Multidisciplinary management of Hunter syndrome.

Hunter syndrome is a rare, X-linked disorder caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase. In the absence of sufficient enzyme activity, glycosaminoglycans accumulate in the lysosomes of many tissues and organs and contribute to the multisystem, progressive pathologies seen in Hunter syndrome. The nervous, cardiovascular, respiratory, and musculoskeletal systems can be involved in individuals with Hunter syndrome. Although the management of some clinical problems associated with the disease may seem routine, the management is typically complex and requires the physician to be aware of the special issues surrounding the patient with Hunter syndrome, and a multidisciplinary approach should be taken. Subspecialties such as otorhinolaryngology, neurosurgery, orthopedics, cardiology, anesthesiology, pulmonology, and neurodevelopment will all have a role in management, as will specialty areas such as physiotherapy, audiology, and others. The important management topics are discussed in this review, and the use of enzyme-replacement therapy with recombinant human iduronate-2-sulfatase as a specific treatment for Hunter syndrome is presented.

Factors associated with thorough skin self-examination for the early detection of melanoma.

BACKGROUND: Regular thorough skin self-examination (TSSE) has potential for detecting melanoma early and reducing melanoma mortality. OBJECTIVES: We sought to model factors associated with skin self-examination (SSE) and test whether efficacy and attitudes about SSE mediated these relationships. PATIENTS/METHODS: The Check-It-Out project is a randomized trial of an intervention to encourage TSSE; 2126 participants were recruited from the practices of primary care physicians. Correlates predicting baseline TSSE included demographic variables, skin cancer risk, physician advice to examine skin, and appropriate conditions for conducting SSE (availability of partner to assist with self-examination, availability of a wall mirror, and use of contact lenses/glasses). RESULTS: Those who were given physician advice, had a wall mirror, and had a partner available were more likely to perform TSSE. LIMITATIONS: We identified the factors associated with concurrent TSSE practices. Further research is needed to determine if these same factors predict future behaviour. Our findings may not be applicable in geographical areas other than our recruitment area. CONCLUSIONS: Primary care providers can recommend SSE and provide materials to increase ability to recognize skin problems. Providing instructions and aids for conducting TSSE may increase self-efficacy.

Tibial tuberosity advancement in 65 canine stifles.

The tibial tuberosity advancement (TTA) procedure was developed to treat dogs with cranial cruciate ligament deficient stifles. A retrospective, descriptive study was performed on 57 dogs that underwent unilateral or bilateral TTA. Medical records were reviewed and pre-, postoperative and follow-up radiographs were evaluated for patellar ligament-tibial plateau angle (alpha), distance of the tibial tuberosity advancement and progression of degenerative joint disease. A questionnaire was sent to all owners to obtain their assessment of the procedural outcome. Sixty-five stifles in 57 dogs received a TTA. Mean age was 5.2 +/- 2.5 years while mean weight was 39.7 +/- 11.9 kg. Eighteen breeds were represented with Labrador retrievers and mixed breeds predominating. The mean duration of lameness prior to surgery was 6.2 +/- 6.7 months, with a median lameness score of 3/4. Fifty-nine percent of cases encountered complications, the majority of which were minor. Major post-operative complications were uncommon but consisted of implant failure, tibial crest displacement and medial meniscal tears. The mean radiographic preoperative angle alpha was 100 degrees, while the postoperative was 95.5 degrees. Mean osteoarthrosis scores were significantly different between preoperative and follow-up radiographs with 67% of cases showing radiographic progression. Seventy percent of owners responded to the survey with overall outcome considered good to excellent in 90%. Activity level was improved in 90% of responses. TTA subjectively appears to be a useful alternative in the management of cranial cruciate ligament disease. Few severe complications were encountered. Good clinical outcome and owner satisfaction was reported with the procedure in this set of cases.

Enhancing skin self-examination with imaging: evaluation of a mole-mapping program.

BACKGROUND: To enhance early detection of melanoma with thorough skin self-examination, we have enrolled patients in a mole-mapping program that uses digital imaging of the skin. OBJECTIVE: The goal of our study was to evaluate the impact of participation in the mole-mapping program on performance of thorough skin self-examination. METHODS: The study was carried out by telephone survey of 64 program participants, using self-report to assess impact. RESULTS: Participants were generally satisfied and found the program useful and effective; 97% would recommend it. Almost half (45%) of those who were not performing thorough skin self-examination before participation reported performing it after receiving their images. After participation, a partner such as a spouse or friend was more commonly assisting in these examinations. We also noted a correlation (of borderline statistical significance) between sun protection and performance of self-examination, and differences among different definitions of thorough skin self-examination. CONCLUSION: Interventions centered around imaging have the potential to substantially enhance and encourage the performance of thorough skin self-examination for the early detection of melanoma.

