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Biomedical subjects

J J Murray

Publications and source records attributed to J J Murray.

At least 19 recordsLinked to original sources
PubMed1999

Laparoscopic colectomy: indications for conversion to laparotomy.

HYPOTHESIS: Although experience with laparoscopic colectomy continues to accumulate, criteria for patient selection for the procedure have yet to be developed. We propose that review of indications for conversion to laparotomy during laparoscopic colectomy should define some of the current technical limitations of the procedure. This information may facilitate development of selection criteria for laparoscopic colon and rectal surgery. DESIGN: Single-institution retrospective medical records review. SETTING: Tertiary referral center. PATIENTS: Two hundred patients who underwent laparoscopic colon surgery, in 47 (23.5%) of whom the procedure was converted to laparotomy. INTERVENTIONS: A registry of 200 patients who have undergone laparoscopic colon surgery was analyzed. Medical records of 47 patients whose procedure was converted were reviewed to assess indications for conversion and identify factors contributing to the need for conversion. RESULTS: Between July 1, 1991, and September 30, 1998, 200 laparoscopic colon procedures were performed: 78 ascending colectomies, 74 descending or sigmoid colectomies, 14 diverting stomas, and 34 "other procedures." The 200 patients were divided into 4 cohorts of 50 consecutive patients to analyze changes with time. The conversion rate was statistically greater in the first quarter (18 patients [36.0%]) than in subsequent quarters (16.0%; P <.05). The rate of conversion to laparotomy for segmental resection of the ascending and descending colon (31/153 [20.3%]) has been equivalent and less than the conversion rate for other procedures (16/33 [48.5%]; P <.05). The distribution of patients by operative indication has been fairly constant. The indication for operation has not influenced the need for conversion. The indications for conversion were technical problems in 15 patients (hypercarbia, unclear anatomy, and stapler misfire), laparoscopic complications in 9 patients (bleeding, cystotomy, and enterotomy), and problems that exceeded the limits of laparoscopic dissection in 23 patients (phlegmon, adhesions, obesity, and adjacent organ involvement by cancer). CONCLUSIONS: Our conversion rate has decreased during our experience, and currently the need for conversion to laparotomy is most frequently caused by situations such as excessive tumor bulk, adhesions, and diverticular phlegmon that exceed the technical limitations of laparoscopic dissection. Colorectal reanastomosis following a Hartmann resection and procedures involving resection of the distal rectum are unlikely to be successfully completed. Although obesity accentuates the technical limitations of laparoscopic dissection, it is an infrequent cause for conversion to laparotomy.

Colectomy↗
PubMed1998

Functional results after perineal complications of ileal pouch-anal anastomosis.

PURPOSE: This study investigated the functional significance of perineal complications after ileal pouch-anal anastomosis. METHODS: Review of a prospective registry of 628 patients was undertaken. Bowel function was assessed by detailed functional questionnaire. Statistical analyses were performed using chi-squared and Fisher's exact probability tests. RESULTS: Of 628 patients, 153 (24.4 percent) had 171 perineal complications. The 277 control patients had no complications. Complications included 66 (10.5 percent) anastomotic strictures, 28 (4.5 percent) anastomotic separations, 36 (5.7 percent) pouch fistulas, 41 (6.5 percent) episodes of pelvic sepsis, and 18 (2.9 percent) patients with multiple complications. After these complications were addressed, the pouch failure rate was low (10 percent); in 90 percent of patients, the pouch could be salvaged. Most pouch failures were the result of pouch fistulas, and most occurred in patients ultimately diagnosed with Crohn's disease. Functional results after cure of these perineal complications revealed no significant functional differences between control patients and those cured of anastomotic separations, anastomotic strictures, and pouch fistulas. Only a few minor differences were demonstrated in function after an episode of pelvic sepsis. The major deterioration in function occurred after treatment for multiple perineal complications. CONCLUSIONS: An appreciable number of perineal complications occur after ileal pouch-anal anastomosis. Pouch-perineal fistulas are associated with the highest pouch failure rate. The majority of these fistulas occur in patients ultimately diagnosed with Crohn's disease or indeterminate colitis. Although there is no substitute for good technique and sound clinical judgment in the success of ileal pouch-anal anastomosis, if perineal complications are successfully treated, functional outcome is equivalent to that in patients without perineal complications.

