Pilot study to enhance HIV care using needle exchange-based health services for out-of-treatment injecting drug users

The introduction of highly active antiretroviral therapy (HAART) has resulted in marked reductions in mortality and acquired immunodeficiency syndrome (AIDS) incidence across all risk groups; however, the proportionate decrease among injecting drug users (IDUs) has been less impressive. Much of the disparity in benefit to IDUs has been a consequence of decreased access to and receipt of potent antiretroviral combinations. Strategies to increase access to and utilization of HAART have included entry into drug treatment and abstinence. Unfortunately, as few as 15%–20% of active drug users in the United States, and in many other countries, are in drug treatment at any one time. We report a pilot project among out-of-drug treatment IDUs infected with human immunodeficiency virus (HIV); HIV therapy was successfully provided to active heroin injectors using the Community Health Care Van (CHCV) at sites of needle exchange. Subjects were willing to initiate, but were not receiving, recommended HIV therapy and were not interested in formal drug treatment. Antiretroviral therapy regimens were selected and linked to heroin injection timing. Weekly visits were scheduled by CHCV staff to assess adverse side effects and encourage adherence. Of the 13 participants, the mean baseline HIV-1 RNA level and CD4 lymphocyte count were 162,369 (log 5.21) copies per milliliter and 265 cells per milliliter, respectively. By 6 months, the proportion whose HIV-1 RNA was below the limits of detection (<400 copies/mL) was 85% (N=11); 77% (N=10) had nondetectable levels by 9 months. By 12 months, 54% (N=7) had a persistently nondetectable viral load, and the net increase in CD4 lymphocyte count was 150 cells per milliliter. As an additional and unintended benefit of this pilot project, 9 (69%) subjects chose to enter drug treatment after achieving a nondetectable viral load. Entry into drug treatment was associated with durability of viral suppression. This small pilot study suggests that health services based on needle exchange may enhance access to HAART among out-of-treatment HIV-infected IDUs. In addition, it demonstrates that this population can benefit from this therapy with the support of a nontraditional, community-based health intervention.     

ENDOTHELIN RECEPTORS IN RAT ADRENAL GLAND VISUALIZED BY QUANTITATIVE AUTORADIOGRAPHY

1. The radioligand [125I]-endothelin was used to map receptors for endothelin in rat adrenal gland using in vitro autoradiography and computerized densitometry. 2. In the adrenal, a high density of binding was found in the adrenal medulla (binding affinity constant 0.18 +/- 0.11 X 10(9)M-1) and zona glomerulosa (binding affinity constant 0.18 +/- 0.07 X 10(9)M-1). Binding was low to undetectable in the zona fasciculata and zona reticularis. Unrelated peptides did not displace endothelin. 3. These results provide evidence of endothelin receptor distribution in adrenal gland and suggest that endothelin might exert multiple actions in the adrenal gland on catecholamine and aldosterone biosynthesis and secretion.     

Duodenal atresia and stenosis: Reassessment of treatment and outcome based on antenatal diagnosis,pathologic variance,and long-term follow-up

Duodenal atresia and stenosis was observed in 103 infants and children from 1972 to 1991. There were 59 girls and 44 boys. Atresia was noted in 79 instances and stenosis in 24. Maternal hydramnios was detected in 33 cases, 46 babies were premature, and 31 had Down's syndrome. Fifty-four infants had significant associated anomalies including 35 with cardiac defects. Diagnosis was achieved by prenatal ultrasound examination in 14 cases, observation of a double-bubble sign on abdominal radiograph in 73, and contrast studies in 30 infants including 24 with stenosis. At operation annular pancreas was noted in 37 cases, malrotation in 37 cases, anterior portal vein in 4, and a second web in 3. Surgical treatment included duodenoduodenostomy in 85, duodenotomy and web excision in 8, and duodenojejunostomy in 10. Operative survival was 95%. Deaths were related to complex cardiac defects. Despite antenatal diagnosis, prompt intervention, and apparent early surgical success (95% survival), late deaths (5%) and late complications including motility disorders, megaduodenum, gastroesophageal reflux, duodenal-gastric reflux, gastritis, peptic ulcer disease, blind loop syndrome, and biliary-pancreatic conditions may be observed months to years after management during the neonatal period. Modifications in surgical technique including early tapering duodenoplasty may be useful, and close long-term follow-up is an essential component of patient care.

