A case of human intramuscular adrenal gland transplantation as a cure for chronic adrenal insufficiency.

Intramuscular endocrine gland transplantation has been well described as it pertains to parathyroid autotransplantation; however, transplantation of the adrenal gland is less well characterized. While adrenal autotransplantation in the setting of Cushing's disease has been described, intramuscular adrenal allotransplantation as a cure for adrenal insufficiency to our knowledge has not been previously carried out. Current treatment for adrenal insufficiency leaves patients without diurnal variation in cortisol release and susceptible to the detrimental effects of chronic hypercortisolism. We describe here the case of a 5-year-old girl with renal failure who had adrenal insufficiency following fulminant meningococcemia that led to requirements for both stress-dose steroid and mineralocorticoid replacement. Ten months after the onset of her disease, she received a simultaneous renal and adrenal gland transplant from her mother. The adrenal gland allograft was morselized into 1 mm(3) segments and implanted into three 2 cm pockets created in her rectus abdominis muscle. Three years after surgery, her allograft remains fully functional, responding well to adrenocorticotropin hormone stimulation and the patient does not require any steroid or mineral-corticoid supplementation. We believe this case represents the first description of successful functional intramuscular adrenal allograft transplantation with long-term follow up as a cure for adrenal insufficiency.

A comparative, volumetric survey of airborne pollen in Philadelphia, Pennsylvania (1991-1997) and Cherry Hill, New Jersey (1995-1997).

BACKGROUND: Aeroallergen sampling provides information regarding the onset, duration, and severity of the pollen season that clinicians use to guide allergen selection for skin testing and treatment. OBJECTIVE: This atmospheric survey reports: 1) airborne pollen contributors in Philadelphia, Pennsylvania (1991 to 1997) and suburban Cherry Hill, New Jersey (1995 to 1997); 2) pollen onset, duration, and peak level; and 3) the relationship between airborne pollen and selected meteorologic variables. METHODS: At both locations, separated by 11 km. sampling was performed with a volumetric Rotorod Sampler (Sampling Technologies, Minnetonka, MN). RESULTS: In Philadelphia and Cherry Hill, respectively, 3-year average measurements included 75.0 and 74.2% tree pollen, 10.2 and 8.3% grass pollen, and 14.8 and 17.5% weed pollen. Prominent airborne pollen taxa were Acer, Quercus, Betula, Pinus, Cupressaceae, Poaceae, Ambrosia, and Rumex. The tree, grass, and weed pollen seasons extended from mid-March to mid-June, late April to mid-June, and mid-August to late September, respectively. A secondary Poaceae pollen peak occurred in September. There was a statistically significant correlation between simultaneous weekly average pollen levels in Philadelphia and in Cherry Hill (Acer, r(p) = 0.987, Quercus, r(p) = 0.645, Betula, r(p) = 0.896, Pinus, r(p) = 0.732, Cupressaceae, r(p) = 0.695, Poaceae, r(p) = 0.950, Ambrosia, r(p) = 0.903, and Rumex, r(p) = 0.572, P <0.001). Daily Poaceae pollen levels were positively influenced by same-day high temperature (r(s) = 0.333 in Philadelphia and r(s) = 0.426 in Cherry Hill, P < 0.05). Daily Ambrosia pollen levels were inversely influenced by same-day total precipitation (r(s) = -0.174 in Philadelphia and r(s) = -0.257 in Cherry Hill, P < 0.05). CONCLUSIONS: This is the first volumetric survey performed in either Philadelphia or Cherry Hill. Copious amounts of airborne pollen were seen from late April to early May and in early September. Pollen onset, duration, and year-to-year variability were similar at both sites. An awareness of local aeroallergen patterns is critical in the effective testing and treatment of atopic individuals.

Stoichiometry of tyrosine hydroxylase phosphorylation in the nigrostriatal and mesolimbic systems in vivo: effects of acute haloperidol and related compounds.

