Intestinal permeability in the newborn

Passive intestinal permeability in 33 newborn babies was studied using feeds containing lactulose and mannitol. Each marker is thought to pass across the gut wall by a different route; lactulose by a paracellular and mannitol by a transcellular pathway. Neither is metabolised and both are wholly and solely excreted by the kidney; urinary recovery is a measure of the intestinal uptake. Babies born before 34 weeks' gestation exhibited a higher intestinal permeability to lactulose than more mature babies, and all preterm babies showed an appreciable decline in lactulose absorption during the first week of oral feeds. Babies of 34 to 37 weeks' gestation achieved a 'mature' intestinal permeability to lactulose within four days of starting oral feeds. These findings may reflect the immaturity of the gut of the preterm baby rather than a process essential to adaptation to enteral nutrition.     

Management of Peyronie's disease with penile prostheses

Peyronie's disease is a common malady affecting men mostly between the ages of 40 and 60. When penile curvature and erectile softening are present and the erectile dysfunction does not respond to Viagra a penile implant will strengthen and usually straighten the penis. If curvature persists after implant placement 'modeling' the erect penis will successfully achieve straightening in most patients. Plaque incision and grafting or a Nesbit procedure are rarely necessary to straighten the penis but will afford excellent results when employed. A thorough explanation of the pathogenesis of Peyronie's disease and effects of the disease and treatment on penile size will help avoid some of the disappointment seen when a shorter erection occurs.     

Circadian and orthostatic blood pressure is abnormal in the carotid sinus syndrome

The authors' objective was to determine circadian blood pressure behavior and the prevalence of orthostatic hypotension in patients with cardioinhibitory carotid sinus syndrome. A prospective consecutive series of 160 patients (mean age, 72 [65–83]) with recurrent syncope attributed to cardioinhibitory carotid sinus syndrome was recruited. Mean maximal slowing of heart rate was 4.5 seconds (3.0–5.5 seconds) during carotid sinus massage. Patients had cardiovascular assessments, including 24-hour ambulatory blood pressure measurements (recordings every half-hour during daytime, hourly at night) and morning orthostatic blood pressures before pacemaker implants. Ambulatory measurements were compared with those of 98 age-and sex-matched controls. Nocturnal systolic blood pressure (130.0±21.0 vs. 122.1±16.7 mm Hg; p< 0.005), diastolic blood pressure (72.8±12.5 vs. 68.7±9.7 mm Hg; p< 0.005), and heart rate (66.5±9.4 vs. 65.2±9.7 bpm; p< 0.005), were significantly higher in patients and independent of cardiovascular medication, cardiovascular diagnoses, and orthostatic hypotension. Almost one half of carotid sinus syndrome patients also had orthostatic hypotension. Blood pressure behavior is abnormal in patients with carotid sinus syndrome as represented by altered nocturnal blood pressures and high prevalence of orthostatic hypotension.     

Pilot study of gemcitabine (10 mg/m<Superscript>2</Superscript> per min) and cisplatin

PURPOSE: Gemcitabine and cisplatin are routinely used in combination. In this combination, gemcitabine at conventional doses of 1000-1500 mg/m(2) is delivered weekly as a 30-minute bolus. Laboratory data suggest that the synthesis of gemcitabine triphosphate is saturable, and that gemcitabine infused at a rate of 10 mg/m(2) per min optimizes accumulation of the triphosphate. Early clinical experience suggests that gemcitabine delivered by a more prolonged infusion is more myelosuppressive. In this pilot study, we wished to assess if full-dose gemcitabine when given with cisplatin could be delivered by this more prolonged infusion. METHODS: In this study, all patients received cisplatin 75 mg/m(2). All gemcitabine doses were delivered at 10 mg/m(2) per min. For the initial cohort (level 1) the gemcitabine dose was 800 mg/m(2) per min. Subsequent escalations were 1000 mg/m(2) per min (level 2), and 1250 mg/m(2) per min (levels 3 and 4). For the first three cohorts, patients received gemcitabine on days 1, 8, and 15 and cisplatin on day 15 on a 28-day cycle. Patients on level 4 received gemcitabine on days 1 and 8 and cisplatin on day 8 on a 21-day cycle. Dose omissions or delays (holds) were mandated for NCI CTC grade 3 or 4 granulocytopenia or grade 2-4 thrombocytopenia. RESULTS: Entered onto this dose-finding study were 23 patients (12 male, 11 female) with advanced solid tumors. Seven patients were treatment-naive. Six patients were treated on level 1, five each on levels 2 and 3 and seven on level 4. Patients received one to seven cycles of treatment. Myelosuppression-related dose holds occurred at all levels. First-cycle dose holds occurred in three of six, four of five, three of five and two of seven patients on successive levels. First-cycle grade 3 or 4 granulocytopenia/thrombocytopenia occurred in three patients on level 1, one patient on level 2, two patients on level 3 and three patients on level 4. There were no partial or complete responses. Four patients were removed for toxicity (three myelosuppression, one nephrotoxicity), one at physician discretion, and 15 with disease progression. Three patients stopped therapy with stable disease after 5-6 months. On level 3, three of five patients remained on therapy for 4 months or more, compared to only one patient on each of the other three levels. CONCLUSIONS Weekly gemcitabine 1250 mg/m(2), utilizing a 10 mg/m(2) per min infusion rate, can be delivered with cisplatin 75 mg/m(2) with tolerable toxicity. When used in combination with cisplatin, however, the benefit of this fixed dose rate infusion gemcitabine compared to standard bolus gemcitabine remains to be determined.     