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Resumen Se encontró atresia duodenal y estenosis en 103 niños, 59 de sexo femenino y 44 de sexo masculino, en el período 1972–91: atresia en 79 casos y estenosis en 24. Se registró hidramnios materna en 33 casos; 46 niños fueron prematuros y 31 presentaban síndrome de Down; 54 exhibían anomalías de significación, incluyendo 35 con defectos cardiacos. El diagnóstico fue establecido por ultrasonido prenatal en 14 casos, mediante la observación de burbuja doble en la radiografía abdominal en 73 y por estudio con medio de contraste en 30, entre los cuales había 24 con estenosis. En la operación se encontró páncreas anular en 37 casos, malrotación en 37, vena porta anterior en 4 y segunda membrana en 3. El tratamiento quirúrgico incluyó duodenostomía en 85 pacientes, duodenotomía y resección de membrana en 8 y duodenoyeyunostomía en 10. La tasa de sobrevida operatoria fue de 95%. Las muertes estuvieron asociadas con los defectos cardfacos complejos. A pesar de su diagnóstico prenatal, una intervención quirúrgica precoz y un aparente éxito operatorio (sobrevida de 95%), se observan muertes tardías (5%) y complicaciones a largo plazo tales como desórdenes de la motilidad intestinal, megaduodeno, reflujo gastroesofágico, reflujo duodeno-gástrico, gastritis, enfermedad ulcerosa péptica, síndrome de asa ciega y alteraciones biliopancreáticas, meses a años después del tratamiento y manejo neonatales. Algunas modificaciones en la técnica quirúrgica, tales como duodenoplastia, pueden ser de utilidad; el seguimiento cuidadoso a largo plazo constituye un componente esencial de la atención de estos pacientes.

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Résumé Entre 1972 et 1991, on a observé 79 cas d'atrésie duodénale et 24 cas de sténose duodénale chez un total de 103 enfants, 59 filles et 44 garçons. Une hydramnios a été retrouvée chez 33 des mères, 46 enfants étaient des prématurés et 31 avait un syndrome de Down. Chez 54 enfants, il y avait des malformations associées, dont 35 cardiaques. Le diagnostic avait été établi dans 14 cas par une échographie anténatale, par l'existence du signe de la double bulle sur les abdomens sans préparation chez 73 patients et par une étude du transit intestinal en double contraste chez 34 enfants, dont 24 avec une sténose. A l'opération, on a retrouvé un pancréas annulaire chez 37 enfants, une malrotation chez 37, une veine porte antérieure chez 4, et une membrane intraluminale chez 3. Le traitement a été une anastomose duodénoduodénale chez 85 enfants, une excision de membrane après duodénotomie chez 8 et une duodénojéjunostomie chez 10. La mortalité opératoire était de 5%, en rapport essentiellement avec des malformations cardiaques complexes. En dépit d'un diagnostic anténatal, une intervention précoce et un succès chirurgical apparent, la morbidité tardive est toujours possible et comprend essentiellement des anomalies de la motilité duodénale, le mégaduodénum, un reflux gastroesophagien, un reflux duodénogastrique, une gastrite, la maladie ulcéreuse, un syndrome de l'anse borgne, et d'autres anomalies biliopancréatiques qui peuvent se voir des mois ou des années après la période néonatale. Les modifications de la technique chirurgicale et notamment la duodénoplastie précoce ainsi qu'une meilleure surveillance à distance, peuvent en améliorer le pronostic.

     

Laparoscopic bowel surgery registry

Laparoscopic surgery has evolved rapidly since 1989. The American Society of Colon and Rectal Surgeons, the Society of American Gastrointestinal Endoscopic Surgeons, and the American College of Surgeons Commission on Cancer jointly sponsored a registry to identify as early as possible the patterns of practice and acute complications of laparoscopic colectomy. METHODS: Cases were voluntarily registered by community and academic surgeons. Information was entered in the EPI-5 database. RESULTS: One thousand fifty-six cases were contributed by 118 surgeons; 763 patients were completed laparoscopically. The most common indication for surgery was cancer in 453 patients. The right colon (n=364) and sigmoid (n=294) were most frequently resected. Respondents felt adequate cancer resections were performed. Although several unique complications were noted, intraoperative complications were similar in type and frequency to open cases. CONCLUSION: Laparoscopic colorectal surgery can be performed with acceptable complications. It remains unclear if this approach is adequate for long-term management of colon and rectal cancer.Read at the meeting of The American Society of Colon and Rectal Surgeons, Orlando, Florida, May 8 to 13, 1994.     

