Clinical characteristics and outcomes of adenovirus infection of the urinary tract after renal transplantation.

BACKGROUND: Urinary tract infection caused by human adenovirus (HAdV) after renal transplantation (RT) results in graft loss because of concomitant nephropathy and acute rejection and may result in death because of systemic dissemination. METHODS: We assessed the time period between RT and disease onset, symptoms, treatment details, disease duration, renal graft function, outcomes, and complications. RESULTS: HAdV infection of the urinary tract occurred in 8 of 170 renal transplant recipients. Symptoms were macrohematuria in all 8 patients, dysuria in 7, and fever in 5. The median period from RT to disease onset was 367 (range, 7-1763) days, and the median disease duration was 15 (range, 8-42) days. The mean serum creatinine (sCr) level prior to onset was 1.35 ± 0.48 mg/dL and the mean maximum sCr level during disease was 2.34 ± 1.95 mg/dL. These values were increased by ≥25% in 5 patients. The mean sCr levels when symptoms resolved was 1.54 ± 0.67 mg/dL, and no significant difference was seen before, during, or after disease onset (P = 0.069). Two patients were diagnosed with HAdV viremia and 1 with acute tubulointerstitial nephritis revealed on biopsy. In addition to a reduction in immunosuppressant dosage, 2 patients received gammaglobulins and 5 received ganciclovir. CONCLUSION: Symptoms of all patients were alleviated, although some patients developed nephritis or viremia. Hence, the possibility of exacerbation should always be considered. Adequate follow-up observation should be conducted, and diligent and aggressive therapeutic intervention is required to prevent the condition from worsening.

Mental and physical distress of field veterinarians during and soon after the 2010 foot and mouth disease outbreak in Miyazaki, Japan.

An outbreak of foot and mouth disease occurred in Miyazaki, Japan, in April 2010, and nearly 290,000 animals were culled to control the disease. This study was conducted to demonstrate the causes and intensity of mental distress felt by the field veterinarians participating in the control programme. A focus group discussion was conducted with ten veterinarians to understand their distress during the outbreak, and a questionnaire to quantify the degree of distress experienced each week was administered to 16 veterinarians. A detailed questionnaire was separately administered to 70 veterinarians six months after the outbreak was controlled, to assess mental distress status and to identify the risk factors for serious mental illness (SMI) using the six-item Kessler scale (K6). Overall, mental distress (mean 3.1) was significantly greater than physical distress (mean 1.9, p < 0.001). The risk factors for mental distress were categorised into three groups: culling, communication with farmers, and gender; each category was qualitatively described. Only two respondents (2.9%) had high K6 scores suggesting SMI. In the final generalised linear models with quasi-Poisson errors, the riskfactorsfor SMI that remained were: disinfecting vehicles (p = 0.01), distress (p <0.001), and increased alcohol consumption (p = 0.057), and a protective factor: participation in culling (p = 0.07), which suggested healthy worker bias. Sensitive individuals had been allocated to non-culling activities during disease control. In conclusion, human resource management was adequate during the outbreak from a public-health perspective. However, monitoring delayed symptoms of post-traumatic stress disorder is recommended.

Induction of tyrosine 3-monooxygenase in adrenal medulla: role of protein kinase activation and translocation.

The transsynaptic induction of tyrosine 3-monooxygenase (TH) in rat adrenal medulla is preceded by an early increase in the ratio of cyclic adenosine monophosphate (AMP) to cyclic guanosine monophosphate, an activation of cytosol cyclic AMP-dependent protein kinase, and a subsequent translocation of protein kinase catalytic subunits from cytosol to subcellular particles. As a result of this translocation, nuclear protein kinase activity increases during the induction of TH. Transection of splanchnic nerve reverts these events and prevents the induction of TH. Thus, adrenal medulla activation and translocation of cyclic AMP-dependent protein kinase may act as a long-range messenger for the genetic regulation of TH synthesis.

Surgical valvulotomy for tricuspid valve stenosis in a dog.

