DCyFIR: a high-throughput CRISPR platform for multiplexed G protein-coupled receptor profiling and ligand discovery.

More than 800 G protein-coupled receptors (GPCRs) comprise the largest class of membrane receptors in humans. While there is ample biological understanding and many approved drugs for prototypic GPCRs, most GPCRs still lack well-defined biological ligands and drugs. Here, we report our efforts to tap the potential of understudied GPCRs by developing yeast-based technologies for high-throughput clustered regularly interspaced short palindromic repeats (CRISPR) engineering and GPCR ligand discovery. We refer to these technologies collectively as Dynamic Cyan Induction by Functional Integrated Receptors, or DCyFIR. A major advantage of DCyFIR is that GPCRs and other assay components are CRISPR-integrated directly into the yeast genome, making it possible to decode ligand specificity by profiling mixtures of GPCR-barcoded yeast strains in a single tube. To demonstrate the capabilities of DCyFIR, we engineered a yeast strain library of 30 human GPCRs and their 300 possible GPCR-Gα coupling combinations. Profiling of these 300 strains, using parallel (DCyFIRscreen) and multiplex (DCyFIRplex) DCyFIR modes, recapitulated known GPCR agonism with 100% accuracy, and identified unexpected interactions for the receptors ADRA2B, HCAR3, MTNR1A, S1PR1, and S1PR2. To demonstrate DCyFIR scalability, we profiled a library of 320 human metabolites and discovered several GPCR-metabolite interactions. Remarkably, many of these findings pertained to understudied pharmacologically dark receptors GPR4, GPR65, GPR68, and HCAR3. Experiments on select receptors in mammalian cells confirmed our yeast-based observations, including our discovery that kynurenic acid activates HCAR3 in addition to GPR35, its known receptor. Taken together, these findings demonstrate the power of DCyFIR for identifying ligand interactions with prototypic and understudied GPCRs.

Laparoscopic versus open splenectomy in the pediatric population: a contemporary single-center experience.

The purpose of this study was to compare a recent contemporaneous experience between laparoscopic (LS) and open (OS) splenectomy in children. All splenectomy cases between 1994 and 1999 at our institution were reviewed. The study included open and laparoscopic cases performed according to surgeon preference. Emergency splenectomies for trauma were excluded. The patient record was reviewed for the diagnosis, indications, postoperative length of stay, operative technique, postoperative complications, blood loss/blood transfusion, total amount of parenteral narcotics, and time to resumption of oral intake. Chi-square and t tests were used to compare measured differences for statistical significance. Between May 1994 and December 1999, 52 splenectomies were performed at Vanderbilt Children's Hospital. Of these, 45 were elective operations with 29 open and 16 laparoscopic procedures. During four OS and five LS operations a concomitant cholecystectomy was performed. The median patient age was 9.2 years (range 0.5 to 17.3). There was no statistical difference between the two groups in terms of age, weight, American Society of Anesthesiologists class, or estimated blood loss. There were no immediate postoperative complications in either group. There were no conversions from LS to OS. The mean duration of surgery was 264 minutes (LS) versus 169 minutes (OS) (P < 0.05). The average time to first oral intake was shorter in patients undergoing LS (1.1 vs 1.6 days, P < 0.05) and the mean postoperative length of stay was also shorter in the LS group (1.3 vs 3.1 days, P < 0.05). The use of postoperative intravenous narcotics (in morphine-equivalent doses) was significantly less in LS patients than in OS patients (7.5 mg or 0.15 mg/kg vs 46.9 mg or 1.5 mg/kg, P < 0.001), as was the need for PCA pump analgesia (90% in the OS group vs 25% in LS group, P < 0.01). Overall the average hospital charge (anesthesia fee, narcotics charge, and hospital room charge) was $5400 (range $4240-6250) in the OS group and $4950 (range $4450-6240) in the LS group (P < 0.05). Among the nine patients undergoing splenectomy with cholecystectomy, findings between the OS and LS groups were similar except for one late complication consisting of a diaphragmatic hernia in an LS patient. Both LS and OS with or without a concomitant procedure can be accomplished safely in children. LS appears to result in longer operative times but shorter lengths of stay, earlier first oral intake, and significantly fewer requirements for intravenous narcotics; all of these contribute to a reduction in hospital charges compared with the open operation.

Twenty-five-year surgical experience with pheochromocytoma in children.