Electrical stimulation of the medial forebrain bundle increases (32)P incorporation into striatal tyrosine hydroxylase (TH) at Ser (19), Ser(31), and Ser(40). In the present studies, the effects of acute haloperidol and related drugs on sitespecific TH phosphorylation stoichiometry (PS) in the nigrostriatal and mesolimbic systems were determined by quantitative blot immunolabeling using phosphorylation statespecific antibodies. The striatum (Str), substantia nigra (SN), nucleus accumbens (NAc), and ventral tegmental area (VTA) from Sprague-Dawley rats were harvested 30-40 min after a single injection of either vehicle, haloperidol (2 mg/kg), raclopride (2 mg/kg), clozapine (30 mg/kg), or SCH23390 (0.5 mg/kg). In vehicle-injected control rats, Ser(19) PS was 1.5- to 2. 5-fold lower in Str and NAc than in SN and VTA, Ser(31) PS was two-to fourfold higher in Str and NAc than in SN and VTA, and Ser(40) PS was similar between the terminal field and cell body regions. After haloperidol, Ser(40) PS increased twofold in Str and NAc, whereas a smaller increase in SN and VTA was observed. The effects of haloperidol on Ser(19) PS were similar to those on Ser(40) in each region; however, haloperidol treatment increased Ser(31) PS at least 1.6-fold in all regions. The effects of raclopride on TH PS were comparable to those of haloperidol, whereas clozapine treatment increased TH PS at all sites in all regions. By contrast, the effects of SCH23390 on TH PS were relatively small and restricted to the NAc. The stoichiometries of site-specific TH phosphorylation in vivo are presented for the first time. The nigrostriatal and mesolimbic systems have common features of TH PS, distinguished by differences in TH PS between the terminal field and cell body regions and by dissimilar increases in TH PS in the terminal field and cell body regions after acute haloperidol.

Chronic glucocorticoid therapy-induced osteoporosis in patients with obstructive lung disease.

Long-term glucocorticoid (GC) therapy has been instrumental in decreasing morbidity and mortality in a variety of chronic inflammatory diseases, including persistent asthma. Long-term GC therapy is also widely prescribed for COPD. One of the important and often unrecognized side effects of chronic GC therapy is secondary osteoporosis. The risk of GC-induced bone loss is roughly correlated with daily dose, duration, and total cumulative lifetime dose of GC treatment. Oral prednisone increases the risk of bone loss and fracture. High doses of inhaled GCs may also increase the risk of osteopenia/osteoporosis, but the risk appears to be less than that associated with oral GCs. Hormone replacement therapy, oral and parenteral bisphosphonates, supplemental calcium and vitamin D, calcitonin, and fluoride compounds have been used, experimentally, in the management of GC-induced bone loss. Asthma and COPD specialists are key prescribers of oral and inhaled steroids and are likely to encounter patients with significant bone loss. Despite known risk factors and the availability of reliable diagnostic tools to recognize bone loss, the opportunity to slow, reverse, and treat bone loss is often missed. We present a review of the current literature regarding the incidence, treatment, and prevention of osteopenia/osteoporosis secondary to chronic GC therapy in adult asthma and COPD patients. Guidelines are presented regarding the identification of patients at risk for developing GC-induced secondary bone loss, and therapeutic alternatives are discussed.

Use of and satisfaction with homeopathy in a patient population.

BACKGROUND: This article describes a survey of new clients entering care with nine practicing classical homeopaths in the Los Angeles metropolitan area between January 1994 and July 1995. METHODS: Participants completed a self-administered questionnaire before undergoing diagnosis by the homeopath. Follow-up interviews were conducted by phone 1 month after diagnosis and face to face 4 months after diagnosis, along with a self-administered questionnaire before the final interview. A total of 104 participants entered the study; 77 completed all data collection. RESULTS: Clients sought homeopathic care for a wide array of largely chronic conditions. Respiratory, gastrointestinal, and female reproductive problems were the most common primary complaints. Most clients were highly educated, but had limited knowledge about homeopathy before entering treatment. Approximately 80% reported earlier, unsuccessful attempts to get relief from mainstream care. Four months after treatment, general measures of health status showed improvement, and only 29% of participants reported no improvement for the primary complaint leading to treatment. Satisfaction with homeopathic treatment was high regardless of outcome. Three outcome measures of perceived change--overall health status, primary condition for which treatment was sought, and outlook on life--were predicted by different combinations of study variables. CONCLUSIONS: Homeopathy does not divert people from seeking mainstream care. The use of alternative modes of care such as homeopathy can be understood as attractive and satisfying to educated individuals with chronic problems.

Scripted imagery manipulations and smoking cue reactivity in a clinical sample of self-quitters.

