Long-term follow-up of Perthes' disease treated nonoperatively

Forty-six patients with Perthes disease treated nonoperatively were reviewed 10 to 43 years later. The median follow-up was 17 years. The patients were analyzed according to sex, age of onset, quantity of head involvement, type of treatment, duration of treatment, functional end result based on the Harris hip scale, and anatomic end result based on Mose templete evaluation. Most patients were treated with an ischial weight-bearing brace. The anatomic results of this treatment tended to be poor, probably worse than no treatment at all. In general, poor results were correlated with late onset, greater quantity of head involvement, and lateral subluxation of the femoral head. As reported in other series, the anatomic results did not correlate well with the functional results, only two patients having Harris hip scales below 70.     

Cyclin-dependent kinase 5-deficient mice demonstrate novel developmental arrest in cerebral cortex

The cerebral cortex of mice with a targeted disruption in the gene for cyclin-dependent kinase 5 (cdk5) is abnormal in its structure. Bromodeoxyuridine labeling reveals that the normal inside-out neurogenic gradient is inverted in the mutants; earlier born neurons are most often found superficial to those born later. Despite this, the early preplate layer separates correctly and neurons with a normal, pyramidal morphology can be found between true marginal zone and subplate. Consistent with their identity as layer VI corticothalamic neurons, they can be labeled by DiI injections into thalamus. The DiI injections also reveal that the trajectories of the cdk5(-/-) thalamocortical axons are oblique and cut across the entire cortical plate, instead of being oriented tangentially in the subcortical white matter. We propose a model in which the cdk5(-/-) defect blocks cortical development at a heretofore undescribed intermediate stage, after the splitting of the preplate, but before the migration of the full complement of cortical neurons.     

Salivary gland tumors after childhood radiation treatment for benign conditions of the head and neck: dose-response relationships

In this study the mechanisms were investigated whereby ACE-inhibitors improve pulmonary diffusion for carbon monoxide (DLco) in chronic heart failure. The two subcomponents of DLco are the alveolar-capillary membrane conductance (DM) and the capillary blood volume (VC). Stress failure of the membrane in chronic heart failure provides a mechanism for reduction of DM and, as a consequence, impairment of DLco. In 27 patients with chronic heart failure in NYHA functional class II to III and in 13 age- and sex-matched normal subjects, we evaluated the pulmonary function and determined DM and VC, according to the classic Roughton and Forster method, while they were given placebo, at 48 hours and 8 weeks after starting enalapril treatment (10 mg bid). ACE-inhibition had no effect in controls at both short- and mid-term. In chronic heart failure patients, a reduction in VC (likely consequence of a decrease in capillary pulmonary pressure) was the only change observed at 48 hours. At 8 weeks, DM was greatly increased even when the effective alveolar volume (VA) was accounted for (DM/VA), resulting in a significant improvement in DLco, despite a decrease in VC. The slow onset DM improvement makes it likely that the modulatory effect of ACE-inhibition on the membrane function emerges gradually, suggesting that it is likely dissociated from changes in pulmonary capillary pressure and VC. Thus, derangements of the alveolar-capillary membrane in chronic heart failure increase gas diffusion resistance; ACE-inhibition restores the diffusive properties of the membrane and gas transfer, and protects the lung when the heart is failing.     

The infrarenal aortic diameter in relation to age: only part of the population in older age groups shows an increase

