Melanocortin receptor accessory proteins in adrenal gland physiology and beyond.

The melanocortin receptor (MCR) family consists of five G-protein-coupled receptors (MC1R-MC5R) with diverse physiological roles. MC1R controls pigmentation, MC2R is a critical component of the hypothalamic-pituitary-adrenal axis, MC3R and MC4R have a vital role in energy homeostasis and MC5R is involved in exocrine function. The melanocortin receptor accessory protein (MRAP) and its paralogue MRAP2 are small single-pass transmembrane proteins that have been shown to regulate MCR expression and function. In the adrenal gland, MRAP is an essential accessory factor for the functional expression of the MC2R/ACTH receptor. The importance of MRAP in adrenal gland physiology is demonstrated by the clinical condition familial glucocorticoid deficiency, where inactivating MRAP mutations account for ∼20% of cases. MRAP is highly expressed in both the zona fasciculata and the undifferentiated zone. Expression in the undifferentiated zone suggests that MRAP could also be important in adrenal cell differentiation and/or maintenance. In contrast, the role of adrenal MRAP2, which is highly expressed in the foetal gland, is unclear. The expression of MRAPs outside the adrenal gland is suggestive of a wider physiological purpose, beyond MC2R-mediated adrenal steroidogenesis. In vitro, MRAPs have been shown to reduce surface expression and signalling of all the other MCRs (MC1,3,4,5R). MRAP2 is predominantly expressed in the hypothalamus, a site that also expresses a high level of MC3R and MC4R. This raises the intriguing possibility of a CNS role for the MRAPs.

Cerebellin1 is a novel orexigenic peptide.

AIM: Cerebellin1 (Cbln1) is highly expressed in the hypothalamus, a region of the brain involved in appetite regulation. However, the effects of Cbn1 on food intake are not known. The present study aimed to investigate the effect of Cbln1 on appetite regulation in rats. METHODS: We determined the effect of (i) intracerebroventricular (ICV) injection of Cbln1 on food intake, behaviour and plasma pituitary hormone levels in male Wistar rats; (ii) Cbln1 on the release of hypothalamic neuropeptides known to modulate food intake from hypothalamic explants and (iii) fasting on hypothalamic Cbln1 mRNA expression. RESULTS: (i) ICV administration of Cbln1 significantly increased food intake in rats and caused no adverse behaviours. ICV administration of Cbln1 significantly reduced plasma thyroid stimulating hormone (TSH) levels 10 min postinjection in rats. (ii) Cbln1 significantly increased the release of neuropeptide Y (NPY) from hypothalamic explants. (iii) Cbln1 mRNA expression levels were increased in the ventromedial nucleus of the hypothalamus in fasted rats. CONCLUSIONS: These data suggest that Cbln1 is a novel orexigenic peptide, which may mediate its effects via hypothalamic NPY.

Intrathecal morphine for postpartum tubal ligation postoperative analgesia.

UNLABELLED: Intrathecal morphine (ITM) provides effective postoperative cesarean delivery analgesia but has not been reported for postoperative postpartum tubal ligation (PPTL) analgesia. We designed this prospective, randomized, double-blinded study to determine the efficacy of 100 microg ITM for postoperative PPTL analgesia. Sixty-six women received spinal anesthesia with 60 mg (1.2 mL) of 5% hyperbaric lidocaine, 10 microg (0.2 mL) of fentanyl, and either 0.2 mL of 0.9% saline (normal saline; NS) or 100 microg (0.2 mL) of morphine (morphine sulfate, MS). Postoperative analgesia was limited to patient-controlled IV analgesia morphine. Six women (three NS and three MS) were excluded because of major protocol violations. Twenty-four-hour patient-controlled IV analgesia morphine use was (mean +/- SD) 39.6 +/- 19.6 mg in the NS group and 1.1 +/- 2.5 mg in the MS group (P < 0.0000001). Visual analog scale scores for crampy and incisional pain (rest and movement) were significantly higher in the NS group compared with the MS group at 4, 8, 12, and 24 h (P < 0.001). The adverse effect profile was similar between groups. Visual analog scale satisfaction scores (mean +/- SD) were 96.6 +/- 16.0 in the MS group and 84.2 +/- 23.6 in NS group (P < 0.05). The results of this study indicate that women experience significant postoperative pain after PPTL surgery, and this pain is effectively obviated by 100 microg ITM. IMPLICATIONS: This investigation documents the extent of the significant postoperative pain experienced by women after routine postpartum tubal ligation surgery and demonstrates the efficacy of a small dose (100 microg) of intrathecal morphine to obviate this pain with minimal adverse effects.

Postpartum postural headache due to superior sagittal sinus thrombosis mistaken for spontaneous intracranial hypotension.