Anastomosis, Surgical↗
PubMed1998

Fatigue rate index as a new measurement of external sphincter function.

PURPOSE: Assessment of sustained voluntary contraction of the external sphincter is helpful in evaluating the patient who has a defecation disorder on presentation. A new index of external sphincter function is described. METHOD: A prospective registry of patients referred for computerized anal manometry using standard protocols was reviewed. Patients were grouped by primary symptoms; those with overlapping complaints were excluded. The rate of fatigue, defined as the change in stationary squeeze over a 40-second period of voluntary contraction, was calculated by linear regression analysis. Fatigue rate index, a calculated measure of time necessary for the external sphincter to become completely fatigued, was determined to permit comparison of external sphincter fatigue in patients with different complaints. RESULTS: Twenty-six healthy volunteers (15 women; mean age, 45 years), 33 patients with a primary complaint of anal seepage (13 women; mean age, 53 years), 75 patients with gross incontinence (61 women; mean age, 53 years), and 49 patients with severe constipation (41 women; mean age, 45 years) were evaluated. Mean resting and squeeze pressures were 55 mmHg and 107 mmHg for volunteers, 37 mmHg and 97 mmHg for patients with seepage, 30 mmHg and 49 mmHg for incontinent patients, and 56 mmHg and 93 mmHg for constipated patients. Pudendal neuropathy, as evidenced by a prolonged pudendal nerve terminal motor latency (> 2.4 ms), was identified in 13 percent of volunteers, 32 percent of patients with seepage, 54 percent of incontinent patients, and 38 percent of constipated patients. Mean fatigue rate index was 3.3 minutes for volunteers, 2.3 minutes for seepage patients, 1.5 minutes for incontinent patients, and 2.8 minutes for constipated patients. Compared with volunteers and patients with seepage, the incontinent patients had a significantly shorter fatigue rate index (P < 0.05; Student's t-test), which was independent of the variations in resting pressure (P < 0.05; two-way analysis of variance). CONCLUSION: The external anal sphincter is normally subject to fatigue. Patients with worsening degrees of incontinence have a predictably lower fatigue rate index. Fatigue rate index is a simple measure of external sphincter integrity, which may be used in assessment of sphincter function and future treatment protocols.

Anal Canal↗
PubMed1998

Controversies in Crohn's disease.

Despite recent advances in the medical therapy of Crohn's disease, surgery continues to play a central role in the treatment of the disease. The strategy for surgical management of Crohn's disease continues to evolve. This chapter reviews many of the controversies surrounding surgical palliation of complications of Crohn's disease. Included is a discussion of indications for strictureplasty in treatment of intractable intestinal obstruction. Factors influencing long-term outcome with sphincter-saving resection in the treatment of Crohn's colitis are reviewed. Experience with definitive treatment of anal Crohn's disease and repair of rectovaginal fistulas is examined. Finally, recent experience supporting ileocolic resection when acute Crohn's ileitis is identified during laparotomy for right lower quadrant pain is critically evaluated. These controversial aspects of the surgical treatment of Crohn's disease reflect an improved understanding of the natural history of the disease as well as refinement in surgical techniques and better definition of criteria for surgical intervention.

Colitis↗
PubMed1998

Whither paediatric dentistry?