Our objective was to analyze the presentation, diagnostic localization, operative management, histology, and long-term outcome of a single center's experience with pheochromocytomas in children. A chart review was done to identify all operatively managed pheochromocytomas in patients age 18 years or younger. Open and laparoscopic cases were included. We reviewed the presentation, diagnostic imaging, localization, operative management, pathology, and postoperative outcome of these patients. Clinic visits, contact with the tumor registry, and telephone interviews were used for follow-up. From 1973 through 1999, there were 11 children (four males and seven females) with 14 pheochromocytomas. Two (18.2%) patients had bilateral adrenal lesions and one patient had both adrenal and extra-adrenal tumors. Six (54.5%) patients had extra-adrenal lesions. The average age at operation was 14.7 years (range 9-18 years). Nine (82%) patients had significant hypertension at presentation. CT was used to localize the tumor in eight patients and urine catecholamine levels were used to confirm the diagnosis. Two of the cases were associated with inherited syndromes (multiple endocrine neoplasia 2A and von Hippel-Lindau). Ten patients underwent an open operation and one patient had a laparoscopic resection. The average patient follow-up was 9.2 years (range 9 months to 25 years). There were no operative complications and all patients were alive and well at the time of last follow-up. Three patients (27.2%) had tumors with microscopic malignant features. No tumors recurred or had evidence for metastatic spread. We conclude that peak incidence of pheochromocytomas in children is in early adolescence. Resection can be carried out safely with minimal morbidity and mortality. Current best management of this entity includes establishment of a biochemical diagnosis, adequate preoperative blockade, appropriate imaging, and an individualized operative approach based on tumor location and size.

Laparoscopic cholecystectomy in children: lessons learned from the first 100 patients.

BACKGROUND/PURPOSE: Laparoscopic cholecystectomy is a very common operation in adults but is relatively infrequently required in children. A retrospective review of 100 consecutive infants and children undergoing laparoscopic cholecystectomies from 1990 to 1998 was performed to see what lessons have been learned from this relatively large population of pediatric patients. RESULTS: The patients ranged in age from 25 to 230 months, with a mean of 105 months. Only 19 patients had hemolytic disease as the etiology for their cholelithiasis. Two patients had biliary dyskinesia. Seventy-eight patients underwent an elective operation. Twenty-two children required urgent hospitalization because of complications from their cholelithiasis: acute cholecystitis (n = 7), jaundice and pain (n = 6), gallstone pancreatitis (n = 5), acute biliary colic (n = 4). All 6 patients who presented with jaundice underwent endoscopic retrograde cholangiopancreatography (ERCP) before their laparoscopic cholecystectomy. Two patients required laparoscopic choledochal exploration. The operating time and postoperative hospitalization were significantly longer (P = .0005) in the complicated group when compared with the elective patients. No significant complications such as the need for reoperation, injury to the choledocuhus or to other viscera, bile leak, or retained choledocholithiasis occurred. CONCLUSIONS: Laparoscopic cholecystectomy is a safe, effective procedure in children for removal of the gallbladder. The exact role of routine cholangiography and ERCP remains unclear.

Clinical experience over 48 years with pheochromocytoma.

OBJECTIVE: To analyze the presentation, localization, surgical management, pathology, and long-term outcome of a large series of patients with pheochromocytomas. SUMMARY BACKGROUND DATA: There are several areas of controversy pertaining to pheochromocytomas. Although many studies report a higher rate of malignancy for extraadrenal pheochromocytomas than for adrenal pheochromocytomas, the number of patients with the former tumor are small and statistical analysis is lacking. There has also been recent debate as to whether microscopic features of the tumor may be predictive of future behavior. METHODS: From 1950 to 1998, the authors observed 108 pheochromocytomas in 104 patients. The outcome of these patients has been followed prospectively. The medical records of these patients were reviewed for data on the presentation, localization, surgical management, pathology, and outcome. Patient survival was analyzed using Kaplan-Meier survival distributions. RESULTS: This study included 66 female patients and 38 male patients. The average age at surgery was 42.3 years. Sporadic cases accounted for 84% of the patients; the other 16% had multiple endocrine neoplasia type 2, von Recklinghausen's disease, von Hippel-Lindau disease, or Carney's syndrome. Of 64 adrenal tumors, 55 were initially considered benign, 6 had microscopic malignant features, and 3 had malignant disease. Mean patient follow-up was 12.6 years. To date, in five additional patients (none with microscopic disease) malignant disease developed (13% overall rate of malignancy). Recurrence occurred as late as 15 years after resection. Of 26 extraadrenal pheochromocytomas, 14 were initially considered benign, 8 had microscopic malignant features, and 4 had malignant disease. Thus, 46% of patients had either malignant disease or tumors with malignant features. Mean patient follow-up was 11.5 years. In one patient with benign disease and in one patient with malignant features, malignant disease developed (23% overall rate of malignancy). The difference in the rate of malignancy was not statistically significant between adrenal and extraadrenal pheochromocytomas. Patients with adrenal and extraadrenal pheochromocytomas also had similar rates of survival (p = NS). CONCLUSIONS: The data suggest that patients with extraadrenal pheochromocytomas have the same risk of malignancy and the same overall survival as patients with adrenal pheochromocytomas. Lifelong follow-up of these patients is mandatory.