PURPOSE: To describe a case of superior sagittal sinus thrombosis in the puerperal period and the difficulties encountered in the diagnosis and management. CLINICAL FEATURES: A 29-yr-old multiparous woman presented with a postural headache four weeks after a normal pregnancy and vigorous delivery. Initial presentation suggested spontaneous intracranial hypotension (SIH) since there was no history of epidural or spinal anesthesia, or trauma or surgery to her back or neck. Conservative therapy was initially offered and then a lumbar epidural blood patch (LEBP) was performed, although it failed to relieve the postural headache. A dural leak could not be demonstrated but an MRV (magnetic resonance venography) revealed a superior sagittal sinus thrombosis (SSST). Although anticoagulant therapy was immediately initiated, the neurologist remained convinced that the postural headache was secondary to SIH, and, consequently, a second epidural blood patch was requested. Anesthesia was reluctant to perform an LEBP at this point and suggested continuing anticoagulation until a subsequent MRV demonstrated recannalization of the SSST. This advice was followed and the postural headache resolved spontaneously with intravenous anticoagulation. CONCLUSION: The present case illustrates the importance of a multidisciplinary approach to the management of this rare complication of pregnancy. This case also highlights the importance of reviewing the differential diagnosis when considering treatment of a postural headache in the puerperium.

Ambulatory labor epidural analgesia: bupivacaine versus ropivacaine.

UNLABELLED: Dilute concentrations of bupivacaine combined with fentanyl have recently been used to initiate labor epidural analgesia in an attempt to balance adequate analgesia and minimal maternal motor blockade. Similar concentrations of ropivacaine have not been evaluated. This prospective, randomized, double-blinded study was designed to compare the efficacy of 20 mL of either 0.08% bupivacaine plus 2 microg/mL fentanyl or 0.08% ropivacaine plus 2 microg/mL fentanyl to initiate ambulatory labor epidural analgesia. Forty nulliparous women in early ( 0 but < 20 at 20 min. The time (mean +/- SD) to visual analog scale score = 0 was BF (n = 18): 12.0 +/- 4.5 min and RF (n = 19): 12.4 +/- 4.0 min (P > 0.05). Spontaneous micturition was observed in 65% (13 of 20) BF compared with 100% (20 of 20) RF (P < 0.01), and ambulation was demonstrated in 75% (15 of 20) BF compared with 100% (20 of 20) RF (P < 0.03). The incidence of forceps delivery was 35% (7 of 20) BF compared with 10% (2 of 20) RF (P < 0.04). The results of this study indicate that dilute ropivacaine combined with fentanyl effectively initiates epidural analgesia while concurrently preserving maternal ability to void and ambulate. IMPLICATIONS: As compared with a similar dilute concentration of bupivacaine, 20 mL of dilute (0.08%) ropivacaine combined with fentanyl (2 microg/mL) effectively initiates epidural analgesia in nulliparous women in early, established labor while preserving their ability to micturate and ambulate. Of importance, it appears that a true ambulatory epidural analgesic for women in labor is now possible.

Congenital leukemia cutis: an unusual manifestation of a rare disease.

This paper discusses a case of congenital leukemia cutis of lymphoblastic type presenting as a solitary frontonasal tumor. The presentation is unusual when compared with other reported cases of neonatal leukemia and represents the only reported case with comparable presenting features to the authors' knowledge. The differential diagnosis with other frontonasal tumors is discussed.

Addition of epinephrine to intrathecal bupivacaine and sufentanil for ambulatory labor analgesia.

BACKGROUND: The intrathecal combination of sufentanil and bupivacaine provides rapid, effective analgesia for labor with a limited duration. Many anesthesiologists have concerns that the use of intrathecal local anesthetics precludes maternal ambulation. This prospective, randomized, double-blind study was designed to determine whether the addition of epinephrine to the combination of sufentanil and bupivacaine would prolong intrathecal analgesia for labor. Patients' ability to ambulate was also assessed. METHODS: Thirty-nine patients received either an intrathecal control dose of 10 micrograms sufentanil plus 2.5 mg bupivacaine plus 0.2 ml normal saline (control group); or 10 micrograms sufentanil plus 2.5 mg bupivacaine plus 0.2 ml (0.2 mg) of epinephrine (EPI group). RESULTS: Seven patients (3 control, 4 EPI) delivered vaginally and two (1 control, 1 EPI) required cesarean delivery before requesting epidural analgesia. The duration (mean +/- SD) of intrathecal labor analgesia was prolonged significantly by the addition of epinephrine: control (n = 15): 145 +/- 23 min; EPI (n = 15): 188 +/- 25 min (P < 0.0001). Maternal ambulation was demonstrated in 100% (19 of 19) of the control group and in 80% (16 of 20) of the EPI group (P = NS). CONCLUSIONS: The addition of 0.2 mg epinephrine to the intrathecal combination of sufentanil and bupivacaine significantly prolonged labor analgesia without causing adverse effects to the mother or fetus. The intrathecal combination of sufentanil and bupivacaine, with or without epinephrine, provided rapid, profound labor analgesia and allowed most patients to ambulate.