The objective of the British Society of Paediatric Dentistry is to promote the oral health of children. This objective is discussed from four different aspects. First, it is necessary to quantify the dental needs of children and to appreciate how these needs have changed over the last 20 years. Using information from national dental surveys, changes between 1973 and 1993 in the prevalence of dental caries, periodontal disease, accidental damage to anterior teeth and occlusal problems, are summarized. Secondly, the development in consultant posts and the specialty of paediatric dentistry are discussed. The impact of research gradings given to Dental Schools in Britain is the third aspect to be considered and its possible effect on research topics directly relevant to improving the oral health of children. Lastly the effect of public perceptions on our specialty must be considered. Although paediatric dentists may not hit the headlines, the public must be convinced that good oral health is the birthright of every child and that we are dedicated to preventing and treating oral disease in children.

Adolescent↗
PubMed1997

Phosphatase activity regulates superoxide anion generation and intracellular signaling in human neutrophils.

Phosphorylation of components of the neutrophil NADPH oxidase plays a critical role in activation and maintenance of superoxide anion (O2-) generation. To investigate the role of dephosphorylation by phosphatases in regulating O2- production, human neutrophils were treated with calyculin A, a potent inhibitor of protein phosphatases 1 and 2A, prior to stimulation. Calyculin A alone did not stimulate O2- production. However, neutrophils exposed to 50 nM calyculin A and the chemotactic peptide formyl-met-leu-phe (FMLP, 100 nM) displayed markedly enhanced O2- production in comparison to cells stimulated with FMLP alone (28.63 +/- 7.00 versus 8.69 +/- 3.69 nmol O2-/1.5 x 10(6) neutrophils/5 min, respectively, n = 18, p < 0.001), with an increased duration of O2- production. In contrast, phosphatase-inhibition decreased oxidative responsiveness to phorbol myristate acetate (PMA, > or = 16 nM). We next examined the effect of calyculin A on products of the phosphatidylcholine-specific phospholipase D (PLD) pathway by assaying the mass levels of phosphatidic acid (PA), choline and diacylglycerol (DAG). Calyculin A increased both PA and choline production to 224 +/- 28% and 315 +/- 61% of FMLP-stimulated controls, respectively (p < 0.01, n = 7) without significantly increasing DAG. Also, membrane protein kinase C activity increased more than 10-fold in FMLP-stimulated cells exposed to calyculin A but decreased in cells stimulated with PMA following calyculin A pre-treatment. These results suggest that phosphatases exert variable and stimulus-dependent effects on pathways leading to O2- production. Further, it appears that phospholipase D activity and PA generation represent important steps in the pathway for NADPH activation triggered by FMLP.

Adult↗
PubMed1997

Naturally occurring mutations in the human 5-lipoxygenase gene promoter that modify transcription factor binding and reporter gene transcription.

Five lipoxygenase (5-LO) is the first committed enzyme in the metabolic pathway leading to the synthesis of the leukotrienes. We examined genomic DNA isolated from 25 normal subjects and 31 patients with asthma (6 of whom had aspirin-sensitive asthma) for mutations in the known transcription factor binding regions and the protein encoding region of the 5-LO gene. A family of mutations in the G + C-rich transcription factor binding region was identified consisting of the deletion of one, deletion of two, or addition of one zinc finger (Sp1/Egr-1) binding sites in the region 176 to 147 bp upstream from the ATG translation start site where there are normally 5 Sp1 binding motifs in tandem. Reporter gene activity directed by any of the mutant forms of the transcription factor binding region was significantly (P < 0.05) less effective than the activity driven by the wild type transcription factor binding region. Electrophoretic mobility shift assays (EMSAs) demonstrated the capacity of wild type and mutant transcription factor binding regions to bind nuclear extracts from human umbilical vein endothelial cells (HUVECs). These data are consistent with a family of mutations in the 5-LO gene that can modify reporter gene transcription possibly through differences in Sp1 and Egr-1 transactivation.

Alleles↗
PubMed1997

Cyclosporine reduces development of obliterative bronchiolitis in a murine heterotopic airway model.