Cavernous sinus involvement by extramedullary plasmacytoma of the sphenoid sinus. An argument for the use of adjuvant chemotherapy

A 63-year-old man with cavernous sinus involvement from extramedullary plasmacytoma (EMP) of the sphenoid sinus is described. Transient resolution of retro-orbital headache and continued progression of the locally extensive tumor were noted after chemotherapy was given following a poor response to 5400 cGy of local irradiation. To determine whether adjunctive chemotherapy will improve the outcome of these particular patients, we propose that a randomized trial comparing radiotherapy to chemoradiation be conducted.     

Surgical management of penile prosthesis complications

Penile implants are mechanical devices used to treat erectile dysfunction. Parts of the implants may wear out with time, and the implants themselves may damage the body cavities in which they have been placed, especially with excessive or aggressive use. Techniques to replace parts, repair body cavities, and deal with infection associated with prosthesis placement have been developed. Satisfaction with the resulting erections is the highest among all the modalities available for treating erectile dysfunction. International Journal of Impotence Research (2000) 12, Suppl 4, S108-S111.     

The conceptual framework of the National Diabetes Education Outcomes System (NDEOS)

PURPOSE: This article describes the systems-based conceptual framework for the definition of diabetes education outcomes and the development of the National Diabetes Education Outcomes System (NDEOS). METHODS: Development of the NDEOS was based on integrating diabetes education into the diabetes care system; identifying and tracking standardized learning, behavioral, and clinical outcomes measurements; and gathering data at the individual, program, and national levels. Each component was formulated based on available literature and through consensus with the American Association of Diabetes Educators (AADE) Outcomes Task Force and other multidisciplinary healthcare professionals. RESULTS: Behavior change is the key outcome measurement for diabetes self-management education (DSME). In addition, diabetes educators should collect other immediate, intermediate, and long-term outcomes for monitoring the impact of DSME. The NDEOS system includes standardized data collection tools for the participant, the educator, and the program manager, and provides reports at the individual, program, and national levels. CONCLUSIONS: By capturing outcomes data using valid, reliable, and evidence-based tools, the NDEOS strives to support diabetes educators and provide a uniform data set that can be used to influence public policy, support reimbursement negotiations, and assist researchers.     

Ki-ras mutations are an early event and correlate with tumor stage in transplacentally-induced murine lung tumors

A previous study from this laboratory demonstrated that treatment of pregnant mice with 3-methylcholanthrene (MC) caused lung tumors in the offspring at 1 year after birth, the incidence of which correlated with fetal inducibility of Cyp1a1. Analysis by PCR amplification and allele- specific hybridization (ASO) of paraffin-embedded tumors generated from that study revealed the presence of point mutations in exon 1 of the Ki- ras gene. This work has now been expanded by PCR amplification and ASO analysis of 31 additional lesions. Point mutations were found in 37 of the 47 (79%) lesions analyzed in this and the previous study, the majority of which were G-->T transversions in the first or second base of codon 12. The mutational spectrum appeared to be dependent on the relative stage of differentiation of the lesion, as both the incidence of mutation and type of mutation produced correlated with malignant progression. Mutations occurred in 60% of the hyperplasias, 80% of the adenomas and 100% of the adenocarcinomas. In the lesions with mutations, GLY12-->CYS12 transversions occurred in 100% of the hyperplasias, 42% of the adenomas and 14% of the adenocarcinomas. The GLY12-->VAL12 transversions occurred in none of the hyperplasias, 42% of the adenomas and 57% of the adenocarcinomas. The remaining mutations, which consisted of ASP12 transitions and ARG13 transversions, occurred only in adenomas (17%) and adenocarcinomas (29%). Between this study and our previous analyses, the identity of the mutations obtained by ASO were confirmed by sequence analysis of eight of the 37 lesions that harbored mutations at the Ki-ras gene locus. There were no differences in the type or incidence of mutations relative to the metabolic phenotype or sex of the mice. These data suggest that mutational activation of the Ki-ras gene locus is an early event in transplacental lung tumorigenesis, and that the type of mutations produced by exposure to chemical carcinogens can influence the carcinogenic potential of the tumor. This may have prognostic significance in determining the malignant progression of the neoplasm.