Spatial heterogeneity of the effects of calcitonin gene-related peptide (CGRP) on the microvasculature of ligaments in the rabbit knee joint

1. Experiments were performed in anaesthetized rabbits to examine the effects of calcitonin gene-related peptide (CGRP) and the CGRP antagonist CGRP_8–37 on blood flow to the medial collateral ligament of the knee joint.
2. Topical application of CGRP (10⁻¹³ to 10⁻⁹  mol) to the exposed external surface of eight knee joints resulted in dose-dependent dilatation of vessels in both the ligament and the joint capsule. The magnitude of this response varied significantly in different regions of the medial collateral ligament, with the 10⁻⁹  mol dose of CGRP giving the maximum response (101.5±25.3% increase) at the femoral insertion site of the medial collateral ligament and lowest (23.1±8.8%) at the tibial insertion site.
3. Topical application of CGRP_8–37 (0.1, 1 and 10  nmol) produced dose-dependent constriction of vessels in the ligament and the joint capsule in five knees, with a trend towards the greatest effect occurring at the femoral insertion site (45.8±8.1% reduction in blood flow). With the 10  nmol dose, the vasoconstrictor response at the femoral insertion site differed significantly (P<0.05) from the responses obtained at the tibial insertion and joint capsule sites.
4. Topical application of CGRP_8–37 (0.1, 1 and 10  nmol) to four chronically denervated knees produced substantially smaller vasoconstrictor responses at all sites. At the femoral insertion site, where 10  nmol CGRP_8–37 normally produces a 45.8±8.1% reduction in blood flow (n=8), ten days following denervation this response was reduced to 6.5±6.1%, this difference being significant (P=0.01).
5. Adrenaline was applied topically to augment blood vessel tone, in order to establish how effectively co-administration of CGRP would offset this increase in tone. Adrenaline (10⁻¹⁰  mol) produced vasoconstriction at all sites (n=6). In the capsule this vasoconstriction was virtually abolished when CGRP (10⁻⁹  mol) was co-administered with adrenaline but in the ligament vasodilatation occurred at all sites. This vasodilatation was significantly greater at the femoral insertion site compared to the tibial insertion and mid ligament sites (P<0.05 for both) and the capsule (P<0.01).
6. Topical application of substance P (10⁻¹⁰ or 10⁻⁹  mol) failed to elicit dilatation of ligament blood vessels.
7. These results suggest that endogenous CGRP may play an important role in regulating blood flow to different structures in and around the knee joint.

     

Conducting qualitative research in the health sector: researcher issues and dilemmas.

This article contributes to bridging the gap between research activity and the practical implementation of management decision making in the health sector by reflecting upon some of the issues and dilemmas for researchers, whether academics or managers, in conducting qualitative research in this sector. The article presents the methodological issues addressed by a team of researchers engaged on a project about manager learning and development in an NHS Trust, and highlights concerns about ethical issues that emerged from the research process. The study had involved a series of interviews with senior managers and clinical staff, doctors, nurses and therapists, and it addressed issues surrounding change within the organization, the impact on individuals' jobs, and the resultant learning and development required and undertaken. The article emphasizes that engaging in reflection on the research process is valuable and suggests that it should become a mainstream part of such research. It concludes that there is an important role of qualitative management research in the health sector and that for it to be acceptable and valued, it must be operationally sensitive, ethically robust and methodologically rigorous.     

Reinforced responding of the 11-day-old rat pup: synergistic interaction of D1 and D2 dopamine receptors.

Reinforced responding of 11-day-old rat pups was assessed after blockade of D1 and D2 dopamine receptors. Initially, rat pups were trained to traverse a straight alley for nipple attachment reward. Rat pups were than injected IP with either the D1 antagonist SCH 23390 (0.01, 0.015, 0.03, or 0.1 mg/kg), the D2 antagonist sulpiride (15 or 50 mg/kg), or a combination of SCH 23390 (0.015 mg/kg) and sulpiride (15 mg/kg). The approach performance of drug-treated pups was then compared to vehicle-treated pups on both reinforcement and extinction trials. Sulpiride (15 mg/kg) did not affect either the extinction or reinforced responding of 11-day-old rat pups. In contrast, SCH 23390-treated pups showed significantly longer response latencies than the vehicle controls in both extinction and reinforcement conditions. Combined treatment with SCH 23390 and sulpiride produced the longest response latencies. Analyses of "best score" and frequency data indicated that the drug-induced decline in responding was due to effects on both reward processes and motor capability. The combined results indicate that D1 and D2 receptors interact complexly to affect reinforced responding.     

Munchausen syndrome by proxy--a cause of preterm delivery.

OBJECTIVE: To present the first case of Munchausen syndrome by proxy involving self-induced preterm delivery. CLINICAL FEATURES: A 27-year-old Caucasian woman induced antepartum haemorrhage and rupture of membranes with a knitting needle at 26 weeks' gestation, leading to delivery of the infant. This "prenatal child abuse" led to a prolonged intensive care stay, extensive treatment and subsequent bronchopulmonary dysplasia. As the child recovered from the effects of extreme prematurity, he became a victim of fabricated illness and recurrent smothering episodes. INTERVENTION AND OUTCOME: After the diagnosis of Munchausen syndrome by proxy was made, the child was removed from the mother and he has since enjoyed good health. CONCLUSION: Self-induction of antepartum haemorrhage can lead to preterm delivery and may be recognisable by certain clinical parameters. The victim of self-induced preterm delivery, if survival ensues, may be subject to further abuse.     