Obliterative bronchiolitis (OB), an important threat to the long-term survival of lung transplant recipients, is characterized histologically by fibroproliferation within small airways. The pathogenesis of OB is thought to involve chronic allograft rejection, and therapy frequently includes augmentation of immunosuppression. We have developed a model that reproduces the pathologic lesion of OB and allows study of interventions designed to limit airway fibrosis. In this model, heterotopic transplantation of murine airways into immune-mismatched recipients results in epithelial abnormalities and fibroproliferation in the airway lumen, changes not seen in heterotopic isografts. Cyclosporine (CsA) inhibits activation and proliferation of T lymphocytes and is commonly administered after lung transplantation. We hypothesized that use of CsA in our model system would reduce fibroproliferation in tracheal allografts. To test this hypothesis, murine tracheas were transplanted heterotopically into allo matched and allomismatched recipients, and then treated with varying doses (5, 10, 15, or 25 mg/kg i.p. q.d.) of CsA. Controls included allografts and isografts not treated with CsA. After 30 days, tracheas were harvested and examined histologically. CsA markedly reduced the development of fibroproliferation in allografts (19% in treated allografts versus 90% in untreated allografts, P<0.0001), but did not reduce inflammation or airway epithelial cell injury. High-dose (25 mg/kg/day) CsA was more effective than lower doses in reducing fibroproliferation (0% in high dose versus 29% in low dose, P=0.04). These findings demonstrate that CsA significantly reduces development of the pathologic lesion of OB, and supports the role of alloimmunity in the pathogenesis of this disease.

Animals↗
PubMed1997

Evolutionary changes in the pathologic diagnosis after the ileoanal pouch procedure.

PURPOSE: Inadequate initial differentiation between ulcerative colitis and Crohn's disease may lead to a diagnosis of indeterminate colitis. Construction of an ileoanal pouch in these patients may result in significant morbidity and pouch failure when the ultimate diagnosis is Crohn's disease. METHOD: We prospectively studied 543 patients with idiopathic inflammatory bowel disease to determine whether a patient's pathologic diagnosis changed with time and how it affected outcome. RESULTS: Preoperative diagnosis was ulcerative colitis in 499 patients, indeterminate colitis in 42 patients, and Crohn's disease in 2 patients. Prior colectomy was performed in 58 percent of patients with ulcerative colitis and in all patients with indeterminate colitis and Crohn's disease. Postoperatively, the diagnosis changed in 20 patients with ulcerative colitis (13 to indeterminate colitis, 7 to Crohn's disease). Another two patients with indeterminate colitis showed evidence of Crohn's disease in the resected rectal specimen. As patients were followed up, an additional 13 patients were found to have Crohn's disease (5 indeterminate colitis, 8 ulcerative colitis). With the current diagnosis, perineal complications and pouch failure occurred, respectively, in 23 and in 2 percent of patients with ulcerative colitis, in 44 and in 12 percent of patients with indeterminate colitis, and in 63 and in 37 percent of patients with Crohn's disease. Pathologic diagnosis was altered in 35 patients (6 percent) overall, with a 12-fold increase in the diagnosis of Crohn's disease. Only 3 percent of patients with ulcerative colitis compared with 13 percent of patients with indeterminate colitis had a change in diagnosis to Crohn's disease (P = 0.006; Fisher's exact test). CONCLUSION: Pouch-related complications, eventual pouch failure, and discovery of underlying Crohn's disease occurred in a significant number of patients with a diagnosis of indeterminate colitis. Until more accurate diagnostic differentiation is available, caution is advised in recommending the ileoanal pouch procedure to patients with indeterminate colitis.

Adolescent↗
PubMed1997

Pudendal neuropathy is the only parameter differentiating leakage from solid stool incontinence.