A 2-year, 4-month-old neutered female Labrador retriever was brought for evaluation of right-sided congestive heart failure. Echocardiographic examination revealed tricuspid valve dysplasia with only two small orifices in the valve resulting in severe tricuspid stenosis. The dog underwent a right fifth lateral intercostal thoracotomy and surgical tricuspid valvulotomy, under cardiopulmonary bypass. The stenosis was relieved by dividing the valve leaflets between the two orifices with continuation to the commissures, creating a 'bileaflet' valve. The dog made a good recovery initially, with echocardiography at 48 h after surgery showing a reduction in tricuspid valve E and A wave velocities and pressure half-time (from 230 ms to 65 ms). She was discharged five days after surgery, and spironolactone, benazepril, pimobendan, and clopidogrel were prescribed. The dog was re-presented two days later having collapsed, with pyrexia, facial swelling, and pitting edema on the ventral neck and intermandibular region. Investigations did not reveal an underlying cause, and the clinical signs resolved with supportive therapy. Two years after surgery, the dog was free of clinical signs with normal exercise tolerance and only mild tricuspid regurgitation on echocardiography, with discontinuation of all medications.

Intravenous dexmedetomidine for cesarean delivery and its concentration in colostrum.

BACKGROUND: Dexmedetomidine is a sedative agent with high α2-adrenoreceptor selectivity. We investigated intravenous dexmedetomidine administration during scheduled cesarean delivery under neuraxial anesthesia; and its concentration in the colostrum. METHODS: Twenty-seven participants having elective cesarean delivery under combined spinal-epidural anesthesia were enrolled. After delivery and cord clamping, 6µg/kg/h of intravenous dexmedetomidine was administered for 10minutes, followed by a dose of 0.7µg/kg/h until peritoneal closure. Sedation, vital signs and side effects were recorded. Blood and colostrum samples were collected from each participant at 6, 12, and 24h after dexmedetomidine administration. Samples were analysed using liquid chromatography tandem-mass spectroscopy. RESULTS: Colostrum samples were collected from 10 patients. The median [95% CI] plasma dexmedetomidine concentration was 333 [303-534] pg/ml at 0h and 19.7 [13.5-25.8] pg/ml at 6h. The colostrum concentration was 12.3 [8.1-20.1] pg/ml at 6h. The dexmedetomidine completely disappeared from both within 24h. The calculated milk-to-plasma ratio at 6h was 0.76 [0.57-0.86]. The relative infant dose was 0.034% [0.020-0.062%]. At dexmedetomidine discontinuation, the Richmond Agitation-Sedation Scale score was -2 (range,-4 to -1). During surgery, no patients complained of nausea, peritoneal irritation or afterbirth pain. CONCLUSIONS: The dexmedetomidine milk-to-plasma ratio did not exceed 1 in any participant, and the relative infant dose was very low. Maternal sedation using dexmedetomidine is unlikely to be harmful for the infant.

Effective and Safe Reduction of Conventional Immunosuppressants Using Everolimus in Maintenance Kidney Transplant Recipients.

BACKGROUND: Adverse events due to conventional immunosuppressive therapy decrease both graft and patient survival. We aimed to establish a new protocol using everolimus (EVR) to safely minimize conventional immunosuppressants in maintenance kidney transplant recipients. METHODS: A total of 86 consecutive kidney transplant recipients with no complications were maintained with triple-drug combination therapy (conventional group). In case of complications, the administration of very low-dose tacrolimus (C0: 5.0 to <3.0 ng/mL), reduced mycophenolate mofetil (1000-1500 to 500-1000 mg), and EVR (C0: 3.0-5.0 ng/mL) and methylprednisolone withdrawal (2-4 to 0 mg) were simultaneously conducted (EVR group). Graft survival and acute rejection rate were compared between groups. Within the EVR group, the dose of conventional immunosuppressants was compared between pre- and post-EVR administration. Renal function was evaluated 1 year post-EVR administration. RESULTS: All grafts survived in the conventional (n = 50) and EVR (n = 36) groups, and biopsy-proven acute rejection rate exhibited no significant difference between these groups (12% vs 17%; P = .55). Furthermore, no acute rejection occurred post-EVR administration. In the EVR group, all immunosuppressants significantly decreased post-EVR administration compared with those pre-EVR administration (P < .01), and serum creatinine significantly improved at postoperative year 1 (P = .031). CONCLUSIONS: EVR administration enables very low-dose tacrolimus administration, helps reduce mycophenolate mofetil and steroid withdrawal, and ameliorates renal function in maintenance kidney transplant recipients experiencing complications associated with conventional immunosuppressive therapy.

