Systemic action of human growth hormone following adenovirus-mediated gene transfer to rat submandibular glands

1. The purpose of this study was to compare the effect of NIK-247 on muscarinic receptor subtypes with that of tacrine (THA) in rats. 2. NIK-247 and tacrine dose dependently inhibited the binding of [3H]pirenzepine (M1), [3H]AF-DX 384 (M2), and [3H]4-DAMP (M3). The IC50 values for NIK-247 were 4.4 x 10(-6) M, 1.1 x 10(-5) M, and 1.5 x 10(-5) M, respectively, whereas those for tacrine were 5.8 x 10(-7) M, 2.0 x 10(-6) M, and 5.8 x 10(-6) M, respectively. 3. Gpp[NH]p, a GTP analogue, slightly shifted the curve of displacement of [3H]AF-DX. 384 binding for NIK-247 to the right. However, Gpp[NH]p did not shift the curve of displacement of [3H]pirenzepine and [3H]4-DAMP binding to the right. 4. NIK-247 moderately decreased the rate of beating in right atrial preparations, but did not decrease it below 50% of control level. 5. These findings indicate that NIK-247 is an M1 antagonist, M2 partial agonist, and M3 antagonist.     

Pharmacological classification of adenosine receptors in the sinoatrial and atrioventricular nodes of the guinea-pig

Factors influencing the change in bone mineral after 3 mo of lactation were investigated in 47 breast-feeding mothers, 11 formula-feeding mothers, and 22 nonpregnant, nonlactating control subjects. At 6-8 wk postpartum, the breast-feeding group had a mean (+/-SD) calcium intake of 34.8+/-13.2 mmol/d and breast-milk volume, calcium concentration, and calcium output of 0.865+/-0.230 L/d, 7.41+/-1.25 mmol/L, and 6.41+/-2.00 mmol/d, respectively. There was no relation between calcium intake and any breast-milk variable. Dual-energy X-ray absorptiometry of the whole body, spine, hip, and forearm was performed at 0.5 and 3 mo. There were significant decreases in bone mineral content at the spine (3.96%; 95% CI: 4.86%, 3.06%), femoral neck (2.39%; 95% CI: 3.61%, 1.17%), total hip (1.51%; 95% CI: 2.45%, 0.60%), and whole body (0.86%; 95% CI: 1.29%, 0.43%) in breast-feeding mothers but not in formula-feeding mothers or nonpregnant, nonlactating women. These changes were not related to calcium intake, breast-milk calcium concentration, vitamin D-receptor genotype, postpartum weight change, or use of the progesterone-only contraceptive pill. After adjustment for bone area, breast-milk volume and height were identified as significant predictors at the spine, such that greater decreases were associated with taller mothers (P = 0.007) and those with greater breast-milk volume (P = 0.001). This finding suggests that the marked bone mineral changes observed in breast-feeding mothers represented a physiologic response to lactation that was independent of dietary calcium supply.     

Fathers and breast feeding: a pilot observational study

A small pilot survey (n = 113) by questionnaire of the fathers of a sample of children under one year of age was undertaken in order to investigate the involvement of fathers with infant feeding and their attitudes to the method of feeding adopted. The response rate was 72% overall and 79% when the partners of 'single parent' mothers were excluded. Nearly 30% of respondents had not discussed the method of feeding with anyone, but over 60% had discussed it with their partner. 64% of fathers sometimes helped with feeding their child and 17% said that they always helped. The majority of fathers did not mind their partner breast feeding in front of friends or relatives but 42% did not like them feeding in front of strangers and over half did not like them breast feeding in a public place. From this study, based on relatively small numbers, we conclude that fathers may feel left out of infant feeding. They should be given more opportunity to become involved from an early stage and take part in the decision about the method of infant feeding to be adopted.     

Effect of calcaneal lengthening on relationships among the hindfoot, midfoot, and forefoot

To better understand the bony component of pes planus and the means by which the Evans calcaneal lengthening corrects them, we studied the standing radiographs of seven adult patients who had undergone calcaneal lengthening to treat symptomatic pes planus. Weightbearing AP and lateral views done preoperatively and postoperatively were used for the study. For each set of films, the following parameters were measured: on the lateral view; overall length of the calcaneus, lateral talometatarsal angle, lateral talocalcaneal angle, and the calcaneal pitch angle; and on the dorsoplantar view, the talometatarsal and talocalcaneal angle. In addition, the relative coverage of the talus by the navicular was described by an angular measurement based on the relationship of the center of the talus to the center of the navicular. The average improvements in lateral talocalcaneal angle (a reflection of hindfoot valgus) was 6.4 degrees when the long axis of the calcaneus was used and 6.8 degrees when the inferior surface of the calcaneous was used for the measurement. The lateral talometatarsal angle improved an average 11.3 degrees (from an average of 19.7 degrees to 8.4 degrees). The dorsoplantar talometatarsal angle (a measure of forefoot adduction/abduction) improved 15.8 degrees (preoperative average 26.8 degrees, postoperative average 11 degrees). The calcaneal pitch angle improved an average 10.8 degrees (preoperative average 3.2 degrees, postoperative average 14 degrees). The relationship between the talus and navicular was defined by an angular measurement based on the center of each articular surface before and after correction using this measurement. An average improvement of 26 degrees occurred in the alignment of these two articular surfaces.(ABSTRACT TRUNCATED AT 250 WORDS)     

