Cystic fibrosis. Gastrointestinal complications and gene therapy

The gastrointestinal and nutritional complications of cystic fibrosis are diverse. As longevity improves in patients with cystic fibrosis, management of these complications is becoming increasingly important . This article provides overviews of the molecular aspects of the pathogenesis of cystic fibrosis, the current status of gene therapy, and a review of the gastrointestinal manifestations and nutritional care.     

Machine milking of dairy goats during lactation: udder anatomy, milking characteristics, and blood concentrations of oxytocin and prolactin

Forty-four goats were milked and milk flow recorded without or with 1 min manual prestimulation in early, mid and late lactation. Ultrasound measurements of cross sections of the whole mammary gland were performed in a water bath. In additional experiments with 15 goats, milk flow was recorded and frequent blood samples were taken for the determination of oxytocin and prolactin concentrations. Milk yield increased from the first to the third lactation and decreased markedly during the course of lactation. Average and peak milk flow rates were closely related to the actual milk yield. The ultrasound cisternal area was 27.4 +/- 1.5% of the entire udder half cross section. Milking characteristics were scarcely different without or with prestimulation, although oxytocin was released within 30 s after the start of prestimulation, whereas oxytocin concentrations without prestimulation increased only after the start of milking. Concentrations of prolactin were higher during July and August than in April, and increased similarly with or without prestimulation during milking. In contrast to dairy cows, prestimulation and an opportune release of oxytocin during milking does not significantly influence the course of milk flow in goats, and this is probably because large amounts of cisternal milk allow milk ejection to be induced only after the start of milking without causing bimodal or otherwise reduced milk flow.     

Acute cadmium exposure and ovarian steroidogenesis in cycling and pregnant rats

The purpose of this study was to evaluate the effect(s) of acute in vivo cadmium (Cd) exposure on steroidogenesis in rat ovaries during different reproductive states. Sprague-Dawley rats were injected subcutaneously on the day of diestrus, or on day 7 or 16 of gestation with a single dose of 0, 3, or 5 mg Cd/kg bw, and evaluated 24 h later. Serum progesterone and estradiol concentrations were determined. Whole-ovary culture was used to evaluate Cd effects on the production of progesterone, testosterone, and estradiol. Liver, kidney, spleen, ovary, placenta, and blood were analyzed for Cd and iron (Fe) concentrations. No general toxic effects, no disruption of estrous cyclicity, and no change in fetal viability were seen. Histologic evaluation revealed moderate Cd-related thecal congestion in ovaries of pregnant rats. The highest Cd concentrations, except for liver, were found in the fetal portion of the placenta. Interestingly, Cd-related decreases in Fe concentration were found in several tissues from rats in proestrus and on gestation day 8, and in fetal placenta from rats on gestation day 17. Cadmium appears to interfere with normal steroidogenesis at a number of sites in the biosynthetic pathway with serum estradiol concentration and ovarian estradiol production the most affected. Acute Cd effects on steroidogenesis are most severe in rats evaluated in proestrus or in early pregnancy, while in late pregnancy steroidogenesis is relatively unaffected.     

Survival of patients with carcinoma of the esophagus treated with combined-modality therapy