Selection Criteria for Kidney Laterality in Retroperitoneoscopic Living Donor Nephrectomy and the Usefulness of Pretransplant Intervention.

OBJECTIVES: To evaluate the selection criteria for kidney laterality and the usefulness of pretransplant intervention in living donor nephrectomy. METHODS: We compared conventional and revised criteria. The conventional criteria were that left kidneys were chosen in preference and provided the kidney with the fewest structural abnormalities and lowest functional decline and that most renal arteries remained in the donor. From April 2013, we allowed the use of left kidneys with double renal arteries. Patient characteristics and surgical outcomes were retrospectively compared between right and left retroperitoneoscopic living donor nephrectomies. RESULTS: We compared data for 30 right kidney and 222 left kidney nephrectomies. Right kidneys were selected because of multiple renal arteries (n = 18), structural abnormalities (n = 10) of the left kidney, or functional decline (n = 2) of the right kidney. Right retroperitoneoscopic nephrectomies were associated with significantly longer operating times (267 minutes vs 241 minutes), larger blood losses (240 g vs 55 g), and higher open conversion rates (10% vs 0.9%). Pretransplant intervention was necessary for structural abnormalities in right kidneys, but the amended selection criteria resulted in fewer right nephrectomies. Pretransplant intervention was still necessary by ex vivo arterial anastomosis for multiple left renal arteries, which increased the total ischemia time (94 minutes vs 64 minutes); however, post-transplantation renal function was not significantly different. CONCLUSIONS: Pretransplant intervention was beneficial both for repairing structural abnormalities and for reducing the difficulties of retroperitoneoscopic living donor nephrectomy.

Impact of Renal Transplantation and Nephrectomy on Urinary Soluble Klotho Protein.

BACKGROUND: Klotho is a single-pass transmembrane protein predominantly expressed in the kidneys. The soluble form of klotho has been shown to participate in various pathophysiological activities. However, information regarding the kinetics of soluble klotho remains limited. We herein assessed serial changes in the amounts of 24-hour urinary excreted soluble klotho among renal transplant recipients and concomitant living donors before and after transplantation. METHODS: A total of 15 recipients and donors were included in the current study, and the amounts of urinary soluble klotho were quantified using a sandwich enzyme-linked immunosorbent assay. RESULTS: Urine samples were available in 6 of the 15 recipients prior to the procedure. The amounts of urinary klotho in these 6 recipients and overall living donors at the baseline were 58.6 ng/day (IR: 29.3-142) and 698.8 ng/day (IR: 62.3-1619.5), respectively. Those in the recipients on postoperative day 2 (median 522.3 ng/day; IR 337.1-1168.5, P < .05) and day 5 (median 723.2 ng/day; IR 254.7-1238.6, P < .05) were significantly higher than the baseline values. Among the living donors, only a transient increase was observed in the amounts of urinary klotho on postoperative day 2. CONCLUSION: The current data regarding the urinary soluble klotho in recipients support the hypothesis that the kidney is a major source of urinary soluble klotho among the numerous components of the urinary tract. In living donors, the complex nature of events associated with acute reductions in the renal mass may modulate the release of soluble klotho from the kidneys into the urine.

Long-lasting inhibitory action of caerulein on climbing fiber system in the cerebellum of the rat.

Caerulein caused a marked decrease in levels of guanosine 3',5'-cyclic monophosphate (cGMP) in the cerebellum in rats. This effect was observed to be dose-dependent after the intraperitoneal administration of caerulein for doses over 20 micrograms/kg and lasted for about 4 hr in doses of 100 micrograms/kg. However, in vagotomized rats, caerulein failed to alter the level of cGMP in the cerebellum. Caerulein suppressed harmaline-induced increases in cGMP in the cerebellum for more than 30 hr. In contrast, the increases in levels of cGMP in the cerebellum, induced by treatment with methamphetamine, apomorphine and picrotoxin, were not inhibited by pretreatment with caerulein. These results suggest that the peripheral administration of caerulein can inhibit the activity of climbing fibers for a long period of time in the cerebellum of the rat through the stimulation of the abdominal vagus nerves.

