Ocular and sinus microsporidial infection cured with systemic albendazole

PURPOSE: To report treatment of a patient with acquired immunodeficiency syndrome (AIDS) and ocular and paranasal sinus microsporidial infection. METHOD: Case report. RESULTS: A patient with AIDS and ocular microsporidial infection experienced resolution of ocular symptoms with topical fumagillin, but symptoms recurred upon cessation of therapy. Paranasal sinus microsporidial infection was diagnosed. The patient received sequential systemic treatment with itraconazole followed by albendazole. Sinus symptoms resolved with albendazole. He remained symptom-free with a normal examination 17 months after concluding therapy. CONCLUSIONS: Although fumagillin and itraconazole may have played a role, systemic albendazole appears to be responsible for clinical resolution of microsporidial infection.     

Stapedectomy in profound cochlear loss

Stapedectomy can be used in certain patients with profound sensorineural hearing loss and stapes fixation to improve hearing to a level at which a hearing aid may be effective. This study reviews the outcomes of 11 patients with profound cochlear loss secondary to otosclerosis who underwent stapes surgery performed by the senior author (M.E.G.) over a 25-year period. Postoperative hearing aid usage was effective in 9 of 11 patients. Preoperatively, these patients derived no benefits from hearing aids. Stapedectomy may be of immense value in patients with the proper history and profound cochlear loss.     

Effect of 6-aminonicotinamide on the pentose phosphate pathway: 31P NMR and tumor growth delay studies

6-aminonicotinamide (6AN) has been shown to enhance radiosensitivity in vitro, although previous in vivo studies failed to show an effect. 31P NMR spectra were obtained by using a one-dimensional chemical shift imaging technique on a first generation transplant of the CD8FI spontaneous mammary carcinoma tumor model. Spectra were obtained both before and 10 h after treatment with 6AN (20 mg/kg). Changes in pH, nucleoside triphosphate/inorganic phosphate, and phosphocreatine/ inorganic phosphate measured at 10 h post-6AN were not significant. A new peak was detected 10 h post-6AN, which was assigned to 6-phosphogluconate (6PG), indicating inhibition of the pentose phosphate pathway (PPP). Based on the spectral data demonstrating inhibition of the PPP at 10 h post-6AN, tumor-bearing mice were irradiated (15 Gy x 3 fractions) on Days 1, 10 or 11, and 21 10 h after administration of 6-aminonicotinamide (20 mg/kg). Tumor-bearing mice receiving 6AN alone (20 mg/kg x 3), radiation alone (15 Gy x 3), or saline were also studied. Tumor growth delay studies indicated that 6AN alone induced a small but significant tumor growth delay (4.3 +/- 0.8 days). Radiation alone induced a tumor growth delay of 34.5 +/- 2.7 days. Treatment with 6AN followed by radiation induced a tumor growth delay of 57.0 +/- 3.8 days. This was significantly greater than the TGD values for treatment with 6AN alone or radiation (P < 0.01). No complete regressions were noted after treatment with 6AN or radiation alone. Concomitant therapy with 6AN plus radiation yielded 6/28 complete regressions (21%), which was significantly greater than radiation (P < 0.05) or 6AN alone (P < 0.01) on this mammary carcinoma.     

Potato lectin: a three-domain glycoprotein with novel hydroxyproline-containing sequences and sequence similarities to wheat-germ agglutinin

Potato (Solanum tuberosum) tuber lectin is a chitin-binding, hydroxyproline-rich glycoprotein, which may be involved in the defence mechanism of the plant. We had previously obtained evidence that it consists of at least two very dissimilar domains. The aim was to use a combination of accurate determinations of molecular weight and protein sequencing to gain more accurate information on the domains. Accurate determinations of the molecular weight of the lectin by a MALDI mass spectrometer have shown that the subunit molecular weight is 65,500 (+/- 1100) and that of a totally deglycosylated sample is 31,250 (+/- 30). This means that the lectin is 52.3 (+/- 1)% carbohydrate with a considerable number of glycoforms being present. Partial sequences and other analyses are consistent with the existence of three distinct domains. These are: (1) an N-terminal region which is rich in proline but poor in hydroxyproline; (2) a glycosylated region with a glycosylated molecular weight of 45,300 (+/- 1100) and a deglycosylated molecular weight of 11,050 (+/- 50) which is extremely rich in glycosylated hydroxyproline residues with a similar sequence to extensins; and (3) a cystine-rich domain which has the sugar binding site shows partial conservation of a repeated motif common to many chitin-binding proteins of the hevin family including wheat-germ agglutinin. The closest similarity seems to be to the sequence of potato basic chitinase.     

