Familial osteoarthritis and Milwaukee shoulder associated with calcium pyrophosphate and apatite crystal deposition.

OBJECTIVE: To characterize and define the phenotypes observed in a large Italo-Argentinean kindred with osteoarthritis, chondrocalcinosis, and Milwaukee shoulder (MS). METHODS: Seventy-five members were evaluated with a history, examination, and radiographs of shoulders, spine, hands, and knees. Superior subluxation of the glenohumeral joint was graded using shoulder radiographs and tomography and nuclear magnetic resonance imaging and 3 dimensional computed tomography was performed on selected members. In 31 family members peripheral blood DNA was utilized for genetic linkage analysis of several candidate gene loci previously linked to chondrocalcinosis phenotypes, as well as those implicated in the proper patterning of skeletal elements and cartilage differentiation. In addition, direct sequence analysis of type II collagen gene (COL2A1), the gene that codes for the major structural protein of cartilage, was undertaken in 3 affected and 3 unaffected members of the family. RESULTS: MS was seen in one member of the first generation and 6 members of the 2nd generation, while 8 members of the 3rd generation showed an incomplete form of MS. Isolated superior subluxation of the shoulder was seen in 16 other family members of the 3rd and 4th generations. Osteoarthritis of the spine and peripheral joints was seen in 31 affected members, while chondrocalcinosis was observed in 6 members of the first generation. Shoulder synovial fluid from 2 patients showed the presence of both apatite and calcium pyrophosphate dihydrate crystals. Direct analysis of the COL2A1 gene indicated no known disease determining mutations in affected members, thus excluding this gene as a candidate gene in this family. Genetic linkage to several candidate loci, including the chondrocalcinosis loci on chromosomes 5p and 8q, as well as loci for HOX A and C were also excluded. Linkage analyses of other loci for the HOX B and D genes and the PAX 1 and 9 genes were uninformative in this kindred. CONCLUSION: This kindred illustrates an unusual type of osteoarthritis with secondary intraarticular and periarticular calcification and MS in the most severely affected elderly members. A search for linkage to some potential candidate genes was either excluded or uninformative. Further linkage analysis to identify potential candidate genes is in progress.

Pharmacoeconomics of intravenous antibiotic use in serious infection.

A pharmacoeconomic study of 15 antibiotics available in Barbados was performed. The antibiotics studied were amoxycillin/clavulanate, ampicillin, ampicillin/sulbactam, cefazolin, cefotaxime, ceftazidime, ceftriaxone, clindamycin, cloxacillin, cotrimoxazole, gentamicin, imipenem, metronidazole, piperacillin, piperacillin/tazobactam, and vancomycin. The costs of use of these compounds were calculated for a five-day course using a formula comprising eight categories: antibiotic purchase cost, maintenance of intravenous access, drug delivery cost, drug monitoring cost, dose readjustment, general monitoring cost, 'sharps' disposal cost and adverse effects. The costs of adverse effects were not included in this study due to lack of accurate data. The total cost of antibiotic use (in U.S. dollars) ranged from $42.52 to $463.73 per five-day course. Generic compounds were less expensive ($45.52 - $98.23) than brand-name compounds ($106.18 - $106.18 - $463.73). Antibiotic purchase costs accounted for proportions of total costs ranging from 7 to 93%. Non-drug costs represented a much greater proportion of total costs of generic compounds. For most compounds the non-drug costs were related to the frequency of dosing, but for gentamicin the non-drug costs were relatively higher because of the need for monitoring of serum gentamicin levels. Efficacy and freedom from side-effects will remain the most important determinants in the choice of antibiotic therapy. However, pharmacoeconomic analyses can provide prescribers with the information required to make cost-effective choices for treatment of their patients.

Pharmacoeconomics of intravenous antibiotic use in serious infections

A pharmacoeconomic study of 15 antibiotics available in Barbados was performed. The antibiotics studied were amoxycillin/clavulanate, ampicillin/sulbactam, cefazolin, cefotaxime, ceftazidime, ceftriaxone, clindamycin, cloxacillin, cotrimoxazole, gentamicin, imipenem, metronidazole, piperacillin/tazobactam, and vancomycin. The costs of use of these compound were calculated for a five-day course using a formula comprising eight categories: antibiotic purchase cost, maintenance of intravenous access, drug delivery cost, drug monitoring cost, dose readjustment, general monitoring cost, 'sharps' disposal cost and adverse effects. The cost of adverse effects were not included in this study due to lack of accurate data. The total cost of antibiotic use (in U.S. dollars) ranged from $42.52 to $463.73 per five-day course. Generic compound were less expensive ($45.52-$98.23) than brand-name compounds ($106.18 - $463.73). Antibiotic purchase costs accounted for proportions of total costs ranging from 7 to 93 percent. Non-drug costs represented a much greater proportion of total costs of generic compounds. For most compound the non-drug costs were related to the frequency of dosing, but for gentamicin the non-drug costs were relatively higher because of the need for monitoring of serum gentamicin levels. Efficacy and freedom from side-effects will remain the most important determinants in the choice of antibiotic therapy. However, pharmacoeconomic analyses can provide prescribers with the information required to make cost-effective choices for treatment of their patients (AU)