Contribution of thromboxane A2 to the antigen-induced immediate asthmatic response mediated by IgG1 antibody by augmentation of bronchial responsiveness in guinea-pigs.

1. IgG1-mediated anaphylactic bronchoconstriction was elicited by intravenous administration of antigen to guinea-pig 2 days after passive sensitization with IgG1-rich serum, and this response was not affected by heating the serum (at 56 degrees C, for 4 h). IgE-mediated bronchoconstriction, provoked 14 days after passive sensitization with IgE-rich serum, was completely abolished by the heating of the serum. 2. S-1452 (10 mg kg-1, p.o.), a selective thromboxane (Tx) A2 antagonist, significantly but incompletely suppressed the IgG1-mediated bronchoconstriction, but did not affect the IgE-mediated one, while diphenhydramine (5 mg kg-1, i.v.), a histamine antagonist, almost completely inhibited both IgG1- and IgE-mediated bronchoconstriction. 3. Pretreatment with propranolol (1 mg kg-1, i.v.), a beta-adrenergic blocker, in addition to diphenhydramine, caused a long-lasting bronchoconstriction following antigen challenge in both animal models. This histamine-independent bronchoconstriction was markedly suppressed by S-1452 at a low dose of 0.1 mg kg-1. 4. A significant increase in bronchial responsiveness to i.v. acetylcholine (ACh), compared to the prechallenge value, occurred as early as 3 min and persisted for 24 h after antigen challenge in the IgG1 model, but was not observed in the IgE model. S-1452 (10 mg kg-1, p.o.) inhibited the IgG1-mediated bronchial hyperresponsiveness, as assessed 60 min after antigen challenge. 5. A marked elevation of TxB2 levels was observed in bronchoalveolar lavage fluid (BALF) 3 min after antigen challenge in the IgG1 model, while levels were not changed in the IgE model. In contrast, the plasma TxB2 level assessed 1 min after antigen challenge was increased in both the IgGI and IgE models.6. The results indicate that the inhibition of IgGl- but not IgE-mediated bronchoconstriction by higher doses of S-1452 may result from the suppression of increased bronchial responsiveness to allergic mediators such as histamine, which is probably due to TxA2 generated in the airway lumen rather than in plasma. In both the IgGI and IgE models, plasma TxA2 appeared to contribute directly to the bronchoconstriction, its action being almost completely masked by histamine-mediated bronchoconstriction.

Inhibition of proliferation of gastric epithelial cells by a cyclooxygenase 2 inhibitor, JTE522, is also mediated by a PGE2-independent pathway.

BACKGROUND: Cyclooxygenase-2 (COX-2) is one of the rate-limiting enzymes for prostaglandin synthesis from arachidonic acid. Although it is known that inhibition of cyclooxygenase activity delays ulcer healing, the regulatory relationship between COX-2 and its metabolites in gastric epithelial cell proliferation is not well known. AIM: To investigate whether COX-2 has an effect on gastric mucosal cell proliferation and further studied whether such effect is mediated only by prostaglandin E2 (PGE2), a representative metabolite of arachidonates in the gastric mucosa. METHODS: Artificial wounds of defined area size were created on complete monolayer cell sheets of isolated rat gastric epithelial cells and rat gastric cell line RGM1 under the addition of arachidonic acid or a COX-2 selective inhibitor, JTE522. Repair of wounds was assessed by monitoring wound size, with cell proliferation detected using 5-bromodeoxyuridine staining. Quantity of secreted PGE2 was measured by enzyme immunoassay. RESULTS: Stimulation of foetal calf serum increased the expression of COX-2 protein and inhibition of COX-2 retarded wound healing with reduction of cell proliferation. Arachidonic acid increased PGE2 production and accelerated restoration. Combination of JTE522 and arachidonic acid resulted in a marked retardation of wound healing compared to the control, but JTE522 did not completely suppress the increase in cellular PGE2 content following the addition of arachidonate. CONCLUSIONS: The difference in the effects of JTE522 on PGE2 production and on wound healing suggest that the involvement of COX-2 in gastric epithelial cell proliferation is not mediated solely by PGE2.