In utero decompression of a cystic grade IV sacrococcygeal teratoma.

Sacrococcygeal teratomas (SCT) are the most common congenital tumors in the newborn. The prevalence rate is approximately 1 per 40,000 births, with 80% occurring in females. The majority of these tumors are external, protruding from the perineal region. Intrapelvic SCTs, by contrast, are extremely rare and difficult to diagnose in utero. Only 15% of the SCTs are entirely cystic, the majority being mixed or solid tumors. We describe a case of a fetal cystic presacral (grade IV) SCT, discovered at 22 weeks of gestation, which resulted in bilateral ureteral obstruction and hydronephrosis. This is the first known reported case of prenatally decompressing a cystic SCT via an amniotic catheter to alleviate a mass effect in the fetus.

Hemorrhagic and obstructive shock in pediatric patients.

Shock in childhood is most commonly related to injury and blood loss, but hemodynamic compromise is occasionally caused by severe head or spinal injury, tension pneumothorax, myocardial injury, arrhythmias, and sepsis. Regardless of the cause, the initial management of the hypertensive child is establishment of a secure airway, maintenance of ventilation, and initiation of volume replacement via an adequate intravenous catheter. At the present time, crystalloid resuscitation with lactated Ringer's solution and buffering of acidosis with sodium bicarbonate is the standard approach, although in the future hypertonic saline solution may play a role. Hemorrhage may be classified according to the percentage of blood volume lost; losses in excess of 30% of blood volume (class III and IV hemorrhage) usually require administration of packed red blood cells and/or albumin as well. With appropriate management, the typical clinical signs of shock will be reversed and the child will demonstrate improved vital signs, peripheral circulation and sensorium, normalization of body temperature, reversal of metabolic acidosis, and resumption of normal urine output. The more aggressive the approach to resuscitation, the more prompt the patient's response and the more likely morbidity and mortality will be minimized.

Laparoscopic evaluation for a contralateral patent processus vaginalis: part III.

OBJECTIVES: Between May 1, 1992 and August 1, 1996, 759 consecutive children younger than 10 years of age were evaluated and treated for known inguinal hernia. These children were participating in a prospective investigation of the potential role of diagnostic laparoscopy in the evaluation of the contralateral inguinal anatomy. The initial two series of data (parts I and II of this three-part series) were previously presented at the 1993 and 1995 American Academy of Pediatrics meetings. METHODS: Of 759 patients, 100 children were diagnosed with bilateral inguinal hernias and therefore did not undergo laparoscopy. Thirty-two patients did not undergo laparoscopic evaluation due to technical difficulties or complicated clinical situations. The patient's contralateral inguinal region was carefully examined under anesthesia, and predictions were made regarding the likelihood of contralateral patent processus vaginalis (CPPV). Six hundred twenty-seven children underwent diagnostic laparoscopy to confirm the presence or absence of CPPV. Laparoscopy was initially exclusively performed through the umbilicus prior to repair of the known hernia, but over the last 26 months, 250 children successfully underwent laparoscopy through the ipsilateral hernia sac. RESULTS: Of patients younger than 1 year of age, 114 were diagnosed with both a known unilateral hernia and CPPV, whereas 132 had a unilateral hernia only (46% versus 54%). Among children older than 1 year of age, 148 (39%) were diagnosed with unilateral hernia and CPPV, and 233 (61%) were diagnosed with a unilateral hernia alone. After examination under anesthesia, 233 of the 627 patients were suspected of having a CPPV, and 107 were confirmed at laparoscopy (46%). The remaining 394 patients were not believed to have a CPPV. Normal inguinal anatomy was confirmed in 234 patients (59%), but 160 patients were found at laparoscopy to have a CPPV (41%). CONCLUSIONS: A contralateral patent processus vaginalis may be present in a surprising number of young patients being evaluated for a known inguinal hernia. Laparoscopy can be performed without a separate incision when the ipsilateral hernia sac is of sufficient width to allow passage of the scope. Laparoscopy is the best method for evaluating the contralateral inguinal region, particularly in younger children, as it prevents unnecessary inguinal exploration and it decreases the risk that the child will later present with a clinical contralateral hernia.