Effects of epidural anesthesia on microcirculatory blood flow in free medial saphenous fasciocutaneous flaps in dogs.

OBJECTIVE: To assess the effects of epidural anesthesia using lidocaine on microcirculatory blood flow, volume, and velocity in free fasciocutaneous flaps in dogs. Study Design-In vivo experimental investigation. Animal Population-Ten adult dogs weighing 20 to 25 kg. METHODS: A medial saphenous fasciocutaneous free flap was removed and an orthotopic transfer was performed by anastomosing the primary flap vessels back to the medial saphenous vessels. Blood flow (mL(LD)/min/100 g), volume (%volume or tissue hematocrit) and velocity (mm/s) in the flap were recorded throughout the procedure. After epidural anesthesia, blood flow, volume, and velocity values were again recorded. RESULTS: Microcirculatory blood flow, volume, and velocity, as measured by a laser-Doppler flowmeter, failed to reveal any significant changes over time. Immediately after epidural anesthesia, mean arterial pressure was significantly reduced and remained depressed throughout the experimental procedure. CONCLUSIONS: Epidural anesthesia combined with general anesthesia does not improve microcirculatory flow in free flaps in the pelvic limbs of dogs. No significant change in blood flow to the medial saphenous fasciocutaneous free flap occurred after division and anastomosis of the vascular pedicle. CLINICAL RELEVANCE: We recommend that epidural anesthesia with 2% lidocaine be used with caution in dogs undergoing microvascular free-flap transfer.

The aspiration-irrigation maneuver.

OBJECTIVES/HYPOTHESIS: To compare cultures obtained from the aspiration-irrigation maneuver (AIM) with other reports and compare diagnostic and therapeutic value after AIM versus the Proetz maneuver and needle aspiration-irrigation. STUDY DESIGN: Patients with radiographic evidence (mucous membrane thickness greater than 6 mm, air-fluid levels, or complete opacification) and symptoms (nocturnal cough, fever, postnasal drainage [PND], otitis, mucopurulent discharge from the nose) of sinus disease who were referred from pediatrician and/or family physician and who otherwise would be candidates for surgery were selected to receive treatment with AIM. The study was divided into three separate groups (54 patients who were age 8 years and younger, 54 patients who were age 9 years and older, and 32 adult patients who were treated with both needle aspiration and AIM. METHODS: Using Bernoulli's principle and the Venturi effect, saline and a vacuum apparatus were used to capture the contents of the sinuses for culture, and results were compared with results of needle aspirate cultures. RESULTS: Children's cultures from group 1 compared favorably with the literature (Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae or a combination of these); cultures in patients age 9 years and older revealed a greater variety of bacteria, depending on chronicity of infection, and a high incidence of Staphylococcus aureus (beta-lactamase positive). There was a 66% correlation of AIM with needle aspiration. CONCLUSIONS: AIM was found to be a safe, simple, painless, and inexpensive adjunct to the diagnosis and treatment of sinus disease.

Thorough skin examination for the early detection of melanoma.

BACKGROUND: Melanoma is a major public health problem for which early detection may reduce mortality. Since melanoma is generally asymptomatic, this requires skin examination. We sought to evaluate the extent to which the general public has their skin examined by themselves, their partners, or health care providers and the frequency of these examinations. METHODS: Random-digit-dial survey of adult Rhode Islanders. RESULTS: Only 9% performed a thorough skin examination (TSE) at least once every few months, although over half of the sample reported conducting skin self-examination "deliberately and systematically." Participants were more likely to perform TSE if they were women and if their health care provider had asked them to examine their skin. Most participants reported that their health care provider never or rarely looked at the areas of their skin in which melanoma is most likely to arise. CONCLUSIONS: The reported frequency of skin self-examination depends critically on the manner of inquiry. TSE by self or a partner is uncommon, and health care providers do not routinely examine the areas of the skin on which melanomas commonly arise.

Inhibition of Na+,K+-ATPase by the cardenolide 6'-O-(E-4-hydroxycinnamoyl) desglucouzarin.