The mechanism of yohimbine-induced renin release in the conscious rat

Summary These studies were designed to determine the role of the central nervous system, the sympathetic nervous system, the adrenal glands and the renal sympathetic nerves in yohimbine-induced renin release in conscious rats. Yohimbine (0.3–10 mg/kg, s.c.) caused time- and dose-related increases in plasma renin activity (PRA) and concentration (PRC) which were accompanied by time- and dose-related elevations of plasma norepinephrine (NE) and epinephrine (Epi) concentrations. Significant positive correlations were found between the increases in PRA and the increases in plasma NE and Epi concentrations caused by yohimbine, and propranolol (1.5 mg/kg, s.c.) blocked 90% of yohimbine (3 mg/kg, s.c.)-induced renin release. Over the entire spectrum of doses of yohimbine, the increases in PRA and plasma NE and Epi concentrations were positively correlated with the decreases in mean arterial pressure (MAP), but the -intercept was positive in every case and the 1 mg/ kg dose of yohimbine consistently increased PRA independent of any change in MAP. Complete renal denervation, as evidenced by a greater than 90% reduction in renal NE content, did not alter the increase in PRA caused by yohimbine (3 mg/kg, s.c.). An increase in circulating plasma catecholamine concentrations appeared to mediate yohimbine-induced renin release since propranolol prevented the rise in PRA caused by yohimbine in renal denervated rats. Prior adrenalectomy (Adx) also failed to prevent the rise in PRA produced by yohimbine (3 mg/kg, s.c.), but a combination of Adx and renal denervation caused a significant impairment of yohimbine-induced renin release. However, neither Adx alone nor the combination of Adx and renal denervation affected the increase in plasma NE concentration caused by yohimbine. Complete transection of the spinal cord at C₈ caused a drastic reduction in plasma catecholamine concentrations but did not change basal PRC. Yohimbine (3 mg/kg, s.c.) did not increase PRC or plasma catecholamine concentrations after spinal transection. Based on these results, we conclude that 1) the stimulation of renin release by yohimbine is a secondary neurohormonal consequence of the generalized increase in sympathetic activity caused by yohimbine, 2) the sympathoadrenal activation produced by yohimbine results from an action in the brain which is amplified by the simultaneous blockade of prejunctional ₂-adrenoceptors and 3) vasodepressor effects of the larger doses yohimbine cause a baroreflexly-mediated increase in sympathetic activity which interacts in a positive fashion with the central and peripheral sympathoexcitatory effects of yohimbine. Send offprint requests to T. K. Keeton     

Intestinal 5-Fluorouracil Absorption: Use of Ussing Chambers to Assess Transport and Metabolism

We have employed an in vitro system to study transport and metabolism of organic molecules by gastrointestinal tissues. Such a system would aid in the evaluation of the potential for oral delivery of organic molecules. Transport and metabolism of 5-fluorouracil (5-FU) were studied using rabbit intestinal preparations. Unidirectional fluxes and metabolism were measured in vitro in Ussing chambers under short-circuit conditions. Results from these studies reveal that in ileum, proximal, and distal colon, steady-state fluxes of 5-FU (10 µM added to both bathing solutions) are established after 30 min and remain constant for at least 110 min. Transport of 5-FU under sink conditions with 10 µM 5-FU present in the mucosal or serosal bathing solution alone demonstrated similar rates of transport as under nonsink conditions. The concentration dependence of 5-FU fluxes indicates that the mucosal (m)-to-serosal (s) flux is composed of both a saturable and a linear component over the range of 1–100 µM in the ileum, whereas the s-to-m flux in the ileum and both fluxes in the colon are linear functions of concentration. Over the concentration range employed and the time course of these studies, 5-FU had no effect on the electrical properties of the ileum or colon. In the ileum, the m-to-s but not the s-to-m flux of 5-FU was reduced by (1) serosal ouabain (0.1 mM); (2) reduction of the bathing solution Na concentration; and (3) addition of uracil, thy mine, thymidine, uridine, 2-deoxyuridine, or uridine-5-monophosphate. These results indicate that 5-FU absorption in the ileum occurs by a Na-dependent mechanism that is inhibited by uracil and structurally related compounds. In distal colon, no evidence for an active transport mechanism was obtained. High-performance liquid chromatography (HPLC) analysis reveals that both ileum and distal colon metabolize 5-FU to more polar compounds. Metabolism in ileum is quantitatively greater than in distal colon. Metabolites are found predominantly on the side to which transport has occurred, suggesting that metabolism occurs concomitantly with transport. Since the intestinal cells metabolize 5-FU to more polar compounds and active absorption is inhibited in a competitive manner by related compounds, these results may provide an explanation for the variable oral activity reported for 5-FU.     