Hyperthermia during repair of pectus excavatum.

We have observed an elevation of body temperature during surgical repair of pectus excavatum. To document this phenomenon and attempt to prevent it, we undertook a combination retrospective-prospective study. The retrospective arm included an analysis of the anesthetic records of patients undergoing repair of pectus excavatum during the past 5 years and included 22 boys and 3 girls. Body temperature increased in all 25 patients, from a starting temperature of 36.1 degrees C +/- 0.5 degree C to 38.0 degrees C +/- 0.6 degree C. The maximum temperature exceeded 38 degrees C in 12 patients and 39 degrees C in 3 patients. An additional retrospective review of the anesthetic records of 15 children undergoing another type of thoracic procedure (thoracotomy) for noninfectious problems revealed only a modest, statistically nonsignificant rise in temperature from a starting point of 35.9 degrees C +/- 0.7 degree C to a maximum of 36.3 degrees C +/- 1.2 degrees C. The maximum temperature was greater than 38 degrees C in one of these 15 patients. The prospective arm of the study included a standardized anesthetic technique in 10 patients. Neither a heated humidifier nor a warming blanket were used, and the ambient temperature of the room was maintained at 70 degrees F. Core body temperature increased from a starting temperature of 36.1 degrees C +/- 0.6 degree C to 36.8 degrees C +/- 0.8 degree C. A significant elevation of body temperature occurs in children during repair of pectus excavatum that may be avoided by eliminating the use of exogenous methods to prevent hypothermia (e.g., heated humidifier, warming blanket).

Laparoscopic evaluation for contralateral patent processus vaginalis: Part II.

Between May 1,1992 and August 1, 1995, 599 consecutively treated children under 10 years of age evaluated by the authors for a known inguinal hernia were involved in a prospective protocol to determine whether diagnostic laparoscopy has a place for evaluation of the contralateral inguinal region. The experience with the first 221 patients was reported at the 1993 AAP meeting. In this total experience, 81 patients had known bilateral inguinal hernias and did not require diagnostic laparoscopy. Five hundred eighteen patients had a unilateral inguinal hernia with the status of the contralateral region being unknown. Between May 1, 1992 and May 1, 1994, 368 children underwent evaluation using an umbilical approach. However, for the past 14 months, 150 patients have undergone the diagnostic laparoscopy through the ipsilateral hernia sac. Among the children under 1 year of age, 98 were found to have a unilateral hernia and also a contralateral patent processus vaginalis (CPPV) and 110 had a unilateral hernia. Of the children older than age 1,116 had a unilateral hernia and CPPV and 194 had only a single hernia. After induction of anesthesia, it was suspected on clinical examination that 195 of the 518 patients had a CPPV. However, laparoscopy showed that only 94 (48%) had a CPPV. In the remaining 323 patients, the surgeon believed that a CPPV was not present based on the examination. This negative finding was verified in only 198 patients (81%), but a surprising 125 (39%) did have CPPV documented at the time of endoscopy. Insufflation alone was very unrellable for documenting the presence of CPPV. Of the 214 patients for whom CPPV on the contralateral side was documented during laparoscopy, only 41 (19%) had a positive finding on insufflation. This experience has convinced the authors that diagnostic laparoscopy is the most accurate means to ascertain whether a patient should undergo contralateral inguinal exploration. In addition, laparoscopy through the ipsilateral inguinal sac is now the preferred approach.

General anesthesia using the laryngeal mask airway during brief, laparoscopic inspection of the peritoneum in children.

