quantity of the partially edentulous molar region of the mandible, which should be considered in dental implant treatment for postmenopausal women. INTRODUCTION: The recovery of oral function with dental implant is clinically effective and highly predictable. Bone quantity and quality at the implant installation site affect its prognosis; however, the effects of menopause on jaw bone have not been well documented. The purpose of this study was to evaluate the effect of menopause on bone mineral density (BMD) and bone width of the mandible. METHODS: The subjects were 72 female patients with a partially edentulous molar region of the mandible: 30 premenopausal and 42 postmenopausal women aged 30 to 70 years. Trabecular BMD was measured with quantitative computed tomography. Trabecular region width (TW) and cortical width (CW) were measured with CT. The BMD, TW, and CW of the two groups were compared. RESULTS: The trabecular BMD of postmenopausal women was lower than that of the premenopausal women. The TW of postmenopausal women was greater than that of premenopausal women, whereas the CW of postmenopausal women was significantly smaller than that of premenopausal women. In all these women, BMD correlated negatively with TW and positively with CW. In the premenopausal women, BMD negatively correlated with TW, but it did not correlate with CW. In the postmenopausal women, there was no correlation between BMD and bone width. CONCLUSION: These results indicate that menopause affects the bone quality and quantity of the partially edentulous molar region of the mandible, which should be considered in dental implant treatment for postmenopausal women.

Effect of recombinant human bone morphogenetic protein-2 on bone formation in alveolar ridge defects in dogs.

This study was designed to evaluate the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) combined with poly D, L lactic-co-glycolic acid (PLGA)/gelatin sponge complex (PGS) on the formation of bone in critically sized marginal defects of the mandible in dogs. Three months after extraction of the pre-molar teeth, rectangular bone defects (10 x 8 x 7 mm) were made in both sides of the mandible. A PGS block soaked in rhBMP-2 (400 microgram/ml) was implanted into one defect (BMP (+) group). As control, an untreated PGS block was implanted into the contralateral defect (BMP (-) group). 2, 4, 8, and 12 weeks after implantation, the defects were examined. In the BMP (+) group, newly formed bone was found in all defects from 4 weeks onward and was marked at 12 weeks. In contrast, the BMP (-) group showed no appreciable new bone formation, even at 12 weeks. Moreover, density of newly formed bone in the BMP (+) group was similar to that of the surrounding cortical bone at 12 weeks. These findings suggest that rhBMP-2/PGS is an effective bone substitute for reconstructive surgery of the dog mandible.

Increased concentrations of 14-3-3 epsilon, gamma and zeta isoforms in cerebrospinal fluid of AIDS patients with neuronal destruction.

BACKGROUND: 14-3-3 proteins are major evolutionarily conserved cytosolic proteins that regulate signal transduction, apoptosis and neurotransmitter synthesis. Five homologous 14-3-3 isoforms, beta, gamma, zeta, epsilon and eta, are reported in mammalian neurones. To elucidate the diagnostic value of 14-3-3 in cerebrospinal fluid (CSF), a highly specific antibody against each isoform and studies on the isoform patterns in patients with neuronal destruction are needed. METHODS: In this study, we raised isoform-specific antibodies against 14-3-3 proteins and established a semiquantitative method of identification of each isoform by Western immunoblotting. RESULTS: We found that three isoforms, 14-3-3 epsilon, gamma and zeta, appeared in the CSF of HIV patients with AIDS dementia complex or cytomegalovirus encephalitis, but not in AIDS patients without neurological symptoms or the non-HIV patients examined. The isoform patterns in AIDS patients were different from those reported in Creutzfeldt-Jakob disease and herpes simplex encephalitis, suggesting that the isoform patterns may facilitate the differential diagnosis. A high frequency of 14-3-3 in CSF was observed in seriously ill AIDS patients, particularly those with CD4 levels of less than 20 mm(3). CONCLUSION: These findings suggested that 14-3-3 proteins were released from destroyed neural cells and are useful real-time markers of the rate and amount of neural cell destruction in these patients.