Among the major cardenolides from the milkweed Asclepias asperula, 6'-O-(E-4-hydroxycinnamoyl) desglucouzarin has not been characterized biochemically. In this study, its binding affinity for a physiological receptor, porcine kidney Na+,K+-ATPase, was found to be lower than the other cardenolides in this plant. The order of affinities from highest to lowest was: uzarigenin (Kd = 1.05 microM) = desglucouzarin (Kd = 0.98 microM) > uzarin (Kd = 4.0 microM) > 6'-O-(E-4-hydroxycinnamoyl) desglucouzarin (Kd = 16 microM). The chemical attachment of the 4-hydroxycinnamoyl group to the 6'-carbon of desglucouzarin significantly inhibits binding. This agrees with predictions that a 5'-methyl group on cardenolides fits the receptor site optimally for the porcine kidney enzyme. The 4-hydroxycinnamic ester was also found to be fluorescent.

The Proteus syndrome: CNS manifestations.

Proteus syndrome is a complex hamartomatous disorder characterized by multiple, diverse, somatic manifestations. We present a case in which severe, evolving CNS abnormalities were also exhibited. Imaging findings at presentation included hemimegalencephaly, subependymal calcified nodules, and periventricular cysts. Subsequently, dural sinus thrombosis developed. Eight previously reported patients may also have had hemimegalencephaly. When neuroimaging studies show hemimegalencephaly in a child with pigmented skin lesions, Proteus syndrome should be considered in the differential diagnosis.

In vitro metabolism of ceftiofur in bovine tissues.

The metabolism of ceftiofur in bovine kidney, liver, muscle and lung, and the effects of the presence of cystine and glutathione in the media were evaluated using S-9 and microsomal tissue fractions. Conversion of ceftiofur to desfuroylceftiofur (DFC) was catalyzed by an esterase which was most active in kidney, followed by liver. It was not very active in muscle and lung. After DFC was liberated, it rapidly bound primarily to tissue proteins (> 56%), and was also conjugated to cysteine and glutathione. Production of DFC-cysteine by disulfide exchange of DFC with cystine and production of DFC-glutathione by conjugation of DFC to glutathione occurred in buffer if glutathione and cystine were present in the medium. These conjugations were also observed in incubations with tissue fractions, indicating that they were not inhibited by the tissues endogenous molecules. In addition, the metabolism of DFC-glutathione to DFC-cysteine was observed when tissue proteins were present. The metabolism of DFC-glutathione to DFC-cysteine was faster in kidney than in liver. Metabolites devoid of an intact beta-lactam ring were not observed in these in vitro studies.

Intra-articular hip arthrodesis without subtrochanteric osteotomy in adolescents: technique and short-term follow-up.

Twenty-five patients, 11 to 19 years in age, were treated with hip arthrodesis for an incapacitating painful and stiff hip. Clinical diagnoses included avascular necrosis (AVN) associated with slipped capital femoral epiphysis (SCFE) (7 patients), posttraumatic AVN (6), septic arthritis (4), complication of treatment of developmental dysplasia of the hip (DDH) (4), pathologic fracture of femoral neck through bone cyst with resulting AVN (2), Perthes disease (1), and idiopathic chondrolysis (1). Preoperative motion was minimal or absent in 13 patients, limited in 12, and very painful in 23 patients. A two-incision surgical approach was utilized, providing for an intra-articular fusion technique and internal fixation with precise positioning. The surgical technique described avoids any dissection of the hip abductor musculature or a deforming osteotomy of the proximal femur. Twelve complications occurred in 10 patients, 9 of which required additional operative treatment. At an average postoperative follow-up of 6 years, 10 months, the overall activity level was greatly increased over the preoperative activity level secondary to the relief of pain. Hip arthrodesis is the acceptable salvage procedure for the otherwise healthy, active adolescent or young adult with unilateral hip disease characterized by incapacitating pain and/or an unacceptable fixed position.

Latent transition analysis for longitudinal data.

Assessing outcome is a critical problem for the study of addictive behaviors. Traditional approaches often lack power and sensitivity. Latent Transition Analysis is an alternative procedure that is applicable to categorical latent variable models such as stage models. The method involves four different types of parameters, each of which may be relevant to different research questions. Two examples that employ the Stages of Change construct are used to illustrate the method. In the first example, three different models of longitudinal change are compared. In the second example, the effects of an expert system intervention for smoking is compared to a control condition. The method permits the investigation of a series of specific comparisons: (1) the effectiveness of the intervention for individuals in different stages can be assessed; (2) the effectiveness of the intervention can be evaluated for different time intervals; and (3) the effects of intervention on both progression through the stages and regression through the stages or relapse can be assessed. Other potential applications of the method are also discussed.

Mutational analysis of HIV-1 gp160-mediated receptor interference: intracellular complex formation.