The authors prospectively examined the cardiorespiratory changes seen with general anesthesia using the laryngeal mask with spontaneous ventilation during brief laparoscopic inspection of the peritoneum in children. Anesthesia consisted of halothane in 50% oxygen/air and a caudal epidural block. The patient was allowed to ventilate spontaneously without assistance. Baseline measurements of heart rate, systolic blood pressure (SBP), end-tidal CO2 (ETCO2), tidal volume, respiratory rate, and oxygen saturation were recorded every 1 min for 5 min prior to the start of laparoscopy and every minute during the laparoscopic procedure. A total of 15 patients were enrolled in the study ranging in age from 15 to 90 months (35.5 +/- 23.8 months) and in weight from 10 to 26.4 kg (14.9 +/- 4.9 kg). The length of the laparoscopy varied from 3 to 9 min (6.1 +/- 2.1 min). Although clinically insignificant, there was an increase in the heart rate from a baseline value of 141 +/- 9 to 148 +/- 9 beats/min (p = 0.0016) and in the SBP from a baseline value of 97 +/- 6 mm Hg to 101 +/- 7 mm Hg (p = 0.0087). The baseline tidal volume prior to the start of laparoscopy was 5.2 +/- 1.1 mL/kg and increased to 6.4 +/- 1.4 mL/kg during laparoscopy (p < 0.0001) while the respiratory rate increased from 32 +/- 4 to 40 +/- 6 breaths/min (p < 0.0001). ETCO2 increased from a baseline value of 47 +/- 6 to 53 +/- 6 torr (p = 0.0059). The maximum value of the ETCO2 was 55 torr or greater in 6 patients, exceeded 60 torr in 3 patients, with a maximum value of 63 torr. The increased ETCO2 returned to baseline within 2 to 7 min (4.7 +/- 1.5 min) following completion of the laparoscopy. There was no significant change in oxygen saturation. Our initial experience suggests that general anesthesia may be provided using the laryngeal mask during brief laparoscopic inspection of the peritoneum.

The use of laparoscopy in the management of the nonpalpable testis.

Fifty-eight children with a nonpalpable testis have been evaluated at our institution between 1988 and 1994. Laparoscopy was performed in these children to effect a treatment plan. The children range in age from 10 months to 14 years. Thirty patients had a nonpalpable left testis, 18 had a nonpalpable right testis, and 10 had bilateral nonpalpable testes. In 28 children, a testis was visualized. Two underwent laparoscopic orchiectomy and 26 underwent either a standard single stage procedure (11), a staged open procedure (3), or a laparoscopically assisted staged procedure (12). Attenuated vessels were seen in 26 patients and inguinal exploration revealed a viable testis in 6 patients and a testis remnant, which was removed, in 20 patients. Four patients had laparoscopic blind-ending vessels. Diagnostic laparoscopy affords the surgeon not only the ability to localize the testis with virtual certainty, but also the advantage of planning a highly successful treatment program. The position of the testis intra-abdominally and the length of the spermatic vessels can be easily evaluated to decide whether a staged approach versus a single stage procedure can be performed. The use of the KTP laser has made the two staged procedure quite easy with only one Trocar site necessary. This experience has allowed us to develop and modify an algorithm for the effective management of the nonpalpable testis.

Recurrent necrotizing jejunitis in a child.

We report the case of a 5-year-old boy with segmental necrotizing jejunitis, present a review of the literature including a single previously described North American child, and give evidence to document disease recurrence. This uncommon disease must be differentiated from Crohn disease because the treatment and prognosis are different.

Continuous caudal anaesthesia with chloroprocaine as an adjunct to general anaesthesia in neonates.

PURPOSE: The authors prospectively evaluated the use of a continuous caudal epidural infusion of chloroprocaine as an adjunct to general anaesthesia during intra-abdominal surgery in neonates. CLINICAL FEATURES: The technique was used in 25 neonates ranging in age from 1 to 28 days and in weight from 2.2 to 4.9 kg. Following anaesthetic induction and tracheal intubation, an initial bolus dose of chloroprocaine 3% (1 or 1.5 ml.kg-1) was followed by a continuous infusion of 1 or 1.5 ml.kg-1.hr-1 administered through a caudal epidural catheter. No parenteral opioids were administered. The duration of the surgical procedures varied from one hour five minutes to three hours 15 min. The first three neonates received a bolus dose of 1.0 ml.kg-1 followed by an infusion of 1.0 ml.kg-1.hr-1 chloroprocaine 3%. These three neonates required an additional bolus dose followed by an increase in the infusion to 1.5 ml.kg-1.hr-1 to provide surgical anaesthesia. Adequate intraoperative anaesthesia was achieved in all 25 neonates with an infusion of 1.5 ml.kg-1.hr-1 of chloroprocaine 3%. This was evidenced by a lack of haemodynamic response to surgical manipulation. No neonate required more than 0.2% isoflurane or 70% nitrous oxide in oxygen. No episodes of haemodynamic instability (decreased blood pressure/bradycardia) related to the caudal epidural anaesthesia were noted. Twenty-three of 25 of the neonates' tracheas were extubated immediately (within 10 minutes) following the surgical procedure. CONCLUSIONS: Caudal anaesthesia with a continuous infusion of chloroprocaine can be used as an adjunct to general anaesthesia during abdominal surgery in neonates. Our initial experience suggests that the combined technique may eliminate the need for parenteral opioids and limit the intraoperative requirements for inhalational anaesthetic agents.