Optimizing form and function with the direct posterior composite resin: a case report

The human testis determining factor (SRY) has been cloned from the Y chromosome. This gene is a dominant inducer of male differentiation. Mutations in the SRY gene result in an XY individual developing as a sex reversed phenotypic female. Sex reversal in humans can also be caused by mutations located in autosomal or X-linked loci. One such sex-reversing locus (SRAI) is associated with the developmental disorder campomelic dysplasia (CD). Both these syndromes were mapped to human chromosome 17q by the identification of balanced reciprocal translocations in five unrelated patients. The translocation breakpoint of one such XY-female CD patient was mapped and the region surrounding it cloned. The closest distal marker used to map the translocation breakpoint was the SOX9 gene. Because of the close proximity of this gene to the breakpoint, it was subjected to mutation analysis in patients without overt chromosome rearrangements. Analysis of DNA from these patients and their parents identified de novo mutations in the SOX9 gene in patients with both autosomal sex reversal and CD. This showed that mutations in the SOX9 gene are responsible for both syndromes.     

Studies on the development of diluents for the transportation and storage of human semen at ambient temperature

Storage of human semen samples at ambient temperature for 24 h resulted in a significant loss of sperm motility from a mean 45.1 +/- 1.8% to 13.8 +/- 1.1% (n = 148). This motility loss was associated with a significant increase in the osmolality of the seminal plasma and the induction of peroxidative damage to the spermatozoa. Both of these detrimental changes could be prevented by diluting the original semen sample 1:1 with a citrate-egg yolk, buffer (CYB). In the presence of this extender all aspects of semen quality were efficiently preserved for 24 h, including sperm movement, penetration of a cervical mucus substitute, the acrosome reaction and sperm-oocyte fusion. CYB extension also permitted the use of chemiluminescent tests of leukocyte contamination to be performed on semen samples stored for 24 h at ambient temperatures. As a preservation medium, CYB was found to be superior to alternative formulations lacking citrate and storage at ambient temperatures was preferable to 4 degrees C. Significant improvements in motility retention were also observed when CYB was supplemented with pentoxifylline, although this treatment significantly stimulated peroxidative damage in the spermatozoa. However, if the pentoxifylline was combined with antioxidants then this collateral peroxidative damage could be reduced and the performance of CYB significantly enhanced. These results have implications for the design of diluents permitting the long-term storage and transportation of human semen samples at ambient temperatures.     

Open reduction and internal fixation of forearm fractures in children

We retrospectively reviewed 16 children younger than 13 years with 17 fractures of the shafts of the radius or ulna or both who had undergone an open reduction-internal fixation (ORIF). ORIF was performed when a closed reduction was deemed unacceptable in 14 radius fractures and for three unstable open fractures of the radius. The average age was 9.4 +/- 2.3 years (range, 5.0-12.5). Of the 14 fractures with an unacceptable closed reduction, soft-tissue interposition was encountered in seven. Fixation was secured by plates and screws, percutaneous Steinmann pins, or intramedullary Steinmann pins. There were no delayed unions or nonunions, no infections, and no neurovascular injuries. The average follow-up was 12.3 months; all 17 fractures had excellent results (forearm rotation loss of < 10 degrees). Our study indicates that excellent results can be expected with no increased risk of complications if the treating physician elects to proceed with an ORIF in a pediatric forearm fracture with proper indications.     

Merkel cell carcinoma of the skin

Primary neuroendocrine carcinoma of the skin or Merkel cell carcinoma is an aggressive primary neoplasm. It is commonly seen in the elderly, on the head, neck and extremities, where it can mimic a benign or less malignant skin tumour. Pathological examination shows a generally dense growth of small dark cells, with immunohistochemical evidence of neuroendocrine differentiation. The microscopic appearance is very similar to metastatic oat cell carcinoma from the lung and this must be excluded by clinical means and appropriate imaging studies. In this study we present 13 new cases of Merkel cell carcinoma (the largest published series in the UK) and summarize 214 cases from the literature in which the survival data are given. In our series, 5 of 13 patients died from spread of the Merkel cell carcinoma. From this and other studies, it appears that early diagnosis and wide local excision may be the only way to prolong survival. No other adjuvant therapy has proved effective.     

