Risk factors for trachoma: 6-year follow-up of children aged 1 and 2 years

The authors investigated the long-term stability of risk factors in predicting the presence of active trachoma and severe inflammatory trachoma in 176 children in Kongwa, Tanzania, who were aged 1 and 2 years in 1989 and were available for follow-up in 1995. Familial cattle ownership, living more than 2 hours away from a water source, and facial cleanliness at both time points were associated with the presence of active trachoma at both time points (odds ratio (OR) = 2.58, 95% confidence interval (CI): 1.15, 5.79; OR = 3.07, 95% CI: 1.23, 7.64; and OR = 0.52, 95% CI: 0.26, 1.03, respectively). An association of familial cattle ownership with facial cleanliness and water accessibility was observed. Having a clean face at both time points was associated with lower odds of active trachoma at both time points for children in non-cattle-herding families (OR = 0.40, 95% CI: 0.18, 0.87). Living more than 2 hours away from a water source at both time points increased the odds of active trachoma at both time points in children of cattle-herding families (OR = 8.00, 95% CI: 1.99, 32.10). Noticeably, severe inflammatory trachoma at baseline predicted mortality in children from villages in which trachoma was less common (OR = 3.75, 95% CI: 1.09, 12.98). The results suggest that risk factor reduction could diminish persistent disease.     

Effects of dietary fat and a vegetable-fruit mixture on the development of intestinal neoplasia in the ApcMin mouse

The variation in colorectal cancer (CRC) incidence worldwide strongly suggests a role for dietary influences. Based on epidemiological data, protective effects of vegetables and fruit intake on CRC are widely claimed, while other data indicate a possible increased CRC risk from (higher) dietary fat intake. Therefore, we have investigated single and interactive effects of dietary fat and a vegetable-fruit mixture (VFM) in the ApcMin mouse, a mouse model for multiple intestinal neoplasia. In this study, four different diets (A-D) were compared, which were either low in fat (20% energy diets A/B) or high in fat (40% energy diets C/D). In addition, 19.5% (wt/wt) of the carbohydrates in diets B and D were replaced by a freeze-dried VFM. The diets were balanced so that they only differed among each other in fat/carbohydrate content and the presence of specific plant-constituents. Because the initiation of intestinal tumors in ApcMin mice occurs relatively early in life, exposure to the diets was started in utero. Without the addition of VFM, mice maintained at a high-fat diet did not develop significantly higher numbers of small or large intestinal adenomas than mice maintained at a low-fat diet. VFM added to a low-fat diet significantly lowered multiplicity of small intestinal polyps (from 16.2 to 10.2/mouse, 15 animals/group), but not of colon tumors in male ApcMin mice only. Strikingly, addition of VFM to female mice maintained on a low-fat diet and to both sexes maintained on a high-fat diet significantly enhanced intestinal polyp multiplicity (from 16.5 to 26.7 polyps/mouse). In conclusion, our results indicate that neither a lower fat intake nor consumption of VFM included in a high-fat diet decreases the development of polyps in mice genetically predisposed to intestinal tumor development.      

Continuous infusion cisplatin and etoposide chemotherapy for cancer of unknown primary site (CUPS) in Taiwan, a region with a high prevalence of endemic viral infections

BACKGROUND: To evaluate the efficacy and toxicity of cisplatin/etoposide continuous infusion chemotherapy for cancer of unknown primary site in Taiwan, a region with a high prevalence of endemic viral infections. METHOD: Between April 1994 and February 1996, 20 patients with a diagnosis of CUPS were treated, including 15 males and five females, of average age 63.3 years (range 41-83 years). Continuous intravenous infusion of etoposide 80 mg/m2 and cisplatin 25 mg/m2 was given for 3 days every 3 weeks. Pretreatment tumor marker and viral serology studies were performed for baseline evaluation. Nearly two-thirds of the patients had poorly differentiated carcinoma. The average number of metastatic sites was 2.65 (range 1-4), with liver and lymph node involvement predominating. RESULTS: The overall response rate was 25% (95% CI 17.7-32.3%); 30.7% for poorly differentiated cancers and 25% for well differentiated cancers. Median survival was 4 months (range 1-12 months), 4.8 months for patients attaining partial response. Toxicity was moderate, grade 3 and 4 neutropenia occurred in 55% and grade 3 and 4 thrombocytopenia in 40%; other toxicities were mild. CA125 and CA199 were elevated in more than 50% of patients. Viral serology studies were not significantly different from those of the indigenous population. CONCLUSION: Etoposide and cisplatin combination chemotherapy has modest activity in patients with extensive CUPS and, at the schedule and dosage given, it is associated with moderate toxicity.      

Toxic cardiogenic shock in a patient receiving weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin

A 54-year-old man was treated with weekly 24-h infusion of high-dose 5-fluorouracil (2600 mg/m2) and leucovorin (100 mg/m2) for metastatic colon cancer. At first, he tolerated the treatment well and no significant toxicity was identified. After a total of eight courses of treatment, a stable disease was observed, but mild shortness of breath was found on occasion. The patient had no previous history of cardiac disease and the heart performance assessed by left ventricular ejection fraction before treatment was normal. Unfortunately, acute pulmonary edema with lethal cardiogenic shock occurred during the ninth course of treatment, in spite of intensive medical treatment. The chest X-ray showed extreme cardiomegaly. Repeated assessment of his heart function by echocardiogram and ventricular ejection fraction revealed a very poor cardiac performance. Toxic cardiogenic shock during weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin is extremely rare. To the best of our knowledge, no case has been reported in the English literature. We report a case and the relevant literature about the incidence, clinical picture and possible pathophysiology on 5-fluorouracil-related cardioxicity is reviewed.      