PURPOSE: Fecal incontinence may occur in several forms. Although some patients are grossly incontinent, other patients experience only leakage. In patients with gross incontinence, severity can range from the mildest forms (limited to loss of control of flatus) to the most severe forms (involving loss of solid stool). This study was undertaken to determine which physiologic parameters differentiate female patients with incontinence of solid stool from patients with control of formed stool and incontinence limited to seepage. METHODS: Thirty-eight consecutive female patients with a primary complaint of seepage or solid stool incontinence were evaluated using water perfusion manometry, balloon inflation assessment of rectal sensitivity, and pudendal nerve terminal motor latency. A prospectively maintained database was used for collection of data. The findings in the two patient groups were compared with patients in a group of normal control individuals. Ages of the women in the three groups were similar. RESULTS: Both groups of patients demonstrated statistically significant (P < 0.05) decreases in rest and squeeze sphincter lengths, pressures, and pressure volumes compared with normal volunteers. The patients also had significantly more asymmetric high-pressure zones and hypersensitive rectums. No significant difference between the two groups of incontinent patients could be identified using any of these parameters. Significant differences between the groups were found in pudendal nerve function. The distal rectoanal excitatory reflex was abnormal in 58.1 percent of grossly incontinent women compared with 28.6 percent of patients with leakage (P < 0.05). The majority of patients with leakage alone (65 percent) had normal pudendal nerve terminal motor latency, whereas only 22.6 percent of women with gross fecal incontinence had normal pudendal nerve terminal motor latency bilaterally (P = 0.01). CONCLUSIONS: Normal bilateral pudendal nerve function can partially compensate for abnormal sphincter symmetry and function, permitting women with grossly abnormal parameters to maintain control of bowel movements. It remains to be seen whether, with advancing age, patients with leakage will have development of slowed pudendal nerve conduction and, if so, whether their condition will progress to gross incontinence.

Anal Canal↗
PubMed1997

Afferent limb obstruction complicating ileal pouch-anal anastomosis.

PURPOSE: Small-bowel obstruction is a common complication after ileal pouch-anal anastomosis (IPAA). Acute angulation of the afferent limb at the pouch inlet is the cause of obstruction in a subset of patients requiring laparotomy. METHODS: Patients were identified from the Lahey Clinic ileoanal pouch registry, a prospective computerized database of all patients who have undergone IPAA since 1980. Records of patients who were identified as having afferent limb obstruction as a cause of bowel obstruction after IPAA were reviewed. RESULTS: A total of 567 patients had undergone total proctocolectomy and ileoanal J-pouch at time of the study. Of 122 patients with one or more episodes of obstruction after IPAA, 48 required operative intervention. Afferent limb obstruction was identified as the cause of obstruction in six patients (12 percent). The most common presentation was recurrent partial obstruction (4 of 6 patients). Contrast small-bowel series and enemas were suggestive of obstruction in four of six patients, the most consistent radiographic finding being small-bowel dilation to the level of the pouch inlet. All patients underwent laparotomy for unresolved obstruction. Intraoperatively, the afferent limb was found to be adherent posterior to the pouch, causing acute angulation at the pouch inlet. Rather than risk injury to the pouch or its mesentery, the obstruction was bypassed by side-to-side anastomosis of the afferent limb to the pouch (enteroenterostomy) in five of six patients. One patient underwent ileostomy only because of technical considerations. Two patients required re-exploration and pexy of the afferent limb to the pelvic sidewall (pouchopexy) to relieve recurrent afferent limb obstruction. CONCLUSION: Afferent limb obstruction should be suspected in patients with recurrent obstruction after IPAA. Bypass of the obstructed segment from distal ileum to the pouch is safe and effective treatment. Because of the risk of recurrent afferent limb angulation, concurrent pouchopexy should be considered.

Adult↗
PubMed1997

"Ideal" length of stay after colectomy: whose ideal?