Alteration of histological gastritis after cure of Helicobacter pylori infection.

BACKGROUND: It is still disputed whether gastric atrophy or intestinal metaplasia improves after the cure of Helicobacter pylori infection. AIM: To clarify the histological changes after the cure of H. pylori infection through a literature survey. METHODS: Fifty-one selected reports from 1066 relevant articles were reviewed. The extracted data were pooled according to histological parameters of gastritis based on the (updated) Sydney system. RESULTS: Activity improved more rapidly than inflammation. Eleven of 25 reports described significant improvement of atrophy. Atrophy was not improved in one of four studies with a large sample size (> 100 samples) and in two of five studies with a long follow-up period (> 12 months), suggesting that disagreement between the studies was not totally due to sample size or follow-up period. Methodological flaws, such as patient selection, and statistical analysis based on the assumption that atrophy improves continuously and generally in all patients might be responsible for the inconsistent results. Four of 28 studies described significant improvement of intestinal metaplasia [corrected]. CONCLUSIONS: Activity and inflammation were improved after the cure of H. pylori infection. Atrophy did not improve generally among all patients, but improved in certain patients. Improvement of intestinal metaplasia was difficult to analyse due to methodological problems including statistical power.

Five-day proton pump inhibitor-based quadruple therapy regimen is more effective than 7-day triple therapy regimen for Helicobacter pylori infection.

BACKGROUND: There have been no reports that describe whether 5-day quadruple therapy (rabeprazole + amoxicillin + clarithromycin + metronidazole; RACM) could substitute for standard 7-day triple therapy as a first-line therapy for Helicobacter pylori. PATIENTS AND METHODS: This study was designed as a randomized prospective single centre study. A total of 160 H. pylori-positive patients who had not received therapy were given either a 5-day RACM regimen (n=80, rabeprazole 20 mg b.d., amoxicillin 750 mg b.d., clarithromycin 200 mg b.d. and metronidazole 250 mg b.d.) or a 7-day RAC regimen (n=80, rabeprazole 20 mg b.d., amoxicillin 750 mg b.d. and clarithromycin 200 mg b.d.). Cure of the infection was assessed by a (13)C urea breath test 1 month after the completion of therapy. RESULTS: The eradication rates of the 5-day RACM regimen and the 7-day RAC regimen were 93% (95% CI: 84--97%) and 81% (95% CI: 71--89%) by intention-to-treat analysis, 94% (95% CI: 86--98%) and 83% (95% CI: 73--91%) by all-patients-treated analysis analysis and 95% (95% CI: 87--98%; P < 0.05) and 82% (95% CI: 72--90%) by per protocol analysis, respectively. No serious adverse effect was observed, and 99% of the patients reported complete compliance. CONCLUSIONS: The cure rate of the 5-day RACM regimen was more effective than the 7-day RAC regimen, suggesting that this regimen could be preferable as a first-line therapy for H. pylori infection.

Is antimicrobial susceptibility testing necessary before second-line treatment for Helicobacter pylori infection?

BACKGROUND: An antimicrobial susceptibility test for Helicobacter pylori before second-line treatment is often performed, although whether the test is truly necessary remains unknown. PATIENTS AND METHODS: Eighty-two patients with H. pylori infection for whom first-line treatment with a 1-week proton pump inhibitor/amoxicillin-clarithromycin (AC) regimen had failed were randomly assigned to two groups: those having or not having the susceptibility test before re-treatment. The cure rates for these two groups were compared. RESULTS: Five of the 82 patients were excluded from the analysis. For 38 patients in the susceptibility-test group, we used what we considered the best regimen based on susceptibility testing: 10 patients [no resistance to clarithromycin (CAM)] received the lansoprazole-amoxicillin-clarithromycin regimen, 22 patients [19 CAM resistant, metronidazole (MNZ) susceptible; three failure of culture] were given the lansoprazole-amoxicillin-metronidazole (LAM) regimen, and six patients (both MNZ and CAM resistant) received dual therapy with omeprazole (OPZ) and amoxicillin (AMOX) in which the OPZ dose was determined by the CYP2C19 gene polymorphism. For 39 patients in the group with no susceptibility testing, LAM regimens were prescribed. The intention-to-treat (ITT)-based cure rates in the groups with and without susceptibility testing were 81.6% (95% confidence interval; 66-92%) and 92.4% (79-98%), respectively, and there was no significant difference between these two groups. CONCLUSION: Susceptibility testing is not necessarily required before second-line therapy if the first-line treatment has been performed using proton pump inhibitor/AC regimens.