The affectively valenced scripts used by S. Tiffany (1990) suggest that different scripts produce relatively equivalent levels of cue reactivity, although it is unclear if these laboratory findings generalize to clinical samples. In this study, cessation-motivated smokers were tested 7 days before they tried to quit smoking and were exposed to 3 audiotaped scripts that depicted different affectively valenced situations (neutral, positive, or negative). The latter 2 scripts also contained smoking cues. The findings using a clinical sample differed considerably from those using analogue laboratory samples across affective, cognitive, and physiological response measures. Reactivity to these standardized scripts failed to predict treatment outcome through a 30-day follow-up. The use of affectively valenced scripts beyond a laboratory sample is questioned.

Sodium ions attenuate the inhibitory effects of neuropeptide Y on norepinephrine release in rat hypothalamus.

Neuropeptide Y (NPY) has a wide and specific distribution both in the central and peripheral nervous systems. In the present study, we have investigated the effects of NPY on norepinephrine release in rat hypothalamus, and further examined the interaction of NPY with alpha 2-adrenergic receptors, as well as the influence of sodium ions on the modulation of norepinephrine release. In an in vitro study, NPY significantly inhibited the stimulation-evoked norepinephrine release from hypothalamic slices in a dose-dependent manner. The alpha 2-adrenergic receptor agonist, UK 14,304, also reduced the stimulation-evoked norepinephrine release. A low concentration of NPY, which had no effects on its own, significantly potentiated the inhibitory effect of UK 14,304 on the stimulation-evoked [3H]norepinephrine release. The blockade of alpha 2-adrenergic receptors by RX 781094 diminished the inhibitory effects of NPY on norepinephrine release. Pretreatment of slices with pertussis toxin (a potent inhibitor of the Gi-proteins) significantly attenuated the suppressive effects of NPY and UK 14,304 on norepinephrine release. When the sodium concentration of the perfusion medium was increased, the inhibitory effects of NPY and UK 14,304 on norepinephrine release were significantly reduced. These results show that NPY might inhibit norepinephrine release that is partially mediated by alpha 2-adrenergic receptors and the pertussis toxin-sensitive Gi-proteins in rat hypothalamus. Moreover, less suppressive effects of NPY and UK 14,304 on norepinephrine release in the presence of excess sodium ions suggest that sodium ions might actively participate in regulating the NPY and alpha 2-adrenergic receptor mediated functions in the central nervous system.

Effects of captopril on [3H]-norepinephrine release in rat central nervous system.

1. The present study was performed to investigate the effects of captopril (an angiotensin converting enzyme inhibitor, ACE-I) on noradrenergic transmission in the rat central nervous system. 2. Slices of rat hypothalamus and medulla oblongata were prepared and prelabelled with [3H]-norepinephrine. Slices were continuously superfused with Krebs-Ringer solution, and electrical stimulation (1 Hz) was performed. 3. Captopril significantly inhibited the stimulation-evoked [3H]-norepinephrine release from rat hypothalamic slices in a dose-dependent manner (S2/S1 ratio: control 0.904 +/- 0.025, n = 6, captopril 1 x 10(-5) mol/L 0.617 +/- 0.043, n = 6, P < 0.05, captopril 5 x 10(-5) mol/L 0.547 +/- 0.037, n = 6, P < 0.05). However, the basal release of [3H]-norepinephrine was not affected by captopril. 4. Captopril also reduced the stimulation-evoked [3H]-norepinephrine release in the medulla oblongata (S2/S1 ratio: control 0.878 +/- 0.018, n = 6, captopril 3.3 x 10(-5) mol/L 0.624 +/- 0.046, n = 6, P < 0.05). 5. These results show that captopril might inhibit the stimulation-evoked norepinephrine release in rat hypothalamus and medulla oblongata. Although the precise mechanisms underlying the neurosuppressive effect of captopril are still uncertain, the finding suggests that the inhibition of noradrenergic transmission might be related to the central action of the ACE-I.

Synergistic effects of Bay K 8644 and bradykinin on norepinephrine release in the hypothalamus of spontaneously hypertensive rats.