Kinetics of duck hepatitis B virus infection following low dose virus inoculation: one virus DNA genome is infectious in neonatal ducks

Using pooled serum from congenitally duck hepatitis B virus (DHBV)-infected ducks as inoculum, we examined the effect of virus dose on the incubation period of infection and on the patterns of spread of virus infection in the liver. The pooled serum inoculum contained 9.5 x 10(9) DHBV genomes per milliliter and had an infectivity titre (ID50) in newly hatched ducks of 1.5 x 10(10) per milliliter with a 95% confidence interval of 3.0 x 10(9) to 6.3 x 10(10) ID50/ml, indicating the equivalence between one DHBV genome and one infectious unit within the limits of the assays. The incubation period of infection was inversely related to the dose of inoculum and the onset of viraemia ranged from Day 6 with the highest dose to Day 14 or 29 with the lowest dose inoculum. To study the spread of virus infection from a low percentage of initially infected cells we inoculated newly hatched ducks intravenously with sufficient DHBV (1.5 x 10(3) ID50) to infect only approximately 0.0001% of total liver cells. DHBV infection first reached detectable levels on Day 4 postinoculation (p.i.) and was detected in approximately 0.035% of hepatocytes, most of which occurred as single cells or pairs of cells, indicating that a number of rounds of infection had occurred with the spread of virus both to adjoining cells, i.e., by cell-to-cell spread, and to cells located in other parts of the liver lobule. Despite some bird-to-bird variation in timing, the percentage of infected hepatocytes increased exponentially with a mean doubling time of 16 hr from Day 4 to Day 14 p.i., by which time replication was seen in > 95% of hepatocytes. This rapid dissemination from a small number of infected hepatocytes suggests that, in neonatal ducks, there are no major delays in virus replication within the liver, that any innate and adaptive defence mechanisms operating during the first 10 to 14 days of infection are insufficient to contain virus spread, and that even a small number of infected hepatocytes produce enough progeny to rapidly infect the remaining hepatocytes.     

Endogenous 7-oxocholesterol is an enzymatic product: characterization of 7 alpha-hydroxycholesterol dehydrogenase activity of hamster liver microsomes

Previously, we described a new metabolite derived from endogenous cholesterol in the presence of hamster liver microsomal protein and NADPH (Song et al., 1991, Biochem. Pharmacol. 41, 1439-1447). Through gas chromatography/mass spectral analysis of the metabolite and its methoxime-3-dimethyl-t-butylsilyl ether derivative, this metabolite has been definitively identified as 7-oxocholesterol. Isotope incorporation experiments using molecular 18O2 demonstrated that no oxygen atoms from molecular oxygen were incorporated into the product, 7-oxocholesterol, when 7 alpha-hydroxycholesterol was used as substrate. In contrast, one atom of 18O was incorporated into cholesterol from 18O2 during its metabolism to form 7 alpha-hydroxycholesterol. Formation of 7-oxocholesterol was dependent upon the presence of NADP+, 7 alpha-hydroxycholesterol, and hamster liver microsomes. This enzyme appears to be a membrane-bound protein and its activity was most abundant in liver microsomal fractions and to a lesser extent in mitochondrial fractions; little or no activity was observed in nuclei or cytosol. The enzyme activity was present in highest content in the livers of hamsters and was also observed in human and bovine liver microsomes, but not those of mouse, rabbit, or rat. The reaction was inhibited by 2'-AMP, but not by anti-NADPH:cytochrome-P450 oxidoreductase globulin, carbon monoxide, metyrapone, nor miconazole. In contrast to the previously characterized 3 beta-hydroxy-delta 5-C27-steroid oxidoreductase activity, NAD+ did not serve as an effective cofactor for 7-oxocholesterol formation. The ability of NADPH to partially serve as a cofactor in this reaction was shown to be due to a high NADPH-oxidase activity of hamster liver microsomes, thereby providing sufficient NADP+ to serve as the oxidizing pyridine nucleotide for the reaction. These results document the existence of a non-P450, NADP(+)-dependent 7 alpha-hydroxycholesterol dehydrogenase in liver microsomes which catalyzes this reaction. The product, 7-oxocholesterol, is produced enzymatically in the livers of hamsters and other mammals and may regulate bile acid metabolism or other processes due to its action as an oxysterol.