Factors involved in the incidence of post-dural puncture headache with the 25 gauge Whitacre needle for obstetric anesthesia.

Parturients have the greatest risk of postdural puncture headache. use of a pencil-point needle, such as the 25 gauge Whitacre, has been associated with a lower incidence of PDPH. This observational study of 1009 obstetrical patients assessed possible factors related to the incidence of PDPH and other complications associated with spinal anesthesia using the 25 gauge Whitacre needle. The independent variables included procedure, maternal position at insertion, ease of insertion, intraoperative i.v. analgesia supplementation, use of intrathecal narcotics, parity and type of local anesthetic. Patients were followed daily during their hospitalization and questioned specifically about the presence of headache, its nature, onset and treatment. Two hundred and twenty-nine patients developed a headache postperatively but only 25 had postdural puncture headaches (overall incidence 2.5%). The PDPH typically presented on day 2 (median), range 1-4). Six patients (0.59%) required epidural blood patch. There were eight (0.8%) failed finals which were converted to general anesthesia. None of the factors evaluated were significant in predicting the occurrence of PDPH.

Incidence of tissue coring with the 25-gauge Quincke and Whitacre spinal needles.

BACKGROUND AND OBJECTIVES: Tissue cores, implanted into the subarachnoid space during subarachnoid injections, can develop into intraspinal lumbar epidermoid tumors. The availability of smaller needles has made spinal anesthesia more popular. Therefore, this prospective, randomized, blinded study was undertaken to determine whether tissue coring occurs with two of the currently used 25-gauge spinal needles. METHODS: Fifteen 25-gauge Quincke and seventeen 25-gauge Whitacre spinal needles, in which cerebrospinal fluid (CSF) was not identified and the local anesthetic solution not injected, were obtained from adult male patients undergoing spinal anesthesia. The needles were then evaluated by a pathologist following randomization with similar sterile, unused spinal needles. Twenty additional needles, ten of each type, in which CSF was identified and through which local anesthetic was injected, were also randomized with similar sterile, unused spinal needles and examined. RESULTS: Tissue cores were identified in 12 of the 15 Quincke and 7 of the 17 Whitacre spinal needles in which CSF was not identified (P < .05). Of the 20 needles in which CSF was identified and local anesthetic injected, no tissue cores were identified in the 10 Whitacre needles and only one small tissue core was identified in the 10 Quincke needles. All the tissue cores were identified as fat tissue. CONCLUSIONS: The 25-gauge Quincke and 25-gauge Whitacre spinal needles currently used in anesthesia can produce tissue coring.

Pattern of burn injury in hang-glider pilots.

High-voltage electrical injury has been well documented in a number of situations, such as the occupational hazard of linesmen and construction workers, and in the context of overhead railway power lines. Two cases of hang-glider pilots contacting 11,000-volt power lines have recently been treated in the Royal Brisbane Hospital Burns Unit. They demonstrate an interesting pattern of injury, not described in current burns literature, involving both hand and lower abdominal burns. Both patients sustained full-thickness patches of burn injury, with underlying muscle damage and peripheral neurological injury. This distribution of injury seems to be closely related to the design of the hang glider.

The addition of bupivacaine to intrathecal sufentanil for labor analgesia.

We designed a prospective, randomized, double-blind study to evaluate the efficacy of the combination of intrathecal sufentanil with a low dose of local anesthetic in an attempt to prolong analgesia in labor. Fifty-two patients received one of the following intrathecal study solutions: 2.5 mg of bupivacaine; 10 micrograms of sufentanil; or 2.5 mg of bupivacaine plus 10 micrograms of sufentanil. The mean duration of analgesia (min +/- SD) was significantly different among all three groups: 70 +/- 34 min for bupivacaine, 114 +/- 26 min for sufentanil, and 148 +/- 27 min for bupivacaine-sufentanil (P < 0.001). Visual analog scale (VAS) scores for pain were significantly higher in the bupivacaine group compared to both the sufentanil group and the bupivacaine-sufentanil group (P < 0.02), and were significantly higher in the sufentanil group compared to bupivacaine-sufentanil at 75 min postinjection and beyond (P < 0.02). Hypotension was not observed in the sufentanil group but occurred transiently in the other two groups (P = 0.09). There was no evidence of motor blockade, excessive somnolence, fetal heart rate (FHR) abnormalities, or postdural puncture headache (PDPH) in any of the patients. The addition of 2.5 mg of bupivacaine to 10 micrograms of intrathecal sufentanil significantly prolonged labor analgesia without adverse maternal or fetal effects.