Two cases of long lasting bacteremia due to Mycobacterium avium complex despite new macrolides-containing regimens in patients with acquired immunodeficiency syndrome.

The prognosis of Mycobacterium avium complex (MAC) infection has been improved by new macrolides-containing regimens and the use of highly active antiretroviral therapy (HAART) in the treatment of acquired immunodeficiency syndrome (AIDS). We report on two AIDS cases with long lasting bacteremia due to MAC under this regimen. Both patients experienced problems due to side effects from the anti-MAC regimen and from an immune-reconstitution syndrome related to HAART. MAC infection persisted despite treatment, however, no anti-MAC drug-resistant isolates emerged throughout the clinical course in either case. These cases demonstrate that therapy for disseminated MAC infection is sometimes difficult even with HAART and macrolides-containing regimens.

Complications during clinical courses of Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome.

OBJECTIVE: To describe the incidence of complications before and during therapy of Pneumocystis carinii pneumonia (PCP) in patients with acquired immunodeficiency syndrome (AIDS). METHODS: A retrospective review of the patient's medical records. PATIENTS: A total of 29 patients with AIDS and PCP who were admitted to the AIDS Clinical Center, International Medical Center of Japan from July 1996 to November 1999. RESULTS: Adverse effects were found in 24 (88.9%) of 27 patients treated with trimethoprim/sulfamethoxazole (T/S), 6 (46.1%) of 13 treated with parenteral pentamidine, and 2 (20%) of 10 treated with inhaled pentamidine. Infectious and/or non-infectious complications were found in 25 (86.2%) of 29 study patients. Regarding infectious complications, 16 (55.2%) were found on admission and 10 cases (34.5%) with infectious complications were identified during admission; including oral candidiasis (37.9% and 17.2%, respectively) and genital herpes (3.4% and 6.9%, respectively). Cytomegalovirus antigenemia was detected in 4 cases (13.8%) on admission and 12 cases (41.4%) during admission. Non-infectious complications affected 11 cases (37.9%) on admission, and 6 cases (20.7%) during admission, the latter included heart failure (10.3%) and pneumothorax (6.9%). PCP was successfully treated in all but one patient who suffered from repeated pneumothorax. CONCLUSION: Treatment of PCP can be problematic and it is important to be aware of the high incidence of various complications that can occur during the treatment of PCP.

Efficient gene activation in cultured mammalian cells mediated by FLP recombinase-expressing recombinant adenovirus.

A recombinant adenovirus (rAd) expressing Cre recombinase derived from bacteriophage P1 has already been extensively used for the conditional gene activation and inactivation strategies in mammalian systems. In this study, we generated AxCAFLP, a rAd expressing FLP recombinase derived from Saccharomyces cerevisiae and carried out quantitative comparisons with Cre-expressing rAd in both in vitro and in cultured cells to provide another efficient gene regulation system in mammalian cells. In the in vitro experiments, the relative recombination efficiency of FLP expressed in 293 cells infected with FLP-expressing rAd was approximately one-thirtieth that of Cre even at 30 degrees C, the optimum temperature for FLP activity, and was approximately one-ninetieth at 37 degrees C. Co-infection experiments in HeLa cells using a target rAd conditionally expressing LacZ under the control of FLP showed that an FLP-expressing rAd, infected at a multiplicity of infection (MOI) of 5, was able to activate the transgene in almost 100% of HeLa cells whereas the Cre-expressing rAd was sufficient at an MOI of 0.2. Since an MOI of 5 is ordinarily used in rAd experiments, these results showed that the FLP-expressing rAd is useful for gene activation strategies and is probably applicable to a sequential gene regulation system in combination with Cre-expressing rAd in mammalian cells.

Sustained cytomegalovirus-specific CD4+ T cell response associated with prevention of recurrence of cytomegalovirus retinitis without secondary prophylaxis after highly active antiretroviral therapy in patients with AIDS.