Formation of CD4-gp160 intracellular complexes represents an important mechanism leading to the induction of receptor interference. Previous studies have demonstrated that cells coexpressing gp160 and CD4 formed complexes of CD4 and gp160 which became blocked within the endoplasmic reticulum (ER), preventing CD4 from reaching the cell surface. In this report we have investigated the domains and residues of CD4 and gp160 involved in intracellular interaction. Accordingly, we have introduced mutations in both CD4 and gp160 at sites previously shown to disrupt CD4-gp120 interactions at the cell surface. Using a T7-vaccinia virus transient expression system, we expressed these gp160 and CD4 mutants in HeLa cells and analyzed their effects on intracellular complex formation and CD4 surface modulation. We observed that a number of gp160 mutants which failed to interact with CD4 at the cell surface also failed to bind and trap CD4 within the ER as expected. However, mutations at a critical residue, W427, did not abrogate intracellular CD4 binding. These gp160 mutants continued to interact with intracellular CD4 and inhibit CD4 transport to the cell surface, although gp120 produced from these mutants did not bind CD4 at the cell surface as expected. A number CD4 mutants also continued to form intracellular complexes with gp160, resulting in the loss of CD4 surface expression. Again, these CD4 mutants did not bind to gp120 at the cell surface, consistent with earlier reports. These results demonstrate that intracellular interactions between gp160 and CD4 in the ER may utilize different contact sites compared to those used during CD4 and gp120 binding at the cell surface. The data provide further evidence that the environment in which CD4 and the HIV-1 envelope glycoprotein interact can have a significant effect on their interaction.

Membrane anchorage of gp160 is necessary and sufficient to prevent CD4 transport to the cell surface.

The HIV envelope glycoprotein gp160 plays a major role in the posttranslational down-regulation of its receptor, CD4. In this report we have analyzed the requirements of both CD4 and gp160 involved in transport block of the gp160-CD4 complex causing the down-regulation of cell surface CD4. Using a transient expression system we observed that both soluble and membrane-bound CD4 were equally blocked by the wild-type gp160, indicating that neither the transmembrane domain nor the cytoplasmic tail of CD4 affected its interaction with gp160 or exocytic transport block of the complex. Similarly, deletions of the gp160 cytoplasmic domain or mutation in the transmembrane domain had little effect on its transport, or its ability to down-regulate CD4 surface expression. Furthermore, substitution of the gp160 transmembrane domain and cytoplasmic tail with that of the influenza virus hemagglutinin or with a glycophosphatidylinositol moiety did not affect its ability to bind CD4 and block its transport. However, soluble envelope glycoprotein constructs (either gp120 or soluble gp160) were unable to block CD4 transport to the cell surface despite their binding to CD4 within the ER. Taken together these results demonstrate that neither the gp160 cytoplasmic tail nor the specific sequences of the transmembrane region of gp160 nor the membrane anchoring of CD4 were involved in ER retention of the CD4-gp160 complex and that anchoring of gp160 to the ER membrane was responsible for gp160-mediated cell surface down-regulation of CD4.

Latent transition analysis to the stages of change for smoking cessation.

A key construct of the Transtheoretical Model of Behavior Change is the stage of change (Precontemplation, Contemplation, Preparation, Action, and Maintenance) (Prochaska & DiClemente, 1983, 1986). This study applies Latent Transition Analysis (LTA; Collins & Wugalter, 1992; Collins, Wugalter, & Rousculp, 1991) to movement through the stages of change for smoking cessation. LTA is an alternative method of assessing categorical outcome that is sensitive to change, diagnostic, and allows for the comparison of alternative models of change. The sample consisted of 545 reactively recruited smokers and former smokers who were assessed five times over a two year period. LTA was used to compare three specified models. The model that fit the data best indicates that in a six month time frame both progression and regression among the stages takes place as well as two stage progression. Examination of the probability of movement among the stages revealed three findings consistent with the Transtheoretical Model. First, movement through the stages is not always linear. Second, the probability of forward movement was greater than backward movement. Third, the probability of moving to adjacent stages was greater than the probability of two stage progression.

Controlled cross circulation in dogs: effects on donor hemodynamics.

Controlled cross circulation (CCC) was performed in six pairs of dogs for 45 minutes with aortic cross clamping and cardioplegia. Data were collected in donor dogs at 10 minute intervals three times before, three times during, and three times after CCC and included arterial blood pressure, pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP), cardiac index (CI), heart rate (HR), blood gas analysis, temperature, maximum rate of rise of left ventricular pressure dP/dt max/End diastolic volume (EDV), blood volume (BV), complete blood count (CBC) and activated clotting times (ACT). Pulse pressure (PP), systemic vascular resistance (SVR), oxygen delivery (DO2), and left ventricular cardiac work (LVCW) were calculated. Arterial blood pressure, CVP, blood gas analysis, temperature, BV, CBC, and ACT were measured in recipient dogs. During CCC, donor hemodynamic changes resembled those observed in models of acute onset arteriovenous fistulas. Insidious BV shifts can occur despite the use of occlusive roller pumps. After CCC, donor hemodynamics resembled acute blood loss, characterized by decreases in mean arterial pressure (MAP), CVP, PCWP, and CI, and increases in SVR and dP/dt max/EDV. These changes were probably caused by pump imbalance and BV shift to the recipient dog.