Attention-deficit/hyperactivity disorder: assessment, diagnosis, and management.

Children and adolescents with attention-deficit/hyperactivity disorder (AD/HD) frequently present to family physicians for evaluation and treatment. Recently, revised criteria for diagnosis of this condition were presented in the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders. Attention-deficit/hyperactivity disorder is often difficult to differentiate from other disruptive behavior syndromes, such as oppositional defiant disorder and conduct disorder. Using a systematic process of differential diagnosis and integrating the mental status examination with history and teacher and parent reports, the family physician will be able to diagnose AD/HD with greater accuracy. Treatment with stimulant medication and behavioral strategies yields positive outcomes with these children.

Cigarette smoking and nonunion after ankle arthrodesis.

The relative risk of nonunion in smokers versus nonsmokers after ankle arthrodesis was determined in a case control study. Twenty-two patients were matched to 22 controls by age, sex, surgeon, surgical technique, and preoperative diagnosis. Information on duration, amount, and past history of smoking was obtained for these 44 patients. Ten of the patients were actively smoking at the time of surgery compared with four of the controls. Six of the patients had no history of smoking and six had stopped smoking before surgery. Eleven of the controls had no history of cigarette smoking and 7 had stopped smoking before surgery. The relative risk of nonunion was increased 3.75 times for active smokers. When patients did not have any known risk factors for nonunion, the risk of nonunion for smokers was 16 times the risk of nonunion for nonsmokers.

Comparison of the 25-gauge Whitacre with the 24-gauge Sprotte spinal needle for elective caesarean section: cost implications.

Spinal anaesthesia provides rapid, safe anaesthesia for Caesarean section. The pencil-point spinal needles (Sprotte and Whitacre) are reported to have a low incidence of post-dural puncture headache (PDPH). As the 25G Whitacre is less expensive than the 24G Sprotte needle, this prospective, randomized, double-blind study was designed to compare the incidence of PDPH and ease of insertion of these needles in 304 ASA 1 and 2 women having elective Caesarean section under spinal anaesthesia. Each patient was assessed daily for five consecutive days following Caesarean section by an investigator blinded to the needle used. The results indicate that the two needles have a similar ease of insertion, number of failed insertions, and failed subarachnoid blockade. An inability to insert the spinal needles occurred in two patients in each group. Therefore, 150 patients in each group completed the study. The incidence of PDPH with the 24G Sprotte needle was 4.0% (6/150) compared with 0.66% (1/150) with the 25G Whitacre (NS). There was no correlation between the occurrence of PDPH and the difficulty of needle insertion, presence of transient hypotension or the effectiveness of anaesthesia delivered. This study indicates that both needles are comparable with respect to ease of insertion and incidence of PDPH. As the Whitacre needle is less expensive it is a reasonable alternative to the more expensive Sprotte needle.

Chronic intrapulmonary foreign bodies.

Two cases of chronically retained foreign bodies are presented, demonstrating that a long delay may exist between a penetrating injury and the manifestation of a severe symptom, such as haemoptysis or recurrent infection, referable to a retained foreign body. In only one of these cases was the diagnosis of retained foreign body considered the most likely pre-operatively. Some diagnostic and management problems arising in such situations are discussed.

Physician-patient sexual contact: ethical and legal issues and clinical guidelines.

Although sexual relationships between mental health professionals and patients have been the subject of research, ethical writing, and legislation during recent years, there has been comparatively little attention given to this problem in primary care medicine. An estimated 11% of family physicians have had sexual contact with at least one of their patients. Recently, the American Medical Association presented ethical guidelines addressing this issue. Acceptable conditions under which a physician may become involved with a former patient are not well addressed by these guidelines. Although sexual involvement with patients appears to exist on an ethical continuum, it inevitably results in diminished patient autonomy. Sexual contact between patients and mental health professionals is now explicitly illegal in many states, but comparable legislation has not been enacted for nonpsychiatric physicians. There is evidence that when sexual contact between a physician and a patient occurs, the patient suffers long-term psychological consequences.

Ethnography and family medicine: issues and overview.

Ethnography is a qualitative research model generally associated with anthropology. Ethnographic methods include inductively oriented strategies such as participant observation, structured interviews, and open-ended interviews. Issues in family medicine such as patient compliance, doctor-patient relationships, and patients' subjective experience of illness may be optimally studied with ethnography. Because it is inductive, ethnography is cognitively similar to clinical reasoning. Making use of ethnography provides family physicians with a greater array of research methods compatible with clinical practice.