Improvement in serum pepsinogens and gastrin in long-term monitoring after eradication of Helicobacter pylori: comparison with H. pylori-negative patients.

BACKGROUND: A decrease in pepsinogen and gastrin levels 1-3 months after Helicobacter pylori eradication is well known. However, few data are available on the long-term progression of these decreases beyond 1 year after eradication, and there has been no investigation into whether pepsinogen and gastrin levels return to normal levels as defined by data from H. pylori-negative patients with dyspepsia. AIM: We studied the effect of H. pylori eradication on pepsinogen and gastrin levels for more than 1 year, and compared levels to those in H. pylori-negative patients with dyspepsia. We also investigated the effect of H. pylori eradication on the course of atrophic corpus gastritis as reflected by histology, and on PGI levels and PG I/II ratio. METHODS: We enrolled 172 H. pylori-positive patients with dyspepsia who had undergone successful eradication therapy of more than 1 year's duration and 101 non-treated H. pylori-negative patients with dyspepsia. H. pylori status was assessed at entry and at each endoscopy after eradication by culture, histological results, the rapid urease test and the urea breath test. In both groups, patients were evaluated for fasting serum pepsinogen I and II and gastrin using a radioimmunoassay technique, and underwent detailed histological assessment according to the updated Sydney System. RESULTS: In the H. pylori-negative patients, mean serum pepsinogen I and II, I/II ratio and gastrin levels were 52.6 +/- 20.8 ng/mL, 9.2 +/- 4.2 ng/mL, 6.0 +/- 1.7 and 53.5 +/- 29.2 pg/mL, respectively. In H. pylori-positive patients with long-term eradication, pepsinogen I and II, I/II ratio and gastrin levels were 81.3 +/- 46.6 ng/mL, 25.9 +/- 17.1 ng/mL, 3.4 +/- 1.3 and 131.9 +/- 130.8 pg/mL, respectively, before treatment. At 1-3 months after eradication, serum pepsinogen I and II levels in the H. pylori-positive patients decreased to levels similar to those in the negative patients, whereas pepsinogen I/II ratio and gastrin levels remained lower and higher, respectively, than in the negative patients. Serum pepsinogen I/II ratio and gastrin levels then became similar between the groups at 12-15 months after eradication. In histological findings, inflammation and neutrophil activity decreased by 1-3 months, and atrophy in the corpus and metaplasia in the antrum decreased by 12-15 months. CONCLUSION: The results suggest that atrophic corpus gastritis and superficial gastritis are reversible, as indicated by both histological and serological findings in a long-term follow-up study.

Oesophageal hypersensitivity in Japanese patients with non-erosive gastro-oesophageal reflux diseases.