Since 1985, 229 cases of carcinoma of the esophagus have been considered for entry into a protocol with the use of preoperative chemotherapy and radiation therapy followed by surgical intervention as the primary element of treatment. One hundred sixty-five patients (93 with adenocarcinoma and 72 with squamous cell carcinoma) had esophagogastrectomy. The 5-year survival of the protocol patients who underwent resection was 25% for both groups--squamous cell carcinoma and adenocarcinoma. Of the protocol patients with squamous cell carcinoma who underwent resection, 40% had a sterilized specimen, whereas of those with adenocarcinoma, 20% had a sterilized specimen. If the patient had a sterilized specimen, the 5-year survival was approximately 60% for adenocarcinoma and 40% for squamous cell carcinoma. Those patients with adenocarcinoma and Barrett's esophagus had a 5-year survival of 55%. Of the patients who underwent only esophagectomy and esophagogastrectomy and had not been entered into the protocol, none lived beyond 3 years. The operative mortality rate for those who had esophagogastrectomy was 5%. Sixty-four patients completed the radiation therapy and chemotherapy but did not undergo surgical procedures because of progressive disease or refusal. Of those patients who completed chemotherapy and radiation therapy without surgical intervention, 5-year survival was 18% in patients with squamous cell carcinoma, whereas no patients with adenocarcinoma survived beyond 3 years. The finding of a sterilized specimen after esophagectomy is a favorable prognostic factor in patients with adenocarcinoma or squamous cell carcinoma. The finding that patients with Barrett's esophagus and adenocarcinoma have an improved chance for survival is perhaps related to an earlier diagnosis. It is clear that some patients with squamous cell carcinoma who did not undergo surgical procedures did have a sterilized specimen, because the survival in this group approached 20% at 5 years.     

Intermodality, retrospective image registration in the thorax

The purpose of this study was to develop an accurate, retrospectively applicable procedure for registering thoracic studies from different modalities in a short amount of time and with minimal operator intervention. METHODS: CT and PET studies were acquired from six patients. The pleural surfaces in both image sets were determined by segmenting based on 50% of the maximum soft-tissue value in the study. These surfaces were converted into three-dimensional volumes and used to register the CT and PET studies in three dimensions using a sum of least squares fitting approach. The registered PET study was then displayed in a hot metal scale overlayed on top of the gray scale CT study. The accuracy of the fit was evaluated through a phantom study and preliminary clinical evaluation. RESULTS: A phantom study was performed to determine the limits of this technique. The accuracy was determined to be less than 2.3 mm in the x and y direction and 3 mm in the z direction. Preliminary clinical evaluation was also performed with encouraging results. CONCLUSION: This technique accurately registers PET and CT images of the thorax, retrospectively, without the need for external fiducial markers or other a priori action.     

Activating and inactivating mutations in LH receptors

In rats, galanin modulates luteinizing hormone (LH) secretion, and gonadotropin-releasing hormone (GnRH) neurons provide a possible source of this galanin. To understand galanin's physiological role in GnRH neurons, we used double-label in situ hybridization and computerized image analysis to examine the regulation of galanin message in GnRH neurons. We found that galanin gene expression in GnRH neurons is regulated by sex steroids, induced coincident with the LH surge, and persists well after the completion of the LH surge, and that the induction of galanin message in GnRH neurons coincident with the LH surge is sexually differentiated neonatally. We postulate that the rise in galanin gene expression in GnRH neurons at the time of the LH surge serves to replenish galanin released with GnRH that is needed for the production of the LH surge, or that galanin is involved in physiological events that occur subsequent to the LH surge.     

Enantioselective synthesis and pharmacology of 11-hydroxy-(1'S,2'R)-dimethylheptyl-delta 8-THC

An enantioselective synthesis of the (1'S,2'R)-dimethylheptyl cannabinoid side chain has been developed and employed in the synthesis of 11-hydroxy-(1'S,2'R)-dimethylheptyl-delta 8-THC (3). Pharmacology, in vivo and in vitro, indicate (3) to be one of the most potent traditional cannabinoids known.     

A precision machine for mounting tissue for Mohs micrographic surgery

BACKGROUND: Mounting specimens onto chucks, so the cryostat knife follows the exact path of the surgeon's knife, poses difficulties even for experienced histotechnologists. Oftentimes, the frozen planar surface of the tissue falls at an angle that requires gimballing the chuck holder to compensate. OBJECTIVE: To demonstrate the use of a precision tissue mounting machine and associated fast freezing chucks. METHODS: Specimens of pickled pig skin were marked with blue dye on the cut surface. The pieces were mounted onto chucks with the blue surface exposed, and then sectioned in a cryostat. RESULTS: A complete section with all edges was obtained after eight turns of the cryostat handwheel, at 12 microns per turn. CONCLUSIONS: A precision machine used in conjunction with a properly adjusted chuck holder can yield results unobtainable by other methods.