It has been demonstrated that the cytomegalovirus (CMV)-specific CD4(+) T cell response could be restored after ganciclovir and highly active antiretroviral therapy (HAART) in AIDS patients. In this study, we first confirmed the above observation cross-sectionally. We then performed a prospective longitudinal study over a period of 48 weeks. The second study included nine patients. All patients had received HAART. Five patients had a history of retinitis that was, however, under control after discontinuation of anti-CMV therapy more than 1 year before this study (group A). The other four had active CMV retinitis at the start of this study and anti-CMV therapy was required to control retinitis (group B). Median periods between commencement of HAART and the start of this study in group A and in group B were 27 and 4.5 months, respectively. Within both groups, the number of CD4(+) T cells that produced tumor necrosis factor alpha in response to CMV antigen did not vary throughout the observation period (Friedman test; p > 0.05). However, the median number of responsive CD4(+) T cells in group A patients was significantly higher than in group B (p < 0.05). Our results demonstrate that the number of CMV-responsive CD4(+) T cells increased when HIV was well controlled with HAART and was then maintained, and suggest that these cells may play an important role in the control of retinitis in patients with AIDS.

A 5-day course of oral desensitization to trimethoprim/sulfamethoxazole (T/S) in patients with human immunodeficiency virus type-1 infection who were previously intolerant to T/S.

BACKGROUND: Trimethoprim/sulfamethoxazole (T/S) is an essential drug in patients with human immunodeficiency virus type-1 (HIV-1) infection to prevent opportunistic infections. About 40% to 60% of them develop skin rash which leads to discontinue the medication. A precise mechanism of the reaction is not known. OBJECTIVE: To make the patients more tolerable to the medication and to make clear whether or not the reaction is caused by serum sulfamethoxazole-specific IgE. METHODS: We established a 5-day protocol, in which T/S was administered orally as a granular form in increasing doses beginning with 0.005 g (it contains trimethoprim 0.4 mg and sulfamethoxazole 2 mg) and doubled every 12 hours until the therapeutic dose was achieved. We tried to desensitize T/S in 17 patients with HIV-1 infection who were previously intolerant to T/S and measured the specific IgE in sera. RESULTS: Desensitization was successfully completed in 15 (88.2%) of the patients. In two patients who failed the desensitization, one was due to fever and the other was gastric irritation. During followup in a mean period of 16.6 months (range, 8 to 23 months) as of May, 1999, none has had Pneumocystis carinii pneumonia (PCP) while receiving T/S after desensitization. Sulfamethoxazole-specific IgE did not increase, indicating that it was not the major cause of skin rash due to T/S in our cases. CONCLUSION: These preliminary results show that most patients who were thought to be intolerant to T/S and had no sulfamethoxazole-specific IgE can be safely desensitized and received the drug subsequently as an effective prophylaxis for PCP.

[The vanishing testis: diagnosis and histological findings].

PURPOSE: Controversy exists on how to diagnose the vanishing testis and the degree of investigation required. In this series, we reviewed anatomical and histological findings in vanishing testes and investigated the effectiveness of diagnostic laparoscopy and imaging studies. MATERIALS AND METHODS: Between 1974 and March 1999, 107 boys with nonpalpable testis underwent surgery. Of the total, 52 had spermatic vessels, vas deferens, and/or nubbin, and as a result the diagnosis of vanishing testis was made. RESULTS: The affected side of vanishing testis was left 41, right 9 and bilateral 2.35 nubbins were found and the lengths of 24 nubbins were 5 mm or less. Histological examinations were performed in 43 cases including 27 nubbins. From that total, 31 had vas deferens and 11 had epididymis. Only two nubbins had seminiferous tubules but they included no germ cells. The two nubbins were greater than 5 mm long. Laparoscopic surgery was undertaken in 12 separate cases of the vanishing testis and as a result hypoplastic spermatic vessels were present in 7 of the 12 cases. CONCLUSION: The incidence of viable testicular tissue in vanishing testes was 4.7% in our series and it ranges from 0-16% in other series. We submit that one can diagnose the inguinal vanishing testis with preoperative imaging and laparoscopy, and that the nubbin seldom contains testicular tissue. Our results do not support the necessity to remove nubbins.

[Clinical study on risk management for dental implant treatment--Part 1. Clinical retrospective study on the medically compromised patients at clinic for oral implant].