Prevalence, incidence, and risks for HIV-1 infection in female sex workers in Miami, Florida.

Annual cross-sectional prevalence, incidence of new infection, and risks for human immunodeficiency virus type 1 (HIV-1) infection were studied in 607 women convicted of prostitution between October 1987 and December 1990 and tested for HIV under court order. Cross-sectional prevalence was stable for 4 years (23-24% positivity in 1987-1991, p = 0.6). However, the incidence of new infections (rate of seroconversion) in 264 women tested more than once increased significantly each year from 12 per 100 person-years in 1987-1988 to 19 per 100 person-years in 1991 (p < 0.03). Seroconverters were more likely to be young black women with a prior history of syphilis or gonorrhea. A new episode of syphilis or rectal gonorrhea during the follow-up period predicted HIV seroconversion in a survival analysis model. Female sex workers are at great risk of acquiring HIV infection. Although HIV prevalence in cross-sectional samples was stable, incidence was increasing. Interpretation of prevalence trends from convenience samples, such as screening programs, may be difficult because changes in incidence may not be detected.

Analgesia after inguinal herniorrhaphy with laparoscopic inspection of the peritoneum in children. Caudal block versus ilioinguinal/iliohypogastric block.

The authors prospectively evaluated the efficacy of caudal epidural block versus local infiltration combined with ilioinguinal/iliohypogastric block for analgesia after inguinal herniorrhaphy with laparoscopic inspection of the peritoneum. During standardized anesthetic care, 24 children were randomized to Group I (caudal epidural block with 1.2 mL/kg of 0.25% bupivacaine) or to Group II (local infiltration with an ilioinguinal/iliohypogastric block). Postoperative pain scores were significantly lower at all four evaluation points in Group I than in Group II. Patients in Group I had a significantly decreased requirement for supplemental intravenous fentanyl. Intra-operative requirements for isoflurane were decreased in Group I. The expired concentration of isoflurane was 0.4 +/- 0.1 (mean +/- SEM) in Group I and 1.5 +/- 0.3 in Group II. Time to extubation was 3.8 +/- 0.5 minutes in Group I and 8.2 +/- 1.1 minutes in Group II. The time from arrival in the postanesthesia care unit until discharge home was 113 +/- 3 minutes in Group I and 152 +/- 11 minutes in Group II. Caudal epidural block was more effective than local infiltration in controlling pain after herniorrhaphy with laparoscopy in children and resulted in earlier discharge home.

Ureterosigmoidostomy: is it a viable procedure in the age of continent urinary diversion and bladder substitution?

Between January 1977 and June 1985, 63 patients requiring supravesical diversion underwent ureterosigmoidostomy with an antireflux technique. Of the patients 49 had bladder cancer and 14 had other conditions. Two patients died in the postoperative period. Postoperatively, all patients were instructed to empty the rectum frequently, and received bicarbonate and potassium supplementation. Median followup was 41 months (range 3 to 70). Renal function remained stable in 92% of the patients. Radiographic deterioration occurred in 23% of the renal units, which was severe in 7%. These results indicate that the short and intermediate followup results with ureterosigmoidostomy are comparable to those of an ileal conduit. The method has the added advantage of being a form of continent diversion. We believe that ureterosigmoidostomy remains a viable and convenient alternative in select patients with bladder cancer who are not suitable for other forms of continent diversion or bladder substitution.

Cardiorespiratory changes in children during laparoscopy.