The aim of the present investigation was to study the relationship between ascorbic acid status during the third trimester of pregnancy and levels of this vitamin in transition milk (days 13-14 of lactation) and mature milk (day 40 of lactation). To this end, the pregnancies and lactation periods of fifty-seven healthy women between 18 and 35 years of age (27 (SD 3.7) years) were monitored. Vitamin intake during the third trimester was determined by recording the consumption of foods over 5 d, and by registering the quantities provided by dietary supplements. Ascorbic acid levels in maternal serum during this stage of pregnancy, and in transition and mature milk samples, were determined by spectrophotometry. Those subjects with ascorbic acid intakes below that recommended (80 mg/d) (group L) showed lower consumption of fruit and vegetables than did those with greater intakes (group H). The consumption of ascorbic acid supplements was very low, and was only seen in three group H subjects. The difference in ascorbic acid intake was reflected at serum level. Group L subjects showed significantly lower serum values than did group H subjects (30.1 (SD 36.3) mumol/l compared with 101.1 (SD 168.1) mumol/l). Vitamin intake also influenced the composition of transition milk. Group L subjects showed significantly lower levels of ascorbic acid in milk than did group H subjects (255.5 (SD 220.3) mumol/l compared with 437.8 (SD 288.4) mumol/l). The results of the present study reveal the need to increase the consumption of fruits and vegetables during pregnancy and to monitor maternal ascorbic acid intake and vitamin C status.     

Indications for laparoscopic colorectal surgery. Results from the Medical Centre Alkmaar, The Netherlands

The Boyden chamber method showed that the invasiveness to reconstituted blood vessel endothelium of metastatic gynecologic cancer cell lines of the uterine cervix (MS751 and ME-180), endometrium (AN3 CA), and ovary (SK-OV-3 and PA-1) was significantly higher than of primary cancer cell lines of the cervix (HeLa and C-33 A), endometrium (Ishikawa, HEC-1-A and HHUA), and ovary (MCAS and Caov-3), and that the invasiveness was inhibited by estradiol or progestin in the metastatic cells but not in the primary cells. These results suggest that metastatic cancer cells by themselves increase the potential of blood vessel invasion, which can be inhibited by estrogen and progestin administration.     

Geographic variations in breast cancer mortality: do higher rates imply elevated incidence or poorer survival?

A 46-year-old women presented with an inoperable low-grade endometrial stromal sarcoma. Two doses of Depo-Lupron, 7.5 mg, and Megace, 160 mg/day, were given to control uterine bleeding and shrink the tumor mass. In 9 weeks, significant reduction in the tumor occurred allowing for surgical resection. Total abdominal hysterectomy with bilateral salpingo-oophorectomy is the mainstay for primary treatment. The role of chemotherapy, radiation therapy, and hormonal therapy is poorly defined. This is a case report of neoadjuvant hormonal therapy which may improve outcomes in patients with endometrial stromal sarcomas. Additional research is needed to define the exact role of these agents.     

Optimization of evening insulin dose in patients using the short-acting insulin analog lispro

OBJECTIVE: A three-way, crossover, open-label, randomized study was designed to compare the evening and night (1800-0800) glycemic control when the evening premeal lispro dose was reduced by 20% and the bedtime basal NPH dose increased by 25%, or when the basal NPH dose was moved to before dinner at 1800, compared with the control arm on standard premeal human regular insulin and pre-bedtime NPH insulin. RESEARCH DESIGN AND METHODS: A total of 13 type 1 diabetic patients who use a premeal plus basal insulin regimen were studied on three separate days, with identical meals and snacks at the same times on each study day. On the control study day, patients received human regular insulin before dinner and NPH at bedtime in their usual doses. On another day, lispro was given before dinner with a dose reduction of 20%, and NPH at bedtime at 125% of usual dose. In the third regimen, the lispro and NPH were administered together in their usual dose before the evening meal by separate injections. The three regimens were tested in random order. RESULTS: Postprandial (1800-2200) blood glucose concentrations were lower after reduced-dose lispro compared with human regular insulin (6.0 +/- 0.3 [SEM] vs. 7.4 +/- 0.3 mmol/l, P < 0.05). Nighttime (2400-0400) blood glucose concentrations were not different (8.6 +/- 0.3 vs. 9.2 +/- 0.3 mmol/l, NS), and prebreakfast concentrations were also unchanged (7.7 +/- 0.9 vs. 8.7 +/- 0.8 mmol/l) after lispro with increased-dose NPH compared with standard insulin. By contrast, both nighttime (10.0 +/- 0.3 mmol/l, P < 0.05) and fasting glucose concentrations (10.8 +/- 0.6 mmol/l, P < 0.05) were significantly higher with dinnertime usual-dose lispro plus dinnertime usual-dose NPH compared with standard human insulin. Hypoglycemia at night (blood glucose < 3.0 mmol/l) did not differ between study days, but it was more frequent postprandially after dinner usual-dose lispro plus early NPH (2 vs. 7 patients, P = 0.062). CONCLUSIONS: With lower mealtime and higher basal bedtime insulin doses, patients using insulin lispro may be able to gain an overall improvement in evening blood glucose control without deteriorated nighttime glucose levels. Earlier basal NPH dosage alone does not ameliorate the nighttime hyperglycemia of short-acting insulin analog regimens.     