BACKGROUND: Visceral hypersensitivity plays a major role in the pathogenesis of non-erosive oesophageal reflux disease (NERD). Prevalence of NERD differs according to the population and geographical region. Oesophageal hypersensitivity in NERD has not been well studied, especially in Japanese patients. AIM: To investigate oesophageal hypersensitivity in Japanese NERD patients. PATIENTS AND METHODS: We performed upper GI endoscopy and the modified acid perfusion test on 14 control subjects and 68 GERD patients, including 26 with NERD, 34 with erosive GERD, and six with Barrett's oesophagus. The stimulus-response function to acid was quantified by three parameters (lag time, intensity rating and the acid perfusion sensory score) and compared among four groups. RESULTS: The mean value of the lag time, intensity rating, and acid perfusion scores in NERD patients (4.6 +/- 3.4, 4.4 +/- 3.4, 27.8 +/- 26.7, respectively) were higher than in erosive GERD (3.2 +/- 3.3, 3.0 +/- 3.2, 18.2 +/- 24.8) and Barrett patients (2.5 +/- 4.0, 1.8 +/- 3.3, 15.0 +/- 28.8), and significantly higher than in the control group (1.7 +/- 2.7, 1.1 +/- 2.0, 5.4 +/- 11.8). The ratio of patients with higher sensory scores was also greater in the NERD group (57.7%) than in erosive GERD (32.3%) and Barrett group (16.7%), and significantly greater than in control group (6.7%). CONCLUSION: Our findings suggest that oesophageal sensitivity is likely to be enhanced especially in NERD patients also in Japanese population in comparison with erosive GERD, Barrett's oesophagus and controls.

Ovoid bodies in choroidal neurofibromatosis.

We studied the ultrastructure of the ovoid bodies in choroidal neurofibromatosis. Ovoid bodies consisted of groups of the same kind of elongated cells arranged in lamellar patterns. The elongated cell was characterized by a fragmented circumferential basal lamina, groups of pinocytotic vesicles, a desmosomelike intercellular contact, and intimate contact with axons. These findings suggest that elongated cells are proliferated Schwann's cells and ovoid bodies do not correspond with real sensory nerve end organs; rather, they are enlarged peripheral nerves due to neoplastic hyperplasia of Schwann's cells around axons.

Sporothrix schenckii endophthalmitis in a patient with human immunodeficiency virus infection.

A 30-year-old homosexual man with a positive serologic test for human immunodeficiency virus and a history of successfully treated disseminated cutaneous sporotrichosis developed a granulomatous uveitis that worsened with topical and subconjunctival steroid therapy. Culture of the aqueous aspirate yielded Sporothrix schenckii. The patient was treated with intravenous amphotericin B and intravitreal amphotericin B, kanamycin sulfate, and amikacin sulfate. Subsequent aqueous and vitreous cultures were negative, but the intraocular inflammatory process progressed and ultimately led to enucleation of the eye. Histopathologic examination revealed granulomatous inflammation of the anterior uvea and scattered S schenckii in the anterior and posterior chambers. Electron microscopy demonstrated that most of the organisms had disorganized protoplasm. Although treatment failed to ameliorate the progressive intraocular inflammatory process, the negative cultures and the electron microscopic observations suggest that the treatment was reasonably effective in killing S schenckii within the eye. To our knowledge, this is the first case report of S schenckii endophthalmitis in a patient with human immunodeficiency virus infection.

Transient improvement of amphetamine-induced rotational behavior by PC12 cell grafts: studies with microdialysis.

The effects of striatal transplantation of PC12 cells on amphetamine-induced rotational behavior and monoamine levels were examined in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions in the nigrostriatal pathway. A total of 9 × 104 or 9 × 105 cells of PC12 was implanted into 3 sites in the striatum and changes in amphetamine (3 mg/kg, i.p.)-induced rotational behavior were observed for 8 weeks. Two weeks after transplantation, a significant reduction in rotation was observed. However, this improvement disappeared after 3 weeks. Three of 7 rats implanted with 9 × 104 cells and 6 of 7 rats with 9 × 105 cells died between 3 and 4 weeks after transplantation. In 6-OHDA-injected control rats, the levels of dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in brain dialysates were profoundly reduced to between 0 and 11% of normal rats, while the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) level remained unchanged. These reductions in DA and its metabolites did not recover at 2 or 8 weeks after the transplantation of 9 × 104 PC12 cells. 5-HIAA was reduced at 2 weeks and recovered to nearly control levels at 8 weeks. Histologically, PC12 cells proliferated to form a large tumor mass at 2 weeks. There were almost no processes growing from the aggregated PC12 cells into the host tissue. These results indicate that PC12 grafts do not release detectable quantities of DA into the deafferented striatum, and suggest that the transient improvements in rotational behavior may be due to a non-specific suppression in neuronal function induced by the growing tumor mass.