Extrahepatic biliary tract obstruction: a retrospective study of 45 cases (1983-1993).

The medical records of 41 dogs and four cats with either surgical or postmortem confirmation of extrahepatic biliary tract obstruction were reviewed. Clinical signs of icterus, vomiting, anorexia, or a combination of these signs were exhibited by 100% of cases. Elevated serum bilirubin was documented in 37 of 41 dogs and two of four cats (86.6%). The predominant, underlying, pathological process was extraluminal obstruction of the biliary tract due to pancreatitis (19 of 45 cases; 42.2%) or neoplasia (11 of 45 cases; 24.4%). Biliary tract surgery was performed in 29 cases, of which 12 (41.3%) recovered. Animals diagnosed with extrahepatic biliary tract obstruction had a relatively good long-term prognosis, provided they were not compromised substantially due to severe necrotizing pancreatitis or neoplasia.

Post-traumatic irreducible nondissociative carpal instability: a case report.

We present a case that is unusual in two respects. To our knowledge, it is the first clearly documented instance in the literature of a post-traumatic, irreducible nondissociative volar intercalated carpal instability to result from a known wrist flexion force and a known dorsal capsuloligamentous tear. Second, the same wrist revealed a coalition at both intraosseous levels of the proximal carpal row: a synfibrosis at the scapholunate joint and a synostosis at the lunotriquetral joint. Treatment by open removal of an interposed capsuloligamentous flap from the radiocarpal joint, followed by alignment of carpal elements, temporary internal fixation, and repair of the damaged dorsal capsule and ligaments gave an excellent result.

Metabolism of mouse growth hormone-releasing factor, mGRF(1-42)OH, and selected analogs from the bovine GRF series in mouse and bovine plasma in vitro.

The presence of Val2 in mGRF(1-42)OH is unique and, as shown in this study, renders this GRF resistant to plasma DPP-IV, the main enzyme responsible for rapid hydrolysis and inactivation of Ala2-containing GRFs from other species via cleavages between Ala2-Asp3. The presence of DPP-IV activity in mouse serum, and mouse and bovine plasma has been demonstrated with Gly-Pro-p-nitroanilide and/or with two DPP-IV-sensitive bGRF analogs, [Leu27]bGRF(1-29)NH2 and [Ala15,Leu27]bGRF(1-29)NH2, which were effectively converted to their respective (3-29) fragments. During incubations of mGRF(1-42)OH in mouse serum or plasma, as well as in bovine plasma in vitro, no major fragments were detectable, except for small amounts of metabolites with HPLC retention times corresponding to those of mGRF(12-42)OH and mGRF(21-42)OH, indicative of possible trypsin-like cleavages between Arg11-Lys12 and Arg20-Lys21. Both mGRF(1-42)OH (t1/2 52-78.5 min) and [Val2,Ala15,Leu27]-bGRF(1-29)NH2 (t1/2 78.5 min) disappeared 5 to 7 times faster in mouse than in bovine plasma, indicating much higher activity of various degrading enzymes in mouse plasma. In summary, our data provide evidence that mGRF(1-42)OH, despite its resistance to plasma DPP-IV, is degraded relatively fast in mouse plasma or serum because of trypsin-like and other, non-DPP-IV-related, proteolytic cleavages.

Endoscopic diagnosis of chronic hypertrophic pyloric gastropathy in dogs.

The endoscopic appearance of chronic hypertrophic pyloric gastropathy (CHPG) in five dogs is described. Several patterns of enlarged mucosal folds that surrounded and obstructed the pyloric canal were observed. Initially, endoscopically obtained biopsy samples of mucosa were judged to be histologically normal. Diagnosis of CHPG was confirmed and relief of pyloric obstruction accomplished at exploratory laparotomy (in four dogs). Retrospective evaluation of pyloric tissue samples, obtained during endoscopy, identified subtle histological characteristics of CHPG. Gastric and duodenal neoplasia or antral polyps can mimic the endoscopic appearance of CHPG but can be differentiated based on their endoscopic and histological appearance. These cases show that endoscopic examination is a valuable procedure for the diagnosis of CHPG in dogs that chronically vomit.