Unilateral vs. bilateral carpal tunnel: challenges and approaches

Conditions affecting either or both extremities offer unique opportunities and challenges for investigators and clinicians. When the condition is purely unilateral, observations on the unaffected extremity may be used as a within-patient control, and thereby strengthen the ability to identify changes in the affected limb. However, such use presumes that the condition will not subsequently develop in the unaffected extremity. Bilateral presentations or subsequent development of disease in the unaffected extremity is common in conditions such as the carpal tunnel syndrome (CTS). Treatment of one extremity may lead to development or aggravation of CTS in the other extremity. Since both extremities may be necessary to perform certain activities, it can be difficult to clearly identify treatment effects when looking at functional outcomes. In an effort to avoid these complexities, investigators have used one of two approaches in studying CTS: either selecting only those patients with unilateral disease, or analyzing results by extremity, often avoiding any outcome measures that might depend upon both extremities (such as driving). We illustrate some of the shortcomings of this approach, such as loss of patients and data, with preliminary information from our ongoing prospective study of carpal tunnel surgery outcomes. We develop a dynamic model that incorporates etiologic factors and treatment effects to describe changes in CTS over time. This model accounts for extremity-specific and systemic factors, as well as possible interaction of the disease process in both hands. The advantages of this model include a more rational approach to research and care of extremity disorders, and research strategies which address a wider scope of patients and outcomes; however, its application is limited by the need for more extensive data collection.     

High-dose chemotherapy with autologous hematopoietic progenitor-cell support as part of combined modality therapy in patients with inflammatory breast cancer

PURPOSE: To evaluate the feasibility of high-dose chemotherapy (HDC) with autologous hematopoietic progenitor-cell support (AHPCS) as part of combined modality therapy (CMT) in patients with inflammatory breast cancer (IBC). PATIENTS AND METHODS: From April 1993 to March 1997, 30 patients with IBC were treated at our program. Twenty-three patients received neoadjuvant chemotherapy (NAC) before HDC; 18 patients also received adjuvant chemotherapy following surgery, but before HDC. All patients received HDC with high-dose cyclophosphamide, cisplatin, and carmustine (BCNU) with AHPCS. Every patient underwent surgery either before (27 patients) or after (three patients) HDC. Patients received radiotherapy after HDC in addition to tamoxifen if their tumors were estrogen receptor-positive. RESULTS: Thirteen patients experienced grade 3 or 4 nonhematologic noninfectious toxicities. In 12 patients (40%), this represented drug-induced lung injury, which in all cases responded to a 10-week course of corticosteroids. The only treatment-related death was secondary to hemolytic-uremic syndrome (HUS). Another patient suffered grade 4 CNS toxicity, which was completely reversible. All patients engrafted promptly. Eight patients relapsed, five of whom had a poor pathologic response to NAC. Relapses were local (five patients), local plus systemic (one), or systemic only (two). Median follow-up time from diagnosis and HDC is 23.5 (range, 7 to 49) and 19 (range, 4 to 44) months, respectively. Twenty-one patients (70%; 95% confidence interval [CI], 51% to 86%) remain alive and free of disease 4 to 44 months after HDC. Median disease-free survival (DFS) and overall survival have not yet been reached. CONCLUSION: HDC as part of CMT is feasible in patients with IBC. The toxicity of this treatment program is significant, but tolerable. Despite the short follow-up duration, the promising DFS observed in this group of patients warrants randomized studies that include a HDC-containing arm in patients with IBC.     

Single-strand breaks, cell cycle arrest and apoptosis in HL-60 and LLCPK1 cells exposed to 1,2-dibromo-3-chloropropane

We investigated 1,2-dibromo-3-chloropropane (DBCP)-induced DNA damage, cell cycle alterations and cell death in two cell lines, the human leukemia HL-60 and the pig kidney LLCPK1, both of which are derived from potential target sites for DBCP-induced toxicity. DBCP (30-300 micromol/L) caused a concentration-dependent increase in the levels of DNA single-strand breaks in both cell lines as well as in cultured human renal proximal tubular cells. After extended DBCP exposure in LLCPK1 cells (100 micromol/L, 30 h), the level of DNA breaks returned almost to control values. Incubation for 48 h showed a clear reduction of growth with DBCP concentrations as low as 10 micromol/L. Flow cytometric analysis showed that DBCP (1-10 micromol/L) exposure for 24 h caused an accumulation of LLCPK1 cells in the G2/M-phase. In HL-60 cells the accumulation in G2/M-phase was less marked, and at higher concentrations the cells accumulated in S-phase. Flow cytometric studies of HL-60 and LLCPK1 cells exposed to 100-500 micromol/L DBCP showed increased number of apoptotic cells/bodies with a lower DNA content than that of the G1 cells. Microscopic studies revealed that there were increased numbers of cells with nuclear condensation and fragmentation, indicating that apoptosis was the dominant mode of death in these cell lines, following exposure to DBCP. The characteristic ladder pattern of apoptotic cells was observed when DNA from DBCP-treated HL-60 cells and LLCPK1 cells was electrophoresed in agarose. The finding that DBCP can cause an accumulation of cells in G2/M-phase and induce apoptosis in vitro may be of importance for the development of DBCP-induced toxicity in vivo.     