Conjoined twin's cephalothoracopagus janiceps monoymmetros: a case report

We present a report on a case of conjoined twin/s (cephalothoracopagus janiceps monosymmetros) diagnosed by ultrasonography and X-ray at 27 weeks' gestation. Accepted: 29 December 1997     

Human metabolism of the proteasome inhibitor bortezomib: identification of circulating metabolites.

Bortezomib [N-(2,3-pyrazine)carbonyl-L-phenylalanine-L-leucine boronic acid] is a potent first-in-class dipeptidyl boronic acid proteasome inhibitor that was approved in May 2003 in the United States for the treatment of patients with relapsed multiple myeloma where the disease is refractory to conventional lines of therapy. Bortezomib binds the proteasome via the boronic acid moiety, and therefore, the presence of this moiety is necessary to achieve proteasome inhibition. Metabolites in plasma obtained from patients receiving a single intravenous dose of bortezomib were identified and characterized by liquid chromatography/mass spectrometry (LC/MS) and liquid chromatography/tandem mass spectrometry (LC/MS/MS). Metabolite standards that were synthesized and characterized by LC/MS/MS and high field nuclear magnetic resonance spectroscopy (NMR) were used to confirm metabolite structures. The principal biotransformation pathway observed was oxidative deboronation, most notably to a pair of diastereomeric carbinolamide metabolites. Further metabolism of the leucine and phenylalanine moieties produced tertiary hydroxylated metabolites and a metabolite hydroxylated at the benzylic position, respectively. Conversion of the carbinolamides to the corresponding amide and carboxylic acid was also observed. Human liver microsomes adequately modeled the in vivo metabolism of bortezomib, as the principal circulating metabolites were observed in vitro. Using cDNA-expressed cytochrome P450 isoenzymes, it was determined that several isoforms contributed to the metabolism of bortezomib, including CYP3A4, CYP2C19, CYP1A2, CYP2D6, and CYP2C9. The development of bortezomib has provided an opportunity to describe the metabolism of a novel boronic acid pharmacophore.     

Differential modulation of auditory thalamocortical and intracortical synaptic transmission by cholinergic agonist

To investigate synaptic mechanisms underlying information processing in auditory cortex, we examined cholinergic modulation of synaptic transmission in a novel slice preparation containing thalamocortical and intracortical inputs to mouse auditory cortex. Extracellular and intracellular recordings were made in cortical layer IV while alternately stimulating thalamocortical afferents (via medial geniculate or downstream subcortical stimulation) and intracortical afferents. Either subcortical or intracortical stimulation elicited a fast, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)-sensitive, monosynaptic EPSP followed by long-duration, polysynaptic activity. The cholinergic agonist carbachol suppressed each of the synaptic potentials to different degrees. At low concentrations (5 μM) carbachol strongly reduced (>60%) the polysynaptic slow potentials for both pathways but did not affect the monosynaptic fast potentials. At higher doses (10–50 μM), carbachol also reduced the fast potentials, but reduced the intracortically-elicited fast potential significantly more than the thalamocortically-elicited fast potential, which at times was actually enhanced. Atropine (0.5 μM) blocked the effects of carbachol, indicating muscarinic receptor involvement. We conclude that muscarinic modulation can strongly suppress intracortical synaptic activity while exerting less suppression, or actually enhancing, thalamocortical inputs. Such differential actions imply that auditory information processing may favor sensory information relayed through the thalamus over ongoing cortical activity during periods of increased acetylcholine (ACh) release.     

Preservation of the thin distal urethra in hypospadias repair

PURPOSE: We report our experience with preserving the thin distal urethra lacking corpus spongiosum for the treatment of hypospadias. MATERIALS AND METHODS: From January 1997 to October 1999 we treated primary hypospadias in 77 boys with a mean age of 4 years 10 months. After degloving the penile skin a segment of thin distal urethra lacking corpus spongiosum was noted in 18 patients (23.4%) with a mean age of 3 years 5 months. The thin distal urethra was preserved and incorporated as part of urethroplasty (group 1). The procedure was primarily completed by tubularized incised plate urethroplasty. We also performed tubularized incised plate urethroplasty in 31 boys (40.3%) with a mean age of 5 years 2 months who had normal coverage of the corpus spongiosum of a hypospadiac urethra (group 2). We compared the results of treatment in these 2 groups. The remaining 28 patients (36.4%) treated with other methods were excluded from study. RESULTS: In group 1 the distance from the original meatus to the urethra covered by healthy corpus spongiosum was 4 to 20 mm. (mean 8.2). If the thin distal urethra had been excised, the urethral meatus would have been relocated more proximal in these boys. Mean followup in groups 1 and 2 was 9.9 and 7.6 months, respectively. Postoperatively there were 2 (11.1%) urethrocutaneous fistulas in group 1 and 4 (12.9%) in group 2. Tubularized incised plate repair was successful in all 10 cases (100%) of distal hypospadias in group 2, and in 15 of 18 (83.3%) and 17 of 21 (81%) of proximal hypospadias cases in groups 1 and 2, respectively. There was no statistically significant difference in the success rate of hypospadias repair in the groups. CONCLUSIONS: We noted a significantly thin distal urethra in 23.4% of our cases of primary hypospadias. Mean length of the thin distal urethra was 8.2 mm. Preserving the thin distal urethra may simplify the operative procedure without compromising the surgical results of tubularized incised plate urethroplasty.