PURPOSE: In response to external pressure to achieve an idealized length of stay after colon resection, a study was designed to define perioperative factors that significantly impact average length of stay (ALOS). METHODS: We retrospectively reviewed the records of 226 patients undergoing open colon resection from 1988 to 1995 to determine the effects of age, type of procedure, nature of the procedure (elective vs. emergency), and postoperative course on ALOS. Statistics were calculated by Student's t-test, chi-squared analysis, and analysis of variance. RESULTS: Average length of stay was 10 (range, 4-34) days, with a significant trend toward lower ALOS in recent years; ALOS in 1988 averaged 11 days, whereas in 1994, ALOS averaged 9 days (r2 = 0.118; P < 0.001). Patients younger than 65 years of age had an ALOS of 9 days vs. 11 days in patients older than 65 years (P = 0.0024). Patients with anastomoses on the right and left side had similar ALOS (8.5 vs. 9.1 days), whereas creation of a stoma was associated with a significantly higher ALOS (12.1 days; P < 0.00001). The need for postoperative nasogastric intubation (14.9 vs. 9.3 days) and the performance of emergency operations (12.2 vs. 6.5 days) were also associated with a significantly higher ALOS (P < 0.00001). CONCLUSIONS: Caution must be exercised in accepting rigid criteria for length of stay for patients undergoing colorectal resections, as uncontrollable clinical variables are involved in defining the "ideal" patient.

Age Factors↗
PubMed1997

Intraoperative colonic lavage in nonelective surgery for diverticular disease.

BACKGROUND: Staged resection of the sigmoid colon has been the traditional strategy for treating patients who require nonelective surgery to manage complications of diverticular disease. Resection and primary anastomosis has not generally been recommended when the clinical setting is compromised by contiguous inflammation or inadequate mechanical cleansing of the colon because of concerns regarding the potential risk of anastomotic dehiscence. Although many reports have confirmed that intraoperative colonic lavage (ICL) is a safe method for relieving fecal loading of the colon to facilitate primary intestinal anastomosis in patients with mechanical obstruction of the distal colon, there is very limited experience with the use of this technique in treating acute inflammatory disorders of the colon. In this report, we present our results with ICL in the nonelective treatment of patients with complications of diverticulitis. METHODS: Records of all patients undergoing urgent operations at the Lahey Clinic to treat complications of diverticular disease from July 1987 to January 1996 were reviewed. RESULTS: Of 62 patients who required nonelective operations, 33 underwent ICL in an attempt to perform primary anastomosis. In five patients, the operation included creation of a colostomy. The indication for surgery was obstruction in 13 patients (39 percent), persistent abscess or phlegmon in 13 (39 percent), perforation in 6 patients (18 percent), and hemorrhage in 1 patient (3 percent). According to Hinchey's classification system, 18 patients had Stage I disease, 10 had Stage II, and 5 patients had Stage III disease. There were no patients with Stage IV disease. The single anastomotic complication in the series was responsible for the sole operative mortality. The morbidity rate of 42 percent, included three intraoperative complications (2 splenic injuries and 1 ureteral laceration), two intra-abdominal abscesses (6 percent), and six wound infections (18 percent). CONCLUSION: In our experience, ICL has proven to be a safe method for accomplishing single-stage resection of the colon in selected patients with diverticulitis who require an urgent operation. When there is no evidence of diffuse purulent or feculent peritonitis, we believe this is the preferred method for treating patients who are hemodynamically stable.

Abdominal Abscess↗
PubMed1997

Reduction of myocardial infarct size in rabbits and inhibition of activation of rabbit and human neutrophils by lidocaine.

Myocardial reperfusion is associated with increased influx of activated neutrophils and intracellular accumulation of sodium in the ischemic zone. Lidocaine is a sodium channel blocker that also inhibits several neutrophil functions. We investigated the effect of lidocaine on infarct size in rabbits undergoing 30 minutes of ischemia and 48 hours of reperfusion. Animals randomly received lidocaine (10 mg/kg, n = 11) or saline (n = 11) during occlusion. The area of necrosis (AN) was measured histologically and expressed as a percentage of the area at risk (AR). Myocardial oxygen consumption and the perfusion bed at risk were similar in the two groups. Lidocaine reduced infarct size compared with control (AN/AR = 30% +/- 4% vs 61% +/- 5%, respectively; p = 0.0001). This reduction was associated with a significant decrease in neutrophil infiltration and in the degree of hemorrhage in the reperfused myocardium. Lidocaine also significantly inhibited superoxide anion production by rabbit and human neutrophils in whole blood. Therefore, lidocaine treatment results in a significant reduction in infarct size in the rabbit model, partly through reduction of neutrophil-mediated injury to viable cells, suggesting that lidocaine may be useful to enhance myocardial salvage in patients undergoing pharmacologic or mechanical reperfusion.