1. In the present study, we examined the effects of Bay K 8644, a dihydropyridine (DHP)-sensitive Ca2+ channel agonist, and bradykinin on norepinephrine release in the hypothalamus of spontaneously hypertensive rats (SHR). 2. In the preliminary studies using Sprague-Dawley rats, Bay K 8644 by itself had no significant effects on the stimulation-evoked [3H]-norepinephrine release from hypothalamic slices. Bradykinin increased the stimulation-evoked [3H]-norepinephrine release in a dose-related fashion. The facilitatory effects of bradykinin on norepinephrine release were potentiated by Bay K 8644. 3. In SHR, Bay K 8644 significantly increased the stimulation-evoked norepinephrine release from hypothalamic slices. However, exposure of slices to Bay K 8644 caused no significant effects on norepinephrine release in Wistar-Kyoto (WKY) rats. The effects of Bay K 8644 in combination with bradykinin on the stimulation-evoked norepinephrine release were also greater in SHR than in WKY rats. 4. These results demonstrate that Bay K 8644 significantly potentiated the facilitatory effects of bradykinin on norepinephrine release in rat hypothalamus. The finding indicates a possible interaction of bradykinin with DHP-sensitive Ca2+ channels in the central nervous system. Furthermore, the pronounced effects of Bay K 8644 and bradykinin in SHR suggest that bradykinin-related Ca2+ channels might have a role in the regulation of norepinephrine release in the hypothalamus of SHR.

Functional magnetic resonance imaging of human auditory cortex.

Magnetic resonance imaging methods recently demonstrated regional cerebral signal changes in response to limb movement and visual stimulation, attributed to blood flow enhancement. We studied 5 normal subjects scanned while listening to auditory stimuli including nonspeech noise, meaningless speech sounds, single words, and narrative text. Imaged regions included the lateral aspects of both hemispheres. Signal changes in the superior temporal gyrus and superior temporal sulcus were observed bilaterally in all subjects. Speech stimuli were associated with significantly more widespread signal changes than was the noise stimulus, while no consistent differences were observed between responses to different speech stimuli. Considerable intersubject variability in the topography of signal changes was observed. These observations confirm the utility of magnetic resonance imaging in the study of human brain structure-function relationships and emphasize the role of the superior temporal gyrus in perception of acoustic-phonetic features of speech, rather than processing of semantic features.

Success rates in producing sympathetic blockade by paratracheal injection.

OBJECTIVE: Cervical paratracheal local anesthetic injections (stellate ganglion blocks) are performed to determine the sympathetic contribution to painful and other conditions of the head, neck, and arm. A block is useful for diagnosis only if the desired physiological effect is confirmed, but the frequency with which sympathetic function is successfully blocked is unclear. The goal of this study is to examine the rates of achieving various endpoints of sympathetic interruption by these injections, using commonly available measures of sympathetic change. DESIGN: Retrospective review. SETTING: Training center. PATIENTS: One hundred unselected consecutive blocks in 40 patients. INTERVENTION: Paratracheal sympathetic block at sixth cervical level. OUTCOME MEASURES: Bilateral hand temperature, ophthalmic changes. RESULTS: Horner's syndrome was successfully produced in 84 blocks and the ipsilateral hand warmed by > or = 1.5 degrees C in 60 blocks. However, the contralateral hand also warmed in 31 blocks so that ipsilateral warming exceeded contralateral warming in only 27 blocks, with diminished success by this criterion when the hand was warm before the block. CONCLUSIONS: We conclude that (a) identifying a Horner's syndrome and ipsilateral warming are not by themselves adequate to confirm selective sympathetic blockade; (b) selective sympathetic blockade of the arm is confirmed only if the temperature increase of the blocked side exceeds that of the contralateral side; and (c) cervical paratracheal blocks frequently fail to produce evidence of sympathetic interruption to the arm. Pathophysiological inferences based on these blocks should be made with caution and only with adequate documentation of physiological evidence of sympathetic blockade.

Effects of bradykinin on [3H]-norepinephrine release in rat hypothalamus.

1. We examined the regulatory actions of bradykinin on norepinephrine release in the hypothalamus of rats. 2. Bradykinin increased the stimulation-evoked [3H]-norepinephrine release from hypothalamic slices of Sprague-Dawley rats in a dose-dependent manner (1 Hz: S2/S1 ratio, mean +/- s.e.m., control 0.868 +/- 0.016, n = 6; bradykinin 1 x 10(-6) mol/L 1.039 +/- 0.018, n = 6, P < 0.05; bradykinin 3.3 x 10(-6) mol/L 1.130 +/- 0.064, n = 6, P < 0.05). The basal release of [3H]-norepinephrine was not affected by the peptide. 3. Bay K 8644, a dihydropyridine-sensitive calcium channel agonist, significantly potentiated the facilitatory effect of bradykinin on norepinephrine release, although Bay K 8644 by itself had no significant effect. By contrast, nicardipine, a dihydropyridine-sensitive calcium channel blocker, reversed the increase in norepinephrine release induced by bradykinin and Bay K 8644. 4. These results indicate that bradykinin may increase norepinephrine release in rat hypothalamus, partially mediated by interactions with dihydropyridine-sensitive calcium channels.