The use of 111in-labeled lymphocyte imaging to evaluate graft rejection following cardiac transplantation in dogs

Lymphocytes separated from venous blood from six dogs who had heterotopic cardiac transplants have been labeled using ¹¹¹In-oxine. Labeled lymphocytes were reinjected into the dogs and imaging of the heart carried out over the successive 3 or 4 days. For comparison serial ECGs and punch biopsies of the heart were obtained. Abnormal uptake of labeled lymphocytes in the donor heart was clearly visible in three of the six dogs, faintly visible in two and not seen in one. 630 Ci ¹¹¹In was used in the dog where no uptake was seen and subsequent studies showed this amount of the radiopharmaceutical was toxic to lymphocytes. In the remaining five dogs the mean ratio of uptake of ¹¹¹In in donor to recipient heart was 14:1 (range 6.5:1–21:1). The lack of substantial uptake in the transplanted heart of two dogs is attributed to a delay in rejection relative to the time the labeled lymphocytes were injected. The results suggest that ¹¹¹In-labeled lymphocytes have potential as a noninvasive test for detecting rejection of cardiac transplants.J. McKillop is a Harkness Fellow of the Commonwealth FundJ. Wallwork is supported by National Heart Research Fund (UK)     

Approach to decortication of simple cysts and polycystic kidneys

Laparoscopic excision and marsupialization of symptomatic of recurrent simple renal cysts is an alternative to open or percutaneous surgery. Such surgery may also be useful for pain relief in patients with autosomal dominant polycystic kidney disease (ADPKD). An occlusion balloon catheter is placed in the renal pelvis at the start of the procedure. Cysts are punctured, and the outer wall of the larger cysts is excised with care not to incise the renal parenchyma. In patients with ADPKD, it is important to mobilize the kidney completely, particularly the upper pole, to treat every visible cyst. A laparoscopic ultrasound probe is used to guide the unroofing of any large cysts within 5 to 10 mm of the renal surface. At the end of the procedure, the integrity of the collecting system is confirmed. Strict criteria must be used in selecting patients with simple cysts for laparoscopic marsupialization to minimize the incidence of unsuspected malignancy, and the cyst wall should be examined by frozen and permanent section. Long-term follow-up is needed to evaluate the effect of laparoscopic decompression in ADPKD.     

Laparoscopic nephroureterectomy. A new standard for the surgical management of upper tract transitional cell cancer

Laparoscopic nephroureterectomy for upper tract TCC still remains somewhat controversial. Unlike laparoscopic radical nephrectomy, which has become widely accepted, LNU is still in its earliest stages. Although there are obvious benefits for the patient who has LNU--less pulmonary complications, less postoperative discomfort, a shorter hospital stay, a better cosmetic result, and a brief convalescence--there are significant concerns. The longer operative time creates a negative financial and professional inducement to learn this technique. Operative times need to fall into the 4-hour range or less to make the procedure cost-effective. Analysis of the efficacy of laparoscopic nephroureterectomy as a curative treatment modality is important. In the short-run, LNU seems to provide similar results to open nephroureterectomy for upper TCC. Although concerns over port site seeding, bladder recurrence, and intraperitoneal seeding have been voiced, these problems have not occurred. The higher incidence of local recurrence noted in the authors' series, however, is of concern and remains an unsettled issue. Despite these local recurrences, the overall cancer survival for a given grade and stage of upper tract TCC seem to be similar to survivals recorded after open nephroureterectomy. Still, the number of LNU cases remains small, and follow-up is brief. These patients need to be monitored closely, with follow-up CT scans over the next decade. The authors believe that there are still several significant hurdles standing in the path of LNU before it can become a widely accepted procedure. Issues of cost, training, and long-term efficacy must be answered definitively. To obtain these types of data, it will be necessary to create a multi-institutional, cooperative study to obtain sufficient numbers of patients with a more than 5-year follow-up on which to base future recommendations.     

Renal physiology. Laparoscopic considerations

Oliguria is a recognized component of the physiologic effect of increased intra-abdominal or retroperitoneal pressure. The cause is multifactorial, emanating from vascular and parenchymal compression, and is associated with systemic hormonal effects. Ureteral obstruction does not play a significant role. These changes are pressure-dependent and are usually not apparent until pressures reach 15 mm Hg or more. This effect is not associated with any histologic pathology or evidence of renal tubular damage. After the release of the pneumoperitoneum or pneumoretroperitoneum, the renal function and urine output return to normal with no long-term sequelae, even in patients with pre-existing renal disease. The entire operative team must understand the physiologic effects of CO2 insufflation, which allows appropriate intraoperative monitoring and management and minimizes intraoperative and postoperative complications.