Pharmacoeconomics of intravenous antibiotic use in serious infections

A pharmacoeconomic study of 15 antibiotics available in Barbados was performed. The antibiotics studied were amoxycillin/clavulanate, ampicillin/sulbactam, cefazolin, cefotaxime, ceftazidime, ceftriaxone, clindamycin, cloxacillin, cotrimoxazole, gentamicin, imipenem, metronidazole, piperacillin/tazobactam, and vancomycin. The costs of use of these compound were calculated for a five-day course using a formula comprising eight categories: antibiotic purchase cost, maintenance of intravenous access, drug delivery cost, drug monitoring cost, dose readjustment, general monitoring cost, 'sharps' disposal cost and adverse effects. The cost of adverse effects were not included in this study due to lack of accurate data. The total cost of antibiotic use (in U.S. dollars) ranged from $42.52 to $463.73 per five-day course. Generic compound were less expensive ($45.52-$98.23) than brand-name compounds ($106.18 - $463.73). Antibiotic purchase costs accounted for proportions of total costs ranging from 7 to 93 percent. Non-drug costs represented a much greater proportion of total costs of generic compounds. For most compound the non-drug costs were related to the frequency of dosing, but for gentamicin the non-drug costs were relatively higher because of the need for monitoring of serum gentamicin levels. Efficacy and freedom from side-effects will remain the most important determinants in the choice of antibiotic therapy. However, pharmacoeconomic analyses can provide prescribers with the information required to make cost-effective choices for treatment of their patients

Familial spondyloepiphyseal dysplasia tarda, brachydactyly, and precocious osteoarthritis associated with an arginine 75-->cysteine mutation in the procollagen type II gene in a kindred of Chiloe Islanders. I. Clinical, radiographic, and pathologic findings.

OBJECTIVE: To characterize a kindred of Chiloe Islanders with spondyloepiphyseal dysplasia tarda (SEDT), brachydactyly, precocious osteoarthritis (OA), and intraarticular calcification. METHODS: Sixteen family members underwent a complete physical examination, anthropometric measurements, radiographic studies of the spine and peripheral joints, and analysis of the type II procollagen gene (COL2A1). RESULTS: Seven family members presented with SEDT, brachydactyly, precocious OA, and periarticular calcification while 2 others had the same syndrome but without brachydactyly. The inheritance was autosomal dominant, and the disease cosegregated with a base substitution in the COL2A1 gene. CONCLUSION: The syndrome o SEDT, precocious OA, and brachydactyly in a kindred of Chiloe Islanders is associated with a point mutation in 1 allele of the COL2A1 gene. The relationship of this type of SEDT to familial calcium pyrophosphate dihydrate deposition disease and idiopathic hip dysplasia, both endemic in Chiloe Islanders, needs to be further investigated.

Headache and painful lymphadenopathy in extracranial or systemic infection: etiology of new daily persistent headaches.

From 108 cases of new daily persistent headaches, clinical or laboratory evidence was found suggesting extracranial or systemic infections in: 28 cases (25.9%) of gastrointestinal mainly Salmonella, 28 (25.9%) urinary Coli, 16 (14.8%) Streptococcal, 4 (3.7%) each of Epstein Barr virus or Toxoplasma, and 1 (0.9%) each of Herpes Zoster or pneumonia. A group of 26 (24.1%) showed high Proteus OX titer or clinical adenoviral involvement. All had normal neurological examinations plus selective negative neuroimaging or spinal taps. The mean headache duration was 13.8 days, and mean age 28.8 years. Prominent symptoms were fever in 37 (34.2%) cases, nausea/vomiting in 30 (27%) and vertigo in 17 (15.7%). Diarrhea, dysuria, and abdominal discomfort were rare. Headache was a solitary symptom in 36 (33.3%). The predominant sign was painful cervical lymphadenopathy in 61 (56.5%). These cases represent 1.2% of our 9060 neurology patients.