Detection of Cryptosporidium oocysts and Giardia cysts in the tissues of eastern oysters (Crassostrea virginica) carrying principal oyster infectious diseases

The potential cross-reactivity of the combined Cryptosporidium/Giardia direct immunofluorescence antibodies (IFA) of MERIFLUOR and HYDROFLUOR-COMBO tests was examined against tissues containing known developmental stages of 12 pathogens causing the principal infectious diseases in oysters. Spores of Haplosporidium nelsoni and Haplosporidium costale produced positive acid-fast stain (AFS) reactions similar in intensity to Cryptosporidium parvum oocysts. Hexamia nelsoni trophozoites produced positive IFA reactions in both IFA tests; however, the intensity of fluorescence was considerably lower and the fluorescein-staining pattern different than those of Giardia cysts. The applicability of AFS for screening oysters for Cryptosporidium oocysts is low, and positive identification of Cryptosporidium oocysts cannot be accomplished based on the AFS. Presumptive IFA identification of the Cryptosporidium oocysts or Giardia cysts in the oyster tissue should fulfill 3 criteria, i.e., bright-green fluorescence of the same intensity as C. parvum oocysts and Giardia cysts in the positive control, correct size and shape of the fluorescein-stained objects, and oocyst or cyst shell clearly visible.     

Screening male intracytoplasmic sperm injection candidates for mutations of the follicle stimulating hormone receptor gene

Follicle stimulating hormone (FSH) is considered to be essential for spermatogenesis. Therefore, genetic abnormalities of FSH signalling on testicular Sertoli cells would be expected to affect sperm production negatively in males. Inactivating FSH receptor mutations have been reported earlier in both males and females. All affected males had elevated FSH serum concentrations and abnormal sperm parameters. We postulated that inactivating FSH receptor mutations might be a cause of oligozoospermia or azoospermia and reviewed the clinical data of 151 male intracytoplasmic sperm injection (ICSI) candidates with special attention to FSH serum concentrations. The exclusion criteria for mutation screening of the FSH receptor gene were: a history of operative sterilization or testicular malignancy, congenital abnormality other than cryptorchidism, and a chromosomal aberration or a Y-chromosome microdeletion. The inclusion criteria were: male (ICSI candidate) with azoospermia or oligoasthenoteratozoospermia (OAT) and elevated FSH serum concentrations. In total, 23 males with OAT and five males with azoospermia were tested for mutations of the coding sequences and the intron-exon boundaries of the FSH receptor gene by polymerase chain reaction (PCR) followed by single strand conformation polymorphism analysis (SSCP). Neutral polymorphisms were readily detected using this technique in both probands and controls. None of the 28 selected patients showed a pathogenic FSH receptor mutation. Mutations in the FSH receptor gene are not a common cause of infertility in ICSI candidates.     

Specific detection of myeloma plasma cells using anti-idiotypic single chain antibody fragments selected from a phage display library

OBJECTIVES: The authors examined how the courts have responded to public and private insurers' use of medical appropriateness criteria to establish coverage and payment policies. METHODS: A structured review of all federal and state court health insurance cases decided between 1960 and June 1994 that involved a dispute involving medical appropriateness was performed. A total of 3,215 published court decisions were analyzed, of which 203 met the criteria of relevance and 124 explicitly mentioned medical appropriateness criteria. The main outcome variable was whether the court ordered the insurer to provide coverage. RESULTS: In 185 cases, a definitive decision was rendered, and the insurer was required to pay in 57% of the decisions. Whether the insurer relied on an assessment or not, whether the assessment process was formal or informal, and who conducted the assessment did not appear to influence courts' decisions, nor did the specificity of the coverage exclusion. Significant predictors of courts ordering coverage were court jurisdiction, contract language assigning discretion to the insurer, severity of patient's condition, and whether the treatment appeared to work for the particular patient. CONCLUSIONS: For practice guidelines to be accepted by the courts, it is more important to focus on how insurance contracts are written than on how medical assessments are performed.