Evidence of genetic susceptibility to Chlamydia trachomatis-induced pelvic inflammatory disease in the pig-tailed macaque

The macaque model of chlamydial pelvic inflammatory disease (PID) demonstrates individual variability in the time of onset of intrapelvic adhesions. Some animals develop adhesions rapidly, within 2 weeks after a single tubal inoculation with Chlamydia trachomatis, while in others, adhesions are not observed until 2 weeks after a second tubal inoculation. To test whether this variability correlates with major histocompatibility complex (MHC) class I haplotype, we used macaque alloantisera and mouse anti-HLA monoclonal antibodies to determine the MHC class I haplotypes of 44 C. trachomatis-infected macaques (Macaca nemestrina). Macaques developing gross tubal adhesions after the first chlamydial inoculation were classified as susceptible (n = 29), while those not developing adhesions until after the second chlamydial inoculation were classified as relatively resistant (n = 15), to adhesion formation. Three antibody specificities correlated with susceptibility (odds ratio [OR] 5.2, P < 0.01; OR 6.1 and 4.3, P < 0.05), and two correlated with relative resistance to adhesions (OR 0.1, P < 0.05; OR 0.2, P < 0.01). Because several of these antibodies are cross-reactive, as many as five different MHC class I alleles (three increasing and two decreasing ORs) or as few as two different MHC class I alleles (one increasing and one decreasing OR) could be correlated with risk of adhesion formation. We conclude that in macaques, susceptibility or relative resistance to rapid formation of tubal adhesions is correlated with expression of MHC class I alleles, consistent with reports of MHC class I restriction of chlamydial immunopathology in humans.     

Somatic hypermutations in the VH segment of immunoglobulin genes of CD5-positive diffuse large B-cell lymphomas

De novo CD5-positive (CD5+) diffuse large B-cell lymphoma (DLBL) has recently been identified as constituting a homogeneous subgroup with distinct clinicopathologic and genotypic characteristics, but its origin remains to be elucidated. Previous studies by sequence analysis of the variable region of the immunoglobulin heavy chain (VH) have shown that CD5+ B-cell malignancies such as mantle cell lymphoma (MCL) and B-cell chronic lymphocytic leukemia (B-CLL) cells represent pre-germinal center (pre-GC) stage B cells in contrast with the post-GC stage of most DLBLs, which show somatic hypermutations in VH genes. In the present study, we investigated the VH sequence of de novo CD5+ DLBL to clarify whether CD5+ DLBL represents the pre-GC stage, as do other CD5+ B-cell malignancies, or the post-GC stage, as is typical of DLBL. All eight cases (four CD5+ DLBL and four CD5-negative (CD5-) DLBL) examined by us showed somatic hypermutations in the VH segment and two of the CD5- DLBL cases showed intra-clonal diversity, suggesting that CD5+ DLBLs were derived from the same maturation stage as CD5- DLBL, but were distinct from the other indolent CD5+ B-cell lymphomas of B-CLL and MCL. These data suggest that de novo CD5+ DLBLs do not merely lie within a continuous spectrum with B-CLL and MCL, but represent a biologically distinct variant within the diagnostic framework of diffuse large B-cell lymphoma.