Failure of absorption of gabapentin after rectal administration

PURPOSE: We wished to determine the extent of absorption of gabapentin (GBP) after rectal administration to children on maintenance therapy. METHODS: Two children scheduled for extensive surgery received GBP rectally and orally. A pharmacokinetic profile was derived after each route of administration. RESULTS: Serum GBP levels after rectal administration decreased at a rate similar to their rate of decrease after oral administration. However, GBP concentrations were much lower after rectal administration; therefore, we concluded that the aqueous solution was poorly absorbed rectally. The GBP half-life (t1/2) for the 2 children after oral doses were 4.2 and 4.8 h. CONCLUSIONS: Rectal administration of GBP is not satisfactory when oral administration is interrupted. When oral GBP therapy is temporarily discontinued, clinicians should consider administration of alternative antiepileptic drugs (AEDs) that can be administered parenterally or rectally.     

Problems in timing of respiration with the nasal thermistor technique

Twelve normal control phakic eyes together with a number of other pseudophakic groups each consisting of 6 eyes were enrolled in this study of spatial and quantitative measurement of glare disabilities in the static visual field (Perimetric Glare Test) using an OCTOPUS 500E automated perimeter with an attached glare source. These groups were a 6 mm no hole lens group, a 6 mm 4 hole lens group, a 5.5 x 6.5 mm 2 hole lens group, a 5.0 x 6.0 mm no hole lens group and a diffractive multifocal group. Glare disabilities in the visual field were minimum in the control group. The 6 mm no hole lens group and the diffractive multifocal group showed no statistical significance compared the control group. Groups with the two types of ovoid lens and the 6 mm 4 hole lens group showed a statistically higher degree and a greater extent of glare disabilities in the static visual field than the control group. Careful selection of appropriate patients to receive implants of small efficient optic IOLs, such as IOLs with positioning holes and ovoid lenses, according to the preoperative pupil size under scotopic or mesopic condition and efficient lens optic size are important in order to reduce hole and edge glare. The diffractive multifocal IOLs group showed a slightly higher degree and a greater extent of glare than the control group and the 6 mm no hole monofocal lens group but the difference was very small and statistically insignificant. Therefore the effects of diffractive microstructure on glare disabilities were considered to be slight and clinically acceptable.     

Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy: initial results of Radiation Therapy Oncology Group 89-03

PURPOSE: To assess the efficacy of neoadjuvant methotrexate, cisplatin, and vinblastine (MCV) chemotherapy in patients with muscle-invading bladder cancer treated with selective bladder preservation. PATIENTS AND METHODS: One hundred twenty-three eligible patients with tumor, node, metastasis system clinical stage T2 to T4aNXMO bladder cancer were randomized to receive (arm 1, n=61 ) two cycles of MCV before 39.6-Gy pelvic irradiation with concurrent cisplatin 100 mg/m2 for two courses 3 weeks apart. Patients assigned to arm 2 (n=62) did not receive MCV before concurrent cisplatin and radiation therapy. Tumor response was scored as a clinical complete response (CR) when the cystoscopic tumor-site biopsy and urine cytology results were negative. The CR patients were treated with an additional 25.2 Gy to a total of 64.8 Gy and one additional dose of cisplatin. Those with less than a CR underwent cystectomy. The median follow-up of all patients who survived is 60 months. RESULTS: Seventy-four percent of the patients completed the protocol with, at most, minor deviations; 67% on arm 1 and 81% on arm 2. The actuarial 5-year overall survival rate was 49%; 48% in arm 1 and 49% in arm 2. Thirty-five percent of the patients had evidence of distant metastases at 5 years; 33% in arm 1 and 39% in arm 2. The 5-year survival rate with a functioning bladder was 38%, 36% in arm 1 and 40% in arm 2. None of these differences are statistically significant. CONCLUSION: Two cycles of MCV neoadjuvant chemotherapy were not shown to increase the rate of CR over that achieved with our standard induction therapy or to increase freedom from metastatic disease. There was no impact on 5-year overall survival.