A retrospective study on medically compromised patients was made using 1,000 outpatients who visited the Clinic for Oral Implant, University Hospital, Faculty of Dentistry, Tokyo Medical and Dental University between April 1995 and June 1998. The results were as follows: 1. 35.3% (353 patients: 140 males and 213 females) of the outpatients were medically compromised. 2. The greatest number of medically compromised patients was in the 50-59 age group (118 cases), followed by those in the 40-49 and 60-69 age groups. 3. The highest ratio of medically compromised patients was in the 60-69 age group (48.2%), followed by those in the 70-79 and 50-59 age groups. 4. Among the 353 patients, 96 (27.2%) underwent surgical treatment such as insertion of implant (68 cases), removal of implant, extraction of tooth, and free gingival graft. 5. Among the 68 patients who underwent insertion of implant, in a classification by type of disease, the patients with cardiovascular diseases were the most numerous (33.9%), followed by metabolic and digestive tract diseases. 6. All surgical treatments of implant insertion were performed under local anesthesia, while monitoring cardiac and respiratory function, and SpO2. Among the 68 patients, 9 underwent operation under intravenous sedation and 2 under nitrous oxide inhalation sedation. All 11 patients had hypertension. The results suggested that identification of preoperative risk factors, precise recognition of general condition, and establishment of control system are important to manage medically compromised patients for dental implant treatment.

[A two-year follow-up of zidovudine plus lamivudine combined with indinavir in antivival naive HIV-infected patients].

Efficacy of a 3-drug combination (Zidovudine (AZT) + Lamivudine (3TC) + Indinavir (IDV)) has been evaluated in 17 anti-viral naive patients with HIV infection for 24 months. Our genotypic resistance assay was able to analyze more than 80% of the patients whose viral load (VL) was over 3,000 copies/ml. This therapy was continued in 11 patients (65%) for 24 months. Among them, VL was undetectable (VL < 400 copies/ml) in patients at 24 month (47% by intent-to-treat, 72% by on treatment). Of the 11 patients, a 3TC resistance-related mutantion was detected in only one case. The therapy was discontinued in 6 cases. Main reasons of the discontinuation were side effects. However, if the therapy was switched to other combinations when VL was undetectable, VL remained undetectable in 5 cases at 24 month.

Human herpesvirus 8-associated solid lymphomas that occur in AIDS patients take anaplastic large cell morphology.

Human herpesvirus type 8 (HHV-8; Kaposi's sarcoma-associated herpesvirus) is a recently isolated human herpesvirus frequently identified in Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. Here we report three cases of HHV-8-bearing solid lymphomas that occurred in AIDS patients (Cases 1-3). All three patients were homosexual men presenting extranodal masses in the lungs (Case 1) or skin (Cases 2 and 3), together with the presence of Kaposi's sarcoma (Case 1), primary effusion lymphoma (Case 2), or multicentric Castleman's disease (Case 3). These solid lymphomas exhibited anaplastic large cell morphology and expressed CD30, corresponding to the recent diagnostic criteria of anaplastic large cell lymphoma (ALCL). The chromosomal translocation t(2;5)-associated chimeric protein p80NPM/ALK was not observed in any of these cases. HHV-8 was detected in all of these cases by polymerase chain reaction, immunohistochemistry of HHV-8-encoded ORF73 protein, and in situ hybridization of T1.1. Epstein-Barr virus was detected only in Cases 2 and 3 by in situ hybridization. It is interesting that inoculation of a cell line obtained from a primary effusion lymphoma cell in Case 2 to severe combined immunodeficiency mice produced HHV-8-positive and Epstein-Barr virus-negative tumors in inoculated sites. These tumor cells exhibited phenotypes of ALCL that were identical to the subcutaneous tumor cells of this particular patient. These findings clearly show that HHV-8 can associate with solid lymphomas and that it can take anaplastic large cell morphology. Those lymphomas should be distinguished from the classical ALCL as were defined by the revised European-American classification of lymphoid neoplasms even though morphology and a part of immunophenotype mimic that of classical ALCL.