Erythropoietin with oral iron in peritoneal and hemodialysis patients. A comparison in an inner city population.

Studies on the comparative efficacy of erythropoietin (rHuEPO) in chronic hemodialysis (HD) and peritoneal dialysis (PD) patients are scarce. The authors compared the use of rHuEPO in 74 stable patients on hemodialysis with 24 on chronic peritoneal dialysis. All patients were on oral iron supplements. In PD patients, hematocrits were 23.1 and 30.1%, rHuEPO dose 80.9 and 89.0 U/kg/wk, whereas in HD patients, hematocrits were 21.2 and 27.5 and rHuEPO dose was 140.2 and 165.0 U/kg/wk at initiation and 6 months, respectively. Serum iron and transferrin saturations were unchanged in peritoneal, but decreased in hemodialysis patients on rHuEPO therapy. These findings suggest that rHuEPO is more effective in peritoneal dialysis patients than in hemodialysis patients receiving oral iron. The improved efficacy of rHuEPO in peritoneal dialysis may be due to decreased blood loss, subcutaneous administration, or better removal of inhibitors of erythropoiesis. Peritoneal dialysis may be more cost effective and desirable than hemodialysis for rHuEPO dependent or resistant patients.

No-scalpel vasectomy.

PIP: Physicians in China have developed a new technique to perform vasectomies which improves men's acceptance of vasectomy. It is called no-scalpel vasectomy. Before performing the vasectomy, the surgeon should determine whether the patient is indeed interested in permanent sterilization. The surgeon should also gather information on patient's age, marital status, and medical history and perform a physical examination. Counseling should consist of clear, simple language to diminish any fears. The surgeon must inform the patient of alternative nonpermanent means of contraception and stress that vasectomy is essentially irreversible. 2 physicians recommend external spermatic fascia injection using 2-3 ml of 2% plain lidocaine to induce vasal nerve blockage. After properly fixing the vas deferens with a ring clamp, the surgeon pierces the scrotal skin, vas sheath, and vas deferens in the midline with a curved dissecting clamp held at a 45 degree angle from horizontal. The surgeon then rotates the clamp 180 degrees to prepare the vas for cutting. The surgeon cuts out a 1 cm segment and then occludes the ends of the vas. The vas is then returned to the scrotal sac via the same puncture hole. No sutures are needed for the puncture hole. The same procedure is followed for the other vas. Hands-on training requires 10-15 procedures to develop proficiency. The no-scalpel technique takes about 40% less time than conventional techniques. The complication rate for the no-scalpel technique is 0.4 events/100 procedures compared to 3.1/100 procedures for conventional techniques. Both the ring clamp and dissecting clamp were developed in China. These instruments are provided through a company in Georgia and through the Association for Voluntary Surgical Contraception (AVSC). AVSC helps medical institutions coordinate physician training of the no-scalpel technique.^ieng

Calcitonin gene-related peptide in noradrenergic transmission in rat hypothalamus.

In the present study, we examined the regulatory mechanisms of calcitonin gene-related peptide on norepinephrine release in rat hypothalamus. Calcitonin gene-related peptide inhibited the stimulation-evoked norepinephrine release from hypothalamic slices of Sprague-Dawley rats in a dose-dependent manner, although the peptide did not affect basal release of norepinephrine. The blockade of the alpha 2-adrenergic receptors by RX 781094 failed to modulate the inhibitory effects of calcitonin gene-related peptide on norepinephrine release. Pretreatment of slices with islet activating protein, a toxin that interferes with the coupling of the inhibitory receptors to adenylate cyclase, did not affect the suppression of norepinephrine release by calcitonin gene-related peptide. However, Bay K 8644, a dihydropyridine-sensitive calcium channel agonist, significantly reversed the inhibitory effects of calcitonin gene-related peptide on norepinephrine release. These results show that calcitonin gene-related peptide might inhibit norepinephrine release in rat hypothalamus, partially mediated by interactions with dihydropyridine-sensitive Ca2+ channels but not by interactions with presynaptic alpha 2-adrenergic receptors and inhibitory guanosine triphosphate binding proteins. Furthermore, the finding suggests the possible involvement of calcitonin gene-related peptide in the regulation of sympathetic nervous activity in the central nervous system.