The authors prospectively examined the cardiorespiratory changes during brief laparoscopy (less than 15 minutes) in children. Intraoperative ventilatory management included a tidal volume of 12 mL/kg, with the rate adjusted to achieve an end-tidal CO2 (PETCO2) of 30 to 35 mm Hg. The initial rate and tidal volume were not changed during the procedure. Baseline measurements of heart rate, blood pressure, peak inflating pressure (PIP), PETCO2, and oxygen saturation were recorded every minute for 5 minutes before the start of the laparoscopic procedure, and every minute during the laparoscopic procedure. Fifty-five patients were enrolled in the study (age range, 1 month to 7 years; weight range, 5.2 to 31 kg). PIP increased from the baseline value of 20 +/- 2.5 to 23 +/- 3.2 cm H2O (P < .01) during laparoscopy. The increase in PIP was 5 or more in six patients, with a maximum of 7. PETCO2 increased from the baseline value of 32 +/- 3.1 to 35 +/- 4.8 mm Hg (P < .01). The PETCO2 returned to baseline within 10 minutes after completion of the laparoscopy. No increase in ventilatory parameters was required during the brief laparoscopic procedure.

HIV-1 incidence determined retrospectively among drug users in Bangkok, Thailand.

OBJECTIVE: To measure trends in the incidence of HIV-1 infection among drug users in treatment at Thailand's largest drug detoxification unit. DESIGN: A retrospective cohort was established using computed, existing HIV-1 test results of 26,396 inpatients and outpatients admitted for 47,907 drug detoxification treatment courses from August 1987 to August 1992. METHODS: Matching of patient record numbers showed that 10,050 (38.1%) patients had been admitted two or more times during the period. From these, we selected a cohort of 7807 initially HIV-negative patients. Subsequent seroconversions among them were assumed to have occurred with uniform probability throughout the interval between the last HIV-negative and the first HIV-positive tests. RESULTS: There were 2311 (29.6%) seroconversions in the cohort. HIV-1 incidence among the 5974 (76.5%) who were injecting drug users (IDU) escalated from 20 new infections per 100 person-years (PY) of observation in 1987 to a peak of 57 per 100 PY in 1988, then gradually declining to a stable rate of about 11 per 100 PY during 1991 and 1992. Non-IDU (smokers, inhalers) constituted 683 (8.8%) of the cohort patients, and had HIV-1 incidence rates varying from 0.2 to five per 100 PY. 'Mixed' drug users, defined as individuals reporting different routes of drug administration on different admissions, composed 1150 (14.7%) of cohort patients and had an HIV-1 incidence rate between that of IDU and non-IDU. Prevalence of HIV-1 seropositivity among all IDU increased rapidly, from about 1% in early 1988 to a peak of about 40% by early 1989, and has remained stable through 1992. CONCLUSIONS: Prevention efforts must continue for IDU, since recent annual HIV-1 incidence remains high at > 10 per 100 PY. Such a high rate suggests that this group should be considered for HIV-1 vaccine efficacy trials. Stable HIV-1 prevalence can mask substantial incidence in a population with high turnover.

Transmission of Mycobacterium tuberculosis associated with air travel.

OBJECTIVE: To investigate potential transmission of Mycobacterium tuberculosis in aircraft from a crew member with tuberculosis. DESIGN: Retrospective cohort study and survey. SETTING: A large US airline carrier. PARTICIPANTS: A total of 212 crew members and 59 passengers who were exposed to a crew member with tuberculosis during a potentially infectious period (May through October 1992). Comparison volunteer sample of 247 unexposed crew members. MAIN OUTCOME MEASURES: Positive tuberculin skin test (TST) result or tuberculosis. RESULTS: Rates of positive TST results were higher among foreign-born persons in all study groups. Among US-born comparisons and contacts, rates of positive TST results did not differ between comparisons and contacts exposed from May through July (5.3% vs 5.9%, respectively). However, contacts exposed from August through October had significantly higher rates of positive TST results than did contacts exposed from May through July (30% vs 5.8%, respectively; P < .001); two had documented TST conversions between September 1992 and February 1993. The risk of infection increased with increasing hours of exposure to the index case. Four (6.7%) of 59 frequent flyers were TST-positive; all flew in October. CONCLUSIONS: Data support the conclusion that M tuberculosis was transmitted from an infectious crew member to other crew members on an aircraft. Because of the clustering of TST-positive frequent flyers in October when the index patient was most infectious, transmission of M tuberculosis to passengers cannot be excluded.