Animals↗
PubMed1997

Clinical factors related to reported satisfaction with oral function amongst dentate older adults in England.

This paper aims to identify the features of a natural dentition, specifically the number and distribution of teeth, which are important for oral satisfaction and freedom from eating problems in the elderly. Data were gathered on the dental condition, satisfaction and function of 1211 dentate adults aged 60 years or over, randomly sampled from three areas in England. Multiple logistic regression was used to identify the clinical factors which contribute to satisfaction with aesthetics and the ability to bite and chew. Satisfaction with biting and chewing was influenced by specific reported eating problems, dry month and increasing age. The presence of these eating problems was related to a complex series of factors describing the number and distribution of teeth and dentures, and some variables describing symptoms and disease. Having 21 or more natural teeth and no removable partial dentures (odds ratio 3.2), 2 or more posterior contacting pairs of teeth (odds ratio 1.7), and few anterior spaces were important factors related to the absence of eating problems. Unfilled anterior spaces (odds ratio 3.9), and widespread caries and periodontal disease were associated with aesthetic dissatisfaction. Many of the principles of shortened dental arch are consistent with good function and satisfaction in the elderly.

Aged↗
PubMed1997

Botulinum toxin type B: a double-blind, placebo-controlled, safety and efficacy study in cervical dystonia.

We enrolled and treated 122 patients with idiopathic cervical dystonia in a double-blind, placebo-controlled safety and efficacy study of botulinum toxin type B (BotB). Both A-responsive and A-resistant patients were enrolled. Patients received intramuscular injections of either BotB (2,500 U, 5,000 U, or 10,000 U) or placebo. The primary outcome measure of efficacy was the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total score at 4 weeks following study drug administration. Secondary measures of efficacy were TWSTRS-Severity, -Disability, and -Pain subscale scores, and Analog Pain Assessment, Investigator Global Assessment, Patient Global Assessment, and Sickness Impact Profile scores. Duration of effect was estimated with an intent-to-treat analysis of responders. Safety measures included clinical parameters, laboratory tests, and adverse events. The primary and most of the secondary analyses indicated a statistically significant treatment effect and a dose response. BotB is safe, well tolerated, and efficacious in the treatment of cervical dystonia at the doses tested.

Adult↗
PubMed1997

Developments in fluoride toothpastes--an overview.

OBJECTIVE: This paper reviews current issues in the development of fluoride toothpastes as a public health measure. DESIGN: The issues examined included low concentration formulations, delivery systems, dispensing instructions and labelling, oral clearance. effect on root caries, additional therapeutic agents and marketing and manufacturing issues. RESULTS: Lower fluoride formulations may carry a lower risk of fluorosis but this must be balanced against a higher risk of caries. Risk factors for fluorosis include inappropriate fluoride supplements but the age at which toothbrushing began, frequency of brushing and residence in an optimum fluoride area have also been implicated. CONCLUSIONS: The dental profession should: clarify the most appropriate fluoride concentration in toothpastes used for children; ensure that other sources of fluoride do not increase the risk of dental fluorosis: investigate the effectiveness of fluoride toothpaste in inhibiting root surface caries in adults. Manufacturers should: continue to improve the performance of fluoride toothpaste; ensure that all pastes maximise fluoride bioavailability; develop active agents to help reduce oral disease; label products clearly with ppm F; review the delivery systems so as to reduce the risk of dental fluorosis.

Adult↗