Anaesthetic experience with paediatric interventional cardiology

Anaesthetic and sedation techniques, complications and outcomes were reviewed in 176 children undergoing 184 interventional cardiologic procedures. Techniques included sedation only, and ketamine, inhalational or narcotic anaesthesia. Ketamine infusion was the technique most frequently used. Ketamine was associated with a higher incidence of respiratory complications (P < 0.05) than the other techniques. The higher incidence of hypercarbia (15.6 per cent), which did not affect outcome, may be attributable to the use of supplemental sedatives. The incidence of upper airway obstruction (7.8 per cent) was similar to that of previous studies. Vascular compromise resulted from the procedure in 33 patients, necessitating surgical correction in 16. Cardiac perforation occurred in four cases, causing one death. Pulmonary valve stenosis was most amenable to balloon dilatation and aortic valve stenosis least amenable. Ketamine was the anaesthetic agent preferred by cardiologists for use in the catheterisation suite when general anaesthesia was required. Vigilant monitoring by anaesthetic staff is necessary during the procedure, and avoidance of concomitant narcotics is recommended if a ketamine technique with spontaneous ventilation is used. Les techniques anesthésiques et de sédation ainsi que les complications et les issues ont été revues chez 176 enfants subissant 184 procedures cardiaques. Les techniques ont inctu soil la sédation seulement, soit l’anesthésie à la kétamine, aux agents d’inhalation ou aux narcotiques. La perfusion de kétamine était la technique la plus fréquemment utilisée. La ketamine était associée à une plus grande incidence de complication respiratoire (P < 0.05) comparativement aux autres techniques. La plus grande incidence d’hypercarbie (15.6 pour cent), n’ayant pas affecté l’issue, pourrait être attribuée à l’utilisation additionnelle de sédatifs. L’incidence d’obstruction des voies aériennes supérieures (7.8 pour cent) était similaire aux études préalables. Un problème vasculaire suite à la procédure fut observé chez 33 patients dont 16 ont requis une correction chirurgicale. Une perforation cardiaque est survenue dans quatre cas provoquant le décès d’un seul patient. La sténose de la valve pulmonaire était la procédure la plus susceptible d’être dilatée et la sténose de la valve aortique la moins susceptible. La kétamine était l’agent anesthésique préféré par les cardiologistes lors des cathétérisations quand une anesthésie générate était requise. Une surveillance vigilante par une équipe anesthésique fut nécessaire durant la procedure. Il faut aussi éviter l’administration de narcotiques si la kétamine est administrée en respiration spontanée.

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Presented in part at the Canadian Anaesthetists’ Society annual meeting in Halifax, June 1988.     

Real-time nested multiplex PCR for the detection of herpes simplex virus types 1 and 2 and varicella zoster virus

One hundred forty-nine specimens were tested in a LightCycler nested multiplex polymerase chain reaction (LCnmPCR) for Herpes simplex virus (HSV)1, HSV2, and VZV. Eighty-one were from genitourinary medicine (GUM) patients and the other 68 specimens were from other patients with skin lesions. The results were compared to a conventional multiplex nested PCR (nmPCR) using agarose gel electrophoresis. Twenty-five specimens were positive in both assays for HSV1 and 29 were positive for VZV. For HSV2 there were 27 positive in the LCnmPCR and 26 positive in the nmPCR assay. The melting temperatures (Tms) of each target were different with a mean of 84.75 degrees C for HSV1, 88.57 degrees C for HSV2, and 83.62 degrees C for VZV. The melting curves of positive specimens directly overlaid the melting curves of the positive controls in the assay. The LCnmPCR assay is a convenient alternative to conventional PCR using agarose gel electrophoresis. It improves specimen turnaround time by eliminating the need for gel electrophoresis, transillumination, and gel photography. It also shows increased sensitivity for HSV2 over our standard assay. This LCnmPCR reduces further the possibility of amplicon contamination with nested PCR protocols.